Hepatitis B associated fulminant polyarteritis nodosa: successful treatment with pulse cyclophosphamide, prednisolone and lamivudine following emergency surgery

For hepatitis B virus associated polyarteritis nodosa, alpha interferon and plasma exchanges have been proposed to be the first-line treatment. We report a case of hepatitis B surface antigen (HBsAg)-positive fulminant polyarteritis nodosa with predominant gastrointestinal involvement who showed good response to pulse cyclophosphamide, prednisolone, and lamivudine therapy. The patient, a 22-year-old man, presented with a short history of epigastric pain. Initial upper gastrointestinal endoscopy revealed gastritis and duodenal erosions. His pain did not respond to H2-receptor antagonists. He had slightly impaired liver function tests, and was HBsAg and hepatitis B e antigen (HBeAg) positive. Around 3 weeks after initial presentation, he developed massive gastrointestinal haemorrhage requiring resuscitation and emergency laparotomy. Microscopic examination of the resection specimens revealed necrotizing vasculitis of small and medium-sized arteries in the submucosa compatible with polyarteritis nodosa. The patient was treated with pulse cyclophosphamide and prednisolone, with lamivudine being added when he showed an acute rise in liver enzymes. He subsequently developed HBeAg seroconversion, and remained well 18 months after cessation of all immunosuppressives. We believe that the efficacy of pulse cyclophosphamide, prednisolone, and lamivudine in the treatment of hepatitis B virus associated polyarteritis nodosa, especially in comparison with interferon and plasma exchanges, deserves further evaluation.     

Gallbladder vasculitis

Five cases of gallbladder vasculitis were encountered during a 10-year period in a community hospital with annual surgical cases of about 12,000. All five patients were clinically diagnosed as having cholelithiasis with or suspected to have cholecystitis. Vasculitis in the form of arteritis identical to that seen in polyarteritis nodosa was present microscopically in the cholecystectomy specimens. One patient presented with systemic symptoms, and the diagnosis of polyarteritis nodosa was established after arteritic lesions were identified in the cholecystectomy, liver biopsy, and appendectomy specimens. In another patient, the diagnosis of polyarteritis nodosa was established after a retrospective identification of one additional site of arteritis in the appendix removed 5 years prior to cholecystectomy. In another, gallbladder vasculitis was associated with scleroderma; the patient was studied thoroughly at autopsy shortly after cholecystectomy, and no evidence of polyarteritis nodosa was found. In the last two, gallbladder vasculitis was not associated with systemic diseases.     

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.     

Immune-mediated pathology following hepatitis B vaccination. Two cases of polyarteritis nodosa and one case of pityriasis rosea-like drug eruption

The association of hepatitis B virus infection and vasculitis or other immune-mediated manifestations is well documented. Reports on such manifestations in relation to hepatitis B vaccination are scarce, however. We report 2 patients who developed polyarteritis nodosa following vaccination against hepatitis B. In one patient this resulted in an ischemic and necrotic digital ulcus, necessitating surgical amputation. The other patient presented with typical cutaneous polyarteritis nodosa which responded well to corticosteroid treatment. A third patient developed a severe pityrias rosea-like eruption. He was treated with topical steroids with healing of the lesions, leaving only post-inflammatory hyperpigmentation. The literature on these associations is reviewed.     

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.     

Immune disorders and rheumatologic manifestations of viral hepatitis

Infection with hepatotropic viruses is not limited to the liver and can lead to the development of various immunological disorders (the formation of cryoglobulins, rheumatoid factor, antinuclear antibodies, autoantibodies specific for autoimmune hepatitis and primary biliary cholangitis, and others), which can manifest as glomerulonephritis, arthritis, uveitis, vasculitis (cryoglobulinemic vasculitis, polyarteritis nodosa, Henoch-Schonlein purpura, isolated cutaneous necrotizing vasculitis), and other rheumatologic disorders, and be a trigger for the subsequent development of autoimmune hepatitis and primary biliary cholangitis. A further study of the association between autoimmune liver diseases and hepatotropic virus infection would be useful to assess the results of treatment of these associated diseases with antiviral drugs. The relationship of these immune disorders and their manifestations with hepatotropic viruses is best studied for chronic hepatitis B and C. Only isolated cases of these associations are described for hepatitis A. These links are least studied, and are often controversial for hepatitis E, possibly due to their relatively rare diagnoses. Patients with uveitis, glomerulonephritis, arthritis, vasculitis, autoimmune liver diseases should be tested for biomarkers of viral hepatitis, and if present, these patients should be treated with antiviral drugs.     

