Drug-induced Cutaneous Reactions Research Articles

Ulcerative colitis and pyoderma gangrenosum presentation of a case and brief literature review

Inflammatory bowel disease (IBD) is a chronic immune-mediated disorder comprised of Crohn's disease and ulcerative colitis. Ulcerative colitis affects the large intestine, while Crohn's disease can affect any part of the gastrointestinal tract (GIT). IBD is a multisystem condition that predominantly affects the gastrointestinal, musculoskeletal, ocular, and cutaneous systems. The following dermatological manifestations associated with IBDs have been identified: Specific manifestations with the same histological features of the underlying only ocurrs in Crohn Disease (CD); cutaneous disorders associated with IBD aphthous stomatitis, erythema nodosum; reactive mucocutaneous manifestations of IBDs pyoderma gangrenosum, Sweet’s syndrome, bowel-associated dermatosis-arthritis syndrome, aseptic abscess ulcers, pyodermatitis y mucocutaneous conditions secondary to treatment including injection site reactions y eczema and manifestations due to nutritional malabsorption such as stomatitis, glossitis, angular cheilitis hair and nail abnormalities. We believe dermatological examination is essential in all IBD patients, especially in candidates to biologic therapies, in whom drug-induced cutaneous reactions may assume marked clinical relevance, such as psoriasiform eruption. One of the cutaneous manifestations associated with UC is pyoderma gangrenosum (PG), which is an inflammatory neutrophilic dermatosis that clinically presents with well-defined ulcers with an erythematous border and mucopurulent or hemorrhagic exudate.We present the case of a 44-year-old female patient, who presented non-specific chronic ulcerative colitis (UC) with active intestinal symptoms, fever, diarrhea and hematochezia, 20 days later it began with pustules on the head, trunk and extremities, which evolved into an ulcer with a border erythematous and well defined whose clinical and histopathological diagnosis corresponded to pyoderma gangrenosum.

Fixed drug eruptions- A Case Report

Fixed drug eruption (FDE) is typically establishes as round or oval, sharply delineated erythematous or edematous plaques. Essentially it is a drug-induced cutaneous reaction that happens at the similar site with each exposure to a specific medication. A extensive spectrum of drugs can occasionally give rise to numerous contrary orofacial manifestations, predominantly dry mouth, taste disturbances, oral mucosal ulceration, and/or gingival swelling. However, the etiology of the FDE is still unknown, it is a delayed type of hypersensitivity reaction that occurs as lesions. By limiting the use of the term allergic to those reactions that are immunologically arbitrated or can reasonably be reputed to be, approximations are that drug allergy may account for 6–10% of these adverse reactions.

Dermatological adverse drug reactions with particular reference to Steven-Johnson syndrome and toxic epidermal necrolysis

Background: Drug therapy is an inevitable cause of cutaneous adverse reactions. Aims and Objectives: The primary aim was to identify the incidence and magnitude of various dermatological adverse reactions including Steven-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). Moreover, secondary aim was to quantify the risks associated with the use of specific medications. Materials and Methods: A prospective and hospital-based study was conducted in the department of dermatology SMHS hospital on hospitalized cases of cutaneous adverse drug reactions (CADRs). Informed consent was sought and reactions were reported on validated questionnaire based on adverse drug reaction (ADR) monitoring form provided by Central Drug Standard Control organization Ministry of Health and Family Welfare, Government of India. These dermatological reactions were assessed for the clinical pattern, causative agents, and prognosis. The WHO-Uppsala Monitoring centre system for standardized case was used for causality assessment of all cases identified. Results: A total of 101 hospitalized patients with varied dermatological ADRs were reported during the study period. Cases were found more in females (n=75, 74.25%) than in males (n=26, 25.75%). CADRs that were reported in our study were exanthematous rash, fixed drug eruptions, urticarial rashes, SJS, TEN, urticarial vasculitis, anticonvulsant hypersensitivity syndrome, erythema multiforme, contact dermatitis, exfoliative dermatitis, mucosal hyperpigmentation, and nail pigmentation, respectively. After a meticulous drug history, the drugs implicated in causing the cutaneous reactions were anticonvalscents such as phenytoin, carbamazepine, lamotrigine, and phenobarbitone. Other drugs identified were non-steroidal anti-inflammatory drugs such as oxicam, antibiotics such as sulfasalazine, cefixime, cefpodoxime, amoxicillin, fluoroquinolones such as levofloxacin and ciprofloxacin, chemotherapeutic agents such as cyclophosphamide, 5FU, and hydroxurea. Conclusion: The present study concluded that skin is most common target for ADRs. Drug-induced cutaneous reactions can be as simple as a mild rash to rare life-threatening SJS and TEN. Moreover, certain group of patients is at increased risk for developing CADR’s as women are more susceptible than men.

