PRURITIC URTICARIAL PAPULES AND PLAQUES OF PREGNANCY (PUPPP)

Aviva Romm

Pruritic urticarial papules and plaques of pregnancy (PUPPP) is the most common specific dermatologic condition affecting pregnant women, with an incidence of 1/120 to 1/300 pregnancies.69 Seventy-five percent of women who develop PUPPP are pregnant for the first time, and it is 8 to 12 times more likely to occur in women with multiple gestations.70 PUPPP usually develops in the third trimester, although the condition may have its onset in the postpartum, and rarely earlier in pregnancy.69 PUPPP is referred to as polymorphic eruption of pregnancy (in the United Kingdom), toxemic rash of pregnancy, and late-onset prurigo of pregnancy, although PUPPP is the name most commonly used in the United States.71

The condition presents as erythematous papules within the striae, usually of the abdomen and thighs, which eventually spread to the extremities and become hives (urticarial plaques). The periumbilical area, breasts, face, palms, and soles usually remain unaffected. The hallmark of this condition is pruritus (itching), which can be extreme, disturbing sleep and preventing normal daily activities. The pruritus of PUPPP can be so uncomfortable as to cause women to feel quite desperate. Pruritus may worsen immediately after delivery, but generally resolves by 10 to 15 days postpartum. Rarely, the condition may resolve prior to birth. Most women do not experience a recurrence with subsequent pregnancies; however, when a recurrence does occur, it is almost always much milder than the original case.69 The condition is not associated with any adverse maternal, fetal, or neonatal outcomes.69

The exact etiology of PUPPP is unknown. One popular theory, supported by the fact that women with larger babies, multiples, or greater maternal weight gain are more likely to develop PUPPP, is that the abdominal stretching of pregnancy leads to an inflammatory response in the connective tissue.69,71 More recently, a maternal response to fetal circulating antigens has been proposed as an etiologic theory, based on the fact that fetal skin tissue has been found in maternal

Lesions.69,72,73

DIAGNOSIS

There are no specific laboratory diagnostic methods for PUPPP. Diagnosis is made clinically and on the basis of exclusion of other conditions (see Differential Diagnosis). Histopathology and immunochemistry are noncontributory to the diagnosis.

DIFFERENTIAL DIAGNOSIS_

Differential diagnosis includes all conditions that may cause hives, and specifically, pemphigoid gestationis, adverse cutaneous drug reaction, allergic contact dermatitis, metabolic pruritus, and atopic dermatitis.

CONVENTIONAL MEDICAL TREATMENT FOR PUPPP

Treatment for PUPPP consists of high-potency topical steroids, ideally tapering these off after 7 days of therapy. Oral prednisone in doses of 10 to 40 mg/day has been used for severe cases when the pruritus is unbearable to the woman. Symptoms are often relieved after 24 hours of oral treatment. Oral antihistamines are generally ineffective. Early delivery is sometimes discussed when the symptoms are unbearable and treatment is ineffective; however, early delivery does not usually give relief of symptoms.71 Fortunately, symptoms are usually greatly improved with several days of steroid treatment.69 The safety of antenatal steroid use remains controversial; short-term or single course use is advisable, and the safety of use is greater in the third trimester than in the first trimester.

BOTANICAL TREATMENT OF PUPPP_

Many women, either unable to achieve adequate relief with conventional therapies, or concerned about the safety of steroid use during pregnancy, prefer to try natural alternatives for treating PUPPP. Treatment strategies include:

•  use of topical and oral anti-inflammatories

•  nervines to improve sleep, which is often seriously impaired owing to physical discomfort

•  nervines to relieve irritability from itching

•  traditional ''hepatic alterative'' herbs, which have been empirically shown to improve a number of skin conditions and

•  use of adaptogens as immunomodulators

In botanical therapy, the health of the skin is believed to reflect the health of the other eliminatory and detoxification organs (i. e., bowels, lymph system, liver). When these are not functioning optimally or are overtaxed, as may be a natural consequence of the increased burden of pregnancy on the body, it is believed this will manifest in skin problems, including inflammatory disorders. Topical treatments are therefore almost universally accompanied by systemic treatments.

