Causative Drug Research Articles

Identification and characterization of lysophosphatidylcholine 14:0 as a biomarker for drug-induced lung disease

Drug-induced interstitial lung disease (DILD) occurs when drug exposure causes inflammation of the lung interstitium. DILD can be caused by different types of drugs, and some DILD patterns results in a high mortality rate; hence, DILD poses a serious problem in clinical practice as well as drug development, and strategies to diagnose and distinguish DILD from other lung diseases are necessary. We aimed to identify novel biomarkers for DILD by performing lipidomics analysis on plasma samples from patients with acute and recovery phase DILD. Having identified lysophosphatidylcholines (LPCs) as candidate biomarkers for DILD, we determined their concentrations using validated liquid chromatography/mass spectrometry biomarker assays. In addition, we evaluated the ability of LPCs to discriminate patients with acute phase DILD from those with recovery phase DILD, DILD-tolerant, or other lung diseases, and characterized their association with clinical characteristics. Lipidomics analysis revealed a clear decrease in LPC concentrations in the plasma of patients with acute phase DILD. In particular, LPC(14:0) had the highest discriminative index against recovery phase and DILD-tolerant patients. LPC(14:0) displayed no clear association with causal drugs, or subjects’ backgrounds, but was associated with disease severity. Furthermore, LPC(14:0) was able to discriminate between patients with DILD and other lung diseases, including idiopathic interstitial pneumonia and lung disease associated with connective tissue disease. LPC(14:0) is a promising biomarker for DILD that could improve the diagnosis of DILD and help to differentiate DILD from other lung diseases, such as idiopathic interstitial pneumonia and connective tissue disease.

Comparative Evaluation Of Knowledge And Awareness About Mucormycosis In Dental And Medical Practitioners In Western Maharashtra

Introduction: The estimated mucormycosis mortality rate in India ranges from 28-52%. High morbidity and mortality have been linked to delayed diagnosis and treatment. Medical and dental practitioners play a crucial role in identifying the disease and formulating a treatment plan. Hence it is important for medical and dental practitioners have adequate knowledge about mucormycosis.Objective: To evaluate and compare knowledge and awareness about mucormycosis amongst dental and medical practitioners.Methods: This cross-sectional survey was conducted among Medical and Dental practitioners in Western Maharashtra. A specially designed prevalidated questionnaire was developed, consisting of 15 questions. It was distributed through electronic mode utilizing google form during July 1st, 2022 to August 31st, 2022. SPSS Version 21 software was used for statistical analysis. The data obtained was statistically analysed using paired T-test.Results: A total of 604 responses were obtained among which 266 (44.04%) were medical practitioners and 338 (54.96%) were dental practitioners. Variations in responses indicated that practitioners from both the groups were nescient regarding causative organisms, predisposing factors, and guidelines for drugs used in treatment of mucormycosis. There was no significant difference observed in the level of knowledge and awareness among both the groups.Conclusions: Majority of the dental and medical practitioners lacked adequate knowledge and awareness about causative agents, predisposing factors, clinical symptoms, and drug regimens used to treat mucormycosis. Periodic continuing professional education programs are required to impart updated knowledge about mucormycosis among these practitioners.

Drug induced secondary angle closure glaucoma- A case series

: We report 3 cases with acute bilateral angle closure glaucoma following intake of oral chlorthalidone, mefenamic acid, topiramate. : Case series. : All patients developed bilateral acute onset painful defective vision with shallow anterior chamber, raised intraocular pressure. Gonioscopy revealed bilateral occludable angle and ultrasonogram B scan showed shallow choroidal detachment, suggestive of drug induced non pupillary block secondary angle closure glaucoma. All patients were managed by discontinuation of causative drug and started on topical antiglaucoma medication and cycloplegic drug. : we would like to bring this potentially sight threatening and reversible ophthalmic condition to general physician, which can be managed effectively by timely referral and intervention.

