Symptoms of graft-versus-host disease (GVHD), a complication of allogeneic hematopoietic stem cell transplant, can be mild to life threatening. Symptoms may affect your skin, gastrointestinal tract, liver, and other areas.

An allogeneic hematopoietic stem cell transplant (allo-HPSCT) — also called a bone marrow transplant — uses stem cells from a donor to replace your blood cells that have been affected by disease. The graft (donor cells) is put into the host (your) bone marrow after chemotherapy or radiation treatment.

Once the graft has been implanted in your bone marrow, functional cells are produced through a process called engraftment.

In GVHD, immune cells from the donor graft identify your host cells as foreign and begin an immune response against them. This can result is a variety of immune-mediated symptoms that can vary in severity and duration.

Symptoms of GVHD can appear at any time after you receive donor stem cells. How quickly symptoms begin and how they appear determines which type of GVHD you have.

The term “acute GVHD” generally refers to GVHD that begins suddenly. It may occur within the first 100 days after an allo-HPSCT.

Skin, liver, and gastrointestinal (GI) symptoms are typical and can range from mild to severe.

Skin symptoms

Dermatitis (a skin rash) is the most common skin symptom of acute GVHD. It can begin anywhere on your body, including your palms or the soles of your feet. You may notice faint redness or other color change that resembles a sunburn.

GVHD rash can spread across your body. It may be tender or itchy. In its more severe forms, it can blister or peel.

Liver symptoms

Acute GVHD that affects your liver does not usually cause symptoms but can be detected by measuring liver enzyme levels.

Elevated liver enzymes help doctors understand the extent of liver damage. The greater the damage from GVHD, the less your liver is able to get rid of the enzyme bilirubin. As a result, testing will show high bilirubin levels.

In more advanced liver GVHD, noticeable symptoms can appear. Bilirubin levels that are too high can cause jaundice (yellowing of your skin and the whites of your eyes).

If your liver becomes significantly damaged from acute GVHD, liver failure is possible.

GI symptoms

Diarrhea due to inflammation in your GI tract is the hallmark GI symptom in acute GVHD. Its severity is determined by volume, or how much diarrhea you eliminate in a single day.

You may also experience nausea, vomiting, appetite loss, or blood in your stool.

Persistent, recurrent, or late onset acute GVHD

The symptoms of GVHD can vary from person to person. While GVHD can usually be categorized as acute or chronic, symptoms sometimes do not align perfectly with either category.

In that case, you may receive a diagnosis of one of the following subtypes of acute GVHD:

  • Late onset acute GVHD: classic acute GVHD symptoms that appear after the 100-day mark
  • Persistent acute GVHD: symptoms that do not resolve with typical treatments
  • Recurrent acute GVHD: symptoms that recur after successful treatment

Chronic GVHD can occur at any time after an allo-HPSCT but usually develops after the 100-day mark and may occur even years later. It has its own classic clinical features. Chronic GVHD has a slower onset and can cause a broader range of symptoms that are persistent and long lasting. The symptoms may never fully resolve.

Because GVHD causes systemic inflammation in your body, and because unusual immune activity can target any organ system, chronic GVHD can have widespread effects. The three most common areas affected are the skin, mouth, and liver.

Symptoms of chronic GVHD can include:

Integumentary (skin, hair, and nails) symptoms

  • rash
  • itchy, dry, or tight skin
  • skin discoloration
  • skin thickening
  • temperature intolerance
  • sores that won’t heal
  • changes in nail texture
  • brittle nails
  • nail loss
  • hair loss (anywhere on your body)
  • graying of hair

Liver symptoms

  • jaundice
  • abdominal swelling

Eye symptoms

  • dry, itchy eyes
  • eye pain
  • blurred vision
  • vision loss

Respiratory symptoms

  • shortness of breath
  • wheezing
  • persistent cough

GI symptoms

  • unintended weight loss
  • decreased appetite
  • nausea and vomiting
  • diarrhea
  • stomach pain
  • a sensation of food caught after swallowing
  • dry mouth
  • trouble swallowing
  • sensitivity to temperature, texture, and acidity
  • mouth sores
  • trouble eating or swallowing
  • gum disease
  • tooth decay

Muscle and joint symptoms

  • cramps
  • muscle weakness
  • stiff joints

Genital and sex organ symptoms

  • pain during intercourse
  • vaginal dryness or pain
  • genital itching and scarring
  • vaginal ulcers
  • vaginal narrowing
  • penis irritation
  • scarring of the urethra

So, what sets the symptoms of acute GVHD apart from those of chronic GVHD?

GVHD is classified by how quickly symptoms appear but also by the symptoms themselves.

Acute GVHD and chronic GVHD can share certain features, but acute GVHD primarily affects your skin, GI tract, and liver, while chronic GVHD has a much broader symptom set.

It’s possible for acute GVHD to become chronic GVHD. You may also develop overlap syndrome, which involves features of both GVHD types.

GVHD should always be addressed by a doctor as soon as possible. Receiving timely treatment can help reduce your symptoms, prevent organ damage, and ensure the long-term success of your allo-HPSCT.

Both acute and chronic GVHD can be mild, moderate, or severe. Your doctor determines the severity based on how many organs are affected and the level of damage to each organ.

It’s not always possible for you to know how serious GVHD is without being evaluated by a doctor. For example, symptoms of liver failure might not be obvious right away.

If you notice any symptoms of GVHD, no matter how mild they may seem, contact your doctor or go to an emergency department immediately.

According to the Leukemia & Lymphoma Society, between 30% and 70% of people who receive an allo-HPSCT develop acute GVHD, and 40% to 50% develop chronic GVHD.

While there’s no way to guarantee that you won’t develop this condition after an allo-HPSCT, there are steps doctors can take to help prevent it.

Prevention strategies include:

  • finding the best allo-HPSCT donor match possible
  • using immunosuppressive drugs before and after an allo-HPSCT
  • eliminating immune T cells from donor grafts (T-cell depletion) before transplant

Your outlook for this condition depends on individual factors such as your overall health, the type and severity of GVHD, and the condition’s response to first-line therapies.

With timely treatment for GVHD, many people can effectively manage the symptoms.

The most severe forms of GVHD are associated with a low 5-year survival rate of about 5%.

GVHD is a potentially serious complication of allo-HPSCT procedures. A doctor will determine which type of GVHD you have based on which symptoms you have and how quickly they develop.

Acute GVHD typically starts suddenly and primarily affects your skin, liver, and GI tract. Chronic GVHD has a broader symptom set and can develop months to years after an allo-HPSCT.