Chapter 30. Dermatologic Disorders in Pregnancy

Essentials of Diagnosis

• Physiologic changes, especially endocrine processes, result in a variety of effects on the skin in pregnancy.
• Most common changes include hyperpigmentation, striae, vascular changes, and hair loss (postpartum).
• Many changes related to pregnancy resolve postpartum without treatment.

Pathogenesis

Immunologic, metabolic, vascular, and endocrine changes in pregnancy cause cutaneous changes in almost all pregnancies. Hyperpigmentation is related to increased levels of melanocyte-stimulating hormone, estrogen, and progesterone. Vascular changes are related to the effect of estrogen causing congestion, distention, and proliferation of blood vessels.

Prevention

Few interventions have been successful at preventing these changes, which occur as the result of physiologic processes. Judicious use of sunscreen may reduce the appearance of hyperpigmentation and melasma. Varicosities in the legs may be prevented by leg elevation, support hose, and avoiding prolonged sitting or standing.

Clinical Findings

Symptoms & Signs

Hyperpigmentation occurs in up to 90% of women, and it is more pronounced in women with darker skin tones. It is most frequently localized in the nipples, areolae, and axillae. The linea alba darkens to become the linea nigra, a dark linear streak on the midline of the abdomen.

Melasma, also known as chloasma or “the mask of pregnancy,” is a symmetric brown hyperpigmentation in malar, mandibular, or central facial areas. It is exacerbated by exposure to the sun and certain cosmetics.

Erythema begins in early gestation and appears either diffuse and mottled or focused in the palmar and thenar areas.

Venous congestion and vascular permeability during pregnancy can lead to varicosities in up to 40% of women. They result from increased venous pressures by the gravid uterus on femoral and pelvic vessels.

Dilation of arterioles leads to central erythematous spots with fine vessels radiating outward, called capillary hemangiomas (spider angiomas). They are most commonly seen around the gums, tongue, upper lip, and eyelids.

Striae, pinkish or purplish lines, may form on the abdomen, buttocks, and breasts. Striae form as a result of structural changes in the skin caused by weight gain and hormonal influence. Increased activity of the adrenal gland during pregnancy may increase their occurrence.

Nonpitting edema of the face, eyelids, and extremities is observed in many pregnant women, with changes most pronounced in the morning and improving throughout the day.

Changes in the distribution and amount of hair are common during pregnancy. Increased hair growth in facial areas and around the breasts occurs, particularly during the second and third trimesters. Importantly, there are no signs of virilization, and hirsutism regresses slightly or remains unchanged postpartum. Increased recruitment of hair follicles into the growing phase (anagen) may result in thickening of scalp hair in late gestation. Postpartum loss of hair is fairly common. During pregnancy, the number of hair follicles in the resting phase (telogen) is decreased by about half and then nearly doubles in the first few weeks postpartum.

Nails may become brittle with transverse grooving, distal onycholysis, and subungual hyperkeratosis. These changes are benign and do not require treatment.

Differential Diagnosis

It is important to distinguish physiologic changes in pregnancy from more worrisome conditions. Erythema, for instance, might be diagnostic of hyperthyroidism, cirrhosis, or systemic lupus erythematosus. Striae are normal findings in pregnancy but may be observed with adrenocortical hyperactivity. Edema, while common, is also an important symptom of preeclampsia, and this condition should be considered in affected women. When pronounced nail onychodystrophy is seen, psoriasis, lichen planus, and onychomycosis should be excluded.

Complications

In general, cutaneous changes of pregnancy are of cosmetic concern only. Some vascular changes result in discomfort that may respond to supportive therapy.

Treatment

Because most changes occurring in pregnancy improve postpartum, no therapy other than reassurance is required. Many remedies have been proposed for striae in pregnancy (vitamin E oil, lubricants, lotions), but none are effective. Laser technology is under investigation as a potential treatment and has shown some promise. If hyperpigmentation does not resolve postpartum, some patients respond to retinoic acid and corticosteroid preparations. Vascular changes are not likely to completely regress postpartum and may be treated with laser, electrodessication, or sclerotherapy.

Prognosis

Hyperpigmentation decreases or, in most cases, disappears postpartum. Vascular changes may become less pronounced but may not resolve completely. Striae usually become silvery-white and sunken, but they rarely disappear. Hair loss usually stops 2–6 months postpartum as the hair follicles enter the growing phase (anagen).

Atopic Dermatitis

Essentials of Diagnosis

• Atopic dermatitis (eczema) is commonly exacerbated in pregnancy.
• Most patients have a history of atopy, but dermatitis may present for the first time in pregnancy.

