Update on vasculitis: an overview and dermatological clues for clinical and histopathological diagnosis - part I

Abstract The term vasculitis refers to the inflammation of vessel walls. It may range in severity from a self-limited disorder in one single organ to a life-threatening disease due to multiple organ failure. It has many causes, although they result in only a few histological patterns of vascular inflammation. Vessels of any type and in any organ can be affected, a fact that results in a broad variety of signs and symptoms. Different vasculitides with indistinguishable clinical presentations have quite different prognosis and treatments. This condition presents many challenges to physicians in terms of classification, diagnosis, appropriate laboratory workup, and treatment. Moreover, it compels a careful follow-up. This article reviews the Chapel-Hill 2012 classification, etiology, recent insights in pathophysiology, some important dermatological clues for the diagnosis and summarizes treatment of some of these complex vasculitis syndromes.

Deferasirox-induced urticarial vasculitis in a patient with myelodysplastic syndrome

Abstract Deferasirox is an iron chelator agent used in the treatment of diseases with iron overload, such as thalassemia and myelodysplastic syndrome. Although the majority of adverse reactions of deferasirox involve gastrointestinal symptoms and increase in serum creatinine and transaminases, skin rashes, such as maculopapular and urticarial eruptions, have also been reported. This study reports a case of myelodysplastic syndrome with urticarial vasculitis due to deferasirox therapy. Drug eruption was been confirmed by means of a challenge test, together with histopathological and clinical findings. To the best of our knowledge, we report the first case of deferasirox-induced urticarial vasculitis. Physicians should be aware of the possibility of urticarial vasculitis on deferasirox therapy and the fact that the discontinuation of the drug generally results in improvement.

Evolución de una vasculitis renal asociada a anticuerpos anti-citoplasma de neutrófilos (ANCA) durante un embarazo: caso clínico / Antineutrophil cytoplasmic antibody (ANCA) associated renal vasculitis and pregnancy: report of one case

ANCA mediated vasculitis mainly occur between the fourth and fifth decade of life; therefore, it is very uncommon to see pregnant patients with the disease. Vasculitis may affect significantly the course of pregnancy; in turn pregnancy can change the course of vasculitis. We report a 20 years old woman with ANCA-mediated renal vasculitis lasting 10 years who consulted with a pregnancy of 15 weeks. She was in remission and had amenorrhea attributed to ovarian toxicity due to cyclophosphamide. Pregnancy had an uneventful course with spontaneous delivery at the 37th week, giving birth to a healthy newborn. Proteinuria increased during the course of pregnancy with a mild deterioration of kidney function. During the year after delivery, she had nephrotic proteinuria and a worsening of renal function.

A study of the clinico-histopathological features of erythematous tender nodules predominantly involving the extremities.

Background: Erythematous tender nodules predominantly involving extremities are frequently encountered in dermatology and rheumatology practice. They are diagnosed based on distinct clinical and histopathological features. However, in clinical situations, considerable overlap is observed that poses a diagnostic challenge. We undertook a study on clinico-histological patterns of inflammatory nodules over extremities. Methods: After detailed history and examination, a preliminary clinical diagnosis was made in 43 cases, followed by skin biopsy from representative nodules. Histological diagnosis made was correlated with clinical features. Results: Of 43 cases, a single clinical diagnosis was made in 25 (58.5%) cases while in the remaining cases more than one diagnosis was considered. On correlating with the histopathological diagnosis, concordance was observed in 51% cases while the remaining showed either histological discordance with clinical diagnosis (14% cases) or were kept in the undecided category (35% cases). Conclusion: Considerable clinico-histological overlap was observed in inflammatory nodules over extremities. Histopathology alone was not helpful in differentiating one entity from another at all times since variable histo-pathological patterns were seen.

Cytomegalovirus (CMV)-related cutaneous necrotizing vasculitis: case report and literature review

Cytomegalovirus (CMV) infection is usually asymptomatic in immunocompetent patients. A mononucleosis-like syndrome may develop in some patients. Various organ involvements (eg: encephalitis, meningitis, retinitis, myocarditis, pneumonia, hepatitis, enterocolitis, neuritis), which rarely occur in immunocompetent patients, have also been reported. Cutaneous necrotizing vasculitis caused by CMV infection has been reported very rarely in the literature. Here, a case with a very rare clinical form of CMV infection, presenting with persistent fever and livedo reticularis on the extremities and cutaneous necrotizing vasculitis of the toes, is described, and the relevant literature is reviewed. This case report aims to highlight the possibility of CMV infection to be a cause of cutaneous necrotizing vasculitis.

