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Mizukawa Y, Shiohara T. Recent advances in the diagnosis and treatment of DIHS/DRESS in 2025. Allergol Int 2025:S1323-8930(25)00046-2. [PMID: 40251070 DOI: 10.1016/j.alit.2025.03.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2025] [Revised: 03/14/2025] [Accepted: 03/21/2025] [Indexed: 04/20/2025] Open
Abstract
Drug-induced hypersensitivity syndrome (DIHS) or drug reaction with eosinophilia and systemic symptoms (DRESS) is a severe drug reaction characterized by a range of clinical manifestations. These range from mild cases resolving upon cessation of the causative drug to severe cases involving complex disease progression and potential fatality. A hallmark of DIHS/DRESS is the sequential reactivation of herpesviruses, particularly human herpesvirus 6 (HHV-6), during the disease course, contributing to recurrent symptoms. Viral reactivation can lead to critical complications, including infectious DIHS/DRESS-associated complications (iDACs) and autoimmune sequelae (aDACs). Managing DIHS/DRESS remains challenging due to its complexity, requiring precise prediction and tailored treatment strategies. Recent studies suggest that early-stage classification using the DIHS/DRESS Severity (DDS) score may help identify refractory cases, including DACs. Furthermore, early intervention with anti-cytomegalovirus (anti-CMV) therapy can mitigate iDACs caused by CMV reactivation, preventing progression to severe CMV-related diseases. Long-term follow-up is crucial, as aDACs can manifest even 3 years postonset. Serial monitoring is recommended, particularly in patients treated with intravenous immunoglobulin or corticosteroid pulse therapy, which are recognized risk factors for aDAC development. This review highlights DIHS/DRESS management strategies, focusing on its clinical features, the role of viral reactivation, and therapeutic interventions.
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Affiliation(s)
- Yoshiko Mizukawa
- Department of Dermatology, Kyorin University School of Medicine, Tokyo, Japan.
| | - Tetsuo Shiohara
- Department of Dermatology, Kyorin University School of Medicine, Tokyo, Japan
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Li X, Li Y, Liu L, Wang L, Zhang L, Jiang X. Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS): A Retrospective Study of 51 Chinese Patients. Clin Cosmet Investig Dermatol 2025; 18:525-532. [PMID: 40061046 PMCID: PMC11890001 DOI: 10.2147/ccid.s486550] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2024] [Accepted: 01/16/2025] [Indexed: 03/17/2025]
Abstract
BACKGROUND Drug reaction with eosinophilia and systemic symptoms (DRESS) is a severe and potentially lethal adverse drug reaction. Its clinical complexity and heterogeneity pose challenges for diagnosis and management. METHODS We retrospectively reviewed the medical records of patients with DRESS who were admitted to our hospital between 2013 and 2022. Data on demographics, culprit drugs, clinical manifestations, laboratory findings, and treatments were collected. RESULTS Fifty-one patients were included in the final analysis, with 16 probable and 35 definite cases. The most common causative drugs were antiepileptic drugs (15.7%), anti-tuberculosis drugs (15.7%), and Chinese herbs (9.8%). Common skin manifestations included extensive skin involvement (76.5%), facial edema (66.7%), polymorphic maculopapular lesions (66.7%), and exfoliation (56.9%). Eosinophilia and atypical lymphocytes were noted in 96.1% and 68.6% of the patients, respectively. The liver is the most frequently affected organ. Facial edema, extensive skin involvement, and atypical lymphocytes were correlated with higher Registry of Severe Cutaneous Adverse Reactions (RegiSCAR) scores (P<0.05). DRESS induced by antiepileptic drugs, antituberculosis drugs, and Chinese herbs exhibited significant differences in platelet and lymphocyte counts, C-reactive protein (CRP) levels, and transaminase levels (P<0.05). CONCLUSION Clinical manifestations of DRESS are complex. Facial edema, extensive skin involvement, and atypical lymphocytes have emerged as significant diagnostic indicators.
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Affiliation(s)
- Xiaoxue Li
- Department of Dermatology, West China Hospital, Sichuan University, Chengdu, People’s Republic of China
- Laboratory of Dermatology, Clinical Institute of Inflammation and Immunology, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, People’s Republic of China
| | - Yanmei Li
- Department of Dermatology, West China Hospital, Sichuan University, Chengdu, People’s Republic of China
- Laboratory of Dermatology, Clinical Institute of Inflammation and Immunology, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, People’s Republic of China
| | - Lian Liu
- Department of Dermatology, West China Hospital, Sichuan University, Chengdu, People’s Republic of China
- Laboratory of Dermatology, Clinical Institute of Inflammation and Immunology, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, People’s Republic of China
| | - Lian Wang
- Department of Dermatology, West China Hospital, Sichuan University, Chengdu, People’s Republic of China
- Laboratory of Dermatology, Clinical Institute of Inflammation and Immunology, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, People’s Republic of China
| | - Lidan Zhang
- Department of Dermatology, West China Hospital, Sichuan University, Chengdu, People’s Republic of China
- Laboratory of Dermatology, Clinical Institute of Inflammation and Immunology, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, People’s Republic of China
| | - Xian Jiang
- Department of Dermatology, West China Hospital, Sichuan University, Chengdu, People’s Republic of China
- Laboratory of Dermatology, Clinical Institute of Inflammation and Immunology, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, People’s Republic of China
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Wang L, Zhang J, Wang X, Xu Y. Drug-induced hypersensitivity syndrome due to phenytoin: Case report and review of the literature. Medicine (Baltimore) 2024; 103:e39715. [PMID: 39331866 PMCID: PMC11441959 DOI: 10.1097/md.0000000000039715] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/08/2024] [Accepted: 08/26/2024] [Indexed: 09/29/2024] Open
Abstract
RATIONALE Drug hypersensitivity syndrome (DIHS) is a rare but potentially fatal adverse drug reaction characterized by fever, rash, and visceral organ damage, particularly affecting the liver. Early recognition and appropriate management are crucial to prevent serious complications. However, there is limited information on the clinical presentation and management of DIHS, especially in the context of antiepileptic drugs. This case report aims to highlight the importance of recognizing subtle clinical signs and symptoms of DIHS, which can be easily overlooked, particularly in the context of antiepileptic drug use. PATIENT CONCERNS We report a case of a 15-year-old male patient who developed DIHS after being prescribed phenytoin sodium for epilepsy. The patient presented with symptoms of fever, sore throat, rash, jaundice, and liver dysfunction. Initially, the patient did not receive glucocorticoids and experienced additional reactions to cefoxitin and phosphatidylcholine, likely due to cross-reactivity. DIAGNOSES The diagnosis of DIHS was made based on the patient's clinical presentation, including fever, extensive rash, organ involvement, and hematological abnormalities. The temporal association with the use of phenytoin sodium, along with the exclusion of other causes of fever and rash, supported the diagnosis. INTERVENTIONS Upon initiation of glucocorticoid therapy with dexamethasone, the patient's symptoms significantly improved. The rash and pruritus decreased, and laboratory values showed improvement, with a decrease in liver enzymes and normalization of white blood cell counts. OUTCOMES The patient's fever resolved within 48 hours of starting corticosteroids, and there was no evidence of ongoing inflammation as indicated by a decrease in C-reactive protein levels. Furthermore, the patient's 30-month follow-up revealed no recurrence of rash, liver dysfunction, or organic damage, indicating the long-term effectiveness of the treatment administered. LESSONS This case highlights the importance of recognizing the subtle clinical signs and symptoms of DIHS, especially in the context of antiepileptic drug use. It underscores the potential benefits of early initiation of glucocorticoid therapy in managing DIHS. The case also serves as a reminder of the potential for drug cross-reactivity in DIHS and the need for cautious drug selection during the acute phase of the syndrome.
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Affiliation(s)
- Ling Wang
- Chongqing Medical University, Yuzhong District, Chongqing, China
- Department of Geriatric, Chongqing General Hospital, Chongqing University, Yuzhong District, Chongqing, China
| | - Jie Zhang
- Department of Geriatric, Chongqing General Hospital, Chongqing University, Yuzhong District, Chongqing, China
- Chongqing Clinical Research Centre for Geriatic Diseases
| | - Xichun Wang
- Department of Geriatric, Chongqing General Hospital, Chongqing University, Yuzhong District, Chongqing, China
- Chongqing Clinical Research Centre for Geriatic Diseases
| | - Yali Xu
- Chongqing Medical University, Yuzhong District, Chongqing, China
- Department of Geriatric, Chongqing General Hospital, Chongqing University, Yuzhong District, Chongqing, China
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Wei BM, Fox LP, Kaffenberger BH, Korman AM, Micheletti RG, Mostaghimi A, Noe MH, Rosenbach M, Shinkai K, Kwah JH, Phillips EJ, Bolognia JL, Damsky W, Nelson CA. Drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms. Part I. Epidemiology, pathogenesis, clinicopathological features, and prognosis. J Am Acad Dermatol 2024; 90:885-908. [PMID: 37516359 DOI: 10.1016/j.jaad.2023.02.072] [Citation(s) in RCA: 6] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2022] [Revised: 02/11/2023] [Accepted: 02/26/2023] [Indexed: 07/31/2023]
Abstract
Drug-induced hypersensitivity syndrome (DiHS), also known as drug reaction with eosinophilia and systemic symptoms (DRESS), is a severe cutaneous adverse reaction (SCAR) characterized by an exanthem, fever, and hematologic and visceral organ involvement. Anticonvulsants, antibiotics, and allopurinol are the most common triggers. The pathogenesis involves a complex interplay between drugs, viruses, and the immune system primarily mediated by T-cells. DiHS/DRESS typically presents with a morbilliform eruption 2-6 weeks after drug exposure, and is associated with significant morbidity, mortality, and risk of relapse. Long-term sequelae primarily relate to organ dysfunction and autoimmune diseases. Part I of this continuing medical education activity on DiHS/DRESS provides an update on epidemiology, novel insights into pathogenesis, and a description of clinicopathological features and prognosis.
