Mortality and cause of death in patients with ANCA-associated vasculitis and polyarteritis nodosa in Australia-a population-based study.

OBJECTIVES: We compared survival and causes of death in Western Australian (WA) ANCA-associated vasculitis (AAV) and PAN patients with controls and the WA population. METHODS: In this data linkage study, we identified patients with incident AAV/PAN and age, sex and temporally matched controls 1980-2014 from the WA Rheumatic Disease Epidemiological Registry. Survival analyses and time-varying analyses were performed. RESULTS: Six hundred and fourteen patients with incident AAV/PAN were compared with 6672 controls; 229 AAV/PAN patients died over 5277 person-years of follow-up and 1009 controls died over 73835 person-years. Survival was reduced in patients with AAV/PAN compared with matched controls [hazard ratio (HR) 3.5 (95% CI: 3.1, 4.1)], and matched WA population rates [standardized mortality ratio 3.3 (95% CI: 2.9, 3.8)]. Greatest excess mortality in AAV/PAN patients was observed in the first year after diagnosis and remained higher than controls throughout follow-up. Greater excess mortality was observed in patients >60 years at diagnosis. In cause-specific analyses, mortality HR for vasculitis, infection and non-infective respiratory disease were greatest early after diagnosis and remained persistently elevated. The HRs for malignancy and cerebrovascular disease related deaths increased during follow-up, and were constant for ischaemic heart disease related deaths. CONCLUSION: Mortality was increased in AAV/PAN patients compared with controls, with patients older at diagnosis at greater risk. These findings provide mortality risk for AAV/PAN in an Australian population, highlighting key contributors to mortality at different time periods over follow-up and potential areas of focus for reducing mortality.

Predictive factors of severe infections in patients with systemic necrotizing vasculitides: data from 733 patients enrolled in five randomized controlled trials of the French Vasculitis Study Group.

OBJECTIVES: Infections remain a major cause of morbidity and mortality in systemic necrotizing vasculitides (SNV). We aimed to identify factors predicting severe infections (SI) in SNV. METHODS: Data from five randomized controlled trials (RCTs) enrolling 733 patients were pooled. The primary end point was the occurrence of SI, defined by the need of a hospitalization and/or intravenous anti-infectious treatment and/or leading to death. RESULTS: After a median follow-up of 5.2 (interquartile range 3-9.7) years, 148 (20.2%) patients experienced 189 SI, and 98 (66.2%) presented their first SI within the first 2 years. Median interval from inclusion to SI was 14.9 (4.3-51.7) months. Age ≥65 years (hazard ratio (HR) 1.49 [1.07-2.07]; P=0.019), pulmonary involvement (HR 1.82 [1.26-2.62]; P=0.001) and Five Factor Score ≥1 (HR 1.21 [1.03-1.43]; P=0.019) were independent predictive factors of SI. Regarding induction therapy, the occurrence of SI was associated with the combination of GCs and CYC (HR 1.51 [1.03-2.22]; P = 0.036), while patients receiving only GCs were less likely to present SI (HR 0.69 [0.44-1.07]; P = 0.096). Finally, occurrence of SI had a significant negative impact on survival (P<0.001). CONCLUSION: SI in SNV are frequent and impact mortality. Age, pulmonary involvement and Five Factor Score are baseline independent predictors of SI. No therapeutic regimen was significantly associated with SI but patients receiving glucocorticoids and CYC as induction tended to have more SI.

Four distinct clinical phenotypes of vasculitis affecting medium-sized arteries.

