Cutaneous Drug Reactions Research Articles

Pharmacogenomic Advances in the Prediction and Prevention of Cutaneous Idiosyncratic Drug Reactions.

Cutaneous idiosyncratic drug reactions (CIDRs) are usually unpredictable, ranging from mild maculopapular exanthema (MPE) to severe cutaneous adverse drug reactions (SCARs) such as drug reaction with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN). Increasing evidence suggests that HLA alleles are strongly associated with drug-induced-CIDRs. The pathomechanisms for CIDRs include genetic polymorphisms affecting complex immune-specific HLA/drug antigen/T-cell receptor interactions and drug metabolism. Pharmacogenomic tests to prevent CIDRs have been widely implemented in clinical practice in recent years.

Rash diagnostics: an update on the diagnosis of allergic rashes.

The purpose of this review is to summarize recent research regarding the diagnosis of allergic rashes and to suggest future directions for the promotion of accurate diagnosis and endotype specification. Multiple cohort studies demonstrate that with appropriate clinical evaluation, drug allergy labels can be removed in up to 90% of cases. Genetic tests can predict severe adverse cutaneous drug reactions in some cases and in vitro tests are being sought to identify causative drugs in others. Biomarkers to define endotypes of atopic dermatitis are needed to predict which patients will benefit from evolving targeted therapies. Hyperspectral imaging is a rapidly evolving technology in medical diagnostics; additional research is needed to demonstrate whether this promising technology can be used to distinguish allergic rashes and/or endotypes in atopic dermatitis. Diagnostic tools for the assessment of allergic rashes are primitive in that they frequently rely on challenges to ascertain whether suspected allergens were causative. Validated in vitro tests with high sensitivity and specificity for drug allergies would benefit the field, particularly in delayed type reactions, as would identification of any hyperspectral signatures that could identify endotypes in atopic dermatitis.

Adverse Cutaneous Drug Reactions in Paediatric patients in a Tertiary Care Hospital-Study of causality, preventability and severity

Adverse Cutaneous Drug Reactions in Paediatric patients in a Tertiary Care Hospital-Study of causality, preventability and severity

Comparative analysis of cutaneous drug reactions among different fluoroquinolones: an experimental study

Background: Fluoroquinolones are generally well tolerated; most adverse effects are mild and common are GI upset. But recent literatures suggest increase reports of Cutaneous Drug reactions (CDRs) including SJS with Fluoroquinolones. However there is insufficient data both in animal and clinical study regarding comparative Analysis of CDRs among different Fluoroquinolones. Hence the present study was under taken to evaluate incidence of comparative CDRs among different Fluoroquinolones.Methods: 96 Albino mice were divided into 16 groups of 6 each. Ciprofloxacin, Ofloxacin, Levofloxacin and Moxifloxacin were administered in Group 1-4, 5-8, 9-12 and 13-16 at the dose of 50/100/150/200mg/kg respectively. The following parameters were observed i.e. Number and % of mice developed CDRs with type and severity. Duration of exposure till development of CDRs, time to Recovery and Mortality in each group.Results: Ofloxacin produced maximum number of CDRs i.e. in 33.3% mice which was significantly higher than that with levofloxacin (p=0.006*). The incidence of CDRs with Ciprofloxacin was 16.67 % and Moxifloxacin16.67 %, but no statistically significant difference than Ofloxacin. The onset for CDRs was significantly earlier with Ofloxacin among the Fluoroquinolones (P=0.013*). The reactions varied from severe dermatitis to serious exfoliation of the skin with ofloxacin and Ciprofloxacin, Alopecia with Moxifloxacin but no cutaneous reactions to Levofloxacin. Mortality was found only with Ofloxacin (12.5%).Conclusions: CDRs are common and may present as severe skin exfoliation or Alopecia with Fluoroquinolones. The CDRs are Maximum with Ofloxacin without significant difference from ciprofloxacin but significantly higher than levofloxacin which has least potential for CDRs. Fatality may occur with Ofloxacin.

Rabeprazole induced Fixed Drug Eruption: A rare case report

Among cutaneous adverse drug reactions, fixed drug eruption is the most common cutaneous drug reaction among the Indian population. The drugsmost commonly implicated in fixed drug eruption are analgesics and antibiotics. Here, we report a case of fixed drug reaction caused by rabeprazole.Keywords: Fixed drug eruption, Rabeprazole, Proton-pump Inhibitor, Naranjo’s scale.

