Molecular evidence of parvovirus B19 in the cutaneous polyarteritis nodosa tissue from a patient with parvovirus-associated hemophagocytic syndrome: Case report.

RATIONALE: Parvovirus B19 has been linked to polyarteritis nodosa (PAN), but there is some controversy about its pathogenesis regarding whether it is triggered by the immune complex or by the activated immune cells that phagocytose viruses. PATIENT CONCERNS: A 38-year-old woman was admitted with fever and bicytopenia. She also complained of a painful palpable nodule in the left forearm. DIAGNOSIS: Her bone marrow aspirate revealed erythroblasts in abnormal megaloblastic changes, some of which presented with pseudopods, and parvovirus B19 was positive in a PCR analysis of her blood, which was compatible with parvovirus B19-induced hemophagocytic syndrome. Skin excisional biopsy of the nodule on the left forearm revealed a heavy inflammatory cell infiltrate throughout whole layers of a medium-sized vessel, the characteristic feature of PAN. PCR analysis of the vasculitis tissue showed a positive result for parvovirus B19. INTERVENTIONS: Her symptoms spontaneously resolved with supportive care. OUTCOMES: She underwent regular follow-up without recurrence of vasculitis-associated symptoms. LESSONS: This case highlights the presence of parvovirus B19 DNA in vasculitis tissues, which can support the role of cellular immune response in the pathogenesis of parvovirus-associated PAN.

Systemic Necrotizing Vasculitis in Sheep Is Associated With Ovine Herpesvirus 2.

Ovine herpesvirus 2 (OvHV-2) is one of the gammaherpesviruses in the genus Macavirus that can cause malignant catarrhal fever (MCF) in ungulates. Sheep are the adapted host for OvHV-2 and it is generally assumed that infection is not associated with disease in this species. However, cases of "polyarteritis nodosa" or idiopathic systemic necrotizing vasculitis reported in sheep are similar to vascular lesions in clinically susceptible species with MCF. Using a recently developed in situ hybridization (ISH) method, we were able to identify OvHV-2 nucleic acids within lesions and correlate the viral distribution with systemic necrotizing vasculitis in 9 sheep, including both naturally and experimentally OvHV-2-infected animals. ISH, combined with polymerase chain reaction and histology, identify OvHV-2 as the likely agent responsible for sporadic, MCF-like vascular disease in sheep.

PAN's labyrinth: a multidisciplinary delayed diagnosis and patient's perspective.

Polyarteritis nodosa (PAN) is a rare, severe form of vasculitis affecting medium-sized vessels. It manifests as a multisystem syndrome, and may be associated with hepatitis B virus-associated PAN (HBV-PAN) although the incidence of this is declining with better vaccination strategies and awareness of bloodborne virus screening. We report a case in which a patient displayed many classical features of the disease, occurring separately over a period of months and leading to contact with various medical specialties. Managing each symptom in isolation led to a number of misdiagnoses (including testicular cancer) and the patient experienced considerable psychological stress and morbidity as a result. The case was complicated by acute pancreatitis developing after an initial treatment response. This may have been iatrogenic (as a consequence of either entecavir or steroids) or secondary to PAN. For our patient, this led to a protracted clinical course but eventual complete resolution of both pathologies.

Vasculitis related to viral and other microbial agents.

Vasculitis due to infection may occur as a consequence of the inflammation of vessel walls due to direct or contiguous infection, type II or immune complex-mediated reaction, cell-mediated hypersensitivity, or inflammation due to immune dysregulation triggered by bacterial toxin and/or superantigen production. As immunosuppressive therapy administered in the absence of antimicrobial therapy may increase morbidity and fail to effect the resolution of infection-associated vascular inflammation, it is important to consider infectious entities as potential inciting factors in vasculitis syndromes. The causality between infection and vasculitis has been established in hepatitis B-associated polyarteritis nodosa (HBV-PAN) and hepatitis C-associated (cryoglobulinemic) vasculitis (HCV-CV). The review summarizes the recent literature on the pathophysiological mechanisms and the approaches to the management of HBV-PAN and HCV-CV. Roles of other viral and microbial infections, which either manifest as vasculitic syndromes or are implicated in the pathogenesis of primary vasculitides, are also discussed.

