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FIXED DRUG ERUPTION

Advisor : dr. Asvina Anis Anwar


Supervisor: dr. Widyawati Djamaluddin, Sp.KK
Dermatovenereology
Department
M e d i c a l Fa c u l t y o f H a s a n u d d i n
University

PRESENTED BY :
o MUHAMMAD SAADILLAH
C11111356
o SITI HARDIYANTI
C11112001
o HARYANTO KENDEK TULING
C11112003
o EKA SARASWATI TAWAINELLA
C11112004

INTRODUCTION
Fixed drug eruptions are so named
because they recur at the same site
with each exposure to the
medication.
The time for ingestion of the
offending agent to the appearance of
symptoms is between 30 minutes
and 8 hours, averaging 2 hours.
InW, most
patients,
six
orW, fewer
lesions
James
Elston D, Berger
T. Drug Reactions.
In James
Elston D, Berger
T, editors.
Andrew's Disease of The Skin. 11th ed. UK: Elsevier; 2011. p. 117-118.
occur, and frequently only one.

INTRODUCTION
They way present anywhere on the
body, but half occur on the oral and
genital mucosa.
In males lesions are usually unifocal
and can effect the glans or shaft of
the penis.
FDE of the vulva is often
symmetrical, presenting as an
erosive
vulvitis,
with
lesions
onT,the
James
W, Elston D, Berger
T. Drug Reactions.
In James
W, Elston D, Berger
editors.
Andrew's Disease of The Skin. 11th ed. UK: Elsevier; 2011. p. 117-118.
labia minora and majora and

INTRODUCTION
Other unusual variants of FDE
includes eczematous, urticarial,
papular, purpuric, linear, giant, and
psoriasiform.
At times, some lesions of FDE will not
reactivate with exposure due to a
presumed refractory period wich
may last from weeks to months.
James W, Elston D, Berger T. Drug Reactions. In James W, Elston D, Berger T, editors.
Andrew's Disease of The Skin. 11th ed. UK: Elsevier; 2011. p. 117-118.

EPIDEMIOLOGY
Approximately 10% FDE occurs in children
and adults, the age of the youngest ever
reported was 8 months
As the clinical manifestations of allergy drug
eruption most of the 58 cases of infants and
children, followed by the eruption
eksentematousa (3%), and urticaria (12%)
the highest number of cases is increasing by
aging. it is due to drug exposure increased
Shear NH, Knowles SR. Inflammatory Diseases Based on Abnormal Humoral Reactivity. In
Goldsmith LA, Katz SI, Gilchrest BA, Paller AS, Leffell DJ, Wolff K, editors. Fitzpatrick's
Dermatology in General Medicine. 8th ed. New York: McGraw-Hill; 2012.

ETIOLOGY
The only provoking factors are
ingested foreign substances, which
are almost exclusively prescription or
proprietary medications.
The following list includes the more
common offenders such as cotrimoxazole, tetracycline, and
NSAIDs.
Shear NH, Knowles SR. Inflammatory Diseases Based on Abnormal Humoral Reactivity. In
Goldsmith LA, Katz SI, Gilchrest BA, Paller AS, Leffell DJ, Wolff K, editors. Fitzpatrick's
Dermatology in General Medicine. 9th ed. New York: McGraw-Hill; 2012. p. 3335

Breathnach S. Drug Reactions. In Burns T, Breaths S, Cox N, Griffith


C, editors. Rook's Textbook of Dermatology. West Sussex: WileyBlackwell; 2010. p. 3974

PATHOGENESIS
The exact mechanism is unknown
According to one hypothesis FDE is
classified as a type IV immunologic
reaction because of latent cytotoxic T
cells in the lesions, which may
become reactivated
JB Wahlang, Sangma KA, Marak MD, Brahma DK, Lynsah KG, Ksih A. Fixed
drug eruption due to Metronidazole : Review of literature and A Case
Report. International Journal of Pharma Sciences and Research (IJSPR):

PATHOGENESIS
Drug Exposure

T Cell Activation

Produce

Interferon
gamma and
TNF-a

TNF-a

Tissue Damage

T. Shiohara, Mizukawa Y, Teraki Y.


Pathophisiology of fixed drug
eruption : The role of-skin residen
T cells. Curr opin Allergy Clin
Immunol. 2002. Aug;2(4):317-23

migration of T
lymphocytes to
the cells of the
epidermis

Increase
Expresion of
ICAM-1
T lymphocytes are settled in the
skin lesions play a role in
immunological memory and
explain the recurrence of the
lesion in the same place

PATHOGENESIS
Activation of CD8 + T cells is
sufficient to trigger the lesions.
However, not enough to cause
extensive tissue damage.
The entry of regulatory T cells into
epidermal lesions observed in fully
developed and will serve to limit the
harmful
immune
reaction
T. Shiohara.
Fixed
Drug Eruption
: Pathogenesis and
Diagnostic Tests. Curr opin Allergy Clin Immunol. 2009. Aug;
9(4):316-

