What is CVID and describe the rheumatologic manifestations of CVID and how these manifestations are diagnosed
CVID is a heterogenous group of immunodeficiency disorders characterized by quantitative IgG levels less than two standard deviations below the mean for patient’s age, low IgA or IgM levels, and poor specific antibody response to vaccinations. Clinically, patients present with recurrent respiratory tract infections and not uncommonly, aseptic arthritis (30%), cytopenias (ITP in ∼20%, AHA, pernicious anemia), and granulomatous (sarcoid-like) or lymphocytic interstitial lung and/or GI disease (5%–10%). Other organ-specific autoimmunity can occur in the liver (autoimmune hepatitis), endocrine (thyroiditis, diabetes), and skin (psoriasis, vitiligo). Septic arthritis with bacteria (extracellular and/or encapsulated) or Mycoplasma (particularly U. urealyticum ) can also occur.
More single-gene defects have been associated with PID syndromes within nonconsanguineous families who have presented with a CVID phenotype (hCTLA4, LRBA, PIK3, ICOS, CD19, TACI, BAFF-R). However, the majority of patients with the CVID phenotype who have been sequenced do not have a monogenetic explanation for their condition. Since the diagnosis of CVID requires a significant deficiency in circulating IgG, IgG-based serologic tests are unreliable and not used to definitely diagnose autoimmune manifestations. As with rheumatologic evaluation for rheumatic diseases, diagnosis is based on a history which would raise concern for inflammatory arthritis or end-organ damage. Clinical examination may reveal synovitis, alopecia, rashes/vitiligo, focal weakness, hepatosplenomegaly, pulmonary crackles, and so on. The arthritis in CVID most commonly involves large- and medium-sized joints, although involvement of proximal interphalangeal and metacarpophalangeal joints have been also reported. Rheumatoid nodules are not common, though erosions and periarticular osteopenia have been reported. While arthralgias may respond somewhat to IVIG therapy, true arthritis with synovitis on exam responds to the same oral DMARDs (hydroxychloroquine, methotrexate, azathioprine, sulfasalazine) used in the treatment of seronegative RA. While biologics may raise the risk of infection in patients, tumor necrosis factor (TNF)-blockade and rituximab have been successfully used in patients with more aggressive (erosive or refractory to oral DMARDs) arthritis as well as granulomatous (infliximab, rituximab) or lymphocytic interstitial lung disease (rituximab in conjunction with azathioprine or mycophenolate mofetil).
