Severe DRESS with myocarditis secondary to naproxen/esomeprazole.

A man in his 60s presented with a widespread erythematous rash and associated chills, paraesthesia and haematuria. He had recently commenced naproxen/esomeprazole. Blood tests showed hypereosinophilia (0.73×109/L) and moderate acute kidney injury. Histology revealed parakeratosis, mild spongiosis with eosinophils. He developed acute coronary syndrome with rapid atrial fibrillation. Coronary angiogram was non-obstructive. Cardiac MRI (CMR) revealed acute myocarditis secondary to Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS). Naproxen/esomeprazole was discontinued, and he was supported with oral corticosteroids. A repeat CMR 3 months later showed resolution of myocarditis. Naproxen/esomeprazole is not a common offending drug. DRESS is a rare drug-induced hypersensitivity reaction with a mortality rate of 10%. The objective of this case report is to highlight the significant but rare cardiac complications that can ensue from DRESS, which warrant prompt recognition and withdrawal of the causative drug.

Clinical Presentation and Diagnosis of Drug Reaction with Eosinophilia and Systemic Symptoms (DReSS) in Children: A Scoping Review.

Effective treatment of drug reactions with eosinophilia and systemic symptoms (DReSS) requires early diagnosis and close monitoring. Diagnosing DReSS is especially challenging in children due to a low incidence rate, heterogeneous clinical presentation, and a lack of (pediatric) diagnostic criteria and clinical practice guidelines. We performed a scoping review, according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, to summarize the clinical presentation and diagnostic process of DReSS in children (aged 0-18 years). Data from 644 individuals showed that DReSS manifests differently in children compared to adults. Children have a higher number of organs involved, including higher rates of cardiac and respiratory involvement compared to adults. Children < 6 years of age appear more prone to develop neurologic symptoms. Conversely, eosinophilia, edema, and kidney involvement are less frequently observed in children. Anti-seizure medications are by far the most common causative drug class, but the range of implicated drugs increases as children get older. This study highlights that children with DReSS not only differ from adults but also that differences exist between children of different ages. As such, there is a need to establish pediatric-specific diagnostic criteria. These efforts will promote earlier diagnosis of DReSS and likely lead to improved clinical care offered to children and their families.

DRESS syndrome: More than just a rash.

ABSTRACT: Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is rare but carries significant mortality and morbidity, making early identification and definitive management crucial. The diagnosis of DRESS is made clinically and involves consideration of a broad list of differential diagnoses. Given variable clinical presentations among patients with DRESS syndrome, clinicians should look for common findings and other hallmarks of the syndrome while monitoring for known complications. Additionally, clinicians should maintain a high index of suspicion to avoid missing more mild presentations, such as in this case patient with DRESS syndrome minor.

DRESS syndrome with multiorgan involvement and HHV-6 reactivation in the absence of a drug trigger.

Drug reaction with eosinophilia and systemic symptoms (DRESS) is a severe drug reaction where patients present with fever, morbilliform rash and multiorgan manifestations, which may include acute renal failure, acute respiratory distress syndrome and eosinophilic myocarditis. We present a case of a 60-year-old woman with acute heart failure, DRESS syndrome features and human herpesvirus 6 reactivation in the absence of a drug trigger. She was diagnosed with eosinophilic myocarditis and successfully treated with corticosteroid therapy.

Pediatric drug reaction with eosinophilia and systemic symptoms: A 12-year retrospective study in a tertiary center.

Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a rare and severe adverse drug reaction involving multiple organs. Data on DRESS syndrome among children are currently limited. The purpose of this study was to determine the clinical features, causative drugs, systemic organ involvement, laboratory findings, disease severity score, and treatment outcomes in pediatric DRESS patients. The medical records of all pediatric DRESS patients, based on the RegiSCAR diagnostic criteria and admitted to King Chulalongkorn Memorial Hospital, Bangkok, Thailand from January 2010 to December 2021, were reviewed. Twenty-two cases were identified (males 54.5%) with a median age of 9.5 years. Anticonvulsants (54.5%) and antibiotics (27.3%) were the leading culprit drugs. Skin rash was reported in all cases, followed closely by liver involvement (95.5%). Eosinophilia and atypical lymphocytosis were identified in 54.5% and 31.8% of cases, respectively. The median latency period was 17.5 days. Liver enzyme elevation was detected at an average onset of 20.0 days and hepatocellular type was the most common pattern of liver injury. Nineteen patients (86.4%) were treated with systemic corticosteroids with prednisolone being the most prescribed medication. One case developed Graves' disease after DRESS and multiple relapses of DRESS. One case (4.5%) died due to refractory status epilepticus that was unrelated to DRESS. Anticonvulsants were the major cause of DRESS in pediatric patients. High suspicion for DRESS is crucial in patients receiving these drugs and presenting with fever, rash, and internal organ involvement.

DRESS Syndrome: Renal Involvement in Two Cases - A Comprehensive Analysis and Literature Review of Improved Diagnosis and Treatment.

BACKGROUND Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a rare hypersensitivity reaction involving the skin and various visceral organs; the kidneys are the second most affected organ. Many drugs are reported to be associated with DRESS, particularly antiepileptic agents and allopurinol. Certain human leukocyte antigen (HLA) haplotypes, in combination with a particular drug, can further contribute to an increased risk of DRESS. Symptoms often develop 2 to 8 weeks after drug initiation. If diagnosis is delayed, DRESS can be a life-threatening condition. CASE REPORT We present cases of 2 patients. The first patient was an 86-year-old Polish woman who developed acute kidney injury and skin lesions with accompanying leucocytosis and eosinophilia during long-term antibiotic therapy with piperacillin/tazobactam and ciprofloxacin. The second patient was a 37-year-old Asian woman with predialysis chronic renal disease stage V in the course of IgA nephropathy. Two weeks after starting allopurinol in a standard dose, she presented with maculopapular rash, facial edema, fever, liver injury, and eosinophilia. Renal function started to deteriorate, but she did not require dialysis. In both cases, the discontinuation of the above-mentioned drugs and the introduction of steroid therapy and intravenous immunoglobulins allowed for clinical improvement and recovery. In the second case, the extended 4-locus HLA typing was performed retrospectively, and allele HLA-B*5801 was found. CONCLUSIONS Due to the rare occurrence and heterogeneous manifestation of DRESS, its diagnosis can pose many difficulties. In-depth analysis of symptoms, medicines taken, and laboratory findings enable the implementation of appropriate treatment and recovery.

Paracetamol (Acetaminophen)-associated SJS, TEN, AGEP, and DRESS Syndromes - A Narrative Review.

INTRODUCTION: Paracetamol (Acetaminophen) is a very common OTC drug that is found in more than 200 OTC products sold as pain, cough and cold remedies. Paracetamol is commonly used as an antipyretic to reduce fever and as an alternative to Non-steroidal anti-inflammatory drugs (NSAIDs) that are contraindicated in certain patients to relieve mild-moderate pain. OBJECTIVE: This review article focuses on SJS, TEN, SJS/TEN overlap, AGEP, and DRESS syndromes associated with the use of paracetamol or paracetamol-containing products. METHODS: To find published articles relevant to paracetamol-associated SJS, TEN, AGEP, and DRESS, we searched the online databases Medline/Pubmed/PMC, Google Scholar, Science Direct, Ebsco, Scopus, Web of Science, Embase, and reference lists using keywords like Stevens-Johnson Syndrome, Acetaminophen, Paracetamol, Toxic epidermal necrolysis, Acute generalized exanthematous pustulosis, Drug reaction with eosinophilia and systemic symptoms. RESULTS: The paracetamol-associated SJS, TEN, SJS/TEN overlap, AGEP, and DRESS syndromes have been identified by a number of publications. CONCLUSION: When evaluating drug-induced hypersensitivity skin reactions, healthcare professionals, including prescribers, pharmacists, and others, should be aware of this rare risk. Patients who exhibit signs and symptoms of paracetamol-associated hypersensitivity should be referred to physicians by pharmacists for further treatment. At the first sign of a skin rash or other hypersensitivity reaction while taking paracetamol, patients should be told to stop taking it and see a doctor right away.

