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We describe a man in his 60s presenting poor scar development following surgical treatment for popliteal aneurysm. The clinical features in a postoperative context and the poor clinical response to intravenous broad-spectrum antibiotics were highly suggestive of bullous pyoderma gangrenosum. Histology, with dense inflammatory infiltrate of neutrophils, subsequently confirmed the diagnosis and the response to systemic corticosteroids was rapid and complete. Further investigations revealed an underlying acute myeloid leukaemia, which is frequently associated with this type of neutrophilic dermatosis., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2025. No commercial re-use. See rights and permissions. Published by BMJ Group.)

Mucinous carcinoma of the skin is a rare, low-grade malignancy often clinically misdiagnosed as a benign lesion. This tumour mostly grows locally and has minimal potential for lymphatic or distant metastasis. Commonly affected sites include the periorbital region, particularly the eyelid, and the scalp. Surgical resection is the preferred treatment. However, recurrences are frequent when resection margins are less than 1 cm. Differential diagnosis with mucinous skin metastases can be challenging. We report a patient with an occipital scalp tumour initially considered benign and left untreated for 10 years. After an initial resection, the tumour recurred, requiring a second resection with adequate margins., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Competing Interests: None disclosed.

Granuloma annulare (GA) is a rare inflammatory granulomatous disorder and its subcutaneous forms are even more uncommon. Only a few familial cases of this condition have been reported in the literature. We report a case of familial subcutaneous GA in two siblings during childhood., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Kul et al.)

There is an increasing interest in the use of facial dermal filler injections, such as hyaluronic acid, for esthetic and rejuvenation purposes. However, their use is associated with a potential risk of complications. We report the case of a woman in her thirties, with rapidly evolving facial skin necrosis following accidental intravascular injection of hyaluronic acid and/or extravascular compression. The necrosis worsened despite early repeated local injections of hyaluronidase. However, rapid and favorable clinical evolution was observed after the patient was treated for seven consecutive days with intravenous infusion of dinoprostone (a prostaglandin E2)., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Gaudissart et al.)

Bullous pemphigoid (BP) is an acquired auto-immune blistering disease, which is uncommon during childhood. Infantile BP usually has a good prognosis with rare recurrence and the suspected triggers are vaccines or viruses. We report the case of a three-month-old infant girl who presented with BP a week after a SARS-CoV-2 infection and three weeks after the first doses of polio, tetanus, diphtheria, pertussis, Haemophilus influenzae type-b, hepatitis, and pneumococcus vaccinations. Both triggers (infection and vaccination) could be implicated as a slight recurrence was observed after the second doses of vaccines. Rapid clinical resolution was obtained with topical corticosteroids., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Moens et al.)

We report a case of congenital multisystem Langerhans cell histiocytosis with cutaneous and hematopoietic involvement. After the failure of first-line (vinblastine and prednisolone) and second-line (vincristine and cytarabine) therapies, treatment with cobimetinib, a mitogen-activated protein kinase (MEK) inhibitor, led to the remission of disease and a sustained response after 11 months of ongoing treatment. Protein kinase inhibitors targeting BRAF or MEK could represent a promising future therapeutic option, also in children with LCH., (© 2024 Wiley Periodicals LLC.)

Disseminated granuloma annulare (DGA) is an inflammatory skin disorder characterized by more than 10 erythematous, raised, ring-shaped plaques. Its treatment remains challenging, with conventional therapies showing variable efficacy. We report the case of a woman in her 50s with a 2-year history of DGA refractory to multiple treatments. Given the recent evidence of the role of the Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway in the granuloma annulare pathophysiology, treatment with upadacitinib 30 mg per day was started with rapid effectiveness and good tolerance. This case underscores the potential of JAK inhibitors as promising therapeutic options for recalcitrant granuloma annulare., (© 2024. The Author(s).)

Atopic dermatitis (AD) is one of the most common, bothersome and difficult to treat skin disorders. Recent introduction of new systemic treatments has revolutionized the management of AD. The goal of this guideline is to provide evidence-based recommendations for the management of patients suffering from atopic dermatitis that easily can be implemented in clinical practice. These recommendations were developed by 11 Belgian AD experts. Comments of all experts on the proposed statements were gathered, followed by an online voting session. The most relevant strategies for the management and treatment of AD in the context of the Belgian health care landscape are discussed. General measures, patient education and adequate topical treatment remain the cornerstones of AD management. For moderate to severe AD, the introduction of biologics and JAK inhibitors show unprecedented efficacy, although currently access is limited to a subgroup of patients meeting the reimbursement criteria.

