C Loussaief

CM Perrett

F Renda

J-C Roujeau

M Tohyama

P Joly

R Tamagawa-Mineoka

S Choudhary

SH Hsiao

SH Kardaun

SJ Sultan

T Shiohara

V Descamps

YC Chen

English

Sholeh Ebrahimpour

Mehdi Mohammadi

Kheirollah Gholami

Crossref

CASE REPORTDrug Reaction with Eosinophilia and Systemic Symptoms(DRESS) with Teicoplanin: A Case ReportSholeh Ebrahimpour1 • Mehdi Mohammadi1 • Kheirollah Gholami1,2Published online: 20 December 2016 The Author(s) 2016. This article is published with open access at Springerlink.comAbstract Intramuscular teicoplanin (400 mg every 12 hfor three doses, then 400 mg daily, intramuscularly) wasprescribed for a 37-year-old woman with presumptivediagnosis of cellulitis. On the 14th day of treatment, shedeveloped generalized maculopapular rash, accompaniedby fever, wheezing, shortening of breath, and lym-phadenopathy. Lab tests revealed abnormal liver enzymes,leukocytosis, and eosinophilia. The treatment was inter-rupted with suspicion of drug reaction. Fever subsided after48 h. Skin eruption and respiratory symptoms began toresolve within 2 weeks. The follow-up lab tests performed1 month later indicated resolution of liver dysfunction.With respect to delayed onset of symptoms including fever,generalized rash, lymphadenopathy, and organ involve-ment, drug reaction with eosinophilia and systemic symp-toms (DRESS) was highly suspected. The causality wasevaluated by conventional scoring systems. The reactionwas rated as probable (score = 5) according to RegiSCARand possible (score = 5) based on Kardaun et al.’s scoringsystem. However, DRESS was not confirmed by theJapanese group’s criteria for diagnosis of DRESS/drug-induced hypersensitivity syndrome (DIHS).Key PointsDrug reaction with eosinophilia and systemicsymptoms (DRESS) is a life-threatening reactionthat necessitates determination and discontinuationof the offending drug.The aromatic structure of teicoplanin is shared bymost other medications involved in DRESS.The use of additional treatment includingintravenous immunoglobulins, corticosteroids andantivirals is generally based on experience ratherthan proven benefits drawn from well-designedclinical trials.IntroductionDrug reaction with eosinophilia and systemic symptoms(DRESS) syndrome is defined as an idiosyncratic, rare, andlife-threatening reaction. The clinical features of the syn-drome, including fever, rash, facial edema, lym-phadenopathy, hematological abnormality, and internalorgan involvement, arise 10–30 days following drugexposure. This late onset of symptoms discriminatesDRESS from some other drug-induced skin reactions suchas erythema morbilliform [1, 2]. The most common sus-pected medicines causing DRESS include aromatic anti-convulsants (carbamazepine, phenytoin, phenobarbital, andlamotrigine), allopurinol, and antibiotics (sulfasalazine,vancomycin, and minocycline) [2]. To the best of ourknowledge, there are limited reports of teicoplanin-inducedDRESS in the literature [2–6]. Here, we report a case of& Kheirollah Gholamikhgholami@tums.ac.ir1 Clinical Pharmacy Department, Faculty of Pharmacy, TehranUniversity of Medical Sciences, Tehran, Iran2 Research Center for Rational Use of Drugs, TehranUniversity of Medical Sciences, 4th Floor, No. 92,Karimkhan Zand Avenue, Hafte Tir Square, Tehran, IranDrug Saf - Case Rep (2017) 4:1https://doi.org/10.1007/s40800-016-0042-8DRESS associated with teicoplanin. This report is impor-tant to enhance our knowledge on severe side effects ofteicoplanin.Case ReportA 37-year-old woman was admitted to hospital with red-ness and edema of inguinal area. The involved area wastender and warm on examination. With a presumptivediagnosis of cellulitis, vancomycin 1 g twice daily wasprescribed. After 24 h, due to the acceptable clinical stateof the patient, treatment was planned to be completed in theambulatory setting. Vancomycin was replaced with teico-planin, considering its ease of administration as an intra-muscular injection (400 mg every 12 h for three doses,then 400 mg daily).On the 14th day of treatment, the patient developedgeneralized maculopapular rash (Fig. 1), accompanied byfever (39 C), wheezing, shortening of breath, and cer-vical and axillary lymphadenopathy. Lab tests revealedabnormal liver enzymes [alanine aminotransferase (ALT)134 IU/L, aspartate transaminase (AST) 141 IU/L, alka-line phosphatase (ALP) 345 IU/L], leukocytosis (whiteblood cell count 17,000/lL) with eosinophilia to morethan 8% (1360/lL), a blood urea nitrogen (BUN) value of24 mg/dL, and a serum creatinine (SCr) value of 0.8 mg/dL. The treatment was interrupted with