Dermatoses of Pregnancy


Article Author:
George Kurien


Article Editor:
Talel Badri


Editors In Chief:
Kranthi Sitammagari
Mayank Singhal


Managing Editors:
Avais Raja
Orawan Chaigasame
Carrie Smith
Abdul Waheed
Khalid Alsayouri
Trevor Nezwek
Radia Jamil
Patrick Le
Anoosh Zafar Gondal
Saad Nazir
William Gossman
Hassam Zulfiqar
Hussain Sajjad
Steve Bhimji
Muhammad Hashmi
John Shell
Matthew Varacallo
Heba Mahdy
Ahmad Malik
Sarosh Vaqar
Mark Pellegrini
James Hughes
Beata Beatty
Beenish Sohail
Nazia Sadiq
Hajira Basit
Phillip Hynes


Updated:
6/11/2019 11:05:18 AM

Introduction

Skin changes during pregnancy may be physiological. However, some dermatoses are specific to pregnancy, while others are altered by pregnancy. These changes occur as a result of an interaction of multiple factors in the body during pregnancy. The dermatoses which are specific to pregnancy include:[1]

  • Gestational pemphigoid (also known as pemphigoid gestationis)
  • Pruritic and urticarial papules and plaques of pregnancy (PUPPP, also known as pruritic eruption of pregnancy and toxemic rash of pregnancy)
  • Intrahepatic cholestasis of pregnancy
  • Impetigo herpetiformis 
  • Atopic eruption of pregnancy: encompasses atopic eczema in pregnancy, prurigo of pregnancy, as well as pruritic folliculitis of pregnancy in earlier classifications.

Etiology

Gestational pemphigoid is an autoimmune subepidermal blistering disease known to be associated almost exclusively with pregnancy. In pruritic urticarial papules and plaques of pregnancy (PUPPP), it is believed that stretching of the abdominal skin damages the underlying connective tissue leads to an inflammatory process. PUPPP is more common in pregnant women with twins or triplets. Impetigo herpetiformis is believed to be a type of pustular psoriasis triggered by pregnancy. Intrahepatic cholestasis of pregnancy is due to intrahepatic obstruction to bile flow occurring late in pregnancy in the absence of any hepatitis. Atopic eruption of pregnancy may occur in atopic subjects or others without atopy. The etiology is unknown. Many patients have elevated IgE.[2]

Epidemiology

Dermatoses of pregnancy is a condition seen throughout the world. It is more common in late pregnancy and those with twin or multiple pregnancies.

Pathophysiology

Gestational pemphigoid is an autoimmune disease, very similar to bullous pemphigoid, almost exclusively associated with pregnancy. It may also occur with trophoblastic tumors, hydatiform mole, or choriocarcinoma. Gestational pemphigoid also recurs following intake of oral contraceptive pills and during subsequent pregnancies. It develops during the second trimester as pruritic urticarial papules, plaques, and vesicles in the umbilical region and later spreads to other areas forming bullae. It remits before delivery and resolves completely in the weeks or months following delivery.

Pruritic urticarial papules and plaques of pregnancy (PUPP) is usually seen in preemies in last trimester or sometimes in the second trimester. The lesions first appear as striae and later spreads to breasts, arm, or thighs. Sparing of the periumbilical area is characteristic. The lesions may be vesicular, pregnancy targetoid, annular polycyclic papules, or plaques. Bullae are not seen.

Impetigo herpetiformis is thought to be related to the hormonal changes occurring in pregnancy. It usually occurs in the third trimester and is frequently associated with hypocalcemia.

Intrahepatic cholestasis of pregnancy is seen during pregnancy. It starts as pruritus without any primary skin lesions. Secondary skin lesions like linear excoriations, erosions, and scabbing may be present. There is no active hepatitis or intake of hepatotoxic drugs. It recurs during subsequent pregnancies.

