HistoryThis section has been translated automatically.
DefinitionThis section has been translated automatically.
Complex multi-organ disease that occurs 3-5 months or later after allogeneic hematopoietic stem cell transplantation (see below Graft-versus-Host Disease) The skin is the most frequently affected organ. Clinical morphology shows an overlap between systemic scleroderma, lichen sclerosus, systemic lupus erythematosus and Sjögren's syndrome. The cGVHD can affect different compartments of the skin (epidermis, corium) as well as the subcutaneous fatty tissue. Epidermal or dermal or subcutaneous changes, or a combination of both, may be the main cause. The 2 most frequent manifestations are lichenoid and sclerodermiform cGVHD (Ziemer M 2013).
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ClassificationThis section has been translated automatically.
Classification of chronic GvHD
- Progressive form (about 32% of cases), which directly follows an acute form with the worst prognosis
- Delayed form (quiescent onset; about 36% of cases) occurring after a disease-free interval after acute GvHD
- De novo form (about 30% of cases), without previous acute GvHD, with the best prognosis.
Occurrence/EpidemiologyThis section has been translated automatically.
Since allogeneic stem cell transplantations (aSZT) are becoming more and more important therapeutically (expansion of indications), cGVHD will gain in importance in the future. About 50% of patients who survive allogeneic stem cell transplantation in the long term develop cGVHD.
EtiopathogenesisThis section has been translated automatically.
Clinical featuresThis section has been translated automatically.
A generalized form must be distinguished from a localized form.
- Generalized cGVHD: Beginning with lichenoid exanthema and hyperpigmentation in the facial area; erosive cheilitis, as well as extracutaneous manifestations such as sicca symptoms, keratoconjunctivitis, buccal mucositis, esophageal and vaginal strictures, intestinal infestation, lupoid hepatitis, general physical deterioration and pulmonary insufficiency. Risk of opportunistic infections. The lichenoid exanthema may develop into manifestations similar (or identical) to systemic scleroderma.
- Late cGVHD shows poikilodermatic conditions with extensive skin sclerosis and contractures.
- Localized cGVHD: Clinical features of lichen sclerosus et atrophicus, also genital lichen sclerosus (w>m) or lichen planus, circumscribed scleroderma ( Morphea), eosinophilic fasciitis ( analogous to Shulman's syndrome) or septal panniculitis.
- Images of pityriasis rosea have also been described. The changes can also spread linearly along the Blaschko lines.
- Nail alterations show as nail fold hyperkeratosis, onycholysis, transverse furrows, splinter hemorrhages, hyperpigmentation (melanonychia).
HistologyThis section has been translated automatically.
There is no specific pattern of chronic GvHD. Rather, there is a morphological substrate that corresponds to the clinical picture (lichenoid pattern, scleroderma-like pattern, etc.). In the papillary dermis, accumulations of melanophages occur during prolonged persistence of the skin lesions. Often there is a compact hyperkeratosis and hypergranulosis. There is a pronounced vacuum degeneration along the basal cell layer as well as keratinocyte apoptosis mainly in the lower epidermal layers and along the pelvic epithelium. Lymphocytic inflammation is usually subepithelial in the form of a band and is accentuated under the image of an interfacedermatitis. In the poicilodermal courses, an atrophy of the epidermis is noticeable in dermal sclerosis, melanin incontinence and telangiectasia. Sclerosing changes reach deep into the subcutaneous fatty tissue and remind of morphea. The extent of interface dermatitis decreases with increasing sclerosis.
TherapyThis section has been translated automatically.
The indication for systemic immunosuppression depends on the extent of organ involvement. At the latest when two organ systems are affected (e.g. skin and liver, skin and intestine, skin and mucous membrane), an immunosuppressive therapy is useful. The therapy belongs in the hands of experienced colleagues.
The chronic GVH reaction is also directed against residual leukemia cells. The aim of therapeutic efforts is therefore not the complete suppression of the GVHR.
