Cutaneous Adverse Drug Reactions Research Articles

An association study of HLA with levofloxacin-induced severe cutaneous adverse drug reactions in Han Chinese

Levofloxacin-induced severe cutaneous adverse drug reactions (LEV-SCARs) remain unexplored. An association study of human leukocyte antigen (HLA) alleles with LEV-SCARs among 12 patients, 806 healthy subjects, and 100 levofloxacin-tolerant individuals was performed. The carrier frequencies of HLA-B∗13:01 (odds ratio [OR]: 4.50; 95% confidence interval [CI]: 1.15-17.65; p= 0.043), HLA-B∗13:02 (OR: 6.14; 95% CI: 1.73-21.76; p= 0.0072), and serotype B13 (OR: 17.73; 95% CI: 3.61-86.95; p= 4.85×10-5) in patients with LEV-SCARs were significantly higher than those of levofloxacin-tolerant individuals. Molecular docking analysis suggested that levofloxacin formed more stable binding models with HLA-B∗13:01 and HLA-B∗13:02 than with non-risk HLA-B∗46:01. Mass spectrometry revealed that nonapeptides bound to HLA-B∗13:02 shifted at several positions after exposure to levofloxacin. Prospective screening for serotype B13 (sensitivity: 83%, specificity: 78%) and alternative drug treatment for carriers may significantly decrease the incidence of LEV-SCARs.

Carbamazepine-Induced Severe Cutaneous Adverse Drug Reactions: A 21-Year Comparison Between Children and Adults in Malaysia.

Severe cutaneous adverse drug reactions (SCARs) are a life-threatening condition. We aimed to identify all carbamazepine-induced SCARs voluntarily reported to the Malaysian pharmacovigilance database and to compare between children and adults. Adverse drug reaction reports for carbamazepine were extracted from 2000 to 2020, and divided into 2 groups, that is, children (aged 0-17years) and adults (aged 18years and above). Age, sex, race, and carbamazepine dose were analyzed using multiple logistic regression. Of 1102 carbamazepine adverse drug reaction reports, 416 reports were SCARs (99 children, 317 adults). Stevens-Johnson syndrome and toxic epidermal necrolysis were the main SCAR types for both age groups. Median time-to-onset for any type of SCAR was 13days, regardless of age. In children, Malay individuals were 3.6 times more likely to report SCARs (95% confidence interval, 1.356-9.546; P=.010) compared to the Chinese population. In adults, carbamazepine-induced SCARs were reported as 3.6 times higher in those with a daily dose of 200 mg or less as compared to a daily dose of 400 mg or more. (95% confidence interval, 2.257-5.758; P<.001) Carbamazepine-induced SCARs reported in Malaysia were predominantly Stevens-Johnson syndrome or toxic epidermal necrolysis, with the majority in Malay individuals. Initiation therapy needs close monitoring between 2weeks and 1month.

Evaluation of Cutaneous Adverse Drug Reactions Reported in a Teaching Hospital of Coastal Andhra

Adverse drug reactions (ADR) can be manifested in different forms, among these cutaneous adverse drug reactions (CADRs) are the commonest. They have been steadily gaining importance and constitute a major proportion of all ADRs. As available data on CADRs is very less, more research is required to have reliable data, hence the current study was undertaken. This prospective study was carried out to evaluate the age and gender distribution, presenting complaints, spectrum of CADRs, causative drugs, causality, severity, and outcomes in patients with or suspected CADRs attending the department of Dermatology of Konaseema Institute of Medical Sciences &amp; Research Foundation Hospital between January 2014 and June 2015. In cooperation with the Dermatologist, patients’ reactions were analyzed based on morphology, and laboratory investigations. Causality was assessed as per the World Health Organization- Uppsala Monitoring Centre (WHO-UMC)causality assessment scale. Modified Hartwig and Siegel Scale was used for the severity assessment of reactions. CADRs occurred most commonly in the 31-40 years age group (32%) with no sign of the difference in both sexes. The most common complaint of CADRs by the patients was skin rash (42%) anddiagnoses were Erythematous drug eruption (ERDE) and Fixed drug eruption (FDE) (28%). The commonest causative drug categories were antimicrobials (52%) and Non-Steroidal Anti-inflammatory Drugs (NSAIDs) (24%).Among antimicrobials, ciprofloxacin, and in NSAIDs, diclofenac were the commonest causative drugs. In causality, majority of the cases were under possible category(42%). Most of the reactions were mild (46%), and moderate (46%) in severity. The majority of the cases showed good recovery without any mortality or disability. The limitations of this study were the relatively small sample size, inability to confirm the particular causative drug in majority of the patients. Future research should focus on the genetic factors concerning to CADRs and molecular-level evaluation should be done for a better understanding of the pathophysiology of various ADRs.

