INTRODUCTION:

SJS/TEN (Steven Johnson Syndrome/ Toxic Epidermolysis Necrosis) is a rare, critical, fatal skin condition characterized by sheet-like sloughing of skin and mucosa.¹ SJS belongs to cutaneous drug reactions which are the most common type of ADR that leads to 2-3% of patient’shospitalisation.² In India, the incidence of SJS is 1.2 to 6 million patients per year.³ The involvement of 10-30% of the Body Surface Area is SJS-TEN.⁴ Ciprofloxacin causedSJS-TEN is rare but it can establish SJS.^5,6 Fluoroquinolones are prescribed for Urinary Tract Infection, Lower Respiratory Tract Infection, and Gastrointestinal Infection.^2,7 They shown antibacterial activity by acting against gram-positive and gram-negative organisms.⁸ Here, we report a severe case of ciprofloxacin-induced SJS-TEN.

Case Report:

A 66-year-old female patient was admitted to the hospital with complaints of peeling off skin in the thigh region from the previous night (12/02/2023).The patient had a history of a known case of allergy to Ciprofloxacin (Quinolone) around seven years back and is now treated for Ciprofloxacin induced Steven-Johnson Syndrome/Toxic epidermal necrolysis (SJS-TEN) which is a very rare adverse effect of Ciprofloxacin, the diagnosis was made according to SCORTEN criteria (Table No.1). Ciprofloxacin injection was given because of diarrhea, generalized weakness and eventually the patient develops denudation of skin. On examination, sheets of necrotic skin in the inner aspect of the thigh with few flaccid blisters and the exfoliation of skin in the lower abdomen and axilla are also seen. Superficial erosions are found in the Labia minora.

During the period of admission, a complaint of pain in eroded areas of skin was reported. In the following days,several fresh blebs in the thigh region, and a few raw erosions in the thigh and axilla were noticed. On examination, erosion in the thigh region persists and healing was observed in the lower abdomen and axilla. The condition got worsened in the subsequent days as the denudation of skin was observed in the upper back, buttocks, and over chest regions. Besides that, erosions in the thigh region were also evident.

Table No. 1: Diagnostic criteria for SJS (SCORTEN)

Prognostic factors	Points
Age >40 years	1
Tachycardia >120 bpm	0
Neoplasia	0
Initial detachment >10%	1
Serum urea >28 mmol/L	0
Serum bicarbonate <20 mmol/L	0
Blood glucose >252 mg/dL	0

According to SCORTEN diagnostic criteria for SJS, we concluded that the patient has SJS-TEN and a mortality rate of 12%.

In Laboratory examination, elevation of Alanine Transaminase and Gamma GT was detectedat about 38 IU/L and 93 U/L and a decrease of A/G ratio to 1 was also noticed. The urine routine examination shows the presence of bacteria and a notable count of pus cells, epithelial cells, and RBCs of about 15-16 cells/hpf, 2-3 cells/hpf, and 9-10 cells/hpf was found.

The patient was on treatment for a total duration of 7 days in the hospital (Table No.2).

Table No.2: Treatment Chart

Name of the drug	Dose	Frequency	ROA	No. of days
Inj. Dexamethasone	2 cc	1-0-1	IV	7
Inj. Pantoprazole	40 mg	1-0-1	IV	7
Inj. Pheniramine	2 cc	OD	IV	7
Calamine lotion		1-0-1	Topical	7
Mupirocin ointment over the erosion		1-0-1	Topical	7
Fluticasone propionate cream			Topical	6
Inj. Ondansetron	4 mg	SOS	IV	1
Inj. Paracetamol	1 g	1-0-1	IV	7
Tab. Levocetirizine	5 mg	0-0-1	PO	4
Inj. Ceftriaxone	1 g	1-0-1	IV	7
Tab. Amlodipine	10 mg	1-0-0	PO	7
Tab. Atenolol	25 mg	1-0-0	PO	4

The patient alert card and appropriate suggestions, and counsellingwere given to the patient, and the drug Ciprofloxacin was withdrawn. Discharge was given on the seventh day of admission as per the patient’s request.

On discharge, the mentioned medications were prescribed (Table No.3).

