Sandrine Benoit

Elevated serum levels of calcium-binding S100 proteins A8 and A9 reflect disease activity and abnormal differentiation of keratinocytes in psoriasis.

Background  The expression of calcium‐binding S100 molecules organized within the epidermal differentiation complex on chromosome 1q21 is disturbed in hyperproliferative skin diseases such as psoriasis.

Treatment of recalcitrant pustular psoriasis with infliximab: effective reduction of chemokine expression

Tumour necrosis factor (TNF)‐α is thought to play a major role in the pathophysiology of psoriasis. Good clinical responses of psoriasis to anti‐TNF‐α‐based therapies have recently been demonstrated. We studied the effect of infliximab, a monoclonal antibody against TNF‐α, on chemokine expression in pustular psoriasis. A 61‐year‐old man with a 2‐year history of severe pustular psoriasis of von Zumbusch type who did not respond to conventional therapies responded rapidly to treatment with infliximab. The clinical response was reflected by an immediate and effective reduction of the neutrophil‐attractant chemokines interleukin (IL)‐8 and growth‐related oncogene (Gro)‐α as well as of monocyte chemoattractant protein (MCP)‐1, as determined by mRNA in situ hybridization of lesional skin. No expression before or after treatment was seen for monokine induced by interferon (IFN)‐γ (MIG) and IFN‐inducible protein (IP)‐10. Thus, in pustular psoriasis the chemokine expression pattern is dominated by neutrophil‐attractant chemokines and MCP‐1 while, in contrast to plaque psoriasis, IFN‐γ‐inducible lymphocyte‐attractant chemokines such as IP‐10 and MIG are not abundant. We conclude that anti‐TNF‐α treatment with infliximab is an effective therapy in severe pustular psoriasis which is reflected by downregulation of disease‐promoting chemokines such as IL‐8, Gro‐α and MCP‐1.

Circumscribed palmar hypokeratosis: partial remission by photodynamic therapy

total scores 3Æ84 ± 1Æ76 vs. 4Æ49 ± 2Æ02 (Mann–Whitney test)]. All patients had been unsatisfactorily treated with H1-receptor antagonists, such as loratadine, fexofenadine, olopatadine or hydroxyzine, with or without corticosteroids. The numbers of previously used drugs were also not significantly different (2Æ90 ± 1Æ37 vs. 3Æ09 ± 1Æ92). These medications were ceased before the screening period in each patient. Two patients in group A had received montelukast 10 mg daily before the study, and they received the same dose of the agent throughout the study. As shown in Figure 1, urticarial activity scores in period 1 were significantly lower than those in the screening period in both groups, indicating the effect of dose increases in controlling the symptoms. In group A, urticarial activity scores improved further in period 2. On the other hand, in group B, urticarial activity scores of weal, itch and total in period 2 were higher than those in period 1 and weal and itch scores in period 2 were not significantly different from those in the screening period. It is known that urticarial activity is usually higher during the early stages in each patient and tends to remit with time. It is thus possible that spontaneous resolution of the disease may affect the study. However, the exacerbation after the decrease of cetirizine observed in group B indicates that the improvement observed in this study is due to dose increment rather than spontaneous resolution. In addition, our results indicate that the continuation of effective doses of cetirizine may lead to further improvement as shown in group A. Concerning adverse effects, two patients in group B complained of drowsiness in period 1, but their complaints disappeared after the decrease of dosage of cetirizine in period 2. Otherwise adverse effects were not observed throughout the study period in all subjects. Although the observation periods of 1–2 weeks could be short for evaluating this fluctuating disease and we could not deny the possible involvement of placebo effect in this study, our results indicate the clinical usefulness of a dose increase of cetirizine. In conclusion, our results support the clinical impressions that dose increases of antihistamines may lead to better control of urticarial activity in patients who have not responded well to initial doses of the same drug, and that the continuation of the effective dose leads to further improvement of the disease severity. For more robust evidence, a longer double-blinded study is indicated and other H1 antagonists should be studied in a similar fashion.

Diagnostics of autoimmune bullous diseases in German dermatology departments.

Background: No consistent data are available on the currently employed diagnostic tools for autoimmune bullous diseases in Germany. The aim of this survey was to describe currently performed diagnostic methods for bullous autoimmune diseases in German dermatology departments.

Kontrollierte schichtweise Abtragung anogenitaler Warzen mittels Argon-Plasma-Koagulation

Hintergrund: Bei ausgedehntem anogenitalen Warzenbefall werden nach den Leitlinien der Deutschen STD‐Gesellschaft als mögliche Behandlungsformen mit vergleichbaren Rezidivraten die Kryotherapie, exzidierende Verfahren, die Elektrodesikkation, CO2‐ und Nd:YAG‐Laserabtragung empfohlen. Bei diesen Verfahren besteht ein unterschiedlich hohes Risiko von Blutungen, Freisetzung potentiell infektionsfähiger Viruspartikel in die Raumluft, tiefer thermischer Destruktion, langer Wundheilungszeit und Vernarbung.

Allelic and copy-number variations of FcγRs affect granulocyte function and susceptibility for autoimmune blistering diseases.