CD12 Citalopram-induced drug reaction with eosinophilia and systemic reaction confirmed by patch testing

Abstract A 46-year-old man was referred for investigation of an acute widespread rash and fever that started 4 weeks after commencing citalopram. Clinical and histological features were consistent with drug reaction with eosinophilia and systemic reaction (DRESS). He was not on any other medication, had no known allergies and had not previously taken a selective serotonin reuptake inhibitor (SSRI). Six months after resolution, he was patch tested to the extended British Baseline Series and citalopram (crushed tablet in 50% petrolatum). Readings on days 2 (D2) and 4 (D4) were positive for citalopram (D2 ++ and D4 +++). To investigate possible crossreactivity, he was subsequently patch tested to fluoxetine, paroxetine and sertraline (crushed tablets in 50% petrolatum), which showed a positive reaction to paroxetine [D2 (–) and D4 (+)]. Patch tests to citalopram and paroxetine were negative with no irritancy in a normal volunteer. SSRIs are extensively and increasingly used for depression and other mental health problems; 45 000 000 UK prescriptions were issued in the last financial year. Despite such widespread use, cutaneous adverse drug reactions (CADRs) appear to be rare. From 1998 to 2022, the Medicines and Healthcare products Regulatory Agency recorded 16 586 adverse reactions to citalopram, of which only 1077 (6.5%) were cutaneous. Various rashes have been reported to arise from SSRI treatment, ranging from maculopapular eruptions to toxic epidermolysis necrolysis/Stevens–Johnson syndrome. There have been isolated reports of DRESS from fluoxetine, sertraline and escitalopram (the S-enantiomer of citalopram). To our knowledge, this is the first reported case of citalopram-induced DRESS. The sensitivity and specificity of patch tests in the diagnosis of delayed CADR varies according to the drug and rash. We have found case reports of positive patch tests to sertraline and paroxetine following maculopapular exanthems. Our findings highlight a diagnostic role for patch tests with an extemporaneous preparation in SSRI-induced DRESS. SSRIs have diverse chemical structures, and we speculate that patch tests may be of benefit in identifying a safer alternative should further SSRI treatment be needed.

BI24 Cutaneous pseudolymphoma secondary to pembrolizumab

Abstract A 35-year-old man presented with a 7-week history of itchy, nontender, indurated erythematous plaques and nodules on his forehead and upper back, with no discriminatory clinical features. He was systemically well. Three months previously, he had completed a 12-month course of adjuvant pembrolizumab for stage IIIC melanoma. The primary melanoma had been excised from his left cheek, with involvement of left parotid and supraclavicular lymph nodes, treated with clearance via superficial parotidectomy and left neck dissection. Clinical and imaging surveillance revealed no evidence of melanoma recurrence. Incisional biopsies of the lesions on his back and forehead both demonstrated a superficial and deep dermal perivascular and periadnexal infiltrate of small- and medium-sized lymphoid cells. There was no epidermotropism and B- and T-cell clonality studies were negative. Morphological appearance and immunophenotype favoured a CD4+-reactive lymphoid process in keeping with cutaneous pseudolymphoma (CPL), secondary to pembrolizumab. The conspicuous forehead lesion was unresponsive to clobetasol propionate under occlusion. A single course of intralesional triamcinolone acetonide 10 mg mL–1 resulted in significant improvement within days, with subsequent complete resolution. The lesion on the back resolved spontaneously. Drug-induced CPL describes an adverse cutaneous drug reaction mimicking B- or T-cell lymphomas clinically and/or histologically. It has been described with anticonvulsants, antidepressants and biologic agents, often with resolution on cessation of the responsible drug (Etesami I, Kalantari Y, Tavakolpour S et al. Drug-induced cutaneous pseudolymphoma: a systematic review of the literature. Australas J Dermatol 2023; 64:41–9). It has been proposed that the drugs affect immune surveillance, leading to an abnormal cutaneous lymphocyte response. A case report (Ayoubi N, Haque A, Vera N et al. Ipilimumab/nivolumab-induced pseudolymphoma in a patient with malignant melanoma. J Cutan Pathol 2020; 47:390–3) has described drug-induced CPL secondary to ipilimumab and nivolumab in a 38-year-old man presenting with erythematous plaques on the hands and face, similar to the presentation of our patient, which responded to prednisolone. As with the other adverse effects of immunotherapy, it is likely that CPL in this cohort is due to an iatrogenic immune dysregulation leading to T-cell overactivity. We present the first reported case of CPL secondary to pembrolizumab and highlight the successful use of intralesional steroid as a treatment option. It is important to recognize CPL as an adverse cutaneous effect of immunotherapy and be aware that it can present after completing treatment due to an ongoing immune response.