Macular arteritis associated with concurrent HIV and hepatitis B infections: a case report and evidence for a disease spectrum association with cutaneous polyarteritis nodosa.

We report the first case of macular arteritis in a 33-year-old Black, African female with concurrent human immunodeficiency virus (HIV) and hepatitis B virus (HBV) infections. Of particular interest in macular arteritis is the striking discordance between the clinical presentation and the histopathological findings, a fact that both dermatologists and dermatopathologists should be aware. Histopathologically, the case showed typical findings of macular arteritis with a perivascular, predominantly lymphocytic, infiltrate and intraluminal thrombosis. Both HIV and HBV have been reported as viral inducers of cutaneous polyarteritis nodosa (PAN). Their association with macular arteritis in this case supports existing evidence that macular arteritis and cutaneous PAN represent a single-disease spectrum of vasculitides, with macular arteritis representing the chronic, lymphocytic and indolent stage, and cutaneous PAN the neutrophilic, acute stage with a risk for systemic progression. Lymphocytic thrombophilic arteritis (LTA), a third, uncommon disease would be in between macular arteritis and cutaneous PAN on a spectrum. Features of this case and other published cases provide strong evidence that there is a single, mild-to-severe disease spectrum of macular arteritis-LTA-cutaneous PAN.

Necrotizing arteritis in a human immunodeficiency virus-infected patient with lupus-like glomerulonephritis.

Human immunodeficiency virus (HIV)-associated lupus-like glomerulonephritis (GN) is a chronic immune complex disease occurring in HIV-infected patients. Although the light, immunofluorescence, and electron microscopy findings indicate features of lupus nephritis, no evidence of systemic lupus erythematosus (SLE) is observed in the affected patients. We present the case of a 45-year-old Caucasian woman with HIV infection who was admitted to the hospital with a nephrotic syndrome 10 years after the HIV diagnosis. A renal biopsy revealed HIV-associated lupus-like GN and necrotizing arteritis affecting two interlobular arteries. Necrotizing arteritis is a type of renal vasculopathy associated with SLE, but has not been reported previously in HIV-associated lupus-like GN. In this case, necrotizing arteritis was found to be a histological feature common to both HIV-associated lupus-like GN and SLE. This histological finding reinforces the resemblance between HIV-associated lupus-like GN and nephritis caused by lupus.

Infections in vasculitis.

Infections, mainly viral, are the cause of some vasculitides, like polyarteritis nodosa (hepatitis B virus) or mixed cryoglobulinemia (hepatitis C virus), and it has been hypothesized that others might be due to infectious agents (HIV, EBV, parvovirus...). Among etiologies of vasculitis, the responsibility of a Burkholderia-like strain has been recently demonstrated as the cause of giant-cell arteritis. On the other hand, patients frequently develop infections, mainly as a consequence of steroids, immunosuppressants and most immunomodulating treatments prescribed to treat vasculitides. Infections occur when patients receive steroids and immunosuppressants, especially in the long term. They are more frequently observed in elderly patients or in patients with poor general condition. Infection risk is not reduced when biotherapies are prescribed to induce or maintain remission. Patients, considered at higher risk for infections, should be followed closely and their immunological status monitored periodically. We recommend especially to monitor neutrophiles, lymphocytes and if needed CD3-, CD4- and CD8-cell counts in patients receiving steroids and cyclophosphamide or other cytotoxic agents. In patients treated with rituximab, CD19 and gammaglobulins should be monitored regularly. Prophylaxis are needed in patients at risk to develop infections.

Sudden death due to polyarteritis nodosa.

