Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence.
INTRODUCTION — The dermatoses of pregnancy are a heterogeneous group of pruritic inflammatory dermatoses that occur exclusively during pregnancy and/or in the immediate postpartum period . These include the following conditions, which are discussed below [2-6]:
●Polymorphic eruption of pregnancy (pruritic urticarial papules and plaques of pregnancy [PUPPP])
●Atopic eruption of pregnancy (eczema in pregnancy, prurigo of pregnancy, pruritic folliculitis of pregnancy)
●Intrahepatic cholestasis of pregnancy (see "Intrahepatic cholestasis of pregnancy")
●Pustular psoriasis of pregnancy
Normal physiologic changes of the maternal skin and appendages during pregnancy (table 1) are reviewed elsewhere. (See "Maternal adaptations to pregnancy: Skin, hair, nails, and mucous membranes".)
Dermatoses occurring in the nonpregnant population that may flare or remit during pregnancy are discussed elsewhere. (See "Management of psoriasis in pregnancy" and "Treatment of atopic dermatitis (eczema)".)
EVALUATION OF THE PREGNANT WOMAN WITH A PRURITIC ERUPTION — Pruritus during pregnancy is a major symptom of specific dermatoses of pregnancy, although it may be physiologic or associated with common inflammatory skin diseases, infections, or infestations (eg, allergic contact dermatitis, pityriasis rosea, scabies) occurring coincidentally during pregnancy. Severe generalized pruritus, especially if predominant on the palms and soles, in the absence of primary skin lesions suggests intrahepatic cholestasis of pregnancy (ICP). (See "Intrahepatic cholestasis of pregnancy".)
A pregnant woman with a pruritic skin eruption requires immediate evaluation in consultation with a dermatologist and diagnosis because delayed diagnosis or misdiagnosis may pose significant risk to the fetus (preterm delivery, small for gestational age) and the mother . The initial assessment involves (table 2):
●Obtaining a detailed medical history, including personal and family history of atopy, obstetric history (primigravida, multiple gestation pregnancy, similar illness in previous pregnancies), and time of onset of the current eruption (early or late pregnancy).
●Total body skin examination for type and distribution of lesions (table 3):
•Eczematous lesions with a flexural distribution suggest atopic eruption of pregnancy (AEP).
•Involvement of striae is common in polymorphic eruption of pregnancy (PEP).
•Nodular lesions on the limbs suggest prurigo of pregnancy (prurigo-type AEP).
•Urticarial lesions are most common with PEP or pemphigoid gestationis, which also can display vesicular lesions.
●Skin biopsy for histopathologic examination and direct immunofluorescence staining if the diagnosis is uncertain and pemphigoid gestationis is suspected. A skin biopsy should also be performed to confirm a clinical diagnosis of pustular psoriasis of pregnancy.
●Laboratory testing (eg, total serum bile acids, metabolic panel, circulating antibodies against the bullous pemphigoid antigen 180) is indicated based upon the clinical findings (table 3) if there is clinical suspicion of a dermatosis associated with fetal and maternal risk, such as pemphigoid gestationis, ICP, and generalized pustular psoriasis.
PEMPHIGOID GESTATIONIS — Pemphigoid gestationis (formerly called herpes gestationis) is a rare autoimmune bullous disease that occurs during the second or third trimester of pregnancy and may be associated with increased fetal risk . A review of 61 pregnancies complicated by pemphigoid gestationis reported 20 (34 percent) preterm births .
Epidemiology — Pemphigoid gestationis is rare. Its incidence has been estimated at 1 in 20,000 to 50,000 pregnancies. It only occurs during pregnancy or, in a minority of cases, as a paraneoplastic manifestation in women with trophoblastic tumors [9-13].
Pathogenesis — Pemphigoid gestationis is caused by circulating immunoglobulin G1 (IgG1) autoantibodies directed against the 180 kilodalton bullous pemphigoid antigen (BP180 or collagen XVII), a transmembrane hemidesmosomal glycoprotein expressed in the basement membrane zone of the skin. The majority of patient sera bind to the extracellular NC16A epitope, but some bind to other epitopes on BP180, both intracellular and extracellular .
As in bullous pemphigoid, the binding of antibodies to antigens within the basement membrane zone stimulates an inflammatory cascade that results in separation of the epidermis from the dermis . (See "Epidemiology and pathogenesis of bullous pemphigoid and mucous membrane pemphigoid", section on 'Pathogenesis'.)
In pemphigoid gestationis, the primary site of autoimmunity seems to be the placenta, as antibodies bind not only to the basement membrane zone of the epidermis, but also to that of chorionic and amniotic epithelia, both of ectodermal origin. It has been theorized that paternal major histocompatability complex (MHC) class II antigens found on the chorionic villi induce maternal antibodies to the amniotic basement membrane. These antibodies can then cross-react with skin and cause maternal (and sometimes newborn) disease .
The hypothesis of a genetic predisposition is supported by the observation of an association between pemphigoid gestationis and class II human leukocyte antigen (HLA) phenotype HLA-DR3/HLA-DR4 [17,18].
Clinical manifestations — Pemphigoid gestationis presents most often in the second or third trimester of pregnancy. Intense pruritus may precede the onset of visible skin lesions. The rash typically begins on the trunk as urticarial plaques or papules surrounding the umbilicus (picture 1A-C and table 3) [9-11]; vesicles may also be present (picture 2). Lesions may be seen on the palms and soles but rarely on the face or mucous membranes. The eruption spreads rapidly and forms tense blisters (picture 3A-B). The entire body surface may be involved, but the mucous membranes are usually spared.
Pemphigoid gestationis may remit prior to delivery. However, 75 percent of patients flare postpartum and at least 25 percent subsequently flare with use of oral contraceptive pills or during menses. Most cases spontaneously resolve in the weeks to months following delivery. The disease usually recurs with subsequent pregnancies and is often worse  but may also skip pregnancies .
Diagnosis — The diagnosis of pemphigoid gestationis is based upon the combination of clinical findings (table 3), examination of a perilesional skin biopsy for routine histopathology and direct immunofluorescence (DIF), and measurement of serum levels of anti-BP180 antibodies by enzyme-linked immunosorbent assay (BP180 NC16A ELISA).