Objective: Within the spectrum of polyarteritis nodosa (PAN), cutaneous PAN (cPAN) is further classified into mild cPAN and severe cPAN which presents with ulcers, necrosis, or neuritis. As distinguishing between severe cPAN and systemic PAN can be difficult, this study evaluated the clinical characteristics of patients with necrotizing arteritis of medium-sized arteries. Methods: Forty-one patients diagnosed with necrotizing arteritis of medium-sized arteries between 2008 and 2017 at our institution were enrolled in this study. Clinical background, laboratory findings, treatments, and rates of relapse and death were evaluated. Results: Thirty-six patients were classified as having cPAN (mild, 15; ulcer, nine; neuritis, eight; both, four), and five cases manifested systemic vasculitis. Clinical characteristics of mild cPAN included female predominance (84.6%) and younger age (median 31 years); those of systemic PAN included older age (median 71 years) and higher levels of inflammatory markers. Severe cPAN manifested with intermediate phenotypes. The median doses of prednisolone used to treat mild cPAN, severe cPAN, and systemic PAN were 20.0, 40.0, and 40.0 mg/day, respectively. Immunosuppressants were used in 20.0% of mild cPAN, 90.5% of severe cPAN, and 80.0% of systemic PAN patients. Although the mortality rates were indistinguishable, the relapse rates of severe cPAN (ulcer type) were significantly higher than those of other types (88.9%). Conclusion: The clinical characteristics of mild cPAN, severe cPAN (ulcer type), severe cPAN (neuritis type), and systemic PAN were distinct from each other. In particular, patients with severe cPAN (ulcer type) had higher relapse rates, indicating the importance of combination therapy.

Mortality in systemic necrotizing vasculitides: A retrospective analysis of the French Vasculitis Study Group registry.

OBJECTIVE: The aim of the study was to describe the evolution of mortality and cause-specific mortality over time in patients with systemic necrotizing vasculitides (SNV), including polyarteritis nodosa (PAN), granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA). METHODS: Patients with SNV from the French Vasculitis Study Group registry were divided into 5 groups according to the date of diagnosis: <1980, 1980-1989, 1990-1999, 2000-2010, and ≥ 2010. The causes of death were classified as vasculitis, infection, cardiovascular, malignancy, miscellaneous, or unknown. RESULTS: Among the 2217 patients included (PAN 16.1%, GPA 41.7%, EGPA 22.6%, MPA 19.6%), overall incidence of death was 2.26 per 100 person-years. The overall survival improved during each period considered. The 5-year survival rate increased from 72.2% (95% confidence interval [CI] 59.7-87.2) for patients diagnosed before 1980 to 94.5% (95% CI 90.4-98.8) after 2010 (p < 0.001). Periods of diagnosis, age, and male gender were independently associated with a poor survival with a non-significant difference between vasculitis. The incidence of mortality between the 1980s and after 2010 significantly decreased for vasculitis-related (p = 0.03) and cardiovascular-related deaths (p = 0.04). Incidence of death by infection remained stable between the 1980s and the 2000s but no death by infection occurred after 2010. The incidence of death by malignancy remained stable over time. CONCLUSION: Overall survival of SNV patients has improved since the 1980s with the decrease of vasculitis- and cardiovascular-related deaths, but cancer-related mortality remained stable. These results highlight malignancy as the current target to improve the overall prognosis.

Association of five-factor score with the mortality in Japanese patients with polyarteritis nodosa.

AIM: To determine mortality and its predictive factors in Japanese patients with polyarteritis nodosa (PAN). METHODS: This retrospective single-center study determined the mortality of 18 patients with PAN who were admitted to Juntendo University Hospital from 1994 to 2016. The variables at baseline, including patient demographics, clinical characteristics, and treatment, were analyzed for their association with mortality. RESULTS: The median age of onset was 57.0 years. The 1-year survival rate was 100% (16/16) and the 5-year survival rate was 80.0% (8/10). The relationship between mortality, as defined by the survival rate and each variable was evaluated by Cox univariate analysis. A higher 2009 five-factor score (FFS) was associated with increased mortality, with a hazard ratio of 2.34 (p = .04). Analysis of the secondary outcome of relapse-free survival time revealed an association with rapid progressive renal failure, Birmingham Vasculitis Activity Score (BVAS), the 1996 FFS, and the 2009 FFS, with hazard ratios of 7.28 (p = .048), 1.26 (p = .02), 2.32 (p = .03), and 1.82 (p = .04), respectively. CONCLUSION: We investigated mortality, relapse-free survival, and their predictive factors in Japanese patients with PAN. The BVAS and the 1996 FFS at diagnosis may be prognostic factors for relapse-free survival, and the 2009 FFS at diagnosis may be a prognostic factor for both mortality and relapse-free survival.

Comparing polyarteritis nodosa in children and adults: a single center study.