Management of Adult Patients With Drug Reaction With Eosinophilia and Systemic Symptoms: A Delphi-Based International Consensus.

Importance: Drug reaction with eosinophilia and systemic symptoms (DRESS) is a rare but potentially fatal drug hypersensitivity reaction. To our knowledge, there is no international consensus on its severity assessment and treatment. Objective: To reach an international, Delphi-based multinational expert consensus on the diagnostic workup, severity assessment, and treatment of patients with DRESS. Design, Setting, and Participants: The Delphi method was used to assess 100 statements related to baseline workup, evaluation of severity, acute phase, and postacute management of DRESS. Fifty-seven international experts in DRESS were invited, and 54 participated in the survey, which took place from July to September 2022. Main Outcomes/Measures: The degree of agreement was calculated with the RAND-UCLA Appropriateness Method. Consensus was defined as a statement with a median appropriateness value of 7 or higher (appropriate) and a disagreement index of lower than 1. Results: In the first Delphi round, consensus was reached on 82 statements. Thirteen statements were revised and assessed in a second round. A consensus was reached for 93 statements overall. The experts agreed on a set of basic diagnostic workup procedures as well as severity- and organ-specific further investigations. They reached a consensus on severity assessment (mild, moderate, and severe) based on the extent of liver, kidney, and blood involvement and the damage of other organs. The panel agreed on the main lines of DRESS management according to these severity grades. General recommendations were generated on the postacute phase follow-up of patients with DRESS and the allergological workup. Conclusions and Relevance: This Delphi exercise represents, to our knowledge, the first international expert consensus on diagnostic workup, severity assessment, and management of DRESS. This should support clinicians in the diagnosis and management of DRESS and constitute the basis for development of future guidelines.

Characteristics of DRESS Syndrome in the Elderly: A Comparative Study of 55 Patients.

Background: Drug reaction with eosinophilia and systemic symptoms (DRESS) is a rare drug reaction characterized by a skin rash, eosinophilia, and organ involvement. Objective: Our purpose is to focus on the clinical and epidemiological characteristics of DRESS in the elderly and to identify the incriminated drugs. Methods: This is a retrospective study including patients, hospitalized for DRESS with a RegiSCAR ≥4. The population was divided into 2 groups according to age: 65 years or older (G1) and <65 years (G2). The statistical study was performed using the comparative and multivariate analysis. Results: We included 55 patients (30.9% G1 and 69.1% G2). Skin manifestations were comparable in both groups. Lymphadenopathy was less common in G1 with a statistically significant difference (P = 0.012). Renal impairment was more frequent in the elderly with a statistically significant result (P = 0.005). DRESS in the elderly group was significantly associated with the occurrence of sepsis (P = 0.008). Allopurinol was the most common culprit associated with DRESS in G1 (P = 0.001). Relapses and recurrences were comparable in both groups (P = 0.71). Conclusions: DRESS in the elderly is associated with a high risk of complications, mainly kidney involvement and sepsis. Allopurinol is the most incriminated drug.

Leukemoid reaction in minocycline-induced drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome: A brief report.

Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is an idiosyncratic drug reaction hallmarked by cutaneous eruption, fever, lymphadenopathy, multiorgan involvement, and hematological abnormalities, most often eosinophilia and atypical lymphocytosis. Leukemoid reactions have rarely been described in DRESS syndrome and here we describe a 16-year-old male who was admitted to the hospital with DRESS syndrome due to minocycline, who had a severe leukocytosis up to 52.08 K/µL. He improved with cessation of minocycline and initiation of systemic steroids. We report this case to add to the literature on hematological abnormalities in pediatric DRESS syndrome.

[Caso clínico: síndrome de DRESS por hidroxicloroquina].

