Drug Reaction Eosinophilia And Systemic Symptoms Research Articles

Pirfenidone Induced Dress Syndrome Post COVID-19 InfectionAn Unusual Case Report

Drug Reaction, Eosinophilia and Systemic Symptoms (DRESS) is an idiosyncratic drug reaction characterised by extensive skin rash, fever, lymphadenopathy and internal organ involvement. Since eosinophilia may or may not always be present, the condition is now more preferably called Drug-Induced Hypersensitivity Syndrome (DIHS). The authors here report a case of DRESS syndrome, secondary to Pirfenidone, an anti-fibrotic given to the patient for post COVID-19 fibrosis. The 51 years old male patient, presented with multiple pus-filled erythematous lesions, 3 months after the initiation of Pirfenidone. Laboratory results showed deranged liver and renal functioning, along with reactive Dengue Nonstructural protein 1(NS 1) antigen. He showed significant improvement in the dermatological lesions and multisystem laboratory involvement with tapering doses of steroids.

Allopurinol: Attention to the Prescription!

Allopurinol is a commun hypo-uricemic drug. However, it is main drug reported to be inducing toxidermy. Our goal is to encourage limiting the prescription of this drug and to reserve it for justified cases after some observations. A Retrospective study was conducted in the Dermatology department between 2012 and 2019. We collected all toxidermy cases following Allopurinol. During the study period,39 cases of severe Allopurinol toxidermia, including 22 women and 17 men, a sex ratio of 0.77. The average age was 65 years old. Most of the patients were "poly-medicated". The average time between medication and clinical symptoms was 28.25 days. Clinical manifestations were: macula-papular rash in 12 cases (30%), erythroderma in 14 cases (35%), purpura in 7 cases (17%) and mucosal involvement in 20 cases. Fever in 29 cases, a state of shock in 5 cases. 10 patients required a transfer in intensive care. On the balance sheet; eosinophilia was found in 23 cases, 18 cases of hepatic cytolysis, CPK mb was elevated in 17 cases, acute renal failure in 24 cases. The biopsy was performed in all cases confirming the toxidermy. The Drug reaction eosinophilia and systemic symptoms (DRESS) retained in 29 cases, Stevens-Johnson syndrome (SJS) in 2 cases, Lyell in 4 cases. The management involved stopping the incriminated drug (Allopurinol) and the introduction of an antihistamine and an emollient were prescribed in all patients. Topical steroid in 21 patients. Oral corticosteroid therapy in 14 patients. A bolus of corticosteroid was administered in 4 patients. The evolution was good for 30 patients (77%). However, we recorded 9 deaths in a context of septic shock and multi-visceral failure. In our series, Allopurinol was the cause of severe toxidermia including Lyell syndrome, StevensJohnson and DRESS syndrome. The severity of these diseases should encourage preserving it for the justified cases, and knowing how to adapt the dosage to the renal function, to introduce the treatment in a progressive way and to stop the treatment in case of less signs of toxidermy. The control of the use of this molecule would reduce the cases of this disease.

Association of cutaneous adverse drug reactions due to antiepileptic drugs with HLA alleles in a North Indian population

