The prevalence and risk factors of rheumatoid arthritis-associated interstitial lung disease: a systematic review and meta-analysis.

BACKGROUND: Interstitial lung disease (ILD) is the most widespread and fatal pulmonary complication of rheumatoid arthritis (RA). Existing knowledge on the prevalence and risk factors of rheumatoid arthritis-associated interstitial lung disease (RA-ILD) is inconclusive. Therefore, we designed this review to address this gap. MATERIALS AND METHODS: To find relevant observational studies discussing the prevalence and/or risk factors of RA-ILD, EMBASE, Web of Science, PubMed, and the Cochrane Library were explored. The pooled odds ratios (ORs) / hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated with a fixed/ random effects model. While subgroup analysis, meta-regression analysis and sensitivity analysis were carried out to determine the sources of heterogeneity, the I2 statistic was utilized to assess between-studies heterogeneity. Funnel plots and Egger's test were employed to assess publication bias. Following the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines, our review was conducted. RESULTS: A total of 56 studies with 11,851 RA-ILD patients were included in this meta-analysis. The pooled prevalence of RA-ILD was 18.7% (95% CI 15.8-21.6) with significant heterogeneity (I2 = 96.4%). The prevalence of RA-ILD was found to be more likely as a result of several identified factors, including male sex (ORs = 1.92 95% CI 1.70-2.16), older age (WMDs = 6.89, 95% CI 3.10-10.67), having a smoking history (ORs =1.91, 95% CI 1.48-2.47), pulmonary comorbidities predicted (HRs = 2.08, 95% CI 1.89-2.30), longer RA duration (ORs = 1.03, 95% CI 1.01-1.05), older age of RA onset (WMDs =4.46, 95% CI 0.63-8.29), positive RF (HRs = 1.15, 95%CI 0.75-1.77; ORs = 2.11, 95%CI 1.65-2.68), positive ACPA (ORs = 2.11, 95%CI 1.65-2.68), higher ESR (ORs = 1.008, 95%CI 1.002-1.014), moderate and high DAS28 (≥3.2) (ORs = 1.87, 95%CI 1.36-2.58), rheumatoid nodules (ORs = 1.87, 95% CI 1.18-2.98), LEF use (ORs = 1.42, 95%CI 1.08-1.87) and steroid use (HRs= 1.70, 1.13-2.55). The use of biological agents was a protective factor (HRs = 0.77, 95% CI 0.69-0.87). CONCLUSION(S): The pooled prevalence of RA-ILD in our study was approximately 18.7%. Furthermore, we identified 13 risk factors for RA-ILD, including male sex, older age, having a smoking history, pulmonary comorbidities, older age of RA onset, longer RA duration, positive RF, positive ACPA, higher ESR, moderate and high DAS28 (≥3.2), rheumatoid nodules, LEF use and steroid use. Additionally, biological agents use was a protective factor.

[Pre-iliac tumor mass syndrome: An atypical rheumatoid nodule]. / Syndrome de masse tumorale pré-iliaque : un nodule rhumatoïde atypique.

Rheumatoid arthritis (RA) is a polymorphous chronic inflammatory disease that is common in general population and is responsible for the occurrence of subcutaneous or visceral rheumatoid nodules. Their typical clinical presentations and localizations do not generally pose any diagnostic or therapeutic problem. We report here an atypical fistulized presentation of an unusual iliac rheumatoid nodule in a 65-year-old female patient. The evolution was favorable without recurrence at 6 months after complete surgical resection and appropriate antibiotherapy.

Rheumatoid arthritis with pulmonary accelerated rheumatoid nodules treated by baricitinib: a case-based review.