Atopic eruption of pregnancy encompasses atopic eczema, prurigo of pregnancy, and pruritic folliculitis of pregnancy. In atopic eczema, the eczematous lesions appear during the first or second trimester. In the majority, lesions are in flexures-atopic sites, and in remaining, about one-third of the lesions are distributed to the trunk and limbs. In prurigo of pregnancy, groups of excoriated papules are seen in the limbs and trunk. In pruritic folliculitis of pregnancy, occurring in the second or third trimester, erythematous follicular papules resembling steroid induced acne are seen.[3]

Toxicokinetics

In gestational pemphigoid, the autoimmune process is activated by a breakdown of protective immunity of fetoplacental unit from maternal allogeneic recognition. The target antigen, BP 180 is found in the basement membranes of skin and the amniotic epithelium. This unusual self-antigen presentation results in a production of autoantibodies that react with collagen XVII in the skin.

In pruritic urticarial papules and plaques of pregnancy, stretching of abdominal skin damages underlying connective tissue leading to an inflammatory process.

Progesterone and hypocalcemia are believed to intervene in impetigo herpetiformis.

In intrahepatic cholestasis of pregnancy, without any parenchymal damage to the liver, obstruction to bile flow occurs within the liver, resulting in pruritus.

In an atopic eruption of pregnancy, elevated IgE is seen which may indicate that the atopic diathesis is reactivated.[4]

History and Physical

Gestational pemphigoid develops in the second or third trimester. It starts as urticarial papules, plaques, and vesicles in umbilical region. Later bullae develop which remit before delivery.  It may recur during subsequent pregnancies and on taking oral contraceptive pills.

Pruritic urticarial papules and plaques of pregnancy (PUPPP) usually present during the third trimester. Urticarial lesions involve striae and later breasts and thighs. PUPPP spares the periumbilical area. It is the most frequent specific pregnancy dermatosis.[3]

Impetigo herpetiformis is a generalized erythematous and pustular rash which is frequently febrile.

Intrahepatic cholestasis of pregnancy presents as a generalized pruritus in the third trimester. There are no primary skin lesions. Secondary lesions like excoriations, erosions, and scabbing are seen. Jaundice may or may not be present. Intrahepatic cholestasis of pregnancy may recur during subsequent pregnancies.

Atopic eruption of pregnancy presents as eczematous lesions in flexures seen in atopic eczema of pregnancy. In prurigo of pregnancy, groups of excoriated papules are seen in the limbs and trunk. In pruritic folliculitis, follicular papules resembling acneiform eruptions are seen. Lesions are not very symptomatic.

Evaluation

Tzanck smear, histopathology, and direct immunofluorescence study are helpful to confirm gestational pemphigoid.

PUPPP is mostly a clinical diagnosis.

In impetigo herpetiformis, hypocalcemia and neutrophilia are frequently observed. The diagnosis is based on histopathology which shows epidermal spongiform pustules. 

In intrahepatic cholestasis of pregnancy, serum total bile acid estimation is the single most sensitive test. Serum alkaline phosphatase may also be elevated in addition to bilirubin.

Serum IgE level may be raised in an atopic eruption of pregnancy.[4]

Treatment / Management

Systemic steroids may be required in gestational pemphigoid and impetigo herpetiformis. Antihistamines and topical steroids are all that is required in treating PUPPP and atopic eruption of pregnancy.

Ursodeoxycholic acid (UDCA) is currently the most effective pharmacologic treatment for intrahepatic cholestasis of pregnancy and has the most benefit for mother and fetus. UDCA 450-1200 mg/day reduces total bile acids in cord blood, colostrum, and amniotic fluid.[4][1]

Pearls and Other Issues

In gestational pemphigoid, though there is no statistically increased risk of fetal loss or premature labor. Small for gestational age babies are common. Impetigo herpetiformis may have serious consequences for the pregnant woman and her fetus and should be treated promptly. In intrahepatic cholestasis of pregnancy, there is an increased risk of fetal complications. Delivery at 37 weeks is associated with better outcomes. Fetal and maternal outcomes are not affected by PUPPP and atopic eruption of pregnancy.[5][4]

Enhancing Healthcare Team Outcomes

When women have skin changes during pregnancy, it is important to work as a multidisciplinary team because there are many causes of dermatosis. The primary care provider, nurse practitioner and obstetrician should seek a consult from a dermatologist before making any recommendations on treatment.