Incidence of antiresorptive agent-related osteonecrosis of the jaw: A multicenter retrospective epidemiological study in Hyogo Prefecture, Japan

Background/purposeThe incidence of medication-related osteonecrosis of the jaw is increasing worldwide, mostly due to the use of antiresorptive agents (ARAs) such as bisphosphonate (BP) and denosumab (Dmab). However, the proportion of BP-related osteonecrosis of the jaw (BRONJ) and Dmab-related osteonecrosis of the jaw (DRONJ) among all ARA-related osteonecrosis of the jaw (ARONJ) cases is not clear; this hinders appropriate treatment, recurrence-prevention planning, and avoidance of unnecessary Dmab withdrawal. Moreover, the causative drug administered at each disease stage remains unknown. Therefore, we conducted a retrospective study of patients with ARONJ who visited oral and maxillofacial surgery departments at hospitals in Hyogo Prefecture, Japan, over 3 years to classify and compare patient characteristics with those having BRONJ and DRONJ. We sought to identify the proportion of DRONJ in ARONJ. Materials and methodsAfter excluding stage 0 patients, 1021 patients were included (471 high-dose; 560 low-dose). ARA treatment for bone metastases of malignant tumors and multiple myeloma was considered high dose, while that for cancer treatment-induced bone loss and osteoporosis was low dose. ResultsLow doses of BP and Dmab accounted for >50% patients; the results differed from those in other countries. DRONJ accounted for 58% and 35% of high-dose and low-dose cases, respectively. Stage 3 ARONJ cases comprised 92 (19.5%) low-dose BRONJ, 39 (20.1%) high-dose BRONJ, 24 (30%) low-dose DRONJ, and 68 (24.5%) high-dose DRONJ. Eighty-nine patients who received switch therapy were divided into BRONJ or DRONJ, but there was no difference in the ratio of each stage compared to the non-switch therapy. ConclusionTo the best of our knowledge, this is the first study to clarify the proportion of BRONJ and DRONJ cases, causative drug, and its doses by disease stages. DRONJ accounted for approximately 30% of the ARONJ, approximately 60% of which was due to high doses.

High Serum Level of TNF-α in Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis

BACKGROUND: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis are severe cutaneous adverse drug reactions. Some immunological and genetic factors are believed to be involved in the pathogenesis of SJS/TEN, including tumor necrotic factor-alpha (TNF-α). Activated T-cells secrete high amounts of TNF-α and interferon-gamma that both cytokines lead to increased expression and activity of keratinocyte inducible nitric oxide synthase playing an important role in the apoptosis of keratinocytes. AIM: This study aims to evaluate the serum level of TNF-α in SJS/TEN and the relation between it 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. Forty-eight SJS/TEN patients, 43 erythema multiforme (EM) patients, and 20 healthy controls (HCs) participated. TNF-α levels were measured 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 serum TNF-α levels of 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 < 0.05. RESULTS: Nineteen SJS patients (39.5%) and 29 TEN patients (60.5%) participated in our study. The mean age was 49.3, range 19−77 years (47.9% of males and 52.1% of females). The most common causative drugs were traditional medicine (29.1%), carbamazepine (12.5%), and allopurinol (12.5%). On the day of hospitalization, the mean serum level of the SJS/TEN group was 32.6 pg/ml with a range from 1.3 pg/ml to 771.2 pg/ml. This level was significantly higher than that of the HCs group (p < 0.05) but not higher than that of the EM group. The mean serum level of TNF-α in the SJS/TEN patients on the day of hospitalization was 32.6 pg/ml, higher than that on the day of re-epithelialization (2.7 pg/ml) and the difference was statistically significant with p < 0.05. CONCLUSION: Serum TNF-α levels are a good biomarker to evaluate the progress of SJS/TEN but it is not good to differentiate SJS/TEN from EM.

Muscle magnetic resonance imaging abnormality in neuroleptic malignant syndrome: a case report

BackgroundNeuroleptic malignant syndrome (NMS) is a rare and occasionally fatal undesirable reaction to dopamine antagonists, and its phenotype is diverse owing to causative drugs. Classically, elevation of serum creatine kinase is described in NMS. Some reports have described muscular pathological findings; however, muscle magnetic resonance imaging (MRI) has not been reported previously.Case presentationA 63-year-old woman with a history of schizophrenia presented to our hospital with a high fever, excessive sweating, muscle weakness, and elevated serum creatine kinase levels. Muscle MRI revealed T2 high-intensity lesions in several muscles with gadolinium enhancement, and the pathology of the muscle biopsy showed a very mild presence of muscle fiber necrosis and regeneration with type 2c fibers without inflammation. Her symptoms resolved by treatment with levodopa/carbidopa, dantrolene. Finally, the patient was diagnosed with NMS.ConclusionsThis is the first report of muscle MRI abnormalities in a patient with NMS. Muscle MRI abnormalities in NMS may be associated with non-inflammatory myopathic changes. The cause of creatine kinase elevation cannot be explained by abnormal strong muscle contraction nor inflammation.