OBJECTIVE: Polyarteritis nodosa (PAN) is a necrotizing vasculitis of medium/small arteries. We aimed to examine the characteristics of adult- and childhood-onset PAN. METHODS: Fifteen pediatric (˂ 18 years) and 22 adult PAN patients who fulfilled the Ankara 2008 and American College of Rheumatology 1990 criteria, respectively, were included in the study. RESULTS: Five children had cutaneous and all the rest of the patients had systemic PAN. Weight loss was more common (59.1% vs. 20%, P = 0.041) and presence of an angiography at diagnosis was more frequent (81.8% vs. 33.3%, P = 0.003) in adults than children. Arthralgia/arthritis and skin involvement were more common in children (86.7% vs. 59.1%; 93.3% vs. 72.7%, respectively) while renal and neurologic involvement were more frequently observed in adult patients (50% vs. 20%; 59.1% vs. 40%, respectively) (P > 0.05 for all). Cutaneous PAN patients were treated with corticosteroids only. All but one adult patient received cyclophosphamide while mycophenolate mofetil was used in five and cyclophosphamide was used in four children as induction treatment. The median duration of induction treatment was longer in adults than children (12 vs. 3 months, respectively; P = 0.004). The most common maintenance drug was mycophenolate mofetil in children and azathioprine in adults. The mortality rate was 13.6% (n = 3) and 0% in adults and children, respectively. CONCLUSION: To our knowledge, this is the first study comparing characteristics of adult and childhood onset PAN. Our results have suggested that juvenile PAN had a more benign course (with less renal and neurologic involvement, shorter duration of induction treatment) than adult onset PAN.

Microscopic polyangiitis and non-HBV polyarteritis nodosa with poor-prognosis factors: 10-year results of the prospective CHUSPAN trial.

OBJECTIVES: To analyse the 10-year outcomes of 64 patients with non-HBV polyarteritis nodosa (PAN) or microscopic polyangiitis (MPA) and Five-Factor Score-defined poor-prognosis factors enrolled (1994-2000) in the prospective, randomised, open-label CHUSPAN trial. METHODS: The 64 patients were randomised to receive 12 (33: 23 MPA, 10 PAN) or 6 (31: 17 MPA, 14 PAN) cyclophosphamide (CYC) pulses combined with glucocorticoids. Ten-year follow-up of these patients included times to relapse(s), failure(s) and/or deaths calculated from treatment onset. Data were censored after 120 months of follow-up. RESULTS: Eleven patients were lost to-follow-up (mean±SD follow-up: 61.9±35.2 months), with no between-group difference. As previously reported, baseline clinical characteristics and laboratory values were comparable for the 2 groups. After induction, 53/64 (83%) entered remission, with comparable percentages for both groups. The regimen was intensified for 11 initial non-responders: 4 achieved remission and 8 died before doing so. During extended follow-up, 26 patients experienced ≥1 relapse(s): 12 in the 12-pulse group and 14 in the 6-pulse group (p=0.47). At 10 years, overall and disease-free survival rates were 57.4% and 29.9%, with no between-group differences (p=0.185 and p=0.367, respectively). Factors associated with shorter disease-free survival were age ≥65 years and alveolar haemorrhage at diagnosis. CONCLUSIONS: Although the 3-year CHUSPAN trial results indicated the superiority of 12 vs. 6 CYC pulses, that early advantage progressively declined and became non-significant by 10 years.

Polyarteritis nodosa in north India: clinical manifestations and outcomes.

OBJECTIVE: There has been a significant decrease in the number of published reports of classical polyarteritis nodosa (PAN) in the post-Chapel Hill consensus conference (CHCC) nomenclature era with only two series published from Asia. We report a case series of PAN from north India. PATIENTS AND METHODS: A retrospective study of all patients diagnosed to have PAN according to American College of Rheumatology criteria/CHCC nomenclature. The details of clinical presentation, investigation findings, treatment details and outcomes were noted from the records. These findings between the hepatitis B positive and negative groups were compared. RESULTS: Twenty-seven patients (20 male, seven female) were diagnosed as having PAN, out of which seven (25.9%) were hepatitis B surface antigen positive. Nervous system involvement was most common with 24 patients (88.9%) having mononeuritis multiplex. Weight loss was present in 20 (74%), fever in 14 (51.9%), renal involvement in 16 (59.3%), cutaneous in nine (33.3%), peripheral gangrene in eight (29.6%), gastrointestinal (GI) involvement in eight (29.6%), testicular pain in 6/20 (30%) and cardiac involvement in four (14.8%). Twenty-three (85.2%) patients recovered, three died (11.1%) and one was lost to follow-up. Median follow-up duration was 37 (interquartile range 22.00-69.75) months. The cumulative survival was 114.16 months (95% CI: 98.27-129.95). There was no significant difference in five factor score (FFS) or revised FFS between those patients who died and those who survived (P = 0.248, 0.894, respectively). Hepatitis B-related PAN had a lower FFS compared to non-hepatitis B-related PAN (P = 0.039). No other significant differences were noted between the two groups. CONCLUSION: In comparison to classic PAN in other populations, classic PAN in north India is associated with higher neurological involvement and lower GI involvement.