PurposeAromatic antiepileptic drugs (AEDs) are frequently implicated in cutaneous adverse drug reactions (cADRs), a few of which are associated with certain human leukocyte antigen (HLA) alleles in some populations. We aimed to find HLA-associations with AED-related cADRs among North Indians. MethodsNorth Indian subjects with cADR due to an AED, and those who were AED-tolerant were recruited as cases and controls, respectively. Genotyping for HLA-A, B and DRB1 were performed. Statistical analysis to compare carrier-rates and allele-frequencies between cases and controls (and healthy population, where necessary), was done for HLA-alleles occurring more than twice in either group. Results120 cases {11 - Lamotrigine (LTG), 14 -Valproic acid (VPA), 8 -Levetiracetam (LEV), 35 -Carbamazepine (CBZ) and 52 - Phenytoin (PHT)}, and 250 controls were recruited. Presence of HLA-A*31:01 and HLA-B*51:01 were found to increase the risk of Maculopapular exanthema (MPE) due to CBZ and PHT (OR = 6.38; 95% CI: 1.46–27.75; OR = 4.60; 95% CI: 1.54–13.72, respectively). Among the severe cADRs, HLA-B*57:01(OR = 11.00 95% CI: 1.41–85.81) and HLA-DRB1*07:01 (OR = 7.25; 95% CI: 1.09–48.18) were noted to be significantly associated with CBZ-induced Stevens Johnson Syndrome (SJS)/Toxic Epidermal Necrolysis (TEN); HLA-B *51:01 was associated with drug reaction eosinophilia and systemic symptoms (DRESS) caused by PHT (OR = 6.90; 95% CI: 1.38–34.29). ConclusionsWe found significant associations of some HLA alleles with specific cADRs to CBZ and PHT in North Indians, which may need to be tested before AED-initiation; only screening for HLA-B*15:02 may not help in this population.

Pattern of adverse drug reaction to antiepileptic drugs in a tertiary care hospital

Background: Adverse drug reactions (ADRs) are a major cause of morbidity and mortality, and are the leading cause of hospital admission. The overall rate of ADRs is estimated to be 6.5% and 28% of these ADRs are preventable. Antiepileptic drugs (AEDs) are authorized for several therapeutic indications and are highly prescribed. ADRs due to AEDs range from minor maculopapular exanthem (MPE) to severe life-threatening reactions like Drug reaction eosinophilia and systemic symptoms (DRESS) and Stevens-Johnson syndrome (SJS). Objective of the study was to evaluate the pattern of ADRs reported with AEDs in an adverse drug reaction monitoring centre (AMC) of a tertiary care hospital.Methods: Retrospective analysis of the records was done for a period 48 months from January 2013 to December 2016. During this period, all the ADRs caused by AEDs reported to the AMC were included in the study. The study evaluated the pattern of ADRs due to AEDs. The study also assessed the gender-wise distribution, predilection for various systems, causality, severity, and preventability of ADRs. Data was analysed using descriptive statistics.Results: A total of 319 ADRs were reported by spontaneous reporting during the entire study period. Out of the total 319 ADR reports received, antiepileptic drugs related ADRs were 35 (11%). Antiepileptic drugs which caused the ADRs included phenytoin, carbamazepine, clobazam and lorazepam. The most common system affected was dermatological (60%), followed by gastrointestinal system (17.14%), vascular system (11.42%), blood (5.8%), respiratory system (5.8%) and central nervous system (2.9%). Among the dermatological ADRs, SJS accounted for 11 cases of which 10 cases were due to phenytoin and one case was due to carbamazepine. DRESS syndrome due to phenytoin was documented in one case.Conclusions: AEDs are the most commonly prescribed drugs for various indications. Uses of AEDs are accompanied by ADRs which vary from mild rashes and itching to SJS and DRESS/TEN. Post-marketing surveillance of the AEDs is important for compliance, therapeutic efficacy and ultimately safety of the patient.

Spectrum of Cutaneous Adverse Reactions to Levetiracetam and Human Leukocyte Antigen Typing in North-Indian Patients.

