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

Human graft-versus-host disease (GVHD) has several cutaneous manifestations, including a lichenoid and a sclerotic injury pattern. A versatile animal model of graft-versus-host skin disease (GVHSD) would facilitate study of the pathophysiology of these two cutaneous injury patterns. We have examined two murine chimeras histologically and have found two distinct patterns. Allogeneically transplanted B1/6 mice show a prolonged lichenoid-interface dermatitis that eventuates in clinical alopecia, whereas LP/J recipients of allogeneic cells do not show hair loss. Their histopathology consists of an early lichenoid phase that abates and is replaced by dermal sclerosis. Because of the versatility of the mouse as a laboratory animal, we feel that this model provides an excellent opportunity to define the immunopathologic mechanisms responsible for skin injury in GVHD. In addition, an understanding of the pathogenesis of the T cell-dependent, lichenoid, and sclerotic patterns of tissue injury in GVHSD might well provide insight into the pathogenesis of the GVHSD analogs, cutaneous lupus erythematosus and scleroderma.
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PMID:Murine graft-versus-host skin disease: a chronologic and quantitative analysis of two histologic patterns. 663 Oct 52

Although bone marrow transplantation (BMT) can eliminate the hematologic manifestations of Fanconi anemia (FA), patients are unusually susceptible to complications associated with the use of cyclophosphamide (CY) in the conditioning regimen. To investigate modifications of the conditioning regimen, we reviewed the records of 24 patients with FA who received an allogeneic BMT. All patients presented with severe pancytopenia. One patient was transplanted with overt leukemia as well. Donors were HLA-identical siblings in 22 cases and 1- and 2-antigen mismatched relatives in two cases, respectively. All conditioning regimens included CY 200 mg/kg in 10 patients; 140 mg/kg with or without antithymocyte globulin in 12 and 20 mg/kg with 400 cGy total body irradiation in two. GVHD prophylaxis comprised methotrexate and/or cyclosporine. Only one of 21 evaluable patients did not show signs of engraftment. Toxicities included grade III/IV mucositis in 20 patients, severe dermatitis in four and veno-occlusive disease in four. Acute GVHD (> or = grade II) occurred in nine of 22 patients. Four patients developed chronic GVHD. With a median follow-up time of 24 months, 14 of the 24 patients are alive with normal hematopoietic function. Eight of the 10 patients with matched sibling donors who were conditioned with CY 140 mg/kg are alive and well. We conclude that BMT is an effective treatment for FA. Conditioning regimens using lower doses of CY are associated with manageable toxicity and can potentially increase the survival rate of patients with HLA-matched donors.
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PMID:Bone marrow transplantation for patients with Fanconi anemia: a study of 24 cases from a single institution. 777 21

An infant suffered from psoriasiform dermatitis complicated by severe constitutional symptoms. During his 12 months of hospitalization, the symptoms exacerbated periodically despite numerous therapeutic trials. Histologic findings revealed lichenoid psoriasiform dermatitis with striking eosinophilic necrosis of epidermal cells and satellite cell necrosis. Immunohistochemically, CD1+ Langerhans cells had almost disappeared, and CD8+ cytotoxic-suppressor T cells were predominant over CD4+ helper-inducer T cells in the epidermis. These findings in the skin biopsy specimens suggested some similarity to graft-versus-host disease but no known cause of that disorder was proved. Finally, methotrexate was effective. The patient became afebrile, and his skin lesions improved, leaving almost no scarring. This patient seems to have had specific clinical features that do not correspond with any of the known dermatitis. Clinical, histologic, and laboratory findings did not uncover any etiologic factors.
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PMID:A case of infantile febrile psoriasiform dermatitis. 779 16

Lethally irradiated Lewis (LEW) rats, reconstituted with syngeneic bone marrow and next given Cyclosporin A (CyA) for several weeks, develop disease (Cyclosporin A-induced autoimmunity; CyA-AI) after withdrawal of CyA. This disease resembles in terms of dermal changes the acute dermatitis and chronic scleroderma also seen in graft-versus-host disease (GVHD). In this study we report the relative resistance of the Brown Norway (BN) rat strain to the induction of CyA-AI. In contrast to LEW rats, in which CyA-AI was originally described, BN rats showed no acute dermatitis or scleroderma-like skin pathology in spite of comparable changes in the thymus and a maturation arrest of CD4+ T cells. The difference was also demonstrated functionally for whereas in LEW rats delayed-type hypersensitivity (DTH) reactions could not be elicited during CyA-AI, these were within normal limits in BN rats subjected to the same protocol; NK activity on the other hand was unaffected in both strains. The observation that BN rats developed very mild late disease as evidenced by a slight though significant weight loss suggests that the BN strain is susceptible to the disease but that lesser effector cell generation or, alternatively, stronger suppressor cell responses may prevent dermal disease. These observations may contribute to the elucidation of the mechanisms involved in this experimental autoimmune disease.
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PMID:Susceptibility and resistance to cyclosporin A-induced autoimmunity in rats. 813 64

