Drug Rash With Eosinophilia And Systemic Symptoms Syndrome Research Articles

A Rare Case of Sulfasalazine-Induced DRESS Syndrome With Acute Liver Injury

Drug rash with eosinophilia and systemic symptoms (DRESS) syndrome is a life-threatening, drug-induced hypersensitivity syndrome, characterized by rash, fever, lymphadenopathy, eosinophilia, and internal organ involvement. Most cases of DRESS involve the liver with transaminitis less than 10 times the upper limit of normal, however, severe disease can also rarely be seen - as presented in this case. A 39-year-old woman with psoriatic arthritis (PsA) presents with progressive whole body pruritic rash for one week. Ten months prior to admission, she started apremilast and then one month prior to presentation also started sulfasalazine for her PsA. One week prior to presentation, she noticed an erythematous, pruritic maculopapular rash on her face, chest, arms, legs, and with associated fever. At that time, her rheumatologist discontinued all PsA medications, and she was treated with penicillin for suspected scarlet fever. Her rash worsened, developing facial edema and confluent blistering of her arms and legs. She also developed painful cervical lymphadenopathy. Upon admission, she had a new transaminitis (AST and ALT > 1000 IU/L), elevated INR (1. 4), leukocytosis (30 x103/uL) with eosinophilia (3300 cells/uL), positive HHV-6, and negative viral and autoimmune hepatitis serologies. She had no infectious or neurologic evidence of symptomatic HHV-6 infection. Dermatology, gastroenterology and infectious disease were consulted. A skin biopsy showed a robust lymphomatoid cellular immune reaction with dermal infiltration of eosinophils, consistent with DRESS syndrome. She was started on intravenous and topical steroids and transitioned to a long oral steroid taper, with subsequent resolution of her rash, leukocytosis, and acute liver injury. DRESS syndrome is associated with a range of drugs, including anticonvulsants (phenytoin), sulphonamides, and rarely sulfasalazine. As seen in our case, the onset of the disease is delayed, and ranges from 2 to 6 weeks after the initiation of the therapy. While most cases of DRESS involve only a mild hepatoxicity, severe disease can rarely induce severe transaminitis (AST and ALT >1000 IU/L), hepatomegaly and fulminant liver failure. Treatment involves withdrawal of the causative drug, systemic high dose corticosteroids, and in rare cases with fulminant liver failure even liver transplantation. DRESS syndrome has a mortality rate of 10%, most commonly due to liver failure, making liver involvement a poor prognostic marker.Figure: Trend of Laboratory Values During Hospital Course.Figure: All samples were stained with Hematoxylin-eosin. The biopsy revealed a striking interface dermatitis with marked papillary edema leading to focal areas of epidermaldermal separation (A, B). The supervening epidermis showed spongiosis and eczematous changes (C, D). Many dermal vessels were surrounded by a dense lymphocytic infiltrate containing scattered transformed immunoblastic elements as well as eosinophils (E). There was vascular mural fibrin deposition with mural edema and concomitant endothelial cell swelling, consistent with a lymphomatoid vasculitis (F). ((A) 4x; (B) 10x; (C) 20x; (D) 40x; (E) 100x; (F) 100x).

LAMOTRIGINE INDUCED DRESS SYNDROME

Drug rash with eosinophilia and systemic symptoms (DRESS) syndrome, is a type of hypersensitivity reaction, mainly due to anti-epileptic drugs. Lamotrigine is a newer broad spectrum antiepileptic that can be used in both children and adults. Lamotrigine induced DRESS syndrome is a rare case with incidence of 1/1000 to 1/10000. This syndrome manifests as rash, fever, tender lymphadenopathies, hepatitis, and eosinophilia. This case highlights the need for early diagnosis and treatment of such a rare and life threatening event because early detection of the condition leads to early recovery of the patient. Further re-exposure to the drug should be avoided.

