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 Table of Contents  
ORIGINAL RESEARCH REPORT
Year : 2015  |  Volume : 12  |  Issue : 2  |  Page : 108-112

Fixed drug eruption at a dermatology clinic in Lagos, Nigeria


Department of Medicine, College of Medicine, University of Lagos, Lagos, Nigeria

Date of Web Publication17-Nov-2015

Correspondence Address:
Olusola Olabisi Ayanlowo
Department of Medicine, Faculty of Clinical Sciences, College of Medicine, University of Lagos, Lagos
Nigeria
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/1595-9587.169692

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  Abstract 

Background: Fixed drug eruption (FDE) is common cutaneous drug eruption characterized by the development of one or more annular, oval, erythematous, and hyperpigmented patches as a result of systemic exposure to a drug. Drugs causing FDE vary with prevailing diseases and prescription pattern in different parts of the world. This study is aimed at reviewing cases of FDE seen at the dermatology outpatient clinic of Lagos University Teaching Hospital (LUTH) over a 9-year period, highlighting the spectrum of drugs implicated and the clinical characteristics. Materials and Methods: Data were obtained from the clinic records and patients' case notes. These included the demographic details, duration of presentation, drugs implicated, and clinical characteristics. Results: FDE was diagnosed in 1.8% (295/16,160) of patients seen. There was a slight female preponderance. Antimalarials were the commonest group of medications implicated (51.0%) followed by antibiotics (27.9%); analgesics (10.2%), herbal toothpaste (6.1%), and oral hypoglycemic agents (4.1%). Sulfonamides were the commonest group of drugs found in 78 patients (53.1%) predominantly as sulfadoxine/pyrimethamine antimalarials and trimethoprim/sulfamethoxazole antibiotics (co-trimoxazole). Conclusion: Concerted efforts are needed to discourage over-the-counter sales and purchase of nonprescription sulfonamide-based medications. A change in prescription pattern from sulfonamides to other classes of antimalarials and antibiotics is desirable and/or recommended. Patients should inform their caregivers at any point of care about their reaction to drugs. It is advised that they have a list of common implicating drugs and they wear a medic alert or carry an ID card bearing this information.

Keywords: Adverse cutaneous eruptions, antibiotics, antimalarials, sulfonamides


How to cite this article:
Ayanlowo OO. Fixed drug eruption at a dermatology clinic in Lagos, Nigeria. J Clin Sci 2015;12:108-12

How to cite this URL:
Ayanlowo OO. Fixed drug eruption at a dermatology clinic in Lagos, Nigeria. J Clin Sci [serial online] 2015 [cited 2020 Jul 9];12:108-12. Available from: http://www.jcsjournal.org/text.asp?2015/12/2/108/169692


  Introduction Top


Fixed drug eruption (FDE) is common cutaneous drug eruption characterized by the development of one or more annular, oval, erythematous, and hyperpigmented patches as a result of systemic exposure to a drug.[1],[2] The lesions may recur at the same site, and/or at new sites with reexposure to the offending drug(s). The reactions may be erythematous, eczematous, urticarial, bullous, and pigmented with a necrotic center sometimes mimicking the target lesions of erythema multiforme. The lesions resolve with postinflammatory hyperpigmentation.[3] Initial eruptions occur within days to 2 weeks of exposure to the offending agent. With subsequent reexposure, lesions occur within 30 min to 16 h of drug ingestion.[3]

FDE is the second most common adverse cutaneous eruption reported in both in- and outpatients units, occurring at all ages and in all races.[3] Drugs causing FDE vary with prevailing diseases and prescription pattern in different parts of the world. The list of drugs keeps growing with the introduction of new medications.[4],[5] Herbal medications and nonmedicinal substances such as nutritional supplements; biocides (insecticides and herbicides); and food additives like colorings, preservatives, and emulsifiers were suspected to cause FDEs in individuals with no prior history of drug exposure.[3],[4],[5] FDEs have also been reported to be caused by dyes.[6]

The exact mechanisms of occurrence of FDE lesions is unknown but it is thought to be a cell-mediated process. Antibody-dependent, cell-mediated cytotoxic responses, with cluster of differentiation 8 (CD8) effector/memory T-cells, are noted to play an important role in reactivating lesions following reexposure to offending agents.[7] A genetic predisposition has been described; and human leukocyte antigen (HLA)-B22 and Cw1 were linked significantly with FDE.[8] Histology shows interface dermatitis, vacuolar change, necrotic keratinocytes, and incontinent pigment in the dermis. Other features that may be seen are mild acanthosis, hyperkeratosis, spongiosis, dermal edema, eosinophils, and occasional neutrophils.[1],[3]

The aim of this study was to review the cases of FDE that presented at the dermatology outpatient clinic of Lagos University Teaching Hospital (LUTH) over a 9-year period (January 2004 to December 2012), highlighting the spectrum of drugs implicated and the clinical characteristics including sites of body affected.


