Rapidly Progressive Glomerulonephritis Clinical Presentation

The most common prodrome of ANCA-associated vasculitis is flulike symptoms characterized by malaise, fever, arthralgias, myalgias, anorexia, and weight loss. This occurs in more than 90% of patients and can occur within days to months of the onset of nephritis or other manifestations of vasculitis.

• Following the prodrome, the most common complaints are abdominal pain, painful cutaneous nodules or ulcerations, and a migratory polyarthropathy.
• When pulmonary or upper airway involvement is present, patients complain of sinusitis symptoms, cough, and hemoptysis.

Hypertension can be present but is not common. Unless specific findings are present, such as those listed below, the physical examination results are usually normal. Organs or systems affected by ANCA-associated disease are listed below.

• Skin

  • Leukocytoclastic vasculitis is common (40-60%) and usually affects the lower extremities.
  • Necrotizing arteritis can result in painful erythematous nodules, focal necrosis, ulceration, and livedo reticularis.
  • Patients with Wegener granulomatosis or Churg-Strauss syndrome can also have granulomatous cutaneous nodules.
  • Nail fold infarcts can be present.
• Nervous system

  • Mononeuritis multiplex is the most common nervous system manifestation of ANCA-associated disease. This condition is caused by inflammation of the epineural arteries and arterioles, which results in ischemia of the nerve tissue.
  • Central nervous system disease can result from involvement of meningeal vessels and manifest as generalized seizures.
  • Nervous system involvement is present in 30% of patients with microscopic polyangiitis and 70% of patients with Churg-Strauss disease.
• Musculoskeletal

  • Pain and elevation in tissue enzyme levels can result from inflammation in the arteries of skeletal muscle.
  • Musculoskeletal involvement is present in 60% of patients with ANCA-associated disease.
  • Arthritis is a very common symptom. It is usually symmetrical and migratory and usually involves the small joints.
  • Arthralgias are also common, but this is not considered a marker of active vasculitis.
• Gastrointestinal

  • Arteritis can result in ischemic ulceration in the GI tract, causing pain and bleeding, which is usually occult.
  • The most serious complications of GI ischemia are intussusception and pancreatitis.
  • GI involvement occurs in 50% of patients with ANCA.
• Renal

  • The diagnostic biopsy finding is proliferative necrotizing crescentic glomerulonephritis.
  • If overt renal disease is not present upon presentation, then the most common finding is microscopic hematuria.
  • The prevalence rate of renal disease is 90% for those with microscopic polyangiitis, 80% for those with Wegener granulomatosis, and 45% for those with Churg-Strauss disease.
• Respiratory

  • Pulmonary manifestations range from fleeting focal infiltrates to hemorrhagic alveolar capillaritis resulting in massive pulmonary hemorrhage and hemoptysis. This is the most deadly complication of ANCA disease.
  • The prevalence rate of pulmonary findings is 50% in those with microscopic polyangiitis, 90% in those with Wegener granulomatosis, and 80% in those with Churg-Strauss disease.
  • Upper respiratory manifestations include sinusitis, otitis media, ulcers in the nasal mucosa, and subglottic stenosis.
• Ocular

  • Iritis, uveitis, and conjunctivitis are the most common ocular manifestations of ANCA.
  • Involvement occurs in approximately 2% of patients with ANCA-associated disease.

The cause of ANCA-associated disease is unknown. A genetic predisposition may exist for the development of this disease. Patients with Wegener granulomatosis are more likely to have abnormal alpha1-antitrypsin phenotypes. Patients who have the Z phenotype are more likely to have aggressive disease. Multiple studies have demonstrated that ANCA-activated neutrophils attack vascular endothelial cells. Because 97% of patients have a flulike prodrome, a viral etiology is possible. However, to date, no evidence exists to support this postulate.