Vasculitis del nervio periférico: revisión clínico-patológica de 13 casos / Peripheral nerve vasculitis: clinicopathological review of 13 cases

Objetivo: Realizar una revisión de las biopsias de nervio y músculo de pacientes con sospecha clínica de neuropatía vasculítica y correlacionarlas con los datos clínicos, de laboratorio y electrofisiológicos. Materiales y métodos: Fueron revisadas retrospectivamente las historias clínicas de pacientes sometidos a biopsia de nervio/músculo debido a sospecha clínica de neuropatía vasculítica en el Hospital General de Agudos Juan A. Fernández de la Ciudad Autónoma de Buenos Aires entre los años 1999 y 2011. Resultados: Se incluyeron 13 pacientes, 8 (61,54 por ciento) de sexo femenino y 5 (38,46 por ciento) de sexo masculino; la edad media fue de 58,85 +/- 15,02 años. Dos tercios de los casos presentaron mononeuropatía múltiple al diagnóstico y en 9 de 12 casos el patrón electromiográfico fue axonal. La anatomía patológica del nervio mostró vasculitis definida en 6 casos (46,15 por ciento) y probable sólo en uno (7,69 por ciento), mientras que la biopsia de músculo evidenció vasculitis en el 90 por ciento de los casos (p=0,077). En el subgrupo de pacientes con diagnóstico definitivo de vasculitis sistémica primaria, el 100 por ciento de las biopsias de músculo y el 62,5 por ciento de las biopsias de nervio resultaron positivas para neuropatía vasculítica (NPV). Conclusiones: La biopsia de nervio es el único procedimiento aceptado actualmente para el diagnóstico definitivo de neuropatía vasculítica. La biopsia combinada de nervio y músculo mostró una clara tendencia, aunque no significativa, hacia una mayor utilidad diagnóstica de neuropatía vasculítica que la biopsia de nervio aislada. Consideramos que el estudio de un mayor número de casos contribuirá a aclarar esta duda.

Objective: To review the nerve and the muscle biopsies from patients with clinical suspicion of vasculitic neuropathy and their correlation with clinical, laboratory and electrophysiologic studies. Materials and methods: We retrospectively reviewed the medical records of patients undergoing nerve/muscle biopsy due to clinical suspicion of vasculitic neuropathy at the Juan A. Fernandez General Hospital in the city of Buenos Aires between 1999 and 2011. Results: Thirteen patients, 8 (61.54 percent) female and 5 (38.46 percent) male, mean age 58.85 +/- 15.02 years, were included. Two thirds of the patients had multiple mononeuropathy at diagnosis, and 9 of 12 cases had axonal pattern in the electromyogram. The histopathology of the nerve showed definite vasculitis in 6 cases (46.15 percent) and probable vasculitis in only one (7.69 percent), whereas muscle biopsy showed vasculitis in 90 percent of cases (p=0.077). In the subgroup of patients with definite diagnosis of primary systemic vasculitis, 100 percent of muscle biopsies and 62.5 percent of nerve biopsies were diagnostic of vasculitis neuropathy. Conclusion: Nerve biopsy in the only currently accepted procedure for definitive diagnosis of vasculitic neuropathy. The combined nerve and muscle biopsy showed a clear trend, but not statistically significant toward increased the diagnostic yield of vasculitis neuropathy that isolated nerve biopsy. A large number of cases will clarify this issue.

Vasculite de pequenos vasos como primeira manifestação clínica de paracoccidiodomicose: relato de caso / Small vessel vasculitis as first manifestation of paracoccidioidomycosis: case report

A paracoccidioidomicose é uma doença sistêmica causada pela inalação de conídios do Paracoccidioides brasiliensis, um fungo dimórfico que acomete, inicialmente, a via respiratória, disseminando-se, principalmente por vias linfáticas e hematogênicas, para diversos órgãos e sistemas, podendo ser fatal na ausência de diagnóstico e tratamento adequados. Os autores têm por objetivo relatar um caso de paciente que apresentou, como manifestação inicial da doença, uma vasculite de pequenos vasos, sendo esta uma forma clínica atípica, com uma única descrição na literatura.

