Dermatological Manifestations Associated With Pregnancy 11-8-2009 CME Credit 1

PRE-ACTIVITY QUESTIONNAIRE

Dermatological Manifestations Associated With Pregnancy To measure the effectiveness of this continuing education activity, please complete the following 2-question pre-assessment. The activity addresses these questions in the content that follows.

1. Which of the following skin manifestations of pregnancy is most likely to recur after pregnancy?

Spider telangiectasia

Acral erythema

Melasma

Cutis marmorata 2. A 35-year-old primiparous woman has a pruritic dermatosis during the third trimester of pregnancy. Which of the following conditions would a skin biopsy be indicated to exclude?

Intrahepatic cholestasis of pregnancy

Atopic dermatitis

Pemphigoid gestationis

Impetigo herpetiformis

Dermatological Manifestations Associated With Pregnancy CME

Boutros Soutou, MD; Stéphanie Régnier, MD; Dany Nassar, MD; Olivier Parant, MD; Kiarash Khosrotehrani, MD, PhD; Sélim Aractingi, MD

CME Released: 08/11/2009; Valid for credit through 08/11/2010

Abstract and Introduction

Abstract

Various types of cutaneous lesions may develop during the course of pregnancy. These may be classified into

four main categories: physiological changes, which are very diverse, specific conditions; dermatoses, that are

linked to pregnancy; cutaneous infections that may influence the course of gestation; and finally, miscellaneous

skin diseases, which may be affected by pregnancy or affect the fetus. All of these categories contain disorders

that are important to recognize, since some may require specific management while in others unnecessary

investigations should be avoided. This review will examine physiological changes and dermatoses.

Introduction

Pregnancy is a physiological and transient period where medical intervention is usually not required, or at least

is restrained to checking expected events. However, in the finely tuned, harmonious and extraordinarily

complex cascade of molecular and cellular phenomenons that gestation brings, many signs and/or symptoms

may target the cutaneous layers. Indeed, the skin is a very large organ, containing three tissues and no less

than ten different cell types. Therefore, it seems logical that during pregnancy, hormonal or other less well-

explained pathways may influence one of the skin cell types. By contrast, some diseases originating in the skin

may affect the course of the gestation. In this review, cutaneous modifications will be classified as physiological

changes, specific dermatoses of pregnancy, cutaneous infections that may modify the prognosis of pregnancy

and, finally, miscellaneous skin diseases that may be affected by pregnancy. Here, only the first two categories

will be discussed.

Physiological Changes in Pregnancy

It is important to recognize and differentiate physiological changes from diseased states in order to explain

them to the patient and avoid unnecessary investigations or treatments.

Indeed, one has to understand that multiple changes occur in a large percentage of pregnant women and are,

therefore, mandatory to diagnose. The three main precipitating factors that induce the development of these

changes are an increase in circulating hormones or other mediators that are secreted by ovaries and/or

placenta, including estrogens, progesterone, human placental lactogen, PlGF, intravascular volume expansion

and a compression from the enlarging uterus.

Estrogens display pleiotropic effects. They stimulate melanogenesis and keratinocyte growth, cause cutaneous

vasodilatation, increase capillary permeability and probably enhance angiogenesis. Progesterone acts

synergistically with estrogens on melanogenesis but intervenes solely to reduce collagenolytic activity.[1] In

addition, an enlargement of the pituitary gland results in increased levels of gonadotrophins,

adrenocorticotrophic hormone and melanocytic-stimulating hormone that have a direct effect on the skin.

All of the changes that will be detailed below have been called physiological as they rely on classical and

expected modifications of the hormonal, vascular, metabolic or immunologic status in pregnant females. In

addition, they affect the majority of these women and, finally, they commonly manifest early on in the course of

gestation and often resolve after delivery. However, these signs may be discrete or, by contrast, severe and,

therefore, may distress the patient and may require an appropriate treatment. They are summarized in Box 1 .

Box 1. Physiologic Changes of the Skin and the Mucosa During Pregnancy

Pigmentary Changes

Nonfacial Hyperpigmentation

Hyperpigmentation is the most frequent skin modification found in pregnancy and is one of its earliest signs. It

takes place usually during the first trimester. The exact pathogenesis, although unclear, is considered to rely on

increased serum levels of melanocytic-stimulating hormone, estrogens, and possibly progesterone, which

stimulate melanocytic activity contributing to pigmentation. Changes are more pronounced in women with a

dark complexion. Generalized, but usually mild, hyperpigmentation can be observed. Areas normally displaying

pigmentation become darker in pregnancy. However, hyperpigmentation is usually more localized, targeting the

areola and/or nipples, which are the most commonly affected site (40%).[2] Other sites of predilection include

the face, the periumbilical skin, the anogenital region, the axillae and the inner thighs. Recent scars, nevi and

freckles may also darken during gestation. Linea alba that corresponds to an aponevrosis extending from the

symphysis pubis to the xiphisternum often becomes hyperpigmented during pregnancy, most markedly below

the umbilicus. It is referred to as linea nigra and found in 75% of pregnant females.[2] Increase of the pigmentary

demarcation lines is frequently observed in black pregnant women, but very rarely in white subjects.[3]

After delivery, pigmentation usually resolves spontaneously even though the outcome may differ widely among

patients.

Melasma

Melasma, chloasma or mask of pregnancy may affect up to 70% of pregnant women. However, this prevalence

can decrease to 5% in white females living in countries devoid of sun exposure.[2] Facial hyperpigmentation

display various symmetrical distributions. The most common is centrofacial melasma developing on the

forehead, cheeks, upper lip, and chin. Maxillary and mandibulary patterns are less frequent.[4] Pigmentation

consists of grey-brown, poorly demarcated plaques. The diagnosis is very easy. Wood’s light examination

helps to differentiate epidermal- (enhanced pigmentation) from dermal-type (unchanged pigmentation). Mixed-

type is less common.

Melasma usually begins after the third month of gestation and is responsible for asthetical prejudice in most

women. Pigmentation usually regresses in postpartum but may persist in some cases and/or worsen again

after sun exposure. Broad-spectrum sunscreen and sun avoidance are therefore preventive measures during

and after pregnancy. First-line therapy for persistent melasma consists of a fixed triple combination, including

4% hydroquinone, 0.05% retinoic acid and 0.01% flucinolone acetonide, which should never be given during

gestation but only after delivery and, moreover, after the end of lactation.[5] Recurrence in future pregnancies or

with oral contraception is common.

Histopathology, although not required, would show characteristically large and dendritic melanocytes. There is

also an increase in melanogenesis without modification in the number of melanocytes.[6] Of note, estrogen

receptor expression is enhanced in melasma-affected skin.[7]

Apart from pregnancy, melasma can be observed in patients taking oral contraceptives or anticonvulsive drugs.

The genetic background, dark complexion and exposure to UV light are aggravating factors.[8]

Vascular Changes

Various molecules can cause functional modifications in the arteries with a decrease in smooth muscle tension

and consequent decrease in vascular resistance. Proliferation of the cutaneous microvasculature also occurs.

Alternatively, expanding intravascular volume and compression from the enlarging gravid uterus explains

venous congestion, dependent edema and varicosities. Thus, hyperemia, vasomotor instability, vascular

proliferation and venous hypertension can cause skin lesions that usually regress postpartum.

Spider Telangiectasias

Spider telangiectasias, also termed spider angiomas, spider nevi or nevi aranei, develop in approximately 60%

of white pregnant women but are found much less frequently in dark-skinned women.[2,9] They are easily

recognized by their punctiform central redness - corresponding to a dilated afferent arteriole with radiating

capillaries and surrounding erythema. Typically, spider nevi appear at the end of the first trimester in the area

of skin drained by the superior vena cava, namely the face, neck, arms and hands. Their number increases

throughout pregnancy. They often disappear within weeks after delivery. However, persistent lesions may be

treated with fine-needle electrocautery, pulsed dye laser or intense pulse light system. It should be mentioned

that when abnormally numerous spider telangiectasias manifest in pregnant women, liver status should

nevertheless be checked, since in hepatic diseases estrogen catabolism may decrease.

Acral Erythema

Palmar erythema appears within the first trimester along with spider telangiectasias.[4] It is more frequent and

noticeable in white than black women. Two patterns have been described; erythema may either be restricted to

the thenar and hypothenar eminences, the metacarpophalangeal joints and the finger pads or, by contrast, it

may present as a diffuse mottled redness of the entire palms.[10] Hyperthyroidism, cirrhosis, lupus and

salbutamol intake are the main differential diagnoses.[4] Palmar erythema in pregnancy is attributed to venous

capillary engorgement and fades within 1 week postpartum.

Venous Hypertension Signs

Secretion of pregnancy-related hormones induces an increased fragility of the elastic fibers in vessel walls.

Furthermore, the enlarging uterus compresses the pelvic and abdominal vessels, increasing venous pressure.

These, as well as other precipitating factors, including genetic predisposition and prolonged standing, lead to

saphenous, vulvar and anal (hemorrhoidal) varicosities.[9] Starting from the second month of pregnancy,

varicose veins and venous telangiectasias appear in 40% of women.[10] They are localized on the legs, the

pelvis and the perineum. Thrombosis can complicate the situation in less than 10% of cases.[4] However, in the

experience of the authors, the figure is lower than that. Varicosities usually regress postpartum. Use of elastic

stockings and surelevation of the legs are therefore recommended to prevent these phenomenons. After

delivery, persisting lesions may be treated, if patients are willing, by sclerosing injections or laser rather than

surgery. Hemorrhoids are common, leading to pain and bleeding.

Prevention of constipation may help to prevent their exacerbation. In the same way, vascular dilatation of the

vestibule and vagina is responsible for varicosities (the Jacquemier sign) and a bluish purple tint of the mucosa

(the Chadwick sign), two early diagnostic features of pregnancy.[11]

The increased hydrostatic venous pressure detailed above may also lead to fluid leakage in the extracellular

milieu. This results in nonpitting edema mainly affecting the legs but possibly also affecting the face and the

eyelids. It is more pronounced in the morning and is observed in almost half of all pregnant women during the

last few months of pregnancy.[4,12] However, one has to keep in mind that edema of the face and hands may be

indicative of preeclampsia. Purpura is due to the excessive fragility and permeability of capillaries and is

common on the legs during the second half of pregnancy. It spontaneously regresses postpartum. When it

persists longer, other causes of purpura should be ruled out.

Vasomotor Instability

Vasomotor instability is frequently observed and includes alternating episodes of pallor, facial flushing, hot and

cold sensations and dermographism. Exaggerated response to cold is sometimes associated with a reticulate

bluish erythema of the lower legs, referred to as cutis marmorata, which usually resolves after delivery.

