Clinical Characteristics and Outcomes of Polyarteritis Nodosa: An International Study

Abstract

Objective: We describe the demographics, clinical features, disease course, and survival of polyarteritis nodosa (PAN) through an international collaboration (GLOBAL-PAN).

Methods: Patients with PAN were recruited between 1990 and 2020 from observational cohorts of nine countries across Europe, Japan, and North America. Eligibility was retrospectively defined using the European Medicines Agency classification algorithm. Patients with PAN related to hepatitis B virus (n = 12) and two monogenic diseases mimicking PAN, deficiency of adenosine deaminase 2 enzyme (n = 16) or familial Mediterranean fever (n = 11), were excluded. Data regarding organ involvement, relapse, disease-related damage, and survival were analyzed.

Results: Three hundred fifty-eight patients (female:male ratio 174:184), including those with systemic PAN (sPAN, n = 282) and cutaneous PAN (n = 76), were included. Twenty-five were pediatric onset. Mean ± SD age at diagnosis was 44.3 ± 18.1 years. Constitutional symptoms (71.5%), cutaneous involvement (70.5%), musculoskeletal findings (69.1%), and neurologic features (48.0%) were common manifestations. Among patients with sPAN, gastrointestinal involvement and proteinuria over 400 mg/day were reported in 52.2% and 11.2%, respectively. During a median (interquartile range) 59.6 (99.5) months of follow-up, relapse occurred in 48.5% of patients. One, 5- and 10-year survival rates for sPAN were 97.1%, 94.0%, and 89.0%, respectively. Predictors of death for sPAN included age ≥65 years at diagnosis, serum creatinine at diagnosis >140 μmol/L, gastrointestinal manifestations, and central nervous system (CNS) involvement.

Conclusion: The spectrum of PAN remains a complex, multifaceted disease. Relapse is common. Age ≥65 years and serum creatinine >140 μmol/L at diagnosis, as well as gastrointestinal and CNS involvement, are independent predictors of death in sPAN.

Figure 1:

Flow-chart of the patient selection and classification

Figure 2:

Evaluation of the first relapse in patients with polyarteritis nodosa. Survival curves for relapse for all patients (Fig2A), comparison of systemic vs cutaneous polyarteritis nodosa (Fig2B) and pediatric-onset polyarteritis nodosa vs adult-onset polyarteritis nodosa (Fig2C)

Figure 3:

Evaluation of the mortality and survival analysis in patients with polyarteritis nodosa Survival curves for all (Fig3A), comparison of systemic vs cutaneous polyarteritis nodosa (Fig3B), relapsing and non-relapsing course polyarteritis nodosa (Fig3C) and pediatric-onset vs adult-onset polyarteritis nodosa (Fig3D). according to the Five Factor Score at diagnosis (Figure 3E)