Skin rash associated with combined cytotoxic chemotherapy and immunotherapy for cancer: A retrospective single-center case series.

In recent years, the development of combination therapies with immune checkpoint inhibitors (ICIs) and cytotoxic anticancer drugs has radically changed the management of diverse malignancies and significantly improved patient outcomes. Several clinical trials have shown that skin rash caused by combination therapy with ICIs and cytotoxic drugs may be more frequent and severe than that developing after administration of ICIs alone or cytotoxic drug monotherapy. However, most reports provide little information on severity, treatment, post-diagnosis course, and recurrence of rashes on drug rechallenges. We aimed to describe the experience of skin rashes developing within 2 weeks from the first administration of combination therapy with ICIs and cytotoxic drugs in 11 patients visiting our dermatology department. This study included seven men and four women, and the patients' median age was 52 years. The primary disease was non-small-cell lung cancer in eight patients, cervical cancer in two patients, and esophageal cancer in one patient. Nine patients had a maculopapular rash and two patients developed erythema multiforme-like eruptions. The skin rash was often accompanied by extracutaneous symptoms, such as fever (n=9), mucositis (n=4), and liver dysfunction (n=2). In all cases, the symptoms improved with topical steroid therapy alone, with no patients exhibiting severe symptoms requiring systemic steroids or immunosuppressive agents. In addition, when the causative drugs were re-administered after recovery from the rash, only two patients relapsed with accompanying systemic symptoms, and all patients except one were able to continue treatment using the same drug regimen. Although it was suggested that the rash caused by the combination therapy of ICIs and cytotoxic drugs may be more prominent than that caused by each agent alone, comprehensive judgment, including histopathological examination, may indicate the feasibility of continuing the treatment regimen for cancer.

Associations of HLA and drug-metabolizing enzyme genes in co-trimoxazole-induced severe cutaneous adverse reactions

Co-trimoxazole is mainly used as a first-line drug for treatment and prophylaxis against Pneumocystis jiroveci pneumonia. This drug, however, has been reported as the most common causative drug for severe cutaneous adverse reactions (SCARs). This study aimed to extensively elucidate the associations between genetic polymorphisms of HLA class I and genes involved in bioactivation and detoxification of co-trimoxazole on co-trimoxazole-induced SCARS in a large sample size and well-defined Thai SCARs patients. A total of 67 patients with co-trimoxazole-induced SCARs, consisting of 51 SJS/TEN patients and 16 DRESS patients, and 91 co-trimoxazole tolerant controls were enrolled in the study. The results clearly demonstrated that the HLA-B∗13:01 allele was significantly associated with co-trimoxazole-induced SCARs, especially with DRESS (OR = 8.44, 95% CI = 2.66–26.77, P = 2.94 × 10−4, Pc = 0.0126). Moreover, the HLA-C∗08:01 allele was significantly associated with co-trimoxazole-induced SJS/TEN in the HIV/AIDS patients with an OR of 8.51 (95% CI = 2.18–33.14, P = 8.60 × 10−4, Pc = 0.0241). None of the genes involved in the bioactivation and detoxification of co-trimoxazole investigated in this study play any major role in the development of all phenotypes of SCARs.

A CASE OF SECONDARY ORGANIZING PNEUMONIA FROM INFLIXIMAB

A CASE OF SECONDARY ORGANIZING PNEUMONIA FROM INFLIXIMAB

S1202 Drug-Induced Liver Injury (DILI) Ascribed to Non-Steroidal Anti-inflammatory Drugs (NSAIDs) in the USA: An Update With Genetic Correlations From the U.S. Drug-Induced Liver Injury Network (DILIN)

