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Dermatologica
Helvetica
Vismodegib und Basaliom Vismodegib et basocellulaire
Trametinib und Melanom Trametinib et mélanome
Keine Antwort auf Hydroxychloroquin Non-réponse à l’hydroxychloroquine
DIRA und generalisierte Pustulose DIRA et pustulose généralisée
Fokus Akne Focus acné
7 / 2012
Volume 24
Acne vulgaris
Überzeugend in der Wirkung:
ACNE CREME PLUS
Für die lokale Behandlung von LIPO SOL LOTION
Acne vulgaris. Durch die Kombination Milde, nicht schälende
von Benzoylperoxid mit Miconazol Reinigungslotion als sinnvolle
ist die ACNE CREME PLUS optimal Therapieergänzung.
wirksam und sehr gut verträglich. Wirkt talgauflösend und
antibakteriell.
ACNE CREME PLUS Widmer
Zusammensetzung: Benzoylis peroxidum 50 mg, Miconazoli nitras 20 mg. Indikation: Acne vulgaris. Kontraindikation: Bekannte
Überempfindlichkeit gegenüber einem Bestandteil des Produktes. Vorsichtsmassnahmen: Kontakt mit Augen und Schleimhäuten
vermeiden. Unerwünschte Wirkungen: Benzoylperoxid kann vor allem zu Beginn der Therapie Reizungen wie Brennen, Rötung der
Haut mit Abschuppung und Austrocknung hervorrufen. Tube zu 30 ml. Liste C. Kassenzulässig.
LIPO SOL LOTION Widmer
Zusammensetzung: Triclosan 2 mg. Indikationen: Reinigung und Desinfektion der Haut bei allen Formen von Akne und Seborrhoe.
Vorsichtsmassnahmen: Kontakt mit Augen und Schleimhäuten vermeiden. Flasche zu 150 ml. Liste D. Kassenzulässig.
Ausführliche Informationen entnehmen Sie bitte dem Arzneimittel-Kompendium der Schweiz.
Louis Widmer AG, CH-8952 Schlieren
LOUIS WIDMER AG, Rietbachstrasse 5, 8952 Schlieren-Zürich
www.louis-widmer.com
Sommaire
4 Journal Club
RUBRIKEN DER DERMATOLOGICA HELVETICA 10 Fokus – Focus
RUBRIQUES DE DERMATOLOGICA HELVETICA
14 SGDV - SSDV
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E-mail : derm.helv@bluewin.ch
Efficacy and Safety of Vismodegib in Advanced Methods: We tested the anti–basal-cell car-
Basal-Cell Carcinoma cinoma efficacy of vismodegib in a random-
ized, double-blind, placebo-controlled trial in
Sekulic A et al. patients with the basal-cell nevus syndrome
Mayo Clinic, Scottsdale, USA at three clinical centers from September 2009
through January 2011. The primary end point
New England Journal of Medicine 2012, was reduction in the incidence of new basal-cell
366:2171-79 carcinomas that were eligible for surgical resec-
tion (surgically eligible) with vismodegib versus
Background: Alterations in hedgehog signaling placebo after 3 months; secondary end points
are implicated in the pathogenesis of basal-cell included reduction in the size of existing basal-
carcinoma. Although most basal-cell carcino- cell carcinomas.
mas are treated surgically, no effective therapy Results: In 41 patients followed for a mean of
exists for locally advanced or metastatic basal- 8 months (range, 1 to 15) after enrollment, the
cell carcinoma. A phase 1 study of vismodegib per-patient rate of new surgically eligible basal-
(GDC-0449), a first-in-class, small-molecule cell carcinomas was lower with vismodegib than
inhibitor of the hedgehog pathway, showed with placebo (2 vs. 29 cases per group per year,
a 58% response rate among patients with ad- P
Behandlung von externen
Genitoanalwarzen
Schonende Behandlung
Tiefe Rezidivrate*
Stimuliert bei Bedarf das körper-
eigene Immunsystem der Haut
* Schöfer H et al. Randomized comparative trial on the sustained effi cacy of topical imiquimod 5% cream versus conventional ablative methods in external genital warts. Eur J Dermatol 2006; 16(6):642–648.
Aldara® 5% Creme (Imiquimod): Immunmodulator. Indikationen: Topische Behandlung des Erwachsenen. 1. Äusserliche spitze Kondylome der Genital- u. Perianalregion. 2. Multiple oberfl ächliche Basalzellkarzinome (Biopsie-
bestätigt; max. 2 cm Tumordurchmesser) am Rumpf (mit Ausschluss der Anal- und Genitalregion), an der Halsregion oder den Extremitäten (ohne Hand und Fuss), wenn chirurgische Entfernung nicht angezeigt und Nachkontrolle
gewährleistet ist. 3. Klinisch typische, nicht-hyperkeratotische, nicht-hypertrophische aktinische Keratosen im Gesicht und auf dem Kopf. Dosierung: Jeweils vor dem Zubettgehen auftragen. Äusserl. spitze Kondylome: 3x
wöchentlich dünn auftragen (max. 16 Wochen) und 6–10 Std. auf der Haut belassen. Oberfl. Basalzellkarzinom: Während 6 Wochen 5x wöchentlich und 8 Std. auf der Haut belassen. Aktinische Keratosen: Während 16 Wochen
3x wöchentlich und 8 Std. auf der Haut belassen. Kontraindikationen: Überempfi ndlichkeit auf Wirkstoff oder einen Hilfsstoff. Behandlung von Kindern und Jugendlichen. Vorsichtsmassnahmen: Offene Geschwüre, Wunden,
chirurgische Eingriffe: erst nach vollständiger Abheilung. Kein Okklusivverband, kein Kontakt mit Augen, Lippen und Nasenschleimhaut, keine Sonneneinwirkung auf die behandelte Haut. Verschlechterung entzündlicher
Hauterscheinungen möglich. Vorsicht bei Patienten mit Autoimmunerkrankungen oder Organtransplantaten. Heftige lokale Entzündungsreaktionen der Haut möglich. Vorsicht bei Vorhautbehandlung unbeschnittener Männer. Nicht
empfohlen bei inneren spitzen Kondylomen der Genitalregion. Während Schwangerschaft und Stillzeit: nur bei absoluter Notwendigkeit. Empfehlungen bzgl. Geschlechtsverkehr und Empfängnisverhütung bei spitzen Kondylomen
sowie weitere indikationsspezifi sche Warnhinweise und Vorsichtsmassnahmen: s. Kompendium. Interaktionen: Nicht untersucht. Interaktionen mit systemisch applizierten Wirkstoffen
sind nur in sehr geringem Masse zu erwarten. Vorsicht bei Patienten mit immunsupressiver Behandlung. Unerwünschte Wirkungen: Sehr häufi g: Reaktionen am Applikationsort (bis 40%).
