Pulmonary Illness Associated With Exposure to Mycobacterium-avium Complex in Hot Tub Water

selected reports Pulmonary Illness Associated With Exposure to Mycobacterium-avium Complex in Hot Tub Water* Hypersensitivity Pneumonitis or Infection? John Embil, MD; Peter Warren, MB; Mitchell Yakrus, MS; Robert Stark, MB; Stephen Come, MD; Donna Forrest, MD; and Earl Hershfield, MD

Background: Mycobacterium avium complex is common in water. When aerosolized, it is frequently inhaled but rarely causes illness in healthy people. Hypersensitivity pneumonitis to inhaled aerosols has been described; these aerosols are from several sources of water. The pneumonitis forms are collectively known as humidifier lung; the responsible agent in the water remains uncertain. Purpose: To report five cases of respiratory illness in healthy subjects using hot tubs contaminated with M avium complex. Design: Descriptive case reports. Setting: Consultations in two teaching hospitals. Patients: Five healthy people developed respiratory illnesses characterized by bronchitis, fever, and "flulike" symptoms after using a hot tub. Acute exacerbations of their illness developed within hours of heavy use of the hot tubs. Investigations: A chest radiograph and sputum culture in all, BAL in one, CT scan and lung biopsy in another were performed. Culture of the water of the two hot tubs also was done. Results: Chest radiographs showed interstitial infiltrates or a miliary nodular pattern. Cultures of all sputum samples, the lung biopsy specimens, lung lavage and water samples were positive for M avium complex. The lung biopsy specimen revealed noncase*From the Department of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada (Drs. Embil, Warren, Corne, Forrest, and Hershfield); the Division of Bacterial and Mycotic Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Public Health Service, US Department of Health and Human Services, Atlanta (Mr. Yakrus); and the Department of Pathology, University of Manitoba, Winnipeg, Manitoba, Canada (Dr. Stark). Manuscript received February 23, 1996; revision accepted August 20, 1996. Reprint requests: Dr. Warren, Respiratory Hospital, 810 Sherbrook Street, Winnipeg , Manitoba, R3A 1R8 Canada

ating granulomas. All patients recovered with no treatment for M avium complex. Conclusion: We conclude that theM avium complex in the water was responsible for the pulmonary illnesses. The symptoms and the results of investigations are more suggestive of a hypersensitivity pneumonitis than of an infection, but no serologic proof of an immunologic reaction to the M avium complex or water was obtained. (CHEST 1997; 111:813-16) Key words: atypical pneumonia; hot tub, water; hypersensitivity pneumonitis; Mycobacterium avium complex

The mystery of Mycobacterium avium complex's role in lung disease is exemplified by a recent clinicopathologic conference.l The organism is opportunistic and infects healthy individuals, but rarely causes disease. 2 We

For editorial comment see page 534 wish to add a piece to the puzzle of diseases associated with this organism and their relationship to potable water. 3 The report will also add a possible agent for humidifier lung, 4 hypersensitivity pneumonitis (extrinsic allergic alveolitis), following exposure to water. We report a case, and a cluster of four similar cases, of a pulmonary illness in subjects who used hot tubs contaminated with M avium complex. Hot tubs are large baths, often shared by several people. Hot water is agitated by powerful jets of air or of water that produce bubbles and hence aerosols. The growth of M avium complex is favored by hot water. 5 REPORT OF CASES CASE

1

A 28-year-old healthy plumber used his indoor hot tub for 1 h daily. It was filled with well water in October and emptied in May without water changes. The temperature of the tub water was 37 to 39°C and the pH level was 7 to 8. In the second year of hot tub use, he developed episodes of a "flu-like" illness consisting of fever (38°C), chills, malaise, and headaches. He was empirically treated for bronchitis and chose to increase his hot tub use to alleviate symptoms. He became progressively dyspneic and lost weight (7 kg). At the time of admission to the hospital, auscultation revealed bilateral pulmonary crepitations. He was hypoxemic (Pa0 2 , 45 mm Hg). The chest radiograph showed patchy infiltrates in the right lower lobe. Because the condition was diagnosed as an atypical pneumonia, he was treated with erythromycin; he recovered in 1 week and returned home. He reused his hot tub and suffered a relapse. This time the chest radiograph showed bilateral infiltrates and a CT scan (Fig 1), with 10 and 1.5-mm resolution slices sampled, revealed a patchy ground-glass infiltrate affecting both central and peripheral areas of the lung accompanied by ill-defined centrilobular nodules. The intervening areas were normal. Due to worsening of his condition, an CHEST I 111 I 3 I MARCH, 1997

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FIGURE 1. Thin-slice CT scan (10- and J .S-mm resolution slices) showing a patchy ground-glass infiltrate affecting both central and peripheral lung areas accompanied b yill-defin ed centrilobular nodul es.