Pathology — Biopsy of a vesiculating lesion (using routine histologic processing) reveals a subepidermal vesicle with a perivascular lymphocytic and eosinophilic infiltrate. Eosinophils may appear at the dermoepidermal junction and filling the vesicle. Basal cell necrosis and edema of the dermal papillae are usually noted.
Direct immunofluorescence — Using a snap-frozen perilesional skin biopsy, DIF reveals a homogeneous, linear deposit of complement C3 at the basement membrane zone (picture 4). The presence of C3 is pathognomonic for pemphigoid gestationis in a pregnant patient. Immunoglobulin G (IgG) deposits are also present in 30 to 40 percent of patients but are not a criterion for diagnosis.
Laboratory tests — Antibodies against the noncollagenous extracellular domain of BP180 known as NC16A (the primary site for antibody binding in bullous pemphigoid) can be detected in the serum by a commercially available enzyme-linked immunosorbent assay (BP180 NC16A ELISA). This test is sensitive and specific for the diagnosis of pemphigoid gestationis, and its positivity can be considered diagnostic in patients with typical clinical features [19,20]. The sensitivity and specificity of BP180 NC16A ELISA test range from 96 to 100 percent [19-21].
The levels of circulating anti-BP180 antibodies correlate with the disease severity and are useful to monitor the response to treatment. The anti-BP180 levels tend to remain elevated up to one year after pregnancy and may persist during subsequent pregnancies even in the absence of a new episode of pemphigoid gestationis .
Differential diagnosis — The differential diagnosis of pemphigoid gestationis includes primarily:
●Polymorphic eruption of pregnancy – The early urticarial plaques of pemphigoid gestationis are clinically and histologically indistinguishable from polymorphic eruption of pregnancy (PEP). A clinical clue to help differentiate the two disorders is that PEP often begins in the striae, while pemphigoid gestationis is truly periumbilical (table 3). DIF of perilesional skin showing linear C3 deposition along the dermoepidermal junction and the demonstration of circulating antibodies against BP180 NC16A by ELISA test will confirm the diagnosis of pemphigoid gestationis. DIF and BP180 NC16A antibodies are always negative in PEP. (See 'Polymorphic eruption of pregnancy' below.)
●Dermatitis herpetiformis – Dermatitis herpetiformis (DH) is a very pruritic, vesicular autoimmune skin eruption associated with gluten sensitivity. In contrast with pemphigoid gestationis, DH lesions are typically located on the elbows, dorsal forearms, knees, scalp, back, and buttocks (picture 5A-B). DIF of perilesional skin showing granular deposits of immunoglobulin A (IgA) within the dermal papillae confirms the diagnosis of DH. (See "Dermatitis herpetiformis".)
●Erythema multiforme – Erythema multiforme, whether due to pregnancy, infection, or drugs, can mimic pemphigoid gestationis clinically, but routine histology usually distinguishes between these disorders. (See "Pathogenesis, clinical features, and diagnosis of erythema multiforme".)
●Allergic contact dermatitis and drug reactions can also appear similar to pemphigoid gestationis on physical examination; thus, a careful history regarding use of medications and exposure to environmental agents may be helpful for the correct diagnosis [10,11]. (See "Clinical features and diagnosis of allergic contact dermatitis" and "Drug eruptions".)
Treatment — The main goals of treatment of pemphigoid gestationis are to decrease blister formation, promote the healing of blisters and erosions, and relieve pruritus. Due to its rarity, the therapies for pemphigoid gestationis have not been evaluated in randomized trials. Treatment is based upon clinical experience and evidence from studies on bullous pemphigoid [23-25]. (See "Management and prognosis of bullous pemphigoid".)
We suggest high-potency topical corticosteroids (groups two and three (table 4)) for initial therapy of localized disease. Vehicles for topical corticosteroids (table 5B) and doses are illustrated in the tables (table 5A-B). Ointments tend to cause less stinging and may be more effective than other topical preparations but are more cumbersome. (See "General principles of dermatologic therapy and topical corticosteroid use", section on 'Use during pregnancy or lactation'.)
If symptoms are not controlled by topical corticosteroids, which is common, then systemic corticosteroids (eg, prednisone 0.5 mg/kg per day) are usually effective. Once the symptoms are stabilized, the dose may be tapered and even discontinued in some patients. However, reinstatement of treatment postpartum will likely be needed [10,11].
The use of systemic corticosteroids during the pregnancy appears to be relatively safe. Although early studies suggested an association between systemic corticosteroids and risk of miscarriage or congenital malformation (oral clefts), larger population-based studies have not confirmed these findings [26,27]. However, limited data suggest an increased risk of preterm birth or low birth weight for women with pemphigoid gestationis or other autoimmune diseases exposed to systemic corticosteroids during the pregnancy.
●A study of 61 women with pemphigoid gestationis found an increased risk of low birth weight for women treated with ≥60 mg prednisone per day, after adjusting for maternal age and comorbidities (odds ratio 16.65, 95% CI 1.15–241.46). However, because of the small sample size and wide confidence interval, the magnitude of the risk remains uncertain.
●In a nationwide Danish cohort study of 900 pregnant women with Crohn disease exposed to various treatments, 73 received systemic corticosteroids . In this group, there were nine (12 percent) preterm births and one (1.4 percent) low birth weight at term.
Severe, persistent postpartum pemphigoid gestationis may require higher doses of systemic corticosteroids or alternative immunosuppressant agents. Prednisone up to 2 mg/kg per day can be given until a clinical response is achieved and then tapered and maintained at the lowest effective dose. Alternative therapies that have been successfully used in a few patients with severe persistent postpartum pemphigoid gestationis include azathioprine, high-dose intravenous immunoglobulins (2 g/kg per cycle) [29-32], cyclosporine , cyclophosphamide , doxycycline and nicotinamide , rituximab , and immunoapheresis .
First-generation oral antihistamine chlorpheniramine or second-generation loratadine and cetirizine may be helpful for the symptomatic control of pruritus. (See "Recognition and management of allergic disease during pregnancy", section on 'Oral antihistamines'.)
