Polyarteritis Nodosa & Microscopic Polyangiitis

Essentials of Diagnosis

POLYARTERITIS NODOSA

• Medium-sized arteries are affected

• Clinical findings depend on the arteries involved; lungs are spared

• Common features

  • Fever

  • Abdominal pain

  • Extremity pain

  • Livedo reticularis

  • Mononeuritis multiplex

  • Anemia

  • Elevated acute phase reactants (erythrocyte sedimentation rate [ESR] or C-reactive protein or both)

• Kidney involvement causes renin-mediated hypertension

• Associated with hepatitis B (10% of cases)

MICROSCOPIC POLYANGIITIS

• Necrotizing vasculitis of small- and medium-sized arteries and veins

• Most common cause of pulmonary-renal syndrome: diffuse alveolar hemorrhage and glomerulonephritis

• Associated with antineutrophil cytoplasmic antibody (ANCA) in 75% of cases, usually anti-myeloperoxidase antibodies (MPO-ANCA) (that cause a P-ANCA pattern on immunofluorescence testing)

• ANCA directed against proteinase-3 (PR3-ANCA) (that cause a C-ANCA pattern on immunofluorescence testing) can also be observed

General Considerations

POLYARTERITIS NODOSA

• A necrotizing arteritis of medium-sized vessels that has a predilection for involving the skin, peripheral nerves, mesenteric vessels (including renal arteries), heart, and brain but spares the lungs

• Relatively rare, with a prevalence of about 30 cases per 1 million people

• Approximately 10% of cases are caused by hepatitis B; most cases of hepatitis B–associated disease occur within 6 months of onset of hepatitis B infection

MICROSCOPIC POLYANGIITIS

• A pauci-immune nongranulomatous necrotizing vasculitis that

  • Affects small blood vessels (capillaries, venules, or arterioles)

  • Often causes glomerulonephritis and pulmonary capillaritis

  • Often is associated with ANCA on immunofluorescence testing (directed against MPO, a constituent of neutrophil granules)

• Appears in a spectrum overlapping with both polyarteritis nodosa and granulomatosis with polyangiitis (formerly Wegener granulomatosis) because it

  • May involve medium-sized as well as small blood vessels

  • Tends to affect capillaries within the lungs and kidneys

• Rarely medications induce a systemic vasculitis associated with high titers of p-ANCA and features of microscopic polyangiitis, particularly

  • Propylthiouracil

  • Hydralazine

  • Allopurinol

  • Penicillamine

  • Minocycline

  • Sulfasalazine

Symptoms and Signs

POLYARTERITIS NODOSA

• Fever, malaise, weight loss, and other symptoms develop over weeks to months

• Pain in the extremities

• Vasculitic neuropathy

• Livedo racemosa, subcutaneous nodules, and skin ulcers reflect involvement of deeper, medium-sized blood vessels

• Digital gangrene is common

• Lower extremity ulcerations, usually occurring near the malleoli

• Renin-mediated hypertension due to involvement of renal arteries

• Acalculous cholecystitis or appendicitis caused by compromised function of major viscera

• Dramatic presentation in some cases

  • Acute abdomen caused by mesenteric vasculitis and gut perforation

  • Hypotension resulting from rupture of a microaneurysm in the liver, kidney, or bowel

• Subclinical cardiac involvement is common; overt cardiac dysfunction occurs occasionally

• Lungs are seldom (if ever) involved

MICROSCOPIC POLYANGIITIS

• "Palpable" (or "raised") purpura and other signs of cutaneous vasculitis (ulcers, splinter hemorrhages, vesiculobullous lesions)

• Pulmonary-renal syndromes (eg, anti-glomerular basement membrane disease)

• Interstitial lung fibrosis that mimics usual interstitial pneumonitis; conveys poor prognosis

• Pulmonary hemorrhage may occur

• Pathologic findings in the lung are typically those of capillaritis

• The renal lesion is a segmental, necrotizing glomerulonephritis, often with localized intravascular coagulation and the observation of intraglomerular thrombi upon renal biopsy

• Vasculitic neuropathy (mononeuritis multiplex)

Differential Diagnosis

• Genetic collagen vascular disorders (such as Ehlers-Danlos, Loey Dietz syndromes)