FIGURE 2. A noncaseating granuloma containing giant cells and with surrounding interstitial inflammation (hematoxylin-eosin , original X 100).

open-lung biopsy was perform ed; this exhibited (Fig 2) interstitial gnmulomas containing histiocytes, lymphocytes, epithelioid cells, and some giant cells. There was no necrosis or fibrosis. Occasional terminal bronchioles had a similar inHltrate, with partial destruction of the wall (Fig 3)and occasional bronchiolitis obliterans. There W sold, and he has been well for 2 years. C ASE 2

Eight years previously, a 48-year-old surgeon had used a h ot tub daily for 6 years. The wate r was changed twice a year using 814

FIG URE 3. A t erminal bronchiole partially obliterated b y inflammatory changes, predomin antly lymphocytes (he matoxylin-eosin, original X 100). chlorinated city wate r obtained from wells . The water t emperature was 37 to 42°C. The hot tub was in th e room he used a s a study. For 4 months, he noticed a dry cough and slight dyspnea which slowly worsened. For this bronchitis, he was given eryth romycin for a month without improve ment. One day, he cleaned th e dirty filter of the tub and within a f ewhours developed s evere dyspnea. Auscultation detected pulmonary crepitations. His chest radiograph showed bilateral patchy nodul ar innltrates. He was considered to have acute asthma and pneumonia. He was hypoxe mic (Pa0 2 , 6S mm Hg). H e discussed his illness \vith a colleague who suspected humidifier lung, but tests of his serum revealed no precipitins against humidifier organi sms, nor were th ey grown in th e water (personal communication; J. Fink; Medical College of Wisconsin ). Humidifier fever was also considered, but the endotoxin level was low ( <1.2S U/mL) in th e water. All blood and sputum cultures w ere negative for bacteria, except that Mycobacteria were seen in his sputum. His tuberculin test STU was negative. A BAL yielded 800 X lOr, cells/L, 74% of which w ere T4; 6%, T8; and 1%, B lymphocytes. M aviwn co mpl ex was cultured from th e lavage fluid. His clinical picture rese mbled a cute allergic alveolitis rath er than tuberculosis. Kn owing that water can contain Mycobacteri a, th e physician examined th e 6lter of the hot tub, and M avium complex was cultured fi·orn a sample removed from it. The patient was given no antituberculous drugs and recovered spontaneously over the next lew weeks. He conve rted his hot tub into an indoor garden and never developed such an illness again . C AS E S

3-S

While patient 2 was being evaluated, two of his daughters , aged 12 and 16 years, and their friend, aged 16, used the hot tub. All three developed cough, dyspnea, feve r,and chills within hours of exposure. Over th e next week, the two 16-year-olds were tired, had cough with clear phlegm, and had wheezing on exertion. The three girls had widespread miliary nodular changes evidenced on an x-ray film. Once M avium had been d ete cted in the fath er's sputum, the three girls were tested. M avium complex was isolated from th e sputum of one and in the gastric lavage of another. The 12-year-old, who spent the least time in th e pool , improved quickly. The other two took several weeks to recover. Non e were given treatment. The wife and th e youngest daughter of patient 2 had not used the hot tub and were well. All the family had negative tube rculin tests. Patient 2 and th e two 16-year-olds had a r estrictive pattern of lung function with a low (CO) gas transfe r. Eight years later, all are well with normal lung function and normal chest radiographs. Selected Reports

The M avium complex cultured from the water of the two hot tubs (cases 1 and 2), the lung biopsy isolate from patient 1, and the sputum from patients 2 to 5 were sent to the Center for Disease Control and Prevention, Atlanta, for typing by seroagglutination and multilocus enzyme electrophoresis 6 All M avium complex isolates from patients were found to be M avium serotype 8 with identical enzyme patterns. The two water isolates failed to serotype and had different enzyme patterns than those from the patients. DISCUSSION

