The many faces of fixed drug eruptions

The many faces of fixed drug eruptions

Dermatologia Kliniczna 2011, 13 (1): 5-8
ISSN 1730-7201
PRACE ORYGINALNE / Original articles
Copyright © 2011 Cornetis; www.cornetis.com.pl
The many faces of fixed drug eruptions
Wiele twarzy rumienia trwałego
Olayinka Abimbola Olasode
Department of Dermatology, Obafemi Awolowo University, Ile Ife, Osun state, Nigeria
ABSTRACT
Fixed drug eruption (FDE) is a form of presentation of recurrent cutaneous drug reaction characterized
by appearance of single or multiple erythematous annular hyperpigmented macules/patch or bullae
that appears each time at the same site whenever the offending drug is used. The lesion heals each time
with typical post inflammatory hyperpigmentation. Diagnosis is based on drug history, drug associated
excercebations and remissions, clinical presentations of typical polycyclic lesions with lack of systemic
symptoms, drug challenge, skin tests and histology of skin biopsy. Diagnosis may not always easy. Unusual and atypical cases of FDE have been reported to raise awareness and raise index of suspicion in non
classical or altered lesions. We report seven different presentations of Fixed Drug eruptions in a Nigerian
population presenting in our skin clinic. The possibility of variant lesions occurring in Fixed Drug Eruptions is hereby highlighted. Typical lesions of FDE can be altered secondarily by chronicity and application of some topical agents before the patient presents making correct diagnosis difficult. We suggest
that attending dermatologist be aware and have these unusual presentations of FDE in mind while making a diagnosis. The role of detailed accurate and precise history taking in these cases cannot be overemphasized.
Key words: diagnosis, drug eruptions
STRESZCZENIE
Rumień trwały polekowy (fixed drug eruption, FDE) jest jedną ze skórnych reakcji niepożądanego działania leków. Nierzadko ma charakter zmian nawracających. Może mieć postać pojedynczych lub wieloogniskowych rumieniowych plam o kształcie pierścieniowym, często z pęcherzem. Cechą charakterystyczną jest występowanie zmian skórnych za każdym razem w tym samym miejscu po zastosowaniu
prowokującego leku. Zmiany ustępują z pozostawieniem charakterystycznego pozapalnego przebarwienia. Rozpoznanie oparte jest na wywiadzie, tj. ustaleniu, że do nasilenia lub wystąpienia zmian dochodzi po przyjęciu prowokującego powstanie zmian leku. Charakterystyczny jest również obraz kliniczny, czyli obecność policyklicznych zmian rumieniowych, oraz brak objawów ogólnych; pomocne może
być badanie histologiczne zmian skórnych. Rozpoznanie czasem może być utrudnione, z uwagi na nietypowy obraz kliniczny. Nietypowe odmiany FDE są coraz częściej opisywane. Publikacje te podnoszą
świadomość lekarzy i ułatwiają rozpoznawanie w wielu przypadkach FDE. W pracy przedstawiono sieAddress for correspondence:
dem przypadków FDE obserwowanych w klinice dermatologii Obafemi Awolowo University (Nigeria).
Dr Olayinka Abimbola Olasode
Zwrócono uwagę na różne odmiany FDE. Autorzy zauważyli, że na zmianę obrazu klinicznego może
MBBCh, FWACP, FACP
Consultant Physician/Dermatologist mieć wpływ zarówno przewlekłe stosowanie prowokujących leków, jak też leczenie miejscowe. Autorzy
zasugerowali, aby brać pod uwagę nietypowe odmiany kliniczne FDE. Jednocześnie szczególnie przy
Department of Dermatology,
Obafemi Awolowo University, Ile Ife podejrzeniu FDE bardzo duże znaczenie ma szczegółowy wywiad.
