Contact allergens for the allergist.

OBJECTIVE: The objective of this article is to provide an overview and describe typically encountered skin contact allergens implicated in allergic contact dermatitis (ACD). DATA SOURCES: Published literature obtained through textbooks, online PubMed, and Google Scholar database searches, author photography, and adapted figures were used. STUDY SELECTIONS: Studies on the evaluation of ACD and specific skin contact allergens were selected, with a focus on original research articles and clinical reviews. RESULTS: Major classifications of common contact allergens include the following: (1) fragrances, (2) preservatives, (3) excipients, (4) rubber chemicals, (5) textile dyes, (6) topical medications, and (6) metals and other biomedical device components. The dermatitis distribution can aid in identifying the suspected contact allergen culprit. Certain contact allergens have features that are important to consider in the patch testing (PT) interpretation; these include possible irritant reactions, false-negative reactions or missed detection, and delayed reactions. Fragrances, preservatives, and excipients are culprits in personal products and facial or neck dermatitis. Patch testing with fragrances, preservatives, and patient-supplied products requires careful interpretation. Hand or foot dermatitis may be attributed to rubber chemicals or textile dyes. The management of topical corticosteroid contact allergy is guided on the basis of structural group classifications. Metal sensitization has been associated with dermatitis or biomedical device complications. CONCLUSION: Each skin contact allergen has unique characteristics with regard to the dermatitis clinical presentation and potential PT nuances. These features are critical to recognize in the evaluation of ACD and PT interpretation and clinical relevance, leading to an accurate diagnosis.

Capturing total steroid burden in patients with atopic dermatitis and asthma.

Background: The cumulative burden of cutaneous, inhaled, intranasal and systemic corticosteroids (CS) in individual patients should be routinely assessed. Methods: Our monitoring tool collected data on CS type, potency, frequency, side effects, interventions and patient counseling in every encounter. Results: 82 AD patients had 151 encounters. Severe AD had more side effects than those without (68.18% vs 41.67% respectively, P < 0.0333). Those with higher TSB had more side effects overall (p < 0.0493). There was also significant positive correlation with higher TSB and the overall number of side effects (p < 0.0116). 101 asthmatics had 193 encounters. Over 50% of asthma patients had other CS. Severe asthmatics had more side effects than those without (62.5% vs 20.8%, p < 0.0001). Patients with higher TSB had more side effects overall (p < 0.0001). There was also significant positive correlation with a higher TSB and the overall number of side effects (p < 0.0001). 80% of AD and 90% of asthma patients were satisfied with the counseling. The EHR in AD and asthma resulted in counseling in 89% and 93% respectively and real-time intervention in 27.8% and 3% respectively. Although patients with side effects had more dose adjustments, those without side effects also warranted adjustments. Physician surveys demonstrated improved satisfaction with the EHR tool over time, and minimal impact on visit time. Conclusion: The utilization of our EHR monitoring tool allows for the identification and tracking of TSB in patients, associated side effects and leads to real-time physician intervention.

Cutaneous Manifestations in Adult Patients with COVID-19 and Dermatologic Conditions Related to the COVID-19 Pandemic in Health Care Workers.

PURPOSE OF REVIEW: COVID-19 (coronavirus viral disease 2019), due to the novel SARS-CoV-2, may present with different types of cutaneous manifestations of varying pathophysiology. During the ongoing pandemic, publications reporting dermatologic findings in COVID-19 continue to emerge. RECENT FINDINGS: Cutaneous vasculopathy and microthrombus-related changes including acral and sacral lesions, retiform purpura, livedo reticularis, and cutaneous vasculitis are notable findings in adult patients. Other exanthems include urticaria or angioedema, morbilliform/maculopapular exanthems, erythema multiforme, and vesicular eruptions. Increased recognition of these findings, especially those consistent with cutaneous microthrombi or vasculitis, is of particular importance. Additionally, occupational dermatologic disease related to extended personal protective equipment (PPE) use, such as skin damage and irritant or allergic contact dermatitis (ACD), represents another emerging problem amidst the pandemic. In this review, we highlight the various cutaneous manifestations associated with COVID-19 in adult patients and occupational dermatitis in health care workers (HCWs) caring for this patient population.

Utilization of high-fidelity simulation for medical student and resident education of allergic-immunologic emergencies.

BACKGROUND: The advantages of clinical simulation used in medical education include the acquisition of clinical skills in a controlled setting, promoting a multidisciplinary approach to patient care, and a high degree of learner satisfaction. OBJECTIVE: We aimed to identify knowledge gaps among Internal Medicine residents and students in the diagnosis and treatment of anaphylaxis and angiotensin-converting enzyme (ACE)-inhibitor-induced angioedema through their participation in a simulation course. METHODS: We conducted a cohort study involving clinical simulations with a high-fidelity, patient-simulator. The cases (antibiotic-induced anaphylaxis and ACE-inhibitor-induced angioedema) were standardized and algorithmic. Participants completed a pre- and post- simulation knowledge assessment and course evaluation. A follow-up knowledge survey was sent out 6 to 12 months after the course completion. RESULTS: Twelve groups comprising 45 medical students and residents completed the anaphylaxis course. All groups diagnosed anaphylaxis after more than 2-organ-system involvement had manifested, and half of the groups made the diagnosis after the patient-simulator was in anaphylactic shock. Half gave an incorrect dose of epinephrine, and most of the participants were inexperienced in epinephrine auto-injector (EAI) administration. Eight groups comprising 27 participants completed the ACE-inhibitor-angioedema course. Six of the groups correctly diagnosed the patient-simulator, but multiple incorrect treatments were given, and only 1 group successfully intubated the patient-simulator. Knowledge improved immediately after the simulation, and knowledge specific to EAI treatment seemed to be retained long-term. All participants agreed that the simulation was practical to their education. CONCLUSION: Clinical simulation improves knowledge on the diagnosis and treatment of anaphylaxis and ACE-inhibitor-induced angioedema. We advocate that clinical simulation be incorporated at institutions with appropriate capabilities.