Vascular Proliferation

Superficial or subcutaneous hemangiomas are reported in 5% of pregnant women.[10] They develop at the

beginning of the third month of gestation, particularly affecting the hand and neck. These hemangiomas grow

slowly until delivery, which is followed in most cases by spontaneous involution. Unsatisfactory sequela may be

treated with vascular lasers.[9] More rarely, glomangiomas and/or hemangioendotheliomas may develop around

the eyes, the breasts and the umbilical skin.[4]

Hyperemia and hyperplasia of the gingival mucosa is observed in pregnant women.[11] It may present with

various degrees of severity, ranging from mild asymptomatic inflammation to intense pain with bleeding. It

develops in the third trimester of pregnancy and progressively resolves postpartum. The interdental papillae are

the most affected site. Pre-existing periodontal disease, poor dental hygiene, nutritional deficiencies and local

irritative factors are costimulatory events.

Similarly, pyogenic granulomas appear to be relatively frequent during pregnancy.[11] They are also known as

pregnancy epulis, epulis gravidarum or granuloma gravidarum and usually develop during the second trimester.

The term ‘pyogenic granuloma’ is a misnomer since it neither corresponds histologically to a granulomatous

formation, nor it is caused by pyogenic microorganisms. The lesions correspond to a benign hyperplasia of

mucosal capillaries and fibroblasts that arise in reaction to triggers, such as physical trauma or irritation (plaque

deposits and gingivitis), as erythematous fragile nodules on gingival mucosa. Pyogenic granulomas are

painless but may bleed. Spontaneous regression is observed in the months after postpartum, but their

recurrence is possible in later pregnancies. Surgical excision is allowed if necessary (e.g., considerable

bleeding).

Structural Changes

Striae Gravidarum

Striae distensae (striae gravidarum) are a cause of great concern for pregnant women. They occur in 60-90%

of white women, but less commonly in black or Asian women.[2,4,12] However, Chang et al. found that dark-

skined women had more striae gravidarum than Caucasian females.[13] The most significant risk factors for

striae in primiparous women include young maternal age and elevated maternal BMI, as well as maternal

weight gain and high neonatal birth weight.[14] Women with a history of breast or thigh striae, or a family history

of striae gravidarum are also at higher risk.[13] The diagnosis is readily performed, but the mechanisms remain

poorly known. These seem to be multifactorial and include physical trauma, such as stretching of the skin, and

hormonal mediation through steroids, estrogens and relaxin, leading to reduction in the elastic fiber network.[15]

During the third trimester, striae begin as red-to-purple linear lesions, fade gradually over time and manifest

initially as white atrophic bands. They develop on the abdomen and sometimes on the breasts, thighs, arms,

buttocks and inguinal areas. They may cause burning or itching but usually the unique symptoms are the

anxiety of women fearing that these will never disappear completely. Preventive measures have no proven

beneficial effect.[16] Treatment with pulsed dye laser or 0.1% tretinoin cream of recent purplish striae may

partially improve their appearance but should of course be given only after delivery.[17,18]

Molluscum Pendulum (Acrochordons)

Molluscum fibrosum gravidarum corresponds to the skin tags or acrochordons that grow during pregnancy. As

in nonpregnant females, these appear as multiple small, cutaneous, fibrous, pedonculated, lightly pigmented

polyps located on skin folds, such as the neck, the axillary, inframammary and inguinal folds. They begin during

the second half of pregnancy and often shrink after delivery. When persisting, these may enlarge in future

pregnancies.[4] They have no malignant potential. Cryotherapy, electrocautery or snipping is effective for

persistent lesions.

Adnexal Changes

Hair

During pregnancy, hair cycle changes resulting in fewer anagen hair follicles entering the telogen phase. This

leads to thickening and brightening of hairs. In addition to the thickening of scalp hair, body hair follicles

increase in size and number, especially on the face, and less often on the arms, legs, and back. This kind of

hirsutism is reversible within 6 months postpartum.[4]

Postpartum, scalp hair enters a prolonged telogen phase causing increased shedding (telogen effluvium), that

may begin 2-4 weeks after delivery and last 3-4 months. After this period, hair completely grows again within 6-

15 months.[10] Evaluation of the possibility of an iron deficiency should usually be performed. A frontoparietal

recession of hair is a rare pattern of hair loss that is possible in pregnancy and may not normalize after

delivery.

Nails

Nails grow faster during pregnancy and rapidly become brilliant and brittle. Pregnant women may notice distal

onycholysis, transverse grooves, longitudinal melanonychia and subungual hyperkeratosis. Most of these

conditions are uncommon and resolve postpartum.[4]

Sudoral & Sebaceous Glands

Sebaceous gland activity appears to increase in the third trimester since many pregnant women complain of

greasy skin, especially on the face, and in many of these, acne develops for the first time during pregnancy.

However, the effect of gestation and hormonal disturbances is unpredictable on pre-existing acne.[4] When

treating this acne it is very important to avoid local (and of course systemic) retinoids, as well as cyclins.

Topical benzoyl peroxide, topical erythromycin or oral zinc salts are allowed.

In approximately half of pregnant women, the sebaceous glands on the areola enlarge and appear as multiple

elevated brown papules called Montgomery’s glands or tubercles.[4] They are visible starting from the sixth

week of gestation, representing an early sign of pregnancy.[10] Regression is classical after delivery.

Eccrine sweat-gland activity progressively increases during pregnancy all over the body, except the palms,

accounting for hyperhidrosis and increased frequency of malaria.[10] Apocrine sweat-gland activity seems to

decrease since Fox-Fordyce disease and hidradenitis suppurativa tend to improve during pregnancy.

Specific Dermatoses of Pregnancy

These conditions are peculiar in the way they represent cutaneous diseases strictly developing during

pregnancy or shortly after. They may, or may not recur in later pregnancies. Their mechanisms are, therefore,

related to the development of the gestation, although the precise pathways are not yet well understood. It is

important that they are recognized by practitioners. Until the 1980s, the literature was busy with several entities

all considered as different types of specific dermatoses of pregnancy.

In 1983, Holmes and Black created an important clarification by grouping most of the entities previously

described as late-onset prurigo of pregnancy (PP), such as pruritic papular eruptions of pregnancy, Sprangler

dermatitis, toxemic rash of pregnancy, toxic erythema of pregnancy and pruritic urticarial papules and plaques

of pregnancy, into a unique entity called polymorphic eruption of pregnancy (PEP).[19] They described three

other groups of specific dermatoses of pregnancy: pemphigoid gestationis (PG), PP and pruritic folliculitis of

pregnancy (PFP).[20] The intrahepatic cholestasis of pregnancy (ICP) and impetigo herpetiformis (IH) did not

appear in this classification because the first entity was not specifically a cutaneous disease and the second

was not restricted to the pregnancy period. More recently, Ambros-Rudolph et al. in London and Vienna

proposed to add to this list an entity called ‘atopic eczema of pregnancy’.[21] Therefore, we have chosen to

discuss PEP, PG and atopic eczema and summarize more quickly ICP and IH.

Polymorphic Eruption of Pregnancy

As mentioned earlier, this entity currently groups various other conditions that were named before 1980 using

multiple and confusing terms. However, all of these clinical presentations develop for an unknown reason,

mainly during the third trimester, present as nonspecific papules or eczematous lesions and lack any feature of

autoimmunity. They were, therefore, regrouped under the name of PEP.[19] The incidence of PEP varies

between 0.4 and 0.8% of pregnant women.[19,22] PEP predominantly affects primiparous women (57.5-70%),

mainly in the third trimester of pregnancy (75-83%).[19,22-27] However, earlier or postpartum onsets are possible.

This disease is characterized by the development of pruritic disseminated cutaneous lesions that usually begin

on the lower abdomen, particularly on the striae distensae. Unlike PG, the periumbilical area is nearly

constantly spared in PEP. Face, palms and soles are rarely affected, although this may still occur. An intense

pruritus is sometimes an early symptom of PEP. The cutaneous lesions are mainly urticarial papules and

plaques.[19,22-26] However, in 51% of cases, vesicular, eczematous, annular or target-like lesions can also be

seen.[28] Of note, Rudolph et al. reported in a large series that 89% of pregnant women with PEP had a familial

or personal history of atopy or had elevated IgE serum levels.[28]

There are a number of important obstetrical findings in women affected with PEP. Indeed, in two series, this

dermatosis appears to be significantly associated with a higher prevalence of delivery of male babies.[26,29] The

higher rate of male fetuses in PEP women found in multivariate analysis remains unexplained and is not

reported in other diseases associated with pregnancy. The predominance of male fetuses in pregnancy-

induced hypertension was suggested once, but not confirmed in a more recent study.[30,31] Interestingly, Ohel et

al. reported that hypertensive disorders were significantly associated with PEP.[32] A higher rate of pregnancy-

induced hypertension in the PEP group was also described by our team, although this did not reach statistical

significance.[29]

A higher risk of Caesarean section (40%) has also been reported in a case-control series of females with

PEP.[29] The reasons for these were mainly inadequate progression of labor. Previously, Yancey et al. noted two

Caesarean sections in a group of 20 PEP patients[33] and more recently Ohel et al. noted higher rates of

Caesarean delivery in PEP, but this was not identified as an independent factor associated per se with PEP.[32]

Of note, several authors, including Mascaro et al., have previously reported similar results in pregnant women

with PG,[34] another specific skin disease of pregnancy whose mechanism is completely different. Therefore, a

speculative hypothesis that can be drawn is that a diffuse cutaneous inflammatory condition developing at the

end of pregnancy, may modify progression of labor and lead to more Caesarean sections.

If PEP is untreated, spontaneous remission occurs within a few weeks after delivery. Otherwise, treatment with

topical steroids is usually successful. Finally, the recurrence rate in further pregnancies is low and PEP does

not influence the outcome of pregnancy, with the exception of Caesarean section if this was confirmed.

The pathogenesis of PEP remains unknown. There are no hormonal abnormalities, no HLA associations and

no circulating or fixed autoantibodies. Multiple gestation pregnancies occur more frequently in women

presenting PEP compared with controls. Indeed, the rate of multiple pregnancy in PEP varies between 10 and

15%.[23,24,26] Since abdominal wall distension appeared to be higher in pregnancies with multiple gestations and

since PEP frequently begins on the abdominal skin, more particularly on striae distensae, some authors

suggested that abdominal skin distension may play a role in the development of PEP.[24] These found a higher

maternal weight gain and newborn birth weight, as well as an increased twin rate in pregnancies with PEP.

