What is PUPPP rash? 

PUPPP stands for Pruritic Urticarial Papules and Plaques and Pregnancy. It starts with itching followed by rash (raised itchy patch), small raised lumps in the skin (papules) and large red darkened inflamed areas (plaques). It can often spread from the thighs to the lower abdomen and buttocks. It is one of the most common skin lesions seen during the third trimester of pregnancy and resolves post-pregnancy in most cases.¹ The incidence of PUPPPS is 0.5% in single pregnancies, 2.9 to 16% in twin pregnancies and 14 to 17% in triplet pregnancies.² 

Causes and risk factors

The exact cause of PUPPP skin rash is unknown but it is linked with increased weight during pregnancy and increased weight of the fetus. It occurs predominantly in women pregnant for the first time, those who have had multiple pregnancies and pregnancies associated with male children. Infants of mothers with PUPPP are born without any skin lesions and complications.

Hormonal abnormalities

Hormonal changes during pregnancy have been linked with itchy rashes.³ Progesterone, a hormone present in placenta, causes receptor mediated inflammation of tissues affecting mothers with PUPPP skin lesions vs those without.

Koebnerization and inflammatory disorders

It is the appearance of new skin lesions on an existing skin condition (lichen planus, psoriasis) or a healthy skin, secondary to trauma such as an insect bite, injury or sunburn.⁴  It causes stretching of the skin and striae, very commonly seen in pregnant women. However, PUPPP is  seen only in 1 in 200 pregnant women.⁴ 

Medication induced

Few studies have shown that women who have been given drugs such as terbutaline, progesterone or albuterol during premature labour to suppress contraction of the uterus or delay pregnancy have developed PUPPP skin lesions.

Other causes linked to PUPPPS are autoimmune, T cell hyperactivity, pregnancy associated with the marriage of brother and sister, paternal influence and presence of fetal DNA in the birth parent’s blood, based on few reports.⁴ However, the real cause remains hidden.

Diagnosis

Due to the lack of specific laboratory, histological and genetic tests and varied clinical features,  it is difficult to diagnose PUPPP.⁵ Absence of cluster of rashes around umbilicus makes it different i from other skin conditions like Pemphigus gestationitis.

Importance of treatment

Although these papular lesions are self-healing, last 4-6 weeks and are harmless to the mother and infant, the itching and discomfort may last longer and can be painful, affecting sleep⁵  and increasing anxiety in pregnant women. Correct diagnosis and treatment are essential to ensure the safety of the mother and fetus and relieve symptoms.

General measures

 If a pregnant woman feels these symptoms, the best treatments to use include cooling baths, oil baths, topical ointments containing moisturiser and menthol, wearing light cotton clothing, topical corticosteroid ointments and taking oral antihistamines. ⁶ Relief is normally seen in 24 -72 hours in mild itching. For severe itching with disturbed sleep, fatigue and anxiety, oral steroids are given. For rapidly progressing rash in twin pregnancies, refractory or autoimmune conditions, a short course of systemic corticosteroid is given.

Role of antihistamines

Antihistamines are given to reduce allergic reactions such as itching and rash.⁶

How do they work?

They act by blocking histamine, a chemical messenger produced by mast cells lining the body, that alerts the immune system to a local trauma or infection, causing the fluid inside the capillaries to move outside to the surrounding tissues. This dilates the blood vessels causing skin redness and itchy swellings.⁷ There are 2 classes of histamine receptors H1 and H2 receptors. The anti-histamines act on the H1 histamine receptor and block it, antagonising the effects of histamine. H2 receptors are responsible for gastrointestinal diseases such as acid accumulation in the stomach. 

Commonly used antihistamines in pregnancy

Antihistamines are divided into first, second and third-generation drugs. 

First-generation agents (Diphenhydramine, Pheneramine, promethazine) can cross the blood- brain barrier and reach the central nervous system, whereas second-generation (Cetirizine, Loratidine) cannot. Third-generation drugs (Fexofenidine, Desloratidine) are derived from second-generation and have fewer side effects but are still under review. NHS recommends using Cetirizine in pregnancy and breastfeeding for itching and allergy.⁸

Safety, efficacy and risk considerations

Common side effects are dryness of the mouth, drowsiness, anxiety and nausea, vomiting, blurred vision, constipation and urinary retention. First-generation drugs are considered safe in pregnancy except hydroxyzine and promethazine (Category C), which may cause birth defects.⁹  Some studies have also shown that H1 blockers don't cause birth defects or fetal abnormalities.^10. Second-generation drugs ( Category B) have higher potency, last longer, have fewer side effects such as reduced drowsiness, no fetal abnormality or birth defects.¹¹  Although it is available over the counter, it is advisable to consult a GP, dermatologist or a health care provider before taking them, who can weigh the risk vs benefit of the drug being prescribed.

