Disseminated Mycobacterium intracellulare infection with multiple abscesses on extremities in a woman with chronic corticosteroid therapy.

A 78-year-old Japanese woman with rheumatoid arthritis was admitted to our hospital due to fever. She had been prescribed prednisolone and bucillamine. Computed tomography revealed abscesses on extremities. M. intracellulare was cultured from her calcaneus osteomyelitis, and this result pointed to a disseminated mycobacterial infection. We drained the abscesses and found M. intracellulare. We started antimycobacterial agents, but the patient died finally. Disseminated mycobacterial infection is rare but critical, and the possibility of such an infection in an immunocompromised patient should be a prime consideration when choosing appropriate drugs and surgical approaches.

CASE REPORT

A 78‐year‐old woman was referred to our hospital due to fever. She had been hospitalized in another hospital for chronic osteomyelitis due to Mycobacterium intracellulare isolated one month before the referral. She had a medical history of rheumatoid arthritis treated with prednisolone at 11.5 mg/d and bucillamine at 200 mg/d for 11 years, type 2 diabetes mellitus, and steroid‐induced osteoporosis. Performing activities of daily living was difficult, and she required a wheelchair for moving. At the age of 71, a pressure bone fracture of 9th to 10th thoracic vertebrae had occurred. Laminectomy (9th to 10th thoracic vertebrae) and posterior spinal fusion (6th thoracic vertebrae to 1st lumbar vertebrae) were performed, and the surgical site infection (SSI) due to M. intracellulare was documented. Clarithromycin and rifampicin were prescribed for the SSI for unknown duration. In addition, 6 years after the SSI, M. intracellulare infection at the same site reappeared, and debridement and removal of the implantation were performed. In this surgical site, M. intracellulare was also documented. Nine months after the recurrence of SSI, new osteomyelitis was detected in her right heel, and M. intracellulare was cultured from a specimen of the heel lesion. One month after the emergence of the recurrence, she was febrile and referred to our hospital (levofloxacin and rifampicin were started 1 day before admission).

Her vital signs were as follows: blood pressure, 143/67 mm Hg; heart rate, 90 beats/min; respiratory rate, 32 breaths/min; body temperature, 36.8°C; and Glasgow Coma Scale, E4V5M6 (total 15/15). Upon physical examination, osteomyelitis was found in her right heel, and elastic soft masses were also found on her left leg. The masses had no tenderness, local heat, or redness. Laboratory data revealed low levels of plasma protein (total protein: 4.63 g/dL; albumin: 2.20 g/dL), high levels of inflammation (c‐reactive protein: 31.61 mg/dL; a high white blood cell count: 18 800/μL (neutrophil: 89%; lymphocyte: 5%)), and low levels of serum immunoglobulins (IgM: 37 mg/dL; and IgG: 339 mg/dL). A noncontrast computed tomography (head to heel) showed large cystic lesions on her left leg (Figure 1) and small bandlike shadows on the right lower lobe of her lung. Infectious diseases consultation was obtained for etiology of the fever. Based on her immunocompromised status and the episode of M. intracellulare infection, we considered that disseminated M. intracellulare infection was most likely. Also, we considered the possibility of either abscesses with bacteremia on her leg or urosepsis. We started vancomycin at a dose of 750 mg administered intravenously every 12 hours and cefmetazole at a dose of 1 g administered intravenously every six hours, after drawing a blood culture (BACTEC™ 23F and 22F, Becton Dickinson Company, USA), and a blood culture for fungi and mycobacterium (BACTEC™ Myco/F Lytic, Becton Dickinson Company, USA). On the day of admission, a drainage operation was performed to clarify the etiology of the masses on her left leg. After an incision of the left tensor fasciae latae muscle and gastrocnemius muscle membrane, whitish, muddy, and odorless pus appeared (Figure 2). The pus was negative for Gram staining but positive for acid‐fast bacilli (AFB) upon Ziehl‐Neelsen staining and was positive for M. intracellulare by PCR. We did not change the dose of immunosuppressive agents. We added oral antimycobacterial drugs: clarithromycin at 400 mg twice a day, rifampicin at 450 mg once a day, and ethambutol at 750 mg once a day. A culture of the pus was also positive for methicillin‐sensitive staphylococcus aureus, and we stopped the vancomycin. The blood cultures were negative for bacteria including mycobacterium. The fever subsided soon; however, the fever reappeared on the sixth day. A noncontrast computed tomography (neck to heel, including upper extremities) was performed again to evaluate the abscesses. Abscesses on her left leg were diminished mostly, but a new lesion was detected on the right upper arm (Figure 3). The mass was incised on the eighth day, and the pus appeared as it had on her leg. The pus was also positive for AFB upon Ziehl‐Neelsen staining (M. intracellulare confirmed by PCR). After 28 days of hospitalization, a mycobacterial culture of the pus taken during the first operation was positive. On the 40th day, the patient was transferred to another hospital with a continuation of antimycobacterial drugs; however, she died 17 days after the transfer. A postmortem was not performed because the consent from the patient's family had not been obtained.