Low-affinity Fcγ receptors (FcγR) bridge innate and adaptive immune responses. In many autoimmune diseases, these receptors act as key mediators of the pathogenic effects of autoantibodies. Genes encoding FcγR exhibit frequent variations in sequence and gene copy number that influence their functional properties. FcγR variations also affect the susceptibility to systemic autoimmunity, e.g. systemic lupus erythematosus and rheumatoid arthritis. This raises the question whether FcγR variations are also associated with organ-specific autoimmunity, particularly autoantibody-mediated diseases, such as subepidermal autoimmune blistering diseases (AIBD). A multitude of evidence suggests a pathogenic role of neutrophil granulocyte interaction with autoantibodies via FcγR. In a two-stage study, we analyzed whether the FcγR genotype affects neutrophil function and mRNA expression, and consequently, bullous pemphigoid (BP) disease risk. We compared this to findings in pemphigus vulgaris/foliaceus (PV/PF), two Fc-independent AIBDs. Our results indicate that both allele and copy number variation of FcγR genes affect FcγR mRNA expression and reactive oxygen species (ROS) release by granulocytes. Susceptibility of BP was associated with FcγR genotypes that led to a decreased ROS release by neutrophils, indicating an unexpected protective role for these cells. BP and PV/PF differed substantially regarding the FcγR genotype association patterns, pointing towards different disease etiologies.

Flagellate dermatitis caused by shiitake mushrooms.

Shiitake (Lentinus edodes) is the second most consumed mushroom in the world. It has long been known in Asian medicine for its anticarcinogenic, antihypertensive and serum cholesterol level reduction properties. Nevertheless, the consumption of raw or not well-cooked mushrooms may cause skin eruptions which usually occur 24 to 48 hours after ingestion and are characterized by linearly arranged pruritic erythematous papules and plaques. We present a 36-year-old patient that developed typical symptoms 24 hours after consumption of shiitake mushrooms and summarize therapeutic options and particularities of this disease.

Polymorphisms in the mitochondrially encoded ATP synthase 8 gene are associated with susceptibility to bullous pemphigoid in the German population

Polymorphisms in the mitochondrially encoded ATP synthase 8 gene are associated with susceptibility to bullous pemphigoid in the German population Misa Hirose, Paul Schilf, Sandrine Benoit, R€ udiger Eming, Regine Gl€ aser, Bernhard Homey, Manfred Kunz, Almut Nebel, Wiebke K. Peitsch, Claudia Pf€ ohler, Mikl os S ardy, Stefan Schreiber, Detlef Zillikens, Enno Schmidt*, and Saleh M. Ibrahim* and the German AIBD Genetic Study Group L€ ubeck Institute of Experimental Dermatology, University of L€ ubeck, L€ ubeck, Germany; Department of Dermatology, Venereology and Allergology, University Hospital W€ urzburg, W€ urzburg, Germany; Department of Dermatology, Venereology and Allergology, Phillip University of Marburg, Marburg, Germany; Department of Dermatology, Venereology and Allergology, Christian Albrecht University of Kiel, Kiel, Germany; Department of Dermatology, Venereology and Allergology, Heinrich Heine University D€ usseldorf, D€ usseldorf, Germany; Department of Dermatology, Venereology and Allergology, University of Leipzig, Leipzig, Germany; Institute of Clinical Molecular Biology, Kiel University, Kiel, Germany; Department of Dermatology, University Medical Center Mannheim, Heidelberg University, Mannheim, Germany; Department of Dermatology, Saarland University Medical School, Homburg/Saar, Germany; Department of Dermatology and Allergology, Ludwig Maximilian University, Munich, Germany; Department of Internal Medicine I, Christian Albrecht University of Kiel, Kiel, Germany; Popgen biobank, Kiel University, Kiel, Germany; Department of Dermatology, University of L€ ubeck, L€ ubeck, Germany; Comprehensive Center for Inflammation Medicine, University of L€ ubeck, L€ ubeck, Germany Correspondence: Saleh M. Ibrahim, L€ ubeck Institute of Experimental Dermatology, University of L€ ubeck, Ratzeburger Allee 160, L€ ubeck 23538, Germany, Tel.: +49-451-500-5250, Fax: +49-451-500-5162, e-mail: saleh.ibrahim@uksh.de *These authors contributed equally to the work and shared the last authorship. See Appendix for German AIBD genetic study group (alphabetical order).

Bullous pemphigoid with localized umbilical involvement.

© 2009 The Authors. doi: 10.2340/00015555-0644 Journal Compilation

Routine detection of serum antidesmocollin autoantibodies is only useful in patients with atypical pemphigus.

Autoantibodies against the 3 desmocollin (Dsc; Dsc1‐Dsc3) isoforms have been described in different pemphigus variants. Here, we developed state‐of‐the‐art detection systems for serum anti‐Dsc1, Dsc2 and Dsc1 IgG and IgA. These assays were applied in 5 different cohorts including pemphigus vulgaris (PV) patients with compatible direct immunofluorescence (IF) microscopy but no reactivity against desmogleins 1 and 3 (n = 24) and sera from patients with autoimmune blistering diseases with positive direct IF microscopy taken at the time of diagnosis (n = 749). We found that detection of anti‐Dsc serum reactivity is not helpful in the routine diagnosis of PV, pemphigus foliaceus and paraneoplastic pemphigus but may be valuable in pemphigus vegetans.