Disseminated tuberculosis in an immunocompetent healthy young male with nonspecific symptoms: challenges toward diagnosis—a case report

Abstract

Background

Disseminated tuberculosis, characterized by spread of Mycobacterium tuberculosis to multiple noncontiguous sites, is rare in immunocompetent individuals. Diagnosing disseminated tuberculosis is challenging due to its varied and often nonspecific symptoms.

Case Presentation

We report the case of a 29-year-old Bangladeshi male with no notable past medical history, who presented with prolonged fever, night sweats, cough, weight loss, and altered bowel habits over 6 months. Initial evaluations in Italy and France did not yield a definitive diagnosis. Further investigations in Bangladesh, including sputum smear, fine-needle aspiration cytology of a postauricular lymph node, abdominal ultrasonography, and magnetic resonance imaging of the brain confirmed disseminated tuberculosis. The patient responded excellently to a standard four-drug antitubercular therapy regimen.

Conclusions

Disseminated tuberculosis should be considered in patients with systemic symptoms, particularly those from regions with a high tuberculosis burden. Early and accurate diagnosis, despite atypical presentations and initial negative findings, is crucial for effective treatment and improved outcomes.

Background

Tuberculosis (TB), a leading global infectious killer that predominantly affects the lungs, although it can manifest in other organs, often presents with nonspecific symptoms that can mimic other conditions and delay diagnosis [1]. With a mortality rate of 24 per 100,000 and an incidence of 221 per 100,000, Bangladesh, among the 30 high-burden countries, is responsible for 3.6% of global TB cases [2]. In 2022, TB resulted in about 1.3 million deaths and affected an estimated 10.6 million people globally. Although TB is curable and preventable, multidrug-resistant TB (MDR-TB) remains a major public health crisis, with only 40% of affected individuals receiving treatment. Since 2000, efforts to combat TB have saved approximately 75 million lives. To meet the 2018 United Nations targets, an annual funding of US$13 billion is needed for prevention, diagnosis, treatment, and care. Ending the TB epidemic by 2030 is a key goal of the United Nations Sustainable Development Goals (SDGs) [3].

Disseminated tuberculosis (dTB) occurs when Mycobacterium tuberculosis spreads to multiple noncontiguous sites via the bloodstream, typically due to primary infection, latent reactivation, or, rarely, iatrogenic causes [4]. Its global incidence in immunocompetent adults is under 2% of all TB cases and up to 20% of extrapulmonary TB cases [5]. Disseminated tuberculosis primarily affects immunocompromised individuals, particularly those with human immunodeficiency virus (HIV), malnutrition, diabetes, genetic predispositions, smoking, or alcohol abuse. The disease can affect organs including the lungs, liver, spleen, bone marrow, kidneys, adrenals, eyes, brain, and thyroid. In developed nations, dTB affecting multiple organs is infrequent in immunocompetent patients [6,7,8,9,10].

Symptoms of dTB are varied and include chronic symptoms such as fever, weight loss, and night sweats, ranging from anorexia and unexplained fever to multiorgan failure, depending on the organs involved. Extrapulmonary TB accounts for one-fifth of TB cases and may occur without pulmonary signs, making diagnosis difficult and often delayed by over a month [5].

Disseminated tuberculosis is a significant global health issue, with high morbidity and mortality, especially in regions with high TB prevalence like Bangladesh. According to a review of the available literature, disseminated TB is estimated to account for less than 2% of TB cases in immunocompetent adults [10,11,12].

This report details the case of a previously healthy adult with no prior medical history who developed widespread TB affecting multiple organs, including the lungs, brain, and spleen. Despite the patient's origin from Bangladesh, a country with a high TB burden, healthcare providers in France initially did not consider TB in their differential diagnosis. This oversight resulted in a delayed diagnosis, highlighting the need for heightened clinical awareness in such cases. The uniqueness of this case lies in the significant contrast between the patient’s high-risk background and the failure to recognize TB promptly. By presenting this case, we aim to provide valuable insights that may assist healthcare professionals in recognizing and managing similar cases effectively.

