Lymphocytic Interstitial Pneumonia

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Overview

Lymphocytic interstitial pneumonia (LIP) is a significant cause of pulmonary pathology in HIV-positive pediatric populations, second only to Pneumocystis infection, and serves as an AIDS-defining condition in approximately 50% of these cases. It is characterized by symptoms such as fever, cough, and dyspnea, accompanied by bibasilar pulmonary infiltrates composed of dense interstitial accumulations of lymphocytes and plasma cells. LIP is rare in adults, affecting less than 1% of individuals, irrespective of HIV status, with a higher prevalence observed in females.

The pathogenesis of LIP may involve autoimmune mechanisms or represent a nonspecific immune response to viral infections such as Epstein-Barr virus, HIV, or other viral agents. The association of LIP with autoimmune and lymphoproliferative disorders—including Sjögren syndrome, systemic lupus erythematosus, rheumatoid arthritis, Hashimoto thyroiditis, myasthenia gravis, pernicious anemia, autoerythrocyte sensitization syndrome, chronic active hepatitis, and common variable immunodeficiency (CVID)[1, 2, 3] —supports an autoimmune etiology. Additionally, LIP is linked to allogeneic bone marrow transplantation, lupus, and lymphoma. Pseudolymphoma represents a localized mass-like variant of LIP, and dysproteinemia has been reported in association with LIP.[4, 5]

Viral etiology is suggested by its frequent occurrence in immunocompromised states, including HIV/AIDS,[6, 7, 8]  combined variable immunodeficiency, and agammaglobulinemia. The detection of Epstein-Barr virus DNA, HIV RNA, and human T-cell leukemia virus (HTLV) type 1 in the pulmonary tissue of LIP patients underscores a potential viral influence. Granulomatous lymphocytic interstitial lung disease (GLILD) is a lymphoproliferative complication of CVID, characterized histologically by the presence of both granulomatous and lymphocytic interstitial pneumonitis (LIP), follicular bronchiolitis, and lymphoid hyperplasia.[9]

Diagnostic workup for LIP includes chest radiography, measurement of gas exchange, and histological examination, with laboratory test results generally being nonspecific. Management strategies vary based on symptomatology; asymptomatic and physiologically unaffected patients may not require treatment, whereas symptomatic patients may benefit from supportive care and immunosuppressive therapy, primarily corticosteroids. Cytotoxic therapy has been occasionally employed, and oxygen supplementation may be considered based on blood gas and/or exercise oximetry findings.

For other discussions on pneumonia, see the following:

Pathophysiology and Etiology

HIV-related lymphocytic interstitial pneumonia (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.[10]

LIP may result from an in situ lymphoproliferative response to chronically presented viral antigens or cytokines and/or recruitment of circulating lymphocytes. Mutations of the B-cell CLL/lymphoma 6 (BCL-6 or zinc finger protein 51) gene have been associated with LIP and mucosa-associated lymphoid tissue (MALT) lymphoma.[11, 12] Viruses (alone or in combination) may be responsible.[13, 14, 15] Potential candidates include Epstein-Barr virus (EBV), human T-lymphotropic virus 1 (HTLV-1), and HIV-1.

Epstein-Barr virus

DNA from EBV is detected in pediatric LIP lung biopsy specimens when accompanied by evidence of primary or reactivated EBV infection at the time of biopsy. Elevated titers of antibodies directed against EBV have been reported in adult patients with LIP.

HTLV-1

HTLV-1 is associated with a spectrum of pulmonary lymphoproliferative syndromes, including LIP. Serologic and molecular studies have correlated HTLV-1 infection with LIP.

The viral transactivating protein p40Tax activates the genes for interleukin-2 (IL-2) and its receptor’s high-affinity alpha chain. Lymphocyte proliferation driven by IL-2 may cause lymphoproliferative pulmonary lesions related to HTLV-1.

HIV-1

The nef gene product induces an LIP-like syndrome in a transgenic mouse model.

