[Trichophyton equinum meets Chanel]. / Trichophyton equinum trifft auf Chanel.

The horse is the most common reservoir of Trichophyton (T.) equinum. However, this zoophilic dermatophyte only rarely causes infections in humans. The following case report describes such a case. In addition to epidemiology, treatment is described and the morphological and physiological characteristics of T. equinum are illustrated. Because of its formation of spiral hyphae and nodal organs, which has not been previously documented for this species, the isolated strain was deposited in the German Collection of Microorganisms and Cell Cultures (DSM No. 114196).

Rheumatoid neutrophilic dermatosis under treatment with the interleukin-6-receptor-antagonist sarilumab in a patient with seropositive rheumatoid arthritis.

Skin manifestations may arise as adverse events following the use of novel drugs. We report a case of a patient with seropositive rheumatoid arthritis who developed a rheumatoid neutrophilic dermatosis (RND) under treatment with the interleukin-6-receptor-antagonist sarilumab. The skin lesions developed 2-3 days after the first injection. RND presents with asymptomatic, symmetrical fixed urticarial-like papules, plaques, and nodules, localized typically on the extensor surfaces of the forearms and hands. After discontinuing the medication, the nodules in our patient disappeared within a month.

[DMARD treatment and skin cancer : Recognition, state of knowledge and prevention]. / DMARD-Therapie und Hautkrebs : Erkennen, Stand des Wissens und Prävention.

BACKGROUND AND OBJECTIVE: Epithelial tumors differ in cellular origin, risk factors, incidence, and treatment. This article discusses the extent to which the use of disease-modifying antirheumatic drugs (DMARD) is associated with an increased risk for the development of skin tumors and for which substances the risk may be increased. In addition, some practical dermatological recommendations for rheumatologists are presented. METHODS: The most frequent tumors of the skin are classified according to their cellular origin into malignant melanoma (MM) and so-called keratinocyte cancer (KC). The clinical presentation of these tumors differs and also the risk for the development of these epithelial skin tumors under DMARD treatment varies depending on the drug and tumor entity. As rheumatologists frequently see these patients for follow-up, it is essential to know the clinical findings as well as the corresponding risk factors of the specific tumor entities. RESULTS: A generally valid and reliable estimation of the risk for the development of epithelial skin tumors under DMARD treatment can only be formulated in the form of tendencies at the present time due to the lack of data. The relevant literature shows that regular intensive dermatological screening is recommended. CONCLUSION: Patients undergoing immunosuppressive or immune-modulating treatment should be instructed in self-inspection of the skin, receive regular dermatological check-ups and be instructed in strict UV protection methods. Lesions that do not heal or recurrently bleed should be referred for a punch biopsy to rule out or diagnose an epithelial skin tumor, as should atypical inflammatory lesions that do not heal with the use of topical glucocorticoids. An interdisciplinary approach in patient management is the key to success in ensuring the maximum quality of life with the lowest possible risk of developing epithelial skin tumors for these patients.

The influence of the commensal skin bacterium Staphylococcus epidermidis on the epidermal barrier and inflammation: Implications for atopic dermatitis.

The skin microbiota is a crucial component in maintaining cutaneous barrier function. Staphylococcus epidermidis is considered as a beneficial commensal member of the cutaneous microbiota promoting skin health. However, S. epidermidis is also frequently detectable in the skin of patients with the inflammatory skin disease atopic dermatitis (AD) and some studies reported a significantly higher presence of S. epidermidis in severe AD as compared to mild AD. Therefore, this study aimed to analyse the impact of S. epidermidis on the expression of cutaneous inflammatory mediators and skin barrier molecules. Various S. epidermidis skin-derived isolates activated the proinflammatory transcription factor NF-kappaB and induced expression of AD-associated proinflammatory cytokines in human primary keratinocytes and 3D skin equivalents. Skin barrier molecules such as filaggrin were downregulated by S. epidermidis. In general, AD-derived S. epidermidis strains elicited a higher response than strains derived from the skin of healthy individuals. Taken together, our results provide further evidence that the abundance of S. epidermidis in AD may trigger the inflammatory scenario associated with this disease.

Staphylococcus aureus Activates the Aryl Hydrocarbon Receptor in Human Keratinocytes.

