Alan L. Schocket

Exercise-induced anaphylactic reaction to shellfish☆

The syndrome of immediate type I food hypersensitivity, mediated by tissue-bound IgE antibody and mast cell histamine release, is well recorded in the medical literature. This case study represents a previously undescribed late food hypersensitivity, induced only by strenuous exercise. Identification of this new syndrome illustrates classical epidemiologic analysis, improves medical advice for the allergic and athletically inclined, and raises new questions in the areas of allergy and immunology.

Delayed pressure urticaria

Delayed pressure urticaria (DPU) is a poorly understood syndrome. We describe 17 patients with DPU. Chronic urticaria was present in 94%. All had negative challenges for immediate demographism and cold urticaria. DPU was induced with a pressure challenge on the shoulder of 15 pounds for 15 min. Average onset of pressure lesions after challenge was 6.5. Lesions were painful, not pruritic, peaked at 9 hr, and disappeared by 24 to 48 hr. Fever, chills, and/or arthralgias occurred in 78%. Positive laboratory abnormalities included leukocytosis in 20% and elevated erythrocyte sedimentation rate in 37.5%. Skin biopsies of lesions showed perivascular round cell infiltrates and negative immunofluorescence. Urticaria responded to antihistamines, but not aspirin, in 100% of patients, while pressure lesions improved with nonsteroidal anti-inflammatory drugs (NSAID), but not antihistamines, in 80% of patients. Both urticaria and DPU were controlled with prednisone, which was necessary in 87.5% of patients. A severe nonremitting course was noted in 7%, 40% had a moderate remitting course requiring intermittent prednisone, and 53% had a mild remitting disease requiring no medication or antihistamines and/or NSAID only. We conclude that DPU is more common than previously appreciated and likely involves mediators other than histamine, possibly the prostaglandin system.

Resolution of chronic urticaria in patients with thyroid autoimmunity

BACKGROUND Autoimmune disease has been implicated as a cause of chronic urticaria, and anti-thyroid antibodies have been found in patients with chronic urticaria. Because some patients with chronic urticaria and autoimmune hypothyroidism have had clinical resolution with thyroid hormone replacement, we investigated the effect of thyroid hormone in euthyroid patients with chronic urticaria and thyroid autoimmunity. METHODS Ten euthyroid patients with refractory hives were treated with thyroxine. Seven patients had elevated anti-thyroid antibodies at baseline. Thyroid function and anti-microsomal and anti-thyroglobulin antibody levels were monitored during treatment. If a clinical response was achieved, thyroxine was discontinued and restarted if symptoms recurred. RESULTS Seven patients with elevated anti-thyroid antibodies reported resolution of symptoms within 4 weeks. Three patients without elevated anti-thyroid antibodies did not respond. Five patients had a recurrence of symptoms after treatment was stopped, which resolved after treatment was restarted. Thyroid-stimulating hormone levels decreased in all patients with a clinical response. No correlation between clinical resolution and anti-thyroid antibody levels was seen. CONCLUSION Thyroid autoimmunity in euthyroid patients may be associated with chronic urticaria, and treatment with thyroid suppression can result in clinical remission.

Acquired Immunodeficiency Syndrome in a Patient with Hemophilia

A patient with hemophilia A developed T-cell deficiency characterized by infection with several opportunistic pathogens. Immunologic investigation showed cutaneous anergy, lymphocyte unresponsiveness to mitogens and antigens, an abnormal ratio of T-helper and T-suppressor cells with absolute lymphopenia and elevated IgA. The clinical and immunologic characteristics of this patient fit the recently described syndrome of opportunistic infections or Kaposis sarcoma in patients with acquired T-cell deficiency; however, this patient does not have any of the associated underlying risk factors such as homosexuality, intravenous drug or amyl nitrite use, or positive serologic tests for syphilis. We conclude that the patients acquired T-cell deficiency can be explained by exposure to a virus or other transmissible agent during factor VIII transfusions.

The effect of H1 and H2 blockade on cutaneous histamine response in man

Histamine-induced cutaneous wheal responses were measured in 10 healthy subjects. The effect of the potent H1 blocker, hydroxyzine HCl, the H2 blocker, cimetidine, and the two drugs in combination was determined. The H1 blocker alone produced a mean wheal suppression of 75% (p less than 0.001). The H1 plus H2 blocker produced 84% suppression. The augmented suppression of H1 plus H2 blocker vs H1 blocker was statistically significant (p less than 0.02). The H2 blocker alone produced suppression that was not statistically significant. The results provide additional evidence that H2 receptors are present in the human cutaneous microcirculation, and add support to the clinical observation of therapeutic efficacy of H1 plus H2 blockers seen in some patients with chronic urticaria.

