Eczema exacerbation following herpes zoster infection in an immunocompetent patient: A case report.

This case report highlights a severe eczematous rash manifesting broadly across the scalp, face, and neck of a 54-year-old female following a resolved herpes zoster infection. Notably, such cutaneous reactions post-varicella zoster virus infection, which may present weeks to years after the acute phase, have been documented but remain poorly understood in their pathogenesis. This patient exhibited a blistering rash diagnosed as shingles with overlying cellulitis, initially treated with valacyclovir and cefalexin. Upon returning with a diffuse rash post-treatment, further examination and tests led to a differential diagnosis that most closely aligned with eczema exacerbation with superimposed bacterial infection, confirmed by the presence of methicillin-resistant Staphylococcus aureus. Treatment encompassed intravenous vancomycin, ciprofloxacin eye drops, topical hydrocortisone, betamethasone lotion, and gabapentin, leading to substantial improvement. This case underscores the complexity of diagnosing and managing cutaneous reactions post-varicella zoster virus infection and suggests a multimodal treatment approach may yield favorable outcomes.

Stepwise Incremental Dose Schedule of Sirolimus Is Successfully Tolerated by a Patient With Lymphangioleiomyomatosis Who Was Initially Allergic to mTOR Inhibitors.

Lymphangioleiomyomatosis (LAM) is a rare disease involving the proliferation of LAM cells in the lungs and the axial lymphatic system and mechanistic target of rapamycin (mTOR) inhibitors are the only effective medicines for treating it. Patients suffering from LAM, who are allergic to mTOR inhibitors can be treated by desensitizing them to the medicine. A 39-year-old woman presented with dyspnea caused by chylous pleural effusion, ascites, and retroperitoneal lymphangioleiomyomas. She was diagnosed with LAM based on the presence of LAM cell clusters (LCCs) in chylous pleural effusion and elevated serum vascular endothelial growth factor D (VEGF-D) concentration. She was allergic to cedars and yellowtails. Although she was started on sirolimus for treating LAM, the drug had to be discontinued on day 45 because of the appearance of a skin rash on her trunk. A year later, another oral mTOR inhibitor, everolimus, was initiated but had to be discontinued because of the appearance of cutaneous reactions. Since mTOR inhibitors are the only effective molecular-target medicines for LAM, desensitization to sirolimus was attempted by initiating exposure to sirolimus at a low dose followed by stepwise dose escalation. Eventually, the patient tolerated a dose of 0.5 mg/day of sirolimus, which resulted in a trough concentration of approximately 2 ng/ml in blood, without adverse cutaneous reactions; furthermore, clinically relevant effects were observed as her LAM condition reduced and stabilized. This case study illustrates that mTOR inhibitor therapy for LAM should not be abandoned because of allergic cutaneous reactions. Physicians must find a dose that balances adverse events and therapeutic effects to ensure continued treatment for patients with LAM. Furthermore, the possible mechanisms for mTOR inhibitor-induced cutaneous reactions have been discussed.

Adverse cutaneous reaction to hydroxychloroquine in a patient with anti-SAE-1-positive dermatomyositis and a history of diffuse large B-cell lymphoma.

This case report details the cutaneous findings of a patient with a history of diffuse B-cell lymphoma and SAE-1-positive dermatomyositis who developed an adverse cutaneous reaction after initiation of treatment with hydroxychloroquine. This adds to the sparse literature available detailing the correlation between anti-SAE-1 autoantibodies in dermatomyositis and the unique adverse cutaneous reactions in patients taking hydroxychloroquine. Additionally, our patient developed dermatomyositis years after a diagnosis of lymphoma. This report highlights the utility of the myositis-specific antibody panel to guide diagnosis and management, as well as the potential for developing dermatomyositis years after a lymphoma diagnosis.

Cutaneous lymphoproliferative disorders after COVID-19 vaccination: clinical presentation, histopathology, and outcomes.

