Vasculitis reumatoidea: una manifestación poco habitual. Presentación de tres casos clínicos y revisión de la literatura

La vasculitis reumatoidea es una complicación sistémica y poco frecuente de la Artritis Reumatoidea. Si bien su incidencia ha descendido en los últimos años con el advenimiento de las nuevas terapias inmunosupresoras y biológicas, continua teniendo una alta morbimortalidad. Predomina en el sexo masculino, en pacientes seropositivos y con un largo período de la enfermedad establecida. Requiere de alta presunción diagnostica, siendo el compromiso cutáneo y nervioso periférico el más frecuente. La biopsia de nervio o piel es requerida habitualmente para su diagnóstico. El tratamiento se basa en corticoides e inmunosupresores. Presentamos tres casos clínicos y realizamos una revisión de la literatura.

Rheumatoid vasculitis is a rare systemic complication of rheumatoid arthritis. Although its incidence has decreased in recent years with the advent of new immunosuppressive and biological therapies, it continues to have a high morbidity and mortality. It predominates in males, in seropositive patients and with a long period of established disease. It requires high diagnostic presumption, with skin and peripheral nervous involvement being the most affected. Nerve or skin biopsy is usually required for diagnosis. Treatment is based on corticosteroids and immunosuppressants. We present three clinical cases and carry out a review of the literature.

A vasculite reumatóide é uma complicação sistêmica rara da artrite reumatóide. Embora sua incidência tenha diminuído nos últimos anos com o advento de novas terapias imunossupressoras e biológicas, continua apresentando elevada morbidade e mortalidade. Predomina no sexo masculino, em pacientes soropositivos e com longo período de doença estabelecida. Exige alta presunção diagnóstica, sendo o envolvimento cutâneo e nervoso periférico os mais afetados. A biópsia de nervo ou pele geralmente é necessária para o diagnóstico. O tratamento é baseado em corticosteroides e imunossupressores. Apresentamos três casos clínicos e realizamos uma revisão da literatura.

Vasculitis reumatoide: a propósito de dos casos / Rheumatoid vasculitis: about two cases

Resumen La vasculitis reumatoide constituye una complicación inusual, pero severa, de la artritis reumatoide, caracterizada por un proceso inflamatorio que compromete vasos sanguíneos de pequeño y mediano calibre, asociada o no a manifestaciones extraarticulares. Algunos factores predisponentes descritos incluyen ciertos haplotipos de antígenos leucocitarios humanos, fumado y enfermedad de larga data. Una disminución en la incidencia ha sido notada desde los años 90 y confirmada en estudios recientes, asociada en particular a un diagnóstico precoz de artritis reumatoide y estrategias terapéuticas que incluyen un aumento en la prescripción de metotrexate. La vasculitis reumatoide se asocia a tasas de mortalidad hasta del 40% a los 5 años y morbilidad importante. Se presentan dos pacientes con diagnóstico previo de artritis reumatoide, con un cuadro crónico de úlceras y disestesias en miembros inferiores, asociado a síndrome anémico. Los estudios histológicos revelaron vasculitis de mediano vaso compatible con vasculitis reumatoide. Se inició manejo con inmunosupresores más esteroides, con resolución del cuadro clínico inicial.

Abstract Rheumatoid vasculitis remains a rare but serious complication of rheumatoid arthritis characterized by an inflammatory process that primarily affects small to medium-sized blood vessels, it can be associated with other extra-articular manifestations. A number of predictor or predisposing factors including certain human leukocyte antigen haplotypes, smoking and long-standing disease. A declining trend in the incidence of rheumatoid vasculitis has been noted since the 1990s and reconfirmed in recent studies, related to early diagnosis of rheumatoid arthritis, and widespread use of methotrexate. Rheumatoid vasculitis is associated with high rates of premature mortality with up to 40% of patients dying by 5 years, as well as a significant morbidity. We present two patients with diagnosis of rheumatoid arthritis with a chronic condition of ulcers and dysesthesias on legs associated with anemic syndrome; the histological study revealed medium size vasculitis. Treatment with inmunosuppresants and steroids was given with resolution of symptoms.