Prognosis — The fetal prognosis is generally good, despite an increased risk of prematurity and small-for-gestational-age babies due to mild placental failure . There is no increased risk of miscarriage.
In a retrospective cohort study of 61 pregnancies complicated by pemphigoid gestationis, 20 out of 58 live deliveries (34 percent) were classified as preterm births and 19 out of 56 neonates with available birth weight data (34 percent) were small for gestational age . Poor prognostic factors included disease onset in the first or second trimester and the presence of blisters on the mother's skin. In another study, 6 of 32 pregnancies were complicated by preterm labor, 2 were associated with intrauterine growth restriction, and 2 ended with abortion or stillbirth .
A few newborns present with blisters (neonatal pemphigoid gestationis), due to the transplacental passage of maternal IgG autoantibodies. The eruption has a mild course and resolves within weeks without treatment [40-42]. There is minimal risk of adrenal suppression in the newborn, even if the mother has been maintained on high-dose corticosteroids.
The mother is at high risk of recurrent pemphigoid gestationis with subsequent pregnancies.
POLYMORPHIC ERUPTION OF PREGNANCY — Polymorphic eruption of pregnancy (PEP), also called pruritic urticarial papules and plaques of pregnancy (PUPPP), is a benign, self-limiting pruritic inflammatory disorder that usually affects primiparous women in the last few weeks of pregnancy or immediately postpartum . Toxic erythema of pregnancy, Bourne's toxemic rash of pregnancy, linear immunoglobulin M (IgM) dermatosis of pregnancy, and Nurse's late-onset prurigo are older terms felt to represent this same entity [10,44-46].
Pathogenesis — The etiopathogenesis of PEP is unknown and may be heterogeneous [10,45]. The degree of stretching of the abdominal skin may play a role; PEP is more common with excessive stretching, especially in women with multiple gestation [44,47-49].
It has been hypothesized that stretching may cause damage to connective tissue, which results in exposure of dermal antigens that trigger an inflammatory response [47,50]. A role of reproductive hormones in the pathogenesis of PEP has not been demonstrated.
Another possibility is that PEP represents an immunologic response to circulating fetal antigens. As an example, one study demonstrated fetal male DNA in maternal skin lesions, a possible result of blood chimerism (fetal cells detected in maternal blood throughout pregnancy) . However, this hypothesis has not been confirmed, although several studies have reported a preponderance of male fetuses in women with PEP [2,52,53].
Clinical manifestations — PEP usually occurs in nulliparous women late in the third trimester (mean onset 35 weeks) but may develop postpartum [45,52,54]. There are also rare case reports of first and second trimester disease .
PEP typically presents as extremely pruritic, erythematous papules within striae (picture 6). Abdominal striae are the most common initial site (with periumbilical sparing) and may be the only initial site . The lesions then spread to the extremities, chest, and back and coalesce to form urticarial plaques (picture 7A-B) . The face, palms, and soles are usually spared.
White halos often surround the erythematous papules in patients with fair skin (picture 8). Over the course of the disease, approximately one-half of the patients develop more polymorphic lesions, including target-like lesions exhibiting three distinct rings/color changes instead of a halo, or erythematous patches and vesicles [9,43,45,55].
The eruption generally lasts four to six weeks and resolves within two weeks postpartum, although it may last longer or resolve prior to delivery .
Diagnosis — The diagnosis of PEP is usually clinical, based upon history and physical examination (table 3). A skin biopsy is generally not necessary for diagnosis but may be performed in cases of diagnostic uncertainty. There are no laboratory abnormalities related to PEP .
Pathology — Histopathologic examination of a skin biopsy reveals a perivascular (superficial and deep) and interstitial lymphocytic infiltrate containing eosinophils . Features of lymphocytic vasculitis may be seen in some cases. Epidermal changes, including mild epidermal hyperplasia, spongiosis, and parakeratosis, are seen in approximately 30 to 50 percent of cases [6,55]. Additional findings include dermal edema and focal deposition of mucin.
Immunohistochemical studies reveal a predominantly T helper lymphocytic infiltrate with an increased number of CD1a+, CD54+ (ICAM-1+) dendritic cells, and CD1a+ epidermal Langerhans cells in lesional skin.
Direct immunofluorescence demonstrates nonspecific deposition of C3 and IgM or immunoglobulin A (IgA) deposits at the dermoepidermal junction or around blood vessels in approximately 30 percent of cases . These deposits are granular, not linear, as in pemphigoid gestationis. Indirect immunofluorescence is always negative.
Differential diagnosis — The early, urticarial phase of pemphigoid gestationis can mimic PEP (table 3). The two disorders can be distinguished by direct immunofluorescence of a biopsy specimen. (See 'Pemphigoid gestationis' above.)
The target-like lesions of PEP may appear similar to erythema multiforme. Drug reactions, viral syndromes, and infestations (scabies) may also present with erythematous papules similar to PEP [10,45]. The clinical history, routine histology, and serology help in differentiating among these entities. (See "Drug eruptions" and "Scabies: Epidemiology, clinical features, and diagnosis".)
Treatment — The goal of treatment is relief of symptoms. We suggest mid- to high-potency topical corticosteroids (groups two to four (table 4)) as initial therapy for PEP. Topical corticosteroids can be applied once or twice daily until improvement occurs. The cumulative amounts of topical corticosteroids used for the treatment of specific body areas in adults are shown in the table (table 5A). (See "General principles of dermatologic therapy and topical corticosteroid use", section on 'Use during pregnancy or lactation'.)
The safety of topical corticosteroid use during pregnancy is supported by several observational studies and meta-analyses [56,57]. However, the use of potent or superpotent topical corticosteroids exceeding 300 g during the whole pregnancy may be associated with an increased risk of low birth weight .
In severe cases, a short course of systemic corticosteroids with a quick taper, such as prednisone or prednisolone 0.5 mg/kg per day for one week, tapered over one to two weeks, may be given for rapid resolution of symptoms .