Acute Phase Reactants: Relevance in Dermatology.

Acute phase reactants (APRs) are a heterogeneous group of plasma proteins whose concentration either increases or decreases by at least 25% during an inflammatory process. The conditions that commonly lead to acute phase response are infection, trauma, burns, tissue infarction, inflammatory conditions, and advanced malignancy. APRs are elevated in all infective conditions. In skin and soft tissue infection, the levels of erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) help to predict the severity of infection. Procalcitonin can be used to differentiate between viral and bacterial infections. During active stages of systemic lupus erythematosus (SLE), ESR is elevated, but CRP either remains normal or shows only moderate elevation. In the case of superadded bacterial infection in SLE, CRP is elevated. In SLE, ferritin levels are elevated during the active stage of the disease. Serum amyloid antigen (SAA) and CRP levels are significantly higher in patients with early and late stages of diffuse systemic sclerosis. Elevated levels of serum ferritin are seen in rheumatoid arthritis and adult-onset Still's disease. CRP, SAA, and α2-macroglobulin (α 2M) are elevated in active psoriasis. In severe psoriasis, the ferritin-iron ratio is elevated. In drug-induced maculopapular rash, drug-induced hyperaemic vasculitis, and severe drug-induced cutaneous adverse reactions, CRP levels are elevated during the active stages. Neoplastic diseases in general are accompanied by increased serum ferritin. Further detailed studies are required to explore the clinical significance of APRs in dermatology and the scope of their possible application as a diagnostic tool.

Association of HLA Alleles with Antiepileptic Drug-Induced Mild Cutaneous Reactions: A Case-Control Study of a Northeast Han Chinese Population.

Human leukocyte antigen (HLA) is associated with drug-induced cutaneous adverse reactions, including antiepileptic drugs (AEDs). HLA gene polymorphism has a regional discrepancy, and it is therefore important to study it in different populations. To investigate the role of HLA in AED-induced mild cutaneous adverse drug reactions (cADRs) in a Northeast Han Chinese population. A case-control study was performed in the First Hospital of Jilin University between August 2016 and March 2017. In total, 26 patients with mild cADRs induced by AEDs and 23 AED-tolerant control patients were included. Sequence-based typing (SBT) was used to detect HLA-A and HLA-B genotypes. Differences in genotype frequencies between groups were assessed using Fisher's exact test. In the mild cADRs group, 22 patients (84.6%) presented with maculopapular exanthema (MPE) and four patients (15.4%) presented with an isolated itch. The median duration between the AED exposure and cADRs was 7.5 days (IQR, 3 - 14 days). We failed to find statistically significant differences in HLA alleles between the cADRs group and the control group when considering all the drugs included in our study together or when considering oxcarbazepine (OXC), carbamazepine (CBZ), and levetiracetam (LEV) alone (P > 0.05). Our findings indicated that there was no correlation between HLA alleles and AED-induced mild cADRs in the Northeast Han Chinese population.

Dermatological Manifestations in Inflammatory Bowel Diseases.

