Volume 5 - Number 2/2014 - edizioni scripta manent planet

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COP EJA_Stesura D’Alessandro 08/10/14 10:57 Pagina 4
Volume 5 - Number 2/2014
Acniben Rx
®
Calmoactive
®
Coadiuvanti specifici per trattamenti farmacologici
dell'acne
NAPOLI
17-18 Ottobre 2014
00Edit_Stesura D’Alessandro 08/10/14 09:26 Pagina 29
Volume 5, Number 2/2014
L’ultima volta che ho visto Riccarda è stato in occasione
dell’Acne and Rosacea Days, a Milano, alla fine di settembre
dell’anno scorso. In seguito, ci siamo sentiti al telefono alcune volte.
In queste occasioni l’ho trovata come è sempre stata,
e come la ricordo, cioè attiva, vivace, brillante.
Non immaginavo che la sua fine terrena fosse così vicina, così
prematura. Quando una persona muore, gli aggettivi, i pregi, le qualità
si sprecano. Ma nel caso di Riccarda, questi erano e sono doverosi e dovuti.
Anche se frequentavamo via Pace più o meno negli stessi anni della scuola di specialità,
ho conosciuto Riccarda, e bene, solo dopo, quando abbiamo fondato insieme i
“Quaderni di Dermocosmetologia Medica e Chirurgica” e, successivamente,
“Dermo Cosmo News”, una rivista che ha rappresentato una piccola novità nel
panorama editoriale italiano. Questi “parti” erano il frutto di lunghe chiacchierate
accompagnate da innumerevoli sigarette (soprattutto sue…).
Ho sempre riconosciuto a Riccarda non pochi meriti professionali. Riccarda ha inventato
la dermocosmetologia in Italia (ricordo i congressi a Saint Vincent) e ha inventato, attraverso le pagine del “Corriere”, un linguaggio scientifico, rigoroso, ma
comprensibile al grande pubblico: Riccarda ha avvicinato la gente
alla figura del dermatologo: non pensate sia un grande merito?
Infine, ma non sarebbe finita, ha inventato una nuova scienza: la
dermatologia ecologica, con tanto di associazione (Skineco) e di
giornale (il Journal of Ecologic Dermatology). Mi fermo qui: sono
molto, molto triste. Cara Riccarda, mi/ci mancherai.
Stefano Veraldi
00Edit_Stesura D’Alessandro 08/10/14 09:26 Pagina 31
European Journal of Acne and Related Diseases
Volume
5, Number 2/2014
Volume 3, n. 3, 2012
Editorial Board
Content
Treatment of mild to moderate acne with a cream containing nicotinamide,
potassium azeloyl diglycinate, salicylic acid and chloroxylenol.
Results of a multicentre, pilot, open, sponsor-free study
pag 33
Editor
Stefano Veraldi Milano
Co-Editor
Mauro Barbareschi Milano
Scientific Board
Vincenzo Bettoli
Stefano Calvieri
Gabriella Fabbrocini
Giuseppe Micali
Giuseppe Monfrecola
Nevena Skroza
Annarosa Virgili
Ferrara
Roma
Napoli
Catania
Napoli
Roma
Ferrara
Daniele Domenico Raia, Giuseppe Alessandrini, Giuseppe Borda, Gianluigi Cappelletto,
Giorgio Filosa, Enrico Scaparro, Francesco Simonacci, Marco Simonacci, Stefano Veraldi
Results of a multicentre, pilot, open, sponsor-free study on the efficacy,
tolerability and impact on quality of life of a cream containing glycolic acid,
retinaldehyde and undecyl-rhamnoside in patients with acne
pag 42
Stefano Veraldi, Mauro Barbareschi
Drug-induced acneiform eruptions
pag 47
Vittorio Berruti, Antonia Gimma, Franca Taviti, Carla Cardinali
Effects of a new multi-component in cream based on Alukina®
and Microsilver BG™ in the treatment of acne vulgaris
pag 53
Antonino Di Pietro, Pietro Cazzola
Managing Editor
Abstracts
Antonio Di Maio Milano
NAPOLI, 17-18 Ottobre 2014
Italian Acne Club
Giuseppe Alessandrini (Ugento), Mario Bellosta (Pavia), Enzo Berardesca (Roma), Carlo Bertana (Roma), Alessandro Borghi (Ferrara), Francesco Bruno (Palermo),
Carla Cardinali (Prato), Maria Pia De Padova (Bologna), Paolo Fabbri (Firenze), Patrizia Forgione (Napoli), Simone Garcovich (Roma), Antonia Gimma (Prato),
Gian Luigi Giovene (Perugia), Massimo Gola (Firenze), Giovanni Lo Scocco (Prato), Mario Maniscalco (Sciacca), Carlo Pelfini (Pavia), Mauro Picardo (Roma),
Maria Concetta Potenza (Roma), Marco Romanelli (Pisa), Alfredo Rossi (Roma), Rossana Schianchi (Milano), Patrizio Sedona (Venezia),
Aurora Tedeschi (Catania), Antonella Tosti (Bologna/Miami), Matteo Tretti Clementoni (Milano)
International Editorial Board
Zrinka Bukvic Mokos (Zagreb, Croatia), Tam El Ouazzani (Casablanca, Morocco), May El Samahy (Cairo, Egypt), Uwe Gieler (Giessen, Germany),
Maite Gutierrez Salmerón (Granada), Marius-Anton Ionescu (Paris, France), Monika Kapinska Mrowiecka (Cracow, Poland), Nayera Moftah (Cairo, Egypt),
Nopadon Noppakun (Bangkok, Thailand), Gerd Plewig (Munich, Germany), Miquel Ribera Pibernat (Barcelona), Robert Allen Schwartz (Newark, Usa),
Jacek Szepietowski (Breslau, Poland), Shyam Verma (Ladodra, India)
Editorial Staff
Direttore Responsabile: Pietro Cazzola
Direttore Generale: Armando Mazzù
Registr. Tribunale di Milano n. 296 del 01/06/2011.
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31
Raia stes_Stesura D’Alessandro 07/10/14 12:42 Pagina 33
Volume 5, n. 2, 2014
Daniele Domenico Raia1, Giuseppe Alessandrini2, Giuseppe Borda3, Gianluigi Cappelletto4,
Giorgio Filosa5, Enrico Scaparro6, Francesco Simonacci7, Marco Simonacci7, Stefano Veraldi1
1 Department
of Pathophysiology and Transplantation, University of Milan, I.R.C.C.S. Foundation,
Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy
2 Private Practice, Ugento (Lecce), Italy
3 Villa Erbosa, Bologna, Italy
4 Data Clinica, Zero Branco (Treviso), Italy
5 Dermatology Unit, ASUR, Marche AV2, Jesi, Italy
6 ASL 3 Genovese, Genova (Italy)
7 Dermatology Unit, ASUR Marche AV 3, Macerata (Italy)
Daniele Domenico Raia
Treatment of mild to moderate acne with a cream
containing nicotinamide, potassium azeloyl diglycinate,
salicylic acid and chloroxylenol.
SUMMARY
We present the results of a multicentre, pilot, open, sponsor-free
study on the efficacy (primary endpoint) and tolerability (secondary
endpoint) of a new cream containing 4% nicotinamide,
3% potassium azeloyl diglycinate, 2% salicylic acid and
1% chloroxylenol in patients with mild to moderate
acne. Acne severity and treatment efficacy were evaluated by means of the Global Acne Grading System.
Wash out period was at least two weeks for topical
drugs, two months for oral antibiotics and six months
for oral isotretinoin. The cream was applied on the face
twice daily for twelve weeks. All patients were examined
every four weeks. No other topical and/or systemic products or drugs were allowed, except for non-comedogenic
cosmetics, moisturizers and sunscreens.
Furthermore, neither chemical peelings nor sunlight
exposure/phototherapy were allowed. A mean percentage of reduction ≥50% of GAGS from baseline was considered as a significant clinical improvement. At least
one month of follow up was considered. Tolerability was
assessed by means of a 0-to-3 scale severity (0 = absent;
1 = mild; 2 = moderate; 3 = severe; maximum global
value = 18) of six clinical parameters: dryness, scaling,
erythema, oedema, stinging/burning and pruritus.
Student’s t-test was used to assess statistical significance
in the difference observed from the beginning to the end
of the study.
A mean percentage reduction of GAGS ± Standard
Deviation equal to 55.7±13.6% was observed. Remission
of all six tolerability parameters was achieved.
This very good tolerability allowed a high adherence of
patients to the treatment: this cream markedly improved
compliance.
Key words: Acne; Nicotinamide; Potassium azeloyl diglycinate; Salycilic acid; Chloroxylenol; Nipacide; Allantoin.
Introduction
Patients and Methods
We present the results of a multicentre,
pilot, open, sponsor-free study on the evaluation of
the efficacy and tolerability of a new cream* for
the treatment of mild to moderate acne.
This cream contains a novel combination of the
following active compounds: 4% nicotinamide,
3% potassium azeloyl diglycinate, 2% salycilic
acid and 1% chloroxylenol.
Fifty-six patients [23 males (41.1 %) and
33 females (58.9 %)], with a mean age of 19.1±5.7
years, with comedonal, papular, pustular, mild to
moderate acne [Global Acne Grading System
(GAGS ≤30)] 1, were treated with a cream containing 4% nicotinamide, 3% potassium azeloyl diglycinate, 2% salycilic acid and 1% chloroxylenol.
Wash out period was at least two weeks for topical
*Acneffe® crema
33
Volume 5, n. 2, 2014
antiseptics, antibiotics, azelaic acid, salycilic acid,
nicotinamide and retinoids; at least two months for
oral antibiotics and at least six months for oral
isotretinoin. The cream was applied on the face
twice daily for twelve weeks. Each application was
preceded by a cleansing. No other topical and/or
systemic products or drugs were allowed, except
for non-comedogenic cosmetics, moisturizers and
sunscreens. Furthermore, neither chemical peelings nor sunlight exposure/phototherapy were
allowed. Acne severity and treatment efficacy (primary endpoint) were evaluated by means of the
GAGS. All patients were examined every four
weeks. A mean percentage of reduction ≥ 50% of
GAGS from baseline was considered as a significant clinical improvement.
At least one month of follow up was considered.
Tolerability (secondary endpoint) was assessed by
means of a 0-to-3 scale severity of six clinical parameters: dryness, scaling, erythema, oedema, stinging/burning and pruritus (0 = absent; 1 = mild; 2 =
moderate; 3 = severe; maximum global value = 18).
Student’s t-test was used to assess statistical significance in the difference observed from the beginning
to the end of the study and tolerability score.
Results
Severity of lesions measured by GAGS
decreased from a mean absolute value ± SD of
25.1±4.9 at baseline to 11.2±4.1 (p < 0·001) after
twelve weeks of treatment (= mean percentage
reduction ±SD = 55.7± 13.6%). Further reduction
to 10.3±3.9 (p < 0.001; mean percentage reduction
±SD = 59.2±13.4%) was observed after one month
of follow-up (Table 1a, 1b; Figures 1a, 1b).
The tolerability final mean score was ≤ 0·3 for all
six parameters after 12 weeks of treatment (Table
2a). Dryness, scaling, erythema, oedema, stinging/burning and pruritus were absent after 12
weeks of treatment in 98%, 100%, 73%, 86%, 93%
and 98% of patients, respectively .
The sum of such parameters showed a decrease
from a mean value of 4.1±3.4 at baseline to
0.5±0.9 after 12 weeks of treatment (reduction:
87.8%; p < 0·001; Table 2b; Figure 2).
34
Table 1. Efficacy assessment.
Table 1a.
Mean GAGS ± SD
in absolute value.
GAGS
GAGS
GAGS
GAGS
GAGS
T0
T1
T2
T3
T4
25.1
19.8
15.2
11.2
10.3
±
±
±
±
±
4.9
4.3
4.4
4.1
3.9
Table 1b.
Mean percentage reduction of GAGS in comparison
to baseline (GAGS T0).
GAGS
T0 →
T0 →
T0 →
T0 →
T0
T1
T2
T3
T4
100%
(21.1 ± 8.4)%
(39.5 ± 14.3)%
(55.7 ± 13.6)%
(59.2 ± 13.4)%
Discussion
As previously mentioned, the study cream
contains nicotinamide, potassium azeloyl diglycinate, salycilic acid and chloroxylenol.
Nicotinamide (N) (also known as niacinamide) is a
water-soluble amide of nicotinic acid (also known
as niacin). They are similarly effective because
they can be converted into each other. Other synonyms are vitamin B3 and vitamin pellagra preventing (vitamin PP). N is a component of two
important enzymes involved in hydrogen transfer:
nicotinamide adenine dinucleotide (NAD, coenzyme I) and nicotinamide adenine dinucleotide
phosphate (NADP, coenzyme II) 2, 3.
These two codehydrogenases supply hydrogen to
the respiratory chain for oxidation and energy production 4.
The clinical activity of N is likely due to the presence of a pyridine ring in the chemical structure 5.
Several theories were proposed to explain the
activity of topical N in acne.
N acts in acne as anti-inflammatory agent. It inhibits
neutrophil chemotaxis 4-7 and synthesis of phosphodiesterase: the resultant increase in cyclic AMP
induces the inhibition of release of proteases from
leucocytes and the inhibition of lymphocyte trans-
Volume 5, n. 2, 2014
Figure 1.
Figure 1a.
Reduction of GAGS in absolute value.
Figure 1b.
Percentage reduction of GAGS in comparison to baseline.
Table 2a.
Dryness
Scaling
Erythema
Oedema
Stinging/burning
Pruritus
Tolerability. Mean absolute value ± SD for each parameter evaluated.
T0
T1
T2
T3
Mean absolute value ± SD
0.6 ± 0.6
0.3 ± 0.5
0.1 ± 0·3
0
0.6 ± 0.5
0.3 ± 0.5
0
0
1.1 ± 0.7
0.1 ± 0.1
0.3 ± 0.4
0.3 ± 0.4
0.5 ± 0.9
0.3 ± 0.6
0.2 ± 0.1
0.1 ± 0.3
0.6 ± 0.9
0.3 ± 0.5
0.1 ± 0.3
0
0.6 ± 0.9
0.4 ± 0.6
0
0
T4
0
0
0.1 ± 0.3
0
0
0
Table 2b.
Sum of the severity degrees of tolerability parameters (mean values of dryness +
scaling + erythema + oedema + stinging/burning + pruritus for each patient).
Time
T0
T1
T2
T3
T4
Mean value ± Standard Deviation
4.1 ± 3.4
2.7 ± 2.5
0.8 ± 1.2
0.5 ± 0.9
0.5 ± 1.1
Figure 2.
Trend of the sum of severity degrees of tolerability parameters.
35
Volume 5, n. 2, 2014
formation 4,5,8,9. N inhibits the synthesis of polyadenosinediphosphate-ribose-polymerase 1 (PARP
1), a nuclear enzyme involved in DNA repair, which,
if overactivated, causes cell necrosis 4.
PARP enhances nuclear factor-kB-mediated transcription, which plays a central role in the expression of cytokines, adhesion molecules and inflammatory mediators 4. N inhibits the expression of
intercellular adhesion molecule-1 and major histocompatibility complex-II, and the synthesis of
interleukins (ILs) 1 and 12, tumor necrosis factor
(TNF)-α and macrophage migration inhibition factor (MIF) 4, 10. MIF inhibition may be responsible
for the steroid-sparing effect of N, as MIF is upregulated by corticosteroids 4. It has been shown that
Propionibacterium (P.) acnes activates IL-8 synthesis by interacting with toll-like receptor (TLR)
2 on the surface of keratinocytes. It was demonstrated that N downregulates IL-8 gene expression
at transcriptional and post-transcriptional levels
and IL-8 synthesis in a dose-dependent manner,
through phosphorylation of the mitogen-activated
protein kinase and TLR-2 degradation. In addition,
N decreases the half-life of IL-8 mRNA by affecting its stability 7, 11. Furthermore, N acts as an electron scavenger 4-6. Topical N improves the epidermal barrier function: the latter induces reduction in
transepidermal water loss and improvement in the
moisture content of the horny layer 12. N increases
protein (keratin, filaggrin and involucrin),
ceramide, free fatty acids and cholesterol synthesis
in the stratum corneum 12 and speeds up the differentiation of keratinocytes 2.
The activity of N on sebum excretion rate (SER)
was studied by Draelos et al. 13. One hundred
Japanese subjects were enrolled in a double-blind,
placebo-controlled study. Fifty subjects applied a
2% nicotinamide product on the face for 4 weeks
and 50 subjects applied a placebo moisturizer for 4
weeks. SER measurements were taken at baseline,
week 2 and week 4. The group treated with N
demonstrated significantly lower SER after 2 and 4
weeks of application 13.
A 4% N cream contains an anti-bacterial adhesive
(ABA) substance: the latter is sucrose stearate.
This substance inhibits the adhesion of P. acnes on
cytoplasmic membrane of corneocytes of the infra-
36
infundibulum. Seven volunteers of both genders
with acne applied once a day on one forearm, for
three days, a gel containing sucrose stearate; the
other forearm was considered as control.
Corneocytes were isolated from the two forearms
of each volunteer and incubated with P. acnes.
Bacterial adhesion to corneocytes was quantified
by flow-cytofluorimetry. Fluorescence intensity of
corneocytes-bacteria complex was measured. ABA
inhibited the adhesion of 50% P. acnes in three
patients and of 82 to 97% in four patients 14.
The first clinical study on the activity and tolerability of topical N in acne was published in 1995 6. In
this double-blind study, 4% N gel was compared to
1% clindamycin (C) gel in the treatment of moderate inflammatory acne. Seventy-six patients were
randomly assigned to apply either N (n = 38) or C
(n = 38), twice daily for eight weeks. Efficacy was
evaluated at weeks 4 and 8 using Physician's
Global Evaluation, Acne Lesion Counts and Acne
Severity Rating. After eight weeks, both treatments
induced comparable (p = 0.19) beneficial results in
the Physician's Global Evaluation: 82% of the
patients treated with N and 68% treated with C
improved. Both treatments induced statistically
similar reduction in acne lesions (papules and pustules: – 60% in the N group versus –43% in the C
group: p = 0.168), and acne severity (–52% in the
N group versus –38% in the C group: p = 0.161) 6.
In 1995, Griffiths 15 published the results of three
multicentre, randomized, double-blind, vehiclecontrolled studies. A total of 969 patients with mild
to moderate inflammatory acne of the face were
treated twice daily for 8-12 weeks with 4% N gel
(= 486 patients) or placebo (= 483 patients): 709
patients were considered evaluable at the end of the
study (356 patients in the N group and 353 in the
vehicle group). Three clinical criteria of evaluation
were used: Acne Severity Rating, Physician’s
Global Evaluation and papule/pustule count. As far
as Acne Severity Rating is concerned, patients
treated with N experienced greater improvement
over baseline at final visit compared with vehicle
(p = 0.013). Physician’s Global Evaluation: a significantly greater improvement at the final visit in
the group treated with N compared with the group
treated with the vehicle (p = 0.016) was observed.
Volume 5, n. 2, 2014
Papule/pustule count: in the group of patients treated with N, papule/pustule count fell from 29.43 ±
0.77 at baseline to 15.40 ± 0.70 at the final visit,
compared with 29.34 ± 0.78 to 16.07 ± 0.69 in the
vehicle group, e.g. a non significant (p = 0.16) difference between the two groups. The high vehicle
response observed in these patients was most likely a consequence of the hydro-alcoholic gel vehicle, which exerted some therapeutic effect. Side
effects were local erythema and dryness 15.
