Oral food challenge in children with contact urticaria in reaction to cow’s milk

Objective: To evaluate the relationship between the occurrence of contact urticaria in reaction to cow’s milk in infants and the diagnosis of cow’s milk allergy (CMA) established by supervised oral food challenge. Methods: In this cross-sectional study, we identified 184 children who had undergone 221 oral food challenge (OFC) at a CMA reference center between July 2015 and August 2019. Of these, 23 (12.5%) had a history of contact urticaria to cow’s milk and underwent a total of 30 OFC. Baked cow’s milk OFC were excluded, and 21 children were included in the study. All data from clinical history and allergy tests (serum-specific IgE dosages and skin prick test [SPT] with reconstituted cow’s milk formula) were recorded on standardized forms. The challenge was conducted with reconstituted cow’s milk formula in increasing volumes every 15–20 min. Results: 24 OFC were performed; 13/24 (54.2%) for diagnostic purpose and 11/24 (45.8%) to evaluate cow’s milk tolerance. Allergy tests were positive in 14 patients (87.5%). Positive oral challenge outcomes were identified in 7/24. One patient had a late flare of atopic dermatitis and five children presented with immediate urticaria (two generalized urticaria and three perioral urticaria). The median papule diameter was 6.5 mm in patients with a positive OFC and 3.75 mm in the negative group (P = 0.02). Conclusion: The occurrence of contact urticaria might be the only manifestation among infants sensitized to cow’s milk with tolerance to oral ingestion. Reactions due to oral challenge were related to a larger wheal diameter on the SPT (AU)

Effect of Diet in Chronic Spontaneous Urticaria: A Systematic Review.

Strategies for diets in chronic spontaneous urticaria (CSU) are controversial. This systematic review assessed the interest in diet for managing CSU. We searched for original reports in MEDLINE, EMBASE, CENTRAL and LILACS. Among the 278 reports screened, 20 were included, involving 1,734 patients. Reports described 3 types of systematic diet: pseudoallergen-free diet (n = 1,555 patients), low-histamine diet (n = 223) and diet without fish products (n = 47), which induced complete remission in 4.8%, 11.7% and 10.6% of patients, respectively, and partial remission in 37.0%, 43.9% and 4.3%. Eight reports described personalized exclusion diets (66 patients) adapted to symptoms/allergological test results and led to complete remission in 74.6% of patients, although the diagnosis of CSU was doubtful. No comparative randomized studies of diets were available. The only randomized studies were based on oral provocation tests with the suspected responsible diet. Population and outcomes were heterogeneous. In conclusion, there is evidence for the benefit of diets in CSU only in individual patients with clinical symptoms. However, the level of evidence is low for the benefit of systematic diets in CSU because systematic double-blind controlled trials of diet are lacking.

Which Fruits and Vegetables Should Be Excluded from a Low-Salicylate Diet? An Analysis of Salicylic Acid in Foodstuffs in Taiwan.

BACKGROUND: Eliminating pseudoallergens is an important element of managing chronic spontaneous urticaria (CSU). Salicylic acid (SA) is a primary pseudoallergen in plant-based foodstuffs. Current dietary recommendations are not applicable in East Asia because data on the SA content of many vegetables and fruits commonly consumed in this region are lacking. METHODS: We therefore determined the concentration of free SA in 79 popular vegetables and fruits frequently consumed in Taiwan using gas chromatography-mass spectrometry. RESULTS: The SA content ranged from 0.09 to 2.3 mg/kg in the fresh vegetables examined, and from 0.01 to 0.48 mg/kg in the fruits. CONCLUSIONS: Data regarding the SA content of East Asian vegetables and fruits could help CSU patients limit their pseudoallergen consumption.

A Popular myth - low-histamine diet improves chronic spontaneous urticaria - fact or fiction?

