Immunological aspects of oral desensitization in food allergy.
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Biomedical subjects
Publications and source records attributed to G Patriarca.
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BACKGROUND: Literature reports dealing with cell-mediated allergy to betalactams have appeared with increasing frequency in the last years. OBJECTIVE: To evaluate patients with such reactions and to identify cross-reactivities among betalactams in order to provide safe guidelines for their further clinical management. METHODS: Thirty consecutive subjects with cell-mediated allergy to betalactams (history of adverse reactions to these antibiotics; serum total IgE within the normal range; absence of serum specific IgE antibodies to penicillin G and V, amoxicillin, and ampicillin; negative skin tests with a wide pattern of betalactam preparations; and positive patch-test to at least one betalactam antigenic determinant) were investigated. The subjects admitted to the study were patch tested with a wide variety of betalactam preparations in order to identify alternative molecules tolerated by the patient. To better evaluate the cross-reactivity pattern, tolerance challenges with patch-negative betalactams were also performed in each subject. RESULTS: Both specific IgE and skin tests were negative in all patients. The skin biopsies performed on the positive patch-tested area in four patients showed a clear T-lymphocyte, CD4+-type infiltrate, thus definitely proving the occurrence of a cell-mediated response. A total of 44 adverse reactions (mean: 1.47 episodes for each patient) were reported in history, with a mean interval of 15 hours after betalactam administration. The reported symptoms were mainly cutaneous (maculo-papular rash and urticaria) and the responsible drugs were chiefly aminopenicillins (86.4% of cases) and penicillin G (9.1%). We were able to identify three separate groups of patients on the basis of clinical history, patch-test, and tolerance challenge pattern: allergy to the side chain of aminopenicillins in 16 patients (53.3%); allergy to the thiazolidine ring in 3 patients (10.0%); undetermined specificity in the remainder 11 patients (36.7%). Cross-reactivity among different betalactam molecules (revealed by positive tolerance tests performed with patch-negative betalactams) was found in 4.8% of cases only (23.3% of all investigated patients). This fact demonstrates a very high (95.2%) predictive value of a negative patch-test in excluding the occurrence of a cross-reactivity. The mis-match between patch and tolerance tests was observed in 3 out of 178 cases only (1.7% of cases, 10.5% of patients) in groups A and B, and in as much as 12.2% of cases (45.5% of subjects) in group C (P < .05). CONCLUSIONS: Delayed allergy to betalactams (mainly to aminopenicillins) may be exerted by a cell-mediated response. Patch tests and tolerance challenges are extremely useful and safe for diagnosis and further clinical treatment of these patients, helping to identify safe alternative betalactam molecules that could be successfully tolerated by the allergic subjects.
Helicobacter pylori, the most important cause of gastritis and peptic ulcer, recently has been associated with several extradigestive diseases. The aim of this study was to assess the prevalence of Helicobacter pylori infection and the effects of bacterium eradication in 42 consecutive patients affected by idiopathic chronic urticaria. Helicobacter pylori was assessed by [13C]urea breath test. Amoxicillin, clarithromycin, and lansoprazole were given to infected patients for seven days. Urticaria and gastrointestinal symptoms were assessed on enrollment and after eradication. Fifty-five percent of patients proved to be infected by Helicobacter pylori. Prevalence of gastrointestinal symptoms did not differ between infected and uninfected patients. Eighty-eight percent of infected patients in whom the bacterium was eradicated after therapy showed a total or partial remission of urticaria symptoms. Conversely, symptoms remained unchanged in all uninfected patients. In conclusion, Helicobacter pylori affects a high percentage of patients with idiopathic chronic urticaria; however, typical gastrointestinal symptoms do not identify infection status. Bacterium eradication is associated with a remission of urticaria symptoms, suggesting a possible role of Helicobacter pylori in the pathogenesis of this skin disorder.
