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Objectives: To elucidate the efficacy and safety of rituximab in special types of rheumatoid arthritis. Methods: We retrospectively reviewed all patients with rheumatoid arthritis with lymphoproliferative disorder or vasculitis treated with rituximab between April 2010 and June 2022 at Keio University Hospital. We assessed the effectiveness of rituximab using the Disease Activity Score for 28 joints‐erythrocyte sedimentation rate (DAS28‐ESR), Clinical Disease Activity Index (CDAI), and safety of rituximab during the disease course. We also assessed the glucocorticoid‐sparing effects of rituximab. Results: We included eight patients with a history of lymphoproliferative disorder and five patients with rheumatoid vasculitis. They were treated with rituximab without high‐dose glucocorticoid. The mean DAS28‐ESR and CDAI scores significantly improved 12 months after rituximab administration (DAS28‐ESR, 4.7 vs. 2.7, p <.001; CDAI, 16.0 vs. 5.1, p =.006, respectively), and the dose of prednisolone was reduced from a mean of 7.4 mg/day to 4.0 mg/day at 12 months (p =.05) and 3.2 mg/day at the last visit (p =.04). During the mean follow‐up period of 52 months, we recorded one recurrence of lymphoproliferative disorder (not B‐cell type) in patients with a history of lymphoproliferative disorder and remarkable improvement of skin ulcers in patients with vasculitis. Conclusion: B‐cell depletion by rituximab may be a useful treatment option for patients with lymphoproliferative disorder and rheumatoid vasculitis. [ABSTRACT FROM AUTHOR]

Background: Rheumatoid Arthritis (RA) is a common systemic inflammatory disease that can present with a plethora of extraarticular manifestations. Many patients with RA from low and middle income countries do not get timely and adequate treatment with disease modifying therapies. This results in the perpetuation of a chronic inflammatory state. Focus: Rheumatoid vasculitis (RV) is one of the most aggressive complications of RA resulting from a prolonged proinflammatory milieu. Usually, it has the involvement of multiple organ systems, with cutaneous manifestations being the most common. Neurological presentation is uncommon but severe when present. Highlight: We present a case of severe RV presenting with an unexpected neurological complication consisting of cranial and peripheral neuropathy with small vessel disease and intracerebral haemorrhage. We intend to highlight the morbidity and long term consequences of inadequately treated RA, the most common inflammatory disease of the connective system especially in light of the neurological presentation. [ABSTRACT FROM AUTHOR]

Background: Rheumatoid Arthritis (RA) is a common systemic inflammatory disease that can present with a plethora of extraarticular manifestations. Many patients with RA from low- and middle-income countries do not get timely and adequate treatment with disease-modifying therapies. This results in the perpetuation of a chronic inflammatory state. Focus: Rheumatoid vasculitis (RV) is one of the most aggressive complications of RA resulting from a prolonged proinflammatory milieu. Usually, it has the involvement of multiple organ systems, with cutaneous manifestations being the most common. Neurological presentation is uncommon but severe when present. Highlight: We present a case of severe RV presenting with an unexpected neurological complication consisting of cranial and peripheral neuropathy with small vessel disease and intracerebral haemorrhage. We intend to highlight the morbidity and long-term consequences of inadequately treated RA, the most common inflammatory disease of the connective system especially in light of the neurological presentation.

Immune complex (IC) vasculitides present inflammations of vessel walls associated with perivascular deposition of immunoglobulins (Igs), mostly ICs. They encompass systemic and skin-limited variants of IgA vasculitis (IgAV), cryoglobulinemic vasculitis (CV), rheumatoid, lupus, and hypocomplementemic vasculitides, serum sickness cutaneous IgM/IgG (non-IgA) vasculitis, and recurrent macular (hypergammaglobulinemic or exertion-induced) vasculitis. Serum sickness and CV fulfill the criteria of a type III hypersensitivity immune reaction as large lattices of the IC precipitate at vessel walls and activate polymorphonuclear neutrophils (PMNs). Immunoglobulin-A vasculitis differs with regard to the causes of perivascular deposition of ICs since here many IgA1 molecules are hypoglycosylated (Gd-IgA1), which appears to facilitate their perivascular deposition in skin and mesangium (via e.g. CD71). The reasons for increased generation of immunoglobulins or formation of IC and their perivascular deposition in either skin or systemic organs are different and not fully explored. A common denominator of OC vasculitides is the activation of PMNs near the vessel wall via Fcy or Fcα receptors. Acute episodes of IgAV additionally require PMNs to become preactivated by IgA1 or by IC already in circulation. This intravascular priming results in increased adherence and subsequently vessel-destructive NETosis when they encounter IgA deposited at the vessel walls. Binding of IgA1 to PMNs in blood stream is associated with increased serum levels of hypogalactosidated IgA1. The characteristic clinical picture of IgAV (and also of so-called IgG/IgM vasculitis) comprises palpable or retiform purpura with a clear predilection for lower legs, probably due to stasis-related reduction in blood velocity, while in other IC vasculitides, additional factors influence the sites of vasculitides. Our knowledge of distinct forms and different pathophysiological pathways of IC vasculitides may lead to in efficacious or targeted therapies. Antibodies to complement components or intestinal budesonide for IgAV are promising agents (the latter suppresses the pathophysiologically related IgA nephropathy by reducing the generation of mucosal IgA.