Classical polyarteritis nodosa (cPAN) refers to a rare, potentially fatal systemic transmural necrotizing vasculitis that usually affects medium-sized, and occasionally small, muscular arteries, primarily involves the kidneys, gastrointestinal tract, skin, nervous system, joints, and muscles, and is rarely, if ever, expressed in the lungs. The incidence of mortality has significantly decreased with recently developed treatment modalities, in particular antiviral medications. Sudden death due to previously undiagnosed cPAN is rarely encountered. We report a case of a young man who had been evaluated on three occasions by medical personnel in the 3 weeks prior to his death. He had complained of nonspecific symptoms of abdominal and perineal/suprapubic pain, nausea, vomiting, sensation of chilling, and constipation. The spectrum of diagnoses included "gastroenteritis," enteric infection, and prostatitis. Found agonal at home and dying despite immediate cardiopulmonary resuscitation (CPR), he underwent a medicolegal autopsy, which revealed vasculitis of various organs, including heart (myocardium and epicardium) and extramural coronary arteries, liver, spleen, kidneys, adrenal glands, stomach and bowel, omentum, gallbladder, and pancreas. His sudden death was cardiac in nature due to PAN associated clinically with hepatitis B surface antigen positivity (hepatitis B virus-associated PAN [HBV-PAN]). A complete autopsy with thorough histopathological examination is necessary to diagnose this uncommon yet potentially fatal vasculitis.

Life-threatening hepatitis C virus-associated polyarteritis nodosa successfully treated by rituximab.

By contrast to cryoglobulinemic vasculitis, polyarteritis nodosa associated with hepatitis C virus (HCV) infection is rare and still a controversial entity. The best treatment for this condition is not established. Cases reported in the literature have been treated with various combinations of corticosteroids, antiviral therapy, and immunosuppressants. We report a case of severe life-threatening HCV-associated polyarteritis nodosa successfully treated with rituximab and a short course of corticosteroids without antiviral therapy. This case, along with recently published data, emphasizes the value of B-cell-targeted therapy in this unusual form of HCV-associated vasculitis.

HIV infection and clinical spectrum of associated vasculitides.

Various infections have been causative in the pathogenesis of systemic vasculitides, and HIV infection is not spared. In an immunocompromised host, cytomegalovirus, Epstein-Barr virus, varicella zoster virus, herpes simplex virus, hepatitis B and hepatitis C virus, and mycobacteria, along with HIV infection can cause vasculitis. Herein we emphasize the spectrum of vasculitides, their pathogenesis, presentation, course, and therapy in the HIV-infected population. Every spectrum and size of the blood vessel involvement have been seen in HIV-associated vasculitides. We review each spectrum in detail and describe our experience with polyarteritis nodosa, the most common presentation occurring in HIV-infected patients. We also discuss the differences in HIV, hepatitis B, and hepatitis C- related polyarteritis nodosa in detail.

[Hepatitis B virus, extrahepatic immunologic manifestations and risk of viral reactivation]. / Virus de l'hépatite B, manifestations extrahépatiques immunologiques et risque de réactivation virale.

Hepatitis B virus (HBV) infection is frequent with about 400 million individuals infected worldwide. Extrahepatic manifestations may be observed in up to 20% of patients infected with HBV, in both acute and chronic infections. The best-described manifestations are polyarteritis nodosa and glomerulonephritis. Besides manifestations related to HBV, patients presenting with primary autoimmune disorders and infected with HBV may exhibit reactivation of hepatitis B during immunosuppressive therapy that may be life-threatening. This article focuses on autoimmune manifestations related to HBV and its treatment, and on the risk of reactivation of HBV hepatitis in patients with primary autoimmune disorders treated with immunosuppressive agents.

Hepatitis C virus-associated polyarteritis nodosa.

