Evaluating and managing chronic idiopathic urticaria in adults.

Chronic idiopathic urticaria (CIU), also known as chronic spontaneous urticaria, is characterized by the presence of hives on most days of the week, for 6 weeks or longer, and without an identifiable or consistent cause. Evaluation is clinical and based on the presence of episodic urticarial lesions. Although patients are subject to overtesting during the diagnosis of CIU, guidelines suggest starting with three basic laboratory tests. Treatment is a stepwise approach, involving second-generation antihistamines, histamine2 antagonists, leukotriene receptor antagonists, first-generation antihistamines, and potent antihistamines. Refractory CIU requires adding alternative agents such as omalizumab, anti-inflammatory agents, and immunosuppressants.

Wheat Allergy and Intolerence; Recent Updates and Perspectives.

The current review paper highlights the complicacies associated with communities relying on wheat as their dietary staple. Although, wheat is an important source of nutrients but is also linked with allergenic responses in genetically susceptible subjects. The wheat proteins especially α-amylase inhibitors, ω-5 gliadins, prolamins, nonprolamin, glucoprotein, and profilins are of significance importance. The allergenic responses are further categorized into IgE-mediated and non-IgE-mediated reactions. Conjugation and degranulation of the IgEs with the allergens results in release of several mediators. In contrary, non-IgE-mediated wheat allergy depends on immune complexes formed by food and food antibodies and cell-mediated immunity. As results, different diseases tend to occur on the completion of these reactions, i.e., celiac disease, baker's asthma, diarrhea, atopic dermatitis, and urticaria. This instant paper highlighted the concept of food allergy with special reference to wheat. The models are developed that are included in this paper showing the wheat allergen, their possible routes, impact on human health, and indeed possible remedies. The paper would provide the basic information for the researchers, common man, and allied stakeholders to cater the issue in details. However, the issue needs the attention of the researchers as there is a need to clarify the issues of wheat allergy and wheat intolerance.

[Risk hidden in the small print? : Some food additives may trigger pseudoallergic reactions]. / Verstecktes Risiko im Kleingedruckten? : Einige Zusatzstoffe können pseudoallergische Reaktionen auslösen.

Some food additives may trigger pseudoallergenic reactions. However, the prevalence of such an overreaction is - despite the increasing number of food additives - rather low in the general population. The most common triggers of pseudoallergic reactions to food are naturally occurring ingredients. However, symptoms in patients with chronic urticaria should improve significantly on a pseudoallergen-free diet. In addition, some studies indicate that certain food additives may also have an impact on the symptoms of patients with neurodermatitis and asthma.

Occupational contact urticaria: lessons from the French National Network for Occupational Disease Vigilance and Prevention (RNV3P).

BACKGROUND: Occupational contact urticaria (OCU) is an occupational contact dermatitis that can cause serious health consequences and disability at work. OBJECTIVES: To describe OCU and its temporal trends by the main causal agents and activity sectors in a nationwide scheme in France. METHODS: Using data from the French National Network for Occupational Disease Vigilance and Prevention (RNV3P), we described OCU reported during the period 2001-10 and analysed the temporal trends of OCU and OCU attributed to the most frequent agents over the study period. Trends analyses were supported by reporting odds ratios using a logistic regression model with reference to 2001, or with time as a continuous variable. RESULTS: During the study period, 251 cases of OCU were reported in RNV3P, half of which were due to natural rubber latex, in particular in the health and social work activity sector (HSW). The number of these cases declined significantly over the study period (19% per year), and particularly after 2006. Conversely, the other causes of OCU did not decrease. CONCLUSIONS: Using surveillance data from a French national network, this study has found that there was a significant decline in OCU due to natural rubber latex, particularly in the HSW, when powdered latex gloves were banned from French hospitals. Our results show the effectiveness of this preventive measure, and suggest that this practice should be extended to other sectors.

Immediate-type hypersensitivity reactions due to antituberculosis drugs: a successful readministration protocol.