Inflammatory bowel diseases (IBDs) may be associated with extra-intestinal manifestations. Among these, mucocutaneous manifestations are relatively frequent, often difficult to diagnose and treat, and may complicate the course of the underlying disease. In the present review, a summary of the most relevant literature on the dermatologic manifestations occurring in patients with inflammatory bowel diseases has been reviewed. The following dermatological manifestations associated with IBDs have been identified: (i) specific manifestations with the same histological features of the underlying IBD (occurring only in Crohn’s disease); (ii) cutaneous disorders associated with IBDs (such as aphthous stomatitis, erythema nodosum, psoriasis, epidermolysis bullosa acquisita); (iii) reactive mucocutaneous manifestations of IBDs (such as pyoderma gangrenosum, Sweet’s syndrome, bowel-associated dermatosis-arthritis syndrome, aseptic abscess ulcers, pyodermatitis–pyostomatitis vegetans, etc.); (iv) mucocutaneous conditions secondary to treatment (including injection site reactions, infusion reactions, paradoxical reactions, eczematous and psoriasis-like reactions, cutaneous infections, and cutaneous malignancies); (v) manifestations due to nutritional malabsorption (such as stomatitis, glossitis, angular cheilitis, pellagra, scurvy, purpura, acrodermatitis enteropathica, phrynoderma, seborrheic-type dermatitis, hair and nail abnormalities). An accurate dermatological examination is essential in all IBD patients, especially in candidates to biologic therapies, in whom drug-induced cutaneous reactions may assume marked clinical relevance.

Amoxicillin induced erythematous maculopapular rashes: a case report

Cutaneous adverse reactions (CAR) can occur with any class of drugs, however more widely caused by various antibiotics. Amoxicillin is a broad-spectrum, bactericidal, beta-lactam antibiotic, widely used for combating various infections. Cutaneous drug eruptions are known to be reported common while using penicillin class of drugs, specifically among children. These immune-mediated bizarre drug eruptions were range from mild to severe drug-induced cutaneous reactions, such as Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). The present case reported with maculopapular, erythematous rashes induced by amoxicillin in a nine-year-old male patient. Amoxicillin was prescribed for his hyperactive respiratory disease and subsequently after three days developed generalized maculopapular erythematous rashes as a result of an antibiotic-induced skin rash. The present case is being reported to add more data, also to emphasize and gather the information for evidence-based practice and to promote efficient pharmacovigilance adverse drug reaction reporting.

HLA-B*1502 is associated with aromatic anticonvulsant drug-induced cutaneous adverse drug reactions among the Hakka population in China.

BackgroundThe purpose of this study was to analyze the correlation between aromatic antiepileptic drug-induced cutaneous adverse drug reactions and HLA-B*1502 genotype in patients from the Hakka population in Meizhou.MethodsA total of 214 epileptic patients taking aromatic (n = 94) or non-aromatic anticonvulsants (n = 120) were included in the study from September 2016 to May 2018. Clinical data for the patients were analyzed retrospectively and HLA-B*1502 genotype testing was carried out.ResultsThirty patients were HLA-B*1502(+) (14.02%). The proportion of HLA-B*1502(−) genotype and incidence of adverse drug reactions (ADRs) differed significantly between the two drug groups. In the aromatic anticonvulsant group, maculopapular eruption (MPE), Stevens–Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and hypersensitivity syndrome (HSS) occurred in 10 patients, including eight HLA-B*1502(+) and two HLA-B*1502(−) patients. MPE, HSS, SJS, and TEN occurred in 26 patients in the non-aromatic anticonvulsant group, including one HLA-B*1502(+) and 25 HLA-B*1502(−) patients. There was a significant correlation between the proportions of HLA-B*1502(+) genotype and induced cutaneous adverse drug reactions in the two groups.ConclusionsHLA-B*1502 is associated with aromatic anticonvulsant drug-induced cutaneous adverse drug reactions among the Hakka population in Meizhou, China.