Häufi g: Infektionen; Kopfschmerzen; Myalgie; Juckreiz, Schmerzen, Brennen am Applikationsort; Müdigkeit. (UW ≤ 1%: s. Kompendium). Packung: OP mit 12 Sachets zum Einmalgebrauch.
(A). Kassenzulässig. Ausführliche Informationen: Packungsbeilage, Arzneimittel-Kompendium oder MEDA Pharma GmbH, 8602 Wangen-Brüttisellen. Stand der Information: Mai 2009.
cline did inhibit MMP activity but did not directly inhibit Authors’ Conclusions: Compared with placebo, there
serine protease activity against a fluorogenic substrate was no significant difference in the rate of MACEs
specific for TLSPs. However, when doxycycline or other observed in patients receiving anti–IL-12/IL-23 anti-
MMP inhibitors were added to live keratinocytes during bodies or anti–TNF-α treatments. This study may have
the production of tryptic KLKs, this treatment indirectly been underpowered to identify a significant differ-
resulted in decreased TLSP activity. Furthermore, doxy- ence.
cycline under these conditions inhibited the generation
of the cathelicidin peptide LL-37 from its precursor pro-
tein hCAP18, a process dependent on KLK activity. These
results demonstrate that doxycycline can prevent cat- Interleukin 1 Receptor Antagonist Deficiency Present-
helicidin activation, and suggest a previously unknown ing as Infantile Pustulosis Mimicking Infantile Pustular
mechanism of action for doxycycline through inhibiting Psoriasis
generation of active cathelicidin peptides.
Minkis K et al.
Weill Medical College of Cornell University, New York,
USA
The Use of Anti-Interleukin-12/23 Agents and Major
Adverse Cardiovascular Events Archives of Dermatology 2012, 148(6):747-52
Bigby M Background: Deficiency of interleukin 1 receptor antag-
Beth Israel Deaconess Medical Center, Boston, USA onist (DIRA) is a recently described autoinflammatory
syndrome of skin and bone caused by recessive muta-
Archives of Dermatology 2012, 148(6):753-54 tions in the gene encoding the interleukin 1 receptor
antagonist. Few studies have been published about this
Question: Is the use of anti-interleukin (IL)-12 and IL-23 debilitating condition. Early identification is critical for
agents to treat chronic plaque psoriasis associated with targeted lifesaving intervention.
an increase in major adverse cardiovascular events? Observations: A male infant, born to nonconsanguine-
Objective: To evaluate a possible association between ous Puerto Rican parents, was referred for management
biologic therapies for CPP [chronic plaque psoriasis] and of a pustular eruption diagnosed as pustular psoriasis.
MACEs [major adverse cardiovascular events] via meta- At 2 months of age, the infant developed a pustular
analysis. eruption. After extensive evaluation, he was confirmed
Data Sources: Randomized controlled trials (RCTs) of to be homozygous for a 175-kb genomic deletion on
anti-IL-12/23 (ustekinumab and briakinumab) agents chromosome 2 that includes the IL1RN gene, commonly
and anti-tumor necrosis factor α (TNF-α) agents (adalim- found in Puerto Ricans. Therapy with anakinra was initi-
umab, etanercept, and infliximab) used in treating CPP ated, with rapid clearance of skin lesions and resolution
were reviewed using the Cochrane Central Register of of systemic inflammation.
Controlled Trials, ClinicalTrials.gov, and Ovid MEDLINE Conclusions: Recent identification of DIRA as a disease
from database inception to May 2011. The results of reg- entity, compounded by the limited number of reported
istered nonpublished completed studies were procured cases, makes early identification difficult. It is critical to
through abstract publications or poster presentations. consider this entity in the differential diagnosis of infan-
Study Selection: Randomized, placebo-controlled, dou- tile pustulosis. Targeted therapy with the recombinant
ble-blind, monotherapy studies (with safety outcome human interleukin 1 receptor antagonist anakinra can
data for MACE) of IL-12/23 antibodies and anti-TNF-α be lifesaving if initiated early. A high carrier frequency
agents in adults. Studies of psoriatic arthritis were ex- of the 175-kb DIRA-associated genomic deletion in the
cluded. Puerto Rican population strongly supports testing in-
Data Extraction: Two investigators independently fants presenting with unexplained pustulosis in patients
searched data while 6 investigators reviewed the ab- from this geographic region.
stracted data.
