Delayed Localized Hypersensitivity Reactions to the Moderna COVID-19 Vaccine: A Case Series.

Importance: In response to the coronavirus disease 2019 (COVID-19) pandemic, 2 mRNA vaccines (Pfizer-BioNTech and Moderna) received emergency use authorization from the US Food and Drug Administration in December 2020. Some patients in the US have developed delayed localized cutaneous vaccine reactions that have been dubbed "COVID arm." Objective: To describe the course of localized cutaneous injection-site reactions to the Moderna COVID-19 vaccine, subsequent reactions to the second vaccine dose, and to characterize the findings of histopathologic examination of the reaction. Design, Setting, and Participants: This retrospective case series study was performed at Yale New Haven Hospital, a tertiary medical center in New Haven, Connecticut, with 16 patients referred with localized cutaneous injection-site reactions from January 20 through February 12, 2021. Main Outcomes and Measures: We collected each patient's demographic information, a brief relevant medical history, clinical course, and treatment (if any); and considered the findings of a histopathologic examination of 1 skin biopsy specimen. Results: Of 16 patients (median [range] age, 38 [25-89] years; 13 [81%] women), 14 patients self-identified as White and 2 as Asian. The delayed localized cutaneous reactions developed in a median (range) of 7 (2-12) days after receiving the Moderna COVID-19 vaccine. These reactions occurred at or near the injection site and were described as pruritic, painful, and edematous pink plaques. None of the participants had received the Pfizer-BioNTech vaccine. Results of a skin biopsy specimen demonstrated a mild predominantly perivascular mixed infiltrate with lymphocytes and eosinophils, consistent with a dermal hypersensitivity reaction. Of participants who had a reaction to first vaccine dose (15 of 16 patients), most (11 patients) developed a similar localized injection-site reaction to the second vaccine dose; most (10 patients) also developed the second reaction sooner as compared with the first-dose reaction. Conclusions and Relevance: Clinical and histopathologic findings of this case series study indicate that the localized injection-site reactions to the Moderna COVID-19 vaccine are a delayed hypersensitivity reaction. These reactions may occur sooner after the second dose, but they are self-limited and not associated with serious vaccine adverse effects. In contrast to immediate hypersensitivity reactions (eg, anaphylaxis, urticaria), these delayed reactions (dubbed "COVID arm") are not a contraindication to subsequent vaccination.

Utilization, cost, and provider trends in patch testing among Medicare beneficiaries in the United States from 2012 to 2017.

BACKGROUND: Patch testing is the best diagnostic test for allergic contact dermatitis. However, there is presently a lack of data on the test's geographic availability and the characteristics of the providers offering this test across the United States. OBJECTIVE: To evaluate the geographic variation in the availability of patch testing for the Medicare population and to characterize the temporal trends of patch testing cost, use, and provider specialty from 2012 to 2017. METHODS: Retrospective cohort study of the Medicare Provider Utilization and Payment Data from 2012 to 2017. RESULTS: As of 2017, patch testing was available in 20.3% of metropolitan counties and in 1.1% of nonmetropolitan counties. From 2012 to 2017 in metropolitan regions, the number of beneficiaries tested by dermatologists grew by an average annual growth rate of 1.84%, whereas those tested by allergists grew by an average annual growth rate of 20.31%. Most providers that averaged use of 80 or more patches per beneficiary were dermatologists (76.3%). LIMITATIONS: Analysis was restricted to Medicare Part B claims; data were unavailable on individuals with commercial insurance. CONCLUSIONS: Most of the increase in patch testing utilization from 2012 to 2017 has been in metropolitan regions. Although growth was especially prominent among allergists in metropolitan counties, the majority of providers performing comprehensive patch testing were dermatologists.

Hand hygiene during COVID-19: Recommendations from the American Contact Dermatitis Society.

