|Year : 2012 | Volume
| Issue : 3 | Page : 152-154
Hypersensitivity pneumonitis caused by Mycobacterium avium subsp. hominissuis in a hot tub, as proven by IS1245 RFLP and rep-PCR typing☆
Rianne J.C van der Zanden1, Cecile Magis-Escurra2, Wiel C.M de Lange3, Wouter Hoefsloot4, Martin J Boeree2, Jakko van Ingen5, Dick van Soolingen6
1 National Mycobacteria Reference Laboratory, Laboratories for Infectious Diseases and Perinatal Screening, National Institute for Public Health and the Environment, Bilthoven, The Netherlands
2 Department of Pulmonary Diseases, Radboud University Nijmegen Medical Center; University Lung Centre Dekkerswald, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands
3 Beatrixoord, Tuberculosis Center, University Medical Center Groningen, Haren, The Netherlands
4 Department of Pulmonary Diseases, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands
5 Department of Clinical Microbiology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands
6 National Mycobacteria Reference Laboratory, Laboratories for Infectious Diseases and Perinatal Screening, National Institute for Public Health and the Environment, Bilthoven; Department of Pulmonary Diseases; University Lung Centre Dekkerswald, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands
|Date of Web Publication||28-Feb-2017|
Rianne J.C van der Zanden
Mycobacteria Department (LIS;pb22), National Institute for Public Health and the Environment (RIVM), P.O. Box 1, 3720 BA Bilthoven
Source of Support: None, Conflict of Interest: None
A symptomatic patient had repeatedly positive cultures of Mycobacterium avium subsp. hominissuis after exposure to a hot tub contaminated with M. avium subsp. hominissuis. The pulmonary and tub water isolates were indistinguishable by IS1245 RFLP as well as rep-PCR typing. Discontinued use of the hot tub resulted in culture conversion.
Keywords: Hot tub lung, Hypersensitivity pneumonitis, M. avium subsp. hominissuis, rep-PCR, IS1245 RFLP
|How to cite this article:|
van der Zanden RJ, Magis-Escurra C, de Lange WC, Hoefsloot W, Boeree MJ, van Ingen J, van Soolingen D. Hypersensitivity pneumonitis caused by Mycobacterium avium subsp. hominissuis in a hot tub, as proven by IS1245 RFLP and rep-PCR typing☆. Int J Mycobacteriol 2012;1:152-4
|How to cite this URL:|
van der Zanden RJ, Magis-Escurra C, de Lange WC, Hoefsloot W, Boeree MJ, van Ingen J, van Soolingen D. Hypersensitivity pneumonitis caused by Mycobacterium avium subsp. hominissuis in a hot tub, as proven by IS1245 RFLP and rep-PCR typing☆. Int J Mycobacteriol [serial online] 2012 [cited 2019 Jan 20];1:152-4. Available from: http://www.ijmyco.org/text.asp?2012/1/3/152/201242
| Case report|| |
A 65-year-old Dutch Caucasian woman presented at the department of pulmonary diseases in a peripheral hospital with fever, fatigue and dyspnea. There were dense airspace opacities in both lungs visible on chest radiographs after a 2-month-period of recurrent pneumonias of various lobes. The patient had a 30-year history of rheumatoid factor positive rheumatoid arthritis for which she had received for 3 years the tumor necrosis factor α neutralizing agent infliximab. Infliximab suppresses the immune system and predisposes to opportunistic infections, including mycobacterial disease . The patient reported no additional risk factors for mycobacterial disease, but she had visited Zimbabwe during the previous year.
In the first month after initial presentation she received the broad-spectrum antibiotics amoxicillin/clavulanic acid and doxycycline because of the recurrent pneumonias. Thereafter infliximab was replaced by methotrexate. This led initially to clinical improvement, however, later the patient experienced relapses of fever up to 38.0 °C, dry cough, malaise and fatigue. After 2 months, a chest radiograph showed infiltrative abnormalities of the right middle lobe. A computed tomography (CT)-scan and a high-resolution-CT-scan (HCRT) revealed some atypical fibrosis, especially in the lower zones of the lungs; also visible on the CT-scan was a small, localized dense nodule in the anterobasal segment of the right lower lobe ([Figure 1A] and [Figure 1B]). A sputum culture grew Mycobacterium avium, as identified by Inno-LiPA Mycobacteria v2 assay (Innogenetics, Ghent, Belgium).
|Figure 1A: CT-scan; basal section showing bronchiolitis and a diffuse mild micronodular pattern.|
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|Figure 1B: CT-scan; the arrow shows a nodular lesion in the right lower lobe, with mild bronchiectasis; “tree-in-bud” aspect of bronchiolitis in the left lower lobe.|
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Four months after initial presentation, the patient was admitted to the rheumatology outpatient clinic because of right middle lobe (RML) pneumonia. She presented with an acute, continued pain in the right hemithorax, a stinging pain under her right breast, and fever up to 39.8 °C. Her symptoms also included cough without sputum, weight loss and night sweats. Auscultation of the chest revealed bilateral basal coarse crepitations and no rhonchi. A chest radiograph revealed dense airspace opacities in the RML. Culture of a bronchoalveolar lavage (BAL) also grew M. avium. Empirical therapy was started with thrice daily amoxicillin/clavulanic acid 1200 mg intravenous and ciproxin 400 mg intravenous twice daily. Thereafter, the patient improved clinically. Follow-up chest radiographs showed improvement, but incomplete resolution of the lesions.
