Patients with erythema covering >10% of their BSA had an increased risk of mortality1
Skin rash is the most common symptom of cGVHD following a stem cell transplant, making it an ideal marker of disease progression1
- Most likely to occur soon after transplant
- Most visible to patients and physicians
- Skin is the most frequently involved organ system in cGVHD
Despite the prevalence of early skin involvement in cGVHD, routine systemic therapy is not prioritized.2,3
Erythema could be a marker of increased risk of death1
- Erythema BSA involvement was associated with:
greater risk of nonrelapse mortality (NRM)
(HR, 1.33; 95% Cl, 1.19-1.48; P<0.001)1
greater risk of death per 10% increase in BSA
(HR, 1.28 per 10% increase in BSA; 95% Cl, 1.14-1.44; P<0.001)1
- Patients with >10% BSA involvement at the first follow-up visit had a greater likelihood of NRM vs those with <10% BSA involvement1
Symptoms across organs
cGVHD manifests as a heterogeneous disease and may be restricted to a single organ or affect multiple organs with varying degrees of severity and impact.4 This is why it is important to educate patients on the importance of monitoring the symptoms of cGVHD progression.
Asking patients contextual questions may help them recognize symptoms and aid in early identification of cGVHD.5 Use this tear sheet to start the conversation.
Use the arrows below to see how cGVHD can manifest across the body.
- Poikiloderma: atrophy, pigmentary changes, and telangiectasia4
- Lichen planus–like features: erythematous/violaceous flat-topped papules or plaques with or without surface reticulations or a silvery or shiny appearance4
- Sclerotic features: smooth, waxy, indurated skin; can be described as thickened or tight skin4
- Morphea-like features: localized patchy areas of movable smooth or shiny skin with leather-like consistency, often with dyspigmentation4
- Lichen sclerosus–like features: discrete to coalescent, gray to white, movable papules or plaques, often with follicular plugs, shiny appearance, and tissue paper–like wrinkled texture4
- Nail ridging or splitting4
- Alopecia; loss of body hair4
- New onset of dry, gritty, or painful eyes4
- Cicatricial conjunctivitis: often ulcerative, with purulent discharge of leukocytes and fibrosis4,6
- Keratoconjunctivitis sicca: lymphocytic infiltration of lacrimal glands leading to punctate keratitis, corneal filaments, persistent epithelial defects, corneal keratinization, and ulceration4,6
- Confluent areas of punctate keratopathy: closely spaced pinpoint defects indicating loss of corneal epithelium4,6,7
- Photophobia4
- Total bilirubin, alkaline phosphatase >2 x ULN4
- ALT >2 x ULN4
- Lichen planus–like features: reticular white lines, erythematous patches, redness, erosive areas, telangiectatic areas, vulvar synechiae, and labial fusion and resorption8
- Lichen sclerosus–like features4
- Vaginal scarring or clitoral/labial agglutination (females)4
- Phimosis or urethral/meatus scarring or stenosis (males)4
- Lichen planus–like changes: white hyperkeratotic reticulations and plaques, erythematous changes, and ulcerations, ranging from mild reticulation to more extensive disease with painful ulcerations4,9
- Mucoceles or ulcers4
- Bronchiolitis obliterans diagnosed with lung biopsy: inflammation of small-airway epithelial cells and subepithelial structures leading to excessive fibroproliferation4,10
- Bronchiolitis obliterans syndrome4
- Cryptogenic organizing pneumonia4
- Air trapping4
- Esophageal web: formation of membranous folds blocking the esophagus4,11
- Strictures or stenosis in the upper to mid third of the esophagus4
- Fasciitis: characterized by inflammatory cells infiltrating the fascia4,12,13
- Joint stiffness or contractures secondary to fasciitis or sclerosis4
- Myositis: lymphocyte infiltration into the muscle4,12,13
- Arthralgia4
Select an icon below to see how cGVHD can manifest across the body.
