Matthew Bremmer, MD; Marcia S. Driscoll, MD, Th e skin disorders of : PharmD; Richard Colgan, MD Department of A family physician’s guide Residency Program (Dr. Bremmer); Department of Dermatology, (Dr. Driscoll); Learn which dermatoses you can manage yourself, Department of Family Medicine (Dr. Colgan), and which will require a referral. University of Maryland School of Medicine, Baltimore [email protected]

The authors reported no potential confl ict of interest relevant to this article.

PRACTICE he dermatoses of pregnancy are a poorly understood RECOMMENDATIONS group of dermatologic conditions. Th e only thing they have in common is a tendency to appear during preg- › Pemphigoid gestatio- T nancy. nis is best managed with Only 3 are considered unique to pregnancy, however; the oral prednisone at doses from 20 to 60 mg per day others are probably exacerbations of preexisting conditions to control symptoms. B triggered by pregnancy. Th ere isn’t even complete agreement on what to call them. And to make management even more › Th e pruritus associated complex, 2 patients—the mother and the —need to be with pruritic urticarial pap- considered. ules and plaques of preg- nancy can be safely and Who will manage these patients is another matter. Th ese eff ectively managed with conditions fall into an overlapping area of health care, where topical corticosteroids and family physicians, obstetricians, and dermatologists all have oral antihistamines. A some share in the responsibility for diagnosis and treatment. › Treat intrahepatic cho- As a family physician who probably cares for any number of lestasis of pregnancy with pregnant patients on a weekly basis, you need to be suffi cient- ursodeoxycholic acid, which ly familiar with these conditions so that you can diff erentiate likely reduces serum bile acids those that can be treated symptomatically and those that re- as well as associated fetal quire a referral to a specialist. Th is review and handy TABLE will morbidity and mortality. B help you toward that end.

Strength of recommendation (SOR)

A Good-quality patient- oriented evidence Dermatoses unique to pregnancy B Inconsistent or limited-quality Pemphigoid gestationis patient-oriented evidence Years ago, this disorder was referred to as herpes gestationis, C Consensus, usual practice, opinion, disease-oriented because the lesions are herpetiform. Pemphigoid gestationis evidence, case series (PG) has an incidence of approximately 1 in 10,000 pregnan- cies.1,2 Th e time of onset is usually about the 21st week of ges- tation, although in about 20% of cases, the eruption appears immediately postpartum.3 ❚ Presentation. Th e disease usually begins with urticarial papules and plaques around the umbilicus and extremities. Bullous lesions tend to develop as the disease progresses, and are often not present on fi rst presentation FIGURE( 1). PG lesions tend to spare the face, palms, and soles. Mucosal

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89_JFP0210 89 1/20/10 12:45:27 PM TABLE Skin disorders of pregnancy: What you’ll see, how to treat

Disorder Lesions Diagnosis and sequelae Treatment Recurrence

PG3,5 Erythematous papules, pro- Mean onset at 21 weeks; Oral corticosteroids Frequent. Skips gressing to vesicles, bullae; postpartum in 20% of cases. 20-60 mg/d, IVIG, or a pregnancy 8% periumbilical distribution, Direct immunofl uorescence cyclosporine in refractory of the time sparing face, palms, and microscopy shows linear C3 cases soles deposition. Newborn may be small for gestational age, but no associated morbidity or mortality

PUPPP8-10 Urticarial papules and Usually present after 34th Topical steroids Uncommon plaques on abdomen, legs, week, but can present at any and antihistamines arms, buttocks, chest, and stage. Diagnosis is clinical. back No increase in fetal morbidity or mortality

ICP14,17,19-22 No primary lesions; second- Onset after 30th week in Ursodeoxycholic acid Frequent ary excoriations in any area 80% of patients. Strongly 450-1200 mg/d patient can reach indicated by serum bile acid >11 mcmol/L. Increased fetal mortality

EP/PP4,10,24 Grouped, crusted erythema- Onset at any point in Symptomatic treatment Frequent tous papules, patches, and pregnancy. Clinical diagnosis. with topical steroids or plaques, most commonly on No increase in fetal antihistamines extensor surfaces of arms morbidity or mortality and legs or on abdomen

