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Post-Transplant

Complications

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Section 2: Infections

General Infection


Since you are on high doses of immunosuppression post-transplant, you are at a high risk for infection. Because of this, it is important to monitor for infections. It is likely that you will be asked to take your temperature daily after your transplant as well as be aware of your constitutional symptoms (e.g. fatigue, muscle aches).

Signs and Symptoms of Infection:

  • Oral temperature > 100.4oF (38 degrees C)
  • Chills or sweats
  • Cough
  • Shortness of breath
  • Sore throat
  • Earache
  • Sores or rashes in mouth or skin
  • Burning with urination
  • Cloudy or foul-smelling urine
  • Pain, redness, warmth on incision site
  • Wound or cut that won’t heal
  • Increased or watery diarrhea with foul smell
  • Redness, swelling, drainage around drainage tubes

Diagnosis: Depending on your signs and symptoms, will determine which type of tests and procedures may be run. In general, tests may include:

  • Bloodwork
  • Urinalysis
  • Blood cultures
  • Stool cultures
  • CT scans of chest or abdomen

Treatment: Treatment is going to be based on the type of infection that you have and whether or not you are able to tolerate oral medications. You will be given either oral or IV antivirals, antibacterials, or antifungals depending on the organism you are infected with.




Cytomegalovirus (CMV)


CMV is a very common virus. Once infected, your body retains the virus for life. Most of the time, people do not realize they have the virus because it does not cause problems in healthy people, however, after transplant you are immunosuppressed and the virus may reactivate. When CMV reactivates, it may cause signs and symptoms and can be a very dangerous infection for transplant patients.

Signs and Symptoms:

  • Fever

  • Chills

  • Sweats

  • Muscle aches

  • Pneumonia

  • Inflammation of the small intestine (CMV enteritis)

  • CMV retinitis (infection with CMV in the eye)

  • Liver inflammation

Prophylaxis for CMV: Usually intestinal transplant patients will be given oral valganciclovir for the first 3-6 months post-transplant as prophylaxis, meaning to prevent, CMV from reactivating in the months right after transplant.

Diagnosis: CMV surveillance is conducted via a blood test which uses CMV PCR. This is able to detect whether or not CMV can be found in the blood. If CMV is suspected to be in other organs, then further testing may be warranted. An ophthalmologist may be consulted in order to test for CMV retinitis and/or a biopsy may be taken of the intestine if CMV enteritis is suspected.

Treatment of CMV: If CMV does reactivate and cause infection, usually a patient will be treated with IV ganciclovir. In the event that the CMV is resistant to ganciclovir, then foscarnet or cidofovir are utilized; however, these medications can be toxic to the kidneys, so they must be used with caution. Your transplant team will determine the best treatment for you.




Urinary Tract Infection (UTI)


UTIs are common with immunosuppressed patients. These infections can involve the urethra, the bladder, and/or the kidneys. A variety of different organisms can cause these infections

Signs and Symptoms:

  • Burning or pain with urination
  • Feeling the urge to urinate more frequently and urgently
  • Foul smelling urine
  • Blood in urine
  • Pain in the lower back (if the kidney is infected)
  • Fever

Prevention:

  • Avoid bubble baths.
  • Wear cotton underwear.
  • Drink plenty of water.
  • After toileting, always wipe front to back.
  • Pee often and avoid ‘holding it.’




Shingles (Varicella)


General Information

  • Caused by a reactivation of the same virus that causes chickenpox (Varicella).
  • When the virus is reactivated, it will cause an outbreak of shingles (rash, blisters). You can get chicken pox when exposed to the drainage from these lesions.

Signs and Symptoms

  • One to three days before rash appears symptoms may include: pain, tingling, and burning on the side of the chest, neck, forehead, back, hip, or leg.
  • Rash and sores appear in clusters of blisters usually in a strip on one side of the body, torso, or face.
  • You will no longer be contagious when all lesions are scabbed over.

Treatment

  • Contact the transplant team immediately.
  • You will need to have a V-ZIG injection (varicella-zoster immunoglobulin) within 3 days of exposure (note- the injection may not prevent shingles, but it will lessen the severity of it).
  • If you do get shingles even after the V-ZIG injection, your transplant team may require you to be admitted and started on acyclovir until the lesions are crusted over and the team feels you are safe to be discharged.




