Common variable immunodeficiency (CVID) is an immunodeficiency characterized by hypogammaglobulinemia and increased susceptibility to infections. In a subset of patients, non-infectious complications such as autoimmunity, granulomas and lymphoproliferative disease are prominent. Granulomatous disease of the lung (GLILD) is a well-recognized entity but the spleen, liver and lymph nodes can also be affected. There is no standard therapy for granulomatous disease in CVID. A recent retrospective study by Chase et al. suggests that therapy with azathioprine and rituximab may be effective for CVID associated GLILD in adults. We present a CVID patient with granulomatous hepatitis and pulmonary nodules who had resolution of the granulomas after azathioprine and rituximab.
Serial imaging and liver biopsies pre- and post- treatment with azathioprine and rituximab were performed.
A 16-year-old female with CVID presented with a rapidly enlarging liver and spleen shortly after diagnosis. Evaluation for infectious etiologies was negative. Liver biopsy showed lobular hepatitis with granulomatous inflammation composed of abundant T cells and histiocytes. Chest CT demonstrated multiple pulmonary nodules and a calcified granuloma. Therapy with azathioprine and rituximab was initiated. After one year of treatment without adverse effects, there was resolution of lung nodules and repeat liver biopsy showed no abnormalities.
Granulomatous disease in CVID can result in severe organ dysfunction. The etiology of these granulomas is unclear but polyclonal lymphocytic infiltration is a prominent finding. Immunosuppressive therapies have been tried with variable results. This is the first report of efficacious azathioprine and rituximab therapy in the treatment of granulomatous hepatitis in CVID.