Granulomatosis with polyangiitis (Wegener’s granulomatosis) is a systemic necrotic vasculitis of small veins and arteries with the formation of granulomas in the vascular walls and surrounding tissues of the respiratory tract, kidneys, etc. organs. Disease is characterized by ulcerative-necrotic rhinitis, changes in the larynx, paranasal sinuses, infiltration of lung tissue with decay, rapidly progressing glomerulonephritis, polymorphic skin rashes, polyarthralgia. The diagnosis is based on the evaluation of clinical and laboratory, radiological data, and biopsy results. Hormonal and cytostatic therapy is indicated for this pathology; the prognosis for the development of the disease in the generalized form is unfavorable.
Information
The incidence of granulomatosis with polyangiitis is equally common among men and women in the age group of about 40 years.
Classification
Taking into account the prevalence of pathological changes, granulomatosis with polyangiitis can occur in a localized or generalized form.
There are 4 progressive stages in the development of granulomatosis with polyangiitis. The first stage of granulomatous-necrotic vasculitis, or rhinogenic granulomatosis, occurs with the clinic of purulent-necrotic or ulcerative-necrotic rhinosinusitis, laryngitis, nasopharyngitis, destructive changes in the bone-cartilaginous skeleton of the nasal septum and eye socket. At the next stage (pulmonary), the lung parenchyma is involved in the pathological process. At the third stage, generalized lesions develop with the involvement of the lower respiratory tract, gastrointestinal tract, cardiovascular system, kidneys. The last, terminal stage of granulomatosis with polyangiitis is characterized by pulmonary-cardiac or renal insufficiency, leading to the death of the patient in the next year from the beginning of its development.
Symptoms
The general symptoms of granulomatosis with polyangiitis include fever, chills, increased sweating, weakness, weight loss, myalgia, arthralgia, arthritis. The leading manifestation of the disease, occurring in 90% of patients, is a lesion of the upper respiratory tract. For the Wegener granulomatosis clinic, a persistent course of rhinitis, purulent hemorrhagic discharge from the nose, ulceration of the mucous membranes up to perforation of the nasal septum, saddle-shaped deformity of the nose is typical. Granulomatous-necrotic changes also develop in the oral cavity, larynx, trachea, auditory passages, paranasal sinuses.
In 75% of patients with granulomatosis with polyangiitis, infiltrative changes in the lung tissue, destructive cavities in the lungs, cough with hemoptysis, indicating the development of pleurisy, pleural effusion are detected. Involvement of the kidneys is manifested by the development of glomerulonephritis with the phenomena of hematuria, proteinuria, disorders of excretory function. The rapidly progressive course of glomerulonephritis in granulomatosis with polyangiitis leads to acute renal failure. Changes on the part of the skin are manifested by a hemorrhagic rash with subsequent necrotization of the elements.
Damage to the organs of vision includes the development of episcleritis (inflammation of the superficial tissues of the sclera), the formation of orbital granulomas, exophthalmos, ischemia of the optic nerve with deterioration of visual function up to its complete loss. With granulomatosis with polyangiitis, the nervous system, coronary arteries, and myocardium are affected.
The localized form of granulomatosis with polyangiitis proceeds with a predominant lesion of the upper respiratory tract – persistent runny nose, difficulty in nasal breathing, nosebleeds, the formation of bloody crusts in the nasal passages, hoarseness of voice. The generalized form is characterized by various systemic manifestations – fever, joint and muscle pain, hemorrhages, polymorphic rash, paroxysmal cough with bloody-purulent sputum, abscessing pneumonia, an increase in cardiopulmonary and renal insufficiency.
Diagnostics
The complex of diagnostic procedures for granulomatosis with polyangiitis includes consultation with a rheumatologist, laboratory tests, diagnostic operations, X-ray examinations. Clinical blood examination reveals normochromic anemia, acceleration of ESR, thrombocytosis, general urine analysis – proteinuria, microhematuria. A biochemical blood test determines an increase in gamma-globulin, creatinine (in renal syndrome), urea, fibrin, seromucoid, haptoglobin. Immunological markers of granulomatosis with polyangiitis are HLA class antigens: DQW7, DR2, B7, B8; the presence of antineutrophilic antibodies, a decrease in complement levels.
During the lung x-ray, infiltrates, decay cavities, pleural exudate are determined in their tissues. Bronchoscopy is performed with a biopsy of the mucous membranes of the upper respiratory tract. The examination of biopsies reveals morphological signs of granulomatous necrotizing vasculitis.
Treatment
With a limited and generalized form of granulomatosis with polyangiitis, immunosuppressive therapy with cyclophosphamide in combination with prednisone is prescribed. The rapidly progressing course of alveolitis or glomerulonephritis is an indication for combined pulse therapy with high doses of methylprednisolone and cyclophosphamide. During the transition of the course of Wegener’s granulomatosis to the stage of remission, the doses of cyclophosphamide and prednisolone are gradually reduced; methotrexate is prescribed for a long (up to 2 years) period.
Generalization of the process in granulomatosis with polyangiitis (hemoptysis, glomerulonephritis, the presence of antibodies to neutrophil leukocytes) requires extracorporeal hemocorrection – cryoapheresis, plasmapheresis, cascade plasma filtration, extracorporeal pharmacotherapy. In the treatment of recurrent granulomatosis with polyangiitis, intravenous immunoglobulin therapy is effective. In order to prolong remission, rituximab therapy can be performed. Stenosing changes of the larynx in granulomatosis with polyangiitis require the imposition of a tracheostomy and reanastomosis.
Complications and prognosis
The course and progression of granulomatosis with polyangiitis can lead to the destruction of facial bones, deafness due to persistent otitis media, the development of necrotic granulomas in the lung tissue, hemoptysis, trophic and gangrenous changes in the foot, renal failure, secondary infections against the background of taking immunosuppressants. In the absence of therapy, the prognosis of the course of granulomatosis with polyangiitis is unfavorable: 93% of patients die in the period from 5 months to 2 years.
The local form of granulomatosis with polyangiitis is more benign. Immunosuppressive therapy improves the condition in 90% and stable remission in 75% of patients. The remission period lasts on average about a year, after which 50% of patients experience a new exacerbation. The progressive course of Wegener’s limited granulomatosis, despite immunosuppressive therapy, is noted in 13% of patients. Measures for the prevention of granulomatosis with polyangiitis have not been developed.