Paracoccidioidomycosis is a systemic disease caused by inhalation of conidia of Paracoccidioides brasiliensis, a dimorphic fungus that initially affects the airway, spreading by lymphatic and hematogenous routes to various organs and systems, and that can be fatal if the diagnosis and treatment are not correct. The authors describe a patient who presents small vessel vasculitis as an initial manifestation of the disease, which is an atypical clinical form with a single description in the literature.

Presentación de un caso de vasculitis de Wegener / Presentation of a case of Wegener’s vasculitis

Se presenta una paciente con granulomatosis de Wegener en su forma localizada y se efectúa una actualización de las manifestaciones clínicas, el diagnóstico y el tratamiento.

Frosted branch angiitis, neuroretinitis as initial ocular manifestation in Behçet disease.

Behçet disease is an idiopathic, multisystem disorder characterized by recurrent episodes of orogenital ulceration and vasculitis of the veins and arteries of all calibers. Ocular involvement may affect the conjunctiva, sclera, uveal tract, vitreous, blood vessels, and retina. Many theories have pointed toward an autoimmune response behind its pathogenesis, which may be triggered by exposure to an infectious agent. Frosted branch angiitis is characterized by vascular inflammation, sheathing, retinal edema, and retinal hemorrhages. The disease may be idiopathic in a majority of the cases or may be associated with ocular and systemic pathology. Association between Behηet disease, Frosted branch angiitis, and neuroretinitis is not reported in literature. This uncommon combination reflects the varied systemic and ocular manifestations in Behηet disease, especially in patients who are not diagnosed and treated in time. We hereby report a case of bilateral frosted branch angiitis and neuroretinitis in a young male from Middle-east, suffering from Behçet disease.

Imunofluorescência direta e indireta / Direct and indirect immunofluorescence

A imunofluorescência é um valioso instrumento auxiliar no diagnóstico das dermatoses bolhosas autoimunes e desordens inflamatórias, uma vez que seus achados clínicos e histopatológicos podem não ser determinantes. Consiste em um método laboratorial factível, que requer profissionais técnicos experientes, e detecta imunocomplexos in situ e/ou circulantes, que podem estar envolvidos na patogênese de tais enfermidades cutâneas.

Immunofluorescence is a valuable auxiliary diagnostic tool for autoimmune bullous diseases and inflammatory disorders, since their clinical and histopathologic findings may be inconclusive. It is a feasible laboratory method that requires experienced technicians and detects in situ and circulating immune deposits that may be involved in the pathogenesis of such skin diseases.

Carotid artery intima-media thickness in Behcet's disease patients without significant cardiovascular involvement

BACKGROUND/AIMS: Behcet's disease (BD) is a systemic disorder associated with a characteristic vasculitis that can involve both veins and arteries of all sizes. Endothelial activation or injury is a characteristic feature of BD. Endothelial dysfunction is widely regarded as being the initial lesion in the development of atherosclerosis. The carotid artery intima-media thickness (IMT) is a widely accepted marker of subclinical atherosclerosis. We aimed to determine the carotid IMT in BD patients with using high-resolution B-mode Doppler ultrasonography. METHODS: We studied 40 patients (24 males, mean age: 39.1+/-8.5 years) who were diagnosed by the international diagnostic criteria of Behcet's disease and 20 healthy controls (13 males, mean age: 40.2+/-5.1 years), and the two groups were matched by age and gender. No subject in either group had a history of atherosclerosis or its complications. The clinical data, including the age of onset, the duration of disease, a history of medication, the activity score and the laboratory data were analyzed. RESULTS: The carotid IMT in the BD group was significantly higher than that in the control group (0.71+/-0.22 mm vs. 0.59+/-0.09 mm, respectively, p<0.01). Cardiac and major vessel involvements were not identified in the BD group. However, minor vascular involvements were documented in 2 patients with deep vein thrombosis, in 4 patients with superficial thrombophlebitis and in 2 patients with pseudoaneurysm. The carotid IMT in the patients with posterior uveitis or retinal vasculitis was higher than that of the patients without these findings (0.85+/-0.21 mm vs. 0.64+/-0.10 mm, respectively, p=0.007), but there was no difference of the IMT according to minor vascular involvement. CONCLUSIONS: Despite that there was no significant cardiovascular involvement in the BD patients, the carotid IMT was significantly higher in the BD patients as compared with the healthy controls.