We believe that the temporal relationship between use of the hot tubs, the presence of the M avium complex in the water, and the isolation of M avium complex from the lung biopsy specimen and BAL specimen as well as from the sputum sample establish that this organism was responsible for the illnesses reported. Though the two isolates from the water did not match those from the patients, the hot tub water may have contained a mixed population of M avium complex, and the specific causal organism might have been detected with more extensive sampling and colony picking. The water of the tub in the first case also grew Pseudomonas sp, Penicillium sp, and Scopulariopsis sp; there was no evidence of pulmonary infection by these organisms by culture. Extensive investigations for other infecting organisms by culture and serologic testing identified nothing. The whirlpool action of a hot tub would have easily aerosolized the contaminated water. Studying the James River, Gruft et aF and Wendt et al 8 have shown that M avium complex is common in natural sea and fresh water. The organism can be concentrated in hot water systems including hospitals. 5 This organism is aerosolized when bubbles form in water9 and thus can be inhaled. Having entered the lung, infection can occur. Pulmonary disease with M avium complex usually occurs in people with damaged lungs, such as those with COPD, bronchiectasis, pneumoconiosis,10 ·11 or AIDS. 12 When disease develops, it has the reputation of producing serious persistent lesions. Teirstein et al13 reviewed 487 patients with pulmonary disease from whom M avium complex was obtained from the lungs; 244 were stated to have true infection because their pulmonary disease followed four patterns: pulmonary nodules, bronchiectasis, cavitary lung disease, or diffuse infiltrates in immunocompromised individuals. The other 243 patients were stated to have false-positive cultures, that is, the cultures were positive, but the physicians could not identifY these patterns of disease in the patients. No information is given as to what illness prompted the culture of the sputum in these 243 people, and the authors may have overlooked other reactions to M avium complex. We are unsure whether the illnesses we observed should be regarded as a transient infection or a hypersensitivity response. The illness we report was different from that in the series of 21 healthy people infected by M avium complex reported by Prince et aJ.2 These researchers observed bronchitis and nodular infiltrates on the chest radiograph but these conditions slowly progressed. In addition , lung biopsy specimens in the study by Prince et al 2 revealed caseating granulomas . Moreover, treatment with antituberculous drugs was needed to halt the disease,

relapse was common, and progression to death occurred in some. In the clinicopathologic case report, 1 the clinician thought the patient had hypersensitivity pneumonitis as judged by the clinical picture, but the lung biopsy showed noncaseating granulomas surrounding terminal bronchioles, and M avium was observed in the biopsy specimen and was cultured from it. The source of the infection and why this healthy young man caught it was not determined, and the consulting physician was left unable to accept the diagnosis of M avium complex infection. Humidifier lung is the generic name for a form of hypersensitivity pneumonitis associated with the inhalation of contaminated water from air-conditioning systems 14 and from domestic,15 office, 16 and industrial humidifiers. 17 The disease also has been reported in showers,18 at a swimming pool,19 and in a sauna. 20 Mycobacteria have not been implicated in these cases, but have been sought in a study of hot water fever. 21 The clinical picture we observed resembled that described in an epidemic of hypersensitivity pneumonitis attributed to tap water in Finland.I8 We favor that our patients had hypersensitivity pneumonitis based on the short time between the exacerbation of the symptoms and the hot tub use, which seemed too quick for infection with mycobacteria. Above all, the spontaneous recovery of all patients with cessation of hot tub use supports a hypersensitivity illness rather than an infection. The investigations also were similar to those reported in the outbreak of hypersensitivity pneumonitis at the swimming pool 19 because of the patchy ground-glass appearance of the lungs with centrilobular nodules that was shown on the CT scan of the lungs. Although increased T8 cells in BAL is the usual finding with hypersensitivity pneumonitis, an excess of T4 cells was also found in the cases at the swimming pooL Most convincing was the lung biopsy which showed changes associated with hypersensitivity pneumonitis: noncaseating granulomas and some bronchiolitis. 22 Unfortunately, we were unable to produce a suitable antigen from the M avium complex that might have been used to detect evidence of sensitization, nor did we simply look for precipitins in the patients' sera to crude extracts of the hot tub water. A number of organisms from cold water have been implicated as the provocative antigens in humidifier lung. They include thermophilic Actinomyces, 14 Sphaeropsidales,23 Penicillium sp,24 protozoa, 25 and Klebsiella oxytoca.26 In the cases involving hot water in the sauna, Pullularia20 was blamed, but for bath water,18 ·19 organisms have not been identified although endotoxin was suggested as the cause for fever in the latter cases. 27 The Penicillium sp cultured from the water in case 1 was not ruled out as a possible cause for the disease. Infections have been recognized from hot tubs specifically. P aeruginosa has produced folliculitis 28 and pneumonia,29 while soft tissue infection with M avium has been reported in a user of a hot tub. 30 We recommend that all patients with atypical pneumonia that defies easy diagnosis should be questioned about hot tub use. It has been suggested that for those infected with HIV, baths would be safer than showers.31 From our experience, we caution against hot tub use by HIV-infected patients and wonder if the tubs of communal bath houses also are a risk The patients we describe here had neglected to follow the manufacture(s instructions to replace the water CHEST I 111 I 3 I MARCH, 1997

