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Purpose: We aimed to describe the clinical, immunological, and genetic features of patients with DOCK8 deficiency (DOCK8-Def) in a tertiary care center for children., Methods: Retrospective chart review of patients' clinical, immunological, and genetic characteristics with DOCK8-Def. Genetic analysis was performed with targeted- or whole-exome sequencing; we also assessed DOCK8 protein expression and a lymphoproliferation assay and analyzed survival by the Kaplan-Meier method., Results: We described 11 patients from 8 unrelated kindreds. The median age at symptoms' onset was 10 months (range 1-54 months). The median follow-up time was 53.4 months (4.8-118.8). All patients presented eczema and recurrent sinopulmonary and cutaneous infections. Besides those symptoms, the most frequent manifestations were bronchiectases (8/11), food allergies (6/11), and severe infections (6/11). Infrequent characteristics were detection of CMV in bronchial lavage, C. parvum-driven sclerosing cholangitis, Takayasu vasculitis, neurological syndromes, pulmonary tuberculosis, and lymphomatoid granulomatosis., Conclusion: DOCK8-Def has a broad spectrum of manifestations, including allergy, autoimmunity, inflammation, infection, and cancer. The hallmark of this inborn error of immunity is IEI-associated eczema with eosinophilia and increased IgE. Here, we report six new mutations causing human DOCK8 deficiency and symptoms previously unrecognized to occur in DOCK8-Def. Therefore, an early diagnosis of DOCK8-Def is essential to facilitate an adequate treatment such as HSCT., (© 2024 European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Chronic granulomatous disease (CGD) presents with granuloma formation and lethal infections. It is inherited in an autosomal or X-linked recessive pattern. We describe a 10-month-old patient with a fatal secondary HLH as a CGD primary manifestation. We carried out an autopsy and found noncaseating granulomas, an aspergilloma in the lung, and hemophagocytosis. We performed a DHR assay on the patient's mother and grandmother, showing a bimodal pattern conclusive of X-linked CGD. Thus, our definitive diagnosis was CGD complicated by macrophage activation syndrome. CGD is caused by phagocytes' inability to control pathogens, resulting in granulomas. Secondary HLH is a severe complication and could be characterized by the proliferation of macrophages and T lymphocytes and the production of proinflammatory cytokines. The early suspicion of this presentation helps establish a specific treatment, and the study of the carriers helps determine the etiology.

Juvenile idiopathic arthritis (JIA) is a heterogeneous group of arthritis of autoimmune aetiology. Systemic-onset juvenile idiopathic arthritis (soJIA) presents with fever, transient erythematous rash, hepatomegaly, splenomegaly, lymphadenopathy, and serositis. SoJIA presents multiple complications, and the most severe is the macrophage activation syndrome (MAS); the timely treatment of MAS must be established early and aggressively to avoid a fatal outcome. Therapeutic plasma exchange has anecdotally been used in refractory cases. A 66-month-old male with a 1-year illness characterized by evening-predominant, intermittent fever, adenomegalies, urticarial-like rash, arthralgia, and arthritis. Biochemical analysis revealed anaemia, leukocytosis, neutrophilia, hypertriglyceridemia, hyperferritinemia, and hypofibrinogenemia; bone marrow aspirate showed hemophagocytosis. He was diagnosed with SoJIA complicated with MAS. He received multiple treatments with IV human gammaglobulin, cyclosporine, dexamethasone, and tocilizumab without improvement. Plasma replacement treatment was performed. Afterwards, he presented significant improvement. After 3-year-follow-up, he remains in good general condition. We present a refractory case of soJIA complicated with MAS successfully treated with plasma exchange., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)