Acrochordons and autoimmunity: Significance of preconceptional counseling

1. Introduction

Skin tags or acrochordons are benign skin growths that appear on the surface of the skin over a thin stalk [1]. They are mostly composed of collagen fibers, fat, and sometimes other kinds of tissues such as blood vessels, mast cells, and Langerhans cells and a nerveless dermis [2, 3]. These lesions are also defined as fibroepithelial polyps [4]. Although a very common entity causing mainly cosmetic concerns, the pathologic mechanisms underlying the occurrence of acrochordons are unclear [5]. They have been associated with diabetes mellitus, insulin resistance, pregnancy, obesity, hypertension, metabolic syndrome, dyslipidemia, and high C-reactive protein levels, and have been suggested as a marker of increased risk of cardiovascular disease [6].

Autoimmunity is defined as loss of tolerance toward self-antigens and a resulting inadequate immune response, sometimes resulting in tissue damage [7]. Disruptions in the immune response are one of the mechanisms through which skin disorders may occur [8]. Scleroderma, psoriasis, dermatomyositis, and autoimmune bullous diseases are among the skin disorders caused by autoimmunity [9, 10, 11, 12, 13]. Autoimmune disorders can affect virtually all tissues in the body and may cause or aggravate various types of obstetrical complications [14, 15, 16, 17, 18]. For this reason, skin disorders should also be the concern of a physician who takes part in preconceptional care program.

This study investigated the co-occurrence of acrochordons and autoimmune disorders in patients with a poor obstetric history.

This retrospective cohort consisted of 350 patients with poor obstetric history who were admitted to a preconceptional care program aiming to investigate the risk factors for obstetric complications. Systemic and gynecological complaints (and their managements) and demographic characteristics together with laboratory test results were obtained from the electronic medical registration software of our hospital (Table 1). These patients were further evaluated (clinical findings and laboratory test results) for the presence of autoimmune disorders (defined by the diagnosis of an autoimmune disease or serum autoimmune antibody positivity) and acrochordons (Table 2). The “autoimmune antibody positive” group was composed of patients with anti-parietal antibody (APA) and anti-nuclear antibody (ANA) positivities.

The Statistical Package for the Social Sciences (SPSS, version 23) was used for statistical analysis. Data were presented as a number, percentage, and mean ± standard deviation (SD). Groups were compared using the Yates’ Chi-square test and Fisher’s exact test. A P -values 0.05 were considered statistically significant. This study was conducted by the approval of Hacettepe University Institutional Review Board with document number GO 19/1064.

3. Results

Clinical characteristics of the 350 patients included in this study were divided according to the presence of acrochordons and are depicted in Table 1. An autoimmune disorder (autoimmune disease or autoimmune antibody positivity) was present in 55.7% (195/350), which will be referred to as the autoimmune group. The autoimmune group was further divided into patients diagnosed with any autoimmune disease (autoimmune disease group) and patients solely presenting with autoimmune antibody positivity (autoimmune antibody-positive group). The remaining 155 patients were attributed to the non-autoimmune control group. The rate of acrochordons was higher in the autoimmune group ( n = 195) compared to the non-autoimmune control group ( n = 155) (8.21% versus 2.58%, respectively) ( p = 0.043) (Table 2). Acrochordons were diagnosed in 13.79% (8/58) versus 5.84% (8/137) in the autoimmune disease group versus the autoantibody-positive group. This difference, however, was not statistically significant ( p = 0.086) (Table 2). Acrochordons were more frequently found in the autoimmune disease group ( p = 0.004). However, there was no statistically significant co-occurrence of autoantibody positivity and the presence of acrochordons ( p = 0.135). A detailed list of autoimmune diseases in patients with and without acrochordons was given in Table 3. The rate of the presence of acrochordons were 6.48% and 3.4% among patients with ANA and APA positive cases, respectively. There was no statistically significant relationship between the presence of these autoantibodies compared to the control group ( p = 0.132 and p = 0.580, respectively). There was also no statistically significant difference between the presence of ANA and APA ( p = 0.464).