Risk-conferring HLA variants in an epilepsy cohort: benefits of multifaceted use of whole genome sequencing in clinical practice

BackgroundWhole genome sequencing is increasingly used in healthcare, particularly for diagnostics. However, its clinically multifaceted potential for individually customised diagnostic and therapeutic care remains largely unexploited. We used existing whole...

Aripiprazole-Induced Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis: A Case Study.

The use of medications in management of disease is an integral part of treatment to patients in both the inpatient and outpatient setting; however, these medications often have risk of adverse effects associated with their benefits of use. Adverse cutaneous reactions are one of the most frequent types of adverse drug reactions. Two major phenotypes of cutaneous adverse drug reactions are toxic epidermal necrolysis (TEN), and Stevens-Johnson syndrome (SJS). Aripiprazole is an antipsychotic drug with a well-documented profile of adverse effects for physicians to be aware of; however, SJS/TEN is not known to be included in that profile. The authors encountered a case of aripiprazole-induced SJS/TEN and used the electronic medical records from this encounter to summarize this novel case in detail. Existing literature was reviewed using public databases for evaluation of similar cases. We present a case of SJS/TEN induced by aripiprazole use for bipolar disorder, type 1, which is not an adverse effect of the drug that has been documented in the literature. We include patient history, hospital course, images, and treatment of disease throughout admission as well as a thorough discussion of the topic. We present a case of an adverse drug reaction that has not previously been documented in the literature with the goal of informing readers of the potential for this life-threatening atypical effect and the severity of disease it may cause.

Drug-Induced Hypersensitivity Reaction and Re-Introduction of Anti-Tubercular Drugs (ATT): A Case Report and Review of Literature

Tuberculosis (TB) is a communicable disease caused by the bacillus Mycobacterium tuberculosis and is the leading cause of death by a single infectious agent overall. According to the WHO Global TB Report, India contributes to 26% of the global burden of TB. Currently, a four-drug regimen comprising Rifampicin, Isoniazid, Pyrazinamide, and Ethambutol is approved for the treatment of drug-sensitive TB. The management of cutaneous adverse drug reactions to anti-tubercular drugs is akin to a double-edged sword, with discontinuation of ATT increasing the risk of developing disseminated and drug-resistant tuberculosis, and continuation leading to persistence or exacerbation of the adverse drug reaction (ADR). The risk of developing an ADR to anti-tubercular therapy (ATT) varies from 8 to 85% in various studies [10]. The prevalence of rashes associated with ATT shows that the maculopapular rash (42.5%) is the most frequently observed type, followed by urticarial, lichenoid, DRESS, AGEP, and exfoliative dermatitis (17). The drugs associated with Cutaneous ADRs from the lowest to the highest risk are Isoniazid, Rifampicin, Pyrazinamide, Ethionamide, Cycloserine, Ethambutol, Para-aminosalicylic acid (PAS), and Streptomycin (25). We present a case and approach to the re-introduction of first-line anti-tubercular drugs after hypersensitivity with fixed-dose combinations.&#x0D; Keywords: Tuberculosis, Mycobacterium tuberculosis, adverse drug reaction, anti-tubercular therapy

Allopurinol non-covalently facilitates binding of unconventional peptides to HLA-B*58:01