Expression of interleukin-18 (IL-18) and IFN-gamma-inducible chemokines IP-10 and Mig is increased in LIP tissues compared with controls.[16] The beta-chemokines RANTES, MIP1-alpha and MIP1-beta, chemotactic for T cells, are increased in pediatric LIP lesions compared with controls.[16]

Infiltrating B cells are polyclonal. Infiltrating T cells in HIV-related LIP are more commonly oligoclonal expansions than in HIV-negative LIP.[17]

BCL-6 mutations in HIV-associated LIP do not show features of immunoglobulin variable heavy chain (IgV[H]) hypermutations, whereas HIV-negative LIP BCL-6 mutations do. The immune dysregulation of HIV-associated LIP appears to be a different type than in HIV-negative LIP.

Enterovirus D68

A case of Enterovirus D68 (EV-D68) infection-caused interstitial pneumonia has been reported.[18] EV-D68 infection is associated with upper and lower respiratory tract symptoms such as fever, cough, and wheezing. Radiologic and pathologic evidence of pneumonia without a bacterial etiology suggests that systemic spread of EV-D68 from a respiratory source may be a component in the pathogenesis of subsequent pneumonia.[19]

Epidemiology

Lymphocytic interstitial pneumonia (LIP) is an uncommon disease. In the United States, however, it 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. Small series have been reported in Europe, southwestern Japan, Africa, and the Caribbean basin.

Most cases of LIP 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, lymphocytic interstitial pneumonia has been designated an AIDS-defining illness by the US Centers for Disease Control and Prevention.[20]

LIP is more common in women when not associated with HIV infection. HIV-associated sicca syndrome occurs most often in males.[21]

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-1–associated LIP among individuals of African ancestry.[22] LIP appears to cluster in southwestern Japan, where HTLV-1 is endemic.

Prognosis

The clinical course and prognosis of lymphocytic interstitial pneumonia (LIP) in adults are not well-defined due to the rarity of the disease and limited follow-up data.[23] The disease exhibits a variable trajectory, with durations ranging from 1 month to 11 years. LIP may remain stable for months without intervention, improve spontaneously, or recur, occasionally progressing to end-stage fibrosis or bronchiectasis.

Treatment outcomes vary; in non-HIV infected populations, approximately half of the patients respond to treatment with corticosteroids or other immunosuppressive drugs, though relapses are frequent. Despite treatment, some cases may progress to end-stage fibrosis. Historically, older patients have shown higher mortality rates.

The overall 5-year survival rate for LIP ranges from 50% to 66%.[23] Common causes of mortality include infections, the development of malignant lymphoma (5%), and progressive pulmonary fibrosis. In patients with HIV-associated LIP, there is a slower decline in CD4+ T-cell counts and longer survival compared to those with HIV who do not have LIP.[24]

The potential outcomes for LIP include spontaneous resolution, resolution after immunosuppressive therapy, progression to lymphoma, or the development of pulmonary fibrosis leading to respiratory insufficiency. The variability in clinical outcomes underscores the need for further research and detailed patient monitoring.

Complications

Bronchiectasis has been associated with lymphocytic interstitial pneumonia (LIP). Whether this is due to LIP or the frequent bacterial infections these patients experience remains unclear. Bronchitis and pneumonia commonly occur in these patients, with or without bronchiectasis or cystic changes.

Pulmonary fibrosis may be a long-term complication. Generally, it is indolent. Respiratory failure has been reported, especially in the pediatric population.

Malignant transformation to lymphoma or association with lymphoid malignancy has been reported.

Patient Education

Instructions to patients with lymphocytic interstitial pneumonia (LIP) should include relating all potential toxicities of corticosteroids, including aseptic necrosis of the femoral head, infections, weight gain, hyperglycemia, and other adverse effects. Patients should be instructed to seek medical attention for increased dyspnea or change in sputum.

Clinical Presentation

Patient history

In adults, lymphocytic interstitial pneumonia (LIP) typically presents with gradually progressive symptoms, manifesting primarily as dyspnea and chronic cough.[23] These symptoms tend to develop over months or years, with the average onset at around 54 years of age. Although less common, constitutional symptoms such as weight loss, low-grade fever, arthralgias, and night sweats also may occur.