A hypereosinophilic syndrome associated with dermatitis has been observed rarely in association with HIV infection. We describe the case of a young man with AIDS who came to us with a diffuse cutaneous eruption, fever, angioedema, eosinophilia, and a mildly elevated serum IgE level. No allergic or infectious cause of this illness could be determined, and the patient was treated with corticosteroids and PUVA therapy, resulting in complete resolution of the dermatitis and associated findings. In this case, there were clinical and histopathologic similarities to the idiopathic hypereosinophilic syndrome and to acute graft-versus-host disease. The serum level of the cytokine interleukin-5 (IL-5), which is associated with eosinophil production, was found to be mildly elevated during the peak of the eruption, while samples drawn previously and subsequently were not. Although it appears that the syndrome we describe is associated with the measurably elevated level of IL-5, further investigation is required to determine whether there is a cause and effect relationship between IL-5 and this entity. A brief review of the literature concerning eosinophils and HIV infection is also presented in the context of this case.
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PMID:Hypereosinophilic syndrome associated with HIV infection. Military Medical Consortium for Applied Retroviral Research. 815 85

Omenn syndrome is a variant of SCID, inherited as an autosomal recessive disorder, and characterized by severe eczematoid dermatitis, eosinophilia, elevated serum IgE and a distinctive histology in enlarged lymph nodes. The etiology of Omenn syndrome is unknown, however, unlike other forms of SCID; patients with Omenn syndrome have activated T lymphocytes in their circulation capable of non-MHC restricted cytotoxic function. Recently, it has been observed that the use of immunosuppressive therapy, particularly cyclosporine, can modify the clinical manifestations of the disorder. Prior to the use of bone marrow transplantation this disease was universally fatal. Death typically occurred in infancy as the result of opportunistic infections and/or malignancies, most notably lymphomas. While bone marrow transplantation has become quite successful for many phenotypes of SCID, even with the use of alternative donors other than histocompatible siblings, in Omenn syndrome it remains a challenge. In our experience, patients with Omenn syndrome exhibit a higher incidence of Gram negative sepsis, before and during transplantation, and carry a significant risk of post-transplant rejection when compared with patients with other phenotypes of SCID. We report the results of six patients treated with bone marrow transplantation from alternative donors, three had unrelated donors (URD) and three had haplo-identical parental donors. Five of the six patients achieved complete and/or durable donor cell engraftment and only one patient experienced acute GVHD. Three patients died of transplant-related complications (infection or EBV-associated B cell lymphoma) between day +22 and day +95 post-transplant. Three patients survived more than 1 year post-transplant.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Mismatched bone marrow transplantation for Omenn syndrome: a variant of severe combined immunodeficiency. 853 10

Rapamycin (RAPA) has been shown to be a highly effective means of reducing the lethality of graft-versus-host disease (GVHD) in B10.BR recipients of allogeneic C57BL/6 donor cells. RAPA-treated mice had no clinical (e.g., weight loss, diarrhea, lethargy) or histologic evidence of classical acute or chronic GVHD but did develop a clinical-pathological syndrome consisting of ulcerative dermatitis, bile duct proliferation, and a nondestructive peribronchiolar pulmonary infiltration. Because RAPA was found to interfere with the deletion of self-reactive T cells, we wondered whether the RAPA-induced syndrome was related to failed negative selection or altered alloreactivity. We now show that the RAPA-induced syndrome is due to effects on mature, donor-derived alloreactive T cells. By titering the number of T cells infused we were able to vary the syndrome incidence. In contrast to the syndrome seen after cyclosporin A (CsA) administration, the RAPA syndrome did not require an intact thymus and the disease could not be adoptively transferred. The addition of CsA (which blocks T-cell cytokine production) to RAPA (which blocks T-cell cytokine response) prevented the generation of this syndrome, suggesting that the tissue manifestations seen in RAPA only treated recipients were caused by cytokine production and release. RAPA also caused this alloimmune syndrome in recipients of minor histocompatibility antigen disparate donor cells, showing that the RAPA effects were not restricted to a single donor-recipient strain combination or to instances in which the donor and recipient were fully major histocompatibility complex disparate. We conclude that RAPA is a highly effective means of preventing murine acute GVHD, and that when combined with CsA, warrants consideration for human investigations.
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PMID:In vivo inhibition of cytokine responsiveness and graft-versus-host disease mortality by rapamycin leads to a clinical-pathological syndrome discrete from that observed with cyclosporin A. 861 33