BACKGROUND: Little is known about drug hypersensitivity reactions from antituberculosis drugs. OBJECTIVE: To determine the frequency, risk factors, and characteristics of immediate-type hypersensitivity reactions from first-line antituberculosis drugs and to evaluate the usefulness of a readministration protocol for culprit drugs in this group of patients. METHODS: The study population consisted of patients with tuberculosis who were hospitalized and treated in the authors' hospital in 2011. Demographics and disease and treatment characteristics of patients with immediate-type hypersensitivity from antituberculosis drugs were compared with the other patients. Culprit drugs were readministered gradually according to a defined protocol to patients with immediate-type hypersensitivity. RESULTS: Tree hundred seventy-nine patients were included in the study. Eighteen immediate-type hypersensitivity reactions were detected in 13 patients (3.43%). The only identified risk factor was female sex (odds ratio 4.085). Isoniazid, rifampicin, pyrazinamide, and ethambutol were readministered in 11 patients and rifampicin was readministered in 2 patients, with 6- to 8-step protocols for each drug. Only in 2 patients did allergic reactions with rifampicin develop during the procedure. In these patients, after treatment and complete remission of allergic symptoms, the last tolerated dose was administered and the protocol was completed with the same adjustments. CONCLUSION: Immediate-type allergic reactions from antituberculosis drugs are not rare and not related to disease or treatment characteristics. The protocols used in this study provide a useful and safe method for readministration of culprit drugs to patients with antituberculosis drug hypersensitivity.

[Delayed anaphylaxis after ingestion of meat. Carbohydrate epitope galactose-α-1,3-galactose as cause of severe anaphylactic reactions]. / Verzögerte Anaphylaxie nach Fleischverzehr. Kohlenhydratepitop Galaktose-α-1,3-Galaktose als Auslöser schwerer anaphylaktischer Reaktionen.

The correlation between anaphylaxis after consumption of meat and the carbohydrate epitope galactose-α-1,3-galactose (α-Gal) was first described in oncologic patients treated with cetuximab. An association with tick bites and parasitosis is suspected. We report on a healthy patient who developed sudden anaphylactic reactions after the ingestion of meat. Serologic and skin tests confirmed sensitization to α-Gal. Avoiding the consumption of mammalian meat led to a complete absence of symptoms.

Solar urticaria.

Solar urticaria is a rare IgE-mediated and chromophore-dependent photodermatosis. In some cases, these chromophores, designated as "serum factor", may be detected in serum or plasma. To date, the exact pathogenesis of solar urticaria has, however, not been elucidated. Typical clinical features include the onset of urticarial lesions within a few minutes after light exposure, which already raises diagnostic suspicion. The most common triggers are UVA and visible light. Determination of the action spectrum as well as the minimal urticarial dose (MDU) is diagnostically crucial. Other photodermatoses such as polymorphic light eruption or porphyrias (especially erythropoietic protoporphyria) have to be ruled out. Apart from sunlight avoidance, which is always required, further therapeutic options used include nonsedating antihistamines as well as light hardening. Newer treatment modalities such as plasmapheresis or the anti-IgE antibody omalizumab are reserved for severe, recalcitrant forms of solar urticaria.

Avoidance of nonsteroidal anti-inflammatory drugs after negative provocation tests in urticaria/angioedema reactions: Real-world experience.

Drug provocation tests (DPTs) are the gold standard in diagnosing nonsteroidal anti-inflammatory drug (NSAID) hypersensitivity; however, only few data about follow-up of patients with negative DPTs are actually available. The aim of this study was to assess patients' behavior in taking NSAIDs again and to evaluate NSAID tolerability after negative allergological workup. This is a follow-up study involving patients evaluated for history of cutaneous reactions (urticaria and or angioedema) after NSAID intake and with negative DPTs with the suspected NSAID. Patients were asked during a phone interview about the intake of NSAIDs, tolerance, or reasons of avoidance. The negative predictive value (NPV) of NSAIDs DPTs was calculated. One hundred eleven of 142 patients were successfully contacted; 46/111 (41.44%) took the same NSAID previously tested with two adverse reactions reported (4.34%). Fifty-three of 111 (47.74%) patients did not take the same NSAID, but 34 of them took at least another strong cyclooxygenase (COX) 1 inhibitor, with 1 adverse reaction (2.94%) and 19 of them took only weak COX-1 inhibitors. Twelve of 111 patients (10.8%) did not take any NSAID. Reasons for drug avoidance were mainly fear of reactions (70.8%) and no need (29.2%). NPV, overall, was 96.97% (95% confidence interval, 91-99%). Although NSAID hypersensitivity diagnosis was ruled out by oral provocation test, the majority of patients with a history of urticaria/angioedema avoided the intake of the tested NSAIDs for fear of new reactions, particularly when strong COX-1 inhibitor NSAIDs were involved. The high NPV value of DPT resulting from this study should reassure NSAID intake.