Brief Report: Childhood-Onset Systemic Necrotizing Vasculitides: Long-Term Data From the French Vasculitis Study Group Registry.

OBJECTIVE: To describe the initial features and long-term outcomes of childhood-onset small vessel and medium vessel systemic necrotizing vasculitides (SNVs), including antineutrophil cytoplasmic antibody-associated vasculitides (AAVs) and polyarteritis nodosa (PAN). METHODS: Data on patients with childhood-onset SNV registered in the French Vasculitis Study Group database were reviewed for demographic characteristics, clinical, laboratory, and histologic features, and outcomes. Disease activity was assessed with the Birmingham Vasculitis Activity Score and the Paediatric Vasculitis Activity Score, and damage was scored using the Vasculitis Damage Index. Relapse and survival rates and causes of death were analyzed. RESULTS: Fifty-six patients (35 with AAV and 21 with PAN) (median age at database enrollment 14 years [range 2-17]) were included in the study. The median duration of followup was 96 months (range 1-336); two-thirds of the patients were followed up beyond 18 years of age. Six patients (11%) died, mostly of SNV-related causes. Relapse rates ranged from 33% for microscopic polyangiitis to 50% for eosinophilic granulomatosis with polyangiitis (Churg-Strauss) and 83% for granulomatosis with polyangiitis (Wegener's), with similar rates among AAV and PAN patients (76% and 75%, respectively); neither overall survival nor relapse-free survival differed significantly between the 2 disease groups. Rates of relapse increased after 18 years of age, both among patients with AAV and among patients with PAN. At the last followup evaluation, AAV patients had more major flares and more severe accrued damage compared with PAN patients. CONCLUSION: Despite similar relapse rates, patients with childhood-onset AAVs experienced more major flares with more cumulative damage than those with pediatric PAN. Treatments aimed at reducing the rates of mortality and relapse in this patient group need to be developed and assessed.

Long-term follow-up of a randomized trial on 118 patients with polyarteritis nodosa or microscopic polyangiitis without poor-prognosis factors.

The purpose of this study was to assess the long-term outcomes of patients with polyarteritis nodosa (PAN) or microscopic polyangiitis (MPA) without Five-Factor Score (FFS)-defined poor-prognosis factors (FFS=0) and enrolled in a prospective clinical trial. Patients were followed (2005-2012) under routine clinical care in an extended study and data were recorded prospectively. Long-term survival, disease-free survival (DFS), relapses, therapeutic responses and sequelae were analyzed. Mean±SD follow-up was 98.2±41.9months. After having initially received glucocorticoids (GC) alone, according to the study protocol, 82% (97/118) patients achieved remission but 18% (21/118) required ≥1 immunosuppressant(s) (IS) before 19/21 achieved remission. Two patients died before entering remission. After remission, 53% (61/116) patients relapsed 25.6±27.9months after starting treatment. The 5- and 8-year overall survival rates were 93% and 86%, respectively, with no difference between PAN and MPA, and between relapsers and nonrelapsers. DFS was shorter for MPA than PAN patients (P=0.02). Throughout follow-up, 47% of patients required ≥1 IS. At the last follow-up visit, 44% were still taking GC and 15% IS. The mean vasculitis damage index score was 1.9±1.9; the most frequent sequelae were peripheral neuropathy, hypertension and osteoporosis. For PAN or MPA patients without poor-prognosis factors at diagnosis and treated initially with GC alone, long-term survival was excellent. However, relapses remained frequent, requiring IS introduction for nearly half of the patients. To lower the frequencies of relapses and sequelae remains a challenge for FFS=0 PAN and MPA patients.

