Patient-reported outcomes in vasculitis.

Systemic vasculitis encompasses a group of multisystem disorders; both the diseases and the treatment strategies can have a significant impact on a patient's health-related quality of life (HRQoL). Using patient-reported outcome measures (PROMs) and patient-reported experience measures (PREMs) to evaluate the patient's view of their condition, treatments, and healthcare journey is essential to the patient-centered care approach. In this paper, we discuss the use of generic, disease-specific, and treatment-specific PROMs and PREMs in systemic vasculitis and future research goals.

Systemic vasculitis: one year in review 2023.

Systemic vasculitides are heterogeneous disabling diseases characterised by chronic inflammation of the blood vessels potentially leading to tissue destruction and organ failure. The recent COVID-19 pandemic has had a significant impact on the epidemiology and management of patients with systemic vasculitis. In parallel, new insights have been provided on systemic vasculitis pathogenetic mechanisms, possible new therapeutic targets, and newer glucocorticoid-sparing treatments with better safety profiles. As in the previous annual reviews of this series, in this review we will provide a critical digest of the most recent literature regarding pathophysiology, clinical manifestations, diagnostic tools and treatment options in small- and large-vessel vasculitis focusing on precision medicine in vasculitis.

Cambio de paradigma en las enfermedades autoinflamatorias monogénicas y las vasculitis sistémicas: el síndrome VEXAS / Paradigm shift in monogenic autoinflammatory diseases and systemic vasculitis: The VEXAS syndrome

A finales de 2020 se describió el síndrome VEXAS, como una enfermedad autoinflamatoria causada por variantes poscigóticas en el gen UBA1. Se presenta en varones adultos con fiebre recurrente, artralgias/artritis, condritis auricular/nasal, dermatosis neutrofílica, inflamación pulmonar, trombosis venosas y diferentes tipos de vasculitis. Los análisis muestran una respuesta de fase aguda elevada y anemia macrocítica. Es frecuente la coexistencia de mielodisplasia, y son características las vacuolas citoplasmáticas en precursores mieloides y eritroides en médula ósea. Los glucocorticoides a dosis medias-altas son eficaces, pero el resto de fármacos inmunodepresores, convencionales o biológicos, muestran una eficacia limitada o ausente. Azacitidina se ha asociado con una buena respuesta, sobre todo en pacientes con síndrome mielodisplásico acompañante. El trasplante alogénico de progenitores hematopoyéticos parece ser la única terapia curativa hasta el momento. El síndrome VEXAS ha supuesto un cambio de paradigma en el diagnóstico y tratamiento de las enfermedades autoinflamatorias y las vasculitis sistémicas. (AU)

VEXAS syndrome was described by the end of 2020 as an autoinflammatory disease caused by post-zygotic variants in the UBA1 gene. VEXAS syndrome occurs in adult males with recurrent fever, arthralgia/arthritis, ear/nose chondritis, neutrophilic dermatosis, lung inflammation, venous thrombosis, and different types of vasculitis. Common laboratory changes include raised acute phase reactants and macrocytic anemia. The coexistence of myelodysplasia is frequent, and bone marrow vacuolization of myeloid and erythroid precursors is characteristic. Glucocorticoids are effective at medium-high doses, but the remaining immunosuppressive drugs, either conventional or biological, have showed limited or absent efficacy. Azacitidine has been associated with a good response, especially in patients with accompanying myelodysplastic syndrome. Allogeneic hematopoietic stem cell transplantation appears to be the only curative therapy by now. VEXAS syndrome has become a paradigm shift in the diagnosis and treatment of autoinflammatory diseases and systemic vasculitis. (AU)

Paradigm shift in monogenic autoinflammatory diseases and systemic vasculitis: The VEXAS syndrome. / Cambio de paradigma en las enfermedades autoinflamatorias monogénicas y las vasculitis sistémicas: el síndrome VEXAS.