Physical examination may reveal pulmonary crackles. Less frequently observed findings include hepatosplenomegaly, arthritis, and lymphadenopathy, which may indicate an accompanying or alternative diagnosis. Pleuritic chest pain and hemoptysis are rare. Additionally, symptoms of Sicca syndrome, such as xerophthalmia (dry eyes) and xerostomia (dry mouth), may be present.[21]

Physical examination

Manifestations of associated diseases may be present. Physical findings vary in children and adults.

Physical examination findings in children may include the following:

Physical examination findings in adults may include the following:

Differential Diagnosis

The differential diagnosis of LIP includes the following:

Other problems to be considered include the following[25, 26, 27] :

Laboratory Studies

The diagnosis of lymphocytic interstitial pneumonia (LIP) typically is considered in patients at risk who exhibit compatible clinical symptoms. Diagnostic approaches include imaging studies, laboratory testing, and occasionally, lung biopsy.[23]

A chest X-ray may display bibasilar linear reticular or nodular opacities, which are nonspecific and observed in various pulmonary infections. In more advanced stages of LIP, alveolar opacities and cysts also many be evident.

High-resolution computed tomography (HRCT) of the chest is instrumental in determining the extent of the disease, clarifying the hilar anatomy, and identifying any pleural involvement. HRCT findings can vary widely but often include centrilobular and subpleural nodules, thickened bronchovascular bundles, nodular ground-glass opacities, and cystic structures. Significant hypoxemia may be present in severe cases.

Bronchoalveolar lavage is recommended to exclude infectious etiologies and typically shows an elevated lymphocyte count. Routine laboratory tests, including serum protein electrophoresis (SPEP), are conducted as approximately 80% of patients present with serum protein abnormalities, predominantly polyclonal gammopathy and hypogammaglobulinemia. Serum protein electrophoresis commonly shows polyclonal hypergammaglobulinemia. In pediatric patients with LIP and HIV, lactate dehydrogenase (LDH) levels may be elevated to 300-500 IU/L, approximately half the levels seen in Pneumocystis jiroveci pneumonia; however, this measurement is not helpful in adults. Additional tests such as serologies, immunoglobulin levels, and HIV testing are performed to explore potential secondary causes of LIP, including testing for HIV-1, HTLV-1, EBV, and rheumatoid factor.

For a definitive diagnosis in adults, a lung biopsy is necessary. This biopsy typically reveals expansion of the alveolar septae with infiltrates of lymphocytes and other immune cells such as plasma cells, immunoblasts, and histiocytes. These infiltrates are primarily located along the alveolar septa, though they occasionally may appear along bronchi and vessels. Immunohistochemical staining and flow cytometry are essential for differentiating LIP from primary lymphomas, as LIP is characterized by a polyclonal infiltrate of both T and B cells, in contrast to the monoclonal infiltrates associated with lymphomas. Other histologic features often include germinal centers and multinucleated giant cells within noncaseating granulomas.

 

Imaging Studies

Chest radiography

Bibasilar interstitial or micronodular infiltrates with coalescence into an alveolar pattern are present in lymphocytic interstitial pneumonia (LIP) (see the image below).



View Image

Chest radiograph of lymphocytic interstitial pneumonia in an adult who is HIV positive and has exertional dyspnea, demonstrating characteristic fine b....

In adults, honeycombing is present in up to one third of cases. Hilar adenopathy and pleural effusion are uncommon. Similar infiltrates are seen in children, often with mediastinal widening and hilar enlargement denoting pulmonary lymphoid hyperplasia.

Computed tomography

Computed tomography (CT) scanning can distinguish LIP from other diffuse pulmonary diseases and reveal the extent of the disease. CT scanning demonstrates the degree of fibrosis and may demonstrate bronchiectasis. Cyst characteristics, ground-glass attenuation, poorly defined centrilobular nodules, and focal consolidations are associated with LIP.[28, 29, 30]

Findings may be used to follow disease progression. Long-term follow-up may show the development of fibrosis, bronchiectasis, micronodules, bullae, and/or cystic changes.[31, 32]

Other Tests

Arterial blood gas measurement

Arterial blood gas measurement may be helpful in assessing the severity of illness, but the findings are nonspecific.

