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On-line version ISSN 1806-4841
An. Bras. Dermatol. vol.84 no.1 Rio de Janeiro Jan./Feb. 2009
Rosana LazzariniI; Ida DuarteII; Juliana Casagrande Tavoloni BragaIII; Samia Leticia LigabueIV
Assistant of Dermatological Division, Santa Casa de Sao Paulo - Sao Paulo (SP),
IIDermatologist, Assistant of Dermatological Division, Joint Professor, Medical School, Santa Casa de Sao Paulo - Sao Paulo (SP), Brazil
IIIFormer intern, Specialization Course, Dermatological Division, Santa Casa de Sao Paulo - Sao Paulo (SP), Brazil
IVPhysician, Specialization Course, Dermatological Division, Santa Casa de Sao Paulo - Sao Paulo(SP), Brazil
Allergic Contact Dermatitis is a common type of dermatitis, but its multiple
etiologies hinder its management.
OBJECTIVE: the objective of this study was to evaluate the frequency of sensitization to topical drugs in a university
center, to study the main characteristics of the affected population, and to identify the allergens related with the dermatitis.
METHODS: a retrospective and descriptive study with patients submitted to patch tests. The study was conducted with subjects whose patch test to topical drugs was positive.
RESULTS: 329 patients were submitted to patch tests and 42 (13%) had positive and relevant patch tests to topical drugs. Among these patients, 36 (85.7%) had positive patch tests to the principal component and 28 (66.7%) to the other components. Some patients had more than one sensitization. Neomycin was the most important allergen.
CONCLUSIONS: Among the studied patients, sensitization to topical agents happened in 13% of the cases, with slight preference for females and Caucasians. There was elevated sensitization to neomycin, a popular agent among patients and medical doctors.
Keywords:Dermatitis, contact; Dermatitis, contact/etiology; Eczema; Neomycin; Neomycin/adverse effects;
Contact dermatitis to topical drugs may be iatrogenic or induced by the patient because of self-medication. It may have occupational nature in some cases of healthcare professionals or pharmaceutical industry workers that handle medications 1. Contact dermatitis by primary irritation (CDPI) by topical agents is triggered by agents that may cause direct tissue damage and allergic contact dermatitis (ACD) resulting from sensitization to a substance inducing reaction of hypersensitivity mediated by cells (type IV, Gell and Coombs).
Clinically, the most frequent type of reaction to topical drugs is contact eczema, accompanied by severe pruritus in all stages. In patients with stasis dermatitis, there may be dissemination to other areas or the whole tegumentum leading to erythrodermia.
The etiological agents present in the topical drugs that cause contact dermatitis are active principles and other ingredients (preservatives, acidulating agents, emulsifiers), many of which are also found in cosmetics 1.
CDPI is sometimes part of a therapeutic action, such as when using tretinoin, benzole peroxide or 5-fluorouracil. Other reactions such as contact urticaria, cutaneous necrosis (gentian violet, 5-fluorouracil and iodine polyvinylpyrrolidone), hyper and hypopigmentation (mercury salts) and contact dermatitis such as multiform erythema (ethylenediamine, neomycin and sulfonamides) may be observed.
ACD caused by repetitive use of medication is of difficult diagnosis because many different topical agents are used by the patient. The incidence of dermatosis varies depending on geographical area, because it depends on the prescription habits, in addition to the variations observed as years go by. Common allergens 20 or 30 years ago, such as sulfonamides, penicillin and topical antihistamines have been replaced by other drugs such as non-steroidal antiinflammatory drugs (NSAID) and corticosteroids, which became new allergens.
Some topical medicines may also induce photoallergic contact dermatitis, which is similarly expressed - acute or subacute eczema, especially in exposed areas. The objectives of the present study were: 1) to assess the frequency of sensitization to topical drugs in an university center; 2) to study the characteristics of the affected population concerning gender, age and disease that lead to medication use, and 3) to check the key sensitizers related with topical medication.