In addition to systemic immunosuppressive treatment, the following therapies can be attempted in the treatment of scleroderma, erythematous and/or lichenoid skin changes:
- PUVA therapy, systemic: initial 0.5-0.25 J/cm2 at 0.6 mg/kg bw/day of methoxsalene (e.g. meladinine), dose increase up to 8 J/cm2 over several sessions. Maintenance therapy 1-2 times/week over 1-2 years.
- Thalidomide: Briefly 200-400 mg/day p.o., then reduction to 100 mg/day. Cave! Off-Label-Use! Strictest indication for women of childbearing age.
- Extracorporeal photopheresis: Every 4 weeks, good results are reported. Due to its good tolerability, it is an increasing supplement to systemic steropid therapy, especially since ECP does not negatively influence the graft-versus-leukemia effect and does not increase the risk of infection. In a larger retrospective study of 71 patients with steroid-refractory cGvHD the response rate of cutaneous manifestations was >50% (Flowers ME et al. 2008).
- Regarding the success of TNF alpha antagonists, the results of the study are awaited.
General therapyThis section has been translated automatically.
Regular intensive physiotherapy exercises are necessary to improve joint mobility.
Progression/forecastThis section has been translated automatically.
Chronic GvHD is the main risk factor for significant morbidity and mortality after allogeneic stem cell transplantation. Approximately 15% of patients die as a result. A further 25% suffer significant impairment of their quality of life. The main risk factor for the occurrence of chronic GvHD is a previous acute GvHD and a high recipient age.
LiteratureThis section has been translated automatically.
- Aubin F et al (1995) Phototherapy in the treatment of cutaneous graft-versus-host disease. Our preliminary experience in resistant patients. Transplantation 59: 151-155
- Barnes DW, Corp MJ, Loutit JF, Neal FE (1956) Treatment of murine leukaemia with X rays and homologous bone marrow; preliminary communication. Br Med J 32: 626-627
- Barnes DWH, Loutit JF (1957) Treatment of murine leukaemia with X-rays and homologous bone marrow. Br J Haematol 3: 241-252
- Cho A et al (2020) Cutaneous manifestations of acute and chronic graft-versus-host disease. G Ital Dermatol Venereol 155:76-87.
- Flowers ME et al (2008) A multicenter prospective phase 2 randomized study of extracorperal photopheresis for treatment of chronic graft versus host disease. Blood 112: 2667-2674
- Heney D et al (1990) Thalidomide in the treatment of graft-versus host disease. Biomed Pharm 44: 99-204
- Jampel RM et al (1991) PUVA Therapy for chronic cutaneus Graft-vs host disease. Arch Dermatol 127: 1673-1678
- Jung AG et al (2010) Unusual chronic scleroderma graft-versus-host disease. Dermatologist 61: 514-517
- Karrer S (2003) Cutaneous graft-versus-host disease. dermatologist 54: 465-480
- Lee JH et al (2003) Graft-versus-host disease (GVHD)-specific survival and duration of systemic immunosuppressive treatment in patients who developed chronic GVHD following allogeneic haematopoietic cell transplantation. Br J Haematol 122: 637-644
- Müller-Serten B et al (1994) Chronic scleroderma Graft-versus-Host Disease (GvHD). Dermatologist 45: 772-775
- Rupec RA, Plewig G (2004) Graft-versus-host-disease: An interdisciplinary problem from the dermatologist's perspective. JDDG 2: 249-259
- Travnik R et al (2011) Graft-versus-host-disease (GvHD) - an update. Dermatologist 62: 139-155
- Volc-Place B (1992) Graft-versus-host reaction (GvHD). dermatologist 43: 669-675
- Ziemer M (2013) Graft-versus-host disease of the skin and irritated mucous membranes. JDDG 11: 477- 496
Incoming links (6)BTK inhibitors and autoimmun diseases; Graft-versus-host disease; Imatinib; Lichen planus exanthematicus; Pseudoscleroderma; Thalidomide;
Outgoing links (15)Antiseptic; Blaschko lines; Circumscripts of scleroderma (overview); Fasciitis eosinophil; Graft-versus-host disease; Immunosuppressive drugs; Lichen planus classic type; Lichen sclerosus (overview); Photopheresis extracorporeal; Pityriasis rosea; ... Show all
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