Case presentation

A 29-year-old Bangladeshi male, with no significant past medical history, presented with a 6-month history of fever, chills, rigors, and night sweats and was admitted to a private clinic. The patient also reported a cough persisting for 2 months, which recently became associated with altered bowel habits, including loose stools occurring two to three times per day over the past month. Significant weight loss was noted, although there was no associated hemoptysis. The patient denied any known direct contact with individuals diagnosed with tuberculosis.

The patient, originally from Bangladesh, moved to Italy 8 months ago. After residing in Italy for 4 months, he relocated to France. It was during his stay in France that he began experiencing the onset of cough, malaise, and loss of appetite. Subsequently, he was hospitalized and evaluated for these symptoms in France; they treated his case as enteric fever, and he was discharged with minimum improvement. He experienced a low-grade fever, cough, and 12-kg weight reduction in the past 6 months. He had returned to Italy, but his condition continued to deteriorate. This led him to return to his home country, where he sought further evaluation at our facility. Unfortunately, he was unable to show any investigation report or documents related to his medical record regarding his treatment and management in France as he did not take these with him upon his return.

Upon physical examination at our clinic, he presented with a high-grade fever of 104 °F (40 °C), a pulse rate of 104 beats per minute, and blood pressure of 100/60 mmHg. Heart sounds were normal, and lung auscultation revealed no abnormalities. Notably, there was bilateral cervical lymphadenopathy; the lymph nodes were nonmatted, firm, and nontender. Abdominal palpation yielded no significant findings.

Initial laboratory tests revealed anemia (hemoglobin 8.3 g/dL), elevated erythrocyte sedimentation rate (ESR 82 mm/hour), and leukocytosis (WBC 11,000 cells/µL) with neutrophilia (80%). Urinalysis showed microscopic hematuria and trace albumin. Serum creatinine was within normal limits. Liver function tests showed slightly elevated SGPT (58.9 U/L). HIV serology was negative. The patient’s total bilirubin was normal at 0.6 mg/dL, with direct and indirect fractions each at 0.3 mg/dL. An HIV test returned negative results.

Despite initial treatment with injectable ceftriaxone, there was no improvement in his condition. Diagnostic imaging included a normal chest X-ray, negative sputum for acid-fast bacilli, and a negative tuberculin skin test, which initially led us away from a pulmonary tuberculosis diagnosis. However, further evaluations with morning sputum were positive for GeneXpert for tuberculosis, and ultrasonography of the spleen showed a normal-sized spleen that was regular in contour and with a uniform echotexture, multiple ill- and well-defined nodular hypoechogenic areas (20–25 in number, with the largest one being 7.13 mm in diameter), and a normal spleno-portal system, consistent with splenic tuberculosis (Fig. 1). Fine-needle aspiration cytology (FNAC) of a lymph node from the left postauricular region showed cellular material composed of epithelioid cells arranged in groups and singly in a background of mature lymphocytes, polymorphs, histiocytes, and caseous necrosis, indicative of chronic granulomatous lymphadenitis favoring a diagnosis of tuberculosis (Fig. 2).

Fig. 1

Ultrasound image of the spleen showing multiple ill- and well-defined hypoechoic nodular lesions (A); Doppler image demonstrating a normal spleno-portal venous system (B)

Fig. 2

FNAC of left postauricular lymph node showing epithelioid cells and caseous necrosis

The QuantiFERON-TB test was initially planned; however, due to its high cost and unavailability at the local center, the patient declined to undergo the test. The comprehensive clinical picture, supported by laboratory and imaging findings, led to the diagnosis of disseminated tuberculosis (Tables 1, 2). This diagnosis was particularly challenging given the atypical presentation and initial negative findings for pulmonary involvement, highlighting the complexities of diagnosing extrapulmonary and disseminated forms of TB.

Table 1 Timeline of case illness and follow-up

Table 2 Investigation summary of case

The patient was started on a standard four-drug antitubercular therapy regimen consisting of isoniazid, rifampicin, pyrazinamide, and ethambutol. Meanwhile, he was undergoing magnetic resonance imaging (MRI) of the brain owing to recent-onset severe headache, which revealed a left cerebral infiltrative mass involving the left thalamus-midbrain and adjacent medial occipital temporal region. Ependymal and plial infiltrates as well as discrete tiny brain parenchymal infiltrates present involving both the cerebral and the cerebellar hemisphere suggested possible central nervous system (CNS) involvement. (Fig. 3).

