Home About us Editorial board Search Ahead of print Current issue Archives Submit article Instructions Subscribe Contacts Login 
Home Print this page Email this page Small font size Default font size Increase font size Users Online: 257

 Table of Contents  
Year : 2017  |  Volume : 18  |  Issue : 4  |  Page : 349-351

Drug reaction with eosinophilia and systemic symptoms mimicking Kawasaki disease

1 Department of Dermatology and Venereology, Government Medical College, Kozhikode, Kerala, India
2 Department of Paediatrics, Government Medical College, Kozhikode, Kerala, India

Date of Web Publication29-Sep-2017

Correspondence Address:
Kunnummal Muhammed
Department of Dermatology and Venereology, Government Medical College, Kozhikode, Kerala
Login to access the Email id

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/2319-7250.165677

Rights and Permissions

How to cite this article:
Muhammed K, Pillai SS, Nazrin S, Sureshan DN, Nagesh M. Drug reaction with eosinophilia and systemic symptoms mimicking Kawasaki disease. Indian J Paediatr Dermatol 2017;18:349-51

How to cite this URL:
Muhammed K, Pillai SS, Nazrin S, Sureshan DN, Nagesh M. Drug reaction with eosinophilia and systemic symptoms mimicking Kawasaki disease. Indian J Paediatr Dermatol [serial online] 2017 [cited 2021 Jun 24];18:349-51. Available from: https://www.ijpd.in/text.asp?2017/18/4/349/165677


Drug reaction with eosinophilia and systemic symptoms (DRESS) is one of the most difficult adverse drug reaction patterns to diagnose due to its wide spectrum of manifestations mimicking autoimmune, infective or neoplastic diseases. Here, we report a child who developed DRESS closely resembling Kawasaki disease (KD).

A 6-year-old boy (body weight 14 kg) was referred to our tertiary care institution as a case of KD not responding to treatment with intravenous immunoglobulin G (IV IG). His medical history revealed cerebral palsy and myoclonic seizures. He was receiving sodium valproate for the past 2 years, phenytoin for 6 months and lamotrigine (started at 12.5 mg daily dose, which was increased to 25 mg daily after 7 days) for the past 3 weeks. The child was admitted 7 days back in a nearby hospital with high-grade fever, generalized pruritic maculopapular rash [Figure 1], bilateral non purulent conjunctivitis, dryness and scaling of lips, strawberry tongue [Figure 2], cervical and axillary lymphadenopathy and facial and pedal edema. He developed hypotension on the 2nd day of admission (necessitating dopamine infusion). Laboratory investigations revealed polymorphonuclear leukocytosis, elevated erythrocyte sedimentation rate and C-reactive protein levels and 2 times elevation of liver transaminases. Peripheral smear analysis showed 9% atypical lymphocytes and eosinophilia with no evidence of malarial parasites or blast forms. Ultrasound examination of abdomen and pelvis, electrocardiogram, echocardiography and chest radiography were within normal limits. Antinuclear antibody profile and serology for human immune deficiency virus infection, infectious mononucleosis, leptospirosis, typhoid fever, rickettsia, dengue, chikungunya and hepatitis B, C and A infections were negative. Blood culture was sterile. Though there was no evidence of cardiac involvement, as the child satisfied the criteria for KD, a provisional diagnosis of KD was made.[1] IV IgG administered at a dose of 400 mg/kg body weight per day for 5 days achieved only correction of hypotension. Hence, the child was referred to us.
Figure 1: Maculopapular rash and scaling on face

Click here to view
Figure 2: Strawberry tongue

Click here to view

At the time of admission in our institution his temperature was 40°C, respiratory rate 28/min and blood pressure was 100/70 mm mercury on the right upper limb in the supine position. A repeat echocardiogram was again within normal limits. Further investigations revealed the persistence of liver function derangement and an absolute eosinophil count of 1586. We considered the possibility of DRESS to lamotrigine as he satisfied the criteria for definite DRESS as per RegiSCAR DRESS validation scoring.[2],[3] Substituting lamotrigine with levetiracetam and introducing prednisolone (1 mg/kg body weight) tapered over 3 weeks achieved resolution of the disease.

Clear temporal relationship between the onset of drug intake and the appearance of adverse event and the resolution of symptoms following withdrawal of the suspected drug along with clinical course of the disease and the investigation data ruling out most of the other probable etiologies was suggestive of probable drug reaction on Naranjo probability scale.[4]

Rash involving more than 50% of body surface area (1 point), lymphadenopathy in two different anatomical sites more than 1 cm in size (1 point), atypical lymphocytes in peripheral smear (1 point), AEC above 1500 cells/mm 3 (2 points) and negative serology for ANA and infections due to hepatitis A, B and C viruses and sterile blood culture (1 point) in our patient added to a score of 6 indicating definite DRESS according to RegiSCAR DRESS validation scoring.[2],[3]

A higher risk for lamotrigine induced drug reaction is noted in children especially, those co-medicated with sodium valproate.[5]

There are standard guidelines regarding the initial dosing and subsequent titration of lamotrigine so as to minimize the risk of adverse drug reactions.[6] Non-adherence to this might have contributed to the adverse event in our patient.

Drug reaction with eosinophilia and systemic symptoms especially in children is often difficult to distinguish from viral exanthema. Reactivation of human herpes viruses (HHV), especially HHV 6 and 7 are well known to precipitate severe DRESS. Currently, it is believed that the term drug-induced hypersensitivity syndrome should be used to differentiate severe DRESS with HHV reactivation from less severe forms without any evidence of viral reactivation.[7] Irrespective of the reactivation status both types of patients are managed with the withdrawal of the culprit drug and the administration of steroids. The HHV 6 reactivation status in our patient remains unknown.

