A pattern of serious adverse drug reactions reported in a tertiary care hospital, Rangaraya Medical College, Kakinada, Andhra Pradesh

Background: Serious adverse drug reactions (ADRs) constitute a major limitation in clinical development of a drug thus necessitating close monitoring. Studies regarding the pattern of serious ADRs are limited in southern India. The present study was conducted in tertiary care hospital in Andhra Pradesh with an objective to evaluate the pattern of severe cutaneous and non-cutaneous ADRs in our hospital and to assess the causality, severity, and preventability of these reactions.Methods: A retrospective observational study was conducted over two years, from January 2016 till January 2018 in our ADR monitoring center. The pattern of serious adverse drug reactions, the nature of ADR, suspected drug, the outcome and preventability were analyzed using Modified Hartwig and Siegel scale, and modified Schumock and Thorton scale.Results: Out of 734 ADRs reported, 42 were serious, while 692 were non-serious. Out of 42, 22 were dermatological in origin while the others were acute kidney injury, acute psychosis, febrile neutropenia, gynecomastia, and lipodystrophy. According to WHO causality assessment scale, 27 were probable while 15 were possible. The majority were reported in the age group of 16 to 65 years with female (34) preponderance. The most common drug category responsible was antimicrobials, followed by antiretrovirals, anti-epileptics, and analgesics.Conclusions: Antimicrobial, anti-epileptics, and analgesics contributed to serious ADRs. Although non-cutaneous ADRs did not result in hospitalization, they caused social inhibition and mental stress in the patient.

A study on drug induced cutaneous adverse drug reactions at a tertiary care hospital, Mysore, India

Background: Drugs, however safe and efficacious, are associated with risk of adverse reactions. Adverse Drug Reactions (ADRs) are one of the leading causes of morbidity and mortality. ADRs was rated as the fifth leading cause of death among all diseases. Consequences of ADRs range from diminished quality of life, increased physician visits, hospitalizations, and even death. The objectives of the study were to obtain information about drug induced cutaneous adverse reactions and to establish the causal relationship.Methods: Observational cross sectional study, a total of 76 patients were recruited for the study,conducted in dermatology outpatient department of K R Hospital Mysore Medical College And Research Institute Mysore for 3 months. The drug reactions were recorded in ADR form of Central Drugs Standard Control Organisation (CDSCO). Causality was assessed using Naranjo algorithm and World Health Organization- Uppsala monitoring centre (WHO-UMC) criteria.Results: 76 patients with CADRs were included in the study during the 3 months study period. Most common age group with CADRs was 20-30 years; with 55.73% of females 20.26% male and the most common suspected drug group causing CADRs was antimicrobial 35.46%. And most common lesion is maculopapular rashes. According to Naranjos scale 67.30% of CADRs were probably caused by drugs.Conclusions: variety of drugs causes CADRs. Awareness among clinicians is required for active reporting of CADRs. Patients need to be educated for the cautious use of drugs causing ADRs to prevent the same.

Analysis of spontaneously reported cutaneous adverse drug reactions in a tertiary care teaching hospital in South India

Background: Skin is the most common organ involved in adverse reactions due to drugs. With newer drugs released into market every year, there is changing pattern of the reported cutaneous adverse drug reactions (ADRs). In order to ensure safer use of medicines in patients, there is need for continuous monitoring of ADRs. This is a retrospective study to analyse spontaneously reported cutaneous ADRs.Methods: All the cutaneous ADRs reported between January 2017 and September 2018 were analysed for clinical patterns, suspected medications, causality, severity and preventability.Results: Of the 1035 reports received during the study period, 232 (22.41%) included cutaneous reactions. 113 (48.7%) were male and 119 (51.29%) were female. Maculopapular rash 70 (30.17%), pruritus 31 (13.36%), palmar plantar erythrodysesthesia 30 (12.93%), acne 19 (8.19%), urticaria 16 (6.89%) and fixed drug eruptions (FDE) 13 (5.6%) were the common clinical patterns. Antimicrobial agents followed by anticancer drugs, nonsteroidal anti-inflammatory drugs (NSAIDs), hormones and related drugs, and antiepileptic drugs were the common suspected group of drugs. Causality assessment as done by WHO-UMC scale showed that 3 (1.29%) were certainly related, 174 (75%) were probably related and 55 (23.7%) were possibly related to the suspected medication.Conclusions: Cutaneous ADRs are most frequently reported ADRs in the present study. With newer drugs released into market, there is a need for continuous monitoring of use of drugs to promote safer use of medicines in patients.

