A60-16 Clinical Phenotypes and Therapeutic Exploration of 10 Cases of Inborn Errors of Immunity With Prominent Allergic Manifestations

Objective Inborn errors of immunity (IEI) are often associated with recurrent infections, autoimmunity, autoinflammation, malignancies, and allergic diseases. IEI cases presenting predominantly with allergies are rarely reported, leading to diagnostic challenges. This study reports the genotypes, clinical features, and treatment outcomes of 10 pediatric IEI patients with primarily allergic manifestations to improve awareness and clinical management. Methods Clinical data, whole-exome sequencing, treatment details, and follow-up information of 10 pediatric patients (2019-2025) were analyzed retrospectively. Results 1. Patient ages ranged from 3 months to 14 years (6 males, 4 females). Diagnoses included WAS (1), high IgE syndrome (4), Omenn syndrome (2), FLG gene mutation (1), chromosomal duplication with FLG mutation (1), and isolated chromosomal duplication (1). Mutated genes included WAS, STAT3, SPINK5, DOCK8, RAG1, and FLG. Two patients had chromosomal abnormalities. 2.All patients primarily presented with allergic symptoms. Except for one DOCK8 mutation and one FLG mutation with onset at age 8, all others developed symptoms in the neonatal period. The most common manifestations were eczema (5/10) and atopic dermatitis (5/10), followed by food allergies and allergic rhinitis. Most patients experienced wheezing or recurrent respiratory infections. Three cases presented with bronchiectasis or chronic infectious pneumonia. Three patients developed erythroderma. They experienced severe pruritus, engaging in incessant scratching during waking hours, with minimal relief from conventional antihistamines. Notably, one DOCK8 mutation case combined with uveitis, representing the first reported complication associated with DOCK8 variation. All patients showed markedly elevated total IgE levels, with five exceeding 1000 kU/L. Nine out of ten had elevated eosinophil counts; in one case, peripheral blood eosinophils rose to 55 after dupilumab treatment. Skin biopsies in three patients confirmed recurrent infections with pathogens including Staphylococcus aureus, Candida albicans, and Epstein-Barr virus.3. Conventional antihistamines were ineffective for pruritus. Prior to biologics, treatment often involved corticosteroids and intravenous immunoglobulin, with recurrent or persistent dermatitis. Biologics like dupilumab showed significant improvement in dermatitis and pruritus, especially in patients with DOCK8, SPINK5, and FLG mutations. One DOCK8 patient with uveitis improved with adalimumab. A patient with chromosome 3 duplication responded to tofacitinib, while one SPINK5 patient had better results with secukinumab after a recurrence on dupilumab. One Omenn syndrome patient died from severe infection. Conclusions 1. Allergic diseases are common in children, but early-onset, refractory allergic conditions warrant vigilance for IEI. 2. Biologics may help improve allergic symptoms in these patients.