D3.326 - A RARE COEXISTENCE: CARD9 DEFICIENCY AND IgG4-RELATED DISEASE IN A PEDIATRIC PATIENT

Background: CARD9 deficiency, a rare immunodeficiency, leads to chronic mucocutaneous and systemic candidiasis. Immunoglobulin G4-related disease (IgG4-RD) is an immune-mediated fibroinflammatory condition that can involve multiple organs. Herein, we present a case where these two rare conditions coexist.

Case presentation: A 14-year-old boy presented with right cervical lymphadenopathy that had persisted for 5 months despite antibiotic treatment. His medical history included hypertension, dilated cardiomyopathy, atrophic right kidney, and growth retardation. Upon admission, with an initial suspicion of malignancy, physical examination revealed growth retardation and multiple bilateral cervical lymphadenopathies, each measuring 2 cm in diameter. Viral serology, Mycobacterium tuberculosis PCR, and tests for Bartonella henselae, tularemia, Histoplasma, and Blastomyces were negative. Laboratory findings showed hypergammaglobulinemia and elevated total IgE, with normal lymphocyte subsets. Ultrasound imaging revealed multiple mediastinal and hilar lymph nodes, as well as conglomerated lymph nodes in the bilateral upper and lower para-aortic areas and the proximal common iliac region. A biopsy of the right cervical lymph node tested positive for Candida species. Computed tomography (CT) angiography of the lower abdomen showed irregular, fibrotic soft tissue density causing significant vascular narrowing and retroperitoneal fibrosis, raising suspicion of IgG4-related disease (IgG4-RD). A biopsy of the retroperitoneal area near the celiac trunk, performed under ultrasound guidance, revealed dense lymphoplasmacytic infiltration, storiform fibrosis, and an increased number of IgG4-positive plasma cells, confirming the diagnosis of IgG4-RD. Additionally, Candida dubliniensis was cultured from the cervical lymphadenopathy tissue biopsy. Whole exome sequencing identified a homozygous R70W mutation in the CARD9 gene.

Conclusion:CARD9 is a critical adaptor molecule in fungal recognition pathways. CARD9 deficiency has been associated with various fungal infections, including superficial or deep dermatophytosis, cutaneous mucormycosis, extrapulmonary aspergillosis, and mucocutaneous or invasive candidiasis. Candida species are the most common pathogens observed in CARD9 deficiency. IgG4-RD is primarily a fibroinflammatory disease that can affect any organ, either simultaneously or at different times. In this case, both fungal hyphae and findings consistent with IgG4-RD were detected in the retroperitoneal biopsy. The disease typically responds well to steroid treatment; however, relapses may occur in high-risk patients, necessitating rituximab therapy for those with active disease