Chlorpheniramine, a first-generation oral antihistamine, or second-generation, nonsedating oral antihistamines, such as loratadine and cetirizine, may be helpful to control pruritus. (See "Recognition and management of allergic disease during pregnancy", section on 'Oral antihistamines'.)
Early delivery to end symptoms is rarely, if ever, necessary . (See "Use of antiinflammatory and immunosuppressive drugs in rheumatic diseases during pregnancy and lactation".)
Prognosis — PEP generally lasts four to six weeks and resolves within two weeks postpartum, although it may last longer. In one series, the process resolved prior to delivery in 6 of 15 patients .
ATOPIC ERUPTION OF PREGNANCY — Atopic eruption of pregnancy (AEP) is a pruritic disorder of pregnancy that presents as an eczematous or papular eruption in patients with an atopic background. It starts during early pregnancy, with 75 percent of cases occurring before the third trimester, and tends to recur in subsequent pregnancies.
AEP is a unifying term that includes eczema in pregnancy, prurigo of pregnancy (also called prurigo gestationis of Besnier, Nurse's early-onset prurigo of pregnancy, Spangler's papular dermatitis of pregnancy, and linear immunoglobulin M [IgM] disease of pregnancy), and pruritic folliculitis of pregnancy, which were previously considered distinct entities . This classification scheme is based upon the presence of shared clinical features, including a possible association with atopy. However, not all experts agree that pruritic folliculitis of pregnancy and prurigo of pregnancy are best "lumped" within a disorder of atopic diathesis .
None of the disorders classified within this group are associated with adverse effects on the fetus .
Epidemiology — AEP is the most common of the pregnancy dermatoses, accounting for over 50 percent of all cases . Its precise incidence is unknown. AEP is associated with a personal or family history of atopy (seasonal rhinitis, asthma, and/or atopic dermatitis) and is in most cases the first manifestation of atopic skin changes [2,3].
Pathogenesis — AEP is thought to be triggered by immunologic changes associated with pregnancy. It is postulated that reduced production of Th1 cytokines and enhancement of Th2 cytokine production, which is known to occur during pregnancy, may contribute to the development of eczema [3,61]. A relationship with a history of atopy has been proposed but remains controversial [2,3,9].
Clinical manifestations — AEP often begins during the first or second trimester and is in most cases the first manifestation of atopic skin changes or the recurrence of atopic dermatitis after years of remission [2,10]. In approximately 20 percent of cases, AEP represents an exacerbation of a preexisting atopic dermatitis.
Eczema — The vast majority of patients with AEP present with a widespread eczematous eruption (the E-type AEP) involving the face, neck, and flexural areas, similar to classic atopic dermatitis (picture 9A-B) . However, any area of the skin may be affected. Lesions may be eczematous patches or intact or excoriated papules. Papules can be follicle based, grouped, or scattered (picture 10). Skin dryness, which may be severe, is invariably present.
Prurigo of pregnancy — A less common presentation of AEP is prurigo of pregnancy, also called P-type AEP, which presents with erythematous, excoriated nodules or papules on the extensor surfaces of the limbs and trunk (picture 11) [2,9,10,62]. Lesions are grouped and may be crusted or appear eczematous. In one series, all 12 patients had abdominal involvement, with some also having the legs, wrists, and hands affected . The eruption usually resolves in the immediate postpartum period , although it can persist for up to three months .
Pruritic folliculitis of pregnancy — In rare cases, AEP presents as a follicular papulopustular eruption (formerly known as pruritic folliculitis of pregnancy). Scattered follicle-based papules and pustules appear initially on the abdomen but may spread to the trunk and extremities and become generalized [2,60,64]. The appearance is similar to that of steroid-induced acne (picture 12) and is only mildly pruritic .
The eruption typically clears within two weeks of delivery [44,65]. However, one report described a case with persistent symptoms for six weeks postpartum , and another series noted all 14 of the cases resolved prior to delivery .
Diagnosis — The diagnosis is usually clinical, based upon the recognition of clinical features in a patient with a personal or family history of atopy. A skin biopsy is generally not helpful, as the findings are nonspecific. However, a biopsy should be performed if there is diagnostic uncertainty or there is suspicion of pemphigoid gestationis. (See 'Pemphigoid gestationis' above.)
Although laboratory testing is generally not indicated, up to 70 percent of patients may have elevated serum immunoglobulin E (IgE) levels . In patients presenting with folliculitis, a pustule should be cultured to rule out bacterial or candidal folliculitis.
Pathology — Spongiosis and a perivascular mononuclear infiltrate are common features of eczematous eruptions . Epidermal hyperkeratosis or parakeratosis may also be present. A dermal perivascular lymphocytic infiltrate without eosinophils can also be noted. The epidermis may show acanthosis, hyperkeratosis, and parakeratosis.
A follicle-centered lymphohistiocytic infiltrate containing neutrophils, eosinophils, and plasma cells and neutrophilic pustules with histopathologic features of sterile folliculitis can be seen in the folliculitis-type AEP [2,64,65].
Direct and indirect immunofluorescence studies are negative.
Differential diagnosis — The differential diagnosis of AEP includes spongiotic dermatitides that are not specifically associated with pregnancy (eg, allergic contact dermatitis, pityriasis rosea, maculopapular drug eruption), polymorphic eruption of pregnancy (PEP), and early stage of pemphigoid gestationis.
Clinically, the eczema-type AEP can be differentiated from PEP and early pemphigoid gestationis by its earlier onset, predilection for involvement of skin flexures, and absence of urticarial plaques in abdominal striae. The clinical differentiation of prurigo-type AEP and from PEP or early pemphigoid gestationis may be difficult. In these cases, a skin biopsy may be helpful for the correct diagnosis. Although prurigo-type AEP and PEP share several histopathologic features, the finding of lymphocytic vasculitis, eosinophils in the interstitial dermis, edema, and mucin deposition in the dermis suggest PEP rather than AEP . (See 'Pathology' above.)
Secondary lesions of intrahepatic cholestasis of pregnancy and eruptions not associated with pregnancy (eg, scabies, drug reactions) should be excluded by history and laboratory testing (eg, bile acids) as indicated .