Aspergillosis


Aspergillus is a common fungus (mold) that lives in decaying vegetable matter, soil, and dusty areas. For healthy people, it is of little concern, however, for those that are immunosuppressed, it can cause a serious fungal infection.

Signs and Symptoms:

  • Fever and chills
  • Bloody cough
  • Shortness of breath
  • Chest pain
  • Joint pain
  • Nosebleed
  • Skin lesions

Diagnosis:

  • Chest CT or Chest X-ray
  • Sputum test
  • Tissue and blood tests

Treatment: If you contract the infection then your team may treat you with antifungal medications such as voriconazole or amphotericin B.




Pneumocystis Jiroveci Pneumonia (aka pneumocystis carinii or PCP)


This is a serious infection that causes inflammation and fluid buildup in your lungs. It is caused by a fungus called Pneumocystis jiroveci that spreads through the air and is very common. For normal, healthy people, this fungus is not harmful, but for transplant patients with a weakened immune system, it can cause a very serious infection.

Signs and Symptoms:

  • Fever
  • Dry cough or wheezing
  • Shortness of breath
  • Fatigue
  • Chest pain while breathing

Diagnosis:

  • Fluid from lungs
  • Biopsy from lungs
  • Blood tests

Treatment: Patients are usually given prophylaxis (preventative treatment) with Bactrim (Sulfamethoxazole / Trimethoprim) three times per week. In the event that you cannot tolerate the oral medication, then a monthly breathing treatment of Pentamidine may be suggested.




Epstein Barr Virus (EBV) and Post-Transplant Lymphoproliferative Disorder (PTLD)


Epstein Barr Virus is a common virus that infects a large portion of the adult population. In healthy adults it usually results in the common manifestation known as ‘mono’ and the individual’s immune system is usually able to fight off in the infection. However, in immunocompromised transplant patients, certain immune cells are suppressed and are not able to keep the proliferating B cells in check.

The Epstein Barr Virus that had been ‘asleep’ in the patient’s immune cells, called B cells, ‘wake up’ and begin to replicate. This viral replication goes uncontrolled by the transplant patient’s immune system and leads to PTLD.

Signs and Symptoms: Mainly an overall feeling of being unwell.

  • Malaise, feeling of unease/ illness
  • Fatigue
  • Night Sweats
  • Fever
  • Weight Loss
  • Swollen lymph nodes

Diagnosis: Diagnosis of PTLD is based on the entire clinical picture and considering many different tests. Your transplant team will conduct a thorough physical and exam, especially taking note of any lymph node enlargement. They most likely will get extensive blood work, possible imaging studies (CT scan, PET scan, and/or MRI), urinalysis, and/or lumbar puncture. Depending upon your unique clinical picture will determine what set of tests your team decides to order.

Treatment: The first line of treatment for PTLD is lowering immunosuppression. If this does not solve the problem your team might consider starting you on a medication called Rituximab, which has been shown to have very positive results in treating PTLD. More refractory cases may be treated with chemotherapeutic agents or localized radiation. As always, your transplant team will choose the treatment best suited to your particular case.





Section 1: Post-Transplant Complications

Acute Cellular Rejection (ACR)


This occurs when your body detects the new intestine as foreign and, as a result, attacks the organ. Most patients will experience some form of rejection in the first 3-6 months post- transplant. This type of rejection can be classified as indeterminate, mild, moderate, or severe based on the histologic findings on your endoscopic biopsy.

Signs and Symptoms:

  • Fever
  • Abdominal pain
  • Abdominal distention or swelling
  • Nausea/ vomiting
  • Increase in stoma output
  • Changes in the appearance of stool
  • Blood in stoma output
  • Change in the appearance or color of stoma
  • Loss of appetite/ weight loss
  • Often causes no physical symptoms

Diagnosis: Diagnosis is made by taking a biopsy of your intestine through your ileostomy with an endoscope. If you are experiencing symptoms, this may prompt your transplant team to order an ileoscopy. On the other hand, since rejection often times does not cause symptoms, acute cellular rejection may be found on your surveillance biopsies. The transplant team will rely on the pathology of the biopsy to confirm the diagnosis and severity of the rejection.

Treatment: Treatment ultimately depends on the severity of the rejection. Mild rejection may just require adjustment of your immunosuppression medications and high doses of corticosteroids. Moderate to severe rejection may require heavier immunosuppression agents such as Thymoglobulin or Campath. Your transplant team will determine the best course of treatment for you based upon your immune status and biopsy results.




