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Acute and Chronic Rejection

Dr. Jaimie Shores, Hand/Arm Transplant Surgeon, talks about preventing transplant rejection.

What Is Rejection?

Rejection happens when a transplant recipient’s immune system thinks that the donated hand/arm is foreign to the recipient’s body and attempts to get rid of it.¹
Rejection episodes are treatable in almost all cases for patients who get the necessary treatment.
Recipients can experience acute or chronic rejection, and the type of rejection a patient experiences will determine the symptoms, treatment, and prognosis of the rejection.²
To preserve your transplant, you will need to take anti-rejection medicines for the rest of your life (as long as you have your transplant).

What Is Acute Rejection?

Acute or short-term rejection occurs when a recipient’s body tries to attack the donated hand/arm soon after a transplant.
Acute rejection usually happens within weeks or months of a transplant but can also happen several years after transplantation.^1,3
Acute rejection can occur multiple times.^4-6
Acute rejection is treatable, and its effects are reversible when treated quickly.⁷
Hand/arm transplant recipients who follow their anti-rejection medicine regimen usually do not lose their transplant due to acute rejection, and acute rejection episodes are usually treated by increasing the dosage of anti-rejection medications.³
If acute rejection is left untreated, it can lead to chronic rejection.^1,3

What Is Chronic Rejection?

Chronic or long-term rejection occurs over a longer time span than acute rejection, typically months to years after hand/arm transplantation.¹
Compared to acute rejection, chronic rejection is typically harder to detect and may need to be confirmed with a skin biopsy.⁸
Factors that are associated with chronic rejection include: untreated acute rejection,⁸ organ donor’s age, recipient’s health conditions (e.g., high blood pressure, diabetes, obesity, high cholesterol), and recipients not taking their anti-rejection medicines.⁶
Unlike acute rejection, chronic rejection may not be reversible and can result in the loss of function, as well as the loss or the removal of the transplanted hand/arm.^3,6,9-10
As of 2015, the rate of hand/arm transplant loss due to chronic rejection in Western Europe, Australia, and the U.S. was 9.5%.¹¹

How Can Rejection Be Prevented?

To prevent rejection, hand/arm transplant recipients need to make a lifetime commitment to taking anti-rejection medicines (i.e., adhering to their anti-rejection medicine regimen) and monitoring the hand/arm.^6,12
The recipient needs to routinely check their hand/arm for visible signs of rejection (for example, a rash in the transplanted area).
Recipients must notify their transplant team if they see any signs of rejection, which may require further medical tests (such as skin biopsies, standard vascular imaging, and antibody screening)^3,6,13
If a hand/arm transplant recipient experiences a serious side effect or health complication from taking anti-rejection medicines, the removal of the hand/arm transplant may be recommended.^14,15

How Can I Tell if My Body Is Attacking My New Hand?

Spotty, patchy, or blotchy rashes may begin to appear on the skin during a rejection episode.
Rejection may start in the palms of the hands or in the nail beds, but this is less common.
Recipients may experience a burning pain or no pain at all.
Recipients should tell their transplant team as soon as they start to experience symptoms of rejection so the team can treat the rejection episode as early as possible.
Rescue therapies to save the limb have been successful at treating and reversing common types of acute rejection. All hand/arm transplant recipients who have followed their anti-rejection medicine regimen as advised have been able to keep their transplanted hand(s)/arm(s).

How Can Rejection Be Detected?

Rejection episodes can be visibly identified and confirmed by medical tests.¹⁶
If recipients notice signs or symptoms of rejection (see below), they should contact their transplant team immediately.
In some cases, rejection episodes can be reversed by increasing the amount of anti-rejection medicines, and by using topical and/or steroid treatments.^15,16

Dr. Jaimie Shores, Hand/Arm Transplant Surgeon, outlines how to recognize early signs of rejection.

Common Signs and Symptoms of Acute and Chronic Rejection Include:

A skin rash or discoloration of the skin, the palm, or nail bed⁷
Pain in the transplant area¹
Swelling¹

Patient-Reported Signs and Symptoms of Acute and Chronic Rejection Include¹:

Fever
Weight gain
Flu-like symptoms (e.g., nausea, headache, chills, vomiting, diarrhea, dizziness, body aches, tiredness)
Change in pulse rate

Mr. White, with unilateral, below-elbow limb loss (6 years after amputation), talks about his fear of transplant rejection.