However, PEP may concern areas not affected with cutaneous distension, such as the extremities, including

the palms and soles.[21] In addition, several series did not find confirmation of higher maternal or fetal weight

gain in females with PEP.[22,26,29] Therefore, the hypothesis of a cutaneous inflammation secondary to a

mechanical distension cannot be kept as a unique factor for this disease. Importantly, PEP has no

consequence on fetal viability and outcome.

In 1998, our group detected fetal cells in the epidermis and dermis of PEP specimens that were absent in

controls.[35] The technique was a PCR on microdissected tissues without identification of the cell type. We,

therefore, proposed two possible mechanisms for this finding. The first relied on the fact that semi-allogenic

fetal lymphocyte cells would be able to migrate to the skin and induce a cutaneous graft-versus-host-like

disease. The second mechanism was that such fetal cells migrated together with their maternal counterparts in

response to a cutaneous damage triggering event. We have recent data using a combination of FISH with

immunohistochemistry demonstrating that, in PEP, fetal cells are indeed keratinocytes [Aractingi S, Pers.

Comm.]. This indicated that fetal cells in PEP are not effector lymphocytes. Various types of fetal progenitors

are found in the maternal circulation during pregnancy; these are able to reach lesional tissue and differentiate

there.[36] Therefore, the presence of fetal keratinocytes probably represents a secondary repair phenomenon

towards an already established damage.

The value of skin biopsy using immunofluorescence is important to realize.[21,26,27] This is paradoxical since

histology is not specific, it displays various degrees of dermal edema, with polymorphous mononuclear

infiltrates with eosinophils being found in half of the cases.[28] In the epidermis, there is a mixture of spongiosis,

acanthosis and parakeratosis. These features are not specific and resemble those that will be described later in

PG. Direct immunofluorescence (DIF) is constantly negative in PEP. In all the recent studies regarding

dermatoses of pregnancy, DIF still remains the standard tool to distinguish PEP from the nonblistering stage of

PG that is clinically and histologically similar.[21,28,29] However, if a BP 180 NC16a ELISA is routinely present in

the laboratory facilities, it could replace DIF to discriminate between these diseases.[37] The clinical importance

for discriminating PEP and nonblistering PG relies on two points. One that is relevant is the contraindication for

estroprogestative contraception in PG but not in PEP. The second is less important but it is necessary to inform

women with PG about the 50-70% risk of recurrence at later pregnancies.

Treatment of PEP is only symptomatic. However, the pruritus is intense and frequently leads to fatigue, stress

and difficulty in sleeping. The main measure is the generous application once daily of potent or even highly

potent topical steroids. Emollients can be added. Antihistamines are less useful, but the authorized ones

(diphenydramine) could be prescribed according to the gestational age of pregnancy.[58] Some authors reported

that they had to give oral steroids, when the pruritus was very intense and lesions resisted topical steroids. In

our experience, we always endeavored to avoid this option.

Atopic Eczema of Pregnancy or Eczema of Pregnancy

The group in London first noted in 1999 a high prevalence of eczema.[21] Later on, analyzing the British and

Austrian series led to a proposal in 2006 to add this entity to the specific dermatoses of pregnancy.[26] The

authors retrospectively reviewed a large series of pregnant females with skin lesions. They considered women

with pruritic lesions (mainly flexural), personal and/or familial history of atopy, and/or elevated IgE levels as

having atopic eczema of pregnancy (AEP). Using these criteria, AEP appeared as the most frequent

dermatosis since it was present in 49% of pregnant females with specific dermatoses.[26] The eczema began in

76% of cases during the first and second trimesters of pregnancy, unlike the common third-trimester onset in

PEP. Women were all described to have an atopic background, but more precisely, only 21% had personal

history of atopy. The patients had either eczematous features (the ‘e-type’ eczema of pregnancy [EP] found in

48% of cases) or the prurigo features (the ‘p-type’ of EP found in 31% of cases). All parts of the body could be

involved. Histology was not given in detail but appeared to be similar to PEP. Cases previously considered as

pruritic folliculitis have been reclassified into EP. Although this appears as a logical issue, since during

pregnancy there is a switch in the immune polarization of T cells towards Th2 cells involved in atopy, there are

still unresolved problems. Indeed, criteria of AEP - if apparently very sensitive - are of low specificity. Therefore,

any PEP can be easily reclassified as AEP if there is a background of atopy. Going back to the British PEP

series, this demonstrates that 89% of women diagnosed with PEP had an ‘atopic background’ and, therefore,

could possibly fulfill the criteria for AEP.[28] In addition, 80% of women diagnosed with AEP had no personal

history of atopy before pregnancy. Therefore, a dilemma remains for such unexplained dermatoses restricted to

pregnancy: is there a disease called PEP or is there a syndrome or a spectrum initially called PEP in which, for

some females, pregnancy acts as a trigger for the induction of a restricted flare of eczema? The answer to this

question requests more investigative studies, such as atopy patch tests and/or filaggrin analysis, to evaluate

the true relations between PEP/AEP and the atopy. Finally, if pruritus gravidarum - which refers to isolated

pruritus usually with dry skin but without any eruption or any liver abnormalities - truly exists, it could also be a

discrete type of AEP.

Pemphigoid Gestationis

Previously known as herpes gestationis, PG is an autoimmune disease of the skin that appears to be

immunologically similar to bullous pemphigoid but develops only during pregnancy, postpartum or, more rarely,

in association with hydatiform moles. It has been reported exceptionally outside pregnancy in situations such

as choriocarcinoma. ‘Herpes gestationis’ was a misnomer and PG is not related to infection by herpes virus.

The incidence of PG is estimated to vary between one in 1600 and one in 50,000 pregnancies, but most

probably occurs in approximately one in 7000.[21,22,26,38] The disease usually develops in multiparous women - in

contrast to PEP - and mainly during the second or the third trimester; although, as mentioned above, onset in

the postpartum period or the first trimester may occur in some cases.

Pruritus classically precedes skin manifestations. Later, urticarial lesions develop initially on the abdomen and

the umbilical skin (50-80% of cases). These are erythematous and pruritic papular plaques sometimes

displaying an annular pattern. The lesions secondarily extend to the trunk, the limbs, and more rarely the palms

and soles. Clear and tense bullae may rise on the edematous plaques. The face and mucous membranes are

usually unaffected. An important point relates to the frequency of blistering lesions. Indeed, in the old series of

literature, the incidence of PG was very low (one in 50,000). Then, more recent series gave much higher

figures, raising the incidence up to one in 1600.[22,39] This relates to the ‘tools’ used for diagnosis. Early series

used the herpes gestationis complement activating factor, a complicated test with a low sensitivity, performed

only when females had blistering eruptions. By contrast, recent series illustrate the fact that PG is detected

through systematic DIF performed in all skin pruritic eruptions as recommended. Therefore, the recent series

reflect the true incidence of PG, while the old incidence reflects, more or less, the incidence of blisters. In a

recent study of ten patients with PG, urticarial presentation without blisters was found to be by far the most

frequent clinical presentation of the disease.[40] By contrast, Chi et al. have recently reported that blisters were

present in 88% of 61 PG patients. Besides, the presence of blisters was significantly associated with decreased

gestational age at delivery and onset of the disease in the second trimester.[41] However, one has to be aware

that this was a retrospective study done in several centers in the UK and Taiwan.

If PG is not treated, it regresses after delivery, although a flare in postpartum is frequently reported (75-85% of

the cases). Persistent PG with a protracted autonomous course may evolve for several years after pregnancy.

PG relapses in 50-70% of later pregnancies, appearing earlier in gestation and in a more severe form.

Recurrences have been reported in 20-50% of cases with subsequent use of oral contraceptives.

Histopathology features of PG include a dermal edema, a mild perivascular infiltrate of lymphocytes, histiocytes

and many eosinophils, a subepidermal vesicle and a spongiotic epidermis. However, these features are not

specific since they are very similar to those of PEP. The diagnosis relies on the DIF that shows a linear deposit

of C3 along the basement membrane zone. In fewer than 40% of cases, IgG is also present but less intense

than C3. Indirect immunofluorescence detects in autoantibodies belonging to the immunoglobulin G1 subclass

and targeting a component of the hemidesmosomes of the basal membrane (herpes gestation factor) in 60-

90% of patients. As for bullous pemphigoid, western blotting shows the presence of circulating antibodies

against two antigens, namely BPAg1 (230 kD) and BPAg2 (180 kD). In most cases of PG, circulating

autoantibodies recognize only the BPAg2, and more rarely BPAg1 and BPAg2. Autoantibodies of PG have a

common antigenic site with the noncollagenic domain (NC16a) of BPAg2.[37,42] DIF can be replaced by a

sensitive and specific ELISA that depicts antibodies against BPAg1 NC16.[37] The titer of circulating IgG

antibodies detected by conventional indirect immunofluorescence correlates neither with the disease activity

nor with pregnancy outcome.[26,41] Pathogenesis of pemphigoid gestationis is in part related to a genetic

background. Indeed, 43-45% of females with PG display the HLA-DR3 allele in contrast to only 3% of the

controls, while up to 90% of PG females had a null C4 allele.[43,44] Some associations with autoimmune

diseases, such as Graves’ disease, alopecia areata universalis, vitiligo or hemorrhagic rectocolitis, have been

reported. Classical class I and II HLA antigens are not normally expressed in the placenta. In PG, it has been

shown that HLA class II antigens were abnormally expressed in the trophoblasts of PG-affected women.[45]

Authors have therefore proposed that an immune response of the maternal immune system toward paternal

HLA antigens abnormally expressed on placenta, would crossreact with collagen XVII, leading to the disease.

This would explain observations of PG not recurring in pregnancies with another man or, by contrast,

developing only in pregnancies with a second father.[46]

The fetal prognosis is good in PG. Neonatal vesicles may appear but the eruption is usually mild, self-limited

and linked to the transient passage of maternal antibodies. However, some abnormalities are important to

know. At least four studies found high percentages of preterm labor ranging from 7-43%.[34,47-49] Reduced birth

weight and low birth weight were associated in one series with early onset of disease and blister formation.[41]

Caesarean section incidence was also high, ranging from 3 to 39%.[34] Of note, the case-control study of

Mascaro et al. found a significantly higher incidence of preterm labor and Caesarean sections in women with

PEP.[34]

Treatment relies on systemic corticosteroids, at a daily dose of 0.5-1 µg/kg and is required to control PG in a

third to half of affected patients.[21,26,40,41] There is no significant association of adverse pregnancy outcomes with

systemic corticosteroid treatment.[41] However, recently, ultrapotent topical steroids have been proposed for

successful first-line therapy of nonextensive PG.[50,51] Actually, it seems that systemic corticosteroids are

indicated for cases of pemphigoid gestationis resistant to ultrapotent topical steroids.

