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.

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.

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.

Rheumatoid Nodule Simulating a Parotid Tumor.

Rheumatoid nodules are an extra-articular manifestation of rheumatoid arthritis that are rarely found in the maxillofacial region. A 59-year-old woman with rheumatoid arthritis treated with methotrexate, leflunomide, and tocilizumab, presented with an enlarging mass in the left parotid region. Magnetic resonance imaging (MRI) displayed a lesion compatible with a neoplasm. However, an incisional biopsy showed features consistent with a rheumatoid nodule. The patient was managed conservatively, including cessation of methotrexate and initiation of treatment with hydroxychloroquine. At 15-month follow-up, the lesion had a significant reduction in size. To our knowledge, this is the first case report of a rheumatoid nodule in the parotid region. Although it is a rare manifestation, clinicians should consider this a possible differential diagnosis of parotid masses in patients with a history of rheumatoid arthritis or connective tissue disease.

Collision Lesions of Calcifying Pseudoneoplasm of the Neuraxis and Rheumatoid Nodules: A Case Report With New Pathogenic Insights.

Calcifying pseudoneoplasm of the neuraxis (CAPNON) is a rare tumor-like lesion with unclear pathogenesis. Collision lesions of CAPNONs with neoplasms are occasionally reported. In this article, we report the first case of collision lesions between CAPNON and rheumatoid nodules (RNs) in a patient with systemic lupus erythematosus. The patient was a 51-year-old female who presented with lower back pain and subsequently a lower back mass over 2 years. Spinal magnetic resonance imaging demonstrated a heterogeneous, partially calcified mass centered in the L3-4 paravertebral regions. A biopsy of the mass was diagnostic of CAPNON. As the mass grew over the following 5 months, it was resected en bloc. Its pathological examination revealed collision lesions of RNs at different histopathological stages and CAPNON lesions, and transitional lesions exhibiting combined RN and CAPNON features, with immune cell infiltrates. Our findings provide new evidence for an immune-mediated reactive process and insights into the pathogenies of CAPNON.

Granulomatous Cutaneous Drug Eruptions: A Systematic Review.

BACKGROUND: Granulomatous drug eruptions are rare entities, where granuloma formation occurs as an attempt to contain an exogenous or endogenous inciting agent. Granulomatous drug eruptions may be localized to the skin or may include major systemic involvement, and their characteristics depend both on the properties of the causative irritant and host factors. Because of the overlapping features amongst noninfectious granulomatous diseases, granulomatous drug eruptions are challenging to diagnose and distinguish both histologically and clinically. OBJECTIVE: The objective of this article is to provide a review and summary of the current literature on the five major types of cutaneous granulomatous drug eruptions: interstitial granulomatous drug reaction, drug-induced accelerated rheumatoid nodulosis, drug-induced granuloma annulare, drug-induced sarcoidosis, and miscellaneous presentations. METHODS: A systematic review was conducted through PubMed using the search terms "granulomatous drug eruption" and "cutaneous" or "skin". English full-text studies that included human subjects experiencing a cutaneous reaction comprising granulomatous inflammation as the direct result of a drug were included. Of 205 studies identified, 48 articles were selected after a full-text review. Evidence was evaluated using the Tool for evaluating the methodological quality of case reports and case series. RESULTS: Polypharmacy and a prolonged lag period from drug ingestion to rash onset may create diagnostic challenges. Ruling out tuberculosis is imperative in the endemic setting, particularly where anti-tumor necrosis factor therapy is the presumed cause. Interstitial granulomatous drug reactions and granuloma annulare are often localized to the skin whereas accelerated rheumatoid nodulosis and sarcoidosis may sometimes be associated with systemic features as well. Granulomatous drug eruptions typically resolve on discontinuing the offending medication; however, the decision for drug cessation is dependent on a risk-benefit assessment. In some situations, supplementation of an additional agent to suppress the reaction may resolve symptoms. In some cases, granulomatous drug eruptions may be pivotal in the successful outcome of the drug, as in cases of melanoma treatment. In all situations, the decision to continue or withdraw the drug should be carefully based on the severity of the eruption, necessity of continuing the drug, and availability of a suitable alternative. CONCLUSIONS: Granulomatous drug eruptions should always be considered in the differential diagnosis of noninfectious granulomatous diseases of the skin. Further research examining dose-response relationships and the recurrence of granulomatous drug eruptions on the rechallenge of offending agents is required. Increased awareness of granulomatous drug eruption types is important, especially with continuous development of new anti-cancer agents that may induce these reactions. CLINICAL TRIAL REGISTRATION: PROSPERO registration number CRD42020157009.