OBJECTIVE: To analyze the main characteristics and outcome of polyarteritis nodosa (PAN)-type vasculitis associated with hepatitis C virus (HCV). METHODS: We reported the characteristics and outcome of 31 patients chronically infected with HCV who satisfied the American College of Rheumatology and Chapel Hill criteria for PAN, seen between 1990 and 2009 in a university center. RESULTS: Among a cohort of 161 patients with HCV-related vasculitis, 31 (19.3%) were diagnosed as having PAN. The median age was 64.5 years (interquartile range 49.5-70.5 years), with 54.8% women. Compared with HCV-associated mixed cryoglobulinemia (HCV-MC) vasculitis, HCV-PAN displayed a more severe and acute clinical presentation with more frequent fever and weight loss (P < 0.0001), severe hypertension (P = 0.0006), gastrointestinal tract involvement (P < 0.0001), severe acute sensory-motor multifocal mononeuropathy (P < 0.0001), kidney and liver microaneurysms (P = 0.002), and increased C-reactive protein level (P < 0.0001). Complete clinical remission of vasculitis was achieved in 79.3% of HCV-PAN patients compared to 57.5% of HCV-MC patients (P = 0.05). In multivariate analysis, skin involvement (odds ratio [OR] 2.81, 95% confidence interval [95% CI] 1.27-6.33) and PAN-type vasculitis (OR 3.01, 95% CI 1.16-8.96) were independently associated with a complete clinical response of HCV vasculitis. A glomerular filtration rate <70 ml/minute (OR 0.54, 95% CI 0.24-1.21) was negatively associated with a complete clinical response of HCV vasculitis. The 5-year survival rate was 86% in the entire cohort, regardless of the vasculitis type. CONCLUSION: HCV-PAN accounts for 19.3% of our cohort of HCV vasculitis. HCV-PAN displays a more severe and acute clinical presentation and a higher rate of clinical remission.

Hepatitis B virus-related polyarteritis nodosa presenting with multiple lung nodules and cavitary lesions.

The patient presented here is a 59-year-old Japanese man with active chronic hepatitis B with precore and core promoter mutated virus, presenting with high fever, bloody sputum, and multiple lung nodules with excavation. Surgical biopsy of the lung nodule showed necrotizing vasculitis affecting pulmonary arteries without granulomatous changes. The pulmonary manifestations of this patient resembled Wegener granulomatosis. However, the pathologic findings showing nongranulomatous necrotizing vasculitis involving the small pulmonary arteries, presence of circulating immune complex, absence of antineutrophil cytoplasmic antibodies, and excellent response to the combination therapy of corticosteroid and an anti-hepatitis B virus agent, entecavir, led us to the diagnosis of hepatitis B virus-related polyarteritis nodosa (PAN). Radiographic evidence of lung nodules or cavitations seen in systemic vasculitis patients has been considered a sign suggestive of granulomatous disease and a diagnostic surrogate marker for necrotizing granulomatous vasculitis, but a clinical relevance to hepatitis B virus-related PAN has not been reported before this case.

Virus-induced vasculitis.

There is a growing understanding of the different syndromes that have a definite, and in some cases a possible, association with viral infections. Hepatitis C virus-associated mixed cryoglobulinemias and hepatitis B virus-associated polyarteritis nodosa are examples of a vasculitis with a definite viral association. However, various types of cutaneous vasculitis are examples of a vasculitis with only a possible association with a viral infection.

Historia natural y manifestaciones clínicas de la hepatitis B crónica / Natural history and clinical manifestations of chronic hepatitis B virus

La infección por virus de la hepatitis B (VHB) representa un importante problema de salud pública en todo el mundo. En las últimas décadas se han producido importantes progresos que han contribuido a una mayor comprensión de la historia natural y las manifestaciones clínicas de esta infección. La fluctuación entre la replicación viral y la respuesta inmunológica del huésped tiene implicaciones en la patogenia y la evolución de la lesión hepática. En el adulto inmunocompetente, la mayor parte de infecciones por VHB se resuelven de forma espontánea, en comparación con una evolución hacia una infección crónica en la mayoría de los recién nacidos. Los pacientes con hepatitis crónica por VHB o hepatitis B crónica pueden presentarse en cuatro fases evolutivas: a) fase de tolerancia inmunológica o inmunotolerancia; b) hepatitis B crónica HBeAg positivo; c) estado de portador inactivo de HBsAg, y d) hepatitis crónica HBeAg negativo. La hepatitis crónica HBeAg positivo o negativo puede evolucionar hacia una cirrosis, una insuficiencia hepática y un carcinoma hepatocelular. Una progresión hacia estas complicaciones es más frecuente en las formas HBeAg negativo, asociadas con mutaciones que afectan a la región pre-core y que mantienen la replicación viral activa. Los factores de riesgo son unos valores altos de ADN-VHB, el aumento de la concentración sérica de transaminasas y algunos genotipos. Estos factores subrayan la necesidad de evaluar y supervisar a todos los portadores del VHB para identificar a los pacientes que pueden beneficiarse de un tratamiento antiviral precoz, evitando de este modo la progresión hasta formas más avanzadas de hepatopatía. Estas medidas pueden contribuir a una mejor prevención y a un tratamiento más eficaz de la hepatitis B(AU)