Human leukocyte antigen-associated severe cutaneous adverse drug reactions: from bedside to bench and beyond

Despite their being uncommon, severe cutaneous adverse drug reactions (SCARs) result in a very great burden of disease. These reactions not only carry with them a high mortality (10%–50%) and high morbidity (60%) with severe ocular complications, alopecia, oral and dental complications and development of autoimmune diseases, but also create a substantial economic burden for patients' families and society. SCARs are, therefore, an important medical problem needing a solution in many countries, especially in Asia. The clinical spectrum of SCARs comprises Stevens-Johnson syndrome, toxic epidermal necrolysis, DRESS (drug rash with eosinophilia and systemic symptoms) (also known as drug hypersensitivity syndrome or drug-induced hypersensitivity syndrome) and acute generalised exanthematous pustulosis. Recent crucial advances in determining genetic susceptibility and understanding how T cells recognise certain medications or their metabolites via the major histocompatibility complex and the effects of cofactors, have led to the implementation of cost-effective screening programs enabling prevention in a number of countries, and to further understanding of the patho-mechanisms involved in SCARs and their significance. In this review, we document comprehensively the journey of SCARs from bedside to bench and outline future perspectives in SCARs research.

A surveillance study of cutaneous adverse drug reactions in a tertiary care teaching hospital in India

Background: Skin is one of the most common targets of adverse drug reactions (ADRs) The practice of pharmacovigilance all over the world is 5% whereas in India, it is below 1%. Hence, the purpose of our study is to monitor and analyze the suspected cutaneous adverse drug reactions (ACDRs) reported at our tertiary care teaching hospital, to characterize the nature and predictability, severity and preventability of ACDRs and identify most common drugs causing cutaneous ACDRs so that they can be given cautiously and with keen surveillance.Methods: An observational study was conducted in patients attending outpatient and inpatient department for a period of 3 years. All ACDRs of patients were referred by health care professionals and the diagnosis were made by concern doctors. The recorded data was filled in the ADR form obtained from pharmacovigilance program of India (2011) and Central Drug Standard Control Organization (CDSCO) website.Results: Out of 1399 ADR reports analyzed, 564 reports (40.31%) were of ACDRs, female to male ratio was 0.85. Redness (44.32%) was most common symptom, followed by itching (44.14%) and rash (19.14%). Antimicrobials (43.97%), NSAIDS (21.63%), Anti-retroviral therapy drugs (13.65%) were common groups. As per WHO-UMC causality classification, modified Hartwig and Siegel severity scale, Thornton and Schumock preventability scale, ACDRs were probable, mild and possibly preventable respectively.Conclusions: Effective ADR monitoring plays a role in safety of medicines. So, awareness regarding early diagnosis and prompt treatment should be created among the health care professionals and reporting of ACDRs should be regularly practiced by all the departments.

Antihypertensives in dermatology Part II - Cutaneous adverse reactions to antihypertensives

Antihypertensive drugs are prescribed frequently and can cause cutaneous adverse reactions. The exact incidence and frequency of these reactions are unknown. Multiple antihypertensive drug consumption has contributed to a substantial increase in the number of cutaneous adverse reactions to them. Thus, there is a need for dermatologists and physicians to be aware of the wide range of available antihypertensives and the type of reactions that can be expected. This review article focuses on the various clinical presentations that have been implicated or associated with them. The diagnosis and management have been discussed in brief.