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Background: Rheumatoid vasculitis (RV) is a rare but potentially devastating complication of rheumatoid arthritis (RA). It typically occurs in patients with extra-articular manifestations. Here we reported a case of PUK with nodular episcleritis and pulmonary nodules that occurred in the same patient without joint involvement. Case presentation: A 43-year-old Chinese woman, exhibited a partial crescent-shaped marginal corneal ulcer in the right eye at admission and the ulcer developed rapidly into nearly 360-degree ulcers in both eyes within one week. Nodular episcleritis was observed in the right eye. Conjunctival biopsy revealed vasculitis. Her rheumatoid factor (RF) and anti-cyclic citrullinated protein antibody were positive, while anti-neutrophilic cytoplasmic antibody (c-ANCA) and anti-protease 3 were negative. Pulmonary nodules were found, without joint involvement. The ocular condition did not relieve under the topical and systemic use of corticosteroids, or under other immunosuppressive agents until the infliximab therapy. PUK recurrence was observed after the discontinuation of infliximab. Conclusions: Rapidly deteriorated PUK with nodular episcleritis and pulmonary nodules occurred in the same patient is a special case of RA without joint involvement. This case reinforces the concept that RV may be the initial sign of RA. Infliximab can be used to prevent further progress of RA-related PUK in some refractory cases. [ABSTRACT FROM AUTHOR]

Abstract Introduction Spinal subarachnoid haemorrhage is extremely rare in cases of subarachnoid haemorrhage and possesses servere characteristics. Additionally, spinal rheumatoid vasculitis is rare for spinal subarachnoid haemorrhage. The pathogenesis is unknown. Case presentation A 52-year-old woman with a 10-year history of seropositive rheumatoid arthritis was managed with leflunomide and celecoxib, and stable low disease activity was achieved. The patient had also been diagnosed with spinal subarachnoid haemorrhage secondary to isolated spinal rheumatoid vasculitis and obtained good therapeutic effects. Conclusion This is the first case to describe spinal subarachnoid haemorrhage secondary to isolated spinal vasculitis in a patient with rheumatoid arthritis, which provides more proof of anomalous neovascularization in the central nervous system in rheumatoid arthritis.

Objectives: Neuropathy is considered a complication of rheumatoid arthritis (RA), whose underlying mechanisms are mainly entrapment, drug‐induced and rheumatoid vasculitis (RV). At Tokyo Women's Medical University, for the purpose of diagnosing vasculitic neuropathy, we carried out nerve and muscle biopsies in nine RA patients. Unexpectedly, we found three cases of demyelinating neuropathy, together with six cases of RV. Our aim was to investigate the neurophysiological features of demyelinating neuropathy in patients with RA, compared with those of patients with RV. Methods: We reviewed the pathological, clinical and electrophysiological findings in patients with RA who underwent nerve and muscle biopsies. We compared patient demographics and nerve conduction study findings between patients with RV and other patients. Results: The histological findings showed necrotizing vasculitis in six of nine patients. Vasculitis was absent in the other three patients, which showed evidence of demyelination and remyelination. The absence of a sensory nerve action potential and compound motor action potential were observed more frequently in the RV cohort. Sural sparing, shown as the sural‐to‐median sensory nerve action potential ratio, was significantly higher in demyelinating neuropathy patients. Treatment was corticosteroid and cyclophosphamide in RV patients, and intravenous immunoglobulin was administered to three demyelinating neuropathy patients. Treatment response was satisfactory in seven of the nine patients. Conclusion: Demyelinating neuropathy was found more often in patients with RA neuropathy than expected. Sural nerve sparing, as well as the absence of sensory nerve action potential or compound motor action potential, are useful for the differential diagnosis of demyelinating neuropathy with RV in RA patients with neuropathy. [ABSTRACT FROM AUTHOR]

Introduction: Spinal subarachnoid haemorrhage is extremely rare in cases of subarachnoid haemorrhage and possesses servere characteristics. Additionally, spinal rheumatoid vasculitis is rare for spinal subarachnoid haemorrhage. The pathogenesis is unknown.Case Presentation: A 52-year-old woman with a 10-year history of seropositive rheumatoid arthritis was managed with leflunomide and celecoxib, and stable low disease activity was achieved. The patient had also been diagnosed with spinal subarachnoid haemorrhage secondary to isolated spinal rheumatoid vasculitis and obtained good therapeutic effects.Conclusion: This is the first case to describe spinal subarachnoid haemorrhage secondary to isolated spinal vasculitis in a patient with rheumatoid arthritis, which provides more proof of anomalous neovascularization in the central nervous system in rheumatoid arthritis. [ABSTRACT FROM AUTHOR]

Rheumatoid vasculitis is a rare, extra-articular manifestation that can be seen in long-standing rheumatoid arthritis. Here we present the case of a 51-year-old man who presented with arthralgias, skin rash, dyspnoea and generalized leg swelling and who was diagnosed with rheumatoid arthritis flare.

Objectives: Malignant rheumatoid arthritis (MRA) is defined as rheumatoid arthritis (RA) with systemic vasculitis or other severe extra-articular manifestations. Japan has a nationwide database for MRA. We analyzed the characteristics of Japanese patients with MRA based on data from the Ministry of Health, Labour and Welfare (MHLW). Methods: We were permitted to use data on 43,108 patients who were registered in the MHLW database from 2003 to 2013. Results: Median age was 65 (interquartile range, 57-72) years. Patients consisted of 71% females. Proportions of patients who had or had experienced interstitial pneumonia and pleuritis were increased, episcleritis was stable, and other MRA manifestations were decreased over time. The number of positive symptoms per patient also decreased over time. The median dose of glucocorticoid, percentage of patients undergoing surgery, and use of non-steroidal anti-inflammatory drugs and apheresis decreased year by year. Steinbrocker stage and class improved over time. Median C-reactive protein levels and erythrocyte sedimentation rate also decreased. Regarding social productivity levels of patients with MRA, the proportion of patients who were working or working from home increased and the proportion of patients recuperating or hospitalized decreased. Conclusion: In patients with MRA, disease activity decreased and social productivity improved from 2003 to 2013. [ABSTRACT FROM AUTHOR]

