Immunoglobulin (IG) replacement is standard of care for prevention of infectious complications in CVID. Subcutaneous IG (SCIG) is as effective as intravenous IG (IVIG) in reducing infection rate. 20% of CVID patients develop autoimmune complications such as ITP likely due to dysregulated B-cell function. Anti-B-cell therapy is sometimes used for autoimmune complications of CVID, but its ability to worsen hypogammaglobulinemia poses challenge for patients on IG replacement. While IVIG is effective in treating ITP, efficacy of SCIG in ITP is unknown.
Methods:
Quantitative immunoglobulin testing, pulmonary function test (PFT), chest CT, abdominal ultrasound (US), MRI, liver biopsy, flow cytometry, intravenous immunoglobulin (IVIG), and subcutaneous immunoglobulin (SCIG) therapy were used for this study.
Results:
16-year-old female with no history of recurrent infections was diagnosed with CVID due to presentation of ITP and hypogammaglobulinemia. Initial labs: Platelet 1x103cells/μl; IgG 249, IgA <8, IgM 6mg/dL; CD4- 238, CD8- 134, CD19- 3 and NK- 58cells/μl. CVID flow cytometry: undetectable CD27+IgD- cells suggesting poor prognosis. Platelet transfusion led to appropriate improvement and subsequent stabilization of count. IVIG started at 0.5g/kg. She developed headaches, fevers, and neutropenia, which led to transition to SCIG. She later developed hepatosplenomegaly (HSM) confirmed by US and MRI. Liver biopsy: granulomatous infiltration. Evaluation for infectious cause was negative. PFT: depressed oxygen diffusion capacity (DLCO). Chest CT: granulomas in lungs and bibasilar groundglass nodules.
Worsening ITP and IVIG intolerance led to trial of SCIG dose increase to 1g/kg/month for possible immunomodulation and recovery of platelets. Tolerated high dose with no complications. Rituximab and azathiopurine were initiated for granulomatous disease. Despite rituximab, IgG levels increased to 1070 and 1149mg/dL over 2 months. Platelets increased from 49 to 121x103cells/μl and remained stable. Chest CT: improved lung pathology. PFT: normalized DLCO. Abdominal US: stable HSM. Both rituximab and immunomodulatory dosing of SCIG may have contributed to improvement in platelet count.
Conclusions:
Autoimmune complications are responsible for significant morbidity in CVID. This is first reported case of high-dose SCIG that is associated with improvement of platelet count in ITP. For patients who do not tolerate IVIG, higher dose SCIG may be considered for immunomodulatory therapy of autoimmune complications of CVID. Higher dose SCIG may be necessary for optimal infection prevention when anti-B cell agents are used in setting of underlying immunodeficiency.