Vasculitides


Frequent

Less frequent

Large blood vessels – giant cell (temporal) arteritis

Takayasu’s arteritis

Sarcoidosis (affects large, medium or small blood vessels)

Cogan’s syndrome (affects large or medium blood vessels)

Medium blood vessels

Polyarteritis nodosa and cutaneous form

Familial Mediterranean fever

Kawasaki disease
 
Medium to small blood vessels

Granulomatosis with polyangiitis

(Wegener’s granulomatosis)

Eosinophilic granulomatosis with polyangiitis

(Churg-Strauss syndrome)

Microscopic polyangiitis (polyarteritis)

Behçet’s disease (affects large blood vessels)

Primary angiitis of the central nervous system

Thromboangiitis obliterans

Small blood vessels

Cutaneous leucocytoclastic vasculitis

IgA vasculitis (Henoch-Schönlein purpura)

Cryoglobulinaemic vasculitis

Degas’ disease

Urticarial vasculitis

Myelodysplastic syndromes

Erythema elevatum diutinum

Hyperimmunoglobulinaemia D


Modified according to Ball et al. [3]



Except for giant cell arteritis, the incidence of vasculitides in the elderly is not very frequent. Different diagnoses are reported only in individual cases or small groups of patients. Relatively larger cohorts were studied in case of the Behçet’s disease.



7.2 Large-Sized Vessel Vasculitis



7.2.1 Takayasu’s Arteritis



Definition

Takayasu’s arteritis (TA) is a chronic inflammatory disease affecting large arteries, primarily the aorta and its main branches [4]. It most commonly occurs in young women in the Middle and East Asia.


Aetiology and Pathogenesis

Aetiology of the disease is unknown. Several aetiologic factors have been proposed, including streptococcal infection and hypersensitivity to tuberculin test. A potential role of circulating immune complexes and circulating antibodies to aortic wall components has also been mentioned. Immunogenetic studies have revealed associations with BW52 and DR4 haplotypes.


Clinical Manifestations

The clinical features typically include symptoms of vascular insufficiency of upper limbs, described as arm claudication or arm numbness; loss of pulse or low blood pressure in an arm; and bruits heard most often over the carotids and abdominal aorta, less frequently over the subclavian and femoral arteries. There is often a difference in blood pressure between the arms of more than 30mmHg. Postural nausea is a sign of occlusion of the carotid and vertebrobasilar arterial systems, which may cause a typical partial flexion of the cervical spine. Visual disorders include blurred vision, diplopia or transient unilateral amaurosis. A regular finding is hypertensive retinopathy. Microaneurysms, dilatation of veins and bleeding resemble diabetic retinopathy. Late sequelae include optic nerve atrophy, retinal detachment and vitreous haemorrhage. In the early stages arthralgia, sometimes lower limb synovitis or symmetrical polyarthritis can be observed. Myalgia is frequent and may be misleading. The inflammatory phase of the disease may last for months. Patients are treated for a “fever of unknown origin” for several years before symptoms of vascular insufficiency develop. Skin lesions have often the form of erythema nodosum and lower leg ulcers. Cardiac involvement consists in changes of coronary artery orifices or of their proximal sections. Heart failure is most frequently caused by this disorder or systemic hypertension; myocardial biopsy has proved also myocarditis. Involvement of large- and medium-sized pulmonary arteries is common and leads to pulmonary hypertension, often without a marked clinical manifestation.

Other repeatedly reported clinical features include mesangial proliferative glomerulonephritis or renal amyloidosis. Renal artery stenosis may be multiple and bilateral and is manifested by hypertension.


Laboratory Findings

Most patients exhibit high ESR and CRP, mild anaemia and leucocytosis, with a finding of elevated levels of all immunoglobulin classes, but no antibodies.


Additional Examinations

The key role is played by angiographic examination focused on all branches of the aorta. Additional arteriography depends on the respective clinical features; the currently most frequently used method is digital subtraction angiography. CT scans show aortic wall thickness and its treatment-induced changes. Early inflammatory phase can be well imaged by positron emission tomography (PET). Histologically, the granulomatous phase represents the period of active inflammation with changes in media and adventitia with a mixed cellular infiltrate of lymphocytes, plasma cells and histiocytes together with typical giant cells. In the late stage, the disease is represented by a mild fibrous intimal hyperplasia, medial degeneration and fibrosis of the adventitia.


