Wegener granulomatosis

What is Wegener granulomatosis?

Wegener granulomatosis is an uncommon but potentially fatal form of vasculitis. There is an immune reaction in which antibodies damage blood vessel walls and surrounding tissues.

Multiple organs are often involved. The most common affected sites are the ear, nose, throat, lungs, eyes and kidneys. Mild forms without kidney involvement may occur.

In 2011, Wegener granulomatosis was renamed granulomatosis with polyangiitis, to reflect its granulomatous pathology in association with small vessel vasculitis.

What causes Wegener granulomatosis?

The cause of Wegener granulomatosis is unknown. It is possible some kind of infection is involved. It does not appear to have a genetic basis.

Who is at risk of Wegener granulomatosis?

Wegener granulomatosis affects both sexes equally. It occurs in patients of all ages with a mean age of 41 years. It occurs more commonly in white patients than in blacks or Asians.

What are the clinical features?

Systemic symptoms

Patients may complain of various non-specific symptoms especially:

• Fever affects 25%-50%
• Weight loss of >10 % of usual body weight affects 15-35%

Upper airway

Symptoms affecting the ear, nose and throat are common, affecting 70% of patients at onset and in 92% of patients during the course of the disease.

ENT manifestations include:

• Sinusitis, nose bleeds or saddle nose deformity
• Ear pain or hearing loss (otitis media)
• Painful mouth ulcers, gum disease (strawberry gums),
• Subglottic stenosis (narrowing of the airway), presenting with hoarseness, stridor (noisy breathing) or life-threatening airway obstruction.

Wegener granulomatosis

Lip ulceration

Lungs

Lung involvement occurs in 45% of patients at presentation and 87% during the course of the disease, most often resulting in:

• Cough
• Hemoptysis (coughing up blood)
• Chest pain (pleuritis)

Chest x-rays may be abnormal, either showing diffuse disease (67%) or isolated areas (58%).

Kidneys

Renal involvement occurs in 20% of patients at presentation and in 85% during the course of Wegener granulomatosis. It may manifest as oliguria 9decreased urine production) and haematuria (blood in urine).

Close monitoring of renal function is required for all patients (blood and urine tests).

Eye

Eye symptoms occur in 28-58% of patients with Wegener granulomatosis and are part of the initial presentation in 8 to 16% of patients. The most common problems are:

• Proptosis (bulging of the eye)
• Pain (which may be very severe)
• Loss of vision.

Skin

The skin may be affected in 40-50% of patients with Wegener granulomatosis. Skin problems include:

• Ulcers
• Palpable purpura (raised dark red spots due to vasculitis)
• Nodules, papules and vesicles (small blisters)
• Pyoderma gangrenosum (rare)
• Raynaud phenomenon (white/purple fingers on exposure to the cold). This is rare in Wegener granulomatosis.

Muscles and joints

Musculoskeletal problems occur in 30-50% of patients at presentation and in 65-75% of patients during the course of the disease. These include:

• Muscle pain (myalgia)
• Aching joints (arthralgia)
• Arthritis.

Nervous system

Neurological symptoms are rarely a presenting feature but may occur in 22-50% of patients during the course of the disease. Peripheral nerves are mostly affected leading to loss of or abnormal sensations or weakenss of some muscles. Involvement of the central nervous system (i.e. the brain and spinal cord) occurs in <10% of cases.

Gastrointestinal tract

The exact frequency of gastrointestinal symptoms is unknown. Symptoms are most often:

• Abdominal pain
• Diarrhoea
• Bleeding.

Heart

Cardiac problems occur in 12-30% of cases. These include:

• Inflamed heart sac (pericarditis)
• Angina (cardiac ischaemia)
• Palpitations (irregular heart rhythm).

How is Wegener granulomatosis diagnosed?

The diagnosis is not always straightforward.

Blood count abnormalities may include:

• Raised white cell count (leucocytosis)
• Reduced haemoglobin (normocytic normochromic anaemia)
• Raised platelet count (thrombocytosis)
• Raised erythrocyte sedimentation rate (ESR)

Antineutrophil cytoplasmic antibody (ANCA) is the most useful blood test. A particular type of ANCA is highly specific for Wegener granulomatosis and affects 70% of patients with the disease. It is recognised by cytoplasmic staining pattern (hence it is called c-ANCA) and is directed against an enzyme, proteinase-3. Protoplasmic-staining perinuclear antineutrophil cytoplasmic antibodies, called p-ANCA, occur in 70% of people with Wegener granulomatosis.

A positive test result for rheumatoid factor occurs in 50-60% of patients and can be misleading because this normally indicates rheumatoid arthritis.

A skin biopsy may be helpful if it demonstrates granulomatous vasculitis (inflamed blood vessels with a certain pattern of inflammation).

What is the treatment?

Treatment for Wegener granulomatosis may include:

• Glucocorticoids
• Cyclophoshamide
• Methotrexate
• Ciclosporin
• Antibiotics
• Intravenous immunoglobulin
• Newer biologic agents, including rituximab

What is the prognosis?

Wegener granulomatosis may be slowly or rapidly progressive. There is often no way to predict which patients will continue to have limited, milder forms of the disease and which will go on to more severe progressive, generalised forms of the disease.

Disease activity should be monitored regularly. It is especially important to closely check kidney function. Many different specialists may need to be involved in the patient’s care. Careful and long-term follow-up is required.