Management — The goal of treatment is relief of symptoms. Similar to nonpregnant patients with eczema, patients with AEP should be encouraged to maintain adequate skin hydration through the frequent use of emollients.
Low- to mid-potency topical corticosteroids (groups 4 to 6 (table 4)) are useful for controlling symptoms. Vehicles for topical corticosteroids and doses are illustrated in the tables (table 5A-B). (See "Treatment of atopic dermatitis (eczema)".)
First-generation oral antihistamine chlorpheniramine or second-generation loratadine and cetirizine may be helpful for controlling pruritus. (See "Recognition and management of allergic disease during pregnancy", section on 'Oral antihistamines'.)
INTRAHEPATIC CHOLESTASIS OF PREGNANCY — Intrahepatic cholestasis of pregnancy (ICP, obstetric cholestasis) is the only pregnancy dermatosis without primary skin changes . Patients experience severe, generalized pruritus, predominantly on the palms and soles, and may present with excoriations secondary to scratching.
ICP carries significant morbidity for the fetus, including prematurity, meconium-stained amniotic fluid, intrauterine demise, and an increased risk for neonatal respiratory distress syndrome. The maternal prognosis is generally favorable, although one study suggests that affected women have an increased risk of later hepatobiliary disease .
The pathogenesis, clinical manifestations, diagnosis, and treatment of ICP are discussed in detail separately. (See "Intrahepatic cholestasis of pregnancy".)
PUSTULAR PSORIASIS OF PREGNANCY — Pustular psoriasis of pregnancy (PPP), formerly called impetigo herpetiformis, is an exceedingly rare variant of generalized pustular psoriasis occurring during pregnancy or triggered by pregnancy. It typically presents during the third trimester but may occur earlier or in the immediate postpartum period. (See "Pustular psoriasis: Pathogenesis, clinical manifestations, and diagnosis" and "Pustular psoriasis: Management".)
Clinical manifestations — PPP can occur anytime during pregnancy but typically presents in the third trimester of pregnancy with symmetric, erythematous plaques studded at the periphery with sterile pustules in a circinate pattern (picture 13) . The plaques then enlarge from the periphery as the center becomes eroded and crusted (picture 14B). There may be concentric rings of pustules. The pustules are typically sterile.
The eruption begins in the flexural areas and spreads centrifugally. The trunk and extremities are usually involved, while the hands, feet, and face are usually spared. Oral and esophageal erosions may occur. The nails may become onycholytic (lifting of the nail plate from the nail bed) [68,69]; pitting has also been described .
Pruritus is usually absent. Systemic symptoms are severe and include malaise, fever, anorexia, nausea, vomiting, diarrhea, and tetany [68,69].
Leukocytosis and elevated erythrocyte sedimentation rate are common. Hypocalcemia may be present, possibly related to hypoparathyroidism  and can lead to tetany, delirium, and seizures. Albuminuria, hypoalbuminemia, pyuria, and hematuria occasionally occur.
Diagnosis — The diagnosis can be made clinically, based upon history and physical examination (picture 14A-B). However, we suggest confirmation by histologic evaluation of a biopsy specimen, given the potential consequences of the disease and its treatment to maternal and child health (eg, side effects of systemic corticosteroids, preterm delivery).
Pathology — The histopathologic features of PPP are the same as those of pustular psoriasis in the nonpregnant patient. Spongiform pustules with neutrophils are observed in the epidermis. Psoriasiform hyperplasia and parakeratosis also occur [68,69]. (See "Pustular psoriasis: Pathogenesis, clinical manifestations, and diagnosis", section on 'Histopathology'.)
Laboratory tests — The initial laboratory evaluation includes a complete blood count with differential and a complete metabolic panel to evaluate for hypocalcemia, other electrolyte abnormalities, hypoalbuminemia, and liver and renal function. Pustule cultures for bacteria or yeasts may be obtained.
Differential diagnosis — An infectious etiology for the pustular eruption (eg, candidiasis, tinea corporis, impetigo) should be excluded by appropriate cultures. Other dermatoses that should be considered in the differential diagnosis of PPP include:
●Subcorneal pustular dermatosis (picture 15) can mimic PPP clinically and histopathologically but is typically asymptomatic. The presence of severe systemic symptoms suggests PPP. (See "Subcorneal pustular dermatosis".)
●Acute generalized exanthematous pustulosis (AGEP) (picture 16) is a severe drug reaction that typically manifests with the rapid development of dozens to hundreds of nonfollicular, sterile, pinhead-sized pustules that usually occurs a few hours to a few days after exposure to an offending drug, most often an antibiotic. The absence of a history of drug exposure helps in distinguishing PPP from AGEP. (See "Acute generalized exanthematous pustulosis (AGEP)".)
●Pruritic folliculitis of pregnancy is pruritic and exclusively perifollicular, neither of which is true of pustular psoriasis of pregnancy. (See 'Pruritic folliculitis of pregnancy' above.)
●Pemphigoid gestationis can present with rings of vesicles or pustules, but histopathology is different. (See 'Pemphigoid gestationis' above.)
Management — Because of the associated risk for the fetus, prompt institution of treatment is required for women with PPP. Fetal monitoring with nonstress tests or biophysical profiles and ultrasound assessment of fetal growth are indicated. Hypocalcemia must be corrected, when present, and fluid and electrolyte balance should be maintained. These patients sometimes require early delivery for relief of symptoms and for fetal safety [68,69,71].
Evidence for the treatment of PPP is limited . We suggest systemic corticosteroids as initial therapy. High-dose systemic corticosteroids, such as prednisolone up to 60 to 80 mg per day, are given for a few days and then slowly tapered as symptoms improve, with monitoring in case a flare occurs.
Low-dose cyclosporine (2 to 3 mg/kg per day) may be a treatment option for patients who fail to respond to systemic corticosteroids [73-76]. Although cyclosporine is a category C drug, data from studies in pregnant patients with organ transplantation indicate that the risk of teratogenicity is low, but premature labor and infants small for gestational age have been reported. (See "Use of antiinflammatory and immunosuppressive drugs in rheumatic diseases during pregnancy and lactation".)
