Immune Restoration Syndrome Manifested by Pulmonary Sarcoidosis

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Radiologic-Pathologic Conferences
of Boston University Medical Center

Immune Restoration Syndrome Manifested by Pulmonary Sarcoidosis

Conrad Wittram¹^,2, Jane Fogg³ and Harrison Farber⁴

^¹ Department of Radiology, Section of Thoracic Radiology, Boston University Medical Center, Atrium 2, 88 E. Newton St., Boston, MA 02118.
^² Department of Radiology, Section of Thoracic Radiology, Massachusetts General Hospital and Harvard University, FND 202, 55 Fruit St., Boston, MA 02114.
^³ Dimock Community Health Center, 55 Dimock St., Roxbury, MA 02119.
^⁴ Pulmonary Center, Boston University Medical Center, 715 Albany St., R-304, Boston, MA 02118.

Received February 2, 2001; accepted after revision May 8, 2001.

Address correspondence to C. Wittram.

Introduction

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Introduction
References

A 45-year-old women presented with a 4-month history of intermittentchest pain and increasing dyspnea with effort. She had no accompanyinghistory of fever, chills, cough, sputum production, or othersymptoms. She had been previously diagnosed, during an admissionfor cryptococcal meningitis, as having HIV infection and hadbeen treated with highly active antiretroviral therapy for 16months. The most recent serum values before onset of the dyspneaand chest pain were a viral load of less than 50 copies/mL anda CD4 cell count of 550 cells/mm³.

Her examination was remarkable only for a few rales from bothlung bases. Pulmonary function tests showed a mild decreasein the diffusing capacity of carbon monoxide. The oxygen saturationon room air was 99% at rest, 95-97% with walking, and 92-93%climbing stairs; the latter activity was associated with dyspnea.

Chest radiography revealed normal mediastinal outlines and adiffuse small nodular interstitial abnormality. Unenhanced helicalCT of the thorax showed a normal mediastinum with no lymphadenopathyor evidence of pleural or skeletal disease. High-resolutionCT revealed nodules having peribronchovascular and fissuraldistributions (Fig. 1A). Open lung biopsy of the right upperand middle lobes was performed; pathologic examination of thetwo 4 x 1 x 1 cm lung-tissue samples revealed numerous noncaseatinggranulomas and associated multinucleated giant cells. Parenchymalfibrosis and thickened septa were also seen. Histopathologicfindings on stains for acid-fast bacilli and fungi were negative(Fig. 1B). The final clinicopathologic diagnosis was sarcoidosis.The patient showed marked clinical improvement with prednisone.

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Fig. 1A. —45-year-old woman with pulmonary sarcoidosis as manifestation of immune restoration syndrome. High-resolution CT scan of lungs at level of bronchus intermedius reveals ill-defined small nodular opacities in peribronchovascular and fissural distribution. Small amount of interlobular septal thickening (arrow) is seen.

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Fig. 1B. —45-year-old woman with pulmonary sarcoidosis as manifestation of immune restoration syndrome. Photomicrograph of histopathologic specimen shows noncaseating tightly formed granulomas and epithelioid histiocytes and lymphocytes. Perilymphatic distribution of granulomas is evident. Normal lung parenchyma and small region of fibrotic interlobular septal thickening (arrow) are seen. (H and E, x125)

Highly active antiretroviral therapy has profoundly affectedthe treatment of HIV infection. The sustained suppression ofviral replication has been shown to reduce mortality and toprolong life in patients with HIV infection [1]. Peripheralblood studies reveal a quantitative and qualitative immune restoration,an indicator of which is an increase in the CD4 cell blood count.Sarcoidosis affecting the lungs after the initiation of highlyactive antiretroviral therapy has been previously reported [2, 3].In the cited reports, diagnosis was made after transbronchialbiopsy; our pathologist had two large samples of lung tissue,allowing a more confident diagnosis of this disease.

Sarcoidosis is a disease of unknown cause resulting in the formationof distinctive granulomas. In a person with HIV infection, itis hypothesized that highly active antiretroviral therapy leadsto a rapid increase in T lymphocytes and restoration of pathogen-specificimmunity. In some patients, sarcoidosis is a manifestation ofthis immune restoration. Our patient showed the characteristicfeatures of sarcoidosis, which is the presence of noncaseatinggranulomas in a perilymphatic distribution [4]. The high-resolutionCT findings in our patient revealed small nodules in a peribronchovascular distribution,along the fissures and interlobular septal thickening. Our patientdid not have mediastinal lymphadenopathy, and three of the four previouscase reports of sarcoidosis in immune restoration syndrome alsodid not have this manifestation of sarcoidosis [2, 3]. The lungchanges of small nodules in a perilymphatic distribution associatedwith a lack of mediastinal lymphadenopathy may be a patternof pulmonary sarcoidosis after immune restoration with highlyactive antiretroviral therapy. Whether this becomes a characteristicset of imaging criteria remains to be seen from a large series inthis group of patients.

Acknowledgments

We thank Ann-Marie Reardon for the preparation of this manuscript.

References

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Introduction
References

Palella FJ Jr, Delaney KM, Moorman AC, et al. Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection: HIV Outpatient Study investigators. N Engl J Med 1998;338:853 -860[Abstract/Free Full Text]
Naccache J, Antoine M, Wislez M, et al. Sarcoidlike pulmonary disorder in human immunodeficiency virus-infected patients receiving antiretroviral therapy. Am J Respir Crit Care Med 1999;159:2009 -2013[Abstract/Free Full Text]
Haramati LB, Lee G, Singh A, Molina P, White CS. Newly diagnosed pulmonary sarcoidosis in HIV-infected patients. Radiology 2001;218:242 -246[Abstract/Free Full Text]
Nishimura K, Itoh H, Kitaichi M, Nagai S, Izumi T. Pulmonary sarcoidosis: correlation of CT and histopathologic findings. Radiology 1993;189:105 -109[Abstract/Free Full Text]