Partial pressure of oxygen (PO2) measurement is normal. Profound hypoxemia and/or an increased alveolar to arterial (A-a) oxygen gradient is present. Pulse oximetry is used for screening, but it may not detect an A-a gradient. It should be checked at rest and following exercise. See the A-a Gradient calculator.

Pulmonary function testing

Pulmonary function testing usually demonstrates restriction with a reduced or normal diffusion capacity. Obstructive airway disease occasionally has been reported.

Biopsy and Histologic Findings

Generally, bronchoscopy with transbronchial biopsy is diagnostic if multiple biopsies are obtained from several affected subsegments. Exact sensitivity and specificity of transbronchial biopsy is not reported.

Open lung biopsy is the criterion standard. It may be required in the face of nonspecific or equivocal findings, as with extensive fibrosis.

Histology shows alveolar septal and intra-alveolar infiltration by small, mature, noncleaved polyclonal lymphocytes and plasma cells. Lymphoid follicles or micronodules also may be present. No intrapulmonary lymphadenopathy, vasculitis, or necrosis is observed. Extensive areas of interstitial fibrosis may be present. Noncaseating granulomata have been reported.

Treatment and Management

Asymptomatic and physiologically unaffected patients may not require treatment. Symptomatic patients may require supportive care and immunosuppressive treatment, chiefly corticosteroids.[23] Occasionally, cytotoxic therapy has been used. No controlled treatment trials have been reported.[33]

Consultation with a pulmonologist or thoracic surgeon may be necessary to obtain transbronchial biopsy or open lung biopsy, respectively. In cases associated with HIV infection, consultation with a specialist familiar with HIV care is recommended.

In pediatric patients with HIV, empiric treatment for lymphocytic interstitial pneumonia (LIP) often is initiated based on the findings of subacute dyspnea, mild hypoxemia, and clubbing.

Medications should be used in patients who are symptomatic or physiologically compromised.

Corticosteroids

Corticosteroids are used if the patient is symptomatic and/or has physiologic compromise due to LIP. Risks for infection, osteoporosis, hyperglycemia, weight gain, dermatologic changes, and other potential toxicities should be weighed against any potential benefit.

After the first month of therapy and if disease activity allows it, gradually taper the prednisone dosage. Use the lowest possible dose to suppress this chronic interstitial pneumonitis. Monitor the patient for signs of infection and other toxicities of corticosteroid or immunosuppressive therapy.

Immunoglobulin therapy

One report describes dramatic improvement in LIP associated with common variable immunodeficiency treated with intravenous immunoglobulin without steroids.[34]

Immunosuppressive drugs and alkylating agents

The most widely used second-line treatment options are azathioprine, cyclosporine A and cyclophosphamide.[35]

Alkylating agents should be considered only in cases clearly unresponsive to corticosteroids used in high dosage. These agents should only be prescribed by physicians familiar with usage and toxicities. They generally are prescribed for several weeks at a time; disease manifestations and complete blood count should be monitored.

A retrospective chart review of patients with CVID and GLILD found that combination chemotherapy with rituximab and azathioprine resulted in significant improvement in pulmonary function and radiographic lung abnormalities. Comparison of pre- and post-treatment HRCT scans of the chest identified improvements in total score (P=0.018), presence of pulmonary consolidations (P=0.041), ground-glass opacities (P=0.020), nodular opacities (P=0.024), and both the presence and extent of bronchial wall thickening (P=0.014, 0.026 respectively).[9]

Other agents

Antibiotics are used for associated pulmonary infections.

LIP has been reported to improve with the use of zidovudine alone. Highly active antiretroviral therapy (HAART) may result in improvement or resolution of LIP in some instances.[10]

Bronchodilators may be used for associated wheezing.