Background and PurposeAromatic antiepileptic drugs are frequently implicated for cutaneous adverse drug reactions (cADRs); there are case-reports of even severe reactions like drug reaction eosinophilia and systemic symptoms (DRESS) and Stevens Johnson syndrome (SJS)-toxic epidermal necrolysis with Levetiracetam (LEV). Certain human leukocyte antigen (HLA)-alleles have strong association with cADRs due to specific drugs - HLA-B*15:02 and HLA-A*31:01 in Carbamazepine (CBZ)-related SJS in Han-Chinese and European populations, respectively. Here, the spectrum of cADRs to LEV was studied, and HLA-typing in patients with cADRs due to LEV and some who were LEV-tolerant was performed, in an attempt to find an association between HLA and such reactions.Methods589 patients taking LEV were screened for skin reactions, and eight patients with LEV-related cADRs and 25 LEV-tolerant controls were recruited - all 33 of North Indian ethnicity, their HLA-A, B, DRB1 genotyping done. Statistical analysis was done to compare carrier-rates and allele-frequencies of HLA-alleles between cases and controls (and healthy population, where necessary) for alleles occurring more than two times in either group.ResultsOut of 589 patients on LEV screened, there were 8 cases of cADR: 5 with maculopapular exanthema (MPE), 2 of SJS, and 1 with DRESS. Although HLA-A*33:01 was seen to occur more in MPE cases as compared to tolerant controls, the difference was not statistically significant (odds ratio [OR] 6.00, 95% confidence interval [CI] 0.30–116.6; p = 0.31). HLA A*11:01 and 24:02 were found to occur more in LEV-tolerant controls than in cases (OR 0.23 [95% CI 0.02–2.36, p = 0.33] and 1.00 [95% CI 0.09–11.02, p = 1.00] respectively).ConclusionsCutaneous reactions to LEV are very unusual, and their association with HLA in North-Indian population was not statistically significant.

Drug Reaction, Eosinophilia, and Systemic Symptoms (DRESS) syndrome associated with allopurinol leading to acute necrotizing eosinophilic myocarditis and death due to papillary muscle rupture

Drug Reaction, Eosinophilia, and Systemic Symptoms (DRESS) syndrome associated with allopurinol leading to acute necrotizing eosinophilic myocarditis and death due to papillary muscle rupture

HLA-B*58:01is a risk factor for allopurinol-induced DRESS and Stevens-Johnson syndrome/toxic epidermal necrolysis in a Portuguese population

HLA-B*58:01 is associated with allopurinol-induced severe cutaneous adverse drug reactions (sCADR) particularly in Han Chinese, but the risk in European populations has seldom been studied. To study the association of HLA-B*58:01 with allopurinol-induced sCADR in a Portuguese population. We studied 25 patients (11 male/14 female, mean age 67·4 years) with sCARD from allopurinol: 19 DRESS (drug reaction eosinophilia and systemic symptoms) and six Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN). HLA was genotyped by reverse sequence-specific oligonucleotide-polymerase chain reaction and results compared statistically with a control group of 23 allopurinol-tolerant individuals and the control population. HLA-B*58:01 was present in 16 patients with sCADR (64%) [12 DRESS (63%), four SJS/TEN (67%)], one allopurinol-tolerant individual (4%) and 63 normal controls (1·96%), with a statistically significant difference between sCADR and the two control groups. When compared with the normal population, HLA-B*58:01 was associated with a higher risk of sCADR, both DRESS [odds ratio (OR) 85·36, 95% confidence interval (CI) 32·52-224·04] and SJS/TEN (OR 99·59, 95% CI 17·91-553·72). There was no statistically different risk between these two types of CADR. Portuguese patients with sCADR from allopurinol, both DRESS and SJS/TEN, have a high frequency of HLA-B*58:01, with an OR similar to European patients with SJS/TEN. This study also extends this association to DRESS in Europeans. The recommendation to genotype systematically before therapy is controversial, particularly when HLA-B*58:01 prevalence in the normal population is low, as in Europe. However it could be an option for patients with other risks factors.

Patch testing is an effective method for the diagnosis of carbamazepine‐induced drug reaction, eosinophilia and systemic symptoms (DRESS) syndrome in an 8‐year‐old girl