Systemic polyarteritis nodosa in the young: a single-center experience over thirty-two years.

OBJECTIVE: Polyarteritis nodosa (PAN) is a rare disease of childhood. The aims of this study were to describe the clinical features, treatment, and outcome of systemic childhood PAN and to identify predictors of relapse. METHODS: A single-center retrospective medical records review of children with PAN fulfilling the European League Against Rheumatism (EULAR)/Paediatric Rheumatology European Society (PRES)/Paediatric Rheumatology International Trials Organisation (PRINTO) classification criteria who were seen over a 32-year period was performed. Data on demographic and clinical features, treatments, relapses (recurrence of clinical signs/symptoms or occurrence of new symptoms after initial remission requiring escalation or resumption of immunosuppressive therapy), and deaths were recorded. A disease activity score was retrospectively assigned using the Paediatric Vasculitis Activity Score (PVAS) instrument. Cox regression analysis was used to identify significant predictors of relapse. RESULTS: Sixty-nine children with PAN were identified; 55% were male, and their median age was 8.5 years (range 0.9-15.8 years). Their clinical features at presentation were fever (87%), myalgia (83%), skin (88%), renal (19%), severe gastrointestinal (GI) (10%), and neurologic (10%) involvement. The PVAS at presentation was 9 of 63 (range 4-24). Histopathologic analysis of the skin showed necrotizing vasculitis in biopsy samples from 40 of 50 children. Results of selective visceral arteriography suggested the presence of PAN in 96% of patients. Treatment included cyclophosphamide and corticosteroids (83%), plasma exchange (9%), and biologic agents (after 2002; 13%). The relapse rate was 35%, and the mortality rate was 4%. Severe GI involvement was associated with increased risk of relapse (P = 0.031), while longer time to induce remission (P = 0.022) and increased cumulative dose of cyclophosphamide (P = 0.005) were associated with lower relapse risk. CONCLUSION: Childhood PAN is a severe inflammatory disease of insidious onset and variable clinical presentation. Relapses occurred more frequently in those with severe GI involvement. A higher cumulative dose of cyclophosphamide was associated with a lower risk of relapse.

The Five-Factor Score revisited: assessment of prognoses of systemic necrotizing vasculitides based on the French Vasculitis Study Group (FVSG) cohort.

The 1996 Five-Factor Score (FFS) for systemic necrotizing vasculitides (polyarteritis nodosa [PAN], microscopic polyangiitis [MPA], and Churg-Strauss syndrome [CSS]) is used to evaluate prognosis at diagnosis. In the current study we revisited the FFS, this time including Wegener granulomatosis (WG).We analyzed clinical, laboratory, and immunologic manifestations present at diagnosis of systemic necrotizing vasculitides for 1108 consecutive patients registered in the French Vasculitis Study Group database. All patients met the American College of Rheumatology and Chapel Hill nomenclature criteria. Univariable and multivariable analyses yielded the 2009 FFS for the 4 systemic necrotizing vasculitides.Overall mortality was 19.8% (219/1108); mortality for each of the SNV is listed in descending order: MPA (60/218, 27.5%), PAN (86/349, 24.6%), CSS (32/230, 13.9%), and WG (41/311, 13.2%) (p < 0.001). The following factors were significantly associated with higher 5-year mortality: age >65 years, cardiac symptoms, gastrointestinal involvement, and renal insufficiency (stabilized peak creatinine ≥150 µmol/L). All were disease-specific (p < 0.001); the presence of each was accorded +1 point. Ear, nose, and throat (ENT) symptoms, affecting patients with WG and CSS, were associated with a lower relative risk of death, and their absence was scored +1 point (p < 0.001). Only renal insufficiency was retained (not proteinuria or microscopic hematuria) as impinging on outcome. According to the 2009 FFS, 5-year mortality rates for scores of 0, 1, and ≥2 were 9%, 21% (p < 0.005), and 40% (p < 0.0001), respectively.The revised FFS for the 4 systemic necrotizing vasculitides now comprises 4 factors associated with poorer prognosis and 1 with better outcome. The retained items demonstrate that visceral involvement weighs heavily on outcome. The better WG prognosis for patients with ENT manifestations, even for patients with other visceral involvement, compared with the prognosis for those without ENT manifestations, probably reflects WG phenotype heterogeneity.

