Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0018133 (graft-versus-host disease)
18,032 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Acute graft-versus-host disease (GVHD) usually involves the skin, gastrointestinal tract, and liver. A 47-year-old woman with fever of unknown origin was referred for a Ga-67 scan. The study showed diffuse uptake of Ga-67 throughout the skin. Subsequently, a skin biopsy confirmed the diagnosis of acute GVHD. The incidence, diagnosis, and pathophysiology of the dermatitis in acute GVHD are discussed.
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PMID:Ga-67 uptake in cutaneous lesions of graft-versus-host disease. 1098 52

Radiation recall dermatitis refers to an inflammatory skin reaction at a previously irradiated field subsequent to chemotherapy administration. A number of antineoplastic agents have been reported to cause this phenomenon. We observed radiation recall dermatitis in a patient with stage IV nodular sclerosing Hodgkin's disease after methotrexate therapy for acute graft-versus-host disease (GVHD) prophylaxis. The patient had previously undergone matched related bone marrow transplantation with busulfan and cyclophosphamide as a preparative regimen. Subsequently, she received cyclosporine and methotrexate for acute GVHD prophylaxis. Two areas of skin previously irradiated to 3,000 cGy developed radiation recall dermatitis after two doses of methotrexate given 2 days apart and exacerbated by the third and fourth doses. This reaction occurred 34 days after the last dose of radiation therapy (RT). We believe this is the first case of radiation recall dermatitis after methotrexate therapy. Given the increased use of methotrexate in several neoadjuvant and adjuvant protocols in association with RT, its potential to produce radiation recall reactions should be considered.
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PMID:Radiation recall dermatitis induced by methotrexate in a patient with Hodgkin's disease. 1131 2

A patient with severe aplastic anemia underwent a matched unrelated bone marrow transplant, following which he developed a complex autoimmune syndrome. This featured transverse myelitis, immune mediated Coombs positive hemolytic anemia and immune thrombocytopenia (Evans syndrome), pulmonary infiltrates, eosinophilia, muscle pains and cramps and lichenoid dermatitis all of which may represent manifestations of graft-versus-host disease as they showed response to immunosuppression. Thus, although immune-mediated cytopenias after an allogeneic bone marrow transplant are rare, they should be considered as a possible cause of cytopenia in post-transplant patients.
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PMID:An immunological syndrome featuring transverse myelitis, Evans syndrome and pulmonary infiltrates after unrelated bone marrow transplant in a patient with severe aplastic anemia. 1114 36

The first topical immunomodulator approved for human use, tacrolimus ointment (Protopic, Fujisawa, Healthcare, Inc, Deerfield, IL), has been shown to be effective and safe in the treatment of children (aged 2 years and older) and adults with atopic dermatitis (AD). Clinical trials conducted worldwide have involved 12,000 patients, with safety and efficacy data available for up to 3 years of treatment. In addition to its beneficial effects in the management of AD, topical tacrolimus has also been reported to be of benefit in other immunologically mediated skin diseases including: hand dermatitis, contact dermatitis, eyelid dermatitis, erosive lichen planus, steroid-induced rosacea, pyoderma gangrenosum, and graft-versus-host disease. This article reviews the clinical experience of topical tacrolimus in the treatment of AD and other skin conditions.
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PMID:Tacrolimus clinical studies for atopic dermatitis and other conditions. 1177 Sep 12