BACKGROUND: Chronic spontaneous urticaria (CsU) is a frequent dermatological disease that might last for months or years with high impact on quality of life. Known causes are autoreactive phenomena, infections or intolerances, rarely IgE-mediated allergies. One-third of CsU patients benefit from a low-pseudoallergen diet. Additionally, it is often discussed, that reducing histamine ingestion alone might improve clinical symptoms and quality of life in CsU patients despite the uncertain role of the histamine-degrading enzyme diamine oxidase (DAO). OBJECTIVE: Aim of this study was to investigate the impact of low-histamine diet on symptoms and quality of life in patients with CsU. METHODS: Patients suffering from CsU accompanied by gastrointestinal symptoms were included in the study. They underwent low-histamine diet for at least 3 weeks. During the whole study, urticaria activity score (UAS) was recorded daily in a patient's diary. Quality of life was assessed during screening, baseline and post diet visits by completing questionnaires (DLQI and Cu-Q(2)oL). DAO activity was measured before and after elimination diet. RESULTS: A total of 75% of the patients had a benefit from the low-histamine diet. Thirty-four of 56 patients (61%) reached the primary endpoint of the study, an improvement of UAS 4 of ≥3. Overall, a significant reduction from 9.05 to 4.23 points (P = 0.004) was achieved; the average reduction in a strongly affected subgroup was 8.59 points (P < 0.001). DAO activity remained stable. CONCLUSION: Low-histamine diet is a therapeutically useful, simple and cost-free tool to decrease symptoms and increase quality of life in CsU patients with gastrointestinal involvement. Further research is needed to understand the role of diamine oxidase.

Diet in dermatology: Part II. Melanoma, chronic urticaria, and psoriasis.

The roles of dietary factors in aggravating, preventing, or treating skin diseases are common questions encountered in dermatology practice. Part II of this two-part series reviews dietary modifications that can potentially be utilized in the management of melanoma, chronic urticaria, and psoriasis patients. Specifically, we examine the effect of alcohol consumption and supplementation with vitamins D and E, polyunsaturated fatty acids, selenium, green tea, resveratrol, and lycopene on melanoma risk. The relationships between chronic urticaria symptoms and dietary pseudoallergens, gluten, and vitamin D are analyzed. We explore weight loss, reduced alcohol consumption, and gluten avoidance as means of reducing psoriasis-associated morbidity, as well as the possible utility of supplementation with polyunsaturated fatty acids, folic acid, vitamin D, and antioxidants. With proper knowledge of the role of diet in these cutaneous disease processes, dermatologists can better answer patient inquiries and consider implementation of dietary modifications as adjuncts to other treatments and preventative measures.

Beneficial role for supplemental vitamin D3 treatment in chronic urticaria: a randomized study.

BACKGROUND: Observational reports have linked vitamin D with chronic urticaria, yet no randomized controlled trial has been conducted. OBJECTIVE: To determine whether high-dose vitamin D supplementation would decrease Urticaria Symptom Severity (USS) scores and medication burden in patients with chronic urticaria. METHODS: In a prospective, double-blinded, single-center study, 42 subjects with chronic urticaria were randomized to high (4,000 IU/d) or low (600 IU/d) vitamin D3 supplementation for 12 weeks. All subjects were provided with a standardized triple-drug therapy (cetirizine, ranitidine, and montelukast) and a written action plan. Data on USS scores, medication use, blood for 25-hydroxyvitamin D, and safety measurements were collected. RESULTS: Triple-drug therapy decreased total USS scores by 33% in the first week. There was a further significant decrease (40%) in total USS scores in the high, but not low, vitamin D3 treatment group by week 12. Compared with low treatment, the high treatment group demonstrated a trend (P = .052) toward lower total USS scores at week 12, which was driven by significant decreases in body distribution and number of days with hives. Beneficial trends for sleep quality and pruritus scores were observed with high vitamin D3. Serum 25-hydroxyvitamin D levels increased with high vitamin D3 supplementation, but there was no correlation between 25-hydroxyvitamin D levels and USS scores. There was no difference in allergy medication use between groups. No adverse events occurred. CONCLUSION: Add-on therapy with high-dose vitamin D3 (4,000 IU/d) could be considered a safe and potentially beneficial immunomodulator in patients with chronic urticaria. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01371877.