In 2003, two Indian studies were published 16, 17. In
the study by Dos et al. 16, eighty patients with
moderate acne were enrolled for the comparative
evaluation of 1% C phosphate (40 patients) versus
1% C phosphate and 4% N gel (40 patients). This
study did not show any added advantage of C in
combination with N over C alone 16. In the other
trial, 17 75 patients with inflammatory acne were
divided into three groups. Group A was treated
with 4% N and 1% C, group B was treated with 1%
C and group C, which was considered to have
resistance to local antibiotics due to no response to
treatment, was treated with the combination. At the
end of eight weeks, the results were compared. It
was concluded that addition of N was of not much
value in treating inflammatory acne 17.
Weltert et al. 18 carried out a double-blind trial in
which 4% N gel was compared to 4% erythromycin gel. Two groups of 80 patients each
with moderate inflammatory acne of the face were
treated for eight weeks. The efficacy was evaluated by means of retention and inflammatory lesion
count and clinical score of seborrhoea. N and erythromycin led to equivalent regression of inflammatory lesions. Seborrhoea score presented a more
significant decrease in the group treated with N 18.
An Italian, multicentre, controlled, sponsor-free study, carried out by the Italian Acne Board (IAB) 19,
demonstrated that 4% N cream, applied twice daily
for 12 weeks, induced a significant clinical
improvement (≥ 50% from baseline) in 21 out of 64
patients (32.8%) with mild to moderate acne.
When N (applied once daily for 12 weeks) was
associated with 0.1% adapalene gel (applied once
daily for 12 weeks), 54 out of 106 patients (50.9%)
improved. This group of patients was compared
with another group of 78 patients who were treat-
ed with adapalene (1 application/day for 12 weeks)
and a moisturizer (1 application/day for 12 weeks).
A significant clinical improvement was observed in
32 out of 78 patients (41%). Acne severity and
treatment efficacy were evaluated by means of the
GAGS. Results of these three studies may be summarized as follows:
a) one-third of patients significantly improved with
N alone. This improvement was sometimes
(approximately in 15% of patients) slow (up to
three weeks).
b) Tolerability was excellent. Topical N lacks of
photoallergic or phototoxic potential: therefore,
it can be used in complete safety also in the
summertime.
c) The association N-adapalene is more effective
than the association adapalene-moisturizer: it is
possible that N and adapalene possess a synergistic effect 19.
A multicentre, double-blind, randomized study
was conducted by clinical and biophysical noninvasive measurements to evaluate the efficacy and
tolerability of a 4% N-phospholipidic (linoleic acid
rich-phosphatidylcholine) emulsion versus 1% C
phosphate, both applied once daily for 12 weeks.
The N-phospholipidic association resulted to be
slightly superior to C for all parameters studied
(better compliance and global clinical improvement) 20.
Finally, a multicentre, prospective, non-randomized, open, parallel-group study was published 21.
Patients with mild to moderate acne, who had been
treated with a topical retinoid for at least one
month and had developed skin irritation, were
assigned to one of the two following treatments:
0.2% myrtacine + 4% vitamin PP (n = 116) or a
moisturizer (n = 48). Myrtacine is an ethanolic
extract obtained from myrtle leaves. It showed several pharmacological properties in vitro: it inhibits
keratinocyte proliferation, inhibits the growth of P.
acnes, decreases the synthesis of pro-inflammatory
mediators via the cyclo-oxigenase and lipo-oxigenase pathways, and decreases lipase activity. Both
treatments were administered twice daily. Study
endpoints were: improvement in signs and symptoms of retinoid dermatitis, global efficacy, reduction in acne severity, overall clinical outcome,
37
Volume 5, n. 2, 2014
patient satisfaction and tolerability. At day 28, the
association myrtacine-vitamin PP significantly
decreased signs (erythema, dryness/scaling and
oedema) and symptoms (itching, stinging and
burning sensation) of retinoid dermatitis (p < 0.01),
compared with the moisturizer. In addition, the
association myrtacine-vitamin PP decreased acne
severity in a significantly greater proportion of
patients (p = 0.023) and was associated with a better clinical outcome (global improvement: p
< 0.001) compared with the moisturizer. The association myrtacine-vitamin PP was also associated
with greater patient satisfaction and was better tolerated than the moisturizer 21.
Results of clinical studies published so far on the
treatment of acne with topical N may be summarized as follows:
a) N can be considered as an effective drug for the
treatment of mild to moderate inflammatory acne;
b) tolerability is excellent: no cases of allergic contact dermatitis were published so far. Furthermore,
topical N lacks of photoallergic or phototoxic
potential: therefore, it can be used in complete
safety also in the summertime. When associated
with 0.2% myrtacine, N is effective for prevention
and treatment of retinoid dermatitis; c) topical N
can be used in association with other topical antiacne drugs, although, to our knowledge, it was
associated so far only with adapalene and phosphatidylcholine. A review on topical N in acne was
recently published 22.
Potassium azeloyl diglycinate (PAD) is a new
water soluble derivative of azelaic acid. It is
obtained by reacting the chloride of azelaic acid
with two molecules of glycine and one molecule of
potassium hydroxide 23-25. PAD, like azelaic acid,
has sebostatic and whitening action; furthermore,
it possesses, thanks to the presence of glycine, a
moisturizing effect 23-25. An experimental study
showed that the combination 5% PAD/1% hydroxypropyl chitosan has an anti-inflammatory effect
that is superimposable to that of 15% azelaic acid,
although with a better tolerability 24. Furthermore,
a pilot, multicenter, randomized, double blind,
placebo-controlled study confirmed the efficacy of
this combination in erythema and dryness in
patients with subtypes I and II of rosacea, using
38
both the Mexameter® and Corneometer® devices 25.
A sponsor-free, multicenter, open study showed
that the combination PAD/hydroxypropyl chitosan
is effective in reducing stinging and burning sensation in patients with erythemato-telangiectatic
rosacea. It is possible that this action is due to both
hydroxypropyl chitosan, that improves the skin
barrier function of defense against environmental
physical and chemical insults, and glycine, that
provides a moisturizing effect and enhances the
stratum corneum hydration 26.
Salicylic acid (SA), as detergent in an alcoholic
vehicle, was used for the first time in the treatment
of acne in 1981 27. From then on, several studies
were published 28-57.
SA was used at different concentrations: 0.5% 29,
46, 50, 1% 56, 1.5% 55 and 2% 28-30, 34, 40, 42. As peel
it was used at 20 39 or 30% 33, 38, 48-50, 57. SA was
employed as cleanser 28, 46, 56, cream 30, 34, 50, 55, gel
36, 56, pads/solution/lotion 29, 40, 50 and peel 33, 37-39,
45, 48-50, 57. A thermoactivable foam of SA was also
marketed: it is activated by skin contact, quickly
evaporates with only negligible residues left on the
skin and increases two times the penetration of SA
through the epidermis 42. As far as the vehicles are
concerned, hydroalcoholic vehicle 30, crown carrier system 35, sandalwood oil 46 and aqueous foam
delivery 51 were used. Also in SA peels several
vehicles were used: polyethylene glycol 37, 38,
hydroethanol 48, 49, triethyl citrate and ethyl
linoleate 50. SA was associated with C phosphate
36, 40, 44, C phosphate and benzoyl peroxide (BPO)
47, BPO 51, mandelic acid 39, glycolic acid 56, capryloyl SA/glycolic acid/citric acid/dioic acid 52.
Clinical studies carried out so far showed that SA,
as detergent in an alcoholic vehicle, was more
effective (significant reduction in comedones) than
10% BPO wash 28. However, in another study, SA,
as thermoactivable foam, was as affective as BPO
42. A total of 23 clinical trials on 7309 patients
were considered in a meta-analysis study 43.
At 2 to 4 weeks, SA/5% BPO had statistically
greater percent inflammatory and noninflammatory lesion reductions over other groups. At 10 to 12week end points, SA/5% BPO and C/5% BPO
were similar in efficacy. At early time points,
SA/5% BPO had the best profile. At later time
Volume 5, n. 2, 2014
points, SA/5% BPO was similar to C/5% BPO 43.
The association SA/C phosphate/BPO is superior
to the association C/BPO 47 and the association
SA/capryloyl SA/glycolic acid/citric acid/dioic
acid is as effective as the association C/BPO 52.
The association SA/C is superior to C alone 40,
whereas the association SA/C phosphate showed
no significant difference in terms of all lesion
counts versus retinoic acid/C phosphate 44.
Finally, 20% SA/10% mandelic acid peel was
more effective than 35% glycolic acid 39. Twenty
per cent SA was also associated with oral
isotretinoin: this study showed that this association
is more effective than isotretinoin alone 53, 54.
Chloroxylenol (CH) (4-chloro-3.5-xylenol or
parachlorometaxylenol or nipacide) is a halogenated derivative of phenol. It is soluble in water,
ethanol and ether. CH is bactericidal against several Gram-positive bacteria, but it is less effective
against staphylococci and Gram-negative bacteria.
It is also fungicidal and viricidal, but it has little
activity on spores 58, 59.
CH is used as household antiseptic. In human medicine it was used as a skin and wound antiseptic.
No statistically significant difference in reduction
of comedones, papules and pustules was observed
in two groups of patients treated, respectively, with
0.5% CH/2% SA cream and 5% BPO gel.
However, erythema and photosensitivity were significantly fewer in the group treated with CH and SA 34.
Forty-one patients with acne completed a doubleblind controlled, randomized study comparing a
cream containing CH and zinc oxide versus 5%
BPO cream and versus the vehicle of the cream
containing CH and zinc oxide. Patients applied the
medications twice daily for 8 weeks. At the end of
the trial there was no significant difference in the
reduction of inflammatory and noninflammatory
lesion counts achieved by the cream containing CH
and zinc oxide and the BPO cream. Both creams
proved to be superior to the vehicle. Efficacy grading by patients and investigators showed no significant difference between the two creams. However,
side effects, such as dryness and peeling, were significantly lower in the group treated with CH and
zinc oxide 58.
Conclusions
The results of our study (open, although
multicentre, sponsor-free and based on a high number of evaluable patients) may be summarized as
follows:
a) the study cream showed to be effective in the
treatment of mild to moderate acne.
This was demonstrated by a decrease > 50% of
GAGS in comparison to baseline, after twelve
weeks of twice-daily application of the cream;
b) despite of the presence of SA, which is a well
known irritating agent, the tolerability of the
cream was very good: this was likely due to the
presence of the two molecules of glycine in
PAD and 0.2% allantoin (2,5-dioxoimidazolidin-4-yl)urea, the end product of purine catabolism. The latter has moisturizing and soothing
effect, increasing the water content of the extracellular matrix.
This good tolerability allows a high adherence of
patients, mainly young patients, to the treatment:
this cream markedly improves compliance.
A controlled clinical study, in order to confirm
these results, is mandatory.
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41
Veraldi stes_Stesura D’Alessandro 08/10/14 10:17 Pagina 42
Volume 5, n. 2, 2014
Stefano Veraldi, Mauro Barbareschi
Department of Pathophysiology and Transplantation, University of Milan, IRCCS Foundation,
on the efficacy, tolerability and impact on quality of life
of a cream containing glycolic acid, retinaldehyde
and undecyl-rhamnoside in patients with acne
Stefano Veraldi
SUMMARY
The aim of this multicentre, pilot,
open, sponsor-free study was to
assess the efficacy, tolerability and
impact on quality of life of a cream
containing glycolic acid, retinaldehyde and undecylrhamnoside, in patients with mild to moderate acne.
Epidemiological data, as well as data on the efficacy of
the cream on scars, were also studied. 252 Italian
patients were included and treated once daily for a mean
period of 61 days. Changes from baseline in acne severity, seborrhoea, acne scar and quality of life were evaluated by means of specific scales.
Acne severity, evaluated by means of the Global
Evaluation of Acne (GEA), decreased from 2.5 to 1.5
(improvement of 39.6%, p<0.0001). Seborrhoea
improved in 59% of patients. The overall percentage of
patients with acne scars, evaluated by means of the
Echelle Clinique des Cicatrices d’Acné (ECCA),
decreased from baseline (40.9%) to visit 1 (34.3%;
p=0.0003). Impact of acne on quality of life, measured
by means of the Cardiff Acne Disability Index (CADI),
decreased from 5 to 3 (p<0.0001).
Treatment was very well tolerated.
The fixed combination of glycolic acid, retinaldehyde
and undecyl-rhamnoside is an effective and well tolerated treatment option for mild to moderate acne.
Key words: Acne; Glycolic acid; Retinaldehyde; Undecyl-rhamnoside; Quality of life; Scars.
Introduction
The addition of an alpha-hydroxy acid,
such as glycolic acid, to a retinoid, such as retinaldehyde, results in a better bioavailability of the
retinoid, thus a higher delivery, which potentiates
the biological activities of the retinoid. This combination therefore allows a delivery of higher
amounts of retinaldehyde in the skin 1.
The combination of glycolic acid with retinaldehyde showed to be effective in both non inflammatory and inflammatory acne lesions with a very
good tolerability 2-4.
Retinaldehyde differs from other topical retinoids,
such as retinol and retinoic acid, because it possesses a specific anti-Propionibacterium acnes
activity. This is likely due to the presence of an
aldehyde group in the isoprenoic lateral chain 5.
Undecyl-rhamnoside (characterized by the presence of 11 atoms of carbonium) is derived from
pentyl-rhamnoside (with 5 atoms of carbonium)
42
and rhamnosium (with 6 atoms of carbonium).
Both of these molecules inhibit the synthesis and
release from keratinocytes of proinflammatory
cytokines; however, they have a low skin bioavailability 6. A 24 hours treatment with undecyl-rhamnoside prior to the P. acnes stimulation down-regulated the P. acnes-induced overexpressed cytokines (interleukins-1α and 8, and matrix metalloproteinase 9) and up-regulated interleukin-1 receptor
antagonist levels in a similar modality than zinc
gluconate 6. Undecyl-rhamnoside possesses a good
skin bioavailability: this is likely due to the fact
that this molecule is highly lipophilic 6.
The aim of this multicentre, pilot, open, sponsorfree study was to assess the efficacy and tolerability
of a cream containing 6% glycolic acid, 0.1% retinaldehyde, 0.1% undecyl-rhamnoside (Efectiose®),
5% Avène thermal water and 5% arginine, at a pH
of 3.5 (TriAcneal® Avène - Pierre Fabre Laborato-
Volume 5, n. 2, 2014
ries) in patients with mild to moderate acne. To our
knowledge, this is the first study investigating the
role of this treatment combination in acne.
Patients and methods
Two hundred and fifty-two patients
(males: 28.4%, females: 71.6%; mean age: 22
years), with mixed (comedonal and inflammatory),
mild to moderate acne of the face, were treated
with the cream. Wash out period was at least two
weeks for topical antiseptics, antibiotics, azelaic
acid, salycilic acid, nicotinamide and retinoids; at
least two months for oral antibiotics and at least six
months for oral isotretinoin. The cream was
applied once daily for 6-12 weeks. Each application was preceded by a cleansing. No other topical
and/or systemic products or drugs were allowed,
except for non-comedogenic cosmetics and sunscreens. Furthermore, neither chemical peelings
nor sunlight exposure/phototherapy were allowed.
All patients were examined every six weeks.
The aims of the study were to assess the efficacy
(first endpoint) and tolerability (second endpoint) of
this fixed combination and the impact on quality of
life (third endpoint). Acne epidemiology was evaluated at baseline (V0) by means of a questionnaire
assessing patients’ medical history and lifestyle.
At baseline (V0) and after 6 weeks of treatment
(V1), the following measures were assessed:
a) acne severity by means of the Global Evaluation of Acne (GEA)7: 0-5 points score; at baseline all patients should have a GEA score ≥2 to
be included in the trial;
b) acne scar by means of the Echelle Clinique des
Cicatrices d’Acné (ECCA) 8 and
c) impact of acne on quality of life by means of
the Cardiff Acne Disability Index (CADI) (0-15
score) 9. Tolerability and patients’ global satisfaction were also evaluated at V1.
Results
Two hundred and fifty-two patients were
enrolled: 94.7% of these patients completed the
study and were therefore considered as evaluable.
Mean treatment duration was 61 days.
Medical history revealed that a family history of
acne was present in 50.8% of patients; these had a
history of acne for nearly 5.1 years. Mean age of
acne appearance and of first oral treatment was
16.6 and 19.4 years, respectively. 26.9% of patients
were affected by acne also in areas of the skin surface other than the face. Acne severity at baseline
was 2.5. Severity decreased to 1.5 (39.6% of
improvement: p < 0.0001) after a mean duration of
the treatment of 61 days (Figure 1). 43.8% of
patients had at baseline a moderate acne severity;
Figure 1.
Acne severity change (n=252 patients) from baseline (V0) to V1.
(After 61 days of mean treatment duration).
43
Volume 5, n. 2, 2014
Figure 2.
Distribution of patients (n=252) along acne severity GEA score:
change from baseline (V0) to V1. 0= no lesion; 1= almost no lesion;
2= mild lesions; 3= moderate lesions; 4= severe lesions; 5= very severe lesions.
Table 1.
Patients (n=252) with acne scars, according to ECCA.
Grading scale: change from baseline to V1 (61 mean days of treatment).
Kind of scars
Baseline
V1
V-shaped
72.7%
68.2%
U-shaped
37.0%
31.5%
M-shaped
10.3%
5.9%
Superficial elastolysis
14.5%
11.6%
Hypertrophic inflammatory (< 2 years of age)
7.1%
2.9%
0%
0%
Keloid (< 2 years of age)
at V1, 39.9% and 41.8% of patients showed complete remission or a mild severity, respectively
(Figure 2).
The overall percentage of patients with acne scars
decreased from baseline (40.9%) to V1 (34.3%;
p = 0.0003). This decrease was reported for each
kind of scar (Table 1). As far as the efficacy on
scars is concerned, 54.2% of patients stated to
observe an improvement that was judged as moderate, good or very good in 22.9%, 17.6% and
13.7% of cases, respectively.
A total of 86.6% of patients reported a global efficacy that was judged as moderate (34.4%), good
(41.1) and excellent (11.2%). Concerning patients’
44
quality of life, mean CADI score decreased from
baseline (5) to V1 (3: p < 0.0001): 79.2% patients
reported an improvement in their quality of life.
At V1, 95.1% of the dermatologists reported that tolerability was good (35%) or very good (60.1%).
14.1% of patients reported adverse events; in 5.6%
of them, it was necessary to stop the treatment.
According to the investigators’ opinion, 9.9% of the
reported adverse effects were related to the treatment. Overall, 89.7% of patients and 93.3% of
physicians were satisfied or very satisfied with treatment. On a 0-10 points scale, patients rated >8 the
acceptance level of treatment (consistency of the
cream, time of penetration and skin comfort after
Volume 5, n. 2, 2014
the application); 92.4% of patients expressed their
willingness to continue to use this cream after the
end of the study.
Discussion
Our study showed, for the first time, that
the fixed combination glycolic acid, retinaldehyde
and undecyl-rhamnoside is effective in decreasing
acne lesions severity, improving seborrhoea and
acne scar, and it is well tolerated.
Previous studies demonstrated the efficacy as well
as the good tolerability of the combination glycolic acid/retinaldehyde. In a multicentre, doubleblind, randomized, vehicle-controlled trial, Poli et
al. 3 demonstrated a significant decrease in both
non inflammatory and inflammatory lesions with a
very good tolerability (only one patient stopped the
treatment). In another study on more than 1700
patients, a very high compliance of the combination glycolic acid/retinaldehyde was shown 2.