Sterols exert a profound influence on numerous cellular processes, playing a crucial role in both health and disease. However, comprehending the effects of sterol dysfunction on cellular physiology is challenging. Consequently, numerous processes affected by impaired sterol biosynthesis still elude our complete understanding. In this study, we made use of yeast strains that produce cholesterol instead of ergosterol and investigated the cellular response mechanisms on the transcriptome as well as the lipid level. The exchange of ergosterol for cholesterol caused the downregulation of phosphatidylethanolamine and phosphatidylserine and upregulation of phosphatidylinositol and phosphatidylcholine biosynthesis. Additionally, a shift towards polyunsaturated fatty acids was observed. While the sphingolipid levels dropped, the total amounts of sterols and triacylglycerol increased, which resulted in 1.7-fold enlarged lipid droplets in cholesterol-producing yeast cells. In addition to internal storage, cholesterol and its precursors were excreted into the culture supernatant, most likely by the action of ABC transporters Snq2, Pdr12 and Pdr15. Overall, our results demonstrate that, similarly to mammalian cells, the production of non-native sterols and sterol precursors causes lipotoxicity in K. phaffii , mainly due to upregulated sterol biosynthesis, and they highlight the different survival and stress response mechanisms on multiple, integrative levels.

The Wsc1, Wsc2, and Wsc3 proteins are essential cell surface sensors that respond to cell wall perturbation by activating the cell wall integrity pathway (CWIP). We show here that in situ production of cholesterol (in place of ergosterol) induces hyper-phosphorylation of Slt2, the MAPK of the CWIP, and upregulates cell wall biosynthesis. Deletion of all three Wsc genes in K. phaffii reverts these phenotypes. In the cholesterol-producing strain, both Wsc1 and Wsc3 accumulate in the plasma membrane. Close inspection of the transmembrane domains of all three Wsc proteins predicted by AlphaFold2 revealed the presence of CRAC sterol-binding motifs. Experiments using a photoreactive cholesterol derivative indicate intimate interaction of this sterol with the Wsc transmembrane domain, and this apparent sterol binding was abrogated in Wsc mutants with substitutions in the CRAC motif. We also observed cholesterol interaction with CRAC-like motifs in the transmembrane domains of mammalian integrins, analogs of Wsc proteins. Our results suggest that proper signaling of the Wsc sensors requires highly specific binding of the native endogenous terminal sterol, ergosterol., Competing Interests: Conflict of interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Introduction: The efficacy of conventional treatments for alopecia areata (AA) has been extremely variable and disappointing, with a high rate of relapse. Recent clinical trials and real-life studies have demonstrated efficacy and safety of baricitinib (an oral Janus kinase 1 and 2 inhibitor) in alopecia areata., Methods: We retrospectively evaluated the effectiveness and tolerance of baricitinib in alopecia areata in a real-life Belgian monocentric adult cohort. The primary outcome was evaluated by the percentage of patients who achieved a Severity of Alopecia Tool (SALT) score of ≤ 20 at the end of the follow-up. All treatment-emergent adverse events were collected., Results: In this 19-patient series, with a median ± interquartile range (IQR) follow-up duration of 13 ± 16.2 months, we demonstrated that: (i) hair regrowth was observed in nearly 90% of patients between 4 and 16 weeks after initiation of baricitinib; (ii) at the end of the follow-up, more than 70% and, in particular, 100% of patients with patchy AA, reached the primary outcome (SALT score ≤ 20); (iii) almost half of the patients, mostly with patchy AA, showed a complete hair regrowth (SALT score = 0), within a median ± IQR treatment time of 8.5 ± 10 months; (iv) baricitinib was discontinued in three patients with total hair regrowth, two of whom relapsed; and (v) no serious adverse events were reported., Conclusion: Baricitinib is effective in treating patients with alopecia areata, particularly for the patchy phenotype, but with a risk of relapse after discontinuation. Safety data are reassuring, with lipid changes being the most frequent adverse event., (© 2023. The Author(s).)