Allopurinol, widely used in gout treatment, is the most common cause of severe cutaneous adverse drug reactions. The risk of developing such life-threatening reactions is increased particularly for HLA-B*58:01 positive individuals. However the mechanism of action between allopurinol and HLA remains unknown. We demonstrate here that a Lamin A/C peptide KAGQVVTI which is unable to bind HLA-B*58:01 on its own, is enabled to form a stable peptide-HLA complex only in the presence of allopurinol. Crystal structure analysis reveal that allopurinol non-covalently facilitated KAGQVVTI to adopt an unusual binding conformation, whereby the C-terminal isoleucine does not engage as a PΩ that typically fit deeply in the binding F-pocket. A similar observation, though to a lesser degree was seen with oxypurinol. Presentation of unconventional peptides by HLA-B*58:01 aided by allopurinol contributes to our fundamental understanding of drug-HLA interactions. The binding of peptides from endogenously available proteins such as self-protein lamin A/C and viral protein EBNA3B suggest that aberrant loading of unconventional peptides in the presence of allopurinol or oxypurinol may be able to trigger anti-self reactions that can lead to Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) and Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS).

EPH98 Cutaneous Adverse Drug Reactions of COVID-19 Vaccines: A Cross-Sectional Study of the Largest Healthcare System in Taiwan

Potential cutaneous adverse drug reactions (cADRs) associated with COVID-19 vaccinations are well-known. However, comprehensive evaluation including detailed patient characteristics, vaccine types, signs and symptoms, treatments and outcomes from such cADRs are still lacking in Taiwan. A cross-sectional study was conducted from December 2019 to October 2022 to analyze spontaneous ADR reporting data from Taiwan’s largest multi-institutional healthcare system. Physicians and pharmacists initially ensured the data quality and completeness of the reported ADR records. Subsequently, we applied descriptive statistics to analyze the patient cohort based on demographic characteristics, administered COVID-19 vaccines, clinical manifestations, and patient management. We identified 242 cADRs from 759 reported COVID-19 vaccine-related ADRs, 88.3% of which were judged as “possible” using the Naranjo Scale. The mean age of patients with cADRs was 48.1±17.5 years, with the majority (44.2%) of cADRs reported in the 40-64yr old age group. cADRs were more common in women (68.2%) and most of the patients had no history of allergy to vaccines (99.6%). Oxford/AstraZeneca (58.6%) accounted for the most reported brand of COVID-19 vaccines. Patients developed cADRs within 1 to 198 days (median = 5.5 days), and mostly after first-dose vaccination (77.8%). The most frequently reported cADR was rash/eruption (18.7%), followed by itchiness/pruritus (11.7%) and urticaria (9.2%), mainly affecting the lower limbs (23.8%) and upper limbs (22.6%). Medications were prescribed for 65.1% of the cADRs, and signs and symptoms were resolved within 1 to 167 days (median = 7 days) after treatment with oral antihistamines (23.0%), topical corticosteroids (14.6%) or oral corticosteroids (14.4%). Our findings provide comprehensive details regarding COVID-19 vaccine-related cADRs in Taiwan. Certain groups, especially women and the middle-aged, who reported a relatively higher rate of cADRs, may benefit from pre-vaccination counseling about the risks of cADRs and the use of appropriate medications.

Suspected cutaneous adverse drug reactions reported with traditional medicines: analysis of data for United Nations Asia region from WHO VigiBase.