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.

Clinical features and outcomes in 348 patients with polyarteritis nodosa: a systematic retrospective study of patients diagnosed between 1963 and 2005 and entered into the French Vasculitis Study Group Database.

OBJECTIVE: Previous studies of polyarteritis nodosa (PAN) included patients with microscopic polyangiitis, because these entities were not distinguished prior to the Chapel Hill Consensus Conference (CHCC). This study was undertaken to describe the main characteristics of and long-term outcomes in patients with well-characterized PAN diagnoses. METHODS: We conducted a systematic retrospective study of 348 patients who were diagnosed as having PAN between March 1963 and October 2005, were registered in the French Vasculitis Study Group database, and satisfied the American College of Rheumatology and CHCC criteria. Patient characteristics and outcomes were analyzed and compared according to hepatitis B virus (HBV) status. RESULTS: At diagnosis, the mean +/- SD age was 51.2 +/- 17.3 years. The most frequent findings were general symptoms (93.1%), neurologic manifestations (79%), skin involvement (49.7%), abdominal pain (35.6%), and hypertension (34.8%); 66.2% had renal artery microaneurysms; 70.1% had histologically proven PAN. Patients with HBV-related PAN (n = 123) had more frequent peripheral neuropathy, abdominal pain, cardiomyopathy, orchitis, and hypertension compared with patients with non-HBV-related PAN (n = 225). During a mean +/- SD followup of 68.3 +/- 63.5 months, 76 patients (21.8%) relapsed (63 with non-HBV-related PAN [28%] versus 13 with HBV-related PAN [10.6%]; P < 0.001); 86 patients (24.7%) died (44 with non-HBV-related PAN [19.6%] versus 42 with HBV-related PAN [34.1%]; P = 0.003). Five-year relapse-free survival rates were 59.4% (95% confidence interval [95% CI] 52.6-67.0) versus 67.0% (95% CI 58.5-76.8) for non-HBV-related PAN and HBV-related PAN, respectively. Multivariate analysis retained age >65 years, hypertension, and gastrointestinal manifestations requiring surgery or at least consultation with a surgeon as independent predictors of death, whereas patients with cutaneous manifestations or non-HBV-related PAN had a higher risk of relapse. CONCLUSION: Our findings indicate that the rate of mortality from PAN remains high, especially for the elderly, and relapses do occur, particularly in patients with non-HBV-related PAN with cutaneous manifestations.

Clinical features and outcomes of microscopic polyangiitis in Korea.

Microscopic polyangiitis (MPA) is a systemic vasculitis affecting small vessels. To determine the clinical features and outcomes of MPA in Korean patients, we retrospectively reviewed the medical records of patients diagnosed with MPA at a single medical center in Korea between 1989 and 2006. The 18 patients who met the Chapel Hill criteria for MPA had a mean (+/-SD) age at the time of diagnosis of 62.4+/-12.7 yr. Renal manifestations and general symptoms were the most common features of MPA, with lung involvement also very common. Antineutrophil cytoplasmic antibodies (ANCA) were present in 17 of the 18 patients (94%). Of 17 patients treated with steroids and cyclophosphamide, 11 (65%) had stable or improved course. One patient treated with steroids without cyclophosphamide showed disease progression. Ten of the 18 patients (56%) died at a median follow-up of 8 months. MPA in Korean patients was distinguished by a higher rate of lung involvement, especially alveolar hemorrhage, which was the leading cause of death in our patients. Korean patients were also older at MPA onset and were more likely positive for ANCA. Other overall clinical manifestations did not differ significantly.

[Trends in mortality from intractable diseases in Japan, 1972-2004].