These data were confirmed in a population of adult
women with acne 4.
Our study provides the first in vivo data of the role
of undecyl-rhamnoside, in combination with glycolic acid and retinaldehyde, in the treatment of
acne and in the potential reduction of scar forma-
tion. As previously mentioned, the overall percentage of patients with acne scar decreased from baseline (40.9%) to V1 (34.3%; p=0.0003).
This decrease was reported for each kind of scar.
Although in this analysis the change is not statistically significant, it has a great relevance from the
clinical point of view. However, a controlled study
is necessary in order to confirm these observations.
Acne is associated with a greater psychological
burden than other chronic skin disorders. Several
studies demonstrated psychological abnormalities,
including depression and anxiety.
Effective treatment of acne is accompanied by
improvement in self-esteem, body image, social
assertiveness and self-confidence 10.
In our study, the treatment has proven to be effective also in significantly improving patients’ quality of life, as measured by the CADI index.
The high tolerability of the study cream has been
confirmed not only by physicians’ judgment, but
also by the adherence rate (almost 95%). Patients’
and physicians’ high level of global satisfaction by
means of this treatment confirms the favorable profile of this combination.
In conclusion, the fixed combination glycolic acid,
retinaldehyde and undecyl-rhamnoside is an effective and well tolerated treatment option for mild to
moderate acne.
Declaration of interest.
The authors report no conflicts of interest. The authors alone are responsible for the content
and writing of the paper.
The following dermatologists attended this study:
Giuseppe Alessandrini (Ugento, Lecce)
Vincenzo Bettoli (Ferrara)
Federica Dall’Oglio (Catania)
Gabriella Fabbrocini (Naples)
Massimo Gola (Florence)
Giuseppe Micali (Catania)
Giuseppe Monfrecola (Naples)
Monica Pau (Cagliari)
Nevena Skroza (Rome)
Aurora Tedeschi (Catania)
Ersilia Tolino (Rome)
45
Volume 5, n. 2, 2014
References
1. Tran C, Kasraee B, Grand D, Carraux P, Didierjean L, Sorg O,
Saurat JH. Pharmacology of RALGA, a mixture of retinaldehyde
and glycolic acid. Dermatology 2005; 210 (Suppl. 1):6–13.
2. Dréno B, Nocera T, Verrière F, Vienne MP, Ségard C, Vitse S,
Carré C. Topical retinaldehyde with glycolic acid: study of tolerance and acceptability in association with anti-acne treatments in
1709 patients. Dermatology 2005; 210 (Suppl. 1):22–9.
3. Poli F, Ribet V, Lauze C, Adhoute H, Morinet P. Efficacy and
safety of 0.1% retinaldehyde / 6% glycolic acid (Diacneal) for
mild to moderate acne vulgaris. A multicentre, double-blind,
randomized, vehicle-controlled trial. Dermatology 2005; 210
(Suppl 1):14–21.
naldehyde. Dermatology 2002; 205:153–8.
6. Isard O, Lévêque M, Knol AC, Ariès MF, Khammari A, Nguyen
JM, Castex-Rizzi N, Dréno B. Anti-inflammatory properties of a
new undecyl-rhamnoside (APRC11) against P. acnes. Arch
Dermatol Res 2011; 303:707-13.
7. Dréno B, Poli F, Pawin H, Beylot C, Faure M, Chivot M,
Auffret N, Moyse D, Ballanger F, Revuz J. Development and evaluation of a Global Acne Severity Scale (GEA Scale) suitable for
France and Europe. J Eur Acad Dermatol Venerol 2011; 25:43-8
8. Dréno A, Khammari A, Orain N, Noray C, Mérial-Kieny C,
Méry S, Nocera T. ECCA grading scale: an original validated
acne scar grading scale for clinical practice in dermatology.
Dermatology 2007; 214:46-51.
4. Dréno B, Castell A, Tsankov N, Lipozencic J, Serdaroglu S,
Gutierrez V, Gadroy A, Merial-Kieny C, Mery S. Interest of the
association retinaldehyde/glycolic acid in adult acne. J Eur Acad
Dermatol Venereol 2009; 23:529-32.
9. Dréno B, Finley AY, Nocera T, Verrière F, Taïeb C, Myon E.
The Cardiff Acne Disability Index: cultural and linguistic validation in French. Dermatology 2004; 208:104-8.
5. Pechère M, Germanier L, Siegenthaler G, Pechère JC, Saurat
JH. The antibacterial activity of topical retinoids: the case of reti-
10. Tan JK. Psychosocial impact of acne vulgaris: evaluating the
evidence. Skin Therapy Lett 2004; 9:1-3, 9.
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Berruti stes_Stesura D’Alessandro 07/10/14 12:51 Pagina 47
Volume 5, n. 2, 2014
Vittorio Berruti, Antonia Gimma, Franca Taviti, Carla Cardinali
Dermatology department, USL 4, Prato, Italy
Vittorio Berruti
SUMMARY
are a frequently observed condition
for dermatologists. Diagnosis is
often difficult and requires a thorough search for the drug involved, since multiple med-
ications are often administered.
There are no specific criteria to diagnose drug-induced
acne; there are, however, specific characteristics that
may help to relate skin eruption to the administration of
a specific drug.
Key words: Drug-induced acneiform eruptions; Drug-induced acne.
Introduction
Drug-induced acneiform eruptions are
acne-like skin manifestations occurring after the
intake of a wide range of medications (Table 1).
They should be suspected in the absence of a previous history of acne or in patients with a mild
form of acne who show a sudden worsening of the
clinical picture.
The clinical pattern is of papulopustular type, with
a monomorphic appearance. There are no cysts and
comedones at the onset, although they may appear
at a later stage. Pruritus is often present.
Localization may involve not only the seborrhoeic
areas, but also limbs, trunk, lower back and genitals. If a clinical remission is achieved after discontinuation of the drug and lesions recur after the
reinstatement of the medication, the drug can be
considered as the etiological agent of the
acneiform eruption 1.
Table 1
Drug-induced acneiform eruptions.
Hormones
Vitamins B1, B6, B12, D
Antidepressants
Antiepileptics
Antipsicotics
Tetracyclines
Isonicotinic acid
Phenobarbiturics
Thyroid-stimulating hormone
Disulfiram
Chloroquine
Azathioprine
Halogen drugs
EGFR-inhibitors
PUVA
47
Volume 5, n. 2, 2014
Differential diagnosis
•
•
•
•
•
•
•
•
•
•
Acne vulgaris
Pseudofolliculitis barbae
Rosacea and perioral dermatitis
(also steroid-induced)
Acneiform secondary syphiloderm/syphilis
Demodicosis
Behçet’s disease
Infective folliculitis
Lupus miliaris disseminatus
Eosinophilic pustular folliculitis
Papular sarcoidosis
Hormonal therapies
Hormonal therapies are one of the most
frequent causes of acneiform eruptions; a distinction should be made between those induced by topical and systemic corticosteroids, by corticotropin
(ACTH), by androgens and anabolic steroids, by
hormonal contraceptives and by other hormones,
such as danazol and thyroid-stimulating hormone.
Steroids
The onset of symptoms begins 2 to 4
weeks after their administration. The eruption is
monomorphic, with small dome-shaped inflammatory papulae and pustules on the seborrhoeic areas
(face and trunk), extending to the proximal region
of the limbs. After resolution of the initial inflammatory phase, comedones or small keratin cysts
may appear. The application of topical corticosteroids may increase the concentration of free fatty
acids on the skin, leading to an increase of bacteria
in the pilosebaceous unit. Manifestations may be
more severe on the face, where the absorption of
liposoluble corticosteroid is greater, as the stratum
corneum is thinner and there is a larger number of
sebaceous follicles. The molecular mechanism that
can explain the “steroid-induced” acneiform eruption has been described in the literature 2: the addition of corticosteroids to cultures of keratinocytes
48
enhances the expression of the Toll-like receptors
2 (TRL2), which when activated by P. Acnes would
induce an inflammatory response. This TRL2P.Acnes receptor activation mechanism may be
responsible both for the exacerbation of acne vulgaris and for the induction of steroid-related
acneiform eruptions.
Anabolic androgenic steroids (AAS) 3
Testosterone represents the treatment of
choice for hypogonadism, azoospermia and male
menopause. After administration, it is converted
into its active metabolite, 5 α-dihydrotestosterone,
capable of stimulating the sebaceous glands and
leading to their hypertrophy and to hypersecretion
of sebum. The clinical manifestation consists in an
eruption of follicular monomorphic papulae and
pustules, located on the face, trunk and limbs, followed by the appearance of comedones. If the drug
cannot be discontinued, the conventional therapy
for acne should be started. Acne induced by anabolic steroids, also called “body building acne” or
“doping acne”, is frequent in athletes who take
high doses of AASs and affects up to 50% of the
individuals 4. Its clinical manifestations are variable and may consist of hypersecretion of sebum,
papulae-pustules, up to conglobate acne and acne
fulminans. It may occur de novo or develop on preexisting acne. The clinical signs that may accompany an acneiform eruption are gynaecomastia,
decrease in testicular volume, appearance of striae,
oedema and increase in body mass 1.
Cases of acneiform eruptions along the jawline
and/or back line have been reported in women using
etonogestrel or levonorgestrel-releasing intrauterine
systems after 1-3 months of their implanting.
Neuropsychiatric drugs
Several classes can be responsible for the
development of acneiform eruption (Table 2).
Amineptine is a non-halogenated tricyclic antidepressant. Even after several years of treatment, it
may trigger an acneiform clinical manifestation
consisting in the appearance of retentional
monomorphic lesions, such as microcysts, macro-
Volume 5, n. 2, 2014
Table 2
Neuropsychiatric drugs.
Non-halogenated tricyclic antidepressant:
amineptina, maprotilina, imipramina
Lithium
Antiepileptics
Aripiprazolo
Serotonin reuptake inhibitors
Antipsicotics
cysts and comedones of varying size 1. The clinical
picture may evolve to actual facial disfigurement
(“monstrous acne”). The drug and its metabolites
are often found in the sebaceous secretions and in
cyst content, as well as in plasma and urine 1.
Since the drug may be found in sebaceous secretions and sweat, there could be metaplastic keratinization in the papulokeratotic lesions in both
eccrine gland (syringometaplasia) and the sebaceous gland.
We can therefore suspect a toxic action of the drug
on the appendages or a chronic inflammatory action,
with dose-dependent severity of the clinical picture.
Therapy should consist in the discontinuation of the
drug and, if necessary, surgical removal of macrocysts and systemic administration of isotretinoin 5.
Lithium
It is considered one of the key drugs in the
treatment of depression. It is used in patients suffering from severe depression and from bipolar disorders. The onset of acneiform eruption is rapid and
not dose-dependent and, in some cases, it may be
accompanied by hidradenitis and conglobate acne.
The most affected areas are face, armpits, groin,
upper and lower limbs, buttocks, and – in males –
often the extremities. By accumulating in the skin,
lithium causes superficial follicular occlusion, leading to dilatation of apocrine and sebaceous glands
with hypersecretion of sebum, and with resulting
trigger of mechanisms of neutrophilic chemotaxis,
inflammation and bacterial infection.
Antiepileptics and serotonin
reuptake inhibitors
They are used to treat depression. Acneiform manifestations 7, 8 usually affect the face and
upper part of the trunk, with prevalence of pustular
lesions and sometimes folliculitis while comedonal
lesions occur in case of prolonged treatment 1.
A few cases, described in the literature,7-9 report
acneiform skin manifestations following the
administration of aripiprazole. These cases have
been explained on the basis of Type III allergic
mechanisms in an already sensitized individual,
and Type IV in a subject with delayed hypersensitivity, which triggered a foreign-body granulomatous reaction in the skin 7.
Vitamins
Cases of drug-induced acneiform eruptions caused by vitamins, such as those of the B
group (B1, B6, B12), have been described in the literature, although their pathogenetic mechanisms
are not yet completely understood. A causal role
played by the iodate particles used for extraction of
Vitamin B12 can be assumed, as described by
Dupré et al.10
It is a sudden eruption in the face of large-sized
monomorphic papulae and pustules with hypersecretion of sebum. It is rapidly reversible after the
discontinuation of the drug.
Cytostatics and immunosuppressants
Actinomycin D has a tricyclic structure,
similar to that of antidepressant drugs, and is used
in the treatment of rabdomyosarcoma, Wilms
tumor, Ewing, Kaposi, sarcoma, corioncarcinoma.
It can increase the levels of androgen hormones by
directly, or possibly indirectly, stimulating an
increase in ACTH. Inflammatory lesions occur
after approximately 5 days of treatment with the
drug, in the typical locations of acne vulgaris, with
comedones appearing at a later stage. The effect is
dose-dependent 11.
Cases of acneiform eruptions accompanied by systemic manifestations caused by immunomodulating molecules, such as topical ciclosporin, azathioprine, sirolimus, tacrolimus and pimecrolimus and
interferon,12, 13 have been reported in the literature.
49
Volume 5, n. 2, 2014
The immunosuppressant action and the lipophilic
nature of cyclosporine seem to stimulate bacterial
proliferation in the sebaceous glands and
infundibulum, resulting in acneic manifestations,
sometimes severe as in case of nodular-cystic acne
and acne keloidalis (15% of patients) 1.
The lipophilic nature of cyclosporine is responsible of its concentration in sebaceous glands.
Switching to another immunosuppressant and
administration of systemic isotretinoin can be the
only therapeutic options in these cases. It is very
important, in case of association of cyclosporine
with isotretinoin, to monitorate serum lipids 1.
Sirolimus, an immunosuppressive macrolide used
in renal transplants, can induce acne via a direct
inhibitory action on the activity of the epidermal
growth factor (EGF), with inhibition of mTOR
(mammalian target of rapamycin), as other EGFRinhibitors used in cancer treatment 1.
It has a toxic effect on the follicles, with chemical
alteration of sebum, and affects testosterone synthesis. There is no correlation between the severity
of the clinical picture and the daily dosage of the
drug and its occurrence is often found in patient
with a history of severe acne. Cases of acne
induced by pimecrolimus and interferon, during
treatment of vitiligo and multiple sclerosis, respectively, have been reported in the literature 14-16.
No remission of acne has been observed after discontinuation of pimecrolimus.
Antibercular drugs
Isoniazid, rifampicin, ethionamide
A work by Nwoko et al. of 1974 reported
cases of serious papular acneiform eruption on the
face, neck and shoulders, induced by rifampicin, in
African patients. The discontinuation of the drug
led to the resolution of the clinical picture 17, 18.
In particular, 8 of 24 patients in treatment with
ripampicin, have developed acne: severe acne in 4,
moderate in 3 and mild in one patient.
These results, however, are in conflict with a work
by Purohit of 1983, which reported rifampicininduced acne of mild type (in 9 of 121 patients),
mainly located on the back, but also on the face,
and often self-resolving.
50
Isoniazid is a drug metabolized via
acetylation in the liver due to the hepatic N-acetyltransferase enzyme, with subsequent renal excretion. This metabolic mechanism depends on the
rate of acetylation of the drug and therefore differs
among various phenotypes. We speak of fast acetylation when the enzyme is capable of rapidly
metabolizing the drug and, as a consequence, making its half-life very short. On the contrary, slow
acetylation leads to a much longer half-life of the
drug and makes the subject more susceptible to its
side effects 19.
The incidence of isoniazid-induced acne is low and
its structural analogy with niacin may be responsible for follicular hyperkeratosis, thus explaining
the possible pathogenesis of acneiform eruption.
Halogen drugs
(iodine, bromine, chlorine)
such as thyroid drugs, expectorant drugs with
potassium iodide, contrast media in radiography,
iodate salts, vitamins, certain sedatives and amiodarone.
Iododerma is caused by the intake of
iodine, especially in renally impaired patients who
are unable to eliminate it. The clinical picture may
show papular eruption, vesicles and pustules, as
well as erythematous, urticarial, furuncular, bullous and vegetating lesions, with possible ulceration. The pathogenetic mechanism can be
explained by cellular mediated immunity in a subject already sensitized,1 or through inflammatory
mechanisms and idiosyncratic reactions. While
discontinuing the intake of iodine is enough to
improve the symptoms, in some cases the use of
topical or systemic corticosteroids may be
required.
Bromoderma is caused by the bromide contained in certain psychiatric medications,
sedatives, spasmolytic drugs and expectorants. It is
clinically similar to iododerma, although it is
rarely found in daily clinical practice today.
Diagnosis is based on the detection of high levels
of bromine in serum and urine. Treatment consists
in the discontinuation of the drug, followed by the
Volume 5, n. 2, 2014
conventional therapy for acne. Occupational and
non-occupational exposure through environmental
contamination caused by halogenated aromatic
hydrocarbons, such as chlorinated dioxins, may
lead to the development of chloracne 20.
Chloracne may develop 6-12 weeks
after exposure. From a clinical viewpoint, it shows
development of large comedones on the face,
cheeks and retroauricular creases. Forehead, back,
chest, lower limbs, genitals and armpits may also
be affected, without pustular elements and excluding the nose area. In the most severe cases, cysts on
the face and neck may occur. Lesions may persist
for up to 15-30 years after exposure.
Cancer drugs
Lenalidomide can cause an acneiform
eruption. It is an innovative antitumor drug, administered in combination with dexamethasone as a
treatment for multiple myeloma, with immunomodulatory and anti-angiogenic activity. By interfering with tyrosine kinases and inhibiting EFG
(Epidermal Growth Factor) at keratinocyte level,
it stops the growth of keratinocytes and leads to
their apoptosis, reducing cell migration and
increasing cell differentiation and inflammation,
resulting in skin reactions 21.
Anti-EGFR (anti-epidermal Growth
Factor Receptor) drugs can be divided into: tyrosine kinase inhibitors, such as gefitinib, erlotinib,
lapatinib, EKB-569, and monoclonal antibodies,
such as cetuximab and panitumumab.
These drugs are used in a number of neoplasms
with EGFR overexpression, such as breast cancer,
colon cancer, pancreatic cancer, kidney and lung
neoplasms. These drugs can cause acneiform eruptions ranging from minimally severe conditions,
consisting of maculae and papulae with erythema
and pruritus, intermediately severe conditions,
with erythroderma or generalized eruption with
maculae, papulae and vesicles, up to severe and
widespread cutaneous toxicity, with blisters, ulceration and generalized exfoliation.
Skin rash is related to the dose administered and
the most frequently involved drug is cetuximab
(88-89%), which can induce a cutaneous adverse
effect in 60% of cases.
Specific criteria to identify the subjects that may
develop skin reactions have not been discovered
yet; however, recent studies excluded a correlation
between skin eruptions and clinical history of acne
in patients 22, 23.
A few studies in the literature have led to define
skin rash as an indicator of the efficacy of the drug.
It was observed that a skin reaction helps to identify the subjects that most benefit from the therapy,
as it occurs more frequently in responders 21.
Treatment of rash induced by anti-EGFR drugs
varies according to the severity of the clinical picture to be treated. Mild rash can be treated with
metronidazole, clindamycin cream or 1% hydrocortisone lotion, whereas moderate to severe rashes require tetracyclines and the discontinuation of
the EGFRI drug, 24, 25 in addition to the above-mentioned medications.
A randomized double-blind study to evaluate the
effect of preventive treatment with tetracyclines in
reducing the skin effects of anti-EGFRs has been
described in the literature. This study reported efficacy in terms of lower number of facial lesions,
reduced pruritus, rash severity and delay in the
onset of adverse reactions, 26-28 following the use of
the above antibiotic.
