OVERVIEW
Goodpasture’s syndrome is an allergic disease of unknown etiology characterized by circulating anti-glomerular basement membrane antibodies and linear deposition of immunoglobulins and complement on the glomerular basement membrane in the blood, resulting in pulmonary hemorrhage with severe progressive development of glomerulonephritis.
Etiology
Immunofluorescence staining reveals immunoglobulin and complement deposits in the glomerular basement membrane and in the alveolar-capillary basement membrane in some patients.
In the lungs and kidneys, the main target site for anti-glomerular basement membrane antibodies is the noncollagenous (NC-1) functional region of collagen chains 2,3 of basement membrane IV. Infection, smoking, and inhalation injury are thought to cause capillary damage via these antibodies, and genetics also plays a role, with HLA-DRW2 being associated with anti-glomerular basement membrane disease.
Symptoms
The onset of the disease is preceded by respiratory infections in some patients and is followed by recurrent hemoptysis, most of which appear prior to renal disease, for years (up to 12 years), months, and in a few cases, after nephritis. In hemoptysis pulmonary diffusion is reduced, hypoxemia occurs and anemia is common. Renal manifestations: proteinuria, erythrocytes and tubular pattern are present in every case, and there may be hematuria of the naked eye. Renal function decreases, however, the rate of progression varies, some patients may present acute renal failure within 1-2 days, most develop uremia within weeks to months, a few evolve more slowly, with stabilization at the original level or relapse after remission.
Examination
1. General examination
Usually, it should include blood routine, blood biochemistry, renal function, arterial blood gas analysis, urine routine and so on.
2. Serologic examination
Primary tests may include antinuclear antibody (ANA) profile, anti-double-stranded (ds) DNA, anti-neutrophil cytoplasmic antibody (ANCA), anti-granulocyte basement membrane (GBM) antibody, and antiphospholipid antibody. patients with SLE may have high titers of ANA and dsDNA, while complement levels are lowered in Goodpasture’s syndrome with positive circulating anti-GBM antibodies. -ANCA), antibodies against myeloperoxidase (MPO) elastase and lactoferrin, and the cytoplasmic type, the latter targeting the antigen serine protein 3 (PR3) distributed in the cytoplasm, i.e., C-ANCA Microscopic polyarteritis, Churg-Strauss vasculitis, and oligoimmune glomerulonephritis (PIGN) may appear positive for P-ANCA.
3. Renal biopsy
In addition to routine light microscopy, direct immunofluorescence staining is usually required. In immune-mediated alveolar hemorrhagic syndrome with concomitant renal involvement, the renal pathology is necrotizing glomerulonephritis, with varying degrees of histologic changes, ranging from mild thickening of the peritubular membranes to severe crescentic glomerulonephritis with renal arterial vasculitis. Immunofluorescence staining of various diseases has different manifestations, anti-basement membrane antibody (ABMA) disease along the glomerular basement membrane wired deposition collagen vasculopathy and idiopathic immune complex-mediated glomerulonephritis is granular deposition, while the immunofluorescence test of PIGN is negative, combined with serological ANCA, ABMA, ANA and other tests can improve the diagnosis, treatment and prognosis of the judgment of significance.
4. Tracheoscopy
Tracheoscopy and alveolar lavage (BAL) examination can help to confirm the diagnosis of alveolar hemorrhage and exclude hemorrhage caused by infections and localized lesions in the airways, thus helping to make a differential diagnosis and search for the cause of the disease. Microscopic examination of ferritin-containing cells is also valuable in confirming alveolar hemorrhage.
5. Lung biopsy
Transbronchial lung biopsy is of limited diagnostic value in DAH, and open lung biopsy is required to identify the cause. Lung biopsy is only suitable for patients who have not been identified by routine examination and whose condition is relatively stable and can tolerate unilateral lung atrophy. Patients with severe pulmonary hemorrhage and expiratory failure are not suitable for open lung biopsy lung biopsy can be accompanied by infection and pneumothorax after the procedure.
Diagnosis
In 1976, Teichman proposed the following diagnostic conditions: ① repeated hemoptysis; ② hematuria, tubular urine and other glomerulonephritis-like changes; ③ small-cell, hypochromic anemia, with iron treatment is effective; ④ fast-absorbing wandering speckled infiltration in the lungs; ⑤ sputum can be found to have ferritin-containing macrophages, the diagnosis can be made; ⑥ direct immunofluorescence or radioimmunoassays, repeated examination of the blood may prove that there is anti-glomerular basal infiltration. (6) Repeated blood tests by direct immunofluorescence or radioimmunoassay can prove the presence of anti-glomerular basement membrane antibodies; (7) In renal or lung biopsy, there are immunoglobulin deposits in the basement membrane of the glomeruli or alveolar sacs, which are arranged in a linear pattern.