Diagnosis

TA diagnosis is based on typical distribution of changes in main branches of the aorta, primarily in the left subclavian artery, superior mesenteric artery and other branches of the abdominal aorta. About 85 % of patients exhibit only stenosis and the rest have combined changes.


Differential Diagnosis

In the first place it is necessary to exclude atherosclerosis – TA primarily affects young individuals without risk factors of this disease. Other diseases to be excluded are SLE, Behçet’s disease, aortitis in ankylosing spondylitis, rheumatic fever, Crohn’s disease and syphilitic aortitis. TA may also resemble GCA, congenital coarctation of the aorta, ergotism and thromboangiitis obliterans.


Therapy

The medications of choice are corticosteroids; in the inflammatory phase, prednisone is administered at the initial dose of 0.5–1 mg/kg/day or another preparation with a slow reduction in dose. Therapy is long term, with a continuous ESR control and, after several months, also PET control. Several cases were reported of regression of inflammatory stenosis. Where the dosage of corticosteroids cannot be successfully reduced, cytotoxic treatment should be initiated, including cyclosporine A, cyclophosphamide pulses or azathioprine and lately also methotrexate. In refractory forms, excellent results were achieved with anti-TNF alpha blockers.

Surgical treatment is reserved for selected cases in the case when the disease is under control and includes percutaneous angioplasty, bypass, endarterectomy, resection of aneurysms and valve replacement and often also renal artery surgeries.


Disease Prognosis

The prognosis depends on specific manifestations (Takayasu’s retinopathy, secondary hypertension, aortic insufficiency, aortic and arterial aneurysms).

Patients with stabilised disease survive in 98 % for 6 years. The main cause of death is heart failure and cerebrovascular stroke.

Two cases of late onset of TA were reported by Nakabayashi et al. [5]. The patients developed the disease at the age over 60, with involvement of distal branch arteries and association with rheumatoid arthritis. Angiography showed in both patients a typical involvement of abdominal aorta and subclavian artery stenosis. In addition, the first patient had occlusive lesions of the superficial femoral arteries, and the latter one manifested occlusion of the axillary artery. Laboratory findings showed increased ESR and CRP in both patients and, in the first of them, a positive rheumatoid factor. Both patients presented with swelling, pain and tenderness in small joints. In one of the patients, radiographic examination revealed destructive changes in joints that were absent in the other patient. The histological findings from femoral artery biopsy showed lesions typical of TA. Based upon these findings, the authors diagnosed the two patients as having atypical Takayasu’s arteritis with arthritic manifestations.


7.3 Medium-Sized Vessel Vasculitis



7.3.1 Polyarteritis Nodosa



Definition

Polyarteritis nodosa (PAN) is a disease of small- and medium-sized arteries involving all three arterial wall layers, leading to multiple aneurysms, thrombi and tissue infarction. PAN may be a manifestation or a complication of RA, SSc and other connective tissue disorders.


Aetiology and Pathogenesis

Aetiology is unknown. The pathogenesis is attributed to deposition of immune complexes in various tissues, probably also to hepatitis C (less frequently B) virus, HIV and cytomegalovirus and parvovirus. The role of ANCA antibodies and hypersensitive reaction has not been clarified, yet.


Clinical Manifestations

The severity of the disease may range from a limited condition up to a rapidly progressing form which is usually fatal [6]. Most patients present with general symptoms, such as fever, weakness, weight loss and sometimes rash, peripheral neuropathy and polyarthritis. Sometimes only a single organ is affected, e.g. the skin, peripheral nerves or kidneys. Cutaneous manifestations may include palpable purpura, ulceration, livedo reticularis and ischaemic changes in distal phalanges. Joint involvement includes arthralgia or arthritis. Asymmetrical episodic nondeforming polyarthritis affects the joints of lower extremities. Neurological symptoms may develop in the form of peripheral neuropathy with an abrupt onset including pain and paresthesia of the peripheral nerve, followed by loss of motor function. Gradual involvement of nerves may result in asymmetrical polyneuropathy. Renal insufficiency is manifested by proteinuria; in the early stages, there may occur haematuria. Involvement of renal arteries or glomeruli often results in hypertension. The disease-related GIT disorders are associated with abdominal pain, and their location correlates with the affected organ. In case of diffuse pain, mesenteric artery thrombosis should be considered.

