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Emergency and Acute Medicine – Transplant Rejection
Transplant rejection is an immune-mediated response against a transplanted organ due to recognition of genetically dissimilar antigens, most commonly related to human leukocyte antigen (HLA) incompatibility. Although blood group incompatibility plays a lesser role, it can still result in severe reactions such as hyperacute rejection, particularly in vascularized organs like the kidney and heart. Rejection remains a significant cause of morbidity in transplant recipients, although infection is a more common reason for emergency department presentation.
Rejection is classically divided into three phases. Hyperacute rejection occurs immediately after transplantation and is caused by preformed antibodies against donor antigens, leading to endothelial injury, platelet aggregation, thrombosis, and rapid graft necrosis. This form is now rare due to improved donor–recipient matching. Acute rejection typically occurs within the first three months but can happen at any time, especially with reduction or noncompliance with immunosuppressive therapy. It is primarily T-cell–mediated and results in inflammatory infiltration and destruction of the graft. Chronic rejection develops over months to years and leads to progressive fibrosis and eventual organ failure.
The epidemiology of transplantation shows that kidney transplants are the most common, followed by liver, heart, lung, and pancreas. Despite advances in immunosuppressive therapy, rejection still accounts for a portion of emergency visits and hospital admissions. A major contributing factor is medication noncompliance or drug interactions affecting levels of immunosuppressive agents such as cyclosporine or tacrolimus.
Clinical presentation varies depending on the transplanted organ. Renal transplant rejection may present with hypertension, decreased urine output, and sometimes swelling or fever, although symptoms may be subtle due to immunosuppression. Liver transplant rejection often manifests as fever, right upper quadrant pain, and jaundice. Heart transplant rejection may present with dyspnea, chest pain, arrhythmias, hypotension or hypertension, and can even be asymptomatic or lead to sudden death. Lung transplant rejection typically presents with cough, dyspnea, fever, and abnormal lung sounds. Bone marrow transplant rejection, including graft-versus-host disease, can involve multiple systems, presenting with fever, rash, gastrointestinal symptoms, pulmonary findings, and neurologic complications.
Evaluation requires a high index of suspicion, as symptoms may be mild or nonspecific. Laboratory testing includes complete blood count, immunosuppressant drug levels, and organ-specific markers such as creatinine for kidney transplants, liver function tests for liver transplants, and cardiac biomarkers for heart transplants. Imaging plays an important role, including chest radiography for lung involvement, ultrasound for renal or hepatic grafts, and echocardiography for cardiac function. In some cases, biopsy is required to distinguish rejection from infection. Opportunistic infections such as Cytomegalovirus infection or fungal infections like Aspergillosis may mimic rejection and must always be considered.
Management in the emergency setting begins with stabilization following standard ABC principles. Shock should be treated with fluids and vasopressors as needed, while hypertensive crises are managed according to standard protocols. A key principle is early communication with the transplant team before initiating or modifying therapy. High-dose corticosteroids are commonly used in suspected acute rejection, and stress-dose steroids should be considered in ill transplant patients. Care must be taken with medications such as NSAIDs and blood transfusions due to potential complications in this population.
Special considerations apply to specific organs. In heart transplant patients, atropine is ineffective for bradycardia due to lack of vagal innervation, and alternative therapies such as dopamine, epinephrine, or pacing are required. Lung transplant patients often require treatment for both infection and rejection simultaneously. Bone marrow transplant patients with graft-versus-host disease typically require systemic corticosteroids and adjustments in immunosuppressive therapy.
Disposition depends on severity. Most transplant patients presenting with symptoms suggestive of rejection, infection, or organ dysfunction require hospital admission, and many need ICU-level care. Patients who are stable and in whom serious causes have been excluded may be discharged with close follow-up in coordination with their transplant team.
Key clinical pearls include maintaining a broad differential diagnosis, as infection and drug toxicity frequently mimic rejection. Even minor complaints in transplant patients warrant thorough evaluation. Early consultation with transplant specialists is essential, and a low threshold for admission is appropriate given the high risk of complications.
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