A woman with cough, fever, and micronodular infiltrates on chest radiograph.

Abstract: Hot tub lung is a form of hypersensitivity pneumonitis (HP) reported to be associated with exposure to large aerosolized inocula of Mycobacterium avium complex (MAC). Although the pathogenesis of the disease is still poorly understood, the pathology of MAC-related HP can be similar to that of sarcoidosis, with well-formed granulomas. We describe a patient with HP featuring well-formed granulomas on transbronchial biopsy specimens, a finding believed to be unique to MAC-related HP, also referred to as "hot tub lung."

Key Words: hypersensitivity pneumonitis, hot tub lung, Mycobacterium avium complex

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Hypersensitivity pneumonitis (HP) is an inflammatory interstitial lung disease due to a hypersensitivity reaction within the lung to specific antigens found in a wide array of organic dust. HP secondary to Mycobacterium avium complex (MAC) in immunocompetent patients has been reported after presumed exposure to large inhaled inoculums during hot tub and swimming pool use, and even after exposure to water-damaged buildings. (1) Most cases present with well-formed granulomas and CD8+ lymphocyte-predominant inflammation. (2,3) We present a case of hot tub-related HP with CD4+ lymphocyte-predominant inflammation and well-formed granulomas.

Case Report

A 66-year-old thin woman presented with complaints of worsening dyspnea on exertion, chest discomfort, profuse sweats, malaise, and a nonproductive cough over 2 months. On physical examination, vital signs were normal except for an oxygen ([O.sub.2]) saturation of 91% on 2 L/min supplemental [O.sup.2] at rest, which dropped to 80% with exertion. She was diaphoretic with moderately labored breathing during conversation. Chest auscultation revealed end-inspiratory crackles in the posterior lower lobes. The rest of the examination was unremarkable. She was admitted to the hospital and started on IV ceftriaxone and azithromycin for presumed community-acquired pneumonia. Chest x-ray and computed tomography (CT) scan of the chest are shown in Figures 1 and 2. She underwent bronchoscopy with bronchoalveolar lavage (BAL) and transbronchial biopsy. Flow cytometry revealed a predominance of T-lymphocytes: 87% CD4+ and 11% CD8+. Histologic evaluation of the biopsy specimens are shown in Figure 3. The stains and cultures for bacteria, acid-fast bacilli (AFB) and fungus of BAL and tissue specimens were negative for any infectious process. Upon further questioning, she reported that she had been using a hot tub twice a week, which she last used approximately 6 days before admission. After failing to improve over three days in the hospital, she was started on oral prednisone with a nearly complete resolution of her cough and dyspnea over the following two weeks. Cultures performed by environmental services from her hot tub and filter revealed a confluent growth of MAC from 10 and 0.1 mL of hot tub water and 3.7 X [10.sup.4] colony forming U/swab from the hot tub filter.

Discussion

HP is an inflammatory interstitial lung disease that results from a hypersensitivity reaction to the repeated inhalation of specific antigens found in a wide array of organic material and dust. HP can present with an acute, subacute, or chronic course. Subacute HP presents with the gradual development of cough, dyspnea, fatigue, and weight loss over weeks to months of ongoing intermittent exposure to the antigen, in this case, aerosolized MAC from a hot tub and/or humidifier. The pathology of subacute HP is typically characterized by bronchiolitis, with or without organizing pneumonia (about 50% of cases) and noncaseating interstitial granulomas. Granulomas in HP are typically poorly formed, in contrast to the well-formed granulomas of sarcoidosis and develop in a centrilobular or peribronchiolar distribution. (4-6) A predominance of CD4+ Th1 cells is generally found in BAL fluid shortly after exposure. CD8+ lymphocytes will typically predominate during the later phase of HP. Only 1% of patients exposed to the antigen will develop disease. (7) Some patients will report the development of symptoms only following an acute respiratory infection, yet will have been exposed to the antigen for several years before the development of HP. This phenomenon has also been observed experimentally in a model of HP in mice, in which the prior exposure to respiratory syncytial virus augments granuloma formation and production of interleukin-8 and interferon alpha. (8) Several species of mycobacteria have been found to cause HP. MAC is mainly reported in association with hot tub use. (1) Khoor reviewed 10 cases of healthy patients who presented with diffuse infiltrates and culture-confirmed MAC disease. Histologic findings were found to contain non-necrotizing granulomas and patchy chronic interstitial pneumonia. Interestingly, granulomas were well formed and reminiscent of sarcoid-type granulomas. (9) Follow up of all patients revealed a range of recovery from complete resolution of symptoms to significant residual dyspnea as long as 6 years after initial presentation.

