V

Vasculitis

Keywords

Vasculitis, primary CNS angiitis, temporal arteritis, giant cell arteritis, Takayasu arteritis, polyarteritis nodosa, Wegener granulomatosis, Churg-Strauss syndrome, systemic lupus erythematosus, Sjögren syndrome, rheumatoid arthritis, Cogan disease, Behçet disease, herpes zoster ophthalmicus hemiplegia

Definition

Vasculitis refers to a clinicopathologic process characterized by inflammation of the blood vessels. Vasculitides can be primary (idiopathic) or secondary, which is related to the known cause (Table 119). Angiographic beading is common (Figure 65).

Table 119

Common key manifestations and evaluation of vasculitis
Vasculitis Type	Key Clinical Feature	Diagnostic Tests
Giant cell arteritis
Temporal arteritis	Blindness, jaw claudication, high ESR	ESR, temporal artery biopsy
Takayasu arteritis	Pulseless disease, pulse deficit	ESR, angiography
Systemic necrotizing arteritis
Polyarteritis nodosa	Painful mononeuritis multiplex + kidney involvement	Inflammatory markers, angiography, and tissue biopsy
Churg-Strauss syndrome	Granuloma, eosinophilia, mononeuritis multiplex + severe asthma	Inflammatory markers and tissue biopsy
Wegener granulomatosis	Peripheral and cranial neuropathy + upper and lower respiratory tract and kidney involvement	c-ANCA-specific and sensitive, biopsy
Connective tissue disease vasculitis
Systemic lupus erythematosus	Neuropsychiatric lupus, seizure, stroke, optic neuritis, myelitis, systemic involvement	ds- and ss-DNA, ANA titers, angiography, biopsy
Sjögren syndrome	Headaches, aseptic meningitis, myelopathy, mononeuritis + dry mouth and eyes	Schirmer test, salivary gland biopsy, inflammatory markers
Rheumatoid arthritis	Atlantoaxial subluxation with myelopathy + deforming arthritis	RF, plain x-rays, other inflammatory markers
Cogan disease	Encephalomyelitis, polyneuropathy, vestibular and auditory + interstitial keratitis	Inflammatory markers, typical clinical features, biopsy
Behçet disease	Meningitic syndrome, and multiple sclerosis-like picture + recurrent oral and genital ulcers + uveitis	Typical clinical features and inflammatory markers
Hypersensitivity vasculitis
Hypocomplementemia	Encephalomyelitis + peripheral nerve involvement + systemic response	Hepatitis C, complements panel
Cryoglobulinemia	Encephalomyelitis + peripheral nerve involvement + systemic response	Hepatitis C, cryoglobulin levels
Infectious vasculitis
Herpes zoster	Eye and ear involvement + contralateral weakness (stroke)	Typical clinical features with viral titers, PCR
Lyme disease	Encephalomyelitis, polyradiculitis, peripheral nerve involvement + erythema migrans	Lyme titers, exposure to tick bite, CSF analysis
HIV infection	AIDS features, dementia, encephalitis, peripheral nerve involvement	Viral titers, typical clinical features, imaging findings
Drug-induced vasculitis Sympathomimetics (amphetamine, cocaine, phenylpropanolamine, pseudoephedrine)	History of exposure to drugs and cold medicine	Positive toxicology titers, negative inflammatory markers, angiogram

AIDS, acquired immune deficiency syndrome; ANA, anti-nuclear antibodies; ds-DNA, double-stranded DNA; ESR, Erythrocyte sedimentation rate; HIV, human immunodeficiency virus; PCR, polymerase chain reaction; RF, rheumatoid factor; ss-DNA, single-stranded DNA.

Isolated angiitis of the CNS

I. Clinical presentation: This rare disease has nonspecific symptoms, including recurrent headaches, confusion, or focal signs such as hemiparesis or aphasia. Systemic symptoms are generally absent.
II. Diagnosis: Cerebrospinal fluid (CSF) shows mild lymphocytic pleocytosis and elevated protein. Erythrocyte sedimentation rate (ESR) is mildly elevated. Angiography has low sensitivity and specificity. Biopsy of the nondominant frontal or temporal pole with leptomeninges is recommended before treatment.
III. Treatment consists of high-dose prednisone plus cyclophosphamide.

Temporal arteritis (Giant cell arteritis)

I. Clinical presentation: Patients are older than 55 years. It mainly affects the extracranial arteries and tends to spare the intracranial vessels. The superficial temporal and the ophthalmic arteries are commonly involved. The most common symptoms are headaches and constitutional complaints. Jaw claudication is seen in 40% of the patients and is due to ischemia of the muscles. Amaurosis fugax is seen in 10% of patients and is likely to progress to blindness if left untreated. More than half of the patients with temporal arteritis have polymyalgia rheumatica.
II. Physical examination often shows erythematous, tender, tortuous, thickened, and pulseless temporal arteries.
III. Diagnosis: ESR is high in almost all cases. Angiography can demonstrate luminal irregularities and alternating stenosis and dilatation. Temporal artery biopsy should be obtained to confirm the diagnosis histologically.
IV. Treatment should be initiated immediately on the basis of the clinical suspicion with high-dose prednisone and a subsequent slow taper within 2 to 4 weeks of initiating therapy. The ESR can be used to monitor the disease activity. Methotrexate is sometimes considered as an adjunct to glucocorticoid therapy.