A practical, clinical approach to the assessment and management of suspected insulin allergy.

BACKGROUND: Although allergic reactions to insulin are uncommon, they can be difficult to diagnose and management may be very difficult in subjects with Type 1 diabetes with severe allergy. Access to allergists and specialist diagnostic tests is limited and few diabetes specialists are familiar with desensitization as a means of treating allergy. People with diabetes may develop symptoms which mimic insulin allergy but are attributable to other conditions. CASE REPORTS: Here we describe three cases of insulin allergy. One patient presented with severe, albeit localized, urticarial reactions at injection sites. The most severe case was a woman with recent-onset Type 1 diabetes who presented with grade 2 anaphylaxis. The third patient presented with generalized urticaria and angioedema. Insulin allergy was confirmed in all three cases. METHODS: Assessment involved measurement of immunoglobulin and anti-insulin antibody levels. Skin testing was performed in two cases. Treatments included desensitization in one case, alternative insulin preparations, antihistamines and continuous subcutaneous insulin infusion. In all three cases of insulin allergy there has been successful resolution of symptoms. CONCLUSIONS: The clinical assessment and investigation in cases of suspected insulin allergy is described, along with detailed algorithms for skin testing and desensitization. This case series demonstrates an approach to challenging cases of suspected insulin allergy which will be helpful for diabetes specialists.

Angioedema without urticaria in childhood.

BACKGROUND: There has been no separate study investigating angioedema without urticaria (Aw/oU) exclusively in children so far. The purpose of this study was to investigate the frequency, clinical presentation, etiology, management and follow-up of Aw/oU in children. METHODS: This is a prospective study that included all consecutive patients with a history of Aw/oU referred to our clinic between January 2011 and May 2012. A standard diagnostic and therapeutic algorithm was applied to all patients. RESULTS: The frequency of Aw/oU was found to be 1.6% during the study period. An etiological factor could be found in only 45 patients (49%). The causes of Aw/oU were infection (21%), allergy (14%), thyroid autoimmunity (TA)-related (8%) and nonsteroid anti-inflammatory drug hypersensitivity (6%), and idiopathic angioedema (51%). There was no hereditary type I, II or acquired type of angioedema or rare syndromes associated with Aw/oU. The median follow-up was 16 months (range: 12-30 months). Antihistamine prophylaxis was initiated at therapeutic doses in 20 patients with frequently recurrent angioedema due to idiopathic and euthyroid TA-related Aw/oU for 3 months. These patients responded to antihistamine prophylaxis for 3 months. Four patients relapsed after cessation of prophylaxis at the end of 3 months. Antihistamine prophylaxis was prolonged to 6 months in three patients and to 9 months in one patient. CONCLUSIONS: Angioedema without urticaria in children is a rare condition and no etiology can be identified in half of them. Antihistamine treatment alone is sufficient, and prognosis is good in recurrent non hereditary cases in a short-term follow-up period.

Comparison between two maintenance feeding regimens after successful cow's milk oral desensitization.

BACKGROUND: Cow's milk allergy is common in infancy, and total avoidance of this food is the only effective approach. In alternative, oral immunotherapy has been proposed to achieve tolerance. Once desensitization is achieved, daily intake of milk is recommended to maintain it, but this may be impractical for children/parents. We assessed whether a twice weekly maintenance regimen is effective. METHODS: Children who were successfully desensitized with oral immunotherapy were randomized to two maintenance regimens for 1 year: group A had to eat 150-200 ml milk daily, group B had to eat 150-200 ml milk twice weekly. Both regimens were associated to a totally free diet. Maintenance of tolerance and adverse events were recorded during 1 year. Specific IgE, IgG4 and prick-by-prick test to milk were carried out before immunotherapy (T0), before maintenance (T1), and after 1 year (T2). RESULTS: Recorded episodes included asthma, oral itching, urticaria, rhinitis, abdominal pain variously combined, usually associated with concomitant illness or exercise. The episodes were 8 in group A and 9 in group B, with no difference. None of the children discontinued the feeding maintenance. Specific IgG4 increased at T1 and remained high at T2. Specific IgE and skin reactivity significantly decreased at T2. There was no difference in those parameters between the groups. CONCLUSION: After achieving desensitization to cow milk with oral immunotherapy, a maintenance regimen with milk given twice weekly is as effective as the daily maintenance.

