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.

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.

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.

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.

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.

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.

[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.

Outcome of patients with small-vessel vasculitis admitted to a medical ICU.

PURPOSES: This study aims to describe the clinical course and prognostic factors of patients with small-vessel vasculitis admitted to a medical ICU. METHODS: We reviewed the clinical records of 38 patients with small-vessel vasculitis admitted consecutively to the ICU between January 1997 and May 2004. The APACHE (acute physiology and chronic health evaluation) III prognostic system was used to determine the severity of illness on the first ICU day; the sequential organ failure assessment (SOFA) score was used to measure organ dysfunction, and the Birmingham vasculitis activity score for Wegener granulomatosis (BVAS/WG) was used to assess vasculitis activity. Outcome measures were the 28-day mortality and ICU length of stay. RESULTS: Nineteen patients (50%) had Wegener granulomatosis, 16 patients (42%) had microscopic polyangiitis, 2 patients had CNS vasculitis, and 1 patient had Churg-Strauss syndrome. Reasons for ICU admission included alveolar hemorrhage in 14 patients (37%), sepsis in 5 patients (13%), seizures in 3 patients (8%), and pneumonia in 2 patients (5%). The median ICU length of stay was 4.0 days (interquartile range, 2.0 to 6.0 days). The APACHE III score was lower in survivors than nonsurvivors (p = 0.010). The predicted hospital mortality was 54% for nonsurvivors and 21% for survivors (p = 0.0038). The mean SOFA score was 11.6 (SD, 2.6) in nonsurvivors, compared to 6.9 (SD, 2.4) in survivors (p = 0.0004). Mean BVAS/WG scores were 8.6 (SD, 3.6) in nonsurvivors and 4.7 (SD, 4.6) in survivors (p = 0.0889). Twenty-six percent of the patients received invasive mechanical ventilation, and 33% underwent dialysis. The 28-day and 1-year mortality rates were 11% and 29%, respectively. CONCLUSIONS: The mortality of patients with small-vessel vasculitis admitted to the ICU is lower than predicted, and alveolar hemorrhage is the most common reason for ICU admission.

[The peculiarities of renal lesion in nodular polyarteritis].

Analysis of the medical records of 122 patients with nodular polyarteritis showed that the most frequent visceral manifestations were renal (93.4%), cardial (72%), and gastrointestinal (57.4%) ones. Central nervous system (CNS), pulmonary, and peripheral arterial lesions were less frequent (36.8%, 17.2%, and 6.6%, respectively). Renal lesions were manifested by arterial hypertension (AH) in 107 patients, urinary syndrome in 97, nephrotic syndrome in 7, and rapidly progressing glomerulonephritis in 5 patients. Monofactor analysis revealed the following predictors of poor prognosis: malignant AH, nephrotic proteinuria, male sex, body mass reduction, intestinal ulcers, gastrointestinal hemorrhage, CNS lesion, heart failure, and pulmonary lesion. The relative risk of lethal outcome was the highest in nephrotic proteinuria (3.5) and malignant AH (2.9). In 56% of cases death was caused by cardiovascular complications, in 18%--chronic renal failure, in 11%--abdominal complications.

Deaths occurring during the first year after treatment onset for polyarteritis nodosa, microscopic polyangiitis, and Churg-Strauss syndrome: a retrospective analysis of causes and factors predictive of mortality based on 595 patients.