Background: Data on traditional medicine-induced cutaneous adverse drug reactions (ADRs) is very scarce. The current secondary analysis based on the WHO database (VigiBase) of individual case safety reports (ICSRs) focuses on the suspected cutaneous ADRs linked to traditional medicines (TMs). Methods: All the ICSRs reported between 1st January 2016 and 30th June 2021 from the UN Asia region in VigiBase where at least one TM was suspected to cause cutaneous ADRs were included in the study. Data regarding demographic details, suspected drug, adverse reaction as per MedDRA term, the seriousness of the reaction, de-challenge, re-challenge, and clinical outcome for suspected cutaneous ADRs associated with TM were obtained from VigiBase and analyzed for frequency of reported events and suspected medicines. Findings: Total 3,523 ICSRs with 5,761 ADRs related to "skin and subcutaneous tissue disorders" were included in the analysis. Amongst these, 6.8% of ICSRs were reported as serious. Pruritus (29.6%), rash (20.3%), urticaria (18.9%), and hyperhidrosis (3.3%) were commonly reported ADRs. Artemisia argyi H.Lév. and Vaniot. (14.9%), Ginkgo biloba L. (5.1%), Vitis vinifera L. (4%), Vitex agnus-castus L. (3.8%), Silybum marianum (L.), Gaertn (3.5%), and Viscus album L. (2.7%) were some commonly suspected TMs for cutaneous ADRs. There were 46 cases of Stevens-Johnson syndrome and toxic epidermal necrolysis reported with TMs during the study period. Death was reported in 5 ICSRs. Interpretation: TMs are linked with various cutaneous ADRS ranging from pruritus to toxic epidermal necrolysis which may have serious consequences. TMs listed as suspected offending agents in this analysis, should be kept in mind while dealing with suspected cutaneous ADRs. Clinicians should be more vigilant in detecting and reporting events associated with TMs.

A highlight on carbamazepine-induced adverse drug reactions in Saudi Arabia: a retrospective medical records-based study

The link between human leukocyte antigen (HLA) alleles and carbamazepine-induced cutaneous, respiratory, and gastrointestinal adverse drug reactions (ADR) has created a window of opportunity for preventing certain forms of cutaneous adverse drug reactions (cADRs); however, there is not enough data to make pharmacogenomic recommendations that can be implemented globally. The aim of this study is to assess and document carbamazepine-induced adverse reactions among prescribed Saudi/non-Saudi patients. A retrospective chart review was performed for patients who received carbamazepine (CBZ) in the period between 2016 and 2020, in the Kingdom of Saudi Arabia. Data were gathered and descriptive statistical analyses were performed on the data for the study sample. Comparisons were made using the chi-square test or independent samples’ t-test. Statistical significance was considered at p < .05. All statistical analyses were performed using IBM SPSS 21.0 (Armonk, NY; IBM Corp). Results from multivariate logistic regression analyses showed that higher likelihood of carbamazepine-induced adverse reactions was significantly associated with younger age, OR = 0.82, 95% CI (0.74, 0.90); p < 0.001. Patients who were prescribed CBZ for reasons other than epilepsy or seizures were significantly more likely to develop carbamazepine-induced adverse reactions (epilepsy vs. other; OR = 0.63, p = 0.013; seizures vs. other; OR = 0.59, p = 0.018). Gender or medication duration were not related to carbamazepine-induced adverse reactions (p > 0.05). The findings of this study are comparable with those of other studies assessing carbamazepine-associated adverse reactions in children and adults. Recommendations include genetic prescreening, educating patients and parents on the possibility of adverse reactions, and routine laboratory monitoring.

Severe Cutaneous Adverse Drug Reactions at a Tertiary Care Center in Saudi Arabia.

Severe cutaneous adverse drug reactions (SCARs), although rare, are known to be associated with significant morbidity and mortality. SCARs include drug reaction with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), and acute generalized exanthematous pustulosis (AGEP). Studies on SCARs are limited in Saudi Arabia. This study aims to characterize SCARs at a tertiary care center in Saudi Arabia. A cross-sectional study was conducted at King Abdulaziz Medical City, Riyadh, Saudi Arabia. All inpatient and emergency department consultations to dermatology were electronically reviewed during the period from January 2016 to December 2020. All patients who developed an adverse cutaneous drug reaction were enrolled. Detailed analysis was performed only for SCARs. The culprit medication was determined based on the latency period, history of previous intake of the medication, and drug notoriety. There were 3050 hospital consultations to dermatology during the study period. Cutaneous adverse drug reactions constituted 253 (8.3%) cases. A total of 41 patients with SCARs were identified, accounting for 16.2% of all cutaneous drug reactions. Antibiotics and anticonvulsants were the most common causative drug groups accounting for 28 (68.3%) and 9 (22%) cases, respectively. DRESS was the most common SCAR. The latency period was the longest for DRESS and shortest for AGEP. Vancomycin was responsible for approximately a third of DRESS cases. Piperacillin/tazobactam was the most common cause for SJS/TEN and AGEP. The majority of drugs causing AGEP were antibiotics. The mortality rate was the highest in SJS/TEN (5/11 (45.5%)), followed by DRESS (1/23 (4.4%)) and AGEP (1/7 (14.3%)). SCARs are rare in Saudis. DRESS appears to be the most common SCAR in our region. Vancomycin is responsible for most cases of DRESS. SJS/TEN had the highest mortality rate. More studies are required to further characterize SCARs in Saudi Arabia and Arabian Gulf countries. More importantly, thorough studies of HLA associations and lymphocyte transformation tests among Arabs with SCARs are likely to further improve patient care in the Arabian Gulf region.

