Graft-versus-host reactions frequently produce cutaneous and systemic complications in patients receiving bone marrow transplants. Characteristic skin involvement typically heralds graft-versus-host reactions and significantly contributes to the morbidity associated with marrow transplants. Familiarity with these reactions and their treatment is important to dermatologists involved in the care of marrow transplant recipients. (J Am Acad Dermatol 1998;38:369-92.) Learning objective: At the conclusion of this learning activity, participants should be able to understand the requirements for development of graft-versus-host disease and the role of bone marrow transplantation and related risk factors. The immunopathophysiologic mechanisms of acute, chronic, and syngeneic graft-versus-host disease should be understood, and participants should be able to describe the clinical aspects of graft-versus-host reactions as well as treatment options for acute and chronic forms of the disease.

Graft-versus-host reactions in dermatology ☆ ☆☆ ★

Certain T lymphocytes display a specific affinity for the epidermis (epidermotropism). Recent studies have suggested that Ia+ Langerhans cells (LCs) are possible targets for the epidermotropism. A variety of self-Ia-reactive cloned T cells were tested for their ability to migrate into the epidermis following intradermal inoculation into the footpads of syngeneic mice. Clone BB5 was chosen as representative of the epidermotropic T cells. We investigated whether the depletion of Ia+ LCs from the epidermis by tape-stripping could alter the migration of BB5 cells into the epidermis. The epidermal invasion of BB5 cells was markedly impaired in those mice whose LCs were depleted by 95% after repetitive tape-stripping. Because production of epidermal-derived thymocyte activating factor (ETAF) by the epidermal cells was augmented after repetitive tape-stripping, the diminished migration of BB5 cells into tape-stripped epidermis did not result from a decrease in ETAF production which is thought to attract T cells chemotactically. These results suggest that Ia+ LCs may play an inductive role in the preferential migration of T cells into the epidermis.

Prostaglandins, leukotrienes, phospholipase, platelet activating factor, and cytokines: an integrated approach to inflammation of human skin.

• Background.— Toxic epidermal necrolysis is a potentially severe mucocutaneous affliction whose cause is usually drug related. To further characterize the nature of the dermal mononuclear infiltrate as well as the epidermal alterations observed by standard microscopy, we studied five cases of toxic epidermal necrolysis using labeled monoclonal antibodies. Results.— On clinically involved areas of skin, the following occurs: (1) the dermal infiltrate is composed mainly of activated T lymphocytes, with a predominant helper phenotype; (2) the number of Langerhans cells is decreased; and (3) keratinocytes express HLA-DR molecules, normally absent on their surface. Conclusions.— These findings, although not specific, are consistent with an immune cellular reaction, but they could also be linked to an inflammatory reaction initiated by epidermal damages whatever its primary mechanism. ( Arch Dermatol. 1992;128:50-53)

https://jamanetwork.com/HttpHandlers/ArticlePdfHandler.ashx?journal=derm&articleId=553758&pdfFileName=archderm_128_1_006.pdf

Immunopathology of Toxic Epidermal Necrolysis: Keratinocytes, HLA-DR Expression, Langerhans Cells, and Mononuclear Cells: An Immunopathologic Study of Five Cases

Superantigenic Staphylococcal Exotoxins Induce T-Cell Proliferation in the Presence of Langerhans Cells or Class II–Bearing Keratinocytes and Stimulate Keratinocytes to Produce T-Cell–Activating Cytokines

• Macular and papular eruptions are ascribed to various causes, often drug-related hypersensitivity or toxicity. We observed patients with cutaneous eruptions during hospital admissions for induction or augmentation chemotherapy in the treatment of leukemia. In 10 of 14 patients, macular and papular eruptions occurred in a strikingly similar pattern, at the earliest recovery of peripheral lymphocytes, after chemotherapy-induced nadir of the leukocyte count. A concomitant sharp, transient rise in temperature accompanied the eruption of lymphocyte recovery. Skin biopsy specimens were obtained from 8 of these 10 patients and showed a superficial, perivascular mononuclear cell infiltrate. Immunohistochemical analysis of the cellular infiltrate was performed. The rash of lymphocyte recovery may be due to the actual return of immunocompetent lymphocytes to the peripheral circulation and skin after the chemotherapy-induced nadir of the leukocyte count. These observations suggest that macular and papular eruptions relate to specific immunologic events. ( Arch Dermatol . 1989;125:1512-1517)

Cutaneous Eruptions of Lymphocyte Recovery

Immunologic aspects of acute cutaneous graft-versus-host disease: decreased density and antigen-presenting function of Ia+ Langerhans cells and absent antigen-presenting capacity of Ia+ keratinocytes.

Zdenko Kovac

Papers

Immunologic aspects of acute cutaneous graft-versus-host disease: decreased density and antigen-presenting function of Ia+ Langerhans cells and absent antigen-presenting capacity of Ia+ keratinocytes.