The majority of cases of tuberculosis (TB) affect the lungs, but around 20% of active cases are extrapulmonary tuberculosis (EPTB), which can affect any part of the human body, including bones, joints and lymph nodes. Most EPTB cases are found in HIV patients; however, the overall incidence increases with the degree of immunosuppression.
A 22-year-old man with uncontrolled type 1 diabetes mellitus, an HbA1c of 11.8% and dermatomyositis (NXP2+) presented to Dr. Caroline Jansen’s team at Emory University School of Medicine in Atlanta, Georgia [1]. The patient had had a fever (max. 39.4°C) for 3 days, severe pain in the left thigh and was unable to walk. Treatment for dermatomyositis included prednisone, methotrexate, tofacitinib, and intravenous immunoglobulin during relapses. He was prescribed 25 U insulin glargine twice daily and 10 to 12 U insulin lispro with meals. He had a history of a left lower extremity (LLE) abscess that had been incised and drained 2 years previously, in which group B Streptococcus and methicillin-susceptible Staphylococcus aureus were proliferating. He was diagnosed with pneumonia four months ago and was treated with levofloxacin/linezolid as per experience. On arrival, he reported that he had no pulmonary symptoms and had not used drugs or been sexually active in the past year. He had recently worked in a funeral parlor.
On arrival, the patient was tachycardic, normotensive and afebrile. Physical examination revealed a painful, warm and reddened left knee and distal lateral thigh with limited range of motion due to pain, point-of-care ultrasound showed no fluid collection over the left distal lateral thigh. Laboratory results were notable for hyperosmolar hyponatremia (122 mmol/l), hyperglycemia (670 mg/dl) with elevated beta-hydroxybutyrate, metabolic acidosis, and thrombocytosis (648×109/l). Further tests revealed an increased D-dimer value, C-reactive protein (50 mg/dl) and an increased erythrocyte sedimentation rate (94 mm/h).
Detection of a M. tuberculosis infection
The infection examination revealed a negative COVID-19 polymerase chain reaction test, a positive (1.3) beta-D-glucan value and a positive QuantiFERON-Gold for the detection of a Mycobacterium tuberculosis infection. Computed tomography of the chest showed a cavitary lesion in the left lower lobe. In addition, bronchoalveolar lavage revealed acid-fast bacilli, and the corresponding culture was positive for M. tuberculosis. In addition, magnetic resonance imaging (MRI) of the left lung showed inflammatory myositis/fasciitis. MRI of the spine showed chronic changes consistent with chronic steroid treatment, with no evidence of Pott’s disease.
On admission, vancomycin + piperacillin/tazobactam, intravenous immunoglobulin (2 g/kg), insulin and increased doses of prednisone were administered. As there were no risk factors for drug-resistant disease, rifampicin, isoniazid, pyrazinamide and ethambutol (RIPE) were administered after confirmation of tuberculosis and a negative GeneXpert MTB/RIF test. After a moderate improvement in symptoms was observed following the start of treatment, the patient was discharged home with the recommendation of further follow-up examinations.
Re-presentation after 3 months
Three months later, the patient presented again complaining of several weeks of increasing back and LLE pain accompanied by facial swelling, fever, malaise and anorexia. He did not report night sweats, cough, sputum production, skin lesions, muscle weakness or dysuria. He was also adherent to TB treatment (rifampicin/isoniazid) and his dermatomyositis treatment regimen, was afebrile and tachycardic. Examination findings revealed diffuse tenderness of the bilateral lower extremities with a sensitive fluctuant area in the center of the left posterolateral thigh.
The laboratory tests revealed hyperglycemia (679 mg/dl), an HbA1c value of 13.0%, a C-reactive protein of 9.9 mg/dl, a erythrocyte sedimentation rate of 93 mm/h and an aldolase of 14.6 U/dl.
