Granulomatosis with polyangiitis (Wegener's granulomatosis)

Granulomatosis with polyangiitis (Wegener's granulomatosis or Wegener's disease) is a primary granulomatous vasculitis of small vessels (arterioles, capillaries, and venules) characterized by the presence of acute circumferential angiitis and necrotizing giant cell granulomas.

It is a rare disease, with a prevalence of 2 to 3/100,000 inhabitants. There is a seasonal predominance during winter and spring. The average age of diagnosis is 40 to 50 years, and there is a slight male predominance.

Its etiology is unknown, but a history of viral or bacterial infection is found in 40% of cases. A genetic predisposition is suspected (existence of rare familial forms).

Clinical Presentation

The symptomatology usually begins with common ENT or pulmonary signs, but its recurrent evolution, resistance to antibiotics but sensitivity to a short course of corticosteroids, or association with other abnormalities (fever of unknown origin, deterioration of general health, visceral involvement) may suggest the diagnosis.

System	Manifestations	% at onset	% over time
Renal	Rapidly progressive glomerulonephritis in 50% of cases: moderate proteinuria, hematuria, leukocyturia,... Can lead to CKD. Hypertension is rare.	18	77
ENT	Sinusitis, bloody crusty rhinitis, otitis, hypoacusis, otalgia, subglottic stenosis	73	92
Pulmonary	Infiltrates, nodules, hemoptysis, pleurisy, atelectasis, bronchial stenosis	45	85
Eyes	Conjunctivitis, dacryocystitis, scleritis, exophthalmos, optic neuritis, uveitis	10	25
Joints	Arthralgia, arthritis	32	67
General	Persistent or recurrent febrile syndrome	23	50
Skin	Very variable skin lesions (++ purpura, ulcerations)	13	46
Peripheral nervous system	Mono or multineuropathies	1	15
Central nervous system	Cranial nerve involvement, granulomas, cerebral hemorrhages	1	8

Digestive involvement is found in 24% of autopsies, and splenic infarcts in 77%. However, these lesions are rarely symptomatic (ulcerations, hemorrhages, mesenteric infarction, intestinal perforation). Cardiac involvement is very rare, potentially presenting as arrhythmias, pericarditis, or even endocarditis.

Biology

Biological abnormalities are frequent, more so in diffuse forms than localized ones.

• Increased neutrophils
• Thrombocytosis
• Inflammatory syndrome with elevation of all inflammatory proteins
• Very specific: c-ANCA (antiPR3 type) present in 90%, ++ in diffuse forms

Diagnosis

In the event of clinical suspicion of Wegener:

• Complete clinical examination
• CT of the sinuses and thorax with fine sections
• ENT examination
• Electromyogram-NCV
• Repeated analysis of urine sediment and proteinuria
• Biology: the presence of c-ANCA is a strong argument, but their absence cannot exclude the diagnosis
• Biopsies (++ multiple) are often necessary and a strong argument if positive

Therapeutic Management - Treatments

Diffuse forms: combination of

• Corticosteroids: prednisone 1 mg/kg/day. In severe forms, treatment can be initiated with methylprednisolone boluses.
• Oral cyclophosphamide 2 mg/kg/day or methotrexate (20 mg/week) or azathioprine (2 mg/kg/day) in forms not life-threatening
• In case of failure: IV immunoglobulins, plasma exchanges, weekly cyclophosphamide boluses, etc.
• In case of tracheobronchial stenoses: local corticosteroid injections, surgical or laser interventions

This treatment should be continued for at least 1 year after remission... without treatment, the average survival is less than 2 years; with treatment, survival is 85% at 1 year and 50% at 10 years… however:

• Relapses are frequent, even several years later.
• In 85% of cases, patients have sequelae: hearing loss, chronic kidney failure, decreased visual acuity, tracheobronchial stenosis, nasal deformity, etc.
• Prognosis mainly depends on initial renal insufficiency, age, and the diffuse nature of the disease
• The main cause of mortality is infections (followed by neoplasms and heart disease) favored by corticosteroids and immunosuppressants. One in five deaths is still related to renal failure.

Localized forms: to be discussed on a case-by-case basis by specialists... approaches vary from a treatment similar to an attenuation of the treatment for diffuse forms or Bactrim forte 2 tablets/day which has shown its effectiveness, at least in preventing relapses.

Bibliography

EMC, Traité de médecine AKOS, Elsevier, 2018

Jameson JL et al., Harrison's Principles of Internal Medicine, 20th edition, McGraw Hill Higher Education, 2018