FDG PET-CT imaging of therapeutic response in granulomatous lymphocytic interstitial lung disease (GLILD) in common variable immunodeficiency (CVID)

Abstract

Common variable immunodeficiency (CVID) is the most common severe adult primary immunodeficiency and is characterized by a failure to produce antibodies leading to recurrent predominantly sinopulmonary infections. Improvements in the prevention and treatment of infection with immunoglobulin replacement and antibiotics have resulted in malignancy, autoimmune, inflammatory and lymphoproliferative disorders emerging as major clinical challenges in the management of patients who have CVID. In a proportion of CVID patients, inflammation manifests as granulomas that frequently involve the lungs, lymph nodes, spleen and liver and may affect almost any organ. Granulomatous lymphocytic interstitial lung disease (GLILD) is associated with a worse outcome. Its underlying pathogenic mechanisms are poorly understood and there is limited evidence to inform how best to monitor, treat or select patients to treat. We describe the use of combined 2-[(18)F]-fluoro-2-deoxy-d-glucose positron emission tomography and computed tomography (FDG PET-CT) scanning for the assessment and monitoring of response to treatment in a patient with GLILD. This enabled a synergistic combination of functional and anatomical imaging in GLILD and demonstrated a widespread and high level of metabolic activity in the lungs and lymph nodes. Following treatment with rituximab and mycophenolate there was almost complete resolution of the previously identified high metabolic activity alongside significant normalization in lymph node size and lung architecture. The results support the view that GLILD represents one facet of a multi-systemic metabolically highly active lymphoproliferative disorder and suggests potential utility of this imaging modality in this subset of patients with CVID.

Keywords: common variable immunodeficiency; fluorodeoxyglucose positron emission tomography; granulomatous lymphocytic interstitial lung disease; rituximab.

Figure 1

2‐[(18)F]‐fluoro‐2‐deoxy‐d‐glucose positron emission tomography and computed tomography (FDG PET‐CT) pre‐ and 3 months post‐rituximab and mycophenolate treatment. Whole body images acquired at 90 min following 285 MBq 18‐F fluorodeoxyglucose. Maximum intensity projection (MIP) whole body images pretreatment showing widespread abnormal uptake of tracer in the lung parenchyma and lymph nodes above and below the diaphragm (a). MIP images following treatment show near resolution of all the areas of abnormal tracer uptake (b). (c,d) Axial fused PET/CT images at the mid‐thoracic level. The level of FDG uptake is represented by the intensity of colour superimposed upon the CT image. There is a combination of interstitial septal thickening and ill‐defined FDG avid peri‐bronchovascular nodules (c). Post‐treatment images at the same level shows improvement of the nodularity with near resolution of abnormal FDG uptake within them (d). Images at the level of the carina show an enlarged lymph node exhibiting intense abnormal FDG uptake prior to treatment (e). Following treatment the lymph node at this site normalizes in size and shows no abnormal tracer uptake (f). Finally, pretreatment images through the abdomen at the level of the right renal hilum demonstrate numerous enlarged FDG avid retroperitoneal lymph nodes (g) which reduce in size and FDG uptake following treatment (h). [Colour figure can be viewed at wileyonlinelibrary.com.]

Figure 2

Lung function pre‐ and post‐rituximab and mycophenolate treatment. Changes in lung function as a percentage of predicted are demonstrated over time. Initially there is a reduction in lung volume [forced vital capacity (FVC), total lung capacity (TLC)], airflow [forced expiratory volume in 1 s (FEV₁) and peak expiratory flow (PEF)] and gas transfer [total lung capacity for carbon monoxide (TLCO)] from 2012 to 2015. Following initiation of treatment (end 2015) there has been an improvement in these measurements. [Colour figure can be viewed at wileyonlinelibrary.com.]

Figure 3

Number of steps per week pre‐ and post‐rituximab and mycophenolate treatment. This figure indicates the weekly total of steps taken as recorded by the ‘Health app’ present on the patient's own iPhone™ prior to and following treatment. The markers (arrows) indicate the administration of rituximab and initiation of mycophenolate which after a delay of approximately 8 weeks is followed by an increase in the weekly steps taken. [Colour figure can be viewed at wileyonlinelibrary.com.]

Figure 4

Clinical and laboratory risk factors for granulomatous lymphocytic interstitial lung disease (GLILD). The figure shows the major findings involved in this multi‐systemic lymphoproliferative disorder in terms of clinical and imaging findings on the right and associated laboratory biomarkers on the left. The reduced T cell and naive T cell abnormalities, if sufficiently pronounced, would exclude these patients from the revised common variable immunodeficiency (CVID) classifications 5, 6, 7. [Colour figure can be viewed at wileyonlinelibrary.com.]