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and change the filters. This may be all that is necessary to prevent the buildup of M avium complex in hot tubs. M avium complex is resistant to chlorination and so it is found in domestic water. 32 The high chlorine concentrations needed for sterilization may be unpleasant for hot tub use. Superheating the water, if possible, to 70°C for up to an hour may help. 3 ·5 If our findings prove to occur more frequently in hot tubs, then a study of how to control the growth of M avium complex must be done. ACKNOWLEDGMENT: We acknowledge the consultation from Dr. A.Pan on the first case, the radiologic ass istance of Dr. B. Maycher for the CT scan, the work of Ms. J. Wolfe in the Mycobacterial Laboratory, Winnipeg, and the expertise of Charlotte Smith for serologic testing in the Centers for Disease Control and Prevention, Atlanta. REFERENCES 1 Scully RE, Mark EJ, McNeely WF, et al. Case 6-1996. Case records of the Massachusetts General Hospital. N Eng! JMed 1996; 334:521-26 2 Prince DS, Peterson DD, Steiner RM , e t al. Infection with Mycobacterium avium complex in patients without predisposing conditions. N Eng! J M ed 1989; 321:863-68 3 von Reyn CF, Maslow JN, Barber TW, e t a!. Persistent colonisation of potable water as a source of Mycobacterium avium infection in AIDS. Lancet 1994; 343:1137-41 4 Marinkovich VA, Novey HS . Humidifier lung. Clin Rev Allergy 1983; 1:533-36 5 du Moulin GC, Stottmeier KD , Pelletier PA, eta!. Concentration of Mycobacterium aviwn by hospital hot water systems. JAMA 1988; 260:1599-1601 6 Yakrus MA, Reeves MW, Hunter SB. Characterization of isolates of Mycobacterium avium serotypes 4 and 8 from patients with AIDS by multilocus enzyme e el ctrophoresis. J Clin Microbial 1992; 30:1474-78 7 Gruft H, Katz J, Blanchard DC. Postulated source of Mycobacterium intracellulare (Battey) infection. Am J Epidemiol 1975; 102:311-18 8 Wendt SL, George KL, Parker BC, et a!. Epidemiology of infection by nontuberculous Mycobacteria: III. Isolation of potentially pathogenic mycobacteria from aerosols. Am Rev Respir Dis 1980; 122:259-63 9 Parker BC, Ford MA, Gruft H, et a!. Epidemiology of infection by nontuberculous Mycobacteria: IV. Preferential aerosolization of Mycobacterium intracellulare from natural waters . Am Rev Respir Dis 1983; 128:652-56 10 Rosenzweig DY. Pulmonary mycobacterial disease due to Mycobacterium intracellulare-avium complex: clinical features and course in 100 consecutive cases. Chest 1979; 75:115-19 11 Engback HC, Vergmann B, Bentzon MW. Lung disease caused by Mycobacterium avium!Mycobacterium intracellulare. An analysis of Danish patients during the period 196276. Eur J Resp Dis 1981; 62:72-83 12 Hawkins CC, Gold JWM, Whimbey E, et a!. Mycobacterium aviurn complex infection in patients with the acquired immunodeficiency syndrome. Ann Intern Med 1986; 105:184-88 13 Teirstein AS, Damsker B, Kirschner PA, et al. Pulmonary infection with Mycoba~terium avium-intracellulare: diagnosis, clinical patterns, treatment. Mt Sinai JMed 1990; 57:209-15 14 Banaszak EF, Thiede WH, Fink JN. Hypersensitivity pneumonitis due to contamination of an air conditioner. N Engl J Med 1970; 283:271-76 15 Hodges GR, Fink JN , Schlueter DP. Hypersensitivity pneumonitis caused by a contaminated cool mist vaporizer. Ann Intern Med 1974; 80:501-04 816

