but can be distinguished by the absence of auricular involvement and the presence of granulomatous lesions in the tracheobronchial tree. Patients with CoganÕs syndrome have interstitial keratitis and vestibular and auditory abnormalities, but this syndrome does not involve the respiratory tract or ears. Relapsing polychondritis may develop in patients with a variety of autoimmune disorders, including SLE, RA, SjšgrenÕs syndrome, and vasculitis. In most cases, these disorders antedate the appearance of polychondritis, usually by months or years. It is likely that these patients have an immunologic abnormality that predisposes them to development of this group of autoimmune disorders.

6.1.8Polyarteritis Nodosa

PAN is a multisystem disease characterized, as it was originally described [293] and later categorized [294], by necrotizing vasculitis of smalland medium-sized arteries. The lesions tend to be segmental, with a predilection for bifurcations and branchings of vessels, with some distal involvement of arterioles and adjacent veins. PAN may be primary (idiopathic) or secondary to drugs or viral infections (e.g., hepatitis B). PAN may involve any organ, but skin, joints, peripheral nerves, gut, and kidney are most frequently involved. Without therapy, the prognosis of PAN is extremely poor, with a 12% 5-year survival in untreated patients. Patients treated with a combination of systemic corticosteroids and immunosuppressive agents have an 80% 5-year survival [295].

6.1.8.1 Epidemiology

PAN is an uncommon disease with an incidence of about 1.8/100,000 population [296]. Onset is most frequent in the fourth or Þfth decade, men are twice as likely to be affected than women, and there is no racial or familial predisposition.

6.1.8.2 Systemic Manifestations

Systemic manifestations of PAN are protean and may range from mild to fulminating. Constitutional symptoms, such as fever, malaise, weight loss, and anorexia, may appear along with skin, joint, or

neurologic manifestations. Visceral involvement, such as gut or kidney, may present concomitantly with, or after, these features [297, 298]. Skin lesions include tender purple nodules (OslerÕs nodes), palpable purpura, ulcerations, livedo reticularis, or gangrenous plaques. Joint involvement consists of an asymmetric, nondeforming polyarthritis involving predominantly the large joints of the lower extremity. Neurologic abnormalities include peripheral nervous system (sensory or sensorimotor neuropathy) and, less commonly, central nervous system (seizures, hemiparesis) manifestations. The presence of sensorimotor neuropathy (mononeuritis multiplex) during the course of PAN does not appear to have as bad prognosis as does sensorimotor neuropathy complicating RA. Gastrointestinal involvement may manifest with abdominal pain, nausea, vomiting, diarrhea, hepatomegaly, ileus, bleeding, infarction, and perforation of visceral organs. Renal disease, occurring in almost 80% of patients, may present as focal or diffuse glomerulonephritis, renal ischemia, or hemorrhagic cystitis. Hypertension is a frequent complication of renal polyarteritis and may lead to uremia, congestive heart failure, and death. Ovarian, testicular, or epididymal involvement is often asymptomatic, but infarction with pain may occur, and in some cases may be the presenting manifestation of PAN.

Other less common clinical Þndings, although frequent pathologically, are cardiac manifestations, such as pericarditis, myocarditis, endocarditis, and myocardial infarction. Pulmonary abnormalities, such as pleuritis and lung inÞltration, also may occur; however, they are more common in patients with granulomatous vasculitis [GPA (Wegener) or allergic granulomatous angiitis (ChurgÐStrauss)].

6.1.8.3 Ocular Manifestations

Ocular manifestations appear in 10Ð20% of PAN patients. PAN may involve every tissue of the eye, depending on which vessels are affected by the vasculitic process. Choroidal vasculitis is the most frequent histologic abnormality [242, 299Ð 305], but the presence of yellow subretinal patches is less often appreciated clinically. Retinal vasculitis may lead to retinal hemorrhages, retinal