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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. [ABSTRACT FROM AUTHOR]

To elucidate the pathogenesis of T cell-mediated inflammatory skin diseases, we examined the exact sites where CD8(+) T cells proliferate, correlating them with the localization of antigen-presenting dendritic cells. We performed CD8/Ki-67 double immunohistochemical staining and single staining for CD1a, CD68, and factor XIIIa on sections of paraffin-embedded tissue samples of inflammatory dermatoses in which T lymphocytes are thought to play a crucial role. The dermatoses were lichen planus (12 samples), acute graft-versus host disease (GVHD) (12 samples), chronic GVHD (10 samples), spongiotic dermatitis (8 samples) and psoriasis (7 samples). Labelling for Ki-67 among CD8(+) T cells was predominantly observed in the subepidermal lymphoid infiltrate, and was scanty in the epidermis. This suggested that proliferation of CD8(+) T cells occurred preferentially in the dermis. The labelling index for Ki-67 among dermal and epidermal CD8(+) cells was quite different among the different diseases studied (P < 0.05). They were rich in the subepidermal portion of the dermis of spongiotic dermatitis, acute GVHD and chronic GVHD, but rare in the dermis of psoriasis and lichen planus. A moderate infiltrate was also observed in lesional epidermis of spongiotic dermatitis, acute GVHD and chronic GVHD, whereas they was almost none in the epidermis of psoriasis and lichen planus. CD1a(+) dermal dendritic cells were densely distributed within the lymphoid infiltrate in the affected dermis of spongiotic dermatitis, psoriasis and lichen planus, whereas they were minimal in GVHD. These dermal dendritic cells are candidates as stimulators on T cells in the dermis. In conclusion, the proliferative status of T cells could be an important clue in the elucidation of the pathophysiology of T cell-mediated inflammatory dermatoses. [ABSTRACT FROM AUTHOR]

A 66-year-old Japanese woman visited our hospital with a complaint of multiple papules on her trunk and extremities. She had a past medical history of appendicitis and blood transfusion 40 years earlier. For the last 10 years, she had noticed multiple, gradually enlarging papulonodular lesions with surrounding erythema on her trunk and extremities. Physical examination revealed multiple, violaceous papules or nodules, less than 10 mm in diameter, with surrounding erythema on her trunk and extremities ( Fig. 1 ). The results of routine laboratory examinations, including blood count, liver function, renal function, serum calcium, and lactate dehydrogenase, were within the normal range. The peripheral blood picture showed a small population of atypical lymphocytes below 1% of the total white blood cells. Human T-cell lymphotropic virus type I (HTLV-I) serology was positive. A microscopic examination of a biopsy specimen from a nodule on the abdomen demonstrated diffuse infiltration of large pleomorphic T cells in the upper and middle dermis, although highly atypical lymphocytes, so-called flower cells, could not be recognized. Infiltrating lymphocytes were positive for CD2, CD3, CD4, CD5, CD7, and CD45, but negative for CD8 and CD20, immunohistologically. Bone marrow biopsy also demonstrated the infiltration of lymphocytes expressing CD2, CD3, CD4, CD5, and CD7, but not CD25. Southern blot analysis of the infiltrating cells in the skin revealed an integration of HTLV-I proviral DNA in T cells. Clonal T-cell receptor γ gene rearrangement was detected in skin and bone marrow biopsies. No abnormal mass or bone defect was detected by chest or abdominal computed tomographic scanning, systemic gallium-67 citrate scintigraphy, or chest radiography. On the basis of these data, the patient was diagnosed with smouldering-type adult T-cell lymphoma/leukemia. The patient was started on topical steroid and electron beam radiation therapy (27 Gy/14 days). Five days after the start of irradiation, she noticed multiple patches of edematous erythema appearing on the trunk and extremities ( Fig. 2 ). As it was initially suspected that these newly emerging erythema multiforme or toxic eruptions were caused by irradiation, therapy was interrupted. Anti-herpes simplex virus antibody was not checked because no typical herpes simplex lesions were noticed. The patient was not taking any systemic drugs. A skin biopsy was taken from a representative lesion on the chest. The pathologic specimen showed epidermotropism, liquefaction degeneration in the basal layer, marked edema, and dense infiltration of mononuclear cells in the upper dermis. Infiltrating cells possessed abundant cytoplasm and large pleomorphic nuclei with distinct nucleoli ( Fig. 3 ). These findings were consistent with the histopathologic findings of erythema multiforme, except for the atypical lymphoid cell infiltration. Immunohistochemical staining demonstrated that the phenotype of the skin-infiltrating cells was identical to that of the atypical cells in the initial lesions. As the eruptions did not disappear in spite of the interruption of radiation, total skin irradiation was restarted. After completion of therapy, both the erythema multiforme-like lesions and the initial adult T-cell lymphoma/leukemia nodules on the trunk and extremities had resolved, leaving brown pigmentation. The patient has been free of any recurrence of skin lesions or systemic symptoms for 6 years after the completion of total skin irradiation. [ABSTRACT FROM AUTHOR]