Asocierea nivelurilor mari de proteină C reactivă cu tulburările de piele la femeile cu istoric ob-stetrical sărac

Introduction

One of the primary concerns of perinatologists should be the determination of risk factors for adverse pregnancy outcomes, instead of dealing with the management protocols of the obstetrical complications. Prevention of the disorders is much easier than the treatment of the resulting complications. It has been reported that inflammatory, metabolic and immunological factors may cause placental inflammation and related obstetrical complications^(1-5). For this reason, “preconceptional care programs” for women with poor obstetric history should focus on systemic disorders, chronic inflammatory diseases, and metabolic/immunological risk factors which may be responsible for end-organ inflammations^(6-10).

C-reactive protein (CRP) is a protein made by the liver and its blood levels increase in response to inflammatory processes^(11,12). It is used as a blood test marker for inflammation in the body. Increased levels of CRP may be observed in chronic diseases and autoimmune dis­orders^(11,13). The skin is highly sensitive to autoimmune disorders, allergic problems, metabolic diseases, internal organ diseases, paraneoplastic syndromes, bacterial/viral infections, inflammation, or epigenetic factors^(14,15). There are different types of skin-related inflammatory diseases, including psoriasis, dermatomyositis, Sjögren syndrome etc.^(16,17) Skin disorders might be the sign of inflammatory disorders which are risk factors for poor gestational outcome.

This study investigated the association of high levels of CRP with skin disorders in women having poor obstetric history. Inflammation and related biological events behind skin disorders may be the risk factors for obstetrical complications and poor gestational outcome.

Patients/materials and method

This retrospective study involved 185 women having poor obstetric history/background. Poor obstetric history was defined as having miscarriage, fetal growth restriction, preterm birth, preeclampsia, stillbirth and neonatal morbidity/mortality in previous gestations. All patients were examined and evaluated for the presence of systemic disorders, as well as skin problems and inflammation within a framework of preconceptional care program.

Necessary laboratory tests, including CRP, were performed. Demographic and clinical data were obtained from the electronic database of the Division of Perinatology (2016-2019). Skin disorders were grouped according to their dermatological findings into seven categories: acne/rosacea/other acneiform disorders, fungal disease, pruritus/xerosis, psoriasis vulgaris, acrochordons and other benign hypertrophic skin conditions, urticaria/dermatitis, and viral diseases.

The statistical analysis was performed using the Statistical Package for the Social Sciences (SPSS, version 23). The groups were compared using the Yates’ Chi-square and Fisher’ exact tests. P-values <0.05 were considered statistically significant. The study was approved by the Local Ethic Committee (GO 19/1064). This study was performed in accordance with the Declaration of Helsinki. The written informed consent was obtained from the patients.

Results

CRP is measured in milligrams of CRP per liter of blood (mg/L). Normal CRP levels are below 3 mg/L. We have demonstrated high levels of CRP (>3 mg/L) in 37.5% and 16.2% of the patients with (n=80) and without (n=105) skin disorders, respectively (p=0.002) – Table 1.

When different skin disease categories were considered, CRP levels above the upper limit were more frequently detected in pruritus/xerosis, acrochordons and other benign hypertrophic skin conditions, fungal disease, and urticaria/dermatitis subgroups (Table 2). However, a statistically significant increase was only found in patients with pruritus/xerosis and acrochordons (p=0.005 and p=0.015).
 

Discussion

Perinatal medicine aims at reducing obstetrical complications. Etiology-based medical management should be encouraged to achieve better pregnancy outcomes. Metabolic, infectious/inflammatory and immunological factors may injure the cellular structures of intervillous space, leading to placental inflammation^(1,6,10). Therefore, physicians should attempt to identify the risk factors leading to placental inflammation and associated obstetrical complications. Thus, inflammation and immune system related biological events behind skin disorders may be the risk factors for placental inflammation and obstetrical complications^(1,1,6,14).

CRP is an acute-phase inflammatory protein and exhibits elevated expression during inflammatory conditions⁽¹¹⁾. There are many factors that may change the baseline CRP levels, including age, gender, smoking, weight, lipid levels and blood pressure⁽¹⁸⁾. CRP is mainly classified as an acute marker of inflammation, but recent studies have indicated the critical roles that CRP plays in inflammatory processes⁽¹¹⁾. It is primarily synthesized by interleukin-6-dependent hepatic biosynthesis⁽¹⁹⁾. CRP can activate the fluid phase complement pathway (activation of C1q molecule), as well as cell-mediated pathways by activating complement. CRP binds to Fc receptors with the resulting interaction leading to the release of proinflammatory cytokines^(11,20,21). CRP is not merely a marker of inflammation, but also plays a role in the inflammatory process⁽¹¹⁾. High CRP levels have been reported in skin diseases such as urticaria, acne, rosacea etc.⁽²²⁾ This study demonstrated that CRP exhibits elevated expression in cases with certain skin disorders. Such skin disorders associated with immunological problems and inflammation may be the reason for high CRP levels.

Xerosis cutis – known as dry skin – usually accompanies pruritus⁽²³⁾. Pruritus is a sensory reaction in response to cutaneous and systemic diseases⁽²⁴⁾. Pruritus can also be seen in urticaria/dermatitis. According to Senturk et al., CRP levels were higher in patients with pruritus in a statistically significant manner (p=0.026)⁽²⁵⁾. Also, higher serum levels of CRP were found to relate to intensity of pruritus in patients with chronic urticaria⁽²⁶⁾. In our study, high CRP levels were more frequent in patients with pruritus and xerosis cutis, with a rate of 80%. There was also a statistically significant relationship between the presence of xerosis/pruritus and high level of CRP (p=0.005).

Acrochordons (skin tags) are benign skin growths on the surface of the skin⁽²⁷⁾. Higher levels of CRP were found in patients with acrochordons^(28,29). In all, 42.9% of patients with skin tags had elevated CRP levels (p=0.015). Acrochordons are highly associated with metabolic syndrome and related disorders, which is now accepted as an inflammatory condition⁽³⁰⁾. This is likely an explanation of the high CRP levels in patients with acrochordons.

The limitations of this study are represented by the limited number of patients in skin disease subgroups and by the absence of follow-up results. Our cohort was diagnosed with a wide spectrum of skin disorders and we believe that disorder-specific studies are necessary in this field. Other inflammation markers should also be considered in future studies in order to have better clinical comments.

The patients with skin diseases should be further evaluated in terms of the existence of inflammat­ory disorders which might be a risk factor for poor gestational outcome. Preconceptional counseling is beneficial for women with poor obstetric history and skin problems.