Rheumatoid vasculitis (RV) is one of the most severe extra-articular manifestations of rheumatoid arthritis, with significant morbidity and mortality, requiring aggressive treatment with corticosteroids and/or immunosuppressants. Recently, biological drugs were included in its therapeutic armamentarium. The objective of this study was to perform a systematic review on the use of biological drugs in the treatment of RV. A systematic literature review was performed based on PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) recommendations and searching articles in MEDLINE/PubMed, Cochrane, SciELO, Scopus, and Virtual Health Library electronic databases. Secondary references were also evaluated. The methodological quality of the selected studies was evaluated by the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) criteria. Altogether, five articles, assessing the use of biological drugs, were included. Globally, 35 patients participated in the studies, of which 21 were treated with rituximab (RTX) in cycles of 1000 mg every 2 weeks; 9 used infliximab 5 mg/kg; 3 used infliximab 3 mg/kg; and 2 used etanercept 25 mg twice/week. In general, an improvement in clinical picture, reduction of the mean daily dose of corticosteroids, and improvement in the Birmingham Vasculitis Activity Score was achieved by the end of the treatment. Complete remission occurred in almost 70% of the cases. The adverse effect rate was 34%, mainly due to infections. There were two deaths, one due to sepsis and the other due to uncontrolled vasculitis, after the biological drug withdrawal, following the development of sepsis. Based on the results of the present review, we believe that the use of biological therapy such as RTX and anti-tumor necrosis factor α can be beneficial in treating this complication. [ABSTRACT FROM AUTHOR]

We describe a fatal case of diffuse alveolar hemorrhage (DAH) complicated by rheumatoid arthritis (RA). A female patient was diagnosed with RA two months earlier and was treated with prednisolone and tacrolimus due to abnormalities in chest images. The patient was admitted to Hamanomachi Hospital for exertional dyspnea and was treated for exacerbation of chronic heart failure. Even after treatment for heart failure, exertional dyspnea remained. Chest CT imaging revealed contractile, patchy consolidations and ground-glass opacities (GGO) with a peribronchial distribution, suggesting an organizing pneumonia (OP) pattern. She was then treated with an additional 25 mg/day of prednisolone following a clinical diagnosis of OP. When the prednisolone dose was tapered, chest imaging showed worsening infiltration. A bronchoscopy was conducted, and bronchoalveolar lavage fluid was sanguineous, indicating DAH. Given that additional workup for the other etiology of DAH was negative, DAH was thought to be related to RA. Intensive treatment, including pulse dose methylprednisolone, failed to halt progression of respiratory failure, leading to a fatal outcome. The clinical presentation proved challenging due to its rarity. DAH might be a differential diagnosis in RA patients with consolidations and GGO in chest CT images. We review past cases of RA-associated DAH and assess potential treatment choices for future cases.

Balloon angioplasty can cause shear stress and tear of the vascular endothelium during mechanical dilatation, leading to increased inflammation and coagulation reactions of the vascular endothelium. Herein, a worst case of active rheumatoid vasculitis is described, where due to progressing ischemic necrosis of the leg, endovascular intervention was unavoidably performed in the presence of active rheumatoid vasculitis. After percutaneous balloon angioplasty, the patient developed recurrent thrombotic occlusion of the leg arteries, and finally, limb amputation resulted in despite vigorous treatment including medication, immunosuppression, catheter-directed thrombolysis, and post-thrombolysis anticoagulation. This case report indicates that endovascular intervention may be detrimental to the active rheumatoid vasculitis. Until the development of treatment guideline to prevent or control inflammatory reaction, endovascular intervention for the active rheumatoid vasculitis may not be appropriate as a first line therapy even though there is progressing ischemic necrosis.

Rheumatoid vasculitis which affects small-to-medium-sized vessels is a rare and late complication of rheumatoid arthritis. It is defined histologically as immune complex deposition in venules, capillaries and arterioles.1 Vasculitis in the vasa nervorum leads to infarction of peripheral nerves which leads to neuropathy. We present a case of mononeuritis multiplex due to rheumatoid vasculitis.

A 55-year-old man with rheumatoid arthritis (RA) presented hyperkeratotic erythematous papules with crusts or blisters on his limbs and buttocks. A histological study showed acquired reactive perforating collagenosis. Soon, skin lesions changed to umbilicated lesions with black necrosis, and the scar from his skin biopsy ulcerated with induration due to rheumatoid vasculitis. Systemic corticosteroids and tacrolimus administration resolved the RA and skin lesions. Rheumatoid vasculitis with acquired reactive perforating collagenosis has not been reported previously. [ABSTRACT FROM AUTHOR]

Significant changes in the epidemiology and natural history of rheumatoid vasculitis (RV) have occurred with the introduction of biological therapies such as TNF inhibitors (TNFi) and rituximab. This scoping review aims to address the key current challenges and propose updated criteria for RV. This will aid future descriptive observational studies and prospective therapeutic trials. The MEDLINE database was searched for eligible articles from inception through December 2022. Articles were selected based on language and publication date after 1998, corresponding to the approval of the first TNFi in rheumatic diseases. Sixty articles were included in the review. The mean incidence of RV has decreased since the approval of biologic therapies in RA, from 9.1 (95% CI: 6.8–12.0) per million between 1988 and 2000 to 3.9 (95% CI: 2.3–6.2) between 2001 and 2010, probably due to significant improvement in RA severity and a decrease in smoking habits. Factors associated with an increased risk of RV include smoking at RA diagnosis, longer disease duration, severe RA, immunopositivity, and male gender (regardless of age). Homozygosity for the HLA-DRB104 shared epitope is linked to RV, while the presence of HLA-C3 is a significant predictor of vasculitis in patients without HLA-DRB104. Cutaneous (65–88%), neurologic (35–63%), and cardiac (33%) manifestations are common in RV, often associated with constitutional symptoms (70%). Histologic findings range from small vessel vasculitis to medium-sized necrotizing arteritis, but definite evidence of vasculitis is not required in the 1984 Scott and Bacon diagnostic criteria. Existing data on RV treatment are retrospective, and no formal published guidelines are currently available. The understanding of RV pathogenesis has improved since its initial diagnostic criteria, with a wider range of clinical manifestations identified. However, a validated and updated criteria that incorporates these advances is currently lacking, impeding the development of descriptive observational studies and prospective therapeutic trials. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. • Profound changes in the epidemiology of rheumatoid vasculitis (RV) are noted since the advent of biologics, in particular TNFi • The criteria for RV remain the same since 1984 and do not take into consideration major organs involvements • We suggest updated criteria for RV, which might help homogenize observational studies and prospective therapeutic trials [ABSTRACT FROM AUTHOR]