There are isolated reports of successful use of infliximab [77,78]. In a review from the medical board of the National Psoriasis Foundation, corticosteroids, cyclosporin, and infliximab were all listed as first-line treatments . For persistent cases, after delivery and in nonbreastfeeding mothers, systemic retinoids or methotrexate are additional therapeutic options . (See "Management of psoriasis in pregnancy".)
Prognosis — PPP usually remits quickly postpartum but may flare after delivery [70,79,80]. Placental insufficiency with severe sequelae such as miscarriage, fetal growth restriction, or stillbirth may occur [81,82].
SUMMARY AND RECOMMENDATIONS
●The dermatoses of pregnancy are a heterogeneous group of pruritic inflammatory dermatoses that occur exclusively during pregnancy and/or in the immediate postpartum period. They include pemphigoid gestationis, polymorphic eruption of pregnancy (PEP), previously known as pruritic urticarial papules and plaques of pregnancy (PUPPP), atopic eruption of pregnancy (AEP), intrahepatic cholestasis of pregnancy (ICP), and pustular psoriasis of pregnancy (PPP). (See 'Introduction' above.)
●A pregnant woman with a pruritic skin eruption requires immediate evaluation and diagnosis because delayed diagnosis or misdiagnosis may pose significant risk to the fetus and the mother. The initial assessment is summarized in the table (table 2). (See 'Evaluation of the pregnant woman with a pruritic eruption' above.)
●Patients suspected to have pemphigoid gestationis or pustular psoriasis should undergo skin biopsy with histopathologic assessment, direct immunofluorescence test, and measurement of circulating antibodies against anti-BP180 to confirm the clinical diagnosis. (See 'Diagnosis' above.)
●PEP and AEP, including prurigo of pregnancy and pruritic folliculitis of pregnancy, can be diagnosed clinically, based upon characteristic findings on history and physical examination alone. Bile acids should be checked in patients with extensive pruritus and no primary skin lesions. (See 'Diagnosis' above and 'Diagnosis' above and 'Intrahepatic cholestasis of pregnancy' above.)
Treatment recommendations depend on the specific disorder:
●For patients with pemphigoid gestationis, we suggest high-potency (group 2 and 3 (table 4)) topical corticosteroid ointments as initial treatment for localized disease (Grade 2C). We administer oral corticosteroids (eg, prednisone 0.5 mg/kg per day) if the symptoms are not controlled by topical therapy. Higher doses of oral corticosteroids or other systemic immunosuppressive agents may be needed in patients with severe persistent postpartum pemphigoid gestationis. (See 'Treatment' above.)
●For patients with PEP, prurigo of pregnancy, and pruritic folliculitis of pregnancy, we suggest low- to medium-potency (group 4 to 6 (table 4)) topical corticosteroid ointments (Grade 2C). Oral antihistamines may be helpful for the symptomatic treatment of pruritus. (See 'Treatment' above and "Recognition and management of allergic disease during pregnancy", section on 'Oral antihistamines'.)
●The management of ICP is reviewed elsewhere. (See "Intrahepatic cholestasis of pregnancy", section on 'Treatment'.)
●Pustular psoriasis is treated with high-dose oral corticosteroids (up to 60 to 80 mg per day). Low-dose cyclosporine (2 to 3 mg/kg per day) may be a treatment option for patients who fail to respond to corticosteroids. Patients should be evaluated for hypocalcemia, which can be symptomatic. (See 'Management' above.)
- Ambros-Rudolph CM. Dermatoses of pregnancy - clues to diagnosis, fetal risk and therapy. Ann Dermatol 2011; 23:265.
- 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; 141:71.
- Ambros-Rudolph CM, Müllegger 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; 54:395.
- Lehrhoff S, Pomeranz MK. Specific dermatoses of pregnancy and their treatment. Dermatol Ther 2013; 26:274.
- Vaughan Jones S, Ambros-Rudolph C, Nelson-Piercy C. Skin disease in pregnancy. BMJ 2014; 348:g3489.
- Massone C, Cerroni L, Heidrun N, et al. Histopathological diagnosis of atopic eruption of pregnancy and polymorphic eruption of pregnancy: a study on 41 cases. Am J Dermatopathol 2014; 36:812.
- 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; 160:1222.
- Huilaja L, Mäkikallio K, Tasanen K. Gestational pemphigoid. Orphanet J Rare Dis 2014; 9:136.
- Roger D, Vaillant L, Fignon A, et al. Specific pruritic diseases of pregnancy. A prospective study of 3192 pregnant women. Arch Dermatol 1994; 130:734.
- Shornick JK. Dermatoses of pregnancy. Semin Cutan Med Surg 1998; 17:172.
- Katz SI. Herpes gestationis (pemphigoid gestationis). In: Fitzpatrick's Dermatology in General Medicine, 5th ed, Freedberg I, Eisen AZ, Wolff K, et al (Eds), McGraw-Hill, New York 1999. p.686.
- Jenkins RE, Hern S, Black MM. Clinical features and management of 87 patients with pemphigoid gestationis. Clin Exp Dermatol 1999; 24:255.
- Jenkins RE, Jones SA, Black MM. Conversion of pemphigoid gestationis to bullous pemphigoid--two refractory cases highlighting this association. Br J Dermatol 1996; 135:595.
- Di Zenzo G, Calabresi V, Grosso F, et al. The intracellular and extracellular domains of BP180 antigen comprise novel epitopes targeted by pemphigoid gestationis autoantibodies. J Invest Dermatol 2007; 127:864.
- Kasperkiewicz M, Zillikens D, Schmidt E. Pemphigoid diseases: pathogenesis, diagnosis, and treatment. Autoimmunity 2012; 45:55.
- Sadik CD, Lima AL, Zillikens D. Pemphigoid gestationis: Toward a better understanding of the etiopathogenesis. Clin Dermatol 2016; 34:378.
- García-González E, Castro-Llamas J, Karchmer S, et al. Class II major histocompatibility complex typing across the ethnic barrier in pemphigoid gestationis. A study in Mexicans. Int J Dermatol 1999; 38:46.
