Severe cutaneous adverse reactions.

Severe cutaneous adverse reactions (SCARs), which include Stevens-Johnson syndrome and toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms (also known as drug-induced hypersensitivity syndrome), acute generalized exanthematous pustulosis, and generalized bullous fixed drug eruption, are life-threatening conditions. The pathogenesis of SCARs involves T cell receptors recognizing drug antigens presented by human leukocyte antigens, triggering the activation of distinct T cell subsets. These cells interact with keratinocytes and various immune cells, orchestrating cutaneous lesions and systemic manifestations. Genetic predisposition, impaired drug metabolism, viral reactivation or infections, and heterologous immunity influence SCAR development and clinical presentation. Specific genetic associations with distinct SCAR phenotypes have been identified, leading to the implementation of genetic screening before prescription in various countries to prevent SCARs. Whilst systemic corticosteroids and conventional immunomodulators have been the primary therapeutic agents, evolving strategies, including biologics and small molecules targeting tumour necrosis factor, different cytokines, or Janus kinase signalling pathways, signify a shift towards a precision management paradigm that considers individual clinical presentations.

Genotyping HLA alleles to predict the development of Severe cutaneous adverse drug reactions (SCARs): state-of-the-art.

Introduction: Pharmacogenomics has great potential in reducing drug-induced severe cutaneous adverse drug reactions (SCARs). Pharmacogenomic studies have revealed an association between HLA genes and SCARs including acute generalized exanthematous pustulosis (AGEP), drug reaction with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN).Areas covered: Pharmacogenomics-guided therapy could prevent severe drug hypersensitivity reactions. The US Food and Drug Administration (FDA), Clinical Pharmacogenetics Implementation Consortium (CPIC), and Dutch Pharmacogenetics Working Group (DPWG) provided guidelines in the translation of clinically relevant and evidence-based SCARs pharmacogenomics research into clinical practice. In this review, we intended to summarize the significant HLA alleles associated with SCARs induced by different drugs in different populations. We also summarize the SCARs associated with genetic and non-genetic factors and the cost-effectiveness of screening tests.Expert opinion: The effectiveness of HLA screening on a wider scale in clinical practice requires significant resources, including state-of-the-art laboratory; multidisciplinary team approach and health care provider education and engagement; clinical decision support alert system via electronic medical record (EMR); laboratory standards and quality assurance; evidence of cost-effectiveness; and cost of pharmacogenomics tests and reimbursement.

Cutaneous Manifestations of COVID-19.

Patients with coronavirus disease 2019 (COVID-19) present with multisystem signs and symptoms, including dermatologic manifestations. The recent literature has revealed that dermatologic manifestations of COVID-19 often are early onset and provide helpful cues to a timely diagnosis. We compiled the relevant emerging literature regarding the dermatologic manifestations of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) so that physicians can be aware of the various clinical cutaneous presentations in this time of high incidence of COVID-19.

Sex Differences in the Risk of Cutaneous Adverse Drug Reactions Induced by Antiseizure Medications: A Systematic Review and Meta-analysis.

BACKGROUND: Cutaneous adverse drug reactions (cADRs) are one of the most common, severe, and life-threatening types of adverse reactions following treatment with antiseizure medications (ASMs). Some studies have reported a higher incidence of ASM-induced cADRs in females than in males. OBJECTIVE: This study sought to perform a systematic review, meta-analysis, and meta-regression to compare the ASM cADR risks between females and males. METHODS: We searched the literature using three databases (EMBASE, PubMed, and Web of Science) between October 1998 and November 2018, later updated to October 2019. Studies were included in the meta-analysis if they met the following criteria: (1) observational studies that estimated the incidence of cADRs related to ASMs; (2) provided the risk or odds ratio (OR) for cADRs among female and male patients exposed to ASMs; and (3) provided information on patients' characteristics. We assessed the impact of study characteristics, publication bias, and measures to reduce bias, and performed a DerSimonian and Laird random effects meta-analysis. RESULTS: We included 28 studies in this review. Of these, seven studies were eligible for inclusion in the meta-analysis, involving a total of 223,209 patients. Overall, females were more likely to develop cADRs to ASMs than males (OR 1.76, 95% confidence interval [CI] 1.55-1.99). The largest differences were observed in patients prescribed lamotrigine (OR 2.17, 95% CI 1.53-3.08, p < 0.001) and carbamazepine (OR 1.63, 95% CI 1.02-2.60, p = 0.042). Also, the OR trended higher for phenytoin (OR 2.46, 95% CI 0.79-7.65, p = 0.12), followed by oxcarbazepine (OR 1.91, 95% CI 0.75-4.85, p = 0.18) and sodium valproate (OR 0.60, 95% CI 0.12-2.99, p = 0.53), but the difference did not reach statistical significance. In the remaining 21 studies, 13 reported numerically higher risk of cADRs among females compared to male patients, and in five of these, the difference was statistically significant. CONCLUSION: Our findings confirmed that females are more susceptible to cADRs induced by ASMs than males. More research is needed to understand the pathophysiological mechanisms for this difference. PROTOCOL REGISTRATION: PROSPERO (CRD42018111943).