Although combining corticosteroids and cyclophosphamide has greatly improved the prognoses of severe necrotizing vasculitides, some patients continue to have fulminating disease and die within the first year of diagnosis. To evaluate the characteristics of these patients, we retrospectively studied the files of 60 patients who died within the first year (20 patients with hepatitis B virus-associated polyarteritis nodosa [HBV-PAN], 18 with non-HBV PAN, 13 with microscopic polyangiitis [MPA], and 9 with Churg-Strauss syndrome [CSS]) and 535 first-year survivors (89 patients with HBV-PAN, 182 with non-HBV PAN, 140 with MPA, and 124 with CSS), 85 of whom died during a mean follow-up of 6.4 years. The 2 groups were compared for prognostic factors defined by the five-factor score (FFS) and Birmingham Vasculitis Activity Score at baseline, clinical signs, treatment, outcome, and causes of death. For first-year nonsurvivors, the clinical signs predictive of death were as follows: renal involvement (hazard ratio [HR], 1.6; 95% confidence intervals [CI], 1.09-2.3) or central nervous system involvement (HR, 2.3; 95% CI, 1.5-3.7), and a trend toward cardiomyopathy (HR, 1.4; 95% CI, 1.000-2.115). Older patients died earlier (HR, 1.04; 95% CI, 1.023-1.051). Gastrointestinal symptoms were most frequently associated with early death from HBV-PAN, while 83% of CSS patients died of cardiac involvement. Treatment had no significant impact on early death, except for patients with FFS > or = 2, for whom steroids alone were associated (p < 0.05). The major cause of early death was uncontrolled vasculitis (58%), followed by infection (26%). Cyclophosphamide-induced cytopenia and infection were responsible for 2 deaths. Despite these iatrogenic complications, early deaths were more frequently the consequence of insufficient or inappropriate therapy.

Clinical review: Vasculitis on the intensive care unit -- part 2: treatment and prognosis.

The second part of this review addresses the treatment and prognosis of the vasculitides Wegener's granulomatosis, microscopic polyangiitis, Churg-Strauss syndrome and polyarteritis nodosa. Treatment regimens consist of an initial remission phase with aggressive immunosuppression, followed by a more prolonged maintenance phase using less toxic agents and doses. This review focuses on the initial treatment of fulminant vasculitis, the mainstay of which remains immunosuppression with steroids and cyclophosphamide. For Wegener's granulomatosis and microscopic polyangiitis plasma exchange can be considered for first-line therapy in patients with acute renal failure and/or pulmonary haemorrhage. Refractory disease is rare and is usually due to inadequate treatment. The vasculitides provide a particular challenge for the critical care team. Particular aspects of major organ support related to these conditions are discussed. Effective treatment has revolutionized the prognosis of these conditions. However, mortality is still approximately 50% for those requiring admission to intensive care unit. Furthermore, there is a high morbidity associated with both the diseases themselves and the treatment.

Primary systemic vasculitis: clinical features and mortality.

BACKGROUND: Wegener's granulomatosis (WG), Churg Strauss syndrome (CSS) and microscopic polyangiitis (MPA) are primary systemic vasculitides (PSV), the clinical features of which have been described from tertiary centres. AIM: To provide the first clinical description of MPA from a general hospital and compare clinical features with WG and CSS. DESIGN: Retrospective analysis of patient records. METHODS: Records of 99 PSV patients attending a single hospital, from 1988 to 2000, were reviewed for: clinical features, date/age at diagnosis, sex, duration of illness, anti-neutrophil cytoplasmic antibodies (ANCA), treatment, comorbidity and deaths. Cases were classified using ACR, CHCC and Lanham criteria/definitions. Birmingham vasculitis activity scores (BVAS) and damage index (VDI) were calculated. Survival was assessed using Cox proportional hazards model and standardized mortality ratios (SMRs). RESULTS: Compared to previous reports there was more ENT (29%) and respiratory (29%) but less renal (92%) involvement in MPA, and less ENT involvement in WG (81%). CSS showed high neurological (72%), cardiovascular (28%) and gastrointestinal (17%) involvement and the highest median (range) VDI (p = 0.01 vs. WG; p = 0.001 vs. MPA). BVAS1 was significantly lower in MPA than in WG [median (range) 15 (4-29) vs. 21 (6-39), (p = 0.001)] but not in CSS [20 (7-28), p = 0.08]. SMR (95%CI) for PSV was 4.8 (3.0-6.6); 5-year survival was 45.1% for MPA, 75.9% for WG and 68.1% for CSS. Age was a significant risk, but only to the same extent as in the reference population. When age was adjusted for, no other significant factor was found. DISCUSSION: The clinical characteristics seen here are similar to those in previous series. There are difficulties in using the MPA CHCC definitions in classification. There is a high proportion of neurological involvement in CSS, causing permanent damage. MPA may have a poorer prognosis than WG or CSS.

Microscopic polyangiitis and polyarteritis nodosa: how and when do they start?