Serum Concentrations of Thelper2-derived Cytokines in Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis

BACKGROUND: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe cutaneous adverse drug reactions. Some immunological and genetic factors are believed to be involved in the pathogenesis of SJS/TEN, including T helper 1 and T helper 2 (Th2)-derived cytokines. AIM: This study aims to evaluate the serum levels of Th2-derived cytokines in SJS/TEN, compare to those of erythema multiforme (EM) patients, and the relation between them and the progress of SJS/TEN. METHODS: This was a sectional descriptive study conducted at the National Hospital of Dermatology and Venereology, in Hanoi, Vietnam, from October 2017 to September 2019. 48 SJS/TEN patients, 43 EM patients, and 20 healthy controls (HCs) participated. Serum interleukin (IL)-4, IL-5, and IL-13 levels were measured by using the fluorescence covalent microbead immunosorbent assay (FCMIA) (ProcartaPlex Immunoassay Panels kit, Thermo Fisher Scientific, USA). The Mann-Whitney U test was used to compare the serum IL levels of the two groups. The Wilcoxon tests were used to compare quantitative variables before and after the treatment. Differences were considered to be statistically significant at p &lt; 0.05. RESULTS: 19 SJS patients (39.5%) and 29 TEN patients (60.5%) participated in our study. The mean age was 49.3, range of 19–77 years (47.9% males; 52.1% females). The most common causative drugs were traditional medicine (29.1%), and allopurinol (12.5%). On the day of hospitalization, the serum level of IL-4 in the SJS/TEN group was 3 ± 7.5 pg/mL, statistically significantly higher than that in the HCs group (p &lt; 0.05), but not higher than that in the EM group (p &gt; 0.05); serum levels of IL-5 and IL-13 in the SJS/TEN group were 4.5 ± 9.8 pg/mL and 1.6 ± 0.6 pg/mL, respectively, similar to those in the EM and HCs groups. On the day of re-epithelialization, in SJS/TEN patients, the serum level of IL-5 was 1 ± 2.8 pg/ml, statistically significantly lower than that on the day of hospitalization (3 ± 7.5 pg/mL) with p &lt; 0.05. Regarding serum levels of IL-4 and IL-13, there was no difference between the two- time points. CONCLUSION: The serum concentrations of Th2-derived cytokines (IL-4, IL-5, and IL-13) were not higher in the SJS/TEN group than in the EM group and there was no significant change in the clinical progression of SJS/TEN, except the serum level of IL-5.

Current understanding of genetic associations with delayed hypersensitivity reactions induced by antibiotics and anti-osteoporotic drugs.

Drug-induced delayed hypersensitivity reactions (DHRs) is still a clinical and healthcare burden in every country. Increasing reports of DHRs have caught our attention to explore the genetic relationship, especially life-threatening severe cutaneous adverse drug reactions (SCARs), including acute generalized exanthematous pustulosis (AGEP), drug reactions with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN). In recent years, many studies have investigated the immune mechanism and genetic markers of DHRs. Besides, several studies have stated the associations between antibiotics-as well as anti-osteoporotic drugs (AOD)-induced SCARs and specific human leukocyte antigens (HLA) alleles. Strong associations between drugs and HLA alleles such as co-trimoxazole-induced DRESS and HLA-B*13:01 (Odds ratio (OR) = 45), dapsone-DRESS and HLA-B*13:01 (OR = 122.1), vancomycin-DRESS and HLA-A*32:01 (OR = 403), clindamycin-DHRs and HLA-B*15:27 (OR = 55.6), and strontium ranelate (SR)-SJS/TEN and HLA-A*33:03 (OR = 25.97) are listed. We summarized the immune mechanism of SCARs, update the latest knowledge of pharmacogenomics of antibiotics- and AOD-induced SCARs, and indicate the potential clinical use of these genetic markers for SCARs prevention in this mini review article.