The recent COVID-19 pandemic has resulted in increased hand hygiene and hand cleansing awareness. To prevent virus transmission, the Centers for Disease Control and Prevention recommends frequent hand washing with soap and water. Hand hygiene products are available in a variety of forms, and while each of these formulations may be effective against COVID-19, they may also alter skin barrier integrity and function. As health care workers and the general population focus on stringent hand hygiene, the American Contact Dermatitis Society anticipates an increase in both irritant contact and allergic contact hand dermatitis. Alcohol-based hand sanitizers with moisturizers have the least sensitizing and irritancy potential when compared to soaps and synthetic detergents. This article provides an overview of the most frequently used hand hygiene products and their associations with contact dermatitis as well as recommendations from the American Contact Dermatitis Society on how to treat and prevent further dermatitis.

Relative Prevalence of Contact Allergens in North America in 2018.

BACKGROUND: The American Contact Dermatitis Society Contact Allergen Management Program (CAMP) database was developed to provide patients with safe alternative products free of selected contact allergens. However, the CAMP database also records valuable information including the frequency of contact allergen searches for patients. OBJECTIVES: The aim of the study was to determine the relative prevalence of contact allergens in North America. METHODS: Data from the CAMP database were analyzed from January 1, 2018, to January 1, 2019. The number of searches performed for each specific allergen served as a measure of the relative prevalence for each contact allergen. Results were then stratified by age, sex, atopic history, and patch screening tray used. RESULTS: The 2018 CAMP data show that many of the prevalent allergens are not currently on any contact allergy screening series. These data strongly indicate that testing only to an 80-item screening series will not provide adequate care for many patients with contact allergy. The most prevalent contact allergens seen were fragrance mix, nickel, balsam of Peru, methylchloroisothiazolinone/methylisothiazolinone, and cobalt. Some important differences are seen when stratifying CAMP data by age, sex, atopic history, and patch screening tray used. LIMITATIONS: Possible sources of data error exist because of lack of uniformity of patch test practices. CONCLUSIONS: The CAMP database can be used to determine the relative prevalence of contact allergens, to help develop North American core screening patch test series, and to document the medical necessity of more comprehensive patch testing for patients with recalcitrant contact allergy.

Patch Testing for Evaluation of Hypersensitivity to Implanted Metal Devices: A Perspective From the American Contact Dermatitis Society.

The American Contact Dermatitis Society recognizes the interest in the evaluation and management of metal hypersensitivity reactions. Given the paucity of robust evidence with which to guide our practices, we provide reasonable evidence and expert opinion-based guidelines for clinicians with regard to metal hypersensitivity reaction testing and patient management. Routine preoperative evaluation in individuals with no history of adverse cutaneous reactions to metals or history of previous implant-related adverse events is not necessary. Patients with a clear self-reported history of metal reactions should be evaluated by patch testing before device implant. Patch testing is only 1 element in the assessment of causation in those with postimplantation morbidity. Metal exposure from the implanted device can cause sensitization, but a positive metal test does not prove symptom causality. The decision to replace an implanted device must include an assessment of all clinical factors and a thorough risk-benefit analysis by the treating physician(s) and patient.

A Pragmatic Approach to Patch Testing Atopic Dermatitis Patients: Clinical Recommendations Based on Expert Consensus Opinion.

Allergic contact dermatitis (ACD) may complicate the clinical course of atopic dermatitis (AD), and patch testing remains the criterion standard for diagnosing ACD. To date, there have been no guidelines or consensus recommendations on when and how to patch test individuals with AD. Failure to patch test when appropriate may result in overlooking an important and potentially curable complicating comorbidity. In this article, we present consensus recommendations regarding when to perform patch testing in the AD patient, best practices, and common pitfalls. Patch testing should be considered in AD patients with dermatitis that fails to improve with topical therapy; with atypical/changing distribution of dermatitis, or pattern suggestive of ACD; with therapy-resistant hand eczema in the working population; with adult- or adolescent-onset AD; and/or before initiating systemic immunosuppressants for the treatment of dermatitis. A suggested patch testing algorithm for AD patients is provided.

Congenital nevi versus metastatic melanoma in a newborn to a mother with malignant melanoma - diagnosis supported by sex chromosome analysis and Imaging Mass Spectrometry.

