Women’s Health: Most Common Physiologic and Pathologic Cutaneous Manifestations During Pregnancy

Pregnant women are susceptible to various physiological and pathological skin and body habitus changes during pregnancy due to the alterations that occur in a multi-organ-system fashion. Pregnancy can be the onset of different dermatological diseases and can exacerbate pre-existing cutaneous conditions. Moreover, management of dermatologic diseases during pregnancy might be challenging as it requires special attention to both mother and fetus. We aim to assess the most common cutaneous changes and conditions that occur during pregnancy by reviewing the previous studies conducted on this subject. The medical literature was explored through PubMed and Google scholar databases starting from 2015 to 2021. The included searching terms were a combination of "Cutaneous changes and pregnancy," Dermal conditions and pregnancy," Pregnancy-associated dermal conditions," and "Dermatological changes and pregnant women." The inclusion criteria included original articles conducted on pregnant women and full text- articles. A total of 134 articles were obtained, 11 articles were eligible for the inclusion criteria. The 11 studies included a total number of 14,813 pregnant women and covered four countries. The most common cutaneous conditions experienced by pregnant women were primarily physiological skin changes, pregnancy-specific dermatopathologies, and exacerbations of other common skin diseases. All in all, this systematic review concluded that pregnant women are more vulnerable to various dermatological conditions during pregnancy. These changes were more commonly physiological such as hyperpigmentations. However, pathological pregnancy-specific skin conditions and exacerbations of pre-existing dermatoses like atopic eruptions were also reported.


Introduction And Background
Pregnancy is associated with multiple physiological changes involving different organ systems like the endocrine, vascular, metabolic, and immune systems of gravid women resulting in several cutaneous changes which can be physiological or pathological [1]. These conditions are due to physiological changes, specific dermatoses of pregnancy, and other common pregnancy non-specific skin diseases in pregnancy [2].
Physiological skin changes during pregnancy primarily involve alterations in the degree of skin pigmentation and skin laxity mainly due to the effect of the elevated hormones [3]. Pregnancy-specific dermatologic pathologies involve impetigo herpetiformis, cholestasis of pregnancy, prurigo of pregnancy, pruritic folliculitis, pruritic urticarial papules, and plaques of pregnancy. Moreover, other existed skin conditions, such as psoriasis and atopic dermatitis, may worsen and present with flares during pregnancy [4,5]. However, improvement in some dermatological skin diseases during pregnancy can also be seen [6].
Pregnant women are mostly aware of most of the common physiological skin changes that occur during pregnancy, and they commonly tend to seek medical advice for actual new-onset pathological skin conditions or exacerbations of pre-existing inflammatory skin disorders [2]. However, the presentation of many dermatological diseases during pregnancy can vary and may have atypical presentation; for example, itching can occur in one among five normal pregnancies, but it can be the presenting symptom of several pregnancy dermatoses. Therefore, the accurate diagnosis of various dermal conditions during pregnancy can be difficult [2]. In addition, pregnancy can change the management of these common skin conditions and make it more challenging; these challenges are mostly related to the safety and harm of medications and other interventions like laser therapy to the developing fetus [2]. Therefore, we conducted this review of the literature to evaluate and discuss the various pregnancy-related dermatological conditions.

Review Method
The PRISMA checklist guidance for systematic review and meta-analysis [7] was followed to write this systematic review. The two databases: PubMed and Google scholar databases were revised searching for literature articles. The eligible research articles between 2015 and 2021 were selected.

Search strategy
Several keywords were used for searching purposes, including a combination of "Cutaneous changes and pregnancy," "Dermal conditions and pregnancy," "pregnancy-associated dermal conditions," and "Dermatological changes and pregnant women." All the titles and abstracts produced from this primary exploration were revised thoroughly to prevent missing potential studies. The findings were then examined to choose only original research articles evaluating the dermatological changes during pregnancy. All fulltext articles written in English were defined as articles of relevance, which were then included in the second stage.