CLINICAL MANIFESTATION
Fixed Drug Eruption can develop from 30
minutes to 816 hours after ingestion of
the medication.
The lesions recurs in the same site each
time a the drug is taken.
Can be found anywhere on the body, but
favor the lips, face, hands, feet and
genitalia.
FDE may be asymptomatic or
may be accompanied by burning
or stinging/ pruritus, or prominent
local or systemic manifestations.
The usual symptoms of itching
and burning pain may only be
localized to the site of the lesions

Sehgal N Virendra. Fixed Drug Eruption


(FDE) : Changing Scenario of
Incriminating Drugs. International
Journal of Dermatology: September

CLINICAL MANIFESTATIONS
The common morphologic
presentation is a single (or a few)
erythematous/pigmented
macule(s)
Generalized bullous FDE, characterized
by multiple, sharply defined, deep-red
macules and blisters of various sizes,
displaying a bilateral, often symmetric,
distribution, may occasionally be
encountered.

After subsidence of the acute


phase, residual hyperpigmentation
will appear as a hallmark
Sehgal N Virendra. Fixed Drug Eruption (FDE) : Changing Scenario of Incriminating
Drugs. International Journal of Dermatology: September 2006

Diagnosis
Anamnesis :
History of exposed by drugs and the onset of
reaction, history of reaction in same drugs.
Some patients may complain of burning or
stinging, and others may have fever, malaise,
and abdominal symptoms.
Breathnach S. Drug Reactions. In Burns T, Breaths S, Cox N, Griffith C,
editors. Rook's Textbook of Dermatology. West Sussex: WileyBlackwell; 2010. p. 3974

Diagnosis
Physical examination :
Skin lesion solitary, erythematous, bright red or
dusky red macules that may evolve into an
edematous plaque; bullous-type lesions may be
present.

Neil H., Sandra R. 2012. Chapter 41. Cutaneous Reactions to Drugs. In


: Neil H., Sandra R, editors. Fitzpatricks Dermatology in General
Medicine. 8th edition. New York: McGrawHill. p. 449 454.

Diagnosis
Supportive Examination :
Patch testing :
Using a drug concentration of 30% in petrolatum or water
applied to a previously reacted site is the recommended
approach.
Patch tests are read at day 2 and day 4 and preferably also at
1 week.
One study used an 6 week time window after lesion
resolution and between tests, which yielded positive results in
up to 32% - 50% of patients.
Breathnach S. Drug Reactions. In Burns T, Breaths S, Cox N, Griffith C, editors. Rook's
Textbook of Dermatology. 8th edition. West Sussex: Wiley-Blackwell; 2011. p. 4113-4116.
Neil H., Sandra R. 2012. Chapter 41. Cutaneous Reactions to Drugs. In : Neil H., Sandra R,
editors. Fitzpatricks Dermatology in General Medicine. 8th edition. New York: McGrawHill. p.

Diagnosis
Supportive Examination:
Oral Provocation (OP)
OP need to be delayed at least 2 weeks from
the last eruption.
If an OP test is considered, the initial
challenge should be 10% of the standard dose.
Patients with widespread lesions (SJS/TENlike) should not be challenged.
Breathnach S. Drug Reactions. In Burns T, Breaths S, Cox N, Griffith C, editors. Rook's Textbook
of Dermatology. 8th edition. West Sussex: Wiley-Blackwell; 2011. p. 4113-4116.
Neil H., Sandra R. 2012. Chapter 41. Cutaneous Reactions to Drugs. In : Neil H., Sandra R,
editors. Fitzpatricks Dermatology in General Medicine. 8th edition. New York: McGrawHill. p.
449 454.

Diagnosis
Supportive Examination :
Intradermal Provocation (IDP)
0.1 ml of available injection of suspected
drugs were given on normal skin
Observed within 5-20 minutes
Producing erythematous nodule or vesicle
or urticarial with hemorrhagic centre.
Breathnach S. Drug Reactions. In Burns T, Breaths S, Cox N, Griffith C, editors. Rook's
Textbook of Dermatology. 8th edition. West Sussex: Wiley-Blackwell; 2011. p. 4113-4116.
Neil H., Sandra R. 2012. Chapter 41. Cutaneous Reactions to Drugs. In : Neil H., Sandra R,
editors. Fitzpatricks Dermatology in General Medicine. 8th edition. New York: McGrawHill. p.
449 454.

Skin biopsy, histopathology:


Interface dermatitis, vacuolar change, necrotic
keratinocytes, and incontinent pigment in the dermis.

Breathnach S. Erythema Multiforme, StevensJohnson Syndrome and Toxic Epidermal


Necrolysis. In Burns T, Breaths S, Cox N, Griffith C, editors. Rook's Textbook of Dermatology.
8th edition.West Sussex: Wiley-Blackwell; 2011. p. 4129-4130.