4. Discussion

The skin is the largest organ in the human body, representing 16% of the total body weight and composed of a multi-layered structure to form a physical barrier for environmental factors such as ultraviolet radiation and infectious agents [19]. The epidermis is comprised of five layers: 1) the basal layer that consists essentially of keratinocytes that are attached to the basement membrane by a structure called the hemidesmosome. The hemidesmosome plays an important role in autoimmune bullous skin. Next to the basal layer are the basal cells, which are cuboidal and migrate to the surface in a process termed cell differentiation [20, 21], 2) the stratum spinosum consists of five rows of polygonal flattened cells. These cells are joined by structures called desmosomes. The desmosome is a molecular complex formed by desmogleins proteins (Dsg) that are involved in triggering a pathogenic immune response in blistering autoimmune diseases, such as pemphigus [21, 22], 3) the granular stratum is the surface formed by three rows of cells containing round nuclei. The keratinocyte layer is characterized by the presence of electron-dense granules composed of sulfur-rich amino acids present in the precursor molecule of filaggrin [19], 4) the stratum lucidum is comprised of two rows of flattened cells that do not contain nuclei and have poorly defined shapes. The cells produce a thin eosinophilic zone containing large amounts of keratins [21], 5) the stratum corneum corresponds to the outermost layer of the epidermis, which consists of between 15 and 20 layers of flattened cells with a dense keratin content, termed corneocytes. The corneocytes are replaced by cells from the basal layer. The epidermic renewal process takes about 21 to 28 days. The last step in this process is termed desquamation, which involves the degradation of lamellar lipids in the intercellular spaces. This process is accelerated in autoinflammatory diseases [20, 21]. The dermis is another component of skin tissue, located below the epidermis. The dermal tissue is distributed in two regions: the innermost region is termed the reticular area, which is extensively vascularized and hosts appendices, such as the hair follicles and the sweat and sebaceous glands. The reticular zone has clinical significance in a number of autoimmune diseases of the skin. The upper area of the dermis is termed the papillary dermis. In this area, blood vessels are involved in superficial vasculitis processes in diseases such as lupus [20, 21].

The outermost of the acrochordons (skin tags) are generally covered by a slightly hyperplastic epithelium characterized by an increase in the number of epidermal cells, especially cells in the stratum spinosum [23]. A flattened basal cell layer and increase in pigmentation were also common pathophysiological features of the skin tag [23, 24]. In the dermal stroma of acrochordons, the amount of collagen and the number of vessels increase [23]. The number of inflammatory cells such as mast and Langerhans cells increase in histological examinations [3]. Mast cells secrete tryptase, heparin, Tumor necrosis factor (TNF), and Tumor growth factor-beta (TGF- β ) to induce fibroblast proliferation and mRNA synthesis collagen [25]. However, the biological mechanism behind the occurrence of these acrochordons is still obscure.

Autoimmune diseases and autoimmune antibody positivity may influence gestational problems [14, 15, 16, 17, 18]. We run a preconceptional care program for patients with poor obstetric history. Autoimmune disorders are routinely searched with autoimmunity related skin changes together with other risk factors for obstetrical complications. We have also noticed that the rate of the presence of acrochordons was more frequent in patients in the autoimmune positive study group ( n = 195) compared to the autoimmune negative control group ( n = 155) (8.21% versus 2.58%, respectively) ( p = 0.043).

Skin tags have been reported to be related with many factors including the presence of metabolic diseases such as diabetes mellitus and obesity, pregnancy, being older than 40, mechanical trauma, HPV infection, acromegaly, Crohn’s disease, and organ transplantation [26, 27, 28, 29]. This is the first study demonstrating the togetherness of acrochordons and autoimmune disorders. However, the limitations of this study include the number of cases and its retrospective design. The most important limitation of this study is the lack of etiology based information. We believe that further basic research is necessary.

There may be immune system related biological disorders behind the occurrence of skin tags, which may also be risk factors for obstetric complications during pregnancy. For this reason, preconceptional counseling is beneficial for women with poor obstetric history and acrochordons.