Antibody-Mediated Rejection


For intestinal transplants, unlike other solid organ transplants, antibody mediated rejection is poorly defined and the frequency and clinical significance remains uncertain.




Chronic Rejection


This type of rejection develops months to years after the transplant has been completed and after acute rejection episodes have subsided. It appears to be a combination of both antibody and cell mediated rejection. Overall, there is fibrosis and scarring of the transplanted organs.

The only way to definitively diagnose chronic rejection is through a full thickness biopsy of the graft to look at the histology. A full thickness biopsy means that an entire portion of the intestine must be removed for full examination, unlike the pin-point biopsies that can be taken during a scope procedure. This is completed in the operating room.

Risks for chronic rejection include:

  • Acute rejection within the first month of transplant.
  • Isolated small bowel graft (in many reports it has been shown that including the liver in the graft has an immunoprotective effect in preventing rejection).
  • Greater number of acute rejection episodes.
  • Older recipient age.

Symptoms of chronic rejection include:

  • Abdominal pain and/or distention.
  • Increased output from ostomy.
  • Poor oral intake and/or decreased appetite.




Graft vs. Host Disease (GVHD)


GVHD occurs in all types of transplant, however, it is of major concern to intestinal transplant due to the large amount of immune tissue that the intestine contains. GVHD results when the donor’s cells (the graft) view the patient’s healthy cells (the host) as foreign and begin to attack and damage them.

Signs and symptoms can vary based on if the disease is local on the skin or effecting a particular organ:

  • Skin reactions: itching; red rash on the upper trunk, neck and feet; blisters on the palm, soles, and abdominal skin.
  • Mouth or tongue lesions.
  • GI manifestations: Diarrhea, nausea, or vomiting.
  • Hepatitis or liver inflammation: May not have symptoms, but may lead to jaundice or yellowing of the skin.

Diagnosis: Usually a tissue biopsy of the affected skin will be used to diagnose GVHD along with clinical picture and patient history. Blood tests will often be taken to help manage the condition and to check liver function. If gastrointestinal symptoms are present, an endoscopy may be ordered.

Treatment: In self-limited, mild skin cases of GVHD no treatment may be necessary. In disseminated disease, steroid therapy is the treatment of choice along with adjustments in immunosuppression.




Chylous Leak


This is a complication that results when the lymphatic system of the donor graft does not grow together properly with the recipient's lymphatic system after transplant, resulting in lipid rich lymph fluid to leak into the abdominal cavity.

Signs and Symptoms:

  • Abdominal distention
  • Early satiety
  • Abdominal pain
  • Nausea/ vomiting

Diagnosis: Diagnosis is based on the clinical picture, observation of a milky fluid coming from JP drains, and/or from imaging studies such as an abdominal CT scan.

Treatment: Treatment is mainly supportive with NPO (nothing by mouth), fat-free diet, and bowel rest. In refractory cases, surgical intervention may be necessary.




Blood Clots (Thrombosis)


  • A blood clot is a clump of blood that has changed from a liquid to a gel-like or semi-solid state.
    • Clotting is a necessary process that your body undertakes in certain circumstances to prevent yourself from losing too much blood, however, there are times when your body forms clots in your veins when they are not needed and these can be dangerous.
    • If the clot in your vein accidentally breaks free from your vein and travels to your lungs or heart, it can get stuck and prevent blood flow, prompting a medical emergency.
  • Blood clots are common after surgery, especially after a big operation like an intestinal transplant.
  • Clots can form anywhere in your body, including your arms, legs, and/or abdominal vessels.
  • It is important to keep yourself up and moving as much as possible after transplant to try and avoid getting any blood clots, but if you do notice any of the following symptoms, you must contact your transplant team immediately.

Signs and Symptoms:

  • Cramping/ pain.
  • Swelling, usually of one area.
  • Reddish or bluish skin discoloration.
  • Area warm to touch.

Diagnosis: Diagnosis of a blood will be based on clinical picture, Doppler ultrasound, venography, MRI, angiogram, and/or blood tests.