A study of cutaneous adverse drug reactions in the outpatient department of Dermatology at a tertiary care center in Gujarat, India

Background: The data for adverse cutaneous drug reactions (ACDRs) is limited in Gujarat. The ACDRs are one of the frequent ADRs and cause of significant morbidity and mortality in patients of all areas of healthcare today. They are responsible for significant number of hospital admissions. Thus, the present study emphasises on the need and importance of an effective pharmacovigilance programme.Methods: A prospective study was undertaken in a 183 cases tertiary care teaching hospital of India. Male to female ratio, most common class of drug, individual drug causing ACDR, common types of ACDRs Parameters were studied. Other Parameters like Causality, preventability and severe or non-severe reactions were analyzed.Results: Majority of the patients (48%) with CADR belonged to the age group 25-44 followed by 45-64 (28%). Most frequent adverse cutaneous drug reactions reported were Urticaria (40%), Maculopapular rash (25%) & Fixed drug eruptions (21%) in decreasing order of frequency. Majority of reactions (96%) were Bizarre/Unpredictable in nature. As a group, antimicrobials (46%) were most frequently associated with CADR followed by NSAIDs (31%) and antiepileptics (11%). Most of the reactions (93%) were mild-moderate and probable (77%) in nature. Approximately 60% of ACDRs reported in this study were preventable.Conclusions: There was slight male preponderance except acneiform eruptions. Cotrimoxazole being the most common offending drug then after Ibuprofen, Phenytoin among the anti-inflammatory, analgesics, antiepileptics class. Causality assessment resulted in high score 77% of probable category.

A clinical study of cutaneous adverse drug reactions

Background: Adverse cutaneous drug reactions pose a diagnostic challenge due to a myriad of clinical manifestations and wide variety of causative agents. Present study aims to record various clinical patterns of adverse drug reactions, their causative agents and to study the pattern of morbidity and mortality in patients with severe cutaneous adverse drug reactions.Methods: 150 patients with adverse cutaneous drug reactions were included who came to Department of Dermatology, Venereology and Leprosy at PDU Govt. Medical College and Hospital, Rajkot, Gujarat from September 2009 to September 2011. Thorough history with all routine haematological and biochemical investigations, septic screening were done. HIV testing was done in severe reactions. Appropriate specific treatment was given with counselling regarding the offending drug.Results: The most common age group was 21-30 years (26.67%) with male to female ratio being 0.92:1. Morbilliform rash was the most common clinical type (42.67%) in both HIV reactive and non-reactive patients. Antimicrobials were the most common group (29.33%) and nevirapine was the most common offending drug (27.33%). Mortality rate was 2% (3 out of 150 cases) and all the patients were of toxic epidermal necrolysis.Conclusions: The pattern of cutaneous adverse drug reactions and the causative drugs are remarkably different in our study. Knowledge of the pattern and the causative agent helps in better management and reduced consequences in these patients particularly in severe adverse cutaneous drug reactions.

Prevalence and pattern of adverse cutaneous drug reactions presenting to a tertiary care hospital

<p class="abstract"><strong>Background:</strong> An adverse cutaneous drug reaction (ACDR) is defined as an undesirable clinical manifestation resulting from administration of a particular drug. With an ever increasing number of drugs and varied formulations being continuously made available it is important that a close watch on the risks of adverse drug reactions is looked for, to ensure safe use of medicines in the interest of the patient. In the present study our aim is to study the prevalence & pattern of cutaneous adverse drug reactions reported to department of dermatology at MediCiti Institute of Medical Sciences, Hyderabad, India<span lang="EN-IN">.</span></p><p class="abstract"><strong>Methods:</strong> All suspected cutaneous adverse drug reactions reported to the department of dermatology at MediCiti Institute of Medical Sciences during the two year period from January 2013 to December 2014 were included in this study. A thorough clinical examination of all these cases & details related to the drug use and clinical manifestations of the cutaneous adverse drug reaction were documented using a structured proforma. Naranjo scale was used to assess causality in all the causes of cutaneous adverse drug reactions.<strong></strong></p><p class="abstract"><strong>Results:</strong> The mean age of the patients was 42 years (age range: 1-64 years). Most of them were in the age group of 30-39 years. The male to female ratio was 1.78:1. The most common type of skin eruptions observed were maculopapular rash (35.55%), urticaria (26.19%) and fixed drug eruption (17.87%). The mean duration between drug intake and appearance of rash was 4 days (range: 1-120 days)<span lang="EN-IN">. </span></p><p class="abstract"><strong>Conclusions:</strong> The pattern of ACDRs and the drugs causing them in this study were similar to that reported in other studies both in terms of disease burden and clinical pattern. Knowledge of adverse cutaneous drug reactions will help to identify common medications contributing to dermatological reactions, so as to anticipate, prevent and limit their undue consequences<span lang="EN-IN">.</span></p>

