This study was conducted to investigate the clinical manifestation and the course of PAN in Korean patients. All patients were collected according to ACR criteria. Chapel Hill Consensus Conference defined PAN as necrotizing inflammation of medium-sized or small arteries without glomerulonephritis or vasculitis in arterioles, capillaries, or venules (2
). Thus patients with glomerulonephritis were not present in our patients population. Overall clinical manifestations and disease courses were similar to those reported by other studies () (8
), which reported high incidence of involvement of; peripheral nerve (51-75%), muscle and joint (51%), skin (11-58%), kidney (22-66%), hypertension (14-32%), gastrointestinal tract (25-53%), central nervous system (2-24%), heart (4-18%), and lung (6-40%)() (8
Clinical features of polyarteritis nodosa as reported previously
The reported incidence of orchitis/epididymitis by autopsy studies vary from 60 to 80% (11
), but symptomatic testicular pain is an infrequent presenting manifestation of PAN, and a few reports quote a rate of at presentation orchitis/epididymitis of 2-18% (11
). Our study showed a high rate (24%) of testicular pain or tenderness. These results suggest that orchitis/epididymitis requires cautious checking in Koreans in the presence of musculoskeletal symptoms, livedo reticularis, or mono- or polyneuropathic symptoms and signs.
Some reports have categorized small vessel vasculitis largely into ANCA-associated vasculitis and immune-complex vasculitis (13
). Several groups concluded after a careful histological examination that ANCA is strongly correlated with small-sized vessel involvement (7
). ANCA-associated vasculitis is the most common primary systemic small vessel vasculitis in adults and includes three major categories: microscopic polyangiitis, Wegener's granulomatosis and Churg-Strauss syndrome (7
). On the contrary, PAN is not known to have a high positive rate of ANCA (13
). Our study shows a 14% ANCA positivity rate which is comparable to other foreign reports which showed up to 20%.
Sergent et al. presented substantial evidence which indicated that at least one subset of PAN patients experienced systemic vasculitis as a result of chronic hepatitis B virus associated immune complex disease(24
). Guillevin et al. in France in a 1981-1992 study also reported that 25-30% of PAN patients are associated with hepatitis B, based on HBsAg positivity (10
); however, the rate in the general French population was only 0.3% (25
). In 1990, ACR proposed PAN classification criteria, which included the presence of HBsAg or HBsAb in serum as criteria (1
). Recent epidemiologic data from northeast Asian countries including Korea, China, Taiwan, and Japan, show that the HBsAg positive rate, even after the 1983 global hepatitis B vaccination program was introduced in Korea, is at 4-6%. Also, taking into consideration HBsAb positive rate of 70-80%, the ACR PAN criteria may produce a bias in the northeast Asian population that causes over-diagnosis of PAN (28
). A large scale epidemiologic study may be necessary to investigate whether the high positive rates of HBsAg and HBsAb influence the diagnosis and prevalence of PAN in Korea.
Old age could be an important prognostic factor. The average age of the four fatal vasculitis patients that died was 62 yr, which exceeded the total patient average age of 47.4 yr. According to Guillevin et al., the critical period in terms of mortality is the first year of the disease (5
). Our study also showed no disease related death occurred after 7 months from the diagnosis.
Guillevin et al. established FFS after subjecting every clinical item to univariate and multivariate analyses (11
), and FFS items found to be significantly associated with an increased mortality, namely, renal insufficiency, proteinuria and/or gastrointestinal tract involvement, were found to be the major factors associated with a poor prognosis. They also suggested that renal insufficiency (Cr >1.58 mg/dL) and severe gastrointestinal involvement necessitating surgery are significant predictors of death (6
). In our study no disease related mortality occurred in those with an FFS of 0, in contrast three of the four disease-related mortality cases had an FFS of 2. Disease-related mortality cases showed the following items of five factors; renal insufficiency (3 cases), cardiac involvement (2 cases), central nervous system involvement (1 case) and gastrointestinal tract involvement (1 case). Patients with a higher FFS tended to have a high HR compared with those with a lower FFS in the present study, even though statistical significance was not achieved due to the small number of cases (). FFS may help clinicians develop a prognostic approach to PAN and guide treatment choice (5
Prednisolone based treatment is a well known treatment modality in PAN. Sometimes a cytotoxic agent and plasmapheresis are added. A cytotoxic agent is indicated for patients with disease refractory to corticosteroids or with serious major organ involvement (7
). Plasmapheresis can be performed in fulminant disease or after the failure of another treatment but it may facilitate infection (6
). Most reports on plasmapheresis are based on anecdotal trials or small scale studies. Our study shows no significant difference between the survival rates of those on prednisolone alone and prednisolone plus cytotoxic therapy. Moreover, long term treatment with a cytotoxic agent (e.g. cyclophosphamide) may result in a higher incidence on lymphoma or some other malignancy. We experienced a mortality in a case with non Hodgkin's lymphoma and pneumonia on cyclosporine treatment.
In conclusion, our study demonstrates that the clinical features of polyarteritis nodosa in Korea are similar to those described in other countries. However, the prevalence of testis involvement appears to be high, and patients with high FFS tended to have a poor prognosis.