High Inborn Errors of Immunity Risk in Patients with Granuloma

Granuloma etiology includes infections, vasculitis, chemicals, malignancies, lymphoproliferative disorders, and immunological diseases. We hypothesized that patients with granuloma have an underlying primary immunodeficiency disease (PIDD).

We retrospectively enrolled 82 patients with immunological evaluation among 294 biopsy-proven granuloma patients (0- to 20-year-old). At the same time frame, we followed up with 1910 patients in the same age group.

Out of 82 patients, male/female ratio was 45/37. Median age at symptom onset was 5 years (28 days-17.4 years), age of granuloma at diagnosis was 8.6 years (36 days-19.4 years). Common symptoms at disease onset were fever (23.2%), lymphadenopathy (19.6%), abdominal pain (12.2%), and cough (12.2%). Granuloma was frequent in lymph nodes (26.8%), skin (19.5%), lung (13.4%), and bone (11%). Common infectious agents isolated were Mycobacterium spp. (23.2%) and EBV (4.9%). We document PIDD in 76.8% (63/82) of patients. 49.4% (40/81) of immunologically evaluated granuloma patients had hypogammaglobulinemia. Granuloma rate in pediatric PIDD was 3.3%(63/1910). Patients with multiple granulomas (n = 16) had a PIDD diagnosis. Lung involvement was three times more in PIDD. Brain involvement was only seen in PIDD. Fibroadipose tissue and liver involvement were more frequent in patients without documented PIDD and patients whose evaluation was not completed. The mortality rate in PIDD with granuloma was 15.9%, whereas there was no mortality in patients without PIDD.

As documented here, even in a university hospital, the immunologic evaluation ratio is about one-third. We showed high PIDD frequency in children with granuloma, and higher mortality in PIDD with granuloma. Thus, an immunologic evaluation performed meticulously by immunologists is a must for accurate diagnosis and decision of individualized therapeutic options.