Mycobacterium tuberculosis remains one of the major pathogens infecting approximately one-third of the population and is responsible for nearly 2 million deaths annually. It is known that rheumatological pathologies such as rheumatoid arthritis can be associated with an increased risk of association with tuberculosis, but it remains unknown what proportion of this risk comes from the immunologic disease itself and what proportion from immunosuppressive therapy. The latent form of tuberculosis can become active (about 10 per cent of the time) and a reactivated TB case can be fatal. Therefore, the patients with PAR should be screened for TB regularly. There are recommended test for TB like tuberculin skin test, interferon gamma release assay, sputum analysis and chest X-ray. (1) In the specialized literature, a lot of opportunistic and non-opportunistic infections are described in patients with PAR who follow treatment with the “anchor drugs” (methotrexate, azathioprine, cyclophosphamide, corticosteroids). An increased risk of developing active tuberculosis has been shown in patients with PAR receiving a mean prednisone dosage/day/year. With the introduction of biological therapy - inhibitors of TNFα in PAR, otherwise very effective, the development of tuberculosis was observed, TNFα representing a factor with a crucial role in the host’s immune response (2). The production of TNFα by alveolar macrophages is essential in tuberculous granuloma formation, cytokine production, leukocyte recruitment and destruction of pathogens, in this case Mycobacterium tuberculosis. Anti-TNFα agents proved to determine a good control of the symptoms and the lowering or arrest of the disease progression. However, it has been recognized that the anti- TNFα agents associate an increased risk of reactivation of latent tuberculosis infection (LTBI). A rare fatal presentation of mycobacterial infection, miliary TB, can occur in patients under immunosuppressive treatment especially when anti-TNFα agents are combine with other non-biological therapy (3).
A 54 years old female, former smoker weaned for 15 years, with professional exposure, diagnosed in 2012 with rheumatoid arthritis, initially treated with Methotrexate and corticotherapy, then with Leflunomide and Adalimumab interrupted in June 2022 due to impaired renal function when she also performed in another medical center a CT scan (computed tomography) which highlighted multiple centrilobular “ground-glass” micronodules, disseminated in both lung areas, suggestive of pulmonary tuberculosis- miliary form (Figure 1) has been admitted in our Institute for dyspnea at moderate-low exertion, cough with mucous sputum, loss of appetite, weight loss and fatigue. She was also known with hepatitis C and high blood pressure. In addition, in the other medical center, infective endocarditis was suspected following a prolonged febrile syndrome and an echocardiography with an image suggestive for vegetation on mitral valve, for which the patient has undergone antibiotic treatment with Vancomycin. We mention that we did not have medical documents to establish whether the patient underwent treatment for hepatitis C.
affected general condition, hemodynamically and respiratory stable, overweight, epigastric pain and right upper quadrant and vomiting.
the results from blood sample highlight nitrogen retention syndrome (increased creatinine=2.55mg/dL), low estimated glomerular filtration rate (22mL/min/1.73m2), mild microcytic hypochromic anemia (Hb=11.7g/dL), hyposideremia and
The ECG tracing (electrocardiogram) showed sinus tachycardia and DI, aVL, V3-V6 T wave inversion. The transthoracic echocardiography showed signs of heart failure with moderate left ventricular systolic dysfunction, signs of ischemic heart disease, moderate mitral regurgitation and no direct or indirect signs of infective endocarditis were observed. Fibrobronchoscopy with bronchial aspirate was also performed for Mycobacterium tuberculosis bacteriology and GeneXpert test result was Mtb complex detected medium, drug-sensitive tuberculosis. Abdominal ultrasound showed an embedded stone in the gallbladder infundibulum.
The clinical and paraclinical investigations led to some diagnoses namely pulmonary tuberculosis-miliary form-Mtb complex detected medium, seropositive rheumatoid arthritis, high blood pressure, heart failure with moderate left ventricular systolic dysfunction, ischemic heart disease, moderate mitral regurgitation, hepatitis C was confirmed, cholelithiasis, chronic kidney disease and microcytic hypochromic anemia.
Canadian researchers have shown through case-control studies a modestly increased risk of tuberculosis in patients receiving methotrexate and the rate of development of tuberculosis in people with rheumatologic pathology who are treated with either methotrexate or biological therapy is generally higher than in the general population. Other studies based on the development rate of tuberculosis in countries such as Spain, South Africa and Canada have shown that this rate is higher in patients who were prescribed methotrexate associated with corticosteroids or other immunosuppressants. The patient in the case report, at the initiation of treatment for rheumatoid arthritis received the combination with corticosteroids (4). Leflunomide can increase the susceptibility of tuberculosis reactivation, as it has an anti-inflammatory and immunomodulatory role.
The patient presented above has had an unfavorable evolution despite the treatment administered, a fact supported by the data mentioned in the discussions. She was in biological treatment for PAR with Adalimumab, a context that greatly contributed to the risk of developing tuberculosis. In addition, the miliary form of tuberculosis determined the unfavorable evolution too (10).
In conclusion, pulmonary tuberculosis associated with rheumatoid arthritis can present atypical manifestations that can lead to an incorrect or delayed diagnosis with unfavorable evolution. Thus, it is very important to evaluate the bacillary status before initiating any immunosuppressive treatment.