The Expanding Field of Biologics in the Management of Chronic Urticaria.

Chronic urticaria (CU) is the occurrence of urticaria with or without angioedema for at least 6 weeks. Management has traditionally involved antihistamines as first-line therapy with various alternative therapies for refractory cases. Largely based on the success of biologics for various diseases, this class of drugs has come to the forefront of medical research. The first and only Food and Drug Administration-approved biologic for the management of CU is omalizumab (humanized anti-IgE mAb). In the past decade, a substantial amount of research has been centered on the mechanism of action, efficacy, dosing, and safety of omalizumab. This review will focus on the data surrounding the management of CU with omalizumab, off-label use of other biologics for CU, and biologics currently under investigation for use in CU. We will also discuss management considerations and areas of interest for future research.

Characterization of hypersensitivity reactions reported among Andrographis paniculata users in Thailand using Health Product Vigilance Center (HPVC) database.

BACKGROUND: Andrographis paniculata (andrographis) is one of the herbal products that are widely used for various indications. Hypersensitivity reactions have been reported among subjects receiving Andrographis paniculata in Thailand. Understanding of characteristics of patients, adverse events, and clinical outcomes is essential for ensuring population safety.This study aimed to describe the characteristics of hypersensitivity reactions reported in patients receiving andrographis containing products in Thailand using national pharmacovigilance database. METHODS: Thai Vigibase data from February 2001 to December 2012 involving andrographis products were used. This database includes the reports submitted through the spontaneous reporting system and intensive monitoring programmes. The database contained patient characteristic, adverse events associated with andrographis products, and details on seriousness, causality, and clinical outcomes. Case reports were included for final analysis if they met the inclusion criteria; 1) reports with andrographis being the only suspected cause, 2) reports with terms consistent with the constellation of hypersensitivity reactions, and 3) reports with terms considered critical terms according to WHO criteria. Descriptive statistics were used. RESULTS: A total of 248 case reports of andrographis-associated adverse events were identified. Only 106 case reports specified andrographis herbal product as the only suspected drug and reported at least one term consistent with constellation of hypersensitivity reactions. Most case reports (89%) came from spontaneous reporting system with no previously documented history of drug allergy (88%). Of these, 18 case reports were classified as serious with 16 cases requiring hospitalization. For final assessment, the case reports with terms consistent with constellation of hypersensitivity reactions and critical terms were included. Thirteen case reports met such criteria including anaphylactic shock (n = 5), anaphylactic reaction (n = 4) and angioedema (n = 4). Time to development of symptoms ranged from 5 minutes to 1 day. The doses of andrographis used varied from 352 mg to 1,750 mg. Causality assessment of 13 case reports were certain (n = 3), probable (n = 8) and possible (n = 2). CONCLUSIONS: Our findings suggested that hypersensitivity reactions have been reported among patients receiving Andrographis paniculata. Healthcare professionals should be aware of this potential risk. Further investigation of the causal relationship is needed; meanwhile including hypersensitivity reactions for andrographis product labeling should be considered.

Pollen count and presentation of angiotensin-converting enzyme inhibitor-associated angioedema.

BACKGROUND: The incidence of angiotensin-converting enzyme (ACE) inhibitor-associated angioedema is increased in patients with seasonal allergies. OBJECTIVE: We tested the hypothesis that patients with ACE inhibitor-associated angioedema present during months when pollen counts are increased. METHODS: Cohort analysis examined the month of presentation of ACE inhibitor-associated angioedema and pollen counts in the ambulatory and hospital setting. Patients with ACE inhibitor-associated angioedema were ascertained through (1) an observational study of patients presenting to Vanderbilt University Medical Center, (2) patients presenting to the Marshfield Clinic and participating in the Marshfield Clinic Personalized Medicine Research Project, and (3) patients enrolled in The Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial (ONTARGET). Measurements include date of presentation of ACE inhibitor-associated angioedema, population exposure to ACE inhibitor by date, and local pollen counts by date. RESULTS: At Vanderbilt, the rate of angioedema was significantly associated with tree pollen months (P = .01 from χ(2) test). When separate analyses were conducted in patients with a history of seasonal allergies and patients without, the rate of ACE inhibitor-associated angioedema was increased during tree pollen months only in patients with a history of seasonal allergies (P = .002). In Marshfield, the rate of angioedema was significantly associated with ragweed pollen months (P = .025). In ONTARGET, a positive trend was observed between the ACE inhibitor-associated angioedema rate and grass season, although it was not statistically significant (P = .057). CONCLUSIONS: Patients with ACE inhibitor-associated angioedema are more likely to present with this adverse drug event during months when pollen counts are increased.

Asthma and the prospective risk of anaphylactic shock and other allergy diagnoses in a large integrated health care delivery system.

BACKGROUND: The association between asthma and anaphylaxis remains poorly understood. OBJECTIVE: To ascertain, in a managed care organization in northern California, the association of asthma and asthma severity with future risk of anaphylactic shock and other selected allergy diagnoses. METHODS: Using electronic data and validated algorithms, we assembled a cohort of 526,406 patients who met the criteria for asthma between 1996 and 2006 and a referent cohort (with no utilization for asthma) individually matched on age, sex, and race/ethnicity. In each cohort, 54% of patients were female and 55% were white; their mean (SD) age was 24 (20) years. The main outcome measures were anaphylactic shock (caused by an adverse food reaction, caused by serum, or other/idiopathic), allergic urticaria, anaphylaxis after sting(s), and angioedema. RESULTS: The incidence of anaphylactic shock was 109.0 per 100,000 person-years in the asthma cohort and 19.9 per 100,000 person-years in the referent cohort. After adjustment for age, sex, race/ethnicity, comorbidities, and immunotherapy, asthma was associated with a 5.2-fold (95% confidence interval, 4.7- to 5.6-fold) increased hazard of anaphylactic shock. Asthma was also significantly associated with an increased risk of the 3 selected allergy diagnoses, with hazard ratios of 1.4 to 1.9. A significant trend by severity of asthma was apparent for food-related and other/idiopathic anaphylactic shock and for anaphylaxis after sting(s). CONCLUSIONS: In this insured population, asthma was prospectively associated with increased risk of anaphylactic shock and other allergy diagnoses. However, the effect of asthma severity was not consistent across outcome measures.

Drug-induced urticaria and angioedema: pathomechanisms and frequencies in a developing country and in developed countries.

A careful drug history should be obtained from all patients with acute or chronic urticaria/angioedema, especially in the elderly. Although strictly comparable data are lacking, drug-induced urticaria appears to be more common in developed countries than in Malaysia, at least in a Hospital setting. Culprit drugs include antibiotics, analgesics and contrast media. Pseudoallergic drug-induced urticaria mimicks true allergic urticaria, but without an evident immunological basis, and is at least as common as the allergic type. In Malaysia, and in many other countries compulsory, ingredient labelling of 'traditional' medicines would do much to reduce the frequency of drug-induced urticaria.