Osun state, Nigeria
e-mail: [email protected] Słowa kluczowe: diagnostyka, skórne reakcje polekowe
Introduction
There is a wide variety of morphological patterns of cutaneous
drug reactions among which are Fixed Drug Eruptions (FDE).Typical
lesions of FDE are annular recurrent hyperpigmented erythematous bordered sometimes bullous lesions (fig. 1, 2). Typical history of
recurrence and association with offending drugs helps the clinician
in diagnosis. Patients intrigued by these typical acute lesions seek
medical consultation quickly. However, late presentations, misdiagnosis of original lesions or application of irritant topical therapy for
cure may alter the original lesions making subsequent diagnosis
difficult. This is likely to occur in areas where access to medical or
5
Olayinka Abimbola Olasode
The many faces of fixed drug eruptions
Table I:
Tabela I:
Figures
Rycina
Dermatologia Kliniczna 2011, 13 (1)
Clinical presentations in patients with diagnosis of FDE presenting in a dermatology clinic, Obafemi Awolowo University, Ile Ife, Osun State,
Nigeria
Objawy kliniczne u pacjentów z FDE leczonych w klinice dermatologicznej, Obafemi Awolowo University, Ile Ife, Osun State, Nigeria
Sex
Płeć
Offending drug
Lek powodujący zmiany
Initial lesion
Rodzaj pierwotnych zmian
Duration
Czas trwania
Clinic presentation
Obraz kliniczny
1
Age
[in years]
Wiek pacjenta
[w latach]
20
F
2
4
F
3
55
F
4
32
M
5
40
M
6
42
M
7
36
F
Sulphonamide
Sulfonamidy
Sulphonamide
Sulfonamidy
Paracetamol
Paracetamol
Sulphonamide
Sulfonamidy
Sulphonamide
Sulfonamidy
Tetracycline
Tetracyklina
Sulphonamide
Sulfonamidy
Macule
Plama
Bullae
Pęcherze
Macule
Plama
Macule
Plama
Bullae
Pęcherze
Bullae
Pęcherze
Macule
Plama
6 months
6 miesięcy
4 weeks
4 tygodnie
9 months
9 miesięcy
8 months
8 miesięcy
10 months
10 miesięcy
2 years
2 lata
2 years
2 lata
Hyperpigmented macules
Hiperpigmentowane plamy
Bullae
Pęcherze
Hyperpigmented patch
Hiperpigmentowane blaszki
Facial hyperpigmentation
Hiperpigmentacja twarzy
Hyperkeratotic lesions
Hiperkeratotyczne zmiany
Lichenified depigmentation
Odbarwienia i lichenifikacja
Vitiligo like lesions
Zmiany typu bielactwa nabytego
F – female / kobieta, M – men / mężczyzna
expert dermatology care is limited or where the initial lesions have
been altered by over the counter medications.
Clinical Presentations
Cases presented at a dermatology clinic of a teaching hospital
and were seen by an attending dermatologist. Demographic
data, drug history, family history and past medical history were
documented. The initial presenting lesions and their progress
were described by the patients. Previous topical therapy applied
was recorded. Diagnosis was based on history, clinical findings
and recurrence of lesions associated with offending drug at same
site. Skin biopsy was used to confirm doubtful cases. Pictures of
lesions were taken.
Results
See table I and figures 1-7.
Fig. 1. Typical polycyclic hyperpigmented macule of FDE
Ryc. 1. Typowe policykliczne przebarwienia w przebiegu FDE
6
Fig. 2. Typical bullous lesion of FDE on the abdomen in a 4-year-old
Ryc. 2. Typowe pęcherze w przebiegu FDE na skórze brzucha
u 4-letniego chłopca
Fig. 3. Flexural hyperpigmented lesion of FDE with erythematous
borders limited to neck area
Ryc. 3. Przebarwienia w okolicach zgięciowych z rumieniową granicą
ograniczone do okolicy szyi
Olayinka Abimbola Olasode
Wiele twarzy rumienia trwałego
Fig. 4. Multiple thick facial hyperpigmented lesions of FDE
Ryc. 4. Wieloogniskowe obrzękowe przebarwienia na twarzy
w przebiegu FDE
Fig. 7. Solitary vitiligo like lesion with perifollicular repigmentation
following FDE on the thigh
Ryc. 7. Pojedyncze ognisko przypominające bielactwo nabyte z repigmentacją przymieszkową powstałe na udzie w przebiegu FDE
Discussion
Fig. 5. Multiple hyperkeratotic lesions following initial bullous lesions of
FDE on the back
Ryc. 5. Wieloogniskowe hiperkeratotyczne zmiany w przebiegu FDE
powstałe w miejscu pęcherzy na plecach
An adverse drug reaction is any unintended or undesirable response to a medication given at an appropriate dose [1]. Any organ
may exhibit an allergic reaction, but the skin is commonly affected
because it has both metabolic and immunologic functions. Clinical
and morphological approaches as well as cutaneous biopsy and
histology may be necessary to make a diagnosis of cutaneous drug
reactions. Histology can distinguish between a drug-induced disease and other diseases but it does not allow for identification of the
causative drug. Often the causative agent is made out from the patient’s history; in some cases, oral challenge or topical testing may
be required.
Fixed drug eruption (FDE) is characterized by the development
of recurrent site-specific lesions on the skin and/or mucosa during
treatment with the drug responsible. Fixed drug eruptions represent an immunologic cutaneous reaction to a systemic medication.
Cell-mediated, rather than humoral immunity is thought to be involved in the pathophysiology of FDE [2]. Drugs that have been associated with FDE include phenolphthalein, sulfonamides, phenylbutazone, barbiturates, dapsone, chlordiazepoxide, indomethacin,
quinine, salicylates and tetracyclines [3]. Typical Fixed drug eruptions have been documented in Nigeria. Olumide [4] observed FDE
among patients being treated with pyrazolone analgesic and benzodiazepine in Lagos, Nigeria.