Individual reports described lymphoproliferative disorders (LPDs) after COVID-19 vaccination; however, the relationship between cases is unexamined. We aim to determine if there are cases of cutaneous LPDs associated with COVID-19 vaccination and their outcomes. We present a review of world literature, vaccine registries, and two unreported cases of LPDs after COVID-19 vaccination. Review of the medical literature, VAERS, and our two cases reveal predominance of Pfizer-BioNTech vaccine, younger patients, and males. All cases resulted in favorable outcomes. Approximately 84% of cases demonstrated CD30+ positivity in their skin biopsies, suggesting that an antigenic trigger may lead to a type IV adaptive immune response, with clonal expansion of CD30+ T-cells and subsequent oncogenic mutational hits eventuating in transient LPDs. LPDs after COVID-19 vaccination appear in the context of the same vaccines (proportionally to their global market shares), share clinical and pathological findings, and have indolent, self-limited character.

Tools for Etiologic Diagnosis of Drug-Induced Allergic Conditions.

Drug hypersensitivity reactions are a serious concern in clinical practice because they can be severe and result in lifelong sequelae. An accurate diagnosis and identification of the culprit drug is essential to prevent future reactions as well as for the identification of safe treatment alternatives. Nonetheless, the diagnosis can be challenging. In vivo and in vitro tests can be helpful, although none are conclusive; therefore, the tests are not usually performed in isolation but as part of a diagnostic algorithm. In addition, some in vitro tests are only available in research laboratories, and standardization has not been fully accomplished. Collaborating research is needed to improve drug hypersensitivity reaction diagnosis. In this review, we update the current available in vivo and in vitro tools with their pros and cons and propose an algorithm to integrate them into clinical practice.

Cutaneous reactions following COVID-19 vaccination assessed by dermatologists: a single-institutional study in Germany.

BACKGROUND AND OBJECTIVES: Cutaneous reactions following COVID-19 vaccination have been frequently described, whereas larger case series by dermatologists are lacking. This study assesses SARS-CoV-2 vaccination-associated skin reactions, severity, treatment, course, eliciting vaccines, allergy test results and tolerance to revaccination. PATIENTS AND METHODS: Single-institutional, non-interventional study of dermatologists assessing cutaneous manifestations in 83 patients in Germany. RESULTS: 93 reactions were presented. Manifestations clustered into immediate (n = 51, 54.8%) and delayed hypersensitivity reactions (n = 10, 10.8%), chronic inflammatory skin diseases (n = 13, 14.0%), reactivation of latent herpes virus infection (pityriasis rosea/herpes zoster; n = 9; 9.7%) and others (n = 10, 10.8%). Vaccination was associated with new (76.3%) - mostly hypersensitivity reactions - or exacerbation of known skin diseases (23.7%), in this case predominantly chronic inflammatory skin diseases. Reactions occurred primarily within the first week (72.8%) and after first vaccination (62.0%). Treatment was required in 83.9% and hospitalization in 19.4%. In 48.8% revaccination led to recurrence of the same reactions. Disease was ongoing at last consultation in 22.6%, primarily in chronic inflammatory skin diseases. Allergy tests were performed in 15 patients (18.1%) and resulted negative. CONCLUSIONS: It can be assumed that vaccination may trigger immune activation-related reactions especially in those patients predisposed to develop respective skin diseases.

Cutaneous Reactions Following COVID-19 Vaccination: A Review of the Current Literature.

The outbreak of coronavirus disease 2019 (COVID-19) represented a new worldwide challenge, strongly impacting on the global economy, overall health and lifestyle. Since then, several strategies have been adopted to contain the widespread of infection. Among these, vaccination is currently the most important measure to fight against the pandemic. However, several concerns such as slower-than-hoped-for rollout, the hurried approval with limited data, the mechanism of action (in particular mRNA-based), and the uncertain duration of protection they afforded were initially raised. Moreover, even if cutaneous reactions have been rarely reported in clinical trials, global mass vaccination showed several dermatologic reactions not initially recognized, leaving dermatologists to decide how to diagnose and treat them. In this scenario, dermatologists should be ready to promptly recognize these clinical manifestations. Thus, the aim of this manuscript is to review current literature on cutaneous reactions following COVID-19 vaccination, particularly inflammatory dermatological diseases, in order to help clinicians to better understand these dermatological conditions and to provide an extensive overview of all the vaccine-related skin manifestations.

Viruses, Variants, and Vaccines: How COVID-19 Has Changed the Way We Look at Skin.

