|Year : 2016 | Volume
| Issue : 1 | Page : 42-46
Topical fluroquinolone-induced Stevens-Johnson syndrome: A case report
Sandhya Ramachandra1, Sandhya Ramyashri2
1 Department of Ophthalmology, Sri Siddhartha Medical Colloege; Department of Ophthalmology, Dr. Murugappa Channaveerappa Modi Eye Hospital, Bangalore, Karnataka, India
2 Department of Ophthalmology, Dr. Murugappa Channaveerappa Modi Eye Hospital, Bangalore, Karnataka, India
|Date of Submission||26-May-2014|
|Date of Acceptance||10-Dec-2014|
|Date of Web Publication||19-Jan-2016|
No 18 Sumeru Shrunga, 1st Cross Vyalikaval House Building Cooperative Society Layout, Behind Shankar Mutt, Bangalore - 560 086, Karnataka
Source of Support: None, Conflict of Interest: None
Stevens-Johnson syndrome (SJS) or erythema multiforme (EM) major is a complex immunological syndrome characterized by acute blistering, affecting skin and at least two mucous membranes. Toxic epidermal necrolysis (TEN) is the most severe form of EM involving skin, which sloughs in sheets. Corneal damage is the most severe long-term complication for survivors of SJS and TEN. Conjunctival inflammation is commonly encountered in Ophthalmic practice. In children, allergy and infections form the most common etiology of conjunctivitis and antibiotics are often prescribed for all conjunctival inflammations presenting with red eye. The purpose of this report is to report the rare case of SJS with topical use of fluroquinolone.
Keywords: Erythema multiforme, steven-Johnsons syndrome, toxic epidermal necrolysis
|How to cite this article:|
Ramachandra S, Ramyashri S. Topical fluroquinolone-induced Stevens-Johnson syndrome: A case report. J Clin Ophthalmol Res 2016;4:42-6
|How to cite this URL:|
Ramachandra S, Ramyashri S. Topical fluroquinolone-induced Stevens-Johnson syndrome: A case report. J Clin Ophthalmol Res [serial online] 2016 [cited 2022 Jul 4];4:42-6. Available from: https://www.jcor.in/text.asp?2016/4/1/42/174424
| Case Report|| |
A 12-year-old female presented with history of pain, redness, discharge in both eyes associated with mouth ulcers since 2 days. On probing further, history of using "ofloxacin" eye drops 3 to 4 times from the past 4 days was elicited. There was no other significant history.
On examination, the best corrected visual acuity (BCVA) was 6/6 in both eyes. Anterior segment examination showed bilateral lid edema, matting of eyelashes, intense conjunctival congestion, and patchy membrane over palpebral and forniceal conjunctiva extending till the gray line of lids. Cornea, anterior chamber, pupil, lens, and posterior segment were normal bilaterally.
| Systemic Examination on Day 1|| |
Oral ulcers noted extending from oral fissure till 2 nd premolar tooth with sloughed mucosa covered by a whitish membrane. Sloughing and ulceration of lips along with severe inflammatory edema was present. The patient was unable to feed even bland liquids due to severe pain. Skin showed "target lesions" on palmar aspect of hands and foot with blisters on left forearm [Figure 1], [Figure 2], [Figure 3], [Figure 4] and [Figure 5].
With provisional diagnosis of Stevens-Johnson syndrome (SJS), the child was started on 4 th hourly dexamethasone and chloramphenicol combination eye drops and lubricating eye drops. Emergency pediatric referral was sought for initiating systemic steroids.
On day 4, she was on day 2 dose of tab Prednisolone 8 mg orally with Fusidic BNF cream for oral lesions. There was significant resolution of conjunctival congestion and membrane over the palpebral conjunctiva but target lesions increased in size and number over hands and foot. Oral ulcers showed hemorrhagic crusting. On day 7, membranes in fornix decreased in thickness, size, and extent; and the target lesions showed signs of resolution. On day 14, conjunctival membrane had resolved completely with almost normal appearing conjunctiva with healed target lesions and oral ulcers. Visual acuity and other eye findings remained normal during the entire follow-up period [Figure 6], [Figure 7], [Figure 8], [Figure 9] and [Figure 10].
The varied nature of this disease may present difficulty in diagnosis, particularly when clinical findings are minimal at initial presentation. A high index of suspicion with detailed history and general physical examination helped to clinch the diagnosis. A definitive diagnosis with histo-pathological examination of the membrane could not be done as the parents did not consent.
If untreated, conjunctival scarring could have caused vision threatening ocular surface complications. Although this is diagnosis of exclusion, the ophthalmologist must be alerted by this case report, because prompt initiation of systemic steroids is the key prognosticating factor.
Literature searches have not shown any reports of SJS with topical use of fluroquinolones. We have also seen an elderly female patient developing SJS for topical Gatifloxacin after an uneventful cataract surgery (unpublished data).
| Discussion|| |
Conjunctivitis was noted to be part of the SJS clinical spectrum by Alibert and Bazin in1822. Terms like Erythema exudativum multiforme proposed by Hebra, erythema polymorphe by Kaposi  are some of the earliest descriptions of clinical features of SJS. Thomas coined the terms erythema multiforme (EM) minor and major: EM minor referred to the disease described by von Hebra as EM, while EM major was applied to patients with oral mucosal involvement, similar to what Stevens and Johnson described.
EM is an acute self-limiting ,, non-progressive inflammatory disorder of skin and mucous membrane with two types: EM minor with only skin involvement and EM major with skin and erosive mucous membrane involvement.