Causative drugs for drug-induced cutaneous reactions in central China: a 608-case analysis

BackgroundReports regarding the causative drugs of drug-induced cutaneous adverse reactions in China are indistinct, such that different regions have reported the spectrum of drugs differs substantially in different clinical conditions. ObjectiveTo explore the causative drugs that led to cutaneous reactions. MethodsAdverse drug reaction reports from central China were collected and divided into cutaneous adverse reactions and severe cutaneous adverse reactions groups. Cases were reviewed retrospectively for causative drugs. ResultsThe male:female ratio was equal in both cutaneous adverse reactions and severe cutaneous adverse reactions. In cutaneous adverse reactions (n=482), the highest incidence happened between 51 and 60 years of age and the top three causative drugs were antibiotics (48%), Chinese medicine (16%), and allopurinol (9%). In severe cutaneous adverse reactions (n=126), the highest incidence happened between 41 and 50 years of age and the top three causative drugs were sedative-hypnotics and antiepileptics (39%), antibiotics (22%), and allopurinol (15%). Carbamazepine was the most frequently used single-drug (16/18) in sedative-hypnotics and antiepileptics. β-lactams were the most frequently used antibiotics that induced both cutaneous adverse reactions and severe cutaneous adverse reactions. Study limitationsThe small sample size, retrospective design, collection of cutaneous adverse reactions and severe cutaneous adverse reactions at different time frames and locations, and exclusion of patients taking more than five medications are limitations of the study. ConclusionsGender does not affect cutaneous adverse reactions and severe cutaneous adverse reactions. The top three drugs to induce cutaneous adverse reactions are antibiotics, Chinese medicine, and allopurinol, while those that triggered severe cutaneous adverse reactions are sedative-hypnotics and antiepileptics, antibiotics, and allopurinol. Carbamazepine is the most frequent single drug that induces severe cutaneous adverse reactions. β-lactams are the most frequently used antibiotics that induce both cutaneous adverse reactions and severe cutaneous adverse reactions.

Drug-induced severe cutaneous adverse reactions: Determine the cause and prevention

BackgroundApproximately 45% of all adverse drug reactions are manifested in the skin. Although most are mild, severe cutaneous adverse reactions (SCARs) are potentially lethal. ObjectiveTo review the etiology and clinical manifestations of severe cutaneous adverse reactions (SCARs) and the demographic characteristics of patients with SCARs. MethodsThis study is a retrospective review of electronic medical records for patients who developed drug-induced cutaneous reactions and were treated for initial or ongoing care at a university medical center from June 4, 2008, to August 10, 2018. Search terms included Stevens-Johnson syndrome(SJS) , drug rash with eosinophilia and systemic symptoms(DRESS), acute generalized exanthematous pustulosis(AGEP), toxic epidermal necrolysis (TEN), and TEN/SJS overlap. ResultsOf 596 cases of drug-induced rash, 35 cases (5.9%) of SCARs were encountered (male-to-female ratio, 1.06:1.0; mean age, 48.5 years). Of those 35 cases, 32 were in white patients (91.4%). The most common manifestations were DRESS (19 [54.3%]), SJS (8 [22.8%]), AGEP (6 [17.1%]), TEN (1 [2.9%]), and overlap (1 [2.9%]). Multiple causative drugs were implicated in 14 cases, whereas a single drug was responsible in 21 cases. The most common drugs implicated were antibiotics (88.1%). The most common causative antibiotics were cephalosporins (23.7%). Most of the patients with SCARs were given triamcinolone cream and prednisone alone (18 [51.4%]), methylprednisolone alone (1 [2.9%]), methylprednisolone and prednisone combined (4 [11.4%]), methylprednisolone and prednisolone (1 [2.9%]) or prednisone and prednisolone (1 [2.9%]). ConclusionThe most common SCARs were, in order, DRESS, SJS, AGEP, TEN, and overlap. The most common causative drugs were, in order, cephalosporins, penicillins, trimethoprim-sulfamethoxazole, and fluoroquinolones.