Hepatitis C virus infection with and without cryoglobulinemia as a case of Churg-Strauss syndrome

Chronic hepatitis C virus (HCV) infection may be associated with numerous immune disorders, with vasculitis including polyarteritis nodosa, or with both. Cryoglobulinemia, which is often present, can also be expressed by vasculitis. We describe 2 cases of Churg-Strauss syndrome (CSS) in patients with HCV infection. We found no previous case of CSS accompanying HCV infection in the literature. The current patients were women aged 40 and 66 years. In both cases, a clinical and laboratory pattern suggesting CSS was found before the HCV infection was discovered. One patient had cryoglobulinemia. One patient was successfully treated with interferon (IFN). The other was treated for 18 months with IFN and corticosteroids. Second-line therapy consisting of IFN with ribavirin was successful. The emergence of HCV infection may have led to an induced form of CSS. The relationship among HCV, cryoglobulinemia, and CSS is not clear, but may be similar to that existing between polyarteritis nodosa and hepatitis B virus. These observations suggest that IFN-alpha therapy may be effective against CSS in HCV infected patients with or without cryoglobulinemia.     

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.     

Another immune-mediated disease associated with hairy cell leukemia: chronic active hepatitis

This report describes a case of hairy cell leukemia (HCL) occurring with autoimmune chronic active hepatitis (CAH). A 74-year-old woman presented with typical clinical and histologic features of HCL for which splenectomy was performed. 2 years later she developed abnormal liver function tests due to auto-immune CAH. The liver function tests improved promptly after prednisolone therapy. HCL has been reported to occur with several immune-mediated diseases including polyarteritis nodosa, rheumatoid arthritis, hemolytic anemia, cutaneous vasculitis and monoclonal gammopathy with amyloidosis. This report adds a further example of HCL coexisting with an immune-mediated disease, in this case autoimmune CAH.     

Classic Polyarteritis Nodosa Presenting Rare Clinical Manifestations in a Patient with Hemophilia A

A 35-year-old patient with hemophilia A presented with rapidly progressive polyarteritis nodosa (PAN). He had been infected with hepatitis B virus (HBV) by repeated transfusion and was positive for hepatitis B surface antigen but negative for hepatitis B surface antibody. The patient presented symptoms of acute epididymitis followed by emergency admission because of acute appendicitis. On day 7 of admission, he complained of severe back pain, and computerized tomography (CT) showed massive perirenal hematoma. On day 49, mild monoplegia in the left arm suddenly developed, and CT and magnetic resonance imaging revealed multiple cerebral infarctions. Factor VIII replacement therapy was attenuated; however, cerebral infarction was progressive and extended throughout the cerebral hemispheres. He was diagnosed with classic polyarteritis nodosa (cPAN), and pulse methylprednisolone was continued. The patient died of supratentorial herniation, and autopsy revealed that vasculitis associated with intimal thickening was present in the liver, pancreas, intestine, kidneys, and larger-sized cerebral arteries. The development of cPAN appeared to have originated from chronic HBV infection, and this is the first report of cPAN in hemophilia patients. Concomitant hemorrhagic and thrombotic manifestations of cPAN are hardly treatable in patients with coagulation disorders, and the current case may represent a rare transfusion-related complication in hemophilia patients.     

Management of hepatitis B and C infections in rheumatologic disease

Hepatitis B and C viruses present dual considerations in rheumatic disease as both etiologic factors and important comorbidities that must be assessed and addressed. This review summarizes the link between hepatitis B and arthritis and polyarteritis nodosa as well as hepatitis C and arthritis, Sicca syndrome and cryoglobulinemic vasculitis. Recent data pertaining to the antiviral management in these conditions, especially regarding the use of the direct-acting antivirals in hepatitis C, are also presented. Additionally, guidance on testing and treatment of hepatitis B and C as comorbidities in the context of systemic inflammatory rheumatic conditions and the use of disease-modifying antirheumatic therapy are discussed.     

