Effect of intravenous immunoglobulin on steroid consumption in patients with severe asthma: a double-blind, placebo-controlled, randomized trial.

BACKGROUND: There is a significant group of patients with severe asthma who require chronic use of systemic steroids for control of their disease. These patients are at risk for severe side effects from oral steroids. Intravenous immunoglobulin (IVIG) has immunomodulatory properties, and a few open-label trials have suggested its possible benefit in individuals with severe asthma. OBJECTIVE: This study was designed to assess the potential benefit of IVIG as a steroid-sparing agent in patients with severe asthma. METHODS: Thirty-eight immunocompetent steroid-requiring patients with severe asthma were randomly enrolled in a double-blind, placebo-controlled trial of IVIG. RESULTS: Of the 38 patients enrolled, 28 patients completed the study. A significant reduction in oral steroid requirement was observed in both the IVIG-treated (n = 16) and the placebo-treated (n = 12) patients. Further exploration of the results showed that IVIG, but not placebo, had a significant steroid-sparing effect in patients requiring high doses of oral steroids (ie, >2000 mg in the year before the study). Within this subgroup, IVIG treatment (n = 9) resulted in a significant decrease in oral steroid requirement, with a median of 16.4 mg/day during the pretreatment period to 3 mg/day during the treatment phase (P =. 0078). No significant decrease in oral steroid requirement was observed in placebo-treated patients (n = 8) within this subgroup. Objective and subjective parameters of the patients' asthma were unchanged in spite of the steroid tapering achieved in the group treated with IVIG. CONCLUSION: IVIG may be a useful steroid-sparing agent in patients with severe asthma requiring high doses of oral steroids.

Local reaction secondary to insulin injection. A potential role for latex antigens in insulin vials and syringes.

OBJECTIVE: To evaluate the possibility that latex antigens (natural rubber) can contribute to or cause local sensitivity at insulin injection sites. CASE: A subject with documented local cutaneous allergic reactions at the site of insulin injections and with systemic latex allergy manifested as anaphylaxis was tested with intradermal injections of insulin diluent from two manufacturers and with two brands of insulin syringes. RESULTS: The subject had high titer anti-latex Ige and elevated total levels of IgE in serum. Anti-insulin IgG and IgE antibodies were absent. Erythema and wheals occurred at the sites of intradermal injection of insulin therapy components (insulin diluent and syringes) that contain natural latex rubber but not at the site of injection of insulin therapy components that do not contain natural latex rubber. CONCLUSIONS: Small quantities of natural latex rubber antigens in insulin injection materials can be sufficient to produce local cutaneous reactions at the site of insulin injection in individuals highly allergic to natural latex rubber.

Milk-sensitive and eosinophilic gastroenteropathy: similar clinical features with contrasting mechanisms and clinical course.

We studied 12 children with peripheral eosinophilia, iron deficiency anemia secondary to blood loss in the stools, protein-losing enteropathy, and eosinophilic infiltration of the stomach and small intestine. On the basis of immunologic features and responses to therapy, these patients could be divided into two groups. In the first group the disease was transient, presented in the first year of life, remitted on withdrawal of milk from the diet, and was not associated with IgE-mediated immediate hypersensitivity (milk-sensitive enteropathy). In contrast, the second group, which we termed eosinophilic gastroenteropathy, represented patients with a chronic disease that had its onset later in childhood, did not respond to dietary manipulations, was associated with atopy and IgE-mediated immediate hypersensitivity reactions to food, and required corticosteroid therapy to establish remission and control. The mechanism by which food causes gastrointestinal damage appears to be different in these two groups even though the clinical syndromes are similar.

Evaluation of clinical data in childhood asthma. Application of a computer file system.

A computer file system was used in our pediatric allergy clinic to assess the value of chest roentgenograms and hemoglobin determinations used in the examination of patients and to correlate exposure to pets and forced hot air with the severity of asthma. Among 889 children with asthma, 20.7% had abnormal chest roentgenographic findings, excluding hyperinflation and peribronchial thickening, and 0.7% had abnormal hemoglobin values. Environmental exposure to pets or forced hot air was not associated with increased severity of asthma, as assessed by five measures of outcome: number of medications administered, requirement for corticosteroids, frequency of clinic visits, frequency of emergency room visits, and frequency of hospitalizations.

Chronic urticaria in childhood: natural course and etiology.

We retrospectively studied 94 children with urticaria longer than six weeks in duration. The disease was equally distributed among the sexes and the following age subgroups (0-3.9 years, 4.0-7.9 years, 8.0-11.9 years and 12.0-15.9 years). A cause of the urticaria was identified or suspected in 15 of the patients. These included eight patients with cold urticaria, two with infection (hepatitis, sinusitis), two with food allergy, one patient with juvenile rheumatoid arthritis, one with arthralgia associated with a positive ANA and one with a low level of total hemolytic complement (CH50). Follow-up of a year of more on 52 patients revealed a median duration of urticarial symptoms of 16.0 months, with 58% of children becoming symptom free for six months or more, whereas the remaining 42% continued to have recurrent symptoms but without the development of an underlying serious illness. Results of the present study indicate that the etiology of chronic urticaria in childhood remains mostly undetermined but that the prognosis is generally favorable. However, one must consider an underlying infection or autoimmune disease as a potential etiology.