Pathogenesis

Estrogen and progesterone modulate immune and inflammatory cell functions, including mast cell secretion. This leads to urticaria and exacerbation of cutaneous inflammatory conditions. For some women, atopic dermatitis may improve with pregnancy, but some women experience worsening of or no change in their disease status during pregnancy.

Prevention

Treatment to decrease pruritus can discourage itching, which may improve symptoms. Additionally, maintaining skin hydration with emollients with a low water content (ie, thick creams or petroleum jelly) can protect against the dry, itchy, scaly skin that is associated with atopic dermatitis.

Clinical Findings

Symptoms & Signs

In most cases, patients will have a history of atopic dermatitis prior to pregnancy. The diagnosis of atopic dermatitis is a clinical one. The hallmark finding is pruritus. Other clinical manifestations include grouped, crusted erythematous papules and plaques present with excoriations. The skin creases and flexural surfaces are commonly involved.

Laboratory Findings

Although there are no laboratory findings specific to the diagnosis of atopic dermatitis, serology, histopathology, and immunofluorescence may show increased levels of immunoglobulin E (IgE).

Differential Diagnosis

Other sources of dermatitis, including contact or allergic dermatitis, tinea infection, and scabies, may mimic these conditions. Additionally, other disorders unique to pregnancy may also manifest in pruritus, including cholestasis of pregnancy and polymorphic eruption of pregnancy. The distribution of any rash can help distinguish between these conditions.

Complications

Bacterial, viral, or fungal superinfections may arise. Patients can have allergic reactions to topical treatments.

Treatment

Symptomatic treatment involves topical corticosteroids, such as hydrocortisone, or systemic antihistamines. For patients who do not respond to topical interventions, oral prednisone may be required. Methotrexate may be used for treatment of severe atopic dermatitis in nonpregnant patients; however, its use is absolutely contraindicated during pregnancy.

Prognosis

Atopic dermatitis is not associated with any adverse effects on the fetus. The prognosis is not affected by pregnancy.

Psoriasis

Essentials of Diagnosis

• Chronic plaque psoriasis is the most common type of psoriasis to develop or worsen in pregnancy.
• Forty percent to 60% of patients with psoriasis improve during pregnancy; only 14% worsen.

Pathogenesis

The pathophysiology is poorly understood. There is a genetic component as well an inciting injury to the skin. The Koebner phenomenon refers to the increased appearance of psoriatic lesions in area of skin trauma. Immune cells move from the dermis to the epidermis, where they stimulate keratinocytes to proliferate. High levels of interleukin-10 in pregnancy may explain the improved prognosis in some patients.

Prevention

No preventative measures have been identified.

Clinical Findings

Symptoms & Signs

In chronic plaque psoriasis, red and white scaly patches appear on the top first layer of the epidermis. Skin accumulates in these sites giving a silvery-white appearance, most commonly on elbows and knees, although any surface may be affected.

Laboratory Findings

Skin biopsy or scraping can confirm the diagnosis.

Differential Diagnosis

Drug reactions, pityriasis rosea, contact dermatitis, and tinea infections may mimic psoriasis.

Complications

Psoriatic arthritis develops in 10–15% of patients with psoriasis.

Treatment

Phototherapy and topical corticosteroids may be of use. Methotrexate, cyclosporine, and retinoids used in treatment of nonpregnant women are not recommended in pregnancy.

Prognosis

There is currently no cure for psoriasis, but various treatments can help to control the symptoms. Patients have an increased risk of nonmelanoma skin cancers and should be in the regular care of a dermatologist.

Cutaneous Lupus Erythematosus

Essentials of Diagnosis

• Chronic cutaneous lupus is rarely affected by pregnancy. Women with systemic lupus erythematosus (SLE) in remission for 3 months or more and who do not have nephropathy or cardiopathy tolerate pregnancy well.
• Cutaneous flares are the most common manifestation of SLE in pregnancy.

Pathogenesis

Binding of autoantibodies to cell membranes in the cutaneous tissues initiates an immunologic cascade that leads to lesion formation.

Prevention

Ultraviolet light may precipitate exacerbations, and avoidance may be helpful in some cases.

Clinical Findings

Symptoms & Signs

Erythematous papules or small plaques with slight scaling form. Lesions may expand and merge into larger plaques.

Laboratory Findings

Most patients have positive antinuclear antibody screens. Anti-Ro (SS-A) and anti-La (SS-B) should be checked in pregnant patients, as well as complete blood count to screen for anemia, leukopenia, and thrombocytopenia. Decreased complement and elevated erythrocyte sedimentation rate may be observed but are nonspecific.

