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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. 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.

Inflammatory Mediated
From those with PUPPP, it has been seen from a immunohistology profile that their are certain immune cells that are in greater ammount compared to that of those without PUPPP.