Acute Graft Versus Host Disease in Skin

Acute graft versus host disease in skin is one of the most common complications after a bone marrow or stem cell transplant, where the donor’s immune cells mistakenly attack the recipient’s skin, often appearing as the first sign that something is wrong.

Table of contents

• What is acute graft versus host disease in skin
• Who gets acute graft versus host disease in skin
• What causes acute graft versus host disease in skin
• When does acute graft versus host disease in skin occur
• Signs and symptoms
• How is it diagnosed
• Treatment options
• What you can do to help yourself

aGVHD, Acute cutaneous GVHD, Acute skin GVHD

D89.810; T86.09

• Skin

What is acute graft versus host disease in skin

Graft versus host disease (GVHD) is a condition that occurs when immune cells from donated tissue recognize the recipient’s body as foreign and attack it^[1]. In this context, the graft refers to the transplanted or donated tissue, while the host refers to the person receiving the transplant^[1].

Acute graft versus host disease in skin is a type of immune-mediated reaction that most commonly follows allogeneic hematopoietic stem cell transplantation, which is a procedure where stem cells come from a person other than the patient^[1]. This procedure is often used to treat blood cancers and certain immune system disorders^[2].

The skin is the most common and usually the first organ affected by acute GVHD^[1]. When it occurs, cutaneous features are not just the most common but are also usually the presenting sign, making skin doctors play a key role in diagnosing and treating the condition from the start^[1].

Acute GVHD in skin is primarily an inflammatory reaction that develops when new immune cells from the donor begin to see the recipient’s skin cells as a threat and launch an attack against them^[5]. This can lead to a range of skin problems that may be mild or, in severe cases, life-threatening^[1].

Who gets acute graft versus host disease in skin

Acute graft versus host disease in skin can affect between 40 and 60 percent of patients who undergo allogeneic stem cell transplantation, depending on various factors related to both the donor and the recipient^[1]. Up to 70 percent of people with acute GVHD will experience skin problems^[15].

Several factors can increase the risk of developing acute GVHD. The strongest risk factor is an immune mismatch between donor and recipient, particularly related to human leucocyte antigen (HLA), which is a protein that helps the body distinguish its own cells from foreign ones^[1]. However, even when HLA matches perfectly, minor differences in other antigens can still trigger the disease^[1].

Other risk factors include older age of either the donor or recipient, gender differences between donor and recipient, a history of pregnancy or blood transfusions in the donor, use of stem cells from peripheral blood rather than bone marrow, having had a spleen removed, or having experienced acute GVHD previously^[2].

Although extremely rare, acute GVHD may also occur after transfusion of non-irradiated blood products, solid organ transplantation, or even after autologous stem cell transplantation, where the stem cells come from the patient themselves^[1].

What causes acute graft versus host disease in skin

Acute graft versus host disease in skin develops when T lymphocytes, which are a type of white blood cell in the donated tissue, recognize the recipient’s skin cells as foreign and attack them^[2]. Normally, immune cells protect the body by fighting off bacteria and viruses, but in GVHD, these protective cells mistake the recipient’s healthy tissues for threats^[3].

The donor’s immune cells can identify a person’s own cells by recognizing proteins called human leukocyte antigens that act like name tags on cells^[3]. When there is a mismatch in these proteins between the donor and recipient, the donated cells may not recognize the recipient’s tissues as safe, leading to an attack^[3].

When does acute graft versus host disease in skin occur

Acute graft versus host disease typically occurs within the first 100 days after transplantation^[4]. Skin involvement usually appears early, with the median time of onset being 19 days after the transplant, though it can range anywhere from 5 to 47 days^[1].

However, it’s important to know that acute GVHD can also start or come back later than 100 days after transplant^[3]. Healthcare providers now classify GVHD not only based on when symptoms start but also on the specific symptoms and clinical signs that appear^[3].

Signs and symptoms

The most common symptom of acute GVHD in skin is a rash that can look similar to a sunburn^[5]. The rash typically consists of red to violet spots and patches, which doctors call a maculopapular rash^[7].

The rash usually begins in specific locations on the body. It typically first appears on the nape of the neck, shoulders, palms of the hands, soles of the feet, ears, and cheeks^[2]. From these areas, it can spread to involve the trunk and other parts of the body^[8]. In some cases, the rash can progress to cover the entire body, a condition called erythroderma^[2].

The rash can be painful, itchy, or both^[2]. In fact, itching is often one of the first symptoms, appearing even before visible skin changes occur^[8]. The skin may feel very faint or severely affected, ranging from a mild sunburn-like appearance to more serious changes^[5].