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Affiliation(s)
- Brian M Wei
- Department of Dermatology, Yale School of Medicine, New Haven, Connecticut
| | - Lindy P Fox
- Department of Dermatology, University of California, San Francisco, California
| | | | - Abraham M Korman
- Department of Dermatology, The Ohio State University, Columbus, Ohio
| | - Robert G Micheletti
- Department of Dermatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
| | - Arash Mostaghimi
- Department of Dermatology, Brigham & Women's Hospital, Harvard Medical School, Boston, Massachusetts
| | - Megan H Noe
- Department of Dermatology, Brigham & Women's Hospital, Harvard Medical School, Boston, Massachusetts
| | - Misha Rosenbach
- Department of Dermatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
| | - Kanade Shinkai
- Department of Dermatology, University of California, San Francisco, California
| | - Jason H Kwah
- Department of Medicine, Section of Rheumatology, Allergy and Immunology, Yale School of Medicine, New Haven, Connecticut
| | - Elizabeth J Phillips
- Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee
| | - Jean L Bolognia
- Department of Dermatology, Yale School of Medicine, New Haven, Connecticut
| | - William Damsky
- Department of Dermatology, Yale School of Medicine, New Haven, Connecticut; Department of Pathology, Yale School of Medicine, New Haven, Connecticut
| | - Caroline A Nelson
- Department of Dermatology, Yale School of Medicine, New Haven, Connecticut.
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Chatproedprai S, Tiasiri N, Chantawarangkul K, Wananukul S. Pediatric drug reaction with eosinophilia and systemic symptoms: A 12-year retrospective study in a tertiary center. J Dermatol 2024; 51:509-517. [PMID: 38214543 DOI: 10.1111/1346-8138.17098] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2023] [Revised: 12/08/2023] [Accepted: 12/18/2023] [Indexed: 01/13/2024]
Abstract
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.
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Affiliation(s)
- Susheera Chatproedprai
- Division of Pediatric Dermatology, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial hospital, Bangkok, Thailand
| | - Nisha Tiasiri
- Division of Pediatric Dermatology, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial hospital, Bangkok, Thailand
| | - Karaked Chantawarangkul
- Division of Pediatric Dermatology, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial hospital, Bangkok, Thailand
| | - Siriwan Wananukul
- Division of Pediatric Dermatology, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial hospital, Bangkok, Thailand
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Carty J, Navarro VJ. Dietary Supplement-Induced Hepatotoxicity: A Clinical Perspective. J Diet Suppl 2024; 22:58-77. [PMID: 38528750 DOI: 10.1080/19390211.2024.2327546] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/27/2024]
Abstract
The consumption of dietary supplements (DS) has resulted in a significant and escalating number of cases involving liver injury. It is crucial for clinicians and consumers to be well informed about the adverse effects of such products, leading to their discontinuation and timely reporting of any harmful cases. This article delves into the clinical perspective of DS-related hepatotoxicity, highlighting key concepts such as a systematic diagnostic approach. The discussion extends to notable examples of both currently popular and potential future dietary supplements, such as garcinia cambogia, turmeric, and ashwagandha, accompanied by an overview of recent findings. Causality assessment tools play a crucial role in establishing a connection between these products and instances of liver injury, with consideration of the advantages and disadvantages associated with their use. Fostering a comprehensive understanding of regulatory standards, coupled with a solid foundation of knowledge of DS, will prove instrumental in preventing DS-related hepatotoxicity. Achieving this goal requires collaborative efforts from both consumers and clinicians.
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Affiliation(s)
- Jordan Carty
- Department of Medicine, Jefferson Einstein Medical Center, Philadelphia, PA, USA
| | - Victor J Navarro
- Department of Medicine, Jefferson Einstein Medical Center, Philadelphia, PA, USA
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Memon A, Yeboah-Korang A, Fontana RJ. Advances in the management of idiosyncratic drug-induced liver injury. Clin Liver Dis (Hoboken) 2023; 21:102-106. [PMID: 37936954 PMCID: PMC10627588 DOI: 10.1097/cld.0000000000000052] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/10/2023] [Accepted: 04/10/2023] [Indexed: 11/09/2023] Open
Abstract
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Affiliation(s)
- Ahmed Memon
- Division of Internal Medicine, University of Cincinnati Medical Center, Cincinnati, Ohio, USA
| | - Amoah Yeboah-Korang
- Division of Digestive Diseases, University of Cincinnati Medical Center, Cincinnati, Ohio, USA
| | - Robert J. Fontana
- Division of Gastroenterology and Hepatology, University of Michigan Health System, Ann Arbor, Michigan, USA
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Sharma A, Roy S, Sharma R, Kumar A. Association of antiviral drugs and their possible mechanisms with DRESS syndrome using data mining algorithms. J Med Virol 2023; 95:e28671. [PMID: 36916721 DOI: 10.1002/jmv.28671] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2022] [Revised: 02/22/2023] [Accepted: 03/11/2023] [Indexed: 03/15/2023]
Abstract
Antiviral drugs are not known for drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome. The current study aims is to find out the association of antiviral drugs and their possible mechanism with DRESS. Data mining algorithms such as proportional reporting ratio that is, PRR (≥2) with associated χ2 value (>4), reporting odds ratio that is, ROR (≥2) with 95% confidence interval and case count (≥3) were calculated to identify a possible signal. Further, molecular docking studies were conducted to check the interaction of selected antiviral drugs with possible targets. The potential signal of DRESS was found to be associated with abacavir, acyclovir, ganciclovir, lamivudine, lopinavir, nevirapine, ribavirin, ritonavir, and zidovudine among all selected antiviral drugs. Further, subgroup analysis has also shown a potential signal in different age groups and gender. The sensitivity analysis results have shown a decrease in the strength of the signal, however, there was no significant impact on the outcome except for acyclovir. The docking results have indicated the possible involvement of human leukocyte antigen (HLA)*B1502 and HLA*B5801. The positive signal of DRESS was found with selected antiviral drugs except for acyclovir.
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Affiliation(s)
- Akash Sharma
- Department of Clinical Research, Delhi Pharmaceutical Sciences and Research University (DPSRU), New Delhi, India
| | - Sweta Roy
- Department of Pharmacology, Delhi Pharmaceutical Sciences and Research University (DPSRU), New Delhi, India
| | - Ruchika Sharma
- Centre for Precision Medicine and Pharmacy, Delhi Pharmaceutical Sciences and Research University (DPSRU), New Delhi, India
| | - Anoop Kumar
- Department of Clinical Research, Delhi Pharmaceutical Sciences and Research University (DPSRU), New Delhi, India
- Department of Pharmacology, Delhi Pharmaceutical Sciences and Research University (DPSRU), New Delhi, India
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Fontana RJ, Liou I, Reuben A, Suzuki A, Fiel MI, Lee W, Navarro V. AASLD practice guidance on drug, herbal, and dietary supplement-induced liver injury. Hepatology 2023; 77:1036-1065. [PMID: 35899384 PMCID: PMC9936988 DOI: 10.1002/hep.32689] [Citation(s) in RCA: 78] [Impact Index Per Article: 39.0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/07/2022] [Accepted: 07/07/2022] [Indexed: 12/14/2022]
Affiliation(s)
- Robert J. Fontana
- Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, Michigan, USA
| | - Iris Liou
- University of Washington, Seattle, Washington, USA
| | - Adrian Reuben
- Department of Medicine, Medical University of South Carolina, Charleston, South Carolina, USA
| | - Ayako Suzuki
- Division of Gastroenterology, Duke University, Durham, North Carolina, USA
| | - M. Isabel Fiel
- Department of Pathology, Mount Sinai School of Medicine, New York City, New York, USA
| | - William Lee
- Division of Gastroenterology, University of Texas Southwestern, Dallas, Texas, USA
| | - Victor Navarro
- Department of Medicine, Einstein Healthcare Network, Philadelphia, Pennsylvania, USA
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Sharma A, Kumar A. Identification of novel signal of clobazam-associated drug reaction with eosinophilia and systemic symptoms syndrome: A disproportionality analysis. Acta Neurol Scand 2022; 146:623-627. [PMID: 36029138 DOI: 10.1111/ane.13690] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2022] [Revised: 08/04/2022] [Accepted: 08/11/2022] [Indexed: 11/27/2022]
Abstract
OBJECTIVES Clobazam is a well-known benzodiazepine used as an anti-anxiety drug as well as an anti-epileptic, particularly for patients who are not responding to first-line treatments. Recent case reports have indicated the association of clobazam with drug reaction with eosinophilia systemic symptoms syndrome (DRESS Syndrome). However, DRESS syndrome is not known to be associated with clobazam. Thus, the main objective of the current study was to identify the potential signal of clobazam-associated DRESS Syndrome. MATERIALS & METHODS US FDA Adverse event reporting system (US FAERS), pharmacovigilance data 2004Q1-2021Q3 was extracted using OpenVigil 2.1-MedDRA-v24. The Proportional Reporting Ratio (PRR), Reporting Odds Ratio (ROR) with a Chi-Square value (95% confidence interval), and number of cases (≥3) were used as disproportionality analysis parameters. RESULTS A total of 141 drug-event combinations were reported and results of disproportionality analysis indicate the positive signal of DRESS syndrome with clobazam. The signal strength was decreased after removing the cases of concomitantly administered drugs (phenytoin, levetiracetam, and valproic acid); however, the association of clobazam with DRESS syndrome remains statistically significant. The subgroup analysis results have shown a greater number of cases in the age group (18-64 years) as compared to other age groups whereas the number of cases in the male and female groups is almost similar. CONCLUSION The DRESS syndrome is identified as a novel signal with clobazam. However, further causality assessment is required.
