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Lymphocytic interstitial pneumonia in children

Lisa R Young, MD
Section Editor
George B Mallory, MD
Deputy Editor
Alison G Hoppin, MD


Lymphocytic interstitial pneumonia (LIP) remains in the differential diagnosis for interstitial lung disease (ILD) in childhood, although it is actually a form of pulmonary lymphoproliferative disease. Other benign lymphoid disorders of the lung include intraparenchymal lymph nodes, bronchial-associated lymphoid hyperplasia, nodular lymphoid hyperplasia, and angioimmunoblastic lymphadenopathy. It is important to distinguish LIP from these other disorders histologically because they have different treatment regimens and prognostic significance [1].

The epidemiology, pathogenesis, clinical manifestations, diagnosis, and treatment of LIP in infants and children will be presented here. LIP in adults is discussed separately. (See "Lymphoid interstitial pneumonia in adults".)


The incidence and prevalence of LIP in children are not known. LIP most often occurs in association with underlying conditions, such as autoimmune disease and immunodeficiencies [2-5], but also occurs in familial and idiopathic forms (table 1) [6,7]. LIP occurs in a substantial number of children with perinatally acquired HIV if they are not treated with antiretroviral agents [8], and usually presents in the second or third year of life.


LIP is characterized by a diffuse infiltrate of mature and immature lymphocytes, plasma cells, and histiocytes in the alveolar septae and pulmonary interstitium (picture 1). Nodular formation of lymphocytes is commonly seen, occasionally with germinal centers. The cellular infiltrate is polyclonal, including both B and T cells, usually with a predominance of CD8 lymphocytes [9]. Fibrosis is not a typical feature. However, if there is a significant nodular component, it may distort the pulmonary architecture [8]. Further, the blood vessels and airways are not involved in classic LIP. However, some cases demonstrate a spectrum of lymphoid hyperplasia including airway involvement, resulting in findings that may be described as follicular bronchiolitis [10].  


Although the pathogenesis of LIP is unknown, several theories have been suggested. LIP may result from an exaggerated immunologic response to inhaled or circulating antigens and/or caused by a primary infection with Epstein-Barr virus (EBV) [11,12], HIV, or an unknown source [3]. Immune dysregulation may play a role in the pathogenesis of LIP, and in some cases, LIP may be a premalignant state [13]. An immunogenetic basis also has been postulated since HLA-DR5 markers have been found in adults with LIP [14]. Cytokines including TNF-alpha and IL-1 are elevated to a greater extent in children with HIV and LIP than in children with HIV without LIP [15].


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Literature review current through: Sep 2016. | This topic last updated: Jun 23, 2016.
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