An atypical case of rheumatoid arthritis serositis

For RA patients presenting with complex pericardial effusions, tuberculosis should be considered as an important differential, with challenges surrounding diagnosis and management making multidisciplinary input essential. Dear Editor, RA, the commonest form of inflammatory arthritis, can have extraarticular manifestations, including serositis. With disease-modifying treatment as a risk factor for tuberculosis (TB) infection, this report expands on differentiating between inflammatory, infective and malignant causes of serositis, with a particular focus on RA serositis and tuberculous pericarditis to guide multidisciplinary management. We present the case of a 36-year-old female with a complex, loculated pericardial effusion, progressing to constrictive pericarditis and concurrent pleural effusions on the background of a potential TB contact. The patient was admitted from clinic following CT evidence of pericardial and right-sided pleural effusions during investigation for a 9-month history of chronic, dry cough. There had been no previous extraarticular manifestations since the diagnosis of seropositive (RF 73 IU/ml, anti-CCP 231 IU/ml) RA 8 years ago, well-controlled on methotrexate and etanercept, withheld on admission with potentially infective causes in mind. Prior to commencing anti-TNFα therapy, the patient had TB screening and a normal interferon-gamma release assay (IGRA). She presented non-specifically with dyspnoea, lethargy, loss of appetite and mild weight loss, with clinical features suggestive of right-sided heart failure, including peripheral oedema, liver congestion, ascites, elevated jugular venous pulse, along with reduced breath sounds over the right lung base. The patient was haemodynamically stable and commenced on diuretic treatment. Upon microbiology advice, respiratory precautions were implemented, with sputum cultures, IGRAs and specific HIV and hepatitis screening bloods checked alongside routine laboratory tests (Supplementary Table S1, available at Rheumatology online). Additional radiological investigations (Fig. 1) identified diffuse pericardial inflammation and a rim-enhancing effusion compressing the right atrium and causing left atrial dilation, coupled with IVC dilation, liver congestion and ascites. Recurrent pleural effusions were managed using chest drains, with samples sent for microscopy, PCR testing for TB and culture. Further surgical intervention included a video-assisted thoracoscopic pericardial window, with biopsies taken for histological analysis, and repeated to further counteract the mass effect. Compilation of relevant radiological investigations. (A) Chest radiograph indicating right-sided pleural effusion with associated atelectasis in the right lower zone. (B) CT chest abdomen-pelvis showing rim-enhancing pericardial effusion causing mass effect on the right atrium particularly, with left atrium dilation. (C) Cardiac MRI evidencing constrictive physiology with diffuse pericardial thickening and enhancement, as well as impaired right atrial filling. (D) Parasternal long axis TTE highlighting a severely dilated left atrium. (E) Subcostal view TTE illustrating dilated IVC with poor inspiratory collapse and hepatic vein dilation Following decongestion, the patient was managed on an ambulatory care basis, and an empiric course of Rifater, pyridoxine and ethambutol was commenced, alongside co-amoxiclav. This was discontinued after 8 weeks, once all TB cultures returned negative results and no clinical response on imaging. Analgesia and a tapering regime of prednisolone were initiated to manage increasing RA disease activity, and methotrexate was later reintroduced. Given radiographic evidence of constrictive physiology, pericardiotomy was considered to definitively manage peripheral oedema and prevent cardiac cirrhosis. Currently, the patient is awaiting surgical management to remove the fibro-inflammatory mass once RA treatment is fully optimized. This case illustrates the extraarticular manifestations of RA, with pericardial involvement especially prevalent in anti-CCP-positive patients [1]. The incidence of tuberculous pericarditis varies around the world but is life-threatening nonetheless, given the development of heart failure [2]. Suspicion of pericardial TB was driven by the increased risks associated with RA and particularly anti-TNFα therapy (Peto odds ratio = 3.98 vs placebo) [3], implicating the role of TNFα in triggering TB. A combination of pleural and pericardial effusions and constrictive pericarditis was typical for pericardial TB [4], further supported by a family contact 6 months prior. An insidious onset of systemic upset was also characteristic, but no overt fevers or pulmonary parenchymal changes were present. The diagnostic challenge arose from the difficulty in identifying or excluding Mycobacterium tuberculosis infection. In the immunosuppressed patient, PCR analysis is more useful, in addition to IGRAs, although this remains negative in around 15% of patients with active TB [5]. Therefore, culture-based techniques remain the gold standard diagnostic tool despite prolonged turnaround times, and interim treatment may be necessary depending on pre-test probability. Initial CT chest–abdomen–pelvis and transthoracic echocardiogram allowed visualization of the loculated effusion and confirmed constrictive pathology leading to right-sided heart failure but could not identify a specific cause. Cardiac MRI revealed the effusion contained haemorrhagic and proteinaceous components. Obtaining tissue for culture and histology was essential, which ruled out malignancy and demonstrated a haemorrhagic effusion comprised of fibrinoid material with cholesterol clefts, not in keeping with the typical granular appearance of RA serositis and unlikely to respond to pharmacological intervention. Treating inflammatory musculoskeletal disease activity, worsened by temporary immunosuppression cessation, on the background of identifying fastidious, potentially life-threatening organisms, provided challenges surrounding management. The initial clinical picture was more in keeping with extrapulmonary TB rather than RA serositis, which is often seen after prolonged periods of high disease activity. However, our patient was in clinical remission, with no corticosteroid requirements prior to admission. Empirical TB treatment was important given the possibility of irreversible complications and potentially false-negative test results. Corticosteroids were continued alongside as per national guidelines to treat either TB or RA serositis to reduce the inflammation leading to constriction. However, these were weaned off before surgical intervention to mitigate risks of infection and delayed wound healing [6]. The absence of a positive TB culture, from various sites taken at numerous different time points, created diagnostic doubt. Multidisciplinary input was paramount in this case, and it was opined that after considering all the imaging, serology and histology, the patient should be treated as having inflammatory cardiac and pleural disease probably secondary to RA. It was noted this was an atypical case of RA serositis, and further treatment with abatacept is being planned given its favourable infection risk profile [7], followed by definitive surgical management. Supplementary material is available at Rheumatology online. Data relevant to the study are available within the article and if further data are required, they will be shared upon reasonable request. No specific funding was received from any bodies in the public, commercial or not-for-profit sectors to carry out the work described in this article. Disclosure statement: The authors have declared no conflicts of interest. Patient consent statement: Consent was obtained directly from the patient prior to the study.