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Affiliation(s)
- Akash Sharma
- Department of Clinical Research, Delhi Pharmaceutical Sciences and Research University (DPSRU), New Delhi, India
| | - Anoop Kumar
- Department of Clinical Research, Delhi Pharmaceutical Sciences and Research University (DPSRU), New Delhi, India
- Department of Pharmacology, Delhi Pharmaceutical Sciences and Research University (DPSRU), New Delhi, India
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Sato H, Takase K, Harada A, Ozono I, Kodama Y, Ishitobi T, Imada T, Ohnuma H, Kin S. Atypical, Levetiracetam-induced Hypersensitivity Syndrome Complicated by Fulminant Liver Failure in a Patient Undergoing Hemodialysis. Intern Med 2022; 61:2911-2916. [PMID: 35228427 PMCID: PMC9593156 DOI: 10.2169/internalmedicine.8985-21] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
Abstract
A 59-year-old man undergoing hemodialysis was administered levetiracetam, after which he developed a systemic rash, high fever, severe liver dysfunction, and leukocytopenia with reactivation of human herpes virus 6. Atypical drug-induced hypersensitivity (DIHS) was diagnosed, and prednisolone was administered at 60 mg/day. However, liver failure rapidly progressed, and the patient died 12 days following treatment. Despite the rarity of DIHS with concomitant fulminant liver failure from levetiracetam and sufficient clearance thereof by hemodialysis, our case suggests that this syndrome may still ensue, resulting in mortality, even in hemodialysis patients. Although no treatment has yet been established, strict monitoring and aggressive treatment may be required.
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Affiliation(s)
- Hirotaka Sato
- Department of Nephrology, Shimane Prefectural Central Hospital, Japan
| | - Kentaro Takase
- Department of Nephrology, Shimane Prefectural Central Hospital, Japan
| | - Aiko Harada
- Department of General Medicine, Shimane Prefectural Central Hospital, Japan
| | - Iori Ozono
- Department of Neurosurgery, Shimane Prefectural Central Hospital, Japan
| | - Yasuhide Kodama
- Department of Gastroenterology, Shimane Prefectural Central Hospital, Japan
| | - Tomoko Ishitobi
- Department of Dermatology, Shimane Prefectural Central Hospital, Japan
| | - Toshihiro Imada
- Department of General Medicine, Shimane Prefectural Central Hospital, Japan
| | - Hideyuki Ohnuma
- Department of Pathology, Shimane Prefectural Central Hospital, Japan
| | - Seikon Kin
- Department of Nephrology, Shimane Prefectural Central Hospital, Japan
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Chen DH, Zhou HR, Zhang YG, Shen GY, Xu C, Guan CL. Drug hypersensitivity syndrome induced by sulfasalazine: A case report. Medicine (Baltimore) 2022; 101:e30060. [PMID: 35984191 PMCID: PMC9388030 DOI: 10.1097/md.0000000000030060] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/05/2023] Open
Abstract
INTRODUCTION Drug hypersensitivity syndrome (DHS) induced by sulfasalazine is a serious systemic delayed adverse drug reaction, which is associated with significant morbidity and mortality. PATIENT CONCERNS A 52-year-old man was hospitalized for developing a rash after 3 weeks of sulfasalazine treatment for ulcerative colitis (UC). DIAGNOSIS The patient was diagnosed with DHS based on his drug history, clinical manifestations, and laboratory test results. INTERVENTIONS The patient was administered intravenous glucocorticoids. The patient's condition improved after treatment with human immunoglobulin and antihistamines. OUTCOMES Combination therapy of glucocorticoid and gamma globulin, the whole-body pruritus disappeared, and no new rash appeared. The whole-body rash subsided or turned dark red. CONCLUSION This article describes the diagnosis and treatment process of a case of sulfasalazine-induced DHS and reviews the relevant literature to improve clinician understanding and avoid misdiagnosis and missed diagnosis.
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Affiliation(s)
- Dong-Hui Chen
- Department of General Medicine, Shenzhen Longhua District Central Hospital, Shenzhen, China
| | - Hai-Rong Zhou
- Department of General Medicine, Shenzhen Longhua District Central Hospital, Shenzhen, China
| | - Yong-Gang Zhang
- Department of Clinical Laboratory, Shenzhen Longhua District Central Hospital, Shenzhen, China
| | - Guan-Yuan Shen
- Department of General Medicine, Shenzhen Longhua District Central Hospital, Shenzhen, China
| | - Chong Xu
- Department of General Medicine, Shenzhen Longhua District Central Hospital, Shenzhen, China
- * Correspondence: Chun-Li Guan and Chong Xu, Department of General Practice, Shenzhen Longhua District Central Hospital, The Affiliated Central Hospital of Shenzhen Longhua District, Guangdong Medical University, Shenzhen, China (e-mail: , )
| | - Chun-Li Guan
- Department of General Medicine, Shenzhen Longhua District Central Hospital, Shenzhen, China
- * Correspondence: Chun-Li Guan and Chong Xu, Department of General Practice, Shenzhen Longhua District Central Hospital, The Affiliated Central Hospital of Shenzhen Longhua District, Guangdong Medical University, Shenzhen, China (e-mail: , )
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Kulkarni MP, Chinta S, Sosa F, Nasr R, Kelly P. Drug Rash With Eosinophilia and Systemic Symptoms (DRESS) Syndrome Due to Vancomycin. Cureus 2022; 14:e26219. [PMID: 35911307 PMCID: PMC9313166 DOI: 10.7759/cureus.26219] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/22/2022] [Indexed: 11/05/2022] Open
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Hama N, Abe R, Gibson A, Phillips EJ. Drug-Induced Hypersensitivity Syndrome (DIHS)/Drug Reaction With Eosinophilia and Systemic Symptoms (DRESS): Clinical Features and Pathogenesis. THE JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY. IN PRACTICE 2022; 10:1155-1167.e5. [PMID: 35176506 PMCID: PMC9201940 DOI: 10.1016/j.jaip.2022.02.004] [Citation(s) in RCA: 98] [Impact Index Per Article: 32.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/25/2021] [Revised: 02/07/2022] [Accepted: 02/07/2022] [Indexed: 05/16/2023]
Abstract
Drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms (DIHS/DRESS) is one example of a severe delayed T-cell-mediated adverse drug reaction. DIHS/DRESS presents with fever, widespread rash and facial edema, organ involvement, and hematological abnormalities, including eosinophilia and atypical lymphocytosis. DIHS/DRESS is associated with relapse 2 to 4 weeks after acute symptoms, often coinciding with reactivation of prevalent chronic persistent human herpesviruses such as human herpesvirus 6, EBV, and cytomegalovirus. The mortality of DIHS/DRESS is up to 10% and often related to unrecognized myocarditis and cytomegalovirus complications, with longer-term consequences that contribute to morbidity including autoimmune diseases such as thyroiditis. It is essential that all potential drug causes, including all new drugs introduced within the 8 weeks preceding onset of DIHS/DRESS symptoms, are identified. All potential drug culprits, as well as drugs that are closely related structurally to the culprit drug, should be avoided in the future. Systemic corticosteroids have remained the mainstay for the treatment of DIHS/DRESS with internal organ involvement. Steroid-sparing agents, such as cyclosporine, mycophenolate mofetil, and monthly intravenous immune globulin, have been successfully used for treatment, and careful follow-up for cytomegalovirus reactivation is recommended. Strong associations between HLA class I alleles and DIHS/DRESS predisposition include HLA-B∗13:01 and dapsone, HLA-B∗58:01 and allopurinol, and HLA-B∗32:01 and vancomycin. These have opened a pathway for prevention, risk stratification, and earlier diagnosis. Single-cell sequencing and other studies of immunopathogenesis promise to identify targeted treatment approaches.
