Send Orders for Reprints to
[email protected] Current Drug Safety, 2016, 11, 000-000
1
A Case Report of Antitubercular Drugs Induced Exanthematous Reaction Complicated by Acute Onset Levofloxacin Induced Toxic Epidermal Necrolysis (TEN) Khushboo Gajjar*,1, Hiren Hirapara2, Chandra Sekhar Jaiswal3, Manish Barvaliya1, Hita Shah3 and C.B. Tripathi1 1
Department of Pharmacology, Government Medical College and Sir Takhtsinhji General Hospital, Bhavnagar-364001 (Gujarat), India
2
Department of Pharmacology, GMERS Medical College, Junagadh (Gujarat) India
3
Department of Dermatology, Government Medical College and Sir Takhtsinhji General Hospital, Bhavnagar-364001 (Gujarat), India Abstract: We report a case of 25 years old male patient with antitubercular drugs induced exanthematous reaction and hepatotoxicity that was complicated by levofloxacin induced toxic epidermal necrolysis. The patient was allergic to ciprofloxacin and ofloxacin. Cross reactivity between ciprofloxacin and levofloxacin might be responsible for causing this reaction. Issues of cross sensitivity should be kept in mind and the same class of drugs should strictly be avoided to prevent such complications.
Keywords: Exanthematous reaction, levofloxacin, toxic epidermal necrolysis, antituberculer drugs, cutaneous adverse reaction. INTRODUCTION
CASE REPORT
Drug induced hypersensitivity and allergic skin eruptions are common adverse reactions seen with the majority of the drugs. It ranges from the most common reactions like rashes, urticaria and vasculitis to the most serious and rare reactions like Stevens-Johnson Syndrome (SJS), Toxic Epidermal Necrolysis (TEN) and DRESS (Drug Reaction with Eosinophilia and Systemic Symptoms). Common groups of drugs causing cutaneous reactions are anticonvulsant drugs; antiretroviral drugs; antifungal agents; Nonsteroidal AntiInflammatory Drugs (NSAIDs); allopurinol, antituberculer and other antimicrobial drugs [1]. Antitubercular drugs can cause rashes, erythema multiforme syndrome, urticaria, lichenoid eruption, SJS and exfoliative dermatitis [2].
A 25 years old male patient (weight 45 kg) taking Category I anti-tubercular drug therapy (Isoniazid, rifampicin, Ethambutol, Pyrazinamide) since 2 months was presented with rashes and itching all over the body for 1 month to the Department of Dermatology, Veneriology and Leprosy, Sir Takhtasinhji General Hospital, Bhavnagar, Gujarat, India. On examination, erythematous exfoliation was present over neck, chest, abdomen, back, buttocks, shaft of the penis, thighs and both extremities. Buccal mucosa showed angular chelitis. Both conjunctivas were yellowish. History shows that, patient had taken Tab. Asera P (Aceclofenac + Paracetamol), Tab. Rabeprazole (20 mg) and Tab. Tolperisone 50 mg for complaints of pain and neck tenderness from a private practitioner before development of rashes that he had stopped immediately on appearance of rashes. He took treatment for rashes but the reaction did not give improved results. His allergy screening test was positive for ciprofloxacin, ibuprofen, paracetamol, ofloxacin and sulfa drugs. Laboratory parameters like SGPT (143 U/L), SGOT (109 U/L), Serum ALP (48 U/L) and bilirubin level (13.3 mg/DL) were raised. Total WBC count was 10,000/cumm with differential count neutrophil 53%, lymphocytes 44 %, eosinophil 01 %, monocytes 02 % and basophil 00%. Hemoglobin level was 11.2 gm/dl. Ultrasonography of abdomen showed mild hepatomegaly. This patient was HIV and HBsAg non-reactive. The event was diagnosed as drug induced examthematous reaction and hepatotoxicity. His anti-tubercular drug therapy was withheld. The patient was given a tablet azithromycin 500 mg 24 hourly and tablet cetrizine 20 mg 12 hourly to treat the reaction. The intensity of the reaction reduced 3 days
SJS/TEN is a rare, severe, life threatening idiosyncratic exfoliative disease involving skin and mucous membrane. The incidence varies between 0.4 and 1.2 cases/million/year worldwide with mortality varying between 14% and 70% [3]. The drugs commonly implicated in SJS/TEN are sulfonamides, phenytoin, carbamazepine, phenobarbital, penicillins, allopurinol, antitubercular drugs and NSAIDs [4]. Drug induced exanthematous reaction and TEN have been seen as a different entity. We represent the case of Antitubercular drugs induced exanthematous reaction which resulted into the fatality due to levofloxacin induced TEN.
*Address correspondence to this author at the Department of Pharmacology, Government Medical College and Sir Takhtsinhji General Hospital, Bhavnagar-364001 (Gujarat), India; Tel: 0278-2430808; Fax: 0278-2422011; E-mail:
[email protected]
1574-8863/16 $58.00+.00
© 2016 Bentham Science Publishers
2
Current Drug Safety, 2016, Vol. 11, No. 3
Gajjar et al.