Cutaneous Adverse Drug Reactions in Sabah: A 3-year study between 2014 - 2016

Introduction:Cutaneous adverse drug reactions are one of the most common adverse drug reactions. Publicationson clinical correlation between cutaneous presentations and causative agents are limited among thelocal population. This study aims to determine the clinical presentations of cutaneous adverse drugreactions and the causative drugs in the local population.Methods:A retrospective, cross sectional study was conducted from the pharmacy cutaneous adverse drugreaction database from January 2014 to December 2016 in Tawau, Keningau & Queen Elizabeth (KotaKinabalu) Hospitals.Results:A total of 859 cases of cutaneous adverse drug reactions were identified. Out of these, 53.3% (n=458)were females and 46.7% (n=401) were males. The mean age was 36 years old. Majority of patients were20-29 years old (16.6%) followed by 50-59 years old (15.1%). Most of the cases were reported amongthe Chinese community (16.4%), followed by the Malay (15.9%), Dusun (14.7%) and Bajau (14.0%)populations. The most common cutaneous manifestations were urticaria and or angioedema (49%, n=421) and maculopapular rash (39.6%, n=340). Severe cutaneous adverse reactions (SCAR) constituted2.8% in total. The major causative agent was antibiotic which accounted for 55.1% (n=473), followedby nonsteroidal anti-inflammatory drugs (NSAIDs), 28.1% (n=241) and analgesics, 10.8% (n=93).Conclusion:The types of cutaneous manifestations and causative drugs in Sabah are similar to those reported inother states of the country and abroad. This study provides evidence of local cutaneous adverse drugreaction characteristics in different ethnic group.

Epidemiology of severe cutaneous adverse drug reactions in a University Hospital: a Five-year review

Introduction@#Severe cutaneous adverse drug reactions (SCAR) is seen in ≤5% of all hospitalized patients. It includes Stevens-Johnson syndrome/toxic epidermal necrolysis spectrum (SJS/TEN), drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms (DIHS/DRESS) and acute generalized exanthematous pustulosis (AGEP).@*Objectives@#The main objective was to determine the epidemiological characteristics of SCAR patients at a tertiary hospital from 2011-2015. Specifi cally, it aimed to determine the prevalence, demographic characteristics and clinical profi le of SCAR patients.@*Methods@#All SCAR patients from 2011-2015 were studied through a single-center, retrospective, descriptive, cross-sectional study.@*Results@#Sixty-eight SCAR cases were diagnosed from 2011-2015 with a prevalence rate of 6.25 per 10,000 people. Majority were 46-55 years old with slight female predominance. The most common SCAR was DIHS/DRESS (50%), followed by SJS/ TEN (30%) and AGEP (20%). Eight percent had previous drug reactions, 69% had co-morbidities and 90% were diagnosed clinically without biopsy. The antibiotics was the most common culprit drug category followed by allopurinol and anticonvulsants. Prompt withdrawal of culprit drug/s, supportive therapy, systemic steroids and antihistamine, topical emollients and saline compress were mainstay of treatment. Mortality rate was 4% for all SCAR categories@*Conclusion@#The epidemiology of SCAR in this study is similar to those reported in other literature. The adults were commonly involved; DIHS/DRESS was the most common SCAR with antibiotics being the most common culprit. Prompt withdrawal and supportive therapy were essential. Systemic steroid, antihistamine; topical emollients and saline compress resulted in improvement of patients. In contrast, there was lower prevalence rate with slight female predominance; and lower mortality rate even with the use of systemic steroids.

Analysis of Dermatologic Diseases in Patients Receiving Anticancer Treatments: A Retrospective Study of 140 Cases / 대한피부과학회지

BACKGROUND: A number of anticancer agents are known to induce many adverse reactions in the skin. Related cutaneous adverse drug reactions influence the morbidity, mortality, and anti-cancer regimen of the patients. A multidisciplinary approach to cancer management has been emphasized. OBJECTIVE: To identify the causative anticancer agents and frequency of adverse reactions in the skin. METHODS: We retrospectively reviewed the medical records of patients who consulted at the Dermatology Department of Busan Paik Hospital and Haeundae Paik Hospital from January 2013 to February 2015. RESULTS: A total of 140 patients were enrolled. Among the 45 patients treated with antimetabolite analogs (30 cytarabine, 7 gemcitabine, 3 methotrexate, 2 fludarabine, 2 doxifluridine, and 1 decitabine), exanthematous drug eruption (49.1%) was the most common reaction, followed by hand-foot syndrome (28.3%). Among the 35 patients treated with fluorouracil (22 5-fluorouracil and 13 capecitabine), hand-foot syndrome (47.2%) was the most common, followed by acneiform eruption (25.0%). Among the 24 patients treated with epidermal grow factor receptor inhibitors (10 erlotinib, 10 cetuximab, and 4 gefitinib), acneiform eruption (54.8%) was the most common, followed by xerosis (19.4%). Among the 11 patients treated with anthracyclines (9 doxorubicin, 1 daunorubicin, and 1 idarubicin), acneiform eruption (45.5%) was the most common, followed by hand-foot syndrome (36.4%). Among the 7 patients treated with taxanes (4 docetaxel and 3 paclitaxel), hand-foot syndrome (42.8%) was the most common. Among the 6 patients treated with angiogenesis-inducing inhibitors (3 sorafenib, 2 pazopanib, and 1 sunitinib), hand-foot skin reaction (66.7%) was the most common. Only 2 patients (1.4%) changed treatments due to intolerable skin reactions. CONCLUSION: Clinicians should be aware of the various skin reactions of anticancer agents and predict their clinical course effectively.

