With this increase in progesterone, it causes there to be an increased level of progesterone receptors present eliciting an immune reaction seen by skin lesions in PUPPP. With multiple gestations, there is an increase in sex hormones that has been seen those with the condition such as an increase in progesterone as previously discussed but also higher levels of estradiol. Currently evidence is weak in the role that sex hormones play when contributing to PUPPP where further research is needed. Immunological Causes
Inflammatory Mediated
From those with PUPPP, it has been seen from an immunohistology profile which is used to determine the of tissue components present within an individual via the use of antibodies, that there are certain immune cells that are in greater amount compared to that of those without PUPPP. Immunohistology profile have shown cells consistent with a delayed hypersensitivity with T helper cell infiltrates, dendritic cells and epidermal Langerhans cells.It has been hypothesized that PUPPP appears in response to fetal antigens that circulate throughout the body. For example, a study showed that fetal male DNA was found within the lesions of the mothers skin which was thought to be caused by the fetal cells seen in the mothers blood throughout pregnancy. Autoimmune
Although this condition has not been determined as an autoimmune condition, from a single study it has been seen that Immunoglobulin M (IgM) deposition at the dermal-epidermal membrane has been associated with a variety of dermatosis including PUPPP.
Although the exact cause of the condition is not known and varying amongst individuals, there have been theories linking the cause of PUPPP to hormonal alterations, damage to the connective tissue during pregnancy, and autoimmune disorder where the evidence for these theories is currently low.This skin condition occurs mostly in first pregnancies (primigravida), in the third trimester and is more likely with multiple pregnancies (more so with triplets than twins or singletons). Estimated 75% of people with typical PUPPP people have never given birth. Occasionally, this condition may also occur postpartum, but rarely does this ever occur in the first and second trimester.Other than additional associations with hypertension and induction of labour, there are no observed difference in the outcome of the pregnancy for mothers or babies. Dermatological Causes
During pregnancy as the abdominal wall rapid stretching, it is hypothesized that there is an inflammatory reaction that occurs due to the exposure of collagen. This reaction has been seen more frequently in those who are having twins or triplets compared to those with single births. This is hypothesized to be due to increased stretching of the abdominal wall while carrying twins or triplets, causing an earlier onset of PUPPP when compared to those undergoing single births. Hormonal Causes
Throughout pregnancy, there are hormonal changes that occur where it has been hypothesized that these changes may contribute to the onset of PUPPP. Although current research is low on this hypothesis, it has been seen that those who have had multiple gestations can exhibit an increased level of progesterone.