APPP27-29 Erythematous plaques and Onset at any point in preg- Prednisone 15-60 mg/d, Unknown pustules starting on inner nancy. Clinical diagnosis by cyclosporine 100 mg thighs and groin and appearance of lesions and twice daily in refractory spreading to trunk association with systemic cases, management of and extremities illness. Increased incidence associated hypocalcemia of and , and maternal mortality

PFP24,29 Papules and pustules Onset most often in third Topical steroids Unknown concentrated around hair trimester. Clinical diagnosis. follicles, often beginning on No associated fetal morbidity abdomen and spreading to or mortality extremities

APPP, acute pustular psoriasis of pregnancy; EP/PP, eczema of pregnancy/pruritus of pregnancy; ICP, intrahepatic cholestasis of pregnancy; IVIG, intravenous im- munoglobulin; PFP, pruritic folliculitis of pregnancy; PG, pemphigoid gestationis; PUPPP, pruritic urticarial papules and plaques of pregnancy.

surfaces are involved in less than 20% of cases. common target of several subepidermal blis- In about 75% of cases, PG fl ares around the tering diseases. time of delivery, regressing spontaneously af- ❚ Differential. Disorders that may have ter the baby is born.4 some of the same features as PG include ❚ Pathophysiology. Th e pathophysiology pruritic urticarial papules and plaques of is nearly identical to that of bullous pemphi- pregnancy (PUPPP), erythema multiforme, goid, a blistering skin disorder more often intrahepatic cholestasis of pregnancy (ICP), seen in elderly patients.5 Pemphigoid dis- contact , and drug reactions. orders are immune processes, involving an ❚ Diagnosis. A biopsy is necessary for immunoglobulin G (IgG) immune response the defi nitive diagnosis. Direct immuno- directed at a 180-kDa hemidesmosome trans- fl uorescence (DIF) microscopy of a sample membrane glycoprotein. Th is protein is the of perilesional skin can show tissue-bound

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FIGURE 1 FIGURE 2 Pemphigoid gestationis Pruritic urticarial papules and plaques of pregnancy FIGURES 1 AND 2 COURTESY OF: RICHARD P. USATINE, MD

immunoreactants. Linear deposition of the ing vesicles and bullae in the newborn.8 An The pruritus complement component protein C3 along increased incidence of small-for-gestational associated with the basement membrane zone is diagnostic age (SGA) infants has also been noted in PG, pemphigoid for PG. IgG is also deposited about 40% of the although no lasting morbidity or mortality in gestationis can time.3 Serum enzyme-linked immunosorbent the off spring has been noted.5 Th is disease interfere with assay (ELISA) studies are also helpful in di- tends to recur with future , but the patient’s agnosis. Th ey have excellent sensitivity and will skip a pregnancy 8% of the time.5 ability to sleep. specifi city, as well as the capacity to monitor levels of antibody, which correlate with the se- Pruritic urticarial papules verity of disease.1 and plaques of pregnancy ❚ Treatment. Oral corticosteroids are Th is condition is known by many names be- the fi rst-line treatment for PG, typically 20 to sides PUPPP: polymorphic eruption of preg- 60 mg per day of prednisone. Oral corticoste- nancy, toxemic erythema of pregnancy, and roids are typically most eff ective in amelio- late prurigo of pregnancy.1 It is a pruritic, in- rating the patient’s symptoms. Prednisone at fl ammatory skin disorder that has been vari- doses of 40 to 80 mg per day for a short time ously estimated to occur in anywhere from 1 has not been associated with congenital ab- in 120 to 1 in 240 pregnancies.8 PUPPP is sec- normalities.6 PG patients can also be treated ond only to eczema as the most common der- successfully with intravenous immunoglob- matosis of pregnancy. ulin (IVIG) and cyclosporine in refractory ❚ Presentation. As the name implies, the cases.7 lesions of PUPPP are itchy, red papules that Pruritus associated with this condition often coalesce into plaques (FIGURE 2). Th e can interfere with day-to-day activity and with lesions usually occur in primigravidas after the patient’s ability to sleep. Patients may also the 34th week of gestation, although they may complain that the rash is painful, particularly be seen at any time from the fi rst trimester if bullae rupture, leading to superfi cial ulcer- through the .9 ations. Fortunately, the patient’s quality of life Lesions are classically found on the ab- can be dramatically improved with systemic domen, sparing the umbilical area, and are corticosteroids—with no signifi cant risk to the found primarily in the striae. Th is distribution fetus. helps to diff erentiate PUPPP from PG, where ❚ Sequelae. PG uniformly resolves within the lesions typically cluster around the umbi- a few weeks, but the mother’s autoantibodies licus. Most PUPPP lesions (80% in 1 study) are can passively be transferred to the fetus, caus- dispersed on the abdomen, legs, arms, but-