Recurrences of PG may occur either if an estroprogestative contraception is given or at later pregnancies, at

levels of 20-50% and 50-70%, respectively.

Prurigo of Pregnancy

Prurigo of pregnancy was formerly known as prurigo gestationis of Besnier or early PP. The incidence of PP

varies from one in 300 to one in 450 pregnancies.[19,22] It presents as excoriated papules and affects the

extensor surfaces of the extremities and the abdomen. We will not discuss this disease here. As previously

mentioned, such manifestations are part of other skin diseases related to atopy or various other causes (e.g.,

scabies). The treatment relies on antihistamines and topical steroids.

Pruritic Folliculitis of Pregnancy

Pruritic folliculitis of pregnancy is a very rare eruption, with only 24 reported cases, which develops during the

third trimester of pregnancy. It is characterized by papules and sterile follicular pustules on the trunk and

sometimes the upper limbs.[26] PFP clears spontaneously after delivery. In a series of 14 cases, the authors

indicated a discrete predominance of male children.[26] The DIF is negative. Serologic test results are normal.

There are no risks for the mother or the baby except a decrease in the fetal birth weight.[26] Treatment of

PFPrelies on topical steroids. Here again, a retrospective examination of a large series allowed the authors to

reclassify patients in AEP or PEP.[21]

Intrahepatic Cholestasis of Pregnancy

Intrahepatic cholestasis of pregnancy is not strictly part of the dermatoses of pregnancy since there are no

primary skin lesions. However, this entity is important to know considering the fetal risk. The incidence of ICP

varies between 0.02 and 2.4% of pregnancies, the higher incidence being found in Chile and China, and is

approximately 0.5% in France.[22] The etiology of ICP is complex and not fully understood, but it is likely to result

from the cholestatic effects of reproductive hormones and their metabolites in genetically susceptible women.

ICP usually manifests in the third trimester by nocturnal itching. Skin lesions are found in only a third of cases.

These are secondary to scratching[22] and correspond to excoriatied lesions or prurigo. Symptoms resolve after

delivery. Recurrence occurs in 60-70% of subsequent pregnancies. In a recent study, it was demonstrated that

the risk of nonalcoholic liver cirrhosis and some other hepatobiliary disorders was significantly elevated in

women with a history of ICP.[52] Hepatitis C infection was over threefold more common in patients with ICP than

in controls.[52] As for PG, oral contraceptive intake may also cause recurrences, and this raised the hypothesis

that estrogens are mediating the development of this disease. The diagnosis relies on biochemical tests.

Alanine aminotransferase level is increased in 95% of cases, and the serum fasting bile salts level is always

increased. However, dosing bile salts is not routinely performed anywhere, and if this test is not available

clinicians should repeat liver enzymes. Bile acid synthesis appears to be reduced in patients with ICP, in whom

primary conjugated bile acids are retained in the blood. The major bile acid in the blood and urine of these

patients is cholic acid instead of chenodeoxycholic acid present in normal pregnancies.[53] This test is essential

for diagnosing cholestasis and quantifying its intensity. It has been demonstrated that for the evaluation of fetal

status, increased total bile acid levels in the mother and increased exposure time for the fetus to these

increased values of total bile acid within the maternal circulation system help to predict increased risk of

asphyxia in newborns to ICP mothers.[54] In contrast with other dermatoses of pregnancy, ICP harbors a risk of

intrauterine growth retardation (17-50%), stillbirth (0.75-3.2%), perinatal death (0.75-6.4%) and preterm delivery

(12-50%).[54,55] When a dermatologist suspects ICP, he must check liver enzymes and bile salts levels. If these

are elevated, referring to an obstetrician is mandatory for management of the disease. Indeed, most authors

recommend the induction of labor in week 38 of gestation in mild cases and even earlier (in week 36) in severe

cases. Meanwhile, cholestyramine (Questran®), a resin that binds bile salts, may be given, a partial response

being observed in 70% of patients. Several days of treatment are required before pruritus improves and

cholestyramine does not improve the circulating abnormalities of ICP. Furthermore, cholestyramine is

responsible for a malabsorption of vitamin K, inducing a risk of hemorrhage. Ursodeoxycholic acid seems to

work faster than cholestyramine and also controls pruritus and plasma abnormalities. It appears to be safe for

mother and fetus and may decrease fetal mortality associated with ICP. However, regulatory authorities, at

least in Europe, do not officially allow it.[55]

Impetigo Herpetiformis

Impetigo herpetiformis is a very rare condition with some cases reported outside pregnancy. It does not belong

to the classification of the specific dermatoses of pregnancy described by Holmes and Black and reviewed

more recently.[19,21] First it should be mentioned that IH it is not related to either bacterial infection (impetigo) or

herpes virus infection, but that this is a historical misleading denomination. Briefly, the clinical and histological

similarities of IH with generalized pustular psoriasis - Von Zumbusch - led many authors to state that IH was

simply a flare of Von Zumbusch psoriasis triggered by pregnancy. Nevertheless, this remains controversial,

since personal history of psoriasis has been reported in only a third of patients. The onset of IH occurs most

commonly in primiparous women during the third trimester of pregnancy. IH presents with symmetric,

erythematous patches the borders of which sterile pustules secondarily develop. The lesions start in the folds

and extend centrifugally. Hyperthermia, nausea, vomiting and diarrhea are common. Hypocalcemia,

hypoalbuminemia or low serum levels of vitamin D should be systematically sought.

True hypocalcemia remains rare and is usually the reflection of hypoalbuminemia. Recurrence in successive

pregnancies may occur with earlier onset. Oral contraception can be another triggering factor. Treatment is

difficult and controversial. It relies on local or systemic steroids, and possibly on cyclosporine in resistant

cases.[56] Replacement treatment is mandatory if low levels of calcium are found.

Conclusion

Skin is constantly modified during pregnancy and/or postpartum. These changes are usually only physiological,

expressing changes in hormones or other factors secreted though the placenta, ovaries or enlarged pituitary

gland. However, various dermatoses may specifically develop during this period and may influence the fetal

outcome or, more rarely, the mother’s health. Therefore, being able to diagnose and manage them is of high

importance. Of note, to perform skin biopsy with DIF remains requested when facing urticarial or eczematous

plaques. In the same way, it is mandatory to evaluate the bile salts levels when facing generalized pruritus.

Expert Commentary

It is interesting that it currently appears easy to manage cutaneous lesions appearing in pregnancy. Although

there is still a lot of uncertainty regarding the pathogenesis of most dermatoses of pregnancy, clear algorithms

have been drawn in the last 10 years.

This review allows us to classify and recognize these eruptions and exposes some guidelines for their

management.

In the case of pruritus sine materia during pregnancy, total biliary salts and transaminases levels must be

measured to exclude ICP (fetal prognosis must be engaged).

In pruritic papular or eczematous plaques of the third trimester of pregnancy, skin biopsy for DIF (or ELISA)

allows differentiation of PEP and prebullous PG. The first-line therapy includes topical steroids and

antihistaminics in both cases. Fetal outcome is different in these two entities, as well as recurrence risk in view

of oral contraception and later pregnancies.

Five-year View

Several domains appear to be able to raise interest from investigators. The first one concerns the pathogenesis

of pruritic eruptions classified as PEP and AEP. Since there are still discussions on their autonomy, differences

and pathogenesis, new series will be required. These will have to investigate patterns of AEP and PEP and

more specifically the relations with the background of atopy. This will most likely require immunological and/or

genetic studies. The second important domain concerns the interactions naturally occurring between skin and

hormones secreted during pregnancy. There are so many changes that develop and which remain unexplained

that biologists will probably take the opportunity to study more deeply into the analysis of these phenomenons.

This kind of study may be able to reveal more about the cutaneous biology of frequent phenomenons such as

striae or even angiogenesis. Finally, transfer of fetal stem cells to the maternal circulation has drawn

considerable interest in the last few years. Such cells escape from the maternal immune system and appear

implicated in repair and/or tumors developing in pregnant females. Investigations on this phenomenon will

target better comprehension of fetal stem cells biology and their possible use in female health.

This article is a CME certified activity. To earn credit for this activity visit:

http://cme.medscape.com/viewarticle/706769

Sidebar: Key Issues

Hyperpigmentation of areola, melasma, spider telangiectasias and striae gravidarum are the most

frequent physiologic skin changes in pregnancy.

These changes are correlated with the hormonal alterations of the gestational period.

Many normal physiologic skin changes are reversed postpartum.

Pregnancy-specific dermatoses include polymorphic eruption of pregnancy, atopic eczema of

pregnancy and pemphigoid gestationis.

Intrahepatic cholestasis of pregnancy and impetigo herpetiformis are not strictly speaking pregnancy-

specific dermatoses; however, they are important to be aware of considering the fetal or maternal risk.

Polymorphic eruption of pregnancy is a pruritic disease that usually occurs in primiparous women

during the last trimester of pregnancy. It seems to be associated with male fetuses, Caesarean

delivery and multiple gestation pregnancy. Topical steroids are the first-line therapy.

Atopic eczema of pregnancy is still controversial as an entity, covering conditions with eczematous

lesions, prurigo or folliculitis, and is inconstantly associated with a personal history of atopy.

Skin biopsy with direct immunofluorescence is mandatory in pruritic dermatoses of pregnancy in order

to rule out pemphigoid gestationis.

Serum bile salts levels should be tested whenever a generalized pruritus develops during pregnancy in

order to rule out intrahepatic cholestasis.

References

1. Huber J, Gruber C. Immunological and dermatological impact of progesterone. Gynecol. Endocrinol.

15(S6), 18-21 (2001).

2. Estève E, Saudeau L, Pierre F, Barruet K, Vaillant L, Lorette G. Signes cutanés lors des grossesses

normales. Étude de 60 cas. Ann. Dermatol. Vénéréol. 121, 227-231 (2004).

3. Bonci A, Patrizi A. Pigmentary demarcation lines in pregnancy. Arch. Dermatol. 138, 127-128 (2002).

4. Elling SV, Powell FC. Physiological changes in the skin during pregnancy. Clin. Dermatol. 15, 35-43

(1997).

5. Rendon M, Berneburg M, Arellano I, Picardo M. Treatment of melasma. J. Am. Acad. Dermatol. 54,

S272-S281 (2006).

•• Detailed review of the different treatments of melasma with recommendations based on published

clinical evidence and expert opinion.