The role of nutrition in dermatologic diseases: facts and controversies.

Many dermatologic diseases are chronic with no definitive cure. For some diseases, the etiology is not completely understood, with treatment being difficult and associated with side effects. In such cases, patients may try alternative treatments to prevent onset, reduce symptom severity, or prevent reoccurrence of a disease. Dietary modification, through supplementation and exclusion, is an extremely popular treatment modality for patients with dermatologic conditions. It is, therefore, important for dermatologists to be aware of the growing body of literature pertaining to nutrition and skin disease to appropriately inform patients on benefits and harms of specific dietary interventions. We address the role of nutrition in psoriasis, atopic dermatitis, urticaria, and bullous diseases and specific dietary modifications as an adjunct or alternative to conventional therapy.

Anisakis simplex hypersensitivity is associated with chronic urticaria in endemic areas.

BACKGROUND: Chronic urticaria (CU) may affect up to 1% of the general population. Anisakis simplex hypersensitivity is frequent in areas where raw fish is consumed and A. simplex allergy represents a relevant cause of acute urticaria. We assessed the possible association between CU and A. simplex sensitization in an area where marinated fish is very frequently eaten. METHODS: A thorough history of CU was sought in 919 adults seen at the Allergy Center, Bari. CU patients and 187 controls underwent skin-prick testing with a commercial extract of A. simplex, and reactors were recommended a 6-month raw-fish-free diet regimen. Responders were followed after a further 3 months. RESULTS: Of 919 subjects, 213 (23%) met the criteria for CU and 106/213 (49.7%) were sensitized to A. simplex with a significant difference between patients aged >65 or <65 years (56 vs. 41%, respectively; p < 0.05). All patients hypersensitive to A. simplex were regular consumers of marinated fish. In a control population without CU, the prevalence of A. simplex sensitization was 16% (p < 0.001). The 6-month diet regimen led to the disappearance of urticaria in 82/106 cases (77%) versus 1/42 (2%) subjects who did not change their dietary habits (p < 0.001). All nonresponders were sensitized to house-dust mites. Of 75 responders who were followed-up after 3 months, CU relapsed in 88% of those who had reintroduced raw fish versus 14% of those who were still on the diet (p < 0.001). CONCLUSION: In areas where raw or marinated fish is frequently eaten, A. simplex hypersensitivity is a frequent cause of CU.

Early neutral prebiotic oligosaccharide supplementation reduces the incidence of some allergic manifestations in the first 5 years of life.

BACKGROUND: A mixture of neutral prebiotic oligosaccharides has been shown to reduce the incidence of atopic dermatitis (AD) and allergy associated symptoms during the first 2 years of life. OBJECTIVE: To evaluate if this protective effect against allergy lasted beyond the intervention period until 5 y of age. METHODS: In a prospective, double blind, placebo-controlled fashion, healthy term infants at risk of atopy were fed either a prebiotic-supplemented (0.8 g/100 ml scGOS/lcFOS) or placebo-supplemented (0.8 g/100 ml maltodextrin) hypoallergenic formula during the first 6 mo of life. Following this intervention period, follow-up continued until 5 y of life. The present study evaluated (i) the cumulative incidence of allergic manifestations during 5 y, and (ii) the prevalence of allergic and persistent allergic manifestations at 5 y. Monitored allergic manifestations were AD, recurrent wheezing, allergic rhinoconjunctivitis and urticaria. RESULTS: Ninety-two children (50 in placebo group, 42 in intervention group) completed the 5-y follow-up. The 5-y cumulative incidences of any allergic manifestation and atopic dermatitis were significantly lower in the scGOS/lcFOS group (30.9, 19.1 %, respectively) compared to placebo group (66, 38 %, respectively) (p< 0.01 and< 0.05). Children in the scGOS/lcFOS group tended to have a lower incidence of allergic rhinoconjunctivitis, and allergic urticaria (4.8 vs 16% for both manifestations, p=0.08). There was no difference in the cumulative incidence of recurrent wheezing. With regard to the prevalences at 5 y, intervention group had significantly lower prevalence of any persistent allergic manifestation and rhinoconjunctivitis (4.8, 2.4 %, respectively) compared to placebo (26, 14 %, respectively) (p < 0.01 and =0.05). Prevalence of persistent AD tended to be lower in the intervention group (2.4 vs 12%, p= 0.09). Although intervention group had 75% reduction in the prevalence of persistent wheezing (4.8 vs 14 %), no significance was shown. CONCLUSION: Oligosaccharide prebiotics (scGOS/lcFOS), when started early in life have a protective effect against allergic manifestations in high risk infants. The protection lasts beyond infancy until 5 y of life, for AD and allergic rhinoconjunctivitis. Long-term follow-up studies in larger populations are warranted to evaluate the potential preventive effect of this mixture on asthma.