FDE manifest as well circumscribed eczematous or bullous lesions on the skin and heals with residual hyperpigmentation (fig.
1, 2). Various and atypical morphological patterns of fixed drug
eruption have been described in various studies [5, 6]. Fixed drug
eruption has been documented to mimick lichen planus, erythema
multiforme, Steven Johnson syndrome, paronychia, cheilitis, psoriasis, housewife dermatitis, melasma, lichen planus actinicus, discoid lupus erythematosus, erythema annulare centrifugum, pemphigus vulgaris, chilblains, pityriasis rosea and vulval and perianal hypermelanosis [5, 6]. Similar diagnostic challenges are yet to be documented in literature in Nigeria. This paper describes some atypical
presentations of FDE presenting at a skin clinic in Western Nigeria.
FDE with Pigmentary loss
Fig. 6. Lesion with post inflammatory depigmentation following itchy
bullous lesions of FDE
Ryc. 6. Zmiana z pozapalnym odbarwieniem w miejscu swędzących
pęcherzy w przebiegu FDE
Figures 6 and 7 both show pigmentary loss in their secondary lesions after 2 years of recurrence. There is primary loss of pigmentation with attempt at follicular repigmentation case presented in fi-
7
Olayinka Abimbola Olasode
The many faces of fixed drug eruptions
gure 7. In figure 6, the initial lesion is typical FDE healing with hyperpigmentation with secondary depigmentation in the middle of the
lesion. Pigmentary loss can be post inflammatory or local loss of
melanocytes. In literature non pigmenting subset of FDE is a distinctive, clinically recognizable entity. Characteristically, the lesions are large, symmetrical, well-circumscribed tender erythematous plaques that suddenly appear and reappear in exactly the
same sites. They fade without pigmentation or any other trace over
a 2- to 3-week period [7]. Shelley and Shelley [8] described three
examples of this overlooked non pigmenting fixed drug reaction
pattern. These presentations can be overlooked but management
requires recognition and avoidance of implicated drugs. The lesions described in figures 6 and 7 do not fit into the picture of non
pigmentary FDE but are a different variant actually with loss of pigment and attempt at repigmentation.
Chronic lesions of FDE
Chronic forms of FDE presentations have also been described.
A case of chronic fixed drug eruption resembling parapsoriasis was
reported, which presented with persistent, stable lesions that were
present for seven months before the diagnosis was established [9].
Chronic alteration of lesions can result from scratching lesions, ulceration, superadded bacterial infections, application of irritants, and
healing with lichenification. Lichenification is thickened and rough
skin characterized by rough skin due to repeated rubbing. Repeated injury to the skin can result in this picture (fig. 5). This is indeed
a challenge to diagnosis of the primary lesion. Chronicity may alter
typical lesions of FDE.
Other variants of FDE
A case of biopsy-confirmed fixed drug eruption (FDE) associated
with paracetamol and presenting like cellulites was reported by
Prabhu, et al. [10]. Another unique morphology of widespread multifocal fixed drug eruption showing a reticulated and bullous pattern caused by mefenamic acid was reported by another group [11].
Attention has been drawn drug eruptions confined to the intertrigenous areas [12]. Other presentations include a wandering fixed
drug eruption in which the lesion keeps on changing its position
and giant fixed drug eruption [11].
Confirming diagnosis of FDE
Drug rechallenge in FDE is a reliable method of identifying causative drugs, but increasingly the use of skin tests has gained the attention of investigators.
Histopathology in FDE
The histopathology in typical FDE is lichenoid dermatitis. The accompanying inflammatory cell infiltrate is a superficial and deep
8
Dermatologia Kliniczna 2011, 13 (1)
perivascular infiltrate. There are also neutrophils and melanophages, indicative of repeat injury at the dermoepidermal junction.
However, occasionally, early lesions may show epidermal spongiosis, dermal edema, neutrophilic microabscesses, and dermal eosinophils.
Conclusion
Atypical and secondary lesions can be a diagnostic challenge to
an otherwise simple straightforward diagnosis. The patient must
be able to adequately describe the original primary lesion, the progression, aggravating and relieving factors. Yet an accurate diagnosis is essential for appropriate therapy. In chronic and altered lesions
histology may not be totally exclusive. An experienced dermatologist knows the value of detailed history of a skin lesion for diagnosis. Late presentations of skin lesions can occur where there are too
few/no dermatologists or long appointments before a patient is
seen. Application of topical agents which are easily available over
the counter may alter the presenting lesion. All these conditions are
present in the developing world. There is a need to increase our
awareness that fixed drug eruptions come in different clinical
forms. It is well known that drug eruptions can mimic a wide range
of skin conditions. Attention is being drawn to drug induced dermatosis mimicry.
References
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Received: 2010.12.02.
Approved: 2011.02.23.