Vasculitis reumatoidea como primera manifestación de artritis reumatoide / Rheumatoid vasculitis as first manifestation of rheumatoid arthritis

Resumen La vasculitis reumatoidea es la complicación extraarticular más grave de la artritis reumatoide, con morbilidad y mortalidad altas. Se trata de un proceso inflamatorio que afecta principalmente los vasos sanguíneos de pequeño y mediano calibre, sus manifestaciones clínicas sobrevienen de forma heterogénea, la vasculitis cutánea y la neuropatía son las más comunes. Su incidencia ha disminuido en las últimas décadas debido a la administración temprana de fármacos modificadores de la enfermedad en la artritis reumatoide. A pesar de la administración de ciclofosfamida y la existencia de medicamentos biológicos, continúa siendo un reto lograr el control de la enfermedad. Comunicamos el caso de un paciente de 50 años de edad, sin antecedentes médicos de importancia, salvo tabaquismo, que inició con neuropatía secundaria a vasculitis con factor reumatoide y anticuerpos antipéptido cíclico citrulinado positivos. La revisión bibliográfica pone al día los conocimientos acerca de la enfermedad para considerarla diagnóstico diferencial.

Abstract 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.

Vasculitis reumatoidea. Estudio de un caso / Rheumatoid vasculitis. Study of a case

Se presenta un caso, portadora de artritis reumatoide de varios años de evolución, que tras abandonar el tratamiento presentó una exacerbación de la actividad de la enfermedad, acompañada de un síndrome general y lesiones dérmicas y neurológicas producidas por una vasculitis leucocitoclastica, fue necesario actualizar el tratamiento con metotrexate y bolos de metilprednisolona obteniendo una respuesta favorable demostrada al desaparecer la actividad de la enfermedad y cicatrización de las lesiones ulcerosas.

present a case, with rheumatoid arthritis of several years of evolution, that after leaving the treatment presented an exacerbation of the activity of the disease, accompanied by a general syndrome and dermal and neurological lesions caused by a leukocytoclastic vasculitis, it was necessary to update the treatment with methotrexate and boluses of methylprednisolone obtaining a favorable response demonstrated when the activity of the disease disappeared and cicatrization of the ulcerous lesions.

Detrimental Effects of Endovascular Intervention in Active Rheumatoid Vasculitis

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.

Vasculite reumatoide - Relato de caso / Rheumatoid Vasculitis - Case Report

Resumo A artrite reumatoide (AR) é uma doença crônica autoimune inflamatória sistêmica e sua principal manifestação é a sinovite persistente, que compromete articulações periféricas de forma simétrica. Apesar do seu potencial destrutivo, a evolução da AR é muito variável. Alguns pacientes podem ter apenas um processo de curta duração oligoarticular com lesão mínima, enquanto outros sofrem uma poliartrite progressiva e contínua e evoluem com acometimento de outros órgãos e sistemas, como pele, coração, pulmões, músculos e mais raramente vasos sanguíneos, que leva à vasculite reumatoide. O objetivo deste estudo foi descrever um caso de vasculite reumatoide, uma condição rara e grave.

Abstract Rheumatoid arthritis (RA) is a chronic systemic inflammatory autoimmune disease and its main manifestation is persistent synovitis affecting peripheral joints symmetrically, In spite of its destructive potential, the evolution of RA is highly variable. Some patients may have only a short-term process oligoarticular with minimum lesion, while others suffer a polyarthritis evolving with progressive and continuous involvement of other organ systems such as skin, heart, lungs, muscles and blood vessels rarely leading to rheumatoid vasculitis. The aim of this study was to describe a case of rheumatoid vasculitis a rare and severe condition.

The role of KIR2DL3/HLA-C*0802 in Brazilian patients with 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. .

Vasculite testicular: uma manifestação rara de artrite reumatoide / Testicular vasculitis: a rare manifestation of rheumatoid arthritis

