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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 "Safety 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 "Safety 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 'Maternal 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.)
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