Treatment of congenital Langerhans cell histiocytosis with cobimetinib.

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.

Sofa dermatitis: Value of patch test with 2-(thiocyanomethylthio)benzothiazole.

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.

Chilblains observed during the COVID-19 pandemic cannot be distinguished from classic, cold-related chilblains

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.

Pyoderma gangrenosum induced by transcutaneous electrical nerve stimulation: a case report with literature review.

Pyoderma gangrenosum (PG) is one of the neutrophilic dermatosis, a heterogenous group of rare inflammatory diseases affecting the skin. It is often associated with systemic diseases such as inflammatory bowel disease, rheumatoid arthritis or hematological malignancies. Classical PG is characterized by painful ulcers with violaceous, undermined border, often developing at sites of injury because of the typical pathergy phenomenon. Because of its polymorphic presentation, misdiagnosis and delayed diagnosis are common. We present a case of PG occurring after transcutaneous electrical nerve stimulation (TENS) in a young female patient with ulcerative colitis. Although electric current has previously been incriminated as a trigger for PG, to the best of our knowledge this is the first case precipitated by TENS. We report a typical case of PG occurring after an unusual stimulus and highlight the challenges that the diagnosis of this relatively rare pathology poses to the clinician.

Sporotrichoid distributed tuberculous panniculitis as a late complication of intravesical bacillus Calmette-Guérin (BCG) immunotherapy.

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.

A case report of cutaneous leishmaniasis: a misleading clinical presentation.

BACKGROUND: The diagnosis of cutaneous leishmaniasis (CL) is often difficult because of the diversity of clinical presentations, its often-misleading appearance and the very long incubation period (time between the endemic stay and the onset of skin lesions). CASE: We report the case of an otherwise healthy 67-year-old man who presented with inflammatory skin lesions on the scalp and face for the past 7 years. The lesions were first mistaken as cutaneous sarcoidosis, mycobacterial infection, and cutaneous lymphoma. Finally, the diagnosis was made by RT-PCR analysis on a punch-biopsy specimen, which was positive for Leishmania infantum. DISCUSSION AND CONCLUSION: To date, the choice of treatment for complex cutaneous leishmaniases is based on the Leishmania species. Our patient successfully responded to liposomal amphotericin B.

Bier anemic spots, cyanosis, and urticaria-like eruption (BASCULE) syndrome: Report of two new cases and literature review.

We herein report two new adolescent cases of Bier anemic spots, cyanosis, and urticaria-like eruption (BASCULE) syndrome. This rare, recently described condition may be associated with postural orthostatic tachycardia syndrome (POTS) and other forms of orthostatic intolerance. This report provides details on two cases and a literature review.

Evaluation of Chilblains as a Manifestation of the COVID-19 Pandemic.

Importance: During the coronavirus disease 2019 (COVID-19) pandemic, several cases of chilblains have been reported. Objective: To determine if chilblains are associated with COVID-19. Design, Setting, and Participants: This monocentric case series was conducted at the Department of Dermatology at Cliniques universitaires Saint-Luc, a tertiary care hospital in Brussels, Belgium, between April 10 and April 17, 2020. We evaluated a total of 31 referred patients who had recently developed chilblains. Main Outcomes and Measures: Real-time reverse transcriptase-polymerase chain reaction (RT-PCR) was used to detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA on nasopharyngeal swabs for all patients and in skin biopsy specimens for 22 patients. Blood samples from all patients were tested for specific anti-SARS-CoV-2 immunoglobulin (Ig) M and IgG antibodies. All patients had extended blood analyses. Histologic (22 patients) and immunofluorescence examinations (15 patients) were performed on the skin biopsy specimens. Results: The 31 patients were generally in good health; most were teenagers or young adults, and 19 were women. Histopathologic analysis of skin biopsy specimens (22 patients) confirmed the diagnosis of chilblains and showed occasional lymphocytic or microthrombotic phenomena. Immunofluorescence analyses showed vasculitis of small-diameter vessels in 7 patients. In all patients, SARS-CoV-2 RNA remained undetected by RT-PCR on nasopharyngeal swabs and in biopsy samples of the skin lesions. The IgM and IgG antibody titers were negative for SARS-CoV-2 in all patients (<1.0 arbitrary unit/mL). No significant abnormalities in blood test results were suggestive of systemic disease. Antinuclear antibody titers were low in 7 patients and higher in 1 patient. Conclusions and Relevance: Chilblains appeared not to be directly associated with COVID-19 in this case series. Lifestyle changes associated with community containment and lockdown measures are a possible explanation for these lesions.

Toll-like receptor 3 increases antigen-presenting cell responses to a pro-apoptotic stimulus, yet does not contribute to systemic lupus erythematosus genetic susceptibility.

