Pediatric Graft Versus Host Disease - Types, Symptoms, Diagnosis, and Management

What Is Pediatric Graft Versus Host Disease?

Graft versus host disease is a complication associated with donor transplantation of stem cells. There are two types of stem cell transplantation; allogeneic stem cell transplantation and reduced-intensity stem cell transplantation. Allogeneic stem cell transplantation is when a related or unrelated healthy person donates stem cells to the patient after high-intensity chemotherapy. Additionally, when a low dose of chemotherapy is given with the conditioning regime to the patient before allogeneic transplantation, it is called reduced-intensity allogeneic stem cell transplantation.

When a donor's transplanted T-cells act hostile toward a patient's healthy cells and attack them, GVHD occurs. This disease can be mild to life-threatening in severity. Except for cases where the donor is the patient's twin sibling, usually, the donor stem cells are treated medically before the transplantation. For instance, T-cells are suppressed or removed in the graft before the transplantation.

What Are the Types of Pediatric Graft Versus Host Disease?

There are two categories of graft versus host disease. These include

1. Acute Graft Versus Host Disease: This type can either occur after 100 days of transplantation or later in life. Patients with this category of GVHD have signs associated with the gastrointestinal tract, liver, or skin.

1. Stages: According to the degree of involvement, the severity of the disease is determined. Types of acute GVHD are divided by the system involvement and severity of the condition. These are:

   1. Stage 0: There will be no skin rash and upper gastric involvement, and bilirubin will be less than 2.

   2. Stage 1: The skin rashes will be less than 25 percent of the body surface area, and there will be severe nausea and vomiting, and bilirubin will range from 2.1 to 3.

   3. Stage 2: The skin rashes will range from less than 25 - 50 percent, there will be no upper gastric involvement, and bilirubin may range from 3.1 to 6.

   4. Stage 3: The skin rashes will be more than 50 percent and it may be presented in the form of generalized erythroderma. No upper gastric involvement, and bilirubin may range from 6.1 to 15.

   5. Stage 4: There will be bullae and desquamation. No upper gastric involvement, and bilirubin may be greater than 15.

2. Symptoms: There are a few symptoms related to this category, and each of them is seen with growing age, such as

1. Skin rashes with redness, appear on palms, feet, trunk, and other extremities.

2. Skin blisters.

3. Flaky skin.

4. Nausea and vomiting.

5. Abdominal cramps.

6. Loss of appetite.

7. Diarrhea.

8. Jaundice.

2. Chronic Graft Versus Host Disease: Chronic GVHD can involve single or multiple organs. It is the most life-threatening and one of the leading causes of death due to allogeneic stem cell transplantation.

1. Symptoms: There are many symptoms related to each part of the body, and with age, each one progresses. These symptoms are

   1. Mouth:

      1. Dry mouth.

      2. Extremely painful ulcers extended to the throat in severe conditions.

      3. Difficulty in swallowing.

      4. Loss of appetite.

      5. Sensitivity to cold, hot, and acidic foods.

      6. Tooth decays.

      7. Gum disease.

   2. Skin:

      1. Red and itchy rashes.

      2. Dry skin.

      3. Tightness of skin.

      4. Thickening of skin later can restrict joint movement.

      5. Change in skin color.

      6. Sensitive to temperature changes.

   3. Nails:

      1. Brittle nails.

      2. Changes in the color of nails.

      3. Nail loss.

   4. Scalp and Body Hair:

      1. Hair loss on the head.

      2. Premature graying of hair.

      3. Loss of body hair.

   5. Gastrointestinal Tract:

      1. Sudden weight loss.

      2. Nausea.

      3. Vomiting.

      4. Diarrhea.

      5. Stomach pain.

   6. Liver:

      1. Swelling in the abdomen.

      2. Jaundice.

      3. Abnormal liver function.

   7. Lungs:

      1. Shortness of breath.

      2. Wheezing.

      3. Chronic cough.

   8. Genitalia:

      1. Female

         1. Vaginal dryness.

         2. Narrowing of the vagina.

         3. Difficult/ painful intercourse.

         4. Vaginal ulceration.

      2. Male

         1. Narrowing and scaring of urethra.

         2. Irritation of penis.

         3. Itching or scaring on the scrotum or penis.

   9. Muscles and Joints:

      1. Muscle weakness.

      2. Muscle stiffness.

      3. Muscle cramps.

How to Diagnose Pediatric Graft Versus Host Disease?

As the condition is associated with a large number of health complications, it is slightly difficult to diagnose it, depending on the symptoms. However, if a child is facing symptoms such as nausea, rash, and voluminous diarrhea right after or right at the time of neutrophil engraftment, it is more likely because of the GVHD condition. Moreover, the tests to confirm the system's involvement in the body are:

• Tissue Biopsy: It can confirm the histologic involvement of the condition and exclude the diagnosis of possible infections or drug reactions.

• Skin Biopsy: To check for any infectious condition on the skin.

• Upper or Lower Gastrointestinal Endoscopy: This is the procedure where a hollow device is inserted down the throat via the esophagus and into the organ or the body. The biopsy of gastrointestinal tissue can reveal patchy ulcers and flattened tissue linings (epithelium).

• Blood Count: It is used to check biomarkers.

How to Manage Pediatric Graft Versus Host Disease?

The treatment plan for graft versus host disease starts with diagnosing which part or system of the body is affected in the body. Moreover, the severity of the condition decides the systemic involvement too, and the treatment plan for each type is

1. Acute Graft Versus Host Disease:

• In the mild form of the condition, systemic steroids are not required. Usually, doctors prescribe a topical steroid for skin conditions like rashes. Mild cases of acute GVHD can be treated with topical steroids and Cyclosporine or Tacrolimus.

• Additionally, if the condition is in moderate to severe form, the skin, liver, and GI tract are involved in young patients. Severe cases with systemic involvement are treated with original immunosuppressive Corticosteroids such as Methylprednisolone or Prednisone.

• Conventional first-line therapy to reduce inflammation is usually prescribed.

• Many patients are treated with corticosteroids, which are increased immunosuppressants.

2. Chronic Graft Versus Host Disease (GVHD): When there is chronic GVHD and one or two tissue and system involvement, the doctors usually recommend localized therapy, like skin ointment. On the other hand, if the condition is more severe and there are multiple organs and system involvement, localized therapy might not be effective. In such cases, doctors usually recommend drugs to suppress the immune system. These drugs are:

• Prednisone.

• Prednisone with Cyclosporine.

• Prednisone with Tacrolimus.

In the condition where the above-mentioned drugs do not work, the other line of treatment is the next option. Other drugs are:

• Methotrexate.

• Low-dose interleukin-2.

• Sirolimus.

• Ibrutinib.

One important thing to keep in mind for a person with GVHD is, if a person feels the symptoms curing after the medication, they should not stop taking it. At least not without the permission of the doctors. Stopping the medication early or halfway can worsen the situation.

Conclusion:

Graft versus host disease is a condition majorly caused by donor cell transplantation. Complications related to health are less in a patient with their cell transplantation. Additionally, due to many complications, the parents need to take their children to the doctors even after the smallest symptoms, such as rash. Medication and follow-up visits to the hospital should be regularly done to avoid a sudden flare of the condition.