Lymphoid interstitial pneumonia (LIP) is lymphocytic infiltration of the alveolar interstitium and air spaces. The cause is unknown. Symptoms and signs are cough, progressive dyspnea, and crackles. Diagnosis is based on history, physical examination, imaging tests and lung biopsy. Treatment is with corticosteroids, cytotoxic drugs, or both, although efficacy is unknown. Five-year survival is 50 to 66%.
LIP is a rare idiopathic interstitial pneumonia (see Interstitial Lung Diseases: Overview of Idiopathic Interstitial Pneumonias) characterized by infiltration of alveoli and alveolar septa with small lymphocytes and varying numbers of plasma cells. Non-necrotizing, poorly formed granulomas may be present but are usually rare and inconspicuous.
LIP is the most common cause of pulmonary disease after Pneumocystis infection in HIV-positive children and is the AIDS-defining illness in up to one half of HIV-positive children. LIP affects < 1% of adults with or without HIV infection. Women and girls are affected more commonly.
The cause is postulated to be an autoimmune disease or a nonspecific response to infection with Epstein-Barr virus, HIV, or other viruses. Evidence of an autoimmune etiology includes its frequent association with Sjögren syndrome (25% of cases of LIP) and other disorders (eg, SLE, RA, Hashimoto thyroiditis—14% of cases). Evidence of an indirect viral etiology includes frequent association with immunodeficient states (HIV/AIDS, combined variable immunodeficiency, agammaglobulinemia—14% of cases) and findings of Epstein-Barr virus DNA and HIV RNA in lung tissue of patients with LIP. According to this theory, LIP is an extreme manifestation of the normal ability of lymphoid tissue in the lung to respond to inhaled and circulating antigens.
Symptoms and Signs
In adults, LIP causes symptoms of progressive dyspnea and cough. These manifestations progress over months or, in some cases, years and appear at a mean age of 54. Weight loss, fever, arthralgias, and night sweats occur but are less common.
Examination may reveal crackles. Findings such as hepatosplenomegaly, arthritis, and lymphadenopathy are uncommon and suggest an accompanying or alternative diagnosis.
Diagnosis is usually suspected in at-risk patients with compatible symptoms. Imaging tests and sometimes lung biopsy are done.
Chest x-ray shows bibasilar linear reticular or nodular opacities, a nonspecific finding that is present in a number of pulmonary infections. Alveolar opacities, cysts, or both may be present in more advanced disease. HRCT of the chest is done and helps establish the extent of disease, define the hilar anatomy, and identify pleural involvement. HRCT findings are highly variable. Characteristic findings are centrilobular and subpleural nodules, thickened bronchovascular bundles, nodular ground-glass opacities, and cystic structures.
Marked hypoxemia may occur. Bronchoalveolar lavage should be done to rule out infection and may reveal an increased number of lymphocytes.
About 80% of patients have a serum protein abnormality, most commonly a polyclonal gammopathy and hypogammaglobulinemia, the significance of which is unknown. In adults, diagnosis requires lung biopsy with demonstration of expansion of the alveolar septae due to lymphocytic and other immune cell (plasma cell, immunoblastic, histiocytic) infiltrates. Infiltrates appear occasionally along bronchi and vessels but most commonly along alveolar septa. Immunohistochemical staining and flow cytometry must be done on the tissue to distinguish LIP from primary lymphomas. In LIP, the infiltrate is polyclonal (both T and B cells), whereas other lymphomas produce monoclonal infiltrates. Other common findings include germinal centers and multinucleated giant cells with noncaseating granulomas.
The natural history and prognosis of LIP are poorly understood. Spontaneous resolution, resolution after treatment with corticosteroids or other immunosuppressive drugs, progression to lymphoma, or development of pulmonary fibrosis with respiratory insufficiency may ensue. Five-year survival is 50 to 66%. Common causes of death are infection, development of malignant lymphoma (5%), and progressive fibrosis.
Treatment is with corticosteroids, cytotoxic drugs, or both, but, as with many other causes of interstitial lung diseases, the efficacy of this approach is unknown.
Last full review/revision April 2013 by Harold R. Collard