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Resolution of lymphocytic interstitial pneumonitis in an HIV infected adult after treatment with HAART
  1. A L Innes1,
  2. L Huang1,3,
  3. S L Nishimura2
  1. 1Division of Pulmonary and Critical Care Medicine, Department of Medicine, San Francisco General Hospital, University of California San Francisco, CA, USA
  2. 2Department of Pathology, San Francisco General Hospital, University of California San Francisco, CA, USA
  3. 3Positive Health Program, Department of Medicine, San Francisco General Hospital, University of California San Francisco, CA, USA
  1. Correspondence to:
 Anh Innes, MD
 Division of Pulmonary and Critical Care Medicine, San Francisco General Hospital, 1001 Potrero Avenue, Room 5K1, San Francisco, CA 94110, USA; ainnesitsa.ucsf.edu

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The optimal therapy for lymphocytic interstitial pneumonitis (LIP) in HIV infected adults is currently unknown. We describe an HIV patient with LIP who improved with protease inhibitor based highly active antiretroviral therapy (HAART) without concurrent corticosteroids.

Case report

A 52 year old heterosexual African-American man, diagnosed with HIV infection 3 years before presentation, was hospitalised for an evaluation of an abnormal chest radiograph obtained during medical screening. His CD4+ lymphocyte count was 198 cells ×106/l, and plasma HIV-1 RNA level >290 000 copies/ml. He denied all symptoms, including cough, shortness of breath, chest pain, fever, and weight loss.

On admission, vital signs included temperature 37.1°C, respiratory rate 16 breaths/minute, and room air oxygen saturation 94%. Complete physical examination was unremarkable, including pulmonary examination. Laboratory data included white blood cell count 5800 ×106/l. Room air arterial blood gas: pH, 7.42; pCO2, 38 mm Hg; pO2, 70 mm Hg; A-a gradient 33 mm Hg. Chest high resolution computed tomography (HRCT) scan revealed diffuse micronodules and right lower lobe consolidation, without pleural effusions or intrathoracic lymphadenopathy (fig 1A). Pulmonary function tests (PFTs) revealed a mild restrictive ventilatory defect and a moderately reduced diffusing capacity (table 1).

Table 1

 Pulmonary function tests

Figure 1

 (A) High resolution computed tomography (HRCT) scan of the chest showing diffuse random nodules with mild septal thickening and right lower lobe consolidation. (B) HRCT scan of the chest after 3 months of HAART demonstrating marked improvement in nodules, septal thickening, and consolidation. Note: The images are from comparable but not identical levels of the lung.

Tuberculosis was considered; multiple induced sputum smears and cultures were negative for acid fast bacilli. Fibreoptic bronchoscopy was performed; bronchoalveolar lavage and transbronchial biopsy smears and cultures were negative for bacteria, fungi, and acid fast bacilli. Mature lymphoid infiltration and proliferation were seen and associated with germinal centre formation and focal invasion and destruction of the bronchial epithelium (fig 2). The histological features are characteristic of LIP.1

Figure 2

 Histopathology showing changes consistent with LIP. (A) Dense lymphocytic infiltrates with widened interstitial septae (arrow). Inset: High magnification of a pink intranuclear inclusion, a so called “Dutcher body.” Bar = 100 µm. (B) High magnification of an airway in which the lymphoid infiltrate has focally invaded the airway epithelium (arrows) and focally disrupted the epithelium (arrowhead). Bar = 100 µm.

Treatment with corticosteroids and/or HAART was considered. Since the patient met criteria for initiating HAART,2 he was started on tenofovir disoproxil fumarate, lamivudine, and lopinavir plus ritonavir. Because he was asymptomatic, concurrent corticosteroids were withheld. After 1 month, his CD4+ lymphocyte count increased to 392 cells ×106/l with a concurrent 100-fold decrease in viral load, now currently undetectable. Repeat PFTs after 2 months on HAART showed significant improvement in all measurements (table 1). Follow up HRCT after 3 months on HAART demonstrated marked improvement (fig 1B). At present, the patient remains on HAART without evidence of pulmonary disease.

Comment

LIP is a common complication of HIV infection in children but is uncommon in adults. Although the clinical, radiographic, and histopathological characteristics of LIP are relatively well described, the aetiology and pathogenesis remain unknown and the optimal treatment is undefined.3 We report a case of a patient with HIV and LIP who improved with HAART alone.

Viral replication and ongoing reaction against lung specific viral strains have been implicated as factors in the aetiology and pathogenesis of LIP.4,5 Mice infected with the LP-BM5 retrovirus (an inducer of murine AIDS) developed interstitial pneumonitis which responded to zidovudine. Treatment resulted in a dose dependent reduction of viral RNA in the lungs of infected, treated mice when compared with untreated mice. Lung biopsies from HIV infected patients with LIP demonstrated oligoclonal expansion of infiltrating T lymphocytes which was significantly greater than that seen in HIV negative LIP and pulmonary MALT lymphomas.5

In light of the possible inflammatory and infectious pathogenesis underlying HIV related LIP, the use of corticosteroids and antiretroviral therapy appears reasonable. However, there are no randomised trials assessing the optimal therapy for LIP. Some patients have responded to corticosteroid treatment, although the optimal dose and duration of this therapy are unknown. Reports of AZT monotherapy have had mixed results; a case using combination nucleoside therapy was successful.6–9 This is the first case report of protease based combination therapy. In the case presented, the increase in CD4+ lymphocyte count and the reduction in viral load indicate an improvement in immune status with concurrent resolution of the pulmonary lymphoproliferative disorder. We suggest that this is likely secondary to HAART, although spontaneous resolution cannot be definitively excluded. In HIV infected patients with LIP, especially if clinically stable, HAART alone without concurrent corticosteroid therapy may be an appropriate initial treatment.

Key messages

  • Lymphocytic interstitial pneumonitis (LIP) is a common complication of HIV infection in children but is uncommon in adults

  • The optimal therapy for LIP in HIV infected adults is currently unknown

  • Our patient responded to a protease inhibitor based HAART therapy with significant improvement in his immune status, pulmonary physiology, and radiology

  • In HIV infected patients with LIP, especially if clinically stable, HAART alone may be an appropriate initial treatment

Contributors

AI, collection of clinical information and specimens, preparation of initial letter, critical revision or letter, approval of final submitted letter; SLN, pathological examination of specimens, preparation of histology figures, preparation of section of letter relating to histological findings, critical revision of letter, approval of final submitted letter; LH, collection of clinical information and specimens, preparation of chest high resolution images and figures, preparation of initial letter, critical revision or letter, approval of final submitted letter.

References

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