Pleomorphic hyalinizing angiectatic tumour of soft parts: a case report and review of the literature

Pleomorphic hyalinizing angiectatic tumour (PHAT) is a recently described, rare, low-grade soft tissue neoplasm. The lesion is characterized by clusters of hyalinized and thrombosed ectatic vessels alternating with a variably cellular stroma composed of atypical cells, many with intranuclear pseudoinclusions. Other features are inflammatory cell infiltration, haemosiderin deposits, focal calcificationand minimal to absent mitoses. No metastases have so far been described; however, the local recurrence rate has been found to be high. To date, approximately 60 such cases of PHAT and its precursor, “early PHAT”, have been described in the world literature. We report the first known case of PHAT from this institution which occurred in the left loin of a 77-year old woman. Three years previously, a smaller lesion excised from the same location had been called an ancient schwannoma on histology. This is the most commondifferential diagnosis offered for this entity even though the two differ in immunohistochemical profile. ‘Early PHAT’ was also identified on the periphery of the recurrent lesion.

El tumor pleomórfico hialinizante angioectásico (TPHA) – entidad rara, de reciente descripción – es un neoplasma del tejido blando, de bajo grado. La lesión se caracteriza por la presencia de racimos de vasos ectásicos trombosados e hialinizados, que alternan con un estroma celular variable compuesto de células atípicas, muchas de ellas con pseudoinclusiones intranucleares. Otrascaracterísticas son: la infiltración celular inflamatoria, los depósitos hemosiderínicos, la calcificaciónfocal, y la mitosis mínima o ausente. Hasta el presente no se han descrito metástasis. Sin embargo, se ha hallado que la tasa de recurrencia local es alta. Hasta la fecha, aproximadamente 60 de estos casos de TPHA y su precursor el “TPHA temprano”, han sido descritos en la literatura mundial. Reportamosel primer caso de TPHA conocido de esta institución – una anciana de 77 años de edad, a quién se le presentó en la región lumbar izquierda. Tres años antes, una lesión más pequeña extirpada del mismolugar, hubiera sido llamada un schwannoma antiguo en histología. Este es el diagnóstico diferencial más común ofrecido para esta entidad, aun cuando los dos difieren en cuando a perfilimunohistoquímico. El TPHA temprano fue identificado también en la periferia de la lesión recurrente.

Síndrome de crioglobulinemia mixta secundario a brucelosis. Reporte de un caso / Mixed cryoglobulinemia (MC) syndrome secondary to brucellosis. A case report

La brucelosis produce diversas manifestaciones clínicas muchas de las cuales son secundarias a alteraciones del sistema inmune desencadenadas por esta infección. Presentamos el caso de una paciente mujer de 71 años de edad que ingresó por un cuadro clínico de fiebre y púrpura, en quien se diagnosticó síndrome de crioglobulinemia mixta por infección brucellar. Este es el quinto caso que se reporta en el mundo. A pesar que la causa mas frecuente de púrpura por crioglobulinemia mixta es infección por VHC, se resalta que se debe sospechar de brucelosis especialmente cuando se presente con fiebre.(Rev Med Hered 2007;18:34-38).

Semiquantitative assessment of surgical lung biopsy: predictive value and impact on survival of patients with diffuse pulmonary infiltrate

PURPOSE: Surgical lung biopsy has been studied in distinct populations, mostly going beyond clinical issues to impinge upon routine histopathological diagnostic information in diffuse infiltrates; however, detailed tissue analyses have rarely been performed. The present study was designed to investigate the prognostic contribution provided by detailed tissue analysis in diffuse infiltrates. METHODS: Medical records and surgical lung biopsies from the period of 1982 to 2003 of 63 patients older than 18 years with diffuse infiltrates were retrospectively examined. Lung parenchyma was histologically divided into 4 anatomical compartments: interstitium, airways, vessels, and alveolar spaces. Histological changes throughout these anatomical compartments were then evaluated according to their acute or chronic evolutional character. A semiquantitative scoring system was applied to histologic findings to evaluate the intensity and extent of the pathological process. We applied logistic regression to predict the risk of death associated with acute and chronic histological changes and to estimate the odds ratios for each of the independent variables in the model. RESULTS: Impact on survival was found for male gender (P = 0.03), presence of diffuse alveolar damage (P = 0.001), and chronic histological changes (P = 0.0004) on biopsy. Thus, being male was associated with a slightly lower risk (O.R. = 0.18; P=0.03) of dying than being female. Death risk was increased 17 times in the presence of acute histological changes such as diffuse alveolar damage and 2.5 times in the presence of chronic histological changes. CONCLUSION: Detailed analysis of histological specimens can provide more than a nosological diagnosis: this approach can provide valuable information concerning prognosis.

