The Influence of Pregnancy and Menstruation on the Deterioration of Atopic Dermatitis Symptoms

Atopic dermatitis (AD) is a chronic inflammatory disease with the lifetime prevalence of 8~17% in adults under 60 years old and it has a number of subtypes1. Intrinsic AD (IAD) is differentiated from the much more common extrinsic type (EAD) by a total serum immunoglobulin E (IgE) level that is within the normal range, by the lack of specific IgE positivities and by the fact that no immediate skin reaction to environmental allergens or respiratory involvement can be observed2-4. In several previous studies, the disease activity of several dermatoses was shown to be influenced by hormonal factors in women, and AD had a higher prevalence in adult females5, 6. According to previous studies, approximately 25% of females who have AD experience improvement during pregnancy, and more than 50% of the AD female patients experience deterioration during pregnancy7, 8. Moreover, female patients with AD often show a deterioration of cutaneous symptoms in relation to the menstrual cycle9. We have experienced that a number of female patients with AD in our clinic have reported their symptoms worsened during pregnancy and even in relation to their menstrual cycle. However, the influence of pregnancy and the menstrual cycle on AD has not been discussed in the Korean dermatologic literature. The purpose of this study is to investigate the influence of pregnancy and the menstrual cycle on the symptoms of AD, which would reflect a hormonal influence on AD, and to compare the results between the intrinsic and extrinsic types of AD.

Although it has long been recognized that female patients with AD often show a deterioration of cutaneous symptoms in relation to the menstrual cycle, the information about this subject is insufficient12, 13. A review of the literature has revealed great variance in the prevalence of the menstrual-cycle-associated worsening of AD skin lesions, ranging from 9% to 100%7, 14-18. Yet in the previous studies that have examined a comparatively large number of patients, the frequency of menstrual cycle-associated aggravation of AD skin lesions was estimated to be around 50~70%15, 18.

In our study, we found out that 46% of the female AD patients have experienced deterioration of symptoms during pregnancy or in relation to the menstrual cycle. Among the patients who experienced aggravation related to the menstrual cycle, 64% experienced deterioration before the menstruation and generally within 10 days before menstrual initiation. The results suggest that there exists a relation between hormonal influences and the clinical manifestations of AD. As Kemmett and Tidman7 reported previously, there might be some association between the premenstrual worsening of AD and the presence of symptoms of premenstrual syndrome. According to a study of Kiriyama et al.9, the physical and psychological symptoms of premenstrual syndrome were present in all the AD patients who showed premenstrual worsening of skin lesions, but these were absent in the group of patients who did not show premenstrual skin aggravation. Systemic evaluations and further interviews of AD patients regarding premenstrual syndrome are required to reveal the definite relation.

Most pregnant women are unwilling to use topical and systemic treatments, and so discontinuation of medications might be a leading cause of aggravation of AD. In our study, among the 14 patients who experienced aggravation during pregnancy, 10 patients experienced aggravation during the 2nd or 3rd trimester, and the 4 patients who experienced aggravation during the 1st trimester did not use any oral medications for several months prior to pregnancy. Therefore, the cessation of medication itself independent to pregnancy did not seem to be the major cause of AD aggravation. The use of medication by AD patients before and after pregnancy should be consistent to firmly determine if pregnancy is a deteriorating factor of AD. Nevertheless, as the continuation of AD symptoms into adulthood, which is when most of females experience pregnancy, is not very common, we included all the AD patients who experienced pregnancy in our study for the purpose of obtaining a large cohort. Therefore, further studies are needed with controlled distributable factors to clarify the relationship between pregnancy and the deterioration of AD symptoms.

The total IgE levels and EASI score did not show statistically significant differences between the patients who noticed some deterioration during pregnancy or in relation to the menstrual period and the patients who were without deterioration of AD symptoms during pregnancy and menstruation. This infers that that worsening during pregnancy or in relation to the menstrual cycle is not related to the severity of the disease. The degree of the premenstrual skin deterioration was different from patient to patient, suggesting there are individual differences in the susceptibility to the aggravation of AD. These results are equivalent with those of the previous studies9. The patient group who experienced deterioration during pregnancy or as related to the menstrual cycle had a larger portion of patients sub-grouped as IAD, as compared to that of the patient group who did not experience any changes. This result suggests that, for IAD, the disease can be more susceptible to hormonal influences as compared to the extrinsic type. In our study, the deterioration of AD as related to pregnancy tended to appear at higher rates for the IAD patients as compared to that of the EAD patients, but the relationship between menstruation and symptom aggravation of AD in the IAD or EAD patients did not reveal statistically significant differences. These results suggest that although IAD patients lack sensitization by allergens and they do not show aggravation by specific allergens, other factors such as hormones or stress may have more impact on the clinical manifestations of IAD. Further studies are required to investigate the susceptibility of hormonal influences in patients with IAD and EAD.

It is now known that pregnancy shifts the T cell immunity towards a type 2 T helper response, and this is thought to be important for continuation of a normal pregnancy19. Ikeno and Takahashi20 described that the Dehydroepiandrosterone (DHEA) and DHEA-sulphate (DHEA-S) levels, which apparently show the immunomodulatory effects probably by enhancing Th1 activity21, 22, decrease during pregnancy20, and this can be one factor that contributes to the shift of the immune response to the type 2 helper response during pregnancy. As the type 2 T helper response is also associated with AD, this shift may explain why AD can deteriorate during pregnancy. There is also some experimental data suggesting sex hormones have an influence on the symptoms of AD, as estrogens were shown to affect mast cell activation, while progesterone was shown to suppress histamine release, but potentiate IgE induction in rodent models6. However, as any actual data from human studies is lacking, further investigations are required.

The mechanisms still remain obscure for the case of deterioration of AD as related to the menstrual cycle. It is reported that for females, skin reactivity to irritants and antigenic substances increases during the premenstrual phase23, 24. It is then possible that female patients with AD show an exaggerated inflammatory skin response to various aggravating substances in the week prior to menstruation, leading to the premenstrual deterioration of the disease9.

In conclusion, although this study is limited by the small number of patients and its retrospective and subjective nature, it is valuable because such a study is rare in the Korean literature. Our results suggest that there exist a relation between hormonal influences and the clinical manifestations of AD, and further investigations with larger cohorts are needed to clarify the relationship between sex hormones and AD.