Although the use of conventional antihistamines has not demonstrated efficacy in the treatment of PUPPP, nettle leaf, which appears to have antihistaminic activity, has been empirically observed to be helpful in the treatment of conditions with hives as a key feature, including PUPPP.

Herbs used to promote sleep are discussed later in Insomnia in Pregnancy.

Treatments are divided into those for topical and internal use, and are recommended to be used in combination. Effects may be expected after 2 to 3 days of regular use, although some women gain relief more quickly and for some it may take up to a week to notice results. Many women report that herbal treatments provide only temporary relief, requiring them to reapply topical remedies often;however, they find this an acceptable alternative to steroid use during pregnancy.

1 TABLE 15-5

Botanical Treatment Strategies for PUPPP

THERAPEUTIC GOAL

THERAPEUTIC ACTIVITY

BOTANICAL NAME

COMMON NAME

Relieve inflammation

Anti-inflammatory

Aloe vera

Aloe vera

Avena sativa

Oatmeal

Glycyrrhiza glabra

Licorice

Hamamelis virginiana

Witch hazel

Matricaria recutita

Chamomile

Scutellaria baicalensis

Chinese skullcap

Antihistaminic

Urtica dioica

Nettle leaf

Hepatic Alternatives/

Rumex crispus

Yellow dock

Aperients

Taraxacum officinale

Dandelion root

Prevent striae gravidarum

Centella asiatica

Gotu kola

Promote relaxation and

Nervine

Avena sativa

Milky oats

Sleep as needed

Sedative

Eschscholzia californica

California poppy

Passiflora incarnata

Passion flower

Immunomodulation

Adaptogen

Withania somnifera

Ashwagandha

Ganoderma lucidum

Reishi

Schisandra chinensis

Schisandra


The effects of using oral corticosteroids and herbs internally simultaneously during pregnancy has not been studied, therefore, owing to unknown safety, is not recommended. However, the use of oral steroids and topical herbal treatments, or conversely, oral herbal treatments and topical steroids may be acceptable. Women using oral medications for the treatment of PUPPP should inform their medical provides about their use of herbs prior to beginning an herbal protocol (Table 15-5).

Topical Applications

The vehicle via which topical applications are delivered in the case of PUPPP will depend entirely on the mother's response to any given preparation. PUPPP presents as itchy, irritating, and inflamed. The urticaric lesions may be discrete, but often, as the condition progress, become contiguous, requiring application of medicine to a large area. Salves may not be the best delivery mode as they may actually feel as if they are ''sealing in'' the hot, inflamed sensation. Similarly, applying tinctures directly to the skin is not advisable, although tinctures may be highly diluted in water or preferably witch hazel extract and used as compresses. Washes made of herbal teas can be used as compresses as well, although they are inconvenient to prepare daily. Similarly, herbal extracts can be added to aloe vera gel and applied this way. A highly absorbent cream base to which herbal extracts are added is perhaps the optimal delivery mode, as the cream is soothing and allows broad application of herbs, and the preparations are easy to make in large batches, store well, and are highly portable should travel or application at work be necessary. Topical applications will need to be reapplied multiple times per day, or as needed, for symptomatic relief. Women should be advised that products containing oil may stain clothing or bedding.

Chamomile

Chamomile has been approved by the German Commission E for the treatment of inflammatory skin conditions.74 Although there appear to be no contraindications to its use topically or internally (with the exception of rare allergy), herbalists have noted that with some conditions, for example, pediatric eczema, chamomile oil extracts may actually exacerbate irritation. For patients wishing to use chamomile for topical treatment of PUPPP, a cream preparation is advised. Chamomile tea may also be taken internally as a relaxing, mild sleep-promoting tea or tincture.

