To better define the inflammatory infiltrates and kinetics of mediator release during the cutaneous late-phase reaction (LPR), we examined skin biopsies at 8 h, and skin chamber cell counts and mediator release for 12 h after antigen challenge. Compared with the control sites, the antigen-stimulated biopsy sites contained 14 times as many basophils (P < 0.01) and six times as many eosinophils (P < 0.001) with one to two fold more mononuclear cells (P < 0.03) and neutrophils (P < 0.01). Similar changes were found in the skin chambers. Although there were neutrophils in the control chamber, they were only twice as numerous in the antigen challenged site (P < 0.01). Eosinophils were 35-fold (P < 0.03) more prevalent in the antigen chamber than the control chamber for hours [8][9][10][11][12] and basophils were noted starting in the eighth hour and were 20-fold (P < 0.03) more concentrated in the antigen chamber during the next 4 h. The mononuclear cells were not significantly different between antigen and control blisters. With respect to inflammatory mediators, there was an initial peak of histamine (13.2±2.9 ng/ml) in the blister fluid at 1 h. The level then fell to -2 ng/ml, followed by a secondary rise starting at the eighth hour and increasing to 9.8±2.8 ng/ml by the twelfth hour. This secondary increase in histamine correlated significantly (r = 0.81, P < 0.05) with the observed influx of basophils. PGD2 in the blister fluid rose to 371±25 pg/ml during the first 4 h and then slowly decreased to half this level during the last 4 h. Thus, the cutaneous LPR has been shown to manifest a secondary increase in histamine levels and a markedly specific increase in eosinophils and basophils with mediator release apparently being derived from the latter cells.

The most frequent site of organ involvement in patients with any form of mastocytosis is the skin. Cutaneous expressions include urticaria pigmentosa, mastocytoma, diffuse and erythrodermic cutaneous mastocytosis, and telangiectasia macularis eruptiva perstans. The cutaneous lesions tend to appear early in life. Although urticaria pigmentosa has been reported in 12 pairs of twins and one set of triplets, the majority of affected individuals have no familial association. Most patients with systemic mastocytosis have skin lesions; however, an occasional patient will have systemic disease with no other skin features than flushing. In lesional cutaneous sites and in non-lesional skin, there is an increase in the number of mast cells. Electron microscopy shows quantitative differences between lesional skin mast cells from patients with and without systemic disease. The mast cells from adult patients with systemic disease have a larger mean cytoplasmic area, nuclear size, and granule diameter. The granules contain predominantly grating/lattice structures. The cutaneous mast cells contain tryptase and chymase. They retain their functional reactivities to relevant secretory stimuli, such as C3a, morphine sulfate, and calcium ionophore A23187. Lesional skin contains histamine, leukotriene B4, prostaglandin D2, 5-hydroxyeicosatetraenoic acid, platelet-activating factor, and heparin. Treatment of the cutaneous manifestations includes the use of H1 and H2 antihistamines, oral disodium cromoglycate, psoralens plus ultraviolet A photochemotherapy, and potent topical corticosteroid preparations.

We studied nine patients with bullous pemphigoid, a generalized cutaneous eruption- for evidence of mast-cell involvement during development of lesions. As in other reports, six of nine patients demonstrated a serum antibody directed against the epidermal basement-membrane zone. Direct immunofluorescence studies of lesions revealed depostion of immunoglobulin and complement proteins at the basement-membrane zone in six of nine and nine of nine patients, respectively. Participation of mast cells was suggested by a sequence of pathologic alterations in which there was progressive mast-cell degranulation and late eosinophil infiltration. In addition, a factor chemotactic for human eosinophils with the size and charge characteristics of the eosinophil chemotactic factor of anaphylaxis was identified in blullous fluid. The data indicate that, in addition to activation of the complement system, involvement of mast cells is an early and continuing event in the development of the cutanenous lesions of bullous pemphigoid.

Comprehensive clinical, histopathologic, and immunohistochemical criteria for the classification of tumid LE are proposed that differentiate tumid LE from other cutaneous disorders that may be clinically and histologically indistinguishable. The chronic, benign course indicates that tumid LE be classified as a form of chronic cutaneous LE, although it may be a cutaneous feature of systemic LE.

A double-blind crossover study of the efficacy of disodium cromoglycate given by mouth to control the cutaneous, gastrointestinal and central-nervous-system manifestations of systemic mastocytosis was carried out in five patients for periods of eight to 32 months. In 15 of 18 trials, disodium cromoglycate produced marked amelioration of the clinical manifestations of pruritus, whealing, flushing, diarrhea, abdominal pain and disorders of cognitive function. By contrast, in all 19 trials with placebo, there was no improvement in these symptoms and signs. Histaminuria and peripheral-blood eosinophilia were unrelated to disease activity and were unaffected by drug therapy. Although it is poorly absorbed after administration by mouth, disodium cromoglycate is of clinical benefit to patients with systemic mastocytosis.