NOVEL TREATMENT PARADIGMS IN GRANULOMATOUS-LYMPHOCYTIC INTERSTITIAL LUNG DISEASE ASSOCIATED WITH COMMON VARIABLE IMMUNE DEFICIENCY

Introduction: Granulomatous-lymphocytic interstitial lung disease (GL-ILD) is type of interstitial lung disease that impacts approximately 10% of patients with common variable immunodeficiency (CVID) and significantly increases mortality. There are currently no established guidelines for treatment of GL-ILD. Previous case reports demonstrate efficacy with different immunosuppressive regimens. Case Description: We describe two cases of GL-ILD with novel therapeutic strategies. A 62-year-old man and 63-year-old woman, both with CVID on maintenance immunoglobulin therapy, were diagnosed with GL-ILD based on histopathologic findings and imaging. Rituximab resulted in mild improvement in symptoms for both patients. Sirolimus maintenance therapy was added with further improvement in symptoms, CT imaging and pulmonary function testing parameters. In addition, they were found to have short lymphocyte and granulocyte telomeres. Initial telomere lengths in the first patient were 4.09 kb in lymphocytes and 5.40 kb in granulocytes; in the second patient, lengths were 4.38 kb and 5.79 kb, respectively. Therapy with reseveratol-quercetin 1000 mg twice daily was initiated. After four months, telomere length in the first patient increased to 4.37 kb in lymphocytes and 5.69 kb in granulocytes. Follow-up testing is pending for the second patient. Discussion: The combination of rituximab and sirolimus appears to be effective in treating GL-ILD that is insufficiently responsive to IVIG or rituximab monotherapy. Flavonoid supplementation may increase lymphocyte and granulocyte telomere length, though the clinical impact of this is unknown. Further research is needed to elucidate the relationship between telomere length and GL-ILD, as well as the impact of flavonoid supplementation on telomere length.