Objectives The aim of this study was to investigate nailfold capillaroscopic (NC) abnormalities and serum interleukin (IL)-17) level among rheumatoid arthritis (RA) patients with or without vasculitis. Patients and methods The study was carried on a group of RA Egyptian patients (n=40) who were diagnosed with RA based on ACR criteria. These 40 patients were further divided into two groups. Group 1 included RA patients with clinical signs of skin vasculitis and NC changes (n=6). Group 2 included RA patients with no clinical signs of skin vasculitis and no NC changes (n=34). All patients were subjected to demographic data collection, clinical examination, Disease Activity Score (DAS) 28 calculation, laboratory measurement (including erythrocyte sedimentation rate, C-reactive protein, rheumatoid factor, antinuclear antibody, antineutrophil cytoplasmic antibody, anticyclic citrullinated peptide, and IL-17), and NC examination. In addition, group 1 (n=6) was further subjected to electrophysiological evaluation by peripheral nerve conduction studies. Results Significantly elevated levels of IL-17 and characteristic NC changes were seen in RA vasculitis patients. Conclusion Rheumatoid vasculitis is associated with significantly elevated levels of serum IL-17 and characteristic NC changes.

Objectives The aim of this work was to study nailfold capillaroscopic (NC) abnormalities and serum interleukin-17 (IL-17) level among rheumatoid arthritis (RA) patients and to find whether IL-17 is causally involved in the changes in the capillary vascular bed, such as autoimmune prevasculitic changes. Patients and methods The study was conducted on a group of RA Egyptian patients (n=40) who were diagnosed as having RA based on ACR criteria. Those 40 patients were further divided into two groups. Group 1 included RA patients with clinical signs of skin vasculitis and NC changes (n=6). Group 2 included RA patients with no clinical signs of skin vasculitis and no NC changes (n=34). All patients were subjected to demographic data collection, clinical examination, disease activity score 28 calculation, laboratory measurement (including erythrocyte sedimentation rate, C-reactive protein, rheumatoid factor, antinuclear antibody, antineutrophil cytoplasmic antibody, anti-cyclic citrullinated peptide, and IL-17) and NC examination. In addition, group 1 (n=6) was further subjected to electrophysiological evaluation using peripheral nerve conduction studies to determine the effect of vasculitis on the peripheral nerves. Results IL-17 level and NC changes showed a significant association in RA vasculitis patients. Conclusion Elevated levels of serum IL-17 and characteristic NC changes raise their importance in the detection of preclinical rheumatoid vasculitis.

OBJECTIVES: Rheumatoid arthritis is a polygenically controlled systemic autoimmune disease. Rheumatoid vasculitis is an important extra-articular phenotype of rheumatoid arthritis that can result in deep cutaneous ulcers. The objective of this study was to establish a correlation between the frequency of major histocompatibility complex class I/II alleles and killer immunoglobulin-like receptor genotypes in patients with cutaneous rheumatoid vasculitis. METHODS: Using the Scott & Bacon 1984 criteria to diagnose rheumatoid vasculitis and after excluding any other causes such as diabetes, atherosclerosis, adverse drug reactions, infection, and smoking, patients who met the criteria were selected. All of the selected rheumatoid vasculitis patients presented deep cutaneous ulcers. Identification of the major histocompatibility complex class I/II and killer immunoglobulin-like receptor genotypes was performed by polymerase chain reaction assays of samples collected from the 23 rheumatoid vasculitis patients as well as from 80 controls (40 non-rheumatoid vasculitis RA control patients and 40 healthy volunteers). RESULTS: An association between the presence of the HLA-DRB1*1402 and HLA-DRB1*0101 alleles and cutaneous lesions in rheumatoid vasculitis patients and a correlation between the inhibitor KIR2DL3 and the HLA-C*0802 ligand in rheumatoid vasculitis patients were found. CONCLUSION: An association was found between the presence of the HLA-DRB1*1402 and HLA-DRB1*0101 alleles and the development of cutaneous lesions in rheumatoid vasculitis patients. Additionally, the HLA-C*0802 ligand protects these individuals from developing cutaneous lesions.

The rheumatoid vasculitis is the most serious complication of rheumatoid arthritis, with high morbidity and mortality. It is an inflammatory process that affects small and medium vessels and that has heterogeneous manifestations, being the cutaneous lesions and neuropathy the most common. Its incidence has declined in the last decades because of the early use of disease modifying antirheumatic drugs. Despite the use of cyclophosphamide and the existence of biologic drugs, achieving the control of the disease continues to be a challenge. We present the case of a 50 year-old man, without relevant antecedents, only tabaco use, that presented with a vasculitic neuropathy, rheumatoid factor and cyclic citrullinated peptide antibody positive. This bibliographic review has the intention to update the knowledge of this entity and to be considered a differential diagnosis. [ABSTRACT FROM AUTHOR]

In this article, we discussed leukocytapheresis (LCAP) for rheumatoid arthritis (RA). Recently, a simple and practical on-line continuous LACP system has been developed. It is equipped with a direct hemoperfusion column (Cellsorba ® , Asahikasei Medical Co., Ltd.) packed with fine-diameter polyester fibers, which are commonly used to adsorb white blood cells to prevent a graft-versus-host reaction during blood transfusion. Clinical trials revealed that LCAP is a effective and safe therapy for patients with drug-resistant RA or RA complicated with vasculitis. Because the procedure is simple and requires no plasma substitutes and the volume needed for extracorporeal circulation is less than that for other plasmapheresis, LCAP might be accepted as an optional therapeutic modality for active RA that was refractory to conventional drug therapy including biological agents. The mechanism of the efficiency of LCAP on RA is unclear. LCAP may cause a reduction of activated T cells from affected joints, down-regulation of Pgp on helper T cells and restoration of Treg function, and that may modify the abnormal cytokine balance. These findings may explain some of the mechanisms by which the articular symptoms are improved by LCAP. [ABSTRACT FROM AUTHOR]

