Utility and Safety of Skin Tests in Drug Reaction With Eosinophilia and Systemic Symptoms (DRESS): A Systematic Review.

BACKGROUND: Determination of culprit drug in drug reaction with eosinophilia and systemic symptoms (DRESS) is crucial. Skin tests have been used, although it remains unclear how sensitive these are. OBJECTIVE: To determine the value of skin tests in the assessment of drug causality in DRESS. METHODS: A systematic literature search was conducted for publications from 1996 onward of skin tests (skin prick test = SPT, patch test = PT, intradermal test = IDT) performed in clearly defined DRESS cases. Outcomes of testing, drug culpability assessments, and challenge test data were extracted. RESULTS: A total of 17 articles met inclusion criteria. In 290 patients with DRESS, patch testing was most frequent (PT = 97.2% [n = 282], IDT = 12.4% [n = 36], SPT = 3.1% [n = 9]). Positive results were noted in 58.4% (n = 160 of 282) of PTs, 66.5% of IDTs, and 25% of SPTs. When confidence of drug causality was high (n = 73 of 194), testing did not correlate well with clinical suspicion: PTs, 37.6%; IDTs, 36.5%. Direct comparison of skin testing with provocation testing (n = 12) showed 83.3% correlation. Positive IDT results were reported in 8 negative PT cases. CONCLUSIONS: Skin tests, particularly PTs and IDTs, have been reported as tools for diagnosis of causal drugs in DRESS. Heterogeneity in methodology, results analysis, and reporting of cohorts make meta-analysis to determine sensitivity and specificity of published literature impossible and highlight weaknesses in the field. We propose that international collaboration is essential to harmonize the methodology and reporting measures from hypersensitivity testing studies in larger cohorts.

Potential Biomarker Identification by RNA-Seq Analysis in Antibiotic-Related Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS): A Pilot Study.

One of the most severe forms of cutaneous adverse drug reactions is "drug reaction with eosinophilia and systemic symptoms" (DRESS), hence subsequent avoidance of the causal drug is imperative. However, attribution of drug culpability in DRESS is challenging and standard skin allergy tests are not recommended due to patient safety reasons. Whilst incidence of DRESS is relatively low, between 1:1000 and 1:10 000 drug exposures, antibiotics are a commoner cause of DRESS and absence of confirmatory diagnostic test can result in unnecessary avoidance of efficacious treatment. We therefore sought to identify potential biomarkers for development of a diagnostic test in antibiotic-associated DRESS. Peripheral blood mononuclear cells from a "discovery" cohort (n = 5) challenged to causative antibiotic or control were analyzed for transcriptomic profile. A panel of genes was then tested in a validation cohort (n = 6) and compared with tolerant controls and other inflammatory conditions which can clinically mimic DRESS. A scoring system to identify presence of drug hypersensitivity was developed based on gene expression alterations of this panel. The DRESS transcriptomic panel identified antibiotic-DRESS cases in a validation cohort but was not altered in other inflammatory conditions. Machine learning or differential expression selection of a biomarker panel consisting of 6 genes (STAC, GPR183, CD40, CISH, CD4, and CCL8) showed high sensitivity and specificity (100% and 85.7%-100%, respectively) for identification of the culprit drug in these cohorts of antibiotic-associated DRESS. Further work is required to determine whether the same panel can be repeated for larger cohorts, different medications, and other T-cell-mediated drug hypersensitivity reactions.

The Successful Use of a Novel Microwave Device in the Treatment of a Plantar Wart.

Plantar warts, caused by the human papilloma virus (HPV), are a commonly encountered condition presenting in clinic. In adults, an array of various therapies exists, frequently with modest results particularly with plantar lesions. Microwaves have had limited uses for medical purposes. Recently a new portable microwave device has been approved for the treatment of skin lesions. Prior research has demonstrated immuno-stimulatory effects against HPV infection. We report the application of a novel portable medical microwave unit to treat a long-standing plantar wart which had failed to respond to other treatment modalities.

Association between Micronutrient Levels and Chronic Spontaneous Urticaria.

