New research has determined factors that independently increase the risk of death in patients with systemic polyarteritis nodosa (sPAN).

Being aged 65 years and over (HR 3.85, p=0.02), having a serum creatinine level of more than 140 μmol/L at diagnosis (HR 4.93, p=0.005); gastrointestinal presentation (HR 3.51, p=0.03); and CNS involvement (HR 3.56, p=0.02) were all found to be independent mortality predictors in patients with the disease.

The international research, which involved nine countries across Europe (including the UK), Japan and North America, also confirmed PAN to be a “complex, multi-faceted disease”, of which relapse is common, researchers said.

The final analysis, published in Arthritis & Rheumatology, included 358 patients (39 from the UK) diagnosed with either systemic (79%) or cutaneous PAN (21%) between 1990 and 2020, and analysed clinical and demographic characteristics of the disease.

Overall, patients were 51% male, had a mean age of diagnosis of 44 years, and the most common manifestations of the disease were were constitutional symptoms (72%), cutaneous (71%), musculoskeletal (69%), and neurologic (48%) involvement.

Significant differences between characteristics of sPAN and cPAN were seen for: male gender (56% versus 36%, respectively, p=0.002; and constitutional symptoms 79% vs 45%, p<0.001.

Cutaneous manifestations were also seen in 63% of patients with sPAN, but in these patients skin nodules occurred less frequently than in those with cPAN (19% vs 48%; p<0.001), researchers said.

In patients with sPAN neurologic involvement was the most frequent organ/system involvement reported (61%), while gastrointestinal involvement occurred in 52%.

Also of note, disease-related hypertension was observed in 36% and a proteinuria level of more than 400mg/day in 11% of sPAN patients, while 8.5% experienced cardiac issues.

Overall, the median disease duration for PAN was 59.6 months, relapse occurred in just under half (49%) of patients.

Eight patients died from PAN: four because of GI disease (perforation, bleeding, intestinal haemorrhage and necrosis), two from cerebrovascular incidents; and two from kidney failure. The five-year survival for sPAN was 94%.

The researchers noted that PAN is “a challenging disease for the physician because of the lack of specific laboratory markers, the multi-system nature of the disease, and the broad list of differential diagnoses” and highlighted the need for better understanding of its causes and the reasons for its heterogeneity.

Nonetheless, the study’s findings will help to “better define the demographic and clinical characteristic of patients with PAN”, which will be of value to treating clinicians as well as patients and researchers, they stressed.