OBJECTIVES: TLR3 mediates skin solar injury by binding nuclear material released from apoptotic keratinocytes, resulting in the production of pro-inflammatory cytokines. Because the TLR3 gene is located in 4q35, a known systemic lupus erythematosus (SLE) susceptibility locus, we wondered whether TLR3 single nucleotide polymorphisms (SNPs) were associated with inflammatory mechanisms relevant to the development of SLE, and disease susceptibility. METHODS: Functional assays were carried out in TLR3-transfected HEK293 cells and in monocyte-derived dendritic cells (moDCs). TLR3 and IFNß immunofluorescence studies were performed in skin samples from 7 SLE patients and 3 controls. We performed a SNP association study in a discovery cohort of 153 patients and 105 controls, followed by a confirmation study in an independent cohort of 1,380 patients and 2,104 controls. RESULTS: TLR3 and IFNß are overexpressed in SLE skin lesions. TLR3 overexpression in HEK293 cells amplifies their sensitivity to a pro-apoptotic stimulus. Taking advantage of a naturally occurring polymorphic TLR3 variant (rs3775291) that weakly versus strongly responds to poly I:C stimulation, we found that TLR3 is associated with amplified apoptotic responses, production of the Ro/SSA autoantigen and increased maturation of myeloid-derived dendritic cells (moDC) after exposure to UV irradiation. However, TLR3 SNPs are not associated with susceptibility to SLE in a large population of patients and controls. CONCLUSIONS: TLR3 is overexpressed in SLE skin lesions and amplifies apoptotic and inflammatory responses to UV-irradiation in antigen-presenting cells in vitro. However, TLR3 SNPs do not impact susceptibility to the development of the disease.

Linear IgA dermatosis in association with angioimmunoblastic T-cell lymphoma infiltrating the skin: A case report with literature review.

Angioimmunoblastic T-cell lymphoma (AITL) is an aggressive form of peripheral T-cell lymphoma, characterized by systemic symptoms, diffuse lymphadenopathy, hepatosplenomegaly and immunodysregulation. Half of AITL is associated with cutaneous symptoms, but only few cases with bullous eruption have been described. Association with a linear IgA dermatosis is extremely rare. Linear IgA dermatosis can be idiopathic, or linked with drug intake or neoplastic disorders. Some cases of linear IgA dermatosis presenting as toxic epidermal necrolysis (TEN) have been described, most of them being drug induced. We here present the case of a 72-year-old man recently diagnosed with AITL who developed a bullous eruption, presenting as TEN. Histopathology showed deep cutaneous involvement of the lymphoma with a sub-epidermal blistering and direct immunofluorescence revealed a heavy IgA linear deposit on the dermal-epidermal junction. A diagnosis of linear IgA dermatosis associated with cutaneous involvement of an angioimmunoblastic T-cell lymphoma was made. Chemotherapy and corticosteroids allowed cutaneous improvement but the patient died of his lymphoma shortly after.

Mechanisms of kidney disease in Sneddon's syndrome: Case report and literature review
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Sneddon's syndrome is a rare, noninflammatory thrombotic vasculopathy characterized by the combination of livedo racemosa, recurrent stroke, and histopathological skin lesions of endarteritis obliterans. Although multiorgan involvement suggests its systemic nature, detailed pathological description of affected organs - including the kidney - is exceptional. We report a case of Sneddon's syndrome with chronic kidney disease, associated with features of endarteritis obliterans in the skin and the kidney. The clinical presentation of our patient is compared to previously reported cases of Sneddon's syndrome with biopsy-proven kidney disease. We also discuss the differential diagnosis, pathophysiological mechanisms, relationship with antiphospholipid syndrome, and management of patients with Sneddon's syndrome and kidney disease. This clinical observation supports the systemic nature of Sneddon's syndrome and provides insights into the mechanisms by which this rare but probably underdiagnosed disease alters kidney function.
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Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome caused by first-line antituberculosis drugs: Two case reports and a review of the literature.

BACKGROUND: Patients suffering from drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome caused by first-line antituberculosis drugs often need to be retreated rapidly. Patch tests prior to the reintroduction of antituberculosis drugs are rarely performed. OBJECTIVES: To highlight those drugs most often involved in DRESS caused by antituberculosis drugs, illustrate the potential value of patch tests to identify these culprit(s), and provide insights into how to rapidly retreat these patients. METHODS: A detailed description of the work-up of two illustrative patients, together with a literature review of similar cases, is provided. RESULTS: All first-line antituberculosis drugs may cause DRESS syndrome, but rifampicin and isoniazid are most frequently involved. Patch tests can be performed sooner than usually advised in the context of DRESS syndrome, and potentially with lower test concentrations, but false-negative results are possible. Sequential reintroduction of patch test-negative drugs is feasible, although the dose and order of drugs to be readministered, as well as the use of concomitant systemic corticosteroids, remain a matter of debate. CONCLUSION: Patch tests in the context of DRESS syndrome caused by antituberculosis drugs, despite their shortcomings, may potentially guide rapid retreatment of these patients.