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Oral granuloma gravidarum: a retrospective study of 41 cases in Southern Brazil

Granuloma gravidarum (GG) is an inflammatory lesion, which develops in the oral mucosa of pregnant women in response to chronic low-grade irritants, under the influence of hormonal factors. Objective: To characterize GG clinically by means of a retrospective study of the cases of the Oral Medicine Division, São Lucas Hospital, Brazil. Material and Methods: Cases of GG diagnosed between 1980 and 2012 were analyzed. Data were obtained referring to the age of the patients, lesion location, clinical features, as well as the presence of local irritants. The gestation period in which the lesion developed was also investigated. Results: Forty-one cases of GG were found. The lesions developed predominantly in the third trimester of pregnancy (51.22%) and the mean age of the patients was 28 years. Most GG was found in the gingiva (73.17%), was reddish color and had a mean diameter of 1.5 cm. Local irritants were involved in 75.6% of the cases. Conclusions: The hormonal conditions of pregnancy can have an impact on the oral cavity, predisposing the patient to inflammatory lesions such as GG.


INTRODUCTION
Granuloma gravidarum (GG) is an inflammatory lesion, which develops in the oral mucosa of pregnant women in response to chronic irritants of low degree such as bacterial biofilm, dental calculus and traumatic agents. Increased concentrations of estrogen and progesterone raises the levels of Prevotella intermedia in the subgingival biofilm, diminishes the host response to bacterial biofilm, increases vascular permeability, favors the infiltration of fluids into the perivascular tissues and enhances the inflammatory response, having an important role in the development of the lesion 10 .
From the histopathological point of view, there are no differences between GG and pyogenic granuloma. There is a variation in the nomenclature of lesions based on their occurrence in the gestation period 4,13 . The lesions are composed of highly proliferative vascular tissue, with numerous channels bordered by endothelium, which can appear obliterated by erythrocytes. There is inflammatory infiltrate mixed with neutrophils, plasmocytes and lymphocytes 1 .
The need for surgical intervention during pregnancy should be carefully examined, considering the high rate of GG recurrence, as well as the possibility of regression after childbirth, due to the normalization of hormonal levels 15 . In general, treatment during pregnancy is necessary if the lesion causes functional or aesthetic harm. On the other hand, its surgical excision is indicated after pregnancy 2 . The control of the bacterial biofilm is of great importance to prevent recurrence after treatment 5,7 .
The aim of this study was to characterize GG, by means of an epidemiological survey of cases diagnosed over a period of 32 years, in the Oral Medicine Division, São Lucas Hospital -Pontifical Catholic University of Rio Grande do Sul (PUCRS), Brazil.

METhODS
A total of 206 medical records of female patients with pyogenic granuloma, diagnosed from 1980 to 2012, were selected in the Oral Medicine Division, São Lucas Hospital -Pontifical Catholic University of Rio Grande do Sul (PUCRS), Brazil. The cases were reviewed to determine if the lesion developed during pregnancy, which characterizes GG. The histological slides were reviewed by a pathologist to confirm the anatomopathological diagnosis.
The following information was obtained from the selected medical records: age of patients, location, size, coloration and type of lesion insertion, as well as the presence of ulceration, bleeding and local irritants (bacterial biofilm, dental calculus, gingivitis or trauma). The gestation period in which the lesion occurred, its time of development and treatment were also examined.

Statistical analysis
The data were initially evaluated by descriptive statistics. The qualitative variables were expressed as absolute and relative frequencies. The quantitative variables were described by mean and standard deviation.
Comparison of the results for age groups, gestation period and lesion size was carried out by constructing contingency tables and applying the chi-square test. Due to the small sample size, the significance of the test was obtained via simulation using the Monte Carlo method. The software used was the SPSS version 17.0.