OBJECTIVE: To describe initial clinical symptoms attributable to microscopic polyangiitis (MPA) or polyarteritis nodosa (PAN). METHODS: We retrospectively reviewed the medical files of 72 patients (mean followup 6.7 years) with biopsy-proven MPA (n = 36) or PAN (n = 36). RESULTS: Initial manifestations were similar in both entities except for peripheral neuropathy (P = 0.02) and gastrointestinal tract involvement (P = 0.006), which were significantly more frequent in PAN, and general signs alone in MPA (8%; P = 0.02). The mean time to diagnosis was 9.8 +/- 19.4 months; 35% of the patients died and 26% relapsed; significantly more MPA than PAN patients relapsed (P = 0.03). Time to diagnosis >/=90 days was associated with a trend toward more patients relapsing (P = 0.12), but not with an increased risk of mortality. CONCLUSION: Initial symptoms of MPA and PAN are usually nonspecific and last for several months before the diagnosis is made. A longer time to diagnosis is associated with a tendency to a higher relapse rate.

[Association of systemic diseases and myelodysplastic syndromes. A retrospective study of 14 cases]. / Association maladies systémiques et syndromes myélodysplasiques. Etude rétrospective portant sur 14 observations.

CONTEXT: The association of a systemic disease (SD) and a myelodysplastic syndrome (MDS) may not be a coincidence. We report 14 cases. METHODS: A retrospective study was conducted in patients presenting with an MDS, hospitalised between 1989 and 1999, in the search for a concomitant systemic disease. RESULTS: Ninety-seven patients, 61 men and 36 women, with a mean age of 74 +/- 11 years suffered from an MDS and 14 of them a concomitant SD: one nodular periateritis, 2 systemic vascularitis, 2 cutaneous vascularitis, 2 atrophic polychondritis, 4 Gougerot-Sjogrën syndrome, 2 systemic lupus and one cutaneous lupus. The systemic disease did not appear to influence survival. CONCLUSION: It is possible that the association is not a coincidence and therefore an MDS should be searched for when confronted with an SD, so that treatment may be adapted appropriately.

Long-term followup of polyarteritis nodosa, microscopic polyangiitis, and Churg-Strauss syndrome: analysis of four prospective trials including 278 patients.

OBJECTIVE: To determine the long-term outcome of patients with polyarteritis nodosa (PAN), microscopic polyangiitis (MPA), and Churg-Strauss syndrome (CSS), to compare the long-term outcome with the overall French population, to evaluate the impact on outcome of the type of vasculitis, prognostic factors, and treatments administered at diagnosis, and to analyze treatment side effects and sequelae. METHODS: Data from PAN, MPA, and CSS patients (n = 278) who were enrolled between 1980 and 1993 were collected in 1996 and 1997 and analyzed. Two prognostic scoring systems, the Five-Factors Score (FFS) and the Birmingham Vasculitis Activity Score (BVAS), were used to evaluate all patients at the time of diagnosis. RESULTS: The mean (+/- SD) followup of the entire population was 88.3 +/- 51.9 months (range 3 days to 192 months). Of the 85 deaths recorded, at least 41 were due to progressive vasculitis or its consequences. Death rates reflected disease severity, as assessed by the FFS (P = 0.004) and the BVAS (P < 0.0002), and the 2 scores were correlated (r = 0.69). Relapses, rarer in hepatitis B virus (HBV)-related PAN (7.9%) than in MPA (34.5%) (P = 0.004), occurred in 56 patients (20.1%) and did not reflect disease severity. Survival curves were similar for the subpopulation of 215 patients with CSS, MPA, and non-HBV-related PAN who were given first-line corticosteroids (CS) with or without cyclophosphamide (CYC). However, CS with CYC therapy significantly prolonged survival for patients with FFS scores > or =2 (P = 0.041). Relapse rates were similar regardless of the treatment regimen; only patients treated with CS alone had uncontrolled disease. CYC was associated with a greater frequency of side effects (P < 0.00001). CONCLUSION: Rates of mortality due to PAN (related or unrelated to HBV), MPA, and CSS reflected disease severity and were higher than the mortality rate in the general population (P < 0.0004). Rates of relapse, more common in MPA than HBV-related PAN patients, did not reflect disease severity. Survival rates were better among the more severely ill patients who had received first-line CYC. Based on these findings, we recommend that the intensity of the initial treatment be consistent with the severity of the disease. The use of the FFS and BVAS scores improved the ability to evaluate the therapeutic response.