Introduction: NSAIDs are widely used throughout the world, mainly for management of chronic inflammatory and painful conditions. NSAIDs rarely cause idiosyncratic, non-dose dependent liver injury. Recent evidence from the US DILIN, as well as elsewhere, implicates host immune responses as central to pathogenesis of such idiosyncratic DILI. Previously, we reported the US DILIN experience with NSAID DILI for 2004-2013.1 Aim: To update our clinical experience and report on HLA and other genetic factors recently described as important in idiosyncratic DILI. Methods: The US DILIN, begun in 2004; is comprised of clinical sites [currently 7 in number], a data coordinating center, and the NIDDK. We enroll subjects with suspected DILI and follow them for at least 6 months.2 We adjudicate causality both with RUCAM, and RECAM3 and by a Delphic approach4 and grade severity from mild to fatal or requiring liver transplant.5 Between Sep 2004 and Mar 2022, we enrolled 2,626 subjects and adjudicated causality at 6 months in 2,498. Following adjudication, we identified 55 [41 (75%) women] as definitely [ >95%], highly likely [75-95%], or probably [51-74% likely] due to NSAIDs. Results: Diclofenac was the causative drug in 29/55 [53%] of cases, followed by celecoxib [7], ibuprofen [5], etodolac and meloxicam [4 each]. Median latency was 51 d. With the notable exceptions of meloxicam and oxaprozin [n=2], the type of liver injury was hepatocellular with median R 15-25. 4 subjects died within 6 mo of onset, and 2 others [1 each due to diclofenac and celecoxib] required liver transplants. 7 had chronic DILI at 6+ mo. HLA DRB1*03:01 was more frequent in those with NSAID DILI than in matched controls, and 6/10 had the ancestral AI extended haplotype. The likelihood of carrying the DRB1*04:03 allele increased with causality score confidence and with more severe DILI [p =0.006]. Conclusion: NSAID DILI is relatively rare in the US. The most common cause is diclofenac, which, if prescribed, should carry with it special warnings of risk and close observation, as in the package insert. The increased frequencies of HLA DRB1*03:01, an HLA type known to be associated with SLE and other auto-immune disorders, and the extended ancestral AI haplotype, suggests that immune-mediated responses are of central importance in pathogenesis.

S2743 Mesalamine-Induced Interstitial Lung Disease in a Crohn’s Patient With COVID-19

Introduction: Extraintestinal manifestations of Crohn’s disease (CD) generally correlate to the disease activity and may be seen in 1 of 4 patients with CD. Though the prevalence of bronchopulmonary manifestations in CD is 0.4%, subclinical pulmonary changes may be seen in up to half of adults with CD, with involvement of the tracheobronchial tree, lung parenchyma or the pleura. Case Description/Methods: A 61-year-old man, with a history of CD diagnosed 2 years ago, currently in remission with mesalamine, was admitted to the ICU with acute hypoxic respiratory failure due to COVID-19. Inflammatory markers were elevated and he needed high-flow nasal cannula. He was started on a 5-day course of dexamethasone. By HOD-9 O2 requirement and inflammatory markers had trended down. However, around HOD-10 his O2 requirement increased to 6-10 L at rest. CT-chest showed peripherally distributed ground-glass opacities and superimposed early diffuse fibrotic lung changes. Superadded bacterial infection was ruled out. Mesalamine was discontinued and the patient was started on a course of iv methylprednisolone, after which oxygen requirements dramatically declined. He was discharged on HOD 24 with 2L O2 at rest and 4L on ambulation and a prednisone taper. Chest x-ray in 8 weeks showed improving infiltrates. On follow-up 5 months later, he was not on O2 anymore and was doing well. Discussion: Latent interstitial pulmonary involvement is seen in around 20%-55% of patients with IBD, with the most common manifestation being drug-induced lung disease, due to sulfasalazine, mesalamine, methotrexate, or anti-TNF agents. Pulmonary function tests can help in early identification of lung injury since respiratory involvement is latent many times. Onset of drug reaction can occur from 5 days to 44 months after initiation of mesalamine therapy and has been reported in the form of eosinophilic pneumonia, organizing pneumonia, nonspecific interstitial pneumonia and hypersensitivity pneumonitis. The absence of other extra-intestinal manifestations, and the remission of CD itself, can be helpful in excluding other pulmonary manifestations of CD from drug-induced lung disease. Discontinuation of the causative drug, along with a course of steroids, can help in reversing the symptoms. Though the differential of mesalamine-induced lung injury, cannot be confirmed nor excluded here, this patient probably had underlying lung pathology from his CD or its treatment, making his recovery from COVID-19 more complicated (Figure).Figure 1.: A: Portable Chest X-ray showing multifocal pneumonia, low lung volumes with bilateral patchy airspace disease; B, C: CT-Chest showing peripherally distributed ground-glass opacities, distributed in upper and lower lobes. There were superimposed early diffuse lung fibrotic changes, without any evidence of pulmonary thromboembolism; D: CT Chest, 5 months post-discharge, showing improvement in opacities.