  Materials and Methods Top


This is a retrospective review of all patients who presented with FDE over a 9-year period. Data were obtained from the clinic records and patients' case notes. Data extracted included the demographic details, duration of presentation, drugs implicated, and parts of the body affected. Diagnosis of FDE is principally clinical: It is based on a history of intake of a drug that is associated with clinical findings of one or more hyperpigmented or inflamed, annular or oval erythematous patches and blisters [Figure 1]. There is a recurrence of lesions at the same location with ingestion of offending or similar drug or drugs leaving deeply pigmented postinflammatory lesions. Skin biopsies were carried out when the history and lesions are not typical. This is to aid with diagnosis of other conditions that have a similar presentation such as erythema multiforme, bullous pemphigus, pemphigus vulgaris, lichen planus, and drug-induced bullous eruptions.
Figure 1: Erythema and blisters in acute fixed drug eruptions

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The data extracted were computed/entered in an excel spreadsheet and were analyzed using Statistical Package for the Social Sciences (SPSS) version 16.0 (IBM, Armonk, NY). The results were displayed with frequency tables.


  Results Top


During the study period, a total of 16,160 patients were studied and 295 (1.8%) presented with FDEs. There was a slight female preponderance with a male-to-female ratio of 1:1.1. FDE was seen in all age groups with peak incidence in the third decade of life and a decline with increasing age [Table 1]. The patients' age ranged 5 months-82 years, with the mean age of 32.12 ± 15.5 years and median age of 28 years. The youngest patient was a 5-month-old boy who developed FDE (with lesions on the trunk and around the mouth) following the use of antimalarials for a febrile illness. The oldest patient was 82 years old and had FDE lesions after using antibiotics (trimethoprim/sulfathiazole). The duration of skin lesions prior to presentation varied from 2 days to 10 years [Table 2].
Table 1: Distribution of patients by age group

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Table 2: Duration of lesions in patients with fixed drug eruption

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Specific drugs were identified as causing typical lesions in 147 (49.8%) out of the 295 patients who presented with FDE. Antimalarials were the commonest group of medications implicated in 75/147 patients (51.0%), followed by antibiotics in 41/147 patients (27.9%), analgesics in 17/147 patients (11.6%), herbal toothpaste in 9/147 patients (6.1%), and oral hypoglycemic agents in 6/147 patients (4.1%). [Table 3] shows frequency of specific drugs implicated in FDEs in this series. Sulfonamides were the commonest group of drugs found in 78 patients (53.1%) with FDE occurring predominantly with sulfadoxine and pyrimethamine containing antimalarials and trimethoprim and sulfamethoxazole containing antibiotics (co-trimoxazole) [Table 3]. The implicated antimalarials containing sulfonamides are Fansidar, Maloxine, Amalar, Malareich, and Metakelfin. Other antibiotics causing FDE are tetracyclines and quinolones (Ciprofloxacin and Ampiclox).
Table 3: Drugs causing fixed drug eruptions

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The trunk was the commonest part of the body affected by this disease that is noted in 56 patients (19.0%), followed by the lower limbs in 45 patients (15.3%), face in 41 patients (13.9%), perioral region in 30 patients (10.2%) [Figure 2], and the genitalia in 13 patients (4.4%) in descending order. Generalized FDE was found in 48 patients (16.3%) [Table 4].
Table 4: Frequency of presentation of fixed drug eruption in different parts of the body

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Figure 2: Perioral fixed drug eruption

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  Discussion Top


FDE is a relatively common dermatosis and is noted to be the second or third most common adverse cutaneous eruption as described in various reports.[3] FDE was found in 1.8% of patients at the dermatology outpatient clinic in this series comparable to what was found in other skin clinics in Nigeria. Surveys in different parts of Nigeria revealed that FDE accounted for less than 1% to 2.2% of total patients' attendance at the dermatology outpatient clinic.[9],[10],[11]

There is a slight female preponderance with a male-to-female ratio of 1:1.1. FDE is a condition of immense cosmetic importance in view of the deeply pigmented postinflammatory lesion.[3] The female preponderance may be assumed to be that the women are often more concerned about their appearance than males. Previous studies in Nigeria and Congo have reported a male preponderance.[12],[13] FDE was seen in all age groups with peak incidence in the third decade of life and decline with increasing age.[1],[3],[12] The youngest patient in this series was a 5-month-old boy and the oldest patient was 82 years old.