Six months after initial presentation, the symptoms – fever and fatigue – continued. A renewed interview revealed that 4 months before initial presentation, the patient had an indoor hot tub installed. A water sample of the hot tub was collected for culture. Ziehl–Neelsen stain of a sediment was reported  and corresponding cultures grew M. avium. The patient was advised to discontinue hot tub use and this led after 4 and 9 months to negative cultures of M. avium.
Genotyping was performed on all three M. avium isolates using IS1245 restriction fragment length polymorphism (RFLP) typing, as previously described . IS1245 RFLP revealed that all three isolates belong to a single M. avium subsp. hominissuis strain ([Figure 2A]). The secondary genotyping method applied to the three isolates was rep-PCR, a commercially available system (DiversiLab®, bioMérieux). For M. avium subsp. hominissuis, the discriminative power of rep-PCR was previously found to equal or exceed that of RFLP typing . Rep-PCR confirmed that all three isolates belong to a single strain ([Figure 2B]).
|Figure 2A: Identical IS1245 RFLP patterns of M. avium subsp. hominissuis isolates from(1) sputum cultured 2months after initial presentation; (2) BAL cultured 5 months after initial presentation; and (3) hot tub water cultured 7 months after initial presentation.|
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|Figure 2B: Dendrogram and similarity matrix for three M. avium subsp. hominissuis isolates analyzed using the DiversiLab® system showing three identical patterns. Reference strains M. avium subsp. avium R19 and M. avium subsp. hominissuis IWGMT49 were used as controls.|
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Kahana et al.  also described a case of M. avium infection in an immunocompetent patient in relation to M. avium cultured from a hot tub. Both strains revealed a high degree of similarity in multilocus enzyme electrophoresis and IS1245 RFLP analysis, although the IS1245 RFLP of the hot tub isolate revealed three additional bands compared with the isolate from an open-lung biopsy specimen.
In the current study, on the basis of two typing methods, indistinguishable M. avium subsp. hominissuis isolates from the patient and the hot tub were found, and this contrasts the study of Kahana et al. The patient also directly improved after discontinuing the hot tub use. Antibacterial therapy was provided, but not focused on treatment of an M. avium infection. The diagnosis of hypersensitivity pneumonitis was initially based on the clinical and radiological presentation, but because typing of the M. avium cultures from the patient and the hot tub yielded identical profiles and the patient directly improved when she discontinued the use of the hot tub, it is conceivable these bacteria were indeed the cause of her infection.
The ATS/IDSA guidelines for nontuberculous mycobacterial disease  state that “[without histological evidence], a diagnosis of M. avium-associated hypersensitivity-like lung disease can be established by the following: subacute onset of respiratory symptoms; hot-tub exposure; characteristic radiographic findings; and M. avium isolates in sputum, BAL, tissue, and hot-tub water.” Our patient matches this case definition.
The treatment of a case of hypersensitivity pneumonitis is the subject of debate. The disease results either from inflammation, infection, or both; as a result, treatment can consist of steroids or antimycobacterial treatment. For the latter, the ATS/IDSA statement  recommends rifampicin, ethambutol and a macrolide antibiotic, for M. avium. Neither antimycobacterial treatment, nor steroids were given.
In summary, a case of M. avium subsp. hominissuis hypersensitivity pneumonitis is described in a patient with rheumatoid arthritis treated with infliximab, related to hot tub exposure. Genotyping revealed that the isolates from sputum, lung lavage and hot tub water belonged to a single strain of M. avium subsp. hominissuis. Discontinuation of the use of the hot tub led to significant improvement.
| References|| |
J. van Ingen, M.J. Boeree, P.N. Dekhuijzen, D. van Soolingen, Mycobacterial disease in patients with rheumatic disease, Nat. Clin. Pract. Rheumatol. 4 (2008) 649–656.
N. Selvakumar, F. Rahman, S. Rajasekaran, P.R. Narayanan, T.R. Frieden, Inefficiency of 0.3% carbol fuchsin in Ziehl–Neelsen staining for detecting acid-fast bacilli, J. Clin. Microbiol. 40 (2002) 3041–3043.
D. van Soolingen, J. Bauer, V. Ritacco, S.C. Leao, I. Pavlik, V. Vincent, et al, IS1245 restriction fragment length polymorphism typing of Mycobacterium avium
isolates: Proposal for standardization, J. Clin. Microbiol. 36 (1998) 3051–3054.
G.A. Cangelosi, R.J. Freeman, K.N. Lewis, D. Livingston- Rosanoff, K.S. Shah, S.J. Milan, et al, Evaluation of a highthroughput repetitive-sequence-based PCR system for DNA fingerprinting of Mycobacterium tuberculosis
and Mycobacterium avium
complex strains, J. Clin. Microbiol. 42 (2004) 2685–2693.
L.M. Kahana, J.M. Kay, M.A. Yakrus, S. Waserman, Mycobacterium avium
complex infection in an immunocompetent young adult related to hot tub exposure, Chest 111 (1997) 242–245.
D.E. Griffith, T. Aksamit, B.A. Brown-Elliott, A. Catanzaro, C. Daley, F. Gordin, et al, ATS Mycobacterial Diseases Subcommittee, American Thoracic Society, and Infectious Disease Society of America. 2007. An official ATS/IDSA statement: Diagnosis, treatment, and prevention of nontuberculous mycobacterial diseases, Am. J. Respir. Crit. Care Med. 175 (2007) 367–416.
[Figure 1A], [Figure 1B], [Figure 2A], [Figure 2B]