Antigen-presenting cells (APCs) participate in the initiation of the inflammatory process in various immune-mediated dermatoses through the activation of antigen-specific T lymphocytes. The skin contains several different subsets of APCs. To investigate the role of these APCs in T-cell immune-mediated inflammation, we examined the distribution and numbers of epidermal and dermal CD1a(+) dendritic cells (DCs), factor XIIIa(+) dermal DCs, and CD68(+) macrophages in five T-cell-mediated inflammatory skin diseases. Immunohistochemistry of CD1a, factor XIIIa, and CD68 was performed using paraffin-embedded tissue obtained from a total of 51 patients with eczematous dermatitis (histologically spongiotic dermatitis), psoriasis, lichen planus, acute graft-versus-host disease (GVHD), and chronic GVHD. The numbers of positive cells for each staining were compared with those in site-matched normal skin control specimens from aged-matched subjects. In spongiotic dermatitis and lichen planus, the numbers of epidermal and dermal CD1a(+) cells and factor XIIIa(+) cells were significantly greater than in normal control skin, while in psoriasis only factor XIIIa(+) cells were significantly increased in number. Acute and chronic GVHD showed a reduced number of dermal CD1a(+) cells. Interestingly, factor XIIIa(+) cells were decreased in acute GVHD while they were increased in chronic GVHD. There was a significant reduction in epidermal CD1a(+) cells in acute GVHD, but not in chronic GVHD. The differences in the numbers of APCs in lesional skin appeared to reflect differences in the pathophysiology of these inflammatory skin diseases.
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PMID:Comparison of the distribution and numbers of antigen-presenting cells among T-lymphocyte-mediated dermatoses: CD1a+, factor XIIIa+, and CD68+ cells in eczematous dermatitis, psoriasis, lichen planus and graft-versus-host disease. 1237 34

Thymectomy of Sprague-Dawley rats on the 3rd day of life failed to influence the time of onset, incidence, clinical, or histologic picture of runt disease produced by the intraperitoneal injection of adult Long-Evans spleen cells. The fact that severe immunologic impairment of the host by thymectomy does not modify runt disease was felt to be consistent with the current view that the if direction of the immunologic event in this syndrome is graft versus host. Following the injection of 800 to 1000 million Long-Evans spleen cells into adult Sprague-Dawley rats, a severe illness comprised of dermatitis, gastrointestinal bleeding, arthritis, weight loss, and death ensued in 37 per cent of adults thymectomized neonatally and 13 per cent of normal controls. Histologic lesions were observed in 69 per cent of adequately thymectomized animals and 17 per cent of normal controls, and involved lymph nodes, spleen, liver, lungs, kidneys, joints, heart, and skin. The time of onset and the histologic and clinical pictures are consistent with the adult disease being a typical graft versus host reaction.
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PMID:The production of runt disease in rats thymectomized at birth. 1401 35

This paper describes our own findings on the role of Langerhans' cells in dermatology and discusses literature data on their detection in seven different dermatoses. The skin is an integral part of immune system. During the past 30 years, increasing evidence has been accumulated that the skin contains cellular elements which are needed for the initiation and expression of immune response. Langerhans' cells (LCs) are dendritic cells originating in the bone marrow. They reside mainly within stratified squamous epithelia and constitute approximately 2-4% of epithelial cells. LCs are epidermal antigen presenting cells which play a crucial role in allergic contact hypersensitivity, viral diseases, graft versus host disease and elimination of neo-plastic cell clones. They express antigens conjugated with major histocompatibility complex (MHC) class II positive molecules on their surfaces for presentation to T-helper lymphocytes. LCs cannot be identified in routinely prepared histologic testing but can be visualised at the light microscope level by histochemical and immunologic techniques. Appropriate methods for the detection of Langerhans' cells in dermatology (also shown by our own experience) are histoenzymatic methods of adenosintriphosphatase (ATP-ase), acid phosphatase (AP), alpha-naphthylacetatesterase (ANAE and peroxidase-antiperoxidase immunohistochemistry method with polyclonal S-100 protein antibody (PAP). LCs are the only cells in normal skin with ATP-ase activity. Histoenzymatic methods used in patients with atopic dermatitis, vitiligo, mycosis fungoides, Behcet's disease, lichen ruber planus, psoriasis vulgaris, irritant dermatitis and allergic contact dermatitis demonstrated LSs in epidermis and dermis. ANAE and AP showed concordance and were suitable histochemical markers for LC distribution and macrophages in the dermis in mycosis fungoides, atopic dermatitis, psoriasis vulgaris, irritant chronic dermatitis and Bechet's disease. Our experience of the human skin showed a strong activity of calcium-activated adenosine triphosphatase in LCs. LCs in the guinea pig skin can be demonstrated by Mg++ and Ca++ activated adenosine triphosphatase, but a stronger activity of Ca++ activated adenosine triphosphatase in LCs after irritation. Ca++ ATP-ase as an indicator of energy-dependent pump is the reflection of intracellular calcium level, which is a significant factor for regulating the growth and metabolism of the cells. LCs are found as target cells during the efferent phase of contact allergic reaction. Immunohistochemical methods, define the role of LCs in dermatology more precisely and allow complete immunologic recognition within the epidermis.
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PMID:[Identification of Langerhans cells in dermatology]. 1528 65