MATERIAL AND METHOD
We selected patients who had undergone contact tests between January 2004 and March 2006 at the Division of Allergy, Dermatological Clinic, Santa Casa de Sao Paulo, with suspicious of allergic contact dermatitis. We have retrospectively selected those who had positive and relevant contact tests to topical drugs, comprising active principle and other components of the formula.
Tests were performed using the Standardized Brazilian Battery of tests comprised by 30 substances (FDA Allergenic - Rio de Janeiro / Brazil). Substances that were not part of this battery were manipulated according to the literature data 2. In all cases, we used FINN Chambers (Oy, Finland) containers and readings were made within 48 and 96 hours, according to the criteria by International Contact Dermatitis Research Group (ICDRG) from 1981, to wit: (-) negative reaction; (?) doubtful reaction; (+) week reaction, with mild erythema and some papules; (++) medium intensity reaction, with erythema, papules and some vesicles; (+++) intense reaction, with erythema, papules and confluent vesicles.
Data were collected based on a protocol used by the Dermatological Clinic in which we had data such as age, gender, time since onset of dermatosis, and results of contact tests. If necessary, patient charts were also analyzed. These data were applied in an Excel® (Microsoft®) spreadsheet and they were quantified and prepared for descriptive analysis of the results.
Between January 2004 and March 2006, 329 patients underwent contact tests at the Allergy Division of Dermatological Clinic, Santa Casa de Sao Paulo. Out of the total 42 (13%) had positive and relevant result to topical drugs, by the active ingredient and/or other components.
Among them 24 were women (57%) and 18 were men (43%). The distribution by ethnic group showed 25 Caucasian patients (60%), nine Brazilian mixed Pardos (21%), seven Black descendents (17%), and one Asian (2%). The key age range was between 40 and 59 years (18 / 43%).
In two patients (5%), dermatoses had begun less than two months before, and in 40 (95%), dermatosis had existed for a long period of time, ranging from 3 to 60 months.
As to location, lower limbs were affected in 22 patients (31%), the head (neck and face) in 20 (25%), in 18 (25%) the upper limbs, and in five (7%), the trunk. In 8 cases dermatosis was disseminated (11%). There was more than one region affected in each patient (Table 1). Among the positive contact tests, 36 (85.7%) corresponded to the active ingredients and 28 (66.7%) to the other formula components, and some of the patients had more than one positive test.
As to active ingredients, there were 19 tests positive for neomycin (27%), 8 (12%) to promethazine, 5 (8%) to nitrofurazone, 2 (3%) to quinoline, one test (2%) each
to silver sulphadiazine and chloramphenicol. The two latter ones are not part of the standardized battery. Other positive components were: ethylenediamine and quaternium 15, with seven positive tests each (11%); parabens, in five (8%); colophonium, in three (5%); lanolin in two (3%); irgasan, perfume-mix, formaldehyde and Peruvian balsam in one test each (2% each) (Table 2).
Topical drugs are sometimes used without criteria owing to the popular belief that they have few adverse effects. Conversely, medical prescription may induce to contact dermatitis transforming it into iatrogenic dermatosis.
Patients with chronic dermatoses, with atopical dermatitis or psoriasis, are more prone to develop this type of dermatitis due to exposure to multiple topical agents on the skin and loss of integrity.
The cases of allergic contact dermatitis to topical drugs represent 13% of the total of tested patients in the described period, similarly to what was found in reports in Europe, in which the incidence of this contact dermatitis in patients submitted to contact tests ranged from 13.2% in Italy to 40% in Sweden 1.
Incidence is related with the type of studied patient. Patients with stasis or anogenital dermatitis have high risk to experience topical drug reactions due to the conditions that favor drug penetration, such as affection of skin barrier and increase in local temperature. In these patients, incidence is high and may vary from 58% to 86%, depending on the studied series.
Cases were more common among women and Caucasian patients. These data are compatible with others already reported in the literature, in which there is increased prevalence of contact dermatitis in female and Caucasian patients.
As to affected age ranges, there is higher occurrence of dermatitis after the age of 40 years. In this period of life, there is increase in the number of cases of allergic contact dermatitis in general, owing to greater exposure to allergens. Moreover, it enhances the frequency of dermatitis and stasis ulcers, chronic eczemas, and thus, greater exposure to topical agents.