Discussion
Incidence of drug-induced acneiform
eruptions is increasing, especially following the
introduction of new target molecules in cancer
treatment.
The interval between the administration of the drug
and the occurrence of the eruption may range from
a few days to many months.
Pathogenetic mechanisms and histopathological
aspects are often different, even though skin
lesions are similar.
The main issue is whether the drug should be discontinued or not. This decision should be carefully
evaluated in consideration of the disease being
treated.
51
Volume 5, n. 2, 2014
References
1. Du-Thanh A, Kluger N, Bensalleh H, Guillot B. Drug-induced
acneiform eruption. Am J Clin Dermatol 2011; 12(4):233-45. .
17. Nwokolo U. Letter: Acneiform lesions in combined rifampicin
treatment in Africans. Br Med J 1974; 3(5928):473.
2. Shibata M1, Katsuyama M, Onodera T, Ehama R, Hosoi J,
Tagami H. Glucocorticoids enhance Toll-like receptor 2 expression in human keratinocytes stimulated with Propionibacterium
acnes or proinflammatory cytokines. J Invest Dermatol 2009;
129(2):375-82.
18. Purohit SD, Gupia PR, Sharma TN, Chawla MP, Gupia DN.
Acne during rifampicin therapy. Ind J Tub 1983; 30:110.
3. Fyrand O, Fiskaadal HJ, Trygstad O. Acne in pubertal boys
undergoing treatment with androgens. Acta Derm Venereol 1992;
72(2):148-9.
4. Melnik B, Jansen T, Grabbe S. Abuse of anabolic-androgenic
steroids and bodybuilding acne: an underestimated health problem. J Dtsch Dermatol Ges 2007; 5(2):110-7.
5. Grimalt R, Mascaró-Galy JM, Ferrando J, Lecha M. Guess
what? Macronodular iatrogenic acne due to amineptine. Eur J
Dermatol 1999; 9(6):491-2.
6. Greenwood R, Fenwick PB, Cunliffe WJ. Acne and anticonvulsants. Br Med J (Clin Res Ed) 1983; 287(6406):1669-70.
7. Mishra B, Praharaj SK, Prakash R, Sinha VK. Aripiprazoleinduced acneiform eruption. Gen Hosp Psychiatry 2008;
30(5):479-81.
8. Warnock JK, Morris DW. Adverse cutaneous reactions to antidepressants. Am J Clin Dermatol 2002; 3(5):329-39.
9. Burrows NP, Ratnavel RC, Norris PG. Pustular eruptions after
chlorpromazine. BMJ 1994; 309(6947):97.
10. Duprè A, Albarel N, Bonafe JL, et al. Vitamin B12 induced
acne. Cutis 1979; 24:210-1.
11. Blatt J, Lee PA. Severe acne and hyperandrogenemia following dactinomycin. Med Pediatr Oncol 1993; 21(5):373-4.
12. Piaserico S, Fortina AB, Cavallini F, Alaibac M. Acne
keloidalis of the scalp in a renal transplant patient treated with
cyclosporine. Acta Derm Venereol 2009; 89(3):312-3.
13. Bidinger JJ, Sky K, Battafarano DF, Henning JS. The cutaneous and systemic manifestations of azathioprine hypersensitivity syndrome. J Am Acad Dermatol 2011; 65(1):184-91.
14. Kunzle N, Venetz JP, Pascual M, Panizzon RG, Laffitte E.
Sirolimus-induced acneiform eruption. Dermatology 2005;
211(4):366-9.
15. Li JC, Xu AE. Facial acne during topical pimecrolimus therapy for vitiligo. Clin Exp Dermatol 2009; 34(7):e489-90.
16. Rosa DJ1, Matias Fde A, Cedrim SD, Machado RF, Sá AA,
Silva VC. Acute acneiform eruption induced by interferon beta1b during treatment for multiple sclerosis. An Bras Dermatol.
2011; 86(2):336-8.
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19. Cohen LK, George W, Smith R. Isoniazid-induced acne and
pellagra: occurrence in slow inactivators of isoniazid. Arch
Dermatol 1974; 109(3):377-81.
20. Tindall JP. Chloracne and chloracne gens. J Am Acad
Dermatol 1985; 13:539-58.
21. Michot C, Guillot B, Dereure O. Lenalidomide-induced acute
acneiform folliculitis of the head and neck: not only the anti-EGF
receptor agents. Dermatology 2010; 220(1):49-50.
22. Agero AL, Dusza SW, Benvenuto-Andrade C, Busam KJ,
Myskowski P, Halpern AC. Dermatologic side effects associated
with the epidermal growth factor receptor inhibitors. J Am Acad
Dermatol 2006; 55(4):657-70.
23. Busam KJ1, Capodieci P, Motzer R, Kiehn T, Phelan D,
Halpern AC. Cutaneous side-effects in cancer patients treated
with the antiepidermal growth factor receptor antibody C225. Br
J Dermatol 2001; 144(6):1169-76.
24. Park J1, Park BB, Kim JY, Lee SH, Lee SI, Kim HY, Kim JH,
Park SH, Lee KE, Park JO, Kim K, Jung CW, Park YS, Im YH,
Kang WK, Lee MH, Park K. Gefitinib (ZD1839) monotherapy as
a salvage regimen for previously treated advanced non-small cell
lung cancer. Clin Cancer Res 2004; 10(13):4383-8.
25. Galimont-Collen AF, Vos LE, Lavrijsen AP, Ouwerkerk J,
Gelderblom H. Classification and management of skin, hair, nail
and mucosal side-effects of epidermal growth factor receptor
(EGFR) inhibitors. Eur J Cancer 2007; 43(5):845-51.
26. Fernández-Guarino M, Pérez García B, Aldanondo
Fernández de la Mora I, García-Millán C, Garrido López P, Jaén
Olasolo P. Treatment of acneiform rash by epidermal growth factor inhibitors with oral tetracyclines. Actas Dermosifiliogr 2006;
97(8):503-8.
27. Scope A, Agero AL, Dusza SW, Myskowski PL, Lieb JA, Saltz
L, Kemeny NE, Halpern AC. Randomized double-blind trial of
prophylactic oral minocycline and topical tazarotene for cetuximab-associated acne-like eruption. J Clin Oncol 2007;
25(34):5390-6.
28. Jatoi A, Rowland K, Sloan JA, Gross HM, Fishkin PA,
Kahanic SP, Novotny PJ, Schaefer PL, Johnson DB, Tschetter
LK, Loprinzi CL. Tetracycline to prevent epidermal growth factor
receptor inhibitor-induced skin rashes: results of a placebo-controlled trial from the North Central Cancer Treatment Group
(N03CB). Cancer 2008; 113(4):847-53.
Di Pietro stef_Stesura D’Alessandro 07/10/14 12:58 Pagina 53
Volume 5, n. 2, 2014
Antonino Di Pietro 1, Pietro Cazzola 2
1 Direttore
Istituto Dermoclinico “Vita Cutis”, Milano, Italy.
in Anatomia e Istologia Patologica, Milano, Italy.
2 Specialista
Antonino Di Pietro
Effects of a new multi-component in cream
based on Alukina® and Microsilver BG™
in the treatment of acne vulgaris
SUMMARY
Background: acne vulgaris is a
very common disease in adolescents and young adults. It is a disorder of the pilosebaceous unit, in
which seborrhoea, poral occlusion and Propionibacterium acnes leads to the formation of comedones,
papules, pustules and cysts.
Aim and design: aim of this pilot trial was to test the
effectiveness of a cosmetic cream (Alusac®) in mild
acne. We enrolled seventy-eight male or female subjects with a basal score of 2 (mild) on the Investigator’s
Global Assessment (IGA) score. All subjects had to use
the product twice daily for eight weeks.
Results: at the end of the study, 61.9% of included subjects were classified as complete responders, with a IGA
score reduction from 2 to 0 (clear skin) (p < 0.05).
The remaining 38.1% was classified as partial responder, with a IGA score reduction from 2 to 1 (skin almost
clear).
In the partial responder group, the regression of non
inflammatory lesions was higher than the inflammatory
lesions (72.7 vs 50.9; p < 0.05).
The test product was well tolerated and no adverse
effects were registered.
Conclusions: the application of this new cosmeceutical
product is effective and safe in mild acne vulgaris.
Key words: Acne; Alukina®; Microsilver BG™.
Introduzione
L’acne è la più frequente affezione cutanea in età giovanile, con un picco di prevalenza
compreso fra il 30% ed il 95% nella fascia di età
12-17 anni.
I tassi di prevalenza variano in relazione alla procedura di rilevamento e all’etnia, con il 15% dei
casi classificati come severi 1, 2. Poiché la malattia
colpisce un’area cutanea particolarmente esposta
in un’età nella quale la sensibilità verso il giudizio
altrui è esasperata, le sequele emotive e psicologiche che accompagnano l’acne possono compromettere gravemente le performance sociali e la
qualità di vita 3, 4.
Le manifestazioni cliniche dell’acne sono primitivamente rappresentate dal microcomedone, lesione
elementare non visibile ad occhio nudo.
Successivamente, il micromedone evolve verso
lesioni rilevabili all’esame obiettivo: queste possono essere non infiammatorie (comedone aperto o
chiuso) o infiammatorie (papule, pustole, noduli e
cisti).
Sulla base del numero e del tipo di lesioni presenti, la Global Acne Alliance (GAA) classifica l’acne
in tre stadi:
•
•
•
lieve (presenza di molti comedoni e alcune
papule/pustole);
moderata (presenza di papule/pustole e qualche nodulo);
severa (presenza di tutte le lesioni precedenti
con numerosi noduli e cisti) 5.
La patogenesi dell’acne coinvolge l’intera unità pilosebacea ed è sostenuta da quattro differenti moventi
patogenetici, operanti in sequenza sinergica:
•
•
•
•
aumentata produzione di sebo;
ipercheratinizzazione del dotto;
colonizzazione batterica anaerobia (P. acnes);
risposta infiammatoria locale 6.
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Volume 5, n. 2, 2014
La malattia ha decorso cronico-recidivante e si
esaurisce in circa il 90% dei casi con l’età adulta.
Qualunque trattamento anti-acne, locale o sistemico, dovrebbe interferire con tutti e quattro i target
eziologici sopra descritti. Ciò impone l’adozione
di trattamenti combinati e di una elevata personalizzazione terapeutica.
In questo studio è stata valutata una nuova linea
cosmeceutica costituita da detergente e crema da
applicarsi due volte al giorno per il trattamento dell’acne.
La formulazione crema, oggetto del lavoro qui presentato è in grado di interferire su tutti e quattro i
moventi patogenetici summenzionati.
Grazie alle sostanze attive in essa presenti, esercita infatti azione sebo-modulante (Alukina®), antibatterica (Microsilver BG™) e lenitiva, antiinfiammatoria, idratante e riepitelizzante (pantenolo,
zinco gluconato ed Echinacea).
è di seguito descritto uno studio pilota volto a verificare efficacia e tollerabilità di questo nuovo
cosmeceutico multicomponente in formulazione
crema in soggetti con acne facciale di grado lieve.
In quest’ultima la GAA prevede l’impiego di retinoidi topici, con aggiunta di acido azelaico o salicilico e di un antimicrobico se sono presenti anche
papule e pustole.
Lo studio ha avuto una durata di otto settimane,
con controllo intermedio a quattro settimane.
Sono stati inclusi 78 soggetti di entrambi i sessi
(maschi 56,4%). L’età media era di 17,4 anni
(range 12-29) con durata della malattia di 21,9
mesi (range 4-48). Tutti i soggetti erano di etnia
caucasica (Figura 1).
Criteri di inclusione ed esclusione
Criterio primario di inclusione era la presenza di
acne del volto di grado lieve secondo la classificazione Investigator’s Global Assesment (IGA). La
classificazione IGA è quella comunemente accettata per la stadiazione dell’acne. Potevano essere
inclusi soggetti con malattia di durata non inferiore a 6 mesi e, ove effettuati precedenti trattamenti,
questi dovevano essere stati interrotti da almeno
due mesi. Erano eleggibili soggetti di tutte le etnie,
di età compresa fra 12 e 30 anni. Sono stati esclusi i soggetti con patologie croniche di qualunque
natura e quelli con intolleranza nota ad una o più
sostanze presenti nel prodotto testato.
Materiali e metodi
Obiettivi
Valutare efficacia e tollerabilità di un nuovo cosmeceutico multicomponente a base di Alukina® e
Microsilver BG™ (Alusac®) in formulazione
crema in soggetti con acne di grado lieve sia secondo lo score IGA sia sulla base del numero delle
lesioni.
Disegno dello studio e campione
Studio monocentrico, aperto, condotto in soggetti
affetti da acne volgare facciale di grado lieve.
Valutazione di efficacia
La valutazione di efficacia dei prodotti antiacne è
da decenni oggetto di controversia a causa dei cri-
T0
T1 (set 4)
T2 (set 8)
n = 78
n = 70
n = 63
Figura 1.
Disegno dello studio e flusso dei soggetti inclusi.
54
Volume 5, n. 2, 2014
teri non univoci utilizzati dai vari gruppi di ricerca.
La Food and Drug Administration (FDA) suggerisce di impiegare la scala IGA, in quanto
attendibile e riproducibile 7. La scala IGA prevede
uno score da 0 a 5, dove 0 corrisponde a cute “pulita” (senza segni evidenti di acne) e 5 corrisponde a
cute con numerose lesioni infiammatorie, inclusi
noduli e cisti.
Secondo la scala IGA, è definita lieve l’acne caratterizzata prevalentemente da lesioni non infiammatorie (comedoni), da poche lesioni infiammate
(papule e pustole) e dall’assenza di noduli e cisti.
A questo quadro clinico la scala IGA attribuisce un
punteggio pari a 2.
Nel presente studio l’efficacia è stata definita
come:
tasso di successo clinico (totale o parziale);
riduzione percentuale del numero delle lesioni.
•
•
Tasso di successo clinico. Il tasso di successo clinico totale è definito come la percentuale di soggetti che migliora di almeno due punti lo score misurato con scala IGA.
Poiché il disegno di questo studio prevedeva solo
l’inclusione di soggetti con acne lieve (score
basale 2), il successo clinico totale misura la percentuale di soggetti che regredisce dal punteggio
2 al punteggio 0 (cute pulita senza segni evidenti
di acne).
Il successo clinico parziale indica una riduzione
dello score inferiore a 2 punti, ovvero il passaggio
da un punteggio 2 ad un punteggio pari a 1.
Un punteggio pari a 1 indica la permanenza di
lesioni.
Riduzione del numero delle lesioni. Le lesioni
sono state contate al basale e quindi alle settimane
4 (T1) ed 8 (T2). La conta ha annotato separatamente le lesioni non infiammatorie da quelle infiammatorie, suddividendo i pazienti in tre gruppi:
quelli con più di 10 lesioni (10-20 lesioni), quelli
con meno di 10 lesioni (1-9 lesioni) e quelli con
nessuna lesione rilevabile ad occhio nudo.
Valutazione di tollerabilità
La tollerabilità cutanea è stata misurata come comparsa di tre eventi avversi direttamente associabili
all’applicazione del nuovo cosmeceutico:
prurito;
bruciore;
eritema.
•
•
•
Ciascuno dei tre eventi è stato annotato come presente/assente.
Prodotto test
I soggetti dovevano applicare su cute detersa il prodotto due volte al giorno, al mattino ed alla
sera prima di coricarsi.
Alusac® crema (Avantgarde SpA) è un prodotto
cosmetico, contenente un mix di sostanze sebomodulanti ed astringenti (Alukina®), argento
metallico micronizzato (Microsilver BG™) in
grado di rilasciare ioni Ag dotati di prolungata
attività antimicrobica, più tre sostanze dotate di
azione lenitiva, idratante e riepitelizzante (pantenolo, gluconato di zinco ed Echinacea).
Analisi statistica
I dati sono stati analizzati con metodi di statistica
descrittiva. La significatività è stata fissata per valori di p < 0.05.
Il confronto tra i gruppi è stato condotto con il test
“t di Student”.
Risultati
Lo studio ha incluso 78 soggetti con punteggio IGA pari a 2.
Al basale (T0) è stata rilevata una media di 34.2
lesioni, di cui 18.7 di tipo non infiammatorio 15.5
di tipo infiammatorio.
Alla settimana 4 (T1) sono risultati valutabili 70
soggetti (89.7%): cinque non si sono presentati per
il controllo e tre soggetti non avevano utilizzato il
prodotto secondo le indicazioni fornite all’arruolamento.
Alla settimana 8 (T2), 7 soggetti non si sono presentati, sicché al termine dello studio sono risultati
valutabili 63 soggetti (80.7%).
Successo clinico completo (assenza di lesioni
acneiche visibili) è stato registrato in 15/70 soggetti (21,4%) al primo controllo e in 39/63 soggetti
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Volume 5, n. 2, 2014
Successo clinico (%)
70
60
50
40
30
20
10
0
-
Basale
*
4 settimane
8 settimane
*p 0.05 vs basale
Figura 2.
Percentuale di soggetti full responders: riduzione dello score IGA da 2 a 0.
Riduzione lesioni (%)
Settimana 4
Settimana 8
0-20 -28
-40 -60 -
-66,3
*
-80 -
*p < 0.05 vs basale
Figura 3.
Riduzione delle lesioni totali alla settimana 4 ed 8
registrata nei partial responders (p < 0.05).
Riduzione lesioni (%)
Settimana 4
Settimana 8
0-20 -40 -
-26,4
-29,4
-50,9
*
-60 -80 Infiammatorie
Non infiammatorie
-72,7
*
*p < 0.05 vs basale
Figura 4.
Riduzione delle lesioni infiammatorie e non infiammatorie
alla settimana 4 ed 8.
La variazione è risultata statisticamente significativa
alla settimana 8 per entrambi i tipi di lesioni (p < 0.05).
56
Volume 5, n. 2, 2014
Figura 5.
Riduzione delle lesioni infiammatorie e non infiammatorie
dopo trattamento con una crema multicomponente
a base di Alukina® e Microsilver BG™.
(61,9%) al termine dello studio (Figura 2).
Questo andamento non lineare, caratterizzato cioè
da una maggiore efficacia nelle ultime quattro settimane rispetto alle prime quattro, suggerisce che
l’azione del nuovo cosmeceutico multicomponente
sia cumulativa e richiede almeno otto settimane
perché i benefici siano apprezzabili, in accordo con
i dati pubblicati in letteratura sui trattamenti topici
per l’acne.
Nei rimanenti 24/63 (38,1%) pazienti che al termine dello studio non avevano raggiunto il successo clinico completo (successo parziale), è stata
comunque registrata una importante riduzione
delle lesioni) (Figura 3).
Anche in questo caso l’andamento nel tempo è stato
di tipo non lineare, con un effetto sensibilmente
maggiore nelle successive quattro settimane di
applicazione rispetto alle prime quattro: al tempo T1
(settimana 4) le lesioni totali erano passate da 34,2
a 24,6, con una riduzione media del 28%.
Al tempo T2 (settimana 8) il numero di lesioni si è
ridotto ulteriormente a 11.5, con una variazione
percentuale pari al 66,3% rispetto a T0 (p < 0.05).
Una ulteriore analisi sui partial responders ha evidenaziato una migliore risposta nella riduzione
delle lesioni non infiammatorie pari rispettiva-
mente al 29,4% alla settimana 4 e al 72,7% alla
settimana 8 (p < 0.05) (Figura 4).
