Goodpasture syndrome is an autoimmune pathology characterized by the formation of autoantibodies to the basal membranes of the renal glomeruli and pulmonary alveoli. Clinically, disease is manifested by recurrent pulmonary bleeding, progressive glomerulonephritis and renal insufficiency. The diagnosis is confirmed by the detection of antibodies to the glomerular basement membrane (Anti GBM), kidney and lung biopsy data, and lung X-ray examination. Treatment includes immunosuppressive therapy (glucocorticosteroids, cytostatics), plasmapheresis, according to indications – hemodialysis, kidney transplantation.
Meaning
Goodpasture syndrome is an immuno-inflammatory lesion of the capillaries of the kidneys and lungs, occurring with the development of glomerulonephritis and hemorrhagic pneumonitis. For the first time, the signs of this pathology were described in 1919 by the American pathophysiologist E.W. Goodpasture, for which the disease was named after him. In rheumatology, Goodpasture syndrome refers to systemic vasculitis and is often referred to as “hemorrhagic pulmonary-renal syndrome”, “hemorrhagic pneumonia with glomerulonephritis”, “idiopathic hemosiderosis of the lungs with nephritis”. The incidence of Goodpasture syndrome is 1 case per 1 million. population. There are two age peaks of morbidity – in 20-30 years and 50-60 years; mostly men are ill. In the absence of treatment for this disease, mortality among patients reaches 75-90%.
Causes
The etiological mechanisms of the disease have not been reliably determined. Clinical observations indicate a connection between the development of Goodpasture syndrome with a viral infection (influenza, viral hepatitis A, etc.), taking medications (carbimazole, penicillamine), industrial hazards (inhalation of organic solvent vapors, lacquers, gasoline), hypothermia, smoking. Genetic predisposition to this syndrome was noted in individuals carrying HLA–DRwl5, HLA-DR4 and HLA-DRB1 alleles. Family cases of Goodpasture syndrome are described.
Under the influence of one or another etiological factor, as a result of changes in the tolerance of the immune system, the body begins to produce autoantibodies to the basal membranes of the pulmonary alveoli and renal glomeruli. It is assumed that the structural component a-3 of the type IV collagen chain, present in the basement membranes of the pulmonary and renal capillaries, acts as an autoantigen. Formed antibodies (GVM antibodies) in the presence of C3 complement bind to antigens; the formed immune complexes are deposited along the basement membranes, inducing immuno-inflammatory damage to the renal glomeruli (glomerulonephritis) and alveoli (alveolitis). Activation of cellular elements (T-lymphocytes, endotheliocytes, monocytes, alveolar macrophages, polymorphonuclear leukocytes), cytokines (insulin-like, platelet-like growth factors, tumor necrosis factors, interleukin-1), free radicals, proteolytic enzymes and other factors that damage kidney and lung tissue plays an important role in the development of autoimmune inflammation.
Pathomorphological substrates of Goodpasture syndrome are hemorrhagic necrotizing alveolitis and nephrosonephritis. Histological examination of renal tissue reveals proliferative-membranous, proliferative or necrotizing glomerulonephritis, glomerular sclerosis and renal parenchyma fibrosis. Morphological examination of the lung tissue reveals capillaritis of the interalveolar septa, pulmonary infiltrates, hemosiderosis, pneumosclerosis.
Symptoms
There are three variants of the clinical course of Goodpasture syndrome: malignant, moderate and slow. The malignant course is characterized by recurrent hemorrhagic pneumonia and rapidly progressing glomerulonephritis. In the second type, the pulmonary-renal syndrome develops more slowly and is moderately pronounced. In the third variant of the Goodpasture syndrome, the phenomena of glomerulonephritis and CRF prevail; pulmonary manifestations develop late.
The malignant variant of the Goodpasture syndrome debuts with pulmonary bleeding and acute renal failure, requiring intensive therapy (elimination of water-electrolyte disorders, compensation for blood loss, oxygen inhalation, ventilator, hemodialysis or peritoneal dialysis). In other cases, the disease may begin with common symptoms: subfebrility, malaise, weight loss. Sometimes the appearance of complaints is preceded by a transferred ARVI. Of the specific symptoms, usually the first signs of lung damage develop – cough, progressive shortness of breath, cyanosis, chest pain, recurrent hemoptysis or pulmonary bleeding. Lung damage in Goodpasture syndrome is often complicated by cardiac asthma and pulmonary edema.
Soon, renal symptoms are added to the pulmonary manifestations: hematuria, oliguria, peripheral edema, arterial hypertension. In 10-15% of patients, Goodpasture syndrome manifests with clinical signs of glomerulonephritis. In many cases, the course of the disease is accompanied by myalgia, arthralgia, hemorrhages of the skin and mucous membranes, intraretinal hemorrhages, pericarditis.
Diagnostics
When examining patients with Goodpasture syndrome, attention is drawn to the pallor of the skin, pasty or swelling of the face. Dry and wet wheezes are heard in the lungs, the number of which increases at the time of hemoptysis and after it. Hypochromic anemia, anisocytosis, poikilocytosis, leukocytosis, a sharp increase in ESR are detected in the general blood test. The general analysis of urine is characterized by proteinuria, cylindruria, erythrocyturia; the Zimnitsky test reveals isohypostenuria. The biochemical analysis of blood determines the increase in the level of creatinine, urea, seromucoid; reduction of iron concentration. For Goodpasture syndrome, it is typical to detect a large number of red blood cells, siderophages and hemosiderin in the general sputum analysis.
The most sensitive and specific method of diagnosing Goodpasture syndrome is the determination of antibodies to the glomerular basement membrane (Anti-GBM) using ELISA or RIA. Multiple focal shadows are detected on lung radiographs. Morphological confirmation of Goodpasture syndrome is based on lung and kidney biopsy data. The results of instrumental diagnostics are of auxiliary importance: spirometry, ultrasound of the kidneys, ECG, EchoCG.
As part of diagnostic measures, it is necessary to exclude lung cancer, tuberculosis, bronchiectasis, idiopathic hemosiderosis of the lungs, systemic lupus erythematosus, nodular periarteritis, hemorrhagic vasculitis, Churge-Strauss syndrome, Wegener’s granulomatosis, microscopic polyangiitis, cryoglobulinemia. Diagnosis and treatment should be carried out jointly by specialists – rheumatologists, pulmonologists, nephrologists.
Treatment and prognosis
In the acute period of Goodpasture syndrome, the appointment of pulse therapy with methylprednisolone or combined pulse therapy (methylprednisolone + cyclophosphane) is indicated, followed by transfer to maintenance therapy after achieving clinical, laboratory and radiological remission. Plasmapheresis is performed in order to eliminate circulating immune complexes. Symptomatic therapy of Goodpasture syndrome includes transfusions of erythrocyte mass and blood plasma, the appointment of iron preparations. With the development of terminal renal insufficiency, hemodialysis sessions are used. It is possible to perform a nephrectomy followed by kidney transplantation, but this does not exclude the recurrence of necrotizing glomerulonephritis in the transplant.
The course of Goodpasture syndrome is steadily progressing; the prognosis is not very encouraging. The death of patients occurs, as a rule, due to profuse pulmonary bleeding, severe renal or respiratory failure. In the malignant variant, death occurs in a matter of weeks; in other cases, the average life expectancy ranges from several months to 1-3 years. Isolated spontaneous remissions of Goodpasture syndrome are described in the literature.