The purpose of this study is to report the efficacy and safety of a combination of tocilizumab (TCZ) and high-dose corticosteroid (CS) in two patients with microscopic polyangiitis (MPA) and review the published current clinical evidence on TCZ in patients with anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV), except for large vessel vasculitis (LVV) and polymyalgia rheumatica (PMR). Two MPA patients were treated with TCZ at 8 mg/kg every month for 1 year and CS (prednisolone 1 mg/kg/day for 2 weeks, followed by tapering) in a prospective single-arm, single-center, cohort, open-label pilot study (UMIN clinical trials: 000012072). We performed a systematic literature search (PubMed and ICHUSHI [Japan Medical Abstracts Society] until June 30, 2017) to identify published reports on patients with all vasculitis other than LVV/PMR, who were treated with TCZ. We successfully treated the first patient. However, the other patient had serious infection probably associated with the combination of TCZ and high-dose CS. The literature review identified 22 reports with a total of 34 patients who received TCZ for AAV, rheumatoid vasculitis, and other types of vasculitis, in addition to our patients. In 15 of 17 patients (88.2%) with primary and secondary AAV, especially MPA, TCZ induced clinical remission, although TCZ use for rheumatoid vasculitis and vasculitis with mucocutaneous lesions is controversial. This study suggested that TCZ therapy is a potential treatment strategy for patients with AAV. However, TCZ combined with high-dose of CS might not be an appropriate treatment. Future studies are needed to confirm our findings. [ABSTRACT FROM AUTHOR]

Blue Finger Syndrome (BFS) is a benign and rare condition with an idiopathic aetiology. It is characterised by an acute bluish discoloration of fingers which may be accompanied by pain. This is a case of a middle aged female who presented with painless bluish discoloration of right hand and was diagnosed to have BFS. Though BFS is idiopathic, our patient on evaluation was found to have an underlying Rheumatoid Arthritis (RA). Patients with RA are subject to Raynaud’s phenomenon; but BFS presenting in a patient with RA is a rare scenario.

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by inflammatory and destructive joint damage and extra-articular manifestations involving various organs and systems in the pathological process. One of systemic manifestations of RA is cutaneous rheumatoid vasculitis (RV). Factors predisposing to the development of RV in RA patients include male gender, high titers of rheumatoid factor (RF), anti-cyclic citrullinated peptide (anti-CCP) antibodies, antineutrophil cytoplasmic antibodies, and presence of other extra-articular manifestations. RV may develop due to immune complex deposition on the vascular walls. RV activity correlates with high level of RF, anti-CCP and anti-nuclear antibodies. The typical signs of RV include peripheral gangrene, mononeuritis multiplex, as well as scleritis, pericarditis and lung damage. However, skin lesions, such as periungual infarction (digital arteritis), capillaritis, livedo reticularis, and chronic leg ulcers, are more common signs. Development of RV worsens the prognosis of the disease. The 5-year survival rate of RV patients was 28–40% until the principle of early administration of basic anti-inflammatory drugs was implemented. RV is not an independent disease; in most cases, RV alone does not impose a threat to a patient and requires no treatment. Special treatment of cutaneous vasculitis is required in case of venous ulcers only. The article discusses the pathogenesis issues and strategies of RV treatment in RA patients.

Purpose of Review: Rheumatoid vasculitis (RV) is an unusual complication of long-standing rheumatoid arthritis, which is characterized by the development of necrotizing or leukocytoclastic vasculitis involving small or medium-sized vessels. In this review, we aim to provide an update on the epidemiology, pathogenesis, clinical presentation, and management of this challenging extra-articular manifestation. Recent Findings: RV is heterogenous in its clinical presentation depending on the organ and size of blood vessels involved. The most common organs involved are the skin and peripheral nerve. Based on recent population studies, the incidence has significantly decreased with early recognition and the advent of immunosuppressive drugs and biologics; however, the mortality rates remain high. Summary: RV remains a serious extra-articular manifestation of RA that needs to be promptly recognized and treated. No consensus is available on treatment, given the ongoing debate of whether the biologics can trigger or treat RV. [ABSTRACT FROM AUTHOR]

Rheumatoid vasculitis which affects small-to-medium-sized vessels is a rare and late complication of rheumatoid arthritis. It is defined histologically as immune complex deposition in venules, capillaries and arterioles.1 Vasculitis in the vasa nervorum leads to infarction of peripheral nerves which leads to neuropathy. We present a case of mononeuritis multiplex due to rheumatoid vasculitis. [ABSTRACT FROM AUTHOR]

The systemic manifestations of rheumatoid arthritis (RA) are fairly diverse. They are associated with high disease activity and an increased risk for deaths, primarily from cardiovascular events. Objective: to study the frequency and spectrum of extra-articular manifestations of RA. Subjects and methods. The trial enrolled 119 patients, including 110 women and 19 men (mean age 47.4+4.3 years), with the reliable and valid diagnosis of RA (mean duration 9.4+3.3 years). The patients were divided into 2 groups: 1) 78 patients with the extra-articular manifestations of RA (a study group); 2) 44 patients without these signs (a comparison group). Clinical, laboratory, instrumental, and morphological studies were made using current diagnostic methods. Results. By and large, the extra-articular manifestations of RA are closely associated with its activity and joint lesion severity. The study group most commonly had anemia (71.4%), rheumatoid nodules (29.4%), generalized amyotrophy (26.9%), lymphadenopathy (26.1%), prolonged fever (24.4%), and rheumatoid vasculitis (18.5%). The development of extra-articular manifestations was associated with the activity and late diagnosis of RA and rheumatoid factor seropositivity.

