In vitro demonstration of IgE antibody to folate-albumin in anaphylaxis from folic acid.

BACKGROUND: Folic acid (the synthetic form of folate B vitamins in foods) is widely used in vitamin supplements. Anaphylaxis from ingestion or injection of folic acid suggests IgE antibody-mediated mechanisms, but this has not been demonstrated previously in vitro. OBJECTIVE: This study was conducted to better define the mechanism of folic acid hypersensitivity and cross-reactivity among folic acid congeners. METHODS: Skin testing was performed with folic acid congeners in a woman who developed anaphylaxis after ingestion of 2 different multivitamin preparations containing folic acid. In vitro immunologic serum studies were conducted using a folate-human serum albumin (HSA) conjugate prepared by a novel application of carbodiimide condensation. RESULTS: The patient had positive immediate-type skin test reactions to folic acid and several folate analogues including leucovorin (folinic acid). Urticaria developed during graded oral test dosing with leucovorin. Using a dot immunoblot assay or an ELISA for IgE antibody to folate-HSA, results of the patient's serum testing were positive, whereas results of sera from normal control subjects were negative, the first in vitro demonstration of IgE to a folic acid-protein conjugate. By ELISA, the positive result of the patient's serum was inhibited significantly by serum coincubation with folate-HSA, but not HSA or folic acid. CONCLUSIONS: Immediate hypersensitivity to folic acid and possibly other vitamins can be mediated by IgE antibody to conjugates formed between vitamins and self-proteins or polypeptides. Leucovorin can have clinically important immunologic cross-reactivity with folic acid. A diet rich in natural folates (pteroylpolyglutamates) appears useful as a management strategy for providing adequate nutrition to patients with folic acid hypersensitivity.

Extensive subcutaneous fibrosis in a patient treated with alum precipitated allergenic extract.

BACKGROUND: Alum-precipitated allergenic extract (Allpyral) used for immunotherapy has been associated with subcutaneous nodule formation at injection sites. OBJECTIVE: We describe a severe localized reaction at the site of Allpyral injections and evaluate possible mechanisms for this reaction. METHODS: Case report with cutaneous patch testing and CAT scan imaging. RESULTS: The patient developed extensive subcutaneous inflammation and fibrosis with overlying skin changes which appear to be permanent. CAT scan findings were corroborative and cutaneous patch testing to aluminium was positive. CONCLUSIONS: Alum-precipitated allergenic extract used for immunotherapy caused extensive subcutaneous fibrosis with overlying skin changes at the site of injections. The lesions are disfiguring and appear to be permanent. This may be due in part to a type IV hypersensitivity response to the aluminum component of Allpyral extract. A CAT scan was valuable in demonstrating structural changes associated with this lesion.

Occupational asthma in a latex doll manufacturing plant.

BACKGROUND: Occupational asthma caused by latex has been reported in health care workers and workers in glove manufacturing plants. OBJECTIVE: We report occupational asthma from latex in a newly identified occupational setting, a latex doll manufacturing plant. METHODS: We evaluated an index case of asthma associated with work in a latex doll manufacturing plant by performing a workplace challenge and evaluating the work environment. We then performed an occupational survey and skin testing of 22 workers in the doll manufacturing plant. RESULTS: The patient, a 21-year-old woman, had severe immediate bronchospasm within minutes of beginning a workplace challenge where sanding of latex parts was performed. Two of 22 workers surveyed (including the patient) reported flushing, rhinoconjunctivitis, and wheezing on exposure to sanded doll parts. These two workers were the only subjects surveyed to have a history of atopy and positive immediate-type skin test responses to a raw latex extract and to common aeroallergens. CONCLUSIONS: Sanding or grinding of solid latex during the manufacturing process may result in a significant incidence of occupational asthma and rhinoconjunctivitis from latex sensitization. Atopic workers appear to be most susceptible to developing latex sensitivity in this setting.

Immunologic analysis of anaphylaxis to protamine component in neutral protamine Hagedorn human insulin.

We report the clinical and immunologic analysis of two patients with diabetes who had anaphylaxis to neutral protamine Hagedorn (NPH) human insulin in the absence of allergy to regular insulin. A 36-year-old woman without a recent history of local insulin reactions or interruption of insulin therapy experienced anaphylaxis within 15 minutes of her usual morning dose of subcutaneously administered NPH human insulin. A 62-year-old man with a history of generalized reactions to NPH human insulin and of anaphylaxis to intravenously administered protamine had generalized urticaria after injection of NPH human insulin. Both patients subsequently tolerated Lente human insulin. Skin test results in both patients were negative to regular and Lente insulin preparations but positive to NPH insulin and to protamine at concentrations tested. In vitro assays demonstrated that both patients had markedly elevated serum levels of IgE and IgG to protamine, but not to regular human insulin, and that their IgE antibodies to protamine recognized protamine antigenic determinants in NPH human insulin. We conclude that the anaphylactic reactions to NPH insulin in our patients were mediated by IgE to protamine, which should be a pathogenetic consideration in the evaluation of immediate-type reactions to protamine-containing insulins.

Emergency medical recognition and management of idiopathic anaphylaxis.