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Conclusion

Although it is possible that another exposure could have been responsible for our patient's HP, MAC-related HP is the only variant described to date with well-formed granulomas on biopsy, and the most widely cited cause of hot tub-related HP. (10) One question that remains unanswered is whether hot tub-related HP is an infectious process, a pure hypersensitivity reaction to antigens from MAC, or a combination of both processes. In a recent review, all patients with MAC-related HP had spontaneous resolution of the disease without antimicrobial therapy, (10) lending strong support to the notion that MAC-related HP, or "hot tub lung," is primarily a hypersensitivity-driven process. The improvement observed in our patient following a short course of steroids and persistent avoidance of her hot tub also support this conviction, and suggest that simple avoidance without antimicrobial therapy is a safe and reasonable first line of treatment for a patient with MAC-related HP.

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References

1. Falkinham JO, 3rd. Mycobacterial aerosols and respiratory disease. Emerg Infect Dis 2003;9:763-767.

2. Yi ES. Hypersensitivity pneumonitis. Crit Rev Clin Lab Sci 2002;39:581-629.

3. Ando M, Konishi K, Yoneda R, et al. Difference in the phenotypes of bronchoalveolar lavage lymphocytes in patients with summer-type hypersensitivity pneumonitis, farmer's lung, ventilation pneumonitis, and bird fancier's lung: report of a nationwide epidemiologic study in Japan. J Allergy Clin Immunol 1991;87:1002-1009.

4. Sharma OP. Hypersensitivity pneumonitis. Dis Mon 1991;37:409-471.

5. Sutinen S, Reijula K, Huhti E, et al. Extrinsic allergic bronchiolo-alveolitis: serology and biopsy findings. Eur J Respir Dis 1983;64:271-282.

6. Cheung OY, Muhm JR, Helmers RA, et al. Surgical pathology of granulomatous interstitial pneumonia. Ann Diagn Pathol 2003;7:127-138.

7. Patel AM, Ryu JH, Reed CE. Hypersensitivity pneumonitis: current concepts and future questions. J Allergy Clin Immunol 2001;108:661-670.

8. Gudmundsson G, Monick MM, Hunninghake GW. Viral infection modulates expression of hypersensitivity pneumonitis. J Immunol 1999;162:7397-7401.

9. Khoor A, Leslie KO, Tazelaar HD, et al. Diffuse pulmonary disease caused by nontuberculous mycobacteria in immunocompetent people (hot tub lung). Am J Clin Pathol 2001;115:755-762.

10. Embil J, Warren P, Yakrus M, et al. Pulmonary illness associated with exposure to Mycobacterium-avium complex in hot tub water. Hypersensitivity pneumonitis or infection? Chest 1997;111:813-816.

Viranuj Sueblinvong, MD and Gilman B. Allen, MD

From the University of Vermont/Fletcher Allen Health Care, Burlington, VT.

Reprint requests to Viranuj Sueblinvong, MD, University of Vermont/Fletcher Allen Health Care, Patrick 204, MCHV, 111 Colchester Avenue, Burlington, Vermont 05401. Email: [e-mail]

Accepted August 31, 2005.

RELATED ARTICLE: Key Points

* In the case of Mycobacterium avium complex (MAC)-related hot tub hypersensitivity pneumonitis (HP), biopsy specimens often reveal well-formed bronchiolo-centric granulomas, unlike the poorly formed granulomas classically described in HP from other sources.

* When a source of exposure can be identified, and the characteristic findings of HP are present on CT-imaging of the lung, disease caused by MAC in the immunocompetent host may represent a hypersensitivity-driven pneumonitis rather than infection. This is supported by the non-necrotizing granulomas seen on biopsy, and the improvement in symptoms following avoidance of further exposure.

* A predominance of CD8+ lymphocytes in bronchoalveolar lavage fluid is not uniformly observed in HP; a predominance of CD4+ lymphocytes can be seen in the early phase of HP.

* In cases where antigen-specific serum antibody assays are not possible, and tissue cultures are unrevealing, home environmental inspection and testing may yield important clues to the etiology of HP.