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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.
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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
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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
Service de dermatologie Hopital Tenon, Paris, France
Disclosure: Stéphanie Régnier, MD, has disclosed no relevant financial relationships.
Dany Nassar, MD
Service de dermatologie Hopital Tenon, Paris, France
Disclosure: Dany Nassar, MD, has disclosed no relevant financial relationships.
Olivier Parant, MD
Service de dermatologie Hopital Tenon, Paris, France
Disclosure: Olivier Parant, MD, has disclosed no relevant financial relationships.
Kiarash Khosrotehrani, MD, PhD
Service de dermatologie Hopital Tenon, Paris, France
Disclosure: Kiarash Khosrotehrani, MD, PhD, has disclosed no relevant financial relationships.
Sélim Aractingi, MD
Service de dermatologie Hopital Tenon, Paris, France
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
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)™
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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
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
Dermatological Manifestations Associated With Pregnancy
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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
Dermatological Manifestations Associated With Pregnancy
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.
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please consult your professional licensing board.
Certificate Number: 22336733
Cyndi Grimes
Director, Continuing Medical Education
MedscapeCME
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New Guidelines Issued for Treatment of Vaginal
Atrophy
Medscape 02/07/09 AMA PRA Category 1
Credit(s)™; AAFP
Prescribed credit(s)
0.25
View Activity | View/Print Certificate
Use of Topical Corticosteroids for Dermatologic
Conditions Reviewed
View Activity | View/Print Certificate
Medscape 02/07/09 AMA PRA Category 1
Credit(s)™; AAFP
Prescribed credit(s)
0.25
Primary Care Management of Skin Pigmentation
Disorders Reviewed
View Activity | View/Print Certificate
Medscape 02/07/09 AMA PRA Category 1
Credit(s)™; AAFP
Prescribed credit(s)
0.25
Osteoporosis Management Reviewed
View Activity | View/Print Certificate
Medscape 02/07/09 AMA PRA Category 1
Credit(s)™; AAFP
Prescribed credit(s)
0.25
Efficacy of 12 New-Generation Antidepressants
Assessed
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Medscape 02/07/09 AMA PRA Category 1
Credit(s)™; AAFP
Prescribed credit(s)
0.25
A 9-Year-Old Boy With a Recurrent Urinary
Tract Infection and Failure to Thrive
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Medscape 02/05/09 AMA PRA Category 1
Credit(s)™
0.25
Abdominal Obesity and Endocannabinoid
Activation: New Targets to Reduce
Cardiometabolic Risk
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Vanderbilt University School of
Medicine
01/29/09 AMA PRA Category 1
Credit(s)™
1.00
The Case of the Missing Shaving Blade!
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Medscape 01/29/09 AMA PRA Category 1
Credit(s)™
0.25
EADV 2008: Psoriasis
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Medscape 01/26/09 AMA PRA Category 1
Credit(s)™
0.50
Rheumatoid Arthritis: Beyond Joint Inflammation
to Treat Nonarticular Symptoms
View Activity | View/Print Certificate
Medscape 01/24/09 AMA PRA Category 1
Credit(s)™
1.00
Managing Rheumatoid Arthritis: A Case of
Diminishing Treatment Effect
View Activity | View/Print Certificate
Medscape 01/24/09 AMA PRA Category 1
Credit(s)™
1.25
Early Diagnosis and Optimal Management of
RA: The Role of Markers in Optimizing RA
Patient Care
Medscape 01/24/09 AMA PRA Category 1
Credit(s)™
1.25
View Activity | View/Print Certificate
Drug-Induced Movement Disorders: A Clinical
Review
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Medscape 01/24/09 AMA PRA Category 1
Credit(s)™
0.50
Slashing Carbs Cuts Medication Use, Improves
or Reverses Type 2 Diabetes, Study Says
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Medscape 01/24/09 AMA PRA Category 1
Credit(s)™; AAFP
Prescribed credit(s)
0.25
Evaluation and Management of an Atypical
Patient With Pulmonary Arterial Hypertension
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Medscape 01/23/09 AMA PRA Category 1
Credit(s)™
1.25
Differential Assessment and Management of
Asthma vs Chronic Obstructive Pulmonary
Disease
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Medscape 01/22/09 AMA PRA Category 1
Credit(s)™
0.75
Diagnosis and Management of Fistulizing
Crohn's Disease
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Medscape 01/22/09 AMA PRA Category 1
Credit(s)™
1.25
Heart Failure and Left Ventricular Thrombus in a
Young Child
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Medscape 01/22/09 AMA PRA Category 1
Credit(s)™
0.25
Archived: Recognizing and Treating Androgen
Deficiency Syndrome in Aging Men
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Medscape 01/19/09 AMA PRA Category 1
Credit(s)™
1.00
Adult ADHD: New Data on Genetics, Treatment,
Epidemiology, and Outcomes
View Activity | View/Print Certificate
Medscape 01/17/09 AMA PRA Category 1
Credit(s)™
1.00
Immunization to Prevent Meningococcal
Disease: Yesterday, Today, and Tomorrow
View Activity | View/Print Certificate
Discovery Institute of Medical
Education
01/17/09 AMA PRA Category 1
Credit(s)™
1.00
Guidelines Updated for Influenza Immunization
in Children
View Activity | View/Print Certificate
Medscape 01/17/09 AMA PRA Category 1
Credit(s)™; AAFP
Prescribed credit(s)
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
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Prescribed credit(s)
A Patient With Treatment-Resistant Depression
View Activity | View/Print Certificate
Medscape 01/15/09 AMA PRA Category 1
Credit(s)™
0.25
A 66-Year-Old Man With Bilateral Nontender
Neck Masses
View Activity | View/Print Certificate
Medscape 01/15/09 AMA PRA Category 1
Credit(s)™
0.25
ACR 2008: RA and Biologics: Lipids and
Cardiovascular Disease, Managing Adverse
Events, and Impact on Patient Outcomes
View Activity | View/Print Certificate
Medscape 01/08/09 AMA PRA Category 1
Credit(s)™
1.00
ACR 2008: Immune Inflammatory Diseases and
Related Conditions: Latest Advances
View Activity | View/Print Certificate
Medscape 01/08/09 AMA PRA Category 1
Credit(s)™
1.25
ACAAI 2008: Update on Anaphylaxis
View Activity | View/Print Certificate
Medscape 01/08/09 AMA PRA Category 1
Credit(s)™
0.25
A 30-Year-Old Woman With Fever and a Rash
View Activity | View/Print Certificate
Medscape 01/08/09 AMA PRA Category 1
Credit(s)™
0.25
Coadministration of Naloxone With Opioid
Medications? A Best Evidence Review
View Activity | View/Print Certificate
Medscape 01/07/09 AMA PRA Category 1
Credit(s)™
0.25
Knowledge and Attitudes of Primary Care
Physicians in the Management of Patients at
Risk for Cardiovascular Events
View Activity | View/Print Certificate
Medscape 01/06/09 AMA PRA Category 1
Credit(s)™
0.50
There Was a Young Man Who Swallowed a
Nail...Perhaps He'll Die
View Activity | View/Print Certificate
Medscape 01/06/09 AMA PRA Category 1
Credit(s)™
0.25
Prostate Cancer Screening -- More Harm than
Good? A Best Evidence Review
View Activity | View/Print Certificate
Medscape 01/06/09 AMA PRA Category 1
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
View Activity | View/Print Certificate
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*)
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