untitled Introduction Lymphoctytic interstitial pneumonitis (LIP) is an interstitial pneumonia, recently included in the radiological/histopatholog- ical classification of the interstitial pneu- monias.1,2 Although known to be AIDS- defining in children, LIP is still thought to be unusual in HIV-positive adults. Materials and meth- ods Between 1996 and 2003, 93 HIV-posi- tive patients with indeterminate chest pathology at Helen Joseph Hospital, Johannesburg were subjected to diagnostic bronchoscopy. Wherever possible, biopsies were taken. The only selection criterion, was an inability to arrive at a diagnosis either clinically or radiologically. Helen Joseph Hospital admits a cross-section of the South African population, namely black, white and Asian patients. A high percentage of admissions are HIV-positive. The findings were evaluated retrospec- tively. Results Thirteen of the 93 patient were found to have LIP. Where the diagnosis came back as LIP histopathologically, the slides were then sent for review to the Pathology Department. Of the 15 cases of LIP origi- nally diagnosed, 13 were confirmed to be LIP, 1 was tuberculosis (TB) and the other was nonspecific interstitial pneumonitis. Discussion LIP is an inflammatory, lymphoprolif- erative non-neoplastic process representing a pulmonary reaction to various external stimuli or systemic diseases.2,3 In 1969, Liebow and Carrington1 classified LIP together with the other interstitial pneu- monias. Subsequently, however, a number of the lesions were found to be low-grade malignant lymphoproliferative diseases. LIP was then excluded from the classifica- tion of interstitial pneumonias. Recently, LIP has been reincluded in the American Thoracic Society and European Respiratory Society 2002 cassification of idiopathic interstitial pneumonia. 1 Pathologically, LIP is a diffuse pul- monary lymphoid proliferation, predomi- nantly in the interstitium, in an alveolar septal distribution.1-5 It appears that a tran- sient lymphocytic alveolitis may develop in some HIV-positive patients, as an immune response to the HIV virus which, in a cer- tain percentage of individuals, evolves into LIP. Both B and T-cells, plasma cells and macrophages are present within the inter- stitial infiltrate. Lymphoid follicules with germinal centres occur. Lung architecture is preserved (Fig.1). Pertinent negative fea- tures are the absence of cell atypia and air- space disease. The lack of tracking along lymphatic routes in the pleura, bron- chovascular bundles and interlobular sep- tae, helps to differentiate LIP from lym- phomas. Lymph node involvement in LIP is now more often recognised than it was in the past. LIP is associated with a number of systemic conditions, typically Sjogren’s syndrome and autoimune diseases. It also occurs post bone marrow transplantation, may be drug induced, e.g. after phenytoin exposure, and may rarely be idiopathic.3 It is twice as common in women. Recently, it has become an AIDS-defining condition in children 6,7, but it has been described as being uncommon or infrequently associat- ed with HIV-positive adults. It was first described in HIV-positive adults, in the Haitian, Afro-Caribbean/Afro-American population in AIDS-related literature between 1983 and 1985.8,9 Sporadic reports of LIP in HIV-positive adults have been published since then.3 Clinically, patients present with pro- gressive cough and dyspnoea. They may, however, remain stable without significant deterioration. Spontaneous resolution may occur. The disease usually follows an indo- lent course and is often an incidental find- ing rather than the patient’s presenting complaint. The mortality of HIV-positive patients afflicted with LIP is not adversely affected.2 LIP is variable in its course. It usually occurs in patients whose CD4 T-cell counts are within the normal range. HIV-positive patients with nonspecific interstitial pneu- monitis usually have lower CD4 T-cell counts, around 200 cells x 106/l,5 but both conditions are reported in patients with normal range CD4 counts. The outcome and prognosis of LIP is significantly affected by its natural history and response to antiretroviral treatment of ORIGINAL ARTICLE 14 SA JOURNAL OF RADIOLOGY • December 2005 Lymphocytic interstitial pneu- monitis (pneumonia) in HIV- positive adults E Joseph MB BCh, FFRad (Diag) G Rubin MB BCh, DA (SA), FCRad (Diag) (SA) Department of Radiology University of the, Witwatersrand Johannesburg J Murray BA, MB BCh, DOH, PGCE (Lond), FFPath National Institute of Occupational Health Johannesburg Fig. 1. A lymphoplasmacytic cellular infiltrate is present in the interstitium forming nodules (A) and expanding the alveolar walls (B). Alveolar spaces (C) are compressed. 