NEUROLEPTIC MALIGNANT SYNDROME: AN UNUSUAL CASE TO INCREASE CLINICAL ATTENTION

A 26-year-young man was taken to the hospital with symptoms of schizophrenia, and treatment began with a high dose of antipsychotic medication. After receiving medication for 3–4 days, the patient experienced persistently high body temperatures, tight muscles, and raised blood levels of CK-MB and CK-NAC. The results of all other investigations were normal. A rare Neuroleptic Malignant Syndrome (NMS) was made and treatment started with immediate withdrawal of the causative drug, and timely supportive therapy led to a successful recovery. This case illustrates the importance of adopting a broad differential diagnosis for fever, carefully reviewing the prescription lists of all patients, and taking NMS into account in patients who have both fever and stiffness.

Utility and Safety of Skin Tests in Drug Reaction With Eosinophilia and Systemic Symptoms (DRESS): A Systematic Review

Determination of culprit drug in drug reaction with eosinophilia and systemic symptoms (DRESS) is crucial. Skin tests have been used, although it remains unclear how sensitive these are. To determine the value of skin tests in the assessment of drug causality in DRESS. A systematic literature search was conducted for publications from 1996 onward of skin tests (skin prick test= SPT, patch test= PT, intradermal test= IDT) performed in clearly defined DRESS cases. Outcomes of testing, drug culpability assessments, and challenge test data were extracted. A total of 17 articles met inclusion criteria. In 290 patients with DRESS, patch testing was most frequent (PT=97.2% [n= 282], IDT= 12.4% [n= 36], SPT= 3.1% [n= 9]). Positive results were noted in 58.4% (n= 160 of 282) of PTs, 66.5% of IDTs, and 25% of SPTs. When confidence of drug causality was high (n= 73 of 194), testing did not correlate well with clinical suspicion: PTs, 37.6%; IDTs, 36.5%. Direct comparison of skin testing with provocation testing (n= 12) showed 83.3% correlation. Positive IDT results were reported in 8 negative PT cases. Skin tests, particularly PTs and IDTs, have been reported as tools for diagnosis of causal drugs in DRESS. Heterogeneity in methodology, results analysis, and reporting of cohorts make meta-analysis to determine sensitivity and specificity of published literature impossible and highlight weaknesses in the field. We propose that international collaboration is essential to harmonize the methodology and reporting measures from hypersensitivity testing studies in larger cohorts.

Adverse drug events leading to emergency department visits: A multicenter observational study in Korea.

Adverse drug events are significant causes of emergency department visits. Systematic evaluation of adverse drug events leading to emergency department visits by age is lacking. This multicenter retrospective observational study evaluated the prevalence and features of adverse drug event-related emergency department visits across ages. We reviewed emergency department medical records obtained from three university hospitals between July 2014 and December 2014. The proportion of adverse drug events among total emergency department visits was calculated. The cause, severity, preventability, and causative drug(s) of each adverse drug event were analyzed and compared between age groups (children/adolescents [<18 years], adults [18-64 years], and the elderly [≥65 years]). Of 59,428 emergency department visits, 2,104 (3.5%) were adverse drug event-related. Adverse drug event-related emergency department visits were more likely to be female and older. Multivariate logistic regression analysis revealed that compared to non- adverse drug event-related cases, adverse drug event-related emergency department visitors were more likely to be female (60.6% vs. 53.6%, p<0.001, OR 1.285, 95% CI 1.025-1.603) and older (50.8 ± 24.6 years vs. 37.7 ± 24.4 years, p<0.001, OR 1.892, 95% CI: 1.397-2.297). Comorbidities such as diabetes, chronic kidney disease, chronic liver disease, and malignancies were also significantly associated with adverse drug event-related emergency department visits. Side effects were the most common type of adverse drug events across age groups, although main types differed substantially depending on age. Serious adverse drug events, hospitalizations, and adverse drug event-related deaths occurred more frequently in the elderly than in adults or children/adolescents. The proportion of adverse drug event-related emergency department visits that were preventable was 15.3%. Causative drugs of adverse drug events varied considerably depending on age group. Adverse drug event features differ substantially according to age group. The findings suggest that an age-specific approach should be adopted in the preventive strategies to reduce adverse drug events.