An Unusual Case of Drug-Induced Linear IgA Bullous Disease

An Unusual Case of Drug-Induced Linear IgA Bullous Disease

Dress Syndrome Associated with Captopril: A Case Report

Drug rash with eosinophilia and systemic symptoms (DRESS) syndrome is an adverse drug reaction commonly associated with the aromatic antiepileptic drugs (such as carbamazepine, phenobarbital). DRESS syndrome was exceptionally associated with Angiotensin-converting enzyme (ACE) inhibitors. We report a case of DRESS syndrome in a man probably associated with captopril. A 48-year-old man with a heart stroke history was prescribed on August 15th 2016 Captopril 150 mg/day, moxonidine 0.4 mg/day, and nimodopine 360 mg/day. On September first 2016, he developed a pruriginous maculopapular eruption with edema, and fever at 39°C. The laboratory findings showed a white blood cell count at 6,960 elements/mm3 with eosinophils at 2,130 elements/mm3 (26.8%) associated with atypical lymphocytes. Liver and renal tests were at normal range. Captopril was withdrawn on September 23th 2016.The other drugs were continued. The clinical and biologic symptoms resolved completely 4 weeks later. The REGISCAR score was 4: probable diagnosis of DRESS. The case was evaluated according to Begaud et al method. Captopril was implicated in this case with an imputation score of I2 mainly because of a suggestive delay and the remission of symptoms after drug withdrawal.

Presence of a single nucleotide polymorphism (RS3758581) in a boy with DRESS syndrome

Drug rash with eosinophilia and systemic symptoms (DRESS) syndrome is a rare, potentially life-threatening, drug-induced hypersensitivity reaction that includes rash, hematologic abnormalities, lymphadenopathy, and internal organ involvement. The pathogenesis of DRESS syndrome is partially understood. Various medications have been described as the cause of DRESS syndrome. Phenytoin and allopurinol are the most commonly reported culprit drugs, although more than 50 drugs can induce DRESS syndrome. Members of the cytochrome P450 (CYP) superfamily are the most commonly involved enzymes in metabolism of drugs such as phenytoin. This case report addresses the influence of CYP2C9 genetic polymorphism (a single nucleotide polymorphism) on phenytoin drug metabolism, thereby causing DRESS syndrome.

Anticonvulsivantes inducen síndrome de reacción a drogas con eosinofília y síntomas sistémicos (DRESS) con falla hepática fulminante

El síndrome de reacción a drogas con eosinofilia y síntomas sistémicos (DRESS, por sus siglas en inglés) es una reacción severa de hipersensibilidad inducida por el uso de medicamentos. Se han reportado más de 100 fármacos asociados a este síndrome y, aunque la mayoría de los pacientes tiene una evolución clínica favorable, cerca del 10% desarrolla falla orgánica múltiple e incluso culmina en la muerte. El presente artículo presenta un caso clínico de síndrome DRESS asociado a terapia anticonvulsivante que evolucionó a falla hepática fulminante; aquí se discuten la etiología, patogenia, manifestaciones clínicas, proceso diagnóstico y posible tratamiento.

Eosinophilic Polymyositis and DRESS (Drug Rash with Eosinophilia and Systemic Symptoms) Syndrome by Antitubercular Agents

Eosinophilic polymyositis (EPM) is a heterogeneous disorder characterized by eosinophilic infiltration into skeletal muscles. EPM is occasionally associated with a systemic disease, such as hypereosinophilic syndrome, connective tissue disease, or parasitic infection. However, EPM is rarely reported in drug rash with eosinophilia and systemic symptoms (DRESS) syndrome. We experienced a 17-year-old female who presented with EPM with DRESS syndrome associated with taking antitubercular agents. Key Words: Polymyositis, DRESS syndrome, Antitubercular agents

Therapeutic Trial of Rifabutin After Rifampicin-Associated DRESS Syndrome in Tuberculosis-Human Immunodeficiency Virus Coinfected Patients.

Elimination of a rifamycin from the treatment regimen for tuberculosis negatively impacts outcomes. Cross-reactivity between the rifamycins after drug eruptions is unclear. We report 6 consecutive human immunodeficiency virus-infected patients with rifampicin-associated drug rash with eosinophilia and systemic symptoms (DRESS) syndrome confirmed on diagnostic rechallenge. The patients subsequently tolerated rifabutin. These data inform clinical management of tuberculosis-associated drug reactions.

