A Case of Uncommon Tuberculosis Infection Involving the Sternoclavicular Joint

Introduction

Mycobacterium tuberculosis has been in existence for 150 million years [1]. Evidence of tuberculosis infection in humans dates back up to 3 million years ago in Africa [2]. In 1720, the English physician Benjamin Martin was the first to publish evidence of the infectious origin of M. tuberculosis [2]. Thus, tuberculosis has historical importance. Today, as per the Global Tuberculosis Report 2024, tuberculosis is the most common cause of death due to an infectious agent, with more than 10 million people becoming ill with tuberculosis each year [3].

Involvement of the muscular and skeletal system in tuberculosis is very rare, accounting for approximately 10% of extrapulmonary tuberculosis cases [4,5]. Of these, only 1% to 2% are infection of the sternoclavicular joint [6–8]. The typical presentation of sternoclavicular joint tuberculosis includes an insidious onset of swelling and pain at the sternoclavicular joint, accompanied by the absence of symptoms or mild systemic features, such as fever. Chronic unexplained shoulder pain can also raise suspicion for tuberculosis of the sternoclavicular joint [9,10]. We report an atypical case of extrapulmonary tuberculosis involving the sternoclavicular joint in a 77-year-old woman, highlighting the importance of high clinical suspicion in certain patients with a high risk of tuberculosis exposure.

Case Report

A 77-year-old Tibetan woman initially presented to an urgent care center with concerns of progressive swelling associated with pain over her left medial clavicular region radiating to the left shoulder and neck. The radiograph at urgent care showed soft tissue swelling (Figure 1), and the patient was sent home on ibuprofen. Her past medical history was significant for recurrent aspiration pneumonia, complicated by nodular changes and bronchiectasis in both lungs, for which she was being followed by a pulmonologist. The patient reported a history of a positive purified protein derivative (PPD) test result, with a negative chest radiograph, but was never treated for latent tuberculosis. She denied fever, chills, night sweats, weight loss, change in appetite, productive cough, shortness of breath, lumps, or swelling in any body part. She had migrated from India to the United States and travelled back and forth almost annually.

The patient was initially referred to the oncology department for further workup, with the initial working diagnosis of malignancy, including multiple myeloma and lymphoma. She underwent a core biopsy of the soft tissue mass at the left clavicular head. Pathology results were negative for malignancy. Acid-fast bacilli staining was negative. However, hematoxylin and eosin staining revealed granulomatous inflammation (Figure 2A) with central caseating necrosis (Figure 2B). The differential diagnoses at that time included sarcoidosis and infectious etiologies, such as mycobacterial infection. The patient was started on prednisone 20 mg once daily for 10 days by her oncologist, as she was symptomatic with worsening neck pain. Anti-tuberculosis therapy for latent infection was not initiated before glucocorticoid treatment. Three weeks later, the culture from the biopsied tissue grew acid-fast bacilli. The patient was then referred to an infectious disease specialist. At that time, her pain and swelling had increased (Figure 3).

On physical examination, when initially evaluated at the infectious disease clinic, the swelling was located at the anterior left medial clavicular region, measured 3 cm × 3 cm in size, was fluctuant but fixed, and was mildly tender. There was no obvious erythema or warmth and no drainage. There was also no lymphadenopathy appreciated in the anterior, posterior, supraclavicular, or infraclavicular areas. Considering the patient’s origin from Tibet and subsequent residence in India, her history of positive PPD and untreated latent tuberculosis raised clinical suspicion for M. tuberculosis infection. Other possible mycobacterium infections included M. avium complex, M. abscessus, M. chelonae, and M. fortuitum. An interferon-gamma release assay was not performed. HIV testing was conducted and returned negative. Polymerase chain reaction testing performed by the state Department of Public Health laboratory confirmed that the acid-fast bacilli from the tissue biopsy were M. tuberculosis complex, which led to the timely initiation of anti-tuberculous therapy. Eventually, culture and susceptibility results indicated sensitivity to rifampin, isoniazid, pyrazinamide, and ethambutol (RIPE).

