Table of Contents  
CASE REPORT
Year : 2012  |  Volume : 3  |  Issue : 3  |  Page : 276-278  

Toxic epidermal necrolysis caused by fluconazole in a patient with human immunodeficiency virus infection


1 Department of Respiratory Medicine, J. L. N. Medical College, Ajmer, Rajasthan and Himalayan Institute of Medical Sciences, Jollygrant, Dehradun, India
2 Department of Pharmacology, J. L. N. Medical College, Ajmer, Rajasthan and Himalayan Institute of Medical Sciences, Jollygrant, Dehradun, India

Date of Web Publication7-Aug-2012

Correspondence Address:
Ramakant Dixit
A-60, Chandravardai Nagar, Ajmer, Rajasthan
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0976-500X.99445

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   Abstract 

Stevens-Johnson syndrome and toxic epidermal necrolysis (TEN) are rare but serious dermatologic disorders. These grave conditions present as medical emergency, requiring prompt diagnosis and management. These are often drug induced and various groups of drugs, such as sulfa drugs, NSAIDS, etc., have been implicated as to cause TEN. Fluconazole is a commonly used drug with mild side effects. TEN caused by fluconazole is rare, and till now only few cases have been reported in the literature. We present a case of TEN in a human immunodeficiency virus infected man following fluconazole therapy in view of its rare occurrence.

Keywords: Fluconazole, HIV infection, toxic epidermal necrolysis


How to cite this article:
George J, Sharma A, Dixit R, Chhabra N, Sharma S. Toxic epidermal necrolysis caused by fluconazole in a patient with human immunodeficiency virus infection. J Pharmacol Pharmacother 2012;3:276-8

How to cite this URL:
George J, Sharma A, Dixit R, Chhabra N, Sharma S. Toxic epidermal necrolysis caused by fluconazole in a patient with human immunodeficiency virus infection. J Pharmacol Pharmacother [serial online] 2012 [cited 2019 Aug 24];3:276-8. Available from: http://www.jpharmacol.com/text.asp?2012/3/3/276/99445


   Introduction Top


Toxic epidermal necrolysis (TEN) is a severe and life-threatening condition involving skin and mucous membrane. Drugs are the most important cause of TEN. The drugs most commonly causing TEN are sulfonamides, penicillins, other antibiotics, non-steroidal anti-inflammatory drugs, anti convulsants, etc. These drugs reaction are more common in individuals having human immunodeficiency virus (HIV) infection/AIDS than the general population. [1]

Fluconazole, an antifungal drug of the azole group, is frequently used for management of candidial infections, coccidiodal meningitis, cryptococcal meningitis, and in empiric treatment of critically ill HIV-infected patients. Surveillance studies show a low incidence of adverse drug reactions to fluconazole. [2] The usual side effects of fluconazole mentioned in the literature are mild like nausea, vomiting, headache, elevation of hepatic transaminases, etc. [3] TEN/ Stevens-Johnson syndrome More Details (SJS) caused by fluconazole in immunesuppressed patients is very rare and reported in only three reports previously. [4],[5],[6] We present an additional case of this type in view of lack of such reports in the Indian literature.


   Case Report Top


A 28 year old male patient, taking anti-tuberculosis treatment for last 3 months for pulmonary tuberculosis, now presented with oral thrush. He was a truck driver and was addicted to tobacco and alcohol. He was not married but gave history of multiple unprotected roadside sexes. On examination, the body mass index was 18. There was pallor and extensive oral thrush over tongue extending up to tonsil, and posterior pharyngeal wall. Other general physical examination was unremarkable. Respiratory system examination revealed crepitations over right upper lung fields. Other systemic examination revealed no abnormality.

In view of high risk behavior and the presence of oral thrush, his sera were subjected to HIV 1 and HIV 2 testing that turned out to be reactive. His other investigations revealed hemoglobin 8 g% with normal leukocyte count, differential count, fasting blood sugar, liver function test, renal function test, etc. A skiagram chest showed regression of pulmonary infiltrates in comparison to previous chest X-ray. His CD4 count was 625 per mm 3 . Throat swab smear and culture confirmed the presence of candidial infection.