In addition, MRI of the lower extremities showed bilateral diffuse intramuscular and myofascial edema and a complex, multilocular, intermuscular, subfascial fluid collection in the proximal-to-midposterior compartment of the left thigh. According to Dr. Jansen, aspiration of the fluid collection was preferred over surgical drainage. Histopathology revealed focal necrotic muscle fibers and perifascicular atrophic fibers with mild endomysial inflammation (Fig. 1). Tissue staining was positive for CD3 and CD20. The anaerobic, aerobic and fungal cultures from the aspirate were negative. Culture to confirm acid-fast bacilli revealed M. tuberculosis, with tests showing pan-sensitivity to RIPE.
Polymicrobial abscess as a harbinger?
This unusual case of EPTB showed a complex presentation of TB myositis in an immunocompromised patient, highlighting the intricate interplay between risk factors and disease development, the complexity of immune mechanisms behind ETPB, and the variability of clinical presentations of pulmonary and extrapulmonary TB, the authors write.
A definitive diagnosis often requires histopathologic, cultural and molecular testing. According to Jansen et al., diagnosis is often delayed due to the extensive differential diagnosis for myositis-like symptoms. The patient’s condition did not improve despite therapy for an episode of dermatomyositis, and improvement in symptoms was not observed until RIPE therapy was started. At his next presentation, a dermatomyositis flare was less likely as the patient’s immunosuppressive therapy had been reduced since his TB diagnosis and he showed no muscle weakness. Due to the improvement in symptoms after starting RIPE therapy, the primary diagnosis was TB-related myositis.
Immunosuppression is a well-described risk for tuberculosis, and the risk of tuberculosis is particularly increased in immunocompromised patients, such as HIV patients or patients taking disease-modifying antirheumatic drugs. In addition, diabetes is associated with a higher risk of tuberculosis and unfavorable treatment outcomes. The mechanism driving this is unknown, although impaired cytokine production may contribute. The patient’s HbA1c worsened between presentations, which could be due to an increase in his steroid therapy or continued difficulty accessing his medications, the authors emphasized. In both cases, his diabetes could have contributed to his infection. Immunocompromised patients, such as those with HIV/TB co-infections, are known to present with atypical symptoms, which could partially explain this patient’s symptomatology.
Increased risk due to work in a funeral home
Although no cultures were taken, the pneumonia that had taken place probably represented the developing TB cavity. The antibiotic regimen would only incompletely treat the TB with little penetration into the musculoskeletal system, which could explain the resolution of his pulmonary symptoms and the appearance of myositis without pulmonary symptoms. This history and the growing suspicion of M. tuberculosis infection led to the chest CT scan on admission. This emphasizes the importance of watching for signs of infection in immunocompromised patients. It may be advisable to opt for definitive, culture-based treatment, especially in immunocompromised patients, as they are at increased risk of TB infection, the US doctors said.
In addition, TB myositis is more common in patients with autoimmune diseases, particularly those with dermatomyositis/polymyositis, and proximal lower limb myositis is typical in these patients. This could be due to the association of these diseases with proximal muscle weakness. However, according to Dr. Jansen, this would not explain the predilection for the presentation of TB myositis in the lower extremities in these patients. On further investigation, the history revealed that her patient had previously had a polymicrobial abscess in his proximal LLE, raising the question of whether this had primed the site for subsequent infection.
The patient had no usual exposures: He had no close contacts, had not migrated from an endemic area, never moved, and never worked in correctional facilities or nursing homes. However, he had recently been employed as a funeral home worker, which involves performing aerosolization procedures and is associated with an increased risk of TB exposure. This could explain the patient’s conversion from a negative QuantiFERON test two consecutive years prior to a positive one at the time of diagnosis and emphasizes the importance of a detailed medical history in establishing a differential diagnosis and diagnostic plan.
Literature:
- Jansen C, et al: Mycobacterium tuberculosis Myositis Without Concurrent Pulmonary Symptoms in a Patient With Immunosuppression. AIM Clinical Cases 2024; 3: e230950; doi: 10.7326/aimcc.2023.0950.
InFo PNEUMOLOGY & ALLERGOLOGY 2024; 6(4): 22-23