- Shornick JK, Jenkins RE, Artlett CM, et al. Class II MHC typing in pemphigoid gestationis. Clin Exp Dermatol 1995; 20:123.
- Powell AM, Sakuma-Oyama Y, Oyama N, et al. Usefulness of BP180 NC16a enzyme-linked immunosorbent assay in the serodiagnosis of pemphigoid gestationis and in differentiating between pemphigoid gestationis and pruritic urticarial papules and plaques of pregnancy. Arch Dermatol 2005; 141:705.
- Al Saif F, Jouen F, Hebert V, et al. Sensitivity and specificity of BP180 NC16A enzyme-linked immunosorbent assay for the diagnosis of pemphigoid gestationis. J Am Acad Dermatol 2017; 76:560.
- Sitaru C, Dähnrich C, Probst C, et al. Enzyme-linked immunosorbent assay using multimers of the 16th non-collagenous domain of the BP180 antigen for sensitive and specific detection of pemphigoid autoantibodies. Exp Dermatol 2007; 16:770.
- Huilaja L, Surcel HM, Bloigu A, Tasanen K. Elevated serum levels of BP180 antibodies in the first trimester of pregnancy precede gestational pemphigoid and remain elevated for a long time after remission of the disease. Acta Derm Venereol 2015; 95:843.
- Joly P, Roujeau JC, Benichou J, et al. A comparison of oral and topical corticosteroids in patients with bullous pemphigoid. N Engl J Med 2002; 346:321.
- Joly P, Roujeau JC, Benichou J, et al. A comparison of two regimens of topical corticosteroids in the treatment of patients with bullous pemphigoid: a multicenter randomized study. J Invest Dermatol 2009; 129:1681.
- Kirtschig G, Middleton P, Bennett C, et al. Interventions for bullous pemphigoid. Cochrane Database Syst Rev 2010; :CD002292.
- Bjørn AM, Nielsen RB, Nørgaard M, et al. Risk of miscarriage among users of corticosteroid hormones: a population-based nested case-control study. Clin Epidemiol 2013; 5:287.
- Bay Bjørn AM, Ehrenstein V, Hundborg HH, et al. Use of corticosteroids in early pregnancy is not associated with risk of oral clefts and other congenital malformations in offspring. Am J Ther 2014; 21:73.
- Nørgård B, Pedersen L, Christensen LA, Sørensen HT. Therapeutic drug use in women with Crohn's disease and birth outcomes: a Danish nationwide cohort study. Am J Gastroenterol 2007; 102:1406.
- Gan DC, Welsh B, Webster M. Successful treatment of a severe persistent case of pemphigoid gestationis with antepartum and postpartum intravenous immunoglobulin followed by azathioprine. Australas J Dermatol 2012; 53:66.
- Rodrigues Cdos S, Filipe P, Solana Mdel M, et al. Persistent herpes gestationis treated with high-dose intravenous immunoglobulin. Acta Derm Venereol 2007; 87:184.
- Nguyen T, Alraqum E, Razzaque Ahmed A. Positive clinical outcome with IVIg as monotherapy in recurrent pemphigoid gestationis. Int Immunopharmacol 2015; 26:1.
- Doiron P, Pratt M. Antepartum intravenous immunoglobulin therapy in refractory pemphigoid gestationis: case report and literature review. J Cutan Med Surg 2010; 14:189.
- Huilaja L, Mäkikallio K, Hannula-Jouppi K, et al. Cyclosporine treatment in severe gestational pemphigoid. Acta Derm Venereol 2015; 95:593.
- Castle SP, Mather-Mondrey M, Bennion S, et al. Chronic herpes gestationis and antiphospholipid antibody syndrome successfully treated with cyclophosphamide. J Am Acad Dermatol 1996; 34:333.
- Amato L, Coronella G, Berti S, et al. Successful treatment with doxycycline and nicotinamide of two cases of persistent pemphigoid gestationis. J Dermatolog Treat 2002; 13:143.
- Cianchini G, Masini C, Lupi F, et al. Severe persistent pemphigoid gestationis: long-term remission with rituximab. Br J Dermatol 2007; 157:388.
- Marker M, Derfler K, Monshi B, Rappersberger K. Successful immunoapheresis of bullous autoimmune diseases: pemphigus vulgaris and pemphigoid gestationis. J Dtsch Dermatol Ges 2011; 9:27.
- Shornick JK, Black MM. Fetal risks in herpes gestationis. J Am Acad Dermatol 1992; 26:63.
- Al-Saif F, Elisa A, Al-Homidy A, et al. Retrospective analysis of pemphigoid gestationis in 32 Saudi patients - Clinicopathological features and a literature review. J Reprod Immunol 2016; 116:42.
- Aoyama Y, Asai K, Hioki K, et al. Herpes gestationis in a mother and newborn: immunoclinical perspectives based on a weekly follow-up of the enzyme-linked immunosorbent assay index of a bullous pemphigoid antigen noncollagenous domain. Arch Dermatol 2007; 143:1168.
- Chorzelski TP, Jablonska S, Beutner EH, et al. Herpes gestations with identical lesions in the newborn. Passive transfer of the disease? Arch Dermatol 1976; 112:1129.
- Katz A, Minto JO, Toole JW, Medwidsky W. Immunopathologic study of herpes gestationis in mother and infant. Arch Dermatol 1977; 113:1069.
- Taylor D, Pappo E, Aronson IK. Polymorphic eruption of pregnancy. Clin Dermatol 2016; 34:383.
- Vaughan Jones SA, Black MM. Pregnancy dermatoses. J Am Acad Dermatol 1999; 40:233.
- Aronson IK, Bond S, Fiedler VC, et al. Pruritic urticarial papules and plaques of pregnancy: clinical and immunopathologic observations in 57 patients. J Am Acad Dermatol 1998; 39:933.
- Alcalay J, Ingber A, Hazaz B, et al. Linear IgM dermatosis of pregnancy. J Am Acad Dermatol 1988; 18:412.
- Cohen LM, Capeless EL, Krusinski PA, Maloney ME. Pruritic urticarial papules and plaques of pregnancy and its relationship to maternal-fetal weight gain and twin pregnancy. Arch Dermatol 1989; 125:1534.
