Association of Bacterial Vaginosis and Skin Disorders in Patients with Autoimmune Antibody Positivity

OBJECTIVE: To investigate the association of bacterial vaginosis and skin disorders in patients with autoimmune antibody positivity. STUDY DESIGN: This retrospective study consisted of 80 patients with autoimmune antibody positivity. All patients were evaluated for the presence of bacterial vaginosis and skin disorders. Cervicovaginal smears were used for the definitive diagnosis of bacterial vaginosis. RESULT: We found bacterial vaginosis in 13.75% (11/80) of the cases. 1 (9.1%) and 10 (90.9%) cases had skin disorders in bacterial vaginosis positive and negative groups respectively (p=0.531). CONCLUSION: There is no relationship between bacterial vaginosis and the presence of skin disorders in patients with autoimmune antibody positivity.

trauterine device usage, and smoking (5). In our previous study, BV was found to be more frequent in patients with AAP (6). BV affects vaginal mucosa and causes pruritus, irritation, and desquamation of the vulvar skin thus leading to a decrease in the quality of life (7).
The skin is composed of a multi-layered structure that forms a physical barrier protecting the body from environmental factors. Various types of skin disorders can be caused by autoimmune disorders, other immunologic discrepancies such as allergies, metabolic syndrome, and bacterial or viral infections (8)(9)(10). The immune system plays a crucial role in the etiopathogenesis of skin diseases. There are many different types of skin-related autoimmune disorders including scleroderma, psoriasis, dermatomyositis, and autoimmune bullous disorders (11)(12)(13).
The presence of autoimmune antibodies not only attracts the attention of gynecologists due to adverse pregnancy outcomes, but also the dermatologists for the maintenance of healthy skin. In this study, we aimed to search the association of BV and skin disorders in patients with AAP.

Introduction
Bacterial vaginosis (BV) is the most common cause of vaginal infection among fertile women with a prevalence that differs widely among different populations between 8 to 75% (1). In Turkey, the prevalence of BV changes between 7.2-23% (2,3). BV is especially important for an increased risk of late miscarriage, preterm labor, fetal growth retardation, chorioamnionitis, postpartum endometritis, and pelvic inflammatory disease (4). Predisposing factors that increase the risk of BV are multiple partners, vaginal douching, in-skin disorders. Cervicovaginal smears were performed for the definitive diagnosis of BV. The cytological evaluation was performed through the Papanicolaou method. Fixed slides were first immersed in decreasing concentrations of alcohol solutions, then washed in distilled water. Rehydrated slides were then stained with Harris' Hematoxylin (Merck, Germany) and washed with tap water. 1% hydrochloric acid-alcohol (v/v) was used for decoloring. The slides were then immersed in a series of solutions containing increasing alcohol concentrations and were stained with Orange G (Merck, Germany) and EA 65 (Merck, Germany). To clean out the excess dye, slides were washed with 95% ethanol after each step. Stained smears were immersed in Xylene (Merck, Germany), then Entellan (Merck, Germany) a mounting medium and were covered with coverslips. Cytological findings were assessed on a light microscope and photographed (Leica DM 400B).
Statistical analyses were performed using the Statistical Package for the Social Sciences (SPSS, version 23). Groups were compared using the Fischer's Exact Test. p-values <0.05 were considered as statistically significant. The study was approved by the Hacettepe University Institutional Review Board with reference number GO 19/1064. The study was performed according to the Declaration of Helsinki.

Results
This retrospective study included 80 patients with serum AAP including anti-smooth muscle antibodies (ASMA), antiparietal antibody (APA), and anti-nuclear antibody (ANA). The rates of autoantibody positivities were given in table I. ANA was the most frequent positive autoantibody with a rate of 57.5%. Eleven of 80 (13.75%) patients included in the study had various skin disorders including viral diseases, psoriasis, urticaria or dermatitis, telogen effluvium, acneiform disease, and skin tags. The most frequent skin disorder was a skin tag in this cohort (36.3%, n=4/11). (Table II).  The cervicovaginal smear slides which involved clue cells covered by adherent bacteria, a lack of Lactobacilli and neutrophil leukocytes, and an increased number of free cocci were detected (Figure 1), were diagnosed as BV (n=11).
When we evaluated the association of skin disorders with BV, only 1 (9.1%) patient had BV and a skin disorder concomitantly. There was no statistically significant relationship between the presence of BV and skin disorders (p>0.05) (Table III).

Discussion
Bacterial vaginosis is characterized by a reduction of Lactobacilli and an overgrowth of other commensal microorganisms in the vagina (14). This causes an imbalance of the vaginal microflora leading various gynecological complaints including fishy odor, thin, milky discharge, pruritus, irritation, and abdominal pain (15). BV also leads to skin manifestations, such as desquamation of the vulvar skin (7). However, BV may be asymptomatic in 50% of women and may be a cause of unfavorable pregnancy outcomes (16).
Autoantibodies are defined as antibodies resulting from immune system discrepancies caused by a failure to distinguish "self" from "non-self", thus targeting self-cellular components (17). Autoantibodies lead to placental inflammation and are associated with adverse pregnancy outcomes such as fetal growth retardation, miscarriage, and stillbirth (18). BV was found to be more frequent in patients with AAP in our previous study (6).
Autoimmune antibodies affect a variety of tissues and organs. The skin is one of the tissues which are commonly affected by autoimmune disorders (17). There are several different types of skin-related autoimmune disorders including scleroderma, psoriasis, dermatomyositis, and autoimmune bullous disorders (11)(12)(13). The incidence and severity of autoimmune skin diseases may vary depending on the type of skin disorders, gender, age, and ethnicity (19,20).
In a study where the prevalence of common skin diseases in the European population (Germany, Italy, the Netherlands, Portugal, and Sweden) were evaluated in 12.377 participants, the most common skin diseases were warts (41.3%), acneiform diseases (19.2%) and contact dermatitis (15.0%) (21). In our study, we found 11 of 80 (13.75%) patients to have various skin disorders including viral diseases, psoriasis, urticaria or dermatitis, telogen effluvium, acneiform diseases, and skin tag. The most frequent skin disorder was a skin tag in our cohort (36.3%, n=4/11).
We found that only 1 (9.1%) of patients in our cohort to have both BV and skin diseases. This patient was diagnosed with chronic urticaria, as well as genital verrucae. We found no statistically significant relationship between the presence of BV and skin disorders.
The main limitations of this study are the inclusion of a relatively low number of cases and its retrospective design. The lack of information explaining the results of this study is another limitation. To the best of our knowledge, this is the first study to investigate the association of BV and skin disorders.
In conclusion, although autoimmune antibodies are important in the occurrence of skin problems, we found no association between the presence of skin disease and BV in AAP patients. Further studies including larger cohorts are warranted to confirm these results.