# Pregnancy Dermatoses

## Introduction

Pregnancy induces significant immunologic, hormonal, and metabolic changes that affect the skin. Pregnancy-specific dermatoses are a group of conditions that occur exclusively during pregnancy or the immediate postpartum period. Accurate diagnosis is critical because some entities carry significant fetal risk while others are merely bothersome to the mother. This lecture covers physiologic skin changes, pregnancy-specific dermatoses, and management considerations unique to the pregnant patient.

## Physiologic Skin Changes in Pregnancy

### Pigmentary Changes

Hyperpigmentation occurs in more than 90% of pregnancies and is most prominent on the areolae, linea alba (which becomes the linea nigra), axillae, and genitalia. Melasma, also known as chloasma, produces symmetric brown-gray facial pigmentation affecting the malar, centrofacial, or mandibular areas. Estrogen and progesterone stimulate melanogenesis, and the condition is worsened by UV exposure. Darkening of pre-existing nevi is common and benign, though any nevus with ABCDE features warrants biopsy.

### Hair and Nail Changes

An increased anagen phase during pregnancy prolongs the growth phase and leads to thicker hair. Telogen effluvium follows 2 to 4 months postpartum as synchronized anagen hairs enter telogen, causing massive hair shedding that is self-limiting over 6 to 12 months. Nail changes include brittleness, transverse grooving, onycholysis, and distal separation.

### Vascular Changes

Spider angiomas are estrogen-mediated, occur in an upper body distribution, and resolve postpartum. Palmar erythema develops in up to 70% of pregnancies. Varicose veins result from increased venous pressure, often in the lower extremities and vulva. Non-pitting edema is physiologic in late pregnancy. Pyogenic granuloma, also known as pregnancy epulis, is a lobular capillary hemangioma common on the gingiva that may regress postpartum.

### Connective Tissue Changes

Striae gravidarum (stretch marks) affect 50 to 90% of pregnancies, appearing as pink or violaceous linear bands on the abdomen, breasts, and thighs that become pale and atrophic postpartum. Genetic susceptibility plays a major role, and no consistently effective prevention has been established.

## Pregnancy-Specific Dermatoses

### Pemphigoid Gestationis (PG, formerly Herpes Gestationis)

#### Pathogenesis

Pemphigoid gestationis is an autoimmune bullous disease in which IgG autoantibodies target BP180 (type XVII collagen) at the basement membrane zone, the same target as bullous pemphigoid. It is associated with HLA-DR3 and HLA-DR4. Cross-reactivity between placental tissue, which expresses MHC class II antigens, and the skin basement membrane zone drives the autoimmune response.

#### Clinical Features

Onset typically occurs in the second or third trimester, with possible flare peripartum. It begins with intensely pruritic, urticarial papules and plaques around the periumbilical area and progresses to tense vesicles and bullae. The face and mucous membranes are spared in most cases. The condition recurs with subsequent pregnancies, often earlier and more severely, and with oral contraceptive use.

#### Diagnosis

Direct immunofluorescence of perilesional skin shows linear C3 deposition at the basement membrane zone, the most consistent finding, with IgG also present. Indirect immunofluorescence demonstrates the HG factor, an IgG1 that fixes complement at the BMZ. ELISA detects anti-BP180 NC16A domain antibodies. Histology shows a subepidermal blister with eosinophilic infiltrate, similar to bullous pemphigoid.

#### Fetal Risk

Some studies report small-for-gestational-age infants and prematurity. Neonatal pemphigoid gestationis occurs in 5 to 10% of cases, causing transient blistering from transplacental transfer of maternal IgG that self-resolves within weeks.

#### Management

Mild cases respond to potent topical corticosteroids and oral antihistamines. Moderate-to-severe cases require systemic corticosteroids, typically prednisone at 0.5 mg/kg/day with tapering as tolerated. Refractory cases may warrant IVIG, plasmapheresis, or rituximab (postpartum). Close obstetric monitoring for fetal growth is essential.

<image>Clinical photograph of pemphigoid gestationis showing periumbilical urticarial plaques with tense vesicles and bullae, alongside direct immunofluorescence image showing linear C3 deposition at the basement membrane zone</image>

### Atopic Eruption of Pregnancy (AEP)

AEP is the most common pregnancy dermatosis, accounting for approximately 50% of pregnancy-specific dermatoses. It encompasses the former entities of eczema of pregnancy, prurigo of pregnancy, and pruritic folliculitis of pregnancy. Onset typically occurs in the first or second trimester, earlier than other pregnancy dermatoses. Two-thirds of affected women have no prior atopic history, while one-third have pre-existing eczema that flares.

Two clinical types are recognized. The E-type (eczematous) follows a typical atopic dermatitis distribution affecting flexural areas, face, and neck. The P-type (papular/prurigo) produces disseminated papules and nodules on the trunk and extensor limbs.

Management includes emollients, mid-potency topical corticosteroids, and oral antihistamines (cetirizine and loratadine are preferred as pregnancy category B). Narrowband UVB phototherapy is safe in pregnancy for refractory cases. There is no fetal risk associated with AEP.

### Polymorphic Eruption of Pregnancy (PEP/PUPPP)

Also known as Pruritic Urticarial Papules and Plaques of Pregnancy (PUPPP), this is the second most common pregnancy-specific dermatosis. Onset occurs in the third trimester, most commonly in primigravidae, and is associated with excessive maternal weight gain, multiple gestations, and male fetus.

The eruption consists of intensely pruritic, urticarial papules and plaques beginning within striae on the abdomen. It characteristically spares the periumbilical area, in contrast to pemphigoid gestationis. It may spread to the thighs, buttocks, and arms but spares the face and palms. Importantly, PEP/PUPPP does not recur in subsequent pregnancies and carries no fetal risk.