Oxygen supplementation

Activity may be limited by exercise-induced oxygen desaturation. Perform exercise oximetry to determine if supplementary oxygen is needed. Consider oxygen supplementation based on blood gas and/or exercise oximetry findings.

Long-term monitoring

Periodically perform pulse oximetry at rest and with exercise. Encourage consistent use of a standardized exercise course, such as a long corridor or several flights of steps.

Obtain periodic chest radiographs and/or chest CT scans, which are used for the following purposes:

Make every attempt to determine if remaining respiratory compromise is related to pulmonary fibrosis or some other pulmonary pathology.

Obtain clinical reevaluation, radiography, and/or chest CT scan if the patient continues to require high-dose steroids. A change in sputum may be the only sign of infection.

Author

Jussi J Saukkonen, MD, Associate Professor, Department of Internal Medicine, Division of Pulmonary/Critical Care Medicine, Boston University School of Medicine, Boston Medical Center

Disclosure: Nothing to disclose.

Specialty Editors

Francisco Talavera, PharmD, PhD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Daniel R Ouellette, MD, FCCP, Associate Professor of Medicine, Wayne State University School of Medicine; Medical Director, Pulmonary Medicine General Practice Unit (F2), Senior Staff and Attending Physician, Division of Pulmonary and Critical Care Medicine, Henry Ford Hospital

Disclosure: Received research grant from: Sanofi Pharmaceutical; AstraZeneca Pharaceutical; aTyr Pharmaceutical; Dompe Pharmaceutical.

Chief Editor

Zab Mosenifar, MD, FACP, FCCP, Geri and Richard Brawerman Chair in Pulmonary and Critical Care Medicine, Professor and Executive Vice Chairman, Department of Medicine, Medical Director, Women's Guild Lung Institute, Cedars Sinai Medical Center, University of California, Los Angeles, David Geffen School of Medicine

Disclosure: Nothing to disclose.

Additional Contributors

Stephen P Peters, MD, PhD, FACP, FAAAAI, FCCP, FCPP, Thomas H Davis Chair in Pulmonary Medicine, Chief, Section on Pulmonary, Critical Care, Allergy and Immunologic Diseases, Professor of Internal Medicine, Pediatrics, and Translational Science, Associate Director, Center for Genomics and Personalized Medicine Research, Wake Forest University School of Medicine; Executive Director of the Respiratory Service Line, Wake Forest Baptist Medical Center

Disclosure: Serve(d) as a speaker or a member of a speakers bureau for: Integrity CE, Merck<br/>Received income in an amount equal to or greater than $250 from: – Array Biopharma, AstraZeneca, Aerocrine, Airsonett AB, Boehringer-Ingelheim, Experts in Asthma, Gilead, GlaxoSmithKline, Merck, Novartis, Ono Pharmaceuticals, Pfizer, PPD Development, Quintiles, Sunovion, Saatchi & Saatichi, Targacept, TEVA, Theron.

