Mycobacterium Immunogenum Flexor Tenosynovitis: A Case Report

Abstract

Background  Nontuberculous mycobacterial (NTM) flexor tenosynovitis represents a rare but potentially devastating manifestation of upper extremity infection. We present a novel case of NTM flexor tenosynovitis in which Mycobacter iumimmunogenum was found to be the causative agent.

Case Description  The patient presented with pain and insidiously progressive swelling and required multiple operative interventions and a complex antimicrobial regimen based on susceptibility profiles. Specifically, our patient was managed with three debridements and empiric antimicrobial agents based on inherent macrolide sensitivity, with later conversion to a complex antimicrobial regimen tailored to sensitivity.

Literature Review  The diagnosis and management of NTM tenosynovitis arechallenging because of low suspicion, nonspecific presentation, and cumbersome laboratory identification techniques. M. immunogenum was only characterized in the past two decades, and, to our knowledge, this is the first reported case of the pathogen causing a musculoskeletal infection.

Clinical Relevance  We present this case primarily because of the novelty of the organism and to demonstrate the recalcitrant nature of the infection. Due to the extensive resistant patterns of M. immunogenum , management requires complex antimicrobial preparations and almost certainly needs multispecialty collaboration between orthopaedic surgery and infectious diseases.

Nontuberculous mycobacteria (NTM) tenosynovitis is an uncommon upper extremity infection. While specific data on NTM tenosynovitis epidemiology is lacking, studies have estimated that only approximately 10% of NTM infections are extrapulmonary, and an even smaller subset of those represent musculoskeletal infections. ¹ In immunocompetent patients, there is more often than not a history of traumatic inoculation—surgery, penetrating injury, corticosteroid injection—preceding presentation. ² Insidious swelling and chronic stiffness are common clinical manifestations of infection, and patients tend to receive a diagnosis of autoimmune or idiopathic synovitis before NTM infection is considered. ^{3 4} There are many reports in the literature to date describing clinical and radiologic presentations of NTM infections of the upper extremity. ^{5 6} These pieces focus on pathogens that are regularly implicated in NTM tenosynovitis such as Mycobacterium marinum , Mycobacterium avium complex , Mycobacterium chelonae , and Mycobacterium intracellulare. To the best of our knowledge, no reports of M. immunogenum musculoskeletal infections exist in the English literature.

This report serves to bolster the body of knowledge available to physicians who treat these hardy infections. The authors hope that by giving our experience with this infection, we will heighten awareness of M. immunogenum (and NTM species as a whole) as a causative agent of flexor tenosynovitis in immunocompetent patients. Furthermore, we aim to provide a rudimentary treatment algorithm when this infection is faced and to highlight potential pitfalls with its use.

Case Report

A 61-year-old male carpenter developed swelling in his left ring finger and palm in November 2018. He initially presented to an outside institution endorsing a prior penetrating injury to his left hand, which progressed to intermittent numbness in all digits but the small finger. He received an oral methylprednisolone taper and ring finger A1 pulley triamcinolone injection, which provided temporary relief.

In January 2019, he presented to our institution with tenderness to palpation along the ring finger flexor tendon, pain with passive extension of all fingers, a positive Durkan's test, and worsening forearm erythema ( Fig. 1 ). His hand MRI (magnetic resonance imaging) revealed fluid pockets surrounding the flexor tendon sheath ( Fig. 2A , B ). Therefore, he was taken for culture and surgical debridement, which revealed extensive flexor tenosynovitis of the hand, wrist, and forearm ( Fig. 3A , B ).

Fig.1.

Swelling in the hand prior to surgery.

Fig. 2.

( A ) Precontrast axial magnetic resonance imaging (MRI) images with fat saturation demonstrating enhancing signal of the tenosynovitis surrounding the flexor tendons. ( B ) Postcontrast axial MRI images with fat saturation demonstrating enhancing signal of the tenosynovitis surrounding the flexor tendons.

Fig. 3.

( A ) Extent of debridement with wound fully open. ( B ) Tenosynovium adherent to the tendons and nerves, and rice pattylike inflammatory changes of the soft tissue.

Mycobacterium immunogenum speciated 16 days postoperatively ( Fig. 4 ). Gene sequencing and susceptibility testing wereperformed at an outside center ( Table 1 ). Intravenous amikacin, tigecycline, and oral azithromycin were started with N-acetylcysteine for ototoxicity protection. N-acetylcysteine was not tolerated, but he had a normal baseline audiometry.

Fig. 4.

Acid-fast bacilli tissue staining demonstrating the presence of atypical (nontuberculous) mycobacterial species in the collected specimen.

Table 1. Mycobacterialsusceptibility profile.

Antibiotics	Microdilution (µg/mL)	Susceptible	Intermediate	Resistant
TMP-SMX	8/152			X
Linezolid	16		X
Ciprofloxacin	>4			X
Imipenem	16		X
Moxifloxacin	>8			X
Cefoxitin	32		X
Amikacin	32		X
Doxycycline	>16			X
Minocycline	>8			X
Tigecycline	0.25
Clarithromycin	0.5	X
Clofazimine	0.25

Abbreviation: TMP-SMX, trimethoprim/sulfamethoxazole.

Two months postoperatively, he transitioned to oral azithromycin, tedizolid, and clofazimine. He required repeat surgical debridements 4, 5, and 6 months postoperatively for symptom recurrence. He restarted his first antimicrobial regimen with the addition of clofazimine. Amikacin was stopped (for sensorineural hearing loss) and oral tedizolid was added. The patient's hearing has not worsened, and he reported improved function and decreased pain at last follow-up in December 2019.