Table No.3: Discharge medications

Name of the drug	Dose	Frequency	ROA	No. of days
Tab. Amoxicillin- Clavulanate	625 mg	1-0-1	PO	7
Tab. Prednisolone	60 mg 40 mg 30 mg	1-0-0 1-0-0 1-0-0	PO PO PO	2 3 3
Tab. Multivitamin		0-1-1	PO	10

DISCUSSION:

ADRs are one ofthe primary causes of morbidity and mortality in hospitalized patients^9,10, about 0.3-7% of ADRs lead to hospitalizations, and 35% of hospitalizedpatients experienced ADR.¹¹ This case report provides description about the importance of monitoring parameter and history collection about the drugs.^12,13 SJS is classified by BSA involvement, SJS (<10% BSA), TEN(>30% BSA), SJS-TEN(10-30%).¹ Females appear to have a greater prediction for developing TEN than males about its immunological etiology.²

Epidermal necrosis has occurredthrough 2 types of mechanisms, they are by extrinsic and intrinsic. The extrinsic route involves monocytes, cytotoxic lymphocytes, granulysin, granzyme, perforin, and Fas/FasL ligand interactions. Intrinsic epidermal necrosisraises keratinocytes generating hazardous composites, which consequentlyproduce reactive oxygen species and ultimately lead to the generation of tumour necrosis factor-alpha inflicting more harm.¹ TEN behaves like a superficial dermal burn with fluid shifts, hypermetabolism, and high nutritional requirements, wound management and pain control are essential.⁴

HLA-B gene disparities cause the immune system to respond abnormally to the assumed drugs recognized to cause SJS. Due to the failure to clear reactive metabolites, the drug causes cytotoxic T cells and natural killer cells to release granulysin that eradicates cells in the skin and mucous membranes.¹⁴ The death of these cells causes the blistering and peeling of the skin, which is a characteristic feature of SJS. The CD8+T cells have been identified as important mediators of blister formation and granulysin concentration in blister fluid associated with the severity of SJS.³

This shows prescribers should be aware before prescribing fluoroquinolone antibiotics.¹⁵ADR’s are the most commonly reported drug related problem in the hospital.^16,17Even though, Ciprofloxacin induced SJS/TEN is rare but becomes fatal² and causes severe conditions.¹⁸ There were previous cases that were persuasive reminders of the ciprofloxacin and fluoroquinolone antibiotics.^1–5,11

CONCLUSION:

Ciprofloxacin is a commonly prescribed fluoroquinolone antibiotic and SJS/TEN is a rare and life-threatening cutaneous skin reaction. Management of SJS consists of early identification and withdrawal of the suspected drug. In this case, SJS/TEN recovered patient again redeveloped SJS/TEN with the same drug due to an error in the history collection. Hence, the healthcare professional should be aware of ADRs and prescribe them with caution and proper vigilant monitoring.

CONSENT:

The patient’s consent was takento report her case, but she was not agreed to take photographs.

ACKNOWLEDGEMENT:

The authors are extremely grateful to all our beloved teachers of Sree Siddaganga College of Pharmacy, Tumkur for their encouragement, support, and guidance.

CONFLICT OF INTEREST:

The authors declare that there is no conflict of interest.

ABBREVIATIONS:

ADR: Adverse Drug Reactions

SJS/TEN:

Steven Johnson Syndrome/ Toxic Epidermolysis Necrosis

ROA:

Route of Administration.

REFERENCES:

1. Memon S, Ahmed N, Nasir Memon M, Zahoor F, Afzal G. Linezolid and Ciprofloxacin-Induced SJS/TEN (Stevens-Johnson Syndrome/Toxic Epidermolysis Necrosis) Overlap in a Patient With Borderline Personality Disorder During a Single Hospital Stay: A Difficult Case to Manage. Cureus. 2023; May 19; 15(5): e39242. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10277191/

2. Mishra AD, Urade PM, Mittal N, Gupta MC. IJBCP International Journal of Basic & Clinical Pharmacology Case Report Fatal case of Ciprofloxacin-Induced Toxic Epidermal Necrolysis. 2014; 3(6): 1090–2. https://www.ijbcp.com/index.php/ijbcp/article/view/1193

3. Arora R, Pande RK, Panwar S, Gupta V. Drug-related Stevens – Johnson Syndrome and Toxic Epidermal Necrolysis : A Review. 2021; 1–5. https://jpc.tums.ac.ir/index.php/jpc/article/view/524