Fine-mapping, trans-ancestral and genomic analyses identify causal variants, cells, genes and drug targets for type 1 diabetes

Fine-mapping, trans-ancestral and genomic analyses identify causal variants, cells, genes and drug targets for type 1 diabetes

Risk factors of anaphylaxis in Korea: Identifying drug-induced anaphylaxis culprits using big data.

Drug-induced anaphylaxis is a fatal medical condition whose incidence has been increasing continuously. Due to differences between genetic backgrounds and health care systems, different populations may be prone to various causative drugs. Using the Health Insurance Service and Assessment Service database, we investigated culprit drugs for drug-induced anaphylaxis and common medication risk factors in the Korean general population. We collected medical prescription histories within 3 days prior to anaphylaxis between January 2011 and December 2019 from the HIRA database. Designed as a case-crossover study, the attributable visits (case visits) were matched to medical visits (control visits) with the drug sets for each visit. We collected a list of medication risk factors for anaphylaxis and calculated the risk ratio of each agent using the chi-square test and conditional logistic regression analysis. A total of 159,473 individuals were listed in the database with a diagnosis of anaphylaxis in the HIRA from 2011 to 2019. After evaluating the suitability of control visits for matching with a case visit, 8168 subjects and 767 drugs were analyzed. The chi-square analysis identified 31 drugs as potential risk factors for drug-induced anaphylaxis in Korea. After applying a conditional logistic regression analysis for each agent, 5 drugs were found to be the common medication risk factors for drug-induced anaphylaxis: cefaclor, iopromide, iohexol, iomeprol, and tolperisone. We found 5 medication risk factors that showed the highest risk of drug-induced anaphylaxis and their degree of risk using an objective methodology in the Korean general population.

Severe cutaneous adverse drug reactions: diagnostic approach and genetic study in a Brazilian case series.

<b>Background.</b> Severe cutaneous adverse reactions (SCAR) are potentially fatal reactions. Genetic predisposition is involved in their pathogenesis related to drugs and ethnicities, however in a mixed population these relationships are still unknown. The aim of this study was to describe phenotypes, suspect drugs and HLA-alleles related to SCAR, identified by a systematized approach in a Brazilian case series. <b>Methods.</b> Patients who were diagnosed with SCAR between March 2011 and July 2019 at our university hospital were included. European Network for Drug Allergy (ENDA) questionnaire was used to collect clinical and laboratory data and algorithms for assessment of drug causality were applied. Socio-demographic variables included age, gender and skin color/ethnicity. Drug patch tests (DPT) and HLA-A, -B, -DRB1 typing were carried out. <b>Results</b>. A total of 74 patients were included: 36 (48.64%) with SJS/TEN, 32 (43.24%) DRESS/DIHS, 3 (4.05%) AGEP, 2 (2.70%) overlap(DRESS/SJS and DRESS/AGEP) and 1 (1.35%) GBFDE. The median age was31.5 years (IQR = 14-52.25), most were female (n = 44/59.46%) and brown (n = 38/51.35%). Anticonvulsants (n = 32/43.24%) were the largest group involved and antibiotics (n = 26/35.13%) were the second most common. Two patients with DRESS died during the acute phase. Positive DPT were shown only in anticonvulsant associated DRESS. HLA related to abacavir, allopurinol and carbamazepine were identified. <b>Conclusions.</b> A systematized approach allowed the phenotypic characterization of SCAR. The HLA-A*31:01, B*57:01 and B*58:01 alleles were identified, reinforcing the causality in SCAR by CBZ, ABC and ALLO in the Brazilian population.

Chronic kidney disease is potentially an independent prognostic factor for death in Stevens-Johnson syndrome and toxic epidermal necrolysis patients.