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91_JFP0210 91 1/20/10 12:45:34 PM tocks, chest, and back. Another 17% appear FIGURE 3 only on the abdomen and proximal thighs, Intrahepatic cholestasis and the remaining 3% on the limbs.10 Nearly of pregnancy 50% of the time, lesions also include discrete vesicles.11 Th ere are no reported cases of mu- cosal involvement. Patients with this condition are often very uncomfortable. Th e associated pruritus is se- vere enough to interfere with sleep. Despite the itching, however, lesions are seldom exco- riated. ❚ Pathophysiology. Th e disorder has been strongly associated with maternal weight gain and multiple gestations. One working hypothesis is that rapid abdominal disten- tion observed in the third trimester leads to damage of the connective tissue, which then releases antigenic molecules, causing an in- fl ammatory reaction.12 Another hypothesis is Given the that increased levels of fetal DNA that have diphenhydramine has the more proven safety signifi cant fetal been detected in the skin of PUPPP patients profi le in pregnancy. mortality may contribute to the pathology. One study Nonpharmacologic treatments such as associated with detected male DNA in 6 of 10 PUPPP suff er- oil baths and emollients should also be con- intrahepatic ers, but found none in any of 26 controls— sidered. If the condition appears classic for cholestasis of pregnant women without PUPPP pathology.5 PUPPP, it can be managed symptomatically. pregnancy, the Th ere is some evidence that patients with at- However, if there is any question about the di- condition should opy may be predisposed to PUPPP, as well as agnosis, referral to a dermatologist is prudent. be managed patients who are hypertensive or obese.10,13 ❚ Sequelae. No increase in maternal or by a clinician ❚ Differential. Initially, PUPPP lesions fetal morbidity or mortality is associated with experienced in can be diffi cult to diff erentiate from urticarial PUPPP. Recurrence is fairly uncommon, as treating the PG lesions. Th e distribution of the lesions is the disease primarily aff ects women during disease, likely the best clue: PG lesions cluster around the their fi rst pregnancy. a gastroenter- umbilicus, whereas PUPPP lesions uniformly ologist. spare the umbilical area. Additional disorders Intrahepatic cholestasis of pregnancy in the PUPPP diff erential are atopic dermati- Th is condition is also called recurrent or id- tis, superfi cial urticarial allergic eruption, viral iopathic jaundice of pregnancy, obstetric exanthema, and contact or irritant dermatitis. cholestasis, and pruritus gravidarum. ICP is ❚ Diagnosis. PUPPP can only be diag- caused by disruption of hepatic bile fl ow dur- nosed through clinical observation. None ing pregnancy. It has been recorded at a rate of of the available laboratory tests—immuno- approximately 10 to 150 per 10,000 pregnan- fl uorescence, histology, serology—yield fi nd- cies in Europe and 70 per 10,000 in the United ings specifi c for PUPPP, although histology States.12 In 80% of patients, the time of onset and immunofl uorescence can readily diff er- is after the 30th week.14 Although this disorder entiate between this condition and PG. is not primarily a dermatosis of pregnancy, it ❚ Treatment. Because the disease holds is a pruritic condition that often presents with no real danger for mother or fetus, treatment excoriations in pregnant women and is asso- can be aimed solely at symptomatic relief. Mild ciated with fetal morbidity and mortality. It’s to potent topical steroids (consider triamcino- important to be able to identify this disease lone or fl uocinonide) should relieve pruritus early to minimize sequelae. within 48 to 72 hours.8 Antihistamines and ❚ Presentation. Th ere are no primary le- occasionally low-dose systemic steroids may sions with ICP. Th e primary presenting symp-

also be used. Consider hydroxyzine, although tom is a generalized pruritus aff ecting the MD USATINE, OF: RICHARD P. FIGURE 3 COURTESY

