Approach

Treatment for Goodpasture's disease involves an aggressive strategy combining corticosteroids, plasma exchange, and cyclophosphamide.[28]​​[29]​​​​

If it is known that a definitive diagnosis will be delayed beyond 24 hours due to an inability to perform renal biopsy or other diagnostic testing, the safest presumptive therapy should be initiated with a plan to perform a diagnostic biopsy the next day.[1]

While there are no trials on which to base specific recommendations for presumptive therapy, a renal biopsy should be performed immediately, and corticosteroids and plasma exchange started as soon as possible.[28][29]​​​​ Continue plasma exchange until the antibody titre is negative (usually 1 to 1.5 times a patient's total plasma volume daily for 2-3 weeks).[28][29]​​​​ Treatment with cyclophosphamide (or an alternative immunosuppressant) might be best reserved until biopsy results are available to confirm the diagnosis. Because Goodpasture's disease is very rare, there are no high quality randomised controlled trials and the literature is largely case series-based.

Treatment decisions must be guided by a nephrology consultant.

Reversible renal disease or any pulmonary involvement

For most patients, urgent aggressive treatment is needed with high-dose oral prednisolone, plasma exchange, and oral cyclophosphamide.[28][29]​​​​ In the past, intravenous boluses of corticosteroids were used for 3 days, followed by oral dosing, but this led to increased adverse effects compared with an oral-only regimen.[31]

  • All patients presenting with pulmonary symptoms require immediate aggressive treatment as pulmonary haemorrhage can be rapidly fatal.

  • Patients with renal disease who do not require dialysis should have immediate, aggressive treatment for the best chance of preventing further irreversible loss of renal function. However, where dialysis is required, the decision to employ toxic therapy requires assessment of the potential risks and benefits.

  • When considering plasma exchange, patients with an initial creatinine <0.3 mmol/L (<5.7 mg/dL) will likely recover kidney function.[28][32]

  • Biopsy findings favouring aggressive treatment are fresh cellular crescents with little scarring, indicating a very acute process, or many preserved glomeruli with a second possible 'reversible' injury that might account for the severity of renal failure, such as acute tubular injury. Conversely, in an adequate biopsy sample, if most glomeruli show crescents (85% to100%) or if >50% glomeruli have global glomerulosclerosis, the prospects for renal recovery are much reduced, thereby favouring early discontinuation of immunosuppression (for renal disease).[29]

  • Initial therapy for patients with positive anti-neutrophil cytoplasmic antibody (ANCA) is identical to initial treatment for patients without ANCA.

  • Patients who are intolerant of oral cyclophosphamide can be trialled on intravenous cyclophosphamide. Alternatively, mycophenolate or rituximab can be considered if cyclophosphamide is not an option.[29]

  • Where anti-GBM antibodies are persistently positive following a three-month course of cyclophosphamide, use of rituximab, azathioprine, or mycophenolate along with systemic corticosteroids has been suggested.[29]​ Treatment with plasma exchange may also be necessary for this patient group.

Pulmonary haemorrhage at presentation

Pulmonary haemorrhage occurs in 25% to 60% of patients, with presentations ranging from mild haemoptysis to life-threatening diffuse alveolar haemorrhage.[28]​ In addition to the usual aggressive therapies, these patients may require further supportive measures and may particularly benefit from cessation of exposure to tobacco smoke.

  • They should be strongly advised to stop smoking.

  • Pulmonary congestion should be avoided as it may exacerbate pulmonary haemorrhage as well as contribute to reduced gas transfer.

  • Supplemental oxygen or intubation may be needed but should be managed as far as possible to avoid hyperoxia and infection, both of which may also exacerbate pulmonary haemorrhage.[33]

  • Correction of spontaneous or plasma exchange-related coagulopathy with cryoprecipitate and fresh frozen plasma should be considered if there is active pulmonary haemorrhage.

Irreversible renal disease

Aggressive treatment (plasma exchange, cyclophosphamide, and corticosteroids) may be withheld if kidney function is unlikely to recover and the patient has no pulmonary symptoms.

Kidney function is unlikely to recover if:[28][29]​​[32]

  • dialysis is needed at presentation and during admission

  • initial creatinine is ≥0.3 mmol/L (≥5.7 mg/dL)

  • kidney biopsy shows 100% crescents or >50% glomerulosclerosis.

The low likelihood of renal recovery in these patients (<10%) mean the risks of aggressive treatment could outweigh the potential benefits.[32][34][35]​​​ Treatment decisions must be highly individualised, taking into account reversibility on renal biopsy and comorbid conditions. Supportive care alone is often appropriate.[1]

Treatment-related adverse effects

Adverse effects should be considered when deciding on treatment. There is a small risk of bleeding with plasma exchange. Corticosteroids can cause adverse effects including gastritis and osteoporosis when used long-term. Immunosuppressants are associated with an increased risk of infection. Specific immunosuppressants also have their own adverse effects (e.g., cyclophosphamide is associated with neutropenia, haemorrhagic cystitis, bladder cancer, and gonadal toxicity; mycophenolate is associated with gastrointestinal disturbances and insomnia; azathioprine is associated with pancreatitis and transaminitis; and rituximab is associated with infusion reactions).

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