Prevention of nonsteroidal inflammatory drug-induced urticaria and/or angioedema.

BACKGROUND: Urticaria and/or angioedema (U/AE) are the most frequent and less severe forms of nonallergic hypersensitivity reactions to nonsteroidal anti-inflammatory drugs (NSAIDs). Management of NSAID-induced U/AE includes (1) the avoidance of the culprit drug and of cyclooxygenase (COX) 1 inhibitors, (2) the use of weak COX-2 inhibitors, and/or (3) desensitization to aspirin. Because these possibilities may have drawbacks, we tested the possibility of preventing NSAID-induced U/AE by the administration of antihistamines and/or a combination of antihistamines and leukotriene antagonists. OBJECTIVE: To test the preventive effect of antihistamines and/or leukotriene antagonists on the development of U/AE in patients with a history of NSAID hypersensitivity confirmed by a positive challenge result. METHODS: A single, placebo-controlled, oral challenge using the culprit NSAID was applied to 65 patients with a history of NSAID-induced U/AE. In the case of recurrence of the symptoms, another oral challenge was performed under premedication with antihistamines alone or combined antihistamines and leukotriene antagonists. RESULTS: A total of 59 of 65 patients (90%) tolerated a normal dose of NSAID, confirming previous data on the poor reproducibility of nonallergic hypersensitivity reactions to NSAIDs on challenge. Of the 6 patients who experienced recurrence of the U/AE on NSAID challenge, antihistamines and combined antihistamines and leukotriene antagonists prevented the hypersensitivity reactions in 2 and 3 of them, respectively. Only 1 patient still developed a moderate NSAID-induced urticaria despite the double premedication. CONCLUSION: Treatment with NSAIDs at normal doses is possible and well tolerated in patients who have experienced NSAID-induced U/AE, which could be prevented by the concomitant use of antihistamines and leukotriene antagonists.

The inhibition by levocetirizine and fexofenadine of the histamine-induced wheal and flare response in healthy Caucasian and Japanese volunteers.

This randomized, double-blind, placebo-controlled crossover study compared inhibition by one 5 mg dose of levocetirizine with two 60 mg doses of fexofenadine separated by 12 h of histamine-induced wheal and flare responses in 9 Caucasian and 9 Japanese healthy male volunteers. Levocetirizine was more inhibitory than fexofenadine on wheal, flare and pruritus (p < 0.005). Variability, evaluated from the standard deviation of inhibition, ranged from 14% to 23.2% for levocetirizine and 65.4% to 112.4% for fexofenadine. Levocetirizine had a faster onset of action (30-90 min versus 2 h), shorter time to maximum effect (3-4 versus 3-6 h) and longer duration of action (at least 24 h versus ~12 h) than fexofenadine. The plasma levels of levocetirizine rose more quickly, reached higher levels, were more consistent and decreased slower than those of fexofenadine. There were no clinically significant ethnic differences in responsiveness to the drugs.

Prebiotics in infants for prevention of allergy.