Prevalence of food avoidance and food allergy in Chinese patients with chronic urticaria.

BACKGROUND: Food avoidance is common among Chinese patients with chronic urticaria because food allergy is considered to be the cause of disease. The benefit of food avoidance and its relationship with food allergy is unknown. OBJECTIVES: The aims of this study were to examine the prevalence and effect of food avoidance and food allergy in patients with chronic urticaria. METHODS: Four hundred and ninety-four patients with chronic urticaria, who attended Peking University Third Hospital from January 2009 to December 2010, were studied. Food avoidance and its effect were investigated with a detailed questionnaire. Food allergy was diagnosed by serum food-specific immunoglobulin E (IgE), elimination diet based on food-specific IgE, and open food challenge. RESULTS: One hundred and fifty-eight patients (32%) avoided fish, shrimp, crab, lamb or beef prior to evaluation and 82·9% of them reported food avoidance ineffective. Out of 341 patients tested for serum food-specific IgE, 75 (22%) were positive, with soy, peanut, beef, lamb, chicken, crab and shrimp as the leading allergens. Chronic urticaria induced by food allergy was found in only 2·8% of patients. CONCLUSIONS: The prevalence of food avoidance is high and mostly ineffective in Chinese patients with chronic urticaria. Foods avoided do not correspond to serum food-specific IgE. The incidence of IgE-mediated urticaria, as demonstrated by open food challenge, is low. Physicians and patients should be aware of unnecessary dietary avoidance while seeking treatment of chronic urticaria.

Effects of low pseudoallergen diet on urticarial activity and leukotriene levels in chronic urticaria.

Pseudoallergens and leukotrienes (LTs) may have a role in chronic urticaria (CU). The aim of our study is to evaluate the response to the low pseudoallergen diet therapy in patients with CU and the change in LT levels in diet responsive and non-responsive patients. 34 patients with CU were put on diet for 4 weeks. All patients kept a daily score sheet of pruritus and whealing symptoms. The urticarial activity score (UAS) of each patient was calculated with the sum of pruritus and wheal score. The sum score of the first 7 consecutive days (UAS7-first week) and last 7 days (UAS7-fourth week) were used to compare the clinical outcome of the diet. A reduction of ≥50% in UAS7-fourth week compared to UAS7-first week was considered as "response". Urinary LTE4 (uLTE4) level of each patient was measured at baseline and after the 4 week of diet therapy. 14 of the patients (41.2%) were responsive to diet therapy. Baseline uLTE4 levels were similar between responsive and non-responsive patients (P = 0.540). Second uLTE4 levels (after the 4 week of diet therapy) were significantly lower in responsives than in non-responsive patients (P < 0.001). Second uLTE4 levels of responsives were significantly lower than the baseline values (P = 0.019), whereas this was not significant for non-responsives (P = 0.070). There was a significant correlation between the change in uLTE4 levels and the change in mean urticarial activity scores (r = 0.554, P = 0.001) in the whole study population. In conclusion, low pseudoallergen diet helps to reduce the urticarial activity in CU. The change in urticarial activity correlates with the change in LT levels.

Eosinophilic esophagitis, celiac disease, and immunoglobulin E-mediated allergy in a 2-year-old child.