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palms and soles, and sometimes extending to Elective delivery is indicated for ICP, the legs and abdomen (FIGURE 3). Th is itch- particularly in patients with signifi cant clini- ing is often so severe that it leads to chronic cal presentations.12 Delivery for ICP should insomnia. You may see secondary skin le- be performed around week 37 to 38, as still- sions, such as erythema and excoriations. births tend to cluster around weeks 37 to 39.14 Observable jaundice occurs in 10% to 20% of Given the signifi cant fetal mortality associated patients.3 Th ese patients do not develop the with this condition (see below), ICP should be encephalopathy that is associated with cho- managed by a clinician experienced with the lestasis in the nonpregnant state, however.14 disease, likely a gastroenterologist. ❚ Pathophysiology. Th e genesis of this ❚ Sequelae. Th e impact of this maternal condition is thought to be a combination of disorder on the fetus can be disastrous: a 10% genetic and environmental factors. A family to 15% rate of perinatal death, and a 30% to history of the disorder is present in half the 40% rate of premature labor have been seen cases, and cases with a familial component with ICP.14 Fortunately, rates of preterm labor tend to be more severe.15 ICP may be an exag- are strongly correlated with levels of bile ac- gerated response to increased estrogen levels ids, so that as bile acid levels are reduced with in pregnancy, but the mechanism of this re- UDCA treatment, rates of preterm labor also sponse is unknown.16 go down. Currently, management of the con- ❚ Differential. Other conditions that must dition has reduced rates of perinatal death to be considered in making the diagnosis are vi- 3.5%. Th ere is no evidence of fetal growth re- If the ral hepatitis, gallbladder disease, PG, PUPPP, tardation.14 progression of drug hepatotoxicity, primary biliary cirrhosis, acute pustular and uremia. psoriasis of ❚ Diagnosis. Laboratory values are the Dermatoses triggered by pregnancy pregnancy is defi nitive diagnostic tool in this condition. In- Eczema of pregnancy/prurigo judged serious creased serum bile acids are the single most of pregnancy enough, early sensitive test. Average levels of serum bile Eczema of pregnancy/prurigo of pregnancy induction of acids in pregnancy are 6.6 mcmol/L, with an (EP/PP) may not actually be correlated with labor is upper limit of 11. Th e average value in women the pregnant state. Both conditions manifest indicated. with ICP is 47 mcmol/L.17 as eczematous lesions in an atopic distribu- While serum acids remain the gold stan- tion. Although they have been described in dard, a recent study showed elevated urine the literature as separate entities, the lack bile acids to have 100% sensitivity and 83% of clinical distinction between them led specifi city for ICP.18 In 55% to 60% of cases, Ambros-Rudolph and colleagues to combine the liver enzymes aspartate aminotransferase them under the umbrella term, atopic erup- (AST) and alanine aminotransferase (ALT) are tion of pregnancy.23 In some patients, at least, mildly increased. Steatorrhea is often noted they may be preexisting conditions that preg- by the patient, and is followed by vitamin K nancy exacerbates. One study of 255 patients defi ciency.17 with the condition found that 20% had had ❚ Treatment. Th e current standard of care the lesions before they became pregnant.23 for ICP is treatment with ursodeoxycholic acid However, the tendency of the condition to be (UDCA). In 4 controlled trials, UDCA showed markedly worsened by pregnancy leads us to a sustained decrease in serum bile acids.19-22 include it here. Doses used in these trials have varied between PP has an estimated incidence of 1 in 450 450 and 1200 mg per day. pregnancies.11 But while many authorities Before UDCA treatment was available, consider EP to be the most common derma- the disorder was treated with cholestyramine, tosis of pregnancy, no clear estimation of its which could bring about a 70% rate of re- prevalence has been established.23,24 Taken sponse. Th e drawback to cholestyramine treat- together, these 2 conditions have the highest ment is that it precipitates vitamin K, which is prevalence of all pregnancy-induced derma- already compromised by the disease process. toses. PP is also known as popular dermatitis Further, its onset of action is slow.3 of Spangler, Nurse’s early prurigo of pregnan-

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93_JFP0210 93 1/21/10 1:53:50 PM FIGURE 4 ❚ Treatment. Th ese conditions are treated Eczema of pregnancy symptomatically with topical steroids or sys- temic antihistamines. ❚ Sequelae. No maternal or fetal increase in morbidity or mortality is associated with these conditions.

