Polyarteritis Nodosa

A necrotising vasculitis affecting medium sized muscular arteries, characteristically sparing the smallest vessels (arterioles, capillaries and venules) and, in its classical idiopathic form, notably not associated with antineutrophil cytoplasmic antibodies, distinguishing it from the antineutrophil cytoplasmic antibody associated small vessel vasculitides with which it can otherwise share overlapping features.

Pathophysiology and associations

Transmural necrotising inflammation of medium sized arteries produces microaneurysm formation, thrombosis and downstream tissue infarction, with the characteristic angiographic finding of multiple microaneurysms and areas of stenosis along affected vessels.

Classical idiopathic polyarteritis nodosa has become substantially less common with the recognition and separate classification of the antineutrophil cytoplasmic antibody associated vasculitides, and a proportion of cases occur in association with hepatitis B infection, an association that has declined with widespread vaccination but remains important to identify given the specific treatment implications.

Constitutional symptoms (fever, weight loss, malaise) are prominent, often accompanying multisystem organ involvement that reflects the pattern of medium vessel disease.

Cutaneous manifestations include livedo reticularis, subcutaneous nodules along the course of affected arteries, and cutaneous ulceration, reflecting the medium vessel distribution of the underlying pathology.

Peripheral neuropathy, characteristically mononeuritis multiplex with sequential, asymmetrical involvement of individual peripheral nerves, is a hallmark feature and an important clinical clue.

Renal involvement in polyarteritis nodosa reflects a vasculopathy of the renal arteries themselves (causing hypertension and renal infarction) rather than the glomerulonephritis typical of the antineutrophil cytoplasmic antibody associated small vessel vasculitides, an important pathophysiological and clinical distinction.

Gastrointestinal involvement, from bowel ischaemia to perforation, presents with abdominal pain and can be a life threatening surgical emergency.

Testicular pain, from involvement of the testicular artery, is a recognised and relatively specific feature, and cardiac and central nervous system involvement, while less common, contribute significantly to morbidity where present.

Antineutrophil cytoplasmic antibody testing is characteristically negative, an important distinguishing feature supporting the diagnosis in the appropriate clinical context, and hepatitis B serology should be checked in every patient given the specific treatment implications if positive.

Tissue biopsy of an affected, accessible site (skin, nerve, muscle) showing necrotising vasculitis of medium sized arteries provides histological confirmation.

Conventional catheter angiography of the mesenteric, renal or hepatic circulation, demonstrating characteristic microaneurysms and areas of stenosis, is often used where biopsy of an accessible superficial site is not diagnostic or where visceral involvement is suspected.

Nerve conduction studies confirm and localise mononeuritis multiplex where peripheral nerve involvement is suspected clinically.

Full blood count, inflammatory markers, renal function and urinalysis (looking specifically for hypertension and renal impairment from arterial involvement rather than an active nephritic urinary sediment, which would suggest an alternative small vessel process) complete the assessment.

Idiopathic polyarteritis nodosa without hepatitis B association is treated with high dose corticosteroids, with the addition of cyclophosphamide for severe, organ or life threatening disease, followed by maintenance immunosuppression with azathioprine or methotrexate once remission is achieved.

Hepatitis B associated polyarteritis nodosa is managed differently, with a brief initial course of corticosteroids to control the most severe inflammatory manifestations, followed promptly by antiviral therapy as the primary treatment, since prolonged immunosuppression risks exacerbating viral replication and worsening the underlying infection, with plasma exchange used as an adjunct in some protocols.

Aggressive management of hypertension, given the frequency and severity of renovascular involvement, is essential alongside disease specific immunosuppressive or antiviral treatment.

Acute abdominal complications (bowel ischaemia, perforation) require urgent surgical assessment and intervention where they occur.

Long term monitoring for disease relapse, for the sequelae of prior vascular damage (aneurysm, chronic organ ischaemia), and for treatment related toxicity underpins ongoing management, with the overall prognosis for idiopathic disease treated with appropriate immunosuppression being generally favourable compared with the historical natural history of untreated disease.