Celiac disease, eosinophilic esophagitis, and urticaria are 3 manifestations of food allergy with different pathogenic mechanisms. We report the case of a 2-year-old child with digestive symptoms, slow growth, and severe asthma. The results of skin prick tests were positive to several foods. Endoscopy revealed eosinophilic esophagitis and celiac disease. Treatment consisted of a gluten-free diet and a 1-month course of oral corticosteroids. Endoscopy and biopsy findings were normal at 5 years of age. A gluten-free diet is the basis of treatment of celiac disease, but the role of an elimination diet in eosinophilic esophagitis is not well established. Our patient also developed urticaria when exposed to milk and egg.We present, to our knowledge, the first report of a patient with celiac disease, eosinophilic esophagitis, and immediate-type immunoglobulin E-mediated food allergy.

Urticaria: an evidence-based update. Conference report.

Summary Evidence-based update meetings are held annually by the Centre of Evidence Based Dermatology, University of Nottingham. Topics are chosen by delegates at the previous year's conference and in the past have included blistering disorders, psoriasis, hair disorders and skin cancers. Once the topic is identified, a trials database search is undertaken with the aim of including speakers who are actively involved in trials that address the subject in question. This year, the eighth Evidence Based Update meeting focused on urticaria and took place in Loughborough University on 14 May 2009. The latest data on the diagnosis and management of acute and chronic urticaria, including cold and solar urticaria, and the impact of food intolerance on chronic urticaria, were presented by an international panel of renowned speakers, who sometimes expressed different viewpoints. The highlights of the meeting included an informal atmosphere, an international perspective, and a practical question and answer session. Over 70% of the delegates stated that they would be changing their clinical practice following on from the meeting. The evidence-based update meeting in 2010 will be devoted to eczema.

Effects of a pseudoallergen-free diet on chronic spontaneous urticaria: a prospective trial.

BACKGROUND: Chronic spontaneous urticaria is a skin disorder that is difficult to manage and can last for years. 'Pseudoallergens' are substances that induce hypersensitive/intolerance reactions that are similar to true allergic reactions. They include food additives, vasoactive substances such as histamine, and some natural substances in fruits, vegetables and spices. Eliminating pseudoallergens from the diet can reduce symptom severity and improve patient quality of life. AIM: To assess the effects of a pseudoallergen-free diet on disease activity and quality of life in patient's chronic spontaneous urticaria. METHODS: Study subjects had moderate or severe chronic spontaneous urticaria that had not responded adequately to treatment in primary care. For 3 weeks, subjects followed a pseudoallergen-free diet. They kept a clinical diary, which recorded their wheal and pruritus severity each day, to yield a clinical rating of chronic spontaneous urticaria severity (the UAS4 score). The subjects also completed the DLQI, a validated quality-of-life instrument. Use of antihistamines and glucocorticoids was minimized, recorded, and analysed. Subjects were classified into nine response categories, according to the changes in symptom severity (UAS4), quality of life (DLQI) and medication usage. RESULTS: From the 140 subjects, there were 20 (14%) strong responders and 19 (14%) partial responders. Additionally, there were nine (6%) subjects who made a substantial reduction in their medication without experiencing worse symptoms or quality of life. CONCLUSIONS: Altogether the pseudoallergen-free diet is beneficial for one in three patients. The pseudoallergen-free diet is a safe, healthy and cost-free measure to identify patients with chronic spontaneous urticaria that will benefit from avoiding pseudoallergens.

Usefulness of the CD63 basophil activation test in detecting Anisakis hypersensitivity in patients with chronic urticaria: diagnosis and follow-up.