Some authors have shown that lysine acetylsalicylate (LAS) may help prevent nasal polyp relapses. As some anti-inflammatory drugs have been found to regulate cell growth, we investigated the antiproliferative effect of LAS on fibroblasts derived from nasal polyps. Moreover, we studied the effect of LAS on the growth of fibroblasts derived from normal skin to determine whether the response was similar to that obtained in the above-mentioned cells. Fibroblasts were obtained from tissue samples of nasal polyps from two aspirin-tolerant and two aspirin-intolerant patients, and from the normal skin of a healthy donor. The cells were treated with LAS (20-2000 microg/ml of culture medium). Cell growth and viability were evaluated after 3 and 6 days of culture. LAS had a growth-inhibitory effect on cells independently of their derivation. A reduction in cell growth was seen at the concentrations of LAS tested, which correspond to those used in the local treatment of nasal polyposis.
Activated mast cells are present in human coronary atheromas, as well as in the adventitia of patients with variant angina, and may play an important role in plaque rupture and coronary vasomotion. To assess whether or not activation of mast cells is a primary event, we measured serum levels of tryptase, a specific marker of mast cell activation, in 8 patients with unstable angina during a spontaneous ischemic episode (Group 1) and in 5 patients with variant angina (Group 2) during ergonovine-induced coronary spasm. Blood samples were collected as soon as possible after the onset of pain and ECG changes (0 min), and after 5, 15 and 60 min. Tryptase levels in Group 1 were 0.13 U/l (range 0.017-0.44) at the onset of pain and significantly raised to 0.75 U/l (range 0.05-2.49) at 5 min, decreasing to 0.076 U/l (range 0.018-0.16) at 15 min and to 0.085 U/l (range 0.01-0.25) at 60 min (p = 0.035). Conversely, tryptase levels in Group 2 were 0.09 U/l (range 0.07-0.13) at 0 min, 0.11 U/l (range 0.07-0.22) at 5 min, 0.10 U/l (range 0.07-0.18) at 15 min, 0.11 U/l (range 0.07-0.17) at 60 min (NS). In conclusion, tryptase levels raise during spontaneous ischemic episodes in unstable angina, but not after ergonovine-provoked ischemia in variant angina, suggesting that a primary, yet unknown stimulus, may activate mast cells during some ischemic episodes in unstable angina.
OBJECTIVES: Recent literature suggests the hypothesis of an immune etiology of Peyronie's disease. In this controlled study, the immune response pattern of the disease is investigated. METHODS: Sixty-six patients with Peyronie's disease and 20 age-matched controls were studied. In all patients, skin test (multitest), in vitro lymphocyte transformation test (LTT), serum immunoglobulin (Ig) A, G, and M, anti-DNA, antinuclear and anti-smooth muscle cell antibodies, C3 and C4 complement fractions, antistreptolysin, and C-reactive protein titers were evaluated. RESULTS: A fair percentage (75.8%) of the patients with Peyronie's disease exhibited at least one abnormal immunologic test, in comparison to only 10% among controls (chi-square = 27.8, df = 1; P < 0.0001). Alterations of cell-mediated immunity (multitest, LTT) were observed in 48.5% of patients, alterations of humoral immunity (Ig) in 31.8%, and alterations of markers of autoimmune disorders (autoantibodies, complement activation) in 37.9% of the cases. CONCLUSIONS: Our results support the hypothesis that there is some involvement of the immune system in the pathogenesis of Peyronie's disease, although the available data still appear to be insufficient to formulate a definite pathogenetic hypothesis.
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Among all the known drug intolerances, adverse reactions to heparin are not very common. No desensitization in patients with heparin hypersensitivity has ever been attempted. We report the case of a 55-year-old female patient with mitral stenosis and insufficiency, and tricuspid and aortic insufficiency. The patient underwent heparin treatment, and urticaria occurred with either s.c. calcium heparin or i.v. sodium heparin. Allergy testing (skin tests and patch tests) was negative. A pseudoallergic intolerance was diagnosed. Mitral valve replacement with the extracorporeal circulation method was necessary; therefore, heparin treatment was administered. A heparin rush desensitization together with antihistamine drugs (4 mg clorpheniramine maleate for 3 d) was started: 50 UI (0.5 mg) s.c. sodium heparin were first administered; within 4 d, 5000 UI (50 mg) sodium heparin was administered i.v. with no side-effects. A full-dosage heparin treatment was then administered and heart surgery was easily performed. During the postsurgical course, i.v. sodium heparin was smoothly replaced with s.c. calcium heparin (25,000 UI s.c. per day) and with oral anticoagulants (sodium warfarin).
