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At a glance

Systemic necrotizing vasculitis affecting medium sized arteries. The subsequent tissue ischemia can affect any organ including skin, kidneys, musculoskeletal, cardiovascular, gastrointestinal, and nervous systems. It is associated with infection or hematological cancers and a recessive loss of function of a growth factor (ADA2).

Synonyms

Periarteritis Nodosa; Kussmaul’s Disease; Necrotizing Arteritis Syndrome.

History

First described in 1866 by Kussmaul and Meier. They identified a condition that consisted of “focal, inflammatory, artery nodules.”

Incidence

Estimated between 3 and 4.5:10,000 population. Onset is generally between the ages of 40 and 50 but may also occur at any age. The male-to-female ratio is 3:1.

Genetics

Autosomal recessive.

Pathophysiology

The variety of pathologic features suggests multiple pathogenic mechanisms. Loss of function mutations in the CECR1 (Cat Eye Syndrome chromosome region, candidate 1) gene on chromosome 22q11.1, encoding adenosine deaminase 2 (ADA2) are associated with a spectrum of vascular and inflammatory phenotypes, ranging from early-onset recurrent stroke to systemic vasculopathy or vasculitis. The severity of the condition may, therefore, also be influenced by the specific mutations and by modifying factors. Spontaneously occurring polyarteritis nodosa occurs in hyperimmunized human volunteers, in animals with experimental serum sickness, and in patients developing hypersensitivity reactions. Drugs (eg, sulfonamides, penicillin, iodide, thiouracil, bismuth, thiazides, guanethidine, methamphetamine), vaccines, bacterial infections (eg, streptococcal, staphylococcal), and viral infections (eg, serum hepatitis, influenza, HIV) have been associated with disease onset. Segmental, necrotizing inflammation of media and adventitia characterizes the lesion. The pathologic process most commonly occurs at points of vessel bifurcation, beginning in the media and extending into the intima and adventitia of medium-sized arteries, often disrupting the internal elastic lamellae. Early endothelial lesions contain polymorphonuclears and occasionally eosinophils; later lymphocytes and plasma cells can be seen. Immunoglobulin, complement components, and fibrinogen are deposited in the lesions, but their significance is unclear. Intimal proliferation with secondary thrombosis and occlusion leads to organ and tissue infarction. Weakening of the muscular vessel wall may cause small aneurysms and arterial dissection. Healing can result in nodular fibrosis of the adventitia.

Diagnosis

Histologically, it is a necrotizing angiitis of small- and medium-size vessels whose manifestations are weight loss, fever, asthenia, peripheral neuropathy, renal involvement, musculoskeletal and cutaneous manifestations, hypertension, gastrointestinal (GI) tract involvement, cardiac failure, and cerebral infarcts.

Clinical aspects

Attacks of fever and cutaneous rash that occasionally progress to gangrene and amputation of distal portions of toes and fingers. The cutaneous PAN is usually restricted to the musculoskeletal system and skin. Clinical findings can range from isolated cutaneous findings to widespread multisystemic involvement (kidney, heart, liver). The illness may present as ischemic colitis. Cardiac failure may be caused by pericardial thickening or by histological changes of the ...

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