Results: A total of 22 RCTs comprising 10 183 patients
met the predefined inclusion criteria. The primary
outcome measure was MACE, a composite end point Gottron’s Papules Exhibit Dermal Accumulation of
of myocardial infarction, cerebrovascular accident, or CD44 Variant 7 (CD44v7) and Its Binding Partner Os-
cardiovascular death during the placebo-controlled teopontin: A Unique Molecular Signature
phase of treatment in patients receiving at least 1 dose
of study agent or placebo. Absolute risk differences Kim JS, Bashir MM, Werth VP
were used as an effect measure. There was no evidence New York University School of Medicine, New York, USA
of statistical heterogeneity across the studies using the
I2 statistic (I2=0), allowing for combination of trial re- Journal of Investigative Dermatology 2012, 132:1825–
J O U R N A L C LU B
sults using the Mantel-Haenszel fixed-effects method. 32
During the placebo-controlled phases of the anti–
IL-12/23 studies, 10 of 3179 patients receiving anti- The accumulated mucin in non-Gottron’s dermato-
IL-12/23 therapies experienced MACEs compared with myositis (DM) lesions is primarily chondroitin-4-sulfate
zero events in 1474 patients receiving placebo (Man- (C4S), which is immunomodulatory in vitro. Gottron’s
tel-Haenszel risk difference, 0.012 events/person-year; papules are a particularly resistant manifestation of
95% confidence interval [CI], −0.001 to 0.026; P=.12). In DM that often persist after other lesions have resolved
the anti-TNF-α trials, only 1 of 3858 patients receiving with therapy. We examined non-Gottron’s DM lesions
anti–TNF-α agents experienced a MACE compared with and Gottron’s papule skin biopsies for C4S, CD44 vari-
1 of 1812 patients receiving placebo (Mantel-Haenszel ant 7 (CD44v7), a chondroitin sulfate-binding isoform
risk difference, −0.0005 events/person-year; 95% CI, causally implicated in autoimmunity, and osteopontin
−0.010 to 0.009; P=.94). (OPN), a CD44v7 ligand implicated in chronic inflamma-
6 Dermatologica Helvetica - Volume 24(7) - Septembre 2012
tion. Gottron’s papule dermis contained more C4S and Conclusion: Monitoring hydroxychloroquine blood con-
CD44v7 than non-Gottron’s lesions. Normal skin showed centrations might improve the management of refrac-
less CD44v7 over joints relative to Gottron’s lesions. All tory CLE.
DM dermis had increased OPN compared with healthy Oral antimalarial agents, most commonly hydroxychlo-
skin. Mechanically stretching cultured fibroblasts for roquine sulfate, are considered the first-line systemic
6 hours induced CD44v7 mRNA and protein, whereas treatment for cutaneous lupus erythematosus (CLE).1
IFN-γ treatment induced OPN mRNA and protein. OPN The prescribed hydroxychloroquine sulfate dosage the-
alone did not induce CD44v7, but stretching dermal fi- oretically depends on the patient’s weight, with a maxi-
broblasts in the presence of OPN increased human acute mal daily dose of 6.0 to 6.5 mg/kg adjusted to the ideal
monocytic leukemia cell line (THP-1) monocyte binding, body weight (calculated in daily use as [body length in
which is blunted by anti-CD44v7 blocking antibody. centimeters − 100] − 10% for men and [body length in
C4S, CD44v7, and OPN are three molecules uniquely centimeters− 100] − 15% for women). 2 Nonetheless, the
present in Gottron’s papules that contribute to inflam- standard daily dosage in France is frequently 2 tablets
mation individually and in association with one another. of hydroxychloroquine sulfate (ie, 400 mg/d), regardless
We propose that stretch-induced CD44v7 over joints, in of the patient’s height and weight. The few studies that
concert with dysregulated OPN levels in the skin of DM have addressed the pharmacokinetic variables under-
patients, increases local inflammatory cell recruitment lying the management of hydroxychloroquine therapy
and contributes to the pathogenesis and resistance of in systemic diseases such as rheumatoid arthritis and
Gottron’s papules. systemic lupus erythematosus (SLE)3 – 5 reveal great
interindividual variability in blood hydroxychloroquine
concentrations and thus raise the question of a relation
between concentration and efficacy and of the utility
Low Blood Concentration of Hydroxychloroquine in of monitoring these concentrations. We have reported
Patients With Refractory Cutaneous Lupus Erythema- that a low blood hydroxychloroquine concentration is a
tosus – A French Multicenter Prospective Study marker of SLE activity and a predictor of lupus flares in
patients with this disease and suggested a target blood
Francès C et al. hydroxychloroquine level of 1000 ng/mL for them.5
Hôpital Tenon, Paris, France To our knowledge, no studies have thus far reported
blood hydroxychloroquine concentration data for pa-
Archives of Dermatology 2012, 148(4):479-84 tients with CLE. We therefore conducted a multicenter
prospective study to evaluate this indicator in a large
Objective: To study the relation between blood concen- series of patients with CLE and to assess the relation be-
tration of hydroxychloroquine and the clinical efficacy of tween the clinical efficacy of the agent and the agent’s
hydroxychloroquine sulfate in a series of patients with blood level.
cutaneous lupus erythematosus (CLE).
Design: Prospective multicenter study. A staff derma-
tologist blinded to blood hydroxychloroquine concen-
trations performed a standardized review of medical Sirolimus and Secondary Skin-cancer Prevention in
records and assessment of hydroxychloroquine efficacy Kidney Transplantation
in the following 3 categories: complete remission, par-
tial remission (clearing of >50% of skin lesions), or treat- Euvrard S et al.
ment failure. Whole-blood samples were collected for Edouard Herriot Hospital Group, Lyon, France.
measurement of blood hydroxychloroquine concentra-
tion. New England Journal of Medicine 2012, 366:2180-88
Setting: Fourteen French university hospitals.
Patients: Three hundred consecutive patients with sub- Background: Transplant recipients in whom cutaneous
acute or chronic CLE who had been treated with hy- squamous-cell carcinomas develop are at high risk for
droxychloroquine for at least 3 months. multiple subsequent skin cancers. Whether sirolimus is
Main Outcome Measures: The statistical significance useful in the prevention of secondary skin cancer has
of correlation between blood hydroxychloroquine not been assessed.
concentration and efficacy of hydroxychloroquine Methods: In this multicenter trial, we randomly assigned
and the statistical associations in univariate and mul- transplant recipients who were taking calcineurin in-
tivariate analyses of complete remission with several hibitors and had at least one cutaneous squamous-cell
variables. carcinoma either to receive sirolimus as a substitute
Results: The study included 300 patients with discoid lu- for calcineurin inhibitors (in 64 patients) or to maintain
pus erythematosus (n=160), subacute CLE (n=86), lupus their initial treatment (in 56). The primary end point was
erythematosus tumidus (n=52), chilblain lupus (n=26), survival free of squamous-cell carcinoma at 2 years. Sec-
and lupus panniculitis (n=16); 38 of these patients had 2 ondary end points included the time until the onset of
J O U R N A L C LU B
or more associated forms. Median blood hydroxychloro- new squamous-cell carcinomas, occurrence of other skin
quine concentration was significantly higher in patients tumors, graft function, and problems with sirolimus.
with complete remission (910 [range,
14 such events in the calcineurin-inhibitor group (aver-
age, 0.938 vs. 0.250). There were twice as many serious
adverse events in patients who had been converted to
sirolimus with rapid protocols as in those with progres-
sive protocols. In the sirolimus group, 23% of patients
discontinued the drug because of adverse events. Graft
function remained stable in the two study groups.
