Omalizumab is effective and safe in chronic inducible urticaria (CIndU): Real-world data from a large multi-national UCARE study.

BACKGROUND: Long-term data on the effectiveness and safety of omalizumab for chronic inducible urticaria (CIndU) in large populations are lacking. OBJECTIVE: To evaluate the effectiveness, safety, estimated omalizumab treatment duration and its predictors, as well as differences between CIndU subtypes, in a large long-term CIndU cohort. METHODS: A multinational multicenter study was conducted at 14 specialized urticaria centres (UCAREs), including all CIndU patients ever treated with omalizumab from 2009 until July 2022. Kaplan-Meier survival and regression analyses were performed. RESULTS: Across 234 CIndU patients (55% female; mean age 37 years), 76% (n = 178) had standalone CIndU and 24% (n = 56) had predominant CIndU plus minor CSU, with an observation period up to 13 years. Most CIndU patients (73%, n = 145/200 with available data on response) had complete/good response to omalizumab treatment, without significant differences between CIndU subtypes. Sixty-two (26%) patients discontinued omalizumab; due to well-controlled disease (47%, n = 29), ineffectiveness (34%, n = 21), side effects (3%, n = 2), combination of ineffectiveness and side effects (3%, n = 2) and other reasons (13%, n = 8). The median estimated omalizumab treatment duration exceeded 5 years (54% drug survival at 5 years) and was mostly determined by well-controlled disease. Higher age predicted a lower chance to discontinue omalizumab due to well-controlled disease (HR 0.969, 95%CI 0.945-0.995). CIndU subtype and presence of minor CSU were not related to response and time until omalizumab discontinuation for any reason. CONCLUSION: Omalizumab is highly effective and safe in CIndU patients, with long estimated treatment duration mainly reflecting long disease duration. Our data show omalizumab's high potential as treatment in any subtype of CIndU and support its clinical use for these patients.

Assessment of validity and reliability of Drug Hypersensitivity Quality of Life Questionnaire: The Dutch experience.

SUMMARY: Drug Hypersensitivity Quality of Life Questionnaire (DrHy-Q) is the first questionnaire that captures health related quality of life impact in patients with drug hypersensitivity. The aim of this study was to translate and validate the original Italian 15-item DrHy-Q for use among Dutch-speaking residents. We also compared the DrHy-Q scores obtained across countries. In a prospective cohort study, the Dutch DrHy-Q was completed by 124 patients (65.3% female, age 56.8 ± 14.0) with a confirmed drug hypersensitivity. Median DrHy-Q score was 12 [0-88]. Validity and reliability of the DrHy-Q was confirmed through, 1, confirmatory factor analysis; 2, concurrent validity with a generic health related quality of life questionnaire (RAND-36); 3, internal consistency; and 4, test-retest reliability. A country specific difference in scores was observed.

Drug allergy passport and other documentation for patients with drug hypersensitivity - An ENDA/EAACI Drug Allergy Interest Group Position Paper.

The strongest and best-documented risk factor for drug hypersensitivity (DH) is the history of a previous reaction. Accidental exposures to drugs may lead to severe or even fatal reactions in sensitized patients. Preventable prescription errors are common. They are often due to inadequate medical history or poor risk assessment of recurrence of drug reaction. Proper documentation is essential information for the doctor to make sound therapeutic decision. The European Network on Drug Allergy and Drug Allergy Interest Group of the European Academy of Allergy and Clinical Immunology have formed a task force and developed a drug allergy passport as well as general guidelines of drug allergy documentation. A drug allergy passport, a drug allergy alert card, a certificate, and a discharge letter after medical evaluation are adequate means to document DH in a patient. They are to be handed to the patient who is advised to carry the documentation at all times especially when away from home. A drug allergy passport should at least contain information on the culprit drug(s) including international nonproprietary name, clinical manifestations including severity, diagnostic measures, potential cross-reactivity, alternative drugs to prescribe, and where more detailed information can be obtained from the issuer. It should be given to patients only after full allergy workup. In the future, electronic prescription systems with alert functions will become more common and should include the same information as in paper-based documentation.

