On-line version ISSN 1806-4841
An. Bras. Dermatol. vol.84 no.1 Rio de Janeiro Jan./Feb. 2009
Antonio Carlos Martins GuedesI; Aline Almeida BentesII; Jackson Machado-PintoIII; Maria de Lourdes Ribeiro de CarvalhoIV
Professor of Dermatology, Department of Internal Medicine, Faculdade de Medicina
da Universidade Federal de Minas Gerais (UFMG). PhD in Dermatology, UNIFESP
- Sao Paulo (SP), Brazil
IIMedical student at Faculdade de Medicina da Universidade Federal de Minas Gerais (UFMG) - Belo Horizonte (MG), Brazil
IIIPhD in Medicine, Santa Casa de Belo Horizonte. Head of the Dermatology Clinic, Santa Casa de Belo Horizonte. Professor, Faculdade de Ciências Médicas de Minas Gerais - Belo Horizonte (MG), Brazil
IVDermatologist. PhD in Science, Field of Immunoparasitology, Instituto de Ciências Biológicas da Universidade Federal de Minas Gerais (ICB/UFMG) - Belo Horizonte (MG), Brazil
We report one case of very severe acne-like lesions associated with amineptine (Survector®). They were most prominent on the face and back, but were also observed on sites not affected by acne vulgaris, such as perineum, arms and legs. The lesions appeared after long-term self-medication of high doses. Keratoacanthoma-like lesions were also present, and the small ones were successfully treated with topical imiquimod. The case is significant since the disease is quite rare.
Keywords: Acne vulgaris; Keratoacanthoma; Drug eruptions
Acne vulgaris is the inflammation of the pilosebaceous units of some areas of the body (face, trunk, and rarely, the gluteal region), that occurs most frequently during adolescence and displays well-defined clinical forms in its preeminent lesion, comedonal acne, papulo-pustulous acne, nodulocystic acne, and acne conglobata. The lesions may lead to deep-pitted, depressed, and hypertrophic scars, and these sequelae are particularly common in nodulocystic acne and in acne conglobata. Serious acne includes persistent or recurring inflammatory nodular manifestations, extensive papulo-pustulous lesions, exuberant scarring, and/or fistulas. 1
In 1987, a special type of acne induced by a tricyclic antidepressant (amineptine) 2 was reported. Amineptine-induced acne is peculiar because of its seriousness, and is qualified as "monstrous"; in the most exuberant cases. It appears at a late age and after prolonged use of high doses of this antidepressant .4,5 It is a characteristic and special form of acne, and its primary cause may be identified by clinical examination. It affects preferentially women during the age of natural involution of juvenile acne. It is particularly explosive, profuse, and surpasses the habitual territories of acne, appearing essentially on the face, ear lobe, neck, chest, fingers, and sometimes, on the extremities and perineum.5-7
It is generally retentional, micro- and macro-cystic, and lesions are two to eight millimeters long, with closed white or black comedons, and very rarely inflamed. 3, 6-9
In most cases, depressed patients consume two to four tablets of amineptine a day; it is an antidepressant routinely prescribed in some countries, such as France.6 It is immensely appreciated by patients due to it rapid euphoria-causing action and shows amphetamine-type activity leading to true toxicomania, which is often dose-dependent. 6
Treatment of the amineptine-induced acneiform lesion consists of drug suppression, reduction of the associated toxicomania, surgical drainage of the cysts, and prolonged use of isotretinoin 1 mg/Kg/day. 5,6
A 52-year-old white female patient, born and coming from Belo Horizonte, MG, presented with chronic depression, having used amineptine (Survector 100 mg) for approximately 30 years (sic). Over the last few years, due to self-medication, she had been taking a dose of eight tablets a day. Subsequently, in light of the cummulative effect of the drug, she developed an acneiform eruption with predominance of cystic lesions located on the face, cervical region, upper limbs, gluteus and vulva. After six years, she presented keratoacanthoma-like lesions in the same locations (Figure 1). The histopathological picture of the keratoacanthoma-like lesions showed dilation of the ostia of the sebaceous or eccrine glands filled in by corneal plugs and accentuated hyperplasia of the Malpighian layer, likely by metaplastic or epidermoid keratinization, and sometimes, keratoacanthoma (Figure 2 and 3). At this time, she used isotretinoin (1.0 mg/Kg/day) and tetracycline at usual doses for acne (500 a 1000 mg/day), alternately, for approximately two years with no adequate therapeutic response. She complained of pruriginous and painful lesions. The larger lesions were surgically removed to alleviate symptoms, and the smaller ones were treated topically with 5% imiquimod (3 times a week), leading to clinical regression, and leaving residual atrophy (Figure 4 and 5). However, the patient never stopped taking amineptine. She progressed to death due to cardiocirculatory problems. The magnetic resonance imaging test showed polypoid lesions with a non-defined pattern in the right ventricle and atria. An autopsy was not allowed.
