Lymphocytic interstitial pneumonitis (LIP) is an uncommon condition that belongs to the group of benign pulmonary lymphoid disorders, which includes lymphocytic interstitial pneumonia, follicular bronchiolitis, nodular lymphoid hyperplasia (pseudolymphoma), inflammatory pseudotumor (plasma cell granuloma), Castleman disease (CD), immunoglobulin G4 (IgG4) related disease, and early post-transplant lymphoproliferative disease. These disorders pose a significant radiologic and histologic diagnostic challenge because they may overlap both in the pathogenesis and in histopathological features (1).
LIP is caused by a diffuse proliferation of polyclonal lymphocytes and plasma cells in the lung parenchyma. It is strongly associated with an underlying systemic disease such as human immunodeficiency virus (HIV) infection, common variable immunodeficiency, and Sjögren syndrome, representing an extraglandular manifestation of the latter disease (2). It can also be found in the setting of Legionella pneumonia, human T cell lymphotropic virus type I (HTLV-I) and EBV infections, and diphenylhydantoin use (1).
In Sjögren syndrome a chronic inflammatory autoimmune disease of exocrine glands leading to xerostomia and xeropthalmia, pulmonary involvement occurs in 9% to 20% of cases; ILD is the most common manifestation and carries high morbidity and mortality. The most common form of ILD is nonspecific interstitial pneumonia followed by usual interstitial pneumonitis, LIP, and organizing pneumonia.
The most common clinical manifestations are dry cough and slowly progressive dyspnea which can be associated with pleuritic chest pain. Systemic symptoms such as weight loss, fever, fatigue, arthralgias, and night sweats are less common and the sicca symptoms may predominate in patients with Sjögren syndrome (3,4).
The main radiologic findings in LIP consist of areas of ground-glass attenuation, poorly defined centrilobular nodules, and subpleural small nodules. Other common features are thickening of bronchovascular bundles, interlobular septal thickening, cystic airspaces, and lymph node enlargement. Less common abnormalities include large nodules, emphysema, airspace consolidation, bronchiectasis, architectural distortion, honeycombing, and pleural thickening (4).
The cysts in LIP are thought to result from the peribronchiolar lymphocytic infiltrate compressing the bronchiolar lumen, causing obstruction and stenosis, and subsequently postobstructive bronchiolectasis. Bronchiectasis is a relatively common finding in HIV-positive children with LIP (5).
The definitive diagnosis often requires thoracoscopic or open lung biopsy specimens, except in HIV positive children in whom the characteristic radiographic pattern and symptoms are sufficiently distinctive for a confident diagnosis of LIP without invasive procedures. In the majority of cases, corticosteroids have been the primary therapy, but other immunosuppressive agents, such as cyclophosphamide, chlorambucil, and rituximab have been used.
The prognosis is variable and unpredictable because the results have been controversial, some patients improve without therapy while others progress to advanced interstitial fibrosis despite immunosuppression. In general, death occurs in approximately 33 to 50% of patients within 5 years of diagnosis (3).
Tian X, Yi E, Ryu J. Lymphocytic Interstitial Pneumonia and Other Benign Lymphoid Disorders. Semin Respir Crit Care Med. 21. 2012;33(05):450-61.
Swartz MA, Vivino FB. Dramatic Reversal of Lymphocytic Interstitial Pneumonitis in Sjögren’s Syndrome With Rituximab: JCR J Clin Rheumatol. 2011;17(8):454.