References

  1. Zdziarski P, Gamian A, Dworacki G. A case report of lymphoid intestitial pneumonia in common variable immunodeficiency: Oligoclonal expansion of effector lymphocytes with preferential cytomegalovirus-specific immune response and lymphoproliferative disease promotion. Medicine (Baltimore). 2017 Jun. 96(23):e7031. [View Abstract]
  2. Tokuyasu H, Watanabe E, Okazaki R, et al. Sjögren's syndrome with multiple bullae caused by lymphocytic interstitial pneumonia. Lung. 2007 May-Jun. 185(3):187-8. [View Abstract]
  3. Luppi F, Sebastiani M, Silva M, et al. Interstitial lung disease in Sjögren's syndrome: a clinical review. Clin Exp Rheumatol. 2020 Jul-Aug. 38 Suppl 126(4):291-300. [View Abstract]
  4. Greenberg SD, Haley MD, Jenkins DE, Fischer SP. Lymphoplasmacytic pneumonia with accompanying dysproteinemia. Arch Pathol. 1973 Aug. 96(2):73-80. [View Abstract]
  5. Liebow AA, Carrington CB. Diffuse pulmonary lymphoreticular infiltrations associated with dysproteinemia. Med Clin North Am. 1973 May. 57(3):809-43. [View Abstract]
  6. Grieco MH, Chinoy-Acharya P. Lymphocytic interstitial pneumonia associated with the acquired immune deficiency syndrome. Am Rev Respir Dis. 1985 Jun. 131(6):952-5. [View Abstract]
  7. Lin RY, Gruber PJ, Saunders R, Perla EN. Lymphocytic interstitial pneumonitis in adult HIV infection. N Y State J Med. 1988 May. 88(5):273-6. [View Abstract]
  8. Zar HJ. Chronic lung disease in human immunodeficiency virus (HIV) infected children. Pediatr Pulmonol. 2008 Jan. 43(1):1-10. [View Abstract]
  9. Chase NM, Verbsky JW, Hintermeyer MK, et al. Use of combination chemotherapy for treatment of granulomatous and lymphocytic interstitial lung disease (GLILD) in patients with common variable immunodeficiency (CVID). J Clin Immunol. 2013 Jan. 33(1):30-9. [View Abstract]
  10. Ingiliz P, Appenrodt B, Gruenhage F, et al. Lymphoid pneumonitis as an immune reconstitution inflammatory syndrome in a patient with CD4 cell recovery after HAART initiation. HIV Med. 2006 Sep. 7(6):411-4. [View Abstract]
  11. Kurosu K, Weiden MD, Takiguchi Y, et al. BCL-6 mutations in pulmonary lymphoproliferative disorders: demonstration of an aberrant immunological reaction in HIV-related lymphoid interstitial pneumonia. J Immunol. 2004 Jun 1. 172(11):7116-22. [View Abstract]
  12. Wu W, Zhou J, Di LG, Chen H. From lymphocytic interstitial pneumonia to MALT lymphoma of lung: a case report with a 5-year diagnostic dilemma. Int J Clin Exp Pathol. 2015. 8(8):9698-702. [View Abstract]
  13. Morris JC, Rosen MJ, Marchevsky A, Teirstein AS. Lymphocytic interstitial pneumonia in patients at risk for the acquired immune deficiency syndrome. Chest. 1987 Jan. 91(1):63-7. [View Abstract]
  14. Semenzato G, Agostini C. Human retroviruses and lung involvement. Am Rev Respir Dis. 1989 Jun. 139(6):1317-22. [View Abstract]
  15. Setoguchi Y, Takahashi S, Nukiwa T, Kira S. Detection of human T-cell lymphotropic virus type I-related antibodies in patients with lymphocytic interstitial pneumonia. Am Rev Respir Dis. 1991 Dec. 144(6):1361-5. [View Abstract]
  16. Teruya-Feldstein J, Kingma DW, Weiss A, et al. Chemokine gene expression and clonal analysis of B cells in tissues involved by lymphoid interstitial pneumonitis from HIV-infected pediatric patients. Mod Pathol. 2001 Oct. 14(10):929-36. [View Abstract]
  17. Kurosu K, Yumoto N, Rom WN, et al. Oligoclonal T cell expansions in pulmonary lymphoproliferative disorders: demonstration of the frequent occurrence of oligoclonal T cells in human immunodeficiency virus-related lymphoid interstitial pneumonia. Am J Respir Crit Care Med. 2002 Jan 15. 165(2):254-9. [View Abstract]
  18. Matsumoto M, Awano H, Ogi M, et al. A pediatric patient with interstitial pneumonia due to enterovirus D68. J Infect Chemother. 2016 Oct. 22(10):712-5. [View Abstract]
