Successful Treatment of Granulomatous-lymphocytic Interstitial Lung Disease in a Patient with CTLA-4 Deficiency

Abstract

Common variable immunodeficiency (CVID) causes granulomatous-lymphocytic interstitial lung disease (GLILD) and has a poor prognosis. We herein report a case of GLILD in a 49-year-old woman with CTLA-4 deficiency-associated CVID. The patient presented with dyspnea that had worsened over the past two years. A laboratory examination revealed hypoglobulinemia and pancytopenia. Chest computed tomography showed diffuse infiltrative and granular shadows in the bilateral interstitium. A flow cytometric analysis of blood cells and genetic testing confirmed CTLA-4 deficiency. We performed video-assisted thoracoscopic surgery for the pathological diagnosis of GLILD and to exclude infection and malignancy. Corticosteroid treatment successfully improved the condition of the patient.

Diagnostic testing for interstitial lung disease in common variable immunodeficiency: a systematic review

“…Flow-cytometry analysis including differential cell count was reported in 15 studies verifying significant lymphocytosis in 96/125 (78%) of patients ( 15 – 17 , 22 , 24 , 26 , 35 , 42 , 44 , 57 – 59 , 64 , 65 , 69 ). In addition, where lymphocyte phenotyping was performed this showed a larger proportion of B cells, predominantly CD21low B cells ( 57 , 65 ).…”

“…Pulmonary function tests (PFT) as assessment tools were reported in 40 studies ( 5 , 13 , 15 – 18 , 20 – 24 , 27 , 28 , 30 – 36 , 38 – 45 , 49 , 52 – 54 , 56 , 57 , 59 , 60 , 62 – 64 , 69 ), and included spirometry, measurement of diffusion capacity and assessment of static lung volumes (i.e., total lung capacity (TLC), and residual volume (RV)). Two studies reported PFT abnormalities as potential diagnostic criteria for CVID-ILD in addition to CT ( 64 , 65 ).…”

“…The diagnosis of CVID-ILD was confirmed by biopsy in 31 case reports and series ( 12 – 22 , 26 – 45 ) and was used as an obligatory inclusion criterium for CVID-ILD patients in eleven studies ( 5 , 24 , 25 , 54 , 56 – 60 , 62 , 63 ). Transbronchial biopsy (TBB) was described in 17 studies involving 57 patients, 28 of whom had definitive results, while the remaining patients underwent a supplemental biopsy modality to confirm the diagnosis ( 16 – 18 , 22 , 30 , 31 , 34 , 38 , 42 , 44 , 50 , 58 , 59 , 62 – 64 , 69 ). The most common diagnostic findings were non-necrotizing granulomatous and lymphocytic inflammation.…”

“…The most common diagnostic findings were non-necrotizing granulomatous and lymphocytic inflammation. The use of video-assisted thoracoscopic surgery (VATS) was reported in 17 studies ( 15 , 16 , 21 , 26 , 33 , 34 , 36 , 39 – 41 , 45 , 47 , 57 , 60 , 62 , 63 , 69 ). The results from 81 patients demonstrated the characteristic histological findings of CVID-ILD.…”

“…Genetic evaluations were reported in seventeen studies ( 23 , 25 , 28 , 32 , 39 , 41 , 43 – 45 , 48 , 50 , 56 , 57 , 62 – 64 , 69 ). 48 of 100 reported patients had cytotoxic T lymphocyte antigen 4 (CTLA-4) haploinsufficiency, or transmembrane activator and calcium-modulating cyclophilin ligand interactor (TACI) (TNFRSF13B) or signal transducer and activator of transcription 3 (STAT-3) mutations.…”