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Affiliation(s)
- Natsumi Hama
- Division of Dermatology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
| | - Riichiro Abe
- Division of Dermatology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
| | - Andrew Gibson
- Institute for Immunology and Infectious Diseases, Murdoch University, Murdoch, WA, Australia
| | - Elizabeth J Phillips
- Institute for Immunology and Infectious Diseases, Murdoch University, Murdoch, WA, Australia; Department of Medicine, Vanderbilt University Medical Center, Nashville, Tenn.
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Benić MS, Nežić L, Vujić-Aleksić V, Mititelu-Tartau L. Novel Therapies for the Treatment of Drug-Induced Liver Injury: A Systematic Review. Front Pharmacol 2022; 12:785790. [PMID: 35185538 PMCID: PMC8847672 DOI: 10.3389/fphar.2021.785790] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2021] [Accepted: 12/30/2021] [Indexed: 12/15/2022] Open
Abstract
Many drugs with different mechanisms of action and indications available on the market today are capable of inducing hepatotoxicity. Drug-induced liver injury (DILI) has been a treatment challenge nowadays as it was in the past. We searched Medline (via PubMed), CENTRAL, Science Citation Index Expanded, clinical trials registries and databases of DILI and hepatotoxicity up to 2021 for novel therapies for the management of adult patients with DILI based on the combination of three main search terms: 1) treatment, 2) novel, and 3) drug-induced liver injury. The mechanism of action of novel therapies, the potential of their benefit in clinical settings, and adverse drug reactions related to novel therapies were extracted. Cochrane Risk of bias tool and Grading of Recommendations Assessment, Development and Evaluation (GRADE) assessment approach was involved in the assessment of the certainty of the evidence for primary outcomes of included studies. One thousand three hundred seventy-two articles were identified. Twenty-eight articles were included in the final analysis. Eight randomized controlled trials (RCTs) were detected and for six the available data were sufficient for analysis. In abstract form only we found six studies which were also anaylzed. Investigated agents included: bicyclol, calmangafodipir, cytisin amidophospate, fomepizole, livina-polyherbal preparation, magnesium isoglycyrrhizinate (MgIG), picroliv, plasma exchange, radix Paeoniae Rubra, and S-adenosylmethionine. The primary outcomes of included trials mainly included laboratory markers improvement. Based on the moderate-certainty evidence, more patients treated with MgIG experienced alanine aminotransferase (ALT) normalization compared to placebo. Low-certainty evidence suggests that bicyclol treatment leads to a reduction of ALT levels compared to phosphatidylcholine. For the remaining eight interventions, the certainty of the evidence for primary outcomes was assessed as very low and we are very uncertain in any estimate of effect. More effort should be involved to investigate the novel treatment of DILI. Well-designed RCTs with appropriate sample sizes, comparable groups and precise, not only surrogate outcomes are urgently welcome.
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Affiliation(s)
- Mirjana Stanić Benić
- Department of Clinical Pharmacology, Clinical Hospital Centre Rijeka, Rijeka, Croatia
| | - Lana Nežić
- Department of Pharmacology, Toxicology and Clinical Pharmacology, Faculty of Medicine, University of Banja Luka, Banja Luka, Bosnia and Herzegovina
| | - Vesna Vujić-Aleksić
- Department of Pharmacology, Toxicology and Clinical Pharmacology, Faculty of Medicine, University of Banja Luka, Banja Luka, Bosnia and Herzegovina
- The Republic of Srpska Agency for Certification, Accreditation and Quality Improvement in Health Care, Banja Luka, Bosnia and Herzegovina
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16
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Role of Multiple Comorbidities and Therapies in Conditioning the Clinical Severity of DRESS: A Mono-Center Retrospective Study of 25 Cases. Int J Mol Sci 2021; 22:ijms22137072. [PMID: 34209467 PMCID: PMC8268599 DOI: 10.3390/ijms22137072] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2021] [Revised: 06/24/2021] [Accepted: 06/27/2021] [Indexed: 12/14/2022] Open
Abstract
DRESS/DiHS is a complex and potentially fatal drug reaction. Little is known about risk factors and elements that can help to identify patients with a severe reaction early. The aim of the study was to investigate those factors favoring the disease and its severity by analyzing the clinical conditions and therapies preceding the reaction. We conducted a retrospective analysis on patients admitted to our center between 2010 and 2020 who were discharged with a diagnosis of DRESS. We used the RegiSCAR diagnostic criteria. We defined the severity of DRESS using the criteria of Mizukawa et al. We included 25 patients (15 females) with a median age of 66 years. Skin involvement, eosinophilia, and liver injury were the most important aspects. Allopurinol was found to be the most involved drug. Reaction severity was significantly associated with the number of daily medications (p = 0.0067) and an age of at least 68 years (p = 0.013). In addition, 75% of severe cases had at least three comorbidities in history, and most of the severe cases were female. In our study the advanced age, the high number of comorbidities and home therapies, and the inflammatory state were found to be predisposing elements to the development of the disease and its severity.
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17
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Kim GY, Anderson KR, Davis DM, Hand JL, Tollefson MM. Drug reaction with eosinophilia and systemic symptoms (DRESS) in the pediatric population: A systematic review of the literature. J Am Acad Dermatol 2020; 83:1323-1330. [DOI: 10.1016/j.jaad.2020.03.081] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2019] [Revised: 03/11/2020] [Accepted: 03/25/2020] [Indexed: 12/17/2022]
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Sharifzadeh S, Mohammadpour AH, Tavanaee A, Elyasi S. Antibacterial antibiotic-induced drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome: a literature review. Eur J Clin Pharmacol 2020; 77:275-289. [PMID: 33025080 PMCID: PMC7537982 DOI: 10.1007/s00228-020-03005-9] [Citation(s) in RCA: 60] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2019] [Accepted: 09/18/2020] [Indexed: 02/06/2023]
Abstract
Background Drug reaction with eosinophilia and systemic symptoms syndrome (DRESS) is a delayed infrequent potentially life-threatening idiosyncratic drug reaction. Aromatic anticonvulsants and allopurinol are the most frequent causative agents. However, various reports of antibiotic-induced DRESS are available. In this review, we try to summarize reports of antibacterial antibiotic-induced DRESS focusing on characteristics of DRESS induced by each antibiotic group. Methods The data were collected by searching PubMed/MEDLINE and ScienceDirect. The keywords used as search terms were “DRESS syndrome,” “drug-induced hypersensitivity syndrome (DIHS),” “antibiotics,” “antimicrobial,” and names of various antimicrobial groups. Finally, 254 relevant cases with a definite or probable diagnosis of DRESS based on RegiSCAR criteria were found until 30 May 2020 and reviewed. Results and conclusion Totally, 254 cases of antibacterial antibiotic-induced DRESS are reported. Most of them are related to antituberculosis drugs, vancomycin, and sulfonamides, respectively. Rash and fever were most frequent clinical findings. Eosinophilia and liver injury were the most reported hematologic and visceral organ involvement, respectively. Most of the patients are managed with systemic corticosteroids. The death occurred in 16 patients which most of them experienced liver or lung involvement. The reactivation of various viruses especially HHV-6 is reported in 33 cases. The mean latency period was 29 days. It is necessary to perform thorough epidemiological, genetic, and immunological studies, also systematic case review and causality assessment, as well as well-designed clinical trials for better management of antibiotic-induced DRESS. Electronic supplementary material The online version of this article (10.1007/s00228-020-03005-9) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Shiva Sharifzadeh
- Department of Clinical Pharmacy, School of Pharmacy, Mashhad University of Medical Sciences, P.O. Box 91775-1365, Mashhad, Iran
| | - Amir Hooshang Mohammadpour
- Department of Clinical Pharmacy, School of Pharmacy, Mashhad University of Medical Sciences, P.O. Box 91775-1365, Mashhad, Iran
- Pharmaceutical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Ashraf Tavanaee
- Department of Infectious Disease, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Sepideh Elyasi
- Department of Clinical Pharmacy, School of Pharmacy, Mashhad University of Medical Sciences, P.O. Box 91775-1365, Mashhad, Iran.
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Jian M, Yang XF, Zhou S, Pi YY, Lei XY. Etiology, diagnosis, and treatment of drug induced liver injury. Shijie Huaren Xiaohua Zazhi 2019; 27:715-720. [DOI: 10.11569/wcjd.v27.i11.715] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Drug induced liver injury (DILI) is a common adverse effect in clinical practice, which can cause acute liver failure and even threaten the life. Currently, there are over 1000 commonly used drugs that are clearly capable of causing DILI, which has become a world medical safety issue of great concern. This article reviews the etiology, pathogenesis, diagnosis, and treatment of DILI, with an aim to provide a reference for prevention and prognosis and further research of this disease.