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are mucocutaneous conditions associated with high mortality and morbidity. Although several prognostic factors have been proposed, some may have yet to be identified. A 14-year retrospective cohort study of patients with SJS/TEN was conducted at a university-based hospital in Bangkok, Thailand, to explore additional prognostic factors for mortality of patients with SJS/TEN. Medical records of all patients aged ≥18 years who were diagnosed with SJS, SJS-TEN overlap, or TEN between 2007 and 2020 were reviewed. Univariate and multivariate analyses were performed to examine associations between death and potential prognostic factors. A total of 76 patients with a mean age of 52 years were enrolled. Among them, 46, 15, and 15 patients were diagnosed with SJS, SJS-TEN overlap, and TEN, respectively. Overall, 10 patients deceased, marking a mortality rate of 13.2%. Based on an algorithm for assessment of drug causality for epidermal necrolysis, drug was the major cause of disease (96.1%). Allopurinol and trimethoprim/sulfamethoxazole were the most frequent culprit drugs. Univariate analysis revealed nine prognostic factors related to death, i.e., age, malignancy, chronic kidney disease (CKD), coronary artery disease, heart rate >120 beats/min, diagnoses of SJS-TEN overlap and TEN, blood urea nitrogen (BUN) >10 mmol/L, hemoglobin <10 g/dL, and serum albumin <2 g/dL. Causality with regard to drug, drug notoriety, time interval from drug intake to onset of reaction, and timing of culprit drug withdrawal were not significantly associated with death. Four independent prognostic factors for mortality were identified from multivariate analysis, i.e., TEN (risk ratio [RR] 8.29, 95% confidence interval [CI]: 2.71–25.38), malignancy (RR 3.34, 95% CI: 1.68–6.69), BUN >10 mmol/L (RR 3.02, 95% CI: 1.28–7.14), and early-stage CKD (RR 4.81, 95% CI: 2.49–9.28). Our findings suggest that CKD is an independent prognostic factor for mortality of patients with SJS/TEN besides those from the SCORTEN.

Drug-induced liver injury after anti tuberculosis drugs administration, how to diagnose? a case report

Drug-induced liver injury (DILI) is a liver injury caused by various drugs, herbs, or other xenobiotics, which causes abnormalities in liver tests or liver dysfunction in the absence of other causes of liver damage. The most common causative drugs are antituberculosis drugs (ATDs), anti-infective drugs, and natural herbal medicines. The diagnosis of DILI can be difficult due to the lack of specific signs, symptoms and tests and is partly a diagnosis based on exclusion. In this case report, we will discuss how to diagnosis DILI TB and causative assessment using RUCAM score. A male, 64 years old, has complained of weakness since 1 week ago and worsened since 1 day ago. The patient also felt persistent nausea for 1 week, so his eating and drinking decreased. Besides, he complained getting abdominal pain, especially in the upper right region and heartburn. The patient has been on first category of TB treatment since 20 days ago. Chest X-ray showed Lung TB with infiltrate in multiple cavities. Abdominal ultrasound showed no abnormality. The patient was discharged from our hospital after 6 days of hospitalization. DILI remains a diagnosis of exclusion based primarily on a detailed history and judicious use of blood tests, hepatobiliary imaging, and liver biopsy. The Roussel Uclaf causality assessment method (RUCAM) system is an assigning point for clinical, biochemical, serologic and radiologic features of liver injury. We use RUCAM score to make an assessment that show the likelihood of the hepatic injury due to a specific medication.

An observational study of severe cutaneous adverse reactions at a tertiary care teaching hospital

BackgroundThe term severe cutaneous adverse reactions to drugs (SCAR) comprises of acute generalized exanthematous pustulosis (AGEP), drug reaction with eosinophilia and systemic symptoms complex (DRESS), Stevens–Johnson syndrome/toxic epidermal necrolysis (SJS-TEN) and drug-induced erythroderma or exfoliative dermatitis (ED). The present study aims at describing the epidemiological and clinical profile, probable cause and the extent of morbidity and mortality in patients with severe cutaneous adverse drug reactions. MethodsAn observational study of all cases of SCAR presenting to our centre during the period from Jun 2018 to July 2019 was carried out. ResultsA total of 24 SCAR patients were studied. Most of the patients were in the age group of 11-20 years. The commonest reactions observed were SJS-TEN (54.2%) followed by DRESS (42%). Antibiotics are the most common cause of SJS-TEN, whereas almost all the drug groups were implicated equally in DRESS. No causative drug could be found in two of the SJS-TEN patients. These patients had raised atypical targetoid lesions as well as evidence of viral reactivation which could have been the probable trigger for the SCAR. A total of five patients (20.8%) died during treatment in hospital, and the percentage mortality was highest in SJS-TEN. ConclusionNondrug aetiologies for SJS-TEN are on the rise, and this was observed in this study too. Viral reactivation may be the commonest aetiology in such cases, and the morphology of the rash can give a clue to such cases.