Systemic Medications of Dermatological Importance in COVID-19.

Early December 2019 witnessed an international outbreak of a novel coronavirus (COVID 19) designated severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2). Since then, a number of therapeutic molecules have been explored to have potential efficacy against the SARS-Cov-2 per se or its sequelae. There are no Food and Drug Administration specific therapies approved so far; however, numerous drugs based on varying levels of evidence, in vitro studies and compassionate drug trials are being established as therapeutic agents, especially drugs approved for previous emergence of the severe acute respiratory syndrome (SARS-CoV-1) and Middle east respiratory syndrome coronavirus (MERS-Cov). Numerous active clinical trials for COVID-19 with more than 150 drugs and products are under study. Needless to say, many dermatological drugs are being employed to mitigate this pandemic threat. We aim to review drugs with potential against SARS-Cov-2 widely used in dermatology practice. Additionally, rampant and overzealous use of these drugs as well as introduction of new molecules might lead to emergence of adverse effects associated with these agents. Dermatologists must be on lookout for any cutaneous adverse effects of these drugs. J Drugs Dermatol. 2020;19(9):889-892. doi:10.36849/JDD.2020.5323.

The use of drug calendars for the diagnosis of cutaneous drug eruptions in the age of electronic medical records.

A morbilliform drug eruption is the most common condition leading to a dermatology consultation for a patient in the hospital. Timing is an important diagnostic tool since the onset of a skin rash usually takes place within days-to-weeks of the start of the implicated drug. A comprehensive, thorough, and reliable drug history by the clinician is essential. Therefore, to assist in the task of determining the causative medication of a new skin rash in a hospitalized patient, the creation of a drug calendar is recommended. The development of an electronic version of the drug calendar offers several benefits over the manual version. As the use of electronic medical records continues to become the standard in medicine, the electronic drug calendar will serve as an invaluable tool for the diagnosis of drug hypersensitivity.

Cutaneous lupus erythematosus induced by drugs - novel insights.

Introduction: There is a growing list of drugs implicated in inducing both subacute and chronic forms of cutaneous lupus erythematosus. It is important to recognize these drugs in order to quickly treat patients with drug induced disease.Areas covered: This paper reviews the current literature describing drugs implicated in causing cutaneous lupus erythematosus. A Pubmed search was used to compile a list of medications implicated up to August 2019. It reviews new classes of drugs identified as causing cutaneous lupus erythematosus, the pathophysiology of the disease process, and current recommendations for treatment of the disease.Expert opinion: Many drugs have been identified as inducing lupus, and many more continue to be described in new reports. Further research is needed to understand this phenomenon, which will aid in the diagnosis and treatment of affected patients.

Acute Management, Diagnosis, and Follow-Up of Suspected Perioperative Hypersensitivity Reactions in Flanders 2001-2018.

BACKGROUND: Despite numerous efforts to describe the clinical manifestations and the epidemiology of perioperative hypersensitivity (POH), there remains room to increase awareness among anesthetists and immunologists/allergists. OBJECTIVE: To report the findings of a 17-year survey of suspected POH in Antwerp, Belgium. METHODS: We analyzed clinical and diagnostic data from 715 patients referred because of a suspected POH reaction, between January 1, 2001, and May 31, 2018. A total of 456 patients demonstrating a POH could be queried about subsequent anesthesia. RESULTS: A total of 608 cases formed the final dataset; 208 had a non-life-threatening reaction and 400 a life-threatening reaction. In life-threatening reactions, hypotension was predominating. In the non-life-threatening reactions, 83.9% of the patients displayed cutaneous manifestations. In life-threatening reactions, intravenous adrenaline and fluids were administered in 75.7% and 31%, respectively, and 41.3% had their intervention abandoned. Mast cell activation (MCA) was mainly, but not exclusively, observed in severe grades but did not predict the mechanistic process nor the culprit. A cause was identified in 77.8% of severe and 48.6% of milder cases. Main culprits were neuromuscular blocking agents, latex, cefazolin, and dyes. A total of 156 cases had uneventful anesthesia, except 1 patient who was inadvertently re-exposed to hidden chlorhexidine. CONCLUSIONS: This study highlights that there is room for an improved acute management and an optimized diagnostic workup that should not be restricted to patients with severe reactions and/or showing MCA.