Figure 1

Multiple abscesses presented as cystic lesions on the patient's left leg (white arrows)

Figure 2

Whitish, muddy, and odorless pus appeared from the abscesses of the left tensor fasciae latae muscle

Figure 3

A second computed tomography revealed an abscess with a small calcification on the right upper arm (white arrow)

DISCUSSION

This case was an immunocompromised patient with disseminated M. intracellulare infection. Among all nontuberculous mycobacterial (NTM) diseases, Mycobacterium avium complex (MAC) including M. intracellulare is the most common pathogen in Japan.1 Also, underlying risk factors for a disseminated NTM infection include immunodeficiencies such as an HIV infection,2 chronic liver diseases,2 corticosteroid therapy,3, 4 organ transplant,4 autoantibody to interferon‐γ,5, 6 and unknown cell‐mediated immune dysfunction7. In this case, the patient's long‐term corticosteroid therapy had more likely contributed to the disseminated NTM infection.

Abscesses on extremities due to NTM, a rare manifestation, was confirmed in this case although a previous case had been reported.4 Sites that are frequently involved among disseminated NTM diseases include pulmonary, bone marrow, bones, liver, lymph nodes, and spleen.3, 7 In this case, because there were distant lesions, the mycobacteria had spread hematogenously and formed abscesses.

The mortality rate of disseminated NTM infections among Japanese cases is approximately 30%.6 We performed surgical intervention and started antimycobacterial drugs immediately, but the patient died. We are convinced there were three major reasons for our patient's death: (i) insufficient drainage of abscesses; (ii). the antimicrobial resistance of the strain and; and (iii) the patient's persistent immunocompromised status. Small abscesses on her left leg were also identified in the second computed tomography. Unfortunately, the duration and the dosage history of antimycobacterial drugs and the antimicrobial resistance of the strain remain unknown; however, we suspected the possibility of the strain's acquiring resistance against antimycobacterial drugs due to the incomplete treatment. We also considered the patient's lifelong immunocompromised status. In HIV cases, the CD4 cell counts of patients rise because of the antiretroviral drugs, and an immunocompromised status might recover. Otherwise, among most of the non‐HIV cases, there are difficulties involved with improving immunological status because the use of drugs such as steroids cannot be stopped. The fact that abscesses on her left leg became larger again before her death supports our hypotheses. Disseminated NTM diseases are critical, but prophylaxis guidelines for non‐HIV patients have not been documented. Recently, an observational study suggested that a secondary prophylaxis against disseminated NTM diseases of non‐HIV patients is beneficial.8 Secondary prophylaxis should also be discussed in lifelong immunocompromised cases.

In conclusion, this was a case of disseminated MAC disease with impaired cellular immunity. Past medical history should generate suspicions of disseminated MAC disease. Despite the smooth collaboration of orthopedic surgeons and infectious diseases physician, unfortunately this patient died. Physicians must be mindful of the possibility of NTM in immunocompromised patients with infections in any site.

ETHICS STATEMENT

The Kurume University Research Ethics Committee (http://www.med.kurume-u.ac.jp/med/joint/rinri/) approved this study (Research No. 16134).

CONFLICT OF INTEREST

The authors have stated explicitly that there are no conflicts of interest in connection with this article.