A vasculite testicular é uma manifestação extra-articular muito rara da artrite reumatoide (AR). Descrevemos o caso de um homem de 53 anos com diagnóstico de AR por oito anos, sem controle adequado da doença. O paciente desenvolveu vasculite reumatoide, manifestada por úlceras de membros inferiores e neuropatia periférica. Apresentou ainda meningite neutrofílica aguda, tendo sido tratado com antibióticos e posterior pulsoterapia endovenosa com metilprednisolona (500 mg/dia) por três dias, seguida de ciclofosfamida (2 mg/kg/ dia) e prednisona orais. O paciente apresentou melhora do quadro, mas 15 dias após a alta hospitalar, houve reativação da meningite bacteriana. O paciente foi reinternado e tratado novamente com antibióticos. Três dias depois da segunda admissão hospitalar, o paciente apresentou dor, aumento de volume do testículo esquerdo e posteriormente gangrena. Foi realizada orquiectomia unilateral e o exame anatomopatológico revelou vasculite linfocítica. O paciente faleceu dois dias após a cirurgia devido a pneumonia aspirativa. Esse caso ilustra a vasculite testicular como uma manifestação rara e grave da vasculite reumatoide.

Testicular vasculitis is a very rare extra-articular manifestation of rheumatoid arthritis (RA). We describe the case of a 53-year-old man diagnosed with RA for eight years, who was poorly controlled and developed rheumatoid vasculitis, which manifested as leg ulcers and peripheral polyneuropathy. The patient also had acute neutrophilic meningitis and was treated with antibiotics and intravenous pulse therapy with methylprednisolone (500 mg daily) for three days, followed by oral cyclophosphamide (2 mg/kg daily) and prednisone. Overall improvement was observed, and the patient was discharged. But 15 days later, the meningitis recurred, and the patient was readmitted and treated again with antibiotics. Three days later, he developed pain and enlargement of his left testicle with gangrene. Unilateral orchiectomy was performed, revealing lymphocytic vasculitis. The patient died two days later due to aspiration pneumonia. This case illustrates a rare and severe manifestation of rheumatoid vasculitis.

Associação do HLA-DRB5*01 com proteção contra manifestação cutânea da vasculite reumatoide em pacientes brasileiros / Association of HLA-DRB5*01 with protection against cutaneous manifestations of rheumatoid vasculitis in Brazilian patients

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.

Valor de la determinación de los niveles de moléculas de adhesión solublesen el diagnóstico de la vasculitis reumatoidea / Value of the determination of levels soluble adhesion molecules in the diagnosis of rheumatoid vasculitis

La Vasculitis Reumatoidea (VR) es una complicación severa de laArtritis Reumatoidea (AR). Varios estudios demuestran que las moléculasde adhesión soluble serían indicadores de activación endotelial y se asociarían a daño vascular. Objetivo: Medir los niveles séricos de moléculas de adhesión solubles en pacientes con VR y evaluar la utilidad de las mismas para elmonitoreo de la respuesta terapéutica.Material y métodos: Se incluyeron en forma consecutiva pacientes con AR según criterios ACR’87 y diagnóstico VR. Por cada paciente con VR, se evaluaron 2 pacientes con AR sin vasculitis apareados por edad, sexo y tiempo de evolución de la enfermedad. Se consignaron datos demográficos, hábitos tóxicos, enfermedades comórbidas, parámetros de laboratorio, datos relacionados a la AR, en el momento previo al proceso vasculítico, en el período activo y 6 meses posterior al inicio del tratamiento específico para vasculitis. Las moléculas de adhesión VCAM-1 y E-selectina fueron medidaspor método de ELISA, en ambos grupos basalmente y luego de 6 meses de iniciado el tratamiento. Resultados: Los pacientes con VR (n = 10) tenían una edad mediana de 51 años (RIC 42,2-55,2) y un tiempo mediano de evolución de la enfermedad de 84 meses (RIC 69-180). El 80% era de sexo femenino. Los pacientes con AR sin VR (n = 20) tenían característicasdemográficas y tiempo de evolución de la enfermedad comparables. El 80% de los pacientes con VR presentaban compromiso cutáneo. El 100% tenía compromiso neurológico. Todos los pacientes recibieron tratamiento con esteroides, 9 pulsos de ciclofosfamida y1 azatioprina. Los niveles de VCAM-1 fueron significativamente mayores en pacientes con VR vs. controles (765 μg/ml vs. 595 μg/ml,p = 0,033). Los valores de E-selectina fueron mayores en vasculitis vs. controles (49,25 μg/ml vs. 40,3 μg/ml), pero esta diferencia noalcanzó significancia estadística. Los niveles VCAM-1 también disminuyeronen forma significativa...