OBJETIVO: Avaliar a frequência do HLA classes I e II e sua associação com a manifestação cutânea da vasculite reumatoide (VR) em pacientes brasileiros. PACIENTES E MÉTODOS: Durante um ano foram selecionados 130 pacientes com artrite reumatoide (AR), classificados de acordo com os critérios do American College of Rheumatology de 1987. Os pacientes foram submetidos a um questionário clínico e laboratorial para exclusão de outras causas de vasculopatia cutânea (neoplasia, infecções, uso de drogas ilícitas, diabetes mellitus e tabagismo). Setenta e três foram excluídos por apresentarem algum fator de risco para outras causas de vasculopatias. Cinquenta e sete foram incluídos no estudo sem fator de risco para outras causas de vasculopatia, dos quais 17 apresentavam VR de acordo com os critérios de 1984 de Scott e Bacon. Foram analisados dados demográficos, tempo de diagnóstico de AR, atividade da doença (DAS28) e presença de fator reumatoide e de anticorpos antipeptídeo citrulinado cíclico. Alelos HLA foram tipificados usando-se a reação em cadeia da polimerase-DNA amplificada por hibridização de baixa resolução com sequências específicas de sondas. RESULTADOS: A comparação entre os 40 pacientes sem VR e os 17 pacientes com VR demonstrou uma frequência aumentada do HLA-B*14 (Pc = 0,168) e do HLA-Cw*08 (Pc = 0,084) em pacientes com VR, e uma frequência aumentada do HLA-DRB5*01 (Pc = 0,048) em pacientes sem VR. CONCLUSÃO: O HLA-DRB5*01 pode conferir proteção contra essa manifestação extra-articular da AR.OBJECTIVE: To evaluate the frequency of HLA classes I and II and their association with the cutaneous manifestation of rheumatoid vasculitis (RV) in Brazilian patients. PATIENTS AND METHODS: During one year we selected 130 patients with rheumatoid arthritis (RA) classified according to the American College of Rheumatology, 1987. All patients underwent a clinical and laboratory questionnaire to exclude other causes of cutaneous vasculopathy (neoplasia, infections, illicit drug use, diabetes mellitus, and tobaccoism). Seventy-three patients with any risk factor for other causes of vasculopathy were excluded. Fifty-seven without risk factors for other causes of vasculopathy were included in the study, 17 with RV according to Scott and Bacon's criteria, 1984. Demographic data, time of RA diagnosis, disease activity (DAS28), presence of rheumatoid factor, and anti-cyclic citrullinated peptide antibodies were analyzed. The HLA alleles were typed using the DNA-amplified polymerase chain reaction with low-resolution hybridization and sequence-specific primers. RESULTS: The comparison between the 40 patients without RV and the 17 patients with RV showed an increased frequency of HLA-B*14 (Pc = 0.168) and HLA-Cw*08 (Pc = 0.084) in patients with RV and an increased frequency of HLA-DRB5*01 (Pc = 0.048) in patients without RV. CONCLUSION: The HLA-DRB5*01 may confer protection against that extra-articular manifestation of RA.

Rheumatoid vasculitis ( RV) is one of the most serious extra-articular complications of rheumatoid arthritis ( RA), generally treated with a high dose of immunosuppressive drugs. Recently, we encountered two cases of ulcerative vasculitis in methotrexate ( MTX)-prescribed RA patients, which simulated RV; however, Epstein-Barr virus ( EBV)-encoded RNA in situ hybridization on their skin biopsies revealed many EBV-positive lymphocytes (over 50 cells/high-power field) within the vessel walls and perivascular stroma, which led us to the diagnosis of EBV-related vasculitis instead of RV. Subsequently, both ulcers regressed after the discontinuation of MTX and no recurrence was noted during the follow-up period. To prevent unnecessary treatment, EBV-positive vasculitis should be added in the differential diagnosis of lymphocytic vasculitis observed in MTX-administered RA patients. [ABSTRACT FROM AUTHOR]

Vasculitides secondary to connective tissue diseases are classified under the category of 'vasculitis associated with systemic disease' in the revised International Chapel Hill Consensus Conference (CHCC) nomenclature. These secondary vasculitides may affect any of the small, medium or large vessels and usually portend a poor prognosis. Any organ system can be involved and the presentation would vary depending upon that involvement. Treatment depends upon the type and severity of presentation. In this review, we describe secondary vasculitis associated with rheumatoid arthritis, systemic lupus erythematosus, sarcoidosis, relapsing polychondritis, systemic sclerosis, Sjogren's syndrome and idiopathic inflammatory myositis, focusing mainly on recent advances in the past 3 years. [ABSTRACT FROM AUTHOR]

Background: Rheumatoid vasculitis is a serious complication of rheumatoid arthritis. Its incidence has decreased in developed countries due to biologic therapies but we can still see it in developing countries. Objective: To document the skin manifestations, response to treatment and prognosis of this disease. Material and method: A retrospective study of patients with diagnosis of rheumatoid arthritis and skin lesions attended at a single private practice over 20 years Results: The most common skin lesions were ulcers, periungueal or digital infarcts, palpable purpura, acrocyanosis, livedo reticularis, Raynaud's phenomenon and blisters. Skin biopsy showed leukocytoclastic vasculitis in all cases. All patients had rheumatoid nodules and neurologic manifestations. Only one patient died. Conclusions: Rheumatoid vasculitis is a little frequent complication of rheumatoid arthritis. Most patients have rheumatoid nodules and high blood pressure. Skin ulcers are the most frequent. [ABSTRACT FROM AUTHOR]

