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Chronic generalized pruritus caused by nitrate intolerance☆☆☆★

1999; Elsevier BV; Volume: 104; Issue: 5 Linguagem: Inglês

10.1016/s0091-6749(99)70098-9

1097-6825

Riccardo Asero,

Mast cells and histamine

For years, a number of studies have suggested that many patients with chronic urticaria have symptoms caused by the ingestion of food additives. Because few of these studies were properly controlled, most such reports remain unproved or anecdoctal.1Simon RA Stevenson DD. Adverse reactions to food and drug additives.in: 4th ed. Allergy: principles and practice. Mosby, St Louis1993: 1687-1704Google Scholar In this article, a case of chronic pruritus caused by intolerance to a single food additive diagnosed by rigorously controlled methods is reported.CASE REPORTA 28-year-old woman was referred to this allergy center because of a 4-year history of persistent generalized pruritus without any visible rash that was markedly enhanced after taking warm showers or baths. For this reason, the patient was receiving long-term antihistamine treatment (terfenadine, 120 mg daily). Physical urticarias such as cholinergic or aquagenic urticarias were ruled out, because the woman had never had urticaria (except for a single occasion following ciprofloxacin treatment 2 years before); moreover, neither exercise nor contact with cold water enhanced the pruritus.2Kaplan AP. Urticaria and angioedema.in: 4th ed. Allergy: principles and practice. Mosby, St Louis1993: 1553-1580Google Scholar She did not use other drugs and did not note any clear relationship between symptoms and specific food intake. The woman had seen several dermatologists who excluded infestations such as pediculosis or scabies and did not find any skin abnormality. Laboratory analyses including complete blood cell counts, erythrocyte sedimentation rate, blood glucose levels, urinalysis, liver function tests, thyroid function tests, thyroglobulin and thyroperoxidase antibodies, renal function tests, and stool tests for ova and parasites had been carried out several times during the past 2 years, and results were always normal. Findings of a chest roentgenogram were normal. A family history of atopic diseases was noted, but the patient had never had eczema or respiratory allergy.METHODSResults of skin prick tests with a large panel of commercial food extracts (Dome-Hollister/Stier 1:20 wt/vol) were negative, as were skin prick tests with airborne allergens. The intradermal injection of autologous serum did not elicit any wheal and flare reaction.3Greaves MW. Chronic urticaria.N Engl J Med. 1995; 332: 1767-1772Crossref PubMed Scopus (380) Google Scholar An elimination diet (free of food additives) was started; on the fifth day of the diet, the pruritus completely disappeared, and the woman could stop taking antihistamines. After 1 month of an additive-free diet, during which the patient remained symptom-free, an open challenge (unrestricted diet for 15 days) was carried out. After some days, this open challenge caused a gradual relapse of pruritus that lasted throughout the entire open-challenge period. The additive-free diet was resumed and, again, symptoms totally disappeared after 4 to 5 days. After 3 weeks without symptoms, double-blind placebo-controlled peroral challenges with food additives were carried out. The patient continued the elimination diet throughout the entire challenge period.Table IFood additives used in challenge testsAdditiveDose (mg)Tartrazine (E 102)10Erythrosine (E 127)10Sodium metabisulfite (E 223)25Sodium benzoate (E 211)100Sodium glutamate (E 621)100Sodium nitrate (E 251)10Sorbic acid (E 200)100Butylated hydroxyanisole (E 320)10Talc (Placebo) Open table in a new tab RESULTSSixty minutes after the ingestion of sodium nitrate, 10 mg, the patient reported generalized pruritus that worsened during the following 30 minutes and disappeared after the intravenous administration of an antihistamine (chlorphenamine, 10 mg). None of the other substances nor the placebos induced any symptoms. Nitrate intolerance was diagnosed.DISCUSSIONItching patients without an apparent skin eruption pose a diagnostic challenge.4Fitzpatrick TB Haynes HA. Generalized pruritus.in: 9th ed. Principles of internal medicine. McGraw-Hill, Tokyo1980: 247-248Google Scholar Hyperthyroidism, lymphomas, infestations and parasitoses, hematologic diseases such as polycythemia vera, and hepatic diseases must be considered in the