Keywords

Overview

  • Definition

    • An uncommon but potentially lethal multisystem nongranulomatous necrotizing vasculitis of small- or medium-sized arteries, principally at branching and bifurcation points.

    • Typically ANCA negative.

    • Associated with certain viral infections (hepatitis B most common), drug abuse, hyposensitization/desensitization treatment, B cell neoplasms, and acute otitis media.

    • Ocular manifestations occur in 10–20% of patients and include necrotizing scleritis, peripheral ulcerative keratitis, uveitis, and choroidal and retinal vasculitis.

  • Symptoms

    • Redness

    • Exquisite pain – periorbital or with extraocular movements

    • Photophobia

    • Blurry vision

  • Laterality

    • Unilateral or bilateral

  • Course

    • Progressive and fatal without treatment due to renal and cardiac complications (5-year mortality rate is 80–95% if untreated)

  • Age of onset

    • 40–60 years

  • Gender/race

    • M:F = 2:1.

    • No racial predilection per se, but polyarteritis nodosa (PAN) has the highest prevalence in Alaskan Eskimo because the population has a very high rate of hepatitis B infection

  • Systemic association

    Multisystem involvement tends to occur early

    • Renal (75%)

      • Glomerulonephritis, hematuria, hypertension

      • Primary cause of death

    • Cardiac (75%)

      • Coronary thrombosis, pericarditis, pericardial hemorrhage, acute aortitis.

      • Myocardial involvement leads to dysrhythmias and infarction.

      • Second leading cause of death.

    • Cutaneous (20–50%)

      • Cutaneous or subcutaneous nodules along superficial arteries around the knee, anterior lower leg, and dorsum of foot

        • Nodules can rupture resulting in cutaneous hematomas or ecchymosis.

      • Infarction or gangrene involving the fingers or toes

    • Gastrointestinal

      • Abdominal pain caused by intestinal or mesenteric ischemia

      • Infarcts in the liver and spleen

      • Other findings: peritonitis, bowel gangrene and perforation, and intra-abdominal hemorrhage

    • Neurologic

      • Ischemia to peripheral nerves, causing mononeuritis multiplex

    • Genitourinary

      • Epididymitis: virtually pathognomonic in appropriate clinical context

    • Musculoskeletal

      • Non-deforming arthritis

      • Myalgia

Exam: Ocular

External

  • Orbital inflammation, sometimes causing exophthalmos/proptosis

Anterior Segment

  • Conjunctival hyperemia, hemorrhage, or infarction

  • Episcleritis

  • Necrotizing scleritis with peripheral ulcerative keratitis (most common type of scleritis in PAN)

  • Acute nongranulomatous anterior uveitis

Posterior Segment

  • Choroidal and retinal vasculitis (most common)

  • Exudative retinal detachment

  • Vascular occlusion

  • Hypertensive retinopathy

Neuro-Ophthalmic Findings

  • Optic nerve vasculitis causing optic disc edema

  • Vasculitis involving the central and peripheral nervous systems leading to third, fifth, sixth, or seventh cranial nerve palsies, hemianopia, nystagmus, amaurosis fugax, and/or Horner’s syndrome

Exam: Systemic

  • Cutaneous or subcutaneous nodules along superficial arteries of lower extremities

  • Peripheral nerve paresis or paresthesia

  • Abdominal tenderness

  • Testicular/epididymal tenderness

Imaging

  • FA

    • Delayed choroidal filling

    • Retinal arteritis

  • ICG

    • Choroidal infarction

Laboratory and Radiographic Testing

  • Diagnosis is made on clinical and histological grounds.

    • Biopsy of involved tissue may show hemorrhagic vasculitis and fibrinoid necrosis

    • Testicular and skin biopsy confirm diagnosis in 50–80% of patients

  • Hepatitis B panel: 33% have positive surface antigen (HBsAg).

  • Other labs are nonspecific and simply reflect the systemic nature of PAN.

    • Elevated ESR/CRP and neutrophil count

    • Hypocomplementemia

    • Elevated BUN and serum creatinine

    • Urinalysis: RBC, red cell casts, or protein

    • p-ANCA is NOT typically associated with PAN, but a subset of PAN called microscopic polyangiitis (involving even smaller vessels) IS associated with p-ANCA

  • Abdominal and renal angiography.

    • Saccular arterial aneurysms in renal, hepatic, and gastrointestinal vasculature

Differential Diagnosis

  • Systemic vasculitides

    • Granulomatosis with polyangiitis

    • Eosinophilic granulomatosis with polyangiitis (Churg-Strauss)

    • Microscopic polyangiitis

  • Rheumatoid arthritis

  • Adamantiades-Behcet’s disease

  • Systemic lupus erythematosus

  • Dermatomyositis

  • Progressive systemic sclerosis

  • Idiopathic retinal vasculitis, aneurysms, and neuroretinitis (IRVAN)

  • Syphilis

  • Mooren’s ulcer (no scleritis)

Treatment

  • Prednisone 1 mg/kg/day + cyclophosphamide 1–2 mg/kg/day.

  • Biologics in refractory cases, including adalimumab, infliximab, rituximab, tocilizumab, and tofacitinib.

  • Treatment of HBV may produce remission.

Referral/Co-management

  • Rheumatology

  • Nephrology

  • Urology

  • Cardiology

  • Neurology

  • Gastroenterology