PURPOSE: In 1972, the Ministry of Health, Labour and Welfare of Japan defined intractable diseases as those with unknown etiology, no established treatment regimens, and severe sequelae of physical, mental and social difficulties. Since then, the Ministry has promoted scientific research on these diseases and offered financial support to those suffering from their effects. The purpose of the present study was to analyze trends in deaths from the diseases in Japan over the period from 1972-2004. METHODS: For the selected intractable diseases with 100 deaths or more per year, crude (CDR) and direct age-standardized death rates (ADR) were computed using the national underlying-cause-of-death mortality database of Japan based on International Classification of Diseases. Joinpoint regression analysis was applied to identify significant changes in the trends. RESULTS: The CDRs in the latest observed year per 1 million persons/year) for males and females were 25.55 and 25.93, respectively, for Parkinson's disease, 5.41 and 6.92 for aplastic anemia, 0.87 and 3.50 for systemic lupus erythematosus, 2.93 and 2.36 for amyloidosis, 1.40 and 1.54 for polyarteritis nodosa, 1.34 and 1.61 for idiopathic thrombocytopenic purpura, and 1.02 and 0.74 for ulcerative colitis. The respective annual percentage changes (APCs) for males and females during the overall period decreased for ulcerative colitis (-5.2% and -7.5%), aplastic anemia (-3.6% and -3.7%), idiopathic thrombocytopenic purpura (-2.1% and -3.0%), and systemic lupus erythematosus (-0.9% and -2.6%), while the APCs increased for amyloidosis (+3.3% and +3.5%), polyarteritis nodosa (+3.2% and +4.0%), and Parkinson's disease (+0.7% in males alone). With the APCs in the latest trend phase, polyarteritis nodosa and Parkinson's disease in females showed appreciable declines; on the other hand, amyloidosis in males demonstrated the significant increase, and ulcerative colitis in males exhibited an apparent leveling off of the decline. CONCLUSION: The ADRs for most of the intractable diseases have declined significantly in Japan over the last 3 decades. The decline might be attributed in large part to improved diagnosis and treatment because of the lack of effective primary prevention measures. Support for the affected patients and further research on etiology and radical cure of the diseases must be considered necessary.

Pancreaticoduodenal arterial rupture and hemoabdomen in ACI/SegHsd rats with polyarteritis nodosa.

Many lesions associated with aging have been well-characterized in various strains of rats. Although documented in Sprague-Dawley and spontaneously hypertensive rats, polyarteritis nodosa has not previously been reported in ACI/SegHsd rats. ACII SegHsd rats were maintained on high-fat (40.5%), low-fat (11.6%), and high-fat to low-fat dietary protocols to examine the correlation between dietary fat and the regulation of prostate 5alpha-reductase gene expression and prostate cancer. Seven rats died unexpectedly with hemoabdomen and rupture of the pancreaticoduodenal artery secondary to polyarteritis nodosa (PAN). The purpose of this study was to analyze the pathologic findings in these and the remaining ACI/SegHsd rats and to correlate the level of dietary fat with the presence of PAN, arterial rupture, and hemoabdomen. Approximately 65% of the rats had evidence of PAN by histopathology, with a 24% incidence of arterial rupture. Additional lesions noted included an 88% incidence of chronic progressive nephropathy (CPN) and a 32% incidence of cartilaginous foci in the aortic valve. We found no association between the percentage of dietary fat and incidence of PAN, CPN, or cardiac cartilage. Although arterial rupture is a known complication of polyarteritis nodosa in humans, this case series is the first to document arterial rupture and hemoabdomen in rats with PAN.

Indication for plasma exchange for systemic necrotizing vasculidities.

Plasma exchanges (PE) are a component of regimens prescribed to treat systemic necrotizing vasculidities. They are also part of the best therapeutic strategy for virus-induced vasculidities. The combination of antiviral agents and PE has proven efficacy against polyarteritis nordosa. This strategy is also effective for human immunodeficiency virus-associated vasculitis and, unlike cytotoxic agents, does not jeopardize the outcome of acquired immunodeficiency syndrome. Concerning the vasculitis seen in the context of hepatitis C virus-related cryoglobulinemia, PE contribute to better outcomes but, because of the poor efficacies of antiviral drugs, only about half of the patients achieve definitive recovery and relapses are frequent. The use of PE to treat antineutrophil cytoplasm antibody-associated vasculidities with severe renal insufficiency leads to improved renal function and thus fewer patients require dialysis. Although PE does not improve survival, their adjunction to corticosteroids and immunosuppressants for patients with alveolar hemorrhage could also limit the severity of this severe manifestation.