4. Cravens MG, Sherman N, Sawaya J. Ciprofloxacin-induced Stevens-Johnson Syndrome with Grapefruit Juice Consumption : A Case Report. 2019; 11(1): 1–4. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6402866/

5. Antony R, Fernandez A, Lekshmi S, Velayudhan S, Jose S. Case report on Fluconazole Induced stevens - Johnson Syndrome. 2019; 12(August): 3735–8. doi:10.5958/0974-360X.2019.00639.5

6. Kawas G, Marouf M, Mansour O, Sakur AA. Analytical Methods of Ciprofloxacin and its Combinations Review. 2018; 11(May): 2139–48.doi: 10.5958/0974-360X.2018.00396.7

7. Kumud Gupta, Surendra Nath Pandeya, Ashish Kumar Pathak AG. Synthesis and Antibacterial Activity of Ciprofloxacin Derivatives. Res. J. Pharm. Tech. 2011; 4(February): 308–14. https://rjptonline.org/HTMLPaper.aspx?Journal=Research%20Journal%20of%20Pharmacy%20and%20Technology;PID=2011-4-2-21

8. Kengar MD, Patole KK, Ade AK, Kumbhar SM, Patil CD, Ganjave AR. Introduction to Pharmacovigilance and Monitoring. 2019; 9(2): 116–22. https://rjptonline.org/AbstractView.aspx?PID=2022-15-6-32

9. V RV, Saranya P. Pharmacovigilance - An Overview in a Pharmacist Perspective. 2020; 13(August): 3941–6. https://rjptonline.org/AbstractView.aspx?PID=2020-13-8-70

10. Annapureddy RR, Navyasree T, Challa SR, Sree GR, Pavani AL. Ciprofloxacin Induced Stevens- Johnson Syndrome. 2018; 12(1): 1–2. https://www.researchgate.net/publication/322951506_Ciprofloxacin_Induced_Stevens-Johnson_Syndrome

11. Rayees NM, Kumar S, C BRK, Rajesh KS, Joel JJ, K PS, et al. A Prospective Observational Study on Adverse Drug Reactions in General Medicine Department of a Tertiary Care Teaching Hospital. 2019; 12(May): 2289–98. https://rjptonline.org/AbstractView.aspx?PID=2019-12-5-41

12. Chandana C, Anusha S, Kavya HB. Diclofenac Induced Rapidly Progressive Renal Failure in Elderly Patient – A Case Report. 2022; 15(4): 315–7. https://ijopp.org/article/953

13. Yakaiah Vangoori, Naga Vishnu Kandra, Praveen Kumar Uppala, U. Upendrarao, S.V. Saibaba, Murali Krishna Balijepalli, Butti Lavanya SMS. Case Reports of Stevens Johnson Syndrome (SJS) Induced by Chemically Unrelated Drugs. Res. J. Pharm. Technol. [Internet]. 2023; 16(5): 2415–8. https://rjptonline.org/AbstractView.aspx?PID=2023-16-5-57

14. Olga Butylchenko, Dmitriy Ermakov DB. Pharmacokinetic properties of Fluoroquinolones in Comparative Aspect of their effect on Pathogenic microflora. Res. J. Pharm. Technol. [Internet]. 2022; 15(12): 5800–6. https://rjptonline.org/HTMLPaper.aspx?Journal=Research Journal of Pharmacy and Technology;PID=2022-15-12-73

15. Lincy S, Greeshma M, Maheswari E, Tharanath S, Viswam S. An Empirical Study to assess the Pattern and Predictors of Adverse Drug Reactions associated with Polypharmacy in the Department of General Medicine. 2018; 11(November): 5042–8. https://rjptonline.org/AbstractView.aspx?PID=2018-11-11-51

16. Chavhan AB, Bhoi DM. Pharmacovigillance : Drug Safety Monitoring. Asian Journal of Pharmacy and Technology. 2019; 9(1): 49–52. doi: 10.5958/2231-5713.2019.00009.6

17. Prafulla M Sabale, Dhiraj S Bhagwat, Karan Parwe. Synthesis, Characterization and Biological Evaluation of Ciprofloxacin N-N Donor Metal Complex. Asian J. Research Chem. 2018; 11(3): 588-592. doi: 10.5958/0974-4150.2018.00105.0

Received on 20.07.2023 Modified on 08.11.2023

Research J. Pharm. and Tech 2024; 17(6):2707-2709.

DOI: 10.52711/0974-360X.2024.00424