A Case of Polyarteritis Nodosa Presenting Initially as Peripheral Vascular Disease

Polyarteritis nodosa is a rare necrotizing vasculitis that can be progressive and fatal, and its initial presenting symptom may be leg claudication due to peripheral vascular ischemia. To date, there have been fewer than ten case reports of polyarteritis nodosa presenting as peripheral vascular disease. We report a case of a 38-year-old man initially diagnosed to have premature peripheral vascular disease who presented 1 year later with symptoms consistent with giant cell arteritis and subsequently developed bowel ischemia leading to a fatal outcome. Based on the autopsy and the patient’s clinical course, the final diagnosis was polyarteritis nodosa. This case illustrates the challenges in diagnosing polyarteritis nodosa and the importance of considering vasculitis in young patients presenting with atypical presentations of diseases such as peripheral vascular disease or giant cell arteritis.     

Hepatitis B-associated polyarteritis nodosa in Alaskan Eskimos: clinical and epidemiologic features and long-term follow-up

We analyzed the demographic, clinical, laboratory and histologic features of 13 patients who were diagnosed as having polyarteritis nodosa associated with hepatitis B virus infection over a 12-year period, 1974 to 1985. All 13 patients were Yupik Eskimos and resided in southwest Alaska, an area hyperendemic for hepatitis B virus infection. The annual incidence of hepatitis B virus-associated polyarteritis nodosa for this population is 7.7 cases per 100,000 population. All patients presented with multisystem disease, and all had biopsy or angiographic findings consistent with polyarteritis nodosa. All 13 were positive for hepatitis B surface antigen and hepatitis B e antigen at diagnosis. Two untreated patients and two of five patients who received corticosteroids died, vs. none of six who received corticosteroids plus cyclophosphamide. None of the patients who survived the initial bout of polyarteritis nodosa has relapsed after a mean follow-up of 55 months, but all have become chronic HBsAg carriers. In eight patients, clinical or serologic evidence indicated that polyarteritis nodosa followed recent hepatitis B virus infection. We concluded that hepatitis B virus-associated polyarteritis nodosa is a serious, life-threatening complication that occurs early in the course of hepatitis B virus infection, is ameliorated by immunosuppressive therapy and can be prevented by hepatitis B vaccine.     

Manifestation of cutaneous polyarteritis nodosa during interferon therapy for chronic hepatitis C associated with primary biliary cirrhosis

Interferon alpha-2b was administered to a 50-year-old Japanese woman with chronic hepatitis C associated with primary biliary cirrhosis. Two months after the beginning of the interferon alpha-2b therapy a systemic nodular, erythematous rash developed. Histological analysis of the skin revealed typical features of necrotizing arteritis. Because there was no microhematuria, and no microaneurysms were detected on abdominal angiography, a diagnosis of cutaneous polyarteritis nodosa was made. A good outcome was achieved after interferon alpha-2b was discontinued and prednisolone was administered instead. The cutaneous polyarteritis nodosa in this patient is thus considered to have occurred as an adverse effect of interferon administration. To our knowledge, this is the first reported case of cutaneous polyarteritis nodosa which developed because of interferton therapy for chronic hepatitis C associated with primary biliary cirrhosis. Received: October 7, 1999 / Accepted: January 28, 2000     

Gastrointestinal involvement in polyarteritis nodosa (1986-2000): presentation and outcomes in 24 patients