Purpose of Review: This review aims to evaluate the spectrum of cutaneous reactions after both SARS-CoV-2 infection and COVID-19 vaccination while simultaneously understanding the evolution of the field of dermatology in the face of an ongoing pandemic. Recent Findings: The most commonly reported cutaneous reactions after COVID-19 infection in the literature to date include morbilliform or maculopapular rashes, chilblains, and urticaria. The incidence of cutaneous reactions after COVID-19 vaccination was 9% in larger cohort studies and more commonly occurred after mRNA-based COVID-19 vaccines than adenovirus vector vaccines. The most frequently reported cutaneous reactions after COVID-19 vaccines were delayed large local reactions, local injection site reactions, urticarial eruptions, and morbilliform eruptions. Summary: With the ongoing pandemic, and continued development of new COVID-19 variants and vaccines, the landscape of cutaneous reactions continues to rapidly evolve. Dermatologists have an important role in evaluating skin manifestations of the virus, as well as discussion and promoting COVID-19 vaccination for their patients.

Adverse cutaneous reactions reported post COVID-19 vaccination in Al Buraimi governorate, Sultanate of Oman.

On March 11, 2020, the World Health Organization (WHO) declared the novel coronavirus (COVID-19) a global pandemic. This has led to the rapid development and emergency approval of vaccines to overcome the alarming spread of the virus. Data on the cutaneous side effects related to the COVID-19 vaccine remains limited. In this prospective observational study, which was conducted from June 20 to September 20, 2021, we evaluated the incidence and various patterns of cutaneous side effects reported post COVID-19 vaccination in Al Buraimi Governorate in Oman. All vaccinated individuals aged 12 years and older, who had a skin reaction within 4 weeks following any dose of the COVID-19 vaccine, were enrolled in the study. The demographic data, medical history, vaccine-related information of all the patients were documented and the analysis was performed using the SPSS version 23 software. In total, 67 cutaneous reactions were reported by 55 patients accounting for 0.11% of all vaccinated individuals. The mean age of the patients was 33.3 years, 80.6% were females, 61.2% of the reactions were reported after the first vaccine dose, and 38.8% were reported after the second dose. We observed a wide range of cutaneous reactions and categorized them into three major patterns: local injection site reaction (2%), new onset rash (81.6%), and flare up of pre-existing dermatological conditions (16.4%). Notably, urticaria was the most common reaction overall, followed by generalized pruritus and maculopapular rash. In general, we reported a diversity of cutaneous side effects that healthcare workers should be aware of as some reactions may be overlooked and not linked to the COVID-19 vaccination.

COVID-19 Vaccine Booster-Induced Dermatographism.

The urgent requirement for a preventative vaccination became more pressing due to the severe repercussions that the SARS-CoV-2 (COVID-19) virus had on society and the economy. The deployment of the COVID-19 vaccination program had to be expedited. As with all vaccinations, adverse events have been recorded with the COVID-19 vaccine. Some patients may experience cutaneous reactions such as rashes, itching, hives, and swelling after receiving the COVID-19 vaccine, but it is unclear how common these events are or how frequently they recur. This article discusses an unusual case of a young man who got chronic severe dermatographism after receiving a booster shot of the Moderna vaccine (Moderna, Inc., Cambridge, Massachusetts).

Pharmacovigilance of cutaneous adverse drug reactions in associations with drugs and medical conditions: a retrospective study of hospitalized patients.

BACKGROUND: Cutaneous adverse drug reaction (CADR) is a common problem in clinical medication. This study aimed to investigate the correlation between clinical drug application and CADR occurrence as evidence for preventive strategies and rational clinical drug use. METHODS: We analyzed the characteristics of CADRs of 858 patients admitted to Shandong Provincial Third Hospital from March 2007 to December 2018. The most significant drugs concerning the common skin symptoms and their significance to CADR were investigated by case-non-case and multiple logistic regression analyses. RESULTS: A total of 266 drugs were involved in 858 cases of CADR. Among the ten most relevant medications, primarily antibiotics and herbal injections, and nutritional support drugs, potassium sodium dehydroandrographolide succinate injection, and cefoperazone sodium and sulbactam sodium injection were found to be 2.1 and 1.45 times statistically more prone to CADRs than to other adverse drug reactions (ADRs), respectively. The main route of administration was intravenous (63.16%), with oral administration accounting for 25.19%. There were 747 cases of ADR, 71 of severe ADR, 2 of new and severe ADRs, and 38 cases of new ADR. Overall, 100 cases of CADR exhibited abnormal alanine aminotransferase, aspartate aminotransferase, and serum creatinine levels. The predictive factors for severe CADR occurrence included allergy and smoking histories, cefoperazone sodium, sulbactam sodium injection, levofloxacin lactate and sodium chloride injection. CONCLUSIONS: Drug-induced CADR symptoms are commonly associated with other ARDs, predominantly rashes and pruritus, and are often accompanied by some medical conditions, especially liver and kidney damage. Detailed attention to a patient's primary diseases, allergy history, and drug safety profile could help prevent or reverse CADR in most patients.