A Retrospective Study of Drug Induced Cutaneous Adverse Reactions (CADR) in Patients Attending a Tertiary Care Hospital

Objectives: Find possible causative agents causing cutaneous adverse reactions; clinical patterns, causality and severity of Drug induced cutaneous adverse reactions (CADR) and treatment outcome. Keywords: Adverse cutaneous drug reactions, Antimicrobials, NSAIDS, Urticaria.

Patch tests: not a useful tool in diagnosing adverse cutaneous drug reactions

Summary Cutaneous adverse drug reactions are common in India. We invited this review on the use of patch tests to diagnose these reactions. The findings show that patch tests are of limited value in diagnosing cutaneous adverse drug reactions.

Generalized bullous fixed drug eruption treated with cyclosporine

Fixed drug eruptions (FDE) comprise 10 percent of alladverse cutaneous drug reactions and generalizedbullous fixed drug eruptions (GBFDE) are a raresubset of FDEs. We present a patient with severeGBFDE caused by ibuprofen successfully treated withcyclosporine. Further work is needed to determine ifcyclosporine can be an effective therapy for GBFDE.

Patch testing and cross sensitivity study of adverse cutaneous drug reactions due to anticonvulsants: A preliminary report.

AIMTo evaluate the utility of patch test and cross-sensitivity patterns in patients with adverse cutaneous drug reactions (ACDR) from common anticonvulsants.METHODSTwenty-four (M:F = 13:11) patients aged 18-75 years with ACDR from anticonvulsants were patch tested 3-27 mo after complete recovery using carbamazepine, phenytoin, phenobarbitone, lamotrigine, and sodium valproate in 10%, 20% and 30% conc. in pet. after informed consent. Positive reactions persisting on D3 and D4 were considered significant.RESULTSClinical patterns were exanthematous drug rash with or without systemic involvement (DRESS) in 18 (75%), Stevens-Johnsons syndrome/toxic epidermal necrolysis (SJS/TEN) overlap and TEN in 2 (8.3%) patients each, SJS and lichenoid drug eruption in 1 (4.2%) patient each, respectively. The implicated drugs were phenytoin in 14 (58.3%), carbamazepine in 9 (37.5%), phenobarbitone in 2 (8.3%), and lamotrigine in 1 (4.7%) patients, respectively. Twelve (50%) patients elicited positive reactions to implicated drugs; carbamazepine in 6 (50%), phenytoin alone in 4 (33.3%), phenobarbitone alone in 1 (8.3%), and both phenytoin and phenobarbitone in 1 (8.33%) patients, respectively. Cross-reactions occurred in 11 (92%) patients. Six patients with carbamazepine positive patch test reaction showed cross sensitivity with phenobarbitone, sodium valproate and/or lamotrigine. Three (75%) patients among positive phenytoin patch test reactions had cross reactions with phenobarbitone, lamotrigine, and/or valproate.CONCLUSIONCarbamazepine remains the commonest anticonvulsant causing ACDRs and cross-reactions with other anticonvulsants are possible. Drug patch testing appears useful in DRESS for drug imputability and cross-reactions established clinically.

