Acute liver failure caused by drug-induced hypersensitivity syndrome associated with hyperferritinemia

Drug-induced hypersensitivity syndrome(DIHS) is a severe reaction usually characterized by fever,rash,and multiorgan failure,occurring 2-6 wk after drug introduction.It is an immune-mediated reaction involving macrophage and T-lymphocyte activation and cytokine release.A 54-year-old woman was diagnosed with rheumatic arthritis and initiated salazosulfapyridine by mouth.About 10 d later,she had a high fever,skin rash and liver dysfunction.She was admitted to hospital and diagnosed with a drug eruption.She was treated with oral prednisolone 30 mg/d;however,she developed high fever again and her blood tests showed acute liver failure and cytopenia associated with hyperferritinemia.She was diagnosed with acute liver failure and hemophagocytosis caused by DIHS.She was transferred to the Department of Medicine and Bioregulatory Science,Kyushu University,where she was treated with arterial steroid injection therapy.Following this treatment,her liver function improved and serum ferritin immediately decreased.We hypothesized that an immune-mediated reaction in DIHS may have generated over-activation of macrophages and T-lymphocytes,followed by a cytokine storm that affected various organs.The measurement of serum ferritin might be a useful marker of the severity of DIHS.

Carbamazepine Induced Ebstein-Barr Virus Reactivation: A Rare Manifestation of Anticonvulsant Hypersensitivity Syndrome

Carbamazepine (CBZ) is an antiepileptic drug which has multiple mechanisms of action including stabilization of the inactivated stage of the voltage-gated sodium channels, potentiating gamma-amino butyric acid (GABA) receptors as a GABA antagonist, as well as the serotonin releasing affect. It is effective in neuropathic pain syndromes such as post-herpetic neuralgia and trigeminal neuralgia, as well as epilepsy. We presented a 29-year-old female patient with the diagnosis of trigeminal neuralgia (TN) who experienced a reactivation of the latent Ebstein-Barr Virus (EBV) infection in terms of anticonvulsant hypersensitivity syndrome after CBZ use, who gave her approval to publish her data. Since the clinical and serological findings of EBV re-infection resolved after the discontinuation of the drug, this clinical and serological manifestation was attributed to CBZ. Since common side-effects of CBZ are drowsiness, dizziness, headaches, skin reactions, cognitive dysfunctions, we reported an activation of EBV infection due to CBZ consumption as a rare side-effect of the drug.

Liver involvement in the drug reaction,eosinophilia,and systemic symptoms syndrome

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.

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

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

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.

Hypersensitive syndrome reaction of antiepileptic drug: two case reports and literature review

Hypersensitivity syndrome reaction of antiepileptic drug （AED） can induce serious cutaneous, hematological and hepatic events. In severe cases, fulminant hepatic failure may necessitate liver transplantation, and most patients die due to the liver failure. Severe adverse cutaneous reactions, including Steven-Johnson syndrome （SJS）, toxic epidermal necrolysis （TEN） and hypersensitivity syndrome, are rare but life-threatening. Its morality rate is as high as 5%-50%. Accurate early diagnosis and timely treatment may contribute to decreased morality rate. In this paper, we reported cases of hypersensitive syndrome reaction to carbamazepine （CBZ） or phenobarbital （PB） in two patients with epilepsy. Clarification of the therapeutic process and the early manifestation of epilepsy may be helpful to improve the epilepsy therapy while avoiding the potential severe adverse cutaneous reactions of AED. The two reported cases highlighted that the therapeutic process of CBZ and PB might lead to the fatal allergic reaction, which was mainly caused by the absence of epoxide-hydroxylase and the defect of hepatocytes.

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.