FDA classification of first-generation antihistamines based on pregnancy complications.¹²

Pregnancy category B - the drug has failed to demonstrate fetal risk in animal studies and insufficient data in pregnant women or animal studies have shown an adverse effect and adequate studies in pregnant women have failed to demonstrate a risk to the fetus.

Pregnancy category C - animal studies have shown a side effect on the fetus and there are no adequate number of studies in humans and the benefits outway the risks of the drug in pregnant women.

FDA classification of second-generation drugs based on pregnancy complication¹²

Role of corticosteroids

Corticosteroids, also called as steroids, are agents used to control inflammation and are given in different  conditions such as allergies, joint problems and skin diseases.

How do they work?

When used for a short time, steroids reduce dilation of vessels and prevent neutrophil migration to sites of inflammation, inhibit the death of neutrophils, inhibit phospholipase A2 enzyme and other inflammatory transcription factors, all of which play a major role in causing inflammation.¹²

Commonly used

Topical steroids used in pregnancy are ​​hydrocortisone, beclometasone, clobetasone, diflucortolone,fluocinolone, fluocortolone, fluticasone and triamcinolone. Moderate to strong topical steroid cream, like triamcinolone or fluocinolone applied once or twice daily on the PUPPP rash relieves itching and reduces inflammation.¹³ Oral prednisolone is given for severe cases 0–40 mg/day for 3–7 days.¹³

Safety, risk and efficacy in PUPPP

Topical steroids are considered safe to use in pregnancy.¹³  Betamethasone and hydrocortisone 0.1% cream have also been effective in treating PUPPP. ¹⁴  Low dose oral steroids when given for a short period of time have occasional side effects.¹² According to the NHS, it is safe to take prednisolone tablets and liquid in pregnancy with minimal side effects.¹⁵

Steroid tablets taken for longer than 3 weeks can cause increased appetite, pimples, mood swings, delayed healing, thinning of skin, diabetes and high blood pressure. ¹⁵

In severe form of itching, recurring and refractory cases, a short course of systemic corticosteroid is given.¹⁶

Combination treatment

First-generation antihistamines have been used together  with topical steroids to treat PUPPP, when the itching is localised.¹⁶

General safety profile

• Antihistamines and topical steroids are used for mild to moderate symptoms and oral steroids for severe problems
• Short-term, low dose of drugs is a safe choice, weighing risk/ benefit of the drug is vital
• Regular monitoring of fetus and pregnant women’s wellness - assessing symptoms, side effects, fetal changes

Preventive measures

• Healthy lifestyle, regular weight checks and stress control⁶
• To control itching - shorter hot water baths to avoid dryness, applying prescribed ointment first followed by moisturiser, using fragrance free toiletries and wearing loose cotton clothes to prevent skin irritation ⁶

Patient education and counselling

Supporting anxious women for their mental well-being through support groups, counselling through this temporary phase of pregnancy, connecting with other women in the same plight and reassuring the shared decision of treatment goal and duration.

FAQs

Do I need to see a doctor for any kind of rash, if I am pregnant?

Only if the rash is painful, itchy and doesn’t relieve symptoms with over-the-counter moisturisers.

Can PUPPP recur?

It usually does not recur and is self-limiting.

Can I take over-the-counter antihistamines?

No, it is advisable to consult a doctor if you are pregnant.

Summary

Although PUPPP is the most common condition seen during pregnancy, there is insufficient data on the exact cause and long-term outcome of drugs in pregnant women. Diagnosis is mainly through clinical presentation. However, women with unusual symptoms may require further investigations. 

Oral antihistamines, emollients and steroids are the drugs of choice to treat itchy PUPP.  A short course of oral steroids can be useful in severe cases, but the treatment varies depending on the severity of symptoms and response to the treatment.