Treatment: Treatment of blood clots is a very tricky balance. Your transplant team will most likely start you on some form of anti-coagulation ‘blood thinning’ medication to treat your blood clots. Usually you first will start with heparin, an IV anti-coagulation medication, and then often will switch to warfarin (Coumadin) the pill form of the anti-coagulation.




Post-Transplant Complications Introduction


Complications are very common after an intestinal or multivisceral transplant. The positive thing is that your transplant team will be vigilant in monitoring you for all complications and will be on top of treating you if any complications do arise. This section contains a sampling of the potential of complications. This is not an all-inclusive list, nor does the explanation for each complication contain every possible symptom, treatment, or scenario. If you are concerned that you are experiencing a complication after your transplant, or are concerned about the possibility of complications, it is always best to contact your transplant team directly.





Section 3: Long-Term Complications

Avascular Necrosis (AVN)


  • Avascular Necrosis or AVN is a condition that results from lack of blood flow to the bones of the joints resulting in bone death.
  • The most common reason for AVN is chronic steroid use.
    • Generally transplant patients are on high doses of steroids during transplant and in the immediate post-operative period, and remain on some level of steroids for the remainder of his or her life.
  • Because of this, many intestinal and multivisceral transplant patients will develop some extent of AVN in one or more of his or her joints.
    • The most common joints for AVN to arise include hips, knees, and ankles; however, it can occur in any joint of the body including the jaw, wrists, hands, elbows, and shoulders.
  • It is a very painful condition, causing a deep, throbbing, aching bone pain that is usually made worse by activity.

Diagnosis: Advanced disease can be detected on an x-ray. Early disease and the gold standard of diagnosis is via an MRI. Other testing modalities can include a CT scan or a bone scan ( in nuclear medicine via a radionuclide injection, not a DEXA or bone density scan like you get for osteoporosis which is a very different condition from AVN, to understand the difference you can click here and read Kayla's Story).

Treatment:

  • In the early stages, treatment is based on symptom relief.
  • If your status allows, your physician may recommend taking NSAIDs, but generally, transplants patients are advised against taking anti-inflammatory medications due to the bleeding risk.
  • Topical anti-inflammatory agents, such as Diclofenac, may be prescribed to help alleviate some of the pain in the joints.
  • Other modalities, such as ice, may help to relieve swelling.
  • The use of assistive devices like crutches or walkers may help to alleviate the stress placed on the joints and reduce pain.
  • In advanced disease, and when joints have collapsed, joint replacement or fusion may be recommended.
  • Every treatment is individualized and will be recommended by your transplant team or by your referred orthopedic doctor.




Osteoporosis


Osteoporosis is a condition that results when the osteoclasts, or the bone cells that breakdown your bone, are working at too fast of a rate compared to the osteoblasts, or the bone cells that are creating new bone. The osteoclasts breakdown too much bone and create a ‘porous’ bone structure, resulting in weak bones.

This occurs mainly in weight-bearing areas of your bone, such as your lower back and spine, hip, or wrist. Sometimes your bone can become so weak and brittle that a small fall or injury can cause your bone to break or fracture. Usually, you do not notice osteoporosis until a fracture or break occurs, in which at that time you may experience pain or swelling in the area.

Diagnosis: Generally, yearly, your transplant team will perform what is known as a DEXA, or Dual-Energy X-Ray Absorptiometry Scan, or a bone density scan. This test uses enhanced x-ray technology to measure the amount of bone loss. You are assigned a z-score for each area of bone and this determines whether your bones are healthy, whether you have osteopenia, or whether you have osteoporosis.

Treatment: Depending on the extent of your bone loss will determine what the best treatment is for you. If you are at the beginning stages, your physician may recommend just supplementing with calcium and vitamin D. If your bone loss is more significant, it may be suggested that you get an infusion of Reclast or Prolia.

Each plan is individualized, and your transplant team may refer you to an endocrinologist so they can determine the best course of treatment for you and if there is an underlying cause that is hastening the progression of your osteoporosis.




Renal (Kidney) Dysfunction


After an intestinal transplant, patients are most likely to be on high doses of immunosuppression medications, particularly tacrolimus, which is in a class of medication known as calcineurin inhibitors. This particular class of medication is particularly hard on the kidneys and can lead to kidney dysfunction and disease. Many post-intestinal transplant patients will develop kidney disease, often times leading to the need for dialysis and ultimately, a kidney transplant.

What is the function of the kidney?