Fig. 3

MRI of the brain showing an infiltrative mass involving the left thalamus, midbrain, and adjacent medial occipito-temporal region (arrow) in axial T1-weighted image (A); contrast-enhanced image showing heterogeneous enhancement of the lesion (B)

He responded to the treatment with a resolution of fever, a 3-kg weight gain in 2 weeks, and an overall improvement in well-being. He continues to be monitored regularly in our outpatient basis.

Discussion

TB is a chronic infectious disease caused by M. tuberculosis that primarily affects the lungs, although it can invade any organ. TB presents with clinical diversity, with symptoms depending on the organ affected. It often appears as nonspecific constitutional symptoms with systemic manifestations leading to diagnostic challenges [13].

The diagnosis of dTB presents considerable challenges due to its diverse clinical manifestations and potential for misdiagnosis. The clinical presentation of dTB was widely varied, often featuring subacute or chronic constitutional symptoms such as fever, weight loss, and night sweats. Symptoms can range from anorexia and unexplained fever to multiorgan failure, reflecting the affected organs. Diagnosis is challenging and frequently delayed, with over 50% of patients seeking medical help after more than a month of symptoms. Adults typically present with anorexia, fatigue, dyspnea, night sweats, fever, abdominal pain, hemoptysis, headache, mental changes, pleural effusion, ascites, and lymphadenopathy. In children, symptoms such as vomiting. diarrhea, seizures, hepatomegaly, splenomegaly, jaundice, and meningism are more common [14].

Our patient presented with persistent low-grade fever with chills and rigor, a cough lasting for 6 months, significant weight loss despite a good appetite, and a recent change in bowel habits (predominantly loose stools) without any hemoptysis or history of TB contact. These symptoms that could be attributed to various conditions, including infections, malignancies, and autoimmune disorders.

During the diagnostic process, we considered several differential diagnoses, including enteric fever, HIV-related opportunistic infections, lymphoma, and systemic infections such as brucellosis and typhoid fever. Initial evaluations in Italy and France did not yield definitive answers, leading to the treatment of the patient as a case of enteric fever, which proved ineffective. This emphasizes the necessity for a high index of suspicion for tuberculosis, particularly in patients with travel histories to endemic regions. The literature indicates that the prevalence of both TB and disseminated TB is very uncommon in developed countries [10]. Since our patient was residing in Italy during the symptomatic period, clinicians did not initially suspect TB. A physician in Bangladesh diagnosed disseminated TB after a lengthy 8 months, by which time the patient had already developed a severe headache due to CNS dissemination. The prolonged suffering and delayed initiation of antitubercular therapy occurred because doctors in Italy did not suspect TB. Due to its nonspecific clinical presentation and the limited tools available for confirmatory laboratory diagnosis, diagnosis is challenging. The tuberculin skin test is unreliable for diagnosing TB, especially in extrapulmonary cases, due to potential false positives and negatives. Interferon gamma release assays (IGRAs) are more accurate, detecting T cells specific to M. tuberculosis antigens, and are valuable when combined with clinical suspicion and radiographic findings. Occasionally, TB is confirmed only after a patient recovers following antituberculous therapy [13].

Imaging studies cannot conclusively diagnose dTB owing to low sensitivity and specificity, but they help to identify affected sites and guide specimen collection. Chest X-rays show a miliary pattern in 85–90% of cases but are not specific. High-resolution computed tomography (CT) scans reveal additional findings such as miliary nodules and septal thickening. Abdominal ultrasound and CT detect liver disease, hepatosplenomegaly, peritoneal thickening, ascites, and lymphadenopathy, although these findings are also nonspecific. MRI is superior for identifying miliary lesions at extrapulmonary sites. Brain CT with contrast and MRI assess TB lesions such as meningeal enhancement and tuberculomas. Echocardiography and positron emission tomography (PET)–CT evaluate other extrapulmonary involvement, but none is confirmatory for TB [4, 14, 15].