A controlled trial of therapy in chronic urticaria

Nineteen patients with chronic idiopathic urticaria (duration 2 to 192 mo) referred to our clinic as therapeutic failures were treated sequentially with five regimens. These were administered orally in a double-blind random sequence and included hydroxyzine pamoate (25 mg q.i.d.) plus one of the following: (1) placebo, (2) terbutaline (2.5 mg q.i.d.), (3) cyproheptadine (4 mg q.i.d.), (4) chlorpheniramine (4 mig q.i.d.), (5) cimetidine (300 mg q.i.d.). Therapeutic response was assessed by patients subjective choice, symptom diary scores, and suppression of wheal response to intradermal injections of histamine and compound 48/80. At least 35% improvement was noted in all patients with an average optimal response of 70%. The hydroxyzine-cimetidine combination was favored by 11 of 19 (58%) patients, in addition to producing the lowest symptom scores and the greatest histamine-48/80 wheal suppression. These results support the efficacy of combination H1 and H2 antihistamines in the management of some patients with difficult chronic urticaria.

The hypocomplementemic urticarial-vasculitis syndrome: Therapeutic response to hydroxychloroquine

We report a patient with hypocomplementemic urticarial-vasculitis syndrome. This case illustrates the continuum between urticaria and purpura characteristic of hypocomplementemic urticarial-vasculitis syndrome. Clq precipitin was demonstrated in the patients serum and in the diethylaminoethylcellulose-ion exchange fraction containing only IgG. A skin biopsy specimen of urticarial and purpuric lesions demonstrated leukocytoclastic vasculitis and granular deposition of C3 and Clq in the basement membrane with IgA, IgM, C3, and Clq in postcapillary venules. Serial total hemolytic complement activity and Clq determinations were performed, and the response to several treatment regimens is presented. Symptomatic and serologic improvement was observed only with hydroxychloroquine.

Treatment of chronic idiopathic urticaria with combined HI and H2 blockers

Combined H1 (cyproheptadine) and H2 antihistamines (cimetidine) were tried in eight patients with chronic urticaria who were previously unresponsive to conventional anti‐urticarial regimens, including type I antihistamines, hydroxyzine, ephedrine and corticosteroids. 50 % of the patients responded with 90 % or greater improvement within 10 days. The remaining 50% showed no benefit. Side effects of the medications were minimal. These results indicate that a 10 day trial of both H1 and H2 antihistamines may be useful in patients with chronic urticaria resistant to all other standard treatment modalities.

Skin histamine in chronic urticaria

Abstract To further study the role of histamine in the pathogenesis of chronic urticaria, the concentration of histamine in tissue extracts from skin biopsy samples and in plasma from patients with chronic urticaria was measured by a sensitive radioenzymatic assay. Tissue histamine levels from urticarial lesions and uninvolved skin were compared with extracts of biopsy samples taken from normal controls. The average tissue histamine content in 15 biopsy samples from the chronic urticaria patients was significantly higher than in those of 15 normal controls. Forty percent of the patients had levels 2 SD greater than the mean of the control group. Elevated histamine levels were also found in biopsy samples of uninvolved skin from some urticaria patients. Circulating histamine levels from chronic urticaria patients were rarely elevated and did not correlate with skin concentration. No correlation was noted between tissue histamine concentration and estimated mast cell concentration on Giemsa-stained sections of five biopsy samples. These results indicate that tissue histamine levels are increased in some patients with chronic urticaria. This suggests that local histamine elevations may be important in the pathogenesis of many patients with this disease. In addition, increased tissue histamine in these patients is not reflected by elevated circulating levels.

Lymphocytotoxic antibodies in multiple sclerosis

Abstract The presence of cold-reactive lymphocytotoxic antibodies has been demonstrated in patients with viral infections and various “autoimmune” diseases thought to be related to viral infection. In the present study we have examined the incidence and possible significance of these antibodies in patients with multiple sclerosis, another disease probably associated with a viral agent. The incidence of lymphocytotoxic antibodies was significantly increased in patients with multiple sclerosis as compared to their siblings, patients with other neurological disease, and normal controls. The level of these antibodies correlated significantly with serum measles antibody titers in the affected patients. No correlation was found between lymphocytotoxic antibody levels and parameters or clinical disease or other viral antibody titers in the serum and cerebrospinal fluid. It was concluded that lymphocytotoxic antibodies in patients with multiple sclerosis probably serve as markers of viral infection.