Rush immunotherapy for wasp venom allergy seems safe and effective in patients with mastocytosis.

BACKGROUND: Patients with mastocytosis and wasp venom allergy (WA) may benefit from venom immunotherapy (VIT). However, fatal insect sting reactions have been described in mastocytosis patients despite previous immunotherapy. We investigated the safety and efficacy of (rush) VIT in patients with mastocytosis and WA. OBJECTIVE: To investigate the safety and efficacy of (rush) VIT in patients with mastocytosis and WA. METHODS: We describe nine patients with cutaneous mastocytosis and WA who received VIT. Cutaneous mastocytosis was confirmed by histopathology and systemic mastocytosis was diagnosed according to World Health Organization criteria. VIT was given according to a rush protocol. Given the difference in safety and efficacy of VIT in patients with WA and honeybee venom allergy, we reviewed the literature for VIT with the focus on WA patients with mastocytosis and addressed the difference between patients with cutaneous versus systemic mastocytosis. RESULTS: Nine patients had WA and mastocytosis, of whom six had cutaneous mastocytosis, two combined cutaneous and systemic mastocytosis and one systemic mastocytosis. All patients received rush IT with wasp venom. Most patients had only mild local side effects, with no systemic side effects during the course of VIT. One patient had a systemic reaction upon injection on one occasion, during the updosing phase, with dyspnoea and hypotension, but responded well to treatment. Immunotherapy was continued after temporary dose adjustment without problems. Two patients with a previous anaphylactic reaction were re-stung, without any systemic effects. CONCLUSIONS: VIT is safe in cutaneous mastocytosis patients with WA, while caution has to be made in case of systemic mastocytosis. VIT was effective in the patients who were re-stung.

Evaluation of the adult patient with atopic dermatitis.

Atopic dermatitis (AD) is a chronic inflammatory skin disease with a large impact on quality of life of the patients and their families. In most cases, the diagnosis of AD can easily be made based on (family) history and clinical examination. If necessary, a practical set of diagnostic criteria such as the UK diagnostic criteria can be used. During the diagnostic phase, it is important to pay attention to atopic comorbidity, such as allergic airway disease (allergic asthma and/or rhinitis), allergic eye disease (atopic (kerato) conjunctivitis) and immediate-type food allergy. This will not have direct consequences for the treatment of AD, but may be important for the overall well-being of the patient. Psychological factors, such as family circumstances, work/school performance and lifestyle factors should also be explored. Severity scoring using properly validated scoring lists may not be necessary for the diagnosis, however, is recommended for monitoring therapy. Simple scoring systems, such as TIS and IGA are easy to perform in daily practice. Several flare factors in AD, such as exposure to irritants or UV light, can be identified by history and clinical examination: in individual cases, additional diagnostic tests may sometimes be useful to confirm clinical suspicion. There is only limited evidence that allergen exposure to aeroallergens and/or food allergens influences AD severity. Therefore, routine allergen testing is not necessary for diagnosis and treatment of AD. The decision to perform allergen tests mainly depends on atopic comorbidity.

Drug resistance in human melanoma: mechanisms and therapeutic opportunities.

In malignant melanoma chemotherapy is very ineffective. This poor prognosis largely results from resistance to conventional chemotherapy. The cellular mechanisms involved in melanoma chemoresistance have yet to be fully elucidated. The relevance of well analyzed drug-resistance mechanisms such as intra-/extracellular transport, drug-resistance by induction of certain enzyme systems and DNA repair is reviewed. The results of many studies suggest that drug resistance in melanoma is most likely caused by a dysregulation of apoptotic processes. Identification of genes and gene products that are responsible for apoptosis, together with emerging information about the mechanism of action and structures of apoptotic regulatory and effector proteins, has laid a foundation for the discovery of drugs, some of which are now undergoing evaluation in human clinical trails for melanoma treatment. The complexity of the molecular variants involved in signal transduction along apoptotic pathways suggests that the cell may have a variety of possibilities for regulating apoptosis and generating apoptosis deficiency. However, identification of drug resistance mechanisms provides new therapeutic targets to overcome chemoresistance in this and other malignancies.