Interstitial Lung Disease in Children With Selected Primary Immunodeficiency Disorders-A Multicenter Observational Study

Abstract

Primary immunodeficiencies (PIDs) are rare disorders of the immune system encompassing inborn errors of immunity. Primary antibody deficiencies constitute the largest group of PID with common variable immunodeficiency (CVID) being the most common symptomatic form. Combined immunodeficiencies (CID) accompanied by antibody deficiency can mimic CVID and these patients need the verification of the final diagnosis. Respiratory involvement, especially interstitial lung disease (ILD), poses a relevant cause of morbidity and mortality among patients with PID and in some cases is the first manifestation of immunodeficiency. In this study we present a retrospective analysis of a group of children with primary immunodeficiency and ILD - the clinical, radiological, histological characteristics, treatment strategies and outcomes. Eleven children with PID-related ILD were described. The majority of them presented CVID, in three patients CID was recognized. All patients underwent detailed pulmonary diagnostics. In eight of them histological analysis of lung biopsy was performed. We noted that in two out of 11 patients acute onset of ILD with respiratory failure was the first manifestation of the disease and preceded PID diagnosis. The most common histopathological diagnosis was GLILD. Among the analyzed patients three did not require any immunosuppressive therapy. All eight treated children received corticosteroids as initial treatment, but in some of them second-line therapy was introduced. The relevant side effects in some patients were observed. The study demonstrated that the response to corticosteroids is usually prompt. However, the resolution of pulmonary changes may be incomplete and second-line treatment may be necessary.

Keywords: CVID; GLILD; children; computed tomography; interstitial lung disease; primary immunodeficiency.

Figure 1

(A) Lung high-resolution computed tomography (HRCT): multiple, poorly defined nodules merging in larger areas of ground-glass opacities and consolidations. (B) Lung HRCT: complete regression of pulmonary changes; residual irregular linear opacities are visible. (C) Chest X-ray: diffuse poorly defined nodules creating larger areas of lung consolidations with adjacent areas of ground-glass opacities. Middle and lower zone predominance is clearly marked. (D) Chest X-ray: complete resolution of pulmonary opacities with residual irregular linear thickenings.

Figure 2

Lung high-resolution computed tomography: multiple ground-glass and solid nodules scattered across the lungs, with perylimphatic distribution. Larger clusters of nodules and tree-in-bud pattern are visible peripherally.

Figure 3

Lung high-resolution computed tomography: multiple small pulmonary nodules with perilymphatic distribution (clearly seen along pleural fissures).

Figure 4

Contrast-enhanced lung computed tomography (soft tissue window): marked enlargement of mediastinal and hilar lymph nodes with areas of subpleural lung consolidations.

Figure 5

Lung parenchyma with diffuse interstitial and peribronchiolar lymphocytic infiltration. Microphotograph: hematoxylin and eosin stain.

Figure 6

Diffuse intensive lymphocytic infiltration, both interstitial and around blood vessels. Alveolar spaces are filled with numerous macrophages. Microphotograph: hematoxylin and eosin stain.

Figure 7

Diffuse interstitial inflammation with small focus of organizing pneumonia (black arrow). The surrounding alveoli are filled with numerous macrophages. Microphotograph: hematoxylin and eosin stain.