Phenytoin Induced Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS): Case Report

Background: Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a rare and potentially life-threatening condition. It presents a long prodromal period, extensive rash, fever, lymphadenopathy, hematologic abnormalities (eosinophilia with or without atypical lymphocytosis), and internal organ involvement. Purpose: To describe a case of phenytoin induced DRESS syndrome, presenting diagnostic and management challenges of clinical interest. Methods: The Consensus-based Clinical Case Reporting Guideline Development (CARE) was observed for data analysis in case reports. Case Report: A 22-year-old man, using phenytoin for 60 days, sought medical attention due to fever and maculopapular cutaneous lesions. He presented lymphocytosis with eosinophilia and severe acute hepatitis 24 hours after admission day. Hepatic transaminases returned to reference levels after phenytoin withdrawal, and eosinophilia and cutaneous manifestations did not respond well to systemic steroids. A forearm biopsy showed findings suggestive of severe cutaneous adverse reaction. The patient’s microscopic and clinical characteristics meet all criteria in the scoring systems of Bocquet et al., Registry of Severe Cutaneous Adverse Reaction (RegiSCAR), and Japanese Research Committee on Severe Cutaneous Adverse Reaction (J-SCAR), being highly suggestive of DRESS syndrome very probably caused by phenytoin. The complete remission of symptoms was achieved weeks after admission. Conclusions: DRESS syndrome is a defiant reaction. Clinicians must be aware of potential causative drugs and perform a complete clinical examination using the available resources, including laboratory tests and histopathological assessment. The clinical remission relies on the withdrawal of the culprit drug. Particular attention should be given to the involvement of internal organs.

Improvement of lenvatinib-induced nephrotic syndrome after adaptation to sorafenib in thyroid cancer:A case report

BACKGROUND Target therapy is licensed by United States Food and Drug Administration on certain cancers.Both sorafenib and lenvatinib are tyrosine kinase inhibitor and indicated on radioactive iodine(RAI)-refractory differentiated thyroid cancer(DTC).Lenvatinib is more effective in cancers'control than sorafenib,but causes more nephrotoxicity than sorafenib does.This case is the second published case about the serial adaptions from lenvatinib to sorafenib for improving the proteinuria and,meanwhile,achieving the therapeutic goal.CASE SUMMARY A 56-year-old man suffered from bilateral edematous lower extremities after 1-mo prescription of lenvatinib of 20 mg/d for RAI-refractory DTC.Aside from this symptom,he also developed hypertension.His laboratory showed grade-3 proteinuria(estimated 24-h urine protein:9993 mg),hypoalbuminemia and hypercholesterolemia.Anti-vascular endothelial growth factor(VEGF)therapyinduced nephrotic syndrome was impressed.After reduced dosage of lenvatinib of 10 mg/d and related symptomatic drugs,limited improvement was observed in both adverse effects and caner control.Under this condition,we substituted sorafenib of 400 mg/d for lenvatinib of 10 mg/d.After a 5-mo prescription,not only hypertension and peripheral edema were greatly improved,but also proteinuria was improved from grade three to grade one(estimated 24-h urine protein:962 mg).At the same time the cancer control was achieved,judged from computed tomography and laboratory evidence[thyroglobulin(Tg)before prescription of sorafenib:354.7 ng/m L;Tg after prescription of sorafenib:108.9 ng/m L].CONCLUSION Adaption from lenvatinib to sorafenib is a feasible method to improve the antiVEGF therapy-induced nephrotic syndrome and achieve the therapeutic goal at the same time.

Severe cutaneous adverse drug reactions： a review on epidemiology, etiology, clinical manifestation and pathogenesis

Purpose To review the current progress in epidemiology, etiology, clinical manifestation, and pathophysiology of severe cutaneous adverse drug reactions （SCADRs）. Data sources Data were acquired by using Blackwell-Synergy, PubMed, original articles published in the main Chinese journals and related medical textbooks materials. Study selection and data extraction Throughout the literature review 49 articles were selected. Results SCADRs cases are rare, however, the implication is life threatening with significant mortality rates. Epidemiology studies have shown various incidences from different regions, gender, age, race and concurrent illness. There are typical signs and symptoms for each type of SCADRs, but this is not always so. Drugs associated with inducing SCADRs are anticonvulsants, antibiotics, NSAIDs and antirheumatic drugs. In some countries, especially in Asia, traditional drugs are often the cause of SCADRs. Genetic polymorphisms and viral infections are predisposition factors of SCADRs. Patients with certain genetic alleles and underlying diseases are vulnerable to SCADRs. The exact pathogenesis of SCADRs is not well defined. Nonetheless, recent study showed that reactive metabolites and immunological processes have a significant role in SCADRs. Conclusions The different SCADRs reactions are attributed by different intrinsic factors, such as genetic polymorphisms, gender, age and race as well as extrinsic factors, such as underlying diseases. Different regions and culprit drugs also play a role in the various types of SCADRs.

Drug Reaction with Eosinophilia and Systemic Symptoms： Retrospective Analysis of 104 Cases over One Decade

Background： Drug reaction with eosinophilia and systemic symptoms （DRESS） is a severe, life-threatening disorder caused by drugs. In the present study, we tried to explore the types of DRESS-inducing drugs, incubation period, features of skin rashes, accompanying visceral damage, and effectiveness of glucocorticoid therapy so as to inform clinical practice. Methods： Patients diagnosed with a drug-induced rash, dermatitis, and DRESS admitted to our hospital from January 2006 to December 2015 were included in the study. The diagnosis followed the criteria and scoring system set by the European Registry of Severe Cutaneous Adverse Reactions. Statistical analyses were carried out using SPSS version 17.0 （IBM, Armonk, NY, USA）, and a value ofP 〈 0.05 was considered statistically significant. Results： Among 104 patients, 38 were male and 66 female （aged 18-83 years）. The latent period was 13 （interquartile range [IQR]： 10-17） days. The most common allergy-inducing drugs were antibiotics （n = 37, 35.6%）, followed by antiepileptic drugs and traditional Chinese medicines （TCMs）. Eighty-two cases （78.8%） had rash with area 〉50% body surface area （BSA）. Liver damage occurred in 90% of cases. Patients were divided into oral antihistamine group and glucocorticoid/immunosuppressive agent/intravenous immunoglobulin （IVIG） group. Sex, age, incubation period, duration of hospital stay, and the number of patients with body temperature 〉38.5℃ were not significantly different between the two groups. However, the number of patients meeting the criteria of＂definite＂ and ＂probable＂ （X2 =5.852, P = 0.016）, with an eosinophilic granulocyte count of〉1.5 x10^9/L 0,2 7.129, P = 0.008）, and with rash area of〉50% BSA （X2 = 4.750, P = 0.029）, was significantly different. Conclusions： Antibiotics were associated with allergic reactions, but TCMs also had an important role. Allergy resulting from repeat use of the same drug was more severe with a shorter incubation period. The most typical rash was widespread erythematous papules. Liver damage accounted for 〉90% of cases.