The most important aspects of disease management are prompt diagnoses and identification of the culprit drug(s).[1],[3] While the rate of mortality is low in case of FDE, persistent recurrence may lead to bullous and generalized lesions that may be similar to toxic epidermal necrolysis and Steven Johnson's syndrome with potentially life-threatening complications. Recurrence also leads to an increase in the number and depth of the disfiguring, postinflammatory hyperpigmented lesions that are most obvious in patients who are dark skinned. The presence of these lesions affects the quality of life of the individuals. Offending drugs were identified in 147 (49.8%) of the 295 individuals who presented with FDE during the study period. Some of the factors identified to precipitate FDE like lesions include fever; menstruation; and consumption of vegetable stew, herbs, and carbonated drinks.[3],[4] It was also suggested that biocides (herbicides and insecticides) and food additives such as colorings, preservatives, and emulsifiers may also be culprits in cases where no drug history was elicited.[4] There is a need for further studies to substantiate this. FDEs have been reported to erythromycin, foods, dyes and following sexual contact with someone who ingested implicated drugs.[3],[6],[14]

FDEs have been noted in the setting of patients taking a concoction of drugs in which all the medications are capable of causing the lesions, this phenomenon is called polysensitivity.[15] Twenty three patients (15.6%) had two different classes of drugs indicted; while four (2.7%) had three classes of drugs involved. It is a common occurrence in Nigeria for people who are sick to be treated at community pharmacies, and by quacks with drug concoctions consisting of analgesics, antimalarials and antibiotics which they may not know the specific names, hence precluding the aetiologic diagnosis. The report from Congo revealed that 81.5% of drugs causing FDE were obtained from illegal markets and outlets.[13]

Sulfonamide-containing drugs have consistently been the most implicated in studies from different parts of the world. Apart from HLA-B22 found generally in FDE, HLA-A30 B13 Cw6 has been significantly linked with trimethoprim - sulfamethoxazole indicating a specific genetic predisposition.[16] Sulfonamide antimalarials are the most prevalent in Nigeria, while sulfonamide antibiotic and co-trimaxazole were the most prevalent in other parts of the world.[12],[13],[17]

Nigeria is a malaria endemic zone and antimalarials are obtained commonly as over-the-counter medications. Sulfonamide antimalarials such as Fansidar®, Maloxine®, Amalar®, Malareich®, and Metakelfin® are noted to be culprits, as found by a previous work done in Southwestern Nigeria.[12] This suggests that the pattern of prescription has not changed in the last 10 years. There is need for public awareness to intimate physicians and general public of this potential side effect of sulfonamide antibiotics and antifungal which are easily available, very cheap over-the-counter medications. It is of note that acetaminophen (paracetamol), a very common “over-the-counter” analgesic, is a major cause of FDE in this series, its frequency is higher than reported in previous studies in Nigeria; on the contrary, anticonvulsant is a culprit in only one patient, showing a marked reduction in frequency [Table 3].[12]

Use of herbal medications and substances are gradually emerging as important culprits in adverse cutaneous drug eruptions and inflammatory reactions. A previous report from our center noted use of herbal concoctions as a cause of erythroderma in 10.9% and aggravating factor in 39.3% of patients.[18] This report revealed FDE occurring with the use of a herbal toothpaste in 9 patients (6.1%).

In human immunodeficiency virus (HIV)-positive patients, adverse cutaneous eruptions commonly occurred due to sulfonamides and nevirapine as documented in many studies.[19] FDE was found secondary to use of antiretrovirals: Nevirapine and efavirenz in two men. In this study, FDE was not associated with use of sulfonamides in HIV-positive individuals, although co-trimoxazole is a commonly prescribed prophylaxis for opportunistic infections. Sulfonamide-based antimalarials was documented to cause Steven Johnson's syndrome in HIV-positive patients in a series at a university hospital in Nigeria.[20] Women were documented to be particularly predisposed to severe hypersensitivity reactions from nevirapine at CD4+ counts greater than 250 cells/uL.[19] However, large studies will be necessary to identify the sex predilection to highly active antiretroviral therapy in Nigeria.

Lesions of FDE occurred in almost all body parts [Table 4] including the oral mucosa in three patients. The significant number of patients [48 (16%)] presented with generalized hyperpigmentation that indicates continuous exposure to offending drug [Figure 3]. Avoidance of offending drugs will forestall recurrence and further pigmentation of the skin. It is pertinent to consider nutritional supplements, over the counter drugs, additives, and preservatives as possible culprits.
Figure 3: The trunk of a young boy with generalized fixed drug eruption