Acute tubular necrosis as a part of vancomycin induced drug rash with eosinophilia and systemic symptoms syndrome with coincident postinfectious glomerulonephritis.

Drug rash with eosinophilia and systemic symptoms (DRESS) syndrome is a rare and potentially fatal condition characterized by skin rash, fever, eosinophilia, and multiorgan involvement. Various drugs may be associated with this syndrome including carbamazepine, allopurinol, and sulfasalazine. Renal involvement in DRESS syndrome most commonly presents as acute kidney injury due to interstitial nephritis. An 11-year-old boy was referred to the Children's Hospital of Pusan National University because of persistent fever, rash, abdominal distension, generalized edema, lymphadenopathy, and eosinophilia. He previously received vancomycin and ceftriaxone for 10 days at another hospital. He developed acute kidney injury with nephrotic range proteinuria and hypocomplementemia. A subsequent renal biopsy indicated the presence of acute tubular necrosis (ATN) and late exudative phase of postinfectious glomerulonephritis (PIGN). Systemic symptoms and renal function improved with corticosteroid therapy after the discontinuation of vancomycin. Here, we describe a biopsy-proven case of severe ATN that manifested as a part of vancomycin-induced DRESS syndrome with coincident PIGN. It is important for clinicians to be aware of this syndrome due to its severity and potentially fatal nature.

Anti-tuberculosis treatment-induced Drug Rash with Eosinophilia and Systemic Symptoms syndrome

Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) syndrome is a life-threatening adverse drug reaction that is distinct from other drug-related reactions. We report a rare case of DRESS syndrome following anti-tuberculosis treatment.

Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) Cause Interstitial Nephritis: a case Report and Review of Literatures

Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) is a potentially life-threatening, complex, and multifaceted disease which may imitate other grave conditions. It presents with cutaneous drug eruptions, fever, hematologic abnormalities (an eosinophil count of 1500/mm3 or atypical lymphocytosis), and systemic involvement including hematologic, renal, pulmonary, hepatic, cardiac, gastrointestinal, neurologic, and endocrine abnormalities. Anticonvulsant therapies (mainly carbamazepine) are among the most important causative drugs. Case report: Herein we present a10-year-old girl who developed skin rash, systemic symptoms, marked eosinophilia, and kidney involvement following anticonvulsive treatment with phenobarbital and sodium valproate. She experienced multiple hospitalizations due to an improper diagnosis and management. Conclusion: Drug Induced Hypersensitivity Syndrome (DIHS) is a severe life-threatening disorder which mostly occurs due to aromatic anticonvulsive drugs. The disease may mimic other serious conditions and delay in the diagnosis and improper treatment may cause organ involvement and more severe outcomes. Key words: Drug Hypersensitivity Syndrome; DRESS Syndrome; Drug Reaction with Eosinophilia and Systemic Symptoms; Drug Eruptions; Interstitial Nephritis.

Lack of cross-toxicity between isoniazid and ethionamide in severe cutaneous adverse drug reactions: a series of 25 consecutive confirmed cases.

Isoniazid and ethionamide are important first- and second-line anti-TB drugs (FLDs and SLDs), respectively. Ethionamide is a structural analogue of isoniazid and the two drugs share other similarities, including their metabolism, therapeutic targets, hepato-toxicity patterns and drug resistance. As a result, there has always been concern about possible cross-reactivity between them. Among 69 patients with drug rash with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN) to FLDs, FLDs were stopped and SLDs added when the skin and laboratory parameters had settled. This was followed by sequential and additive rechallenge with FLDs. We report 25 consecutive cases that developed confirmed cutaneous adverse drug reactions (CADRs) to isoniazid or ethionamide used as FLD and SLD, respectively. Sixty-nine participants who developed CADRs on FLDs were enrolled in the study. Twenty developed a rechallenge reaction to isoniazid and five reacted to ethionamide. Four of the 20 isoniazid cases were patch test positive, 3/20 were skin prick test positive and 13/20 reacted to oral rechallenge. All seven cases that were patch and skin prick test positive were associated with systemic reactions. Twenty of the 25 cases had DRESS and 5 had SJS/TEN. Twenty-three of the 25 cases with rechallenge reactions were HIV infected. Importantly, none of the cases that reacted to ethionamide during the rechallenge reacted to isoniazid and none who subsequently reacted to isoniazid reacted to ethionamide. Our findings strongly suggest that the risk of cross-reactivity of isoniazid and ethionamide in DRESS syndrome and SJS/TEN is low. These findings have implications for clinical management.

