Lymphoid Interstitial Pneumonia (LIP)

In adults, lymphoid interstitial pneumonia typically causes progressive dyspnea and cough. These manifestations progress over months or, in some cases, years and appear at a mean age of 47 years (1). Weight loss, fever, arthralgias, pleuritic chest pain, 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 (eg, lymphoma).

• High-resolution CT (HRCT)

• Laboratory testing for identification of underlying disorder

• Pulmonary function tests

• For confirmation, biopsy

Diagnosis of lymphoid interstitial pneumonia is usually suspected in at-risk patients with compatible symptoms. Imaging tests and sometimes lung biopsy are performed.

Chest radiograph 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 should be performed to 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.

Pulmonary function testing reveals a restrictive lung disease pattern with evidence of reduced lung volumes (total lung capacity and forced vital capacity) and reduced diffusing capacity of the lung for carbon dioxide (DLCO).

Lymphoid Interstitial Pneumonia

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This image courtesy of Tami Bang, MD.

Marked hypoxemia may occur.

Bronchoalveolar lavage should be done to exclude infection and may reveal an increased number of lymphocytes.

Routine laboratory testing and serum protein electrophoresis (SPEP) are done because approximately 80% of patients can have a dysproteinemia (serum protein abnormality), most commonly a polyclonal gammopathy or hypogammaglobulinemia, the significance of which is unknown (1). Other laboratory tests (eg,, antinuclear antibodies [ANA], anti-Ro/SSA, anti-La/SSB, rheumatoid factor [RF], immunoglobulin levels including immunoglobulin subclasses, HIV testing) are obtained to identify potential causes of secondary lymphoid interstitial pneumonia.

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 lymphoid interstitial pneumonia from primary lymphomas. In lymphoid interstitial pneumonia, the infiltrate is polyclonal (both T cells and B cells), whereas other lymphomas produce monoclonal infiltrates. Other common findings include germinal centers and multinucleated giant cells with noncaseating granulomas.

• Glucocorticoids or cytotoxic drugs

Treatment of lymphoid interstitial pneumonia, when indicated for symptomatic and/or progressive disease, is with glucocorticoids. Cytotoxic drugs may be added to or used instead of glucocorticoids for patients who have progressive disease despite ongoing treatment, experience adverse effects from glucocorticoids, or require prolonged treatment due to relapsing disease. As with many other causes of interstitial lung diseases, this approach has not been studied in randomized trials and is largely based on prior treatment experience. Treatment is also directed to the cause of lymphoid interstitial pneumonia if present (eg, HIV, immunodeficiency, autoimmunity).

The natural history and prognosis of lymphoid interstitial pneumonia in adults are poorly understood. Spontaneous resolution, resolution after treatment with glucocorticoids or other immunosuppressive medications, progression to lymphoma, or development of pulmonary fibrosis with respiratory insufficiency may ensue. The median survival is estimated to be 11.5 years (1). Common causes of death are infection, development of malignant lymphoma (5%), and progressive fibrosis.