The bcl-2 gene family plays a significant role in the propagation of cell survival and tissue modeling. Bcl-2 was originally described in follicular lymphomas and is associated with the suppresion of cellular apoptosis. Evaluation for this protein has been performed for a variety of benign and malignant cutaneous tumors but not to any significant extent on inflammatory disorders. Therefore, we stained biopsy specimens from diseases with interface inflammation (lichen planus, acute graft-versus-host disease, and erythema multiforme) for Bcl-2. Epidermal expression of this protein was minimal for all three diseases; however, lymphocytes stained prominently in lichen planus. The data suggest that Bcl-2 is not prominently involved in the epidermal changes in these diseases. The role of other members of this oncogene family in interface dermatitis still needs to be elucidated.
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PMID:Expression of bcl-2 in lichen planus, acute graft-versus-host disease, and erythema multiforme. 905 54

Research into the pathogenesis of psoriasis has been hampered by the lack of an animal disease resembling this common human skin disorder. Over the past few years, however, various rodent models that mirror aspects of the psoriatic phenotype and pathogenesis have become available. Here, the most prominent models are compared with human psoriasis and potential uses for psoriasis research are reviewed. Asebia (ab), flaky skin (fsn), and chronic proliferative dermatitis (cpd) are spontaneous mouse mutations with psoriasiform skin alterations of unclear pathogenesis. Transgenic mice with cutaneous overexpression of cytokines, such as interferon-gamma, interleukin-1alpha, keratinocyte growth factor, transforming growth factor-alpha, interferon-6, vascular endothelial growth factor, or bone morphogenic protein-6, are valuable tools for studying in vivo effects of individual cytokines in the pathogenesis of psoriasiform features. Psoriasiform lesions also were seen in beta2-integrin hypomorphic mice backcrossed to the PL/J strain and in beta1-integrin transgenic mice. A T cell-based immunopathogenesis of psoriasiform features was shown in a form of graft-versus-host disease in scid/scid mice reconstituted with CD4+/CD45RB(hi) T lymphocytes as well as in HLA-B27/hbeta2m transgenic rats, demonstrating that dysregulated T cells can induce psoriasiform skin alterations without a primary epithelial abnormality. Finally, xenotransplantation models using human skin grafted on to immunodeficient mice are attractive, as different cell types and some environmental factors leading to psoriasiform features may be studied in human tissue. Overall, although there is no animal model imitating psoriasis completely, many aspects of this common human skin disorder are mirrored in the currently available models and psoriatic plaques can be created in xenotransplantation models.
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PMID:Animal models of psoriasis - what can we learn from them? 1046 48

A 42-year-old woman developed severe erythema with exfoliative scaling on the bilateral palms and soles and erosive dermatitis on the axillae and groin eight days after an autologous peripheral blood stem cell transplantation for the treatment of non-Hodgkin's lymphoma. She also developed exanthema; however she did not show intestinal, hepatic, or renal involvement. The skin biopsy revealed characteristic apoptotic cell death of the epidermis with eosinophilic necrosis, and she was diagnosed with acute graft-versus-host disease (GVHD). The cutaneous lesions responded to topical corticosteroid treatments and improved within a month without systemic immunosuppressing therapies. The cutaneous GVH reaction did not recur. However, she was treated with an intermittent thrombocyte transfusion because of persistent thrombocytopenia. On day 130, she developed intestinal pneumonia and died due to respiratory dysfunction. Unlike an allo-bone marrow graft, GVHD after an autologous stem cell transplantation is not common. Even for an autologous transplantation, GVH may develop with less characteristic clinical manifestations.
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PMID:A case of acute graft-versus-host disease following autologous peripheral blood stem cell transplantation. 1093 41


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