  • Filter waste materials out of the blood and pass them out of the body as urine.
  • Regulate blood pressure and the levels of water, salts, and minerals in the body.
  • Produce hormones that control other body functions.

Your transplant team will take blood on a consistent basis to monitor the function of your kidneys. Your serum creatine, BUN, and glomerular filtration rate (GFR) are indicators of kidney dysfunction.

  • Serum creatinine: This is a waste product that comes from muscle activity. When kidneys are working well, they remove creatinine from the blood.
  • Glomerular filtration rate (GFR): A math formula using the person’s age, race, gender and their serum creatinine is used to calculate a GFR. This number is used to figure out the stage of chronic kidney disease (CKD).
  • Blood Urea Nitrogen (BUN): A normal waste product in your blood that comes from the breakdown of protein from the foods you eat and from your body metabolism. It rises with decreased kidney function as well as when you are dehydrated.

What are the 5 stages of chronic kidney disease?

Stage 1 with normal or high GFR (GFR > 90 mL/min)

Stage 2 Mild CKD (GFR = 60-89 mL/min)

Stage 3A Moderate CKD (GFR = 45-59 mL/min)

Stage 3B Moderate CKD (GFR = 30-44 mL/min)

Stage 4 Severe CKD (GFR = 15-29 mL/min)

Stage 5 End Stage CKD (GFR <15 mL/min)

If you are in stage 4 or stage 5, it is likely that you will need dialysis and/or a kidney transplant.

Please refer to The National Kidney Foundation for more information.




Cancer (Malignancy) after Transplant


Malignancy rates are higher in all transplant recipients. The risk of cancers such as Kaposi sarcoma, non-Hodgkin lymphoma, nonmelanomatous skin cancers, and cancers related to viral infections, are significantly increased.

Non-melanoma squamous cell and basal cell skin cancers are the most common malignancies in transplant recipients.

  • Squamous cell cancers tend to develop at a younger age, are typically more aggressive, and metastasize (spread) more often.
  • Because of this, yearly skin checks with a dermatologist is recommended for all intestinal transplant recipients.
  • If a transplant patient has the presence of a suspicious lesion, there should be a low threshold for biopsy and more aggressive treatment for precancerous lesions.
  • Patients with repeated precancerous lesions may benefit from switching immunosuppression and overall lowering of immunosuppression is recommended to allow control of the malignancy by your own immune system.

Reduce your risk of skin cancer by:

  • Using sunscreen whenever you go outside.
  • Cover up when you go outside, including arms, legs, and neck.
  • Use lip balm, lips can get sunburned!
  • Get a skin check yearly by a dermatologist and do routine skin checks on yourself weekly.
  • Avoid direct sunlight at all times.
  • Wear hats when in the sun.

Risk factors for developing skin cancer include:

  • History of skin cancer prior to transplant.
  • Presence of premalignant skin lesions (warts or keratosis).
  • History of exposure to UV rays.
  • Older age.
  • Male gender.
  • Fair skin phenotype.
  • Immunosuppression: duration and type.

For other cancers, such as prostate, cervical, breast, and colon, transplant patients are at least at a two-fold increase in risk.

All transplant patients should receive appropriate screenings for each of these cancers or as their transplant team sees fit based on his or her:

  • History and individual needs.
  • Existing co-morbidities.
  • Overall life expectancy.
  • Preference for screening.

Most transplant centers require annual mammography and pap smear for female intestinal transplant patients as well as an annual prostate exam for male patients. Talk to your transplant team about appropriate screenings and about you and your family’s cancer history so appropriate recommendations are made.





Section 4: Additional Resources

Helpful Downloads from Transplant Unwrapped


Sign-Up or Log-In to Access: Infection Prevention: A handbook on ways you can help prevent infections when you are immunosuppressed.




Transplant Unwrapped Webinars


Go to our webinars page to view the following (you will need to log-in or sign-up): Past Live Webinar: Overview of Intestinal and Multivisceral Transplant Patient Pre-Recorded Webinar: Post-Transplant Complications




Video Library: Links to Post-Transplant Videos


Post-Transplant Videos: Links to a variety of videos explaining some common post-transplant complications.




Page References


References here.




Transplant Unwrapped Video: Post-Transplant Lymphoproliferative Disorder


Watch this video explaining PTLD, including Kayla's personal experience with the condition.