Skin testing and drug challenge outcomes in antibiotic-allergic patients with immediate-type hypersensitivity.

BACKGROUND: The evaluation of antibiotic immediate-type hypersensitivity is intricate because of nonstandardized skin testing and challenge method variability. OBJECTIVE: To determine the safety outcomes and risk factors for antibiotic challenge reactions in patients reporting a history of antibiotic immediate-type hypersensitivity. METHODS: A 5-year retrospective review of patients evaluated for immediate-type antibiotic allergy was conducted. Data analyzed included patient demographics, index reaction details, and outcomes of skin testing and challenges, classified as single-step or multistep. RESULTS: Antibiotic hypersensitivity history was identified in 211 patients: 78% to penicillins, 10% to fluoroquinolones, 7.6% to cephalosporins, and 3.8% to carbapenems. In total, 179 patients completed the challenges (median age 67 years, range 50-76 years, 56% women), and compared with nonchallenged patients, they reported nonanaphylactic (P < .001) and remote index (P = .003) reactions. Sixteen patients (8.9%) experienced challenge reactions (5 of 28 for single-step challenge, 11 of 151 for multistep challenge), and 11 of these patients had negative skin testing results before the challenge. Challenge-reactive patients were significantly younger (P = .007), more often women (P = .036), and had additional reported antibiotic allergies (P = .005). No correlation was detected between the reported index and observed challenge reaction severities (κ = -0.05, 95% confidence interval -0.34 to 0.24). Anaphylactic rates were similar during single-step and multistep challenges (3.6% vs 3.3%). CONCLUSION: In the present population, younger women with multiple reported antibiotic allergies were at greatest risk for challenge reactions. Negative skin testing results did not exclude reactions, and index severity was not predictive of challenge outcome. The multistep and full-dose methods demonstrated a comparable reaction risk for anaphylaxis.

Sequential Amyloid-ß Degradation by the Matrix Metalloproteases MMP-2 and MMP-9.

Matrix metalloproteases (MMPs) MMP-2 and MMP-9 have been implicated in the physiological catabolism of Alzheimer's amyloid-ß (Aß). Conversely, their association with vascular amyloid deposits, blood-brain barrier disruption, and hemorrhagic transformations after ischemic stroke also highlights their involvement in pathological processes. To better understand this dichotomy, recombinant human (rh) MMP-2 and MMP-9 were incubated with Aß40 and Aß42, and the resulting proteolytic fragments were assessed via immunoprecipitation and quantitative mass spectrometry. Both MMPs generated Aß fragments truncated only at the C terminus, ending at positions 34, 30, and 16. Using deuterated homologues as internal standards, we observed limited and relatively slow degradation of Aß42 by rhMMP-2, although the enzyme cleaved >80% of Aß40 during the 1st h of incubation. rhMMP-9 was significantly less effective, particularly in degrading Aß(1-42), although the targeted peptide bonds were identical. Using Aß(1-34) and Aß(1-30), we demonstrated that these peptides are also substrates for both MMPs, cleaving Aß(1-34) to produce Aß(1-30) first and Aß(1-16) subsequently. Consistent with the kinetics observed with full-length Aß, rhMMP-9 degraded only a minute fraction of Aß(1-34) and was even less effective in producing Aß(1-16). Further degradation of Aß(1-16) by either MMP-2 or MMP-9 was not observed even after prolonged incubation times. Notably, all MMP-generated C-terminally truncated Aß fragments were highly soluble and did not exhibit fibrillogenic properties or induce cytotoxicity in human cerebral microvascular endothelial or neuronal cells supporting the notion that these truncated Aß species are associated with clearance mechanisms rather than being key elements in the fibrillogenesis process.

Matrix metalloproteinase 2 (MMP-2) degrades soluble vasculotropic amyloid-beta E22Q and L34V mutants, delaying their toxicity for human brain microvascular endothelial cells.

Patients carrying mutations within the amyloid-beta (Abeta) sequence develop severe early-onset cerebral amyloid angiopathy with some of the related variants manifesting primarily with hemorrhagic phenotypes. Matrix metalloproteases (MMPs) are typically associated with blood brain barrier disruption and hemorrhagic transformations after ischemic stroke. However, their contribution to cerebral amyloid angiopathy-related hemorrhage remains unclear. Human brain endothelial cells challenged with Abeta synthetic homologues containing mutations known to be associated in vivo with hemorrhagic manifestations (AbetaE22Q and AbetaL34V) showed enhanced production and activation of MMP-2, evaluated via Multiplex MMP antibody arrays, gel zymography, and Western blot, which in turn proteolytically cleaved in situ the Abeta peptides. Immunoprecipitation followed by mass spectrometry analysis highlighted the generation of specific C-terminal proteolytic fragments, in particular the accumulation of Abeta-(1-16), a result validated in vitro with recombinant MMP-2 and quantitatively evaluated using deuterium-labeled internal standards. Silencing MMP-2 gene expression resulted in reduced Abeta degradation and enhanced apoptosis. Secretion and activation of MMP-2 as well as susceptibility of the Abeta peptides to MMP-2 degradation were dependent on the peptide conformation, with fibrillar elements of AbetaE22Q exhibiting negligible effects. Our results indicate that MMP-2 release and activation differentially degrades Abeta species, delaying their toxicity for endothelial cells. However, taking into consideration MMP ability to degrade basement membrane components, these protective effects might also undesirably compromise blood brain barrier integrity and precipitate a hemorrhagic phenotype.