Pulmonary accelerated rheumatoid nodules (ARN) represent a rare occurrence within the context of rheumatoid arthritis (RA), with conventional treatment typically involving corticosteroids. In this report, we present a unique case of pulmonary ARN managed with baricitinib, a Janus kinase inhibitor. The patient, a 46-year-old woman diagnosed with RA, initially displayed no evident pulmonary nodules upon pulmonary imaging. Her treatment regimen encompassed corticosteroids, methotrexate, and leflunomide. Nevertheless, a chest computed tomography (CT) scan conducted after a year unveiled the presence of multiple bilateral pulmonary nodules. A thoracoscopic biopsy of these nodules confirmed the presence of rheumatoid nodules. Treatment with baricitinib, a Janus kinase inhibitor or synthetic disease-modifying antirheumatic drug (DMARD), effectively reduced the size of the nodules. Our review of 45 articles on ARN published since 1986 found that nine of them reported 13 cases of pulmonary ARN. These nodules may be caused by certain synthetic and biological DMARDs and often present with respiratory symptoms. CT scans typically reveal multiple solid nodules or ground-glass opacities, some of which may have cavities. Treatment customarily involves discontinuing the suspected drugs and administering corticosteroids. This case suggests that Janus kinase inhibitors may be an effective treatment option for ARN.

A case report of extra-articular manifestation of rheumatoid arthritis: Rheumatoid nodules in lungs.

Rheumatoid arthritis is a systemic inflammatory disorder primarily affecting joints but not limited to the joints alone. Extra-articular manifestations involve skin, ocular, gastrointestinal, pulmonary, cardiac, renal, neurological, and hematological systems. Among them, skin manifestations (20%) are most common, presenting as nodules on the extensor surfaces of the upper and lower extremities. In rare cases these nodules can also be detected within the heart and lungs. Interestingly, rheumatoid nodules are often seen in patients on leflunomide, methotrexate, or tumor necrosis factor-alpha antagonists. Nevertheless, definitive diagnosis requires a histopathological analysis. In this case report, we presented a 49-year-old male patient with a relatively short period of disease activity leading to rheumatoid nodules in the lungs. Considering the ongoing COVID-19 pandemic and that tuberculosis was still endemic in Kazakhstan, achieving the definite diagnosis was challenging. Initial imaging study revealed bilateral polysegmental pneumonia. The tests for COVID-19 and pulmonary tuberculosis were negative. A follow-up chest computed tomography scan had signs of disseminated lung lesions of unknown origin. Lung biopsy showed a morphological picture of productive granulomas characteristic for tuberculosis. However, at the second look, typical scarring granulomas typically seen in rheumatoid nodules were observed.

A large pulmonary nodule in a rheumatoid arthritis patient treated with tofacitinib.

Pulmonary rheumatoid nodules are rare extra-articular manifestations of rheumatoid arthritis (RA). They are usually asymptomatic but may form cavities and cause clinical symptoms. These nodules are difficult to differentiate clinically and radiologically from tuberculosis, fungal infection, or lung malignancies. Histopathological studies help in the differential diagnosis of pulmonary nodules in patients with RA; however, an effective treatment for rheumatoid lung nodules has not yet been established. This study reports a case of active RA with interstitial lung disease and a large inflammatory lung nodule that was improved with tofacitinib treatment.

Mitral valve rheumatoid nodule complicated by infective endocarditis.

We report a case of a 73-year-old male with rheumatoid arthritis presenting with acute abdominal and back pain and rapidly developing multiorgan failure. A positive blood culture (Staphylococcus aureus, Candida species) followed by transoesophageal sonography established a diagnosis of mitral valve infective endocarditis. At the autopsy, the heart examination revealed fibrinous pericarditis and multiple small vegetations on the mitral valve. The mitral valve itself showed no significant damage. Surprisingly, the histological examination of the mitral valve showed granulomatous inflammation with central fibrinoid necrosis and peripheral palisade of histiocytes, with occasional giant cells and lymphocytic inflammatory infiltrate - findings consistent with a rheumatoid nodule. Infective vegetations were overlying the nodule. Due to its relative frequency, a possibility of cardiac involvement by rheumatoid arthritis and its potential infective complications should be considered in patients with appropriate history and clinical symptoms.

Rheumatoid nodules: a narrative review of histopathological progression and diagnostic consideration.