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Affiliation(s)
- Ming Jian
- Institute of Pharmacy and Pharmacology, University of South China, Hengyang 421001, Hunan Province, China
| | - Xue-Feng Yang
- Department of Gastroenterology, Nanhua Hospital, Nanhua University, Hengyang 421002, Hunan Province, China
| | - Shuang Zhou
- Institute of Pharmacy and Pharmacology, University of South China, Hengyang 421001, Hunan Province, China
| | - Yi-Yuan Pi
- Institute of Pharmacy and Pharmacology, University of South China, Hengyang 421001, Hunan Province, China
| | - Xiao-Yong Lei
- Institute of Pharmacy and Pharmacology, University of South China, Hengyang 421001, Hunan Province, China
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20
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Han XD, Koh MJA, Wong SMY. Drug reaction with eosinophilia and systemic symptoms in a cohort of Asian children. Pediatr Dermatol 2019; 36:324-329. [PMID: 30920020 DOI: 10.1111/pde.13812] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
BACKGROUND/OBJECTIVES Drug reaction with eosinophilia and systemic symptoms (DRESS) is rare but potentially fatal in children. Fever and rash, which are salient features of DRESS, may mimic other commonly encountered pediatric conditions. We profiled the DRESS cases in a tertiary children's hospital in Singapore. METHODS The medical records of all pediatric DRESS patients diagnosed from 2006 to 2016. Data on epidemiology, inciting drugs, clinical, pathologic manifestations, and treatment were assessed. RESULTS Ten patients aged 4-16 years old were diagnosed with DRESS within the 10-year period. Drugs implicated were antibiotics, such as trimethoprim-sulfamethoxazole, and anticonvulsants, such as carbamazepine, phenobarbitone, and levetiracetam. All patients had fever and pruritic exanthems. Desquamation, purpura, and oral mucositis were also observed. Lymphadenopathy, hepatomegaly, and facial edema occurred frequently. There was liver involvement in all cases, but none progressed to liver failure. Seven patients had eosinophilia, and nine had atypical lymphocytosis. Other laboratory abnormalities included low hemoglobin, thrombocytosis, and prolonged coagulation times. All patients received systemic corticosteroids of varying durations and dosages. Systemic steroids were weaned after 19 days to 4 months. Disease resolution, with liver enzyme levels returning to normal, occurred within 28-90 days. One patient developed TSH-receptor-antibody-positive hyperthyroidism 6 months after the onset of DRESS, while another patient developed chronic urticaria 4 months after resolution of DRESS. CONCLUSION Early recognition of DRESS is important to ensure that the inciting drug is discontinued, and supportive treatment started expediently. Liver involvement was very common but responded well to systemic steroids.
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Affiliation(s)
- Xiuhui D Han
- Dermatology Service, KK Women's and Children's Hospital, Singapore, Singapore
| | - Mark J-A Koh
- Dermatology Service, KK Women's and Children's Hospital, Singapore, Singapore
| | - Sharon M Y Wong
- Dermatology Service, KK Women's and Children's Hospital, Singapore, Singapore
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21
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Arnold KA, Gao J, Stein SL. A review of cutaneous hypersensitivity reactions in infants: From common to concerning. Pediatr Dermatol 2019; 36:274-282. [PMID: 31025427 PMCID: PMC7167752 DOI: 10.1111/pde.13827] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Cutaneous hypersensitivity reactions in infants present in a variety of patterns. These skin eruptions can be dramatic, causing alarm in parents and medical personnel. Many of these syndromes have overlapping features, which adds to the confusion and uncertainty regarding diagnosis and management. This review discusses the spectrum of hypersensitivity responses with a focus on their presentation in infants. The clinical findings, pathophysiology, histopathology, management, and complications of these conditions will be reviewed.
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Affiliation(s)
- Kathryn A Arnold
- University of Chicago Pritzker School of Medicine, Chicago, Illinois
| | - Jingyun Gao
- Section of Dermatology, Department of Medicine and Pediatrics, University of Chicago, Chicago, Illinois
| | - Sarah L Stein
- Section of Dermatology, Department of Medicine and Pediatrics, University of Chicago, Chicago, Illinois
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22
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Drug Reaction with Eosinophilia and Systemic Symptoms (DReSS): How Far Have We Come? Am J Clin Dermatol 2019; 20:217-236. [PMID: 30652265 DOI: 10.1007/s40257-018-00416-4] [Citation(s) in RCA: 34] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Drug reaction with eosinophilia and systemic symptoms (DReSS), also known as drug-induced hypersensitivity syndrome (DiHS), is an uncommon severe adverse reaction to medications. It is important to recognize it as it is potentially fatal and can cause significant morbidity. From the first reports of drug reactions related to certain anticonvulsants characterized by fever, liver enzyme elevation, and skin changes, our continuously growing understanding of this entity has allowed us to describe its physiopathology and clinical features even further. The relationship of genetic factors, viral activation, and specific drug exposure is now known to play a role in this disease. There is still not a widely accepted marker for DReSS/DiHS, but the spectrum of clinical and laboratory features has now been better outlined. The mainstay of treatment is the use of systemic corticosteroids, but other options such as intravenous immunoglobulin, cyclosporine, mycophenolate mofetil, rituximab, and cyclophosphamide have been described. We present a comprehensive review of the literature on DReSS/DiHS, focusing on its history, etiopathogenesis, diagnosis, therapeutic approach, and outcome.
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23
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Martinez-Cabriales SA, Shear NH, Gonzalez-Moreno EI. Liver involvement in the drug reaction, eosinophilia, and systemic symptoms syndrome. World J Clin Cases 2019; 7:705-716. [PMID: 30968035 PMCID: PMC6448072 DOI: 10.12998/wjcc.v7.i6.705] [Citation(s) in RCA: 27] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/04/2018] [Revised: 02/05/2019] [Accepted: 02/26/2019] [Indexed: 02/05/2023] Open
Abstract
First described in 1996, the drug reaction, eosinophilia, and systemic symptoms syndrome (DReSS) is considered, along with Stevens-Johnson syndrome and toxic epidermal necrolysis, a severe cutaneous drug reaction. It is characterized by the presence of a maculopapular erythematous skin eruption, fever, lymphadenopathy, influenza-like symptoms, eosinophilia, and visceral involvement such as hepatitis, pneumonitis, myocarditis, pericarditis, nephritis, and colitis. The prognosis of patients with DReSS is related to the severity of visceral involvement. The mortality ranges from approximately 5% to 10%, and death is mainly due to liver failure, which is also the organ most commonly involved in this syndrome. Although it was previously hypothesized in 1994, DReSS syndrome can lead to reactivation of one or more human herpesvirus family members. Now being included as diagnostic criteria in a proposed diagnostic score system, this reactivation can be detected up to 2-3 wk after DReSS syndrome onset. Other causes of mortality in DReSS syndrome include myocardial or pulmonary lesions and hemophagocytosis. We reviewed the literature of previously reported case-series of DReSS and liver involvement, highlighting the pattern of liver damage, the treatment used, and the outcome.
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Affiliation(s)
- Sylvia A Martinez-Cabriales
- Department of Medicine, Division of Dermatology, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario M4N 3M5, Canada
- Internal Medicine Department, Dermatology Division, Hospital Universitario “Dr. José Eleuterio González”, Universidad Autónoma de Nuevo León, Monterrey, Nuevo León 64460, Mexico
| | - Neil H Shear
- Department of Medicine, Division of Dermatology, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario M4N 3M5, Canada
| | - Emmanuel I Gonzalez-Moreno
- Department of Medicine, Division of Gastroenterology, University of Calgary, Calgary, Alberta T2N 4Z6, Canada
- Internal Medicine Department, Gastroenterology Division, Hospital Universitario “Dr. José Eleuterio González”, Universidad Autónoma de Nuevo León, Monterrey, Nuevo León 64460, Mexico
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24
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Mori F, Caffarelli C, Caimmi S, Bottau P, Liotti L, Franceschini F, Cardinale F, Bernardini R, Crisafulli G, Saretta F, Novembre E. Drug reaction with eosinophilia and systemic symptoms (DRESS) in children. ACTA BIO-MEDICA : ATENEI PARMENSIS 2019; 90:66-79. [PMID: 30830064 PMCID: PMC6502175 DOI: 10.23750/abm.v90i3-s.8167] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/29/2019] [Indexed: 02/07/2023]
Abstract
Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) is a severe reaction to drugs. Incidence of DRESS in children is not well known and the mortality rate seems to be lower than 10%. Anticonvulsants are the main drugs involved both in adults and in children. The treatment of choice is intravenous immunoglobulins and corticosteroids used in synergy. Today there are not controlled clinical trials regarding DRESS treatment in children. Anyway, the prompt withdrawn of the offending drug is of paramount importance for a better prognosis. DRESS sequels may occur, consequently, follow-up visits are required at least until the first year after the reaction. (www.actabiomedica.it)
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Affiliation(s)
- Francesca Mori
- Allergy Unit, Department of Pediatric Medicine, Anna Meyer Children's University Hospital, Florence, Italy.