Eligibility criteria
The second step was deciding on the inclusion criteria to select the eligible studies. Abstracts were assessed manually to select the relevant studies for revision. The inclusion criteria were studies conducted on pregnant women and investigated the physiological changes and cutaneous conditions during pregnancy. Reviews and studies that had incomplete or overlapped data were excluded. Also, unavailable full-text articles or inappropriate study designs were excluded. The full description of the search strategy is shown in Figure 1.

Data review and analysis
A specially designed excel sheet was used for data extraction. The chosen data from eligible research articles were then revised via the excel sheet. Any research articles published by one research group examining similar variables were reviewed for any potential duplication.

Results
This systematic review included 11 articles that met the eligibility criteria and were published between 2015 and 2021 ( Table 1) [8][9][10][11][12][13][14][15][16][17][18]. In regard to the study designs of included articles, there were two cross-sectional studies [14,18], three cross-sectional were observational studies [10,16,17], one observational [8], one prospective observational cohort [9], one retrospective [11], and one prospective [13] whereas one study did not specify the design [12]. The total number of participants in the 11 studies was 14,813 participants, the least number of subjects included in a study was 100 pregnant women [12], and the largest number included was 9,679 [8]. The included studies were conducted in only four countries; one study in Nigeria [9], one study in Libya [13], one study in Brazil [18], whereas the remaining eight studies were all in India [8,[10][11][12][15][16][17]. The overall major dermatological conditions during pregnancy were physiological skin changes [11][12][13][14][15][16][17][18] and pregnancy-specific dermatopathologies [8,9]. However, only one study reported that STDs and other infectious skin disorders were the major presenting dermatosis during pregnancy [10]. *98.05% presented with physiological skin changes of pregnancy; pigmentary changes (97.35%) *38.31% had pregnancy-specific dermatosis, 60.06% had pregnancy non-specific dermatosis. *The most common pregnancy-specific dermatosis was atopic eruption (44.8%), polymorphic eruption of pregnancy (32.2%) * In non-specific dermatoses, infectious diseases were more common * Lower socioeconomic strata and overcrowding may be the reasons behind a large number of infectious dermatoses that we saw in our study. hyperpigmentation with linea nigra 82% *100% had physiological skin changes of pregnancy *2% had specific dermatoses of pregnancy; 2% cases had Pruritic Urticarial Papules and Plaques of Pregnancy *14% presented with other dermatoses associated with pregnancy *The most common infectious dermatosis affected by pregnancy in this study group was vulvovaginal candidiasis (5 cases). *82% hyperpigmentation with linea nigra, followed by 68% changes of connective tissue (steriae gravidarum) *Skin changes are common during pregnancy and are usually benign and selflimiting. Pregnancy specific dermatoses though few are symptomatic can be associated with severe fetal outcomes such as fetal distress, stillbirth, and premature birth *Differentiating physiological skin changes of pregnancy from pregnancy-specific dermatosis/ other disease conditions can avoid unnecessary investigations and management and aid in better patient care and counseling  atopic eruption (70.88%) * Physiological changes were seen more in the 3rd quarter, as well as the specific dermatoses