Conclusions: Switching from calcineurin inhibitors to si-
rolimus had an antitumoral effect among kidney-trans-
plant recipients with previous squamous-cell carcinoma.
These observations may have implications concerning
immunosuppressive treatment of patients with cutane-
ous squamous-cell carcinomas.
Improved Survival with MEK Inhibition in BRAF-mu-
tated Melanoma
Flaherty KT et al.
Massachusetts General Hospital Cancer Center, Boston,
USA
New England Journal of Medicine 2012, 367(2):107-14
Background: Activating mutations in serine-threonine
protein kinase B-RAF (BRAF) are found in 50% of patients
with advanced melanoma. Selective BRAF-inhibitor
therapy improves survival, as compared with chemo-
therapy, but responses are often short-lived. In previous
trials, MEK inhibition appeared to be promising in this
population. v
Methods: In this phase 3 open-label trial, we randomly
assigned 322 patients who had metastatic melanoma
with a V600E or V600K BRAF mutation to receive either
trametinib, an oral selective MEK inhibitor, or chemo-
therapy in a 2:1 ratio. Patients received trametinib (2
mg orally) once daily or intravenous dacarbazine (1000
mg per square meter of body-surface area) or paclitax-
el (175 mg per square meter) every 3 weeks. Patients in
the chemotherapy group who had disease progression
were permitted to cross over to receive trametinib. Pro-
gression-free survival was the primary end point, and
overall survival was a secondary end point.
Results: Median progression-free survival was 4.8 months
in the trametinib group and 1.5 months in the chemo-
therapy group (hazard ratio for disease progression or
death in the trametinib group, 0.45; 95% confidence in-
terval [CI], 0.33 to 0.63; P
LES APPARENCES SONT SOUVENT TROMPEUSES...
...LE DANGER EST À L‘AFFÛT!
• EPROUVÉ EN CAS DE
DERMATITE ATOPIQUE1, 2, *
• PLUS EFFICACE QUE
LE PIMÉCROLIMUS CRÈME 3
• PAS D’ATROPHIE CUTANÉE 4, 5
* Protopic® est indiqué pour le traitement d’exacerbations aiguës de la dermatite atopique modérée enduire 2 fois par jour les lésions cutanées d’une mince couche de pommade à 0.03%. Le traitement
à sévère en tant que traitement de seconde intention, au cas où le traitement conventionnel ne doit être limité aux seules lésions cutanées. Une utilisation continue à long terme devrait être
serait pas assez efficace ou si des effets secondaires devaient survenir. évitée. CI: Protopic® est contre-indiqué chez les patients ayant une hypersensibilité connue aux
macrolides en général, au tacrolimus ou à I’un des excipients de la pommade. Préc: La pommade
Références: 1. Rustin MH. The safety of tacrolimus ointment for the treatment of atopic dermatitis: Protopic® n’a pas été évaluée chez I’enfant de moins de 2 ans. Pendant toute la durée du traitement,
a review. Br J Dermatol, 2007; 157(5): 861-873. 2. Reitamo S et al. A 4-year follow-up study of atopic I’exposition excessive de la zone traitée aux rayons UV (UVA ou UVB), par exemple soleil et solarium,
dermatitis therapy with 0.1% tacrolimus ointment in children and adult patients. Br J Dermatol, doit être évitée. Des méthodes de protection solaire appropriées doivent être recommandées par
2008; 159(4): 942-951. 3. Paller AS et al. Tacrolimus ointment is more effective than pimecrolimus le médecin traitant. Des préparations émollientes peuvent être utilisées simultanément à Protopic®,
cream with a similar safety profile in the treatment of atopic dermatitis: results from 3 randomized, en respectant un délai de 2 heures entre les applications des deux produits sur la même zone.
comparative studies. J Am Acad Dermatol 2005; 52(5): 810-822. 4. Kyllönen H et al. Effects of 1-year Grossesse et allaitement: Protopic® ne doit pas être utilisé pendant la grossesse, sauf en cas de
intermittent treatment with topical tacrolimus monotherapy on skin collagen synthesis in patients raison impérieuse. Bien que l’absorption systémique de tacrolimus soit limitée après l’application
with atopic dermatitis. Br J Dermatol, 2004; 150(6): 1174-1181. 5. Reitamo S et al. Tacrolimus de pommade, l’allaitement est déconseillé pendant le traitement avec Protopic®. IA: Le tacrolimus
ointment does not affect collagen synthesis: results of a single-center randomized trial. J Invest n’étant pas métabolisé par la peau, il n’y a pas de risque d’interaction percutanée qui pourrait
Dermatol, 1998; 111(3): 396-398. affecter le métabolisme du tacrolimus. Utiliser avec prudence en cas d’administration simultanée
Information professionnelle abrégée de Protopic®: C: Protopic® pommade à 0.03% et Protopic® systémique d’inhibiteurs du CYP3A4. El: Irritations cutanées au site d’application: sensation de
APCHPRTIN0612f
pommade à 0.1% contiennent respectivement: tacrolimus 0.3 mg/g et 1 mg/g. I: Protopic® est brûlures (31,3%), prurit (20,4%), sensation de chaleur, érythème, douleur, irritation, éruptions,
indiqué pour le traitement d’exacerbations aiguës de la dermatite atopique modérée à sévère, folliculite, paresthésies et dysesthésies. Autres: infections à herpès virus, acné, intolérance à l’alcool.
pour le traitement de seconde intention au cas où le traitement conventionnel ne serait pas assez Prés: Pommade 0.1% 10 g, 30 g et 60 g, pommade 0.03% 10 g, 30 g et 60 g. Catégorie de remise B,
efficace ou s’il survenait des effets secondaires. Pos: Adultes: enduire 2 fois par jour les lésions admis aux caisses-maladie. Pour de plus amples informations, veuillez consulter le Compendium
cutanées d’une mince couche de pommade à 0.03% ou 0.1%. Enfants dès deux ans et adolescents: Suisse des Médicaments. Astellas Pharma SA, Grindelstrasse 6, 8304 Wallisellen.