An update on HLA alleles as pharmacogenetic markers for antiepileptic drug-induced cutaneous adverse reaction

Epilepsy is a common neurological disorder affecting approximately 50 million people worldwide. Antiepileptic drugs (AEDs) are commonly used to treat the disease depending, mainly on the type of seizure. However, the use of AEDs may also lead to cutaneous adverse drug reactions (cADR) such as toxic epidermal necrolysis (TEN), Stevens–Johnson syndrome (SJS), exfoliative dermatitis (ED) and drug‐induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms (DIHS/DRESS), which are unwanted comorbidities in epilepsy. It was first discovered that the HLA-B*15:02 allele was strongly associated with carbamazepine (CBZ)-induced SJS/TEN among Han Chinese and this led to the discovery of other HLA alleles and cytochrome P450 (CYP) genes that were significantly associated with various AED-induced cADRs across various populations. This mini review is an update on the latest findings of the involvement of various HLA alleles and CYP alleles in cADRs caused by CBZ, phenytoin (PHT), oxcarbazepine (OXC) and lamitrogine (LTG) in different case-control studies around the world. From our review, we found that CBZ- and PHT-induced cADRs were more commonly reported than the other AEDs. Therefore, there were more robust pharmacogenetics studies related to these AEDs. OXC- and LTG-induced cADRs were less commonly reported, and so more studies are needed to validate the reported association of the newer reported HLA alleles with these AEDs. It is also important to take into account the allelic frequency within a given population before drawing conclusions about the use of these alleles as genetic markers to prevent AED-induced cADR. Overall, the current body of research point to a combination of alleles as a better pharmacogenetic marker compared to the use of a single gene as a genetic marker for AED-induced cADR.

Association Between HLA Genotype and Cutaneous Adverse Reactions to Antiepileptic Drugs Among Epilepsy Patients in Northwest China.

This study aimed to investigate the association between HLA genotypes and antiepileptic drug-induced cutaneous adverse reactions (AEDs-cADRs) among patients with epilepsy in Ningxia Hui Autonomous Region of Northwest China. Fifteen patients with AEDs-cADRs and 30 matched AEDs tolerant controls from anested case-control study were tested the HLA-A, HLA-B, and HLA-DRB1 genotype using the polymerase chain reaction sequence-based typing (PCR-SBT). Significant difference was not observed between AEDs-cADRs and AEDs tolerant groups in terms of HLA-A, HLA-B, and HLA-DRB1 genotype frequencies. Future studies using larger cohorts are needed to verify this observation.

The influence of acute kidney injury on the outcome of Stevens-Johnson syndrome and toxic epidermal necrolysis: The prognostic value of KDIGO staging.

BackgroundStevens–Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and SJS/TEN overlap syndrome are severe drug-induced cutaneous adverse reactions with high mortality. Acute kidney injury (AKI) was a common complication in an SJS/TEN group and noted as an independent risk factor for mortality in patients with SJS/TEN. To determine whether AKI staging can predict the outcome of patients with SJS/TEN, we compared the discriminative power of an AKI KDIGO staging system with that of SCROTEN, APACHE II, APACHE III, and SOFA.Materials and methodsWe retrospectively analyzed the data of 75 patients who were diagnosed with SJS, TEN, or SJS/TEN overlap syndrome at a tertiary care university hospital between January 1, 2011 and December 31, 2014. The baseline characteristics, biochemical analysis data, medication use, and outcomes of the patients were assessed, and the discriminative ability for predicting mortality was determined for each prognostic model.ResultsOf the 75 patients, 23 (30.7%) had AKI, of whom 13 (56.5%) died during the index admission. Of the prognostic risk models analyzed, the KDIGO staging system showed similar discriminative ability in predicting in-hospital mortality as did the other models. In addition, combining KDIGO with other scoring systems yielded significantly more accurate risk prediction for in-hospital mortality compared with the other individual scores alone, as measured by net reclassification index. The patients with KDIGO stages 2 and 3 exhibited a significantly lower 1-year survival rate than did those with KDIGO stages 0 and 1.ConclusionAKI KDIGO staging has good discriminative ability and is easy to utilize for predicting mortality.

Is acetaminophen associated with a risk of Stevens-Johnson syndrome and toxic epidermal necrolysis? Analysis of the French Pharmacovigilance Database.

