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A 4-year-old boy presented with blistering on his face and distal upper and lower extremities. Subepidermal blisters containing neutrophils and eosinophils visualized on histology supported the diagnosis of linear IgA bullous dermatosis of childhood (LABDC). The dermatosis presents with vesicles and tense blisters in an annular distribution, erythematous papules, and/or excoriated plaques. Histopathology shows subepidermal blisters with a neutrophilic infiltrate in the dermis, mainly concentrated at the tips of dermal papillae in the early stage of the disease, which can be mistaken for the pattern of neutrophilic infiltration as seen in dermatitis herpetiformis. Dapsone is the treatment of choice, which is started at a dosage of 0.5mg/kg/day. Linear IgA bullous dermatosis of childhood is a rare autoimmune disease that can be mistaken for other conditions with similar presentations but should always be considered in the differential diagnosis of children with blistering.

Background Hyperkeratosis lenticularis perstans (HLP), also known as Flegel disease, is a rare skin disease presenting with asymptomatic small hyperkeratotic papules. The lesions often appear on the dorsal feet and lower legs, and typically develop after the fourth decade of life. A genetic basis for HLP is suspected; however, so far no gene defect linked to the development of HLP has been identified. Objectives We aimed to identify the genetic cause of HLP. Methods For mutational analysis we studied a cohort of five patients with HLP using next-generation sequencing (NGS). We used DNA -extracted from fresh skin biopsies alongside ethylenediamine tetraacetic acid (EDTA) blood samples from two patients, and formalin-fixed -paraffin-embedded skin biopsy material from three patients. In addition, immunofluorescence staining of HLP lesions from four patients was investigated. Results In all samples from the five patients with HLP we identified by NGS rare variants in the SPTLC1 gene. In four patients we detected small deletions/frameshift variants and in one patient a splicing variant, predicted to disturb the splicing process. In blood samples the detected variants were heterozygous with an allele frequency of 49% and 50%, respectively. In skin biopsies the allele frequency was within the range of 46–62%. Immunofluorescence staining revealed reduced SPTLC1 protein levels in skin of patients. Conclusions Our findings suggest that pathogenic variants in the SPTLC1 gene are the underlying genetic cause of HLP. Of note, the identified variants were either frameshift- or splicing variants probably leading to nonsense-mediated mRNA decay and thus reduced SPTLC1 protein levels. We conclude that diminished SPTLC1, the key enzyme in sphingolipid biosynthesis, leads to the development of HLP, which highlights the sphingolipid pathway as a new therapeutic target. [ABSTRACT FROM AUTHOR]

A 65-year-old woman presented with painful nodules on her back after returning to Switzerland from Congo. The nodules were furunculoid in nature and had central ulceration. Dermoscopically, erythematous lesions with a central larval breathing hole, resembling a periscope, were observed. The larvae were identified as Cordylobia anthropophaga. Furuncular myiasis is rare in Switzerland and is often seen in patients returning from regions where these flies are prevalent. The authors suggest using the "periscope sign" as a dermatoscopic finding to aid in the diagnosis of this condition. [Extracted from the article]

In addition, we did not detect increased serum IgE in our patient and we did not find IgE autoantibodies at the DIF. Dear Editor, Bullous pemphigoid (BP) is the most frequently reported autoimmune blistering skin disease.[1] BP usually affects patients between 60 and 80 years old.[1] Localized BP represents up to 29% of all BP cases.[2] Dyshidrosiform pemphigoid (DP) is an uncommon variant of localized BP,[2] characterized mainly by vesiculobullous lesions on the soles and/or palms. [Extracted from the article]

The article discusses the potential link between the use of ultra-high potency topical corticosteroids, such as clobetasol propionate, and the development or exacerbation of reactive perforating collagenosis in patients with eczema or prurigo. Reactive perforating collagenosis is characterized by the trans-epithelial elimination of altered collagen and is associated with various factors, including microvascular disorders. The authors suggest that the vasoconstrictive properties of high-potency steroids may disrupt microcirculation, leading to the formation of reactive perforating collagenosis. They also propose a hypothesis involving decreased collagen synthesis mediated by p38 in the skin. Further research is needed to confirm these hypotheses and improve understanding and treatment of this condition. [Extracted from the article]