16 Miller MM , Patterson R, Fink JN, et al. Chronic hypersensitivity lung disease with recurrent episodes of hypersensitivity pneumonitis due to a contaminated central humidifier. Clin Allergy 1976; 6:451-62 17 Friend JAR, Pickering CAC, Palmer KNV, et a!. Extrinsic allergic alveolitis and contaminated cooling-water in a factory machine. Lancet 1977; 1:297-300 18 Muittari A, Kuusisto P, Virtanen P, et al. An epidemic of extrinsic allergic alveolitis caused by tap water. Clin Allergy 1980; 10:77-90 19 Lynch DA, Rose CS , Way D, et a!. Hypersensitivity pneumonitis: sensitivity of high-resolution CT in a population-based study. AJR 1992; 159:469-72 20 Metzger WJ, Patterson R, Fink J, eta!. Sauna-takers diseases: hypersensitivity pneumonitis due to contaminated water in a home sauna. JAMA 1976; 236:2209-11 21 Atterholm I, Hallberg T, Ganrot-Norlin K , eta!. Unexplained acute fever after a hot bath. Lancet 1977; 2:684-86 22 Coleman A, Colby TV. Histologic diagnosis of extrinsic allergic alveolitis. Am J Surg Pathol. 1988; 12:514-18 23 Baur X, Behr J, Dewair M, et al. Humidifier lung and humidifier fever. Lung 1988; 166:113-24 24 Solley GO, Hyatt RE. Hypersensitivity pneumonitis induced b y Penicillium species. J Allergy Clin Immunol 1980; 65:65-70 25 Edwards JH, Griffiths AJ, Mullins J. Protozoa as sources of antigen in "humidifier fever." Nature 1976; 264:438-39 26 Kane GC, Marx JJ, Prince DS. Hypersensitivity pneumonitis secondary to Klebsiella oxytoca: a new cause of humidifier lung. Chest 1993; 104:627-29 27 Muittari A, Rylander R, Salkinoja-Salonen M. Endotoxin and bath water [letter]. Lancet 1980; 2:89 28 Sauske r WF, Aeling JL, Fitzpatrick JE , et a!. Pseudomonas folliculitis acquired from a health spa whirlpool JAMA 1978; 239:2362-65 29 Rose HD, Franson TR, Sheth NK, et a!. Pseudomonas pneumonia associated with use of a home whirlpool spa. JAMA 1983; 250:2027-29 30 Aubuchon C, Hill JJ, Graham DR. Atypical mycobacterial infection of soft tissue associated with use o f ahot tub. J Bone Joint Surg 1986; 68A:766-68 31 Montecalvo MA, Forester G, Tsang AY, eta!. Colonisation of potable water with Mycobacterium avium complex in homes of HIV-infected patients [letter]. Lancet 1994; 343:1639 32 Pelletier PA, du Moulin GC, Stottmeier KD. Mycobacteria in public water supplies: comparative resistance to chlorine. Microbial Sci 1988; 5:147-48

Another Hot Tub Hazard* Toxicity Secondary to Bromine and Hydrobromic Acid Exposure Michael]. Burns, MD; and Christopher H. Linden, MD

We describe the clinical course of two patie nts w ho develope d acute pne umonitis followed b y er active *From the Section in Toxicology, Division of Emergency Medicine, Beth Israel Hospital, Boston (Dr. Burns); and the Department of Emergency Medicine, Division of Toxicology, University of Massachusetts Medical Center, Worcester (Dr. Linden). Manuscript received April 29, 1996; revision accepted September 19. Reprint requests: Dr. Michael Burns, 26 Edmunds Way , Northboro, MA 01532 Selected Reports