Descriptive analysis of adverse drug reaction reports for hypersensitivity reactions stratified in relation to different beta-lactam antibiotics.

ß-lactam antibiotics (BLA) are commonly reported to induce hypersensitivity reactions. However, ß-lactam antibiotic-stratified analyses are rare. In the presented study, ß-lactam antibiotic associated hypersensitivity reactions were analyzed in the European adverse drug reaction (ADR) database. 923, 38, 222, and 99 hypersensitivity reports for penicillins and first-, second- and third-generation cephalosporins were reported. Differences with regard to demographical parameters, seriousness and types of hypersensitivity reactions, as well as in the number of hypersensitivity reports per outpatient prescriptions were observed between the different ß-lactam antibiotics. The number of ADR reports classified as serious was higher for all generations of cephalosporins compared to penicillins. Additionally, anaphylactic reactions were more often reported for first- and second-generation cephalosporins compared to third-generation cephalosporins and penicillins, while bullous reactions were more often reported for first- and third-generation cephalosporins as opposed to second-generation cephalosporins and penicillins. The observed differences may be caused by differences between ß-lactam antibiotics and their routes of administration (oral, intravenous), the patient populations, or the reporting of ADRs. Due to the methodological limitations of ADR database analysis, no conclusions can be drawn whether and to what extent the aforementioned factors influenced our results.

Cutaneous and Allergic reactions due to COVID-19 vaccinations: A review.

INTRODUCTION: The pandemic caused by the novel coronavirus disease 2019 (COVID-19) has had an unprecedented impact on the overall health and the global economy. Vaccination is currently the most dependable strategy to end the pandemic, despite the slower-than-hoped-for rollout, particularly for low-to-middle-income countries, and the uncertain duration of protection afforded by vaccination. The spike protein of the virus (immunodominant antigen of the virus) is the main target of the approved and candidate SARS-CoV-2 vaccines. This protein binds to the ACE2 receptor of the host cell, initiating the entry of the virus into the cell and the chain of subsequent events ending to Acute Respiratory Distress Syndrome. The safety profile of these vaccines needs is closely assessed. METHODS: This comprehensive review includes searching the PubMed, EMBASE, and Web of Science databases using the keywords "coronavirus", "COVID-19", "vaccine", "cutaneous reactions", "allergic reactions", and "SARS-CoV-2". Manual searching of reference lists of included articles augmented the research. The research was updated in June 2021. RESULTS: In this narrative review, we tried to investigate and discuss the cutaneous and allergic reactions related to SARS-CoV-2 vaccines currently available in the literature. As a result, although COVID-19 vaccines can be reported to develop allergic and anaphylactic reactions, especially after m-RNA vaccines, they remain at a low rate, and it is observed that these reactions may develop more frequently, especially in patients with previous allergies and mast cell disorders. Fortunately, these reactions are generally transient, benign, self-limited. CONCLUSION: Although there is still no definitive evidence, as dermatologists, we must be aware of the possibility of cutaneous reactions, newly diagnosed dermatoses, or exacerbation of existing dermatoses that may develop after the COVID-19 vaccinations.

Iodixanol activation of mast cells: Implications in the pathogenesis of iodixanol-induced delayed cutaneous adverse reactions.