  19. Kreuter JD, Barnes A, McCarthy JE, et al. A fatal central nervous system enterovirus 68 infection. Arch Pathol Lab Med. 2011 Jun. 135(6):793-6. [View Abstract]
  20. Caldwell MB, Oxtoby MJ, Simonds RJ, et al. 1994 Revised classification system for human immunodeficiency virus infection in children less than 13 years of age. MMWR Recomm Rep. 1994 Sep 30. 43(RR-12):1-10.
  21. Couderc LJ, D'Agay MF, Danon F, Harzic M, Brocheriou C, Clauvel JP. Sicca complex and infection with human immunodeficiency virus. Arch Intern Med. 1987 May. 147(5):898-901. [View Abstract]
  22. Rio B, Louvet C, Gessain A, et al. [Adult T-cell leukemia and non-malignant adenopathies associated with HTLV I virus. Apropos of 17 patients born in the Caribbean region and Africa]. Presse Med. 1990 Apr 21. 19(16):746-51. [View Abstract]
  23. Lee J. Lymphocytic Interstitial Pneumonia. Porter RE. The Merck Manual of Diagnosis and Therapy. Rahway, NJ: Merck & Co Inc; Reviewed/Revised July 2023.
  24. Qin L, Wang W, Liu H, et al. Prognosis of nonspecific interstitial pneumonia correlates with perivascular CD4+ T lymphocyte infiltration of the lung. BMC Pulm Med. 2015 Oct 24. 15:127. [View Abstract]
  25. Strimlan CV, Rosenow EC 3rd, Weiland LH, Brown LR. Lymphocytic interstitial pneumonitis. Review of 13 cases. Ann Intern Med. 1978 May. 88(5):616-21. [View Abstract]
  26. Travis WD, Fox CH, Devaney KO, et al. Lymphoid pneumonitis in 50 adult patients infected with the human immunodeficiency virus: lymphocytic interstitial pneumonitis versus nonspecific interstitial pneumonitis. Hum Pathol. 1992 May. 23(5):529-41. [View Abstract]
  27. White DA, Matthay RA. Noninfectious pulmonary complications of infection with the human immunodeficiency virus. Am Rev Respir Dis. 1989 Dec. 140(6):1763-87. [View Abstract]
  28. Barreto MM, Rodrigues RS. Chest computed tomography to evaluate lymphocytic interstitial pneumonia. Radiol Bras. 2020 Sep-Oct. 53(5):V-VI. [View Abstract]
  29. Baldi BG, Carvalho CRR, Dias OM, Marchiori E, Hochhegger B. Diffuse cystic lung diseases: differential diagnosis. J Bras Pneumol. 2017 Mar-Apr. 43(2):140-9. [View Abstract]
  30. Panchabhai TS, Farver C, Highland KB. Lymphocytic interstitial pneumonia. Clin Chest Med. 2016 Sep. 37(3):463-74. [View Abstract]
  31. Becciolini V, Gudinchet F, Cheseaux JJ, Schnyder P. Lymphocytic interstitial pneumonia in children with AIDS: high-resolution CT findings. Eur Radiol. 2001. 11(6):1015-20. [View Abstract]
  32. Johkoh T, Ichikado K, Akira M, et al. Lymphocytic interstitial pneumonia: follow-up CT findings in 14 patients. J Thorac Imaging. 2000 Jul. 15(3):162-7. [View Abstract]
  33. Saito M, Hatakeyama S, Wakabayashi Y, Yanagimoto S, Takemura T, Yotsuyanagi H. A pathologically proven case of adult-onset HIV-related lymphocytic interstitial pneumonia with acute exacerbation treated with steroid and antiretroviral therapy. J Infect Chemother. 2015 Dec. 21(12):868-72. [View Abstract]
  34. Arish N, Eldor R, Fellig Y, et al. Lymphocytic interstitial pneumonia associated with common variable immunodeficiency resolved with intravenous immunoglobulins. Thorax. 2006 Dec. 61(12):1096-7. [View Abstract]
  35. Schupp JC, Kohler T, Muller-Quernheim J. Usefulness of cyclophosphamide pulse therapy in interstitial lung diseases. Respiration. 2016. 91(4):296-301. [View Abstract]

Chest radiograph of lymphocytic interstitial pneumonia in an adult who is HIV positive and has exertional dyspnea, demonstrating characteristic fine bibasilar interstitial markings

Chest radiograph of lymphocytic interstitial pneumonia in an adult who is HIV positive and has exertional dyspnea, demonstrating characteristic fine bibasilar interstitial markings