The patient’s computed tomography (CT) scan of the chest showed a 1.7-cm lytic lesion involving the medial aspect of the left clavicle, with a soft tissue mass measuring 3.5×3.1 cm. There was re-identification of right hilar calcifications, which were noted in prior multiple imaging studies from a few years earlier, attributed to prior tuberculosis exposure. Multiple nodular opacities and areas of bronchiectasis were also noted. These findings were reviewed with the patient’s pulmonologist, who determined that the lesions were stable over the years and most consistent with sequelae of recurrent aspiration pneumonia (Figure 4A, 4B). Given that the patient denied any respiratory symptoms, including productive cough, hemoptysis, and shortness of breath, the possibility of active pulmonary tuberculosis was considered unlikely.

The patient was started on a 2-month course of the RIPE regimen of isoniazid 300 mg once daily, rifampin 450 mg once daily, pyrazinamide 1 g daily, and ethambutol 800 mg once daily. She was also prescribed pyridoxine (vitamin B6). After 2 weeks of therapy, she developed drug-induced pruritus without rash, which resolved with antihistamines, and the treatment regimen was continued without interruption.

Four weeks after therapy initiation, the lesion became soft and ulcerated with mild purulent drainage (Figure 5). Repeat CT of the chest showed the prior lytic lesion and a lytic lesion in the manubrium, with the soft tissue mass increasing in size compared with the previous scan. A new adjacent cystic or necrotic mass also extended into the anterior mediastinum (Figure 6A–6D). These findings were considered consistent with paradoxical worsening during tuberculosis treatment, likely contributing to the lesion’s expansion in the context of significant bone involvement, rather than indicating treatment failure, particularly as the patient was still early in her therapy. Treatment was continued without the use of steroids. The patient was taking her medications daily through direct observed therapy supervised by a state tuberculosis nurse.

The RIPE regimen was switched to isoniazid and rifampin after 2 months. The patient was planned to complete a total of 12 months of anti-tuberculosis therapy in the setting of bone and joint infection. She maintained good adherence to medications. Repeat CT of the chest and CT of the neck 7 months after treatment revealed anterior mediastinal collection resolution, with resolution of soft tissue edema over the left clavicular head area (Figure 7). During a follow-up visit after completing almost 12 months of anti-tuberculous therapy, the patient showed a significant clinical response, with a completely resolved ulcerative nodular lesion (Figure 8).

Discussion

Although the incidence of tuberculosis has substantially decreased worldwide, the rate of reduction is slow in Western countries due to the increasing immigrant population [11]. Extrapulmonary tuberculosis accounted for an overall estimated 20.9% of cases, of which 10% involved the musculoskeletal system [4,5]. This was predominantly seen in women, older adults (≥65 years), and people with a history of tuberculosis [5], such as our patient. Infection of the sternoclavicular joint is rare, with an incidence of less than 0.5%, and of those cases, approximately 1% to 2% are extrapulmonary tuberculosis [6–8].

The most common symptoms of tuberculosis are weight loss, decreased appetite, fever, chills, night sweats, weakness/fatigue, chronic cough with or without production of sputum, and hemoptysis. Tuberculosis of the sternoclavicular joint most commonly occurs without any systemic symptoms, which was also demonstrated in our patient [10].

Due to the low incidence of sternoclavicular joint involvement in tuberculosis, the theories behind the pathogenesis are still up for discussion. A more accepted hypothesis describes hematogenous spread from fresh or reactivated pulmonary foci to the sternoclavicular joint. This pathway is the more accepted pattern of osteoarticular tuberculosis of other joints. Other plausible mechanisms include development from continuous spread from an apical pulmonary focus nearby [12,13], which was not the case for our patient, as the lung lesions had remained stable over the years.

Sternoclavicular joint tuberculosis is difficult to diagnose because of its atypical presentation. Extrapulmonary tuberculosis can closely mimic other inflammatory disorders or malignancies, making microbiological and histological confirmation important [14]. Mycobacterial infection can also involve unexpected anatomical sites, requiring a high index of suspicion [15]. In our patient, malignancy was the initial working diagnosis; however, biopsy revealed granulomatous inflammation with central caseating necrosis, narrowing the differential diagnosis to sarcoidosis and mycobacterial infection. A comprehensive workup – including polymerase chain reaction, culture, histopathology, Ziehl-Neelsen staining, and acid-fast bacilli smear – is therefore necessary [8,12]. Epidemiological context should be taken into consideration when evaluating patients. Our patient had lived in and frequently travelled to Tibet and India, both regions endemic for tuberculosis. According to the WHO Global Tuberculosis Report 2024, India accounted for approximately 26 % of global incident tuberculosis cases in 2023, while China accounted for approximately 6.8 % [3]. Within China, tuberculosis incidence in the Tibet Autonomous Region remains substantially higher than the national average [3,16]. Histopathology in tuberculous lesions typically demonstrates chronic granulomatous inflammation [3].