Systemic steroids may be required in gestational pemphigoid and impetigo herpetiformis. Antihistamines and topical steroids are all that is required in treating PUPPP and atopic eruption of pregnancy.

Ursodeoxycholic acid (UDCA) is currently the most effective pharmacologic treatment for intrahepatic cholestasis of pregnancy and has the most benefit for mother and fetus. UDCA 450-1200 mg/day reduces total bile acids in cord blood, colostrum, and amniotic fluid.[4]

The outcome of women with skin disorders of pregnancy are generally good with no adverse effect on the fetus.


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Dermatoses of Pregnancy - Questions

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A primipara in her third trimester presents with urticarial lesions on trunk and limbs. On examination, periumbilical area is spared. What is the probable diagnosis?



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What do the lesions of pruritic folliculitis of pregnancy resemble?



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Which of the following is not an atopic eruption of pregnancy?



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What are the cutaneous findings in intrahepatic cholestasis of pregnancy (ICP)?



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What is the first-line therapy for intrahepatic cholestasis of pregnancy?



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A pregnant woman in the second trimester of her second pregnancy complains of severe itchy rashes and vesicular lesions on the abdomen. She gives a history of similar illness during the first pregnancy and also while taking oral contraceptive pills. Examination shows urticarial papules and plaques and vesicles around the umbilicus. A few lesions are present in trunk and thigh. What is the most likely diagnosis, and what investigation is most appropriate to confirm it?



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A 35-year-old primigravid in her third trimester presents to the hospital complaining of generalized itching of 2 weeks duration. No family members have similar symptoms. The itching is present throughout the day. Physical examination shows no skin lesions except for excoriation marks all over and minimal jaundice. What is the most likely diagnosis, and what specific investigation is most likely to reveal the diagnosis?



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A 25-year-old lady in the second trimester of pregnancy presents to the clinic with multiple follicular papules on the trunk of 3 weeks duration. The lesions were mildly pruritic. The lesions resembled acne vulgaris, but comedones were absent. What is the most likely diagnosis, and what is its most likely effect on the fetus?



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A 26-year-old pregnant lady in the second trimester of her first pregnancy presents to the hospital with complaints of fever and pustular lesions on the body 1-week duration. It started in the flexures and later spread to other areas. She has no history of psoriasis or any significant dermatological illness. What is the most likely diagnosis and the treatment of choice?



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Dermatoses of Pregnancy - References

References

Maglie R,Quintarelli L,Verdelli A,Fabbri P,Antiga E,Caproni M, Specific dermatoses of pregnancy other than pemphigoid gestationis. Giornale italiano di dermatologia e venereologia : organo ufficiale, Societa italiana di dermatologia e sifilografia. 2018 Oct 29;     [PubMed]
Almeida FT,Sarabando R,Pardal J,Brito C, Pemphigoid gestationis successfully treated with intravenous immunoglobulin. BMJ case reports. 2018 Apr 7;     [PubMed]
Dominguez-Serrano AJ,Quiroga-Garza A,Jacobo-Baca G,De La Fuente-Villarreal D,Gonzalez-Ramirez RA,Vazquez-Barragan MA,Guzman-Lopez A,Elizondo-Omaña RE,Guzman-Lopez S, Polymorphic eruption of pregnancy in Mexico. International journal of dermatology. 2018 Dec 13;     [PubMed]
Bechtel MA, Pruritus in Pregnancy and Its Management. Dermatologic clinics. 2018 Jul;     [PubMed]
Hydrogen peroxide 40% (Eskata) for seborrheic keratoses. The Medical letter on drugs and therapeutics. 2018 Sep 24;     [PubMed]

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