Contact dermatitis had acute progression, below two months, in two cases only (5%), whereas 95% of the cases had had dermatosis for more than 3 months. This fact reflects the difficulty to diagnose the etiology of dermatosis and the increase in likelihood of building sensitivity to the drugs in patients who have dermatosis that progresses to loss of skin barrier function. Allergic contact dermatitis was present in lower limbs of 22 cases (33%), most related with stasis dermatitis, data which are in accordance with the literature. In such cases, the most common agent causing reactions was neomycin, followed by ethylenediamine and nitrofurazone. There was also built sensitivity to Peruvian balsam, quaternium 15, chloramphenicol, colophonium, fragrances and silver sulphadiazine. The literature has also shown that neomycin is a very frequent allergen in this location. However, corticosteroids have a key role as allergens in other regions of the world, a fact not observed in our country. These differences may be related to regional habits 3.
Promethazine, whose contact tests were positive in 12% of the cases, is an antihistaminic in the phenothiazine group, used for oral, intramuscular and topical administration. The topical use is very frequent in Brazil and in some European countries, capable of triggering ACD and photoallergic and phototoxic reactions.
Nitrofurazone was responsible for 14% of the cases of sensitization and it is used as antiseptic cream or lubricant in dressings for ulcers and burns. This drug is used in our country as dressing material for emergency centers. It is a strong sensitizer, capable of producing severe cases of contact dermatitis. 4
Quinoline was responsible for 3% of positive tests. This antimicrobial agent is used in topical drugs, associated with corticosteroids, other anti-bacterial agents and anti-fungal agents. In 1989 Goh, in Singapore, found 2.4% sensitization to quinoline among 514 patients with
ACD to topical antibiotics 5. The data reported here showed higher frequency of sensitization, probably because of the broader use of drugs in Brazil and also because of the different methodology used in both studies.
Among the studied patients, we observed one case of ACD caused by silver sulphadiazine in a patient with lower limb stasis ulcer, which had progressed from photosensitization. Silver sulphadiazine is a topical antibacterial agent used in lower limb ulcers and chemical burns whose antibacterial property results from the combined effect of silver and sulphadiazine 6. This is sensitive reaction is not very likely in Brazil.
One of the observed cases had sensitization to chloramphenicol, antibiotic used topically through eye drops and some creams to wounds, normally associated with collagenase. The patient underwent tests with the drug as it is sold and pure chloramphenicol at 5% in solid Vaseline, with positive results to both. Cases of sensitivity to this agent are not frequent in Europe because it is not widely used. In Brazil, the frequency of sensitivity to the agent is unknown 7.
Other agents present in formulations of topical drugs have also resulted positive, such as ethylenediamine (emulsifier), quaternium 15, parabens and formaldehydes (preservatives), perfume-mix, Peruvian balsam, and colophonium (fragrances) and lanoline (vehicle). These agents are common causes of ACD, because they are present in different products and should be reminded and considered when the results of the contact tests are interpreted 8-11.
An interesting topic to be pointed out is the previous presence of contact eczema by other etiological agents, such as nail polisher, cement and rubber, whose diagnosis was not initially made, leading to inappropriate use of drug and cause of secondary sensitization. Other dermatoses, such as psoriasis, chronic simple liquen, nummular eczema, and atopical dermatitis have also served as a basis to ACD by topical drugs.
We have observed among studied patients that allergic contact dermatitis to topical drugs occurred in 13% of the cases, with slight preference to female gender and greater number of cases among Caucasian patients. Neomycin was the most frequent sensitizing agent, commonly used among patients as OTC and also as part of medical prescription. This fact may serve as warning to physicians - specialists or not - when prescribing, especially to people with chronic dermatosis, the ones that are more prone to develop allergic contact dermatitis to topical drugs.
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How to cite this article: Lazzarini R, Duarte I, Braga JCT, Ligabue SL. Dermatite alérgica de contato a medicamentos de uso tópico: uma análise descritiva. An Bras Dermatol. 2009;84(1):30-4.