Potential risks with the use of amineptine are the development of acneiform lesions, neurophysiological changes, and difficulty in "weaning"; the patient from the drug. Iatrogenically induced acne appears at a later phase in life (on average, around the age of 42 years, with extremes of 26 and 76 years) and predominates in females. Lesions are exclusively retentional, micro- and macro-cystic; they appear profusely and, in the most severe cases, lead to facial disfigurations, called by some authors as "monstrous. "; 5 Lesions appear after months or years, when the drug consumption is at supratherapeutic or toxic doses. 7,8 Intensity of the lesions is directly related to the daily dose and to the cummulative effect of the medication. 4,5,10 Prognosis is related to the possibility of complete and definitive "weaning"; of the drug. 4 Analysis by mass spectrometry allows identifying the presence of amineptine and of its metabolites in the plasma, urine, and even in the cyst content, which could explain the persistence of acne after abstinence of the drug. 4,7,10,11 The medication is concentrated not only in the sebaceous glands, but also in sweat. 4
Keratoacanthoma is a tumor that probably originates in the rapid growth follicular infundibulum and predominates in areas exposed to the sun. Its benign nature is controversial, since some consider it benign with a pseudomalignant aspect, a malignant condition in regression, and even, a variant of squamous cell carcinoma. It is an affection of the elderly, with an annual incidence rate of 104/100000. Keratoacanthomas may develop in sites of prior trauma. Most are "crateriform";, which grow rapidly, have a quiescent period, and then suffer spontaneous regression. Less than 2% belong to destructive variants, with no regression and persistent invasive growth.12
After years of use and a high dose of amineptine, the patient described displayed multiple lesions similar to keratoacanthomas, both clinically and histopathologically. Since the follicular origin of the keratoacanthoma is recognized, it is not possible to affirm the origin in this patient since her lesions also occurred in areas with no hair, such as palms and soles, and were associated with dilations of both the sebaceous and eccrine gland ostia, which were filled in with corneal plugs. This could be a case of accentuated hyperplasia of the Malpighian layer through possible metaplastic or epidermoid keratinization, similar to a keratoacanthoma. It was not possible to investigate drug metabolites within these lesions. Since the drug may be found in sebaceous secretions and sweat, there could be metaplastic keratinization in the papulokeratotic lesions in both eccrine gland (syringometaplasia) and the sebaceous gland, producing the hyperplastic acanthotic aspect and vitreous appearance. This type of keratinization is benign, and is not exclusive of this drug, since it may occur in several tumoral and inflammatory dermatoses after the administration of toxic exogenous substances, such as chemotherapy agents (doxorubicin, cytarabine), 2,3,7,8-tetrachlorodibenzo-p-dioxin (chloracne), pantomime (injection of oil), and non-steroidal anti-inflammatory agents (benoxaprofen). The mechanism of formation of this metaplasia is not well defined; it likely originates by chronic inflammatory action or toxic action. Inflammation would be responsible for the cell necrosis that would lead to posterior epithelial metaplasia in the eccrine excretion channel. Accumulation of toxic substances, especially medications, would be responsible for the catalyst effect of different types of processes, such as keratinization of the excretion channels, proliferation of the ductal epithelium, neutrophilic eccrine hydradenitis with necrosis of eccrine glands, and keratinization associated with foci of necrosis. It is acknowledged that there would be direct chemotoxicity on skin appendages (sebaceous and sudoriparous glands), placing amineptine with other drugs responsible for these types of manifestations grouped as toxidermia of skin appendages. 4
Topical 5% imiquimod is an immunomodulating drug that has recently been used in the treatment of cutaneous neoplasms such as basal cell carcinoma and keratoacanthoma. 13-16 There was a good response of the smaller keratoacanthoma-like lesions to the use of topical 5% imiquimod (three times a week).
The report of this case is significant because of its rare nature. We call attention to an acneiform eruption in which the etiological diagnosis may be facilitated by its relation to the abusive use of amineptine, a fact that is frequently hidden by patients.
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How to cite this article: Guedes ACM, Bentes
AA, Machado-Pinto J, Carvalho MLR. Acne induzida por amineptina. An Bras Dermatol.
How to cite this article: Guedes ACM, Bentes AA, Machado-Pinto J, Carvalho MLR. Acne induzida por amineptina. An Bras Dermatol. 2009;84(1):71-4.