Clinical and Laboratory Characteristics of an Acute Chikungunya Outbreak in Bangladesh in 2017.

From April to September 2017, Bangladesh experienced a huge outbreak of acute Chikungunya virus infection in Dhaka. This series describes the clinical and laboratory features of a large number of cases (690; 399 confirmed and 291 probable) suffered during that period. This observational study was carried out at Dhaka Medical College Hospital, Bangladesh. The median age of the patients at presentation was 38 years (IQR 30-50) with a male (57.3%) predominance. Hypertension and diabetes were the most common comorbidities. The mean (±SD) duration of fever was 3.7 (±1.4) days. Other common manifestations were arthralgia (99.2%), maculopapular rash (50.2%), morning stiffness (49.7%), joint swelling (48.5%), and headache (37.6%). Cases were confirmed by anti-chikungunya IgG (173; 43.3%), IgM (165; 42.3%), and reverse transcription polymerase chain reaction (44; 11.0%). Important laboratory findings include high erythrocyte sedimentation rate (156; 22.6%), raised serum glutamic pyruvic transaminase (73; 10.5%), random blood sugar (54; 7.8%), leukopenia (72; 10.4%), thrombocytopenia (41; 5.9%), and others. The oligo-articular (453; 66.1%) variety of joint involvement was significantly more common compared with the poly-articular (237; 34.5%) variety. Commonly involved joints were the wrist (371; 54.1%), small joints of the hand (321; 46.8%), ankle (251; 36.6%), knee (240; 35.0%), and elbow (228; 33.2%). Eleven cases were found to be complicated with neurological involvement and two of them died. Another patient died due to myocarditis. Public health experts, clinicians, and policymakers could use the results of this study to construct the future strategy tackling chikungunya in Bangladesh and other epidemic countries.

Efficacy of acupressure to prevent adverse reactions to anti-tuberculosis drugs: Randomized controlled trials.

AIM: To determine whether acupressure can prevent or relieve the adverse drug reactions (ADRs) of anti-tuberculosis drugs. BACKGROUND: People receiving drug treatment for TB often experience ADRs that may cause them to stop taking their medication. Acupressure is a form of traditional Chinese medicine that can be applied to alleviate or prevent disease symptoms. DESIGN: A double-blinded, repeated-measures clinical trial in hospitals in Taiwan was carried out from April 2015 - May 2017. METHODS: Convenience sampling was used to select 32 people (15 for the experimental group and 17 for the control group) aged >20 years who were taking anti-tuberculosis drugs. The people were randomized to receive 4-week of true acupressure and 4-weeks of sham acupressure. Acupressure therapy was given by a researcher in all cases. Both groups received treatment once per day on weekdays, with 15 min for each acupressure session. Outcomes (gastrointestinal irritation and adverse skin reactions) were assessed according to the people feedback and the physicians' recordings during the treatment course, and during monthly follow-up visits for 6 months thereafter. RESULTS: Both groups typically experienced gastrointestinal irritation and adverse skin reactions within 2 months of beginning anti-tuberculosis drug treatment. The 4-weeks intervention involving relevant acupressure points successfully relieved both types of side effects in both immediate and delayed manner. CONCLUSIONS: When correctly implemented, acupressure can prevent and relieve the ADRs of anti-tuberculosis drugs, and motivate people to complete their treatment course.

Cutaneous Adverse Drug Reactions: How to Identify the Trigger. / Reacciones cutáneas adversas a medicamentos: cómo identificar el desencadenante.

It is estimated that 10% to 15% of medicated patients develop adverse drug reactions (ADR). Despite the high prevalence of ADR, the identification of the trigger drugs remains a medical challenge, mainly in polymedicated patients. Our goal is to update the diagnostic tools to identify enhancer drugs of type B-ADR that compromise the skin and /or mucous membranes, in order to optimize patients' follow-up and improve their quality of life. We develop the review in two stages: I- we review the pathophysiological mechanisms of the ADR; II- we developed the clinical approach for the identification of the triggering drug.