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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: Nov 2017. | This topic last updated: Jun 23, 2016.
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  1. Fan LL. Pediatric interstitial lung disease. In: Interstitial Lung Disease, Schwarz MI, King TE (Eds), BC Decker, Hamilton 2003. p.134.
  2. Lovell D, Lindsley C, Langston C. Lymphoid interstitial pneumonia in juvenile rheumatoid arthritis. J Pediatr 1984; 105:947.
  3. Hepburn B. Interstitial lung disease in childhood rheumatic disorders. In: Interstitial Lung Disease in Children, Laraya-Cuasay LR, Hughes WT (Eds), CRC Press, Boca Raton 1988. Vol 3, p.114.
  4. Joshi VV, Oleske JM, Minnefor AB, et al. Pathologic pulmonary findings in children with the acquired immunodeficiency syndrome: a study of ten cases. Hum Pathol 1985; 16:241.
  5. Church JA, Isaacs H, Saxon A, et al. Lymphoid interstitial pneumonitis and hypogammaglobulinemia in children. Am Rev Respir Dis 1981; 124:491.
  6. Rogers BB, Browning I, Rosenblatt H, et al. A familial lymphoproliferative disorder presenting with primary pulmonary manifestations. Am Rev Respir Dis 1992; 145:203.
  7. Franchi LM, Chin TW, Nussbaum E, et al. Familial pulmonary nodular lymphoid hyperplasia. J Pediatr 1992; 121:89.
  8. Andiman WA, Shearer WT. Lymphoid interstitial pneumonitis. In: Pediatric AIDS: The Challenge of HIV Infection in Infants, Children, and Adolescents, 3rd, Pizzo PA, Wilfert CM (Eds), Lippincott Williams & Wilkins, Baltimore 1998. p.323.
  9. Koss MN. Pulmonary lymphoid disorders. Semin Diagn Pathol 1995; 12:158.
  10. Dishop MK. Diagnostic Pathology of Diffuse Lung Disease in Children. Pediatr Allergy Immunol Pulmonol 2010; 23:69.
  11. Andiman WA, Eastman R, Martin K, et al. Opportunistic lymphoproliferations associated with Epstein-Barr viral DNA in infants and children with AIDS. Lancet 1985; 2:1390.
  12. Montagnier L, Gruest J, Chamaret S, et al. Adaptation of lymphadenopathy associated virus (LAV) to replication in EBV-transformed B lymphoblastoid cell lines. Science 1984; 225:63.
  13. Laraya-Cuasay LR. Lymphoproliferative disorders of the lung. In: Interstitial Lung Disease in Children, Laraya-Cuasay LR, Hughes WT (Eds), CRC Press, Boca Raton 1988. Vol 3, p.151.
  14. Pitt J. Lymphocytic interstitial pneumonia. Pediatr Clin North Am 1991; 38:89.
  15. Arditi M, Kabat W, Yogev R. Serum tumor necrosis factor alpha, interleukin 1-beta, p24 antigen concentrations and CD4+ cells at various stages of human immunodeficiency virus 1 infection in children. Pediatr Infect Dis J 1991; 10:450.
  16. Joshi VV, Kauffman S, Oleske JM, et al. Polyclonal polymorphic B-cell lymphoproliferative disorder with prominent pulmonary involvement in children with acquired immune deficiency syndrome. Cancer 1987; 59:1455.
  17. Katz BZ, Berkman AB, Shapiro ED. Serologic evidence of active Epstein-Barr virus infection in Epstein-Barr virus-associated lymphoproliferative disorders of children with acquired immunodeficiency syndrome. J Pediatr 1992; 120:228.
  18. Bhoopat L, Rangkakulnuwat S, Okonogi R, et al. Cell reservoirs of the Epstein-Barr virus in biopsy-proven lymphocytic interstitial pneumonitis in HIV-1 subtype E infected children: identification by combined in situ hybridization and immunohistochemistry. Appl Immunohistochem Mol Morphol 2010; 18:212.
  19. Toro AA, Altemani AM, da Silva MT, et al. Epstein-Barr virus (EBV) gene expression in interstitial pneumonitis in Brazilian human immunodeficiency virus-1-infected children: is EBV associated or not? Pediatr Dev Pathol 2010; 13:184.
  20. Malamou-Mitsi V, Tsai MM, Gal AA, et al. Lymphoid interstitial pneumonia not associated with HIV infection: role of Epstein-Barr virus. Mod Pathol 1992; 5:487.
  21. Mueller GA, Pickoff AS. Pediatric lymphocytic interstitial pneumonitis in an HIV-negative child with pulmonary Epstein-Barr virus infection. Pediatr Pulmonol 2003; 36:447.
  22. Pfleger A, Eber E, Popper H, Zach MS. Chronic interstitial lung disease due to Epstein-Barr virus infection in two infants. Eur Respir J 2000; 15:803.
  23. Milner JD, Vogel TP, Forbes L, et al. Early-onset lymphoproliferation and autoimmunity caused by germline STAT3 gain-of-function mutations. Blood 2015; 125:591.