Rheumatoid vasculitis (RV) is a severe complication in patients with RA. Some studies demonstrated that the soluble adhesion molecules are associated with endothelial activation and vascular damage. Objective:To measure serum levels of soluble adhesion moleculesin RA patients with RV and to evaluate their utility for monitoring thetherapeutic response. Material and methods:Consecutive patients with RA (ACR’87) and RV were included. For each patient with RV, 2 patients with RA and without RV matched by age, sex and disease duration were used as controls. Demographical data, toxic habits, comorbidities, laboratory, RA characteristics were registered previously vasculitis, in the active period and 6 months after the beginning of the specific vasculitis treatment. The adhesion molecules VCAM-1 and E-selectin were measured by ELISA, in both groups, basally and 6 months afterof the therapy beginning. Results: RV patients (n = 10) median age 51 years (IQR 42.2-55.2) and median disease duration 84 months (IQR 69-180) and80% female sex. RA patients without RV (n = 20) had comparabledemographical and disease duration. 80% RV patients had skin involvement. 100% had neurological involvement. All the patients received steroids treatment, 9 IV cyclophosphamide and 1 azathioprine. VCAM-1 levels were significantly greater in RV patients vs.controls (765 μg/ml vs. 595 μg/ml, p = 0.033). E-selectin levels were also greater in vasculitis vs. controls (49.25 μg/ml vs. 40.3 μg/ml), but this difference did not reach statistical significance. VCAM-1 levels significantly decreased after 6 months of treatment, 765 μg/ml (592.5-975) vs. 555 μg/ml (455-685), p = 0.01. We did not observe difference in E-selectin levels.Conclusion: VCAM-1 levels are increased in RV patients versus RA patients without RV and these soluble adhesion molecules decreased after treatment. The VCAM-1 measurement could be a useful vascular inflammation indicator in RV and would allow to monitoring treatment.

A Case of Acute Myocardial Infarction and Multiorgan Involvement Secondary to Rheumatoid Vasculitis

Rheumatoid arthritis patients have an increased risk of subclinical cardiovascular disease, and they also have a high prevalence of carotid disease and peripheral arterial disease as a form of vasculitis. Rheumatoid arthritis patients have an increased cardiovascular mortality rate and an increased premature death rate, and they have a higher incidence of atherosclerosis. Myocardial infarction due to vasculitis is a rare complication for patients with rheumatoid vasculitis. We report here on a case of a patient with multiorgan involvement who developed myocardial infarction, right carotid artery occlusion and left renal artery occlusion secondary to his rheumatoid vasculitis.

A Case of Rheumatoid Vasculitis / 대한피부과학회지

Rheumatoid vasculitis usually occurs in patients with long standing, seropositive, erosive rheumatoid arthritis. It involves typically small to medium-sized vessels and is associated with peripheral neuropathy, digital gangrene, nail fold infarcts, livedo reticularis, and palpable purpura. Histologic examination of skin biopsy specimens usually shows leukocytoclastic vasculitis. We report a case of rheumatoid vasculitis developed on both extremities in a 63-year-old female with rheumatoid arthritis for 15 years.

Rheumatoid vasculitis manifesting as ischemic colitis / 대한내과학회지

Rheumatoid vasculitis is a necrotizing arteritis of unknown causes that affect a subset of patients with rheumatoid arthritis. Vasculitis associated with rheumatoid arthritis was first recognized in 1898. It was described frequently in the 1940s through 1960s but is now rarely diagnosed. Typical clinical features include constitutional symptoms, mononeuritis multiplex, skin infarction, ulceration, peripheral gangrene and visceral infarction. Gastrointestinal involvement occurs in 10 to 38% of cases of rheumatoid vasculitis and may include bowel infarction, ulceration, perforation, colitis, stricture, or bleeding. Ischemia of the intestine is the end result of interruption or reduction of its blood supply. However, the clinical manifestations of intestinal ischemia range from mild chronic symptoms to a catastrophic acute episode, depending on the vascular supply involved, the extent of the occlusion or ischemia, and the rapidity of the process. Physicians caring for patients with rheumatoid arthritis should be aware that intestinal ischemia or infarction may occur without overt clinical evidence of systemic rheumatoid vasculitis. Herein we describe a case of rheumatoid vasculitis manifesting as ischemic colitis which was intractable to medical therapy and led to subtotal colectomy.