Background: In 2008, numerous cases of allergic contact dermatitis caused by leather chairs (sofa dermatitis) were reported, with dimethylfumarate being the culprit allergen. However, octylisothiazolinone, methylisothiazolinone and cobalt have also been associated with cases of sofa dermatitis. An antifungal agent, 2-(thiocyanomethylthio)benzothiazole (TCMTB), has also previously been described as a contact allergen in leather., Materials and Methods: Seven patients were referred to the Department of Dermatology of the Cliniques universitaires Saint-Luc, Brussels, Belgium with suspicion of allergic contact dermatitis caused by leather sofas. They were patch tested with the European Baseline Series, additional series (according to the patients' history and clinical aspect of the eruption), dimethylfumarate (4/7 patients) and with TCMTB., Results: All seven patients presented a positive reaction to TCMTB and only one presented a concomitant positive reaction to dimethylfumarate. All patients showed clinical improvement after avoiding contact with their leather sofa., Conclusion: 2-(Thiocyanomethylthio)benzothiazole (TCMTB) is probably an underestimated allergen present in leather chairs (responsible for the so-called 'sofa dermatitis'), and more generally in leather objects. It is, therefore, important to test with TCMTB 0.1% petrolatum in case of contact dermatitis related with leather products., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Introduction: The efficacy and safety of upadacitinib in atopic dermatitis have been defined in clinical trials, but long-term real-life experience, essential for clinical decision-making, is still limited. We aimed to assess the effectiveness and tolerance of upadacitinib in a real-life cohort of adults and adolescents with severe atopic dermatitis in whom previous systemic therapies largely failed., Methods: Retrospective cohort study collecting data from adults and adolescents treated with upadacitinib 15 or 30 mg per day between July 2021 to August 2022. The outcomes for effectiveness were evaluated by the percentage of patients who achieved a validated Investigator's Global Assessment for atopic dermatitis (vIGA-AD) of 0 (clear) or 1 (almost clear) and/or an improvement of at least 75% on the Eczema Area and Severity Index (EASI 75) at the end of the follow-up. All treatment-emergent adverse events were collected., Results: A total of 29 patients were included (22 adults and 7 adolescents), with a median follow-up of 54.4 weeks. At the end of the follow-up, 23 patients (79.3%) reached a vIGA-AD of 0/1, and 24 patients (82.7%) achieved EASI 75. Among patients treated with upadacitinib after initial failure of first- and/or second-line treatment with biologics or baricitinib, 5/7 patients (71.4%) reached a vIGA-AD score of 0/1. Disease control was slightly better in adults than in adolescents (81.8% vs 71.4% reached the efficacy endpoint, respectively). Response rate in patients with upadacitinib 15 mg seemed better than in clinical trials or network meta-analysis. Safety data were reassuring; lipid changes were the most frequent adverse event., Conclusion: This real-life study confirms the effectiveness of upadacitinib, particularly for the treatment of atopic dermatitis recalcitrant to conventional systemic agents, biologics or baricitinib. Induced lipid changes require close follow-up., (© 2023. The Author(s).)

Background: Tralokinumab, the first fully human monoclonal antibody that binds specifically to interleukin-13, was safe and effective for treating atopic dermatitis (AD) in clinical trials, but real-life experience is still limited., Objectives: The objective of this study was to evaluate the effectiveness and safety of tralokinumab in severe AD in a real-life multicenter prospective cohort., Methods: Adult patients with severe AD were enrolled between January 2022 and July 2022 and received tralokinumab subcutaneously for 16 weeks. Objective and subjective scores were collected at baseline, weeks 6 and 16. Adverse events were reported throughout the study., Results: Twenty-one patients were included. An improvement of at least 75% on the Eczema Area and Severity Index (EASI 75) was achieved in 66.7% of patients at week 16. The median objective and subjective scores at week 16 were significantly (p < 0.001) lower than those at baseline. Combination with cyclosporine was sometimes necessary at the beginning of treatment, and addition of upadacitinib was required for some patients with very severe disease during the treatment. The most frequent adverse events were flares of eczema (23.8%) and reactions at injection site (19.0%). No cases of conjunctivitis were reported. Four patients (19.0%) discontinued treatment., Conclusions: Tralokinumab is an effective first-line biotherapy for severe AD. However, therapeutic response may be progressive. Safety data were reassuring. Atopic dermatitis flares or reactions at the injection site may lead to discontinuation of treatment. A history of conjunctivitis on dupilumab is not a contraindication to the initiation of tralokinumab., (© 2023. The Author(s).)

General practitioners (GPs) are first-line clinicians in melanoma diagnosis. It is, therefore, important to ensure that they maintain their melanoma diagnostic accuracy over time. The objective of this study was to assess the short- and long-term competences of GPs after a training session in naked-eye melanoma diagnosis. An interventional prospective study was conducted whereby, over a 6-month period, GPs attended a 1-h melanoma diagnostic training session. To assess their acquired competences, GPs were asked to fill in a questionnaire on basic melanoma knowledge and to evaluate 10 clinical images of pigmented skin lesions prior to training, immediately after and 1 year later. In total, 89 GPs completed the questionnaire prior and immediately after training. As expected, the number of GPs who appropriately managed [Formula: see text] 50% of the melanoma cases increased after training (P < 0.001). One year after training, only 27 (30%) of the 89 GPs completed the questionnaire. This number of participants was too low to obtain significant figures but the GPs' mean overall score of appropriately managed clinical cases was much lower than in the immediate post-test. In conclusion, although this short training improved the GPs' diagnostic accuracy and management of melanoma in the short-term, participating GPs do not seem to have maintained these competences in the long-term. Further studies are needed to assess whether refresher training sessions are able to sustain acquired diagnostic and management skills., (© 2021. American Association for Cancer Education.)