An Expanded Multilocus Sequence Typing facial acne vulgaris. Evaluation included lesion
Scheme for Propionibacterium acnes: Investi- count, adverse effects and patient-reported
gation of "Pathogenic", "Commensal" and An- outcome. Monitoring of laboratory parameters
tibiotic Resistant Strains included differential blood counts, electrolytes,
urine analysis, and liver and kidney function
The Gram-positive bacterium Propionibacte- tests. Skin melanin density was measured by re-
rium acnes is a member of the normal human flectance spectrophotometry.
skin microbiota and is associated with various Results: The total number as well as the num-
infections and clinical conditions. There is ten- ber of inflammatory acne lesions declined in
tative evidence to suggest that certain lineag- all patients 56 days after the first injection of
es may be associated with disease and others afamelanotide. Life quality as measured by Der-
with health. We recently described a multilocus matology Life Quality Index likewise improved
sequence typing scheme (MLST) for P. acnes in all 3 patients 56 days after the first injection
based on seven housekeeping genes (http:// of afamelanotide. There were no adverse effects
pubmlst.org/pacnes). We now describe an ex- except mild and short-term fatigue in one pa-
panded eight gene version based on six house- tient. All patients experienced increased pig-
keeping genes and two ‘putative virulence’ mentation especially on the face. Clinically rel-
genes (eMLST) that provides improved high res- evant changes in laboratory parameters were
olution typing (91eSTs from 285 isolates), and not detected.
generates phylogenies congruent with those Conclusions: Afamelanotide appears to have
based on whole genome analysis. When com- anti-inflammatory effects in patients with mild-
pared with the nine gene MLST scheme devel- to-moderate acne vulgaris. Future trials are
oped at the University of Bath, UK, and utilised needed to confirm the anti-inflammatory action
by researchers at Aarhus University, Denmark, of this melanocortin analogue in patients with
the eMLST method offers greater resolution. acne vulgaris.
Using the scheme, we examined 208 isolates
from disparate clinical sources, and 77 isolates Journal of the European Academy of Derma-
from healthy skin. Acne was predominately as- tology 2012. Epub ahead of print.
sociated with type IA(1) clonal complexes CC1,
CC3 and CC4; with eST1 and eST3 lineages be-
ing highly represented. In contrast, type IA(2)
strains were recovered at a rate similar to type Comparative Analysis of Adverse Drug Reac-
IB and II organisms. Ophthalmic infections were tions to Tetracyclines: Results of a French Na-
predominately associated with type IA(1) and tional Survey and Review of the Literature
IA(2) strains, while type IB and II were more fre-
quently recovered from soft tissue and retrieved Summary Background: The question of quan-
medical devices. Strains with rRNA mutations titative and qualitative differences between
conferring resistance to antibiotics used in acne adverse drug reactions (ADRs) to tetracyclines
treatment were dominated by eST3, with some was raised many years ago, especially for mino-
evidence for intercontinental spread. In con- cycline and doxycycline.
FOCUS – Acne
trast, despite its high association with acne, only Objectives: To assess and compare ADRs related
a small number of resistant CC1 eSTs were iden- to tetracyclines according to sales figures in
tified. A number of eSTs were only recovered France through a national survey.
from healthy skin, particularly eSTs representing Methods: ADR data were collected from the
CC72 (type II) and CC77 (type III). Collectively our French Pharmacovigilance Database (FPD), mar-
data lends support to the view that pathogenic keting authorization holders (MAH) and the lit-
versus truly commensal lineages of P. acnes may erature. Sales analyses were based on MAH data
exist. This is likely to have important therapeutic provided annually to the French Drugs Agency.
and diagnostic implications. Results: Among the tetracyclines available in
France, doxycycline and minocycline are the
PLoS One. 2012, 7(7):e41480 most frequently used. However, their sales de-
creased between 1995 and 2007, more sharply
for minocycline than doxycycline. According to
the FPD, based on MAH data and published re-
Beneficial Effects of the Melanocortin Ana- ports, minocycline-associated ADRs were more
logue Nle(4) -d-Phe(7) -α-MSH in Acne Vulgaris serious and were reported more frequently
than for the other tetracyclines. Minocycline
Background: α-Melanocyte-stimulating hor- and doxycycline ADR patterns differed: gastro-
mone (α-MSH) is a melanocortin peptide that intestinal disorders (especially oesophageal le-
increases skin pigmentation during ultraviolet sions) predominated with doxycycline, while
light-mediated tanning. As α-MSH has been intracranial hypertension and hepatic disorders
shown to possess anti-inflammatory effects, we were primarily reported with minocycline. Au-
assessed the clinical potential of a superpotent toimmune disorders, drug reaction with eo-
α-MSH analogue, afamelanotide (Nle(4) -d- sinophilia and systemic symptoms (DRESS) and
Phe(7) -α-MSH), in patients with acne vulgaris, other hypersensitivity reactions were also more
the most common inflammatory skin disorder. frequent with minocycline. ADRs reported with
Methods: Afamelanotide (16 mg) was given in a lymecycline and metacycline were essentially
phase II open-label pilot study subcutaneously cutaneous and gastrointestinal disorders.
