Dermatoses Of Pregnancy: A Retrospective Cohort Study In Spain

Background: Dermatoses of pregnancy (DP) is a heterogeneous group of pruritic inflammatory dermatoses that occur exclusively during pregnancy and/or puerperium. The objective of this study was to assess the specific DP and non-specific dermatoses in a Mediterranean population living in Spain. Methods: This five-year retrospective study included 79 pregnant women with dermatologic disease from a total of 10533 pregnancies. Obstetric and clinical variables were assessed. Physiological skin changes of pregnancy were excluded. Those dermatoses that may also be observed beyond pregnancy and puerperium were also excluded. Results: The mean age was 32 years. The most common DP were: Polymorphic eruption of pregnancy (PEP) – 36%, Atopic eruption of pregnancy (AEP) – 26%, Intrahepatic cholestasis of pregnancy (ICP) – 8% and Pemphigoid gestationis (PG) – 6%. The other 24% presented non-specific dermatoses. Only in one case of PG the newborn showed comorbidity. Discussion: Multiple gestations were observed in 10,3% of PEP, in association with a rapid abdominal distention. In AEP, there was a predominance of nulliparous women in the second trimester of pregnancy, an atopic dermatitis background and female newborns. In PG, there was a majority of nulliparous in the second and third trimesters. PG was the only dermatoses associated to comorbidity of the newborn. In ICP, all patients had pruritus in the palms along with excoriations, with predominance of nulliparous and multiple gestations.

3 What is already known on this subject? Pregnancy results in various physiological skin changes. As a consequence, some common dermatoses can present more frequently in pregnant women. In addition, there are a number of skin eruptions unique to pregnancy.
The etiology of physiological skin changes in pregnancy is uncertain but is thought to be due to hormonal and physical changes of pregnancy.
In Spain and all Mediterranean area, limited attention was given to Dermatosis of Pregnancy (DP) and actual data on healthcare professionals' practice on this topic did not exist.
What this study adds? This study explores the specific DP and non-specific dermatoses in a Spanish population.
Currently, there are four recognized DP: Polymorphic eruption of pregnancy (PEP), Atopic eruption of pregnancy (AEP) Pemphigoid gestationis (PG) and Intrahepatic cholestasis of pregnancy (ICP). Some studies describe the prevalence of DP that ranges from 0.5 to 2% in European Anglo-saxon (Holmes R, Ambros-Rudolph -1, 2) and Austrian population (Ambros-Rudolph − 4) and American population , but there are no case series that analyze DP in Mediterranean population.
Besides DP, physiologic skin changes and other skin diseases which are not exclusive of pregnancy can occur. Our objective is to analyze the frequency of DP and other non-specific dermatoses during pregnancy in Spanish population (Mediterranean) and compare with the literature reported.

METHODS:
A retrospective study was made from January 2014 to December 2018 in the University Hospital of Salamanca. During 5 years, we included all pregnant and postpartum women that presented with a skin disease in a tertiary hospital, excluding physiologic skin changes. Total number was 79. The study was approved by the research ethics committee of the hospital. Other dermatosis that may be seen during pregnancy and puerperium, but which can also occur in other contexts were excluded.
We assess 1) obstetric history variables a) gestational age, b) primiparous, multiparous, c) multiple gestation pregnancy d) full-term pregnancy, preterm The SPSS statistical software version 23 for PC was used for the statistical analysis.

RESULTS:
We included a total number of 79 pregnant women. The mean age was 32 (21-41).
Prevalence of DP was of 0.75%. Pruritus was a constant symptom in all patients.
76% of them were diagnosed with specific DP, whereas 24% with non-specific DP.
(Tables 1 and 2). The most frequent specific DP was PEP (36%) followed by AEP (26%) and PG (6%). ICP affected 8% of the patients. The most frequent non-specific 5 DP was acute urticaria. 20% of the patients with AEP had a history of atopic dermatitis. None of the NI suffered comorbidities. Only one NI had a vesicular eruption in scalp. (Fig. 1