  24. Griese M, Zarbock R, Costabel U, et al. GATA2 deficiency in children and adults with severe pulmonary alveolar proteinosis and hematologic disorders. BMC Pulm Med 2015; 15:87.
  25. Svobodova T, Mejstrikova E, Salzer U, et al. Diffuse parenchymal lung disease as first clinical manifestation of GATA-2 deficiency in childhood. BMC Pulm Med 2015; 15:8.
  26. Lo B, Zhang K, Lu W, et al. AUTOIMMUNE DISEASE. Patients with LRBA deficiency show CTLA4 loss and immune dysregulation responsive to abatacept therapy. Science 2015; 349:436.
  27. Scott GB, Hutto C, Makuch RW, et al. Survival in children with perinatally acquired human immunodeficiency virus type 1 infection. N Engl J Med 1989; 321:1791.
  28. Zar HJ. Chronic lung disease in human immunodeficiency virus (HIV) infected children. Pediatr Pulmonol 2008; 43:1.
  29. Katkin JP, Hansen TN, Langston C, Hiatt PW. Pulmonary manifestations of AIDS in children. Semin Pediatr Infect Dis 1990; 1:40.
  30. Rubinstein A, Morecki R, Goldman H. Pulmonary disease in infants and children. Clin Chest Med 1988; 9:507.
  31. Fan LL, Mullen AL, Brugman SM, et al. Clinical spectrum of chronic interstitial lung disease in children. J Pediatr 1992; 121:867.
  32. Marks MJ, Haney PJ, McDermott MP, et al. Thoracic disease in children with AIDS. Radiographics 1996; 16:1349.
  33. Fan LL, Kozinetz CA. Factors influencing survival in children with chronic interstitial lung disease. Am J Respir Crit Care Med 1997; 156:939.
  34. Marquis JR, Berman CZ, DiCarlo F, Oleske JM. Radiographic patterns of PLH/LIP in HIV positive children. Pediatr Radiol 1993; 23:328.
  35. Schneider RF. Lymphocytic interstitial pneumonitis and nonspecific interstitial pneumonitis. Clin Chest Med 1996; 17:763.
  36. Bragg DG, Chor PJ, Murray KA, Kjeldsberg CR. Lymphoproliferative disorders of the lung: histopathology, clinical manifestations, and imaging features. AJR Am J Roentgenol 1994; 163:273.
  37. Lynch DA, Hay T, Newell JD Jr, et al. Pediatric diffuse lung disease: diagnosis and classification using high-resolution CT. AJR Am J Roentgenol 1999; 173:713.
  38. Kurland G, Noyes BE, Jaffe R, et al. Bronchoalveolar lavage and transbronchial biopsy in children following heart-lung and lung transplantation. Chest 1993; 104:1043.
  39. Rothenberg SS, Wagner JS, Chang JH, Fan LL. The safety and efficacy of thoracoscopic lung biopsy for diagnosis and treatment in infants and children. J Pediatr Surg 1996; 31:100.
  40. Kurland G, Deterding RR, Hagood JS, et al. An official American Thoracic Society clinical practice guideline: classification, evaluation, and management of childhood interstitial lung disease in infancy. Am J Respir Crit Care Med 2013; 188:376.
  41. Fan LL, Kozinetz CA, Wojtczak HA, et al. Diagnostic value of transbronchial, thoracoscopic, and open lung biopsy in immunocompetent children with chronic interstitial lung disease. J Pediatr 1997; 131:565.
  42. Rubinstein A, Bernstein LJ, Charytan M, et al. Corticosteroid treatment for pulmonary lymphoid hyperplasia in children with the acquired immune deficiency syndrome. Pediatr Pulmonol 1988; 4:13.
  43. Desmarquest P, Tamalet A, Fauroux B, et al. Chronic interstitial lung disease in children: response to high-dose intravenous methylprednisolone pulses. Pediatr Pulmonol 1998; 26:332.
  44. Fan LL, Deterding RR, Langston C. Pediatric interstitial lung disease revisited. Pediatr Pulmonol 2004; 38:369.
  45. Waters KA, Bale P, Isaacs D, Mellis C. Successful chloroquine therapy in a child with lymphoid interstitial pneumonitis. J Pediatr 1991; 119:989.
  46. Campos JM, Simonetti JP. Treatment of lymphoid interstitial pneumonia with chloroquine. J Pediatr 1993; 122:503.
  47. Hallowell RW, Danoff SK. Interstitial lung disease associated with the idiopathic inflammatory myopathies and the antisynthetase syndrome: recent advances. Curr Opin Rheumatol 2014; 26:684.
  48. Sharland M, Gibb DM, Holland F. Respiratory morbidity from lymphocytic interstitial pneumonitis (LIP) in vertically acquired HIV infection. Arch Dis Child 1997; 76:334.
  49. Sheikh S, Madiraju K, Steiner P, Rao M. Bronchiectasis in pediatric AIDS. Chest 1997; 112:1202.