Non sono stati registrati effetti avversi riconducibili al prodotto testato.
Discussione
È opinione condivisa che l’acne debba
essere trattata precocemente ed in modo efficace
anche quando le lesioni non sono gravi, al fine di
ridurre il disagio psicologico e gli esiti cicatriziali 8, 9.
Le linee guida non prevedono tuttavia l’uso della
via sistemica per le forme lievi 5.
Nel contesto clinico da noi studiato, l’uso di un
cosmeceutico multicomponente appare dunque
particolarmente appropriato.
I risultati ottenuti sono superiori a quelli riportati
da altri studi, e ciò è probabilmente da attribuire
sia alla elevata compliance sia allo stadio di malattia 10, 11.
Un tasso di successo completo pari al 61,9% ad
otto settimane appare molto buono e, se confermato da studi di maggior durata, è da considerarsi
clinicamente rilevante (Figura 5).
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Volume 5, n. 2, 2014
Nel 38,1% dei soggetti che hanno evidenziato un
miglioramento dello score IGA da 2 ad 1, risulta di
particolare interesse la riduzione delle lesioni non
infiammatorie (-72,7%; p < 0.05). Questi effetti sono
il risultato dell’azione sinergica dell’Alukina® e del
Microsilver BG™. L’Alukina modula la secrezione
sebacea, intervenendo sul movente patogenetico
primario dell’acne, mentre l’argento micronizzato
interviene sulla colonizzazione follicolare, interrompendo il circolo vizioso che porta all’accumulo di sebo, infiammazione e infezione. Ciò spiega
la notevole riduzione dei comedoni piuttosto che
delle papule e delle pustole. Inoltre, già alla quarta settimana i soggetti presentavano una pelle
meno lucida ed untuosa, di aspetto più uniforme e
meno infiammata. Ciò suggerisce che il prodotto
possa essere impiegato con profitto anche in associazione alla terapia farmacologica.
Conclusioni
I risultati del presente studio indicano che
il nuovo cosmeceutico multicomponente in formulazione crema può essere usato con elevate percentuali di successo clinico nei soggetti con acne di
grado lieve.
L’applicazione deve avere una durata di almeno
otto settimane. Ulteriori studi sono necessari per
verificare se l’applicazione per periodi più lunghi
possa recuperare alla risposta una quota maggiore
di soggetti.
Sarebbe inoltre interessante esplorare le potenzialità
del prodotto su forme di acne medio-gravi in associazione alle terapie farmacologiche convenzionali,
per esempio per ridurre la secchezza cutanea ed il
prurito che spesso si associano all’uso dei retinoidi
(topici e sistemici) ed al benzoilperossido.
Bibliografia
1. Ghodsi SZ, Orawa H, Zouboulis CC. Prevalence, severity,
and severity risk factors of acne in high school pupils: a community-based study. J Invest Dermatol. 2009; 129:2136-41.
2. Shen Y, Wang T, Zhou C, et al. Prevalence of acne vulgaris
in Chinese adolescents and adults: a community-based study
of 17,345 subjects in six cities. Acta Derm Venereol. 2012;
92:40-4.
3. Yosipovitch G, Tang M, Dawn AG, et al. Study of psychological stress, sebum production and acne vulgaris in adolescents.
Acta Derm Venereol. 2007; 87:135-9.
4. Misery L. Consequences of psychological distress in adolescents with acne. J Invest Dermatol. 2011; 131(2):290-2.
5. Thiboutot D, Gollnick H, Bettoli V, et al. New insights into
the management of acne: an update from the Global Alliance
to Improve Outcomes in Acne group. J Am Acad Dermatol.
2009; 60(5 Suppl):S1-50.
Tratto da: JPD 2014; 2:81
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6. Stollery N. Acne. Practitioner. 2007; 251:86-91.
7. http://www.fda.gov/ohrms/dockets/ac/02/briefing/3904B1_
03_%20Acne%20Global%20Severity%20Scale.pdf
8. Goodman G. Acne and acne scarring - the case for active
and early intervention. Aust Fam Physician. 2006; 35:503-4.
9. Zaenglein AL. Making the case for early treatment of acne.
Clin Pediatr. 2010; 49:54-9.
10. Bartenjev I, Oremovic L, Rogl Butina M, et al. Topical
effectiveness of a cosmetic skincare treatment for acne-prone
skin: a clinical study. Acta Dermatovenerol Alp Panonica
Adriat. 2011; 20:55-62.
11. Capitanio B, Sinagra JL, Weller RB, et al. Randomized
controlled study of a cosmetic treatment for mild acne. Clin
Exp Dermatol. 2012; 37:346-9.
EJA CongrAbstract ultimo stef_Stesura D’Alessandro 07/10/14 12:28 Pagina 59
Giuseppe Monfrecola
Section of Dermatology, Dept. of Clinical Medicine and Surgery
University Federico II, Napoli, Italy
ACNE DAY 2014
Presidente
Giuseppe Monfrecola
Presidente Onorario
Fabio Ayala
Coordinatrice
Attività Scientifiche
Napoli
17-18 OTTOBRE 2014
Why an Acne Day?
For two main reasons: first, acne is a very frequent disease attracting the attention
of great part of the population and of mass media that have to identify dermatologists as specialists for acne; second, dermatologists need to be continuously updated on acne in order to
manage it at the best.
Acne is a common inflammatory disorder affecting the pilosebaceous follicles.
Epidemiologic data indicate that, by the age of 21 years, 80-90% of adolescents have had acne
and that, after the age of 25 years, approximately 50% of the population still suffers of acne.
The scientific part of Acne Day 2014 will be focused on the four main processes
playing a central role in the development of acne lesions: inflammatory mediators released
into the skin; sebaceous hypersecretion; abnormal keratinization involving the walls of the
pilosebaceous follicle; follicular colonization by Propionibacterium acnes.
Particular attention will be devoted to the role of P. acnes on inflammatory process. P. acnes not only secretes lipases, metalloproteases and chemotactic factors that
damage keratinocytes through the generation of oxygen reactive species, but also interacts
with different markers of the innate immunity such as toll-like receptors, antimicrobial peptides, protease-activated receptors and matrix metalloproteinases.
As a consequence a loop is generated between activation of the innate immunity
and production of inflammatory cytokines (IL-1α, IL-1β, IL-6, IL-8, IL-12, TNF-α) from
keratinocytes, sebocytes or macrophages.
Moreover it has been demonstrated:
1) that strains of P. acnes are able to modulate the expression of genes coding for
proteins involved in the differentiation of keratinocytes and
2) that P. acnes stimulates the sebum synthesis via the corticotrophin-releasing
hormone/CRH-receptor system increasing the activity of sebocytes.
One session of the Acne Day 2014 will be centered on the influences induced by
the food intake. Hormones and growth factors play a crucial role on sebaceous glands and
on keratinocytes of the pilo-sebaceous duct.
Dairy products contain more than 50 growth factors and micronutrients; in particular drinking milk provokes an increase of insulin-like growth factor (IGF-1) through
elevation of both blood sugar and insulin serum levels. Moreover high glycemic load
foods are able to increase DHT through elevated levels of IGF-1.
It has been demonstrated that a particular population of young males affected with
acne suffers from a metabolic imbalance and that insulin resistance seems to play the
Volume 5, n. 2, 2014
main role for the development of acne lesions in
these subjects.
A relevant part of the Acne Day 2014 will
be dedicated to the guidelines for treatment of acne
and to new therapeutic perspectives. In particular a
session will be focused on the mechanisms of
P.acnes resistance to antibiotics, that is how to
reduce or avoid it.
Acne is a typical chronic disease that lasts
for several years, therefore an effective management should take into account two steps: an initial
treatment aimed to the reduction of the severity of
acne lesions and a maintenance treatment aimed to
avoid relapses.
Treatment options for acne range from
topical treatments to the use of oral antibiotics or
oral retinoids and often they determine annoying
side effects.
Therefore dermatologists must choose the
treatment not only on the basis of the severity and
extension of the disease but also on the patient’s
compliance. This means that adherence is fundamental for any acne treatment to be really effective.
Poor adherence with treatments represents the main
problem in the acne management as it is well known
that many patients, particularly teenagers, do not
adequately utilize dermatologist’s prescriptions.
Finally, during the Acne Day 2014 three
courses concerning respectively hyperhidrosis
botulinum peelings and laser will be held in order
to give the participants practical knowledge about
these topics.
In conclusion, the phenotypic appearance
of acne is the result of several genetic influences,
mainly involving immunologic and metabolic aspects, and environmental conditions, it is likely
that it is time to consider acne as “acneic disease”.
The hope is that Acne Day 2014, thanks
to the quality of the speakers and to the active contribute of the participants, could represent an
opportunity for a full immersion in a very complex
dermatologic topic.
Volume 5, n. 2, 2014
NAPOLI, Palazzo Salerno
17-18 Ottobre 2014
Abstracts
Lettura Magistrale
Acne cheloidea, idrosadenite suppurativa e chirurgia: what’s new?
Nicolò Scuderi
Unità di Chirurgia plastica, ricostruttiva ed estetica, Dipartimento di Chirurgia, Università “Sapienza”, Roma
Descritta per la prima volta nel 1860 da Hebra come sycosis framboesiformis e poi nel 1869 da
Kaposi come dermatite papillare del capillizio, fu Bazin nel 1872 a coniare il termine di acne cheloidea (AC).
Per AC si intende una condizione patologica caratterizzata dalla formazione di papule e pustole a livello dei
follicoli piliferi che in seguito a stimolo infiammatorio persistente evolvono in cicatrici cheloidee e\o ipertrofiche. Pertanto, la dizione “acne cheloidea” risulta impropria poiché le lesioni fanno seguito ad una follicolite piuttosto che ad un’acne volgare. L’AC interessa maggiormente giovani afro-americani di età compresa fra
14-25 anni, manifestandosi prevalentemente a livello del cuoio capelluto e della regione posteriore del collo.
Le lesioni papulari iniziali sono asintomatiche, le pustole invece sono caratterizzate da prurito e dolore; in
alcuni casi possono associarsi ascessi e sinus purulenti e maleodoranti. Una corretta diagnosi differenziale
(acne conglobata, acne vulgaris, eruzioni acneiformi, idrosadenite suppurativa, perifolliculitis capitis) si
impone per impostare una terapia comportamentale e medica corretta. Il trattamento può essere farmacologico (principalmente orientato a ridurre l’infiammazione e le possibili infezioni) o chirurgico (escissione a losanga, laser terapia). La terapia chirurgica si avvale di crioterapia, utilizzo di laser ablativi ed escissioni più o
meno ampie delle zone patologiche.
L’Idrosadenite Suppurativa (IS), conosciuta anche come Acne Inversa o Sindrome di Verneuil, è una malattia cronica caratterizzata dalla comparsa di noduli ed ascessi dolorosi e ricorrenti localizzati ad ascelle, inguine ed area genitale. Le lesioni tendono ad evolvere in esiti cicatriziali fibrotici e fistole. L’IS interessa l’1%
della popolazione in età postpuberale con un picco nella terza decade con un rapporto donne/uomini di 3:1 e
con un forte impatto sulla qualità della vita dell’ammalato. L’etiologia e la patogenesi sono ancora da elucidare, tuttavia l’IS riconosce come primum movens l’occlusione dell’unità pilo sebacea che porta a rottura follicolare, formazione di ascessi e susseguente formazione di fistole. La diagnosi è, purtroppo, spesso ritardata;
il trattamento di prima linea può essere rappresentato da antibiotici sistemici e drenaggio; cortisonici sistemici, antiandrogeni, retinoidi e farmaci biologici costituiscono opzioni alternative. L’approccio chirurgico si propone come principale obiettivo la bonifica delle aree colpite con incisione e drenaggio di eventuali raccolte,
messa a piatto delle ferite e guarigione delle stesse per seconda intenzione. Qualora molto estese si può optare per l’asportazione en-block delle zone patologiche con ricostruzione tramite lembi di vicinanza. Particolare
cura dovrà essere posta nel postoperatorio.
65
Volume 5, n. 2, 2014
SESSIONE
Nuove acquisizioni nella patogenesi dell’acne
Approcci metabolomici nello studio dei lipidi nell’acne
Emanuela Camera, Mauro Picardo
Laboratorio di Fisiopatologia Cutanea, Istituto Dermatologico San Gallicano (IRCCS), Roma
L’alterata secrezione sebacea ed il rilascio di mediatori infiammatori sono annoverati tra i meccanismi patogenetici alla base dell’acne. Linee di studio recenti stanno prendendo in esame apporto, metabolismo
e distribuzione dei grassi, insieme ad un eccessivo carico glicemico e ad un’alterata sensibilità insulinica quali
fattori predisponenti o aggravanti delle manifestazioni. Le alterazioni biochimiche associate con l’acne sono
state ricercate principalmente nel sebo, che costituisce il prodotto finale dell’attività e secrezione della ghiandola sebacea. Tuttavia, le conoscenze attuali sui complessi meccanismi che intervengono nelle alterazioni del
sebo sono ancora molto limitate. L’indagine dettagliata del lipidoma sebaceo può essere un utile supporto per
la definizione del sebo quale reporter delle vie lipogenetiche coinvolte nell’acne e della possibile interazione
tra genetica e apporto ed elaborazione dei nutrienti. Il sebo è un’elaborata miscela lipidica sintetizzata durante il differenziamento dei sebociti che giunti al termine del ciclo vitale riversano i lipidi accumulati nel dotto
ghiandolare. Il sebo umano è costituito da tre frazioni principali date dallo squalene e da miscele di esteri del
glicerolo (maggiormente trigliceridi) e degli alcoli a lunga catena (esteri delle cere). A sottolineare la loro
sebospecificità, squalene e cere raggiungono concentrazioni molto più elevate nel sebo che in qualunque altro
distretto dell’organismo. Al contrario, le basse concentrazioni di colesterolo ed i suoi esteri hanno fatto ritenere che queste specie derivino dalla contaminazione da parte della frazione epidermica dei lipidi. Digliceridi ed
acidi grassi liberi, quest’ultimi nettamente preponderanti rispetto ai primi, vengono descritti come prodotti dell’idrolisi dei trigliceridi sebacei per opera della microflora cutanea, di cui il P. acnes fà parte. La considerazione che gli acidi grassi liberi siano prodotti secondari del metabolismo microbico ha fatto probabilmente sottovalutare il valore di queste specie nella patogenesi dell’acne. Gli acidi grassi sono al contempo le componenti
elementari coinvolte nella sintesi di una varietà di specie lipidiche cutanee e prodotti del metabolismo microbico. Gli acidi grassi sebacei presentano caratteristiche peculiari non riscontrate in altre matrici lipidiche. Infatti,
il sebo contiene acidi grassi ramificati, cioè con gruppi metilici in diverse posizioni dello scheletro carbonioso e
acidi grassi monoinsaturi e diinsaturi con posizioni dei doppi legami non convenzionali. La desaturazione di tipo
sebaceo è catalizzata dall’enzima Δ6 desaturasi (fatty acid desaturase-2, FADS-2), che converte preferenzialmente l’acido palmitico (C16:0) in acido sapienico (C16:1n-10). L’acido sapienico è poi elongato ed ulteriormente desaturato a formare acido sebaleico (C18:2n-10,13).
La seborrea e la severità dell’acne sembrano essere associate ad un aumento della proporzione di acidi grassi monoinsaturi (MUFA), di cui l’acido sapienico è il maggiore rappresentante (25% degli acidi grassi liberi
totali), suggerendo un ruolo delle desaturasi nella sebogenesi e nella comedogenesi. Di contro, nei lidi superficiali cutanei di pazienti acneici è stato riscontrato un ridotto livello di acido linoleico (C18:2n-6,9). In particolare, il deficit di C18:2n-6,9 sembra incidere maggiormente sui livelli degli esteri delle cere, facendo ritenere che l’apporto di acidi grassi essenziali sia coinvolto direttamente nelle vie metaboliche sebogenetiche.
Inoltre, la ridotta disponibilità di acido linoleico è causa dell’alterata funzione barriera alla base dell’aumentata permeabilità della parete comedonica a sostanze infiammatorie.
Al di là dei componenti specificamente indagati negli studi precedenti, si intuisce come il sebo sia costituito da
uno spettro ampio di strutture lipidiche presenti a concentrazioni notevolmente diverse tra loro. L’avanzamento
delle nostre conoscenze sul ruolo fisiologico e patologico dei componenti della miscela lipidica sebacea è stato
impedito dalla complessità della matrice stessa e dalla mancanza di strumenti d’indagine in grado di fornire
una visione d’insieme. Nel nostro laboratorio abbiamo sviluppato una piattaforma analitica che ha permesso
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la caratterizzazione della maggior parte dei lipidi presenti nel sebo. Il disegno analitico applicato ha fornito il
primo strumento di indagine in grado di delineare il lipidoma sebaceo. Per ottenere le “signature” lipidiche
caratteristiche dell’acne, abbiamo studiato più di 60 adolescenti con diverso grado di severità della patologia.
La valutazione statistica univariata e multivariata dei dati ha fatto emergere numerose sostanze come significativamente alterate nel sebo dei soggetti affetti. La maggior parte dei composti la cui concentrazione era significativamente modificata appartenevano alle classi di digliceridi ed acidi grassi. In minor misura anche specie
appartenenti alle altre classi di lipidi sebacei, quali trigliceridi, cere, esteri del colesterolo e lo squalene, sono
interessate nella condizione patologica. Inoltre, dati di correlazione sono indicativi dell’associazione tra livelli
di digliceridi ed acidi grassi ed il grado di severità delle manifestazioni cliniche. L’identificazione sulle alterazioni più significative riscontrabili nel sebo in soggetti affetti da acne è un importante contributo alla comprensione delle specifiche vie metaboliche interessate e alla definizione dei meccanismi patogenetici dell’acne.
Cutaneous fragility in acne
Gabriella Fabbrocini, Rosanna Izzo
Department of Clinical Medicine and Surgery, Section of Dermatology, University of Naples Federico II, Italy
Introduction: Acne and skin fragility
Acne is a common inflammatory skin disease, characterized by comedones, papules, pustules, and
nodules, distributed on face, chest, and back. Propionibacterium acnes (P. acnes) identified in acne lesions,
plays, together with the sebaceous gland, an important role in the pathogenesis of the condition: P. acnes, in
fact, secretes lipases, chemotactic factors, metalloproteases and porphyrins, inducing an inflammatory response, with production of free radicals, and causing keratinocyte damage 1. Keratinocyte damage lead to an alteration of the “epidermal barrier”: this barrier include homeostatic control of water content and flux (permeability barrier), recognition and neutralization of microbial organisms (antimicrobial barrier), countering of
reactive oxygen species (antioxidant barrier), protection from effects of ultraviolet light exposure (photoproFigure 1. Pathogenesis of Skin Fragility
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tection barrier), and response to exogenous allergens and haptens (immunologic barrier) 2. The alteration of
epidermal barrier lead to a “fragile skin”, showing lower resistance to aggressions; it can be classified into
four categories up to its origin: physiological fragile skin (age, location), pathological fragile skin (acute and
chronic), circumstantial fragile skin (due to environmental extrinsic factors or intrinsic factors such as stress)
and iatrogenic fragile skin 3. When epidermal permeability barrier (stratum corneum, SC) impairment persists without correction, signal amplification produces cascades that lead to clinically evident cutaneous abnormalities (ie, xerosis, fissuring, desquamative changes, eczematous dermatitis, hyperkeratosis) 4.
