Sai priya et al / Int. J. of Res.

in Pharmacology & Pharmacotherapeutics Vol-3(3) 2014 [169-172]

International Journal of Research in

Pharmacology & Pharmacotherapeutics

ISSN Print: 2278-2648

ISSN Online: 2278-2656

IJRPP |Vol.3 | Issue 3 | July-Sep - 2014

Journal Home page: www.ijrpp.com

Research article

Open Access

Ofloxacin induced multiple fixed drug eruptions A case report

*

Sai priya marrapu, Mounika sanaka, Shaik faizan ali, Shaik shafiya, Raghu ram.v,
Rama rao Nadendla.
Department of pharmacy practice, Chalapathi institute of pharmaceutical sciences, lam,
Guntur-522034, Andhra Pradesh, India.
* Corresponding author: Sai priya.M,
E-mail id: priyapharma1993@gmail.com

ABSTRACT
Adverse drug reactions are the major hazards of modern medicine. Among all these, cutaneous drug reactions are
given utmost importance as they are sometimes life threatening. Ofloxacin is a first generation floroquinolone and
these class of drugs can cause Fixed drug eruption , which is a adverse reaction , is commonly seen with
antimicrobials , analgesics and anticonvulsants etc. In the pathogenesis intraepidermal CD8+ T cells play a major
role and may represent double-edged swords of the skin immune system with protective and destructive capacity.
Here we report a case of a 38 year old female patient with Multiple Fixed Drug Eruptions due to Ofloxacin
administration.
Key Words: Fixed drug eruption , Ofloxacin , Adverse reaction.

INTRODUCTION
Ofloxacin is a fluorinated quinolone which is an
intermediate between ciprofloxacin and norfloxacin
in activity against gram negative bacteria , but it is
comparable to or more potent than ciprofloxacin for
gram positive organisms and certain anaerobes.It is
particularly suitable for chronic bronchitis and other
respiratory or
ENT infections[21].Fixed drug
eruptions(FDE) are known to arise from a variety of
medications such as analgesics , anti convulsants ,
sedatives
,
antifungal
medications
and
[1][2]
antibiotics
.Among
antibiotics
,
trimethoprim/sulfamethoxazole and tetracyclins are
most commonly associated with FDE , but rarely
floroquinolones result in FDE[3].The prevalence of

drug eruptions has been reported in the range of 2-5%

. Fixed drug eruptions may account for as much as
16-21% of all cutaneous drug eruptions[4].However ,
there have been reports of cases in which
ciprofloxacin and norfloxacin has been implicated in
fixed drug eruptions , but very few were reported
with Ofloxacin.Here we present a case of bullous
fixed drug eruptions following treatment with
ofloxacin as this type of presentation is very rare.

CASE SUMMARY
A 38 yr old Indian female patient who is suffering
from upper respiratory tract infection went to a
private practitioner and she was prescribed with
ofloxacin 200mg twice daily. Within few hours of

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first dose administration of ofloxacin patient

experienced itching and burning sensation on few
areas of hands and feet. These areas turned into
purplish plaques upon the administration of second
dose. She still continued taking the drug and
experienced erosions on her lips which are prominent
on her lower lip, swelling of eye and few more new
lesions on her limbs. Within 48 hours her lesions
became painful and now few are filled with pus.
Upon further questioning it was revealed that patient
has a similar history when she has taken the same
drug 13 months back for the treatment of upper

respiratory tract infection. Lesions were developed

after 48hrs of ofloxacin administration in the past
which were few and are asymptomatic , so no
treatment was sought. But on the current admission
lesions developed within hours of drug
administration. For the present painful lesions she
consulted a private dermatologist and the diagnosis of
fixed drug eruptions was made. On the current
consultation she was prescribed with topical
hydrocortisone cream and her antibiotic regimen was
stopped. These lesions were improved over 2 weeks ,
leaving post inflammatory hyperpigmentation.