differential diagnosis.4Fitzpatrick TB Haynes HA. Generalized pruritus.in: 9th ed. Principles of internal medicine. McGraw-Hill, Tokyo1980: 247-248Google Scholar All of these conditions were excluded by proper laboratory and radiographic investigations, and chronic pruritus was eventually found to be caused by intolerance to a food additive.Despite their widespread use as preservatives and as flavoring and coloring agents in processed meats (eg, salami and frankfurters), nitrates and nitrites have been rarely associated with adverse pseudoallergic reactions: a total of 11 cases of nitrate-dependent chronic urticaria are reported in the literature.5Juhlin L. Recurrent urticaria: clinical investigation of 330 patients.Br J Dermatol. 1981; 104: 369-381Crossref PubMed Scopus (319) Google Scholar, 6Zanussi C Ortolani C Pastorello E. Dietary and pharmacologic management of food intolerance in adults.Ann Allergy. 1983; 51: 307-310PubMed Google Scholar, 7Moneret-Vautrin DA Einhom C Tisserand J. Le role du nitrate de sodium dans les urticaries histaminiques d’origine alimentaire.Ann Nutr Alim. 1980; 34: 1125-1132PubMed Google Scholar This patient showed a more subtle form of intolerance characterized by chronic generalized pruritus without any visible rash. A nonspecific response to challenge tests seems unlikely for the following reasons: (1) the patient did not show any reactivity to placebos or substances other than sodium nitrate; (2) the administration of sodium nitrate exactly reproduced the clinical symptoms present during the past 4 years; and (3) the study design (double-blind and multiple placebos) should have minimized possible bias. As in other cases of other food additive intolerance, pathogenetic mechanisms remain elusive. This case suggests that food additive intolerance should be included in the differential diagnosis of patients with chronic persistent pruritus of unknown origin. For years, a number of studies have suggested that many patients with chronic urticaria have symptoms caused by the ingestion of food additives. Because few of these studies were properly controlled, most such reports remain unproved or anecdoctal.1Simon RA Stevenson DD. Adverse reactions to food and drug additives.in: 4th ed. Allergy: principles and practice. Mosby, St Louis1993: 1687-1704Google Scholar In this article, a case of chronic pruritus caused by intolerance to a single food additive diagnosed by rigorously controlled methods is reported. CASE REPORTA 28-year-old woman was referred to this allergy center because of a 4-year history of persistent generalized pruritus without any visible rash that was markedly enhanced after taking warm showers or baths. For this reason, the patient was receiving long-term antihistamine treatment (terfenadine, 120 mg daily). Physical urticarias such as cholinergic or aquagenic urticarias were ruled out, because the woman had never had urticaria (except for a single occasion following ciprofloxacin treatment 2 years before); moreover, neither exercise nor contact with cold water enhanced the pruritus.2Kaplan AP. Urticaria and angioedema.in: 4th ed. Allergy: principles and practice. Mosby, St Louis1993: 1553-1580Google Scholar She did not use other drugs and did not note any clear relationship between symptoms and specific food intake. The woman had seen several dermatologists who excluded infestations such as pediculosis or scabies and did not find any skin abnormality. Laboratory analyses including complete blood cell counts, erythrocyte sedimentation rate, blood glucose levels, urinalysis, liver function tests, thyroid function tests, thyroglobulin and thyroperoxidase antibodies, renal function tests, and stool tests for ova and parasites had been carried out several times during the past 2 years, and results were always normal. Findings of a chest roentgenogram were normal. A family history of atopic diseases was noted, but the patient had never had eczema or respiratory allergy. A 28-year-old woman was referred to this allergy center because of a 4-year history of persistent generalized pruritus without any visible rash that was markedly enhanced after taking warm showers or baths. For this reason, the patient was receiving long-term antihistamine treatment (terfenadine, 120 mg daily). Physical urticarias such as cholinergic or aquagenic urticarias were ruled out, because the woman had never had urticaria (except for a single occasion following ciprofloxacin treatment 2 years before); moreover, neither