Chinese Skullcap

Chinese skullcap, ''scute,'' is used in traditional Chinese medicine to clear heat and drain dampness, which, from a modern medical perspective, might be interpreted as treating inflammation.75 The anti-inflammatory effects are attributed to the herbs flavonoids, and antioxidant and antihistamine activity.75,76 Only recently is this herb finding its way into Western herbal medicine practice. Little published data was identified specifically on the use of Chinese skullcap for skin conditions;

However, clinical evidence from herbal practice suggests a high degree of efficacy and safety in the treatment of inflammatory skin conditions including eczema and dermatitis. Tincture may be added to a cream base and applied topically, either alone or mixed with or herbs, for example, licorice root and St. John's wort extracts. Internal use of Chinese skullcap is not recommended during pregnancy because of teratogenicity in animal studies. It may be used internally, short term, during the postpartum should PUPPP arise during that period, or persists past the time of birth.77

Cotu Kola

Because one of the theories on the etiology of PUPPP is connective tissue damage as a result of abdominal stretching, with manifestation in the striae, it seems a reasonable consideration to minimize striae development if at all possible. A Cochrane Collaboration review of topical agents for stretch mark prevention identified two randomized trials involving a total of 130 women. One study, involving 80 women, indicated that, compared to placebo, massage with a cream (Trofolastin) containing Centella asiatica extract, alpha tocopherol and collagen-elastin hydrolysates was associated with less women developing stretch marks. A second study of 50 women compared massage using an ointment (Verum) containing tocopherol, panthenol, hyaluronic acid, elastin, and menthol with no treatment. Massage with the ointment was associated with fewer women developing stretch marks. The two papers reviewed may show that any cream massaged onto the abdomen, thighs, and breasts (areas most affected by stretch marks) may be of some benefit. There may be additional benefit from certain ingredients in the cream and the ointment described, but it is unknown which constituent(s) is beneficial. Neither preparation is widely available.78 Gotu kola is widely used by herbalists for the treatment of connective tissue damage. Practitioners should be aware that a number of cases of contact dermatitis from topical use were identified in the literature (nonpregnant patients); therefore, caution is advised and patch testing recommended before general use.79-81

Oatmeal Baths

To apply oats topically, the rolled oats are moistened and the milk extracted and added to bath water or rubbed on the body in a bath or shower.82 Two handfuls (about 1 cup) of rolled oats are placed into a large clean sock or rolled in a towel or bandana that can be tied at the top. The sac is taken into the bath or the shower, and as the oats soak up the water the cloth is squeezed firmly in the palm of the hand. A milky liquid will begin to be exuded, and it is this liquid that is allowed to fill the tub or rubbed over the body in the shower, and then rinsed off. This oat milk is very soothing and emollient. This can be repeated as needed even several times daily.

St. John's Wort

St. John's wort oil is a classic topical burn treatment.83 Both St. John's wort extract and hyperforin have demonstrated inhibitory effects in epidermal immune response when applied topically, and suggest a role for this soothing application in the treatment of inflammatory skin conditions. It is popularly used by herbalists for inflammatory and microbial skin conditions. St. John's wort demonstrates good cosmetic skin tolerance.84,85

Witch Hazel, Aloe Vera

Witch hazel extract, applied as a compress, has long been used as a topical agent for reducing inflammatory and pruritic skin conditions. It is recognized by ESCOP and approved by the German Commission E as a treatment for skin irritations and minor inflammatory dermatologic and mucosal conditions.74,86 A comparative study looking at witch hazel versus cortisone for the treatment of erythema found it to be slightly less effective than cortisone but still noteworthy in its effects, whereas a study on the outcome of treatment of sunburn with witch hazel vs. no treatment found that it led to a significant reduction in erythema and visible skin damage. It has demonstrated a mild anti-inflammatory effect in patients suffering from atopic neurodermatitis and psoriasis.86

Aloe vera gel is a soothing topical liquid from the aloe vera plant. Popular for pain relief and healing from burns and other skin conditions for thousands of years, some women find temporary relief from the itching of PUPPP with topical application of the gel. Promising preliminary research suggests that aloe has immunostimulatory properties that may improve wound healing and dermatologic inflammation.87 There is no contraindication to liberal topical use during pregnancy; aloe should not be used internally during pregnancy.

Internal Use

California Poppy, Passion Flower

See Insomnia in Pregnancy, as well as Plant Profiles, for discussion of the safety and efficacy of these herbs commonly used to treat sleep difficulties in pregnancy.

