Wegener’s Granulomatosis

Synonyms

2

Overview

Wegener's granulomatosis is a form of vasculitis that affects the lungs, kidneys and other organs. Due to its end-organ damage, it can be a serious disease that requires long-term immune suppression. It is named after Dr. Friedrich Wegener, who described the disease in 1936. Wegener's granulomatosis is part of a larger group of vasculitic syndromes, all of which feature the presence of an abnormal type of circulating antibody termed ANCAs (antineutrophil cytoplasmic antibodies) and affect small and medium-size blood vessels. Apart from Wegener's, this category includes Churg-Strauss syndrome and microscopic polyangiitis. Although Wegener's granulomatosis affects small and medium-sized vessels, it is formally classified as one of the small vessel vasculitides in the Chapel Hill system.

Symptoms

  • rhinitis is usually the first sign 
  • upper airway issues: eye and ear diease
  • nose pain or stiffness
  • nosebleeds and crusting
  •  saddle nose deformity due to a perforated septum 
  • conductive hearing loss due to auditory tube dysfunction
  • sensorineural hearing loss 
  • strawberry gingivitis
  • underlying bone destruction learing to tooth loosening 
  • non-specific ulcerations throughout oral mucosa
  • pseudotumors of the eyes 
  • scleritis
  • conjunctivitis
  • uveitis
  • episcleritis
  • subglottal stenosis
  • pulmonary nodules referred to as "coin lesions"
  • infiltrates often interpreted as pneumonia
  • cavitary lesions
  • pulmonary hemorrhage 
  • rapidly progressive segmental necrotising glomerulonephritis of kidney
  • chronic renal failure 
  • arthritis
  • pain and swelling of joints 
  • nodules on the elbow
  • purpura
  • sensory neuropathy
  • mononeuritis multiplex heart, gastrointestinal tract, brain, and other organs

Causes

Its causes are unknown, although microbes, such as bacteria and viruses, as well as genetics have been implicated in its pathogenesis.

Prevention

There is no known prevention.

Diagnosis

Wegener's granulomatosis is usually only suspected when a patient has had unexplained symptoms for a long period of time. Determination of ANCAs can aid in the diagnosis, but positivity is not conclusive and negative ANCAs are not sufficient to reject the diagnosis. Cytoplasmic staining ANCAs that react with the enzyme proteinase 3 (cANCA) in neutrophils (a type of white blood cell) are associated with Wegener's. If the patient has renal failure or cutaneous vasculitis, these are the most logical organs to obtain a biopsy from. Rarely, thoracoscopic lung biopsy is required. On histopathological examination, a biopsy will show leukocytoclastic vasculitis with necrotic changes and granulomatous inflammation (clumps of typically arranged white blood cells) on microscopy. These granulomas are the main reason for the appellation of "Wegener's granulomatosis," although it is not an essential feature. Unfortunately, many biopsies can be nonspecific and 5% provide too little information for the diagnosis of Wegener's. Differential diagnosis (alternative possible diagnoses) can be extensive. ANCAs can be positive after the use of certain drugs and other forms of vasculitis can present with very similar symptoms. The saddle-nose deformity may also be seen in relapsing polychondritis, cocaine abuse and in congenital syphilis.

Prognosis

Today, with corticosteroids and cyclophosphamide, 5-year survival is over 80%. Long-term complications are common (86%), mainly chronic kidney failure, hearing loss and deafness.

Before modern treatments, the 2-year mortality was over 90% and average survival five months. Death usually resulted from uremia or respiratory failure.

Treatment

The standard treatment for Wegener's granulomatosis  is cyclophosphamide and high dose corticosteroids for remission induction and less toxic immunosuppressants like azathioprine, leflunomide, methotrexate or mycophenolate mofetil. Trimethoprim/sulfamethoxazole may also help prevent relapse. Rituximab may be substituted for cyclophosphamide in inducing remission. A systematic review of 84 trials examined the evidence for various treatments in Wegener's granulomatosis. Many trials include data on pooled groups of people with wegener's granulomatosis and microscopic polyangiitis. In this review, cases are divided between localised disease, non-organ threatening, generalized organ-threatening disease and severe kidney vasculitis and immediately life-threatening disease.

  • In generalised non-organ-threatening disease, remission can be induced with methotrexate and steroids, where the steroid dose is reduced after a remission has been achieved and methotrexate used as maintenance.
  • In case of organ-threatening disease, pulsed intravenous cyclophosphamide with steroids is recommended. Once remission has been achieved, azathioprine and steroids can be used to maintain remission.
  • In severe kidney vasculitis, the same regimen is used but with the addition of plasma exchange.
  • In pulmonary haemorrhage, high doses of cyclophosphamide with pulsed methylprednisolone may be used, or alternatively CYC, steroids, and plasma exchange.