Staphylococcus aureus is an important pathogen causing various infections, including - as most frequently isolated bacterium - cutaneous infections. Keratinocytes as the first barrier cells of the skin respond to S. aureus by the release of defense molecules such as cytokines and antimicrobial peptides. Although several pattern recognition receptors expressed in keratinocytes such as Toll-like and NOD-like receptors have been reported to detect the presence of S. aureus, the mechanisms underlying the interplay between S. aureus and keratinocytes are still emerging. Here, we report that S. aureus induced gene expression of CYP1A1 and CYP1B1, responsive genes of the aryl hydrocarbon receptor (AhR). AhR activation by S. aureus was further confirmed by AhR gene reporter assays. AhR activation was mediated by factor(s) <2 kDa secreted by S. aureus. Whole transcriptome analyses and real-time PCR analyses identified IL-24, IL-6, and IL-1beta as cytokines induced in an AhR-dependent manner in S. aureus-treated keratinocytes. AhR inhibition in a 3D organotypic skin equivalent confirmed the crucial role of the AhR in mediating the induction of IL-24, IL-6, and IL-1beta upon stimulation with living S. aureus. Taken together, we further highlight the important role of the AhR in cutaneous innate defense and identified the AhR as a novel receptor mediating the sensing of the important skin pathogen S. aureus in keratinocytes.

Effective and Safe Treatment of Psoriatic Disease with the Anti-IL-23p19 Biologic Tildrakizumab: Results of a Real-World Prospective Cohort Study in Nonselected Patients.

BACKGROUND: After registration of drugs, evidence about efficacy and safety is solely based on data of phase 2/3 clinical trial programs. A major drawback is the selection of patients following inclusion/exclusion criteria. There is a considerable time and knowledge gap between study and registry data that evaluate real-world evidence (RWE). To close this gap, prospective cohort data are helpful. OBJECTIVES: Soon after tildrakizumab, an interleukin 23p19-inhibitor, was registered for moderate-to-severe plaque psoriasis, a prospective single-center cohort study was established to evaluate efficacy and safety of tildrakizumab in daily practice. METHODS: Following approval of tildrakizumab, patients with moderate-to-severe plaque psoriasis eligible for systemic treatment were included into the Kiel Tildra Cohort (KTC) and followed using routine assessments of efficacy, psoriasis area and severity index (PASI), body surface area (BSA), dermatology life quality index (DLQI), itch (visual analog scale), and safety. Data of the KTC were compared to the respective phase 3 clinical trials. RESULTS: The KTC included 150 patients differing substantially from those in the trial program. There was a high rate of previous systemic (87.3%) and biologic (31.8%) therapy and of comorbidity in the KTC as compared to the phase 3 studies. Due to the best practice approach, baseline PASI was lower in the KTC, but DLQI was similar in both groups. At the time of this analysis, 126 patients completed week 28, 92 patients week 52, and 58 patients week 76, respectively. There was a constant improvement in PASI, BSA, DLQI, and itch from baseline until week 76. There was no clinically meaningful laboratory abnormality. CONCLUSIONS: Patients treated in routine practice with tildrakizumab differed substantially from the phase 3 studies. Despite systemic pre-treatment and increased comorbidity, tildrakizumab showed comparable efficacy and safety in the KTC. Prospective cohort studies are a suitable tool to generate RWE before registry data become available.

A new era has begun: Treatment of atopic dermatitis with biologics.

The era of biologics for the treatment of moderate-to-severe atopic dermatitis (AD) began in 2017 with the approval of dupilumab, a monoclonal antibody that binds to the α-subunit of the interleukin IL-4 receptor. Until then, only conventional immunosuppressants were available for systemic treatment, of which only cyclosporine is approved for the treatment of severe AD. In the meantime, the therapeutic landscape of AD has been changing rapidly, and additional biologics have been developed which target IL-13, the IL-31 receptor, OX40, and OX40L, among others. Many of these substances have already shown promising results in phase 1, 2, and in some cases also phase 3 trials. In June 2021, tralokinumab, an IL-13 antibody, has been approved in Europe for the treatment of moderate-to-severe AD in adults. In addition to antibody-based therapies, "small molecules" that, e.g., inhibit Janus kinases enrich the armamentarium of systemic AD therapies. With all these agents, not only will many more targeted therapies become available, but also will the complex and heterogeneous pathophysiological processes of this disease be better understood.