6. Grimes PE, Yamada N, Bhawan L. Light microscopic, immunohistochemical, and ultrastructural

alterations in patients with melasma. Am. J. Dermatopathol. 27, 96-101 (2005).

7. Lieberman R, Moy L. Estrogen receptor expression in melasma: results from facial skin of affected

patients. J. Drugs Dermatol. 7, 463-465 (2007).


8. Costin GE, Hearing VJ. Human skin pigmentation: melanocytes modulate skin color in response to

stress. FASEB J. 21, 976-994 (2007).

9. Henry F, Quatresooz P, Valverde-Lopez JC, Piérard GE. Blood vessel changes during pregnancy: a

review. Am. J. Clin. Dermatol. 7, 65-69 (2006).

10. Roger D, Boudrie JL, Vaillant L, Lorette G. Peau et Grossesse. In: Encyclopédie Médico-Chirurgicale

(Dermatologie). Scientifiques et Médicales Elsevier SAS. 200198-858-A-10 (2001).

•• Comprehensive review of the physiologic modifications of the skin with discussion of potential

mechanisms.

11. Torgerson RR, Marnach ML, Bruce AJ, Rogers RS 3rd. Oral and vulvar changes in pregnancy. Clin.

Dermatol. 24, 122-132 (2006).

• Detailed review of various physiologic and pathologic conditions of the mucosa during pregnancy.

12. Kroumpouzos G, Cohen LM. Dermatoses of pregnancy. J. Am. Acad. Dermatol. 45, 1-19 (2001).

13. Chang AL, Agredano YZ, Kimball AB. Risk factors associated with striae gravidarum. J. Am. Acad.

Dermatol. 51, 881-885 (2004).

14. Atwal GS, Manku LK, Griffiths CE, Polson DW. Striae gravidarum in primiparae. Br. J. Dermatol. 155,

965-969 (2006).

15. Salter SA, Kimball AB. Striae gravidarum. Clin. Dermatol. 24, 97-100 (2006).

16. Young GL, Jewell D. Creams for preventing stretch marks in pregnancy. Cochrane Database Syst.

Rev. 2, CD000066 (2000).

17. Jiménez GP, Flores F, Berman B, Gunja-Smith Z. Treatment of striae rubra and striae alba with the

585-nm pulsed-dye laser. Dermatol. Surg. 29, 362-365 (2003).

18. Rangel O, Arias I, García E, Lopez-Padilla S. Topical tretinoin 0.1% for pregnancy-related abdominal

striae: an open-label, multicenter, prospective study. Adv. Ther. 18, 181-186 (2001).

19. Holmes RC, Black MM. The specific dermatoses of pregnancy. J. Am. Acad. Dermatol. 8, 405-412

(1983).

20. Zoberman E, Farmer ER. Pruritic folliculitis of pregnancy. Arch. Dermatol. 117, 20-22 (1981).

21. Ambros-Rudolph CM, Müllegger RR, Vaughan-Jones SA, Kerl H, Black MM. The specific dermatoses

of pregnancy revisited and reclassified: results of a retrospective two-center study on 505 pregnant

patients. J. Am. Acad. Dermatol. 54, 395-404 (2006).

•• Large recent study that detailed clinical characteristics of specific dermatoses of pregnancy.

22. Roger D, Vaillant L, Fignon A et al. Specific pruritic diseases of pregnancy: a prospective study of 192

pregnant women. Arch. Dermatol. 30, 734-739 (1994).

23. Roger D, Vaillant L, Lorette G. Pruritic papules and plaques of pregnancy are not related to maternal

or fetal weight gain. Arch. Dermatol. 126, 1517 (1990).

24. Cohen LM, Capeless EL, Krusinski PA, Maloney ME. Pruritic urticaria papules and plaques of

pregnancy and its relationship to maternal-fetal weight gain and twin pregnancy. Arch. Dermatol. 125,

1534-1536 (1989).

25. Aronson IK, Bond S, Fielder VC, Vomvouras S, Gruber D, Ruiz C. Pruritic urticarial papules and

plaques of pregnancy: clinical and immunopathologic observations in 57 patients. J. Am. Acad.

Dermatol. 39, 933-939 (1998).

26. Vaughan Jones SA, Hern S, Nelson-Piercy C, Seed PT, Black MM. A prospective study of 200 women

with dermatoses of pregnancy correlating clinical findings with hormonal and immunopathological

profiles. Br. J. Dermatol. 141, 71-81 (1999).

•• Prospective study of clinical, obstetrical, and biological data of various dermatoses of pregnancy.

27. Borradori L, Saurat JH. Specific dermatoses of pregnancy: toward a comprehensive view. Arch.

Dermatol. 130, 778-780 (1994).

28. Rudolph CM, Al-Fares S, Vaughan-Jones SA, Mülleger RR, Kerl H, Black MM. Polymorphic eruption of

pregnancy: clinicopathology and potential trigger factors in 181 patients. Br. J. Dermatol. 154, 54-60

(2006).

29. Regnier S, Fermand V, Levy P, Uzan S, Aractingi S. A case-control study of polymorphic eruption of

pregnancy. J. Am. Acad. Dermatol. 58, 63-67 (2008)

•• Detailed case-control study of clinical and obstetrical findings in polymorphic eruption of pregnancy.

30. Makhseed M, Musini VM, Ahmed MA. Association of fetal gender with pregnancyinduced hypertension

and preeclampsia. Int. J. Gynaecol. Obstet. 63, 55-56 (1998).

31. Toivanen P, Hirvonen T. Sex ratio of newborns: preponderance of males in toxemia of pregnancy.

Science 170, 187-188 (1970).

32. Ohel I, Levy A, Silberstein T, Holcberg G, Sheiner E. Pregnancy outcome of patients with papules and

plaques of pregnancy. J. Matern. Fetal Neonat. Med. 19, 305-308 (2006).

33. Yancey KB, Hall RP, Lawley TJ. Pruritic urticarial papules and plaques of pregnancy: clinical

experience of

34. patients. J. Am. Acad. Dermatol. 10, 473-480 (1984).

35. Mascaro JM Jr, Lecha M, Mascaro JM. Fetal morbidity in herpes gestationis. Arch. Dermatol. 131,

1209-1210 (1995).

36. Aractingi S, Berkane N, Bertheau P et al. Fetal DNA in skin of polymorphic eruption of pregnancy.

Lancet 352, 1898-1901 (1998).

37. Nguyen Huu S, Dubernard G, Aractingi S, Khosrotehrani K. Feto-maternal cell trafficking: a transfer of

pregnancy associated progenitor cells. Stem Cell Rev. 2, 111-116 (2006).

38. Powell AM, Sakuma-Oyama Y, Oyama N et al. Usefulness of BP180 NC16a enzyme-linked

immunosorbent assay in the serodiagnosis of pemphigoid gestationis and in differentiating between

pemphigoid gestationis and pruritic urticarial papules and plaques of pregnancy. Arch. Dermatol.

141,705-710 (2005).

39. Jenkins RE, Hern S, Black MM. Clinical features and management of 87 patients with pemphigoid

gestationis. Clin. Exp. Dermatol. 24, 255-259 (1999).

40. Zurn A, Celebi CR, Bernard P, Didierjean L, Saurat JH. A prospective immunofluorescence study of

111 cases of pruritic dermatoses of pregnancy: IgM anti-basement membrane zone antibodies as a

novel finding. Br. J. Dermatol. 126, 474-478 (1992).

41. Castro LA, Lundell RB, Krause PK, Gibson LE. Clinical experience in pemphigoid gestationis: report of

10 cases. J. Am. Acad. Dermatol. 55, 823-828 (2006).

42. Chi CC, Wang SH, Charles-Holmes R et al. Pemphigoid gestationis: early onset and blister formation

are associated with adverse pregnancy outcomes. Br. J. Dermatol. 160, 1222-1228 (2009).

43. Amato L, Mei S, Gallerani I, Moretti S, Fabbri P. A case of chronic herpes gestationis: persistent

disease or conversion to bullous pemphigoid? J. Am. Acad. Dermatol. 49, 302-307 (2003).

44. Shornick JK, Jenkins RE, Briggs DC et al. Anti-HLA antibodies in pemphigoid gestationis (herpes

gestationis). Br. J. Dermatol. 129, 257-259 (1993).

45. Shornick JK, Artlett CM, Jenkins RE et al. Complement polymorphism in herpes gestationis:

association with C4 null allele. J. Am. Acad. Dermatol. 29, 545-549 (1993).

46. Borthwick GM, Sunderland CA, Holmes RC, Black MM, Stirrat GM. Abnormal expression of HLA-DR

antigen in the placenta of a patient with pemphigoid gestationis. J. Reprod. Immunol. 6, 393-396

(1984).

47. Villegas M, Goff HW, Kraus EW, Usatine RP. Blisters during pregnancy-just with the second husband.

J. Fam. Pract. 55, 953-956 (2006).

48. Shornick JK, Black MM. Fetal risks in herpes gestationis. J. Am. Acad. Dermatol. 26, 63-68 (1992).

49. Shornick JK, Bangert JL, Freeman RG, Gilliam JN. Herpes gestationis: clinical and histologic features

of twenty-eight cases. J. Am. Acad. Dermatol. 8, 214-224 (1983).

50. Holmes RC, Black MM. The fetal prognosis in pemphigoid gestationis (herpes gestationis). Br. J.

Dermatol. 110, 67-72 (1984).

51. Valeyrie L, Lebrun-Vignes B, Bodak N et al. Pemphigoid gestationis: treatment by topical class I

corticosteroid. Ann. Dermatol. Venereol. 128, 638-640 (2001).

52. Saidi W, Joly P. Topical or systemic corticosteroids in patients with pemphigoid gestationis and

polymorphic eruption of pregnancy. Ann. Dermatol. Venereol. 135, 865-866 (2008).

53. Ropponen A, Sund R, Riikonen S, Ylikorkala O, Aittomäki K. Intrahepatic cholestasis of pregnancy as

an indicator of liver and biliary diseases: a population-based study. Hepatology 43, 723-728 (2006).

54. Geenes V, Williamson C. Intrahepatic cholestasis of pregnancy. World J. Gastroenterol. 15, 2049-2066

(2009).

55. Oztekin D, Aydal I, Oztekin O, Okcu S, Borekci R, Tinar S. Predicting fetal asphyxia in intrahepatic

cholestasis of pregnancy. Arch. Gynecol. Obstet. DOI: 10.1007/s00404-009-1052-x (2009) (Epub

ahead of print).

56. Kroumpouzos G, Cohen L. Specific dermatoses of pregnancy: an evidencebased systematic review.

Am. J. Obstet. Gynecol. 188, 1083-1092 (2003).

