British Lung Foundation/United Kingdom Primary Immunodeficiency Network Consensus Statement on the Definition, Diagnosis, and Management of Granulomatous-Lymphocytic Interstitial Lung Disease in Common Variable Immunodeficiency Disorders

Abstract

A proportion of people living with common variable immunodeficiency disorders develop granulomatous-lymphocytic interstitial lung disease (GLILD). We aimed to develop a consensus statement on the definition, diagnosis, and management of GLILD. All UK specialist centers were contacted and relevant physicians were invited to take part in a 3-round online Delphi process. Responses were graded as Strongly Agree, Tend to Agree, Neither Agree nor Disagree, Tend to Disagree, and Strongly Disagree, scored +1, +0.5, 0, -0.5, and -1, respectively. Agreement was defined as greater than or equal to 80% consensus. Scores are reported as mean ± SD. There was 100% agreement (score, 0.92 ± 0.19) for the following definition: "GLILD is a distinct clinico-radio-pathological ILD occurring in patients with [common variable immunodeficiency disorders], associated with a lymphocytic infiltrate and/or granuloma in the lung, and in whom other conditions have been considered and where possible excluded." There was consensus that the workup of suspected GLILD requires chest computed tomography (CT) (0.98 ± 0.01), lung function tests (eg, gas transfer, 0.94 ± 0.17), bronchoscopy to exclude infection (0.63 ± 0.50), and lung biopsy (0.58 ± 0.40). There was no consensus on whether expectant management following optimization of immunoglobulin therapy was acceptable: 67% agreed, 25% disagreed, score 0.38 ± 0.59; 90% agreed that when treatment was required, first-line treatment should be with corticosteroids alone (score, 0.55 ± 0.51).

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

“…This case therefore demonstrates the challenges associated with diagnosis and management of this pulmonary complication and highlights the many questions that remain to be elucidated. While no diagnostic or treatment guidelines exist for GLILD, the British Lung Foundation and United Kingdom Primary Immunodeficiency Network (BLF/UK PIN) recently published consensus statements on the definition, diagnosis, and management of this clinicopathological entity based on the shared clinical experience of over 30 consultants, including immunologists, chest physicians, radiologists, and pathologists, who combined care for over 100 patients with GLILD [11••]. We will highlight some of these BLF/UK PIN consensus statements in our concise literature review on GLILD, with a focus on diagnosis and management as well comparing features of GLILD with those of sarcoidosis.…”

“…Additionally, certain clinical, laboratory, and radiographic features may suggest a diagnosis of GLILD even prior to histological analysis (as discussed in more detail below). To this effect, the BLF/UK PIN suggest the following consensus definition: “GLILD is a distinct clinico-radio-pathological ILD occurring in patients with CVID, associated with a lymphocytic infiltrate and/or granuloma in the lung, and in whom other conditions have been considered and where possible excluded” [11••]. While this consensus definition focuses on patients with CVID, we suggest its extrapolation to include other immunodeficiencies in which GLILD is becoming increasing recognized, such as in the case of our patient with 22q11.2DS.…”

“…Patients with GLILD, however, may often be asymptomatic [11••] as our patient has been over the last 2 years despite disease relapse radiographically. Similarly, pulmonary function testing may vary considerably from being normal to displaying a severe restrictive pattern with reduced diffusion capacity [2••, 11••, 15•]. Thus, a high index of suspicion for GLILD is necessary in the setting of other clinical and radiographic features.…”

“…Some of these features, such as adenopathy and splenomegaly, histologically mimic the granulomatous lymphocytic processes occurring in the lungs, suggesting GLILD may be a pulmonary manifestation of a more multisystem granulomatous lymphocytic inflammatory disease [11••]. Mannina and colleagues compared 34 CVID patients with GLILD to 52 CVID patients without GLILD and found the presence of splenomegaly and polyarthritis to be independent predictors for the development of GLILD [16].…”

“…Small sample sizes and inconsistencies among these studies, however, likely led to disagreement among consultants of the BLF/UK PIN consensus statements regarding further immunological testing beyond that necessary to characterize a patient’s immune deficiency [11••]. On the other hand, this group did agree that genetic mutation analysis should be pursued following a diagnosis of GLILD.…”