A Study of Cutaneous Adverse Drug Reactions at a Tertiary Care Center in Andhra Pradesh, India.

Practically all physicians encounter a diverse range of suspected cutaneous adverse drug reactions (CADRs) in their daily clinical practice. The skin and mucosa are the most often encountered areas for the early presentation of numerous adverse drug reactions. Cutaneous adverse drug reactions are classified as benign or severe. The clinical manifestations of drug eruptions can range from mild maculopapular exanthema to severe cutaneous adverse drug reactions (SCARs). To determine the varied clinical and morphological presentations of CADRs and to identify the culprit drug andcommon drugs causing CADRs. Patients with clinical features suspected of CADRs presenting to the outpatient department (OPD) of dermatology, venereology, and leprosy (DVL) between December 2021 to November 2022 at Great Eastern Medical School and Hospital (GEMS), Srikakulam, Andhra Pradesh, India, were considered for the study. This was a cross-sectional, observational study. The patient's clinical history was taken in detail. This included chief complaints (symptoms, site of onset, duration, drug history, latency time between drug administration and the appearance of cutaneous lesions), family history, associated diseases, the morphology of lesions, and mucosal examination. Upon drug discontinuation, improvement in cutaneous lesions and systemic features were noted. A complete general examination, systemic examination, dermatological tests, and mucosal examination were performed. A total of 102 patients were involved in the study, of whom 55 were males and 47 were females. The male-to-female ratio was 1.17:1, with a slight male majority. The most common age group was 31 to 40 years for both males and females. Itching was the predominant complaint in 56 patients (54.9%). The mean latency periodwas shortest in urticaria (2.13+/- 0.99 hours) and longest in lichenoid drug eruption (4.33+/- 3.93 months). Most patients developed symptoms after a week of taking the drug (53.92%). A history of similar complaints was present in 38.23% of patients. Analgesics and antipyretics (39.2%) were the most common culprit drugsfollowed by antimicrobials (29.4%). Among analgesics and antipyretics, aceclofenac (24.5%) was the commonest culprit drug. Benign CADRs were observed in 89 patients (87.25%), and severe cutaneous adverse reactions (SCARs) were observed in 13 patients (12.74%). The common CADRs presented were drug-induced exanthem (27.4%). Imatinib-induced psoriasis vulgaris and lithium-induced scalp psoriasis were observed in one patient each. Severe cutaneous adverse reactions were observed in 13 patients (12.74%). Anticonvulsants, nonsteroidal anti-inflammatory drugs (NSAIDs), and antimicrobials were the culprit drugs for SCARs. Eosinophilia was present in three patients, deranged liver enzymes was present in nine patients, a deranged renal profile was present in seven patients, and death occurred in one patient with toxic epidermal necrolysis (TEN) of SCARs. Before prescribing any drug to a patient, a detailed drug history and family history of drug reactions need to be obtained. Patients should be advised to avoid over-the-counter usage of medications and self-administration of drugs. If adverse drug reactions occur, it is advised to avoid readministration of the culprit drug. Drug cards mustbe prepared and given to the patient, mentioning the culprit drug as well as the cross-reacting drugs.

Platelet-to-lymphocyte ratio predicts the duration of glucocorticoid therapy in the treatment of cutaneous adverse drug reactions

