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Griscelli syndrome type 2 (GS-2) is a rare congenital immune dysfunction characterized by partial albinism and recurrent episodes of hemophagocytic lymphohistiocytosis (HLH). It is caused by a variant in the gene encoding Rab27a leading to a degranulation defect in melanocytes, natural killer (NK)- and T cells. Prognosis of patients with GS-2 is limited by repetitive episodes of life-threatening HLH with onset in early childhood. The only curative treatment is an allogeneic hematopoietic stem cell transplantation (HSCT). Here, we report on an 18 year old female patient with a homozygous missense p.Arg50Glnfs*35 variant in exon 2 of RAB27A who presented with an exceptionally late onset of severe HLH. Her phenotypically inapparent albinism complicated to correctly diagnose GS-2. Immune function assays confirmed a T- and NK cell degranulation deficiency characteristic for patients with primary HLH, while microscopic hair analysis revealed melanin clumps secondary to melanocyte functional impairment. To understand why disease onset occurred unusually late in this patient, we investigated the patient’s T cell and polymorphonuclear neutrophil (PMN) function in more detail. We could show that intracellular granzyme B storage in cytotoxic T cells was increased compared to healthy donors and that the patient’s T cells maintained some degranulation activity. Both, antigen-specific cytotoxic response and proliferation capacity of the patient’s T cells were preserved. We demonstrate for the first time that also PMN degranulation, assessed as stimulation-induced CD66b and CD11b cell membrane expression, is dysfunctional in patients with Rab27a deficiency-associated primary HLH. The patient was treated with steroids and cyclosporine A for immunosuppression to control the HLH. After two severe episodes within only a few months, she eventually received an allogeneic HSCT and has not experienced further HLH episodes for now more than 3 years after the HSCT procedure. This case should raise awareness for the possibility of initial manifestation of primary, genetically-determined HLH even in adult patients.

Leukocyte adhesion deficiency type 1 (LAD-1) is a rare disease resulting from mutations in the gene encoding for the common β-chain of the β2-integrin family (CD18). The most prominent clinical symptoms are profound leukocytosis and high susceptibility to infections. Patients with LAD-1 are prone to develop autoimmune diseases, but the molecular and cellular mechanisms that result in coexisting immunodeficiency and autoimmunity are still unresolved. CD4+FOXP3+ Treg are known for their essential role in preventing autoimmunity. To understand the role of Treg in LAD-1 development and manifestation of autoimmunity, we generated mice specifically lacking CD18 on Treg (CD18Foxp3), resulting in defective LFA-1 expression. Here, we demonstrate a crucial role of LFA-1 on Treg to maintain immune homeostasis by modifying T cell-DC interactions and CD4+ T cell activation. Treg-specific CD18 deletion did not impair Treg migration into extralymphatic organs, but it resulted in shorter interactions of Treg with DC. In vivo, CD18Foxp3 mice developed spontaneous hyperplasia in lymphatic organs and diffuse inflammation of the skin and in multiple internal organs. Thus, LFA-1 on Treg is required for the maintenance of immune homeostasis.

There are few reports of snake bites by western hognose snakes (Heterodon nasicus), most of which have been associated with local reactions. We report a patient with pronounced local swelling after a bite by a western hognose snake. Local antiseptic therapy and systemic antibiotics are recommended for infection prophylaxis; in addition, laboratory tests should be run to exclude systemic involvement. Regarding tetanus vaccination status, a booster should be considered according to current guideline recommendation.There are few reports of snake bites by western hognose snakes (Heterodon nasicus), most of which have been associated with local reactions. We report a patient with pronounced local swelling after a bite by a western hognose snake. Local antiseptic therapy and systemic antibiotics are recommended for infection prophylaxis; in addition, laboratory tests should be run to exclude systemic involvement. Regarding tetanus vaccination status, a booster should be considered according to current guideline recommendation.