Special Tests

Biopsy of skin shows deposition of immunoglobulin and complement at the dermoepidermal junction. Biopsies of unaffected skin may be higher yield than those of skin lesions. Immunofluorescence may not be helpful with older lesions.

Differential Diagnosis

Drug eruptions and allergic reactions may mimic cutaneous lupus erythematosus.

Complications

If conception occurs during the active phase of systemic lupus erythematosus (SLE), 50% of patients will worsen during pregnancy. Patients with SLE have an increased risk of pregnancy loss, and premature birth is not uncommon. Patients are at increased risk of preeclampsia. Neonatal lupus and congenital heart block may be seen especially in patients with circulating SS-A (anti-Ro) and SS-B (anti-La) antibodies.

Treatment

Topical and intralesional therapy is with steroid treatment. Scarring from lesions may lead to alopecia. Antimalarial treatments such as hydroxychloroquine and systemic corticosteroids may also be used for cases unresponsive to local treatment.

Prognosis

Cutaneous lupus erythematosus without SLE has a good prognosis. Some patients may experience intermittent exacerbations, often in the warmer months of the year, and some patients may experience remission.

Cutaneous Tumors

Essentials of Diagnosis

• Tumors may appear for the first time, enlarge, or increase in number during pregnancy.
• Granuloma gravidarum (pyogenic granuloma) is a vascular tumor that occurs in 2% of patients between the second and fifth months of pregnancy.
• Desmoid tumors, leiomyomas, and keloids may grow rapidly during pregnancy.
• Melanocytic nevi may develop, enlarge, or darken during pregnancy.

Pathogenesis

Proliferation of capillaries causes granuloma gravidarum to develop. Molluscum fibrosum gravidarum is also a result of the hormonal effects on vasculature. An increase in estrogen and progesterone receptors has been observed on melanocytes, which may explain changes in melanocytic nevi.

Prevention

No preventative measures have been identified.

Clinical Findings

Symptoms & Signs

Granuloma gravidarum is a red or purple nodule that most commonly occurs on gingival surfaces in the mouth but may also occur at other sites such as fingers. Molluscum fibrosum gravidarum are soft fibromas appearing later in pregnancy on the face, neck, and chest wall. Melanocytic nevi are dark, raised nodules of varying size that can occur anywhere on the body.

Laboratory Findings

If appearance is classic for a common benign lesion, biopsy is not necessary. Care should be taken in biopsying vascular lesions.

Differential Diagnosis

A wide variety of epidermal, melanocytic, fibroblastic, vascular, follicular, sebaceous, nervous, smooth muscle, and eccrine tumors may be considered. Metastatic tumors should be considered and biopsy performed if suspicion for malignancy exists.

Complications

Complications are limited to maternal cosmetic and physical effects. No fetal impact should be anticipated.

Treatment

In most cases, observation is all that is required. If symptoms exist, surgical resection may be considered.

Prognosis

Many lesions regress postpartum and do not require surgical resection.

Pruritic Urticarial Papules and Plaques of Pregnancy

Essentials of Diagnosis

• The most common pruritic dermatosis unique to pregnancy.
• Pruritic, erythematous papules that coalesce into plaques forming usually after the 34th week of gestation.
• The lesions usually appear during the third trimester and disappear completely within 2 weeks after delivery.

Pathogenesis

Pruritic urticarial papules and plaques of pregnancy (PUPPP) are also known as polymorphic eruption of pregnancy. The pathogenesis of PUPPP is still unclear. However, it is likely that overdistension of abdominal connective tissue exposes antigens in collagen bundles that provoke an allergic-type reaction, leading to lesions within the striae gravidarum. It affects approximately 1 in 160 to 1 in 300 pregnancies.

Prevention

No preventative measures have been identified.

Clinical Findings

Symptoms & Signs

The diagnosis of PUPPP is based on clinical signs and symptoms. Generally red, unexcoriated papules and plaques are found principally on the abdomen. A marked halo may surround the plaques. Lesions are found on the striae, legs, and arms. Notably, the characteristic papules spare the periumbilical region, leaving what may appear to be a periumbilical “white halo.”

Laboratory Findings

No relevant laboratory studies yield specific findings for PUPPP. However, immunofluorescence can distinguish PUPPP from pemphigoid gestationis because no immunoglobulin component will be identified with PUPPP.

Differential Diagnosis

Lesions cluster on the striae and tend to spare the umbilical area, differentiating PUPPP from pemphigoid gestationis. The differential diagnosis also includes erythema multiforme, drug reactions, viral syndromes, and scabies.