The “epidermal barrier” in acne: Surface epidermis
The facial skin of acne patients differs from normal skin of people without acne for the higher sebum
production and the size of sebaceous glands; for the higher TEWL (Transepidermal Water Loss) and lower SC
hydration (decreased conductance), supporting the SC permeability barrier impairment associated with acne 5.
In addition, acne patients had significantly reduced free sphingosine and total ceramides in their SC, which is
indicative of a deficient intercellular lipid membrane and correlates with impairment of the SC permeability
barrier. The increase in TEWL and decrease in SC hydration (conductance) were of greater magnitude in
patients with acne of moderate severity as compared to those with mild acne severity 5, 6.
The “epidermal barrier” in acne: Follicular epidermis (epithelium)
In acne, the proliferation of P. acnes within the follicle induces several inflammatory cascades related
to innate, acquired, and humoral immunological responses 5. When intrafollicular and perifollicular inflammatory processes markedly intensify, attenuation of the follicular wall can lead to various degrees of rupture with
subsequent leakage of sebum, keratin, bacteria into the dermis 5. These foreign substances to the dermis increase inflammation that is deeper, inducing the emergence of a nodular or nodulocystic acne lesion 5, 6.
Filaggrin and Acne
Filaggrin is a key protein in epidermal differentiation and contributes to the structural and functional integrity of the SC. Alteration of filaggrin expression are associated to modification in skin barrier, and
lead to some skin diseases, such as atopic dermatitis 7. Within acne lesions, there is an increase in filaggrin
expression in keratinocytes lining the follicle wall. In addition, P. acnes has been shown to increase filaggrin
expression in cultured keratinocytes and also in explants of human skin. Importantly, it is not known if the
changes in filaggrin expression noted in acne are primary or secondary events 8.
Acne treatments and skin barrier
Some topical medications, systemic medications, and physical procedures used to treat acne and/or
acne scarring can lead to alterations in SC permeability barrier function based on documentation of increased
TEWL and in some cases visible signs of xerosis. Increases in TEWL have been reported with benzoyl
peroxide, tretinoin, tazarotene, and isotretinoin 5, 9-13.
Topical retinoids induce acanthosis, hypergranulosis, a relative decrease in SC thickness and desquamation:
all these conditions are associated to an alteration in permeability barrier function.
Oral isotretinoin can alter the structure, function, immunology, and bacteriology of the skin: it causes increased
epidermal turnover and skin fragility, with propensity to intraepidermal separation; loss of desmosomes and
decrease in tonofilaments occurs. Oral isotretinoin causes easier separation of corneocytes of the outermost SC,
accounting for the superficial desquamative changes that are frequently observed in patients treated 2.
A dermo-cosmetic approach to acne, included strategies to mitigate the altered effects of epidermal barrier
functions, is very important to ensure a correct topical barrier repair.
References
1. Beylot C, Auffret N, Poli F, Claudel JP, Leccia MT, Del Giudice P, Dreno B. Propionibacterium acnes: an update on its role in the
pathogenesis of acne. J Eur Acad Dermatol Venereol 2013. doi: 10.1111/jdv.12224.
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2. Del Rosso JQ. Clinical relevance of skin barrier changes associated with the use of oral isotretinoin: the importance of barrier repair
therapy in patient management. J Drugs Dermatol 2013; 12(6):626-31
3. Stalder JF1, Tennstedt D, Deleuran M, Fabbrocini G, de Lucas R, Haftek M, Taieb C, Coustou D, Mandeau A, Fabre B, HernandezPigeon H, Aries MF, Galliano MF, Duplan H, Castex-Rizzi N, Bessou-Touya S, Mengeaud V, Rouvrais C, Schmitt AM, Bottino R, Cottin
K, Saint Aroman M. Fragility of epidermis and its consequence in dermatology. J Eur Acad Dermatol Venereol 2014; 28 Suppl 4:1-18. doi:
10.1111/jdv.12509.
4. Haftek M, Coutanceau C, Taïeb C. Epidemiology of "fragile skin": results from a survey of different skin types. Clin Cosmet Investig
Dermatol 2013; 6:289-94. doi: 10.2147/CCID.S55223. eCollection 2013.
5. Thiboutot D, Del Rosso JQ. Acne Vulgaris and the Epidermal Barrier: Is Acne Vulgaris Associated with Inherent Epidermal
Abnormalities that Cause Impairment of Barrier Functions? Do Any Topical Acne Therapies Alter the Structural and/or Functional
Integrity of the Epidermal Barrier? J Clin Aesthet Dermatol 2013; 6(2):18-24.
6. Yamamoto A, Takenouchi K, Ito M. Impaired water barrier function in acne vulgaris. Arch Dermatol Res 1995; 287(2):214-218.
7. Levin J, Friedlander SF, Del Rosso JQ. Atopic dermatitis and the stratum corneum: part 2: other structural and functional characteristics of the stratum corneum barrier in atopic skin. J Clin Aesthet Dermatol 2013; 6(11):49-54.
8. Kurokawa I, Mayer-da-Silva A, Gollnick H, et al. Monoclonal antibody labeling for cytokeratins and filaggrin in the human pilosebaceous unit of normal, seborrhoeic and acne skin. J Invest Dermatol 1988; 91:566-571
9. Draelos ZD, Ertel KD, Berge CE. Tretinoin facilitating facial retinization through barrier improvement. Cutis 2006; 78:275-281.
10. Weber SU, Thiele JJ, Han N, et al. Topical tocotrienol supplementation inhibits lipid peroxidation but fails to mitigate increased transepidermal water loss after benzoyl peroxide treatment of human skin. Free Radic Biol Med 2003; 34:170-176.
11. Herane MI, Fuenzalida H, Zegpi E, et al. Specific gel-cream as adjuvant to oral isotretinoin improved hydration and prevented TEWL
increase-a double-blind, randomized, placebo-controlled study. J Cosmet Dermatol 2009; 8(3):181-185.
12. Stucker M, Hoffman M, Altmeyer P. Instrumental evaluation of retinoid-induced skin irritation. Skin Res Technol 2002; 8:133-140.
13. Tagami H, Tadaki T, Obata M, et al. Functional assessment of the stratum corneum under the influence of oral aromatic retinoid (etretinate) in guinea-pigs and humans. Comparison with topical retinoic acid treatment. Br J Dermatol 1992; 127:470-475.
SESSIONE
Acne e dintorni
Effectiveness and tolerability of a topical gel containing hydrogen peroxide,
salicylic acid and d-panthenol in the treatment of mild-moderate acne
Gabriella Fabbrocini, Luigia Panariello, Marianna Donnarumma, Caterina Mazzella
Acne is a chronic inflammatory disease with multifactorial pathogenesis, showing a prevalence of
about 85% in adolescence 1. It has negative impact on patients’ quality of life.
European guide lines for the treatment of mild to moderate papulopustular acne recommend a treatment based
on the use of benzoylperoxide in combination with adapalene or benzoylperoxide in combination with clindamycin 2.
The benzoylperoxide, however, can cause significant side effects that may lead to interrumption of the therapy. The benzoylperoxide, after application, decomposes into benzoic acid and hydrogenperoxide. The benzoic acid appearsto be responsible for skinirritation 3.
The hydrogenperoxide is an antimicrobial agent that causes significant alteration of the microenvironment of
the pilosebaceous unit, reducing the degree of inflammation and number of lesions in patients with acne. It
has been shown that hydrogenperoxide has got efficacy comparable to the BPO in acne treatment associated
with a good tolerability 4.
Salicylic acid is a beta hydroxy acid used for its anti-inflammatory and comedolytic action in the treatment
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of comedonal and papulopustular acne 5. It has been shown that the application of a topical containing benzoylperoxide and salicylic acid can lead to a reduction of acne lesions in patients with mild, moderate, and
severe acne 6. The D-panthenolis an analogue of pantothenic acid with moisturizing and anti-inflammatoryproperties 7, 8. We evaluated the efficacy and tolerability of a gel containing hydrogenperoxide (4%), salicylic acid (0.5%) and D-panthenol in the treatment of mild to moderate acne.
Material and Methods
10 patients (14-30 years), with mild to moderate acne have been selected. The topical product was applied
twice a dayfor 2months. The evaluations were carried out at the beginning of treatment (T0), after 30 days
(T1) and after 60 days (T2) evaluating: GAGS, lesion counts, photographic assessment with digital images
by Reveal, questionnaire filled by the patient to assess the tolerance and the presence of side effects.
Figure 1.
T0
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Results
The GAGS score showed a reduction of 54% from T0 to T2. The comedonic lesions showed a reduction of
90% from T0 to T2. The counts of papular lesions showed a reduction of 60% from T0 to T2. The countsof
pustular lesions showed a reduction of 100% from T0 to T2 (Figure1).
The tolerability according to 60% of the patients was excellent at T1, good according to 30% and moderate
according to 10%. At the end of treatment 60% of the patients considered the tolerability of the product excellent and 40% good. Only one patient reported a side effect,burning sensation at T1. The same patient at T2
did not report any symptoms.
Discussion and Conclusions
The association of hydrogenperoxide and salicylic acid, with a substance with restructuring and anti-inflammatory characteristics, such as D-panthenol, is able to reduce GAGS score (the results are comparable to those
found in literature for the combination of BPO and salicylic acid) and to limite the side effects typical of acne
therapy. Due to these findings, this association could be useful in the treatment of mild-to-moderate, especially in cases of sensitive and intolerant skin to the BPO.
References
1. Knutsen-Larson S, Dawson AL, Dunnick CA, Dellavalle RP. Acne vulgaris: pathogenesis, treatment, and needs assessment. Dermatol
Clin 2012; 30(1):99-106, viii-ix. doi: 10.1016/j.det.2011.09.001. Epub 2011 Oct 21. Review.
2. Nast A, Dréno B, Bettoli V, Degitz K, Erdmann R, Finlay A, Ganceviciene R, Haedersdal M, Layton A, Lopez Estebaranz JL,
Ochsendorf F, Oprica C, Rosumeck S, Rzany B, Sammain A, Simonart T, Veien NK, Vurnek Zivkoviü M, Zouboulis CC, Gollnick H.
Guidelines for the treatment of acne. European Dermatology Forum 13/09/2011
3. Ives TJ. Benzoyl peroxide. Am Pharm 1992; NS32(8):33-8
4. Milani M1, Bigardi A, Zavattarelli M. Efficacy and safety of stabilised hydrogen peroxide cream (Crystacide) in mild-to-moderate acne
vulgaris: a randomised, controlled trial versus benzoyl peroxide gel. Curr Med Res Opin 2003; 19(2):135-8.
5. Shalita AR. Treatment of mild and moderate acne vulgaris with salicylic acid in an alcohol-detergent vehicle. Cutis 1981; 28:556-558.
6. Kircik LH1, Gwazdauskas J, Butners V, Eastern J, Green LJ. Evaluation of the efficacy, tolerability, and safety of an over-the-counter acne regimen containing benzoyl peroxide and salicylic acid in subjects with acne. J Drugs Dermatol 2013; 12(3):259-64.
7. Girard P, Berand A, Goujou C, Sirvent A, Foyatier J-L, Alleaume B, de Bony R. Effect of Bepanthen® Ointment on the graft-donor
site wound-healing model: double-blind biometrical and clinical study, with assessment by the patient, versus the vehicle. Nouv Dermatol
1998; 17:559-570.
8. Romiti R, Romiti N. Dexpanthenol cream significantly improves mucocutaneous side effects associated with isotretinoin therapy.
Pediatr Dermatol 2002; 19(4):368.
Acne e cosmetici
Caterina Mazzella
Acne is a diffused condition with negative physical and emotional effects, and significant societal
costs. However, recent epidemiological studies have shown that a significant number of female patients aged
> 25 years is affected by acne. The reasons for persistent acne are not fully understood. External factors such
as use of certain cosmetics, ingestion of drugs, and endocrine abnormalities can be considered in the managing of these patients. Adult acne in females can be divided into: persistent acne that represents a pursuance
of acne from adolescence into adult life and late-onset acne, which describes significant acne occurring sometimes for the first time after the age of 25 years. Acne treatment should aim to reduce sebum, comedogenesis,
Propionibacterium acnes and inflammation, while the maintenance therapy plays an important role in managing of patients. A cosmetic is defined as an “article intended to be rubbed, poured, sprinkled, or sprayed on
the human body for the purpose of cleansing, beautifying, promoting attractiveness, or altering the appearan-
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ce without affecting the body’s structure or function.” There are over 5000 cosmetic ingredients (Table1).
Appropriate cosmetics for skin cleansing are capable of contributing to a reduction of inflammatory lesions
and to help the pharmacological treatment in patients with acne. Cleansing in the acne patient involves several considerations, including matching skin type, the right type of cleanser, optimal times and methods of
cleansing. The goal of cleansing for acne or acne-prone skin is to gently remove surface dirt, sweat, and
excessive skin lipids without irritating or drying the skin. The ideal cleanser for acne skin should be: non
comedogenic, no-irritating, and no-allergenic . The hydratation is an important time in acne patients, because many treatments as retinoids may cause xerosis. Moisturizing prevents and alleviates skin irritation. Many
liquid face cleansers are also moisturizers, and they may be all that is needed for a patient with seborrheic
skin; besides sebum-controlling agents are used to absorb sebum, and their action is due to the presence of
matifiant agents. Antinflammatory agents are very important, considering the role of inflammatory in the
pathogenesis of acne, they can be associated with pharmacological therapies; the main products are: salycilic
acid, zync, resveratrol, nicotinamide, piroctone olamine and antimicrobial peptides (AMP). There is a group
of cosmetics indicated for comedonal acne that have a comedolytic effects, they can be used in patients that
don’t tolerate pharmacological treatment such as topical retinoids or benzoyl peroxide. Hydroxyacids belong
to this group. They are represented by the alpha-hydroxyacids, the beta-hydroxyacids, the polyhydroxy acids,
and the bionic acids . Protection from sun is important for all patients, and while sunscreens are often irritants, the best options for patients to have a water or
Table 1. Cosmetic products for acne
light liquid base. Moisturizing sunscreens are appropriate for patients with dry, sun-damaged skin, as
Cleansers
well as those who wear makeup, have other skin
Moisturizing agents
diseases, or are easily irritated by products. Overall,
Sebum controlling agents
treating acne patients should include education in
Antinflammatory agents
patient-friendly terms and promoting healthy daily
Cornedolytic agents
skin care practices, including cleansing and protection against environmental damage.
Photoprotective agents
References
Camouflage
1. Goodman G. Am J Clin Dermatol 2009; 10 Suppl 1:1-6.
2. Dréno B, Layton A, Zouboulis CC, López-Estebaranz JL, Zalewska-Janowska A, Bagatin E, Zampeli VA, Yutskovskaya Y, Harper JC
Adult female acne: a new paradigm. J Eur Acad Dermatol Venereol 2013; 27(9):1063-70.
3. Ella L. Toombs. Cosmetics in the treatment of acne vulgaris. Dermatol Clin Dermatol Clin. 2005; 23(3):575-81.
4. Draelos ZD. Cosmetics in acne and rosacea. Semin Cutan Med Surg. 2001; 20(3):209-14.
5. Harder J, Tsuruta D, Murakami M, Kurokawa I. What is the role of antimicrobial peptides (AMP) in acne vulgaris? Exp Dermatol
2013; 22(6):386-91.
6. Green BA, Yu RJ, Van Scott EJ. Clinical and cosmeceutical uses of hydroxyacids. Clin Dermatol 2009; 27(5):495-501.
7. Del Rosso JQ. The Role of Skin Care as an Integral Component in the Management of Acne Vulgaris: Part 1: The Importance of
Cleanser and Moisturizer Ingredients, Design, and Product Selection. J Clin Aesthet Dermatol 2013; 6(12):19-27.
Acne or acneiform rash?
Sara Cacciapuoti, Gabriella Fabbrocini
Acneiform rash is the most common side effect of epidermal growth factor receptor (EGFR) inhibitors (EGFRIs). EGFR belongs to a family (ErbB) of tyrosine kinase receptors which regulate tumor cell differentiation, survival, and proliferation. EGFR can be inhibited by the monoclonal antibodies cetuximab
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(Erbitux®) and panitumumab (Vectibix®) and by the
Figure 1.
Acneiform rush in a patient treated with Panitumumab
small molecule tyrosine kinase inhibitors (TKIs) erlotinib (Tarceva®) and gefitinib (Iressa®). Because the
EGFR is expressed in many different cell types in normal tissues, such as epithelial tissue, skin, hair follicles, and the gastrointestinal tract, it should not be surprising that treatment with EGFR inhibitors is complicated by cutaneous adverse events in up to 90% of
patients. This impacts the quality of life and sometimes prompts discontinuation of antineoplastic therapy
1. The most common cutaneous side effect is a dosedependent follicular papulopustular (acneiform) eruption on the face, scalp, chest and upper back (Figure
1). Acneiform rash is a dose-dependent skin drug
reaction, that usually develops at the first 1-2 weeks,
peaks at 3-4 weeks on therapy, and then most of the
time diminishes in intensity over the next couple of
weeks but often persists in mild form throughout the
course of therapy. For not clear reasons, monoclonal
antibodies are the most frequent trigger of acneiform
rash 2, 3. This skin reaction is defined “acneiform” rash
because patients with acneiform eruptions present with
acnelike lesions such as papulonodules and pustules.
However, they typically do not present with comedones, which is a distinguishing factor. The physical location is outside of the area in which acne vulgaris
occurs. Acneiform rash can be distinguished from acne vulgaris by monotonous lesion morphology, and development of the eruption at an age outside the range typical of acne vulgaris, with a clear anamnestic link with
the start of an EGFRIs therapy. Several recent prospective studies have addressed and evaluated different
interventions to mitigate or reduce the severity of EGFRI-associated skin rash 4-6.
Some important general recommendations are necessary: avoidance of prolonged sun exposure, products that
lead to drying of the skin such as alcohol-based products, soaps, common topical antiacne agents such benzoyl peroxide, which has the potential to cause skin irritation and excessive drying.
Pharmacological management requires topical antibiotics (gentamicin, clindamycin in combination with zinc
oxide, mupirocin and erythromycin) in greasy formulation (ointments or cream).
If the inflammatory component is evident, a 1% hydrocortisone ointment can be recommended for the first
days of therapy. Systemic antibiotics (e.g. tetracycline: doxicicline 200 mg/die) can be used when topical
agents seems to be ineffective or when rash is particularly severe.
References
1. Wagner L, Lai SE, Aneja M, et al. Development of a functional assessment of side-effects to therapy (FAST) questionnaire to assess
dermatology-related quality of life in patients treated with EGFR inhibitors (EGFRI): The FAST-EGFRI. J Clin Oncol 2007; 25(18s):
Abstr. 19532.
2. Hecht JR, Patnaik A, Berlin J, et al. Panitumumab monotherapy in patients with previously treated metastatic colorectal cancer.
Cancer 2007; 110:980-988.
3. Fukuoka M, Yano S, Giaccone G, et al. Multiinstitutional randomized phase II trial of gefitinib for previously treated patients with
advanced non-smallcell lung cancer (The IDEAL 1 Trial) (corrected). J Clin Oncol 2003; 21:2237-2246.
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4. Fabbrocini G1, Romano MC, Cameli N, et al. “Il corpo ritrovato”: dermocosmetological skin care project for the oncologic patient.
ISRN Oncol 2011; 2011:650482. doi: 10.5402/2011/650482.