A study of fixed-drug reactions at a rural-based tertiary care center, Gujarat

Context: Adverse cutaneous drug reactions (ACDRs) are very common due to a wide variety of drugs available in markets. Fixed-drug reaction (FDR) is a type of ACDR that dermatologists are facing frequently nowadays. There is a need to identify various drugs responsible for FDR and to ensure the safety of the patients with proper counseling. Aim and Objective: The aim and objective was to study the demographic details, clinical patterns, and the offending drugs causing FDR. Setting and Design: This was a cross-sectional, observational study. Materials and Methods: The study was carried out from April 2010 to March 2015 in the Department of Dermatology at a rural-based tertiary care center of Gujarat, India, after taking approval from the hospital's research ethical committee. A detailed history taking and thorough clinical examination were done for all the patients having FDR and were recorded in a predesigned pro forma. Analysis was done using frequencies, proportions, and Chi-square test. All the patients were educated regarding ACDRs and given a list of drugs causing FDR to avoid recurrence. Results: A total of 59 patients were studied for FDR among which 32 (54.23%) were males and 27 (45.76%) were females. Fever (20.34%) was the most common illness for which patients had taken the culprit drug. Antimicrobials (26 [44.07%]) were the most common group of drugs causing FDR followed by nonsteroidal anti-inflammatory drugs (21 [35.59%]). As a single molecule, diclofenac was the most common drug causing FDR followed by metronidazole 5 (8.47%) and cotrimoxazole, fluconazole, and ciprofloxacin 4 (6.78%) each. The most common complaint following intake of the culprit drug was pigmented patch (31 [52.54%]) followed by blisters (13 [22.03%]). Conclusion: FDR is one of the important ACDRs seen in patients. Antimicrobials are the most common group while diclofenac is the most common drug causing FDR.

Pityriasis lichenoides-like drug reaction: A clinical histopathologic study of 10 cases

Lymphomatoid drug reactions can mimic endogenous T and B cell lymphoproliferative diseases. We present a novel form of cutaneous drug reaction with features of pityriasis lichenoides (PL), a recognized form of T cell dyscrasia. Ten cases were studied where a cutaneous eruption exhibiting semblance to PL within a few weeks to months after starting a particular drug. The patient cohort comprised 7 females and 3 males with the mean age of 60 years. Widely distributederythematous cutaneous lesions were present in 6 cases whereas a more localized distribution was seen in three cases. The most frequently implicated drugsassociated with the eruption were antidepressants and statins. Histologic examination showed a morphologic picture identical to PL including marked epitheliotropism of mildly atypical lymphocytes, psoriasiform epidermal hyperplasia, dyskeratosis, hemorrhage, and a thick parakeratotic scale. Therewas a significant reduction in the expression of CD7 and CD62L amid the T cells. Regression of the eruption occurred in all cases excluding one. Thefindings conform the categorization of this process as a form of T-cell dyscrasia albeit one that is reversible, dependent on the drug withdrawal. The limitationof our study includes the retrospective design of the study.

Cutaneous drug reactions notified by ADR monitoring centre in a tertiary care hospital of Bihar

Background: Cutaneous drug reactions are most frequent drug related adverse events which lead to early treatment discontinuations, high treatment cost and leading cause of morbidity and mortality. The aim of this study is to analyze the clinical patterns and offending drugs as well as their causality, severity and preventive strategies.Methods: All adverse drug reactions (ADRs) forms filled from May 2015 to April 2016 were scrutinized and forms with cutaneous drug reactions were analyzed and assessed for causality, severity and preventability.Results: Out of 300 ADR forms, 160 (53.34%) included cutaneous drug reactions. 68 (42.50%) patients were male and 92 (57.50%) were female. Maculopapular rash 58 (36.25%), fixed drug eruption (FDE) 31 (19.37), pruritus 27 (16.87%) and urticaria 19 (11.87%) were the common clinical patterns of cutaneous drug reactions. Most common offending drug classes included antibiotics, anti-inflammatory and steroidal agents. Causality assessment was done by using Naranjo’s algorithm. The result showed that out of 160 cutaneous drug reactions 141 (88.12%) ADRs were probable, 15 (9.37%) were classified as possible; 2 (1.25) doubtful and 2 (1.25%) were definitely related to the drug.Conclusions: The present study shows cutaneous drug reactions are commonly reported at ADR monitoring centre of this tertiary care hospital. Our study suggests that there is a need of intensive monitoring for ADRs in tertiary care hospital for early detection and to ensure the patient safety.

Histopathological study of six types of adverse cutaneous drug reactions using granulysin expression.