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare but severe mostly drug-induced cutaneous reactions. Acetaminophen is an over-the-counter drug used worldwide to treat pain and reduce fever. In 2013, the US Food and Drug Administration informed the public that acetaminophen was associated with a rare risk of SJS/TEN. The aim of the present retrospective study was to analyse reports of acetaminophen as a possible suspect in the development of SJS/TEN from the French Pharmacovigilance Database (FPDB). Cases of TEN/SJS with acetaminophen as a suspect drug registered in the FPDB, collected from January 2002 to December 2013, were analysed by an expert group. The algorithm of drug causality for epidermal necrolysis (ALDEN) was used as a reference tool for SJS/TEN to assess the causality of each suspect drug. After exclusion of 16 nonvalidated cases, 112 cases (47 TEN, 51 SJS, 14 SJS/TEN overlaps) involving 574 suspected drugs (5⋅1/case) were analysed. In 80 cases, the acetaminophen ALDEN score was inferior or equal to that of other drugs, associated with a higher suspicion for causality. In 32 cases, acetaminophen had the highest score but matched with a 'very unlikely' or 'unlikely' causality in 12 cases. For the 20 remaining cases with a 'possible' or ' probable' causality, a protopathic or a confounding bias was likely in 14 cases. After analysis of the French pharmacovigilance data using the ALDEN algorithm, we found no obvious SJS/TEN risk related to the use of acetaminophen in this large national series.

Spotlight on the June 6 issue

#### Notable in Neurology This issue features an article that evaluates the burden of deep and lobar lacunes in intracerebral hemorrhage due to cerebral amyloid angiopathy and hypertensive small vessel disease, and another that investigates the involvement of human leukocyte antigen loci in aromatic antiepileptic drug-induced cutaneous adverse reactions. A featured article examines placebo and nocebo responses in restless legs syndrome. ### Poststroke epilepsy in long-term survivors of primary intracerebral hemorrhage![Graphic][1] In a long-term follow-up study, the authors sought … [1]: /embed/inline-graphic-1.gif

SNP-based HLA allele tagging, imputation and association with antiepileptic drug-induced cutaneous reactions in Hong Kong Han Chinese.

Human leukocyte antigen (HLA) genes control the regulation of the human immune system and are involved in immune-related diseases. Population surveys on relationships between single nucleotide polymorphisms (SNP) and HLA alleles are essential to conduct genetic association between HLA variants and diseases. Samples were obtained from our in-house database for epilepsy genetics and pharmacogenetics research. Using 184 epilepsy patients with both genome-wide SNP array and HLA-A/B candidate gene sequencing data, we sought tagging SNPs that completely represent sixHLA risk alleles; in addition, a Hong Kong population-specific reference panel was constructed for SNP-based HLA imputation. The performance of our new panel was compared to a recent Han Chinese panel. Finally, genetic associations of HLA variants with mild skin rash were performed on the combined sample of 408 patients. Common SNPs rs2571375 and rs144295468 were found to successfully tag HLA risk alleles A*31:01 and B*13:01, respectively. HLA-B*15:02 can be predicted by rs144012689 with >95% sensitivity and specificity. The imputation reference panel for the Hong Kong population had comparable performance to the Han Chinese panel due to the large sample size for common HLA alleles, though it retained discordance for imputing rare alleles. No significant genetic associations were found between HLA genetic variants and mild skin rash induced by aromatic antiepileptic drugs. This study provides new information on the genetic structure of HLA regions in the Hong Kong population by identifying tagging SNPs and serving as a reference panel. Moreover, our comprehensive genetic analyses revealed no significant association between HLA alleles and mild skin rash in Hong Kong Han Chinese.

Levofloxacin-induced bullous fixed drug eruption: A rare case report

Drug-induced cutaneous adverse drug reactions are very much common, especially with antibiotics. Fluoroquinolones are widely used antibiotics for different types of infective conditions. However, dermatological adverse drug reactions to this category of antibiotics are very rare but many times fatal. Bullous fixed drug eruption (FDE), being one of them, is very important to watch for. Here, we are reporting levofloxacin-induced bullous FDE in elderly hypertensive patient.

