Disseminated Mycobacterium chelonae infection with Hughes-Stovin syndrome

Abstract

Mycobacterium chelonae usually causes localized cutaneous infections and abscesses but has the potential to cause disseminated infections, especially in immunocompromised hosts. We report a 27-year-old man with Hughes-Stovin syndrome and catastrophic antiphospholipid syndrome who was on chronic immunosuppressant therapy and developed disseminated M. chelonae infection. To the best of our knowledge, this is the first case report of M. chelonae infection in a patient with Hughes-Stovin syndrome.

Mycobacterium chelonae is a nontuberculous mycobacterium (NTM) first isolated from a turtle in 1903. This nonmotile, non–spore-forming, gram-positive, acid-fast bacillus is classified as a rapidly growing mycobacterium and is commonly associated with skin and soft tissue infections, catheter-related infections, and postsurgical infections (especially after implants, transplants, and cataract surgeries).^1,2 The eye is the second most frequent organ involved. Pulmonary infections from M. chelonae are extremely rare, but colonization of the respiratory tract can be seen in cystic fibrosis.³ M. chelonae can cause invasive infections such as osteomyelitis, intraabdominal abscesses, and disseminated cutaneous infections, and can be fatal if hematogenously disseminated.^4,5

CASE PRESENTATION

A 27-year-old man had Hughes-Stovin syndrome (HSS) with aneurysms of pulmonary arteries, the left renal artery, and the superior mesenteric artery, recurrent deep venous thromboses, and pulmonary emboli. He had a recent hospital admission for massive hemoptysis due to left pulmonary artery aneurysm rupture. A left lobectomy was performed. His chest computed tomography revealed a postsurgical left-sided hydropneumothorax and diffuse bilateral ground-glass opacities thought to be secondary to alveolar hemorrhages. He was noted to have high titers of lupus anticoagulant with concerns for catastrophic antiphospholipid syndrome, for which he underwent plasmapheresis and was started on monthly infliximab intravenous infusions and azathioprine. He ultimately required tracheostomy and gastrostomy due to inability to wean off ventilation.

His hospital course was further complicated by hypoalbuminemia with nephrotic-range proteinuria, for which a renal biopsy was performed. It revealed candida and rare acid-fast bacilli (AFB) (Figure 1a). AFB blood cultures and standard blood cultures were obtained and remained sterile. The patient’s three consecutive sputum culture samples revealed AFB (Figure 1b), which was further characterized as NTM. Infectious diseases consultants believed the presence of NTM in the sputum and renal biopsy was suggestive of an invasive NTM infection. It was decided to wait for the final cultures to identify the NTM species before initiating treatment. For the candida infection, the patient was treated with 3 weeks of micafungin and discharged home on high-dose fluconazole. At the time of discharge, he was weaned to 8 L of oxygen via the tracheostomy and started on prednisone 20 mg/day for maintaining immunosuppression for the HSS.

Figure 1.

(a) Clusters of acid-fast bacilli (arrows) were seen in one of the areas of mixed inflammation noted on renal biopsy. The lack of a granulomatous response can be seen in immunosuppressed patients (400×). (b) Acid-fast bacilli in the patient’s sputum sample (Auramine stain, 400×).

The patient returned to the hospital 5 days after discharge with acutely worsening hypoxemia. Chest computed tomography revealed a stable left hydropneumothorax with worsening ground-glass opacities with new opacities in upper lobes bilaterally. Sputum culture, blood culture, respiratory viral panel, and COVID-19 testing were negative. The patient’s sputum obtained during the last hospital admission had revealed NTM growth and was ultimately identified as M. chelonae. He was started on antimicrobial therapy with clarithromycin 500 mg twice a day, imipenem-cilastatin 500 mg four times a day, linezolid 600 mg twice a day, and amikacin 25 mg/kg three times per week. He continued to improve clinically and was successfully weaned off mechanical ventilation. Susceptibility testing for the M. chelonae isolate revealed it to be imipenem resistant. His regimen was then changed to clarithromycin, linezolid, and amikacin with a plan to continue amikacin for 4 weeks. Clarithromycin and linezolid were to be continued for at least 4 to 6 months from sterilization of repeat AFB sputum cultures. At the time of this case report, the patient continued to make good clinical recovery and was planned for outpatient follow-up with infectious diseases specialists.

DISCUSSION

HSS is a rare disorder of unknown etiology that predominantly affects young men and is characterized by the presence of venous thromboembolism and multiple pulmonary and/or bronchial aneurysms. The treatment primarily involves immunosuppressive therapy, usually a combination of glucocorticoids and cyclophosphamide. Patients on immunosuppressive medications (such as steroids, monoclonal antibodies, tumor necrosis factor inhibitors, azathioprine, and cyclophosphamide) and those with malignancies and rheumatologic diseases are particularly susceptible to M. chelonae infections.^6,7 Our patient was immunosuppressed from chronic prednisone use for his HSS. He had also received azathioprine and infliximab.

The incidence of M. chelonae infection is unknown because there is no mandatory reporting of cases and the bacillus exists in the environment.⁸ The symptoms of M. chelonae infection are nonspecific and include chronic nonhealing ulcers, cellulitis, subcutaneous abscesses, chronic pulmonary infections manifesting as cough, weight loss, night sweats, and fatigue. Due to nonspecific clinical, examination, and radiologic findings in NTM infections, the diagnosis can be challenging. The American Thoracic Society criteria for diagnosing NTM pulmonary infections include the presence of pulmonary symptoms, nodules or cavitation on chest radiograph, and a computed tomography scan showing bronchiectasis/multiple nodules after all other appropriate diagnoses have been excluded. Also, at least two sputum samples should be positive, or one bronchoalveolar lavage sample should be positive for NTM. In patients who undergo lung biopsy, granulomatous inflammation and/or AFB should be visualized on the histologic specimen.⁹

To date, there have not been any controlled clinical trials comparing different treatment modalities for M. chelonae infection. Treatment of all NTM infections is species specific and based on in vitro susceptibility patterns. M. chelonae has consistently shown good susceptibility to clarithromycin, tobramycin, imipenem, amikacin, and doxycycline.⁹ Surgery can be performed in those with extensive cutaneous disease or abscesses or for removal of infected foreign bodies (such as breast implants, percutaneous catheters).

To the best of our knowledge, this is the first case reported of M. chelonae infection in a patient with HSS. With this case report, we aim to sensitize physicians to the wide spectrum of presentation of NTM infection.