ANCA Associated Vasculitis

 

• Background

  Comprises 3 related clinico-pathological syndromes:

  • Granulomatosis with polyangiitis (GPA, formerly Wegener's).
  • Eosinophilic granulomatosis with polyangiitis (EGPA, formerly Churgg-Strauss).
  • Microscopic polyangiitis (MPA).

  Pathphysiology and definition

  • Inflammation and necrosis of small and medium vessels.
  • Characterised by presence of anti-neutrophil cytoplasmic antibodies (ANCA), which may play a role in pathological activation of neutrophils.

  Epidemiology

  • Prevalence 1/4000. GPA commonest > EGPA > MPA rarest.
  • Peak diagnosis 65-74 years, though any age can be affected.
  • Slightly commoner in men.

• Presentation

  Can all manifest with a rash (palpable purpura), glomerulonephritis, pulmonary haemorrhage, and/or mononeuritis.

  GPA

  Commonly features respiratory (presenting complaint in 90%), renal, and constitutional symptoms.

  Upper respiratory:

  • Ears: discharge, pain, muffled hearing, tympanic perforation.
  • Sinus pain.
  • Nose: discharge, epistaxis, nasal septal perforation, ulcers, saddle nose deformity.
  • Mouth/throat: hoarse, stridor, ulcers, mucosal bleeding.

  Lower respiratory:

  • SOB and cough.
  • Haemoptysis due to pulmonary haemorrhage.
  • Chest pain.

  Other features:

  • Renal (later feature): microscopic haematuria, oedema, hypertension, rapidly progressive glomerulonephritis.
  • Constitutional: fatigue, weight loss, anorexia, fever, night sweats.
  • Skin: purpura, ulcers, nodules. Affects 10% at presentation, but later 50%.
  • Mononeuritis multiplex.
  • Eyes: (epi)scleritis, pain, tearing, blurring.
  • Arthralgia
  • Clots and bleeding: intracranial haemorrhage, GI bleed, DVT.

  EGPA

  • Adult-onset asthma.
  • Other allergic symptoms: rhinitis, eosinophilia.
  • Skin: palpable purpura, ecchymoses, nodules, livedo reticularis.
  • Peripheral neuropathy.
  • Renal involvement less common than in other systemic vasculitides (30%).

  MPA

  Distinguished by absence of eosinophilia and granulomas, and sparing of the upper airways.

• Investigations

  Basic bloods:

  • ↓Hb, ↑eosinophils (EGPA), ↑creatinine/urea, ↑ESR/CRP.

  Immunological:

  • ANCA +ve on immunofluorescence, which may have a cytoplasmic pattern (cANCA, commoner in GPA) or perinuclear pattern (pANCA, commoner in EGPA).
  • Follow +ve immunofluorescence with quantitative testing of the actual antibodies using ELISA: anti-PR3 (proteinase-3; commoner in GPA) and anti-MPO (myeloperoxidase; commoner in EGPA).
  • Around 10% are ANCA -ve, with the diagnosis based on other clinical and pathological features.

  Urine:

  • Dipstick: blood, protein.
  • Microscopy: RBC casts.

  Lungs:

  • CXR and CT chest: cavitating nodules, infiltrates.
  • Bronchoscopy: haemorrhage, eosinophils (EGPA).
  • Lung function test: ↑DLCO if there is pulmonary haemorrhage.

  Confirm diagnosis with histology if possible:

  • Renal biopsy: pauci-immune glomerulonephritis i.e. minimal immunoglobulin deposits.
  • Lung biopsy (endoscopic or open): granulomas (but not in MPA).
  • Skin biopsy: leukocytoclastic vasculitis (non-specific).

• Management

  Inducing remission:

  • {Corticosteroids PO/IV} plus {cyclophosphamide or rituximab}.
  • If there is no organ-threatening involvement, methotrexate or MMF monotherapy are possible alternatives.
  • If life-threatening or severe organ involvement, add plasma exchange.

  Maintenance:

  • {Prednisolone PO} plus {azathioprine, methotrexate, or rituximab}.
  • Should continue for at least 2 years.

  Manage treatment side effects:

  • Regular FBC, U&E, LFT.
  • Screen and treat osteoporosis from steroids: Ca2+, bisphosphonates.
  • Co-trimoxazole for Pneumocystis jiroveci prophylaxis.
  • Vaccination: flu, pneumococcal, hep B, HPV.
  • Folate if on methotrexate.

• Complications and prognosis

  Complications:

  • Chronic kidney disease.
  • Side effects of immunosuppressants.

  Prognosis:

  • GPA and EGPA have 80% 5 year mortality if untreated; treatment changes this to 80% survival.
  • Chronic relapsing course if treated. 50% relapse within 5 years.