The antituberculosis treatment was continued and oral fluconazole 150 mg daily was started with povidone iodine gargles. On the second day of fluconazole therapy, the patient developed generalized body ache along with pruritic rash over face, trunk, and extremities. The rashes first appeared over the trunk and then spread to involve extremities and face. Next day, these maculopapular eruptions became necrotic and surrounded by erythema. Later, vesiculobullous lesions appeared over face and trunk along with conjunctivitis. Nikolsky's sign was positive. The lesions subsequently ruptured with sloughing of large sheets of skin, leaving behind erythematous areas involving more than 70% of the body surface area. [Figure 1]. The patient also became febrile. Skin biopsy could not be taken. Based on clinical course following fluconazole therapy, a diagnosis of fluconazole-induced TEN (Naranjo Score 6) was made. Laboratory investigations this time revealed normal total leukocyte counts, but slight elevation of liver enzyme (ALT-50 IU/L, AST-64 IU/L). Fluconazole was stopped immediately. The patient was managed conservatively with local soothing agents, analgesics, azithromycin, antihistaminics, and eye care with adequate parenteral hydration. The patient improved with above therapy. Skin lesions resolved gradually and disappeared completely after 3 weeks.
Figure 1: Photograph of a patient showing erythematous lesions over face with sloughing of skin.

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   Discussion Top


TEN and SJS are acute and life-threatening disorder of unclear pathophysiology, characterized by epidermal necrosis, erosions of mucous membrane, and detachment of epidermis with constitutional symptoms. [7] Cases having less than 10% of epidermis involvement are designated as SJS, while those having 30% epidermis involvement are labeled as TEN. Cases with between 10% and 30% involved areas are defined as overlap SJS-TEN. [8]

The estimated incidence of TEN is about 1.17-1.89 cases per million inhabitants per year in observational studies. [9] The risk of TEN is much higher in individuals having HIV infection and other autoimmune disorders. [10],[11],[12] TEN is almost always induced by drugs. Although a long list of drugs have been implicated as a cause for TEN, the drugs commonly associated with TEN are sulfonamides, anticonvulsants, allopurinol, non-steroidal anti-inflammatory drugs, etc. [1],[7] Another drug commonly causing SJS/TEN in HIV patients is thioacetazone sodium. This drug has thence been contraindicated in HIV patients. [13]

TEN/SJS induced by fluconazole is very rare and till date only three cases have been reported. The very first case involved a 30-year-old gay, HIV positive man developing SJS following fluconazole therapy for oral candidiasis. [4] The second case involved a 33-year-old HIV positive male who developed TEN following treatment with fluconazole for dysphagia and recurrent oral thrush. [5] The third one was a 52-year-old immunosuppressive woman developing TEN after fluconazole for the treatment of esophageal candidasis. [6] Our case also developed TEN following fluconazole therapy for severe oral candidiasis.

The exact mechanism for drug-induced TEN is unclear but immunological mechanisms, reactive drug metabolites and interactions between the two have been proposed. [14] TEN is also linked to genetic differences in patient's metabolite reactions to drugs. [1] Multiple prior cutaneous drug reaction or prior reaction to a specific drug is also found to be a risk factor for TEN in HIV infected individuals. [10] The higher incidence of TEN among HIV-infected patients may also be related to glutathione deficiency. [15] Further, patients with AIDS also have increased number of abnormal polyclonaly activated 'B' cells which are defectively activated to secrete immunoglobulins leading to circulatory immune complexes and autoimmune phenomenon. [16] All these mechanism makes HIV-infected individuals more vulnerable to TEN due to drugs. Therefore in all patients with drug-induced TEN, an underlying HIV infection should always be ruled out. To our knowledge this is the fourth reported case and probably be the first one in India of TEN secondary to fluconazole in a patient having HIV infection.

