Sarcoidosis and Common Variable Immunodeficiency

Abstract

The occurrence of sarcoidosis in combination with common variable immunodeficiency (CVID) has been described in a small number of patients. In these patients, sarcoidosis consisted of lymphadenopathy, mild to moderate pulmonary involvement and hepatosplenomegaly. However, severe and rapidly progressive pulmonary fibrosis in combination with a severe defect of the cellular and humoral immune system has not been described yet. In our patient, defects of the T and B cell system resulted in severe immunodeficiency. The defect of the humoral immune system was characterized by the impairment of specific antibody production in vivo. In addition, hypogammaglobulinemia with missing IgA and IgE along with a marked defect in IgM and IgG production was noted. There was a progressively reduced lymphocyte proliferation in response to T cell mitogens, while proliferation after specific IL-2 stimulation was normal. A Th1 lymphocyte-subset-like profile might thus play a role in the pathogenesis and might form the connecting link between sarcoidosis and CVID. This is the report of a so far new and unique combination of severe immunodeficiency and sarcoidosis also associated with a congenital dysmorphia consisting of a palatal cleft. The findings of the 40 patients with CVID and sarcoidosis reported so far are discussed in order to point out the typical features of patients with this uncommon syndrome.

On the Edge of Facts and Hypotheses

“…Most of the times authors who deal with cases of unknown origin or of obscure etiology summarize their reports with hypotheses or ask for further studies. This is also the case in the paper presented by Gerd-Christian Sutor and Helmut Fabel in this issue of Respiration [1]. …”

Common Variable Immunodeficiency: Etiological and Treatment Issues

“…In patients with X-linked agammaglobulinemia, a non-CVID disorder characterized by an extremely reduced B cell count, the remaining B cells are enriched in autoreactive clones [73]. CVID-associated autoimmune diseases may range across the spectrum of rheumatologic disorders, but granulomatous disease and autoimmune cytopenias are most common [62,74], with the former potentially impacting survival [49,75,76,77,78]. Nonmalignant lymphoproliferative diseases commonly manifest as lymphadenopathy and splenomegaly, and are not uncommon in CVID, with clustering of B cell subsets determined on flow cytometry [79].…”

What Works When Treating Granulomatous Disease in Genetically Undefined CVID? A Systematic Review

“…As reported in seven case reports where steroids were administered as monotherapy, initial association with remission of granulomatous disease was observed, but not maintained after discontinuation of steroid therpy (42). (17,34,47,48,51) These relapses after discontinuation of steroid therapy suggest steroid monotherapy not to have an sustained effect on granulomatous disease. This indicates a potential need for long term therapy, or combination therapy with other immunosuppressive therapy, to maintain granulomatous remission.…”

“…For CVID+EGD, steroid monotherapy was the most frequently reported regimen (21 of 53 treatment courses), with 85.7% of treatment courses scored as effective ( Table 5) (17,19,20,(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40). For CVID+PGD, steroid monotherapy also was the most frequently reported treatment regimen (15 of 64 treatment courses); 66.7% of these treatment courses were associated with remission of granulomatous disease (Table 6) (29,(41)(42)(43)(44)(45)(46)(47)(48)(49)(50). Apart from monotherapy, steroids were frequently prescribed as part of a treatment regimen containing one or more other drugs, both in CVID+EGD and CVID+PGD.…”

“…Overall, these results suggest that steroid therapy is a beneficial therapeutic option, either as monotherapy or as part of combination therapy, for granulomatous disease in CVID. However, various studies reported relapse of granulomatous disease after discontinuation or termination of steroid therapy, in both the CVID+EGD (17,30,34,39,51,52) and CVID+PGD (39,42,47,48,53,54) group.…”