VEXAS syndrome was described by the end of 2020 as an autoinflammatory disease caused by post-zygotic variants in the UBA1 gene. VEXAS syndrome occurs in adult males with recurrent fever, arthralgia/arthritis, ear/nose chondritis, neutrophilic dermatosis, lung inflammation, venous thrombosis, and different types of vasculitis. Common laboratory changes include raised acute phase reactants and macrocytic anemia. The coexistence of myelodysplasia is frequent, and bone marrow vacuolization of myeloid and erythroid precursors is characteristic. Glucocorticoids are effective at medium-high doses, but the remaining immunosuppressive drugs, either conventional or biological, have showed limited or absent efficacy. Azacitidine has been associated with a good response, especially in patients with accompanying myelodysplastic syndrome. Allogeneic hematopoietic stem cell transplantation appears to be the only curative therapy by now. VEXAS syndrome has become a paradigm shift in the diagnosis and treatment of autoinflammatory diseases and systemic vasculitis.

Predictive Factors of Severe Behçet's disease: A Longitudinal, Prospective Cohort Followed Between 1981–2020 / Factores predictivos de la enfermedad de Behçet grave: una cohorte prospectiva longitudinal seguida entre 1981-2020

Introduction: Behçet's disease (BD) is a systemic vasculitis of unknown cause. The spectrum of the disease ranges from mucocutaneous manifestations to other organ diseases with relevant morbidity. Associations between disease severity and male sex, earlier age at onset, and the presence of erythema nodosum have been described. Objectives: To evaluate clinical factors associated with manifestations of severe disease in a single-center cohort. Methods: A longitudinal, prospective, unicentric cohort study with patients followed in a specialized outpatient clinic between 1981 and 2020. Severe BD was defined as a Krause total clinical severity score >4 points. Results: We included 243 patients, of whom 31% were male, with an average follow-up time of 14.6 years. Regarding organ manifestations, all patients had mucous manifestations (N=243, 100%), 133 (55%) skin, 104 (43%) joint, 71 (29%) ocular, 48 (20%) vascular, 47 (19%) neurological, 22 (9%) gastrointestinal and 1 (0.4%) cardiac involvement by BD. One hundred fifty-six (64%) patients were classified as having severe BD. Severe BD was more frequent in men (OR=2.004, p=0.024), increasing with age (OR=1.021 per year, p=0.037), in the presence of skin manifestations (OR=4.711, p<0.001), specifically erythema nodosum (OR=8.381, p<0.001), and pseudofolliculitis (OR=2.910, p<0.001). In the multivariate model, variables independently associated with severe BD were male gender (Adjusted OR=1.961, p=0.047), erythema nodosum (Adjusted OR=8.561, p<0.001) and pseudofolliculitis (Adjusted OR=2.372, p=0.007).Discussion: Male gender, erythema nodosum, and pseudofolliculitis were independently associated with severe BD forms and therefore should serve as warning signs to the clinician.(AU)

Introducción: La enfermedad de Behçet (EB) es una vasculitis sistémica de causa desconocida. El espectro de la enfermedad abarca desde manifestaciones mucocutáneas hasta otras enfermedades de órganos con morbilidad relevante. Se han descrito asociaciones entre la gravedad de la enfermedad y el sexo masculino, la edad de inicio más temprana y la presencia de eritema nudoso. Objetivos: Evaluar los factores clínicos asociados con las manifestaciones de enfermedad grave en una cohorte de un solo centro. Métodos: Estudio de cohorte longitudinal, prospectivo y unicéntrico con pacientes seguidos en una clínica ambulatoria especializada entre 1981 y 2020. La EB grave se definió como una puntuación Krause total clinical severity score≥4 puntos. Resultados: Se incluyeron 243 pacientes, de los cuales el 31% eran varones, con un tiempo de seguimiento medio de 14,6 años. En cuanto a las manifestaciones orgánicas, todos los pacientes presentaron manifestaciones mucosas (n=243, 100%), 133 (55%) piel, 104 (43%) articular, 71 (29%) ocular, 48 (20%) afectación vascular, 47 (19%) neurológica, 22 (9%) gastrointestinal y 1 (0,4%) cardiaca por EB; 156 (64%) pacientes fueron clasificados como con EB grave. La EB severa fue más frecuente en hombres (OR=2,004, p=0,024), aumentando con la edad (OR=1,021 por año, p=0,037), en presencia de manifestaciones cutáneas (OR=4,711, p<0,001), específicamente eritema nodosum (OR=8,381, p<0,001) y pseudofoliculitis (OR=2,910, p<0,001). En el modelo multivariado, las variables asociadas de forma independiente con el EB grave fueron el sexo masculino (OR ajustado=1,961, p=0,047), eritema nudoso (OR ajustado=8,561, p<0,001) y pseudofoliculitis (OR ajustado=2,372, p=0,007). Discusión: El sexo masculino, el eritema nudoso y la pseudofoliculitis se asociaron de forma independiente con formas graves de DB y, por lo tanto, deberían servir como signos de advertencia para el médico.(AU)

Systemic vasculitis: one year in review 2022.