Peripheral blood eosinophilia and hypersensitivity reactions among patients receiving outpatient parenteral antibiotics

Although drug-induced peripheral eosinophilia complicates antimicrobial therapy, little is known about its frequency and implications. We aimed to determine the frequency and predictors of antibiotic-induced eosinophilia and subsequent hypersensitivity reactions (HSRs). We evaluated a prospective cohort of former inpatients receiving intravenous antibiotic therapy as outpatients with at least 1 differential blood count. We used multivariate Cox proportional hazards models with time-varying antibiotic treatment indicators to assess the effect of demographic data and antibiotic exposures on eosinophilia and subsequent HSRs, including documented rash, renal injury, and liver injury. Possible drug rash with eosinophilia and systemic symptoms (DRESS) syndrome cases were identified and manually validated. Of 824 patients (60% male; median age, 60 years; median therapy duration, 41 days), 210 (25%) had eosinophilia, with median peak absolute eosinophil counts of 726/mL (interquartile range, 594-990/mL). Use of vancomycin, penicillin, rifampin, and linezolid was associated with a higher hazard of having eosinophilia. There was a subsequent HSR in 64 (30%) of 210 patients with eosinophilia, including rash (n = 32), renal injury (n = 31), and liver injury (n = 13). Patients with eosinophilia were significantly more likely to have rash (hazard ratio [HR], 4.16; 95% CI, 2.54-6.83; P < .0001) and renal injury (HR, 2.13; 95% CI, 1.36-3.33; P = .0009) but not liver injury (HR, 1.75; 95% CI, 0.92-3.33; P = .09). Possible DRESS syndrome occurred in 7 (0.8%) of 824 patients; 4 (57%) were receiving vancomycin. Drug-induced eosinophilia is common with parenteral antibiotics. Although most patients with eosinophilia do not have an HSR, eosinophilia increases the hazard rate of having rash and renal injury. DRESS syndrome was more common than previously described.

Challenges in Diagnosis, Management, and Treatment of Allopurinol-Induced DRESS Syndrome

We describe the presentation, diagnosis, management, and treatment of a 62-year-old woman with a medical history of gout who presented with a maculopapular rash, facial and tongue edema. Her initial presentation, coupled with a history of recent allopurinol use for systematic relief, led to the diagnosis of allopurinol-induced drug rash with eosinophilia and systemic symptoms (DRESS) syndrome, further confirmed by the RegiSCAR scoring criteria including a skin biopsy. The patient was initially treated conservatively but required systemic corticosteroid therapy as she developed severe multi-organ dysfunction. This article will highlight the challenges involved in diagnosing DRESS syndrome from other adverse cutaneous drug reactions, delayed systemic complications, and the need for evidence-based treatment modalities and regimens using the most recent published literature and analysis of case reports. Among treatment modalities, pulsed parenteral steroids show promise in a few case reports. We also discuss the newer alternative gout therapies since the mainstay of gout treatment, allopurinol, is potentially associated with morbidity and mortality risks as manifested in our patient with DRESS.

