VASCULITIDES

The vasculitides are a group of diseases characterized by a noninfectious necrotizing vasculitis and resultant ischemia. Considerable overlap in the clinical manifestations of these diseases makes it difficult to develop categories with strict criteria. A practical approach has been to classify them into groups by the size of vessels involved, the specific anatomic sites involved, and the clinical manifestations. Some of the more important ones are discussed here.

Polyarteritis Nodosa

Polyarteritis nodosa has been considered the prototype of the vasculitides. This rare disease has an incidence of less than 1 in 100,000 per year. It affects males and females equally and is seen in all racial groups. Patients are usually in the fifth and sixth decades of life at presentation. The vasculitis involves small and medium-sized arteries and can be the result of hepatitis B infection. Tissues involved include the gastrointestinal tract, hepatobiliary system, kidney, pancreas, skin, testicles, peripheral nerves, and the skeletal muscles. Symptoms at presentation are primarily constitutional (fever, weight loss, and malaise) with peripheral neuropathy (mononeuritis multiplex).

Despite widespread arterial involvement, otolaryngologic manifestations are few, but sudden bilateral sensorineural hearing loss can be seen. Vestibular disturbances also have been reported. The proposed mechanism of cochleovestibular damage is thromboembolic occlusion of the end arteries of the inner ear. Other head and neck manifestations include cranial nerve palsies, in which the seventh nerve is most commonly involved and skin or mucosal lesions.

Churg-Strauss Syndrome

Churg-Strauss syndrome, also called allergic angiitis granulomatosis, is a disease consisting of systemic small-vessel vasculitis, extravascular granulomas, and hyperesosinophilia. It occurs in patients with preexisting asthma and allergic rhinitis. The vasculitis generally presents with peripheral neuropathy or pulmonary infiltrates. Tissue eosinophilia is another feature of this disease.

Hypersensitivity Vasculitides

The hypersensitivity vasculitides are a heterogeneous group of small-vessel vasculitides that universally involve the skin, arteritic involvement of small vessels (particularly postcapillary venules), and leukocytoclasis. Diseases in this group include hypersensitivity angiitis, Henoch-Schönlein purpura, and cryoglobulinemia vasculitis. These syndromes appear immune complex mediated and may be triggered by a foreign antigen, which is often not identified. Therapy is concentrated on identification and elimination of inciting antigens. Glucocorticoids, immunosuppressive drugs, and plasmapheresis are commonly used in treatment.

Wegener Granulomatosis

Wegener granulomatosis is a rare (incidence of less than 1 in 100,000 per year) form of vasculitis characterized by the triad of respiratory tract granulomas, vasculitis, and glomerulonephritis (Wegener’s triad). There is no sex predilection. Most patients are white and present in the fifth decade of life. The typical clinical features include bilateral pneumonitis (95% of patients), chronic sinusitis (90%), mucosal ulceration of nasopharynx (75%), and evidence of renal disease (80%). The nasal symptoms usually occur early in the disease and include crusting, epistaxis, and rhinorrhea. Erosion of the septal cartilage with saddle-nose deformity and nasal stenosis may occur after the vasculitis and granulomata destroy cartilage.

Recurrent sinusitis is the most common problem in patients with Wegener granulomatosis. In some cases, the clinical picture of vasculitis first becomes apparent when the patient has a workup before nasal sinus surgery. In others, it is not until excised sinus mucosa is evaluated histopathologically that the diagnosis of vasculitis is established. Repeated nasal mucosal biopsies are often required as acute inflammation can obscure the subtle changes of vasculitis.

The most common oral cavity findings of Wegener granulomatosis include hyperplasia of the gingiva and gingivitis. Edema and ulceration of the larynx are seen in 25% of patients. Significant subglottic stenosis develops in 8.5% of patients and is a poor prognostic sign. Salivary glands may also be involved. Otologic problems develop in 20% to 25% of patients and include conductive hearing loss secondary to serous otitis media; suppurative otitis media, with or without granulation tissue in the middle ear; sensorineural hearing loss, often profound and bilateral; and pinna changes similar to those seen with polychondritis . Facial nerve palsies also have been documented.

The diagnosis is based on the clinical, pathologic, and laboratory findings. The hallmark pathologic lesion in Wegener granulomatosis is necrotizing granulomatous vasculitis. The discovery of cytoplasmic staining antineutrophil cytoplasmic antibody (c-ANCA) has revolutionized the diagnosis of Wegener granulomatosis. The sensitivity of c-ANCA for Wegener granulomatosis ranges from 65% to 90%, and the specificity is quite high, although this test may be positive in patients with polyarteritis nodosum and Kawasaki disease. Despite the high specificity, however, tissue diagnosis must be used to confirm the diagnosis.

Left untreated, Wegener granulomatosis is fatal within 2 years in 93% of cases. However, good control is achieved with corticosteroids and low-dose daily cyclophosphamide. Azathioprine or methotrexate may be alternatives to cyclophosphamide. Isolated sinus disease may be treated with low-dose steroids, topical nasal steroids, saline irrigations, and antibiotics when bacterial superinfection is suspected. Airway compromise may be alleviated with systemic steroids, although significant subglottic stenosis may require tracheostomy.