Es gibt bisher wenige beschriebene Fälle von Bissen durch die Hakennasennatter (Heterodon nasicus), die meist zu einer Lokalreaktion führten. Wir berichten über eine ausgeprägte Lokalreaktion nach dem Biss einer als Haustier gehaltenen Hakennasennatter (Heterodon nasicus). Eine antiseptische Lokaltherapie und Antibiose zur Infektionsprophylaxe sind zu empfehlen, ebenfalls Laborkontrollen zum Ausschluss einer systemischen Beteiligung. An die Überprüfung des Tetanusschutzes sollte gedacht werden.

Background: Lichen planopilaris (LPP) is an inflammatory cicatricial alopecia characterized by an irreversible destruction of the hair follicle resulting in its permeant destruction. The clinical presentation of LPP is a progressive patchy scarring alopecia. A variety of systemic agents is used to treat LPP with varying success. The aim of this retrospective, real-life analysis was to evaluate the treatment of hydroxychloroquine for LPP. Method: In this retrospective, single-center study, we analyzed 110 patients with LPP and frontal fibrosing alopecia (FFA) who received treatment over a 12-month period from March 2014 to March 2021 at the Department of Dermatology, University of Mainz Medical Center. Patient records were analyzed for response to treatment, co-morbidities, disease progression-free survival (DPFS), and safety. Clinical parameters associated with treatment response were determined with Cox regression modelling and logistic regression. Results: Overall, 77 of 110 patients were treated with a systemic agent. There was a clear association between LPP and the occurrence of Hashimoto thyroiditis. Topical treatment with corticosteroids did not improve clinical symptoms in the majority of patients (15 out of 101). In 71% of patients treated with systemic cyclosporine A and 62% of patients treated with hydroxychloroquine, we observed a significant resolution of the inflammatory process, which correlated with a robust durable clinical response (p < 0.001). Toxicity was observed in 17% (n = 9) of patients receiving systemic treatment with hydroxychloroquine and correlated with the duration of systemic treatment (p < 0.001). Treatment discontinuation was associated with a flare-up of clinical symptoms (29%), which required the re-initiation of second-line therapy in 13 out of 51 patients. Overall, the initiation of second-line treatment, either hydroxychloroquine or Cyclosporine A (CsA), yielded positive results, especially in the patient cohort treated with hydroxychloroquine (overall response rate, ORR = 100%), who showed disease progression during CsA or retinoids. Conclusions: Our results from this contemporary cohort of patients with LPP and FFA indicate that hydroxychloroquine and cyclosporine are effective systemic agents in decreasing clinical symptoms. However, our data also show that the discontinuation of treatment is often associated with the exacerbation of clinical symptoms. Response rates to second-line treatment were especially favorable in the patient cohort with hydroxychloroquine.

Nannizzia incurvata is a geophilic dermatophyte that is rarely detected in Germany. We report on a 17-year-old traveler returning from Indonesia in whom Nannizzia incurvata was isolated as the causative agent of tinea corporis. Targeted, local antimycotic therapy and clinical follow-up was recommended. This report shows the importance of a detailed travel history and targeted mycological diagnostic workup.

Zusammenfassung Es gibt bisher wenige beschriebene Fälle von Bissen durch die Hakennasennatter ( Heterodon nasicus ), die meist zu einer Lokalreaktion führten. Wir berichten über eine ausgeprägte Lokalreaktion nach dem Biss einer als Haustier gehaltenen Hakennasennatter ( Heterodon nasicus ). Eine antiseptische Lokaltherapie und Antibiose zur Infektionsprophylaxe sind zu empfehlen, ebenfalls Laborkontrollen zum Ausschluss einer systemischen Beteiligung. An die Überprüfung des Tetanusschutzes sollte gedacht werden.

Zusammenfassung Nannizzia incurvata ist ein geophiler Dermatophyt, der hierzulande selten nachgewiesen wird. Wir berichten über einen 17-jährigen Reiserückkehrer aus Indonesien, bei dem Nannizzia incurvata als Erreger einer Tinea corporis isoliert werden konnte. Eine kalkulierte antimykotische Lokaltherapie sowie klinische Verlaufskontrollen sind zu empfehlen. Eine dezidierte Reiseanamnese und eine gezielte mykologische Diagnostik sollten erfolgen.