- Poikiloderma: atrophy, pigmentary changes, and telangiectasia4
- Lichen planus–like features: erythematous/violaceous flat-topped papules or plaques with or without surface reticulations or a silvery or shiny appearance4
- Sclerotic features: smooth, waxy, indurated skin; can be described as thickened or tight skin4
- Morphea-like features: localized patchy areas of movable smooth or shiny skin with leather-like consistency, often with dyspigmentation4
- Lichen sclerosus–like features: discrete to coalescent, gray to white, movable papules or plaques, often with follicular plugs, shiny appearance, and tissue paper–like wrinkled texture4
- Nail ridging or splitting4
- Alopecia; loss of body hair4
- New onset of dry, gritty, or painful eyes4
- Cicatricial conjunctivitis: often ulcerative, with purulent discharge of leukocytes and fibrosis4,6
- Keratoconjunctivitis sicca: lymphocytic infiltration of lacrimal glands leading to punctate keratitis, corneal filaments, persistent epithelial defects, corneal keratinization, and ulceration4,6
- Confluent areas of punctate keratopathy: closely spaced pinpoint defects indicating loss of corneal epithelium4,6,7
- Photophobia4
- Total bilirubin, alkaline phosphatase >2 x ULN4
- ALT >2 x ULN4
- Lichen planus–like features: reticular white lines, erythematous patches, redness, erosive areas, telangiectatic areas, vulvar synechiae, and labial fusion and resorption8
- Lichen sclerosus–like features4
- Vaginal scarring or clitoral/labial agglutination (females)4
- Phimosis or urethral/meatus scarring or stenosis (males)4
- Lichen planus–like changes: white hyperkeratotic reticulations and plaques, erythematous changes, and ulcerations, ranging from mild reticulation to more extensive disease with painful ulcerations4,9
- Mucoceles or ulcers4
- Bronchiolitis obliterans diagnosed with lung biopsy: inflammation of small-airway epithelial cells and subepithelial structures leading to excessive fibroproliferation4,10
- Bronchiolitis obliterans syndrome4
- Cryptogenic organizing pneumonia4
- Air trapping4
- Esophageal web: formation of membranous folds blocking the esophagus4,11
- Strictures or stenosis in the upper to mid third of the esophagus4
- Fasciitis: characterized by inflammatory cells infiltrating the fascia4,12,13
- Joint stiffness or contractures secondary to fasciitis or sclerosis4
- Myositis: lymphocyte infiltration into the muscle4,12,13
- Arthralgia4
ALT=alanine transaminase; BSA=body surface area; cGVHD=chronic graft-versus-host disease; CI=confidence interval; HR=hazard ratio; ULN=upper limit of normal.
References: 1. Baumrin E, Baker LX, Byrne M, et al. Prognostic value of cutaneous disease severity estimates on survival outcomes in patients with chronic graft-vs-host disease. JAMA Dermatol. 2023;159(4):393-402. 2. Link-Rachner CS, Sockel K, Schuetz C. Established and emerging treatments of skin GvHD. Front Immunol. 2022;13:838494. doi:10.3389/fimmu.2022.838494. 3. Strong Rodrigues K, Oliveira-Ribeiro C, de Abreu Fiuza Gomes S, Knobler R. Cutaneous graft-versus-host disease: diagnosis and treatment. Am J Clin Dermatol. 2018;19(1):33-50. 4. Jagasia MH, Greinix HT, Arora M, et al. National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: I. The 2014 Diagnosis and Staging Working Group report. Biol Blood Marrow Transplant. 2015;21(3):389-401.e1. 5. Carpenter PA. How I conduct a comprehensive chronic graft-versus-host disease assessment. Blood. 2011;118(10):2679-2687. 6. Nassar A, Tabbara KF, Aljurf M. Ocular manifestations of graft-versus-host disease. Saudi J Ophthalmol. 2013;27(3):215-222. 7. Singh P, Tripathy K. Keratopathy. In: StatPearls. StatPearls Publishing; 2024. Accessed June 5, 2024. https://www.ncbi.nlm.nih.gov/books/NBK562153. 8. Smith Knutsson E, Björk Y, Broman AK, et al. A prospective study of female genital chronic graft-versus-host disease symptoms, signs, diagnosis and treatment. Acta Obstet Gynecol Scand. 2018;97(9):1122-1129. 9. Treister N, Duncan C, Cutler C, Lehmann L. How we treat oral chronic graft-versus-host disease. Blood. 2012;120(17):3407-3418. 10. Barker AF, Bergeron A, Rom WN, Hertz MI. Obliterative bronchiolitis. N Engl J Med. 2014;370(19):1820-1828. 11. Ghazaleh S, Patel K. Esophageal webs and rings. In: StatPearls. StatPearls Publishing; 2024. Accessed June 4, 2024. https://www.ncbi.nlm.nih.gov/books/NBK539771. 12. Koh S, Koh H, Nakashima Y, et al. Plasma kinetics of Th1, Th2 and Th17 cytokines in polymyositis related to chronic graft-versus-host disease. Intern Med. 2016;55(16):2265-2270. 13. Oda K, Nakaseko C, Ozawa S, et al; for the Kanto Study Group for Cell Therapy. Fasciitis and myositis: an analysis of muscle-related complications caused by chronic GVHD after allo-SCT. Bone Marrow Transplant. 2009;43(2):159-167.