Iodinated contrast media (ICM) is widely used in radiological examination and interventional therapy. In the commonly used ICM, iodixanol is considered to be the safer one. However, compared with other ICMs, it has a higher incidence of delayed cutaneous adverse reactions. The underlying mechanisms are unclear. In this study, mice with positive allergic reactions were selected based on the mouse clinical allergy symptom score and skin and blood samples taken 1, 6, 24, 48, and 72 h after ICMs (6 g iodine/kg) injection for histological and blood analyses. ICMs-induced pseudo-allergic reactions were investigated through in vivo intravital vascular imaging and passive cutaneous anaphylaxis (PCA) not mediated by IgE and through, calcium imaging degranulation of mast cells (MCs), and western blot assays in vitro. Results shows iodixanol-induced systemic anaphylaxis caused severe extravasation of plasma proteins and degranulation of skin MCs, and increased levels of plasma histamine, cytokines and inflammatory chemokines. Mechanistically, iodixanol increases degranulation of MCs and promotes the synthesis of inflammatory factors by activating PLC-γ and PI3K-related pathways. Trigonelline inhibit iodixanol-induced MC-related pseudo-allergic reactions in vitro and in vivo. These results suggest that mice in the iodixanol group had a higher incidence of delayed cutaneous reactions, characterized by cytokine release over time and delayed cutaneous MC degranulation. Iodixanol's delayed cutaneous adverse reactions may be due to a delayed phase of MC-related pseudo-allergic reactions. Trigonelline revealed anti-allergic activity in iodixanol-induced MC-related pseudo-allergic reactions.

Cutaneous manifestations of chimeric antigen receptor T-cell therapy: An introduction for dermatologists.

Chimeric antigen receptor T-cell therapy is an emerging immunotherapy with promising efficacy for the treatment of previously refractory or relapsed malignancies. As a personalized medicine approach, T cells are genetically engineered to express a receptor designed to bind a specific tumor antigen, leading to selective immune-mediated destruction of tumor cells. Due to the novelty of chimeric antigen receptor T-cell therapy, the safety profile continues to evolve with limited information currently available on cutaneous adverse events. Improved understanding of the spectrum of cutaneous adverse events may facilitate earlier recognition and appropriate management of these toxicities. To explore this knowledge gap, we discuss the available case reports and clinical trial results of cutaneous reactions associated with chimeric antigen receptor T-cell therapy.

Incidence of Adverse Cutaneous Reactions to Epidermal Growth Factor Receptor Inhibitors in Patients with Non-Small-Cell Lung Cancer.

BACKGROUND: Epidermal growth factor receptor (EGFR) inhibitors are routinely used in advanced non-small-cell lung cancer (NSCLC) harboring EGFR mutations. However, their use is associated with gastrointestinal and cutaneous toxicities, including acneiform eruptions, pruritus, xerosis, nail and hair changes. Aside from reducing patients' quality of life, such cutaneous reactions have a considerable impact on the oncologic treatment given that dose reduction or even drug discontinuation may be necessary, especially for the severe forms. OBJECTIVES: To assess the incidence, impact on treatment and management of EGFR inhibitor-related cutaneous reactions in patients with NSCLC. METHODS: We conducted a prospective observational study on 87 consecutive patients with advanced NSCLC treated with EGFR-tyrosine kinase inhibitors from January to December 2019. Patients who developed mucocutaneous reactions were evaluated and treated by both oncologists and dermatologists, and underwent dermatologic follow-up until resolution of the cutaneous reaction. Demographic and clinical data were collected for each patient, and the severity of the cutaneous reaction was graded using the Common Terminology Criteria for Adverse Events. RESULTS: Seventy-one patients (81.6%) developed cutaneous reactions. The number of cutaneous reactions per patient was 1 in 37%, 2 in 41% and 3 or more in 22%. The most common cutaneous reactions included acneiform eruptions (56.3%), xerosis ± asteatotic eczema (48.3%), nail changes (39.1%), mucositis (29.9%), pruritus (24.1%) and hair changes (12.6%). Afatinib was associated with a higher rate of nail changes and mucositis (p < 0.01 and p < 0.005, respectively) compared to other agents, while no patient-related predictive factors were identified. Dose reduction was performed in 18% of patients. Multidisciplinary management involving dermatologists allowed to resume the drug in all patients who had discontinued it due to the cutaneous reactions. CONCLUSIONS: A multidisciplinary approach to EGFR inhibitor-related cutaneous reactions is advantageous and can reduce the need to discontinue oncologic treatment.