Increased serum immunoglobulin E levels following allogeneic bone marrow transplantation.

IgE levels were determined before and serially after allogeneic bone marrow transplantation (BMT) in 12 patients. Six patients had aplastic anemia, four leukemia, and one each Wiskott-Aldrich syndrome and infantile agranulocytosis. IgE levels increased sharply (7- to 2,000-fold) in 10 of the 12 as early as 14 days after BMT. They all returned to baseline levels by 60 days. In six of these patients, the rise accompanied clinical and biochemical evidence of acute graft-versus-host disease (GVHD). All of the patients who received rabbit antihuman thymocytic serum (ATS) in preparation for transplantation and were tested for IgE antirabbit serum antibody by radioallergosorbent test (RAST) (n = 6) developed a strongly positive RAST which paralleled their total IgE levels. These high IgE levels detected during the period of acute GVHD may be a manifestation of a transient lack of suppressor T cell activity.

Management of acute asthma in childhood. A randomized evaluation of beta-adrenergic agents.

We examined the efficacy of several beta-adrenergic agents commonly used to treat asthma and evaluated the optimum route of administration. Two hundred and sixty-nine persons aged 5 to 21 years who came to the emergency ward while suffering from acute asthma were treated with either (1) inhalation isoetharine hydrochloride or (2) subcutaneous epinephrine or terbutaline sulfate. Patients were evaluated using clinical scores and pulmonary function tests and were monitored for adverse side effects. Regardless of mode of therapy, the acute attack was either treated successfully, terminated in hospital admission, or required further therapy within 24 hours in a comparable number of patients. Adverse side effects were more common with terbutaline sulfate than with either epinephrine or isoetharine in the doses used. Thus, inhalation of beta-adrenergic agents is as effective as subcutaneous administration in the treatment of acute asthma in childhood.

Delayed cold-induced urticaria: a dominantly inherited disorder.

A delayed cutaneous response to cold, characterized by areas of erythematous, edematous deep swelling at 9 to 18 hr after experimental ice challenge, was recognized in a 10-yr-old boy and several members of his family. Biopsy of the cold-induced lesion showed edema and an infiltrate of mononuclear cells; mast cells were normal, and immunoglobulins, complement factors, and fibrin were not detected by immunofluorescence techniques. Local cold challenge did not release histamine or induce alterations in the complement system or the enzymes, histaminase, and histamine methyl transferase. The delayed cutaneous response to cold could not be passively transferred with serum or tissue extracts to monkey skin. Family studies suggested an autosomal-dominant mode of inheritance.

Immediate hypersensitivity to cockroach. Isolation and purification of the major antigens.

Crude cockroach extract elicited positive skin tests in 50% of patients with positive and in 4% with negative environmental history for cockroach exposure, suggesting a possible role of cockroach in perennial atopic disease. Three major allergens in crude American and German cockroach extracts have been identified using sequential purification steps on Sephadex G-75, diethylaminoethyl (DEAE) cellulose, and agarose gel electrophoresis. Cr-I elicits positive skin tests in 70% of patients sensitive to the crude extracts. It has a molecular weight of approximately 25,500 daltons, is highly acidic, and resists boiling for four hours. Boiling in 4 N acetic acid completely abolishes its allergenicity. The purified allergen elicits positive skin tests at a concentration of 3 mug/ml and is capable of inducing greater than 50% histamine release from sensitive leukocytes at 0.05 ng/ml. A second antigen, Cr-II, elicits positive skin tests also in approximately 70% of cockroach-sensitive individuals, has a molecular weight of approximately 63,000 to 65,000 daltons, and has similar heat stability and acid hydrolysis characteristics to Cr-I. A third, less well-characterized antigen, Cr-III, has a molecular weight less than 10,000 daltons and elicits positive skin tests in 30% of individuals sensitive to the crude extract.

Hypersensitivity to pancreatic extracts in parents of patients with cystic fibrosis.

Because immediate hypersensitivity reactions can occur in individuals exposed to powdered pancreatic extracts, 36 patients with cystic fibrosis and 51 patents of such patients wwer studied for evidence of sensitization. Sensitivity to the extracts as evidence by history and skin testing was infrequent in the children with cystic fibrosis. However, skin testing for immediate hypersensitivity with either crude pancreatic extracts or inactivated trypsin correlated well in their patents with a history of clinical symptoms. IgE mediation of these reactions in sensitized individuals was demonstrated by antigen-induced histamine release from leukocytes, passive transfer studies, and immediate response to inhalation challenge.