BACKGROUND: Prebiotics (commonly oligosaccharides) added to infant feeds have the potential to prevent sensitisation of infants to dietary allergens. OBJECTIVES: To determine the effect of prebiotic given to infants for the prevention of allergy. SEARCH METHODS: We performed an updated search in August 2012 of the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2012, Issue 8), MEDLINE, EMBASE, conference proceedings, citations, expert informants and clinical trials registries. SELECTION CRITERIA: Randomised and quasi-randomised controlled trials that compared the use of a prebiotic to no prebiotic, or a specific prebiotic compared to a different prebiotic in infants for prevention of allergy. DATA COLLECTION AND ANALYSIS: Assessment of trial quality, data extraction and synthesis of data were performed using the standard methods of The Cochrane Collaboration. MAIN RESULTS: The 2012 update identified 13 studies classified as ongoing or awaiting classification (yet to report allergy outcomes). Forty-three studies were excluded, primarily as no allergy data were reported, although none of these enrolled infants were at high risk of allergy. Four studies enrolling 1428 infants were eligible for inclusion. All studies were at high risk of attrition bias. Allergy outcomes were reported from four months to two years of age.Meta-analysis of two studies (226 infants) found no significant difference in infant asthma although significant heterogeneity was found between studies. Meta-analysis of four studies found a significant reduction in eczema (1218 infants, typical risk ratio 0.68, 95% CI 0.48 to 0.97; typical risk difference -0.04, 95% CI -0.07 to -0.00; number needed to treat to benefit (NNTB) 25, 95% CI 14 to > 100; P = 0.03). No statistically significant heterogeneity was found between studies. One study reported no significant difference in urticaria.No statistically significant subgroup differences were found according to infant risk of allergy or type of infant feed. However, individual studies reported a significant reduction in asthma and eczema from supplementation with a mixture of galacto- and fructo-oligosaccharide (GOS/FOS 9:1 ratio) (8 g/L) in infants at high risk of allergy; and in eczema from supplementation with GOS/FOS (9:1) (6.8 g/L) and acidic oligosacccharide (1.2 g/L) in infants not selected for allergy risk. AUTHORS' CONCLUSIONS: Further research is needed before routine use of prebiotics can be recommended for prevention of allergy in formula fed infants. There is some evidence that a prebiotic supplement added to infant feeds may prevent eczema. It is unclear whether the use of prebiotic should be restricted to infants at high risk of allergy or may have an effect in low risk populations; or whether it may have an effect on other allergic diseases including asthma.

Hypersensitivity to antihistamines.

Antihistamines are the cornerstone of allergy therapy and are not expected to cause hypersensitivity reactions. We describe two cases, one had urticaria to multiple anti-H1-preparations and the other had anaphylaxis to hydroxyzine. We also provide a review of the English literature on reported reactions regarding causative preparations and manifestations. The latter showed a wide range; most commonly urticaria/angioedema, contact dermatitis, anaphylaxis, and fixed drug eruption (FDE). Most reported cases were young to middle age adults, with apparent predilection to female subjects. The onset of reactions varied from a few minutes for anaphylaxis and urticaria/angioedema, several hours for maculopapular rashes, or longer for contact dermatitis and FDE. Almost all antihistamines have been reported as causing reactions; cetirizine was the most common oral preparation followed by its parent drug, hydroxyzine. Doxepin cream was the most commonly implicated topical preparation in causing contact dermatitis. A causal relationship is often difficult to recognize because the reaction may be similar to the disease being treated with that antihistamine preparation. Reactions to one preparation are likely to occur, but not always, to other members of the same class. Diagnosis is based on clinical suspicion and may be verified by challenge testing. Except for patch testing in contact dermatitis or fixed eruption, other tests have not shown optimal reliability. In most cases, challenge testing with multiple preparations would identify one or more preparations that can be tolerated. Although hypersensitivity to antihistamines seems to be very rare, awareness of the problem would reduce its misdiagnosis.

[Urticaria and treatment fails]. / Urtikaria und die Therapie versagt!

According to the guidelines the treatment goal for all types of urticaria is to achieve complete symptom relief. Therefore the available literature for urticaria treatment was reviewed regarding this aim and treatment failure, respectively. Systematic studies are not available. Standard doses of H1-antihistamines are the only approved therapy. Review of the limited data where statements are made about complete alleviation of symptoms shows that standard doses of H1-antihistamines rarely achieve this. Even when the dosage is increased up to four-fold, the failure rate is high. Additional therapy with montelukast, dapsone, and cyclosporine A also often fails to produce complete control. For severe chronic spontaneous urticaria, controlled studies using omalizumab have shown low failure rates over long time periods. It has not been investigated whether up-dosing or reduced injection intervals could further improve this rate. Taken together, the small amount of available data on complete symptom relief in urticaria treatment is astonishing. Moreover, the studies can not be compared due to different inclusion criteria (severity of urticaria, allowed basic treatment) and evaluated parameters. Further controlled studies are vitally needed to achieve the goal of complete symptom relief in urticaria.