5. Lynch TJJr, Kim ES, Eabyet B, al. Epidermal growth factor receptor inhibitor associated cutaneous toxicities: an evolving paradigm in
clinical management. Oncologist, vol. 12, no. 5, pp. 610-621, 2007.
6. Boucher J, Olson L, Piperdi B. Pre emptive management of dermatologic toxicities associated with epidermal growth factor receptor
inhibitors. Clinical Journal of Oncology Nursing, vol. 15, pp. 501-508, 2011.
Acne in infancy
Lawrence A. Schachner
Invited speaker to Acne day
Neonatal and Infantile acne are usually benign processes BUT may also signify
serious underlying hormonal abnormalities and tumors.
There are also numerous conditions that imitate neonatal/infantile acne that need to be
considered.
We will review the clinical presentation, differential diagnosis and treatment of neonatal/infantile acne and
when appropriate a further work up should take place to rule out serious underlying disorders.
Lawrence A. Schachner, M.D., is chairman and Harvey Blank professor of the Department of Dermatology and
Cutaneous Surgery at the University of Miami Miller School of Medicine.
A member of the Miller School of Medicine faculty since 1978, he is also professor of pediatrics and director of the
Division of Pediatric Dermatology. Dr. Schachner has written more than 200 scientific publications.
He is the lead author of the Schachner & Hansen textbook, Pediatric Dermatology edition 1 (1988), edition II (1995),
edition III (2003), and Pediatric Dermatology edition IV (2011).
Editions III and IV were nominated for the British Medical Association’s “Medical Book of the Year”. Edition III won
first prize. He is also co-author of eight other books.
La sensibilizzazione nei pazienti acneici
Cataldo Patruno
AOU Policlinico Federico II – AASSLL NA1 Centro/NA3 Sud
Summary
Both irritant contact dermatitis (ICD) and allergic contact dermatitis (ACD) due to drugs can occur during
topical treatment of acne vulgaris. ICD is a very frequent occurrence and is often considered as an integral part of the
mechanism of action of some drugs, such as retinoids or benzoyl peroxide. On the contrary, ACD is a rare occurrence,
despite the large use of these treatments. Indeed, it is reported that only 0,2% of patients in long-term treatment experiences allergic contact sensitization. Benzoyl peroxide is the main sensitizer, while some sporadic cases with other
molecules such as antibiotics, retinoids or antiseptics have been reported. Acute eczema is the main clinical pattern. On
the other hand, sometimes ACD is similar to common ICD; so, all patients with late appearance dermatitis should patch
tested. Patch test should performed with the single substance and not with the trade product, due to the high occurrence of false positive responses. Repeated open application test (ROAT) is sometimes required for the diagnosis.
La dermatite da contatto irritante (DCI) è frequentemente osservata nei pazienti in trattamento topico per acne ed è spesso parte integrante del meccanismo d’azione dei farmaci. La secondaria alterazione della
barriera cutanea, d’altra parte, predispone alla maggiore penetrazione delle molecole e quindi ad una maggiore possibilità di indurre, secondariamente, una sensibilizzazione allergica da contatto di tipo cellulo-mediato.
Valutando, però, la diffusione delle terapie topiche per acne e il loro utilizzo per lunghi periodi, il numero di
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sensibilizzazioni da contatto è esiguo ed è attualmente calcolato come inferiore a 0,2% dei pazienti trattati. Il
perossido di benzoile è senza dubbio la molecola più frequentemente implicata, mentre esistono casi aneddotici riguardanti altre molecole come antibiotici, retinoidi ed antisettici.
Clinicamente, la dermatite allergica da contatto (DAC) da topici per acne si manifesta spesso come eczema
acuto. Talvolta, però, la manifestazione clinica è più sfumata e non sempre è agevole la diagnosi differenziale rispetto alla comune DCI; è pertanto necessario sottoporre al patch test tutti i pazienti nei quali i segni di
irritazione si manifestino a distanza di settimane o mesi dall’inizio del trattamento. Inoltre, è necessario che
il patch test sia praticato con le molecole pure e non con i preparati del commercio potendo questi ultimi essere causa di reazioni falsamente positive. Utili in qualche caso dubbio sono i test d’uso, in particolare il repeated open application test (ROAT). Recentemente sono stati descritti casi di reazioni sistemiche acute gravi,
fino alla anafilassi, in seguito alla applicazione di preparati contenenti perossido di benzoile o di acido salicilico, anche se il reale ruolo di tali molecole nella etiologia di queste forme è ancora dibattuto.
Acne nucale e skin type: clinica e terapia
Antonia Gimma, Carla Cardinali
U.O. Dermatologia, USL 4, Prato
Summary
Acne keloidalis nuchae (AKN) is an inflammatory disease related to the spectrum of keloidal scarring alopecias. No
association with internal disease has been described so far. Several treatment options including topical and oral antibiotics are available for the early inflammatory stage of AKN. However, many patients present with more pronounced
fibrotic lesions for which treatment modalities are limited. The current surgical and conservative treatments of fibrotic papules and plaques including excision, topical and intralesional steroids, and cryotherapy often lead to unsatisfactory results. To date, there are very few rigorous studies examining novel, noninvasive, efficacious, and cost-effective
treatment options with few side effects for the prevention or treatment of the dermal fibrosis seen in AKN.
Il termine acne cheloidea della nuca (AKN) si riferisce alla presenza di papule e placche simil-cheloidee nella regione occipitale del cuoio capelluto e della nuca, quasi esclusivamente in soggetti maschi AfroAmericani con skin type V e VI della classificazione di Fitzpatrick.
L’AKN venne per prima descritta da Kaposi nel 1869 come dermatite papillare del capillizio. Tre anni dopo,
Bazin denominò la malattia “acne cheloidea”. Da allora, vari nomi sono apparsi in letteratura: follicolite cheloidale, sicosi della nuca, lichen cheloidale e follicolite sclerotizzante della nuca. Lo sviluppo prima della
pubertà o dopo i 50 anni è raro. Colpisce soprattutto i maschi adulti con rapporto di 20:1 rispetto alle donne.
Rappresenta approssimativamente lo 0.5% di tutte le dermatosi degli uomini Afro-Americani.
L’eziologia rimane sconosciuta. Contrariamente al suo nome, non è né una variante di acne volgare, né è legata alla tendenza e alla formazione di cheloidi. Lo studio condotto da Knable et al. non ha dimostrato un’associazione tra presenza di AKN, storia familiare di AKN né con una storia personale o familiare di cheloidi. Non è
stato identificato nessun fattore genetico predisponente a questa malattia. George et al. hanno invece descritto
una storia familiare nel 15% dei pazienti, un’associazione con la dermatite seborroica, incrementati livelli di
testosterone ematico e, in un terzo dei casi, AKN era associata alla pseudofollicolite della barba (PFB).
Negli individui di pelle scura la particolare morfologia dei capelli con fusto spiraliforme o a cavatappi, sezione di taglio ellittica o appiattita, insieme all’abitudine di rasarli corti, può essere un fattore precipitante perché la ricrescita del capello riccio può traumatizzare il cuoio capelluto determinando una reazione infiammatoria e lo sviluppo di AKN. Il motivo per cui la patologia interessi solo la nuca e la regione occipitale del cuoio
capelluto rimane oscuro. Forse altri fattori contribuenti allo sviluppo della patologia potrebbero ricercarsi in
meccanismi irritativi come la frizione del colletto delle camicie sul collo e dei caschi o un collo troppo corto.
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Verna et al. hanno descritto dei pazienti obesi indiani in cui la AKN era associata all’acanthosis nigricans
proponendo pertanto l’acne cheloidea un possibile marker cutaneo delle sindromi metaboliche. Goethe e
Berger hanno riscontrato similitudini istologiche con la follicolite perforante mentre Sperling ha annoverato
la malattia nell’ambito delle alopecie cicatriziali.
Azurdia ha riportato casi di AKN in soggetti bianchi dopo trattamento con ciclosporina. Altri Autori hanno
invece descritto la patologia in pazienti in terapia con difenilidantoina e carbamazepina: le lesioni regredivano alla sospensione dei farmaci suddetti.
Dal punto di vista istopatologico è presente una infiammazione follicolare e perifollicolare con neutrofili e
linfociti che inizia nel 3°superiore del follicolo pilifero, con marcata diminuizione delle ghiandole sebacee.
Successivamente si verifica la distruzione del follicolo pilifero con sviluppo di infiammazione granulomatosa e fibrosi dermica e cicatriziale
Clinica: inizia dopo la pubertà con papule tonde e fisse dai 2 ai 4 mm nella regione nucale e occipitale del cuoio capelluto. Quando presenti, le pustole sono fugaci e di solito traumatizzate dal grattamento. I
comedoni sono assenti. Man mano che la malattia progredisce, le papule aumentano di numero e di dimensioni e tendono a confluire formando placche simil-cheloidee prive di capelli che possono coprire gran parte
della regione occipitale del cuoio capelluto in una disposizione orizzontale. Il dolore e la possibile formazione di ascessi con secrezioni maleodoranti possono determinare un importante discomfort al paziente sia fisico che psicologico.
Terapia: la prima linea terapeutica è la prevenzione. I pazienti con AKN non devono usare rasoi
manuali ed elettrici lungo la regione occipitale e nucale, né tagliare troppo corti i capelli. Inoltre vanno evitati
stimoli irritativi di frizione (caschi, colletti di camicia…). Se la malattia si è sviluppata, la terapia deve essere
iniziata il più presto possibile per evitare la progressione delle lesioni. I corticosteroidi sistemici bloccano l’infiammazione portando a una parziale o completa regressione. Le lesioni si riacutizzano dopo qualche settimana
o mese dalla sospensione dello steroide e vanno quindi prese in considerazione altre opzioni terapeutiche. Tra
le terapie topiche in grado di attenuare l’AKN possiamo utilizzare gli steroidi di I e II classe.
Se c’è una infezione batterica va utilizzato un antibiotico topico o/e sistemico specifico. Recenti risultati con
imiquimod si sono osservati in alcuni casi. Altre terapie riportate in letteratura sono: iniezioni intralesionali
di corticosteroidi, applicazione di gel con silicone, rimozione delle singole papule con punch e guarigione per
seconda intenzione. Inoltre anche la laser terapia con apparecchiatura a diossido di carbonio o Nd:YAG, la
crioterapia e la fototerapia con UVB possono essere considerate altre scelte terapeutiche. L’escissione chirurgica può essere indicata nelle lesioni fino ad 1 cm con losanga orizzontale. Se le lesioni sono molto grandi e non rispondono alle terapie mediche e ad interventi di piccola chirurgia, l’escissione in più tempi con
guarigione per seconda intenzione può essere considerata.
Bibliografia
1) Verna SB, et al. Acne keloidalis nuchae. Am Clin Dermatol 2010; 433-436.
2) Kelly AP. Pseudofolliculitis barbae and acne keloidalis nuchae. Dermatol Clin 2003; 21:645-653.
3) Sperling LC, et al. Acne kelodalis is a form of primary scarring alopecia. Arch Dermatol. vol 136, Apr 2000.
4) Ogunbiyi A, at al. Acne keloidalis in females: case report and review of literature. J National Med Ass. vol. 97, n.5, may 2005.
5) Carqueville JC. Acne keloidalis nuchae: surgical management with elettrosection and second-intention healing. Cosmetology Nov. 2013.
6) Knable AL, et al. Prevalence of acne keloidalis nuchae in football players. J Am Acad Dermatol 1997; 37(4):570-4.
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SESSIONE
Acne, Rosacea e dintorni
La nostra esperienza con l’azeloglicina
Stefano Veraldi1, Daniele Domenico Raia1, Rossana Schianchi2, Mauro Barbareschi1
1
Department of Pathophysiology and Transplantation, University of Milan, I.R.C.C.S. Foundation,
2 European Institute of Dermatology, Milan, Italy
Un campione di trentasette pazienti di razza Caucasica ( 9 maschi e 28 femmine) affetti da rosacea eritemato-teleangectasica associata a sintomi di bruciore, è stato trattato con una crema contenente potassium azeloyl diglycinate 5 % e hydroxypropyl chitosan 1 %. Tutti i pazienti erano stati precedentemente
trattati in altri centri con acido azelaico topico e/o metronidazolo. La crema è stata applicata due volte al giorno per 12 settimane. L’obiettivo dello studio consisteva nella valutazione dell’effetto lenitivo: i sintomi di bruciore e “stinging” (sensazione puntoria) sono stati misurati su una scala di 4 punti (0 = assente; 1 = lieve; 2
= intermedio e 3 = grave). Tutti i pazienti sono stati valutati clinicamente ogni 4 settimane. Trenta pazienti su
37 (81.1%) sono stati considerati valutabili. Prima dell’ inizio dello studio, lo score totale dei sintomi di bruciore e “stinging” era pari a 66 (media 2.2 punti/paziente); alla fine dello studio, esso era pari a 37 punti (-29)
(media: 1.2 punti/paziente), con una riduzione del 56.1% . Non sono stati riferiti né osservati effetti collaterali. Tale studio mostra che una combinazione fissa di potassium azeloyl diglycinate-hydroxypropyl chitosan
è efficace nel ridurre i sintomi di bruciore e “stinging” nei pazienti con rosacea eritemato-teleangectasica.
Sovrainfezione da Citrobacter koseri in paziente acneico
Stefano Veraldi, Daniele Domenico Raia, Mauro Barbareschi
Department of Pathophysiology and Transplantation, University of Milan, I.R.C.C.S. Foundation, Ca’ Granda Ospedale Maggiore
Policlinico, Milan, Italy
Citrobacter koseri è un bacillo Gram-negativo, aerobio, mobile, non sporigeno appartenente alla
famiglia delle Enterobacteriaceae. Si tratta di un commensale della flora intestinale umana, e raramente causa
infezioni, soprattutto delle vie urinarie, ma anche in altre sedi (apparato respiratorio, sistema nervoso, sepsi),
in particolare in neonati (per trasmissione verticale dalla madre), anziani ed ospiti immunocompromessi.
Una proteina di superficie è stata identificata come possibile fattore di virulenza in ceppi che causano ascessi
cerebrali nei neonati. Casi di infezioni della cute sono molto rari. Descriveremo un caso di sovrinfezione da
Citrobacter koseri sul volto di un adolescente affetto da acne, risoltasi in seguito a terapia topica (antisettica) e sistemica (antibiotica, cortisonica e retinoide).
SESSIONE
Terapia dell’acne e suo monitoraggio
Acne resistente alle terapie tradizionali: casistica clinica del Polo
Pontino
Ersilia Tolino, Sara Zuber
Sapienza Università di Roma, Facoltà di Medicina e Farmacia, Polo Pontino, UOC di Dermatologia “Daniele Innocenzi”, Italy
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Attualmente l’acne è considerata una malattia infiammatoria ad andamento cronico-recidivante che
insorge in soggetti geneticamente predisposti. Clinicamente è caratterizzata da polimorfismo lesionale ed evoluzionale e può presentarsi con aspetti diversi nel corso del tempo in correlazione ai fattori scatenananti.
Sebbene l’algoritmo terapeutico sia d’ausilio per la cura della patologia a volte si osservano casi resistenti alle
terapie tradizionali topiche e sistemiche. Oltre alla variabile suscettibilità antimicrobica dei ceppi di P. acnes
sono numerosi i fattori endogeni ed esogeni che potrebbero intervenire nel determinare la mancata risposta al
trattamento. Lo studio dei non responders offre degli spunti sulle variabili che influenzano l’esito del trattamento. Presentiamo la casistica del Polo Pontino.
Post peeling care: a cosmetological approach
Mariateresa Cantelli, Giuseppe Monfrecola, Gina Panariello, Gemma Caro,
Department of Clinical Medicine and Surgery, Section of Dermatology Federico II, Naples, Italy
Acne is a common condition experienced by up to 80% of people between 11 and 30 years of age
and by up to 5% of older adults 1. In some patients, the severe inflammatory response to Propionibacterium
acnes results in permanent, disfiguring scars, the severity of which may depend on delays in treating acne
patients 2. The prevalence and severity of acne scarring in the population has not been well studied, although
the available literature is usually correlated to the severity of acne 3. Over the past several decades, numerous
descriptive terms and surgical techniques have been used to diagnose the types of scarring and improve them
in acne patients. Jacob et al. proposed a descriptive, simple, universally applicable acne scar classification
system that includes 3 scar’s types: icepick, rolling, and boxcar 1 (Table 1).
New acquisitions by the literature have showed that prevention is the main step to avoid the appearance of
post-acne scars 4. A number of treatments are available to reduce the appearance of scars. First, it is important to reduce as far as possible the duration and intensity of the inflammation, thus stressing the importance
of the acne treatment. The possible treatment options are: chemical peels, dermabrasion/microdermabrasion,
laser treatment, punch techniques, dermal grafting, tissue augmenting agents, needling and combined therapy
2. By chemical peeling we mean the process of applying chemicals to the skin to destroy the outer damaged
layers and accelerate the repair process 5. Dyschromias, wrinkles, and acne scars are the major clinical indiTable 1. Acne scar morphological classification (adapted from 1).
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Acne Scars Subtype
Clinical Features
Icepick
Rolling
Icepick scars are narrow (< 2 mm), deep, sharply marginated
epithelial tracts that extend vertically
to the deep dermis or subcutaneous tissue.
Rolling scars occur from dermal tethering of otherwise relatively
normal-appearing skin and are usually wider than 4 to 5 mm.
Abnormal fibrous anchoring of the dermis to the subcutis leads to
superficial shadowing and a rolling or undulating appearance to the
overlying skin.
Boxcar
Shallow
< 3 mm diameter
> 3 mm diameter
Boxcar scars are round to oval depressions with sharply demarcated
vertical edges, similar to varicella scars.
They are clinically wider at the surface than icepick scars and
do not taper to a point at the base.
Deep
< 3 mm diameter
> 3 mm diameter
They may be shallow (0.1-0.5 mm) or deep (≥ 0.5 mm)
and are most often 1.5 to 4.0 mm in diameter.
Volume 5, n. 2, 2014
cations for facial chemical peeling 6, 7. As regards to acne scars, the best results are achieved in macular scars.
Icepick and rolling scars cannot disappear completely and need sequential peelings together with homecare
treatment with topical retinoids and alpha hydroxy acids 8. Erythema, edema, itching and burning are common
adverse reactions that can reduce patient’s compliance. The aim of this study is to evaluate the efficacy and
safety of a collagen matrix facial mask in reducing side effects of chemical peels and skin needling.
50 patients of both sex, aged between 18 and 60 years, affected by acne scars, have been enrolled. Patients
were randomly divided in two groups, each one composed by 25 patients: group A received collagen matrix
facial mask, group B received allantoin mask. In each group, 10 patients underwent 33% salicylic acid peel,
8 patients underwent 33% trichloroacetic acid peel and 7 patients underwent skin needling therapy.
Figure 1.
Photographic images taken with Reveal of patient treated with trichloroacetic acid peel:
they clearly show the decrease in erythema and edema after the mask application.
Figure 2.
Photographic images taken with Reveal of patient treated with skin needling:
they clearly show the decrease in erythema and edema after the mask application.
Figure 3.
Confocal microscopy of a patient underwent 33% salicylic acid peel:
reduction of scales and detached keratinocytes, and a decrease in Furrow’s size in stratum corneum.
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Assessments was performed at T0 (before starting any treatment), at T1 (after peeling or needling therapy),
at T2 (after the mask removal) and before and after each following application of the mask (once a week for
4 weeks). Evaluated parameters were: skin hydration using corneometry; smoothness using Reveal; elasticity using elastometry; erythema using X-rite; structure of epidermidis and derma using confocal microscopy.