Polyarteritis nodosa: a report from Israel.

BACKGROUND: The clinical manifestations and outcome of all adult patients with polyarteritis nodosa (PAN), allocated during a 15-year period in the largest medical center in Israel, were examined. METHODS: A retrospective analysis of patients with PAN who fulfilled the American College of Rheumatology (ACR) 1990 Classification Criteria and were either biopsy- or angiography-proven. RESULTS: Nine patients were included in the report. The clinical and laboratory manifestations were similar to those in previous studies. All patients were treated with combinations of cyclophosphamide and corticosteroids. There were two (22%) deaths, 2 and 5 months after initiation of treatment in patients who probably had microscopic polyangiitis (MPA) rather than classical PAN. Considering the patients with a complete follow-up, 71% had a complete and long-term remission. Moreover, by exclusion of the two patients with probable MPA who died, all of the five patients with classical PAN were alive and well as of this writing. Two patients (22%) had a long history, since childhood, of familial Mediterranean fever (FMF). CONCLUSIONS: The clinical presentation and course of PAN in Israeli patients is comparable with reports elsewhere. However, a distinction should be made between PAN and MPA. The present report emphasizes the good long-term prognosis of patients with typical PAN who are treated adequately. In addition, a possible association of PAN with FMF in Israeli patients is suggested.

Pneumocystis carinii pneumonia in patients with connective tissue diseases: the role of hospital experience in diagnosis and mortality.

OBJECTIVE: Pneumonia due to Pneumocystis carinii has been increasingly reported in patients with connective tissue diseases, but the frequency of this complication is not known. We sought to determine the frequency of P carinii pneumonia (PCP) in patients with connective tissue diseases, and to determine the role that a hospital's acquired immunodeficiency syndrome (AIDS)-related experience may have in the diagnosis of PCP in these patients. METHODS: We used a state hospitalization registry to identify all patients with PCP and either rheumatoid arthritis, systemic lupus erythematosus, Wegener's granulomatosis, polymyositis, dermatomyositis, polyarteritis nodosa, or scleroderma who had an emergent or urgent hospitalization in California from 1983 to 1994. We compared patient and hospital characteristics between these patients and patients with connective tissue diseases hospitalized with other types of pneumonia. RESULTS: Two hundred twenty-three patients with connective tissue diseases were diagnosed with PCP in the 12-year study period. The frequency of PCP ranged from 89 cases/10,000 hospitalizations/year in patients with Wegener's granulomatosis to 2 cases/10,000 hospitalizations/year in patients with rheumatoid arthritis. Compared with 5,457 patients with connective tissue diseases and pneumonia due to other organisms, patients with PCP were more likely to be younger, to be male, to have private medical insurance, and to have systemic lupus erythematosus, Wegener's granulomatosis, inflammatory myopathy, or polyarteritis nodosa rather than rheumatoid arthritis, and were less likely to be African American. Hospital size, teaching status, urban/rural location, proportion of admissions due to AIDS or PCP, and proportion of patients with pneumonia undergoing bronchoscopy were each associated with the likelihood of diagnosis of PCP in univariate analyses, but only the number of patients with PCP being treated at a hospital (odds ratio [OR] 1.03 for each additional 10 cases/year, 95% confidence interval [95% CI] 1.01-1.05) was associated with the likelihood of diagnosis of PCP in multivariate analyses. Patients were also somewhat more likely to be diagnosed with PCP if there had previously been a case of PCP in a patient with a connective tissue disease at the same hospital (OR 135, 95% CI 0.98-1.85). In-hospital mortality was 45.7%, and was unrelated to hospital characteristics. CONCLUSION: PCP is an uncommon, but often fatal, occurrence in patients with connective tissue disease. A hospital's prior experience with patients with PCP is associated with the likelihood that this condition is diagnosed in patients with connective tissue diseases who present with pneumonia, suggesting that diagnostic suspicion is an important factor in the correct identification of affected patients.