Acute pustular psoriasis of pregnancy Whether or not APPP is actually a pregnancy- induced dermatosis is subject to debate. Th ere is evidence that APPP is not unique to pregnancy, but is simply a manifestation of ordinary psoriasis. Clinically and histologi- cally, APPP is indistinguishable from pustular

FIGURE 5 psoriasis. Unlike most cases of acute psoriasis, . 2003;28(5):22-26. Pruritic folliculitis however, APPP often appears in pregnancy of pregnancy without any personal or family history of pso- riasis, and usually ceases when the pregnancy is concluded. Th is fact, combined with reports FEMALE PATIENT of increased fetal and maternal morbidity and mortality associated with APPP, lead us to in- clude it here.27 ❚ Presentation. APPP is a rare condition that may have an onset at any point in preg- nancy. Th e characteristic lesions begin as ery- thematous plaques with pustules on the inner thighs, fl exural areas, and groin and spread to the trunk and extremities. As the plaques en- large, the center becomes eroded and crusted. Nails may become onycholytic. Th e hands,

feet, and face are usually spared. Oral and OF PREGNANCY. GALARIA NA, MERCURIO MG. DERMATOSES esophageal erosions can occur. Pruritus is typ- cy, and linear IgM disease of pregnancy.3,23,25 ically mild, although the lesions are often pain- ❚ Presentation. Th e typical presentation ful and fl u-like symptoms are often present.28

consists of grouped, crusted, erythematous ❚ Pathophysiology. Th e pathophysiology THE FEMALE PATIENT. papules, patches, and plaques—frequently of this disease is unknown. with excoriations. Th e lesions typically pres- ❚ Differential. Conditions with similar ent on the extensor surfaces of the arms and presentations include an adverse drug reac- legs or on the abdomen (FIGURE 4).4 Recur- tion, pityriasis rosea, lichen simplex chronicus, rence in later pregnancies is common. eczema, lupus, and pityriasis rubra pilaris. ❚ Pathophysiology. Th e pathophysiology ❚ Diagnosis. Clinical history and associa- of EP/PP is not understood. Many patients who tion with systemic illness are the basis for a di- present with EP/PP have a history of atopy.10 agnosis of APPP. Cultures of the pustules are ❚ Differential. Conditions that need to negative for any infective pathology, though as be considered in making the diagnosis include the disease progresses, pustules may become tinea infection, scabies, contact dermatitis, ICP, superinfected. Lab tests may show an in- pruritic folliculitis of pregnancy (PFP), and PG. creased erythrocyte sedimentation rate (ESR), ❚ Diagnosis. History and physical ex- hypocalcemia, and low levels of vitamin D. amination determine the diagnosis. Serology, ❚ Treatment. Prednisone 15 to 60 mg per histopathology, and immunofl uorescence are day is often suffi cient to control the disease.28 not specifi c, and correlation with increased Cyclosporine 100 mg twice daily has also been 24,26 29

IgE is marginal, at best. shown to be useful. Cyclosporine in pregnan- OF: PHOTO RESEARCHERS. FIGURE 5 USED WITH PERMISSION OF FIGURE 4 COURTESY

