Granulomatous‐lymphocytic interstitial lung disease as the first manifestation of common variable immunodeficiency

Abstract

Common variable immunodeficiency (CVID) is one of the most common primary immunodeficiencies, which is characterized by reduced serum immunoglobulin levels and B-lymphocyte dysfunction. There are many clinical manifestations of this disease, the most common of which are recurrent respiratory tract infections. Among the most recently recognized autoimmune manifestation of CVID is a disease described as granulomatous-lymphocytic interstitial lung disease (GLILD), where CVID coexists with a small airway lymphoproliferative disorder, mimicking follicular bronchiolitis, or lymphocytic interstitial pneumonitis (LIP) on histology specimens. We herein describe the clinical and radiological features of GLILD in a 55-year-old woman where the diagnosis of CVID was actively pursued and eventually confirmed after her lung biopsy showed characteristic features of GLILD. The patient had dramatic response to treatment with IVIG and corticosteroids for 3 months followed by Mycophenolate mofetil for maintenance therapy. K E Y W O R D Scommon variable immunodeficiency, follicular bronchiolitis, granulomatous-lymphocytic interstitial lung disease, lymphoproliferative disorder, lymphocytic interstitial pneumonitis | I NTR ODU CTI ONCommon variable immunodeficiency (CVID) is estimated to affect 1/25,000 to 1/50,000 individuals worldwide. Approximately, 20% of CVID patients have associated autoimmune diseases, including hemolytic anemia, thrombocytopenia, neutropenia, rheumatoid arthritis, vitiligo, pyoderma gangrenosum, and others. [1][2][3][4][5][6][7] Granulomatous-lymphocytic interstitial lung disease (GLILD) is a pathologic diagnosis characterized by granulomas with benign lymphoproliferative infiltrates involving diffuse areas of the pulmonary parenchyma. [8][9][10] It is the most common cause of diffuse parenchymal lung disease in patients with CVID, occurring in approximately 10%-30% of all patients. 8-13 GLILD can be detected on lung biopsies many years prior to the diagnosis of CVID, 14 and is often associated with other organ granulomas, splenomegaly, adenopathy, and autoimmune cytopenias. 12,15 | C AS E PR ES ENTATI ONA 55-year-old woman was evaluated in the pulmonary clinic for progressively worsening dyspnea on exertion for 3 months. Her symptoms began with a dry cough, which failed to respond to two courses of antibiotics that were prescribed by her primary care physician for a possible respiratory tract infection. Her medical history was significant for Hashimoto's thyroiditis, Type I diabetes mellitus and Morphea-form skin rash. She had no history of smoking, recurrent infections, or chronic respiratory diseases, with no significant occupational or Figure 1) showed bilateral lower lung zone patchy and nodular opacities. Her pulmonary function test showed mild restriction with a moderately reduced diffusing capacity of the lung for carbon monoxide (DLCO). On chest computed tomography (CT) scan (Figure 2) diffuse bilateral ground glass opacities with bulky mediastinal and hilar lymphadenopathy was noted. Other ...

Efficacy of mycophenolate on lung disease and autoimmunity in children with immunodeficiency

“…Pulmonary disease is a frequent complication of PIDs. While for bronchiectasis there is common agreement on treatment, which focuses on prevention of infections, adequate Ig trough levels, swift antibiotic treatment in case of infection and chest physiotherapy, for GLILD there was until recently no consensus on therapy and very little literature available for reference . A recent statement from the British Lung Foundation/United Kingdom Primary Immunodeficiency Network has indeed established a consensus on the definition, diagnosis and treatment of GLILD in CVID patients.…”

“…Until recently its efficacy on other immunological complications such as GLILD was only anecdotal. 6 We here present three patients diagnosed with PID during childhood who developed severe autoimmune manifestations in the course of the disease and showed good response to mycophenolate both for cytopenias and, notably, for GLILD.…”

“…Mycophenolate is an inhibitor of lymphocyte proliferation and is used to treat chronic autoimmune cytopenias. Until recently its efficacy on other immunological complications such as GLILD was only anecdotal …”

Granulomatous-Lymphocytic Interstitial Lung Disease in 22q11.2 Deletion Syndrome: a Case Report and Literature Review

“…Moreover, GLILD may even be the first manifestation of an underlying PID [42•]. To our knowledge, this is only the second reported case of GLILD in a 22q11.2DS patient.…”

Approach to Peribronchovascular Disease on CT

“…Although frequently small, nodules can be large in size between 3 and 12 mm with ill-defined borders. 28,30 Patchy ground-glass opacities and, less commonly, peribronchovascular consolidation can occur. 28,31 Adenopathy is not a frequent feature.…”