Faculty Bibliography

Comparison of the [35S]mucopolysaccharides extracted after in vitro incubation of skin biopsy specimens from nonlesional and lesional sites of a patient with mastocytosis showed that lesional sites incorporated sulfate into heparin. After in vitro incorporation of the [35S]sulfate, the tissues were extracted sequentially by a 3-step procedure which utilized high salt concentrations, enzymatic digestion and base hydrolysis to liberate essentially all the counts. The extracted [35S]mucopolysaccharides were separated from free [35S]sulfate, histamine, protein, and hyaluronic acid by ion-exchange chromatography utilizing Dowex 1. The [35S]mucopolysaccharide extracts of the nonlesional skin were completely degraded by treatment with chondroitinase ABC, as they age predominantly dermatan sulfate with small amounts of chondroitin sulfates. The absolute quantity of sulfated mucopolysaccharides after Dowex 1 chromatography in micrograms of uronic acid per mg wet weight of starting tissue was higher in the lesional than the nonlesional specimen, while the specific incorporation of [35S]sulfate per microgram of uronic acid was the same. Approximately one-half of the [35S]mucopolysaccharides obtained in the 3 sequential extracts of lesional tissue was resistant to degradation by chondroitinase ABC as determined by gel filtration before and after enzyme treatment, indicating the presence of sulfated mucopolysaccharides in addition to chondroitin and dermatan sulfates. Heparinase treatment of the chondroitinase ABC-resistant [35S]mucopolysaccharides followed by gel filtration revealed an equal distribution of label between heparin and heparinase-resistant material presumed to be heparan sulfate. Heparin was also directly demonstrated in extracts of lesional mastocytosis skin by chemical and functional criteria

Cholinergic urticaria was elicited in seven subjects by experimental challenge that consisted of running on a treadmill in a plastic occlusive suit. A sensation of generalized warmth of the skin was followed by pruritus, erythema, urticaria, and transient respiratory-tract symptoms consisting of shortness of breath or wheezing or both. Statistically significant falls in one-second forced-expiratory volumes (FEV1), maximal midexpiratory flow rates (MMF), and specific conductance (SGaw) and a rise in residual volume were detected. The serum histamine concentration rose, with an augmentation of eosinophil and neutrophil chemotactic activities. Gel-filtration chromatography showed that the eosinophil chemotactic activity consisted of at least two principles. The chemotactic activities are similar in magnitude to those recognized in other skin disorders dependent on mast cells. These observations extend to the lungs the manifestations of a condition previously thought to be restricted to the skin

Erythema multiforme (EM) is an episodic, variable, self-limited, and often recurrent inflammatory disorder of the skin and mucous membranes. In this article a definition of EM is proposed, its known clinical and histopathologic spectrum is reviewed, an approach to diagnosis and treatment is suggested, and documented evidence regarding its etiology and pathogenesis is presented. EM would appear to be a hypersensitivity reaction to a variety of precipitating agents. It has been directly linked to Mycoplasma pneumoniae and herpes simplex virus infections and possibly is triggered by a number of other infectious agents and by certain drugs. Accumulating observations of diverse immunologic phenomena suggest an underlying immune mechanism of as yet unclear type. Future investigation should be directed toward defining diagnostic criteria, evaluating reported etiologic associations, and clarifying the immunologic basis of this complex and enigmatic disorder

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

Palpable purpura was noted to occur late in the course of some patients with cystic fibrosis. Skin biopsy specimens showed necrotizing venulitis characterized by a perivenular infiltrate composed of neutrophilic leukocytes, fibrin, hypogranulated mast cells, and endothelial cell necrosis. Circulating immune complexes were detected. Recurrent pulmonary infections and the chronic administration of therapeutic agents provide sources of potential antigens