PROPOSIÇÃO: A biópsia pulmonar cirúrgica tem sido estudada em populações distintas, geralmente abordando aspectos histopatológicos puramente diagnósticos em infiltrados pulmonares difusos, além de dados clínicos. Contudo, análises teciduais detalhadas em tais casos têm sido pouco exploradas. O presente estudo foi delineado com o intuito de se investigar a contribuição prognóstica fornecida pela análise histológica detalhada em infiltrados difusos. MÉTODOS: Foram examinados retrospectivamente os prontuários e biópsias pulmonares cirúrgicas de 63 pacientes maiores de 18 anos, com infiltrados difusos, de 1982 a 2003. O parênquima pulmonar foi dividido em 4 compartimentos histológicos: interstício, vias aéreas, vasos e espaços alveolares. Alterações histológicas de cada compartimento histológico foram então avaliadas de acordo com seu caráter evolutivo agudo ou crônico. Um escore semiquantitativo foi aplicado a achados histopatológicos com o intuito de se avaliar a intensidade e a extensão do processo patológico. Aplicamos regressão logística para predizer o risco de morte para alterações histológicas agudas e crônicas e para estimar a razão de probabilidades para cada uma das variáveis independentes do modelo. RESULTADOS: O impacto sobre a sobrevida foi observado para o gênero masculino (p=0.03), para a presença de dano alveolar difuso (p=0.001) e para alterações histológicas crônicas (p=0.0004) em biópsias. Assim, homens apresentariam menor chance (O.R. = 0.18; P=0.03) de morrer do que mulheres. O risco de morte foi 17 vezes maior na presença de alterações histológicas agudas como dano alveolar difuso e 2,5 vezes na presença de alterações histológicas crônicas. CONCLUSÃO: A análise detalhada de espécimes histológicos pode proporcionar maiores e mais valiosas informações de valor prognóstico do que o simples diagnóstico nosológico.

Estudo da camada elástica das arteríolas pulmonares em portadores de granulomatose de Wegener / Study of the elastic fibers of the pulmonary arteriolas of patients with Wegener granulomatosis

A Granulomatose de Wegener é uma síndrome clínico-patológica caracterizada por vasculite granulomatosa necrozante que acomete o trato respiratório superior, pulmões e rins. A vasculite granulomatosa afeta os vasos pulmonares com destruição das camadas elásticas das artérias.. O objetivo do presente estudo foi quantificar o sistema elástico da parede das artérias pulmonares de pacientes portadores de Granulomatose de Wegener comparado com o de pacientes normais. Foram estudadas 36 artérias de pequeno calibre ( diâmetro < 62 micra) e 36 artérias de médio calibre ( diâmetro entre 62 e 213 micra) obtidas de tecido pulmonar de 6 pacientes portadores de Granulomatose de Wegener comparadas com 36 artérias de pequeno e 36 artérias de médio calibre obtidas de 6 pacientes normais...

Wegener Granulomatosis is a clinico-pathologic syndrome characterized by necrotizing granulomatous vasculitis that affects the upper respiratory tract, the lungs and the kidneys. The granulomatous vasculitis affects the pulmonary vessels with destruction of the elstic system fibers of the vessels walls that can be visualized with the Verhoff staining technique . The objective of the present study was to quantify the area of the elastic system fibers of the walls of the pulmonary arteries of patients with the diagnosis of Wegener Granulomatosis compared to the area of the elastic system fibers of normal patients. We studied 36 small size pulmonary arteries ( diameter < 62 µ) and 36 medium size pulmonary arteries ( diameter between 62 and 213µ) taken from lung tissue of 6 patients with the diagnosis of Wegener Granulomatosis compared to 36 small size and 36 medium size pulmonary arteries taken from lung tissue of normal patients. The elastic system fibers of the pulmonary arteries walls was atained by resorcine-fucsine technique e the área of the elastic system was quantified through a special softer for área calculation of the Image analyser FOX pro of the Faculty of Medicine of the University of São Paulo. The medium area of the elastic system fibers of the small size pulmonary arteries of Wegener Granulomatosis was 73,6 ± 20,9 µ² ( 29,76 to 109,05 µ²) compared to 680,8 ± 256,1 µ² ( 263,34 to 1380,75 µ²) of the normal patients ( p< 0,0001- ANOVA -2 factors)...