• Fibromuscular dysplasia

• Segmental arterial mediolysis

Laboratory Tests

POLYARTERITIS NODOSA

• Slight anemia and leukocytosis are common

• Acute phase reactants (ESR, CRP) are often (but not always) strikingly elevated

• Patients are ANCA-negative

• Rheumatoid factor or antinuclear antibodies may be present in low titers

• Tests for active hepatitis B infection (HBsAg, HBeAg, hepatitis B viral load) should be performed

MICROSCOPIC POLYANGIITIS

• Microscopic hematuria, proteinuria, and red blood cell casts may be present in the urine

• Careful scrutiny of the urine sediment is essential to assess for active renal disease

• 75% of patients are ANCA-positive

• Elevated acute phase reactants are also typical of active disease

Diagnostic Procedures

POLYARTERITIS NODOSA

• Requires confirmation with either a tissue biopsy or an angiogram

• Biopsies of symptomatic sites such as skin (from the edge of an ulcer or the center of a nodule), nerve, or muscle have sensitivities of approximately 70%

• The least invasive tests should usually be obtained first, but biopsy of an involved organ is essential

• If performed by experienced physicians, tissue biopsies normally have high benefit-risk ratios because of the importance of establishing the diagnosis

• Angiographic finding of aneurysmal dilations in the renal, mesenteric, or hepatic arteries is diagnostic when PAN is suspected based on mesenteric ischemia or new-onset hypertension occurring in the setting of a systemic illness

• Angiography must be performed cautiously in patients with baseline kidney disease

Medications

POLYARTERITIS NODOSA

• Corticosteroids in high doses (up to 60 mg of prednisone orally daily) may control fever and constitutional symptoms and heal vascular lesions

• Pulse methylprednisolone (eg, 1 g intravenously daily for 3 days) may be necessary for patients who are critically ill at presentation

• Immunosuppressive agents, especially cyclophosphamide, appear to improve the survival of patients when given along with corticosteroids

• Methotrexate or azathioprine are used to maintain remissions induced by cyclophosphamide

• For cases associated with hepatitis B, the treatment of choice is a short course of prednisone accompanied by antiviral therapy (eg, entecavir) and plasmapheresis (three times a week for up to 6 weeks)

• Inhibitors of TNF are first-line therapy for the polyarteritis associated with deficiency of adenosine deaminase 2

MICROSCOPIC POLYANGIITIS

• Treated in the same way as granulomatosis with polyangiitis

• Patients with severe disease, typically involving pulmonary hemorrhage and glomerulonephritis, require urgent induction treatment with corticosteroids and either cyclophosphamide or rituximab

• If cyclophosphamide is chosen, it may be administered either in an oral daily regimen or via intermittent (usually monthly) intravenous pulses

• Following the induction of remission, treatment with azathioprine, rituximab, or methotrexate (provided the patient has normal kidney function) should be continued

• In cases of drug-induced MPO-ANCA-associated vasculitis,

  • The offending medication should be discontinued

  • Significant organ involvement (eg, pulmonary hemorrhage, glomerulonephritis) requires immunosuppressive therapy

Complications

• Mesenteric vasculitis can cause bowel ischemia with bleeding or perforation

Prognosis

POLYARTERITIS NODOSA

• Without treatment, the 5-year survival rate in these disorders is about 10%

• With appropriate therapy, remissions are possible in many cases and the 5-year survival rate has improved to 60–90%

• Poor prognostic factors

  • Chronic kidney disease with serum creatinine > 1.6 mg/dL (> 141 mcmol/L)

  • Proteinuria > 1 g/day

  • Gastrointestinal ischemia

  • CNS disease

  • Cardiac involvement

• In the absence of any of these five factors, 5-year survival is nearly 90%

• Survival at 5 years drops to 75% with one poor prognostic factor present and to about 50% with two or more factors

• Relapses following the successful induction of remission occur in only about 20% of cases

MICROSCOPIC POLYANGIITIS

• Early diagnosis is key to a good outcome

• Patients with microscopic polyangiitis are more likely than those with granulomatosis with polyangiitis (formerly Wegener granulomatosis) to have significant fibrosis on renal biopsy

• The likelihood of disease recurrence following remission is about 33%

When to Refer

• Refer to a rheumatologist to assist with establishing the diagnosis and planning therapy

When to Admit

• Admit for therapy whenever new visceral complications, such as bowel ischemia, cardiomyopathy, or rapidly progressive neuropathy, develop