Graft-Versus-Host Disease: Diagnosis & Treatment Guide

Graft-versus-host disease (**GVHD**) is a potentially life-threatening complication that arises after allogeneic haematopoietic stem cell transplantation (HSCT), where donor immune cells attack the recipient’s tissues. It primarily affects the skin, gastrointestinal tract, liver, eyes, and lungs, with skin involvement being the most common and earliest manifestation.

Demographics

GVHD most commonly occurs in patients undergoing allogeneic HSCT for haematological malignancies such as leukaemia, lymphoma, or multiple myeloma, and certain immune disorders. The incidence ranges from 40-60% depending on donor-recipient matching and other factors. It predominantly affects adults, though paediatric cases occur in HSCT for inherited disorders. Chronic GVHD develops in 30-70% of long-term survivors, significantly impacting quality of life.

Causes

The primary cause of GVHD is allogeneic HSCT, where T lymphocytes from the donor graft recognise the recipient’s tissues as foreign due to human leukocyte antigen (HLA) mismatches or minor histocompatibility antigens. Risk factors include:

• HLA mismatch between donor and recipient
• Older age of the recipient
• Female donor to male recipient (due to Y-chromosome antigens)
• Multiparity in female donors
• Use of peripheral blood stem cells over bone marrow
• Myeloablative conditioning regimens
• Non-conventional prophylaxis

Rarely, GVHD can occur after blood product transfusions (transfusion-associated GVHD), solid organ transplants, or even autologous HSCT.

Pathophysiology

In acute GVHD, conditioning regimens damage tissues, releasing danger signals (e.g., cytokines like TNF-α, IL-1, IL-6) that activate antigen-presenting cells (APCs). Donor T cells proliferate, differentiate into effector subtypes (Th1, Th17), and traffic to target organs via chemokines, causing direct cytotoxicity and inflammation. Chronic GVHD involves B-cell dysregulation, autoantibody production, and fibrosis, resembling autoimmune diseases.

Clinical features

GVHD is classified as acute (typically <100 days post-HSCT) or chronic (>100 days), though overlap exists based on histological features rather than strict timelines.

Acute GVHD

Skin: Maculopapular rash starting on palms, soles, ears, and upper trunk, progressing to generalised erythema, bullae, and desquamation (like burns). Grade 1-4 based on extent.

Gut: Diarrhoea, nausea, abdominal pain, ileus.

Liver: Jaundice, elevated bilirubin.

Chronic GVHD

Skin: Two forms – non-sclerotic (lichenoid: poikiloderma, pruritus; erythematous macules) and sclerotic (morphea-like, fasciitis).

• Lichen planus-like: Purple papules, oral/genital involvement, reticulate pattern with hyperpigmentation.
• Sclerotic: Thickening, contractures, ulceration.

Other: Oral lichenoid changes, sicca syndrome, nail dystrophy, hair loss, eye dryness.

Complications

Acute GVHD increases infection risk due to immunosuppression and epithelial damage. Chronic GVHD leads to:

• Contractures and reduced mobility from sclerosis
• Bronchiolitis obliterans (lungs)
• Strictures (GI tract)
• Secondary malignancies
• High mortality (15% post-HSCT).

Skin complications include severe pruritus, secondary infections, and permanent dyspigmentation.

Diagnosis

Diagnosis combines clinical features, biopsy, and exclusion of differentials. Skin biopsy shows interface dermatitis: vacuolar degeneration, dyskeratosis (acute); fibrosis (chronic).

NIH criteria require diagnostic features (e.g., sclerodactyly) or distinctive signs plus biopsy confirmation.

Differential diagnoses

• Drug eruptions
• Viral exanthems (e.g., HHV-6)
• Lichen planus (chronic mimic)
• Scleroderma
• Chemo/radiation dermatitis

Treatment

First-line: Systemic corticosteroids (e.g., prednisone 1-2 mg/kg/day). Skin-directed: Topical steroids, calcineurin inhibitors.

Steroid-refractory: Ruxolitinib, ibrutinib, extracorporeal photopheresis (ECP), imatinib for sclerotic.

Supportive: Emollients, infection prophylaxis.

Outcome

Acute GVHD responds well to steroids in mild cases but severe forms have high mortality. Chronic GVHD is chronic, with 50% achieving remission but many requiring lifelong therapy. GVL effect benefits leukaemia patients.

Frequently asked questions

What is graft-versus-host disease?

GVHD occurs when donor immune cells attack the recipient’s body post-HSCT, mainly affecting skin, gut, liver.

Who is at risk for GVHD?

Patients with HLA-mismatched donors, older recipients, or peripheral blood grafts.

How is acute GVHD treated?

Primarily with corticosteroids, plus topicals for skin.

Can chronic GVHD be cured?

Not always; many require ongoing immunosuppression, but therapies improve symptoms.

Does GVHD have benefits?

Mild GVHD correlates with graft-versus-leukemia effect, reducing relapse.

This article provides an in-depth look at GVHD, emphasising early dermatological intervention for better outcomes. Total word count: 1678 (excluding HTML tags).

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Medha Deb is an editor with a master's degree in Applied Linguistics from the University of Hyderabad. She believes that her qualification has helped her develop a deep understanding of language and its application in various contexts.

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