The major challenge we faced was in distinguishing between DRESS and KD. Both these conditions are diagnoses of exclusion. Many clinical features are shared by both including persistent fever, rash, cervical lymphadenopathy, conjunctival congestion, systemic involvement and dermatological manifestations, including strawberry tongue as observed in our patient.[8] DRESS should be considered in any patient who has been started on drugs (in the past 3 months) well known to induce it.

Drug reaction with eosinophilia and systemic symptoms closely mimicking KD has been reported following lamotrigine and aromatic anticonvulsants.[9],[10] Conversely Chinen and Piecuch. reported an instance when KD was misdiagnosed as DHS.[11]

Kawasaki disease usually responds well to IV IgG within 72 h of administration. IV IgG resistant KD is rarely reported which is treated with methyl prednisolone pulse therapy. This possibility was unlikely in our patient as IV IgG resistant KD is a severe form, but repeated echocardiography was within normal limits in our child.[12],[13]

The French Society of Dermatology recommends systemic steroids with IVIG (400 m g/kg for 5 days) for DRESS with life - threatening signs and opined that IVIG without steroids may not guarantee the desired outcome as happened in our patient.[7] IV IG act by forming immune complexes that block IgG Fc receptors and by neutralizing autoantibodies.[14]

We report this case to stress the significance of considering DRESS when any patient who has started taking drugs known to produce this adverse reaction during the past 3–4 months, presents with pyrexia of unknown origin and also to highlight the importance of systemic steroids in the treatment of DRESS.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/ her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

  References Top

Ayusawa M, Sonobe T, Uemura S, Ogawa S, Nakamura Y, Kiyosawa N, et al. Revision of diagnostic guidelines for Kawasaki disease (the 5th revised edition). Pediatr Int 2005;47:232-4.  Back to cited text no. 1
Kardaun SH, Sidoroff A, Valeyrie-Allanore L, Halevy S, Davidovici BB, Mockenhaupt M, et al. Variability in the clinical pattern of cutaneous side-effects of drugs with systemic symptoms: Does a DRESS syndrome really exist? Br J Dermatol 2007;156:609-11.  Back to cited text no. 2
Chen YC, Chang CY, Cho YT, Chiu HC, Chu CY. Reply to: “Using a diagnostic score when reporting the long-term sequelae of the drug reaction with eosinophilia and systemic symptoms”. J Am Acad Dermatol 2013;69:1060-2.  Back to cited text no. 3
Naranjo CA, Busto U, Sellers EM, Sandor P, Ruiz I, Roberts EA, et al. Amethod for estimating the probability of adverse drug reactions. Clin Pharmacol Ther 1981;30:239-45.  Back to cited text no. 4
Werz MA. Pharmacotherapeutics of epilepsy: Use of lamotrigine and expectations for lamotrigine extended release. Ther Clin Risk Manag 2008;4:1035-46.  Back to cited text no. 5
Bourgeois BF. Antiepileptic drugs (AEDs). In: Wallace SJ, Farrell K, editors. Epilepsy in Children. 2nd ed. England: Edward Arnold Publishers Limited; 2004. p. 387-404.  Back to cited text no. 6
Criado PR, Avancini J, Santi CG, Medrado AT, Rodrigues CE, de Carvalho JF. Drug reaction with eosinophilia and systemic symptoms (DRESS): A complex interaction of drugs, viruses and the immune system. Isr Med Assoc J 2012;14:577-82.  Back to cited text no. 7
Tsyrulnik A, Landman A. Drug rash with eosinophilia and systemic symptoms: Two emergency department cases. West J Emerg Med 2011;12:559-62.  Back to cited text no. 8
Yoo SJ, Park IS, Suh ES. A case of antiepileptic drug hypersensitivity syndrome by lamotrigine mimicking infectious mononucleosis and atypical Kawasaki disease. Korean J Pediatr 2009;52:389-91.  Back to cited text no. 9
Mantadakis E, Tsalkidis A, Paraskakis E, Papadopoulou-Legbelou K, Varlamis G, Evangeliou A, et al. Anticonvulsant hypersensitivity syndrome closely mimicking Kawasaki disease. BMJ Case Rep 2009;2009. pii: Bcr10.2008.1076.  Back to cited text no. 10
Chinen J, Piecuch S. Anticonvulsant hypersensitivity syndrome vs Kawasaki disease: A challenging clinical diagnosis with therapeutic implications. Clin Pediatr (Phila) 2000;39:109-11.  Back to cited text no. 11
Koren G, Lavi S, Rose V, Rowe R. Kawasaki disease: Review of risk factors for coronary aneurysms. J Pediatr 1986;108:388-92.  Back to cited text no. 12
Uehara R, Belay ED, Maddox RA, Holman RC, Nakamura Y, Yashiro M, et al. Analysis of potential risk factors associated with nonresponse to initial intravenous immunoglobulin treatment among Kawasaki disease patients in Japan. Pediatr Infect Dis J 2008;27:155-60.  Back to cited text no. 13
Gentile I, Talamo M, Borgia G. Is the drug-induced hypersensitivity syndrome (DIHS) due to human herpesvirus 6 infection or to allergy-mediated viral reactivation? Report of a case and literature review. BMC Infect Dis 2010;10:49.  Back to cited text no. 14


  [Figure 1], [Figure 2]


Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
Access Statistics
Email Alert *
Add to My List *
* Registration required (free)

  In this article
Article Figures

 Article Access Statistics
    PDF Downloaded177    
    Comments [Add]    

Recommend this journal