Rare interstitial lung diseases: a narrative review

Abstract

Background and objective: Interstitial lung diseases (ILDs) encompass over 200 entities. Among them, fibrosing lung diseases, have recently generated special interest due to the emerging therapies for their management. However, it is important to deepen our knowledge of other less prevalent ILD, since many of them are associated with a poor prognosis. This narrative review aims to provide a practical and up-to-date description of some poorly recognized ILD. It covers rare idiopathic interstitial pneumonias and their histologic patterns, genetic disorders with interstitial lung involvement (Hermansky-Pudlak syndrome), and ILD associated with benign proliferation of pulmonary lymphoid tissue, namely follicular bronchiolitis and granulomatous-lymphocytic interstitial lung disease.

Methods: Electronic searches of PubMed and Google Scholar using specific keywords were conducted. Articles underwent screening for relevance, covering review articles, meta-analyses, systematic reviews, case series, prospective studies, society guidelines, editorials in peer-reviewed journals; scientific books on the subject. The data included was limited to English and Spanish publications.

Key content and findings: Despite the low prevalence of these diseases, the increased recognition of radiological patterns, pathological features, and diagnostic procedures, have permitted their better characterization. This review highlights epidemiology, clinical presentation, diagnosis, natural history, and treatment.

Conclusions: Lesser-studied ILD represent a diagnostic and therapeutic challenge and can be frequently misdiagnosed. Also, due to the lack of randomized controlled trials, there are no well-established therapeutic options. Further studies or registries are needed to improve accurate diagnosis and management.

Keywords: Hermansky-Pudlak syndrome (HPS); Rare idiopathic interstitial pneumonias; acute fibrinous organizing pneumonia (AFOP); granulomatous-lymphocytic interstitial lung disease (GLILD).

Figure 1

Lymphoid interstitial pneumonia. (A,B) HRCT views showing scattered randomly distributed thin-walled cysts (arrowheads) and interspersed patches of ground glass-opacification (arrows). (C) The biopsy shows thickened septa with chronic inflammation and the presence of abundant mature lymphocytes (hematoxylin eosin staining, ×2) and (D) CD20 (immunohistochemical staining, ×2). Courtesy of Dr. J. L. Mate. HRCT, high-resolution computed tomography.

Figure 2

Pleuroparenchymal fibroelastosis. (A) Chest radiography shows upper-lobe volume loss, distortion of the pulmonary hila, as well as biapical pleural thickening. (B) Lateral view shows flattening of the chest, observed by the decreased anteroposterior diameter of the rib cage (arrow). (C) A prominent supra-sternal notch due to decreased volume in the upper thoracic region and ongoing weight loss (arrowhead). (D) HRCT and (E) HRCT coronal reconstruction section show pleural thickening and signs of pulmonary fibrosis, mainly in the left upper lobe, with multiple traction bronchiectasis, superimposed with ground-glass opacities. HRCT, high-resolution computed tomography.

Figure 3

Pleuroparenchymal fibroelastosis. (A) HRCT demonstrates pleural thickening and right pneumothorax (arrowheads). (B) Microscopic examination of explanted lung demonstrates dense pleural and subpleural fibrosis with abrupt transition to non-affected pulmonary parenchyma Weigert-Van Gieson stain ×4. Courtesy of Dr. I. Sansano. (C) HRCT after lung transplantation. HRCT, high-resolution computed tomography.

Figure 4

Acute fibrinous organizing pneumonia. (A-C) High-resolution computed tomography showing bilateral consolidations in lower lobes. (D) The biopsy shows mainly intra alveolar fibrin “balls” (black arrows). Hematoxylin-eosin staining ×2. Courtesy of Dr. López-Vilaró.

Figure 5

Hermansky-Pudlak syndrome. (A,B) HRCT shows subpleural reticulation (mainly in left lung), with traction bronchiectasis and honeycombing changes. (C,D) The patient presented acute exacerbation of pulmonary fibrosis. HRCT revealed patchy ground-glass infiltrates superimposed on fibrotic changes. (E) Left lower lobe lung biopsy: unspecific changes, normal areas alternating with others with inflammation and lax fibrosis with collagenized fibrosis. Hematoxylin-eosin staining ×2. Courtesy of Dr. J. L. Mate. HRCT, high-resolution computed tomography.

Figure 6

Follicular bronchiolitis. (A,B) The high-resolution computed tomography shows centrilobular nodules and peribronchiolar opacities with a “tree-in-bud” distribution. (C,D) The lung biopsy reveals lymphocytic infiltrates in germinal centers distributed around the bronchioles and extending to the interlobular septa, avoiding the alveolar septa. Hematoxylin-eosin staining ×4 and ×2. Courtesy of Dr. A. Hernández Gallego.

Figure 7

GLILD. (A,B) HRCT shows multiple bilateral nodular images and ground-glass opacities with peribronchovascular distribution. (C) Lung biopsy. Peribronchiolar and interstitial lymphocytic infiltration in GLILD. There are nodular lymphoid aggregates associated with bronchioles and dense, nodular and diffuse interstitial lymphocytic infiltration. Hematoxylin-eosin staining ×4. Courtesy of Dr. J. L. Mate. (D) HRCT 6 months after starting treatment with immunoglobulins replacement and prednisone showing improvement of ground glass opacities and interstitial infiltrates in the lungs. GLILD, granulomatous-lymphocytic interstitial lung disease; HRCT, high-resolution computed tomography.