Fig. (1).
after quiting antitubercular drugs. Patient was referred to pulmonary medicine department for resuming the antitubercular therapy. The rescheduled antitubercular regimen contained tab levofloxacin 100 mg and 500 mg on day 1 and 2, respectively; on day 3 and 4, tab ethambutol 100 mg and 800 mg, respectively; injection streptomycin 125 mg and 500 mg on day 5 and 6, respectively. The patient was given tab levofloxacin 100 mg and 500 mg under monitoring. But on day 3, recovering exenthemic reaction was aggravated and also new vesicobullous lesions appeared on palm, maculopapular rashes all over the body along with edema on both feet. The patient was diagnosed to have toxic epidermal necrolysis. Levofloxacin was not given further and next anti-tubercular regimen was withheld. Treatment was started with injection dexamethasone 8 mg. The reaction worsened with the development of large bullae in the eye and erosion in oral cavity. Patient’s general condition became poor after 5 days. The patient expired due to cardiorespiratory arrest. Causality assessment was done by using Naranjo algorithm. Naranjo’s score was 6 for levofloxacin and TEN (probable causal relationship) [5]. According to the Modified Schumock and Thornton’s criteria, this reaction was definitely preventable [6]. DISCUSSION In the present case, initial drug induced exnthematous reaction might be due to the antitubercular drugs. Though patient took medicines Asera-P, rabeprazole, tolperisone before development of rashes, reaction did not improve on de-challenge of these drugs and with treatment. Reaction continued with the same intensity for 1 month that required admission at our hospital. Whereas from the day 3 of
admission, intensity of exnthematous reaction was reduced significantly on withdrawal of antitubercular therapy and treatment. Moreover, patient also had antitubercular drugs induced hepatotoxicity. Isoniazid and rifampicin both are hepatotoxic and can cause rashes, so they were avoided in rescheduled antitubercular therapy. Restarting antitubercular therapy with levofloxacin complicated the cutaneous reactions. Patient developed TEN involving more than 80% of body surface area. As, ethambutol and streptomycin were not given; levofloxacin was the main culprit for the development of TEN. Cases with levofloxacin induced SJS/TEN have been reported [7]. Incubation period for TEN is 2 to 8 weeks. This patient developed TEN within 3 days after giving two subsequent doses of levofloxacin. Patient was sensitive to ciprofloxacin and ofloxacin as per allergic sensitivity testing report. Ciprofloxacin and levofloxacin have similar core structure and cross sensitivity is found between the two drugs and between other flouroquinolones [8]. However, reports also suggest chances of low cross sensitivity to levofloxacin [9]. Whether its high incidence or low for cross sensitivity, drugs from same group should be avoided. In patients of drug induced cutaneous reaction, other common culprit drugs should also be avoided to prevent further complications. The present case shows complexity in therapeutic decisions due to development of adverse drug reaction. CONFLICT OF INTEREST The authors confirm that this article content has no conflict of interest.
Antitubercular Drugs Induced Exanthematous Reaction
Current Drug Safety, 2016, Vol. 11, No. 3 [5]
ACKNOWLEDGEMENTS Declared none.
[6]
REFERENCES [1] [2] [3] [4]
[7]
French LE. Toxic epidermal necrolysis and Stevens Johnson syndrome: our current under- standing. Allergol Int 2006; 55: 9-16. Dua R, Sindhwani G, Rawat J. Exfoliative dermatitis to all four first line oral anti-tubercular drugs. Indian J Tuberc 2010; 57: 53-6. Trent J, Halem M, French LE, Kerdel F. Toxic epidermal necrolysis and intravenous immunoglobulin: a review. Semin Cutan Med Surg 2006; 25: 91-3. Downey A, Jackson C, Harun N, Cooper A. Toxic epidermal necrolysis: review of pathogenesis and management. J Am Acad Dermatol 2012; 66: 995-1003.
Received: February 16, 2016
[8]
[9]
3
Naranjo CA, Busto U, Sellers EM, et al. A method for estimating the probability of adverse drug reactions. Clin Pharmacol Ther 1981; 30: 239-45. Schumock GT, Thornton JP. Focusing on the preventability of adverse drug reactions. Hosp Pharm 1992; 27(6): 538. Davila G, Ruiz-Hornillos J, Rojas P, De Castro F, Zubeldia JM. Toxic epidermal necrolysis induced by levofloxacin. Ann Allergy Asthma Immunol 2009 ; 102: 441-2. Anovadiya AP, Barvaliya MJ, Patel TK, Tripathi CB. Cross sensitivity between ciprofloxacin and levofloxacin for immediate hypersensitivity reaction. J Pharmacol Pharmacother 2011; 2: 1878. Lobera T, Audícana MT, Alarcon E, Longo N, Navarro B, Munoz D. Allergy to quinolones: low cross-reactivity to levofloxacin. J Investig Allergol Clin Immunol 2010; 20: 607-11.
Revised: March 17, 2016
Accepted: March 27, 2016