Liver rheumatoid nodules imitating liver malignancy: a rare occurrence.

We describe a case of a 61-year-old man with a background of rheumatoid arthritis who presented to the emergency department with a single-reported episode of haemoptysis on the background of an upper respiratory tract infection. A CT scan revealed an incidental 40 mm mass in upper right lobe of the liver abutting the diaphragmatic surface. A subsequent positron emission tomography scan confirmed the mass and raised the possibility of another lesion in the liver raising the suspicion of malignancy. The case was complicated by the inability to perform a fine needle aspiration biopsy due to the mass' proximity to the diaphragm. After discussion with the patient, it was decided to resect the affected liver segment. Histological analysis of the mass revealed localised necrotising granulomatous inflammation suggestive of a rheumatoid nodule, which is seldom reported in the literature.

Case for diagnosis. Subcutaneous nodules in the plantar region

Abstract The authors report a case of mobile and painful nodules on the bilateral plantar surface of a female patient referred by the rheumatology service, where she was being followed-up for rheumatoid arthritis. A nodule excision was performed for differential diagnosis and symptom relief; the histopathological analysis was compatible with a rheumatoid nodule. Although rheumatoid nodules are a common manifestation of rheumatoid arthritis, exclusive plantar involvement is seldom described in the literature.

Rheumatoid arthritis with necrotic lung nodules.

Rheumatoid arthritis is a multisystemic in˜flammatory disease. Lungs are the commonest site of extra-articular involvement. Rheumatoid lung nodules occur infrequently and can undergo necrosis giving rise to necrobiotic lung nodules. Infections, malignancy and granulomatosis with polyangiitis are more common causes of cavitating lung nodules. Presence of rheumatoid factor, history of smoking and use of methotrexate increase the chances of developing rheumatoid lung nodulosis. Histopathological examination of the nodule is essential to make a correct diagnosis. We present a 74-year-old male with long-standing rheumatoid arthritis who had multiple cavitating lung nodules. Biopsy from the lung nodule could not be performed as the patient refused to consent. However, infection, malignancy and granulomatosis with polyangiitis were ruled out on the basis of blood investigations and bronchoscopy. He was empirically treated with a moderate dose of glucocorticoid along with conventional synthetic disease-modifying antirheumatic drugs. After three months of treatment, the lung nodules disappeared completely and his articular symptoms showed marked improvement.

Pseudorheumatoid nodule: a variant of granuloma annulare?

We present an adult woman with subcutaneous nodules without any signs or symptoms of rheumatoid arthritis. These nodules are believed to be pseudorheumatoid nodules, which are considered a deep form of granuloma annulare. This case is unique because these are typically found in children and have rarely been reported in adults. These nodules are typically asymptomatic and do not require treatment. However, attempts have been made to treat them with intralesional corticosteroids, cryotherapy, or excision. Owing to the fact that this is considered a deep form of granuloma annulare, they are sometimes treated similarly with a combination of monthly rifampin, ofloxacin, and minocycline.

Case for diagnosis. Subcutaneous nodules in the plantar region.

The authors report a case of mobile and painful nodules on the bilateral plantar surface of a female patient referred by the rheumatology service, where she was being followed-up for rheumatoid arthritis. A nodule excision was performed for differential diagnosis and symptom relief; the histopathological analysis was compatible with a rheumatoid nodule. Although rheumatoid nodules are a common manifestation of rheumatoid arthritis, exclusive plantar involvement is seldom described in the literature.