Author: Sebabatso C. Mthakathi Presenter: Lineo Maja Faculty of Health Sciences

1. IDENTIFICATION OF THE CAUSES OF STEVENS-JOHNSON SYNDROME ON PATIENTS ADMISSIONS AT QUEEN ELIZABETH II HOSPITAL: A PHARMACOVIGILANCE APPROACH Author: Sebabatso C. Mthakathi Presenter: Lineo Maja Faculty of Health Sciences Department of Pharmacy

2. Introduction Stevens-Johnson Syndrome (SJS) is a serious mucocutaneous illness with systemic symptoms characterized by the presence of flat, atypical target lesions and the epidermal detachment is < 10% of the total body surface area (BSA).1

3. Stevens-johnson syndrome • SJS is a very painful and distressing condition • It is also a physically and psychologically dreadful disease • It is an immune complex hypersensitivity reactions of drugs • Some of drugs that may cause SJS include2: • Antibiotics • Sulphonamides, e.g. cotrimoxazole • Beta-lactams, e.g. penicillins, cephalosporins • Antifungals • Imidazoleantifungals • Antivirals • Nevirapine (NNRTI) • Allopurinol

4. Stevens-johnson syndrome • Non-steroidal anti-inflammatory drugs (NSAIDS) • Naproxen, ibuprofen • Anti-convulsants • Carbamazepine, phenytoin, phenobarbital, valproic acid • It affects both genders of all ages Epidemiology of SJS • The reported incidence varies from 1.2 to 6 per million patient-years for SJS.3

5. Stevens-johnson syndrome • The incidence rises with increasing age and is at least a 1,000-fold higher in patients with HIV/AIDS.3 • Regional differences in drug prescription, the genetic background of patients (human leukocyte antigen [HLA], metabolizing enzymes), the co-existance of cancer, or concomitant radiotherapy, can have an impact on the incidence of SJS and toxic epidermal necrolysis (TEN).4

6. Aim and objectives • The aim of the study was to identify the general causes of SJS • Objective was to identify the following: • Drugs which were implicated in SJS and those which were suspected to have caused SJS • The other causative factors • The number of deaths associated with SJS

7. methods • A retrospective review of cases of patients admitted at Queen Elizabeth II hospital with SJS diagnosis was carried out • Data to be captured were for time period of five years • (January 2005 to February 2010) • Data from clinical notes/patients’ files in the Medical Records Department was used

8. methods • Pre-designed data collection form was used to capture data • Parameters included: • Demographic information • Causative agents of SJS • Management outcome • Drugs prescribed during hospitalization • Drugs prescribed during hospital discharge

9. methods • To ensure confidentiality, names of patients were not used • Origin 6.0 statistical package was used for data analysis • Ethical approval was granted by the Ministry of Health and Social Welfare

10. results • A total of 31 cases of SJS were seen • 81% were females while 19% were males with ages ranging from 16-64 with the mean age of 33.5 years • Among SJS diagnosed patients; • 18 (58%) patients were retro viral disease (RVD) positive • RVD status of the remaining 13 (42%) patients was unknown

11. results • 76% cases of SJS were drug induced • 24% cases of SJS were due to other causes • Nevirapine had the highest incidence with 10 (34.5%) cases followed by Cotrimoxazole with 6 (20.7%) • Allopurinol and benzyl penicillin both had one incidence of 3.4%

12. results • There were also other drugs suspected to have caused SJS: • 3 cases (10.3%) of SJS were suspected to have been due to penicillins • 2 cases (6.9%) due to anti-TB drugs, isoniazid • Conditions suspected to predispose patients to SJS were: • Allergies with the highest incidence of 4 • Pneumonia with the incidence of 3 • HIV with the incidence of 2

13. results • Management outcomes were as follows: • 6 deaths were noted (19%) • 25 cases (81%) had improved and were therefore discharged • Drugs which were prescribed for patients and why they were given: • Antibiotics- to treat the infections • Topical corticosteroids- to reduce inflammation • Analgesics- to alleviate pain • Thymol mouth wash- it has antibacterial activity • Intravenous fluids- for rehydration

14. conclusion • Awareness about the drugs implicated in life threatening drug reactions will help physicians in preventing them by judicious use of the drugs.

15. Study limitations • Due to improper filing in the Medical Records Department, finding study subjects was difficult • Documentation in the patients’ medical files was incomplete • The etiology of SJS was easy to postulate but difficult to prove because there were no skin biopsy done or laboratory tests available, skilful collection of patient histories remained the best tool for identifying a particular drug as the trigger of SJS

16. recommendations • A careful drug history is especially important to identify and quickly discontinue possible inciting medications. • Nevirapine (NVP) had the highest incidence of SJS cases as a result, physicians have to consider seriously the risk of these life-threatening cutaneous reactions when prescribing a HAART regimen containing NVP. • When NVP has advantages over other NNRTIs, doctors and pharmacists must inform their patients of the risk of cutaneous reactions and provide clear guidelines of what to do in the case of skin eruptions.

17. references 1. Sharma K. V., Sethuraman G. & Minz A. 2008. Stevens Johnson syndrome, toxic epidermal necrolysis and SJS-TEN overlap: A retrospective study of causative drugs and clinical outcome. Indian journal of dermatology venereology leprology, 74 (3): 238-240 2. Devi K., George S., Criton S. & Suja V., Sridevi P. K. 2005. Carbamazepine- The commonest cause of toxic epidermal necrolysis and Stevens Johnson Syndrome: A study of 7 years. Indian journal of dermatology venerelogy leprology, 71 (5): 325-328.

18. references 3. Tan S.-K. & Tay Y.-K. 2012. Profile and pattern of Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis in a general hospital in Singapore: Treatment outcomes. ActaDermatoVenereologica, 92: 62-66. 4. Harr T. & French E. L. 2010. Toxic epidermal necrolysis and Stevens-Johnson syndrome. Orphanet journal of rare diseases, 5: 39.

19. Rea leboha • Thank you