DISCUSSION
In 1889, Bourns described a series of sharply
demarcated hyperpigmented lesions on the lips and
tongue of a patient who had recently ingested 20g of
antipyrine. A few tears later , Brocq coined the
French term , eruption erythemato-pigmentee fixe ,
from which we derive the term , fixed drug
eruption[5].Fixed drug eruption is characterised by the

sudden onset of round and/or oval, oedematous,

dusky-red macules on the skin and/or mucous
membranes accompanied by burning and/or itching.
The acute phase is usually followed by residual
pigmentation[6].Typically FDE begins with a sharply
demarcated oval of circinate macule[7].Less
commonly FDE appear as plaques , bullae or
eruptions and may koebnerize[8].It characteristically

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recurs in the same sites each time a particular drug is

taken. FDE is usually solitary in the initial attack,
but with each subsequent exposure, the number of
involved sites may increase and pre-existing ones
may increase in size.The lesions usually develop
within 30 minutes to 8 hours of taking a drug. The
lesions are often painful, clearly demarcated oval or
round erythematous plaques, becoming violaceous 12 days later. As healing occurs, after about 1 week,
crusting and scaling are followed by a persistent
dusky brown colour[9].The genetalia , lips and hands
are among the most commonly affected sites ,
although any site may be affected including
conjunctivae andoropharynx[10].
The diagnosis of fixed drug eruption is not always
easy; as in the case of nonpigmenting fixed drug
eruptions, which do not have any residual
hyperpigmentation. The development of molecular
biology may help to unfold the exact pathogenesis of
fixed drug eruptions but as of now the reason for
their recurrence on the same sites is still unknown.
Importantly, the causative drug and cross-reactants
should be avoided to prevent recurrence. Till date,
rechallenge is the most reliable method of identifying
causative drugs, but increasingly the use of skin tests
has gained the attention of many investigators[11].
A genetic susceptibility to developing a fixed drug
eruption with an increased incidence of HLA-B22
has been reported[13][12].Pathogenesis of FDE is
unknown , antibodies , antibody-dependent cell
mediated cytotoxicity , and serum factors have been
implicated[14].
Recent
findings
shows
that
Intraepidermal CD8+ T cells with an effector
memory phenotype resident in xed drug eruption
lesions have a major contributing role in the
development of localized tissue damage. Activation
of these CD8+ T cells is sufcient for triggering the
lesion, however, but not sufcient to cause extensive

tissue damage observed in the fully evolved lesions;

additional recruitment of CD4+ and CD8+ T cells to
a specic tissue site would also contribute to the late
stage of lesion development. The inux of regulatory
T cells into the epidermis observed in fully evolved
lesions would serve to limit harmful immune
reactions. Consistent with this, positive patch test
reactions are only observed at the site of previous
lesions
harboring
signicant
numbers
of
[20]
intraepidermal CD8+ T cells .The peak incidence
of FDE is 21-30 years , although any age may be
affected , ratio of male:female incidence is generally
equal. Genetic predisposition to FDE appears to
occur in individuals with a family history of diabetes
mellitus , atopy and drug allergies[15].
Causality assessment for this ADR was made using
Naranjo causality assessment scale and the naranjo
score was found to be 9 , thus ADR was classified as
definite one.To the best of our knowledge there are
only 3 previous reports of FDE to this drug
ofloxacin[16][17][18][19].

CONCLUSION
Because of widespread use of fluoroquinolones, it is
important to consider these as possible etiologic
agents of FDE.Therefore , one must include ofloxacin
also in the etiologic differential when making the
diagnosis of FDE.

ACKNOWLEDGEMENT
We take this golden opportunity to express our
thanks to Dr.Rama rao Nadendla, Principal,
Chalapathi institute of pharmaceutical sciences, and
also Raghu Ram.V and Shaik shafiya, Assistant
professors of chalapathi institute of pharmaceutical
sciences, for providing necessary facilities, valuable
guidance and continuous encouragement.