Discussion
During pregnancy, several changes occur to optimize fetal and maternal well-being which should eventually result in the delivery of a healthy baby, these changes include changes in the function of the endocrine system to regulate the various hormone secretions, immune system, and the various metabolic pathways that ensure delivery of nutrients and metabolic fuel to the fetus. Some of these changes contribute to a spectrum of physiological and pathological physical changes seen during pregnancy, such as the development of various skin conditions [4]. In the current systematic review, we found that skin pigment disorders account for the most common physiological skin conditions in gravid women, whereas atopic eruptions were the major dermatoses specific to pregnancy.
Physiological dermatological changes in pregnancy involve pigmentary changes such as hyperpigmentation, which occurs among 90% of pregnant women. It usually occurs in a localized area and may be due to the regional differences in the density of melanocytes within the epidermal layer of the skin. However, generalized hyperpigmentation can occasionally occur [19,20]. A dark line that forms from the mid suprapubic area to the umbilicus called linea nigra is a common finding in pregnant women as well [4]. Melasma, which is known as the mask of pregnancy, is a common, pregnancy-specific pigmentation caused by excess estrogen. It is more obvious in women with darker skin tones and occurs in topographical areas such as cheeks, upper lip, and forehead. It mostly appears in the second trimester of pregnancy [21] and can affect up to 50% to 70% of women [22]; in this systematic review, however, only one study [18] reported that half of the pregnant women experienced melasma. Though some studies have shown that these pigmentary lesions could affect a wide range of pregnant women [13,17], The prevalence of such pigmentary skin lesions during pregnancy can truly vary depending on various factors, but some studies have reported that almost every single gravid woman may complain from pigmentary skin changes during pregnancy [12,14,15].
Besides pigmentary changes, striae gravidarum or stretch marks are common structural skin changes commonly seen in pregnancy due to the rapid change in weight and the effects of elevated hormones on the integrity of collagen and other skin constituents [17,18]. Striae gravidarum are structural skin changes, and they occur in up to 90% of pregnant women in the third trimester [21,23]. They occur commonly at the lower abdomen as the connective tissue beneath the skin tear during pregnancy due to excessive stretch, which helps accommodate the rapidly growing fetus [4].
Dermatoses specific to pregnancy are skin pathologies that commonly occur in pregnancy or exacerbations of pre-existed dermatologic diseases seen in gravid women. The most common pregnancy-specific dermatosis was the atopic eruption of pregnancy which was seen in 4% to 72.72% of women with pregnancy-associated dermatosis [9,13] and it was also reported in other four studies as well but with lower frequency [9,11,13,18]. Prurigo of pregnancy can be considered in the second rank as it has been reported in up to 47% [8,14], and there were two studies that reported the presence of this condition [8,14]. In the third rank, pruritic urticarial plaques and papules of pregnancy have a range between 0.5% and 43.93% [8,14].
Atopic eruption of pregnancy is a benign pruritic condition that is characterized by popular lesions or eczema in patients with a history of atopic dermatitis or predisposition to atopic dermatitis or even with new-onset atopic dermatitis during pregnancy. Its prevalence was stated to be in the range of 5%-20% [5]; however, the included studies reported a much higher prevalence (4%-72.72%). Prurigo of pregnancy belongs to the pregnancy-specific dermal diseases and this condition involves different variants; the mild and most common variant, which is characterized by localized lesions only, and the generalized variant, which is known as popular dermatitis [3]. Pruritic urticarial plaques and papules of pregnancy are other pregnancy-specific dermatological diseases. It is a pruritic inflammatory cutaneous disease with an incidence of one in 160 pregnant women [24]. Although it was reported that Pruritic urticarial plaques and papules of pregnancy are the most common pregnancy-specific dermatoses [24], the current systematic review showed that atopic eruption was the most common dermatoses specific to pregnancy.
This systematic review has few limitations, such as the majority of the studies included were from India; however, these studies were included as they met the inclusion criteria.

Conclusions
Pregnant women are more prone to several cutaneous conditions during pregnancy, such as physiological skin changes, pregnancy-specific dermatoses, and flares of pre-existing chronic skin conditions. The most common physiological skin changes are hyperpigmentary changes, whereas atopic eruption is the most common dermatoses form. Eczematous eruptions have been the most common exacerbation of a chronic skin condition during pregnancy. These pathological skin conditions can be a source of considerable distress to pregnant women and may warrant immediate interventions, though their diagnosis and management can be challenging and require a thorough knowledge of their different presentations and special treatments to ensure maternal and fetal safety. Therefore, a physician's knowledge about the profile of these various dermatoses during pregnancy is necessary in order to plan preventive measures and provide comprehensive care for the mother and her baby.

Conflicts of interest:
In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work.