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.

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.

Case 238: Spontaneous Pneumothorax Secondary to Intrapulmonary Necrobiotic Rheumatoid Nodule.

History A 54-year-old white woman with a history of rheumatoid arthritis who was taking glucocorticoids and methotrexate presented to the emergency department in December with worsening shortness of breath and chest heaviness for 1 week. She reported additional symptoms of weakness, headache, and arthralgia primarily involving her bilateral hands, wrist, ankles, and feet. She denied experiencing fevers, syncope or presyncope, focal neurologic deficits, chest pain, nausea, vomiting, unintentional weight loss, or recent trauma. Additional medical history included hypertension, asthma, degenerative disk disease, and migraine, all of which were reportedly controlled with medications. This patient had a smoking history of 80 pack-years, but she had quit smoking 2 months prior to presentation. She denied abuse of alcohol or recreational drugs and reported she was up-to-date on her immunizations, including those for pneumonia and flu. Family history was pertinent for breast cancer in her mother, sister, and maternal aunt. The patient reported normal findings at screening mammography and colonoscopy. A physical examination was remarkable for slightly asymmetric breath sounds, which appeared to be diminished on the right side. This patient had multiple joint deformities, most notably in the bilateral metacarpophalangeal joints. Initial electrocardiography findings and cardiac biomarkers were negative. Her complete blood count and basic metabolic profile were unremarkable. Posteroanterior and lateral chest radiographs were obtained in the emergency department. Subsequently, computed tomography (CT) of the chest was performed.

Ascites and other incidental findings revealing undiagnosed systemic rheumatoid arthritis.

We describe a case of a 43-year-old man presenting to the gastroenterology outpatient department with exudative ascites. Mediastinal lymphadenopathy, pericardial effusion and pleural effusion were detected on further imaging. Further clinical examination revealed subcutaneous nodules on the left arm, which were confirmed to be rheumatoid nodules on histology. Inflammatory markers were elevated with positive serology for rheumatoid factor and anticyclic citrullinated protein antibody. Our investigations excluded tuberculosis, pancreatitis and malignancy in the patient. Following review by a rheumatologist, a diagnosis of systemic rheumatoid arthritis (RA) was made. Pleuritis and pericarditis are well recognised as extra-articular manifestation of RA. Ascites, however, is rarely recognised as a manifestation of RA. Our literature search revealed two other cases of ascites due to RA disease activity, and both patients had long-standing known RA. This case adds to the discussion on whether ascites and peritonitis should be classified as extra-articular manifestations of RA.

Carotid atherosclerosis in patients with rheumatoid arthritis and rheumatoid nodules.

OBJECTIVE: To determine whether an association exists between the presence of rheumatoid nodules and thickening of the intima-media and plaque of the carotid artery, which is evidence of atherosclerosis. MATERIALS AND METHODS: Observational, cross-sectional study of 124 patients with rheumatoid arthritis from a University Hospital clinic from 2005 to 2006. We divided the patients into 2 groups, 62 with rheumatoid nodules and 62 without rheumatoid nodules, matched for age and sex. Medical history, erythrocyte sedimentation rate, anti-cyclic citrullinated peptide, rheumatoid factor, and a high resolution doppler ultrasound of the carotid arteries were performed. RESULTS: Women comprised 89.5% of the patients. The prevalence of a carotid plaque was 57% in our population. The presence of a plaque was associated with age, arterial hypertension and abdominal circumference. Average intima-media thickness (IMT) in patients with a plaque was 0.085 cm (± 0.02). There was no correlation between laboratory parameters and thickening of the intima-media of the carotid artery. Subcutaneous nodules were present in 33 (47%) of the 70 patients with a carotid plaque and in 29 (54%) of patients without a carotid plaque (p=.471). CONCLUSIONS: We did not find an association between rheumatoid nodules and the presence of a carotid plaque and thickening of the intima-media of the carotid in patients with rheumatoid arthritis.

Bamboo nodes associated with mixed connective tissue disease as a cause of hoarseness.

Vocal fold lesions related to autoimmune diseases are rheumatoid nodules and, to a lesser extent, bamboo nodes. Mostly transverse, they are located in the middle third of the vocal cord and exhibit a yellowish appearance. The characteristic shape of these lesions led to their name. These vocal fold deposits may interfere with the normal vibratory cycle during phonation and thus may be an unusual cause of hoarseness. We present a 43-year-old woman with known mixed connective tissue disease and a dysphonia. Laryngostroboscopy showed bamboo nodes as described above. We applied several laryngeal injections of cortisone as described previously in the literature. Since this treatment did not lead to a sufficient voice improvement, we attempted to surgically remove the deposits. After the surgery, the voice improved considerably. In all patients with rheumatic diseases who suffer from a rough, breathy, or unstable voice, a laryngostroboscopic examination should be done. If, however, a bamboo node lesion of the vocal folds is found by the laryngologists, an associated autoimmune disorder must be assumed, and adequate diagnostic procedures have to be initiated. Local laryngeal injections (1-3 times) with steroids should be the first line of therapy. In unsuccessful cases, subsequent surgery can be a useful treatment of bamboo nodes to stabilize and improve voice quality.