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cy is a category C drug. Data on fetal malforma- all of the literature, while others indicate that tion associated with cyclosporine therapy are the prevalence is equivalent to that of PG, limited, but the risk appears to be minimal.6 1 in 10,000.3,11 PFP most commonly presents Maternal hypocalcemia should be monitored in the third trimester. It often resolves before and treated appropriately. If disease progres- delivery, but uniformly clears within 2 weeks sion is judged serious enough, early induction of delivery. of labor is indicated, since delivery will almost ❚ Presentation. PFP presents as papules always lead to swift resolution. and pustules concentrated around hair fol- ❚ Sequelae. Th ere have been a number of licles (FIGURE 5). Often lesions begin on the case reports that link APPP to serious sequelae, abdomen and spread to the extremities.24,29 including fetal growth retardation, hypocalce- Th e condition is often, but not always, pru- mia, and stillbirth.28,30,31 Th e condition is too ritic. Patients are more likely to be concerned rare, however, for good data on specifi c se- about what the condition means for their quelae. While the disease does give signifi cant health, rather than being distressed by the cause for concern, it would appear that some of symptoms. the traditional apprehension comes from older ❚ Pathophysiology. Like so many of publications reporting a rate of maternal mor- these conditions, the pathophysiology of PFP tality of 70% to 90%.32 Th is statistic has not been is unknown. Th ere is little evidence that the borne out in clinical practice. It does appear condition is immunologically or hormonally that the mother will frequently suff er from sys- mediated, and there is no evidence of an in- temic symptoms, including fever and malaise. fectious component.24,29 ❚ Differential. PFP must be distinguished Pruritic folliculitis of pregnancy from infectious folliculitis, acneiform disor- Accounts of PFP’s prevalence vary widely: ders, HIV-associated eosinophilic folliculitis, Some sources report fewer than 30 cases in and a drug reaction. CONTINUED

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Faculty Click on CME/Supplements/Newsletters at jfponline.com. Or, visit • William D. Chey, MD, FACG (Chair) http://www.jfponline.com/ • Richard H. Davis, Jr, PA-C supplements.asp?id=7581

• Margaret M. Heitkemper, PhD, RN, FAAN This activity was submitted by DIME and the Duke University School of Medicine and supported by an independent educational grant from Sucampo Pharmaceuticals, Inc., and Takeda Pharmaceuticals North America, Inc.

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95_JFP0210 95 1/20/10 12:45:55 PM ❚ Diagnosis. Th e clinical diagnosis is based wash can be eff ective. on presenting symptoms and third trimester ❚ Sequelae. One study reports an in- onset. No specifi c lab or histological analysis creased incidence of low birth weight, but cur- can be used to make a defi nitive diagnosis. rently no associated morbidity or mortality has ❚ Treatment. As the condition is, by defi - been reported.24 nition, a nonmicrobial folliculitis, the most eff ective therapy tends to be with mid- to low- CORRESPONDENCE Matthew Bremmer, MD, 419 W Redwood Street, Depart- potency topical steroids such as triamcinolone ment of Dermatology, Baltimore, MD 21230; Mbrem001@ or desonide. Additionally, benzoyl peroxide umaryland.edu

