IPSIndian Journal of Pharmacology
Home  IPS  Feedback Subscribe Top cited articles Login 
Users Online : 9923 
Small font sizeDefault font sizeIncrease font size
Navigate Here
Resource Links
 »  Similar in PUBMED
 »  Search Pubmed for
 »  Search in Google Scholar for
 »Related articles
 »  Article in PDF (702 KB)
 »  Citation Manager
 »  Access Statistics
 »  Reader Comments
 »  Email Alert *
 »  Add to My List *
* Registration required (free)

In This Article
 »  Abstract
 » Introduction
 » Case Report
 » Discussion
 » Conclusion
 »  References
 »  Article Figures
 »  Article Tables

 Article Access Statistics
    PDF Downloaded54    
    Comments [Add]    

Recommend this journal


 Table of Contents    
Year : 2021  |  Volume : 53  |  Issue : 5  |  Page : 391-393

Sulfasalazine-induced drug rash with eosinophilia and systemic symptoms syndrome in a seronegative spondyloarthritis patient: A Case report

Department of Pharmacy Practice, Karnataka College of Pharmacy, Bengaluru, Karnataka, India

Date of Submission05-Aug-2019
Date of Decision27-Mar-2021
Date of Acceptance31-Aug-2021
Date of Web Publication24-Nov-2021

Correspondence Address:
Dr. Balakeshwa Ramaiah
Department of Pharmacy Practice, Karnataka College of Pharmacy, #33/2, Tirumenahalli, Hegde Nagar Main Road, Bengaluru - 560 064, Karnataka
Login to access the Email id

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ijp.IJP_129_18

Rights and Permissions

 » Abstract 

The objectives were to evaluate drug rash with eosinophilia and systemic symptoms syndrome due to sulfasalazine and to carry out the pharmacoeconomic assessment associated with this adverse drug reaction (ADR). A 37-year woman was presented with rashes, fever, cough, and dyspnea. In the past 3 months, she was on sulfasalazine for inflammatory polyarthritis and seronegative spondyloarthritis. The diagnosis was based on raised eosinophils count, breathing difficulty, and typical pattern of rashes. Significant improvement was seen after discontinuation of sulfasalazine and with the initiation of parenteral corticosteroids. The casualty of this ADR was “probable” based on RegiSCAR, WHO, and Naranjo casualty assessment scales. Preventability, severity was assessed and total cost for management of the ADR was found to be ' 12,126. Thus, ADRs not only adds to patient sufferings but also increase the economic burden. Health-care providers need to be made aware of potentially fatal ADRs associated with sulfa drugs and should be keen to report such ADRs to drug safety authorities.

Keywords: Adverse drug reaction, drug rash with eosinophilia and systemic symptoms syndrome, pharmacoeconomics, RegiSCAR scale, sulfasalazine

How to cite this article:
Sah N, Ramaiah B, Koneri R. Sulfasalazine-induced drug rash with eosinophilia and systemic symptoms syndrome in a seronegative spondyloarthritis patient: A Case report. Indian J Pharmacol 2021;53:391-3

How to cite this URL:
Sah N, Ramaiah B, Koneri R. Sulfasalazine-induced drug rash with eosinophilia and systemic symptoms syndrome in a seronegative spondyloarthritis patient: A Case report. Indian J Pharmacol [serial online] 2021 [cited 2023 May 30];53:391-3. Available from: https://www.ijp-online.com/text.asp?2021/53/5/391/331102

 » Introduction Top

Drug rash with eosinophilia and systemic symptoms (DRESS) syndrome, a drug-induced adverse reaction often misconceived as a viral infection and manifested by exanthem, pyrexia, elevated white blood cells with eosinophilia or abnormal lymphocytes, swollen lymph nodes, and kidney or hepatic disorders. The incidence of DRESS ranges from 0.01% to 0.1% and contributes to death rate of 10% to 40%.[1],[2] The quiescence span ranges from 21 days to 90 days postadministration of culprit drug.[3] Although 50 drugs are said to cause DRESS syndrome, sulfasalazine has been very rarely described before.[2],[4] The pathogenesis of DRESS syndrome is not established clearly and usually hypothesized to be explained by complex interaction of detoxification defects leading to the formation of reactive metabolite.

 » Case Report Top

Nine months back before the incident, a 37-year-old woman came to the orthopedic outpatient department with complaints of polyarthralgia with duration of 3 months (morning stiffness) and fever. She was diagnosed with seronegative spondyloarthritis and treatment was started with deflazacort, methotrexate, folic acid, hydroxychloroquine, and Vitamin D3. Sulfasalazine 500 mg once daily was added in the next visit, it's dose was escalated to 500 mg twice daily and then to 500 mg in morning and 1000 mg at night on the following two subsequent visits. The very next month of dose escalation of sulfasalazine, she turned up again with the complaints of rashes all over the body for 3 days [Figure 1]a, intermittent fever for 15 days, yellowish cough with dyspnea for 15 days. During medication history interview after her admission, she was suspected to have DRESS syndrome secondary to sulfasalazine and methotrexate-induced pneumonitis. Tropical pulmonary eosinophilia (TPE) was ruled out with the evidence of normal immunoglobulin E levels, skin involvement (not typically in TPE), and use of suspected drug (sulfasalazine) in the past.
Figure 1: (a) Characteristic rashes on the upper limb (b) The pattern of absolute eosinophil count with the progression of days

