Introduction 

Pruritic Urticarial Papules and plaques of pregnancy (PUPPP) is a rash which pregnant individuals can develop normally in the third trimester . Although it is a benign condition, the symptoms can often be uncomfortable, leading to interrupted sleep. The symptoms include severe itching caused by a rash which starts in the abdomen, where stretch marks typically form. This rash can also eventually affect other parts of the body where there are no stretch marks. The causes of PUPPP remain uncertain, but there are many propositions which have attempted to explain it. All these propositions do have supporting evidence but also have some limitations. In this article, we will explore these several theories individually to hopefully understand this condition a little better. 

What is PUPPP?

PUPPP is a dermatological condition which affects 1 in 160 to 1 in 300 pregnancies worldwide.¹ It is known to be the most common type of dermatology, which is more typically seen in primiparous individuals or individuals or pregnancies with more than one fetus.¹

Classically, PUPPP presents initially with small, raised bumps on stretch marks, which are typically found on the abdominal region. Sometimes, a pale halo can also appear around each bump.¹ These bumps can join and form larger plaques and spread down to the buttocks and thigh region. Some individuals can also experience a PUPPP rash on their legs and arms.¹ Apart from the rash not being pleasing to the eye, the intense itching is reported to be the most significant symptom, causing disrupted sleep. This type of rash usually appears in the third trimester of pregnancy and resolves with no permanent damage after birth. The causes remain unknown, but the lack of medical threat and health recovery is reassuring. 

What causes PUPPP?

Theory 1: Stretching Skin 

As mentioned above, the exact cause of this skin condition is unclear. One theory explains that the increased and rapid stretching of the skin on the abdomen causes micro-tears in the connective tissues.⁴ These micro-tears cause inflammation, which presents in the form of a rash. This theory is supported by the fact that PUPPP is more common in primiparous individuals and multiple pregnancies. Where pregnancy is experienced for the first time, the skin has not stretched before, making the inflammation and this level of reaction more likely. Where there is more than one fetus, the skin usually needs to be distended more and again, inflammation may be more likely. However, like all theories, this theory also has limitations. This spreading of the rash to other areas of the body is not explained by this proposition. 

Theory 2: Changes in the hormones 

During pregnancy, there is a massive fluctuation of hormones. The most fluctuations are seen in estrogen, cortisol and progesterone.⁶  These fluctuations are known to cause many changes in the body, including skin changes.  The next theory suggests that these hormonal changes can contribute to the initiation of the PUPPP rash.⁵ The changes in the equilibrium of these hormones may initiate inflammation responses or influence the skin barrier function.⁵ This theory is supported by the way PUPPP rash is resolved almost instantly (within a few days to 4 weeks) after childbirth.⁷ After childbirth, these hormone levels go back to normal, with estrogen and progesterone dropping rapidly. Although there is a relationship between hormonal changes and skin changes, no hormone which links to the development of PUPPP has been identified at this current time. There is no consistent pattern between high levels of pregnancy hormones and PUPPP observed, and more research needs to be done to clarify this. 

Theory 3: Fetal cells 

During pregnancy, the body can sometimes view the fetus as foreign to its own body. Another theory which attempts to explain PUPPP explores the possibility that an abnormal immune response may be triggered by fetal cells found on the pregnant individual’s skin through microchimerism.³ These cells from the fetus, which embed into the mother's tissue, trigger an inflammatory response. Like the other theories, this theory also has some supporting evidence and limitations. Some of the supporting evidence includes that some studies found fetal DNA in the rash of PUPPP sufferers when inspected. There were also some similarities between the way the PUPP rash looks under a microscope and how other immune-mediated dermatological conditions like urticaria look. However, with this theory, you’d expect more pregnant individuals to experience PUPP. Also, these fetal cells, which were identified in one study, were not found in other studies. 

Can PUPPP be genetic?

Whether PUPPP can be genetic or not also remains unclear. However, some studies suggest that there could be a genetic predisposition. The occurrence of PUPPP in female family members such as sisters, mothers, aunts and daughters has been observed in some studies.² There does seem to there can be inheritable factors involved in the predisposition of PUPPP, but specific genetic markers or patterns are yet to be identified. There is a possibility that these observations can be in fact random as the evidence is purely observational. Genetics can likely affect hormonal and immunological triggers, but direct links to PUPPP will require further research. 

Links between PUPPP and the sex of the fetus 

The development of PUPPP has been reported to be higher in pregnancies resulting in male babies. This brought up the question about where there can be links between the sex of the fetus and the occurrence of the PUPPP rash. Some studies suggested that the sex of the fetus may directly contribute to the hormonal equilibrium and immune responses of the pregnant individual, which may, in turn, trigger the PUPPP rash. As previously mentioned, in one study, fetal DNA was found in the rashes.³ This was male fetal DNA. This male fetal DNA may be more likely to be identified as foreign to the pregnant individual, causing an immune reaction. However, the data remains inconsistent, and again, these findings can be coincidental. PUPPP can also develop in pregnancies with female fetuses. Male fetal DNA may increase the incidence of PUPPP, but it cannot be the sole cause of it. 

Management of PUPPP

Definitive treatment or cure of PUPPP is difficult due to the lack of clarity surrounding the cause. Therefore, management tends to focus on symptomatic relief.⁴ The aim remains to provide the pregnant individual with some comfort during the third trimester until birth, when PUPPP recovery occurs. Some of the management methods include:

• Antihistamines: used to relieve the pregnant individual from the itching 
• Topical corticosteroids may be used where antihistamines do not provide effective relief of itching. Inflammation can also be reduced with these steroids 
• Moisturisers can be used to calm the irritation of the skin 
• Loose clothing is recommended to reduce discomfort and friction, which can increase symptoms.

Summary 

With not one single theory providing a definitive cause, the mechanism of PUPPP remains unclear, proving its complexity. The cause of PUPPP seems to be multifactorial with hormonal,  immunological and possibly genetic roots. Treatment and management also remain symptomatic relief. More research is required to pinpoint the definitive causes of PUPPP, so hopefully, more targeted and preventative methods can be developed in the future. The third trimester can be difficult for pregnant individuals regardless of PUPPP, so reassurance and access to the current management techniques are the best way forward in terms of support. Regardless, it is important to remember that this is a benign and temporary condition with probable relief after birth.