Few studies have been published on the histopathology of cutaneous adverse drug reactions (CADR), and most of these lack information on skin allergological tests. The histopathology of drug reaction with eosinophilia and systemic symptoms (DRESS) is also seldom described. The purpose of our study was to examine six types of well-documented CADR (maculopapular exanthema, DRESS, fixed drug eruption, Stevens-Johnson syndrome, toxic epidermal necrolysis [TEN], and acute generalized exanthematous pustulosis) using histopathology and immunohistochemistry to evaluate the expression of granulysin, a key molecule in TEN. We retrospectively included 106 skin biopsies performed in proven cases of CADR (by chronological investigation, single attributable drug, or/and skin tests). All slides were reviewed, and microscopic changes were analyzed using a standardized form. Granulysin expression was studied by immunohistochemistry. In DRESS, we observed spongiosis, edema, and basal vacuolization, with rare necrotic keratinocytes and constant lymphocytic infiltrate in the superficial dermis. Eosinophils were often present, and pustules were found in 15% of cases. Necrotic keratinocytes are often absent in maculopapular exanthema. Granulysin was expressed in six types of CADR with a trend toward more intense expression in DRESS and TEN. We detailed further about the histopathology of DRESS. Granulysin expression was observed in all CADR with a marked overlap of expression pattern between the six types.

Stevens-Johnson syndrome and toxic epidermal necrolysis: a review.

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are uncommon, acute and potentially life-threatening adverse cutaneous drug reactions. These pathologies are considered a hypersensitivity reaction and can be triggered by drugs, infections and malignancies. The drugs most often involved are allopurinol, some antibiotics, including sulfonamides, anticonvulsants such as carbamazepine, and some non-steroid anti-inflammatory drugs (NSAIDs). Necrosis of keratinocytes is manifested clinically by epidermal detachment, leading to scalded skin appearance. The rash begins on the trunk with subsequent generalization, usually sparing the palmoplantar areas. Macular lesions become purplish, and epidermal detachment occurs, resulting in flaccid blisters that converge and break, resulting in extensive sloughing of necrotic skin. Nikolsky's sign is positive in perilesional skin. SJS and TEN are considered to be two ends of the spectrum of one disease, differing only by their extent of skin detachment. Management of patients with SJS or TEN requires three measures: removal of the offending drug, particularly drugs known to be high-risk; supportive measures and active interventions. Early diagnosis of the disease, recognition of the causal agent and the immediate withdrawal of the drug are the most important actions, as the course of the disease is often rapid and fatal.

Practice Gaps: Drug Reactions.

The term "drug reactions" is relevant to dermatology in three categories of reactions: cutaneous drug reactions without systemic features, cutaneous drug reactions with systemic features, and systemic drugs prescribed by the dermatologist with systematic adverse effects. This article uses examples from each of these categories to illustrate several important principles central to drug reaction diagnosis and management. The information presented will help clinicians attain the highest possible level of certainty before making clinical decisions.

Histopathological evidence of involvement of eccrine sweat glands in adverse cutaneous drug reactions

Histopathological evidence of involvement of eccrine sweat glands in adverse cutaneous drug reactions

Pharmacovigilance of cutaneous drug reactions: A prospective observational study

Objective: To determine the frequency, severity and morphological pattern of ACDRs and their correlation with various risk factors.Methodology: A prospective, observational study was conducted in Muzaffarnagar Medical College & hospital, Muzaffarnagar Uttar Pradesh from Feb 2013 to Jan 2014 for one year. All patients of either sex and all age groups with suspected ACDRs attending/referred to Dermatology department were included.Results: Total of 90 cases were reported over a period of one year. ACDRs were observed with 0.5% incidence of patients attending OPD. ACDRs were commonly seen in adult age group (mean age 36.93 yrs) and have 3 or more drugs prescribed with equal gender distribution. As per Naranjo Algorithm, maximum number of ACDRs were of Possible type (74%), while 23 cases were of Probable category with female and male preponderance respectively. 71 of ACDRs were Moderate in severity (79%) followed by 11% of mild and 10% of severe category. Most common clinical pattern was Urticaria with 32 cases followed by 24 cases of Maculopapular Eruptions, 9 cases of Acneiform eruptions and 8 of fixed drug reactions and SJ Syndrome. Commonest Drug groups causing ACDRs were Antibiotics (38%) and Antiepileptics (30%).This was followed by NSAIDs induced ACDRs (9%). Phenytoin was the most common drug causing 12 ACDRs followed by 6 with Cabamazipine and Ceftrixone each and 5 cases with ATT.Conclusion: Incidence was low as compare to global incidence; better steps must be needed to strengthen the activity of pharmacovigilance in this state of the country.