57. Imai N, Watanabe R, Fujiwara H, Ito M, Nakamura A. Successful treatment of impetigo herpetiformis

with oral cyclosporine during pregnancy. Arch. Dermatol. 138, 128-129 (2002).

Papers of special note have been highlighted as:

• of interest

•• of considerable interest

Website

58. Centre de Référence sur les Agents Tératogènes www.lecrat.org

AUTHORS AND DISCLOSURES

As an organization accredited by the ACCME, MedscapeCME requires everyone who is in a position to control

the content of an education activity to disclose all relevant financial relationships with any commercial interest.

The ACCME defines "relevant financial relationships" as financial relationships in any amount, occurring within

the past 12 months, including financial relationships of a spouse or life partner, that could create a conflict of

interest.

MedscapeCME encourages Authors to identify investigational products or off-label uses of products regulated

by the US Food and Drug Administration, at first mention and where appropriate in the content.

Author(s)

Boutros Soutou, MD

Service de dermatologie Hopital Tenon, Paris, France

Disclosure: Boutros Soutou, MD, has disclosed no relevant financial relationships.

Stéphanie Régnier, MD


Disclosure: Stéphanie Régnier, MD, has disclosed no relevant financial relationships.

Dany Nassar, MD


Disclosure: Dany Nassar, MD, has disclosed no relevant financial relationships.

Olivier Parant, MD


Disclosure: Olivier Parant, MD, has disclosed no relevant financial relationships.

Kiarash Khosrotehrani, MD, PhD


Disclosure: Kiarash Khosrotehrani, MD, PhD, has disclosed no relevant financial relationships.

Sélim Aractingi, MD


Disclosure: Sélim Aractingi, MD, has disclosed no relevant financial relationships.

Editor(s)

Elisa Manzotti

Editorial Director, Future Science Group, London, United Kingdom

Disclosure: Elisa Manzotti has disclosed no relevant financial relationships.

CME Author(s)

Désirée Lie, MD, MSEd

Clinical Professor, Family Medicine, University of California, Orange; Director, Division of Faculty Development,

UCI Medical Center, Orange, California

Disclosure: Désirée Lie, MD, MSEd, has disclosed no relevant financial relationships.

Disclaimer The material presented here does not necessarily reflect the views of MedscapeCME or companies that support educational programming on www.medscapecme.com. These materials may discuss therapeutic products that have not been approved by the US Food and Drug Administration and off-label uses of approved products. A qualified healthcare professional should be consulted before using any therapeutic product discussed. Readers should verify all information and data before treating patients or employing any therapies described in this educational activity. Reprint Address

Sélim Aractingi, Service de dermatologie Hopital Tenon, ApHp and Univ Paris 6, Inserm UMR S 938, 4, rue de la Chine, 75020

Paris, France Tel.: +33 156 016 462 Fax: +33 156 016 458; Email: [email protected]

Expert Review of Dermatology CME. 2009;4(4) © 2009 Expert Reviews Ltd.

This article is a CME certified activity. To earn credit for this activity visit: http://cme.medscape.com/viewarticle/706769

mailto:[email protected]


CME Information

CME Released: 08/11/2009; Valid for credit through 08/11/2010

Target Audience

This activity is intended for primary care clinicians, obstetricians, dermatologists, and other specialists who care for pregnant women.

Goal

The goal of this activity is to review the physiologic skin conditions and dermatoses associated with pregnancy, their prevalence, presentation, management, and prognoses.

Learning Objectives

Upon completion of this activity, participants will be able to:

1. Describe the categories of dermatologic conditions in pregnancy 2. List the effects of estrogens on the skin 3. Describe the patterns of physiologic skin pigmentation common to pregnancy 4. Identify the skin conditions in pregnancy that are most likely to recur or persist 5. Identify hair changes associated with pregnancy 6. Describe indications for skin biopsy for dermatoses during pregnancy

Credits Available

Physicians - maximum of 1.25 AMA PRA Category 1 Credit(s)™

All other healthcare professionals completing continuing education credit for this activity will be issued a certificate of participation. Physicians should only claim credit commensurate with the extent of their participation in the activity.

Accreditation Statements

For Physicians

This activity has been planned and implemented in accordance with the Essential Areas and policies of the Accreditation Council for Continuing Medical Education through the joint sponsorship of MedscapeCME and Expert Reviews Ltd.

MedscapeCME is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians.

MedscapeCME designates this educational activity for a maximum of 1.25 AMA PRA Category 1 Credit(s)™ . Physicians should only claim credit commensurate with the extent of their participation in the activity.

Contact This Provider

For questions regarding the content of this activity, contact the accredited provider for this CME/CE activity noted above. For technical assistance, contact [email protected]

Instructions for Participation and Credit

There are no fees for participating in or receiving credit for this online educational activity. For information on applicability and acceptance of continuing education credit for this activity, please consult your professional licensing board. This activity is designed to be completed within the time designated on the title page; physicians should claim



only those credits that reflect the time actually spent in the activity. To successfully earn credit, participants must complete the activity online during the valid credit period that is noted on the title page. Follow these steps to earn CME/CE credit*:

1. Read the target audience, learning objectives, and author disclosures. 2. Study the educational content online or printed out. 3. Online, choose the best answer to each test question. To receive a certificate, you must receive a

passing score as designated at the top of the test. MedscapeCME encourages you to complete the Activity Evaluation to provide feedback for future programming.

You may now view or print the certificate from your CME/CE Tracker. You may print the certificate but you cannot alter it. Credits will be tallied in your CME/CE Tracker and archived for 6 years; at any point within this time period you can print out the tally as well as the certificates by accessing "Edit Your Profile" at the top of your Medscape homepage. *The credit that you receive is based on your user profile.

Hardware/Software Requirements

MedscapeCME is accessible using the following browsers: Internet Explorer 6.x or higher, Firefox 2.x or higher, Safari 2.x or higher. Certain educational activities may require additional software to view multimedia, presentation or printable versions of their content. These activities will be marked as such and will provide links to the required software. That software may be: Macromedia Flash, Adobe Acrobat, or Microsoft Powerpoint.

CME/CE TEST

Dermatological Manifestations Associated With Pregnancy

Click here to view activity content in a new browser window.

Please answer the test questions below.

Questions answered incorrectly will be highlighted.

1. Which of the following is least likely to be a category of pregnancy-related skin conditions?

Physiologic changes of pregnancy

http://www.adobe.com/

http://get.adobe.com/reader/

http://office.microsoft.com/en-us/powerpoint/default.aspx

Cutaneous infections

Autoimmune conditions

Dermatoses

2. Which of the following is least likely to be a physiologic effect of estrogens on the skin?

Cutaneous vasoconstriction

Keratinocyte growth

Angiogenesis

Melanogenesis

3. A 25-year-old, white, pregnant woman in the second trimester is distressed by the cosmetic effect of

facial melasma, which has darkened in the past 2 months. Which of the following is the most appropriate

management strategy during pregnancy?

Broad-spectrum sunscreen and sun avoidance

Triple hydroquinone, retinoic acid, and fluocinolone topical therapy

Topical moderate-potency corticosteroid

Ruby laser therapy

4. Which of the following skin manifestations of pregnancy is most likely to recur after pregnancy?

Cutis marmorata

Melasma

Spider telangiectasia

Acral erythema

5. Which of the following patterns of hair changes is least likely to resolve after delivery?

Alopecia associated with iron deficiency

Hirsutism

Telogen effluvium

Frontoparietal recession

6. A 35-year-old primiparous woman has a pruritic dermatosis during the third trimester of pregnancy.

Which of the following conditions would a skin biopsy be indicated to exclude?

Atopic dermatitis

Pemphigoid gestationis

Impetigo herpetiformis

Intrahepatic cholestasis of pregnancy


You have successfully completed the CME/CE test.

This activity is designated for a maximum of 1.25 AMA PRA Category 1 Credit(s)™. Physicians should only claim credit commensurate with the extent of their participation in the activity. Please select the amount of time you spent in this activity, rounding up to the nearest quarter hour. The amount

you choose will determine the amount of credit you receive for this activity. 75 minutes (1.25 credits)

Save and Proceed

Below are all the test questions with an explanation of the correct answer.

Questions answered incorrectly will be highlighted.

Which of the following is least likely to be a category of pregnancy-related skin conditions?

Answer: Autoimmune conditions

The main categories of skin conditions during pregnancy include normal physiologic changes, dermatoses

specific to pregnancy, cutaneous infections, and miscellaneous existing skin conditions affected by pregnancy.

Which of the following is least likely to be a physiologic effect of estrogens on the skin?

Answer: Cutaneous vasoconstriction

Estrogens display pleiotropic effects. They stimulate melanocytes and increase pigmentation, and they

increase keratinocyte growth. There is increased nail growth during pregnancy. They also cause cutaneous

vasodilation with increased capillary permeability and enhance angiogenesis.

A 25-year-old, white, pregnant woman in the second trimester is distressed by the cosmetic effect of facial

melasma, which has darkened in the past 2 months. Which of the following is the most appropriate

management strategy during pregnancy?

Answer: Broad-spectrum sunscreen and sun avoidance

Melasma, chloasma, or mask of pregnancy are common and affect up to 70% of pregnant women. During and

after pregnancy, prevention with sunscreen use and avoidance of sun are the most appropriate actions. Triple

topical therapy, including a corticosteroid, is only indicated for persistent melasma and should not be given

during pregnancy or lactation. Topical corticosteroid therapy may not be efficacious. Recurrence is common,

and oral contraceptives may exacerbate the condition.

Which of the following skin manifestations of pregnancy is most likely to recur after pregnancy?

Answer: Melasma

Spider telangiectasia and acral erythema of the palms occurring during pregnancy regress within weeks of

delivery. Also, cutis marmorata due to vascular instability in the lower legs also resolves soon after pregnancy.

Melasma is due to melanocytic changes and may persist or recur after pregnancy or with use of oral

contraceptives.

Which of the following patterns of hair changes is least likely to resolve after delivery?

Answer: Frontoparietal recession

Hair changes during pregnancy include thickening of scalp and body hair with resulting hirsutism, which

resolves after delivery, and hair loss associated with iron deficiency and telogen effluvium (or increased

shedding), which also resolve within 6-15 months. The frontoparietal pattern of balding is least likely to resolve

after delivery.

A 35-year-old primiparous woman has a pruritic dermatosis during the third trimester of pregnancy. Which of

the following conditions would a skin biopsy be indicated to exclude?