Objective. The aim of this study was to determine the clinical correlates and predictors of rheumatoid vasculitis (RV). Methods. A retrospective cohort of patients with RV evaluated at a tertiary referral centre between 1 January 2000 and 1 January 2010 was identified. RV cases were compared in a 1:2 ratio to controls (RA without vasculitis) to identify risk factors for developing RV. Results. Eighty-six RV cases (58% women, 88% white) were identified. Histopathological confirmation was available for 58% of patients. Cutaneous vasculitis was the most common presentation, followed by vasculitic neuropathy. The median age at presentation was 63 years and the median duration of RA was 10.8 years. One third were current smokers. The majority were seropositive and had elevated inflammatory markers. Treatment was with a range of immunomodulating agents. At 6 months, 38% of patients achieved complete remission, 52% had partial improvement and 10% noted no clinical improvement. Thirty-six per cent relapsed by 5 years and 26% died. After adjusting for age and disease duration, current smoking at RA diagnosis [odds ratio (OR) 1.98], coexistent peripheral vascular disease (OR 3.98), cerebrovascular disease (OR 6.48), severe RA (OR 2.02) (characterized by radiographic erosions, nodulosis on clinical examination or requirement of joint surgery) and the use of biologics (OR 2.80) were found to increase the odds for developing RV; the use of HCQ (OR 0.54, CI 0.31, 0.94) and low-dose aspirin (OR 0.42, CI 0.21, 0.85) was associated with decreased odds for developing RV. Conclusion. This largest single-centre series of patients with RV suggests that even in recent years, RV remains a serious complication of RA and is associated with significant mortality. [ABSTRACT FROM AUTHOR]

Leg ulcers are often complicated in patients with rheumatoid arthritis ( RA), however, the etiology is multifactorial. We examined the cases of leg ulceration or gangrene in seven RA patients who were hospitalized over the past 3 years. One patient was diagnosed as having pyoderma gangrenosum. Although vasculitis was suspected in three patients, no histological evidence was obtained from the skin specimens. In these patients, angiography revealed the stenosis or occlusion of digital arteries. In the remaining three patients, leg ulcers were considered to be due to venous insufficiency. Treatment should be chosen depending on the causes of leg ulcers. [ABSTRACT FROM AUTHOR]

The vasculature plays a crucial role in inflammation and atherosclerosis associated with the pathogenesis of rheumatoid arthritis. Vasculitis in rheumatoid arthritis is associated with longstanding disease, has an important impact on a patient's quality of life and influences patient life expectancy. Seropositivity, specific human leukocyte antigen variations, antibodies to cyclic citrullinated peptides, and cigarette smoking are among the genetic and environmental predictors of rheumatoid vasculitis. Atherosclerosis is an early and common finding in rheumatoid arthritis and it correlates with disease duration, activity, and severity. Apart from conventional risk factors such as cigarette smoking, physical inactivity, obesity, arterial hypertension, dyslipidemia and diabetes mellitus, rheumatoid arthritis-related risk factors including disease duration, severity and activity, rheumatoid factor and antibodies to cyclic citrullinated peptides status, functional impairment, C-reactive protein, radiographic changes, presence of the shared epitope, and treatment modalities are all implicated in the development of accelerated atherosclerosis. Atherosclerosis is also considered an inflammatory disease; thus, it may share common pathogenic mechanisms with rheumatic diseases such as rheumatoid arthritis. Advances in treatment of rheumatoid arthritis with disease-modifying biologic and nonbiologic agents will probably continue to reduce the incidence of vasculitis. Since the goal of treatment for rheumatoid arthritis is to decrease inflammatory burden, successful treatment may theoretically reduce the risk of accelerated atherosclerosis. [ABSTRACT FROM AUTHOR]

We report a case of rheumatoid vasculitis (RV) that responded well to abatacept, a cytotoxic T lymphocyte-associated antigen 4 (CTLA4)-immunoglobulin fusion protein. A 38-year-old woman developed RV despite treatment with methotrexate and tumor necrosis factor (TNF) inhibitors. The effects of steroid therapy, immunoabsorption plasmapheresis, and interleukin-6 inhibitor were insufficient, however, administration of abatacept rapidly improved her clinical symptoms with almost normalization of the immunological findings. This is the first published case report of the successful treatment of RV with abatacept. [ABSTRACT FROM AUTHOR]

Macrophage migration inhibitory factor (MIF) is recognized to be an important mediator in several inflammatory disorders, including rheumatoid arthritis (RA) and vasculitis. To evaluate the role of MIF in rheumatoid vasculitis (RV), we determined serum levels of MIF by enzyme-linked immunosorbent assay in RA patients with and without vasculitis and assessed their relationship to disease activity. Serum was obtained from 95 RA patients during active disease states [49 without vasculitis, 35 with extra-articular manifestations without histologically proven vasculitis, and 11 with histologically proven vasculitis] and from 22 healthy individuals. Vasculitis disease activity was assessed using the Birmingham Vasculitis Activity Score (BVAS). MIF levels were significantly higher in RA patients than in controls. Moreover, MIF levels were significantly higher in RA patients with vasculitis than in those without vasculitic complications. In all RA patients, a statistically significant positive correlation was observed between serum MIF levels and each of the following: serum levels of C-reactive protein, rheumatoid factor, and thrombomodulin; and the erythrocyte sedimentation rate. In the RV group, the elevation of MIF levels correlated with the BVAS. Our findings suggest that MIF may serve as an additional serologic inflammatory marker of disease activity in RV, and it may be implicated in the pathogenesis of RV. [ABSTRACT FROM AUTHOR]

Background: Anti-neutrophil cytoplasmic antibodies are typically detected in anti-neutrophil cytoplasmic antibody associated vasculitis, but are also present in a number of chronic inflammatory non-vasculitic conditions like rheumatoid arthritis. Rare cases of granulomatosis with polyangiitis (formerly known as Wegener's granulomatosis, a vasculitic disorder frequently associated with the presence of anti-neutrophil cytoplasmic antibodies) in patients with rheumatoid arthritis have been described in literature.Case presentation: We report two middle-aged female patients with rheumatoid arthritis who developed anti-neutrophil cytoplasmic antibodies and symptoms reminiscent of granulomatosis with polyangiitis. Despite the lack of antibodies specific for proteinase 3 and the absence of a classical histology, we report a probable case of granulomatosis with polyangiitis in the first patient, and consider rheumatoid vasculitis in the second patient.Conclusion: Taken together with previous reports, these cases highlight that anti-neutrophil cytoplasmic antibodies have to be evaluated very carefully in patients with rheumatoid arthritis. In this context, anti-neutrophil cytoplasmic antibodies detected by indirect immunofluorescence appear to have a low diagnostic value for granulomatosis with polyangiitis. Instead they may have prognostic value for assessing the course of rheumatoid arthritis. [ABSTRACT FROM AUTHOR]