Desensitization to Oxcarbazepine: Long-Term Efficacy and Tolerability

BACKGROUND AND PURPOSE: Antiepileptic drug (AED)-associated cutaneous adverse drug reactions can lead to the discontinuation of medications. The aim of this study was to determine the long-term efficacy and safety of performing desensitization to oxcarbazepine. METHODS: This study involved 20 patients who exhibited cutaneous adverse drug reactions associated with oxcarbazepine use between July 2009 and March 2016 at Samsung Medical Center. All of the participants had to discontinue oxcarbazepine despite presenting initially positive responses. Human leukocyte antigen genotyping was performed to detect the genetic predisposition to Stevens-Johnson syndrome. The desensitization to oxcarbazepine was performed with a starting dosage of 0.1 mg/day. Efficacy was evaluated by comparing the frequency of seizures before and at 1 and 3 years after desensitization. Adverse events occurring during desensitization and the retention rate after desensitization were also investigated. RESULTS: Nineteen patients (95%) safely completed the desensitization protocol. One withdrew owing to emotional problems that appeared to be associated with oxcarbazepine. The follow-up period was 4.6±1.2 years (mean±SD), and oxcarbazepine was maintained for more than 3 years after desensitization in 15 patients (83.3%). The response rates were 84.2% and 77.8% at 1 and 3 years after desensitization, respectively. Eight patients remained seizure-free for 3 years, and two discontinued all AEDs. Transient adverse reactions such as mild rash and itching were reported by five patients during desensitization. CONCLUSIONS: This study has demonstrated the long-term efficacy and safety of desensitization to oxcarbazepine in patients exhibiting cutaneous adverse drug reactions. This favorable outcome should encourage the implementation of desensitization in patients presenting with hypersensitivity to oxcarbazepine as an alternative strategy in clinical practice.

HLA-A*24:02/B*51:01 haplotype and lamotrigine-induced cutaneous adverse drug reactions in Koreans

Antiepileptic drugs (AEDs) have been known to induce cutaneous adverse drug reaction (cADR), ranging from a mild maculopapular eruption (MPE) to potentially life-threatening cADRs such as Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). Despite studies examining mechanisms associated with human leukocyte antigen (HLA), the association between lamotrigine (LTG)-induced cADR and HLA alleles still has room to investigate. We investigated HLA-A,-B, and -C alleles in LTG-induced cADR. The medical records of four patients with LTG-induced cADR were retrospectively reviewed. All patients were treated with LTG for epilepsy. All recovered from cADR after stopping LTG treatment and receiving intensive care. HLA-A, -B, and -C genotyping was performed in all four patients using a PCR-sequence-based typing (SBT) method. Two patients had SJS, and the other two had MPE due to LTG. The range of latency to cADR after the initial LTG dose was 19–42 days. Two patients experienced cross-reactivity with other aromatic or new AEDs. Expression of the HLA-A*24:02/B*51:01 haplotype was detected in three (75%) patients with LTG-induced cADR. The other patient carried homozygous HLA-B*58:01 alleles. The results suggest that Korean individuals with the HLA-A*24:02/B*51:01 haplotype may be susceptible to LTG-induced cADR. Further investigations are necessary to confirm these findings.