Cutaneous necrobiotic conditions associated with rheumatoid arthritis: important extra-articular involvement.

Rheumatoid arthritis (RA) presents with various skin conditions as extra-articular manifestations. Rheumatoid nodule is the representative specific skin lesion, histologically exhibiting central necrosis (necrobiosis) surrounded by palisaded macrophages, and being further perivascularly infiltrated with inflammatory cells in the outer regions. Also, there are several skin lesions which histologically show necrobiotic conditions with altered connective tissue degeneration. Necrobiosis may be closely associated with the pathogenesis of RA, i.e., collagen degeneration, recruitment of activated neutrophils, production of various cytokines, and vascular injury. On the other hand, rheumatoid nodule is suggested to develop during therapies with certain drugs such as methotrexate and biologics. These findings may be a clue to understanding the pathomechanisms of rheumatoid nodules. This paper describes several necrobiotic conditions associated with RA, and also discusses the possible pathogenesis and differential diagnosis of rheumatoid nodules. Necrobiosis is the major pathologic condition of cutaneous involvement associated with RA.

Rheumatoid nodule and combined pulmonary carcinoma: topographic correlations; a case report and review of the literature.

An association between rheumatoid arthritis (RA) and malignancies has been ascertained and patients with RA appear to be at higher risk of lymphoma and lung cancer. The higher risk of the latter malignancy may be related to rheumatoid interstitial lung disease and immunosuppressive therapies. Herein we illustrate the case of a 59-year-old male smoker affected by RA and treated with cortisone, methotrexate and TNF-α antagonists, who underwent right lower lobectomy for a nodular lesion. On microscopic examination, the lesion consisted of two distinct areas: a central area of fibrinoid necrosis, bordered by histiocytes in a palisaded arrangement, lymphocytes and a 0.4 cm thick peripheral area constituted by a combined small cell anaplastic carcinoma, adenocarcinoma and squamous cell carcinoma. The combination of three histotypes is very rare in such a small tumour. In our case, it may be hypothesized that synchronous, heterogeneous mutations occurred in different type of committed cells or in stem cells, due to the production of cytokines by RA nodule histiocytes and lymphocytes, which are contiguous to the carcinomatous area. Since few studies have evaluated the topographic correlation between tumors and rheumatoid lung lesions, further morphological and molecular studies are needed to clarify this association and the pathogenetic relationship between RA and cancer of the lung.

Cutaneous nodules in patients with rheumatoid arthritis: a case report and review of literatures.

We report a case of 57-year-old Japanese woman with an overlap syndrome of both rheumatoid arthritis (RA) and autoimmune hepatitis, who developed multiple skin nodules. An extensive biopsies of the nodules revealed rheumatoid neutrophilic dermatitis, showing panniculitis without vasculitis, combining with granulomatous formation histopathologically. Since cutaneous nodules in patients with RA are very complex, differential diagnosis should be done according to disease activities, medications used, and pathological findings. We suggest that the differences in histopathological findings of cutaneous nodules in patients with RA depend on their immunological conditions based on disease activities including therapeutic effects.

[Pleuropulmonary involvement leading to bilateral pneumothorax in a patient being treated for rheumatoid arthritis]. / Atteinte pleuropulmonaire conduisant à un pneumothorax bilatéral chez une patiente traitée pour une polyarthrite rhumatoïde.

INTRODUCTION: Rheumatoid arthritis (RA) is a systemic illness where the development of pulmonary nodule has been described in from 4 to 20% of patients. Symptomatic pleural manifestations occur in 3 to 5% of cases. Rarely, pulmonary nodules become necrotic and lead to pleural complications. Bilateral pneumothorax has only rarely been described. CASE REPORT: We report the case of a 64-year-old woman, who had been treated for RA for several years and presented with bilateral pneumothorax secondary to necrobiosis of one or several pulmonary rheumatoid nodules. The management of the pneumothorax was very prolonged and difficult, and despite surgical pleurodesis, the lung did not reexpand fully. Pathological examination of the pleura revealed a noncaseating granulomatous pattern. The diagnosis of a sarcoidosis like disease, possibly induced by anti-TNFα, or of pleural tuberculosis were suggested, but we concluded that the final diagnosis was of pleural rheumatoid involvement. CONCLUSION: Bilateral pneumothorax secondary to rheumatoid nodule is a rare entity. The management of such a complication is difficult, particularly in patients who receive an immunosuppressant regimen. A granulomatous pattern has been described rarely in the pleural tissue of these patients. Specific RA pleural involvement has to be taken in consideration when other diagnoses are eliminated, especially tuberculosis or sarcoidosis-like disease.