DISCUSSION:
We conducted a five-year retrospective study of 79 patients in a tertiary Spanish hospital. We observed a frequency of specific DP of 0.75% which is similar to others case series. PEP was the most frequent followed by AEP, ICP and PG and its rates are consistent with the literature [8,6].
PEP occurs more frequently in primiparous women and multiple gestation pregnancy during the last weeks of pregnancy or immediate postpartum and male fetus [8,10,11]. It is associated with a higher abdominal distension in pregnant women, which can be explained by a higher incidence in multiple gestations [4,8,11,12]. Overall the prognosis both of pregnant women and newborns is good. [6,8,12], Our study did not find more primaparous women affected (50%) but a higher frequency of multiple gestations (10.3%) occurrence in third trimester and immediate postpartum and a slightly higher ratio of male fetus (52%). Pruritus preceded the skin changes 1-2 weeks. Urticarial lesions set in the lower part of abdomen in all of patients, and in breasts and members in 20% of them. The prognosis was good in our series, and NI had a normal weigh, pH and APGAR.
The AEP is a benign pruritic dermatosis of unknown etiology that appears during first and second trimester. It is more frequent in multiparous women with atopic background or elevated IgE [6,8,10]. Typically, lesions are monomorphic papulenodules or eczematous. [6,8,10,11]. Diagnosis of AEP is clinical and supported by 7 an elevation of IgE [8]. Biopsy is not specific and immunofluorescence is negative [6,10,11]. Papule-nodules can persist few months after delivery [8,11]. AEP lasted more days than the others DP (mean of 11 days). It was not related to any comorbidity, as it is shown in other studies [8,10,11] although one suggest a slight decrease of NI weigh [13]. In our case series, there was a predominance of primiparous women (75%) in her second trimester; that makes sense when we think that AEP is more frequent in women with atopic backgroung or elevated IgE, so prompt to this disease. 20% of them had suffered from atopic dermatitis (Table 1).
In all the cases, there were rubbing and scratching lesions due to the severe pruritus. In 8 patient's lesions were predominantly type E (eczematous) whereas in 13 were type P (papules).
PG is an autoimmune bullous DP predominantly in the 2nd and 3rd trimester and/or immediate postpartum. Urticarial lesions became bullae due to the action of antibodies that binds the NC16A site of BP180-collagen XVII (an hemidesmosome protein) [10,11]. Some authors described a predominance of PG in multiparous women [10] although it has not proved in other reports [8]. PG is associated with bad fetal prognosis [8,12]. There was higher frequency of PG in the 2nd and 3rd trimester in our case series. All of them had very pruritic erythematous-edematous plaques that evolved to vesicles and bullae in periumbilical region, spreading to the rest of the body and affecting palms and soles [6,8,10,11]. All the patients with PG in our study were primiparous with no predominance of any NI sex. Despite PG is associated with bad fetal prognosis, in our study PG only was associated with preterm delivery (40%) but with normal NI weigh, pH and APGAR. Occasionally, NI present bullae [8] as in one case that exhibited a self-limited vesicular eruption in scalp (Fig. 1).
8 ICP manifests as a generalized pruritus in the 3rd trimester presenting rubbing lesions. It usually starts in palms and soles and then affect the rest of the body [6,8,11]. It occurred in the third trimester and scratching signs were visible. Some authors indicated its association with multiple gestations [6]. It is well-known the defect of bile acids excretion in these patients [8]. Serum Bile acids, transaminases, and sometimes bilirubin, are elevated. [6,8,11]. Some studies showed a bad fetal prognosis due to respiratory distress in 12-22%, meconium in 25-45% and preterm delivery in 12-22% of cases, along with fetal death in utero and intracranial hemorrhage. We find that all the patients with ICP had pruritus in palms, 80% in soles and 30% generalized. We observed a predominance in primiparous women maybe because there are less multiparous women in our society, and no prevalence of any NI sex. We only observed preterm delivery in 30% of affected women. Apart from that, NI weigh, pH and APGAR were normal.

CONCLUSION:
Patients profile with specific DP in our Spanish case series is similar to other reported studies. PEP is the most frequent DP. Except ICP and PG, specific DP were not associated with poor fetal prognosis. Third trimester and summer months (particularly August) were the most frequent periods in which DP take place. All DP, except PEP, were more frequent in primiparous women, as we said before maybe it is due to the less and less multiparous women in the today society. However, this also could be explained because primigravida women were more frequent than multiparous women in our study. We registered a much higher percentage of patients with PG and ICP had c-sections compared to those with PEP and AEP, this could be explained with the fear to extend the pregnancy that the obstetricians 9 could have in those diseases due to the serious obstetric consequences that we can find in both. We detected a prevalence of DP of 0.75% similar to the literature reported. More studies are needed in order to assure the results found in our case series.