Amoxicillin induced toxic epidermal necrolysis: a case report

Adverse reactions are the recognized hazards of drug therapy and they can occur with any class of drugs and many studies revealed that the incidence is more in case of antibiotics. Amoxicillin is a broad spectrum, bactericidal, beta lactam antibiotic, commonly used to combat various infections. Penicillin group of drugs are known to cause cutaneous drug eruptions especially in paediatric population. Most of the time, these eruptions are mild in nature, however, sometimes they represent the early manifestation of rare, severe drug-induced cutaneous reactions, such as Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). Toxic epidermal necrolysis (TEN) is a rare, life threatening dermatological disorder that is usually induced by medications. Seventy percent of the cases of TEN are drug induced, most commonly implicated drugs being anticonvulsants, antibiotics and non-steroidalanti-inflammatory drugs (NSAIDS). Here, we report a case of toxic epidermal necrolysis induced by amoxicillin in a 12 year old male patient. Treatment with strong antibiotics, immunosuppressant and other supportive measures helped in recovery of the patient. The case is being reported to emphasize the need for efficient pharmacovigilance in order to motivate adverse drug reaction reporting so as to gather more and more data regarding adverse drug reactions. Through this report, we also seek the support of every-one concerned, to detect and, if possible, prevent adverse reactions to drugs.

HLA Allele Frequencies in 5802 Koreans: Varied Allele Types Associated with SJS/TEN According to Culprit Drugs.

PurposeStevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are very serious forms of drug-induced cutaneous adverse reaction. SJS/TEN induced by certain drug is well known to be associated with some human leukocyte antigen (HLA) gene type. We aimed to explore HLA allele frequencies and their association with SJS/TEN according to culprit drugs in Korea.Materials and MethodsWe enrolled 5802 subjects who had results of HLA typing test from August 2005 to July 2014. Total 28 SJS/TEN patients were categorized based on culprit drugs (allopurinol, lamotrigine, carbamazepine) and identified the presence of HLA-B*58:01, HLA-B*44:03, HLA-B*15:02, and HLA-A*31:01.ResultsHLA-A*24:02 (20.5%), HLA-B*44:03 (10.0%), and HLA-Cw*01:02 (17.1%) were the most frequent type in HLA-A, -B, and -C genes, respectively. Allele frequencies of HLA-B*58:01, HLA-B*44:03, HLA-A*31:01, and HLA-B*15:02 were 7.0%, 10.0%, 5.0%, and 0.3%, respectively. In 958 allopurinol users, 9 subjects (0.9%) were diagnosed with SJS/TEN. Among them, 8 subjects possessed HLA-B*58:01 allele. SJS/TEN induced by allopurinol was more frequently developed in subjects with HLA-B*58:01 than in subjects without it [odds ratio: 57.4; confidence interval (CI) 7.12-463.50; p<0.001]. Allopurinol treatment, based on screening by HLA-B*58:01 genotyping, could be more cost-effective than that not based on screening. HLA-B*44:03 may be associated with lamotrigine-induced SJS/TEN (odds ratio: 12.75; CI 1.03-157.14; p=0.053). Among carbamazepine users, only two patients experienced SJS/TEN and possessed neither HLA-B*15:02 nor HLA-A*31:03.ConclusionHLA gene frequencies varied in Korea. Screening of HLA-B*58:01 before the use of allopurinol might be needed to anticipate probability of SJS/TEN.

Rash in lapatinib-treated patients is not associated with human leukocyte antigen polymorphisms.

Rash is a common side effect of lapatinib treatment. Since human leukocyte antigen (HLA) alleles have been implicated in multiple drug-induced cutaneous reactions, this study investigated the association of HLA alleles with lapatinib-induced rash. 1191 participants from a large lapatinib monotherapy trial underwent HLA genotyping, and allele carriage frequencies between rash cases and controls were compared. This analysis had adequate power to detect an association of common HLA alleles with rash, similar to those reported previously. No HLA alleles were significantly associated with lapatinib-induced rash, including the previously identified lapatinib hepatotoxicity biomarker HLA-DRB1*07:01 (p = 0.87). The present study is consistent with the view that lapatinib-induced rash is not the consequence of HLA-restricted, immune-mediated mechanisms.