Allergo Journal International最新文献

Purpose

Most medications for antihistamine-refractory chronic spontaneous urticaria (CSU) have not been compared head-to-head. This systematic review and network meta-analysis evaluates their relative efficacy and safety.

Methods

Electronic databases were searched until 05 May 2022 for randomized controlled trials investigating systemic medications for antihistamine-refractory CSU. The change in the urticaria activity score over seven days (UAS7) and occurrence of adverse events were compared between treatments using random-effects network meta-analysis models.

Results

In all, 32 studies with 3641 patients receiving 31 different systemic medical interventions were included. Among currently available drugs, omalizumab 300 mg injected every 4 weeks and cyclosporine 3–5 mg/kg daily per os were most effective in reducing the UAS7 with a reduction of −10.45 (95% confidence interval [CI]: −12.35, −8.55) and of −10.40 (95% CI: −19.4, −1.4) compared to placebo. Similar efficacies were shown by the nonapproved agents ligelizumab 72 mg injected every 4 weeks (−11.67, 95% CI: −16.80, −7.15) and fenebrutinib 400 mg daily per os (−9.50, 95% CI: −17.56, −1.44). The odds ratio for the occurrence of an adverse event with placebo as comparator was 1.09 for omalizumab (95% CI: 0.83, 1.42), 2.16 for cyclosporine (95% CI: 0.77, 6.07: GRADE; moderate certainty), 0.89 for ligelizumab (95% CI: 0.47, 1.69), and 2.14 for fenebrutinib (95% CI: 0.62, 7.38) in the mentioned dosages.

Conclusion

Omalizumab 300 mg injected every 4 weeks and cyclosporine 3–5 mg/kg daily per os are the most effective currently available drugs for antihistamine-refractory CSU. Cyclosporine shows a relatively less favorable safety profile.

House dust mite allergens are common triggers for allergic rhinoconjunctivitis and allergic asthma; they can aggravate atopic dermatitis and rarely lead to anaphylactic reactions due to dust mite allergens in food. Typical symptoms are nasal obstruction, sneezing, and irritation, and more often than in pollen allergy, allergic asthma also develops. The symptomatology exists in principle throughout the year with maximum complaints in autumn and winter. Of particular importance are sleep disturbances due to nasal obstruction, which lead to restrictions in the quality of life and performance of affected patients. Sensitization can be proven by skin tests and detection of serum allergen-specific IgE antibodies; proof of allergy is achieved by nasal or conjunctival provocation tests. The diagnosis of local allergic rhinitis can only be made by provocation or by determination of allergen-specific IgE antibodies in nasal secretions. The quality of the allergen extract used is essential for all tests; it must contain the allergens to which a patient is sensitized. The concentration of Der p 23 in house dust mite extracts is particularly critical.

House dust mite extracts for allergen-specific immunotherapy (AIT) require in Germany as other common allergens (pollen from sweet grasses [except maize], birch, alder, hazel; bee and wasp venom) marketing authorisation according to the German Therapy Allergen Ordinance (“Therapieallergene-Verordnung”, [TAV]). Mite allergen extracts that have been approved and also those which are in the approval process are subject to government batch testing. Batch test passing is a prerequisite for marketability. Appropriate quality, efficacy, and safety are prerequisites for the approval of house dust mite extracts. Five HDM allergen extracts from four manufacturers are currently approved in Germany for subcutaneous or sublingual therapy; further extracts are in the approval process. The allergen strength of different products is not comparable; manufacturers use company-specific units to describe the strength. Of the three known major allergens (Group 1 allergens: Der p 1, Der f 1, Group 2 allergens: Der p 2, Der f 2 and Group 23: Der p 23, Der f 23) only Group 1 and Group 2 allergens are usually used to standardize the extracts. Group 23 allergens are localized in the outer membrane of mite faeces, and elution requires special extraction methods. To be efficacious in a single patient an allergen extracts used for AIT must contain all allergen components against which the patient is sensitised. Based on post hoc analyses of large clinical studies, it has been proven for house dust mite tablets that Der p 23 is also contained. In Germany, the Paul Ehrlich Institute is responsible for the approval of therapeutic allergens. For the marketing authorisation information on production procedures, and quality are necessary efficacy and safety (positive benefit risk ratio) of the product must be demonstrated in clinical trials according to the current state of the art.

House dust mites and storage mites have a high allergenic potential and lead to sensitization through the formation of specific IgE antibodies. Due to their preferred residence in houses, they belong to the group of house mites, which are referred to as “domestic mites” in English. Their anatomy and biology account for their amazing adaptability to changing environmental situations (including temperature, humidity, food) and make it understandable that measures to reduce their abundance are usually difficult to implement in practice.

Domestic mites is the term used to describe dust mites and storage mites that prefer to live in houses and to which many people develop sensitization through the formation of specific IgE antibodies due to the high allergenic potency of mite allergens. As a result, mites can trigger allergic diseases of the upper and lower respiratory tract as well as cross-reactions to other allergens. Sensitization to house mites is widespread in the German population. About 11 million adults are sensitized in Germany (15.9%). Men are more frequently affected than women, and sensitizations occur more frequently in large cities and with higher socioeconomic status. Sensitizations are less frequent in old age. They can lead to diagnostic problems as clinically silent sensitizations, which is the case in about 40% of sensitizations.

The path from first symptoms to initiation of allergen-specific immunotherapy (AIT) is too long in our survey, at just under 12 years. Even from diagnosis to AIT, it still takes 8.5 years. The reasons are manifold. The complaints are mostly sneezing (75%), runny and stuffy nose (65 and 63%, respectively), itching of the eyes and nose (59%), but also breathing difficulties (40%). Most of our patients were polysensitized (78%) and had asthma (63%). AIT should be considered earlier in mite allergic patients.