Vancomycin-Induced Drug Rash With Eosinophilia and Systemic Symptoms

Drug rash with eosinophilia and systemic symptoms (DRESS) is a severe drug-induced hypersensitivity reaction associated with 10% mortality rate with an incidence ranging from 1/1,000 to 1/10,000 drug exposures. Symptoms include fever, rash, eosinophilia and multi-organ failure. DRESS has been most commonly reported with anticonvulsants, allopurinol, sulfonamides and less commonly with vancomycin. This is a case of a 34-year-old female with history of osteomyelitis being treated with vancomycin in a rehabilitation facility. After 3 weeks on vancomycin, patient started to have fever and generalized rash and was still continued on vancomycin. One week thereafter, patient was noted to be hypoxic and tachycardic, and initially admitted and treated as severe sepsis. Initial laboratory studies were remarkable for WBC 21.6 × 10 3 /?L, eosinophils 2.2 × 10 3 /?L, creatinine 1.51 mg/dL, AST 710 unit/L, ALT 659 unit/L and lactic acid 2.8 mg/dL. CMV and HHV-6 were detected in serum. Chest CT showed ground glass opacities and lymphadenopathies. Liver ultrasound showed mild hepatosplenomegaly. Patient continued to be on broad spectrum antibiotics and showed no improvement. Due to worsening liver function tests and kidney injury, all antibiotics were withdrawn, after which she showed significant improvement of symptoms. During her 4 weeks of prolonged clinical course she had one relapse of symptoms with fever, rash and leukocytosis. Eventually, patient slowly recovered with supportive treatment. DRESS syndrome usually has a delayed onset with known relapse of symptoms throughout its clinical course. Addition of new drugs and herpesvirus reactivation have both been shown to cause relapse of symptoms. The mainstay of treatment remains to be withdrawal of drug and treatment with steroids. This case demonstrates DRESS syndrome secondary to vancomycin exposure with relapse of symptoms most likely associated with addition of new drugs, herpes viral reactivation and absence of steroid therapy. Vancomycin, as a commonly used drug especially with increasing MRSA, warrants increased awareness of its association with DRESS for prompt early recognition of symptoms and withdrawal of offending drug. J Med Cases. 2015;6(5):201-204 doi: http://dx.doi.org/10.14740/jmc2103w

Histopathology of drug rash with eosinophilia and systemic symptoms syndrome: a morphological and phenotypical study.

The histopathological features of drug rash with eosinophilia and systemic symptoms (DRESS) syndrome remain poorly characterized. To better characterize the histopathological features of DRESS syndrome, and define the phenotype of the effector cells in the skin and compare it with maculopapular rash (MPR). We conducted a retrospective study on 50 skin biopsies from patients with DRESS syndrome (n = 36). Histopathological and immunophenotypical features were studied and compared with a series of MPRs (n = 20). Foci of interface dermatitis, involving cutaneous adnexae, were frequently seen in cases of DRESS. Eosinophils were seen in only 20% of cases and neutrophils in 42%. Eczematous (40%), interface dermatitis (74%), acute generalized exanthematic pustulosis-like (20%) and erythema multiforme-like (24%) patterns were observed. The association of two or three of these patterns in a single biopsy was significantly more frequent in cases of DRESS than in a series of nondrug-induced dermatoses (P < 0.01), and appeared to be more marked in DRESS syndrome with severe cutaneous lesions (P = 0.01) than in less severe cases of DRESS and MPR. A higher proportion of CD8(+) and granzyme B(+) lymphocytes was observed in cases of DRESS with severe cutaneous eruptions (erythroderma and/or bullae). Atypical lymphocytes were found in 28% of biopsies, and expressed CD8 in most cases; a cutaneous T-cell clone was rarely found (6%). The histopathology of DRESS syndrome highlights various associated inflammatory patterns in a single biopsy. Cutaneous effector lymphocytes comprise a high proportion of polyclonal CD8(+) granzyme B(+) T lymphocytes.