Competing Interests: None disclosed.

Competing Interests: None disclosed.

Background: Type 1 interferon (IFN-I) response induced by SARS-CoV-2 has been hypothesized to explain the association between chilblain lesions (CL) and SARS-CoV-2 infection., Objective: To explore direct cytopathogenicity of SARS-CoV-2 in CL and to focus on IFN-I expression in patients with chilblains., Materials & Methods: A monocentric cohort of 43 patients presenting with CL from April 2020 to May 2021 were included. During this period, all CL were, a priori, considered to be SARS-CoV-2-related. RT-qPCR on nasopharyngeal swabs and measurements of anti-SARS-CoV-2 antibodies were performed. Anti-SARS-CoV-2 immunostainings as well as SARS-CoV-2 RT-qPCR were performed on biopsy specimens of CL and controls. Expression of MX1 and IRF7 was analysed on patients’ biopsy specimens and/or PBMC and compared with controls and/or chilblains observed before the pandemic. Serum IFN-α was also measured., Results: RT-qPCR was negative in all patients and serological tests were positive in 11 patients. Immunostaining targeting viral proteins confirmed the lack of specificity. SARS-CoV-2 RNA remained undetected in all CL specimens. MX1 immunostaining was positive in CL and in pre-pandemic chilblains compared to controls. MX1 and IRF7 expression was significantly increased in CL specimens but not in PBMC. Serum IFN-α was undetected in CL patients., Conclusion: CL observed during the pandemic do not appear to be directly related to SARS-CoV-2 infection, either based on viral cytopathogenicity or high IFN-I response induced by the virus.

Chagas disease caused by Trypanosoma cruzi, remains one of the leading public health problems in Latin America. The number of infections in nonendemic countries continues to rise as a consequence of migratory flows. Updated information on prevalence, especially in treatable stages, together with vector eradication programs are key factors in an attempt to control the disease. We aim to estimate the prevalence of T. cruzi infection in an endemic area of Argentina and to describe epidemiological and clinical factors related to the disease. This is a cross-sectional study in an endemic rural area of Argentina. Our target population was people between 10 and 20 years of age, collecting demographic, clinical, and electrocardiographic data and seroprevalence against T. cruzi. We included 460 subjects; 76.7% did not have drinking water; 49.3% reported the presence of Triatoma infestans at home; 79.1% had pets or birds; 72.6% lived close to a chicken coop; 24.6% lived in adobe houses; 27.8% lived in overcrowded conditions. Seroprevalence was 9.33%. In the multivariate analysis, the presence of Triatoma infestans at home (OR 2.08, P = 0.03) had an association with seropositivity. No relevant findings indicating acute or chronic organ involvement were detected. We found no correlation of right bundle branch block (RBBB) and Chagas disease in our population. None of the infected patients were previously aware of their condition, highlighting the importance of active surveillance to detect infection in a potentially treatable stage, especially in areas with difficult access to health programs.

The exact etiopathology of chilblains observed during the Coronavirus Disease 2019 (COVID-19) pandemic is still unclear. Initially, SARS-CoV-2 appeared as the obvious causing agent, but two years of various investigations have failed to convincingly support its direct implication. Most affected individuals have no detectable virus, no anti-SARS-CoV-2 antibodies and no symptoms of COVID-19. Analyses of skin biopsies similarly failed to unambiguously demonstrate presence of the virus or its genome. In a recent hypothesis, SARS-CoV-2 would cause the lesions before being promptly eliminated by unusually strong type I interferon responses. With others, we feel that environmental factors have not been sufficiently considered, in particular cold exposure related to unprecedented containment measures. The cause of pandemic chilblains remains a stimulating puzzle which warrants further investigation., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

An 82-year-old man presented with unilateral oedema of the right lower limb overlaid with multiple sporotrichoid distributed panniculitis lesions. These symptoms appeared in a context of immunodepression and were associated with significant weight loss and a deterioration in general condition. The patient's medical history, the histological findings, PCR testing, and bacterial culture led to a diagnosis of cutaneous tuberculosis due to Mycobacterium bovis. This infection occurred as a late complication of intravesical bacillus Calmette-Guérin (BCG) instillations that the patient had received as an adjunctive immunotherapy for bladder cancer. This is an unusual clinical presentation and aetiology of cutaneous tuberculosis. Indeed, the observed sporotrichoid pattern is uncommon for tuberculous mycobacteria. Moreover, the occurrence of tuberculous skin lesions after intravesical BCG instillations is extremely rare, with only a few cases described, and, to the authors' knowledge, none with such a clinical presentation. This case report suggests that a medical history of BCG immunotherapy should always be considered when assessing any infectious-type cutaneous lesions and that skin should be regarded as a possible late localization of infectious complications of this treatment., (Copyright © 2021. Published by Elsevier Ltd.)