Systemic vasculitis are rare heterogeneous disorders potentially involving any organ and system with a relevant burden of mortality and comorbidity.As in the previous annual reviews of this series, in this review we will provide a critical digest of the most recent literature regarding pathophysiology, clinical manifestations, diagnostic tools and treatment options in small- and large-vessel vasculitis.

Different epidemiologic profiles of systemic vasculitis between Brazil and Peru-preliminary results in two referral centers from both countries.

Little is known about the epidemiology of systemic vasculitis in South American countries. The aim of this study is to compare the prevalence of systemic vasculitides in two vasculitis referral centers from Brazil and Peru. A cross-sectional study was performed and all patients above 18 years of age, with at least 6 months of follow-up and who met classification or diagnosis criteria for the most common forms of vasculitis, were included. A total of 562 patients with systemic vasculitis were analyzed, 345 (61.4%) from Brazil and 217 (38.6%) from Peru. The frequency of Behçet's disease (37.9% vs. 1.8%; p < 0.0001), Takayasu arteritis (TAK) (25.2% vs. 6.9%; p < 0.0001), and giant cell arteritis (9.8% vs. 0.9%; p < 0.0001) was higher in the Brazilian center than the Peruvian one. On the other hand, the frequency of microscopic polyangiitis (MPA) (67.3% vs. 2.8%; p < 0.0001) and renal-limited vasculitis (2.8% vs. 0.0%; p = 0.009) was higher in the Peruvian center. No differences were found concerning other forms of vasculitis. At diagnosis, Brazilian patients with TAK, granulomatosis with polyangiitis, and MPA were younger than Peruvian patients. Epidemiologic differences in the frequency of systemic vasculitis are observed between a vasculitis referral center from Brazil and another from Peru. Key Points • Significant differences are observed regarding the epidemiologic profile of systemic vasculitis between Brazil and Peru. • MPA is the predominant form of vasculitis in Peru while BD and TAK are the most frequent forms of vasculitis in Brazil. • The age at diagnosis of TAK, MPA, and GPA was lower in Brazilian patients than in Peruvian patients.

A case report of a severe neonatal systemic vasculitis on the first day of life.

BACKGROUND: Neonatal systemic vasculitis syndromes have been reported in infants born to mothers with systemic lupus erythematosus, Sjögren's syndrome, BehÒ«et's disease, cutaneous polyarteritis nodosa and anti-neutrophil cytoplasmic antibody-associated vasculitides. Here we report a novel association of a case of new-onset maternal seronegative inflammatory arthritis associated with a transient systemic vasculitis in a neonate. CASE PRESENTATION: In the first 24 h of life, a preterm Caucasian baby boy was noted to have blue discoloration to all four extremities. Despite antibiotics, fresh frozen plasma and anticoagulation, the discoloration remained, particularly in the left index finger. This was associated with fever and a maximum C-reactive protein (CRP) of 148 mg/L. Intravenous immunoglobulin (IVIG) was given with short-term improvement. Initial echocardiogram showed enlarged coronary arteries with normalization on repeat 1 week later. Clinical signs and symptoms responded to high dose oral steroid administration. MRI angiography (MRA) of the body and heart showed tortuosity of arteries in the upper and lower extremities with gadolinium uptake, suggestive of vasculitis. Autoantibody profile negative. Genetic panel for hereditary autoinflammatory diseases was negative as was whole exome sequencing performed on the trio. The baby was weaned off steroids by 5 months of age. A small distal autoamputation of the left index finger occurred. He was born to a 28-year-old woman who developed new onset severe symmetrical polyarthritis at 8 weeks gestation. This was presumed a reactive arthritis secondary to a dental infection. Infectious work up and autoantibodies were negative. She was treated with high dose prednisone for the remainder of her pregnancy. The mother was weaned off prednisone, treated with hydroxychloroquine for 8 months post-partum and remains in remission. A repeat MRA done at 1 year old showed mild residual tortuosities of the arteries in the forearms. The remainder of the medium and large vessels were within normal limits with no gadolinium enhancement to suggest active disease. The child is now 4 years old with normal growth and development. CONCLUSION: This is a unique case of new-onset seronegative presumed reactive arthritis in a mother with the rare development of a successfully treated medium vessel vasculitis in an infant.