Tuberculosis of the skeletal system will further require imaging studies such as X-ray, and CT can be useful in detecting pulmonary tuberculosis. Magnetic resonance imaging plays a major role in detecting spondylitis from tuberculosis. In other skeletal tuberculosis, magnetic resonance imaging, Technetium-99 scan, arthrogram, and fistulogram can aid in diagnosis [8,17]. Studies also support the use of the Xpert M. tuberculosis/rifampicin assay, an automated nucleic acid amplification test that detects M. tuberculosis complexes and rifampicin resistance directly from clinical specimens, including specimens from extrapulmonary sites, as a valuable diagnostic tool for extrapulmonary tuberculosis [18]. In the absence of positive studies, it is often seen that initiating treatment is vital if clinical suspicion is high due to the risk to public health.

Multiple clinical trials have found that the multidrug treatment of tuberculosis is necessary to achieve bacterial clearance [19,20]. Rifampin, isoniazid, pyrazinamide, and ethambutol are the 4 common drugs used. Treatment includes an intensive phase with the typical RIPE regimen of rifampin, isoniazid, pyrazinamide, and ethambutol, followed by a continuation phase of isoniazid and rifampin. In addition to this, pyridoxine is given to the patients to prevent isoniazid-induced peripheral neuropathy [13,19,20]. The total duration of treatment for sternoclavicular joint tuberculosis can vary from 6 to 18 months based on the severity of the infection or treatment response from the patient [8].

During anti-tuberculosis therapy in an immunocompetent patient with lytic bone lesions and expanding soft tissue masses at the sternoclavicular joint, the development of new cystic or necrotic masses and ulceration after 4 weeks of treatment is consistent with immune reconstitution inflammatory syndrome (IRIS), a paradoxical inflammatory response characterized by clinical or radiographic worsening despite appropriate treatment and adherence. The Infectious Diseases Society of America, Centers for Disease Control and Prevention, and American Thoracic Society guidelines note that IRIS can manifest as development of abscesses, new or worsening lesions, and increased tissue inflammation [13]. IRIS typically occurs within the first 4 to 9 weeks of therapy [21]. In contrast, treatment failure should be suspected with persistent or recurrent positive cultures beyond 4 months or lack of clinical improvement despite adherence and drug-susceptible therapy. Most IRIS episodes do not worsen long-term outcomes. Management is primarily symptomatic, with the continuation of anti-tuberculosis therapy. Close monitoring is essential to distinguish IRIS from true treatment failure and to ensure resolution of inflammatory manifestations [13]. Consistent with this, our patient subsequently demonstrated clinical improvement on continuation of the initial anti-tuberculosis regimen.

Early detection and diagnosis are key to avoiding joint disability. Overall, sternoclavicular joint tuberculosis has a good prognosis and responds well to anti-tuberculosis therapy. Therapy is more effective when there is early detection without extensive damage to the affected joint. Advanced tuberculosis arthritis of the sternoclavicular joint has been shown to have better clinical progress with surgical debridement and standard therapy, especially in cases of multidrug resistance [22]. Steroid usage in arthritic tuberculosis is indicated only if signs of tubercular meningitis exist. The role of steroids in skeletal tuberculosis is an area that needs to be studied further [13]. Our patient had a successful outcome, with resolution of anterior mediastinal collection and complete healing and closure of her clavicular ulcerative wound with 12 months of antituberculosis therapy; she has not required any surgical intervention or steroid use.

Conclusions

Diagnosis of tuberculous involvement of the sternoclavicular joint is challenging, as its presentation can mimic malignancy or inflammatory disorders, such as sarcoidosis. A multimodal diagnostic approach, including imaging, histopathology, and microbiologic studies, is essential to exclude these conditions. A high index of suspicion remains crucial, particularly in patients with epidemiologic or clinical risk factors for exposure. With timely diagnosis and an appropriate course of anti-tuberculous therapy, favorable outcomes can be achieved.