IL-7-dependent and -independent lineages of IL-7R-dependent human T cells.

Infants with biallelic IL7R loss-of-function variants have severe combined immune deficiency (SCID) characterized by the absence of autologous T lymphocytes, but normal counts of circulating B and NK cells (T-B+NK+ SCID). We report 6 adults (aged 22 to 59 years) from 4 kindreds and 3 ancestries (Colombian, Israeli Arab, Japanese) carrying homozygous IL7 loss-of-function variants resulting in combined immunodeficiency (CID). Deep immunophenotyping revealed relatively normal counts and/or proportions of myeloid, B, NK, and innate lymphoid cells. By contrast, the patients had profound T cell lymphopenia, with low proportions of innate-like adaptive mucosal-associated invariant T and invariant NK T cells. They also had low blood counts of T cell receptor (TCR) excision circles, recent thymic emigrant T cells and naive CD4+ T cells, and low overall TCR repertoire diversity, collectively indicating impaired thymic output. The proportions of effector memory CD4+ and CD8+ T cells were high, indicating IL-7-independent homeostatic T cell proliferation in the periphery. Intriguingly, the proportions of other T cell subsets, including TCRγδ+ T cells and some TCRαß+ T cell subsets (including Th1, Tfh, and Treg) were little affected. Peripheral CD4+ T cells displayed poor proliferation, but normal cytokine production upon stimulation with mitogens in vitro. Thus, inherited IL-7 deficiency impairs T cell development less severely and in a more subset-specific manner than IL-7R deficiency. These findings suggest that another IL-7R-binding cytokine, possibly thymic stromal lymphopoietin, governs an IL-7-independent pathway of human T cell development.

Cerebral Aneurysms and Recurrent TIAs in a 42-Year-Old Patient With DADA2 Mutation: A Case Report.

Objectives: Deficiency of adenosine deaminase 2 (DADA2) is a rare, recessively inherited autoinflammatory disease with a wide clinical spectrum of manifestations, including strokes and vasculitis. Methods: We report a case of a patient with DADA2 who presented with neurologic manifestations. Results: A 42-year-old woman with a known diagnosis of polyarteritis nodosa experienced several episodes of TIAs. Neuroimaging revealed 2 aneurysms in unusual locations. Her young age, ethnic origin, absent of cardiovascular risk factors, and skin involvement raised the suspicion of DADA2. Genetic testing confirmed the diagnosis, and a directed treatment with anti-TNF was initiated. Discussion: DADA2, although thought to be rare, needs to be borne in mind when evaluating patients with a combination of neurologic and systemic symptoms, as early diagnosis and treatment are imperative in preventing permanent disability.

Pediatric Contact Dermatitis: A 10-Year Multicenter Retrospective Study.

Background: Although allergic contact dermatitis (ACD) is relatively common in the adult and pediatric populations alike, few studies describe the special features of contact sensitization among the Israeli pediatric populations, none of them is multicenter. Our study aims to describe and analyze patch test results and trends in 4 tertiary care centers between 2012 and 2022. Methods: We assessed the results of 357 patch tests performed on children 0-18 years old between 2012 and 2022 in designated clinics in 4 tertiary medical centers. All patients were tested using the European baseline series and additional series as clinically indicated. We assessed the demographic features, atopic features, and influence, as well as the main allergens to cause sensitization and allergic contact dermatitis among the pediatric population. Results: In total 69% of the study population were females, mainly 12-18 years old, 35% of the study population were previously diagnosed with atopic dermatitis, and 57% had an atopic diathesis. Females were more commonly sensitized (P < 0.05). Patients without atopic dermatitis were more commonly diagnosed with ACD and had more reactions on patch test (P < 0.05). The most common allergens to cause ACD are preservatives and metals, as previously described, however, acrylate sensitivity is an emerging group that has not been described among the Israeli pediatric population in previous studies. Fragrance mix 2 and Mroxylon pereirae are relatively rare allergens among the Israeli pediatric population, whereas linalool hyperoxide might be considered an emerging allergen. Methylisothiazolinone causes ACD more frequently among patients without atopic dermatitis (P < 0.05). Conclusions: Among the Israeli pediatric population, ACD is more common in females without atopic dermatitis. Acrylates become a common culprit and should be included in baseline series. Patients with atopic dermatitis are less frequently sensitized by methylisothiazolinone.

Exacerbation of Hailey-Hailey Disease Following SARS-CoV-2 Vaccination.

is missing (Short communication).

[CHRONIC DERMATITIS OF THE DORSUM OF THE FEET AND SHINS, DUE TO ALLERGIC CONTACT DERMATITIS TO LEATHER PRODUCTS].

INTRODUCTION: A 40 year old woman presented with dermatitis mainly involving her dorsal feet and shins, a condition which was present for a prolonged period of time. The distribution was suggestive of allergic contact dermatitis, possibly to her shoes. Patch tests disclosed allergy to chromates, cobalt, colophony, all present in leather products, and allergy to myroxylon pereirae (Balsam of Peru). The patient was instructed to avoid wearing some of her shoes and sitting on her leather sofa. As a consequence, her symptoms ameliorated. This case demonstrates the importance of patch testing with correct interpretation and advice to improve quality of life in patients with dermatitis.

Lymphatic Dissemination in Cutaneous Leishmaniasis Following Local Treatment.

Cutaneous leishmaniasis (CL) is diverse in its clinical presentation but usually demonstrates an erythematous, infiltrated, ulcerated, and crusted papule or nodule in exposed areas of the body. Rare clinical features have been reported including lymphatic dissemination, usually with subcutaneous nodules along lymphatic channels. Herein, we present six patients suffering from Old World CL with lymphatic dissemination characterized by sporotrichoid subcutaneous nodules along the lymphatic channels draining the primary lesion. Patients' history, clinical and laboratory findings were collected and summarized. Lymphatic dissemination of CL in our patients manifested as subcutaneous nodules without epidermal involvement within the axis of lymphatic drainage toward the regional lymph node, at times accompanied by regional lymphadenopathy. In all patients, the lymphatic dissemination was not present at initial diagnosis of CL, appearing only after local (topical or intralesional) treatment was initiated. In three patients, the subcutaneous nodules resolved without systemic treatment. Lymphatic dissemination of Old World CL is not uncommon and may possibly be triggered by local treatment. It should be recognized by dermatologists, especially those working in endemic areas. Systemic treatment may be not necessary since spontaneous resolution may occur.

Valproic acid hypersensitivity and desensitization.

Rash, a hypersensitivity reaction, is a common cause of withdrawal from an effective antiepileptic drug (AED) in patients with epilepsy. We present a case of successful desensitization to valproic acid in a 12-year-old male with childhood absence epilepsy and a hypersensitivity reaction, whose epilepsy did not respond to other AEDs. Desensitization is a practical therapeutic solution for patients who develop a non-life-threatening hypersensitivity reaction to an AED for which there may be no substitute.