Symptoms and Diagnosis of Graft Versus Host Disease (GVHD)

There are two manifestations of graft vs host disease (GVHD), acute and chronic, which differ in the organs affected and when they present in patients.

Acute GVHD

The symptoms of acute GVHD affect the skin, gut and liver:

Skin – an erythematous, maculopapular rash starts to appear on the palms of the hands, soles of the feet, shoulders and ears. This is quite often pruritic (i.e. itchy). In the worst cases, it can cause blisters and ulcers. In mild forms of the disease, this rash might cover up to just 25% of the body. In more severe cases it covers most areas and the skin can start to peel off.

Stomach – if a person has a moderate presentation of acute GVHD, they will start to feel nauseous. This can be accompanied by vomiting and an aversion to eating. The patient may experience early satiety and may also have signs of bloating.

Intestines -the patient develops green, watery diarrhoea, abdominal discomfort and sometimes mucus and blood in their stool.

Liver – liver function is affected as GVHD increases in severity. The patient may present with jaundice (i.e. yellowing of the skin and eyes and darkening urine). This may be accompanied by right upper abdominal pain. With further worsening of the disease, the symptoms will become more severe as liver failure may ultimately ensue.

Temperature – the patient may develop a raised temperature.

Infections – the patient may have an increased susceptibility to infections from viruses, bacteria and other microorganisms.

Changes in the blood – patients tend to exhibit low levels of red blood cells and platelets.

Chronic GVHD

The symptoms for chronic GVHD affect the skin, gut and liver areas as with the acute manifestation, but they can also extend to many other organs of the body. The condition can be mild, moderate or severe:

Skin, hair and nails – the patient will develop thickening of their skin texture. They will develop a rash which causes the skin to become dry and itchy. Alongside this, the patient’s nails will also break more easily and the hair may start to fall out or turn grey.

Liver – the patient can suffer from liver damage and/or failure.

Eyes – in ocular GVHD, the eyes can become dry, painful and uncomfortable. The patient’s vision can also become blurry and they may be unable to tolerate bright lights.

Lungs – a persistent cough can develop with the patient struggling to breathe. They can also be at risk of chest infections.

Joints and tendons – Joints can become painful and stiff while movement of the legs will become more difficult due to inflamed tendons.

Mouth – sores can form inside the mouth. The patient may feel pain as well and find it difficult to open their mouth.

Genital region – this can become inflamed. Sexual activity can be uncomfortable

Diagnosis

Doctors will tend to use biopsies, which entail the removal and analysis of tissue from an affected area. A pathologist will analyse the tissue to decide whether the symptoms and findings correspond with suspected GVHD. The process of diagnosing is often one where the doctor rules out different diseases based on the results.

Skin biopsy – the doctor will numb the skin to snip a little bit of flesh from the affected area. Elafin, also known as the protein peptidase inhibitor 3, tends to be abundant in skin affected by GVHD. It modulates inflammation.

Liver biopsy – the patient will undergo an ultrasound or CT scan to help the doctor see the affected area more clearly for the liver biopsy. A needle is then used to take a little sample of the flesh for analysis. Doctors will look out for an increase in alkaline phosphatase and bilirubin, which indicate that the liver is not functioning properly.

Endoscopy, gastroscopy and colonoscopy – the stomach and intestinal areas may need to be assessed as well. The doctor will use a camera to look into the oesophagus or insert one through the anus to look at the bowel or colon area. A little snip of flesh is obtained for analysis.

X-rays or CT – the doctor can also use x-rays or CT to look at the health of the lungs. This diagnostic tool can also be supplemented with further lung function tests.

References

• Be the Match on the symptoms for GVHD: https://bethematch.org/for-patients-and-families/life-after-transplant/graft-versus-host-disease/gvhd-signs-and-symptoms/
• Cancer Research UK on diagnosing GVHD: http://www.cancerresearchuk.org/about-cancer/coping-with-cancer/coping-physically/gvhd/diagnosing-gvhd
• BCSH Guidelines on Chronic GVHD diagnosis: http://www.bcshguidelines.com/documents/BCSH_Guideline_Chronic_GVHD_Diagnosis_and_Management_v1.pdf
• Biology of Blood and Marrow Transplantation Journal, Histopathologic Diagnosis of Chronic Graft-versus-Host Disease: National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: II. Pathology Working Group Report: http://www.sciencedirect.com/science/article/pii/S1083879105007226 Reviewed by Jonas Wilson, Ing. Med.

Further Reading

• All Graft Versus Host Disease Content
• What is Graft Versus Host Disease (GVHD)?
• Types of Graft Versus Host Disease (GVHD)
• Treatment of Graft Versus Host Disease (GVHD)
• Causes and Risk Factors of Graft Versus Host Disease (GVHD)

Written by

Deborah Fields

Deborah holds a B.Sc. degree in Chemistry from the University of Birmingham and a Postgraduate Diploma in Journalism qualification from Cardiff University. She enjoys writing about the latest innovations. Previously she has worked as an editor of scientific patent information, an education journalist and in communications for innovative healthcare, pharmaceutical and technology organisations. She also loves books and has run a book group for several years. Her enjoyment of fiction extends to writing her own stories for pleasure.