English Version
C. Gaik · T. Wiesmann

Goodpasture syndrome

Goodpasture syndrome

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Keywords Goodpasture syndrome; ICD 10: M31.0; Synonyms: Goodpasture’s syndrome (GS), anti-glomerular basement membrane disease, crescentic glomerulonephritis type 1, GPS
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Goodpasture syndrome is a rare and organ-specific autoimmune disease (Gell and Coombs classification type II). It is mediated by anti-glomerular basement membrane (anti-GBM) antibodies [7]. The disease was first described by Dr Ernest Goodpasture in 1919 [6], whereby the glomerular basement membrane was first identified as an antigen in the 1950s. More than one decade later, researchers succeeded in defining the association between antibodies taken from diseased kidneys and nephritis [7].

The disorder is characterised by autoantibodies targeting at the NC1 domain of the α3 chain of type IV collagen in the glomerular and alveolar basement membrane with activation of the complement cascade, among other things [7,17]. The exclusive location of this α3 subunit in basement membranes in lung and kidney only is responsible for the unique affection of these two organs in GPS [7].

Nevertheless, the aetiology and the triggering stimuli for anti-GBM production remain unknown. Due to the fact that patients with specific human leukocyte antigen (HLA) types are more susceptible, a genetic HLA-associated predisposition seems possible [4,7]. However, because this strongly associated allele is frequently present, there seem to be additional behavioural or environmental factors influencing immune response and disease expression. The latter may include respiratory infections (e.g., influenza A2), exposition to hydrocarbon fumes, organic solvents, metallic dust, tobacco smoke, certain drugs (i.e., rifampicin, allopurinol, cocaine), physical damage to basement membrane (e.g., lithotripsy or membranous glomerulonephritis) as well as lymphocyte-depletion therapy (such as alemtuzumab), but unequivocal evidence is lacking [4,7,9,17].

The incidence is estimated to be about 0.5 to 2 cases per million per year in European Caucasoid and Asian populations [7,19,20]. Uncommon for autoimmune diseases, Caucasians males are more affected than females, however, the disease is even more common among the Maori people of New Zealand [19]. It is also a cause of acute renal failure in approximately 10–20 % of all cases of rapidly progressive or crescentic glomerulonephritis. The age distribution shows two peaks: the first occurs between 20 and 30 years (with more frequent haemorrhagic features) and second between 60 and 70 years of age. Regarding age patterns, men have a higher prevalence in the younger age group, whereas it is higher for women in the older age group [4,7].

GPS typically presents as acute renal failure caused by a rapidly progressive glomerulonephritis. This is often accompanied by pulmonary haemorrhage that may be life-threatening, especially without prompt diagnosis and treatment [7,17]. Symptoms may begin slowly and become rapidly progressive in a matter of days [1]. Fatigue, weakness, lethargy, nausea, vomiting, diarrhoea, pruritus, loss of appetite and weight, malaise, chills, fever, headache, arthralgias, a pale appearance and general discomfort or even seizures may be rather unspecific and initial symptoms [4,7,21,22,23]. About 60–80 % of the cases display clinically apparent renal and pulmonary manifestations, whereas 20–40 % have renal disease alone, and in less than 10 % of the patients, manifestation is limited to the lungs [4,7,19]. Pulmonary symptoms include haemoptysis, dry cough, shortness of breath, inspiratory crackles over lung bases, chest pain, cyanosis, dyspnoea, tachypnoea up to respiratory failure [7]. Regarding children, they do not present commonly with pulmonary findings before puberty [15]. Affection of the kidney may lead to haematuria, foamy urine, swelling of the hands and feet, high blood pressure, oedema, uraemia, oliguria, anuria and back pain in the kidney area [4,7,9]. Autoimmune inner ear disease (AIED) may be associated and present with vertigo, a ringing, hissing or roaring sound in the ear up to a sudden hearing loss in one ear progressing rapidly to the second ear (within weeks or months) [7].

More than 90 % of the patients with GPS have circulating serum anti-GBM antibodies [2]. A definitive diagnosis is substantiated by percutaneous kidney biopsy (preferred in comparison to a lung biopsy) and confirmed by immunofluorescent techniques and tested by an enzyme-linked immunosorbent assay (ELISA) for the presence of pathognomonic circulating anti-GBM serum antibodies [7].

There is a lack of systematic data of this rare syndrome. As yet, no causal therapy or, at least, controlled therapeutic trials are available. Nevertheless, rapid recognition and treatment is crucial in GPS. The three principles in therapy of GPS are (1) rapid removal of circulating antibodies (primarily by plasmapheresis), (2) stopping any further production of antibodies by drug-induced immunosuppression (high-dose corticosteroids and cyclophosphamide represent the standard therapy, but other immunosuppressive agents like azathioprine or rituximab are also established) and (3) removal of offending agents that may have initiated the antibody production [7]. Renal-replacement therapy as well as renal transplantation may help to replace renal function. Most centres therefore recommend a 6-month period of sustained negative testing for anti-GBM antibodies before undertaking transplantation surgery [14]. There are several case reports of necessary extracorporeal membrane oxygenation (ECMO) due to refractory hypoxemic respiratory failure in GPS with severe pulmonary haemorrhage [1,3,9,12,15].

GPS has a poor prognosis and it largely depends on the  diagnosis and treatment timeline of this rapidly progressive disease. Untreated, the lethality of GPS ranges from 77 to 96 % [9]. Under the triple therapeutic regime comprising corticosteroids, immunosuppressive therapy and plasmapheresis, a survival of 70–90 % in one year and up to 80 % in five years may be obtained [4,7]. Besides, in patients with dialysis due to end-stage renal disease in New Zealand and Australia, the median survival was nearly six years [20]. In addition to age, a history of pulmonary haemorrhage is associated with an increased risk of mortality on dialysis [12,20]. Dialysis dependency at presentation rarely generates full recovery of renal function. Nevertheless, patients requiring temporary dialysis may recover a good renal function and only less than 30 % of the surviving patients require long-term dialysis [4,7,12,13]. Double positivity for serum ANCAs and anti-GBM is another indicative of a worse renal prognosis and higher mortality [4]. Pulmonary patients can also often fully recover from lung damage with fast and adequate treatment [3,19]. The long-term outcome of GPS might be better in children than in adults [15].