Background: DRESS syndrome (Drug reaction with eosinophilia and systemic symptoms) is an idiosyncratic reaction characterized by peripheral eosinophilia and systemic symptoms: fever, exanthema, lymphadenopathy, hepatitis, atypical lymphocytes and elevated liver enzymes. The incidence is 1 per 10,000 exposures, mortality 10-20%. Treatment is based on suspension of the suspected drug and steroids. Case report: A 42-year-old male with the following important antecedents. AHF: mother and father with Diabetes Mellitus type 2. APP: Arterial Hypertension, Diabetes Mellitus type 2, and bee sting allergy. Current Condition: He started 8 days after ingestion of hydroxychloroquine for probable SARS-COV-2 infection, with headache, facial and neck edema, desquamative dermatosis on trunk and upper extremities, went to private clinic with torpid evolution sent to third level for increased facial and neck edema, which merited orotracheal intubation, management with intravenous steroids and antihistamines. Labs on admission: Leukocytes 20090, platelets 322 thousand, eosinophilia (5%), elevated liver enzymes and acute kidney injury, fulfilling J-SCAR criteria. The patient was discharged due to adequate evolution with follow-up by Allergy and Clinical Immunology, the patient persists with desquamative lesions after 4 weeks and normalization of laboratory parameters. Conclusions: DRESS is a delayed adverse reaction. It is important the diagnostic presumption and the causal relationship with the drugs due to the high mortality rate.

Antecedentes: El síndrome DRESS (Drug reaction with eosinophilia and systemic symptoms) es una reacción idiosincrática, se caracteriza por eosinofilia perifé- rica y síntomas sistémicos: fiebre, exantema, linfadenopatía, hepatitis, linfocitos atípicos y elevación de enzimas hepáticas. La incidencia es de 1 por cada 10,000 exposiciones, mortalidad de 10 a 20%. El tratamiento se basa en la suspensión del fármaco sospechoso y en la aplicación de esteroides. Reporte de caso: Masculino de 42 años con los siguientes antecedentes de importancia. AHF: madre y padre con Diabetes Mellitus tipo 2. APP: Hipertensión Arterial, Diabetes Mellitus tipo 2, y alergia a picadura de abeja. Padecimiento Actual: Lo inicia posterior a 8 días tras la ingesta de hidroxicloroquina por probable infección por SARS-COV-2, con cefalea, edema facial y de cuello, dermatosis descamativa en tronco y extremidades superiores, acude a clínica particular con evolución tórpida enviado a tercer nivel por aumento de edema facial y cuello, que amerito intubación orotraqueal, manejo con esteroides intravenosos y anti- histamínicos. Laboratorios a su ingreso: Leucocitos 20090, plaquetas 322 mil, eosinofilia (5%), elevación de enzimas hepáticas y lesión renal aguda, cumpliendo criterios J-SCAR. Se egresa por adecuada evolución con seguimiento por Alergia e Inmunología Clínica, el paciente persiste con lesiones descamativas posterior a 4 semanas y normalización de parámetros de laboratorios. Conclusión: DRESS es una reacción adversa retardada. Es importante la presunción diagnóstica y la relación causal con los fármacos por la alta tasa de morta- lidad.

Periportal necrosis and successful liver transplantation following Lamotrigine drug-induced liver injury in a child.

Lamotrigine is one of the most prescribed antiepileptics in children and a well-known cause of drug-induced liver injury (DILI). The typical presentation usually includes a drug rash with eosinophilia and systemic symptoms (DRESS syndrome). Cases are typically mild and self-limiting, requiring supportive care only. We report a severe Lamotrigine-induced DILI with a non-typical presentation with hyperammonaemia and rapid clinical deterioration. We present a literature review exploring contributing factors, transplant considerations and liver histology. Histology showed periportal necrosis, which is recognised as a pattern of DILI but has not been previously described with Lamotrigine. Our patient proceeded to transplant and is the first reported liver transplant for Lamotrigine DILI in a child. A directed and rapid diagnostic approach is crucial to avoid delays and rule out multisystemic metabolic and genetic conditions that preclude liver transplantation.

A Case of Olanzapine-Induced Cutaneous Eruption.