as a sustained-release resorbable implant for- Conclusions: In the absence of markedly better
mulation to 3 patients with mild-to-moderate efficacy against the various indications for tet-
10 Dermatologica Helvetica - Volume 24(7) - Septembre 2012INNOVATION
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• Begleitend bei starken Hautunreinheiten
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nach dermatologischen Aknebehandlungen
bei Spätakne
• Vorbeugung von Aknenarben2
Signifikante Erfolge in der Erhaltungstherapie
1
nach Isotretinoinbehandlung
T0 T59
Patientin direkt nach Isotretinoinbehandlung (T0). Anwendung: Täglich Triacneal (1X), Cleanance Reinigungsgel
(2X) über 57 Tage. GEA Skala 1. (3 auf 2).1
Fordern Sie weitere Informationen zur
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1 Internationale, multizentrische Anwenderstudie 2011 in 5 Ländern mit über 3000 Patienten (Schweiz 24 Patienten)
2 Phase III Klinische Studie Pierre Fabre, 2009racyclines, the minocycline benefit/risk ratio was clearly trol group. However, levels of IL-17 (P < 0.0001) after
lower than that of doxycycline, and possibly those of isotretinoin treatment were higher than those of the
lymecycline and metacycline. In light of these findings, control group, despite a significant decline after treat-
minocycline should no longer be considered first-line ment. Levels of IFN-γ (P < 0.0001) after isotretinoin treat-
therapy for inflammatory skin disorders, especially acne. ment were lower than those of the control group. Con-
clusions: This study shows that isotretinoin treatment
British Journal of Dermatology 2012, 166(6) :1333-41 significantly decreases TNF, IL-4, IL-17 and IFN-γ levels in
patients with acne. We failed to show that isotretinoin
redirects naive T helper (Th) differentiation preferential-
ly towards the Th2 cell lineage.
Early Chemabrasion for Acne Scars After Treatment
with Oral Isotretinoin British Journal of Dermatology 2012, 167(2):433-5
Background: Acne is an inflammatory disease of the pi-
losebaceous follicles. Oral isotretinoin is the treatment
of choice for severe acne. Exaggerated cicatrization re-
lated to oral isotretinoin was reported in the 1980s and Exogenous Inflammatory Acne due to Combined Ap-
1990s. Currently, dermabrasion for acne scar revision is plication of Cosmetic and Facial Rubbing
only recommended 6 to 12 months after the completion
of oral isotretinoin treatment. Exogenous acne refers to acneiform lesions due to ex-
Objective: To evaluate the evolution of healing from ternal factors such as cosmetic agents, exposure to vari-
manual chemabrasion of depressed scars resulting from ous oils, skin rubbing or friction or chloracne, now better
acne conducted within 1 to 3 months after oral isotretin- called metabolizing acquired dioxin-induced skin hama-
oin treatment. rtoma (MADISH). Here we report a new form of severe
Methods and material: This was an interventional, pro- inflammatory exogenous acne due to the association of
spective study involving 10 patients with depressed fa- two factors: facial friction with cosmetic agents.
cial scars. A medium-depth chemical peel was applied Observations: A 15-, 17- and 19-year-old female pre-
to the entire face. Manual sandpaper dermabrasion was sented at the department with severe inflammatory
performed to areas of scarring until the appearance of acne. In all cases, the face had been strongly rubbed in
bloody dew. A 6-month reepithelization follow-up was a compulsory manner in the previous weeks with cos-
conducted. metic agents. The disease has not responded to various
Results: All of the patients presented with normal cicatri- conventional acne treatments and was well controlled
zation, and neither hypertrophic scars nor keloids were by a combination of oral corticosteroids and low-dose
observed. Depressed acne scar revision was satisfac- isotretinoin.
tory. Conclusion: Because cosmetic face friction as a cosmetic
Conclusion: Our observations may contribute to the dis- care becomes more and more fashionable, dermatolo-
cussion of the negative influence of oral isotretinoin on gists should be aware of this severe clinical condition,
wound healing. Other studies are necessary to reevalu- which can occur in patients without a personal history
ate the current recommendation of a 6- to 12-month of acne.
waiting period after oral isotretinoin treatment before
performing dermabrasion or fractional ablative laser for Dermatology. 2012, 224(3):221-3
acne scar revision.
Dermatologic Surgery 2012. Epub ahead of print.
Immunohistological Pointers to a Possible Role for
Excessive Cathelicidin (LL-37) Expression by Apocrine
Sweat Glands in the Pathogenesis of Hidradenitis Sup-
Immunoregulatory Effects of Isotretinoin in Patients purativa/Acne Inversa
with Acne
Summary Background: The cause of follicular occlusion,
Background: In vitro studies have shown that retinoids a key early event in the pathogenesis of hidradenitis
influence T-cell differentiation. suppurativa (HS), also known as acne inversa, remains
Objectives: To study the effect of isotretinoin on T-cell unknown.
differentiation markers in patients with acne. Objectives: To identify changes, if any, in the antimicro-
Methods: A total of 37 patients with acne vulgaris (25 fe- bial peptide (AMP) and cytokine expression profile of HS
male, 12 male, age 19.6 ± 3.7 years) and 30 age- and sex- affected human skin.
matched healthy controls (19 female, 11 male, age 20.5 Methods: Quantitative immunohistomorphometry was
± 4.4 years) were included in the study. Screening for used to compare the in situ protein expression of se-
biochemical parameters in serum samples were done lected AMPs and cytokines in lesional HS skin from 18
just before initiation (pretreatment) and after 3 months patients with that in healthy skin (n=12). The lesional
of isotretinoin treatment (post-treatment) in the acne skin from patients with HS was histologically subclas-
group. sified based on the predominance of inflammation vs.
Results: Baseline levels of tumour necrosis factor scarring.