RESULTS
Forty-one cases of GG were found in patients aged 19 to 44 years, with a mean of 28 years (SD± 6.45). In 51.22% of the cases, the lesion had developed in the third trimester of pregnancy, in 24.39% in the second trimester and in 17.07% in the first trimester. This information was not available in the medical records of 7.32% of the patients.
The most prevalent location of GG was the gingiva, corresponding to 73.17% of the cases, with no statistically significant difference between the upper and lower region. The other affected sites were the tongue (14.63%), lip (7.32%), palate and buccal mucosa (4.88%). The lesions appeared as nodules with diameters of 0.5 to 3.5 cm with a mean of 1.46 cm (SD±0.89). Reddish coloration was observed in 92.68% of the cases, an ulcerated surface was present in 31.71%, and the occurrence of bleeding, spontaneous or upon touch, occurred in 48.78% of the GG cases. Pedunculated base was observed in 60.98% of the cases, while in the other cases, the lesions were sessile (Figures 1 and 2).
The mean time of development was 168 days, but most lesions (65.85%) had up to 3 months of duration. Local irritant factors were reported in 75.61% of the cases. The irritants described in the medical records were bacterial biofilm (29.27%), gingivitis (21.95%), calculus (12.20%) and trauma (12.20%). These characteristics are described in Figure 3.
Regarding treatment, 82.93% of the lesions were surgically excised. In 41.18% of the cases, the excision was performed a few weeks or months after childbirth and in 58.82% of the cases, it was performed during pregnancy. After the removal of local irritants, three lesions (7.32%) had spontaneous remission, two of them during pregnancy. In 9.75% of the cases, patients did not return, so there was no information about their treatment.
There was a significant association between age and gestation period since the pregnant women up to 25 years old showed a tendency to develop GG

DISCUSSION
There are various retrospective studies that have reported on the clinicopathological characteristics of pyogenic granuloma, among which cases of GG are often included. However, a series of cases specifically examining the clinical characteristics of GG are not found in the literature. Thus, the present study aimed to retrospectively review 41 cases of GG diagnosed in the Oral Medicine Division, São Lucas Hospital, Brazil.
GG can start developing during the first trimester of pregnancy and its incidence increases as of the seventh month 14 . These characteristics were demonstrated in the present study, in which the pregnant women up to 25 years old showed a tendency to develop the lesion in the first trimester, but the majority of lesions occurred in the third trimester. The lesions were more prevalent in the third decade of life, where the mean age of the patients was 28 years. These results were similar to those described in the literature regarding pyogenic granuloma 6,8,16 . This is the first study to date to specifically describe the age of patients with GG.
In the present study, 73.17% of the lesions were located in the gingiva, without a difference between the upper or lower region. According to the literature, the gingiva is the most affected region, and the upper lesions are more prevalent 12   detected in 75.61% of the cases studied. Bacterial biofilm and dental calculus were the main local irritants associated with GG, explaining the greater involvement of the gingiva by inflammatory lesions.
Other sites such as the tongue, lip, palate and buccal mucosa can be affected due to traumatic factors. Thus, the presence of local irritants associated with hormonal factors increases the probability of the development of GG, mainly in the gingiva. During pregnancy, marked inflammatory characteristics are usually observed in the gingiva, with the presence of edema, intense erythema, hyperplasia and an increased tendency of bleeding 3 . This is due to the capacity of pregnant women to produce large amounts of progesterone and estrogen, which potentiate the vascular response.
Despite of the possibility of regression of GG with the regularization of hormone levels after childbirth 15 , in 58.82% of the cases surgical excision was performed during the 2 nd trimester. In these cases, surgery was an option of the patients due to the aesthetic harm, bleeding and halitosis caused by the lesions. Moreover, in 41.18% of the cases, even after childbirth, there was no remission and the lesions were also surgically treated.
In this study, the lesions were clinically observed as pedunculated or sessile nodules, usually reddish color, capable or not of bleeding and ulceration. These findings are compatible with those described in the international literature with respect to the clinical appearance of pyogenic granuloma 7,8,11,12 , and therefore demonstrate that there are no clinical differences between the two lesions 9 . Pregnancy alters female hormonal conditions considerably. These alterations can have repercussions on the oral cavity, predisposing the pregnant woman to periodontal inflammation, where GG is a reactional lesion resulting from this inflammation.

CONCLUSIONS
The hormonal conditions of pregnancy can have an impact on the oral cavity, predisposing the patient to inflammatory lesions such as GG.