Click here to view

With working diagnosis of DRESS, sulfasalazine and methotrexate were discontinued. Treatment was started with hydrocortisone 100 mg IV stat dose, fexofenadine 120 mg orally once daily, hydroxyzine 10 mg orally at night, acetaminophen 1000 mg orally three times daily. The main supportive positive investigation was elevated absolute eosinophil count and its postintervention levels as shown in [Figure 1]b. In addition, the C-reactive protein (20 mg/L) and erythrocyte sedimentation rate (35 mm/h) were also increased. The dermatologist reassured the diagnosis of DRESS and advised fluticasone cream, levocetirizine 5 mg orally at night and increased the hydroxyzine dose to 25 mg orally at night. Furthermore, added a short course of dexamethasone injection 8 mg two times daily for 2nd day, then 4 mg twice daily for 3rd day. On 3rd and 4th day, she was found to be improving symptomatically and was discharged on 5th day with prednisolone 40 mg orally once-a-day for 3 days, then decreased to 30 mg orally once-a-day for 4 days. Alert card was issued to prevent the reoccurrence of adverse drug reaction (ADR). On the review visit, methotrexate was restarted, and dose of prednisolone was tapered to 20 mg followed by 10 mg and then to 5 mg once daily consecutively for every 3 days.

 » Discussion Top

The appearance of elevated eosinophils, temporal association of the manifestation with the initiation of therapy with sulfasalazine, and notable progress on removal of drug along with the introduction of parenteral corticosteroids were attributes congruent with the diagnosis of DRESS. The RegiSCAR score established the diagnosis of probable DRESS syndrome with the score of 4 (fever = 1, skin rash = 1, eosinophilia = 1, organ involvement = 1). The onset of manifestation of DRESS occurs usually at 2–6 weeks after starting with the therapy.[1] Postmaximum escalation of sulfasalazine, this event occurred approximately after 4 weeks in this case. This patient showed the pulmonary symptoms and a typical pattern of development of rash (from the trunk region). The cytochrome CYP450 enzymes transforms, phenytoin, phenobarbital, and carbamazepine into toxic arene oxides. Finally, these arene oxides get detoxified by glutathione transferase or epoxide hydroxylase. Any malfunction of this epoxide hydroxylase leads to the deposition of arene oxides which in turns mediates immune response or direct cellular toxicity.[5] The ADR was detected at early stage, and culprit drug was withdrawn immediately. Thus, aggressive management such as introduction of short-term methylprednisolone (30 mg/kg intravenously for 3 days), plasmapheresis and intravenous immunoglobulin, or N-acetylcysteine to neutralize reactive metabolites were not required.[4]

The ADR was documented and reported to the Pharmacovigilance Program of India (PvPI) after carrying out all assessments systematically [Table 1]a. The computerized hospital in-patients billing system was contacted for accessing the billing details, and then, total cost (calculated as the sum of direct and indirect cost) for the management of this syndrome was found to be ' 12,126 as shown in [Table 1]b. The social service department stated that the monthly earning of the patient was ' 5,000. This estimates the intensity of the severity of ADR in terms of economy which indicates, almost 3 months of her earning costs for compensation of the same.
Table 1: Assessment of the reactions as per the standard scales (a) causality, severity, and preventability assessment, (b) Pharmacoeconomic assessment

Click here to view

 » Conclusion Top

Escalation of sulfasalazine dose without proper monitoring can trigger DRESS. Clinicians need to be made aware of these potentially fatal adverse effects associated with sulfa drugs. Our study also demonstrated that ADR not only amplify patient sufferings but also augment the financial burden. The pharmacist should be keen to report such ADR to PvPI and raise awareness about such reaction among the health-care professionals.


We thank the Indian Pharmacopoeia Commission (IPC) Ghaziabad, for accepting this report and generating the World Wide Unique Number (2017-65828) for this ADR.

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

Aquino RT, Vergueiro CS, Magliari ME, de Freitas TH. Sulfasalazine-induced DRESS syndrome (drug rash with eosinophilia and systemic symptoms). Sao Paulo Med J 2008;126:225-6.  Back to cited text no. 1
Karakayali B, Yazar AS, Çakir D, Cetemen A, Kariminikoo M, Deliloglu B, et al. Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome associated with cefotaxime and clindamycin use in a 6 year-old boy: A case report. Pan Afr Med J 2017;28:6-9.  Back to cited text no. 2
Kavala M, Serap Karadag A, Topaloglu D, Zindanci I, Turkoglu Z, Oman B, et al. Case report drug rash with eosinophilia and systemic symptoms syndrome induced by allopurinol case report conflict of interest. J Med Cases 2014;5:420-2.  Back to cited text no. 3
Walsh SA, Creamer D. Drug reaction with eosinophilia and systemic symptoms (DRESS): A clinical update and review of current thinking. Clin Exp Dermatol 2011;36:6-11.  Back to cited text no. 4
Criado PR, Criado RF, Avancini JM, Santi CG. Drug reaction with eosinophilia and systemic symptoms (DRESS)/drug-induced hypersensitivity syndrome (DIHS): A review of current concepts. An Bras Dermatol 2012;87:435-49.  Back to cited text no. 5


  [Figure 1]

  [Table 1]


Print this article  Email this article


Site Map | Home | Contact Us | Feedback | Copyright and Disclaimer | Privacy Notice
Online since 20th July '04
Published by Wolters Kluwer - Medknow