1. Clinical features
The onset of the disease is rapid, most of the first signs of respiratory tract infection, and there is a tendency to progressive aggravation, first hemoptysis, soon appeared nephritis changes, and renal failure manifestations. The disease may also begin with glomerulonephritis of varying severity, while pulmonary abnormalities may show up at a later stage of the disease.
2. Laboratory tests
Leukocytosis, proteinuria, urine sediment with red and white blood cell tubular pattern. In addition to red blood cells, epithelial cells containing “ferritin” can be seen in the sputum.
3.Auxiliary examination
X-ray examination, pathological examination of kidney and other tissues can help to confirm the diagnosis.
4. The triad of signs in a typical patient
(1) Pulmonary hemorrhage with linear deposition of IgG in the alveolar basement membrane.
(2) Acute nephritis syndrome with massive crescent formation in the kidney (extracapillary proliferative nephritis), which may be accompanied by capillary necrosis, and GBM with line-like deposition of IgG.
(3) Positive serum anti-GBM antibody.
5. Precautions for diagnosis
(1) In some patients, the lungs and/or kidneys show mild manifestations, or the two organs develop lesions asynchronously. Sometimes the anti-basement membrane autoimmune process occurs only in either the lungs or the kidneys.
(2) There is sometimes a transition between anti-GBM nephritis and other types of glomerular disease (mainly membranous nephropathy).
(3) Occasionally autoimmune dysfunction produces nonspecific basement membrane antibodies that can also cause damage to organs other than the lungs and kidneys.
(4) In some cases, such as the highly active autoimmune period, a large number of anti-GBM antibodies are deposited, and a transient negative serum anti-GBM antibody may occur. A case of a patient with typical renal clinical and pathological manifestations of Goodpasture syndrome and concomitant lung damage with negative serum anti-GBM antibodies has been reported, and he believes that this may be due to the massive deposition of antibodies in the target organs during the highly active period.
(5) Goodpasture syndrome coexisting with vasculitis.Rydel et al. reported an 18-year-old male patient with Goodpasture syndrome who developed refractory epilepsy during plasma exchange and cytotoxic medications.MRI showed Multiple Lacunar Infarcts (MLIs), and cerebral spinal membrane biopsy showed vasculitis, but serum ANCA was persistently negative. Administration of high doses of corticosteroids and cytotoxic drugs followed by antiepileptic drugs resulted in symptomatic control.Kalluri et al. reported a patient with nodular pulmonary infiltrates with acute renal failure, positive for c-ANCA, and histologic examination of the kidneys showed crescentic and necrotizing nephritis with linear deposition of IgG and C3 in the glomeruli, and serum with high titers of anti-GBM-IgG.
Differential diagnosis
Many of the diseases that can cause hemorrhage in the lungs need to be carefully differentiated from Goodpasture’s syndrome before effective treatment can be given. For example, pulmonary hemorrhage in patients with advanced renal failure may be due to coagulation disorders. On the other hand, pulmonary hemorrhage may also occur in the early stages of certain diseases. Common causes of pulmonary hemorrhage are, in order of prevalence, vasculitis, including Weil’s granulomatosis and systemic necrotizing vasculitis; anti-glomerular basement membrane antibody (AGBM) disease; collagen vascular disease; IgA nephropathy (IgAN); pulmonary renal syndrome not otherwise classified; and IPH.
Complications
The most common complication is hemorrhage in the lungs of hemolytic uremic syndrome, which can lead to respiratory failure and asphyxia.
Treatment
In the acute phase tracheal intubation, assisted ventilation and hemodialysis are often required. Subsequent management depends on the use of high-dose corticosteroids (methylprednisolone), the immunosuppressive agent cyclophosphamide and repeated hemodialysis to eliminate circulating anti-glomerular basement membrane antibodies. The course of immunosuppressive therapy is highly variable and may take 12 to 18 months in some patients. A combination of these measures can protect renal function in the early stages, while long-term hemodialysis or renal transplantation is feasible in advanced renal disease.
1. Intensive plasmapheresis with 2 liters of plasma each time, once a day or every other day. Combined with prednisone, cyclophosphamide treatment.
2. Methylprednisolone shock therapy. Supplemented with prednisone and cyclophosphamide orally.
3. Dialysis and renal transplantation: When acute renal failure meets the indications for dialysis, dialysis should be performed in time, and maintenance dialysis or renal transplantation should be given in the late stage.