Dagmar Wilsmann-Theis

IL-36γ (IL-1F9) Is a Biomarker for Psoriasis Skin Lesions

In recent years, different genes and proteins have been highlighted as potential biomarkers for psoriasis, one of the most common inflammatory skin diseases worldwide. However, most of these markers are not only psoriasis-specific but also found in other inflammatory disorders. We performed an unsupervised cluster analysis of gene expression profiles in 150 psoriasis patients and other inflammatory skin diseases (atopic dermatitis, lichen planus, contact eczema, and healthy controls). We identified a cluster of IL-17/tumor necrosis factor-α (TNFα)-associated genes specifically expressed in psoriasis, among which IL-36γ was the most outstanding marker. In subsequent immunohistological analyses, IL-36γ was confirmed to be expressed in psoriasis lesions only. IL-36γ peripheral blood serum levels were found to be closely associated with disease activity, and they decreased after anti-TNFα-treatment. Furthermore, IL-36γ immunohistochemistry was found to be a helpful marker in the histological differential diagnosis between psoriasis and eczema in diagnostically challenging cases. These features highlight IL-36γ as a valuable biomarker in psoriasis patients, both for diagnostic purposes and measurement of disease activity during the clinical course. Furthermore, IL-36γ might also provide a future drug target, because of its potential amplifier role in TNFα- and IL-17 pathways in psoriatic skin inflammation.

Mutations in IL36RN in patients with generalized pustular psoriasis.

ing of activated EGFR is AP-2 dependent and occurs through preformed clathrin spots. J Cell Sci 122:1301–5 Stevens H P, Kelsell D P, Leigh I M et al. (1996) Punctate palmoplantar keratoderma and malignancy in a four-generation family. Br J Dermatol 134:720–6 Zhang XJ, Li M, Gao TW et al. (2004) Identification of a locus for punctate palmoplantar keratodermas at chromosome 8q24.13-8q24.21 J Invest Dermatol 122:1121–5

New reasons for histopathological nail-clipping examination in the diagnosis of onychomycosis

Background  Onychomycosis is a common problem. Today, the gold standard in the diagnosis of onychomycosis is the direct microscopy and fungal culture. But direct microscopy is regarded as having a low sensitivity and fungal culture takes long time. In addition, in cases of controlling the antifungal treatment course, the present gold standard is often not a reliable tool because of the inhibition of the fungal growth in the culture.

Palmoplantar Pustular Psoriasis Is Associated with Missense Variants in CARD14, but Not with Loss-of-Function Mutations in IL36RN in European Patients

Cite this article as: Rotraut Mössner, Yvonne Frambach, Dagmar WilsmannTheis, Sabine Löhr, Arnd Jacobi, Ansgar Weyergraf, Michael Müller, Sandra Philipp, Regina Renner, Heiko Traupe, Harald Burkhardt, Külli Kingo, Sulev Kõks, Steffen Uebe, Michael Sticherling, Heinrich Sticht, Vinzenz Oji, Ulrike Hüffmeier, Palmoplantar Pustular Psoriasis is Associated with Missense Variants in CARD14, but not with loSs-of-Function Mutations in IL36RN in European Patients, Journal of Investigative Dermatology accepted article preview 19 May 2015; doi: 10.1038/jid.2015.186.

Facing psoriasis and atopic dermatitis: are there more similarities or more differences?

Atopic dermatitis (AD) and psoriasis vulgaris (Pso) represent the most frequent chronic inflammatory skin diseases. It has been assumed for a long time that these diseases have a completely different background. Recent findings about the genetic, epidemiologic and pathophysiologic factors of both diseases have remarkably improved our knowledge about the complex mechanisms underlying AD and Pso. Beyond that, in view of these findings, the question arises, which similarities and differences between AD and Pso exist. In order to address this point, we provide an overview about the current knowledge in the field of AD and Pso.

Combination of adalimumab with traditional systemic antipsoriatic drugs – a report of 39 cases

Background: Monotherapy with TNF‐α inhibitors does not always produce a sufficient response in psoriasis patients. Combinations of TNF‐α antagonists such as adalimumab with systemic antipsoriatic therapies such as methotrexate are not approved for use in psoriasis, and the published data are scarce.

Pyoderma gangrenosum: another cutaneous side‐effect of sunitinib?