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25
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Hassan A, Fontana RJ. The diagnosis and management of idiosyncratic drug-induced liver injury. Liver Int 2019; 39:31-41. [PMID: 30003672 DOI: 10.1111/liv.13931] [Citation(s) in RCA: 53] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/15/2018] [Revised: 06/25/2018] [Accepted: 07/10/2018] [Indexed: 12/13/2022]
Abstract
Drug-induced liver injury (DILI) is an uncommon but important cause of liver disease that can arise after exposure to a multitude of drugs and herbal and dietary supplements. The severity of idiosyncratic DILI varies from mild serum aminotransferase elevations to the development of severe liver injury that can progress to acute liver failure resulting in death or liver transplantation within days of DILI onset. Chronic liver injury that persists for more than 6 months after DILI onset is also becoming increasingly recognized in up to 20% of DILI patients. Host demographic (age, gender, race), clinical and laboratory features at DILI onset have been associated with the severity and outcome of liver injury in DILI patients. In addition to cessation of the suspect drug, other medical interventions including the use of N-acetylcysteine and corticosteroids in selected patients have shown some clinical benefit, but additional prospective studies are needed. A number of promising diagnostic, prognostic and mechanistic serum and genetic biomarkers may help improve our understanding of the pathogenesis and treatment of idiosyncratic DILI.
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Affiliation(s)
- Ammar Hassan
- Division of Gastroenterology, Department of internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan
| | - Robert J Fontana
- Division of Gastroenterology, Department of internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan
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26
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Iriki H, Ouchi T, Ito H, Sawada M, Mukai M, Nomura H, Baba Y, Adachi T, Funakoshi T, Amagai M, Takahashi H. Case of lamotrigine-induced drug adverse reaction under tocilizumab treatment with clinical and virological features of drug-induced hypersensitivity syndrome. J Dermatol 2018; 45:738-741. [DOI: 10.1111/1346-8138.14288] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2017] [Accepted: 02/06/2018] [Indexed: 11/26/2022]
Affiliation(s)
- Hisato Iriki
- Department of Dermatology; Keio University School of Medicine; Tokyo Japan
| | - Takeshi Ouchi
- Department of Dermatology; Keio University School of Medicine; Tokyo Japan
| | - Hiromi Ito
- Department of Dermatology; Keio University School of Medicine; Tokyo Japan
| | - Miho Sawada
- Department of Dermatology; Keio University School of Medicine; Tokyo Japan
| | - Miho Mukai
- Department of Dermatology; Keio University School of Medicine; Tokyo Japan
| | - Hisashi Nomura
- Department of Dermatology; Keio University School of Medicine; Tokyo Japan
| | - Yuko Baba
- Department of Dermatology; Keio University School of Medicine; Tokyo Japan
| | - Takeya Adachi
- Department of Dermatology; Keio University School of Medicine; Tokyo Japan
| | - Takeru Funakoshi
- Department of Dermatology; Keio University School of Medicine; Tokyo Japan
| | - Masayuki Amagai
- Department of Dermatology; Keio University School of Medicine; Tokyo Japan
| | - Hayato Takahashi
- Department of Dermatology; Keio University School of Medicine; Tokyo Japan
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27
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Histomorphology and Immunophenotype of Eczematous Skin Lesions Revisited—Skin Biopsies Are Not Reliable in Differentiating Allergic Contact Dermatitis, Irritant Contact Dermatitis, and Atopic Dermatitis. Am J Dermatopathol 2018; 40:7-16. [DOI: 10.1097/dad.0000000000000842] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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Criado PR. Adverse Drug Reactions. DERMATOLOGY IN PUBLIC HEALTH ENVIRONMENTS 2018. [PMCID: PMC7123670 DOI: 10.1007/978-3-319-33919-1_26] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
Adverse events and adverse drug reactions are common in clinical practice. Side effects range from the common to the rare and may be confused with other mucocutaneous manifestations resulting from several medications to treat infections, other medical conditions, and in the clinical setting of oncologic treatment. The objective of this chapter to review current data on adverse drug reactions, here classified as (i) severe adverse drug reactions, (ii) uncomplicated cutaneous adverse drug reactions, and (iii) adverse drug reactions caused by chemotherapy drugs, particularly those cases whereby the dermatologist is requested to issue a report and asked to comment on the safety and viability of readministration of a specific drug. We describe aspects associated with these events, presenting a detailed analysis of each of them.
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29
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Maxfield L, Schlick T, Macri A, Thatcher J. Vancomycin-associated drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome: masquerading under the guise of sepsis. BMJ Case Rep 2017; 2017:bcr-2017-221898. [PMID: 29054953 DOI: 10.1136/bcr-2017-221898] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/03/2022] Open
Abstract
A patient presented with what appeared to be severe urosepsis. After admission and antibiotic administration, a newly developed rash and subsequent facial swelling appeared to be a reaction to penicillin class antibiotics. However, despite changing class of therapy with continued antimicrobial coverage, end organ damage continued, the rash worsened and facial oedema developed. Drug reaction with eosinophilia and systemic symptoms was ultimately diagnosed and was consistent with clinical and histopathological findings, as well as meeting all criteria for scoring systems. The patient was started on intravenous methylprednisolone 125 mg per 8 hours with rapid improvement of rash, swelling and end organ damage. Initial challenge to decrease dose failed, but the patient was ultimately able to be discharged on an extended taper.
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Affiliation(s)
- Luke Maxfield
- Transitional Rotating Internship, Sampson Regional Medical Center, Clinton, NC, USA
| | - Toni Schlick
- College of Medicine, Campbell University College of Osteopathic Medicine, Clinton, North Carolina, USA
| | - Angela Macri
- Dermatology, Sampson Regional Medical Center, Clinton, North Carolina, USA
| | - James Thatcher
- Family Medicine, Sampson Regional Medical Center, Clinton, NC, USA
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De Luca F, Losappio LM, Mirone C, Schroeder JW, Citterio A, Aversano MG, Scibilia J, Pastorello EA. Tolerated drugs in subjects with severe cutaneous adverse reactions (SCARs) induced by anticonvulsants and review of the literature. Clin Mol Allergy 2017; 15:16. [PMID: 29026345 PMCID: PMC5627447 DOI: 10.1186/s12948-017-0072-5] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2017] [Accepted: 09/04/2017] [Indexed: 12/16/2022] Open
Abstract
Background Anticonvulsant hypersensitivity syndrome represents a rare but potentially fatal kind of adverse drug reaction. This clinical picture often hampers the flexibility with which alternative anticonvulsants or even other classes of drugs are prescribed in these patients, negatively affecting the efficacy of treatment and the course of the disease. The aim of this study was to analyse a group of six patients with severe cutaneous drug reactions induced by anticonvulsants and to report which alternative antiepileptic drugs and which drugs of other classes were tolerated. Case presentation A total of six patients (2 males and 4 females, age 11–73 years) are described in this study. In all the patients the onset of the severe cutaneous drug reactions was 2–4 weeks after initiating the anticonvulsant therapy: 2 out of 6 patients presented with a drug reaction with eosinophilia and systemic symptoms under therapy with phenytoin; 2 out of 6 presented with Stevens–Johnson syndrome under therapy with lamotrigine; and 2 out of 6 presented with a toxic epidermal necrolysis, one of them under therapy with valproic acid, and the other one under therapy with lamotrigine. Alternative anticonvulsants tolerated after the reaction were: clonazepam, levetiracetam, diazepam, delorazepam and lormetazepam. Conclusions In our cases we observed that non aromatic anticonvulsants and benzodiazepines were well tolerated as alternative treatments in six patients with reactions to aromatic anticonvulsivants and that the risk of hypersensitivity reactions to other drug classes was not increased as compared to general population.
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Affiliation(s)
- Fabrizio De Luca
- Department of Allergology and Immunology, Ospedale Metropolitano Niguarda Ca' Granda, Piazza Ospedale Maggiore, 3, 20162 Milan, Italy
| | - Laura Michelina Losappio
- Department of Allergology and Immunology, Ospedale Metropolitano Niguarda Ca' Granda, Piazza Ospedale Maggiore, 3, 20162 Milan, Italy
| | - Corrado Mirone
- Department of Allergology and Immunology, Ospedale Metropolitano Niguarda Ca' Granda, Piazza Ospedale Maggiore, 3, 20162 Milan, Italy
| | - Jan Walter Schroeder
- Department of Allergology and Immunology, Ospedale Metropolitano Niguarda Ca' Granda, Piazza Ospedale Maggiore, 3, 20162 Milan, Italy
| | - Antonella Citterio
- Department of Burn/Intensive Care, Ospedale Metropolitano Niguarda Ca' Granda, Milan, Italy
| | - Maria Gloria Aversano
- Department of Allergology and Immunology, Ospedale Metropolitano Niguarda Ca' Granda, Piazza Ospedale Maggiore, 3, 20162 Milan, Italy
| | - Joseph Scibilia
- Department of Allergology and Immunology, Ospedale Metropolitano Niguarda Ca' Granda, Piazza Ospedale Maggiore, 3, 20162 Milan, Italy
| | - Elide Anna Pastorello
- Department of Allergology and Immunology, Ospedale Metropolitano Niguarda Ca' Granda, Piazza Ospedale Maggiore, 3, 20162 Milan, Italy
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Wang L, Mei XL. Drug Reaction with Eosinophilia and Systemic Symptoms: Retrospective Analysis of 104 Cases over One Decade. Chin Med J (Engl) 2017; 130:943-949. [PMID: 28397724 PMCID: PMC5407041 DOI: 10.4103/0366-6999.204104] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
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 of P < 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°C were not significantly different between the two groups. However, the number of patients meeting the criteria of “definite” and “probable” (χ2 = 5.852, P = 0.016), with an eosinophilic granulocyte count of ≥1.5 × 109/L (χ2 = 7.129, P = 0.008), and with rash area of >50% BSA (χ2 = 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.