(TNF)-α (P < 0.0001), interleukin (IL)-4 (P < 0.0001), IL-17 Results: Compared with healthy controls, significantly
(P < 0.0001) and interferon (IFN)-γ (P=0.002) were sig- increased immunoreactivity for cathelicidin (LL-37) was
nificantly higher in the acne group compared with the noted in the apocrine sweat gland and distal outer root
Fo c u s
control group. TNF-α (P < 0.0001), IL-4 (P < 0.0001), IL- sheath (ORS) of the hair follicle (HF) epithelium in lesion-
17 (P < 0.0001) and IFN-γ (P < 0.0001) levels decreased al HS skin. Immunoreactivity for LL-37, psoriasin, human
after isotretinoin treatment. TNF-α and IL-4 values after β-defensin 3 (hBD3), α-melanocyte stimulating hormone
isotretinoin treatment were similar to those of the con- (α-MSH), macrophage migration inhibitory factor (MIF),
12 Dermatologica Helvetica - Volume 24(7) - Septembre 2012tumour necrosis factor (TNF)-α and interleukin (IL)-8 was
significantly increased in HS epidermis. LL-37 and TNF-α
immunoreactivity was also increased in the dermis of le-
sional HS skin. In contrast, lysozyme expression was de-
creased in the epidermis of lesional HS skin, while that of
TNF-α and IL-8 was decreased in the proximal ORS of HFs
in HS lesions. These differences were most pronounced
in HS with predominant inflammation.
Conclusions: Our observations raise the question as to
whether excessive secretion of AMPs by the skin, in par-
ticular by the apocrine sweat glands, distal HF epithe-
lium, and epidermis, may attract inflammation and thus
facilitate or promote HS development.
British Journal of Dermatology 2012, 167(5):1023-34
Ocular Adverse Effects of Systemic Treatment With
Isotretinoin
Objective: To examine whether isotretinoin therapy
could result in deleterious ocular effects, as previously
described in case report studies.
Design: Retrospective cohort study.
Setting: The study was conducted using the electronic
medical databases of a large health maintenance orga-
nization in Israel.
Patients: The study population consisted of 14 682 ado-
lescents and young adults who were new users of isot-
retinoin for acne and 2 age- and sex-matched compari-
son groups (isotretinoin-naive patients with acne and
acne-free patients).
Main Outcome Measures: Ocular adverse effects (AEs) or
purchases of ophthalmic medications within 1 year after
the first dispensed isotretinoin prescription.
Results: In total, 13.8% of the isotretinoin group experi-
enced ocular AEs vs 9.6% of the isotretinoin-naive group
and 7.1% of the acne-free group. During a 1-year fol-
low-up period, the isotretinoin group had significantly
higher risk for any ocular AEs (hazard ratio, 1.70; P < .001)
compared with the acne-free group. No such increased
risk was observed for the isotretinoin-naive group. The
isotretinoin group had higher relative risks for inflamma-
tory and structural AEs.
Conclusion: Isotretinoin use may be associated with
short-term ocular events, especially conjunctivitis, un-
derscoring the importance of educating patients and
caregivers about these potentially important AEs of the
therapy.
Archives of Dermatology 2012, 148(7):803-8
"a fully informed patient is a fully
frightened patient"
Shelley, Walter B. "Advanced Dermatologic
Diagnosis"
W.B. Saunders 1992
Fo c u s
Dermatologica Helvetica - Volume 24(7) - Septembre 2012 13Merci à la Dresse Christa Prins ! – Bienvenue au Prof. Wolf-Henning Boehncke !
Das "Interregnum" in Genf ist vorbei. Dr. Christa Auf diese Zeit geht auch einer seiner wichtigsten
Prins hat den Service de Dermatologie de l’Hôpital Beiträge zur Grundlagenforschung zurück, die Ent-
Universitaire de Genève vom 01.10.2009 bis zum wicklung einer spezifischen Anwendung der Intra-
14.04.2012 interimistisch geführt, und sich dabei vitalmikroskopie, welche es erlaubt, die Adhäsion
unser aller Respekt verdient. und Migration von Entzündungszellen durch das
SGDV – SSDV
In dieser Position ist kein Raum für Visionen und Endothel aufzuzeichnen. Während seiner späteren
Kreativität: Oberstes Ziel ist die Schadensbegren- Weiterbildung in Kiel und Ulm setzte er seine in der
zung. Und dieses Ziel hat Christa Prins unbeirrt Grundlagenforschung gewonnenen Kenntnisse
verfolgt und in allen Belangen erreicht. Sie hat dies konsequent in der translationellen Forschung um,
mit der ihr eigenen freundlichen Hartnäckigkeit in welcher die Psoriasis als Modellkrankheit eine
und mit der Kraft der Argumente erreicht – nota zentrale Rolle spielte. Nach seiner Habilitation 1995
bene ohne Gewaltanwendung: Chapeau et notre in Ulm wurde er 1996 zum Leiter der Abteilung All-
admiration, Christa! ergologie und Immunologie der Johann Wolfgang
Die Dermatologische Poliklinik des Service de Der- Goethe-Universität in Frankfurt am Main ernannt,
matologie am HUG läuft wie eh und je hervorra- und seit 2003 bekleidete er in der gleichen Funk-
gend, die Bettenstation blieb unangetastet und tion eine C3-Professur innerhalb des Zentrums für
in der Dermatohistopathologie gelang es immer- Dermatologie und Venerologie der J. W. Goethe-
hin, die Labors und Befundräume unverändert im Universität Frankfurt. Die letzten fünfzehn Jahre
topographischen Bereich der Dermatologischen seiner klinischen Tätigkeit und Forschung waren
Klinik zu behalten, während ein administrativer ganz auf die translationelle Forschung, d.h.die
Zusammenschluss mit der Pathologie leider unab- Übertragung der Erkenntnisse aus der Grundla-
wendbar war und als Tatsache akzeptiert werden genforschung in die Klinik, gewidmet. Neuere Ar-
musste. beiten befassten sich mit dem Th17-Untertyp der
So kann der Nachfolger von Herrn Prof. J. H. Saurat T-Helfer-Lymphozyten und mit den Zusammen-
den Betrieb in seiner ursprünglichen stattlichen hängen zwischen Psoriasis und dem metaboli-
Grösse und Ausstattung übernehmen und weiter- schen Syndrom, zwei sehr aktuellen Themen der
führen. Herr Prof. Wolf-Henning Boehncke stammt dermatologischen Entzündungsforschung, die wie
aus Karlsruhe (Baden-Württemberg) und hat nach gesagt an der Nahtstelle zwischen Grundlagenfor-
seinem Medizinstudium in Kiel ein Postdoc-Stu- schung und Klinik anzusiedeln sind.
