Faculty Bibliography

In a patient with eosinophilic fasciitis, a biopsy specimen obtained within 4 weeks of the onset of symptoms showed infiltration of the subcutis and fascia with mast cells, and there was up to a 19-fold increase in plasma histamine levels. The patient improved and experienced softening of the skin when treated with systemic corticosteroids and a histamine2-receptor antagonist, and her plasma histamine level returned to normal. Tissue mast cell infiltration and excessive plasma histamine levels were not present in two otherwise similar patients with eosinophilic fasciitis who were studied 7 months after disease onset. It is possible that mast cells play a pathogenic role in some patients with eosinophilic fasciitis

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 less than 0.01) and six times as many eosinophils (P less than 0.001) with one to two fold more mononuclear cells (P less than 0.03) and neutrophils (P less than or equal to 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 less than 0.01). Eosinophils were 35-fold (P less than or equal to 0.03) more prevalent in the antigen chamber than the control chamber for hours 8-12 and basophils were noted starting in the eighth hour and were 20-fold (P less than or equal to 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 approximately 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 less than 0.05) with the observed influx of basophils.(ABSTRACT TRUNCATED AT 250 WORDS)

Four metabolic products of arachidonic acid lipoxygenation, 5-hydroxyeicosatetraenoate (5-HETE), 12-HETE, 15-HETE, 5(S),12(S)-DiHETE, were injected intradermally into depilated dorsae of albino guinea pigs. The presence of intravenously injected 125I-bovine serum albumin (10uCi/kg) in 13-mm punch biopsy specimens served as a marker for altered vascular response; histologic changes were evaluated at 6 and 24 h after the injection in 1-micron-thick sections. Thirty minutes after the injections of 15 nanomoles and 60 nanomoles of 5-HETE, the ratios of radioactivity in HETE-injected to that in buffer-injected sites were 1.35 +/- 0.06 (mean +/- SE) and 2.80 +/- 0.27, respectively. Corresponding effects of 15-HETE were 1.39 +/- 0.17 and 1.63 +/- 0.21, respectively. Values for 60 nanomoles of 12-HETE and 5,12-DiHETE were intermediate in comparison with the above eicosanoids. The most notable histologic changes were a neutrophilic infiltrate induced by 12-HETE at 6 and 24 h, and neutrophilic and eosinophilic infiltrates in response to 5,12-DiHETE injection at 6 and 24 h. Effects of topically applied eicosanoid pathway inhibitors were also evaluated, using intradermally injected sodium arachidonate (AA) as agonist. Three mixed cyclooxygenase/lipoxygenase inhibitors, BW755C, phenidone, and nordihydroguaiaretic acid, suppressed vascular response by 9%, 9%, and 6% for 150 nmol of AA, and by 9%, 13%, and 12% for 300 nmol of AA, respectively. The cyclooxygenase inhibitor, indomethacin, induced suppressions of 39% for 150 nmol AA and 22% for 300 nmol AA, respectively. These data demonstrate that metabolites of both cyclooxygenase and lipoxygenase eicosanoid pathways are involved in alteration in vascular response accompanying cutaneous inflammation

The routine examination of skin biopsy specimens embedded in paraffin and strained with hematoxylin-eosin has failed to allow differentiation of atopic eczema from other types of eczematous dermatitis. The use of 1-micron plastic-embedded sections permits the recognition of infiltrating cell types and blood vessel alterations, thus allowing a refined method to examine cutaneous lesions and permit better definition of cutaneous structures than can be achieved in routinely-processed specimens. Acute vesicular lesions exhibited marked epidermal intercellular edema (spongiosis) and a dermal inflammatory infiltrate of lymphocytes, and activated lymphocytes with normal numbers of mast cells that exhibited various degrees of hypogranulation. Only rare eosinophils, neutrophils, and basophils were noted. Venular alterations included endothelial cell hypertrophy without necrosis. In lichenified plaques there was epidermal hyperplasia with a dermal inflammatory infiltrate that included increased numbers of fully granulated mast cells and increased numbers of lymphocytes and monocyte-macrophages. Alterations of venules included marked endothelial cell hypertrophy and basement membrane thickening. Cutaneous nerves exhibited demyelination and fibrosis. Also, increased numbers of Langerhans' cells have been noted in the epidermis of chronic lesions. Despite the absence of eosinophils, major basic protein has been demonstrated in the dermis by direct immunofluorescence techniques. Studies of lymphocyte subsets have shown increased numbers of CD4+ T lymphocytes