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Affiliation(s)
- Li Wang
- Department of Dermatology, Allergy and Clinical Immunology Centre, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China
| | - Xue-Ling Mei
- Department of Dermatology, Allergy and Clinical Immunology Centre, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China
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Lee JY, Lee SY, Hahm JE, Ha JW, Kim CW, Kim SS. Clinical features of drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome: a study of 25 patients in Korea. Int J Dermatol 2017; 56:944-951. [PMID: 28718873 DOI: 10.1111/ijd.13667] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/24/2016] [Revised: 02/24/2017] [Accepted: 05/03/2017] [Indexed: 12/17/2022]
Abstract
BACKGROUND Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a rare adverse drug reaction. This study aimed to evaluate the incidence of association with individual drugs, clinical manifestations, disease course, and outcomes of DRESS. METHODS Using the criteria of the European Registry of Severe Cutaneous Adverse Reactions (RegiSCAR), the medical records of 25 patients diagnosed with DRESS between 2006 and 2015 were retrospectively reviewed. Demographic data, culprit drugs, latency periods, clinical and laboratory findings, and outcomes were investigated. RESULTS The study group comprised 11 men (44%) and 14 women (56%) with an age range of 13-93 years (mean, 58 ± 19.86 years). The drugs most commonly implicated were carbamazepine (28%), allopurinol (16%), and antituberculosis drugs (12%). Individual latency periods ranged from 4 to 40 days (mean, 17.6 ± 9.95 days). Latency periods for anticonvulsants were significantly longer than those for other drugs (P < 0.05). However, no statistical differences were found between the RegiSCAR scores for anticonvulsants and those for other drugs. Disease severity, based on RegiSCAR score, was correlated with blood count abnormalities (P < 0.05). CONCLUSIONS The results of our study revealed that anticonvulsants were the leading culprit drugs for DRESS, and carbamazepine was the individual drug most commonly associated with DRESS in Korea. Further studies of the mechanisms of action of these drugs are required in order to facilitate prompt diagnosis and effective management, which can affect prognosis and clinical outcome, of DRESS.
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Affiliation(s)
- Jin Y Lee
- Department of Dermatology, Kangdong Sacred Heart Hospital, Hallym University College of Medicine, Seoul, Korea
| | - Suh-Young Lee
- Department of Pulmonary, Allergy and Critical Care Medicine, Kangdong Sacred Heart Hospital, Hallym University College of Medicine, Seoul, Korea
| | - Ji E Hahm
- Department of Dermatology, Kangdong Sacred Heart Hospital, Hallym University College of Medicine, Seoul, Korea
| | - Jae W Ha
- Department of Dermatology, Kangdong Sacred Heart Hospital, Hallym University College of Medicine, Seoul, Korea
| | - Chul W Kim
- Department of Dermatology, Kangdong Sacred Heart Hospital, Hallym University College of Medicine, Seoul, Korea
| | - Sang S Kim
- Department of Dermatology, Kangdong Sacred Heart Hospital, Hallym University College of Medicine, Seoul, Korea
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Yip VLM, Meng X, Maggs JL, Jenkins RE, Marlot PT, Marson AG, Park BK, Pirmohamed M. Mass Spectrometric Characterization of Circulating Covalent Protein Adducts Derived from Epoxide Metabolites of Carbamazepine in Patients. Chem Res Toxicol 2017; 30:1419-1435. [DOI: 10.1021/acs.chemrestox.7b00063] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2023]
Affiliation(s)
- Vincent L. M. Yip
- MRC
Centre for Drug Safety Science, Department of Molecular and Clinical
Pharmacology, The University of Liverpool, Liverpool L69 3GE, United Kingdom
- The
Wolfson Centre for Personalized Medicine, Department of Molecular
and Clinical Pharmacology, The University of Liverpool, Liverpool L69 3GL, United Kingdom
| | - Xiaoli Meng
- MRC
Centre for Drug Safety Science, Department of Molecular and Clinical
Pharmacology, The University of Liverpool, Liverpool L69 3GE, United Kingdom
| | - James L. Maggs
- MRC
Centre for Drug Safety Science, Department of Molecular and Clinical
Pharmacology, The University of Liverpool, Liverpool L69 3GE, United Kingdom
| | - Rosalind E. Jenkins
- MRC
Centre for Drug Safety Science, Department of Molecular and Clinical
Pharmacology, The University of Liverpool, Liverpool L69 3GE, United Kingdom
| | - Philippe T. Marlot
- MRC
Centre for Drug Safety Science, Department of Molecular and Clinical
Pharmacology, The University of Liverpool, Liverpool L69 3GE, United Kingdom
- The
Wolfson Centre for Personalized Medicine, Department of Molecular
and Clinical Pharmacology, The University of Liverpool, Liverpool L69 3GL, United Kingdom
| | - Anthony G. Marson
- MRC
Centre for Drug Safety Science, Department of Molecular and Clinical
Pharmacology, The University of Liverpool, Liverpool L69 3GE, United Kingdom
| | - B. Kevin Park
- MRC
Centre for Drug Safety Science, Department of Molecular and Clinical
Pharmacology, The University of Liverpool, Liverpool L69 3GE, United Kingdom
| | - Munir Pirmohamed
- MRC
Centre for Drug Safety Science, Department of Molecular and Clinical
Pharmacology, The University of Liverpool, Liverpool L69 3GE, United Kingdom
- The
Wolfson Centre for Personalized Medicine, Department of Molecular
and Clinical Pharmacology, The University of Liverpool, Liverpool L69 3GL, United Kingdom
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Mazzanti G, Moro PA, Raschi E, Da Cas R, Menniti‐Ippolito F. Adverse reactions to dietary supplements containing red yeast rice: assessment of cases from the Italian surveillance system. Br J Clin Pharmacol 2017; 83:894-908. [PMID: 28093797 PMCID: PMC5346868 DOI: 10.1111/bcp.13171] [Citation(s) in RCA: 61] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2016] [Revised: 10/11/2016] [Accepted: 10/23/2016] [Indexed: 01/02/2023] Open
Abstract
AIMS Red yeast rice (RYR) is contained in dietary supplements for patients with dyslipidemia. RYR supplements contain monacolin K, which is chemically identical to lovastatin, a licensed drug with a well-known risk profile. We aim to describe the safety profile of RYR by analysing spontaneous reports of suspected adverse reactions (ARs). METHODS Within the Italian Surveillance System of Natural Health Products, suspected ARs were collected and evaluated by a multidisciplinary group of experts to assess causality using the WHO-UMC system or the CIOMS/RUCAM score, for hepatic reactions. The public version of the WHO-Vigibase was also queried. RESULTS From April 2002 to September 2015, out of 1261 total reports, 52 reports concerning 55 ARs to RYR dietary supplements were collected. ARs consisted in myalgia and/or increase in creatine phosphokinase (19), rhabdomyolysis (1), liver injury (10), gastrointestinal reactions (12), cutaneous reactions (9) and other reactions (4). Women were involved in 70% of cases. In 13 cases, the reaction required hospitalization, and 28 patients were taking other medications. Dechallenge was positive in 40 reactions (73%), rechallenge was positive in 7. Causality resulted as certain (1), probable (31, 56%), possible (18, 34%), unlikely (3) or unassessable (2). Similar distribution emerged from the WHO-Vigibase. CONCLUSIONS The potential safety signals of myopathies and liver injury raise the hypothesis that the safety profile of RYR is similar to that of statins. Continuous monitoring of dietary supplements should be promoted to finally characterize their risk profile, thus supporting regulatory bodies for appropriate actions.
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Affiliation(s)
- Gabriela Mazzanti
- Department of Physiology and Pharmacology ‘Vittorio Erspamer’Sapienza University of RomePiazzale Aldo Moro 500185RomeItaly
| | - Paola Angela Moro
- Poison Control CenterNiguarda Ca' Grande HospitalPiazza Ospedale Maggiore 320162MilanItaly
| | - Emanuel Raschi
- Pharmacology Unit, Department of Medical and Surgical SciencesUniversity of BolognaVia Irnerio 4840126BolognaItaly
| | - Roberto Da Cas
- Centre for EpidemiologyNational Institute of HealthViale Regina Elena 29900161RomeItaly
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Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) Syndrome and the Rheumatologist. Curr Rheumatol Rep 2017; 19:3. [DOI: 10.1007/s11926-017-0626-z] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
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Wolski TP, Blasick S, Blackford MG. The Case of the Previously Shaky, Unimmunized, Itchy Infant With Rash and Pancytopenia. Clin Pediatr (Phila) 2016; 55:1366-1368. [PMID: 26961688 DOI: 10.1177/0009922816629618] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Affiliation(s)
| | | | - Martha G Blackford
- 1 Akron Children's Hospital, Akron, OH, USA.,2 Northeast Ohio Medical University, Rootstown, OH, USA
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Webb PS, Al-Mohammad A. Enigma: infection or allergy? Vancomycin-induced DRESS syndrome with dialysis-dependent renal failure and cardiac arrest. BMJ Case Rep 2016; 2016:bcr-2016-215911. [PMID: 27571915 DOI: 10.1136/bcr-2016-215911] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/15/2023] Open
Abstract
A man aged 73 years with infective endocarditis presented with septic shock and was started on immediate antimicrobial therapy. His blood culture yielded no organism. Subsequently, he developed a severe allergic reaction to prolonged empirical vancomycin therapy. This manifested as fever, widespread maculopapular rash and severe progressive acute kidney injury ultimately requiring dialysis. In the context of eosinophilia, this was determined to be drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome. Deciphering this complication as allergy in the context of severe infection required extreme caution due to the polarity of treatment with immunosuppression. Ultimately, this was used, with improvement of renal function, resolution of symptoms and absence of recurrence of infection. In summary, we present a case of vancomycin-related DRESS syndrome leading to dialysis-which is unique in the literature-complicating the treatment of culture-negative infective endocarditis.