Safety of the mask was evaluated trough a questionnaire about subjective symptoms (such as itch and burning sensation) and objective signs (such as erythema and skin lesions).
Corneometry showed statistically significant results: in group A the values of hydration increased after each
mask application more than in group B.
Photographic images taken with Reveal showed: a decrease in erythema and oedema after each mask application which was more visible in group A compared to group B. Elasticity increased of 1 grade from T0 to
T10 in both groups (Figures 1-2).
Colorimetry using X-rite showed statistically significant results: in group A values increased after each mask
application more than in group B, showing a significant reduction of erythema in patients treated with collagen mask respect to allantoin mask.
Confocal microscopy showed in both groups a reduction of scales and detached keratinocytes, and a decrease in Furrow’s size in stratum corneum (Figure 3); at spinosum-granulosum level a progressive increased
interkeratinocyte reflectance and a reduction of inflammatory infiltrate.
These modifications were earlier and more significant in group A than in group B. No patients referred side
effects related to collagen matrix mask application. We can conclude that Collagen matrix mask showed a
better profile of efficacy and tolerability in reducing side effects of chemical peels and skin needling compared with an allantoin mask.
References
1. Jacob CI, Dover JS, Kaminer MS. Acne scarring: a classification system and review of treatment options. J Am Acad Dermatol 2001;
45(1):109-17.
2. Fabbrocini G, Annunziata MC, D’Arco V, De Vita V, Lodi G, Mauriello MC, Pastore F, Monfrecola G. Acne Scars: Pathogenesis,
Classification and Treatment. Dermatology Research and Practice Volume 2010, Article ID 893080, 13 pages doi:10.1155/2010/893080.
3. Layton AM, Henderson CA, Cunliffe WJ. A clinical evaluation of acne scarring and its incidence. Clinical and Experimental
Dermatology 1994; vol. 19, n. 4, pp. 303-308.
4. English RS, Shenefelt PD. Keloids and hypertrophic scars. Dermatologic Surgery 1999; vol. 25, n. 8, pp. 631-638.
5. Ghersetich I, Brazzini B, Lotti T. Chemical peeling, in European Handbook of Dermatological Treatments, Lotti TM and Katsambas
AD, Eds., Springer, Berlin, Germany 2nd edition, 2003.
6. Ghersetich I, Teofoll P, Gantcheva M, Ribuffo M, Puddu P. Chemical peeling: how, when, why? Journal of the European Academy of
Dermatology and Venereology 1997; vol. 8, n. 1, pp. 1-11.
7. Landau M. Chemical peels. Clinics in Dermatology 2008; vol. 26, n. 2, pp. 200-208.
8. Goodman GJ. Management of post-acne scarring: what are the options for treatment? American Journal of Clinical Dermatology 2000;
vol. 1, n. 1, pp. 3-17.
Retinoidi di nuova generazione
Maria Vitale
IFC Cantabria, Madrid
Acne treatment with topical retinoids is a well known therapy for its efficacy, due to its capacity to
reduce hyperseborrhoea and induce normalisation of keratinization. However, retinoid dermatitis is a very
common adverse event that happens during treatment with the majority of topicals retinoids and particularly
one of the major causes of treatment dropouts.
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Retinsphere® technology is a new retinoid generation based on the combination of two retinoids, retinol encapsulated in glycospheres and hydroxypinacolone retinoate in a base enriched with natural humectant factors.
Retinsphere® acts on the same receptor as retinoic acid and maintains efficacy but without adverse events like
irritation or dermatitis.
This new combination has been demonstrated to be effective in the treatment of non-inflammatory acne and
shown to be effective in reducing acne relapses or maintaining the results obtained by acne patients after treatment with oral isotretinoin.
Acne radar and evaluation of a new topical product for the treatment
of mild-moderate acne
Giuseppe Monfrecola, Gabriella Fabbrocini, Sara Cacciapuoti, Marianna Donnarumma,
Claudio Marasca
Dipartimento di Medicina Clinica e Chirurgia, Sezione di Dermatologia, Università di Napoli Federico II, Naples
Introduction. The purpose of the study has been to evaluate in Acne patients the effectiveness of a
topical product that consisting of micronized silver, Lauric Acid and Zinc acetate through an objective assessment (Global Acne Grading Score and Sebutape) and a subjective one with the help of a new tool that allows
the evaluation of psychological component in acne patient: the Acne Radar. We have applied an intuitive
graph representation, the “Radar graph” associated to a self completed questionnaire, allowing a quick assessment of the impact of acne on patients, based on 10 items classified according to 3 different area: sobjective
symptoms (negative perception of their image, insomnia, heartburn), subjective symptoms (depression, perception of pain, sadness), relationship difficulties (social relationships, work and intimate).
Materials and Methods. Our sample consisted of 20 patients aged between 16 and 28 years old with
mild and moderate acne: 4 men and 16 women. The evaluations were performed at baseline (T0) and after 60
days (T1). The methods were as follows: evaluation of acne severity classification by GAGS (Global Acne
Grading system); photographic assessment with digital images using the Reveal photo imaging system; evaluation of sebum production by Sebutape, a special adhesive film sebosensibile that allows an accurate assessment of the degree of activity of pilosebaceous follicles, sebaceous uniformity and distribution on the surface of the skin; Acne radar.
Results. All patients completed the study. The average value for the GAGS at T0 was 21.8 decreasing to 12.2 at time T1 with a reduction of 45%. The measurement obtained by Sebutape showed a value of
6.9 at T0, while at T1 it decreases to 2.6 (62% percentage reduction). The Acne Radar has revealed the following data:
a) Objective symptoms: the average score given by patients compared to the imperfections was 8 at T0 and
4 at T1 (Δ 4), the burning sensation was 7 at T0, while it decreases to 2.5 at T1 (Δ 4.5) and insomnia from
5 at T0, while we registered a value of 2 at T1 (Δ3).
b) Relationship problems: the impairment of social relations at T0 is about 8.2 and 4.3 at T1 (Δ3.9), for labor
relations 5.5 to 2 (Δ3.5), intimate relationships 6.8 to 2 (Δ4.8) .
c) Subjective symptoms: impaired serenity of patient 6 (T0) to 2.5 (T1) (Δ4.5), shame 8 (T0) 2 (T1) (Δ6),
depression 5 (T1) 2 (T2) (Δ3) and disease by 5 (T1) to 2 (T2) (Δ3). with an average reduction of 40%.
Acne radar has revealed an overall reduction in average 6:45 to 2.53, with Δ average of 3.92 and a reduction
of 60.8%
Discussion. The micronized silver leads to the formation of "pits" that damage the bacterial cell wall,
inducing lysis. Zinc acetate inhibits the action of 5-alpha reductase type 1, having antiandrogenic action and
sebostatic. It also has anti-inflammatory and protective effects against the development of bacterial resistance to P. acnes. Lauric acid, a fatty acid of vegetable origin, has an important bactericidal action directed
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towards P. acnes showing a MIC 15 times lower than that of BPO. The combined use of these three products
could allow to increase the therapeutic effect and reduce the side effects of the individual therapies. The
impact on patient's psychological sphere was evaluated by acne radar, a new tool for monitoring the patient's
emotional state. It revealed an overall reduction in average 6.45 to 2.53, with Δ average of 3.92 and a reduction of 60.8%, correlating positively with the reduction of GAGS and Sebutape score. Acne radar reveals that
the parameters that showed a significant improvement are those that relate to the subjective sphere: the shame
and impairment of serenity. This data is very significant as the subjective sphere since it plays a key role in
the psychological well-being of the patient. In compiling Acne Radar a significant reduction in the parameter of imperfections has been noticed suggesting patient satisfaction at the end of treatment.
Presidi dermocosmetologici riparativi nella gestione del paziente acneico
Corinna Rigoni
Milano, Italy
La verità è nuda; ma sotto la pelle giace l'anatomia (Paul Valéry)
La gestione della salute e del benessere della pelle, specie in una patologia come l’acne, è attualmente legata
all’esigenza che ogni persona manifesta nel voler apparire sana. La bellezza e la cura del proprio corpo ormai
rispondono sempre di più al concetto generale di benessere. Una buona informazione scientifica, correggendo
convinzioni sbagliate o sfatando miti assai radicati, quali ad esempio il rapporto tra malattia ed igiene personale, possono già dissolvere in parte l’ansia del paziente acneico e fidelizzare un rapporto che per forza di cose
sappiamo protrarsi più a lungo di altri pazienti. Infatti l’acne ha bisogno di cure continuative e di un “supporto
ed un sostegno specialistico” importante. Il successo del trattamento dell’acne, oltre a dipendere da una diagnosi corretta o da una terapia efficace da parte del dermatologo, deve basarsi anche su regole dermocosmetiche pre-
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cise che contribuiscono non solo a ridurre i sintomi, ma anche ad accettare le prescrizioni mediche spesso legate ad effetti collaterali evidenti, e a prevenire i danni estetici. È necessario che esista una buona conoscenza da
parte del dermatologo anche dei prodotti utilizzati, con rigorosa selezione degli elementi incorporati nelle formule, delle sostanze potenzialmente allergizzanti. Ciò costituirà una completezza di risposta al fabbisogno del
paziente, mantenendo un aggiornamento olistico alla richiesta della “Medicina cosiddetta moderna”.
SESSIONE
Acne e idrosadenite
Idrosadenite suppurativa: come e perché
Vincenzo Bettoli, Stefania Zauli, Michela Ricci, Annarosa Virgili
Dipartimento di Scienze mediche, Università di Ferrara, Ferrara
L’Idrosadenite Suppurativa-Acne Inversa è una patologia infiammatoria cronica-recidivante che si
localizza prevalentemente alle grandi pieghe. Clinicamente si manifesta tipicamente con noduli, ascessi, placche indurate e fistole. Le lesioni infiammatorie esitano in cicatrici fibrose a volte retraenti. La diagnosi si basa
sulle aspetto clinico e sul carattere recidivante delle lesioni. Il sovrappeso e il fumo ne favoriscono l’insorgenza e sembrano legati ad una patologia più severa. Il ruolo degli ormoni rimane controverso mentre è stata
dimostrata una predisposizione familiare secondaria a mutazioni nei geni della gamma-secretasi. Si tratta di
una patologia rara, con una prevalenza stimata tra 0,053% e 4% e una netta predominanza del sesso femminile. L’Idrosadenite Suppurativa-Acne Inversa tipicamente esordisce tra la II e la III decade di vita. In letteratura pochi casi con insorgenza in età pediatrica sono stati descritti. Riportiamo il caso di una bambina di 9
anni in cui abbiamo diagnosticato un’Idrosadenite Suppurativa-Acne Inversa a livello inguino-crurale e intergluteo. Riportiamo inoltre la nostra esperienza per quando riguarda l’insorgenza di tale patologia in età pediatrica discutendo le problematiche correlate a questo esordio precoce.
Hidradenitis Suppurativa and TNA-alpha inhibitors:
our (up till now limited) experience in Naples
Valerio De Vita, Marianna Donnarumma, Gabriella Fabbrocini
Dipartimento di Medicina Clinica e Chirurgia, Sezione di Dermatologia, Università di Napoli Federico II, Naples
Hidradenitis Suppurativa (HS) is painful a chronic inflammatory follicular disease which causes a
great impact in the quality of life. HS affects flexural areas with a high density of apocrine glands, such as
axillas, groin, buttocks, inframammary region, and perianal region. Knowledge of the pathogenesis of HS is
fragmented, and treatment choices have up till now been empiric without an exact understanding of the scientific rationale for their use. Anyway, HS has shown a poor response to traditional treatments, such as antibiotics, retinoids, and surgical approaches. Recent studies have revealed elevated levels of TNF-alpha in patients
with HS1. Consequently, TNA-alpha inhibitors have been proposed for the treatment of HS2-3. The treatment
of HS with TNF-alpha inhibitors also illustrates a clear relationship between clinical treatment success and
pathophysiologic mechanisms of disease. The earliest and most complete data on treatment of HS with antiTNF-alpha agents are with infliximab. A PubMed search of articles indexed for MEDLINE using the search
terms infliximab and hidradenitis suppurativa yielded more than 80 results as of July 2014. We report the case
of a 55-years-old, non-smoking man with severe HS diagnosed at the age of 48 and that had worsened over
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Pre
Post
the previous 4 years. He presented abscesses subcutaneous and suprafascial abscesses, cysts, painful erythematous papules and plaques, open ulcerations, chronic sinuses and fistulas in perianal region.
He had received several treatments for HS: daily antiseptic washes, topical clindamycin and fusidic acid, a 2month course of daily clindamycin 300 mg plus rifampicin 600 mg, oral retinoids for 6 months, orale dapsone for other 6 months. He had previously undergone surgical drainage of abscesses. The response to all these
treatments had been poor. The patients was also affected by psoriasis, so he began treatment with infliximab
in April 2014. He has received infusions of infliximab (5 mg/kg) in weeks 0, 2, 6, 10, and 14. Results were
evaluated using the Sartorius severity score, a physician and patient overall assessment, and the Skindex-29
quality-of-life index. At week 6, a substantive improvement was observed. He continued the treatment with
infliximab and the clinical course of the HS was favourable. No adverse events have occurred. TNF-alpha
inhibitors could be a potential and effective therapeutic option for patients with severe HS. According to literature, complete and persistent clinical responses are rarely obtained and partial responses are achieved in
approximately 50% of patients. Further studies are needed to identify specific markers for a therapeutic
response to anti-TNF-alpha agents and to best define dosage schedules associated with higher response rates.
References
1. van der Zee HH, de Ruiter L, van den Broecke DG, Dik WA, Laman JD, Prens EP. Elevated levels of tumour necrosis factor
(TNF)-α, interleukin (IL)-1β and IL-10 in hidradenitis suppurativa skin: a rationale for targeting TNF-α and IL-1β. Br J Dermatol
2011; 164:1292-8.
2. Grant A, González T, Montgomery MO, Cárdenas V, Kerdel FA. Infliximab therapy for patients with moderate to severe hidradenitis
suppurativa: a randomized, double-blind, placebo-controlled crossover trial. J Am Acad Dermatol 2010; 62:205-17.
3. Miller I, Lynggaard CD, Lophaven S, Zachariae C, Dufour DN, Jemec GB. A double-blind placebo-controlled randomized trial of adalimumab in the treatment of hidradenitis suppurativa. Br J Dermatol 2011; 165:391-8.
Acne ed inosotolo: quali novità
Silvia Savastano e Gabriella Fabbrocini*
Dipartimento di Medicina Clinica e Chirurgia, Unità di Endocrinologia e *Unità di Dermatologia, Università Federico II, Napoli
Sempre maggiori evidenze cliniche indicano il coinvolgimento dell’insulino-resistenza nella patoge-
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Volume 5, n. 2, 2014
nesi dell’acne, sia nel sesso femminile che nel sesso maschile. L’iperinsulinemia, conseguenza dell’insulinoresistenza che si riscontra a livello del recettore insulinico, agisce sull’ovaio in modo sinergico con l’LH determinando, in tal modo, un aumento della produzione di androgeni da parte della teca ovarica. Inoltre, l’insulina induce la riduzione dei livelli di SHBG, con incremento della biodisponibilità della frazione libera del
testosterone. Infine, l’iperinsulinemia interagisce con il signaling di IGF-1, il mediatore anabolico dell’ormone somatotropo che è coinvolto con meccanismi autocrini e paracrini nella lipogenesi a livello delle ghiandole sebacee e nella proliferazione dei cheratinociti e dei sebociti. In particolare, l’iperinsulinemia aumenta l’espressione epatica di IGF-1, interagisce con i suoi recettori, inclusi quelli espressi dai cheratinociti e dalle
ghiandole sebacee, ed aumenta la sua biodisponibilità per riduzione dei livelli circolanti di IGFBP-1, una delle
principali proteine veicolanti l’IGF-1 che ne regola sia l’emivita che l’interazione con il recettore.
Su questa base, negli ultimi anni gli agenti insulino-sensibilizzanti sono stati impiegati come coadiuvanti nel
trattamento dell’acne. In particolare, studi clinici e sperimentali evidenziano importanti effetti dell’inositolo
nella trasmissione del segnale insulinico e che la deficienza di inositolo possa essere coinvolta nella patogenesi dell’acne. L’inositolo è un polialcol presente in discreta quantità nei semi di carruba e nella frutta in genere, ma che viene anche sintetizzato nell’organismo a partire dal glucosio. L’inositolo è presente in due forme
isomeriche, il myo-inositolo e il D-chiro-inositolo. Il myo-inositolo è la forma più abbondante nell’uomo; la
sua epimerizzazione, una tappa enzimatica insulino-dipendente, induce la formazione del D-chiro-inositolo.
Sebbene entrambi agiscano come mediatori dell’insulina come inositol-fosfoglicani, in realtà è il D-chiro-inositolo il secondo messaggero della risposta insulinica, che interviene nella sintesi del glicogeno negli organi
che sono deputati al suo deposito, come fegato, muscolo e tessuto adiposo. Riduzioni dei livelli di D-chiroinositolo, per ridotta conversione a partire dal myo-inositolo (per deficit dell’epimerasi) e/o ad un aumentato
catabolismo del myo-inositolo, sono stati riscontrati in condizioni di insulino-resistenza, come in pazienti con
diabete mellito di tipo 2 e nella sindrome dell’ovaio policistico (PCOS), configurando un’alterazione del
metabolismo degli inositoli denominata “inositol imbalance”. A partite dal 1998 quando la Insmed
Pharmaceuticals Company brevettò il D-chiro-inositolo nel trattamento della PCOS, gli effetti positivi della
somministrazione di inositolo sull’insulino-resistenza e sui segni clinici dell’iperandrogenismo, incluso l’acne, sono stati ampiamente riportati nella pazienti con PCOS. Tuttavia sono ancora stati poco valutati gli effetti dell’inositolo sul signaling di IGF-1 ed il suo potenziale uso nell’acne maschile.
PDT dell’acne e idrosadenite suppurativa
Maria Teresa Rossi, Piergiacomo Calzavara-Pinton
Clinica Dermatologica, Università di Brescia
La terapia fotodinamica con MAL/PDT è registrata in Europa e negli Stati Uniti per il trattamento
del basalioma, malattia di Bowen e cheratosi attinica. Sulla base della dimostrazione di un ampio spettro di
attività sulle vie infiammatorie e immunologiche di tutte popolazioni cellulari presenti nella cute e di effetti
su varie specie di microorganismi patogeni o saprofiti, il suo uso è stato anche investigato nel trattamento di
numerose patologie tumorali, infettive e infiammatorie della cute con risultati variabili e in genere sostenuti
da studi con un disegno sperimentale alquanto debole. L’uso off label della PDT è sostenuto da solide evidenze solo nel caso di poche patologie, e tra queste l’acne volgare. I risultati clinici, in termini di efficacia, tollerabilità e eventi avversi sono del tutto incoraggianti e meritevoli di studi registrativi in quanto l’uso della PDT
si dimostra particolarmente utile nel trattamento dei pazienti con malattia resistente alle terapie standard o che
presentano controindicazioni o effetti collaterali al loro uso. L’uso della PDT nella idrosadenite suppurativa
è stato riportato da studi non controllati su casi anedottici o piccole casistiche e i risultati sono contrastanti. Il
suo uso appare pertanto giustificato solo in caso di inefficacia delle altre terapie.
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Volume 5, n. 2, 2014
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