Gynecological Endocrinology, August 2009; 25(8): 543545

CASE REPORT

Oral stomatitis induced by endogenous progesterone: Case report

ELIANA M. MINICUCCI1, ALINE B. CARRENHO1, SILKE A. T. WEBER2, FERNANDA M. BOMBINI1, RENATA A. M. A. RIBEIRO1, MARIANGELA E. A. MARQUES3, & DANIEL A. RIBEIRO4
Department of Dermatology and Radiotherapy, 2Department of Otorhinolaryngology and Ophthalmology, 3Department of Pathology, Botucatu Medical School, Sao Paulo State University, UNESP, Sao Paulo, Brazil, and 4Department of Biosciences, Federal University of Sao Paulo, UNIFESP, Santos, Sao Paulo, Brazil (Received 21 February 2008; revised 12 April 2009; accepted 27 April 2009)
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Abstract Oral stomatitis induced by endogenous progesterone is a rare clinical condition which may be associated with cutaneous involvement. That is probably due to the peak of progesterone production during the luteal phase of the menstrual cycle. In the present case report, a 21-year-old patient displayed recurrent ulcerative lesions located on the buccal mucosa or the upper lip, on a monthly basis since the age of 15. Such lesions would always manifest themselves on the second day until the end of the menstrual cycle.

Keywords: Oral stomatitis, progesterone

Introduction Hypersensitivity induced by female sexual hormones is a rare clinical condition in which the patient develops a hypersensitivity reaction to endogenous progesterone. Such pathological condition occurs in patients ranging from 16 to 48 years of age with a predominance of young people [1]. Clinical manifestation is triggered every month during the luteal phase of the menstrual cycle, when the peak of progesterone production is reached. The clinical manifestations are variable [2] and include urticaria [3,4], erythema multiforme like-reaction [5], and eczema [6]. However, after the menstrual cycle, lesions disappear spontaneously. To date, a large number of studies have addressed clinical manifestations, especially on the skin, induced by endogenous progesterone. To the best of our knowledge, there are a few case reports addressing lesions specically in the oral mucosa [2]. Therefore, such a circumstance justies this case report as well as others; and, by taking into consideration, the current article describes a case report of oral stomatitis induced by endogenous progesterone.

Case report A 21-year-old Caucasian woman was referred to the Department of Dermatology, at the Ambulatory Care Center of Stomatology at Botucatu Medical School Sao Paulo State University (UNESP), Brazil complaining of ulcerative lesions in the perioral region, buccal mucosa, and upper lip (Figures 1 and 2). The patient reported that those lesions were painful. She also added that they had rst appeared when she was 15 years old, on a monthly basis. However, the general conditions of health were good. Under clinical examination, no skin abnormalities were found. No drugs were used for minimizing the symptomatology. To exclude herpes as putative diagnosis, Tzancks test was performed [7]. The result was negative; and, as a consequence, incisional biopsy was performed. Microscopically, the lesion had sub- and intraepithelial vesicles associated with necrosis in the basal layer (Figure 3). Moderate inammatory inltrate consisting of lymphocytes, neutrophils and eosinophils was present, with some of the inammatory cells located in the perivascular region (Figure 3). Skin testing

Correspondence: Daniel Araki Ribeiro, DDS, PhD, Departamento de Biocie ncias, Universidade Federal de Sa o Paulo UNIFESP, Av. Ana Costa 95, 11060001 Santos, SP, Brazil. Tel: 55-1332218058. Fax: 55-1332232592. E-mail: daribeiro@unifesp.br ISSN 0951-3590 print/ISSN 1473-0766 online 2009 Informa UK Ltd. DOI: 10.1080/09513590903015585

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E. M. Minicucci et al. followed a consultation with her gynecologist, in which it was prescribed Tamoxifen (Nolvadex), an antiestrogen agent, at a dosage of 20 mg/day for 2 months as described elsewhere [8]. The patient reported that her clinical symptoms began to decline gradually over a few weeks, and no recurrences were detected up to now (8 months after initial diagnosis). Discussion Autoimmune reaction triggered by endogenous progesterone is a rare clinical condition. The picture is characterized by recurrent cutaneous lesions during the luteal phase of the menstrual cycle, when the levels of endogenous progesterone are increased. Patients have reported cyclic lesions mainly in the skin. Such lesions appear before menstruation and remain even after the menstrual cycle is over [2]. In this case report, we have been able to report the instance of a woman with oral manifestations induced by endogenous progesterone. The lesions occurred in the perioral region, buccal mucosa, and upper lip with symptomatology. The early clinical pattern seemed to be a herpes infection, but Tzancks test presented a negative result. Moghadam et al. [8] have postulated that lesions induced by endogenous progesterone disappear 1 week after the menstrual cycle. Other authors have assumed hypersensitivity to be induced by endogenous progesterone, such as anaphylaxis during the menstrual cycle [9]. All symptoms disappear after some days [10,11]. Skin testing with estrogen (1 mg/ml) and Depo-Provera (1 mg/ml), a derivative of progesterone, was performed and no reaction in skin areas developed after 48-h evaluation. There is no relationship between oral stomatitis induced by progesterone and positive response in this test. Therefore, nal diagnosis was perfomed taking into consideration the clinical history only. The underlying mechanisms by which endogenous progesterone becomes antigenic remain unknown so far. It has been suggested that abnormalities in the composition of the hormone are present in women able to develop such autoimmune reaction [11]. The occurrence of antibodies against endogenous progesterone has been demonstrated in patients presenting history of oral ulcers since their rst menstruation [12]. Another possibility is a crossreaction between endogenous progesterone and circulating antibodies produced by putative antigen present in the body, such as in the case of a viral infection [11,12]. Growing evidence suggests that synthetic progesterone may stimulate antibodies against endogenous progesterone in contraceptive users [13]. Therapy is the use of anti-estrogenic drugs, such as Tamoxifen [14], estrogens (Premarin), which are

with estrogen (1 mg/ml) and Depo-Provera (1 mg/ ml), a derivative of progesterone, was performed and no reaction in skin areas developed after 48-h evaluation. Taken as a whole, these ndings supported the nal diagnosis of oral stomatitis induced by endogenous progesterone. After that, the patient

Figure 1. Clinical aspects of lesions in the upper lip.

Figure 2. Clinical aspects of lesions in the buccal mucosa.

Figure 3. Photomicrography of the lesion (H.E. stain, 640 magnication).

Stomatitis and progesterone able to interrupt the ovulation process as well as the production of endogenous progesterone [2,3]. Nevertheless, several patients do not undergo any therapy [15]. In this case, the patient received Tamoxifen (Nolvadex) after establishing the nal diagnosis, at a dosage of 20 mg/day for 2 months as described elsewhere [8]. The patient reported that her clinical symptoms began to decline gradually over a few weeks, and no recurrences were detected up to now (8 months after initial diagnosis). As a conclusion, oral stomatitis induced by endogenous progesterone is a rare disease. Histological conrmation of the clinical diagnosis is not essential in most cases. Gynecologists, dentists and/ or endocrinologists should be aware of such concerns. Declaration of interest: The authors report no conicts of interest. The authors alone are responsible for the content and writing of the article.

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