suspicion of drugreaction. After 48 h, the patient defervesced. Skin erup-tion and respiratory symptoms began to resolve within2 weeks. The follow-up lab test performed 1 month laterindicated resolution of liver dysfunction (ALT 22 U/L,AST 18 U/L).DiscussionWith respect to diversity in scoring systems and differentialdiagnoses, the exact incidence of DRESS, as a life-threat-ening skin reaction, remains unknown. This could be par-tially because there is no gold-standard test for diagnosis ofDRESS, and as a result, the diagnosis remains a challengeand is mainly based on conventional proposed scoringsystems. The most common scoring systems to stratifyDRESS are RegiSCAR [7], the Japanese group’s criteriafor diagnosis of DRESS/drug-induced hypersensitivitysyndrome (DIHS) [8], and a system proposed by Kardaunet al. [9] (Table 1).DRESS is classified as a type IV drug-induced hyper-sensitivity reaction that is characterized by delayed onset ofsymptoms. The rising of eosinophil count and non-necro-tizing lesions differentiate DRESS from other type IVdrug-induced hypersensitivity reactions such as Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN).In regard to delayed onset of signs and symptoms includingskin rash (more than 50% of body surface area), fever(more than 38.5 C), and enlarged lymph node (more than1 cm in two sites), DRESS was highly suspected. Thesefindings are in concordance with previous reports of tei-coplanin-induced DRESS [3, 4, 6]. Additional work-up wasperformed to evaluate hematological abnormalities andorgan involvement, which revealed leukocytosis witheosinophilia and liver involvement.It is noticeable that the patient work-up remainedincomplete. Chest x-ray or computerized tomography (CT)scan and skin biopsy were not performed due to patientnon-compliance. Therefore, pulmonary involvement wasjudged only on the basis of clinical symptoms. TheFig. 1 Generalizedmaculopapular rash on the neckand trunk1 Page 2 of 4 S. Ebrahimpour et al.association of viral reactivation with DRESS has beenreported in previous publications [10]. Testing for humanherpesvirus-6, human herpesvirus-7, and Epstein-Barrvirus antibodies was not requested because of limitedresources. In general, our presumptive diagnosis wasmainly based on clinical signs and symptoms and acces-sible lab tests.On the basis of the scoring systems mentioned above,the reaction was rated as probable (score = 4) according toRegiSCAR and possible (score = 5) according to Kardaunet al.’s scoring system. Since presence of atypical lym-phocytes and reactivation of human herpesvirus were notinvestigated, DRESS was not confirmed by the Japanesegroup’s criteria for diagnosis of DRESS/DIHS.Regardless of the aforementioned limitations, the clini-cal picture was in favor of DRESS.Anticonvulsants with aromatic structure are the mostcommon agents associated with DRESS. The aromaticstructure of vancomycin and teicoplanin may explain theoccurrence of DRESS with these agents [2].In this case, teicoplanin was used instead of vancomycinaccording to the Summary of Product Characteristics(available at http://www.sanofi.com.au). Given the similarstructure of vancomycin and teicoplanin, cross-reactivity isanticipated. Therefore, vancomycin may have promptedthe reaction with teicoplanin. Resolution of symptoms afterdiscontinuation of teicoplanin highlights it as the causativeagent.Withdrawal of the offending medication and supportivecare are the mainstay of management. The implementationof additional treatment including intravenousimmunoglobulins, corticosteroids and antivirals is gener-ally based on experience rather than proven benefits drawnfrom well-designed clinical trials [11–13]. Administrationof corticosteroids in severe pulmonary involvement seemsto be reasonable according to results from some studies[13, 14]. However, we did not implement these interven-tions, considering the lack of proven benefit and thepatient’s overall state of health. Furthermore, withoutperforming imaging tests, pulmonary involvement couldnot be confirmed.Acknowledgements We would like to thank Dr. Hamid-reza TaghvaMasoumi for his expert advice and encouragement through this work.Compliance with Ethical standardsWritten informed consent was obtained from the patient for publi-cation of this case report and any accompanying images. A copy ofthe written consent may be requested for review from the corre-sponding author.Conflicts of interest Sholeh Ebrahimpour, Mehdi Mohammadi, andKheirollah Gholami declare that they have no conflicts of interestrelating to the content of this article.Author contributions