Complications

This condition poses no real danger for mother or fetus. It is not associated with adverse fetal or maternal outcomes.

Treatment

Symptomatic treatment with antihistamines, topical steroids, and antipruritic medications usually is helpful. Occasionally, oral corticosteroid therapy is necessary for control of extreme pruritus unresponsive to initial treatment.

Prognosis

PUPPP is self-limited and resolves after pregnancy. It is unclear if women who experience PUPPP with one pregnancy are at increased risk of recurrence in future pregnancies.

Intrahepatic Cholestasis of Pregnancy

Essentials of Diagnosis

• Seen only in pregnancy; results in pruritus and exclusively secondary skin lesions.
• Usually arises after the 30th week of pregnancy.
• Cholestasis is more prominent in South American and Scandinavian populations.

Pathogenesis

Intrahepatic cholestasis of pregnancy (ICP) affects between 0.3 and 5.6% of pregnancies in the United States. The incidence of ICP appears to vary according to ethnicity, with higher incidence rates among Araucanos Indians in Chile and people of Bolivian descent. The cause of ICP is not well understood. Certain genetic mutations have been associated with an increased predisposition to ICP. Alterations in estrogen and progesterone metabolism have also been associated with ICP. Increased levels of both hormones have been associated with ICP. Intrahepatic dysfunction of biliary secretion leads to elevation of bile acids in serum and deposition of bile salts in the skin, causing pruritus. Hormonal factors are likely to contribute to the condition.

Prevention

No preventative measures have been identified.

Clinical Findings

Symptoms & Signs

Patients with ICP typically present with a generalized pruritus (often severe) without an identifiable rash focused on palms and soles and sometimes extending to legs and abdomen. Symptoms tend to be worse at night. On physical examination, patients may show signs of excoriations.

Laboratory Findings

Testing of serum bile acids and liver function tests should be performed for every pregnant woman with pruritus. Serum total bile acid concentrations are increased in women with ICP. Serum cholic acid is often increased more than chenodeoxycholic acid. Serum aminotransferases may also be elevated. The prothrombin time is usually normal in women with ICP.

Differential Diagnosis

The diagnosis of ICP is made on the basis of pruritus with elevated bile acids and/or abnormal liver enzymes. However, viral hepatitis, gallbladder disease, pemphigus gestationis, and the papular dermatoses of pregnancy should be considered. The absence of a rash helps to distinguish ICP from other dermatoses. The presence of pruritus distinguishes ICP from other causes of abnormal liver function tests.

Complications

ICP is associated with an increased risk of adverse perinatal outcomes, including preterm birth and stillbirth. The earlier in gestation the onset of pruritus, the greater is the risk of prematurity. Patients with higher levels of bile acids have been found to have higher rates of spontaneous preterm birth. Additionally, the incidence of fetal demise appears to be 1–3%. Stillbirths cluster around weeks 37–39 of pregnancy. Although the absolute cause of stillbirth is poorly understood, there is some evidence suggesting that the increased levels of circulating bile acids interfere with cardiac electrical conduction leading to fetal arrhythmia and sudden stillbirth. Because stillbirth in these women appears to be a sudden and unpredictable event, fetal surveillance with nonstress testing and/or biophysical profiles has not been shown to reduce the risk of adverse outcome. Nonetheless, most practitioners advise the initiation of fetal surveillance twice per week once a diagnosis of ICP has been made.

Treatment

Ursodeoxycholic acid (UDCA) may result in a sustained decrease in serum bile acids that improves maternal symptoms. UDCA has not been shown to reduce the risk of stillbirth, primarily because the studies evaluating the effect of UDCA on ICP were not powered to address the effect on fetal/neonatal outcomes. However, in theory, reducing circulating bile acids with UDCA may also reduce the risk of adverse fetal outcomes. Once a diagnosis of ICP is made, fetal surveillance twice per week with nonstress testing and/or biophysical profiles is recommended. The optimal timing of delivery is unclear, but many experts advise delivery at 37–38 weeks or delivery at 36 weeks after confirmation of fetal lung maturity with amniocentesis.

Prognosis

The pruritus typically resolves within days after delivery. ICP is associated with a substantial recurrence risk, which has been reported to be in the range of 40–70%. Women with a history of ICP may also experience recurrent pruritus and cholestasis with oral contraceptives. If a patient with ICP desires oral contraception, a pill with a low dose of estrogen should be prescribed.