Vancomycin-Induced Drug Rash With Eosinophilia and Systemic Symptoms

Drug rash with eosinophilia and systemic symptoms (DRESS) is a severe drug-induced hypersensitivity reaction associated with 10% mortality rate with an incidence ranging from 1/1,000 to 1/10,000 drug exposures. Symptoms include fever, rash, eosinophilia and multi-organ failure. DRESS has been most commonly reported with anticonvulsants, allopurinol, sulfonamides and less commonly with vancomycin. This is a case of a 34-year-old female with history of osteomyelitis being treated with vancomycin in a rehabilitation facility. After 3 weeks on vancomycin, patient started to have fever and generalized rash and was still continued on vancomycin. One week thereafter, patient was noted to be hypoxic and tachycardic, and initially admitted and treated as severe sepsis. Initial laboratory studies were remarkable for WBC 21.6 × 10 3 /μL, eosinophils 2.2 × 10 3 /μL, creatinine 1.51 mg/dL, AST 710 unit/L, ALT 659 unit/L and lactic acid 2.8 mg/dL. CMV and HHV-6 were detected in serum. Chest CT showed ground glass opacities and lymphadenopathies. Liver ultrasound showed mild hepatosplenomegaly. Patient continued to be on broad spectrum antibiotics and showed no improvement. Due to worsening liver function tests and kidney injury, all antibiotics were withdrawn, after which she showed significant improvement of symptoms. During her 4 weeks of prolonged clinical course she had one relapse of symptoms with fever, rash and leukocytosis. Eventually, patient slowly recovered with supportive treatment. DRESS syndrome usually has a delayed onset with known relapse of symptoms throughout its clinical course. Addition of new drugs and herpesvirus reactivation have both been shown to cause relapse of symptoms. The mainstay of treatment remains to be withdrawal of drug and treatment with steroids. This case demonstrates DRESS syndrome secondary to vancomycin exposure with relapse of symptoms most likely associated with addition of new drugs, herpes viral reactivation and absence of steroid therapy. Vancomycin, as a commonly used drug especially with increasing MRSA, warrants increased awareness of its association with DRESS for prompt early recognition of symptoms and withdrawal of offending drug. J Med Cases. 2015;6(5):201-204 doi: https://doi.org/10.14740/jmc2103w

Isoniazid-induced Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) Syndrome Presenting as Acute Eosinophilic Myocarditis

It has been reported that hypereosinophilic syndrome may be induced by antituberculosis drugs. We herein report the case of a 43-year-old man who had been on antituberculosis drugs for two months to treat tuberculous meningitis. During therapy, he suffered from drug rash with eosinophilia and systemic symptoms (DRESS) presenting as acute eosinophilic myocarditis, as confirmed on a histopathologic examination. According to the patient's medication history, clinical features and accessory examination findings, the eosinophilic myocarditis was thought to be possibly induced by isoniazid. Although further investigations are needed to confirm causality, isoniazid may be added to the list of drugs with the potential to cause DRESS syndrome.

DRESS syndrome due to Anti-Tuberculous Drug

DRESS (Drug Rash with Eosinophilia and Systemic Symptoms) is a potentially life threatening syndrome caused by exposureto certain medications. That may cause skin rash, fever, inflammation of internal organs, lymphadenopathy, and characteristichematologic abdnormalities such ad eosinophilia, thrombocytopenia, and typical atypical lymphocytosis. The interval between thestarting of drug therapy and the onset of cutaneous reactions may be at least one month. Aromatic anticonvulsants(phenytoin, phenobarbital, carbamazepine) and sulfonamides are the most common causes of DRESS. There has been only afew case reports of DRESS syndrome induced by anti-tuberculous medication, Ethambutol, Rifampin, Isoniazid, Pyrazinamide. Wereport a case of Ethambutol induced DRESS syndrome and multiple drug hypersensitivity to other antituberculosis drugs thatwere used at after DRESS syndrome developed.

DRESS syndrome induced by piperacillin‐tazobactam

Background DRESS (drug rash with eosinophilia and systemic symptoms) syndrome is quite difficult to diagnose due to its mimic nature and an absence of a specific diagnostic confirmation technique. In fact, this entity used to be misdiagnosed. Different drug families have been described as causative agents, being the aromatic anticonvulsants the most frequent drugs involved, although other drugs as allopurinol or sulfonamides must be kept in mind too. Until now, piperacillin-tazobactam has been scarcely reported as the culprit drug.