How are organ or tissue threatening autoimmune problems treated in patients with a PID syndrome?
In general, autoimmunity that is organ-threatening should be treated, and the options for treatment are generally the same as for immunocompetent patients. Rigorous exclusion of infection, to the extent that is practically possible, and closer follow-up of the PID syndrome patient, is required. Patients with IgG deficiency as part of their PID syndrome should concomitantly be treated with adequate IgG replacement. While arthralgias may respond somewhat to IVIG therapy, our experience is that true synovitis on exam responds to the same oral DMARDs (hydroxychloroquine, methotrexate, azathioprine, sulfasalazine) used in the treatment of seronegative RA. Biologics should be used with extreme caution only if oral DMARDs fail. In patients with CVID or combined T and B immunodeficiency (CID), TNF-blockade and abatacept, have been successfully used in patients for more aggressive (erosive or refractory to oral DMARDs) arthritis as well as in granulomatous lung and GI disease (infliximab, rituximab) or lymphocytic interstitial lung disease (rituximab in conjunction with azathioprine or mycophenolate mofetil). Rapamycin has also been used CVID, CID, and SCID patients with lymphocytic end-organ disease (lung, liver). CVID or CID syndromes with arthritis, lung, liver, CNS, and/or GI tract underlying CTLA haploinsufficiency or LRBA deficiency may respond well to abatacept, although norovirus and Legionella pneumophila infection were reported in this population. John Cunningham virus infection, cytomegalovirus, and hepatitis B reactivation have been described with use of rituximab therapy, but patients are at a lower risk if on sufficient IVIG replacement. High-dose IVIG given as 1–2 g/kg divided over 3–4 days has also been used successfully in patients with a PID syndrome and inflammatory arthritis or SLE-like disease, including dermatomyositis. This can be an option if immunosuppressive therapies need to be avoided.