Introduction: Enfortumab vedotin (EV) combined with pembrolizumab (EV+P) is a promising first-line therapy for metastatic urothelial carcinoma. While it has shown significant efficacy, severe cutaneous adverse events such as Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) have been reported. We present this case as another example of severe skin off-target toxicity associated with this treatment, emphasising the importance of recognising this potential complication., Case Description: A 67-year-old male with metastatic urothelial carcinoma, chronic kidney failure and liver cirrhosis presented with fever, respiratory symptoms and a pruritic rash after two doses of EV+P. The rash rapidly worsened, leading to extensive skin desquamation affecting 20-30% of his body surface area. Skin biopsies confirmed SJS with early-stage TEN (SJS/TEN overlap). The patient was treated with high-dose intravenous steroids, empirical antibiotics for neutropenia and intensive topical care. Significant re-epithelialisation occurred by day 13, and the patient was discharged on day 15 with cessation of EV+P therapy., Conclusion: This case demonstrates the potential for severe cutaneous toxicity in patients receiving EV+P, especially those with complex comorbidities. Early recognition and prompt, aggressive management with systemic corticosteroids are essential for improving outcomes. The case highlights the need for vigilance in monitoring for such adverse events and reporting them to improve patient safety., Learning Points: High clinical suspicion recognition of early signs of dermolysis is essential in managing severe cutaneous toxicity associated with enfortumab vedotin. A multidisciplinary approach the management of Stevens-Johnson syndrome/toxic epidermal necrolysis should involve a multidisciplinary team, especially in patients with complex comorbidities. Pharmacovigilance continuous monitoring and prompt reporting of adverse events to health authorities are vital for improving patient safety and therapeutic outcomes., Competing Interests: Conflicts of Interests: The Authors declare that there are no competing interests., (© EFIM 2024.)

Background: Dermatitis herpetiformis (DH) is typically characterized by granular IgA deposition in the papillary dermis on direct immunofluorescence (DIF), and linear IgA bullous dermatosis (LABD) is characterized by linear deposition of IgA along the basement membrane. Other DIF findings in both conditions may include IgG, IgM, and C3 deposition in various patterns. In cases where immunofluorescence findings are unclear, such as continuous but somewhat granular IgA deposition along the dermal-epidermal junction, additional DIF patterns may be helpful in the diagnostic process., Methods: Forty-five cases of digitized images of LABD and 48 digitized images of DH cases were analyzed. The data regarding the positivity and patterns of immunoglobulins were documented and analyzed., Results: None of the LABD cases had a picket fence pattern, while 47.9% (n = 23) of the DH cases had the pattern. Elevated levels of IgG and IgM were found in LABD compared with DH. In DH, higher IgM and kappa light chain levels were observed in the deposited particles compared with those in LABD., Conclusions: The "picket fence pattern" is highly specific for DH (Specificity 100%) but less sensitive (Sensitivity 47.9%). It may be helpful to differentiate between DH and LABD for a more accurate diagnosis., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Porokeratoses are a heterogeneous group of keratinization disorders. For linear porokeratosis and disseminated superficial actinic porokeratosis, a heterozygous pathogenic germline variant in a mevalonate pathway gene and a postzygotic second hit mutation present in affected skin have been shown to be the patho-genetic mechanism for the development of the lesions. However, the molecular mechanism leading to development of porokeratosis plantaris, palmaris et disseminata is not known. This study analysed a cohort of 4 patients with linear porokeratosis and 3 patients with porokeratosis plantaris, palmaris et disseminata, and performed mutation analyses of DNA extracted from blood samples and skin biopsies. All of the study patients carried the heterozygous germline variant c.70+5G>A in the MVD gene. Loss of heterozygosity due to a second hit mutation was found in affected skin of 3 patients with linear porokeratosis and 2 patients with porokeratosis plantaris, palmaris et disseminata. These results suggest that porokeratosis plantaris, palmaris et disseminata shares the same pathogenetic mechanism as other porokeratosis subtypes and belongs to the phenotypic spectrum of MVD-associated porokeratosis.

Pathophysiologically, bullous autoimmune dermatoses are caused by autoantibodies directed against adhesion molecules or structural proteins of the skin and mucous membranes, clinically resulting in blister formation. Depending on the respective target proteins of the autoimmune response and their location in the skin, a distinction is made between intraepidermal (pemphigus disorders), junctional (pemphigoid disorders), and subepidermal (epidermolysis bullosa acquisita, dermatitis herpetiformis) autoimmune blistering diseases. The most common bullous autoimmune dermatosis, bullous pemphigoid is characterized by marked clinical variability and intense pruritus. Predominantly affecting elderly individuals, there has been a significant increase in its incidence in recent years. While mucosal lesions occur in less than 30 % of bullous pemphigoid patients, the second most common bullous autoimmune dermatosis, pemphigus vulgaris, typically presents with oral erosions as the predominant and - frequently - initial symptom. Its onset is usually in the 4 th to 6 th decade of life. Scarring is typically found in subepidermal blistering disorders such as epidermolysis bullosa acquisita or mucous membrane pemphigoid. Diagnosis is based on clinical and histological findings as well as direct and indirect immunofluorescence and detection of circulating autoantibodies. Although a number of controlled clinical trials have been conducted in recent years, treatment of bullous autoimmune disorders is still primarily based on clinical experience. Therapeutic options include topical and systemic corticosteroids as well as adjuvant immunosuppressants. Recalcitrant cases may require treatment with immunoadsorption, intravenous immunoglobulins, or the monoclonal anti-CD20 antibody rituximab., (© 2018 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd.)