Idiopathic anaphylaxis (IA) is a diagnosis of exclusion that is made when no identifiable causative factors can be found for an episode of anaphylaxis. IA is a potentially life-threatening disease that is the result of a nonimmunologic mast cell activation syndrome. Acute presentation and treatment of these patients is most often in the emergency department and is clinically the same as anaphylaxis from allergens. Since these episodes are unpredictable and often recurrent, these patients are at risk of death if not identified on acute presentation and managed appropriately. As an increasing number of patients are being diagnosed with IA, they will be presenting to emergency departments with initial and recurrent episodes of IA. Therefore, increased awareness of IA and coordinated care is needed so that the morbidity and mortality of this potentially fatal disease can be kept at a minimum.

Angioedema and C1 inhibitor deficiency.

Deficiency of C1 inhibitor resulting in episodes of angioedema causes significant morbidity and mortality in affected patients, yet often goes undiagnosed for years. As biochemical understanding of the disorder has improved, competing theories for the pathophysiologic mechanism of angioedema have emerged. Further, existing therapeutic interventions have been refined by experience and newer modalities currently available in Europe may soon become available in the United States.

Malignant idiopathic anaphylaxis: three additional cases and extended evaluation.

Northwestern University's Division of Allergy and Immunology (NUAI) has evaluated and treated 225 patients with idiopathic anaphylaxis (IA) over a period of 16 years. Four patients have been identified with malignant IA. The term "malignant" is used to identify those patients with the most severe form of IA that is resistant to standard therapy. The diagnosis of malignant IA is made in patients with IA whose controlling oral corticosteroid dose was not able to be reduced below 60 mg of prednisone (or its equivalent) every other day or 20 mg of prednisone (or its equivalent) every day without an exacerbation of IA. Presented here is the long-term evaluation of one patient as well as three additional patients with malignant IA managed by our service. At the time of this report we have had no deaths due to IA in patients treated with pharmacologic regimen.

Idiopathic anaphylaxis: diagnostic variants and the problem of nonorganic disease.

We report on an expanding series of cases of idiopathic anaphylaxis (IA) with development of a classification, therapeutic regimens, and control of disease and induction of remission. Simultaneously, a growing series of cases referred for diagnosis and management of IA do not have IA. These cases, which approximate 10% of our series of IA cases, present serious time-consuming diagnostic problems for physicians. We present a series of nine cases of this type of nonorganic disease and describe the presenting symptoms, failure to document clinical abnormalities, and the lack of a response to a regimen shown to be effective in altering the course of true IA. The classification of IA has been expanded to include IA variants for patients in whom the symptoms complex varies significantly from other types of IA. Diagnostic suggestions and the problems of management are reviewed.

Stevens-Johnson syndrome (SJS): effectiveness of corticosteroids in management and recurrent SJS.

To confirm that corticosteroids are beneficial in the treatment of Stevens-Johnson syndrome (SJS), 15 patients with the syndrome were evaluated by the same group of physicians over 2 years. All patients had cutaneous and most had mucosal lesions. Patients were treated with corticosteroids ranging from prednisone 40 mg daily to methylprednisolone 750 mg daily. The same group of physicians participated in the management of these patients until recovery. No deaths occurred among the 15 patients. Recovery was complete in all cases, and there was no residual skin, mucosal, or visceral damage except for minimal scarring in one patient. In some cases, reversal of disease after onset of corticosteroid therapy was sufficiently dramatic to demonstrate a benefit. The use of corticosteroids in the treatment of SJS remains controversial. We conclude that corticosteroids are beneficial in treatment of the syndrome. They may be lifesaving in some patients and should be the standard of therapy. SJS should be considered to be erythema multiforme with either bullous lesions or visceral involvement or both.

Idiopathic anaphylaxis: total experience with 225 patients.

Idiopathic anaphylaxis (IA) is defined as anaphylaxis with no identifiable precipitating agent or event. Episodes of IA can be life threatening, and onset of episodes is unpredictable and usually recurrent. The epidemiologic features and clinical course of 225 patients diagnosed with IA and managed according to the described protocol with prednisone, H1 antagonists, and beta adrenergic agents were evaluated. There were no fatalities from IA in our series. There was a sevenfold reduction in the average rate of episodes requiring emergency care after initiation of pharmacologic management. Ninety five of 147 patients being observed are in remission, defined as absence of episodes for 1 year without corticosteroid therapy. During 636 patient years of observation, no inciting cause of anaphylaxis or alternative organic disease was defined. The diagnosis of IA was highly reliable in this series. Long-term prognosis is good, with the majority of patients experiencing remission.

Systemic cold urticaria in a five-year-old boy.

A 5-year-old white boy had a history of generalized urticaria on total body exposure to a cold environment. Standard ice cube testing was negative. Plasma analysis revealed the presence of cryofibrinogen. Systemic cold challenge with serial plasma assays for complement, histamine, and prostaglandin D2 disclosed an elevation and peak of plasma histamine and prostaglandin D2 levels after the onset of generalized urticaria with no change in serum complement levels.

Severe angioedema related to ACE inhibitors in patients with a history of idiopathic angioedema.

Angiotensin converting enzyme (ACE) inhibitors have been associated with the onset of angioedema in a small subset of treated patients. The angioedema commonly involves the face and oropharyngeal tissues and may result in life-threatening airway compromise. The mechanism by which ACE inhibitors precipitate angioedema has not been well-defined, and retrospective analysis of reported cases has failed to identify a group of patients at high risk. We report four cases of ACE inhibitor-related angioedema that required immediate medical intervention. All four cases occurred in patients with a prior history of idiopathic angioedema, an otherwise uncommon clinical entity. These observations suggest that patients with a history of idiopathic angioedema are at increased risk for the development of ACE inhibitor-related angioedema and should be treated cautiously with this class of drugs.