Answer: Pemphigoid gestationis

Pruritic dermatoses of pregnancy may be diagnosed by various methods. Intrahepatic cholestasis may be

diagnosed by history and liver function tests, and atopic dermatitis and impetigo herpetiformis by clinical

presentation. Pemphigoid gestationis is a condition with pruritic papular plaques that may be associated with

increased risk for preterm labor, and treatment relies on systemic corticosteroids in one third to half of patients.

Biopsy with direct immunofluorescence is needed for accurate diagnosis.

CONTINUING MEDICAL EDUCATION CERTIFICATE

certifies that

Muhammad Beiruti, MB [email protected]

Damascus none

has participated in the educational activity titled


on the Internet at http://www.medscapecme.com

November 24, 2009

and is awarded 1.25 AMA PRA Category 1 Credit(s)™.

MedscapeCME designates this educational activity for a maximum of 1.25 AMA PRA Category 1

Credit(s)™. Physicians should only claim credit commensurate with the extent of their participation

in the activity.

This activity has been planned and implemented in accordance with the Essential Areas and policies

of the Accreditation Council for Continuing Medical Education through the joint sponsorship of

MedscapeCME and Expert Reviews Ltd.

MedscapeCME is accredited by the Accreditation Council for Continuing Medical Education

(ACCME) to provide continuing medical education for physicians.

For information on applicability and acceptance of continuing education credit for this activity,

please consult your professional licensing board.

Certificate Number: 22336733

Cyndi Grimes

Director, Continuing Medical Education

MedscapeCME

http://www.medscapecme.com/

CME TRACKER

92.75 Earned Credits

CME Tracker

Our records identify you as Muhammad Beiruti; username: mmbeiruti.

If this is not your account, please Log Out and log in again.

View State CME Requirements.

Print Version for AMA PRA Application »

Add Activities from Other Sources »

Total Credits Earned from 01

/ 2009

Through 12

/ 2009

Change Date Range

COMPLETED CME ACTIVITIES ON MEDSCAPE

Activity Title Provider Participated Credit Type Credits

Dermatological Manifestations Associated With

Pregnancy

View Activity | View/Print Certificate

Medscape 11/24/09 AMA PRA Category 1

Credit(s)™

1.25

An 84-Year-Old Woman With a Blistering Rash



Credit(s)™

0.25

Walking Speed Predicts CV Mortality in Older

People



Credit(s)™; AAFP

Prescribed credit(s)

0.25

Treatment of Rheumatoid Arthritis: State of the

Art 2009



Credit(s)™

1.00

Management of New-onset Type 2 Diabetes


Primary Care Network, Inc. 09/29/09 AMA PRA Category 1

Credit(s)™

0.50

http://cme.medscape.com/activitytracker


https://profreg.medscape.com/px/logout.do?cid=med

http://cme.medscape.com/public/staterequirements

http://cme.medscape.com/activitytracker?fyear=2009&tyear=2009&fmonth=01&tmonth=12&type=trackerPrint

http://cme.medscape.com/activityexttracker?ext_new=true&yearInd=2009


http://cme.medscape.com/activitytracker?view=true&resultId=22336733










Shoulder Pain in a 57-Year-Old Man



Credit(s)™

0.25

The Basic Geriatric Respiratory Examination



Credit(s)™

1.00

An Unusual Presentation of a Lingual Ulcerative

Lesion



Credit(s)™

0.25

Guideline Issued for Evaluation and

Management of Hoarseness



Credit(s)™; AAFP


0.25

A 16-Year-Old Boy With a Fever of Unknown

Origin



Credit(s)™

0.25

Clinical Guide to Managing Advanced Gouty

Arthritis and Associated Complications


University of California Irvine

College of Medicine

09/10/09 AMA PRA Category 1

Credit(s)™

1.00

Abdominal Pain and Syncope in a 61-Year-Old

Woman



Credit(s)™

0.25

Young Girl With Clumsiness, Dystonia, and

Speech Difficulty



Credit(s)™

0.50

Sleep-Disordered Breathing Strongly Linked to

Increased Risk for Mortality



Credit(s)™; AAFP


0.25

Best Practices for Treating Obsessive-

Compulsive Disorder in Primary Care Setting



Credit(s)™; AAFP


0.25

Primary Care Management of Keloids and

Hypertrophic Scars Reviewed



Credit(s)™; AAFP


0.25

WHO Issues Guidelines for Antiviral Treatment Medscape 09/05/09 AMA PRA Category 1

Credit(s)™; AAFP

0.25























of H1N1 and Other Influenza



Bilious Emesis in a Newborn



Credit(s)™

0.25

A 14-Year-Old Girl With Purulent Ear Discharge

and Double Vision



Credit(s)™

0.25

Necrotic Skin Lesions in a 61-Year-Old Woman



Credit(s)™

0.25

An Abnormal Fetal Ultrasound



Credit(s)™

0.25

New Test May Detect Early Alzheimer's Disease



Credit(s)™; AAFP


0.25

A 14-Year-Old Boy With Progressive Weakness

and Dyspnea



Credit(s)™

0.25

Lumbar Spinal Stenosis: Syndrome, Diagnostics

and Treatment



Credit(s)™

1.25

Managing Summer Ear Infections



Credit(s)™

1.50

Decreased Alertness in a 10-Month-Old Girl



Credit(s)™

0.25

Severe Abdominal Pain in a Young Girl After a

Hug



Credit(s)™

0.25

Current Targets and Treatment Gaps in Lipid

Therapy: Focus on HDL-C


National Lipid Association 06/15/09 AMA PRA Category 1

Credit(s)™

0.75













http://cme.medscape.com/viewprogram/17455












Abdominal Aortic Aneurysms: Stent Versus

Surgery


American College of Cardiology 06/03/09 AMA PRA Category 1

Credit(s)™

0.25

Give Blood Pressure Drugs to All



Credit(s)™; AAFP


0.25

The Topical Treatment of Psoriasis, Volume 2



Credit(s)™

1.50

Increased Risk of Reinfarction With Clopidogrel

and Proton-Pump Inhibitors



Credit(s)™; AAFP


0.25

An Unusual Presentation of Recurrent Iron-

Deficiency Anemia



Credit(s)™

0.25

Less Is More: Simplified 4-Step Algorithm

Improves BP Control



Credit(s)™; AAFP


0.25

New Guidelines Address Treatment of

Hospitalized Patients With High Blood Glucose

Levels



Credit(s)™; AAFP


0.25

The Clinicians' and Nurses' Guide to

Parkinson's Disease


We Move 05/18/09 AMA PRA Category 1

Credit(s)™

2.00

Upstream Adjunctive Therapy: The Importance

of Early Timing in the Treatment of NSTEMI



Credit(s)™

0.50

Improving Outcomes for Children With Genetic

Growth Disorders


American Academy of CME, Inc. 05/18/09 AMA PRA Category 1

Credit(s)™

1.50

An Uncommon Cause of Chest Pain in a

Healthy Young Man



Credit(s)™

0.25























Diagnosis and Treatment of Chronic Stable

Angina: A Case Study for Clinical Practice



Credit(s)™

1.50

A Pustular Rash and Fever in a 45-Year-Old

Woman



Credit(s)™

0.25

Effective Management of Dyslipidemia in

Minority Populations - Applying Current Data to

Practice


Association of Black

Cardiologists, Inc.


Credit(s)™

0.50

Aesthetic Medicine CME/CE Collection: Volume

6



Credit(s)™

1.00

A 31-Year-Old Woman With a Painful Right

Wrist



Credit(s)™

0.25

Managing Gout -- From Acute Relief to Long-

term Control



College of Medicine


Credit(s)™

1.00

The Neurologic Examination



Credit(s)™

0.75

It Must Be Cardiac!



Credit(s)™

0.25

A 40-Day-Old Boy With Facial Swelling



Credit(s)™

0.25

Optimal Pain Management in Fibromyalgia

Syndrome: Current and Emerging Therapeutic

Options -- An Interactive Symposium with

Patient Case Videos


Purdue University School of

Pharmacy and Pharmaceutical

Sciences Continuing Education

Division


Credit(s)™

1.25

A Young Athlete in Cardiac Arrest



Credit(s)™

0.25























Trauma in the Obstetrical Patient



Credit(s)™

1.25

An Update on Sick Building Syndrome



Credit(s)™

0.50

Improving the Outlook for Refractory

Rheumatoid Arthritis: Evidence for Biologic Use

and Quantifying Treatment Response


Discovery Institute of Medical

Education


Credit(s)™

1.00

Management of Gout: An Up-to-date

Perspective



College of Medicine


Credit(s)™

1.00

A 42-Year-Old Man With Acute Chest Pain



Credit(s)™

0.25

Rheumatoid Arthritis: Treatment Selection for

the Complex Patient



Credit(s)™

1.25

Rheumatoid Arthritis: Treatment Selection for

the Complex Patient



Credit(s)™

1.25

Oral Manifestations of Sjogren's Syndrome



Credit(s)™

1.00

New Strategies in the Treatment of Hepatitis B



Credit(s)™

1.50

Statin Therapy Linked to Lower Total

Testosterone Levels in Men With Type 2

Diabetes



Credit(s)™; AAFP


0.25

Recurrent Hemoptysis and Renal Impairment in

a 45-Year-Old Man



Credit(s)™

0.25

Reducing Cardiovascular Risk: Multiple Risk-

Factor Intervention

Joslin Diabetes Center 04/13/09 AMA PRA Category 1

Credit(s)™

1.50
























The Future of Diabetes Care: Impact of Weight

Control, Cardiovascular Risk, and Hypoglycemia



Credit(s)™

0.75

Delirium in Elderly Adults: Diagnosis, Prevention

and Treatment



Credit(s)™

1.00

The Skin-Mind Connection: Treatment of

Eczema and Other Common Skin Disorders -

Beyond the Use of Pharmacologic Interventions



College of Medicine


Credit(s)™

1.00

Gout: New Advances in the Diagnosis and

Management of an Old Disease



Credit(s)™

1.25

Progressive Neurologic Deterioration in a 23-

Year-Old Man



Credit(s)™

0.25

Walk, Don't Run, to Prevent or Reverse

Metabolic Syndrome



Credit(s)™; AAFP


0.25

Two Hamburgers, an Order of Fries, and the

Metabolic Syndrome to Go, Please!