Takayasu arteritis (The pulseless disease)

I. Clinical presentation: It affects young women (usually before age 30) of Asian and South American descent. It involves the tunica media of the aortic arch and its proximal branches. The carotids are more affected than the vertebral arteries. The intracranial arteries are typically spared. Constitutional symptoms such as malaise, fever, weight loss, night sweats, myalgia, and arthralgia may be the presenting symptoms. Visual changes, vertigo, syncope, recurrent headache, focal neurologic deficits such as hemiparesis or aphasia, and seizures are common neurologic symptoms.
II. Physical examination reveals pulse deficits and multiple vascular bruits in most cases.
III. Diagnosis: High ESR and angiography are essential for the diagnosis.
IV. Treatment: High-dose oral steroids. If response to the steroids is poor, then methotrexate, azathioprine, or other immunosuppressive therapies can be considered. The ESR is not as reliable a parameter to follow as it is with temporal arteritis. Aggressive surgical treatment, angioplasty, or bypass grafts may improve prognosis significantly in certain cases.

Polyarteritis nodosa

I. Clinical presentation: It usually develops in the fifth or sixth decade of life and affects men almost twice as often as women. This chronic disease causes patchy necrosis in the walls of medium-sized and small arteries. Kidney, heart, and liver are the most frequently affected organs. Central nervous system (CNS) involvement presents with headache, changes in mental status, seizures, visual change, or hemiparesis. The peripheral nervous system is affected in 50% to 60% of the patients. Painful mononeuritis multiplex is common, but polyneuropathies, plexopathies, and radiculopathies can also occur.
II. Diagnosis: The diagnosis is based on angiography or tissue biopsy. Many of the patients are seropositive for hepatitis B or C.
III. Treatment: Steroids combined with cyclophosphamide are the treatment of choice.

Wegener granulomatosis

I. Clinical presentation: Granulomatous, necrotizing vasculitis involves the small arteries and veins in the upper and lower respiratory tract, kidney (glomerulonephritis), skin or eye (50%), CNS, and peripheral nervous system (PNS). Besides the constitutional symptoms, the most common neurologic manifestations are peripheral and cranial neuropathies. Strokes and seizures are less common. The cytoplasmic antineutrophil cytoplasmic antibodies (c-ANCA) titers are sensitive and specific for active Wegener granulomatosis. ESR is usually markedly elevated.
II. Diagnosis: Biopsy of respiratory tract or renal tissues provides the diagnosis.
III. Treatment consists of prednisone combined with cyclophosphamide. Once remission has been established, it is recommended to stop these agents and instead treat with methotrexate, mycophenolate mofetil, leflunomide, or azathioprine.

Churg-strauss syndrome

I. Clinical presentation: Granulomatous vasculitis of the small and medium-sized arteries. Most commonly affects the lungs. There is a strong association with allergic rhinitis, severe asthma, and peripheral eosinophilia. Mononeuritis multiplex may occur, but it is not common.
II. Treatment consists of steroids, and cyclophosphamide may be added.

Systemic lupus erythematosus

I. Clinical presentation: Systemic lupus erythematosus (SLE) is a disease involving multiple organs and mainly affecting women. Besides systemic symptoms, neurologic involvement in SLE is common and includes headaches, cognitive and behavioral changes, psychosis, depression, seizure, cerebral ischemia, myelitis, optic neuritis, cranial and peripheral neuropathies, and movement disorders.
II. Diagnosis: Markers, angiography, and biopsy (noninflammatory vasculopathy) provide the diagnosis.
III. Treatment: For severe CNS manifestations, high-dose IV steroids are given and then slowly tapered to an oral dosage. Cyclophosphamide or azathioprine can be used if steroids fail. Intravenous immunoglobluin (IVIG) and plasmapheresis trial was also reported in the literature.

Sjögren syndrome

I. Clinical presentation: This chronic inflammatory and autoimmune disorder affects lacrimal and salivary glands and causes dry mouth (xerostomia) and dry eyes (xerophthalmia). Neurologic symptoms include headaches, aseptic meningitis, myelopathy, mononeuritis multiplex, and focal deficits.
II. Treatment is supportive, but steroid and immunosuppressive agents are used in life-threatening conditions.

Rheumatoid arthritis

I. Clinical presentation: Systemic arthritis can be seen in up to 25% of adult patients, but the CNS is rarely involved. Myelopathy, brainstem, or cranial nerve deficits and headache can occur due to atlantoaxial subluxation. Peripheral nerve involvement is relatively common, including distal sensory or sensorimotor neuropathy, mononeuropathy multiplex and entrapment, or compression neuropathy.
II. Treatment: High-dose steroid and cyclophosphamide. Other agents such as rituximab have been used.

Cogan disease

I. This is a rare disease of the young. It presents with interstitial keratitis, vestibular and auditory dysfunction, encephalomyelitis, and polyneuropathy.
II. Treatment: Steroids are the treatment of choice. Additional immunosuppressive agents such as methotrexate may be used.

Behçet disease

I. Clinical presentation: Recurrent oral and genital ulcers, uveitis, and nondeforming arthritis are seen. It affects mostly young patients and is more common in eastern Mediterranean countries and in Japan. Neurologic symptoms (10%) are headache, meningitic syndrome, dementia, psychosis, and a multiple sclerosis-like picture.
II. Treatment: Uveitis and CNS involvement require high-dose prednisone in conjunction with azathioprine or cyclosporine.

Herpes zoster ophthalmicus hemiplegia

I. Clinical presentation: This form presents weeks or months after herpes zoster ophthalmicus in an older adult. Involvement of the ipsilateral anterior and middle cerebral arteries causes contralateral hemiparesis.
II. Treatment: Acyclovir and steroids provide treatment.