Rejection Rates based on Social, Emotional, and Mental Health Factors: An International Sample of n=43 Hand/Arm Transplant Recipients, 1998-2016

    Condition
    Number and percent of recipients with
the condition
    Number and percent of recipients who rejected the hand/arm transplant by condition
    Statistical significance of the rejection rate condition comparison
  


    Total recipients who completed the survey
    43
    5 (12% of total 
respondents)
    Not applicable
  

    Reported having intact upper extremity transplant(s)
    38 (88%)
    Not applicable
    Not applicable
  

    Reported having anxiety
    29 (67%)
    5 of 29 respondents
with anxiety (17%)
    
Significant
difference

  

    Reported not having anxiety
    14 (33%)
    0 respondents 
without anxiety (0%)
  

    Reported being treated 
for depression
    14 (33%)
    2 of 14 respondents with depression (14%)
    
Not a significant
difference

  

    Reported not having depression
    29(67%)
    3 of 29 respondents without depression (10%)
  

    Reported having PTSD*
    18 (42%)
    4 of 18 respondents 
with PTSD (22%)
    
Significant
difference

  

    Reported not having PTSD*
    25(58%)
    1 of 25 respondents 
without PTSD (4%)
  

    Reported having realistic functional expectations
    34 (79%)
    2 of 34 respondents with realistic expectations (6%)
    
Significant
difference

  

    Reported having unrealistic functional expectations
    9 (21%)
    3 of 9 respondents with unrealistic expectations (33%)
  

    Reported having strong 
family support
    33 (77%)
    2 of 33 respondents with 
strong family support (6%)
    
Not a significant
difference

  

    Reported having poor or 
fair family support
    10 (23%)
    3 of 10 respondents with poor 
or fair family support (30%)
  

    Reported being actively engaged in Occupational Therapy (OT) and home exercises
    28 (65%)
    1 of 28 respondents 
engaged in OT (7%)
    


Not a significant
difference

  

    Reported not being actively engaged in Occupational Therapy (OT) and home exercises
    15 (35%)
    3 of 15 respondents 
not actively engaged 
in OT (20%)
  

Condition	Number and percent of recipients with the condition	Number and percent of recipients who rejected the hand/arm transplant by condition	Statistical significance of the rejection rate condition comparison
Total recipients who completed the survey	43	5 (12% of total respondents)	Not applicable
Reported having intact upper extremity transplant(s)	38 (88%)	Not applicable	Not applicable
Reported having anxiety	29 (67%)	5 of 29 respondents with anxiety (17%)	Significant difference
Reported not having anxiety	14 (33%)	0 respondents without anxiety (0%)
Reported being treated for depression	14 (33%)	2 of 14 respondents with depression (14%)	Not a significant difference
Reported not having depression	29(67%)	3 of 29 respondents without depression (10%)
Reported having PTSD*	18 (42%)	4 of 18 respondents with PTSD (22%)	Significant difference
Reported not having PTSD*	25(58%)	1 of 25 respondents without PTSD (4%)
Reported having realistic functional expectations	34 (79%)	2 of 34 respondents with realistic expectations (6%)	Significant difference
Reported having unrealistic functional expectations	9 (21%)	3 of 9 respondents with unrealistic expectations (33%)
Reported having strong family support	33 (77%)	2 of 33 respondents with strong family support (6%)	Not a significant difference
Reported having poor or fair family support	10 (23%)	3 of 10 respondents with poor or fair family support (30%)
Reported being actively engaged in Occupational Therapy (OT) and home exercises	28 (65%)	1 of 28 respondents engaged in OT (7%)	Not a significant difference
Reported not being actively engaged in Occupational Therapy (OT) and home exercises	15 (35%)	3 of 15 respondents not actively engaged in OT (20%)

Source: Kinsley SE, et al. Psychosocial Predictors of Upper Extremity Transplantation Outcomes: A Review of the International Registry 1998-2016. Plast Reconstr Surg Glob Open. 2020;8(9):e3133.
Context: De-identified survey data for 43 upper extremity transplant recipients were used from the International Registry on Hand and Composite Tissue Transplantation (IRHCTT) 1998-2016. The mean follow-up time from the date of upper extremity transplantation was 7 years.
*PTSD = Post-Traumatic Stress Disorder