REFERENCES
[1] Mahboob A, Haroon TS. Drugs causing fixed eruptions : a study of 450 cases. Int Dermatol. Nov 1998 Volume
37, Issue 11,Pages:833-8.
[2] Patel Raksha M, Marfatia Y S. Clinical study of cutaneous drug eruption in 200 patients. Indian J Dermatol
Venereol Leprol 2008:74:80.
[3] Wilton L V , Pearce G L , Mann R D.A comparision of ciprofloxacin , ofloxacin , azithromycin and cefixime
examined by observational cohort studies. Br J Clin Pharmacol 1996; Volume 41 Pages:277-284.
[4] Sonia Pramod Jain , Pramod Ajit Jain , .Bullous fixed drug eruption to ciprofloxacin : A case report. Journal of
Clinical and Diagnostic Research [serial online]2013-04[cited:2014 Apr 18] Pages 4774-745.
www.ijrpp.com

~ 171~

Sai priya et al / Int. J. of Res. in Pharmacology & Pharmacotherapeutics Vol-3(3) 2014 [169-172]

[5] Nordlund J J, Boissy R E , Hearing V J , King R A , Portonne J . The Pigmentary System : Physiology and
Pathophysiology. New York: Oxford Univ . Press, 1999.
[6] Sanchez-Morillas ,L.;Rojas perez Ezquerra , P.;Gonzalez Morales , M.L.;et al , Fixed drug eruption due to
Norfloxacin and Cross reactivity with older Quinonoles , ELSEVIER .
[7] Ozkaya E.Fixed drug eruption : state of the art. J Dtsch Dermatol Ges. Nov 2008; Volume 6 Pages: 181-188.
[PubMed].
[8] Shiohara T , Mizukawa Y : Fixed Drug Eruption: Easily Overlooked but Needing New Respect. Dermatology
2002; Volume 205 Pages:130-104.
[9] Rahmeh Fayez MD, Nidal Obaidat MD, Ayman Al-Qaqaa MD, et al ., Drugs Causing Fixed Drug Eruption:
A Clinical Study , JOURNAL OF THE ROYAL MEDICAL SERVICES , Vol. 18 No. 3 September 2011.
[10] Wolff K, Johnson RA, Suurmond D, editors. Fitzpatricks color atlas and synopsis of clinical dermatology. 5 th
ed.New York : McGraw Hill;2005.Volume.20 Pages:556-558.
[11] Lee Ai-Young, American Journal of Clinical Dermatology September/October 2000; Volume 1, Issue 5,
Pages:277-285
[12] Pellicano R, Ciavarella G, Lomuto M, Di Giorgio G, Genetic susceptibility to fixed drug eruption: evidence for
a link with HLA-B22 J Am Acad Dermatol Jan 1994; Volume 30, Issue 1, Pages:52-4.
[13] Pellicano R, Lomuto M, Ciavarella G, Di Giorgio G, Gasparini P, Fixed drug eruptions with feprazone are
linked to HLA-B22 J Am Acad Dermatol May 1997; Volume 36(5 Pt 1) Pages:782-4.
[14] Scherer K, Bircher AJ: Hypersensitivity reactions to fluoroquinolones. Curr Allergy Asthma.Rep 2005; Volume
5: Pages 15-21.[PubMed].
[15] Dhar S, Sharma V K: Fixed drug eruption due to ciprofloxacin. British Journal of Dermatology 1996; Volume
134: Pages 156-158.[PubMed].
[16] Akira Kawada, Masataro Hiruma , Koukichi Morimoto., et al.,Fixed drug eruption induced by ciprofloxacin
followed by ofloxacin , Contact dermatitis , Volume 31 , Issue 3, Pages 182-183 , September 1994.
[17] Hazano S, Kume A, Higashi N. A case of fixed drug eruption from ofloxacin [in Japanese]. Hifu 1991, Volume
33: Pages 229-31.
[18] Kitagawa K, Fukuda T, Yamazaki Y. A case of fixed drug eruption from ofloxacin [in Japanese]. Rinsho Derma
(Tokyo) 1991, Volume 33: Pages 1472-3.
[19] Jonathan L Hager MD, Mohsin R Mir MD, Sylvia Hsu MD , Fluoroquinolone induced generalized fixed drug
eruption , Dermatology online journal Volume 15,Issue 12 : Page 8.
[20] Tetsuo Shiohara , Fixed drug eruption: pathogenesis and diagnostic tests , Current Opinion in Allergy and
Clinical Immunology 2009, Volume 9 Pages:316321.
[21] KD Tripathi , Essentials of MEDICAL PHARMACOLOGY , 6 th edition , New Delhi , JAYPEE brothers
medical publishers (P) LTD , 2006 , Pages:691-692.

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