Pustular Psoriasis of Pregnancy

Essentials of Diagnosis

• Also called impetigo herpetiformis.
• Characterized by a pustular eruption on an erythematous base with total-body distribution.
• This rare condition may represent an acute form of psoriasis that occurs during pregnancy.
• Most patients have personal or family history of psoriasis.

Pathogenesis

Impetigo herpetiformis, or pustular psoriasis of pregnancy, is a very rare skin disorder with few cases described in the medical literature. The pathogenesis is still unclear, although it may be associated with high levels of progesterone and low levels of calcium in the last trimester of pregnancy. Reduced levels of epidermal skin-derived antileukoproteinase (elafin) have been implicated in the formation of pustules.

Prevention

No preventative measures have been identified.

Clinical Findings

Symptoms & Signs

Generalized erythematous patches covered with sterile pustules occur. Lesions start on the intertriginous or flexor surfaces and extend centrifugally, including mucosal membranes. Fever, nausea, diarrhea, and malaise often accompany this presentation. Pruritus is not common. Patients may have associated hypocalcaemia.

Laboratory Findings

Biopsy confirms presence of spongiform pustules with neutrophils in the epidermis. Immunofluorescence is negative.

Differential Diagnosis

Biopsy and culture can distinguish between pustular psoriasis of pregnancy and other pustular dermatoses and infections such as candidiasis and impetigo. Lesions may become superinfected, causing difficulty with diagnosis.

Complications

Skin lesions that develop superimposed infections may lead to sepsis. Severe hypocalcemia can cause tetany, seizures, and delirium.

Treatment

Treatment generally starts with oral corticosteroids. The steroids are then slowly tapered. Hypocalcemia should be corrected with calcium supplementation.

Prognosis

Increased maternal and perinatal mortality has been reported, but these cases may be related to secondary infection and sepsis. These patients may be at increased risk of placental insufficiency with adverse pregnancy outcomes such as miscarriage, fetal growth restriction, and stillbirth. Consequently, fetal surveillance with biophysical profiles and ultrasound assessment of fetal growth are advised. The skin lesions typically resolve quickly in the postpartum period. Pustular psoriasis of pregnancy may recur with subsequent pregnancies with an earlier gestational age at onset.

Pemphigoid Gestationis (Herpes Gestationis)

Essentials of Diagnosis

• Rare condition; appears in second and third trimesters.
• Lesions present as erythematous plaques with vesicles that soon form bullae in the periphery of the lesion (herpetiform appearance).
• Lesions start on the trunk and tend to spare the face, palms, and soles.

Pathogenesis

Despite the name, the herpes virus is not the causative agent. An autoimmune reaction against a placental matrix antigen has been implicated. Autoantibodies form that lead to deposition of immune complexes in the skin and complement activation, resulting in tissue damage and blister formation.

Prevention

No preventative measures have been identified.

Clinical Findings

Symptoms & Signs

Urticarial papules and plaques usually begin on the trunk and spread to the entire body including the distal extremities. Bullous lesions develop as the disease progresses. Lesions on mucous membranes are uncommon; however, they may occur. The vesicles are not clustered and are more peripheral than herpes. Systemic signs include malaise, fevers, and chills.

Laboratory Findings

Biopsy is necessary for diagnosis. Most patients have circulating immunoglobulin G that will fix C3 complement. Immunofluorescence testing of bullous lesions demonstrates C3 in a homogeneous, linear band at the basement membrane zone.

Differential Diagnosis

Pemphigus vulgaris can be excluded by histologic examination. The pustules, fever, and hypocalcemia of impetigo herpetiformis are not present in herpes gestationis. Dermatitis herpetiformis is pruritic, but the clusters of vesicles do not form bullae, and no plaques are present. In herpes gestationis, a crust forms, and a hyperpigmented area, but little or no scarring, occurs after the lesion heals.

Complications

Pruritus can interfere with daily activities and sleep. Ruptured bullae may be painful and develop superficial ulcerations that interfere dramatically with quality of life. Newborns may be small for gestational age at birth, but usually do not have associated morbidity and mortality.

Treatment

Topical or oral corticosteroids are the treatment of choice, typically prednisone 20–60 mg daily. Oral antihistamines may also relieve symptoms. Cyclosporine and intravenous immunoglobulin have been used in refractory conditions.

Prognosis

Exacerbations and remissions occur during pregnancy. The condition usually abates by 6 weeks postpartum, although exacerbations may occur during the postpartum period. Pemphigoid gestationis is associated with placental insufficiency, which increases the risk of intrauterine growth restriction and prematurity. Fetal surveillance with biophysical profiles and ultrasound assessment of fetal growth is advised in these women. The disease tends to recur in subsequent pregnancies.