Granulomatous disease in common variable immunodeficiency

Abstract

Granulomatous disease occurs in 8-22% of patients with common variable immunodeficiency (CVID). We examined the clinical and immunologic information of all 37 of 455 (8.1%) CVID subjects with this complication. The median age at diagnosis of CVID was 26 (2 - 59). 14 had granulomas 1 - 18 years before diagnosis of CVID. In 6 detection of granulomas coincided with this diagnosis; for 17, granulomas were documented later. 54% had lung granulomas, 43% in lymph nodes and 32% in liver. 54% of the group had had autoimmune diseases, mostly immune thrombocytopenia and hemolytic anemia. 24% had had a splenectomy. Nineteen (51.3%) required steroid treatment for granulomas; other immune suppressants were used in some. Over 25 years 28.5% died (median age 37.5), but not significantly more when compared to our CVID patients without granulomas (19.8%). Those with lung granulomas had similar mortality to those with granulomas in other tissues.

Common variable immunodeficiency: Crossroads between infections, inflammation and autoimmunity

“…Crohn's disease, while granulomatous disease is not frequent (10,20). Unlike classical IBD, lamina propria lymphocytes from CVID patients with large bowel enteropathy are skewed toward the production of Th1 proinflammatory cytokines, such as interleukin-12 (IL-12) and gamma interferon (IFN-) rather than TNF-alpha, IL17, or IL23, suggesting that the pathogenesis of the lesions differs at least partially (21).…”

“…In some CVID patients, granulomas resulted in localized, circumscribed diseases, such as njunctivitis and uveitis (20,23).…”

“…It is worthy of note that when granulomas are discovered first, the diagnosis of CVID is often delayed since the patient is considered as being affected by uncomplicated sarcoidosis (20). Therefore, in the presence of systemic granulomatous disease, screening for hypogammaglobulinemia is strongly recommended.…”

“…SMB develop in the germinal centers of lymph-nodes in a T-dependent manner, and their reduction may depend on functional defects in either B or T helper cells. Clinically, a severe reduction in SMB is associated with a higher risk of granulomatous disease and splenomegaly (39), suggesting that a most profound lack of B cell maturation is likely to be associated with the abnormal cellular or cytokine environment that supports granuloma formation (20). CVID patients had significantly fewer Treg than controls, and a low frequency of Treg is clinically associated with splenomegaly (46,47), granulomatous disease (48), and autoimmune cytopenia (49).…”

Enhanced formation of giant cells in common variable immunodeficiency: Relation to granulomatous disease

“…Granulomatous reactions are a recognised feature of common variable immunodeficiency (CVID) with about 20% of patients developing unexplained chronic inflammation, often with granuloma formation, involving many different organs, most commonly the spleen, lymph nodes, liver or lungs (Ardeniz and Cunningham-Rundles, 2009;Bates et al, 2004). Although recurrent bacterial infections due to failure of antibody production is the predominant clinical problem in CVID, the circulating T cells and monocytes in many patients show features of persistent activation (Holm et al, …”