PURPOSE: Gastrointestinal involvement in polyarteritis nodosa carries a poor prognosis. A 1982 review from our institution reported acute abdominal syndromes in 31% of patients with polyarteritis nodosa, and that all 5 patients with acute surgical abdomens died. We reviewed our more recent experience to determine if outcomes have changed since. SUBJECTS AND METHODS: We reviewed the records of all patients with polyarteritis nodosa in our vasculitis database between 1986 and 2000. Inclusion criteria were a diagnosis of polyarteritis nodosa, symptoms or signs of gastrointestinal involvement, and either a mesenteric angiogram consistent with polyarteritis nodosa or histopathologic proof of a medium-vessel vasculitis. We calculated a prognostic (5 factor) score for all patients. RESULTS: We identified 24 patients with polyarteritis nodosa who had gastrointestinal involvement during their illness. Thirteen (54%) of the patients developed acute surgical abdomens, 3 of whom died (P = 0.02 by comparison with the historical cohort). Mean (+/- SD) prognostic scores were higher among patients in the acute abdomen group compared with those who did not have acute abdominal syndromes (1.7 +/- 0.9 vs. 0.6 +/- 0.7, P = 0.002), corresponding with the observed mortality in these groups. CONCLUSION: Gastrointestinal involvement occurs commonly in polyarteritis nodosa and carries a poor prognosis. Compared with a historical cohort at our institution, mortality from this complication may have decreased, perhaps because of earlier diagnosis.     

Vasculitic multiplex mononeuritis: polyarteritis nodosa versus cryoglobulinemic vasculitis

A 76-year-old female patient presented with a progressive motor-sensory multiplex mononeuritis (MM). Combined muscle and nerve biopsy showed the typical findings of a polyarteritis nodosa (PAN). Despite treatment with corticosteroids paresthesias increased and purpura of the legs newly appeared. Hepatitis screening revealed chronic hepatitis C-infection associated with cryoglobulinemia Type II (IgM-kappa Ig A). Finally, we diagnosed a hepatitis C-associated cryoglobulinemic vasculitis based on clinical and laboratory findings.     

Successful treatment of hepatitis B virus associated polyarteritis nodosa with a combination of prednisolone, alpha-interferon and lamivudine

Therapy of hepatitis B virus (HBV)-associated poly-arteritis nodosa is still evolving. Here we report a successful treatment with a short-term steroid administration in combination with a-interferon and lamivudine and a complete sequence analysis of the HBV genome. A 58-year-old man presented with the symptoms of mononeuritis multiplex associated in time with the onset of highly replicative hepatitis B. Polyarteritis nodosa was confirmed by biopsy. During an initial course with alpha-interferon and prednisolone no clinical improvement or hepatitis B virus seroconversion was observed. After addition of lamivudine to the protocol with fast tapering of prednisolone, HBV DNA fell to undetectable levels within 1 month and liver transaminases normalized. After 6 months of treatment HBeAg seroconversion took place, followed by HBsAg seroconversion 2 months later. Clinical symptoms of polyarteritis improved. No relapse of polyarteritis or hepatitis B was seen during the follow up of 9 months. Complete sequence analysis of the HBV genome revealed 6 nucleotide mutations but none in a relevant antigenic epitope. The present protocol of short-term prednisolone administration combined with alpha-interferon and lamivudine was effective for the treatment of HBV-related polyarteritis nodosa and may be a promising new therapeutic approach.     

Juvenile cutaneous polyarteritis nodosa associated with streptococcal infection

Polyarteritis nodosa is a rare vasculitis of small and medium arteries. It can occur in a systemic form with multi-organ involvement, or as a limited form confined to the skin, muscles, joints and peripheral nerves called cutaneous polyarteritis nodosa. Both forms are rare in adults and even more in children. The caues of this vasculitis remain unknown but some viruses and bacteria have been implicated, specially, Streptococcus. We present the case of a 6-year-old child who developed cutaneous polyarteritis nodosa following a probable streptococcal infection.     

Management of virus-induced systemic vasculitides

The best therapeutic strategy in virus-induced vasculitides should take into account the etiology of the disease and be adapted to the pathogenesis. The combination of antiviral treatments and plasma exchanges has been proven effective in polyarteritis nodosa. In HIV-related vasculitis, this strategy is effective and does not jeopardize the outcome of AIDS, as do cytotoxic agents. In vasculitis related to hepatitis C virus-associated cryoglobulinemia, plasma exchanges improve the outcome, but the poor effectiveness of antiviral drugs usually does not favor a definite recovery of the patients. Relapses are frequent.