Investigating the forensic pathological characteristics of systemic vasculitis: A retrospective study of 20 deaths caused by systemic vasculitis.

Systemic vasculitis (SV) is a condition characterized by vascular inflammatory disease that often involves the medium and small arteries of various organs throughout the body. SV is difficult to diagnose due to the diversity of clinical symptoms and manifestations, and only tissue biopsy is of great significance. Even so, complications or secondary lesions of SV can also lead to death. In forensic medicine, we can often observe multiple vasculitis in histological observations, which is easily overlooked as a primary cause of death in the final diagnosis. Twenty SV cases were registered in our institution from a total of 1088 completed autopsies, which represents 1.83% of the total autopsies. The ages of these 20 SV patients ranged from 16 to 73 years, and the mean age was 41.1 ± 15.9 years. SV usually involves multiple organs, such as the heart, lung, liver, kidney, gastrointestinal system and brain, simultaneously. The intensity of the lesions in the heart and kidney seemed to be more severe than the lesion intensity in other organs in most cases. The causes of death were identified as acute myocarditis (8 cases), acute heart failure (3 cases), cerebral artery rupture (3 cases), cardiovascular artery rupture (2 cases), acute interstitial pneumonia (2 cases), aortic aneurysm rupture (1 case) and acute renal failure (1 case). The typical histopathological changes (smooth muscle degeneration, fibrinoid necrosis, inflammatory cell infiltration and microthrombosis) of arteries observed in this study were of great significance for diagnosing SV. In this article, we try to analyse and summarize the lesion characteristics in cases of death caused by SV in order to provide some help for forensic workers in identifying such cases.

Cutaneous Vasculitis: Review on Diagnosis and Clinicopathologic Correlations.

Cutaneous vasculitis is an inflammatory disease affecting the dermal blood vessel walls. The skin is a privileged organ in the setting of vasculitis since it is easily accessible for physical examination and safe biopsy, allowing an accurate characterization of inflammatory lesions. The skin is often involved. Also, cutaneous vasculitis can reflect a cutaneous component of a systemic vasculitis, a skin-limited or skin-dominant expression or variant of a systemic vasculitis, or be a single-organ vasculitis per se. Vasculitis lesions are multiple and polymorphic. They may induce a wide spectrum of clinical manifestations depending on the location and the size of the vessels involved. The depth of affected vessels is correlated with the type of cutaneous lesions. Involvement of small superficial vessels results mostly in urticarial, but relatively persistent plaques, papules, and palpable purpura. Involvement of vessels in the dermohypodermic junction or hypodermis results in ulcers, nodules, or livedo. The type of inflammatory infiltrate is also a key finding for the diagnosis of cutaneous vasculitis. Leukocytoclastic vasculitis is not a disease per se but the result of a pathophysiological process common to different causes. A better knowledge of the vascular anatomy of the skin, elementary lesions, and histological characteristics of dermatologic manifestations would allow a more relevant and more efficient diagnostic approach. We also propose a list of additional exams to be performed in front of skin lesions suggestive of vasculitis. The aim of our article is to provide an overview of elementary skin lesions and clinicopathologic correlations in cutaneous and systemic vasculitis.

Pulmonary Manifestations of Systemic Vasculitis in Children.

Vasculitides are defined according to the vessel size involved, and they tend to affect certain organ systems. Pulmonary involvement is rare in the common childhood vasculitides, such as Kawasaki disease, IgA vasculitis (Henoch Schonlein purpura). On the other hand, lung involvement is common in a rare pediatric vasculitis, granulomatosis with polyangiitis (GPA) (Wegener granulomatosis), where respiratory system findings are common. A criterion in the Ankara 2008 classification criteria for GPA is the presence of nodules, cavities, or fixed infiltrates. The adult data suggest that rituximab may be an alternative to cyclophosphamide in induction treatment.