 
   References Top

1.Backer DS. Toxic epidermal necrolysis. Lancet 1998;351:1417-20.  Back to cited text no. 1
    
2.Bradbury BD, Jick SS. Itraconazole and fluconazole and certain rare, serious adverse events. Pharmacotherapy 2002;22:697-700.  Back to cited text no. 2
[PUBMED]    
3.Bennett JE. Antimicrobial Agents - Antifungal agents. In Brunton LL, Lazo JS, Parker KL, editors. Goodman and Gilman's The Pharmacological Basis of Therapeutics. New York: Mc Graw - Hill; 2006. p. 1225-41.  Back to cited text no. 3
    
4.Gussenhoven MJ, Haak A, Peereboom-Wynia JD, van't Wout JW. Stevens-Johnson syndrome after fluconazole. Lancet 1991;338:120.  Back to cited text no. 4
    
5.Azon-Masoliver A, Vilaplana J. Fluconazole-induced toxic epidermal necrolysis in a patient with human immunodeficiency virus infection. Dermatology 1993;187:268-9.  Back to cited text no. 5
    
6.Ofoma UR, Chapnic EK. Fluconazole induced toxic epidermal necrolysis: A case report. Cases J 2009;2:9071.  Back to cited text no. 6
    
7.Roujeau JC, Stern RS. Severe cutaneous adverse reactions to drugs. N Engl J Med 1994;331:1272-82.  Back to cited text no. 7
[PUBMED]    
8.Bastuji-Garin S, Rzany B, Stern RS, Shear NH, Naldi L, Roujeau JC. Clinical classification of cases of toxic epidermal necrolysis, Stevens-Johnson syndrome, and erythema multiforme. Arch Dermatol 1993;129:92-6.  Back to cited text no. 8
[PUBMED]    
9.Rzany B, Mockenhaupt M, Baur S, Schröder W, Stocker U, Mueller J, et al. Epidemiology of erythema: Exsudativum multiformr majus, Stevens Johnson Syndrome and toxic epidermal necrolysis in Germany (1990- 92). Structure and results of a population based registry. J Clin Epidemiol 1996;49:769-73.  Back to cited text no. 9
    
10.Proteous DM, Berger TG. Severe cutaneous drug reactions (stevon Jhonson Syndrome and toxic epidermal necrolysis) in human immunodeficiency virus infection. Arch Dermatol 1991;127:740-1.  Back to cited text no. 10
    
11.Burge SM, Dawber RP. Stevens-Johnson syndrome and toxic epidermal necrolysis in a patient with systemic lupus erythematosus. J Am Acad Dermatol 1985;13:665-6.  Back to cited text no. 11
    
12.Dixit R, Sharma S. Toxic epidermal necrolysis caused by cotrimoxazole in a patient with human immunodeficiency virus infection. Indian J Allergy Asthma Immunol 2008;22:19-21.  Back to cited text no. 12
    
13.Centers for Disease Control and Prevention. Treating opportunistic infections among HIV-exposed and infected children: Recommendations from CDC, the National Institutes of Health, and the Infectious Diseases Society of America. MMWR 2004;53(No. RR-14):65.  Back to cited text no. 13
    
14.Roujeau JC, Chosidow O, Saiag P, Guillaume JC. Toxic epidermal necrolysis (Lyell syndrome). J Am Acad Dermatol 1990;23:1039-58.  Back to cited text no. 14
    
15.Paquet P, Pierard GE, Quatresooz P. Novel treatments for drug-induced toxic epidermal necrolysis (Lyell's Syndrome). Int Arch Allergy Immunol 2005;136:205-16.  Back to cited text no. 15
    
16.Bowen DL, Lane HC, Fauci AS. Immunopathogenesis of the acquired immunodeficiency syndrome. Ann Intern Med 1985;103:704-9.  Back to cited text no. 16
    


    Figures

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