Previous reports have suggested a possible role for vitamin D in the etiology of chronic spontaneous urticaria (CSU); however, little information is available regarding the role of other micronutrients. We, therefore, analyzed vitamin D, vitamin B12, and ferritin levels in CSU patients (n = 282) from a preexisting database at Southampton General Hospital. Data were compared against mean micronutrient levels of the general population of the UK, obtained from the National Diet and Nutrition Survey. Vitamin D levels of CSU patients were found to be higher than those of the general UK population (P = 0.001). B12 levels were lower in patients with CSU (P < 0.001) than in the general population. Ferritin levels were found to be lower in male CSU patients than in the general male population (P = 0.009). This association between low B12 and iron levels and CSU might indicate a causal link, with micronutrient replacement as a potential therapeutic option.

An Observational Study of the Diagnosis and Management of Chronic Urticaria in the UK.

BACKGROUND: Patients with chronic urticaria (CU) in the UK could be referred to health care professionals (HCPs) with diverse specialties using different guidelines. The aims of the present study were to determine which CU guidelines HCPs in the UK use, which tests they use for the diagnosis of CU, and how they manage CU. METHODS: In this UK-wide survey, we designed a questionnaire covering the diagnosis and management of CU based on current guidelines. The link to the questionnaire was sent to the British Society for Allergy and Clinical Immunology (BSACI), the British Association of Dermatologists (BAD), the British Society of Immunology (BSI), and the Food Allergy and Intolerance Specialist Group (FAISG) of the British Dietetic Association (BDA), who distributed the link to their members. RESULTS: The questionnaire was completed by 55 allergists/immunologists, 64 dermatologists, and 43 dietitians. More dermatologists used the BAD guidelines in comparison with allergists and immunologists (93.6 vs. 12.5%; p < 0.001). On the other hand, the BSACI guidelines (83.3 vs. 14.9%; p < 0.001) and the European Academy of Allergy and Clinical Immunology (EAACI)/Global Allergy and Asthma European Network (GA(2)LEN)/European Dermatology Forum (EDF)/World Allergy Organization (WAO) guidelines (2013) (52.1 vs. 10.6%; p < 0.001) were used by more allergists and immunologists compared to dermatologists. Differences were found between allergists/immunologists and dermatologists with regard to guidelines used, investigations performed, preference of first-line antihistamine, and prescription of alternative treatment methods. CONCLUSION: In conclusion, differences in the diagnosis and management of CU between HCPs of diverse specialties were identified, which reflected differences among the guidelines used.

Persistent central memory phenotype of circulating Fel d 1 peptide/DRB1*0101 tetramer-binding CD4+ T cells.

BACKGROUND: Although substantial evidence suggests that T cells are important in the pathogenesis of atopic dermatitis (AD), little is known of the differentiation status of CD4+ T cells specific for common environmental allergens. OBJECTIVE: To determine the frequency, differentiation phenotype, and function of circulating allergen-specific CD4+ T cells in adult individuals with severe persistent AD and controls. METHODS: Using tetrameric complexes of an HLA DRB1*0101 restricted epitope from Fel d 1, the major IgE-reactive component of cat dander, we studied ex vivo and cultured T-cell frequency and phenotype in individuals with AD and healthy controls. Cytokine secretion was measured by ex vivo and cultured IFN-gamma, IL-4, and IL-10 enzyme linked immuno-spot analysis. RESULTS: Ex vivo Fel d 1-specific DRB1*0101-restricted CD4+ T cells express high levels of CCR7, CD62L, CD27, and CD28 and proportionately low levels of tissue-specific homing receptors and TH1 and TH2 cytokine production, placing the cells largely within the central memory subgroup. CONCLUSION: Circulating Fel d 1-specific DRB1*0101-restricted CD4+ T cells maintain central memory capacity, consistent with a potential to contribute to persisting clinical atopic disease. CLINICAL IMPLICATIONS: Persisting central memory characteristics of allergen-specific CD4+ T cells in individuals with AD may contribute to chronic disease.