D2.30 - A Case of Kimura’s Disease with Atypical Presentation and Novel Genetic Findings

Rationale: Kimura’s disease (KD) is a rare chronic inflammatory disorder of unknown etiology, characterized by subcutaneous masses, lymphadenopathy, peripheral eosinophilia, and elevated IgE. Diagnosis is challenging due to its overlap with hypereosinophilic syndrome, vasculitis, and neoplasms. We present a complex case highlighting diagnostic difficulties and novel genetic findings.

Anamnesis: A 43-year-old male presented with recurrent, transient, non-pruritic subcutaneous masses and a persistent, painful edema of the anterior neck and chin since December 2023. History included childhood allergic rhinoconjunctivitis, atopic dermatitis , and newly diagnosed bronchial asthma (April 2024). Previous evaluations for eosinophilia, angioedema, and suspected hypereosinophilic syndrome were inconclusive. Episodes of facial swelling were noted.

Laboratory Findings: Peripheral eosinophilia (20%, 1340 cells/µL), elevated total IgE (333 IU/mL). Normal C1-esterase inhibitor (functional/quantitative), C3, C4;. ANA, ANCA, parasitic and brucellosis serologies negative. Excluded myeloproliferative mutations (JAK2, CALR, c-KIT). Imaging (US, CT, MRI, PET-CT) revealed cervical and mediastinal lymphadenopathy, diffuse subcutaneous edema, polyps, and chronic sinusitis. Multiple biopsies (scalp, chin subcutaneous tissue, nasal mucosa, colon) showed chronic inflammation with eosinophilic infiltrates, without granulomas or vasculitis, consistent with KD.

Genetic Findings: Whole-genome sequencing revealed two novel, likely compound heterozygous, structural variants in the DOCK8 gene (a large duplication and a deletion). Pathogenic DOCK8 variants are associated with autosomal recessive Hyper-IgE syndrome (HIES). The clinical significance of these heterozygous variants in KD remains uncertain.

Treatment: Initiated combination biologic therapy with omalizumab (300 mg s.c. every 4 weeks) and benralizumab (30 mg s.c. every 8 weeks). The patient showed a positive clinical response with complete resolution of the chin edema and no recurrence of scalp lesions.

Conclusions: This case underscores the diagnostic complexity of KD, requiring exclusion of numerous mimics. The novel finding of heterozygous DOCK8 structural variants raises questions about a potential genetic predisposition or overlap with hyper-IgE phenotypes. The combination of anti-IgE (omalizumab) and anti-IL-5Rα (benralizumab) therapy proved highly effective, suggesting a synergistic approach for severe or refractory KD. Further research is needed to explore the role of DOCK8 and similar immunoregulatory genes in KD pathogenesis