12 11/25/05 12:24 PM Page 14 ORIGINAL ARTICLE 15 SA JOURNAL OF RADIOLOGY • December 2005 the underlying HIV infection. In most cases, LIP in HIV-infected patients improves in response to corticosteroids. The literature also suggests that improve- ment of LIP occurs in parallel to a decrease of HIV viral load and with an increase in CD4 cell count.3 Paradoxically, however, the stronger the immune system the more severe the interstitial infiltration is likely to be.3,8 Thus resolution in the absence of anti- retroviral or corticosteroid therapy can herald a worsening of immune suppres- sion. It should be noted, however, that spontaneous clinical and radiographic res- olution without immune deterioration can also occur.2,3,5 The classical chest radiograph presen- tation is of bilateral, predominantly lower- zone nodular or reticular-nodular opaci- ties. Four radiographic categories have been most recently described (Figs 2-5).3 These presenting histories are typical for HIV-positive adults with LIP. The res- piratory symptomatology is minimal and the disease process is indolent. The chest X-ray opacities are con- firmed on high-resolution computed tomography (HRCT) to be centrilobular and subpleural nodules of various sizes. Patchy bilateral and diffuse ground glass opacities on HRCT contribute to the infil- trates seen on chest X-ray, and represent a summation of lymphoid cellular infiltrates within the interstitium, rather than air space disease. CT also helps identify hilar and mediastinal lymphadenopathy, both of which have been found to be more com- mon than previously thought. The high frequency of cysts noted on CT in LIP patients is a consequence of post-obstruc- tive bronchiolar ectasia from infiltrate compressing the bronchioles.1,3,4,5 The differential diagnosis of the radi- ographic findings and patterns of LIP includes infection with Pneumocystis carinii and special stains are done to exclude the presence of the microorganism.2-4 Viral dis- eases such as infectious mononucleosis, fungal pneumonias and TB may mimic LIP, as does post-transplant lymphoprolifera- tive disorder. Nonspecific interstitial pneu- monia is described more commonly in HIV-positive adults, and other benign lym- phoproliferative disorders such as follicular TYPE II. Coarse reticularnodular opacities, nodules, < 3 - 5 mm. Fig. 3. Twenty-five-year-old female patient, presented with dysphagia due to oral candidiasis. She was on anti-TB treatment for 2 months. No respiratory symptoms. TYPE 1. Fine reticularnodular opacities, nodules, < 3 mm. Fig. 2. Fifty-year-old female patient, relatively well, with a non-productive cough of some months’ duration. 12 11/25/05 12:24 PM Page 15 broncholitis are considered together with LIP to be along the same morphological spectrum, with some overlap.3 Differentiation from hypersensitivity pneu- monitis, organising pneumonia and usual interstitial pneumonia needs to be consid- ered. Importantly, the major differential diagnosis is the separation of LIP from low- grade lymphoma, where tracking along lymphoid routes, invasion of parietal pleu- ra and lymph nodes are present, together with destruction of lung architecture and the presence of intranuclear inclusions in B-lymphocytes. In HIV-positive patients LIP is not considered pre-lymphomatous.2,6 In most cases where LIP was followed by the development of lymphoma in an indi- vidual patient, the lesion was subsequently thought to have represented malignant lymphoma from the beginning, rather than LIP. Conclusion Our observation leads us to believe that at least in the South African context, LIP in HIV-positive adults is more common than reports in the world literature suggest. We believe that LIP should be included in the differential diagnosis in an interstitial pneumonitis presenting in the HIV-posi- tive adult population. References 1. Wittram C, Mark F, McLoud TC. CT histological correlation of the ATS/ERS 2002 classification of idiopathic interstitial pneumonias. Radiographics 2003; 23: 1057-1071. 2. Travis WD, Galvin JR. Non-neoplastic pulmonary lymphoid lesions. Thorax 2001; 56: 964-971. 3. Swigris JJ, Berry GJ, Raffin TA, et al. Lymphoid interstitial pneumonia, a narrative review. Chest 2002; 122: 2160-2164. 4. McGuinness G, Scholes JV, Jagirdar JS, et al. Unusual lymphoproliferative disorders in nine adults with HIV or AIDS: CT and pathological findings. Radiology 1995; 197: 59-65. 5. Das S, Miller RF. Lymphocytic interstitial pneumo- nia in HIV infected adults. Sex Transm Infect 2003; 79: 88-93. 6. McGuinness G. Changing trends in the pulmonary manifestations of AIDS. Radiol Clin North Am 1997; 35: 1029-1082. 7. Miller CR. Paediatric aspects of AIDS. Radiol Clin North Am 1997; 35: 1191-1221. 8. Oldham AA, Castillo M, Jacobson FL, et al. HIV- associated lymphocytic interstitial pneumonia: Radiologic manifestations. and pathologic corre- lation. Radiology 1989: 170: 83-87. 9. Heitzman ER. Pulmonary neoplastic and lympho- proliferative diseases in Aids: A review. Thoracic Radiology 1990; 177: 347-351. 16 SA JOURNAL OF RADIOLOGY • December 2005 ORIGINAL ARTICLE TYPE III. Findings of either type I or type II plus at least one patchy opacity. Fig. 4. Forty-year-old female patient. No history available. TYPE IV. Findings of either type I or type II with focal alveolar consolidation resembling pneumonia. Fig. 5. Thirty-five-year-old male patient. Treated for bacterial infection for 1 month. A febrile, persis- tent non-productive cough. Chest X-ray was done for follow-up of his pneumonia. 12 11/25/05 12:24 PM Page 16