exercise nor contact with cold water enhanced the pruritus.2Kaplan AP. Urticaria and angioedema.in: 4th ed. Allergy: principles and practice. Mosby, St Louis1993: 1553-1580Google Scholar She did not use other drugs and did not note any clear relationship between symptoms and specific food intake. The woman had seen several dermatologists who excluded infestations such as pediculosis or scabies and did not find any skin abnormality. Laboratory analyses including complete blood cell counts, erythrocyte sedimentation rate, blood glucose levels, urinalysis, liver function tests, thyroid function tests, thyroglobulin and thyroperoxidase antibodies, renal function tests, and stool tests for ova and parasites had been carried out several times during the past 2 years, and results were always normal. Findings of a chest roentgenogram were normal. A family history of atopic diseases was noted, but the patient had never had eczema or respiratory allergy. METHODSResults of skin prick tests with a large panel of commercial food extracts (Dome-Hollister/Stier 1:20 wt/vol) were negative, as were skin prick tests with airborne allergens. The intradermal injection of autologous serum did not elicit any wheal and flare reaction.3Greaves MW. Chronic urticaria.N Engl J Med. 1995; 332: 1767-1772Crossref PubMed Scopus (380) Google Scholar An elimination diet (free of food additives) was started; on the fifth day of the diet, the pruritus completely disappeared, and the woman could stop taking antihistamines. After 1 month of an additive-free diet, during which the patient remained symptom-free, an open challenge (unrestricted diet for 15 days) was carried out. After some days, this open challenge caused a gradual relapse of pruritus that lasted throughout the entire open-challenge period. The additive-free diet was resumed and, again, symptoms totally disappeared after 4 to 5 days. After 3 weeks without symptoms, double-blind placebo-controlled peroral challenges with food additives were carried out. The patient continued the elimination diet throughout the entire challenge period.Table IFood additives used in challenge testsAdditiveDose (mg)Tartrazine (E 102)10Erythrosine (E 127)10Sodium metabisulfite (E 223)25Sodium benzoate (E 211)100Sodium glutamate (E 621)100Sodium nitrate (E 251)10Sorbic acid (E 200)100Butylated hydroxyanisole (E 320)10Talc (Placebo) Open table in a new tab Results of skin prick tests with a large panel of commercial food extracts (Dome-Hollister/Stier 1:20 wt/vol) were negative, as were skin prick tests with airborne allergens. The intradermal injection of autologous serum did not elicit any wheal and flare reaction.3Greaves MW. Chronic urticaria.N Engl J Med. 1995; 332: 1767-1772Crossref PubMed Scopus (380) Google Scholar An elimination diet (free of food additives) was started; on the fifth day of the diet, the pruritus completely disappeared, and the woman could stop taking antihistamines. After 1 month of an additive-free diet, during which the patient remained symptom-free, an open challenge (unrestricted diet for 15 days) was carried out. After some days, this open challenge caused a gradual relapse of pruritus that lasted throughout the entire open-challenge period. The additive-free diet was resumed and, again, symptoms totally disappeared after 4 to 5 days. After 3 weeks without symptoms, double-blind placebo-controlled peroral challenges with food additives were carried out. The patient continued the elimination diet throughout the entire challenge period. RESULTSSixty minutes after the ingestion of sodium nitrate, 10 mg, the patient reported generalized pruritus that worsened during the following 30 minutes and disappeared after the intravenous administration of an antihistamine (chlorphenamine, 10 mg). None of the other substances nor the placebos induced any symptoms. Nitrate intolerance was diagnosed. Sixty minutes after the ingestion of sodium nitrate, 10 mg, the patient reported generalized pruritus that worsened during the following 30 minutes and disappeared after the intravenous administration of an antihistamine (chlorphenamine, 10 mg). None of the other substances nor the placebos induced any symptoms. Nitrate intolerance was diagnosed. DISCUSSIONItching patients without an apparent skin eruption pose a diagnostic challenge.4Fitzpatrick TB Haynes HA. Generalized pruritus.in: 9th ed. Principles of internal medicine. McGraw-Hill, Tokyo1980: 247-248Google Scholar Hyperthyroidism, lymphomas, infestations