dium in dermatologischer Grundlagenforschung Die Mitglieder und der Vorstand gratulieren Herrn
angeschlossen, welches ihn ans National Institute Prof. Boehncke ganz herzlich zu seiner Wahl zum
of Allergy and Infectious Diseases (NIAID), einem Ordinarius für Dermatologie an der Universität
der NIH-Institute in Bethesda / Maryland brachte. Genf und zum Chefarzt des Service de Dermato-
14 Dermatologica Helvetica - Volume 24(7) - Septembre 2012logie et Vénéréologie am HUG. Wir alle wünschen Maryland. C'est à cette époque que remonte éga-
ihm bei dieser neuen faszinierenden beruflichen lement l'une de ses principales contributions à la
Herausforderung viel Erfüllung und Glück. Wir hei- recherche fondamentale, le développement d'une
ssen Sie in Genf und in der Schweiz ganz herzlich application spécifique de la microscopie intravi-
willkommen und freuen uns auf eine gute und in- tale, qui lui permet de mettre en évidence l'adhé-
tensive Zusammenarbeit. sion et la migration de cellules inflammatoires via
l'endothélium. Pendant sa formation postgraduée
Un tout grand merci à vous, Dresse Christa Prins ! à Kiel et Ulm, il appliqua logiquement les connais-
Et bienvenue à vous, Prof. Dr W. H. Boehncke ! sances qu'il avait acquises dans sa recherche fon-
damentale dans la recherche translationnelle, où
le psoriasis joua un rôle crucial à titre de maladie
modèle. Après son habilitation en 1995 à Ulm, il
fut nommé en 1996 Chef du département d'aller-
A Genève, l’"interrègne" a pris fin. La Dresse Christa gologie et d'immunologie à l'Université Johann
Prins a assuré à titre intérimaire la direction du Ser- Wolfgang Goethe à Francfort sur le Main et, de-
vice de Dermatologie de l'Hôpital universitaire de puis 2003, il a assumé dans la même fonction une
Genève, du 1.10.2009 au 14.04.2012, et a gagné le chaire C3 au sein du Centre de Dermatologie et de
respect de nous tous. Vénérologie de l'université précitée à Francfort. Les
A ce poste, il n'y a pas de place pour les visions et la quinze dernières années de son activité clinique et
créativité: le but suprême consiste à limiter les dé- de recherche ont été entièrement consacrées à la
gâts. Et ce but, Christa Prins l'a poursuivi impertur- recherche translationnelle, autrement dit au trans-
bablement et l'a atteint sous tous ses aspects. Elle fert des découvertes issues de la recherche fonda-
l'a fait avec l'opiniâtreté empreinte de cordialité mentale au domaine clinique. Des travaux récents
qui lui est propre, tout en recourant à la force des ont porté sur le sous-type TH17 des lymphocytes
arguments – sans utiliser la force, il faut le relever: T-aide et sur le rapport entre le psoriasis et le syn-
chapeau et notre admiration, Christa! drome métabolique, deux thèmes très actuels de la
La Policlinique dermatologique du Service de Der- recherche sur l'inflammation dermatologique qui,
matologie des HUG fonctionne remarquablement comme mentionné, se situent à un point charnière
depuis toujours, la division hospitalière est demeu- entre la recherche fondamentale et le domaine cli-
rée intacte avec sa station de lits et en dermatohis- nique.
topathologie, il a été possible de maintenir sans Les membres et le comité félicitent très cordiale-
changement les laboratoires dans le secteur to- ment Monsieur le Prof. Boehncke pour sa nomina-
pographique de la clinique dermatologique alors tion en qualité de professeur ordinaire de Derma-
que, malheureusement, une fusion administrative tologie et Vénéréologie à l'Université de Genève
avec la pathologie s'est avérée inévitable et a dû et de médecin-chef du Service de Dermatologie
être acceptée comme un fait. et de Vénéréologie aux HUG. Nous lui souhaitons
Ainsi le successeur du Prof. J. H. Saurat pourra re- tous beaucoup de satisfaction et de bonheur dans
prendre et poursuivre l'exploitation dans sa taille ce nouveau défi professionnel fascinant. Nous vous
et sa forme initiales et imposantes. Le Prof. Wolf- souhaitons la très cordiale bienvenue à Genève et
Henning Boehncke vient de Karlsruhe (Bade-Wurt- en Suisse et nous nous réjouissons d'entamer avec
temberg) et, après ses études de médecine à Kiel, vous une bonne et intense collaboration.
il a achevé des études postdoctorales dans la re-
cherche fondamentale en dermatologie, ce qui l'a
amené au National Institute of Allergy and Infec- Un tout grand merci à vous, Dresse Christa Prins!
tious Diseases (NIAID), un institut NIH à Bethesda / Et bienvenue à vous, Prof. Dr W.H. Boehncke!
Ernennungen – Nomination
SGDV – SSDV
Es freut uns mitteilen zu können, dass Dr. med. An- C’est avec plaisir que nous annonçons que le Dr André
dré Skaria, Vevey und Dr. med. Severin Läuchli, Zü- Skaria, Vevey, et le Dr Severin Läuchli, Zurich, ont
rich als Mitglied in das Board der ESMS – European été nommés membres dans le Board de l’ESMS –
Society of Mohs Surgery – aufgenommen worden European Society of Mohs Surgery.
sind.
Dermatologica Helvetica - Volume 24(7) - Septembre 2012 15Sie können auch lesen