Reacciones cutáneas adversas a antimicrobianos sistémicos en pacientes hospitalizados: estudio transversal analítico retrospectivo / Inpatient cutaneous adverse reactions to systemic antibiotics: an analytical cross-sectional retrospective study

Introduction: The reported literature about the types of cutaneous adverse antibiotic reactions (ATB-CAR) and the responsible antimicrobial class is scarce. Aim: to describe the clinical and histopathological profile of these reactions, and potential associations between different types of ATB-CAR and causal antibiotic class in a tertiary hospital in Chile. Material and Methods: Cross-sectional retrospective study performed at the Hospital of the Pontificia Universidad Católica de Chile. Results: A total of 58 patients were included. The most common type of ATB-CAR was morbilliform (n: 37, 63.8%). The antibiotics most frequently involved were the penicillins and cephalosporins (n: 34, 69.3%). The most common histological pattern in all types of ATB-CAR was superficial perivascular dermatitis with or without spongiosis. There was significant association between urticarial, morbilliform, DRESS and PEGA types, with the use of penicillins, cephalosporins, cotrimoxazole, and lincomycin, respectively (n: 4,100%, n: 15, 40.5%, n: 2; 50%, n: 1, 50%, p < 0.05, respectively). Discussion: This is the first description of the ATB-CAR patterns in South American hospitalized patients. Both clinical and histopathological patterns of ATB-CAR are similar to other published series, however the types of causal antibiotics are different.

Introducción: La literatura médica reportada acerca de los tipos de reacciones cutáneas adversas a antimicrobianos (ATM-cRAM) y la clase de antimicrobiano responsable es escasa. Objetivo: Describir el perfil clínico e histopatológico de estas reacciones, y establecer posibles asociaciones entre los distintos tipos de ATM-cRAM y la clase de antimicrobiano causal, en un hospital terciario en Chile. Material y Método: Estudio transversal analítico retrospectivo realizado en el Hospital de la Pontificia Universidad Católica de Chile. Resultados: Fue incluido un total de 58 pacientes. El tipo más frecuente de ATM-cRAM fue el morbiliforme (n: 37; 63,8%). Los antimicrobianos más frecuentemente implicados fueron penicilinas y cefalosporinas (n: 34; 69,3%). El patrón histopatológico más frecuente en todos los tipos de ATM-cRAM fue el de dermatitis perivascular superficial, con o sin espongiosis. Hubo asociación significativa entre las ATM-cRAM tipo urticaria, morbiliforme, DRESS y PEGA, con el uso de penicilinas, cefalosporinas, cotrimoxazol y lincomicina, respectivamente (n: 4,100%; n: 15, 40,5%; n: 2; 50%; n: 1; 50%, p < 0,05, respectivamente). Discusión: Este estudio corresponde a la primera descripción de los patrones de ATM-cRAM en pacientes hospitalizados sudamericanos. Tanto los patrones clínicos como histopatológicos de ATM-cRAM son similares a otras series publicadas; sin embargo, los tipos de antimicrobianos causales no coinciden con lo previamente descrito.

A 5 Year Retrospective Study on the Clinical Patterns and Treatment Outcomes of Severe Cutaneous Adverse Drug Reactions (SCARS) in Hospital Tengku Ampuan Rahimah, Malaysia

Introduction: Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) , and drug reaction with eosinophilia and systemic symptoms (DRESS) are severe cutaneous adverse drug reactions (SCARs) related to a variety of medications. Objectives: We aim to document the epidemiological features, the causative drugs and clinical outcomes of patients with SCARs treated in Hospital Tengku Ampuan Rahimah (HTAR) between January 2009 and December 2013. Materials & Methods: A retrospective review of the data of all patients with SJS, TEN and DRESS treated from January 2009 to December 2013 was retrieved and analyzed. Results: A total of 33 SCARs patients were seen, which included SJS (25), TEN (3) and DRESS (5). The mean age was 42.8 years. The male-to-female ratio was 1.36:1. Allopurinol (33.3%) was the commonest offending drug, followed by antibiotics (30.3%), anticonvulsants (12.1%), non-steroidal anti-inflammatory drugs (12.1%) and traditional medications (6.1%). Eighty percent of SJS and all TEN and DRESS patients were given systemic corticosteroids. One patient with TEN (33.3%) was concurrently given intravenous immunoglobulin. All SJS patients survived. Two patients with TEN (66.7%) and one patient with DRESS (20%) succumbed due to sepsis. Conclusion: The commonest drugs implicated for SCARs in our study were allopurinol and antibiotics. Inappropriate use of these drugs leads to increased risk of SCARs. Early recognition and prompt treatment of patients with SCARs may improve their outcome.