Dandelion Root, Yellow Dock

An entire category of herbs, known historically and to this day as ''alteratives,'' and referred to colloquially as ''blood cleansers,'' are included in the treatment of skin conditions many. Dandelion root is perhaps one of the most commonly used, and is popularly cited on ''mother blogs'' on the Internet as prescribed by midwives in the treatment of PUPPP. No human clinical trials have been conducted to support the use of dandelion root for skin conditions and there are no data in the scientific literature of dandelion either being safe or contraindicated during pregnancy.88-90 Yellow dock is used similarly to dandelion root. Note that yellow dock is sometimes considered contraindicated in pregnancy because it is a mild anthraquinone laxative; however, clinically, it has not been observed to be associated with increased uterine activity or other adverse outcomes.

Licorice

Glycyrrhizin has exhibited a range of corticosteroid-like activities when injected in animals and humans, including inhibition of prostaglandin synthesis similar to cortisone. Compounds in the root inhibit 5-lipoxygenase formation and leukotriene biosynthesis in vitro.91 It is commonly used by herbalists for a wide variety of inflammatory complaints ranging from gastrointestinal disorders, for which it is best studied, to inflammatory skin conditions such as eczema. Its use for PUPPP is empirically based. Two recent reports on high-dose licorice consumption throughout pregnancy, in the form of licorice candy containing actual licorice extract rather than licorice flavor, demonstrated no increase in maternal hypertension or low birth weight; however, both studies, demonstrated a significant increased in preterm (<37 weeks) delivery. In one study, the risk of preterm delivery was greater than double the risk of women not consuming licorice.92,93 No studies demonstrate harm or adverse outcomes with short-term use of modest doses of licorice, including a study of 110 case reports on the use of glycyr-rhizin injections for treating viral hepatitis during pregnancy that showed no adverse effects.88 It is recommended that licorice not be used in excessive doses or for prolonged periods during pregnancy; however, use for up to a week at a time appears to be safe. A comparative study of the safety and efficacy of licorice vs. cortisone use during pregnancy for the treatment of PUPPP would be informative. Women with hypertension should not take licorice during pregnancy (see Plant Profiles for safety information).

Milky Oats

The tincture of milky oats is considered a reliable nerve tonic, especially for use when there is nervous exhaustion or general debility. The medicinal use of oats during pregnancy has not beem studied; however, taken as food, no adverse effects have been noted in pregnancy.82 The tincture may be used alone, but it is more commonly taken in combination with other nervine or sedating herbs, for example, chamomile, St. John's wort, California poppy, passion flower, and lavender.

Nettle Leaf

Stinging nettle leaf has demonstrated significant antiinflammatory activity; it is used for the treatment of rheumatoid arthritis and allergic rhinitis.86 Herbalists have found nettle to be a reliable herb in the treatment of numerous systemic and dermatologic inflammatory conditions. It may be taken as tea or in freeze-dried capsules. No serious adverse effects were reported in five clinical studies with a total of 10,368 patients using hydroethanolic extracts corresponding to an equivalence of 9.7 g of dried leaf daily for periods ranging from 3 weeks to 12 months. Minor side effects included GI upset and allergic reaction (1.2% to 2.7% of cases).86 Nettle leaf is one of the most commonly used herbs by midwives who commonly recommend it to help build iron levels (see Chapter 15). It has been suggested, although not demonstrated, that the astringency of this herb might interfere with iron absorption. A 1975 review article by Farnsworth et al. reported that stinging nettle was a potential abortifacient, and that its constituent 5-hydroxytryptamine was a uterine stimulant; however, frequent use of large doses of this herbal infusion in midwifery practice has demonstrated no evidence of such activity.

Adaptogens

Adaptogens and their immunoregulatory properties are discussed extensively in Chapter 8.

Baking Soda Paste

Baking soda paste is reported by women on ''mother blogs'' (Internet) to relieve itching from PUPPP. Enough water is mixed with baking soda to form a paste and this is applied directly to affected areas.

NUTRITIONAL CONSIDERATIONS_

Essential Fatty Acids

Some women report finding relief from the daily addition of essential fatty acids (EFAs) to their diets. A high-quality combination EFA product containing plant source oils and fish oils is recommended. Women supplementing with fish oils during pregnancy should not exceed daily recommended allowances for vitamins A and D and should only take products that exclude the presence of heavy metal contaminants.

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