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In conclusion, educating medical practitioners and other health-care workers such as pharmacists and nurses about this striking adverse cutaneous drug reaction will aid health-care workers in appreciating the magnitude of this condition and to limit occurrence and recurrence. Concerted efforts are needed to discourage over-the-counter sales and purchase of nonprescription sulfonamides in order to limit the occurrence of this adverse cutaneous drug eruption. The public will also benefit from awareness campaign on the dangers of over-the-counter and nonprescription purchase of drugs that includes FDEs and life-threatening conditions such as Steven Johnson's Syndrome and FDE. There are a retinue of antimalarials and antibiotics that may be used instead of sulfonamide-based antimalarials and antibiotics hence a change in prescription pattern is advocated. The identification of this cutaneous drug reaction is to be reported by any health-care workers to the state pharmacovigilance team. This will ensure that we have regular and updated figures on the occurrence of FDE and the implicating drugs.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
  References Top

1.
Breathnach SM. Drug reactions: Fixed drug eruptions. In: Burns T, Breathnach S, Cox N, Griffiths, editors. Rooks Textbook of Dermatology. 7th ed. Vol. 4. United Kingdom: Blackwell Science Ltd.; 2004. p. 20-9, 73.  Back to cited text no. 1
    
2.
Ozkaya-Bayazit E. Specific site involvement in fixed drug eruption. J Am Acad Dermatol 2003;49:1003-7.  Back to cited text no. 2
    
3.
Butler DF, Ilse JR, Schwartz RA, Vinson RP, Callen JP, Quirk CM, et al. Fixed Drug Eruptions. Available from: http://www.emedicine.medscape.com/article/1336702-followup#showall. [Last accessed on 2013 Oct 14].  Back to cited text no. 3
    
4.
Sehgal VN, Srivastava G. Fixed drug eruption (FDE): Changing scenario of incriminating drugs. Int J Dermatol 2006;45:897-908.  Back to cited text no. 4
    
5.
George AO, Ogunbiyi AO. Fixed drug eruption and fixed drug-like eruption. Int J Dermatol 2005;44:349-50.  Back to cited text no. 5
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6.
Klevansky H, Kingsley HJ. Fixed drug eruptions caused by dyes. S Afr Med J 1964;38:216.  Back to cited text no. 6
[PUBMED]    
7.
Shiohara T. Fixed drug eruption: Pathogenesis and diagnostic tests. Curr Opin Allergy Clin Immunol 2009;9:316-21.  Back to cited text no. 7
    
8.
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 1994;30:52-4.  Back to cited text no. 8
    
9.
Onayemi O, Isezuo SA, Njoku CH. Prevalence of different skin conditions in an outpatients' setting in North-Western Nigeria. Int J Dermatol 2005;44:7-11.  Back to cited text no. 9
    
10.
Nnoruka EN. Skin diseases in south-east Nigeria: A current perspective. Int J Dermatol 2005;44:29-33.  Back to cited text no. 10
    
11.
Ogunbiyi AO, Daramola OO, Alese OO. Prevalence of skin diseases in Ibadan, Nigeria. Int J Dermatol 2004;43:31-6.  Back to cited text no. 11
    
12.
Nnoruka EN, Ikeh VO, Mbah AU. Fixed drug eruption in Nigeria. Int J Dermatol 2006;45:1062-5.  Back to cited text no. 12
    
13.
Ognongo-Ibiaho AN, Atanda HL. Epidemiological study of fixed drug eruption in Pointe-Noire. Int J Dermatol 2012;51(Suppl 1):30-1, 33-5.  Back to cited text no. 13
    
14.
Lim WS, Kim DH, Jin SY, Choi YS, Lee SH, Huh HJ, et al. A case of fixed drug eruption due to doxycycline and erythromycin present in food. Allergy Asthma Immunol Res 2013;5:337-9.  Back to cited text no. 14
    
15.
Gantsho N, Khumalo NP. Skin focus: Fixed drug eruptions. Curr Allergy Clin Immunol 2008;21:138-40.  Back to cited text no. 15
    
16.
Ozkaya-Bayazit E, Akar U. Fixed drug eruption induced by trimethoprim-sulfamethoxazole: Evidence for a link to HLA-A30 B13 Cw6 haplotype. J Am Acad Dermatol 2001;45:712-7.  Back to cited text no. 16
    
17.
Mahboob A, Haroon TS. Drugs causing fixed eruptions: A study of 450 cases. Int J Dermatol 1998;37:833-8.  Back to cited text no. 17
    
18.
Ayanlowo OO, Akinkugbe AO. Erythroderma at the dermatology outpatient clinic of a tertiaty hospital in Lagos, Nigeria. Nig J Dermatol 2013;1:7-13.  Back to cited text no. 18
    
19.
Amerson EH, Maurer TA. Dermatologic manifestations of HIV in Africa. Top HIV Med 2010;18:16-22.  Back to cited text no. 19
    
20.
Ogunbiyi AO, George AO, Falodun O. Steven Johnson's syndrome and toxic epidermal necrolysis in Ibadan. Niger Med J 2009;56:57-61.  Back to cited text no. 20
    


    Figures

  [Figure 1], [Figure 2], [Figure 3]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4]



 

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