Acute and Chronic Cutaneous Graft-versus-Host Disease: Diagnosis, Treatment, and Emerging Directions.

Update on graft versus host disease.

Diverse T Cell Responses Lead To The Different Manifestations Of Cutaneous Graft-Versus-Host Disease

Organ-Specific Protection By Bortezomib On The Treatment Of Cutaneous Chronic and Acute GvHD

Graft-versus-host disease (GVHD) is an immunologically mediated disease occurring most frequently after allogeneic bone marrow transplantation. The aim of this study was to evaluate the contribution of immunohistochemistry in the diagnosis of cutaneous GVHD. Patients transplanted for either leukemia or beta-thalassemia were included in the study. Skin lesions of acute and chronic GVHD were examined both by direct immunofluorescence to detect immunoglobulin deposits and by an avidin-biotin-peroxidase complex technique to evaluate the inflammatory cell infiltrate. Epidermal and dermal fluorescent bodies (IgG and IgM) were frequently found in both acute and chronic GVHD. Most of the infiltrating cells were CD3+ T lymphocytes, with CD8+ cells representing the major cell population invading the epidermis both in acute GVHD and in chronic lichenoid GVHD. A small proportion of the dermal cells were CD14+ macrophages; no B cells were detected. HLA-DR, but not HLA-DQ antigens, were variably expressed by keratinocytes in all cases of acute GVHD and in chronic lichenoid GVHD. KL-1, a monoclonal antikeratin antibody specific for the 56.5 KD acidic polypeptide usually present in suprabasal keratinocytes, stained all epidermal layers, including the basal layer. Langerhans cells were dramatically reduced in number in the epidermis of both acute and chronic lichenoid GVHD. It is concluded that immunohistologic analysis may be supportive in the diagnosis of acute and early chronic lichenoid cutaneous GVHD.

Acute and chronic cutaneous graft-versus-host disease (GVHD) are common complications following hematopoietic stem cell transplantation (HSCT) in pediatric patients. In this retrospective study, we explored the risk factors and clinical characteristics of acute and chronic cutaneous GVHD in a case series of children undergoing HSCT at a tertiary referral hospital. We found that 36% of acute cutaneous GVHD was severe and these patients were more likely to have an unrelated donor, and that children with acute cutaneous GVHD who progressed to chronic cutaneous GVHD had a higher proportion of malignant diseases, total body irradiation, and bronchiolitis obliterans compared to those who did not progress to chronic cutaneous GVHD. Our study highlights the importance of identifying and monitoring these high-risk patients to improve the clinical management and outcomes of cutaneous GVHD in pediatric HSCT recipients.

Extra-Domain-A Fibronectin: A New Marker of Fibrosis in Cutaneous Graft-Versus-Host Disease

Graft versus host disease (GVHD) is a significant complication following hematopoietic stem cell transplantation in the pediatric population. The most common clinical manifestation of GVHD is in the skin. This article will present a review of key concepts related to pediatric cutaneous GVHD, including pathophysiology, clinical epidemiology, diagnosis, and treatment options. GVHD is an immune-mediated process characterized by an inflammatory immune response in acute GVHD and mixed inflammatory and fibrotic states in chronic GVHD. The clinical presentations of cutaneous GVHD are heterogeneous. Acute cutaneous GVHD classically presents as an erythematous morbilliform eruption appearing within a few weeks after transplantation. Chronic cutaneous GVHD may manifest as poikiloderma, lichenoid lesions, or sclerodermatous changes. The sclerodermatous form of cutaneous GVHD is associated with substantial long-term morbidity, including joint contractures, myalgias, and mobility restriction. First-line pharmacologic treatment options typically include corticosteroids and in some cases, calcineurin inhibitors. Biologics and immunotherapies are an active area of investigation for GVHD that is refractory to corticosteroid treatment. Non-pharmacologic treatment options that have shown benefit for cutaneous GVHD include extracorporeal photopheresis and phototherapy. Accurate diagnosis and treatment of cutaneous GVHD is essential to preventing and alleviating the long-term sequelae and morbidity associated with this condition.

Graft-versus-Host Disease: State of the Science

Highlighting TH-1 Rather Than TH-17 Cytokine Network in Acute Cutaneous Gvhd

Impact of anti-HLA antibodies on allogeneic hematopoietic stem cell transplantation outcomes after reduced-intensity conditioning regimens

To evaluate the characteristics of cataracts following hematopoietic stem cell transplantation (HSCT), 561 patients without any ocular complications before HSCT were reviewed. Ocular complications occurred in 196 patients (34.9%). Cataract was diagnosed in 45 of 561 patients. The 10-year estimated cataract incidence was 14%. The median onset time was 498 days after transplant (range, 38-4,535 days). The onset of cataracts was later than that of other ocular complications. Phacoemulsification was performed in 13 patients (29%) at a median of 1,028 days after HSCT (range, 375-4,549 days). In 6 of 13 patients (46%) who underwent cataract surgery, visual acuities gradually deteriorated because of the development of posterior capsule opacification. YAG (yttrium-aluminum-garnet) laser posterior capsulotomy successfully recovered their sight without any sequelae. A multivariate analysis revealed that age, acute and chronic graft versus host disease (GVHD), and systemic infection were significant risk factors for cataract, whereas neither steroid nor total body irradiation (TBI)-containing regimens affected the development of cataract. Our results showed that the clinical outcomes of cataract after HSCT are favorable and comparable to those in the general population. Hyperfractionated TBI with eye shielding may be effective for the prevention of cataract.

JAK1/2 Inhibition As a Salvage Therapy for Steroid Refractory Acute and Chronic Graft Versus Host Disease in Pediatric Allogeneic Hematopoietic Stem Cell Transplant Recipients

Risk Factors For Chronic Eye and Mouth GVHD In Unrelated Hematopoietic Cell Transplantation: T Cell Depletion Is The Only Risk Factor Identified and Appears To Be Favorable

The Changing Face of Graft-Versus-Host Disease

Background: Graft-versus-host disease (GVHD) is a major complication after allogeneic hematopoietic stem cell transplantation (HSCT) and skin is involved in acute and chronic disease. Immune-mediated vessel attack and subsequent microvessel loss have been observed in skin of patients with chronic GVHD. Objectives: To test whether long-term survivors (LTS) after allogeneic HSCT without cutaneous GVHD show signs of persistent vascular remodeling. Methods: Microvessels in skin biopsies were investigated in a cohort of 32 LTS with a median follow-up of 17 years (range 11–26). Five were currently classified as having chronic GVHD other than skin involvement. Results: LTS showed no significant difference in median microvessel density and relative vessel size distribution pattern compared to healthy controls. Past experience of GVHD and current status of chronic GVHD other than skin involvement had no impact on vessel density. In contrast, recipients with chronic cutaneous GVHD of sclerotic type and patients with lichen sclerosus have significant microvessel loss in the upper dermis. Conclusion: The complex therapy of allogeneic HSCT had no sustained effect on the microvascular architecture of LTS when clinicopathological evidence of cutaneous GVHD is absent. Microvascular remodeling as observed during chronic GVHD recovers completely after resolution of chronic cutaneous GVHD.