A 37-year-old pregnant woman presented with a 2-cm irregular reddish nodule on her left upper arm during pregnancy. A biopsy from the lesion showed a 2.2-mm thick malignant melanoma with intravascular invasion, 25 mitosis/mm(2) and no ulceration. Following induction of labor, the patient underwent re-excision with sentinel lymph node biopsy. This showed no residual melanoma and no lymph node metastasis. The newborn boy had multiple pigmented lesions on the trunk, some of which were large and irregular. Two were biopsied and histologic examination showed dense dermal proliferation of medium sized melanocytes with multiple mitotic figures and no maturation with their descent into the dermis, raising suspicion of transplacental metastases. Examination of the placenta failed to show metastatic lesions. Multiplex polymerase chain reaction (PCR)-based genotyping, including testing for amelogenin locus for sex chromosome determination, demonstrated the presence of Y chromosome material in the melanocytes of the newborn's lesions excluding maternal origin. A diagnosis of congenital nevi was rendered. Subsequently, Imaging Mass Spectrometric analysis of the mother's lesion showed proteomic signature expression indicative of malignant melanoma, whereas the two lesions in the newborn showed changes indicative of nevi. This case demonstrates the utility of genotyping and Mass Spectrometry analysis in this challenging clinical scenario.

Allergic Contact Dermatitis to Benzoyl Peroxide Resembling Impetigo.

A 17-year-old boy presented with recurring severe dermatitis of the face of 5-months duration that resembled impetigo. He had been treated with several courses of antibiotics without improvement. Biopsy showed changes consistent with allergic contact dermatitis and patch testing later revealed sensitization to benzoyl peroxide, which the patient had been using for the treatment of acne vulgaris.

Cross-comparison of patch test and lymphocyte proliferation responses in patients with a history of acute generalized exanthematous pustulosis.

An adverse cutaneous reaction to a systemically administered drug may rarely manifest as acute generalized exanthematous pustulosis (AGEP). Several recent reports have documented positive patch test results in patients with a history of AGEP, while two have demonstrated drug-specific in vitro lymphocyte proliferative responses. These findings suggest that drug-specific T cells mediate AGEP. We describe two patients with a history of AGEP who each demonstrated positive patch test results specific for the inciting drug: Patient #1 to the antibiotic metronidazole, and Patient #2 to the calcium channel-blocker diltiazem. Histologic examination of biopsy specimens taken from the patch test sites of these patients revealed spongiotic dermatitis and perivascular lymphocytes consistent with a delayed-type hypersensitivity reaction, rather than demonstrating subcorneal neutrophilic pustules more typical of AGEP. In vitro testing by measuring peripheral T cell proliferative responses to chemically purified drug correlated with the clinical response. In a direct cross-comparison, patch test results were shown to correlate with in vitro lymphocyte proliferative responses in two patients with a history of AGEP to different drugs. These findings provide additional evidence that the pathogenesis of AGEP involves a T cell-mediated immune response.

Patch testing for corticosteroid allergy.

During the 1990s, contact allergy to topical corticosteroids became a well-recognized complication of dermatologic therapy. Groups of related corticosteroids were subsequently identified on the basis of their chemical structures, and some investigators have found these helpful in identifying potential cross-reactions. The widespread use of hydrocortisone as an over-the-counter medication and its addition to a wide array of topical products make hydrocortisone the most common allergen. Awareness of the risk of corticosteroid allergy and the availability of newer topical immunomodulating agents such as tacrolimus and pimecrolimus may eventually reduce the incidence of contact allergy to corticosteroids. Rokea el-Azhary, MD, PhD, Professor of Dermatology at the Mayo Clinic in Rochester, MN; Erin Warshaw, MD, Associate Professor of Dermatology at the University of Minnesota, Veterans Affairs Medical Center; and Kalman L. Watsky, MD, Associate Clinical Professor, Department of Dermatology, Yale University School of Medicine, and Section Chief of Dermatology, Hospital of Saint Raphael, were invited to give their opinions on strategies for detecting allergens and recommending allergen substitution for patients with suspected topical corticosteroid allergy.