This pain causes also abdominal distension, sometimes even peritonitis, quite often with gastrointestinal bleeding. Cardiac involvement includes heart failure is caused by coronary insufficiency or hypertension. Myalgia induces diffuse involvement of muscle arteries, sometimes in the form of intermittent claudication. Eye manifestation is commonly in the form of retinal detachment or toxic retinopathy.


Laboratory Findings

Include elevated ESR, normochromic anaemia, thrombocytosis and lower serum albumin levels. Part of the patients is HCV or HBsAg positive. The sign of disease activity is decreased complement levels. In the active phase, circulating immune complexes (CICs) are usually elevated.


Additional Examinations

Arteriography appears to be of great value, usually showing saccular or spindle-shaped aneurysms or conical narrowing of arteries. Aneurysms can be found in renal, hepatic, mesenteric, cerebral, lumbar, intercostal, lower phrenic, hypogastric and gastroduodenal arteries. The common examination method is biopsy of skin, skeletal muscles, the sural nerve and the testes. Histological findings include involvement of small- and medium-sized arteries with a predilection at the site of arterial ramification. Typical signs include fibrinoid transformation and massive infiltration of all three arterial wall layers with polymorphonuclear cells and eosinophils. Thromboses and aneurysms typically occur at the sites of changes. Inflammatory foci heal with fibrous tissue causing arterial occlusion. Glomerulonephritis is in most cases segmental and proliferative.


Diagnosis

Diagnosis should be always verified by biopsy, if the affected organ is accessible or by arteriography which shows typical aneurysms.


Differential Diagnosis

It is important to distinguish between IgA vasculitis (IGAV) (formerly Henoch-Schönlein purpura) and anti-GBM nephritis. The renal biopsy finding may be identical to granulomatosis with polyangiitis (GPA) (formerly Wegener’s granulomatosis) and to eosinophilic granulomatosis with polyangiitis (EGPA) (formerly Churg-Strauss syndrome). A number of PAN clinical symptoms may occur also in other diseases. Unless aneurysms are clearly seen, a similar angiographic image can be found in GPA, vasculitis in SLE, thrombotic thrombocytopenic purpura, infective endocarditis and tumours metastasizing to peritoneum. A problem may be dissecting arterial aneurysms.


Therapy

All patients receive corticosteroids, at the beginning preferably in the form of intravenous bolus of methylprednisolone. In case of rapidly progressing extensive visceral involvement, cyclophosphamide pulse therapy should be added. In case of contraindication of cyclophosphamide, azathioprine or methotrexate may be used instead. If these combinations are ineffective, plasmapheresis is used as an adjuvant therapy. In cases associated with hepatitis B, corticosteroids are administered for several days, in combination with antiviral medications. Local, primarily cutaneous, forms respond well to colchicine in combination with topical corticosteroids.


Disease Prognosis

The prognosis depends on the scope of involvement of vital organs. Uncontrollable vasculitis (heart failure and stroke) or infectious complications during immunosuppressive treatment may have fatal consequences.

With the treatment based on corticosteroids alone, 60 % of patients survive for 5 years.

Several cases were described, of PAN with the onset in old age [7]. The reported cohort included also three patients, namely, two women (86 and 75 years old) and one man (75 years old), two of which suffered from hypertension and one from ischaemic heart disease. Of the main signs, all patients had at the onset of the disease fever and fatigue, two of them also polyneuropathy, one had a history of stroke, and two of them had arthritis. Laboratory tests in all of them showed high inflammatory reactants and one positive urine finding. Two patients were positive for perinuclear (pANCA) and one for cytoplasmic (cANCA) antineutrophil cytoplasmic antibodies. All of them were treated with corticosteroids, two with antibiotics and one with addition of cyclophosphamide. Two patients died and in one patient the disease was stabilised.


7.3.2 Kawasaki Syndrome



Definition

Kawasaki syndrome (KS) is a vasculitis affecting coronary arteries with formation of aneurysms and occlusions and a tendency to spontaneous remission. It is characterised by long-term fever, oral mucosal inflammation, skin disorders and cervical lymphadenopathy. It most often affects children younger than 5 years, with a slight predominance in boys.

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Jul 16, 2017 | Posted by in MUSCULOSKELETAL MEDICINE | Comments Off on Vasculitides
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