OVERVIEW
Polyarteritis nodosa (PAN), first reported in 1866 by Kussmaul and Maier, is a necrotizing vasculitis characterized by involvement of small and medium-sized vessels in multiple systems. The lesions are segmental, occurring at the bifurcation of blood vessels, may invade adjacent veins, and may occasionally involve arteries or microvessels distal to the vessels.PAN may affect any organ, but the skin, joints, peripheral nerves, gastrointestinal tract, and kidneys are most susceptible to the disease. If left untreated, the prognosis is very poor.
Etiology
In 1970, Gocke et al. reported that PAN was associated with hepatitis B surface antigen (HBsAg) positivity, and immune complexes containing HBsAg could be seen in the vessel wall, which provided a strong support for the hypothesis that PAN is usually secondary to the precipitation of soluble immune complexes. However, there are many HBsAg carriers in China, while this disease is rare, and PAN can be spontaneous or secondary to the application of certain drugs. Most causes remain unknown.
Symptoms
1. Ocular manifestations
Depending on the extent of vascular damage, almost every part of the eye can be involved. Choroidal vasculitis is the most common histologic abnormality. Retinal vasculitis can cause retinal hemorrhage, edema with cotton-wool exudates, abnormal retinal vessel diameters, and vascular occlusion Retinopathy can also occur secondary to hypertension. Optic nerve vasculitis can lead to optic disc edema or optic discitis Orbital vasculitis can lead to proptosis. Central and peripheral nervous system vasculitis leading to paralysis of pairs III, V, VI and VII cerebral nerves presenting with isotropic hemianopsia, nystagmus, transient black blindness, and cervical sympathetic paralysis syndrome (Horner’s syndrome) Rarely anterior uveal vasculitis may cause anterior uveitis, with exudation of proteins from the anterior chamber. Conjunctival infarction may present with yellowish elevated brittle damage, bulbar conjunctival edema and subconjunctival hemorrhage Superficial sclera, sclera, and corneoscleral limbal vasculitis may produce scleritis externa, scleritis, and scleritis corneosclerae Ophthalmologic symptoms may be the first manifestation of PAN.
(1) Scleritis The most common type of PAN scleritis is necrotizing anterior scleritis, often accompanied by limbal ulcerative keratitis. Unless correctly diagnosed and treated with systemic control medications, scleritis becomes intensely painful and highly destructive. The corneal ulcer progresses progressively peripherally or centrally, with the ulcerated surface toward the center forming a lip-like raised rim of the cornea The presence or absence of scleritis is used clinically to differentiate Mooren’s ulcer from corneal ulcers in vasculitis-associated disorders (e.g., RAWG, PAN) In most cases, corneal scleritis occurs after the diagnosis of PAN Occasionally, scleritis can be the first clinical manifestation of PAN.
(2) Scleral episcleritis Despite histologic findings of superficial scleral vasculitis clinically scleral episcleritis is very rare and may present as simple or nodular scleral episcleritis.
2. Non-ocular manifestations
Clinical manifestations are varied and can be mild or fulminant with systemic symptoms such as fever, malaise, weight loss and loss of appetite, which may occur in conjunction with cutaneous, joint or neurologic symptoms. Visceral lesions, such as gastrointestinal or renal damage, accompany or follow these characteristic manifestations. Skin lesions include the most characteristic tender purple nodules (Osler’s nodes), purpuric ulcers, reticulocyanosis, and gangrene. Joint involvement is asymmetric, wandering, and does not result in deformity. Rarely, central nervous system manifestations (convulsive hemiplegic encephalopathy and psychiatric symptoms) occur in patients late in the course of the disease.
Mononeuritis or multiple mononeuritis with asymmetric, pain along the course of the nerves or hyperalgesia can be caused by involvement of the blood vessels that nourish the nerves. This lesion has a poorer prognosis than sensory-motor neuropathy complicating RA. Arterial damage is commonly seen in 1 or more abdominal organs Patients have gastrointestinal symptoms manifested by abdominal pain, nausea, vomiting, hepatomegaly, intestinal obstruction, and hemorrhage, infarction, and perforation of internal organs. Patients had renal lesions manifesting as focal or diffuse glomerulonephritis and renal ischemia. Manifestations of renal involvement include intermittent proteinuria, microscopic or microscopic hematuria, cellular tubular pattern, and progressive renal failure Renal polyarteritis can cause hypertension, uremia, congestive heart failure, and death. Ovaries, testes and epididymis are commonly affected. Hemorrhagic cystitis may cause significant hematuria and dysuria.
Examination
1. Laboratory tests
There is no specific laboratory test to confirm the diagnosis of PAN. more than 75% of PAN have elevated leukocytes, eosinophils, increased ESR, hematuria, proteinuria suggesting renal involvement, and liver function abnormalities in HBsAg positive patients.
2.Other auxiliary examinations
Angiography reveals small hemangiomas in the liver, kidneys and gastrointestinal tract, which is helpful in the diagnosis of PAN. The occurrence of small hemangiomas is not limited to this disease, but can also be seen in SLE and fibromuscular dysplasia.
Diagnosis.
Tissue biopsy is the most powerful diagnostic tool for PAN, and the diagnosis is confirmed when necrotizing vasculitis of small and medium-sized arteries is found and coincides with a multisystemic clinical picture. Biopsies from symptomatic sites such as the skin, testes, epididymis skeletal muscle and peripheral nerves are most valuable but biopsies from sites without lesions are generally difficult to confirm the diagnosis.
Treatment
A treatment regimen combining prednisone and cyclophosphamide (CTX) is mandatory for patients with PAN scleritis, regardless of the type of scleritis. With prednisone, the dose is reduced after 2 months; after remission, the dose is reduced for maintenance, and both are administered for at least 1 year. If the patient is intolerant to cyclophosphamide (CTX), other immunosuppressive agents including azathioprine, methotrexate, and cyclosporine A may be used.
Prognosis.
Patients with PAN who are not given cytotoxic immunosuppressive agents have a high 5-year mortality rate despite other therapeutic measures. Most deaths are due to renal failure, heart failure, and severe gastrointestinal disorders.