SIR, Pyoderma gangrenosum (PG) is a rare, noninfectious, reactive neutrophilic dermatosis which usually begins with pustules or bullae and rapidly evolves to painful ulcers with violaceous borders. Histopathology reveals only nonspecific changes. However, early PG can show a perivascular and intramural lymphocytic infiltration with a peripheral neutrophilic component and fibrinoid necrosis. The underlying pathogenic mechanisms remain unclear. Immune deregulation was proposed, including neutrophil dysfunction and overexpression of inflammatory cytokines such as interleukin (IL)-8 and IL-16, and 50–70% of cases are associated with systemic diseases such as ulcerative colitis or Crohn disease. PG does not belong to the typical drug-induced diseases. However, PG-like lesions have been reported in the context of treatment with haematopoietic growth factors such as granulocyte colonystimulating factor and granulocyte-macrophage colony-stimulating factor. Tyrosine kinase receptors and their ligands play an important role in tumour growth and angiogenesis. Tyrosine kinase inhibitors such as sunitinib, which blocks several tyrosine kinases, have recently proved effective in patients with cancer. Therapy is often complicated by cutaneous side-effects such as acral erythema, hair depigmenation and subungual splinter haemorrhages. We present a patient with a gastrointestinal stromal tumour (GIST), who repeatedly developed PG in association with sunitinib intake. A 76-year-old woman had a history of GIST diagnosed 6 years previously and had been treated with sunitinib in an open-label trial for 10 months. The oral dosage varied from 25 mg to 50 mg daily for 1 month followed by a break of 2 weeks. Additional therapy included antihypertensives and thyroid replacement therapy. The patient was referred to our outpatient clinic with a painful ulcer on her lower left leg, which had progressed constantly for the previous 2 months. She reported a local trauma to her lower leg which had preceded the ulceration. Closer inquiry revealed that 6 months earlier she had been affected by a similar ulcer on her left arm which also followed a minor injury. Before treatment with sunitinib was introduced, the patient had never developed any ulcer. On physical examination, there was a 10 · 10 cm ulcer with a green-necrotic base and an undermined violaceous border on her lower left leg (Fig. 1a) and a scar (approximately 5 cm in diameter) on the left arm. In addition, acral erythema was observed (Fig. 2). Histopathological examination of the ulcer margin showed a dermal mixed inflammatory cell infiltration. Direct immunofluorescence revealed complement C3 around small vessels in the dermis. Tests for rheumatoid factor, antinuclear antibodies and electro(a)

Successful treatment of acrodermatitis continua suppurativa with topical tacrolimus 0·1% ointment

Acrodermatitis continua suppurativa of Hallopeau (ACS) is a rare pustular variant of psoriasis in which numerous treatment modalities have been used without any consistent long‐term effect. We report for the first time two patients with ACS which was successfully treated with topical tacrolimus 0·1% ointment. Our observations raise hopes that this new treatment strategy for ACS may constitute a novel effective therapeutic option for this recalcitrant condition.

Photodynamic Therapy as an Alternative Treatment for Cutaneous Sarcoidosis

Sarcoidosis is a systemic granulomatous disease. In more than 90% of the cases, sarcoidosis affects the lung with bilateral hilar adenopathy, while skin involvement occurs in about 25% of the cases. Whereas sarcoidosis of the lung is often successfully treated with oral corticosteroids, therapy of cutaneous sarcoidosis is frequently frustrating because some of the lesions may be refractory to treatment or recur quickly after resolution. We report two cases of cutaneous sarcoidosis successfully treated with photodynamic therapy, which represents an effective alternative therapy with fewer side effects.

An intensified dosing schedule of subcutaneous methotrexate in patients with moderate to severe plaque-type psoriasis (METOP): a 52 week, multicentre, randomised, double-blind, placebo-controlled, phase 3 trial

BACKGROUND Methotrexate is one of the most commonly used systemic drugs for the treatment of moderate to severe psoriasis; however, high-quality evidence for its use is sparse and limited to use of oral dosing. We aimed to assess the effect of an intensified dosing schedule of subcutaneous methotrexate in patients with moderate to severe plaque-type psoriasis. METHODS We did this prospective, multicentre, randomised, double-blind, placebo-controlled, phase 3 trial (METOP) at 16 sites in Germany, France, the Netherlands, and the UK. Eligible patients were aged 18 years or older, had a diagnosis of chronic plaque psoriasis for at least 6 months before baseline, had currently moderate to severe disease, and were methotrexate treatment-naive. Participants were randomly assigned (3:1), via a computer-generated random number sequence integrated into an electronic data capture system, to receive either methotrexate at a starting dose of 17·5 mg/week or placebo for the first 16 weeks, followed by methotrexate treatment of all patients up to 52 weeks (methotrexate-methotrexate vs placebo-methotrexate groups). Dose escalation to 22·5 mg/week was allowed after 8 weeks of methotrexate treatment if patients had not achieved at least a 50% reduction in baseline Psoriasis Area and Severity Index score (PASI), with corresponding volume increases in placebo injections. Treatment was combined with folic acid 5 mg/week. Group allocation was concealed from participants and investigators from the time of randomisation until an interim database lock at week 16, and was open label from week 16 onwards, with no masking of participants or investigators. The primary efficacy endpoint was a 75% reduction in PASI score (PASI 75) from baseline to week 16. We did analysis by modified intention to treat, with non-responder imputation. This study is registered with EudraCT, number 2012-002716-10. FINDINGS Between Feb 22, 2013, and May 13, 2015, we randomly assigned 120 patients to receive methotrexate (n=91) or placebo (n=29). At week 16, a PASI 75 response was achieved in 37 (41%) patients in the methotrexate group compared with three (10%) patients in the placebo group (relative risk 3·93, 95% CI 1·31-11·81; p=0·0026). Subcutaneous methotrexate was generally well tolerated; no patients died or had serious infections, malignancies, or major adverse cardiovascular events. Serious adverse events were recorded in three (3%) patients who received methotrexate for the full 52 week treatment period. INTERPRETATION Our findings show a favourable 52 week risk-benefit profile of subcutaneous methotrexate in patients with psoriasis. The route of administration and the intensified dosing schedule should be considered when methotrexate is used in this patient group. FUNDING Medac.