A 28-year-old woman developed SLE in 2005, with symptoms of a high fever and arthritis. She had lupus manifestations in the central nervous system with disturbance of consciousness and multiple intracranial lesions, as well as proliferative lupus nephritis (Class IV-G[A/C]+V, ISN/RPS classification). She was treated with high-dose corticosteroid therapy, intravenous injection of high-dose cyclophosphamide (4 g total), tacrolimus, and plasmapheresis. Her symptoms improved, and clinical remission was maintained with daily administration of 11 mg prednisolone and 100 mg azathioprine. In August 2014, she experienced pain of the left buttock and a high temperature of 38.8C; she was admitted to our hospital with a diagnosis of cellulitis. Palm-sized redness, swelling, and partial induration were observed on the left buttock.
A laboratory examination revealed mild cytopenia: white blood cell count, 4.57x103/muL; hemoglobin, 8.4 g/dL; and platelet count, 10.5x104/muL. Blood cultures were negative, with normal procalcitonin levels; however, C-reactive protein (12.5 mg/dL) levels were elevated. In addition, anti-DNA antibody was not elevated (9.7 IU/mL), and hypocomplementemia was not evident (CH50, 70.6 IU/mL). Despite administering 3 g cefozopran, no therapeutic efficacy was noted, and a fever of 39C persisted. The antibiotics were then changed to 3 g cefazolin plus 1,800 mg clindamycin in addition to 3 g meropenem plus 2 g vancomycin. However, the local redness and pain extended further (Fig. 1a).
To distinguish between an infectious disease and skin lesion due to SLE, we performed a skin biopsy. The histopathological findings revealed inflammatory cell infiltrates that were mainly composed of lymphocytes and plasma cells extending from the dermis into the subcutaneous fat as well as granuloma formation (Fig. 2a). Furthermore, a microscopic examination of a direct smear showed slight positivity for acid-fast bacilli (+/-, equivalent to Gaffky scale of 1) (Fig. 2b). The polymerase chain reaction test was negative for tubercle bacillus. Accordingly, this patient was diagnosed with cutaneous nontuberculous mycobacteriosis, although the strain was unknown at this point. She was administered 4-drug combination therapy with isoniazid, rifampicin, ethambutol, and 800 mg clarithromycin daily to cover M. avium complex (MAC) and M. kansasii, which are the most common causes of nontuberculous mycobacteriosis. Her fever was immediately alleviated, and the skin findings improved. One week later, M. abscessus was detected from a Mycobacterium culture of the tissues and was considered to be the pathogenic bacteria.
Although remission was maintained until the end of September, relapse occurred with a fever and a painful new cutaneous lesion consisting of redness and swelling at the initial infection site on her foot. Based on the possible emergence of resistant bacterium, the antituberculosis drugs were discontinued, except for clarithromycin, and amikacin and imipenem/cilastatin were additionally administered in accordance with the guidelines (ver. 2) of the American Thoracic Society (ATS) and Infectious Diseases Society of America (IDSA). However, a fever of 39C persisted, and her general condition gradually worsened. A second skin biopsy, which was performed to clarify either the deterioration of SLE or relapse of M. abscessus, indicated similar histopathological findings to the previous results but showed stronger positivity for acid-fast bacilli (2+; equivalent to Gaffky scale of 5) on the smear specimen; cultivation later also showed M. abscessus. Because of concerns about resistance to clarithromycin, clarithromycin was changed to azithromycin, which contributed to the immediate alleviation of the fever. The drug susceptibility test results, which were obtained 4 weeks later, revealed resistance; the minimal inhibitory concentration of clarithromycin was 0.25 mug/mL at the first biopsy and >32 mug/mL at the second biopsy (Table). Subsequently, azathioprine was reduced to 50 mg daily.
A three-drug combination of azithromycin, amikacin, and imipenem/cilastatin was continued for one month, and her symptoms were stable; therefore, we switched the treatment to oral antibiotics consisting of azithromycin, faropenem, and levofloxacin at the beginning of November. However, she experienced a relapse three weeks later, and cutaneous redness and induration occurred at a new lesion on the wide area of the inside of the left thigh and on the right buttock (Fig. 1b). By switching amikacin and levofloxacin to kanamycin and moxifloxacin, respectively, therapeutic efficacy was achieved. Accordingly, a four-drug combination of macrolide, carbapenem, aminoglycoside, and a new quinolone was continued for four months. The cutaneous lesion gradually improved, and her general condition was stable; however, the subcutaneous induration partially remained (Fig. 1c). She developed high tone deafness during treatment and was diagnosed with auditory nerve disorders because of long-term aminoglycoside use. Therefore, aminoglycoside was switched to minocycline. Although linezolid was also temporarily used, it was discontinued because she developed malaise and thrombocytopenia. Finally, a three-drug combination of azithromycin, moxifloxacin, and minocycline was administered, and she was discharged in the tenth month after hospitalization (Fig. 3). She was then continuously treated in the outpatient department for 12 months and showed no recurrence of skin lesions; in addition, her SLE was stable.