- Elling SV, McKenna P, Powell FC. Pruritic urticarial papules and plaques of pregnancy in twin and triplet pregnancies. J Eur Acad Dermatol Venereol 2000; 14:378.
- Kroumpouzos G, Cohen LM. Specific dermatoses of pregnancy: an evidence-based systematic review. Am J Obstet Gynecol 2003; 188:1083.
- Beckett MA, Goldberg NS. Pruritic urticarial plaques and papules of pregnancy and skin distention. Arch Dermatol 1991; 127:125.
- Aractingi S, Berkane N, Bertheau P, et al. Fetal DNA in skin of polymorphic eruptions of pregnancy. Lancet 1998; 352:1898.
- Yancey KB, Hall RP, Lawley TJ. Pruritic urticarial papules and plaques of pregnancy. Clinical experience in twenty-five patients. J Am Acad Dermatol 1984; 10:473.
- Regnier S, Fermand V, Levy P, et al. A case-control study of polymorphic eruption of pregnancy. J Am Acad Dermatol 2008; 58:63.
- Lawley TJ, Hertz KC, Wade TR, et al. Pruritic urticarial papules and plaques of pregnancy. JAMA 1979; 241:1696.
- Rudolph CM, Al-Fares S, Vaughan-Jones SA, et al. Polymorphic eruption of pregnancy: clinicopathology and potential trigger factors in 181 patients. Br J Dermatol 2006; 154:54.
- Chi CC, Wang SH, Kirtschig G. Safety of Topical Corticosteroids in Pregnancy. JAMA Dermatol 2016; 152:934.
- Chi CC, Wang SH, Wojnarowska F, et al. Safety of topical corticosteroids in pregnancy. Cochrane Database Syst Rev 2015; :CD007346.
- Chi CC, Wang SH, Mayon-White R, Wojnarowska F. Pregnancy outcomes after maternal exposure to topical corticosteroids: a UK population-based cohort study. JAMA Dermatol 2013; 149:1274.
- Beltrani VP, Beltrani VS. Pruritic urticarial papules and plaques of pregnancy: a severe case requiring early delivery for relief of symptoms. J Am Acad Dermatol 1992; 26:266.
- Roth MM, Cristodor P, Kroumpouzos G. Prurigo, pruritic folliculitis, and atopic eruption of pregnancy: Facts and controversies. Clin Dermatol 2016; 34:392.
- Wilder RL. Hormones, pregnancy, and autoimmune diseases. Ann N Y Acad Sci 1998; 840:45.
- Holmes RC, Black MM. The specific dermatoses of pregnancy. J Am Acad Dermatol 1983; 8:405.
- Nurse DS. Prurigo of pregnancy. Australas J Dermatol 1968; 9:258.
- Kroumpouzos G, Cohen LM. Pruritic folliculitis of pregnancy. J Am Acad Dermatol 2000; 43:132.
- Zoberman E, Farmer ER. Pruritic folliculitis of pregnancy. Arch Dermatol 1981; 117:20.
- Hillman SC, Stokes-Lampard H, Kilby MD. Intrahepatic cholestasis of pregnancy. BMJ 2016; 353:i1236.
- Marschall HU, Wikström Shemer E, Ludvigsson JF, Stephansson O. Intrahepatic cholestasis of pregnancy and associated hepatobiliary disease: a population-based cohort study. Hepatology 2013; 58:1385.
- Bellman B, Berman B. Skin diseases seriously affecting fetal outcome and matemal health. In: Skin Changes and Diseases in Pregnancy, Harahap M, Wallach RC (Eds), Marcel Dekker, Inc., New York 1996. p.129.
- Charles-Holmes R. Skin diseases specifically associated with pregnancy. In: Skin Changes and Diseases in Pregnancy, Harahap M, Wallach RC (Eds), Marcel Dekker, Inc., New York 1996. p.55.
- Breier-Maly J, Ortel B, Breier F, et al. Generalized pustular psoriasis of pregnancy (impetigo herpetiformis). Dermatology 1999; 198:61.
- Henson TH, Tuli M, Bushore D, Talanin NY. Recurrent pustular rash in a pregnant woman. Arch Dermatol 2000; 136:1055.
- Robinson A, Van Voorhees AS, Hsu S, et al. Treatment of pustular psoriasis: from the Medical Board of the National Psoriasis Foundation. J Am Acad Dermatol 2012; 67:279.
- Hazarika D. Generalized pustular psoriasis of pregnancy successfully treated with cyclosporine. Indian J Dermatol Venereol Leprol 2009; 75:638.
- Kapoor R, Kapoor JR. Cyclosporine resolves generalized pustular psoriasis of pregnancy. Arch Dermatol 2006; 142:1373.
- Shaw CJ, Wu P, Sriemevan A. First trimester impetigo herpetiformis in multiparous female successfully treated with oral cyclosporine. BMJ Case Rep 2011; 2011.
- Patsatsi A, Theodoridis TD, Vavilis D, et al. Cyclosporine in the management of impetigo herpetiformis: a case report and review of the literature. Case Rep Dermatol 2013; 5:99.
- Sheth N, Greenblatt DT, Acland K, et al. Generalized pustular psoriasis of pregnancy treated with infliximab. Clin Exp Dermatol 2009; 34:521.
- Puig L, Barco D, Alomar A. Treatment of psoriasis with anti-TNF drugs during pregnancy: case report and review of the literature. Dermatology 2010; 220:71.
- Arslanpence I, Dede FS, Gokcu M, Gelisen O. Impetigo herpetiformis unresponsive to therapy in a pregnant adolescent. J Pediatr Adolesc Gynecol 2003; 16:129.
- Katsambas A, Stavropoulos PG, Katsiboulas V, et al. Impetigo herpetiformis during the puerperium. Dermatology 1999; 198:400.
- Bukhari IA. Impetigo herpetiformis in a primigravida: successful treatment with etretinate. J Drugs Dermatol 2004; 3:449.
- Oumeish OY, Parish JL. Impetigo herpetiformis. Clin Dermatol 2006; 24:101.