Discussion

This case of NTM tenosynovitis was unique because of the novel causative agent, M. immunogenum , and the tortuous antibiotic regimen required to treat the infection. It is also noteworthy that our patient was immunocompetent but still had extreme difficulty fighting the infection. He had a history of trauma as well as corticosteroid injection in the infected extremity, both of which could have represented inoculation events. He presented to our hand surgery clinic with a chronically swollen and painful extremity and abnormal albeit nonspecific imaging findings consistent with an infectious inflammatory process of the flexor tendons. He responded to multiple surgical debridements in concert with an extended and complicated antimicrobial regimen that was based on intrinsic sensitivity at first and then tailored to susceptibility profiles.

Nontuberculous mycobacteria are frequently encountered in nature but are rare causes of infection in immunocompetent patients when compared with tuberculous species. ⁵ NTM tenosynovitis classically presents with insidiously progressive pain, swelling, and dysfunction of the hand or digits in the setting of some prior local trauma. ¹ With M. immunogenum in particular, exposure to natural or industrialized water sources has been previously described as a possible risk factor. ^{7 8} Radiographic findings are often inconclusive, but the presence of rice bodies in the tendon sheath with sparing of surrounding soft and bony tissues may indicate infection. ⁵ Granulomatous inflammatory changes are common with NTM infections but are unfortunately nonspecific findings for this disease. ¹ Diagnosis remains challenging likely due to the relatively low clinical suspicion of NTM infection in the musculoskeletal system, inability of patients to recall a small index trauma, the need for specialty laboratory testing, and nonspecific clinical and radiographic findings. Early diagnosis is key in the management of these patients as delays in diagnosis and treatment of NTM tenosynovitis are more likely to lead to worse functional outcomes. ^{1 4}

Even after diagnosis, the treatment of NTM infections generally proves challenging for both patients and clinicians. Clearance of disease often requires long courses of surgical and medical management. No current consensus exists for a standard algorithm of treatment, though most consider surgical debridement in combination with antibiotics to be necessary for clearance of NTM infections. ^{1 4 5 6} Cheung et al ⁴ used a protocol of synovectomy in concert with antimicrobial agents in the management of almost 30 years and more than 150 cases of Mycobacterium marinum tenosynovitis at their institution. Each of the patients in their review received open biopsy, extensor or flexor synovectomy, and some combination of antituberculosis drugs (rifampin, ethambutol) and adjuvant antimicrobials (clarithromycin, minocycline, levofloxacin, pyrazinamide, isoniazid). Choice of antimicrobial therapy was based on sensitivity and tolerance to the drugs, with nearly half of their patients needing only rifampin and ethambutol regimens. Duration of antimicrobial treatment was based on clinical appearance in their study and was 7.2 months long on average. Sotello et al ¹ in their review of 15 years and more than 40 culture-positive NTM infections of the upper extremity found that more than two-thirds of patients were treated with a combination of surgery and antibiotics. In that same study, patients who received antibiotics alone compared with dualtherapy tended to have worse outcomes. The authors also proposed that antibiotic choice should be based on susceptibility testing and recommend at least two active drugs for the treatment of NTM infections.

It is important to differentiate between M. immunogenum and other members of the rapidly growing nontuberculous mycobacterium (RGNTM) group due to extensive antimicrobial resistance patterns. ⁹ Mycobacterium immunogenum belongs to a subset of RGNTM group that does not have a functional erythromycin ribosomal methylase (erm) gene, which makes it intrinsically sensitive to macrolides. ¹⁰ Other case reports discussing the treatment of M. immunogenum infection found success when aminoglycosides and fluoroquinolones, as well as macrolides were employed in the management algorithm. ^{7 9 11} When Shenoy et al ⁹ managed their case of M. Immunogenum peritoneal dialysis catheter site infection, treatment involved surgery and antibiotics. Their initial antibiotic regimen before susceptibility profiles were available was a macrolide (azithromycin) based on intrinsic sensitivity. Due to progression of disease, the authors went on to add amikacin based on previously reported susceptibility and tigecycline due to known susceptibility of RGNTM to that drug. This knowledge helped to guide the early empiric antimicrobial regimen for our patient, which was composed of azithromycin, amikacin, and tigecycline. Once sensitivity profiles were available and side effect profiles were established, our patient's regimen was tailored to provide an optimal outcome.

The diagnosis and management of NTM tenosynovitis arechallenging because of low suspicion, nonspecific presentation, and cumbersome laboratory identification techniques. Mycobacterium immunogenum was only characterized in the past two decades, and, to our knowledge, this is the first reported case of the pathogen causing a musculoskeletal infection. That being said, early diagnosis is crucial and relies heavily on having a high index of suspicion for NTM as a cause of flexor tenosynovitis. When common clinical findings (water-related exposures, prior local trauma, subacute–chronic infection) of NTM infection present in the absence of symptoms of more common diseases, surgeons should have a low threshold for testing for uncommon agents such as NTM. Culture and acid-fast bacilli smear are important, but they are not sensitive as negative results often do not rule out atypical disease such as nontuberculous mycobacteria. ^{1 4} Diagnosis should rely on the aforementioned tests as well as prompt gene sequencing at centers able to perform transcription-based specimen identification such as polymerase chain reaction. Our patient was managed with four debridements and empiric antimicrobial agents based on inherent macrolide sensitivity, with later conversion to a complex antimicrobial regimen tailored to sensitivity.

Funding Statement

Funding None.