Disseminated TB should be confirmed through bacteriological methods acid-fast bacilli (AFB) smear and culture in liquid and solid media), polymerase chain reaction (PCR), or histological evidence. Diagnosis is established if any of the following are present: isolation of M. tuberculosis, positive PCR, or histological evidence of caseating granulomatous inflammation from bone marrow, blood, liver biopsy, or at least two noncontiguous organs, with or without miliary lung lesions. Alternatively, confirmation can be made with isolation of M. tuberculosis, positive PCR, or histopathological identification of caseating granulomas from one organ alongside radiographic evidence of miliary lung lesions.

This case illustrates several key points in the diagnosis of disseminated TB. The absence of pulmonary findings and a negative tuberculin skin test initially misdirected the diagnostic process. The persistence of systemic symptoms, suggestive splenic nodules, and the eventual positive findings in sputum (positive GenXpert for TB) and FNAC from postauricular lymph node were critical in confirming the diagnosis. This case emphasizes the need for a high index of suspicion and comprehensive evaluation in patients with unexplained systemic symptoms, particularly in those with recent residence in areas with high TB prevalence.

No randomized controlled trials specifically address the treatment of disseminated TB, with most evidence derived from pulmonary TB studies. Although there is no consensus on the optimal treatment duration for disseminated TB, early initiation of therapy significantly improves outcomes. Generally, treatment duration mirrors that of pulmonary TB but may require individual adjustments, especially in cases of high organism burden, slow clinical response, immune suppression, CNS infection, or bone and joint involvement.

The standard treatment involves a four-drug regimen for the first 2 months, followed by rifampicin and isoniazid for an additional 4–7 months. Response to first-line anti-TB drugs is generally good. For multidrug-resistant TB, treatment includes at least one susceptible injectable drug and three additional susceptible drugs to prevent further resistance development. The role of corticosteroids in disseminated TB remains unclear, as most evidence comes from TB infection trials rather than those specific to disseminated TB. However, adjunct corticosteroid therapy can be beneficial in cases of TB meningitis, pericarditis, adrenal insufficiency, and refractory hypoxemia [13, 16, 17].

Comparing this case with similar cases in the literature highlights common diagnostic dilemmas faced by clinicians managing dTB in immunocompetent individuals. Studies indicate that dTB often manifests with vague symptoms, leading to delays in diagnosis [18, 19]. This case contributes to the growing body of evidence suggesting that, although dTB is rare in immunocompetent individuals, it should not be overlooked, particularly in patients presenting with atypical manifestations.

The delay in diagnosis can also be attributed to factors related to the patient’s travel history. Initially presenting in Italy and France, the patient faced healthcare systems that may not have prioritized TB testing given the nonspecific symptoms and lack of a clear epidemiological link. Negative findings from initial sputum tests and imaging may have further misdirected clinicians toward alternative diagnoses. The absence of accessible medical records from previous treatments added to the complexity of the clinical picture.

Conclusion

This case highlights the diagnostic challenges posed by disseminated tuberculosis (dTB), particularly in immunocompetent individuals presenting with nonspecific symptoms. The patient’s prolonged symptoms, initial misdiagnoses, and ultimate confirmation of dTB after extensive evaluation underscore the need for heightened clinical suspicion and comprehensive diagnostic approaches, especially in individuals from regions with a high TB burden. Early and accurate diagnosis is critical for effective treatment and better prognosis. This case also emphasizes the importance of considering extrapulmonary TB manifestations and the role of thorough clinical and diagnostic evaluations in managing complex TB cases. The patient’s positive response to standard antitubercular therapy further demonstrates the efficacy of prompt and appropriate treatment interventions. Key takeaways from this case include the necessity of maintaining a high index of suspicion for disseminated TB in patients with prolonged, unexplained systemic symptoms, particularly those originating from areas with a high TB burden. Furthermore, the potential for improved diagnostic tools and approaches—such as enhanced imaging techniques or rapid molecular testing—could significantly aid in the earlier identification of dTB in similar patients. This underscores the need for ongoing research and development in diagnostic methodologies to better address the complexities of TB management in diverse clinical settings.