Hepatitis B virus (HBV) infection is a serious public health problem worldwide. In the last few decades, major advances have been achieved that have contributed to greater understanding of the natural history and clinical manifestations of this infection. The fluctuation between viral replication and the host¿s immune response has implications in the pathogenesis and progression of the hepatic lesion. In immunocompetent adults, most HBV infections resolve spontaneously in contrast with progression to chronic infection in most infants. Patients with chronic hepatitis due to HBV or chronic hepatitis B can present at four phases: 1) the immune tolerance phase, 2) HBeAg-positive chronic hepatitis B, 3) inactive HBsAg carrier state, and 4) HBeAg-negative chronic hepatitis. HBeAg-positive or ¿negative chronic hepatitis can progress to cirrhosis, liver failure and hepatocellular carcinoma. Progression to these complications is more frequent in HBeAg-negative forms, associated with mutations that affect the pre-core region and maintain active viral replication. Risk factors are HBV-DNA positive serum levels, an increase in serum transaminase levels and some genotypes. These factors highlight the need to evaluate and monitor all HBV carriers to identify those who could benefit from early antiviral treatment, thus avoiding progression to more advanced forms of liver disease. These measures could improve prevention and treatment of hepatitis B(AU)

Choroidal and optic nerve infarction in hepatitis C-associated polyarteritis nodosa.

A 39-year-old man presented with headache, weight loss, bilateral subdural hematomas, pansinusitis, and visual loss. The neuro-ophthalmologic examination disclosed deep choroidal lesions and bilateral optic disc edema. Orchiectomy for testicular torsion showed acute vasculitis consistent with polyarteritis nodosa (PAN). Polymerase chain reaction (PCR) testing revealed hepatitis C. This is the first reported case of PAN due to hepatitis C with early findings of choroidal and optic nerve infarction.

[Hepatitis B associated polyarteriitis nodosa with cerebral vasculitis]. / Hepatitis-B-assoziierte Panarteriitis nodosa mit zerebraler Vaskulitis.

HISTORY AND ADMISSION FINDINGS: A 53-year-old male was admitted with an acute brainstem syndrome. He developed a severe fluctuating psychosis. Because of the worsening neurological symptoms he was admitted to our neurological clinic five months after onset of the disease. On admission he showed signs of a productive psychosis in addition to akinetic-rigid parkinsonism and cerebellar symptoms. INVESTIGATIONS: Laboratory tests revealed a HBeAg-negative hepatitis B. The initial neuroradiolgical studies showed multiple supratentorial and periventricular ischemic and hemorrhagic lesions. MR-angiography and conventional cerebral angiography demonstrated multiple irregularities of the intracranial vessels and vascular occlusions, findings which were compatible with cerebral vasculitis. DIAGNOSIS, THERAPY AND COURSE: The laboratory and neuroradiological studies indicated a hepatitis B-associated polyarteriitis nodosa and cerebral vasculitis. He was given oral immunsuppressive therapy (prednisolone 60 mg daily) and virostatic drug (lamivudine 100 mg daily). When the steroid dosis was reduced to 40 mg prednisolon a severe relapse of the encephalopathy occurred which was treated with the atypical antipsychotic drug risperidon, 3 mg daily, and intravenous methylprednisolone plus plasmaphereses. Later he was given prednisolone (60 mg daily) and lamivudine (100 mg daily) again which has so far stabilized the clinical course. CONCLUSION: The main treatment of the rare hepatitis B-associated polyarteriitis nodosa with cerebral vasculitis consists of oral steroids in combination with antiviral drugs. Depending on the course of the disease an escalating steroid pulse administration and plasmaphereses should be considered.