BackgroundGlucocorticoid (GC) remains the mainstay of treatment for cutaneous adverse drug reactions (cADRs) but has been associated with side effects, emphasizing the importance of precisely managing the duration of high-dose GC treatment. Although the platelet-to-lymphocyte ratio (PLR) has been proven to be closely related to inflammatory disorders, its ability to predict the timing of GC dose reduction (Tr) during cADRs treatment remains obscure. MethodsHospitalized patients diagnosed with cADRs treated with glucocorticoids were analyzed in the present study to evaluate the association between PLR values and Tr values using linear, locally weighted scatter plot smoothing (LOWESS) and Poisson regression. Subgroup and ROC curve analyses were conducted to identify confounding variables and assess the predictive performance, respectively. ResultsA total of 308 patients were included in the study, with a median age of 47.0 (31.0–62.0) years old and a median incubation period of 4 days. Antibiotics (n = 113, 36.7%) were the most common cause of cADRs, followed by Chinese herbs (n = 76, 24.7%). PLR values were positively correlated with Tr values during linear regression (P < 0.001, r = 0.414) and LOWESS regression analyses. Poisson regression showed PLR was an independent risk factor for higher Tr values (the incidence rate ratio ranged from 1.016 to 1.070 and P < 0.05 for all). The area under the curve of PLR for predicting Tr < 7 days was 0.917. ConclusionsPLR is a simple and convenient parameter with huge prospects for application as a biomarker to assist clinicians in optimally managing patients treated with glucocorticoid therapy for cADRs.

General medicine and notification of adverse reactions: contributions of health insurance representatives

In order to reduce the under-reporting of adverse drug reactions (ADR) in general practice, the Caen Normandie regional pharmacovigilance center (CRPV) has implemented a training program for the French health insurance representatives (DAM) of the Manche department in order to raise awareness among general practitioners (GPs) to ADR reporting. During quarterly visits of DAM to GPs, the mode of operation and the value of pharmacovigilance reporting was presented. This pilot study presents the impact of these DAM visits to GPs in term of ADRs reporting quantification. Assessment of this first year showed a doubling of ADR reporting by GPs of the Manche department in 2019 compared to 2017 and 2018. This phenomenon was not found in the two control departments (departments of Calvados and Orne) where the information had not been issued. These ADRs first concerned drugs of the renin-angiotensin system, then psychotropic drugs and anti-infectives. These were cutaneous, then neurological and gastrointestinal ADRs, preferentially affecting women. This experimentation should continue on a larger scale. The longer-term evaluation of this tool also requires evaluating its relevance.

Allergy on HIV Infections: A Narrative Literature Review

HIV infection causes not only immune insufficiency but also immune dysregulation. Following HIV infection, cytokine profiles change, with a production of IL-4 rising along with IL-5 and a decrease in INF-g. This literature review aimed to describe allergy on HIV infection. At the initial phase after infection, cytokines produced by Th1 and Th2 are balanced, but later as the infection progresses, cytokines produced by Th2 will rise, while cytokines produced by Th1 will fall. Elevation of IL-4 will make B cells produce more IgE. Patients with even lower CD4 still have this allergic phenomenon caused by IgE. Allergic manifestations of HIV include rhinitis, asthma, adverse cutaneous drug reactions (ACDR), immune reconstitution inflammatory syndrome, hyperallergic state (IRIS), and atopic dermatitis. In conclusion, it is important to consider allergic manifestations even in AIDS patients, especially incidents of ACDR and IRIS, which can be life-threatening.

Validation of a genotyping technique for a surrogate marker of HLA-B∗58:01 for allopurinol-induced Stevens–Johnson syndrome and toxic epidermal necrolysis in the Japanese population

Stevens–Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) are rare but severe cutaneous adverse drug reactions. Certain human leukocyte antigen (HLA) types have been associated with SJS/TEN onset, e.g., HLA-B∗58:01 with allopurinol-induced SJS/TEN, but HLA typing is time-consuming and expensive; thus, it is not commonly used in clinical situations. In the previous work, we demonstrated that the single-nucleotide polymorphisms (SNP) rs9263726 was in absolute linkage disequilibrium with HLA-B∗58:01 in the Japanese population, and can be used as a surrogate marker for the HLA. Here, we developed a new genotyping method for the surrogate SNP using the single-stranded tag hybridization chromatographic printed-array strip (STH-PAS) technique and performed an analytical validation. The results of genotyping rs9263726 using STH-PAS correlated well with those obtained using the TaqMan SNP Genotyping Assay for 15 HLA-B∗58:01-positive and 13 HLA-B∗58:01-negative patients (analytical sensitivity and specificity were both 100%). Additionally, at least 1.11 ng of genomic DNA was sufficient to digitally and manually detect positive signals on the strip. Robustness studies showed that the annealing temperature (66 °C) was the most important condition related to reliable results. Collectively, we developed an STH-PAS method that can rapidly and easily detect rs9263726 for predicting SJS/TEN onset.