Rheumatoid nodules (RNs) are the most common extra-articular manifestation of rheumatoid arthritis and are also seen in patients with other autoimmune and inflammatory diseases. The development of RNs includes histopathological stages of acute unspecified inflammation, granulomatous inflammation with no or minimal necrosis, necrobiotic granulomas typically with central fibrinoid necrosis surrounded by palisading epithelioid macrophages and other cells, and likely an advanced stage of "ghost" lesions containing cystic or calcifying/calcified areas. In this article, we review RN pathogenesis, histopathological features in different stages, diagnostically related clinical manifestations, as well as diagnosis and differential diagnosis of RNs with an in-depth discussion about challenges in distinguishing RNs from their mimics. While the pathogenesis of RN formation remains elusive, it is hypothesized that some RNs with dystrophic calcification may be in transition and may be in coexistence or collision with another lesion in patients with RA or other soft tissue diseases and comorbidities. The diagnosis of typical or mature RNs in usual locations can be readily made by clinical findings often with classic RN histopathology, but in many cases, particularly with atypical or immature RNs and/or unusual locations, the clinical and histopathological diagnosis can be challenging requiring extensive examination of the lesional tissue with histological and immunohistochemical markers to identify unusual RNs in the clinical context or other lesions that may be coexisting with classic RNs. Proper diagnosis of RNs is critical for appropriate treatment of patients with RA or other autoimmune and inflammatory diseases.

Complete disappearance of pulmonary rheumatoid nodules after long term rituximab treatment: case report.

The natural history of pulmonary rheumatoid nodules in rheumatoid arthritis remains uncertain. We present a case of a patient with rheumatoid arthritis with pulmonary rheumatoid nodules diagnosed while receiving etanercept in whom pulmonary nodules resolved completely after 5 years of rituximab treatment. Rituximab has been evaluated in case series of patients with pulmonary rheumatoid nodules, resulting in most cases in no progression or a reduction in the size of the nodules, although the complete resolution is uncommon probably due to the short follow-up period. Complete disappearance of pulmonary rheumatoid nodules may be expected after long-term treatment with rituximab.

Drug-induced accelerated nodulosis: review of the literature.

Accelerated nodulosis, the rapid progression/extension of preexisting nodules, is a recognized complication of immunomodulatory therapy, occurring mostly in patients with rheumatoid arthritis treated with methotrexate. As of today, its physiopathology remains incompletely understood, and there are no standardized guidelines regarding its management. Here, we conduct a literature review of the reported cases of drug-induced accelerated nodulosis and add our case of a 79-year-old female with an atypical clinical presentation.

Hyoepiglottic Rheumatoid Nodule Mimicking Head and Neck Malignancy on 18 F-FDG PET/CT.

ABSTRACT: A 54-year-old man with a history of tonsillar squamous cell carcinoma treated with chemoradiotherapy and an 18-year history of seropositive rheumatoid arthritis in remission without maintenance therapy presented with right cervical pain and dysphagia for several months. Flexible laryngoscopy did not show any lesion, and MRI revealed a necrotic lesion inside the thyro-hyo-epiglottic space attached to the hyoid bone. 18 F-FDG PET/CT demonstrated a moderately increased metabolic activity of the lesion without any other suspected lesions. Surgical resection was performed, and pathology revealed a necrotizing granuloma compatible with a rheumatoid nodule.

Intracranial rheumatoid nodule causing recurrent transient neurological deficits.

A 67-year-old man with rheumatoid arthritis developed recurrent acute onset of stereotyped focal neurological abnormalities. Cerebral imaging showed a mass lesion in the left parieto-occipital lobe. Imaging did not show the time evolution expected in stroke and so he underwent an extensive workup, which was inconclusive. Brain biopsy identified a rheumatoid nodule causing an extensive inflammatory reaction that mimicked a mass. Following treatment with intravenous corticosteroids and rituximab infusions, his clinical condition improved. While rheumatoid meningitis is well recognised, a rheumatoid nodule in the brain rarely presents as a mass lesion. Nevertheless, it is important to consider rheumatoid nodule in the differential diagnosis of a cerebral mass lesion in patients with rheumatoid arthritis.