A young woman (26 years old), with gastrointestinal candidosis of 8 months duration, was hospitalized in our department to study her cell immunity. Five minutes after an id injection of PHA (bactophytohaemoagglutinin M, Difco, 1 mg), mix monilieae, mix tricophyton and PPD Berna, she showed an extensive wheal and flare reaction in the PHA injection area, eyelid oedema and respiratory distress. In spite of adrenaline, corticosteroid and antihistamine drug administration, the patient collapsed and was admitted to the resuscitation department, where she quickly recovered. In the following days, the patient underwent immune and allergy testing: 1) total Ige immuno-enzymatic assay: 72 KU/1; 2) specific IgE and IgE immuno-enzymatic assay for Candida: negative; 3) in vitro lymphocyte transformation test (thymidine 2-C14) with PHA Difco was positive. This finding and the positivity of the id injection with PHA could indicate an allergic type I immunoreaction, the description of which we have not found in the international literature (the presence of IgG STS cannot be totally excluded).
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In order to evaluate pseudoallergic reactions to drugs, we studied a particular group of patients intolerant towards many drugs, pharmacologically dissimilar and administered during different periods of time. These patients consider themselves as "allergic" to "all" drugs. Twenty female patients, all with a history of intolerance to at least three drugs, chemically and antigenically dissimilar and not belonging to the same category of drugs, were studied. These patients underwent an allergological testing (negative in all cases) and a psychodiagnostic test (Rorschach's test); the latter was also performed in 20 normal control subjects. The psychodiagnostic findings demonstrated the negative psychological constitution of the experimental group in which the presence of a smaller quantity of energy leads to a minor capability of expressing emotions and to a major expression of depressive feelings. These patients suppress emotions to a greater extent, probably because of an expressive inhibition, while in the control group there is a possibility of mental elaboration. This implies that during the early period of emotional development with their parents, attempts to express affection received negative and frustrating replies. Therefore in later development, the expression of affection was suppressed. This last dynamic consideration, together with the former energetic and structural findings, demonstrates the pathogenic complexity of multiple drug intolerance, including, together with dysmetabolic, hormonal (clear prevalence of female subjects), autonomic and dysreactive factors, an important psychosomatic component. The diagnosis therefore also includes a careful psychodiagnostic test.
Forty-three patients suffering from nasal polyposis underwent intranasal treatment with increasing doses of lysine acetylsalicylate (LAS) corresponding to 20, 200, and 2000 micrograms of aspirin (ASA), until a maximal dose of 2000 micrograms weekly was reached. The patients were divided in two groups: a group of 28 patients with ASA intolerance, including 20 with ASA triad, and a group of 15 patients without ASA intolerance. The local treatment was usually started 1 month after polypectomy and was well tolerated without side effects. A control group included 191 subjects with nasal polyposis, 130 of whom had ASA intolerance. After polypectomy the controls received no further medical treatment. Patients were examined every 3 months and radiographs of the paranasal sinuses were obtained every 6 months. After 24 months 34 of 43 patients (79.1%) treated with topical LAS had suffered no relapse of polyposis. Only 45 of 191 control patients (23.6%) failed to relapse after 24 months (P less than .0001). Nine of 28 (32.1%) ASA-intolerant patients treated with LAS and 105 of the 130 (80.77%) control subjects relapsed (P less than .0001). None of the 15 ASA-tolerant patients treated with LAS relapsed, but 41 of the 61 (67.21%) nontreated control subjects relapsed (P less than .00001). These data indicate topical LAS is effective in preventing recurrence of nasal polyps after polypectomy.