Graft-versus-host disease (GvHD) is a frequent and serious complication of bone-marrow transplantation (BMT), and carries a high morbidity and mortality if not promptly recognized and treated. The rash of acute GvHD is often difficult to distinguish clinically from a drug eruption, and skin biopsies are often performed in an attempt to render a diagnosis. Histologically, eosinophils are classically associated with hypersensitivity reactions, and their presence in inflamed tissue is considered suggestive of a drug-induced dermatitis. We present 3 cases of acute exanthema in BMT recipients in whom the presence of eosinophils on skin biopsy specimen led to an initial diagnosis of drug eruption over GvHD. As a result, these patients experienced delays in the institution of definitive immunosuppressive therapy for GvHD. We review the growing literature suggesting that no single or combined histologic feature, including tissue eosinophils, is useful in differentiating GvHD from drug eruptions in BMT recipients. Indeed, in most cases, the cause of a new-onset blanchable erythematous rash in a BMT recipient is most accurately determined by close examination and follow-up of the clinical features without a skin biopsy.
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PMID:Tissue eosinophils and the perils of using skin biopsy specimens to distinguish between drug hypersensitivity and cutaneous graft-versus-host disease. 1538 88

Tacrolimus is one of the newer immunosuppressants that act by inhibiting T-cell activation and cytokine release. It is approved for the treatment of atopic dermatitis, and its safety and efficacy have been extensively studied in large-scale randomized controlled trials and open-label studies worldwide involving over 12,000 patients and up to 3 years of follow-up. Since its introduction, anecdotal reports and case series have found topical tacrolimus also to be effective and well tolerated in patients with a variety of other skin disorders, including other types of eczema, papulosquamous disorders, disorders of cornification, rosacea, other inflammatory skin conditions, vesiculobullous diseases, vitiligo, connective-tissue diseases, graft-versus-host disease, and follicular disorders. This paper reviews the currently available evidence on the use of topical tacrolimus for these conditions, as well as its safety profile and cost-effectiveness. Tacrolimus does appear to offer a safe and efficacious alternative that minimizes the need for topical glucocorticoids and does not cause skin atrophy. However, the risk of systemic absorption is increased with generalized disruption of the skin barrier. Further large-scale studies are needed to clarify the efficacy of topical tacrolimus in a variety of conditions for which anecdotal reports of success exist, especially in regard to different racial groups and in comparison to (as well as in combination with) other existing therapies. Long-term safety data should continue to be monitored and reported.
Dermatitis 2005 Mar
PMID:Topical tacrolimus: a review of its uses in dermatology. 1599 45

Allogeneic stem cell transplantations (SCT) are currently being used as a therapy for hematological malignancies, some solid tumors and nonmalignant bone marrow deficiencies. Nevertheless, clinical applicability is limited due to toxicity of conditioning regimens, graft-versus-host disease (GVHD) and the scarcity of HLA-identical family donors. New concepts are based on nonmyeloablative conditioning to reduce toxicity, prevention or amelioration of GVHD and the use of haploidentical donors to increase donor availability. To combine these requirements, we have developed a nonmyeloablative conditioning regimen, consisting of low-dose total body irradiation and cyclophosphamide-based chemotherapy. In a haploidentical F1 --> F1 mouse model, this nonmyeloablative transplantation protocol resulted in stable full donor chimerism, but also in the development of severe GVHD. Administration of keratinocyte growth factor (KGF) reduced GVHD, evident as reduced weight loss and a lesser degree of dermatitis, compared to saline-treated controls. KGF preserved plasma citrulline and tumor necrosis factor-alpha levels, both indicative for reduced injury to the gastrointestinal tract. This was confirmed by histological findings. At 6 months after transplantation, survival rates were significantly higher in KGF-treated animals as compared to phosphate buffered saline-treated controls. These results indicate that KGF preserves gut integrity and might therefore contribute substantially to reduction of lethal GVHD in (nonmyeloablative) haploidentical transplantation.
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PMID:Keratinocyte growth factor ameliorates acute graft-versus-host disease in a novel nonmyeloablative haploidentical transplantation model. 1615 17


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