In severe cases, the skin may develop blisters or fluid-filled sacs called bullae^[2]. The outer layer of skin may peel off, a process called desquamation^[2]. At worst, the injury to the top layer of skin can resemble second-degree burns or a serious condition called toxic epidermal necrolysis^[8].

The severity of acute GVHD in skin is determined by how much of the body’s surface is affected by the rash^[6]. Healthcare providers grade the condition from stage 1 (mild) to stage 4 (very severe) based on the percentage of skin involved^[7].

How is it diagnosed

Healthcare providers can often diagnose acute GVHD in skin based on the signs and symptoms you’re experiencing, particularly if they appear within the expected time frame after transplant^[5]. Since cutaneous manifestations are the most common and often the presenting sign of GVHD, skin doctors play a key role in making the diagnosis^[1].

Sometimes additional tests are needed to confirm the diagnosis. A skin biopsy, which involves taking a small sample of skin tissue for examination under a microscope, may be performed^[5]. However, diagnosing GVHD can be challenging because both the clinical appearance and the tissue findings can overlap with other skin conditions^[1].

The disease may mimic well-known inflammatory and autoimmune skin disorders, making it difficult to establish a definite diagnosis in some cases^[1]. For this reason, doctors consider multiple factors, including the timing after transplant, appearance of the rash, and results of any tests performed.

Treatment options

Treatment for acute graft versus host disease in skin depends on how severe the condition is^[10]. The goal of treatment is to manage symptoms and control the immune reaction that’s causing the skin damage^[10].

For mild cases (stage 1 or grade 1), you may not need any treatment at all^[10]. Instead, your doctor may recommend simply watching the condition closely. In some mild cases, treatment with a steroid cream applied directly to the affected skin may be sufficient^[10]. A common example is triamcinolone 0.1 percent cream^[11].

For moderate cases (grade 2), you may receive either a steroid cream, a course of steroid tablets taken by mouth, or steroids given directly into a vein, which doctors call intravenous steroids^[10]. The most common treatment for systemic cases involves continuing any immunosuppressive medication you were already taking to prevent GVHD and adding a steroid medication called methylprednisolone^[11].

For severe cases (grades 3 and 4), you will need intravenous steroids^[10]. The typical starting dose is 2 milligrams per kilogram of body weight per day, given in two divided doses^[11]. The median time for acute GVHD to resolve with treatment is 30 to 42 days^[11].

Some patients may also receive other medications along with steroids. One commonly used drug is ciclosporin, which you can take as a capsule or receive through a vein^[10]. These medicines work by dampening down the immune system so it doesn’t attack the body’s tissues^[10].

When steroids and ciclosporin don’t control the GVHD, doctors call this steroid-resistant GVHD^[10]. In these cases, other treatments may be used. These can include a type of light therapy called extracorporeal photopheresis (ECP), which is a procedure where white blood cells are collected, treated with a light-sensitive drug, exposed to ultraviolet light, and then returned to the body^[11].

Additional treatment options for resistant cases include monoclonal antibodies, which are laboratory-made proteins that target specific parts of the immune system, chemotherapy drugs, and various medicines that suppress the immune system or reduce inflammation^[10].

Your doctor might also refer you to a skin specialist called a dermatologist for expert advice on how to treat and manage your skin^[10]. The dermatologist may prescribe special creams, ointments, and bath oils^[10]. You might also receive treatment to help relieve itching and pain^[10].

What you can do to help yourself

While medical treatment is essential for managing acute GVHD in skin, there are several things you can do yourself to help keep your skin more comfortable^[10].

Clothing choices can make a difference. Try wearing cotton clothes, which are gentler on sensitive skin^[10]. Avoid getting too hot or too cold, as temperature extremes can worsen symptoms^[10].

When washing, use unperfumed soaps and warm water rather than hot water^[10]. After washing, let your skin air dry or gently pat it dry with a towel instead of rubbing, which can irritate damaged skin^[10]. However, if you have severe skin GVHD, you might find that air is painful on your skin, so you may prefer to keep the area covered^[10].

Keeping your skin well moisturized is very important^[10]. Use unperfumed creams or lotions regularly throughout the day. Some people find it helpful to apply lots of cream at night and wear old nightclothes and socks to bed^[10].

Protecting your skin from the sun is also crucial. Cover up when going outside, stay in the shade when possible, and always use sunscreen^[10]. Damaged skin is more vulnerable to sun damage than normal skin.

It’s important to contact your transplant team right away if you notice any new symptoms or if symptoms get worse after you start treatment^[5]. Early diagnosis and intervention are important for the best outcomes^[5]. You should document any new rashes or skin changes and share them with your healthcare provider promptly^[6].