BACKGROUND Different medication classes have been implicated in cutaneous eruptions that may lead to significant morbidity and mortality. In drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome, the patient may initially present with a cutaneous eruption and hematologic abnormalities which can lead to acute visceral organ involvement if the offending drug is not discontinued. There is also a potential for long-term sequelae such as autoimmune disorders. CASE REPORT A 47-year-old woman with an unknown past medical history and no known drug allergies was admitted to the Behavioral Health Unit, where she was diagnosed with disorganized schizophrenia and started on olanzapine. On day 17 of admission, she developed a diffuse, macular, and erythematous rash on her abdomen, which spread to involve over 50% of her total body surface area. Occipital and posterior auricular lymphadenopathy was present. The patient was treated with prednisone and diphenhydramine. Olanzapine was subsequently discontinued and the patient's rash cleared up. CONCLUSIONS This case report highlights the challenges in diagnosing DRESS syndrome and the potential for antipsychotics to cause DRESS syndrome. DRESS syndrome is a clinical diagnosis augmented by laboratory tests with a wide range of patient presentations. Although there are probability criteria to assist with diagnosis, not all patients will fall exactly into these criteria, which can lead to missed diagnoses and poor patient outcomes. A challenge with DRESS syndrome diagnosis is the latency period between drug initiation and cutaneous eruption. Thus, in differential diagnoses for skin eruptions, temporal associations (minutes, days, weeks) with medications are crucial.

Antituberculosis drug-induced non-blistering systemic severe reactions: A 10-year (2012-2022) literature review.

Drug reaction with eosinophilia and systemic symptoms (DRESS) and drug-induced liver injury (DILI) can hamper therapeutic strategy, contribute to multiple drug resistance and serious public health burden. Diagnosis (including allergy assessment) and management of these two severe hypersensitivity reactions in clinical practice are somewhat difficult and published scientific evidence is rather weak and limited. The first step is always represented by stopping all anti-tuberculosis (TB) drugs, treating reaction with systemic corticosteroids, and identifying the offending drug, even if it is often complicated by the patient's simultaneous intake of antibiotics. Patch tests and in vitro tests, such as lymphocyte transformation test, could bridge this diagnostic gap, but the available data are scarce and their sensitivity low. The re-challenge test is often necessary but places patients at risk for serious adverse reactions. The desensitization protocols are quite varied and not universally accepted. In this narrative review, we provide an update to the literature data on the management of DRESS and DILI with particular attention to the allergological work-up in the last decade.

Unraveling the complexities of drug reaction with eosinophilia and systemic symptoms (DRESS): Insights into clinical, laboratory, and histopathologic features of a case series from an Italian tertiary center.

Drug reaction with eosinophilia and systemic symptoms (DRESS) is a severe and potentially life-threatening drug hypersensitivity reaction. The diagnosis and management of DRESS are complicated due to its heterogeneous clinical and pathologic presentations, delayed onset of signs and symptoms, and unpredictable outcome. This retrospective study aimed to analyze cases of DRESS from a single Italian referring tertiary hospital center (Grande Ospedale Metropolitano Niguarda, Milan, Italy) with a focus on clinical features, causative drugs, histopathologic findings, and treatment. We have included 18 of 32 patients with a probable or definite diagnosis of DRESS. The study observed a slight predominance of women, with antimicrobials and allopurinol identified as the main causative drugs. Clinical manifestations varied, with a monomorphic maculopapular eruption being the most common, whereas facial edema and mucosal involvement were less frequently observed. Multiple organs were commonly affected, with liver and kidney involvement being prominent. Cardiac involvement was associated with the severity of eosinophilia. Laboratory evaluations showed elevated eosinophil levels and increased eosinophil cationic protein levels, supporting the role of eosinophils in DRESS pathogenesis. Histopathologic analysis revealed various patterns often coexisting in the same biopsy in 83% of cases, with interface dermatitis being the most frequent, followed by the perivascular pattern and the spongiotic/eczematous pattern. We observed eosinophils in the biopsy samples in about 50% of patients, and the relationship between peripheral eosinophilia and eosinophils in skin biopsies was not significant. In addition to the RegiSCAR score, age may play a role in predicting disease severity, as older patients with lower scores had poorer outcomes. The prognosis of DRESS depended on early identification, discontinuation of the causative agent, and appropriate therapy. Systemic corticosteroids were the primary treatment option.