Fred M. Atkins

Evaluation of immediate adverse reactions to foods in adult patients. I: Correlation of demographic, laboratory, and prick skin test data with response to controlled oral food challenge

Forty-five adult patients, referred to here as the index population, with a history of immediate adverse reactions after food ingestion were evaluated by history, physical examination, laboratory studies, and skin testing. Fifty-six percent of these patients reported adverse reactions to only one food, whereas 84% of the patients reported up to three foods as being capable of eliciting reactions. The average age obtained by history at which adverse reactions began to occur was 19 4/5 yr. The occurrence of these reactions persisted over an average of 14 4/5 yr. Most reactions involved the gastrointestinal tract alone or in combination with the skin or respiratory tract. The most frequently involved foods were shellfish, peanuts, eggs, fish, tomatoes, and walnuts. Twenty-five of the patients participated in oral challenge with the suspected food. The food challenge was positive in 10 patients. Comparison of information obtained by history including personal or family history of any other allergic disease, age of onset of sensitivity, the length of time of suspected sensitivity in years, and the number of foods to which the sensitivity was believed to exist revealed no significant differences between food challenge-positive (FC+) and food challenge-negative (FC-) patients. However, a significant difference in the reaction patterns reported by history in the FC+ and FC- patients was noted in that FC+ patients more often described reactions in which a combination of gastrointestinal, respiratory, and dermatologic symptoms occurred. The complete blood count with differential, blood chemistries, and serum immunoglobulin levels were similar in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Evaluation of immediate adverse reactions to foods in adult patients: II. A detailed analysis of reaction patterns during oral food challenge

Eighty-three oral food challenges were performed on 25 patients with a history of immediate adverse reaction to foods. Seventy-one food challenges were performed in 24 patients, whereas 12 placebos were administered to nine patients. Of the 71 food challenges observed, 12 were positive in 10 patients. All challenges with placebo were negative. Doses of challenge foods provoking observable reactions ranged from 5 to 100 gm. The clinical signs and symptoms noted on food challenge reproduced those reported by history. Reactions were mild, generally self-limited, and were not accompanied by elevations in urinary histamine. A plasma histamine elevation was observed in one patient. A 10- to 12-mo follow-up survey of nine patients with negative food challenges revealed that six patients had resumed eating the challenge food on a regular basis without experiencing adverse reactions, whereas three patients continued to avoid the challenge food. All 10 patients with positive food challenges continued to avoid the challenge food.

Interactions between Mast Cells, Fibroblasts and Connective Tissue Components

It has long been recognized that mast cells occur throughout connective tissues. Histologic studies have revealed that such cells release their granules into the surrounding environment upon exposure to both immunologic and nonimmunologic stimuli. By microscopy these extracellular granules appeared to be phagocytosed by fibroblasts and by blood-borne phagocytic cells as they entered the site of mast cell degranulation. Such in vivo observations led to the suggestion that mast cells both altered connective tissue components and influenced fibroblast function through these discharged granules. Recent in vitro studies using cultured fibroblasts and isolated mast cells and mast cell granules have confirmed both these hypotheses. In addition, such studies have also documented that fibroblasts degrade ingested mast cell granules. Such studies document that a number of critical interactions may occur between mast cells and connective tissue components.

Failure of sulfites to produce clinical responses in patients with systemic mastocytosis or recurrent anaphylaxis: Results of a single-blind study

Although sulfite sensitivity can precipitate asthma in a subpopulation of subjects with asthma, its role in precipitating anaphylaxis or as a nonspecific mast cell degranulator in systemic mastocytosis has not been examined. To evaluate critically the importance of sulfites in these diseases, eight patients with systemic mastocytosis and 25 patients with unexplained, recurrent anaphylaxis were challenged in a single-blind fashion; sodium bisulfite in capsules was administered in increasing doses of 1, 5, 10, 25, 50, 100, and 200 mg every 30 minutes. On separate occasions a liquid suspension of 200 mg of sodium bisulfite was administered to one patient with systemic mastocytosis and nine patients with anaphylaxis. Vital signs, pulmonary function tests, plasma histamine levels, and clinical reactions were monitored. There were no observable responses in either the mastocytosis group or in 23 of 25 patients in the anaphylaxis group. Two patients in the anaphylaxis group with initial positive challenges had similar symptoms on subsequent placebo challenge. One subject with asthma and with a history suggestive of sulfite sensitivity responded to oral challenge with 5 mg of sodium bisulfite and 100 micrograms of sodium bisulfite intradermally with a dramatic reduction in FEV, requiring treatment with bronchodilators. A comparison of baseline plasma histamine levels with those obtained after the sulfite challenge procedure in each category demonstrated a significant rise (p less than 0.05) in the systemic mastocytosis group. The overall level of significance determined by applying paired sample t tests to the histamine data from all subjects was p less than 0.01.(ABSTRACT TRUNCATED AT 250 WORDS)

Phagocytosis of mast cell granules by cultured fibroblasts

Cultured rat embryonic skin fibroblasts phagocytosed rat mast cell granules added to the medium or released from co-cultured mast cells by rabbit anti-rat IgE or Compound 48/80. Electron microscopy of fibroblasts incubated with mast cell granules revealed that granules adjacent to the plasmalemma were engulfed by long, thin cytoplasmic processes. Internalization proceeded to fusion of encircling processes and formation of phagosomes. Microtubules and 60 A microfilaments became closely associated with the phagosomal membrane to which small vesicles and cisternae of endoplasmic reticulum fused. The rate of uptake of mast cell granules by fibroblasts was dependent upon temperature and granule concentration. Cytochalasin B inhibited granule uptake whereas colchicine and nocodazole had little effect. Phagocytosis was not influenced by actinomycin D and cycloheximide, was partially inhibited by fluoride, and was markedly inhibited by cyanide, azide, and 2,4-dinitrophenol. Supernatants from fibroblast cultures incubated with mast cell granules for 24 and 48 hr, during which period phagocytosis occurred, contained elevated levels of collagenase and beta-hexosaminidase, but normal levels of lactate dehydrogenase and superoxide dismutase. These results support the concept that immediate hypersensitivity reactions are in part terminated by phagocytosis of biologically active discharged mast cell granules by resident connective tissue fibroblasts. Further, it is suggested that a consequence of this process is an alteration in fibroblast behavior, providing a unique link between immediate hypersensitivity reactions and connective tissue responses to inflammation.