Síndrome de Behçet ou úlcera de Lipschütz: desafio diagnóstico / Behçet's syndrome or Lipschütz ulcer: diagnostic challenge

A ocorrência de úlceras genitais em adolescentes e mulheres jovens tem impacto emocional para as pacientes e seus familiares, pela frequente associação com uma possível etiologia de transmissão sexual. Porém, úlcera de Lipschütz e síndrome de Behçet não têm etiologia infecciosa e devem ser lembradas como possíveis diagnósticos diferenciais. O diagnóstico dessas duas patologias é clínico e pode ser desafiador. Dessa forma, foi realizada uma revisão na literatura com o objetivo de comparar as duas entidades. A úlcera de Lipschütz é causada por uma vasculite local e caracteriza-se pelo surgimento súbito de úlceras na vulva ou vagina inferior. Já a doença de Behçet é causada por vasculite sistêmica, com episódios de remissão e exacerbação, que pode envolver quase todos os sistemas orgânicos. Em ambos os casos, é essencial o referenciamento para reumatologia. O tratamento objetiva suprimir exacerbações, controlar a dor e prevenir infecção secundária.(AU)

The occurrence of genital ulcers in adolescents and young women have an emotional impact for the patient and their families, due to the frequent association of its etiology with a sexually transmitted disease. However, Lipschütz ulcer and Behçet's syndrome do not have an infectious etiology and should be remembered as a possible differential diagnoses. As the diagnosis of these two pathologies is clinical and can be challenging, a review of literature was carried out. The objective of this review of literature was to compare both diseases. Lipschütz ulcer is caused by local vasculitis and is characterized by the sudden appearance of ulcers in the vulva or lower vagina. Behçet's syndrome is caused by systemic vasculitis, with episodes of remission and exacerbation, which can affect almost all organ systems. In both cases, referral to rheumatology is essential. Treatment aims to suppress exacerbations, control pain and prevent secondary infection.(AU)

Vasculitis Involving the Gastrointestinal System Is Often Incidental but Critically Important.

OBJECTIVES: This study was aimed to investigate the significance of unexpected vasculitis identified in gastrointestinal (GI) specimens by determining its prevalence and correlation with clinical outcomes. METHODS: GI specimens with histologic evidence of vasculitis were identified in our pathology database over a 10-year period (January 2008 to August 2018). Clinical history, treatment, and follow-up were reviewed. RESULTS: Of the 131,367 GI pathology cases received over the 10-year study period, 29 (0.02%) cases showed histologic evidence of GI vasculitis. The majority (69%, 20/29) were not clinically suspected. Of these, 20% (4/20) of patients were subsequently diagnosed with systemic vasculitis. During the mean follow-up period of 34.0 months, 24% (4/17) of the patients with this unexpected diagnosis died as the result of direct complications of GI vasculitis. We also found that 95% of cases with unexpected vasculitis in their GI pathology specimens were communicated in a timely manner to the ordering physicians, which necessitated the immediate initiation of additional workups in 85% of these patients. CONCLUSIONS: The GI involvement of vasculitis is rarely encountered by pathologists, but its diagnosis carries tremendous clinical significance with a high mortality rate. Therefore, timely communication is highly recommended for the early diagnosis and treatment of this disease.

Pregnancy Outcomes in Systemic Vasculitides.

PURPOSE OF REVIEW: In recent years, improvements in the recognition of primary vasculitides and increased treatment options have led to greater survival rates and a better quality of life for patients. Therefore, pregnancy in women with vasculitis has become a more frequent consideration or event. Literature on pregnancy outcomes in this population has grown and allowed us, in this article, to review the effects of pregnancy on disease activity, as well as maternal and fetal outcomes for each type of vasculitides. RECENT FINDINGS: Successful pregnancies in patients with vasculitides are possible, especially when conception is planned, and the disease is in remission. The risk of vasculitis flare is highly dependent on the type of vasculitis, but overall limited. The most frequent complication associated with large-vessel vasculitis (mainly Takayasu arteritis) is hypertension and preeclampsia. Preterm deliveries and intrauterine growth restriction occur more frequently with small- and medium-vessel vasculitis. Pregnancies in patients with vasculitis should be considered high risk and followed by a multidisciplinary team with expertise in the field. Flares should be managed as in the non-pregnant population, while avoiding medications with unknown safety in pregnancy or known teratogens. Although commonly prescribed for the prevention of preeclampsia, there is limited evidence supporting the use of low-dose aspirin for pregnant women with vasculitis. Prospective registries or studies are needed, to better assess the value of aspirin, the place and long-term impact of new biologics and, to identify predictors of pregnancy outcomes other than disease status at conception.