Lymphocytic interstitial pneumonia is a rare idiopathic interstitial pneumonia Overview of Idiopathic Interstitial Pneumonias Idiopathic interstitial pneumonias (IIPs) are interstitial lung diseases of unknown etiology that share similar clinical and radiologic features and are distinguished primarily by the histopathologic... read more 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 Pneumocystis jirovecii Pneumonia Pneumocystis jirovecii is a common cause of pneumonia in immunosuppressed patients, especially in those infected with human immunodeficiency virus (HIV) and in those receiving systemic... read more in HIV-positive children Human Immunodeficiency Virus (HIV) Infection in Infants and Children Human immunodeficiency virus (HIV) infection is caused by the retrovirus HIV-1 (and less commonly by the related retrovirus HIV-2). Infection leads to progressive immunologic deterioration and... read more 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 Infectious Mononucleosis Infectious mononucleosis is caused by Epstein-Barr virus (EBV, human herpesvirus type 4) and is characterized by fatigue, fever, pharyngitis, and lymphadenopathy. Fatigue may persist weeks or... read more , HIV Human Immunodeficiency Virus (HIV) Infection Human immunodeficiency virus (HIV) infection results from 1 of 2 similar retroviruses (HIV-1 and HIV-2) that destroy CD4+ lymphocytes and impair cell-mediated immunity, increasing risk of certain... read more , or other viruses. Evidence of an autoimmune etiology includes its frequent association with Sjögren syndrome Sjögren Syndrome Sjögren syndrome is a relatively common chronic, autoimmune, systemic, inflammatory disorder of unknown cause. It is characterized by dryness of the mouth, eyes, and other mucous membranes ... read more and other disorders (eg, systemic lupus erythematosus Systemic Lupus Erythematosus (SLE) Systemic lupus erythematosus is a chronic, multisystem, inflammatory disorder of autoimmune etiology, occurring predominantly in young women. Common manifestations may include arthralgias and... read more , rheumatoid arthritis Rheumatoid Arthritis (RA) Rheumatoid arthritis is a chronic systemic autoimmune disease that primarily involves the joints. Rheumatoid arthritis causes damage mediated by cytokines, chemokines, and metalloproteases.... read more , Hashimoto thyroiditis Hashimoto Thyroiditis Hashimoto thyroiditis is chronic autoimmune inflammation of the thyroid with lymphocytic infiltration. Findings include painless thyroid enlargement and symptoms of hypothyroidism. Diagnosis... read more ).
Evidence of an indirect viral etiology includes frequent association with immunodeficient states (HIV/AIDS, combined variable immunodeficiency, agammaglobulinemia) 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 of Lymphocytic Interstitial Pneumonia
In adults, lymphocytic interstitial pneumonia causes 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 of Lymphocytic Interstitial Pneumonia
High-resolution CT (HRCT)
For confirmation, biopsy
Diagnosis of lymphocytic interstitial pneumonia 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.
Routine laboratory testing and serum protein electrophoresis(SPEP) are done because about 80% of patients have a serum protein abnormality, most commonly a polyclonal gammopathy and hypogammaglobulinemia, the significance of which is unknown. Other laboratory tests (eg, serologies, immunoglobulin levels, HIV testing) are obtained to identify potential causes of secondary LIP.
Lung biopsy with demonstration of expansion of the alveolar septae due to lymphocytic and other immune cell (plasma cell, immunoblastic, histiocytic) infiltrates is required for diagnosis in adults. 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.
Treatment of Lymphocytic Interstitial Pneumonia
Corticosteroids or cytotoxic drugs
Treatment of lymphocytic interstitial pneumonia is with corticosteroids, cytotoxic drugs, or both, but, as with many other causes of interstitial lung diseases, the efficacy of this approach is unknown.
Prognosis for Lymphocytic Interstitial Pneumonia
The natural history and prognosis of LIP in adults 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.
Lymphocytic interstitial pneumonia is rare overall, but is one of the most common lung disorders in HIV-positive children.
Symptoms and signs tend to be nonspecific.
Do high-resolution CT, bronchoalveolar lavage, and sometimes lung biopsy.
Treat patients with corticosteroids, cytotoxic drugs, or both.