Giant Cell Arteritis

Giant cell (“temporal”) arteritis is characterized by focal granulomatous inflammation of arteries of medium and small size. Giant cell arteritis is the most common of the vasculitides, and its prevalence increases with age to about 20 per 100,000 persons aged 50 years and older. It is a general arteritis of which temporal arteritis is only one local manifestation. Many believe this disease also encompasses polymyalgia rheumatica. Polymyalgia rheumatica is a clinical syndrome of muscular pain and morning stiffness in the proximal muscle groups without inflammatory joint or muscle disease. Patients with polymyalgia rheumatica have histologic changes in the arteries that are like those in temporal arteritis. In addition, polymyalgia rheumatica is seen in 50% of patients with classic giant cell arteritis. Systemic symptoms, such as low-grade fever, weight loss, and malaise, may precede localized symptoms in all manifestations of the disease. Polymyalgia rheumatica alone is usually self-limiting and responds well to low-dose prednisone therapy. The symptoms of classic giant cell arteritis reflect involvement of the cranial blood supply by the vasculitis. Headache is the initial symptom in 47% of patients. It is the most common symptom, of variable character, and occurs in as many as 90% of patients.

Despite the name, the temporal artery is erythematous and tender in only 50% of patients with giant cell arteritis. The scalp, however, is often very tender. Jaw claudication occurs in as many as 50% of these patients, and 25% have lingual claudication. Vertigo and hearing loss also have been reported. Involvement of the ascending pharyngeal artery can lead to dysphagia. Cranial nerve deficits, vertebrobasilar insufficiency, and psychosis reflect intracranial disease. Blindness occurs in a third of untreated patients and may be heralded by field defects or amaurosis fugax.

In giant cell arteritis, as with several of the vasculitides, the erythrocyte sedimentation rate (ESR) is usually more than 50 mm/h. Although cases with normal or slightly elevated ESRs have been reported, those results usually lead the clinician away from the diagnosis. Confirmation of diagnosis of giant cell arteritis is accomplished with a biopsy of the temporal artery on the most symptomatic side. If the initial biopsy is negative, the contralateral side should be biopsied. False-negative results range from 5% to 40%.

The treatment is with corticosteroids. Normalization of the ESR or C-reactive protein and loss of symptoms are the therapeutic guidelines. The purpose of treatment is both the elimination of pain and prevention of blindness and other vascular complications. Therapy may be required for 5 years or longer.

Behçet Disease

Behçet disease is a vasculitis affecting Japanese and Mediterranean populations that usually presents in the third decade with oral and genital ulcers and uveitis or iritis. These aphthous-like ulcers are characteristically punched out, with or without surrounding erythema, and are covered with a pale pseudomembrane. They are frequently the first symptom of the disease. They are painful lesions that occur singly or in clusters on the lips, gingiva, buccal mucosa, and tongue and are seen less often on the palate and in the oropharynx. The genital ulcers are similar but are deeper and larger. Healing occurs in a few days or weeks, and some scarring results. Symptoms may occur simultaneously or months apart. Morbidity is secondary to CNS involvement, arthritis, and large-vessel arteritis. Eye involvement is seen in 43% to 72% of patients and loss of sight occurs in 25%. Local treatment for oral and genital ulcers is primarily through the use of corticosteroid creams. Local treatment for eye involvement includes topical mydriatics and corticosteroid injections. Fever is treated with antipyretics or nonsteroidal antiinflammatories. Colchicine, azathioprine, methotrexate, corticosteroids, and dapsone are used systemically.

Cogan Syndrome

Cogan syndrome is a rare disease of young adults (median age 22) characterized by Ménière-like audiovestibular dysfunction, interstitial keratitis, and nonreactive tests for syphilis. The symptoms frequently begin after an upper respiratory infection. Audiovestibular manifestations are usually bilateral and can include fluctuating hearing loss, vertigo, tinnitus, and aural pressure. These symptoms may resolve spontaneously and reappear months later. The hearing loss is progressive and severe and usually associated with decreased or absent vestibular responses on caloric testing. Bilateral deafness results in 65% of cases. The ear symptoms may precede or follow the ocular disease by several years. Often, Cogan syndrome is accompanied by a large- or medium-vessel systemic vasculitis. Pathologic features suggest end-organ specific autoimmune mechanisms rather than vasculitis damage to the inner ear. Hearing outcomes are improved with early initiation of systemic corticosteroid treatment so early diagnosis is critical. Permanent visual loss is rarely seen.

Kawasaki Disease

Kawasaki disease, also known as mucocutaneous lymph node syndrome, is a disease of the pediatric age group and the most common cause of acquired heart disease in children in the developing world. The cause is unknown, but epidemiologic data suggest an infectious cause. Clinical characteristics include fever, conjunctivitis, red and dry lips, erythema of the oral mucosa, polymorphous truncal rash, desquamation of the fingers and toes, and cervical lymphadenopathy. Although cervical adenopathy is the least common feature, seen in 50% to 75% of patients, this disease must be considered in febrile children with cervical lymphadenopathy unresponsive to antibiotics without an alternative diagnosis. Twenty percent to 25% of untreated children develop coronary artery dilation or aneurysms, and a small percentage die from myocardial infarction due to thrombosis or rupture of coronary aneurisms, usually from 2 to 12 weeks after onset of disease. Treatment with intravenous d-globulin and aspirin in the first 10 days of illness reduce the incidence of coronary abnormalities 10-fold.