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Affiliation(s)
- Philip Simon Webb
- Department of Academic Research, Sheffield Teaching Hospitals, Sheffield, South Yorkshire, UK
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Bommersbach TJ, Lapid MI, Leung JG, Cunningham JL, Rummans TA, Kung S. Management of Psychotropic Drug-Induced DRESS Syndrome: A Systematic Review. Mayo Clin Proc 2016; 91:787-801. [PMID: 27126302 DOI: 10.1016/j.mayocp.2016.03.006] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/07/2016] [Revised: 03/01/2016] [Accepted: 03/08/2016] [Indexed: 11/18/2022]
Abstract
Drug rash with eosinophilia and systemic symptoms (DRESS) is a severe cutaneous eruption that has been linked to several common drugs and drug categories, including antiepileptics, allopurinol, sulfonamides, and various antibiotics; however, because of a number of recent case reports linking psychotropic medications to this condition, DRESS is increasingly recognized among psychiatrists. We systematically reviewed all psychotropic drugs linked to DRESS syndrome, and this article summarizes the clinical management relevant to psychiatric professionals. A comprehensive search was performed using Ovid MEDLINE, Ovid EMBASE, Ovid Cochrane Database of Systematic Reviews, Web of Science, Scopus, and Litt's Drug Eruption and Reaction Database for articles published in English during the past 20 years (1996-2015) using the search terms (1) psychotropic drugs OR serotonin uptake inhibitors AND DRESS or (2) psychotropic drugs AND drug reaction (or rash) eosinophilia systemic syndrome, and all article abstracts were screened for inclusion and exclusion criteria by 3 reviewers. Two independent reviewers examined the full text of 163 articles, of which 96 (25 original articles, 12 review articles, 55 case reports, and 4 letters to the editor) were included in the systematic review. We identified 1072 cases of psychotropic drug-induced DRESS, with carbamazepine, lamotrigine, phenytoin, valproate, and phenobarbital being the most implicated drugs. Based on our review of the literature, we outline management principles that include prompt withdrawal of the causative drug, hospitalization, corticosteroid therapy, and novel treatments, including intravenous immunoglobulin, cyclophosphamide, and cyclosporine, for corticosteroid-resistant DRESS. Finally, we outline strategies for treating comorbid psychiatric illness after a DRESS reaction to the psychotropic medication.
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Affiliation(s)
- Tanner J Bommersbach
- Mayo Medical School, Mayo Clinic College of Medicine, Mayo Clinic, Rochester, MN
| | - Maria I Lapid
- Department of Psychiatry and Psychology, Mayo Clinic, Rochester, MN.
| | | | | | - Teresa A Rummans
- Department of Psychiatry and Psychology, Mayo Clinic, Rochester, MN
| | - Simon Kung
- Department of Psychiatry and Psychology, Mayo Clinic, Rochester, MN
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Gould J, Callis CM, Dolan DG, Stanard B, Weideman PA. Special endpoint and product specific considerations in pharmaceutical acceptable daily exposure derivation. Regul Toxicol Pharmacol 2016; 79 Suppl 1:S79-93. [PMID: 27233924 DOI: 10.1016/j.yrtph.2016.05.022] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2016] [Accepted: 05/19/2016] [Indexed: 12/12/2022]
Abstract
Recently, a guideline has been published by the European Medicines Agency (EMA) on setting safe limits, permitted daily exposures (PDE) [also called acceptable daily exposures (ADE)], for medicines manufactured in multi-product facilities. The ADE provides a safe exposure limit for inadvertent exposure of a drug due to cross-contamination in manufacturing. The ADE determination encompasses a standard risk assessment, requiring an understanding of the toxicological and pharmacological effects, the mechanism of action, drug compound class, and the dose-response as well as the pharmacokinetic properties of the compound. While the ADE concept has broad application in pharmaceutical safety there are also nuances and specific challenges associated with some toxicological endpoints or drug product categories. In this manuscript we discuss considerations for setting ADEs when the following specific adverse health endpoints may constitute the critical effect: genotoxicity, developmental and reproductive toxicity (DART), and immune system modulation (immunostimulation or immunosuppression), and for specific drug classes, including antibody drug conjugates (ADCs), emerging medicinal therapeutic compounds, and compounds with limited datasets. These are challenging toxicological scenarios that require a careful evaluation of all of the available information in order to establish a health-based safe level.
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Rosa G, Fernandez AP, Vij A, Sood A, Plesec T, Bergfeld WF, Billings SD. Langerhans cell collections, but not eosinophils, are clues to a diagnosis of allergic contact dermatitis in appropriate skin biopsies. J Cutan Pathol 2016; 43:498-504. [DOI: 10.1111/cup.12707] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2015] [Revised: 01/12/2016] [Accepted: 03/05/2016] [Indexed: 11/26/2022]
Affiliation(s)
- Gabriela Rosa
- Department of Pathology; The Cleveland Clinic; Cleveland OH USA
| | - Anthony P. Fernandez
- Department of Pathology; The Cleveland Clinic; Cleveland OH USA
- Department of Dermatology; The Cleveland Clinic; Cleveland OH USA
| | - Alok Vij
- Department of Dermatology; The Cleveland Clinic; Cleveland OH USA
| | - Apra Sood
- Department of Dermatology; The Cleveland Clinic; Cleveland OH USA
| | - Thomas Plesec
- Department of Pathology; The Cleveland Clinic; Cleveland OH USA
| | - Wilma F. Bergfeld
- Department of Pathology; The Cleveland Clinic; Cleveland OH USA
- Department of Dermatology; The Cleveland Clinic; Cleveland OH USA
| | - Steven D. Billings
- Department of Pathology; The Cleveland Clinic; Cleveland OH USA
- Department of Dermatology; The Cleveland Clinic; Cleveland OH USA
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Díaz-Molina V, Tirado-Sánchez A, Ponce-Olivera R. Clinical, aetiological and therapeutic findings in Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) syndrome, four years experience in a third-level Mexican hospital. REVISTA MÉDICA DEL HOSPITAL GENERAL DE MÉXICO 2016. [DOI: 10.1016/j.hgmx.2015.08.004] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022] Open
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Stine JG, Lewis JH. Current and future directions in the treatment and prevention of drug-induced liver injury: a systematic review. Expert Rev Gastroenterol Hepatol 2015; 10:517-36. [PMID: 26633044 PMCID: PMC5074808 DOI: 10.1586/17474124.2016.1127756] [Citation(s) in RCA: 69] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
While the pace of discovery of new agents, mechanisms and risk factors involved in drug-induced liver injury (DILI) remains brisk, advances in the treatment of acute DILI seems slow by comparison. In general, the key to treating suspected DILI is to stop using the drug prior to developing irreversible liver failure. However, predicting when to stop is an inexact science, and commonly used ALT monitoring is an ineffective strategy outside of clinical trials. The only specific antidote for acute DILI remains N-acetylcysteine (NAC) for acetaminophen poisoning, although NAC is proving to be beneficial in some cases of non-acetaminophen DILI in adults. Corticosteroids can be effective for DILI associated with autoimmune or systemic hypersensitivity features. Ursodeoxycholic acid, silymarin and glycyrrhizin have been used to treat DILI for decades, but success remains anecdotal. Bile acid washout regimens using cholestyramine appear to be more evidenced based, in particular for leflunomide toxicity. For drug-induced acute liver failure, the use of liver support systems is still investigational in the United States and emergency liver transplant remains limited by its availability. Primary prevention appears to be the key to avoiding DILI and the need for acute treatment. Pharmacogenomics, including human leukocyte antigen genotyping and the discovery of specific DILI biomarkers offers significant promise for the future. This article describes and summarizes the numerous and diverse treatment and prevention modalities that are currently available to manage DILI.
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Affiliation(s)
- Jonathan G. Stine
- University of Virginia Health System, Department of Medicine, Division of Gastroenterology and Hepatology, JPA and Lee Street, MSB 2145, PO Box 800708, Charlottesville VA 22908
| | - James H. Lewis
- Georgetown University Medical Center, Department of Medicine, Division of Gastroenterology and Hepatology, 3800 Reservoir Rd NW, Washington, DC 20007
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