Diagnosis is clinical; biopsy shows non-specific spongiotic dermatitis, and DIF is negative, which distinguishes it from pemphigoid gestationis. Treatment involves potent topical corticosteroids and oral antihistamines, with a short course of oral prednisone rarely needed. The condition resolves rapidly after delivery.

### Intrahepatic Cholestasis of Pregnancy (ICP)

ICP is the most important pregnancy dermatosis from a fetal standpoint. Onset occurs in the third trimester, and incidence varies by geography, being higher in Scandinavia, Chile, and Bolivia.

The hallmark is intense pruritus, often beginning on the palms and soles and then generalizing, worst at night. There is no primary skin lesion -- only secondary excoriations are found. Mild jaundice occurs in 10 to 20% of cases.

Diagnosis rests on elevated serum bile acids (greater than 10 micromol/L, with levels above 40 micromol/L indicating higher fetal risk), elevated transaminases (usually 2 to 10 times normal), and normal GGT (which distinguishes ICP from other cholestatic conditions).

Fetal risk is the defining concern: premature delivery, fetal distress, and intrauterine fetal death can occur, with risk increasing when bile acid levels exceed 40 micromol/L. Meconium staining and sudden fetal death from bile acid-induced cardiac arrhythmia in the fetus are recognized complications. Active obstetric management includes close fetal monitoring and consideration of early delivery at 37 weeks when bile acids exceed 40.

First-line treatment is ursodeoxycholic acid (UDCA) at 10 to 15 mg/kg/day, which improves pruritus and biochemical markers and may reduce fetal complications. Cholestyramine, a bile acid sequestrant, is less effective than UDCA and can impair fat-soluble vitamin absorption. Topical emollients and antihistamines provide symptomatic relief. Close obstetric surveillance with non-stress testing and biophysical profiles is essential.

<image>Diagnostic comparison chart of the four major pregnancy-specific dermatoses showing typical onset trimester, primary lesion morphology, distribution pattern, DIF findings, fetal risk level, and recurrence in subsequent pregnancies for pemphigoid gestationis, AEP, PEP/PUPPP, and intrahepatic cholestasis of pregnancy</image>

| Dermatosis | Typical Onset | Primary Lesion | Distribution | DIF | Fetal Risk | Recurrence |
|-----------|--------------|----------------|--------------|-----|-----------|------------|
| Pemphigoid gestationis | 2nd–3rd trimester | Urticarial plaques → vesicles/bullae | Periumbilical, spreading | Linear C3 at BMZ | SGA, prematurity, neonatal blisters (5–10%) | Yes (earlier/worse) |
| AEP | 1st–2nd trimester | Eczematous patches or papules/nodules | Flexural (E-type) or trunk/extensors (P-type) | Negative | None | Variable |
| PEP/PUPPP | 3rd trimester | Urticarial papules/plaques within striae | Abdomen (spares periumbilical), thighs | Negative | None | No |
| ICP | 3rd trimester | No primary lesion (excoriations only) | Generalized pruritus (palms/soles onset) | N/A | Premature delivery, fetal death, meconium | Yes (45–70%) |

## Drug Safety in Pregnancy

### Generally Safe

Topical corticosteroids in mild-to-moderate potency are preferred, with short courses of potent steroids acceptable. Oral antihistamines including cetirizine and loratadine (category B) are considered safe, though first-generation agents should be avoided if possible. Narrowband UVB phototherapy is safe throughout pregnancy. Systemic corticosteroids such as prednisone and prednisolone are largely inactivated by placental 11-beta-hydroxysteroid dehydrogenase.

### Contraindicated

Retinoids (isotretinoin, acitretin, tazarotene) are absolutely contraindicated as teratogens. Methotrexate is both an abortifacient and teratogen. Mycophenolate mofetil is teratogenic. Thalidomide causes phocomelia. Fluoroquinolones and tetracyclines carry fetal toxicity. PUVA (psoralen plus UVA) is avoided because psoralen is potentially mutagenic.

## Clinical Pearls

Periumbilical onset of urticarial plaques and vesicles suggests pemphigoid gestationis, and DIF should be checked for linear C3 at the BMZ. PEP/PUPPP starts within striae and spares the periumbilical area, the opposite distribution from pemphigoid gestationis. Intrahepatic cholestasis of pregnancy has no primary skin lesion -- only pruritus with excoriations -- and bile acids should be checked urgently because fetal risk is significant. AEP is the most common pregnancy dermatosis and typically presents earlier (first or second trimester) than other entities. Drug safety should always be verified before prescribing in pregnancy, as retinoids, methotrexate, and mycophenolate are absolutely contraindicated.

## References

1. Ambros-Rudolph CM, Mullegger RR, Vaughan-Jones SA, et al. The specific dermatoses of pregnancy revisited and reclassified: results of a retrospective two-center study on 505 pregnant patients. *J Am Acad Dermatol*. 2006;54(3):395-404.
2. Vaughan Jones SA, Hern S, Nelson-Piercy C, et al. A prospective study of 200 women with dermatoses of pregnancy correlating clinical findings with hormonal and immunopathological profiles. *Br J Dermatol*. 1999;141(1):71-81.
3. Williamson C, Geenes V. Intrahepatic cholestasis of pregnancy. *Obstet Gynecol*. 2014;124(1):120-133.
4. Chi CC, Wang SH, Charles-Holmes R, et al. Pemphigoid gestationis: early onset and blister formation are associated with adverse pregnancy outcomes. *Br J Dermatol*. 2009;160(6):1222-1228.