Rheumatoid vasculitis is a rare but serious complication of rheumatoid arthritis. Herein we examine the pathophysiology, epidemiology, clinical diagnosis, and treatment of rheumatoid vasculitis. Seropositivity, specific HLA variations, and tobacco use are among the genetic and environmental predictors of rheumatoid vasculitis. Fortunately, recent reports have noted declines in the prevalence of rheumatoid vasculitis. Nevertheless, proper recognition of systemic manifestations may assist in pathologically confirming the diagnosis, determining the extent of disease, and guiding treatment. Contemporary treatment reports are discussed in the context of the ongoing debate regarding whether new agents may trigger, treat, or even prevent rheumatoid vasculitis. Evolving genetic, histopathologic, and immunologic studies partnered with ongoing clinical experience with biologics offer promise to inform future prevention and treatment of rheumatoid vasculitis. [ABSTRACT FROM AUTHOR]

Particulate matter (PM) air pollution less than 2.5 μm in diameter (PM2.5), which is now an all-pervading element of modern-day society, is associated with heightened cardiovascular morbidity and mortality. Not only can short-term PM2.5 exposure trigger acute cardiovascular events, but longer-term exposure over years augments cardiovascular risk to an even greater extent. One biological mechanism capable of explaining this observation is that chronic exposure may promote the progression and vulnerability of atherosclerotic plaques. Indeed, recent epidemiologic studies have demonstrated an association between ambient PM2.5 exposure and the presence or extent of atherosclerosis in humans. Several animal experiments have provided corroborating evidence that chronic exposures in fact do enhance the progression and perhaps vulnerability of atherosclerotic lesions. Due to the billions of people continually exposed to PM2.5, the long-term pro-atherosclerotic effects of this ubiquitous air pollutant are likely to be of enormous and growing global public health importance. [ABSTRACT FROM AUTHOR]

In search of a noninvasive diagnostic test for rheumatoid vasculitis (RV), this study addressed the questions whether changes in capillary blood cell velocity (CBV) detected by laser Doppler anemometry in patients with rheumatoid arthritis (RA) were correlated with the levels of soluble adhesion molecules and whether cutaneous flow abnormalities may reflect extraarticular manifestations in RA. In 31 RA patients and 20 patients with osteoarthritis (OA), CBV was measured in the skin above the left ring finger at rest and after 3-min arterial occlusion. Serum levels of soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble E-selectin (sE-selectin), and soluble P-selectin (sP-selectin) were assessed by enzyme linked immunosorbent assay. Peak CBV was reduced in RA patients compared to OA patients (0.42 ± 0.07 mm/s vs. 0.70 ± 0.13 mm/s; P = 0.013). Both CBV during rest and reactive hyperemia were not correlated with the levels of soluble adhesion molecules. There were no significant differences in resting or peak CBV between RA patients with or without extraarticular manifestations. The lack of an inverse correlation between the levels of soluble adhesion molecules and CBV during rest and reactive hyperemia contradicts the assumption that inflammatory vascular damage indicated by increased levels of soluble adhesion molecules was the main reason for the impairment of microcirculation. The present results do not suggest that cutaneous flow abnormalities may reflect extraarticular manifestations in RA. [ABSTRACT FROM AUTHOR]

Abstract: Early detection of synovitis in rheumatoid arthritis (RA) and distinction from osteoarthritis (OA) are important to establish the most appropriate treatment. Increased perfusion over affected joints observed by laser Doppler perfusion imaging was supposed to arise from the underlying joint, because it was detected only by a near-infrared laser and not by a less penetrating red laser source. Using laser Doppler anemometry, this study addressed two questions: (1) whether capillary blood cell velocity (CBV) is increased in the skin over finger joints affected by RA or OA; (2) whether there is a difference between RA and OA in CBV above affected proximal interphalangeal (PIP) joints. Levels of soluble adhesion molecules were measured, because they indicate rheumatoid vasculitis raising flow resistance. Thirty-one patients with RA and 20 with OA were investigated. Compared to 18 controls, CBV (mean ± SEM) was elevated above PIP joints clinically affected by RA (0.35 ± 0.06 mm/s vs. 0.21 ± 0.02 mm/s; P < 0.05) and over PIP (0.27 ± 0.02 mm/s vs. 0.21 ± 0.02 mm/s; P < 0.05) and distal interphalangeal joints (0.27 ± 0.02 mm/s vs. 0.17 ± 0.01 mm/s; P < 0.001) affected by OA. Levels of soluble adhesion molecules were not correlated with CBV over PIP joints in RA. These observations demonstrated that elevated blood cell velocity is detectable by laser Doppler anemometry in skin capillaries over interphalangeal joints affected by RA or OA and contradict the previous assumption that there is hyperemia only in the affected joint. The lack of a significant difference in CBV over PIP joints between RA and OA patients might be due to some inflammation also occurring in OA rather than to vasculitic processes in RA associated with elevated levels of soluble adhesion molecules. [Copyright &y& Elsevier]

A 63-year-old male with a 5-year history of malignant rheumatoid arthritis (MRA) developed recurrent massive melena and abdominal pain. Methylprednisolone pulse therapy and high doses of oral prednisolone markedly improved the clinical symptoms and normalized immunological disorders. However, he died of disseminated intra-vascular coagulation secondary to pneumonia caused by methicillin-resistant Staphylococcus aureus. Although a high dose of glucocorticoid therapy is effective for ischemic colitis complicated with MRA, intensive care to avoid any opportunistic infection is required. [ABSTRACT FROM AUTHOR]