References

1. Cassian S, Powell J, Messer G, et al. Immunoblotting and enzyme- 18. Huang WM, Seubert DE, Donnelly JG, et al. Intrahepatic cholesta- linked immunosorbent assay for the diagnosis of pemphigoid sis of pregnancy: detection with urinary bile acid assays. J Perinat gestationis. Obstet Gynecol. 2004;103:757-763. Med. 2007;35:486-491. 2. Engineer L, Bohl K, Ahmed AR. Pemphigoid gestationis: a review. 19. Palma J, Reyes H, Ribalta J, et al. Ursodeoxycholic acid in the Am J Obstet Gynecol. 2000;183:483-491. treatment of intrahepatic cholestasis of pregnancy: a random- 3. Kroumpouzos G, Cohen LM. Specifi c dermatoses of pregnancy: ized, double blind study controlled with placebo. J Hepatol. 1997; an evidence based systematic review. Am J Obstet Gynecol, 27:1022-1028. 2003;188:1083-1092. 20. Diaferia A, Nicastri PL, Tartagni M, et al. Ursodeoxycholic acid 4. Shornick JD. Dermatoses of pregnancy. Semin Cutan Med Surg. therapy in pregnant women with cholestasis. Int J Gynaecol 1998;17:172-181. Obstet. 1996;52:133-140. There is little 5. Shornick JK, Bangert JL, Freeman RG, et al. Herpes gestationis: 21. Nicastri PL, Diaferia A, Tartagni M, et al. A randomised placebo- evidence that clinical and histological features in 28 cases. J Am Acad Dermatol. controlled trial of ursodeoxycholic acid and S-adenosylmethio- 1983;8:214-224. nine in the treatment of intrahepatic cholestasis of pregnancy. Br J Obstet Gynaecol. 1998;105:1205-1207. pruritic 6. Leachman S, Reed B. Th e use of dermatologic drugs in pregnancy folliculitis of and lactation. Dermatol Clin. 2004;24:167-197. 22. Glantz A, Marschall HU, Lammert F, et al. Intrahepatic cholesta- sis in pregnancy: a randomized controlled trial comparing dexa- 7. Hern S, Harman K, Bhogal BS, et al. A severe persistent case of methasone and ursodeoxycholic acid. Hepatology. 2005;42:1399- pregnancy is pemphigoid gestationis treated with intravenous immunoglobu- 1405. immunologically lins and cyclosporine. Clin Exp Dermatol. 1998;23:185-188. 8. Fitzpatrick TP. Diseases in pregnancy. Color Atlas and Synopsis of 23. Ambros-Rudolph CM, Mullegger MM, Vaughan-Jones SA, et al. or hormonally Clinical Dermatology. New York, NY: McGraw Hill; 1997:414-419. Th e specifi c dermatoses of pregnancy revisited and reclassifi ed: results of a retrospective two-center study on 505 pregnant pa- mediated, 9. Aractingi D, Berkane N, Bertheau P, et al. Fetal DNA in skin of poly- tients. J Am Acad Dermatol. 2006;54:395-404. morphic eruptions of pregnancy. Lancet. 1998;352:1898-1901. and there is no 24. Vaughan-Jones SA, Hern S, Nelson-Piercy C, et al. A prospective 10. Rudolph CM, Al-Fares S, Vaughan-Jones SA, et al. Polymorphic study of 200 women with dermatoses of pregnancy correlating evidence of eruption of pregnancy: clinicopathology and potential trigger fac- clinical fi ndings with hormonal and immunopathological pro- an infectious tors in 181 patients. Clin Lab Invest. 2006;154:54-60. fi les.Br J Dermatol. 1999;141:71-81. 11. Roger D, Vaillant L, Fignon A, et al. Specifi c pruritic diseases of 25. Shornick JK. Dermatoses of pregnancy. Semin Cutan Med Surg. component. pregnancy. A prospective study of 3192 pregnant women. Arch 1998;17:172-181. Dermatol. 1994;130:734-739. 26. Holmes RC, Black MM. Th e specifi c dermatoses of pregnancy. J 12. McDonald J. Cholestasis of pregnancy. J Gastroenterol Hepatol. Am Acad Dermatol. 1983;8:405-412. 1999;14:515-518. 27. Bukhari IA. in a primagravida: success- 13. Ohel I, Levy A, Silberstein T, et al. Pregnancy outcome of pa- ful treatment with etretinate. J Drugs Dermatol. 2004;3:449- tients with pruritic urticarial papules and plaques of pregnancy. J 451. Maternal-Fetal Neonat Med. 2006;19:305-308. 28. Oumeish OY, Parish JL. Impetigo herpetiformis. Clin in Dermatol. 14. Geenes V, Williamson C. Intrahepatic cholestasis of pregnancy. 2006;24:101-104. World J Gastroenterol. 2009;15:2049-2066. 29. Kroumpouzos G, Cohen LM. Pruritic folliculitis of pregnancy. J 15. Shaw D, Frohlich J, Wittmann BA, et al. A prospective study of Am Acad Dermatol. 2000;43:132-134. 18 patients with cholestasis of pregnancy. Am J Obstet Gynecol. 1982;142:621-625. 30. Sahin HG, Hasin HA, Metin A, et al. Recurrent impetigo her- 16. Reyes H. Th e spectrum of liver and gastrointestinal disease petiformis in a pregnant adolescent: a case report. Eur J Obstet seen in cholestasis of pregnancy. Gastroenterol Clin North Am. Gynecol Reprod Endocrinol. 2002;101:201-203. 1992;21:905-921. 31. Aka N, Kuscu NK, Yazicioglu E. Impetigo herpetiformis at the 36th 17. Lammert F, Marschall H, Glantz A, et al. Intrahepatic cholestasis week of gestation. Int J Gynecol Obstet. 2000;69:153-154. of pregnancy; molecular pathogenesis, diagnosis and manage- 32. Wade TR, Wade SL, Jones HE. Skin changes and diseases associ- ment. J Hepatol. 2000;33:1012-1021. ated with pregnancy. Obstet Gynecol. 1978;52:233-242.

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