Oxidative stress and leukocyte migration inhibition response in cutaneous adverse drug reactions.

Background: Cutaneous adverse drug reactions (CADRs) may either be immunological or non-immunological. The precise mechanisms, however, are largely obscure. Other concomitant mechanisms may amplify and/or contribute to the severity and duration of a reaction. One such mechanism could be oxidative stress, a state of imbalance between reactive oxygen species, and their subsequent detoxification by antioxidants. Aims: (a) to assess the oxidative stress status in the blood of cutaneous drug reaction patients by assaying for reduced glutathione (GSH) and malondialdehyde (MDA) levels, (b) to determine the leukocyte migration inhibition (LMI) response in these patients in response to the suspected drug (s), and (c) to look for the association between oxidative stress parameters and LMI. Methods: Ethical committee approval was obtained for this study. Fresh venous blood samples were obtained from the patients of CADRs (group A) during the acute phase of reaction and healthy control subjects (group B). MDA levels, a measure of oxidative lipid damage, and reduced GSH levels, a measure of anti-oxidant capacity, were assayed in the blood samples of both groups using spectrophotometry. LMI response was measured by challenging the patients' peripheral blood mononuclear cells with the suspected drug to confirm immunological perturbation. Results: Totally 66 participants, 33 cases in group A and equal number of controls in group B, were studied. The mean MDA levels were found to be raised (P < 0.001), but GSH levels were significantly reduced in group A when compared with group B (P = <0.001). LMI response against drug(s) was performed in 33 cases (group A), out of which 25 cases showed a positive LMI response as follows: fixed drug eruption (10/25), SJS (5/25), urticaria (3/25), exfoliative dermatitis (2/25), morbilliform rash (2/25), erythroderma (1/25), vasculitis (1/25), and dapsone syndrome (1/25). The mean MDA levels were found to be significantly higher in the LMI positive CADRs (P < 0.001) when compared with LMI-negative ones, while no significant difference was seen for GSH (P = 0.100). Furthermore, there was a significant positive correlation between MDA levels and LMI response (r = 0.831, P < 0.001). On the other hand, a negative but statistically insignificant correlation was found between GSH and LMI response (r = -0.248, P = 0.271). Conclusion: CADR patients were found to be under oxidative stress based on MDA and GSH levels in the peripheral blood. There is a significant positive correlation of LMI response (against the causative drug) with MDA levels, which strongly associates oxidative stress with the immunopathogenesis in CADRs.

Causality Assessment of Cutaneous Adverse Drug Reactions

BACKGROUND: Cutaneous adverse drug reactions (ADRs) are the most common adverse reactions attributed to drugs. A systematic and effective approach to a patient with suspected drug eruption allows for prompt recognition, classification and treatment of cutaneous ADRs. A standardized and effective approach for objective causality assessment is necessary to make consistent and accurate identification of ADRs. OBJECTIVE: Although the Naranjo algorithm is the most widely used assessment tool, it contains many components which are not suitable for clinical assessment of ADRs in Korea. The purpose of this study is to compare correlations of the Naranjo algorithm and the Korean algorithm to evaluate usefulness of both algorithms in order to make a causal link between drugs and cutaneous ADRs. In addition, this study classifies the clinical types and causative agents of cutaneous ADRs. METHODS: The authors retrospectively reviewed the clinical types and laboratory findings of patients who were diagnosed with cutaneous ADRs in the dermatology clinic at Gil hospital. One hundred forty-one patients were enrolled in this evaluation. The causal relationship of ADRs was assessed by using the Naranjo algorithm and Korean algorithm (version 2.0). RESULTS: A cross-tabulation analysis was applied to the Naranjo algorithm and Korean algorithm (version 2.0). Simple correlation analysis and a Bland-Altman plot were used for statistical analysis. Correlation analysis confirmed that the two assessment algorithms were significantly correlated. Exanthematous eruptions (68.8%), Stevens- Johnson syndrome (10.6%), and urticaria (8.5%) were the most common types of cutaneoues ADRs. The most common causative agents were antibiotics/antimicrobials, antipyretics/non-steroidal anti-inflammatory drugs, and central nervous system depressants. CONCLUSION: The Naranjo algorithm and Korean algorithm (version 2.0) were significantly correlated with each other, and thus reliable assessment methods to determine cutaneous ADRs.