Granulomatous-Lymphocytic Interstitial Lung Disease Mimicking Sarcoidosis

Abstract

Common variable immunodeficiency (CVID) is one of the most common primary immunodeficiency disorders characterized by hypogammaglobulinemia and inadequate antibody response to immunizations. The impaired antibody response occurs due to the failure of B cells to differentiate into plasma cells resulting in low immunoglobulins levels and increased frequency of infections. Granulomatous and Lymphocytic Interstitial Lung Disease (GLILD) is a non-infectious complication of CVID that is seen in 10-30% of cases. GLILD is a multisystem inflammatory disease involving the lungs, lymph node, liver, spleen and gastrointestinal tract that mimics sarcoidosis. This report describes a series of cases who presented with dyspnea, recurrent respiratory infections or autoimmunity and on further evaluation revealed features suggestive of GLILD. There is very limited understanding of GLILD in terms of clinical presentation, the histo-pathological logical findings, and the diagnostic criteria by itself are limited. A diagnosis of GLILD is established in cases of CVID when there is evidence of lymphoproliferation, cytopenia, autoimmune processes and a lung biopsy demonstrating lymphocytic interstitial pneumonia, follicular bronchiolitis, lymphoid hyperplasia, and/or non-necrotizing granulomas. We review the treatment strategies, including replacement of immunoglobulin and agents targeting B and T lymphocytes. Systematic characterization of GLILD cases and long term follow up studies are sorely needed to understand the natural history of GLILD.

Keywords: CVID; Common variable immunodeficiency; GLILD; granulomatous lymphocytic interstitial lung disease; hypogammaglobulinemia.

Figure 1.

(A) HRCT of chest demonstrating upper lope predominant peribronchial micronodular infiltrates with consolidation and fibrosis with some central airway narrowing. Spiculated and flame shaped nodules in a perilymphatic distribution were also noted, along with bilateral hilar and mediastinal calcifies and non-calcified lymph nodes. (B) Splenomegaly was seen on the coronal images. This was interpreted as compatible with sarcoidosis.

Figure 2.

(A Low Power) Right lung endobronchial biopsy shows multiple large non-necrotizing granulomas present in the respiratory submucosa. (B High Power) Shows presence of scattered multinucleated giant cells and minimal, if any, associated lymphocytic infiltrate, giving the appearance of so-called “naked granulomas”, characteristic for sarcoidosis.

Figure 3.

(A Low power) Excisional biopsy of right axillary lymph node shows multiple non-necrotizing granulomas completely effacing the lymph node architecture. Rare multinucleated giant cells are observed (white arrow). (B High Power) The granulomas are formed of tightly packed histiocytes (white arrow) in a background of lymphoid tissue representing the lymph node (black arrow).

Figure 4.

(A) CT of chest demonstrating peri lymphatic nodular infiltrates, airway centered fibrotic changes with traction bronchiectasis. (B) Coronal images also suggested pulmonary hypertension based on increased diameter of the pulmonary artery and bronchial artery collaterals. Splenomegaly was also noted.

Figure 5.

(A) Chest CT scan demonstrated bilateral perilymphatic nodules without significant mediastinal lymphadenopathy. (B) No splenomegaly or axillary adenopathy was present on coronal images.

Figure 6.

Transbronchial biopsies of right middle and lower lobes show large peribronchiolar lymphoid aggregates associated with diffuse interstitial lymphocytic infiltrate with granulomatous inflammation, consistent with granulomatous-lymphocytic interstitial lung disease (GLILD). GMS and AFB special stains were performed to exclude fungal and acid-fast infections, respectively, and were negative.