Lymphocytic Interstitial Pneumonia

Introduction

Background

Lymphocytic interstitial pneumonia (LIP) is a syndrome of fever, cough, and dyspnea, with bibasilar pulmonary infiltrates consisting of dense interstitial accumulations of lymphocytes and plasma cells.

LIP may be associated with autoimmune and lymphoproliferative disorders, including rheumatoid arthritis, Hashimoto thyroiditis, myasthenia gravis, pernicious anemia, autoerythrocyte sensitization syndrome, chronic active hepatitis, common variable immunodeficiency, Sjögren syndrome, allogeneic bone marrow transplantation, lupus, and lymphoma. Pseudolymphoma represents a localized masslike variant of LIP.

LIP is also associated with infection via human immunodeficiency virus (HIV) type 1, Epstein-Barr virus, and human T-cell leukemia virus (HTLV) type 1.

Pathophysiology

Patients may have symptoms related to the above disorders.

HIV-related LIP may be part of a continuum of lymphocytic infiltrative disorders, such as pulmonary lymphoid hyperplasia in children and radiographically clear lymphocytic alveolitis in adults. Patients positive for HLA-DR5 and HLA-DR6 alleles are predisposed to developing a diffuse visceral lymphocytosis syndrome with LIP.

LIP has been reported to occur as part of immune reconstitution syndrome.

Frequency

United States

LIP is an uncommon disease. However, LIP is found in 22-75% of pediatric patients with HIV who have pulmonary disease. In contrast, among adult patients with HIV, LIP accounts for only 3% of HIV-related pulmonary pathology.

International

Small series have been reported in Europe, southwestern Japan, Africa, and the Caribbean basin.

Mortality/Morbidity

Mortality and morbidity data are inexact because of the lack of reported follow-up and the rarity of the disease.

• In the population who does not have HIV infection, half the patients improve with treatment but relapse is common. End-stage fibrosis may follow despite treatment. In the past, high mortality was reported in older patients.
• Patients with HIV-associated LIP display slower decline in CD4⁺ T-cell counts and longer survival than individuals who have HIV infection but do not have LIP.
• Patients with HIV infection but not LIP generally respond to treatment.

Race

• LIP has been found in every race and HIV risk group. Whether racial or geographic predispositions are crucial remains unclear.
• Many reports describe HIV and HTLV type 1–associated LIP among individuals of African ancestry.³
• LIP appears to cluster in southwestern Japan, where HTLV type 1 is endemic.

Sex

• LIP is more common in women when not associated with HIV infection.
• HIV-associated sicca syndrome occurs most often in males.⁴

Age

• Most cases not associated with HIV occur in the fourth and seventh decades of life, at an average age of 56 years.
• LIP is common only in children with HIV. In children with HIV infection, LIP has been designated an AIDS-defining illness by the US Centers for Disease Control and Prevention.