BACKGROUND: The basophil activation test (BAT) has been recently described as a useful in vitro tool for diagnosis of allergy to Anisakis species in patients with acute urticaria. AIM: To evaluate the relationship between sensitization to Anisakis simplex and chronic urticaria (CU), using flow cytometry analysis of in vitro BAT. Methods. A. simplex sensitization was evaluated in patients with CU (n = 57) and in atopic (n = 22) and healthy controls (n = 20) by means of skin prick test (SPT), specific IgE and Anisakis-induced BAT using a triple-labelled strategy with anti-CD123, anti-human leucocyte antigen DR and anti-CD63 antibodies. During a follow-up period of 6 months in 10 patients with CU who accepted a fish-free dietary regimen, the diagnostic performance of the in vivo and in vitro methods was calculated, and changes in specific IgE and BAT were evaluated with respect to clinical response. RESULTS: A significant association between CU and A. simplex sensitization was found, with an overall prevalence of 75.4% in patients with CU (43/57) compared with 18% (4/22) and 10% (2/20) of the atopic and healthy controls, respectively (P < 0.0001). BAT (cut-off > 13%) had the highest sensitivity and specificity, with significantly better ability than specific IgE testing for the identification of A. simplex sensitization in patients with CU. During the 6-month follow-up, clinical improvement was seen in all patients, and specific IgE and BAT results decreased to normal values in 6/10 (60%) and 10/10 (100%) patients, respectively. CONCLUSIONS: BAT can be considered a reliable new in vitro method to evaluate A. simplex hypersensitivity in patients with CU, supplementing standardized procedures in both diagnosis and follow-up.

Italian position paper on urticaria. Italian Board on Urticaria.

The Italian Board on Urticaria has prepared a document focusing on the definition and classification of urticaria, taking into account the recent progress in identifying the causes, eliciting factors, and pathomechanisms of this disease. As urticaria has a profound impact on the quality of life, effective treatment is important. Therefore, specific treatment options for the management of urticaria are evaluated on the basis of the recent literature. Non-sedating H(1) antihistamines are recommended as the first-line treatment as they have proven effective in several randomized double-blind controlled studies. Dosages higher than those recommended may be necessary in some cases. However, additional or alternative therapies may be required for different urticaria subtypes and in view of individual variations in the course of the disease and response to treatment. Immunosuppressive drugs such as corticosteroids are not recommended for long-term treatment due to unavoidable, severe adverse effects.

Incremental build-up food challenge--a new diagnostic approach to evaluate pseudoallergic reactions in chronic urticaria: a pilot study: stepwise food challenge in chronic urticaria.

BACKGROUND: The remission rate of patients with chronic urticaria (CU) due to elimination diets varies between 31% and 71%. However, the diagnostic value of subsequent traditional oral provocation tests with food additives in capsules remains unsatisfactory. OBJECTIVES: A newly incremental build-up food challenge (IBUF) for patients with CU was designed and implemented in an open pilot study. Primary endpoint was the percentage of patients developing urticaria during at least one step of IBUF after an initial complete remission due to a pseudoallergen-free elimination diet. METHODS: In total, 153 patients with CU were submitted for 5 weeks to a pseudoallergen-free diet. All patients with remission were included to the 6-week IBUF protocol, containing pseudoallergen-rich foods in a systematic and additive manner. The recurrence and severity of CU was evaluated by urticaria score. Subjective disturbance and quality of life were evaluated by patients' diary, visual analogue scale and quality of life questionnaire (CU-Q2oL). Subsequently, patients were followed up for 3-24 months after IBUF by a telephone interview. RESULTS: A total of 104 patients completed the pseudoallergen-free diet, whereby 51% reported partial, 17% complete and 32% no remission due to the diet. All diet responders showed a decrease in subjective impairment, urticaria and quality of life score (P<0.001 each). Eighty-six percent (12/14) of the patients reaching complete remission, showed a recurrence of urticaria symptoms during the IBUF protocol. Fifty-eight percent (7/12) of these patients still remained free of symptoms due to avoidance of IBUF-identified foods at telephone follow-up. In patients with partial remission to pseudoallergen-free diet, however, IBUF did not provide information about the cause of urticaria symptoms. CONCLUSIONS: The newly developed IBUF protocol seemed to be a promising method for identifying individually incompatible foods in some CU patients. IBUF should be verified by randomized controlled trials to gain additional evidence for its diagnostic value.