Differential Diagnose
Postinflammatory hyperpigmentation (PIH)
PIH is a common condition caused by numerous
preceding cutaneous insults such as drug and phototoxic
reactions, infections, physical injury or trauma, allergic
reactions, and inflammatory diseases.
PIH consists of a macular hyperpigmentation at the site
of inflammation.
Hilde, L., Barbara, B. 2012. Chapter 75. Post Inflammatory Hyperpigmentation. In : Hilde
L, Barbara B, Sofie D, Evelien V, Mireille G, Katia O, Nanja G, Jo L, Lieve B, editors.
Fitzpatricks Dermatology in General Medicine. 8th edition. New York: McGrawHill.p. 824

Differential Diagnose

Postinflammatory hyperpigmentation (PIH)

Differential Diagnose
Erythema Multiforme
Erythema multiforme (EM) is an acute self-limited,
usually mild, and often relapsing mucocutaneous
syndrome.
Most cases of EM are related to infections. Herpes
virus is definitely the most common cause, principally
in recurrent cases.
EM is defined only by its clinical characteristics :
target-shaped plaques with or without central blisters,
predominant on the face and extremities.
Hilde, L., Barbara, B. 2012. Chapter 75. Post Inflammatory Hyperpigmentation. In : Hilde L,
Barbara B, Sofie D, Evelien V, Mireille G, Katia O, Nanja G, Jo L, Lieve B, editors. Fitzpatricks
Dermatology in General Medicine. 8th edition. New York: McGrawHill.p. 824

Differential Diagnose

Erythema
Multiforme

TREATMENT
1. CAUSAL TREATMENT
Implemented by avoiding the originator
drugs. It is recommended anyway to
avoid drugs and foods that have a
chemical structure similar to the
originator drug
Djuanda, Dr et all. Ilmu Penyakit Kulit dan Kelamin, edisi kelima. Bagian
Ilmu Penyakit Kulit dan Kelamin Fakultas Kedokteran Universitas
Indonesia. Balai Penerbit FKUI, Jakarta, 2012:154-157

2. ANTIHISTAMIN
The second-generation H1 antihistamines
is recommended as a first-line therapy by
the published guidelines of allergy and
dermatology. These drugs free of
anticholinergic effects (unlike the first
generation agents) and has a frequency of
administration that is less common than
the first generation agents (ex, cetirizine,
loratadin, fexofenadine, etc).
Zuberbier T, Asero R, Bindslev-Jensen C, et al. EAACI/GA(2)LEN/EDF/WAO guideline:
management of urticaria. Allergy 2009.
Geha RS, Meltzer EO. Desloratadine: A new, nonsedating, oral antihistamine. J
Allergy Clin Immunol 2001.
Grattan C, Powell S, Humphreys F, British Association of Dermatologists. Management and
diagnostic guidelines for urticaria and angio-oedema. Br J Dermatol 2001 .

3. CORTICOSTEROID
(GLUCOCORTICOID)
Given to patients with early
symptoms are severe and for people
with prominent angioedema and
urticaria can also be added for
persistent.
Grattan C, Powell S, Humphreys F, British Association of
Dermatologists. Management and diagnostic guidelines for urticaria
and angio-oedema. Br J Dermatol 2001.

4. TOPICAL
Topical treatment of depend on the
circumstances from skins disorder , whether
dry or wet.
dry: Salisilat talk 2% given with antipruritus
drug,example mentol - 1% to reduce
itching.
wet: compress 1 % salicylic acid solution
Djuanda, Dr et all. Ilmu Penyakit Kulit dan Kelamin, edisi kelima.
Bagian Ilmu Penyakit Kulit dan Kelamin Fakultas Kedokteran
Universitas Indonesia. Balai Penerbit FKUI, Jakarta, 2012:154-157

PROGNOSIS
Basically, skin eruption due to drugs
will heal if the underlying drug is
detected and eliminated
immediately.

Djuanda, et all. Ilmu penyakit kulit dan kelamin edisi keenam.


2013. Penerbit FKUI, Jakarta. Hal.154,156

CONCLUSION
Fixed Drug Eruption (FDE) is a disorder that
would occur repeatedly in the same place.
Predilection place around the mouth, lips
and the area under the penis in men.
There are some medications that most
often cause of FDE is cotrimoxazole,
tetracycline and NSAIDs. According to the
survey UK Dermatology obtained NSAIDs
(25%), paracetamol (24%), cotrimoxazole
(5%) and tetracycline (5%).

Conclusion
Pathogenesis FDE allegedly is delayed type
hypersensitivity reactions and is associated with CD8 +
T cells as memory cells
Diagnosis is made by history and characteristic clinical
features.
Gold standard examination is an oral provocation test,
but must be under the supervision of trained medical
personnel.
Its management is primarily suspected drug withdrawal
sparked FDE, oral treatment with antihistamines and
topical treatment depending on the lesion, if given a
compress wet and when dry kortikosterioid given
topically.