SE performed patient follow-up and preparedthe initial manuscript. KH and MM contributed to interpretation ofdata and manuscript revision.Open Access This article is distributed under the terms of theCreative Commons Attribution-NonCommercial 4.0 InternationalLicense (http://creativecommons.org/licenses/by-nc/4.0/), which per-mits any noncommercial use, distribution, and reproduction in anymedium, provided you give appropriate credit to the originalauthor(s) and the source, provide a link to the Creative Commonslicense, and indicate if changes were made.References1. Choudhary S, McLeod M, Torchia D, Romanelli P. Drug reactionwith eosinophilia and systemic symptoms (DRESS) syndrome.J Clin Aesthet Dermatol. 2013;6(6):31–7.Table 1 Kardaun et al.’sscoring system [9] Reproducedfrom Kardaun et al. [9], withpermissionItem Present Absent Patient’sscoreFever C38.5 C (101.3 F) 0 -1 0Enlarged lymph nodes ([1 cm size, at least two sites) 1 0 1Eosinophilia: C700 or C10% (leucopenia); C1500 or C20% (leucopenia) 1; 2 0 1Atypical lymphocytes 1 0 0Rash C50% of body surface area 1 0 1Rash suggestive (C2 of facial edema, purpura, infiltration, desquamation) 1 0 0Skin biopsy suggesting alternative diagnosis -1 0 0Organ involvement: 1; C2 1; 2 0 2Disease duration[15 days 0 -2 0Investigation for alternative cause (blood cultures, ANA*, serology forhepatitis viruses, mycoplasma, Chlamydia), C3 done and negative1 0 0Total score 5Total score\2: excluded; 2–3: possible; 4–5: probable; C6: definite*ANA antinuclear antibodyDrug Reaction with Eosinophilia and Systemic Symptoms with Teicoplanin: A Case Report Page 3 of 4 12. Renda F, Landoni G, Bertini Malgarini R, Assisi A, Azzolini ML,Mucchetti M, et al. Drug reaction with eosinophilia and systemicsymptoms (DRESS): a national analysis of data from 10-yearpost-marketing surveillance. Drug Saf. 2015;38(12):1211–8.3. Tamagawa-Mineoka R, Katoh N, Nara T, Nishimura Y, Yama-moto S, Kishimoto S. DRESS syndrome caused by teicoplaninand vancomycin, associated with reactivation of human her-pesvirus-6. Int J Dermatol. 2007;46(6):654–5.4. Loussaief C, Kooli I, Ben Fradj N, Ben Brahim H, Aouam A, ToumiA, et al. Note technique DRESS syndrome induit par la teicopla-nine. Revue Francaise d’Allergologie. 2015;55(4):308–11.5. Perrett CM, McBride SR. Teicoplanin induced drug hypersensi-tivity syndrome. BMJ. 2004;328(7451):1292.6. Hsiao SH, Chen HH, Chou CH, Lin WL, Liu Yeh PY, Wu TJ.Teicoplanin-induced hypersensitivity syndrome with a precedingvancomycin-induced neutropenia: a case report and literaturereview. J Clin Pharm Ther. 2010;35(6):729–32.7. Roujeau J-C, Allanore L, Liss Y, Mockenhaupt M. Severe cuta-neous adverse reactions to drugs (SCAR): definitions, diagnosticcriteria, genetic predisposition. Dermatol Sinica. 2009;27:203–9.8. Shiohara T, Inaoka M, Kano Y. Drug-induced hypersensitivitysyndrome (DIHS): a reaction induced by a complex interplayamong herpesviruses and antiviral and antidrug immuneresponses. Allergol Int Off J Jpn Soc Allergol. 2006;55(1):1–8.9. Kardaun SH, Sidoroff A, Valeyrie-Allanore L, Halevy S, Davi-dovici BB, Mockenhaupt M, et al. Variability in the clinicalpattern of cutaneous side-effects of drugs with systemic symp-toms: does a DRESS syndrome really exist? Br J Dermatol.2007;156(3):609–11.10. Tohyama M, Hashimoto K, Yasukawa M, Kimura H, HorikawaT, Nakajima K, et al. Association of human herpesvirus 6 reac-tivation with the flaring and severity of drug-induced hypersen-sitivity syndrome. Br J Dermatol. 2007;157(5):934–40.11. Joly P, Janela B, Tetart F, Rogez S, Picard D, D’Incan M, et al.Poor benefit/risk balance of intravenous immunoglobulins inDRESS. Arch Dermatol. 2012;148(4):543–4.12. Chen YC, Chiu HC, Chu CY. Drug reaction with eosinophiliaand systemic symptoms: a retrospective study of 60 cases. ArchDermatol. 2010;146(12):1373–9.13. Descamps V, Ben Said B, Sassolas B, Truchetet F, Avenel-Au-dran M, Girardin P, et al. Management of drug reaction witheosinophilia and systemic symptoms (DRESS). Ann DermatolVenereol. 2010;137(11):703–8.14. Sultan SJ, Sameem F, Ashraf M. Drug reaction with eosinophiliaand systemic symptoms: manifestations, treatment, and outcomein 17 patients. Int J Dermatol. 2015;54(5):537–42.1 Page 4 of 4 S. Ebrahimpour et al.

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Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) with Teicoplanin: A Case Report

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Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) with Teicoplanin: A Case Report

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