Chronic urticaria: a mystery


C hronic urticaria (CU) has various causes such as intolerance to certain food additives and nonsteroidal anti-inflammatory drugs, and presence of various internal and infective diseases ( 1, 2). Despite careful research, the pathogenesis of CU has not yet been identified. We present the results of a study performed at the departments of dermatology of Milan and Bergamo, Italy, on patients with chronic urticaria.

A total of 348 (208 women and 140 men aged 24–59 years) consecutivepatients, excluding those with obvious physically induced urticaria ( 3), underwent a complete investigation consisting of their medical history and objective signs of the episode, and their personal and family history of allergies. Laboratory and instrumental investigations were carried out on all patients at their first visit, including routine blood tests and specific tests: CAP PRIST, CAP Phadiatop test ( 4), ELISA for specific IgG antibodies to Helicobacter pylori (HP), free T3, free T4, TSH, urine and stools tests for blood, parasites, and yeast, and chest radiograph. A psychosomatic examination of the last 66 patients and an autologous intradermal test in 113 were performed. The results are shown in Table 1.

Table 1.  Results of tests performed on 348 patients
 No. of
No. of
CAP tests
 CAP PRIST102 (36 patients≥600 kIU;
44 patients≤600≥300 kIU)
 CAP Phadiatop performed on 96 patients 71
CAP RAST and prick test concomitantly performed on 71 patients with 111
 Pollens 43=
 Dermatophagoides pteronyssinus 20=
 D. farinae 11=
 Wheat and other cereals 17 2
 Peas 10 1
 Peanuts 10 2
Dietary results performed on 202 patients
 Withdrawal 41
 Negative results 35
 Good results12642
Placebo-controlled oral exposure to foods performed on 202 patients with 15
positive patients (5 to several foods)
 Fish  1=
 Tomato  4 1
 Milk  2=
 Peas  6=
 Egg  3 1
 Peaches  4=
 Bananas  2=
 Apples  2=
 Peanuts  6 3
Placebo-controlled oral exposure to food additives performed on 202 patients
with 47 positive patients
 ASA 36 7
 Tartrazine  5=
 ASA and tartrazine  3
 Sodium benzoate  2
 P-oxy benzoate  1
Blood, stool, and RX tests
 Helicobacter pylori ab 78 4
 Parasites (giardiasis) 22 (13) 5 (5)
 Focal infections 20 5
 Viral infections 16=
Low complement and A.N.A.+  4 4
Thyroid alterations 10 1
Tumors  2?
ID test with autologous serum
performed on 110 patients
Psychosomatic problems evaluated
in 66 patients

There were more female than male patients (208 vs 140), and we found a high total eosinophil count in 129 patients, a high level of total IgE in 102 patients, and positive Phadiatop tests in 96 patients. The specific allergens included at least one of the allergens in the pollen/inhalant series and/or foods. A total of 202 patients whose history led to suspicion of a dietary causative factor were also prescribed a standardized diet, as described by Zuberbier et al. ( 5). Forty-one patients discontinued the diet because of low compliance, and 35 declared that they followed regularly without real improvement. A total of 126 patients who were fully compliant for the prescribed period reported an improvement in subjective symptoms lasting for at least 3 months; 47 out of 126 were positive to placebo-controlled tests of food additives.

The other 75 patients underwent commercially available food prick tests and the CAP-RAST test. When positive, a double-blind, placebo-controlled oral challenge (DBPCOC) was used: 15 patients were positive, the majority to peas and peanuts, as confirmed by DBPCOC with the suspected foods. ESR was high in 48 patients, but only 20 patients had also markedly increased inflammation indexes. Further specific diagnostic tests revealed that 20 of these patients presented a clear focus of infection in dental arcades, paranasal sinuses, urogenital tracts, and gallbladder. Only five were relevant, showing remission on appropriate therapy. Intestinal parasitic infections caused by Giardia or other organisms (eight cases of Ascaris lumbricoides, one case of Tenia solium) were detectable by means of parasitologic stool examinations.

Four patients suffering from urticaria showed a reduced value of complement-altered inflammation indexes and joint pains, and biopsy showed a classical picture of cutaneous vasculitis that could be considered definitely relevant. An association between CU and neoplastic diseases was observed in only two cases. Only 10 patients of the 113 patients who underwent an intradermal autologous serum test were positive The relevance was difficult to assess because the response to treatment did not correlate with the test. In terms of thyroid alterations, four patients had a hypothyroid state with positive antimicrosomial and antiperoxidase antibodies, whereas six had a hyperthyroid state. Of the 125 patients studied, 78 had circulating antibodies to HP (62%) ( 6). Eradication of the bacterium led to the subsidence of urticaria in only 4 of 31 patients who received eradication therapy.

Twenty-five of 66 consecutive patients (54 women and 12 men) who underwent psychosomatic examination gave suggestive replies for the presence of somatoform disorders, thus showing the importance of psychosomatic examination.

Since the number of positive results was greater than the number of our patients, several doubts arise concerning the possibility of attaining etiologic resolution in cases of CU; in fact, only 100 of our 348 patients presented a relevant pathologic pattern of being frequently positive to multiple investigations.


  1. 1 In only 100 of 348 consecutive cases was a pathogenic mechanism found.