Credit(s)™; AAFP


0.25

Red and Processed Meat Intake Linked to

Mortality



Credit(s)™; AAFP


0.25

AHA Updates Advice on Strep Throat,

Preventing Rheumatic Fever



Credit(s)™; AAFP


0.25

Understanding the Role of GLP-1 and Its Impact

on the Beta-cell and Body Weight


Postgraduate Institute for

Medicine


Credit(s)™

2.00

A 5-Year-Old Boy With an Abnormal Left Eye Medscape 04/02/09 AMA PRA Category 1 0.25























View Activity | View/Print Certificate Credit(s)™

A Teenager With Confusion and an Empty

Bottle of Pills



Credit(s)™

0.25

A 47-Year-Old Man With Acute Epigastric Pain



Credit(s)™

0.25

Recurrent Gastrointestinal Bleeding in a 64-

Year-Old Woman



Credit(s)™

0.25

Be Wary of Radiographs and Monitoring

Paraphernalia!



Credit(s)™

0.25

A 3-Year-Old Boy With Intense Itching



Credit(s)™

0.25

Combing Wet Hair May Be Best to Identify

Active Head Lice Infestation



Credit(s)™; AAFP


0.25

The Treatment of Osteoporosis: Where Are We

Now, and Do the Emerging Therapeutic Agents

Offer a Brighter Future?


Postgraduate Institute for

Medicine


Credit(s)™

2.25

Body Mass Index Above Ideal Range Linked to

Large Increase in Mortality Rate



Credit(s)™; AAFP


0.25

Empiric Antimicrobials in Pneumonia: Balancing

Risk Against Benefit in an Era of Resistance


Penn State College of Medicine 03/20/09 AMA PRA Category 1

Credit(s)™

1.00

A 55-Year-Old Man With Recurrent Renal

Stones



Credit(s)™

0.25

A 34-Year-Old Pregnant Woman with Acute

Severe Abdominal Pain


Credit(s)™

0.25
























A 50-Year-Old Man With Left Upper Quadrant

Pain and Pyrexia



Credit(s)™

0.25

New Studies Improve Evidence Base for

Colorectal Cancer Screening



Credit(s)™; AAFP


0.25

Colonoscopy Is Preferred Test for Colorectal

Cancer Screenings, Says American College of

Gastroenterology



Credit(s)™; AAFP


0.25

Management of Common Childhood Poisonings

Reviewed



Credit(s)™; AAFP


0.25

Once-Daily Oral Amoxicillin Effective for

Streptococcus Pharyngitis in Children



Credit(s)™; AAFP


0.25

Management of Streptococcal Pharyngitis

Reviewed



Credit(s)™; AAFP


0.25

Glycemic Control in Type 2 Diabetes: Clinical

Trends and Controversies


Joslin Diabetes Center 03/12/09 AMA PRA Category 1

Credit(s)™

1.50

Suspicion of Steatohepatitis From a General

Examination of a Patient With Type 2 Diabetes



Credit(s)™

0.25

A 60-Year-Old Man With Chest Pain



Credit(s)™

0.25

Diverticulitis in the United States: 1998-2005:

Changing Patterns of Disease and Treatment



Credit(s)™

0.75

A 44-Year-Old Man With Chronic Phase Chronic

Myelogenous Leukemia, a History of Asthma,

education | outcomes | science 03/09/09 AMA PRA Category 1

Credit(s)™

0.75























and a Poor Response to Imatinib Mesylate


Even Low to Moderate Alcohol Consumption

Increases Risk for Cancer in Women



Credit(s)™; AAFP


0.25

Advances in Glucagon-like Peptides for the

Treatment of Type 2 Diabetes -- Volume 3



Credit(s)™

1.00

Advances in Glucagon-like Peptides for the

Treatment of Type 2 Diabetes



Credit(s)™

1.25

Shortness of Breath in a 62-Year-Old Man 26

Months After Cardiac Transplantation



Credit(s)™

0.25

The Application of New ACR Recommendations

in the Medical Management of RA: A Case

Study Approach



Credit(s)™

1.00

Lower Abdominal Pain in a 30-Year-Old Woman



Credit(s)™

0.25

Clinical Risk Factors for Severe Clostridium

difficile-Associated Disease



Credit(s)™

0.75

Diabetes Dialogues -- Experts' Review of

Optimal Diabetes Management: Highlights From

the AADE 35th Annual Meeting


Annenberg Center for Health

Sciences


Credit(s)™

1.00

Diagnosis and Management of Atherosclerotic

Renal Artery Stenosis: Improving Patient

Selection and Outcomes



Credit(s)™

1.00

The Differential Diagnosis of Bipolar Disorder



Credit(s)™

1.50























A 40-Year-Old Woman With IBS-C: Evaluation

and Current Management.



Credit(s)™

1.25

Ingrown Toenail Management Reviewed



Credit(s)™; AAFP


0.25

A 67-Year-Old Man Presents With Fever and

Malaise for 1 Week


American College of Cardiology 02/20/09 AMA PRA Category 1

Credit(s)™

0.25

Treating Type 2 Diabetes: How Safe Are

Current Therapeutic Agents?



Credit(s)™

1.00

Doppler Ultrasonography in Rheumatoid

Arthritis Therapy Monitoring



Credit(s)™

0.50

ACAAI 2008: What If It Is Not Asthma?



Credit(s)™

0.25

Appropriate Use of Combination Therapy in

Adult Asthma



Credit(s)™

1.00

Educational Initiative on Constipation (EIC)


Johns Hopkins University School

of Medicine


Credit(s)™

1.50

Recurrent Syncope in a 10-Year-Old Boy



Credit(s)™

0.25

Advancements in Oral Antibiotic Therapy for the

Treatment of Moderate-to-Severe Acne Vulgaris


University of Cincinnati College of

Medicine


Credit(s)™

1.00

A 25-Year-Old Woman With Hypotension and a

Rash



Credit(s)™

0.25

New Guidelines Issued for Treatment of Vaginal

Atrophy


Credit(s)™; AAFP


0.25
























Use of Topical Corticosteroids for Dermatologic

Conditions Reviewed



Credit(s)™; AAFP


0.25

Primary Care Management of Skin Pigmentation

Disorders Reviewed



Credit(s)™; AAFP


0.25

Osteoporosis Management Reviewed



Credit(s)™; AAFP


0.25

Efficacy of 12 New-Generation Antidepressants

Assessed



Credit(s)™; AAFP


0.25

A 9-Year-Old Boy With a Recurrent Urinary

Tract Infection and Failure to Thrive



Credit(s)™

0.25

Abdominal Obesity and Endocannabinoid

Activation: New Targets to Reduce

Cardiometabolic Risk


Vanderbilt University School of

Medicine


Credit(s)™

1.00

The Case of the Missing Shaving Blade!



Credit(s)™

0.25

EADV 2008: Psoriasis



Credit(s)™

0.50

Rheumatoid Arthritis: Beyond Joint Inflammation

to Treat Nonarticular Symptoms



Credit(s)™

1.00

Managing Rheumatoid Arthritis: A Case of

Diminishing Treatment Effect



Credit(s)™

1.25

Early Diagnosis and Optimal Management of

RA: The Role of Markers in Optimizing RA

Patient Care


Credit(s)™

1.25
























Drug-Induced Movement Disorders: A Clinical

Review



Credit(s)™

0.50

Slashing Carbs Cuts Medication Use, Improves

or Reverses Type 2 Diabetes, Study Says



Credit(s)™; AAFP


0.25

Evaluation and Management of an Atypical

Patient With Pulmonary Arterial Hypertension



Credit(s)™

1.25

Differential Assessment and Management of

Asthma vs Chronic Obstructive Pulmonary

Disease



Credit(s)™

0.75

Diagnosis and Management of Fistulizing

Crohn's Disease



Credit(s)™

1.25

Heart Failure and Left Ventricular Thrombus in a

Young Child



Credit(s)™

0.25

Archived: Recognizing and Treating Androgen

Deficiency Syndrome in Aging Men



Credit(s)™

1.00

Adult ADHD: New Data on Genetics, Treatment,

Epidemiology, and Outcomes



Credit(s)™

1.00

Immunization to Prevent Meningococcal

Disease: Yesterday, Today, and Tomorrow


Discovery Institute of Medical

Education


Credit(s)™

1.00

Guidelines Updated for Influenza Immunization

in Children



Credit(s)™; AAFP


0.25

Advisory Committee on Immunization Practices Medscape 01/17/09 AMA PRA Category 1

Credit(s)™; AAFP

0.25























Issues 2009 Adult Immunization Schedule



A Patient With Treatment-Resistant Depression



Credit(s)™

0.25

A 66-Year-Old Man With Bilateral Nontender

Neck Masses



Credit(s)™

0.25

ACR 2008: RA and Biologics: Lipids and

Cardiovascular Disease, Managing Adverse

Events, and Impact on Patient Outcomes



Credit(s)™

1.00

ACR 2008: Immune Inflammatory Diseases and

Related Conditions: Latest Advances



Credit(s)™

1.25

ACAAI 2008: Update on Anaphylaxis



Credit(s)™

0.25

A 30-Year-Old Woman With Fever and a Rash



Credit(s)™

0.25

Coadministration of Naloxone With Opioid

Medications? A Best Evidence Review



Credit(s)™

0.25

Knowledge and Attitudes of Primary Care

Physicians in the Management of Patients at

Risk for Cardiovascular Events



Credit(s)™

0.50

There Was a Young Man Who Swallowed a

Nail...Perhaps He'll Die



Credit(s)™

0.25

Prostate Cancer Screening -- More Harm than

Good? A Best Evidence Review



Credit(s)™

0.25

Total: 91.75























LETTERS OF COMPLETION ON MEDSCAPE

Activity Title Provider Participated Credit Type Credits

Highlights of the National Association of Pediatric Nurse

Practitioners (NAPNAP): 29th Annual Conference on

Pediatric Health Care


National Association of

Pediatric Nurse

Practitioners

02/19/09 NAPNAP

Contact Hour(s)

1.00

Total: 1.00

Total Credits Earned from 01/2009 through 12/2009: 92.75 (0.00 Rx Credits*)

The AMA accepts Medscape's CME Tracker from physicians claiming AMA PRA Category 1 Credit(s)™. Simply Print

out your tracker, attach it to the Application, and mail both to the AMA to document your CME activities.

For information on the eligibility of this continuing education credit toward meeting your CME/CE requirements, please consult your professional association or state licensing board.

For questions regarding CME/CE activities, please email [email protected].

Medscape MedscapeCME eMedicine Drugs MEDLINE All



http://cme.medscape.com/activitytracker?year=2007&type=trackerPrint

http://cme.medscape.com/activitytracker?year=2007&type=trackerPrint


Dermatological Manifestations Associated With Pregnancy 11-8-2009 CME Credit 1

Documents

Transcript of Dermatological Manifestations Associated With Pregnancy 11-8-2009 CME Credit 1