Drug reaction, eosinophilia and systemic symptoms (DRESS) is an acute and life-threatening disease, characterised by fever, rash and systemic symptoms, including lymphadenopathy, abnormal liver function, interstitial nephritis, pulmonary and cardiac infiltrates and haematological abnormalities with eosinophilia and atypical lymphocytes. The drugs mostly associated with DRESS are anticonvulsants, allopurinol, minocycline and sulfonamides. This syndrome is rarely seen in childhood even though a large number of children have anticonvulsant treatment. An 8-year-old girl was admitted with fever, lymphadenopathy and skin eruptions on her trunk. Her medical history was notable for epilepsy and carbamazepine treatment had been started 5 weeks previously. Laboratory studies showed a white cell count of 6200/µL (normal, 4100-11 200/µL) with 22% eosinophils and a γ-glutamyl transpeptidase level of 296 U/L (normal, 0-23 U/L). Laboratory tests for infections and collagen diseases were in the normal range. Persistence of fever and maculopapular eruption with generalised desquamation and the appearance of cheilitis and facial angioedema suggested a hypersensitivity reaction to carbamazepine. The carbamazepine was replaced with levetiracetam. All clinical symptoms improved within a week with corticosteroids and antihistamine treatment. Six weeks after complete recovery an epicutaneous patch test with carbamazepine was performed and a carbamazepine-induced positive skin reaction was observed at 48-h. Carbamazepine-induced DRESS syndrome is a rare entity in children. An epicutaneous patch test is a useful tool for identifying the inducing agent for the DRESS syndrome and for identifying a safe anticonvulsant drug.

Possible drug reaction, eosinophilia and systemic symptoms (DRESS) syndrome in an infant : letter

To the Editor: It was with interest I read the article on the DRESS syndrome in the December issue of SAJCH. The toxicology of Spirostachys africana is well recognised. Commonly known as tamboti, it produces copious milky latex which was apparently used in the treatment of the patient.

Possible drug reaction, eosinophilia and systemic symptoms (DRESS) syndrome in an infant from ingestion of Spirostachys africana complicated by measles co-infection

Drug reaction with eosinophilia and systemic symptoms (DRESS) is an adverse syndromic reaction to medications that is rare in infants. The pathognomonic signs are a rash, often morbilliform, spreading from an oedematous face to the torso and extremities, hypereosinophilia and organ involvement.

P01-362 - Dress induced by anti-epileptic drugs in the elderly population: delay in recognition

BackgroundIn the eldery population anti-epileptic drugs (AED) are used in epilepsy, neuralgiform pain, psychiatric disorders and behavioral problems in dementia. The prevalence of AED- treatment in the community is 1%; among nursing home residents 10%. A complex of adverse effects, known as Drug Reaction Eosinophilia and Systemic Symptoms (DRESS), is associated with several drugs, in particular AED. The incidence of DRESS syndrome is estimated between 1 in 1000 and 1 in 10000. DRESS syndrome has a high mortality rate (around 10%), primarily due to doctor's delay in recognition.Case reportsAs AED-induced DRESS syndrome is rarely described in elderly patients, we describe two with dementia-related behavioural problems, treated with carbamazepine. Both patients developed severe rash, eosinophilia and fever after three weeks of administration. Patient 1 also developed anemia, diarrhoea and delirium; Patient 2 suffered from a severe edema of arms and face. Initially the clinical presentation of inflammatory and hypersensitivity symptoms was attributed to several diseases and/or medication other than carbamazepine. After recognition of DRESS by carbamazepine and stopping this drug, both patients fully recovered.ConclusionsRecognition of DRESS syndrome induced by AED is difficult as the condition is rare, symptoms occur 1 to 8 weeks after start of treatment; there may be slow progression and similarity with infections and neoplastic disorders exists. Withdrawal of the offending drug is the primary treatment of the DRESS syndrome and patients relatives must be informed since the incidence of the DRESS syndrome is higher amongst first- degree relatives.

Carbamazepine-induced acute liver failure as part of the DRESS syndrome

Carbamazepine is a widely used drug. It is commonly associated with hepatic abnormalities, ranging from an asymptomatic rise in liver function tests to acute liver failure. The most severe reaction occurs as part of a generalised hypersensitivity reaction, also known as drug reaction, eosinophilia and systemic symptoms (DRESS). We describe a case of a young adult who presented with non-specific symptoms, which progressed to fulminant hepatic failure, displaying the hallmarks of DRESS. We highlight the need for awareness of such an association.