and parasitoses, hematologic diseases such as polycythemia vera, and hepatic diseases must be considered in the differential diagnosis.4Fitzpatrick TB Haynes HA. Generalized pruritus.in: 9th ed. Principles of internal medicine. McGraw-Hill, Tokyo1980: 247-248Google Scholar All of these conditions were excluded by proper laboratory and radiographic investigations, and chronic pruritus was eventually found to be caused by intolerance to a food additive.Despite their widespread use as preservatives and as flavoring and coloring agents in processed meats (eg, salami and frankfurters), nitrates and nitrites have been rarely associated with adverse pseudoallergic reactions: a total of 11 cases of nitrate-dependent chronic urticaria are reported in the literature.5Juhlin L. Recurrent urticaria: clinical investigation of 330 patients.Br J Dermatol. 1981; 104: 369-381Crossref PubMed Scopus (319) Google Scholar, 6Zanussi C Ortolani C Pastorello E. Dietary and pharmacologic management of food intolerance in adults.Ann Allergy. 1983; 51: 307-310PubMed Google Scholar, 7Moneret-Vautrin DA Einhom C Tisserand J. Le role du nitrate de sodium dans les urticaries histaminiques d’origine alimentaire.Ann Nutr Alim. 1980; 34: 1125-1132PubMed Google Scholar This patient showed a more subtle form of intolerance characterized by chronic generalized pruritus without any visible rash. A nonspecific response to challenge tests seems unlikely for the following reasons: (1) the patient did not show any reactivity to placebos or substances other than sodium nitrate; (2) the administration of sodium nitrate exactly reproduced the clinical symptoms present during the past 4 years; and (3) the study design (double-blind and multiple placebos) should have minimized possible bias. As in other cases of other food additive intolerance, pathogenetic mechanisms remain elusive. This case suggests that food additive intolerance should be included in the differential diagnosis of patients with chronic persistent pruritus of unknown origin. Itching patients without an apparent skin eruption pose a diagnostic challenge.4Fitzpatrick TB Haynes HA. Generalized pruritus.in: 9th ed. Principles of internal medicine. McGraw-Hill, Tokyo1980: 247-248Google Scholar Hyperthyroidism, lymphomas, infestations and parasitoses, hematologic diseases such as polycythemia vera, and hepatic diseases must be considered in the differential diagnosis.4Fitzpatrick TB Haynes HA. Generalized pruritus.in: 9th ed. Principles of internal medicine. McGraw-Hill, Tokyo1980: 247-248Google Scholar All of these conditions were excluded by proper laboratory and radiographic investigations, and chronic pruritus was eventually found to be caused by intolerance to a food additive. Despite their widespread use as preservatives and as flavoring and coloring agents in processed meats (eg, salami and frankfurters), nitrates and nitrites have been rarely associated with adverse pseudoallergic reactions: a total of 11 cases of nitrate-dependent chronic urticaria are reported in the literature.5Juhlin L. Recurrent urticaria: clinical investigation of 330 patients.Br J Dermatol. 1981; 104: 369-381Crossref PubMed Scopus (319) Google Scholar, 6Zanussi C Ortolani C Pastorello E. Dietary and pharmacologic management of food intolerance in adults.Ann Allergy. 1983; 51: 307-310PubMed Google Scholar, 7Moneret-Vautrin DA Einhom C Tisserand J. Le role du nitrate de sodium dans les urticaries histaminiques d’origine alimentaire.Ann Nutr Alim. 1980; 34: 1125-1132PubMed Google Scholar This patient showed a more subtle form of intolerance characterized by chronic generalized pruritus without any visible rash. A nonspecific response to challenge tests seems unlikely for the following reasons: (1) the patient did not show any reactivity to placebos or substances other than sodium nitrate; (2) the administration of sodium nitrate exactly reproduced the clinical symptoms present during the past 4 years; and (3) the study design (double-blind and multiple placebos) should have minimized possible bias. As in other cases of other food additive intolerance, pathogenetic mechanisms remain elusive. This case suggests that food additive intolerance should be included in the differential diagnosis of patients with chronic persistent pruritus of unknown origin. I thank the nurses of the allergy center—Stefania Arienti, Ombretta Dolcino, and Aurelio Tirloni—for their cooperation in carrying out the double-blind challenges.