EM, SJS, and toxic epidermal necrolysis (TEN) have traditionally been regarded as across-the-spectrum manifestations of the same clinical entity, affecting the skin and mucous membranes.
Males have a higher incidence as compared to females 3:1. Peak incidence is in the second and third decades of life. TEN is slightly more common in women, with a ratio ranging from 1.5/2:1. The elderly have an increased incidence of TEN and also have a higher rate of morbidity and mortality.  Indian scenario as per L.V. Prasad Eye Institute (LVPEI) study gives a prevalence of 0.0004%. Some human leukocyte antigen (HLA) association has been advocated with HLA Bw44, HLADRw53, and HLAB12. ,
Presentation begins with fever, malaise, headache, and upper respiratory infection. Drugs and infection are precipitating factor, as symptoms begin within hours to few weeks after the initial exposure. Within days, the typical dermatologic and mucosal lesions begin to break out. In typical SJS, mucosal involvement begins at the same time as, or succeeding, the skin manifestations. The disorder is usually self-limited, with a typical total duration of 4 to 6 weeks. Definite criteria have been established for the diagnosis of EM major and minor. 
Drug-related cases of EM have a clinical spectrum typically arises within 3 weeks after initiation of drugs like antimicrobials, non-steroidal anti-inflammatory drugs (NSAIDS); central nervous system (CNS); and care, convenience, and value (CVS) drugs; etc. If the patient is re-exposed to the inciting drug, a reaction may begin within hours. EM and TEN appear to be due to a poorly understood immune-mediated responses to certain drugs and infectious organisms. Histopathology shows a lymphocytic infiltrate at the dermal - epidermal junction (more pronounced in EM major) with a characteristic vacuolization of epidermal cells and necrotic keratinocytes within the epidermis.
Keratinocyte death occurs from extensive apoptosis. Some studies have shown that the apoptosis is induced by interaction between Fas and Fas ligand (FasL) which is either membrane bound on keratinocytes or soluble. Abe et al. have postulated that soluble FasL is secreted by peripheral blood mononuclear cells and is elevated in acute stage of EM and TEN patients.  This correlation is confirmed in Japanese and similar association have also been postulated in non-Japanese population. 
Management: In the acute stage, it involves conjunctival irrigation with saline and prophylactic antibiotics to combat secondary infection. Use of topical steroids, although controversial, reduces the ocular surface inflammation but cannot prevent the formation of symblepharon, which can be prevented by frequent glass rod application. Lamellar or penetrating keratoplasty is advocated in cases with impending perforation.
Robin and Dugel have suggested using clear plastic wrap or a symblepharon ring with a bandage soft contact lens to line the palpebral surface and prevent symblepharon formation and amniotic membranes is used to restore the surface regularity. 
In chronic cases, management of complications like trichiasis, entropion takes the upper hand and restoring the anatomy of fornices with reconstruction surgeries. Finally, restoration of vision with keratoplasty or keratoprosthesis can be tried.
Topical tacrolimus as immunosuppressant to reduce surface inflammation may be tried. , Ophthalmic management of the SJS presenting with primary ocular inflammation is challenging because of the serious systemic disorder manifestations requiring multi-speciality care.
| Conclusion|| |
SJS by use of topical fluroquinolones is rare. A careful history of use of offending drugs with clinical examination for skin and mucous membrane involvement should raise high suspicion for the disease. Although the recovery in our case was satisfactory, a long-term follow-up is warranted to look into complications and appropriate management. Antibiotics, even when used in topical eye drops form, can cause serious systemic problems like SJS as shown by this case report. Therefore, over the counter or casual use of these medications must be discouraged.
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.
| References|| |
Wolff JE. Ocular complications in erythema exudativum multiforme with mucous membrane lesions. Br J Ophthalmol 1949;33:110-20.
Krachmer JH, Mannis MJ, Holland EJ. Cornea Fundamentals, diagnosis and management. 2 nd
ed. Vol. 1, Ch. 52. p. 691-702.
Venkateshwarlu M, Radhika B. Diagnosis and management of drug induced stevens johnson syndrome. J Indian Acad Oral Med Radiol 2011;23:S429-33.
Yeung AK, Goldmann RD. Use of steroids for erythema multiforme in children. Can Fam Physician 2005;51:1481-3.
Kompella VB, Sangwan VS, Bansal AK, Garg P, Aasuri MK, Rao GN. Ophthalmic complications and management of a stevens johnson syndrome at a tertiary eye care centre in south India. Indian J Ophthalmol 2002;50:283-6.
Chan HL, Stern RS, Arndt KA, Langlois J, Jick SS, Jick H, et al
. The incidence of erythema multiforme, stevens-johnson syndrome, and toxic epidermal necrolysis. A population-based study with particular reference to reactions caused by drugs among outpatients. Arch Dermatol 1990;126:43-7.
Ueta M, Sotozono C, Inatomi T, Kojima K, Hamuro J, Kinoshita S. Association of Fas Ligand gene polymorphism in Stevens Johnson syndrome. Br J Ophthalmol 2008;92:989-91.
Okan G, Yaylaci S, Peker O, Kaymakoglu S, Saruc M. Vanishing bile duct and Stevens-Johnson syndrome associated with ciprofloxacin treated with tacrolimus. World J Gastroenterol 2008;14:4697-700.
Zhai J, Gu J, Yuan J, Chen J. Tacrolimus in the treatment of ocular diseases. BioDrugs 2011;25:89-103.
[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7], [Figure 8], [Figure 9], [Figure 10]