8.6 Pregnancy dermatoses

Dermatoses of pregnancy are a group of disorders seen throughout the world. They are usually seen more commonly late in pregnancy and in those twin or multiple pregnancies.

Polymorphic eruption of pregnancy (PEP): Represents the most common specific dermatosis of pregnancy. Incidence: 1:160 pregnancies. More frequent in multiple gestation pregnancies (twins or triplets).

Pemphigoid gestationis (PG): 1 in 40-50,000 pregnancies. Worldwide distribution. Association with the haplotypes HLA-DR3 (60-80%) and HLADR4 (50%).

Atopic eruption of pregnancy (AEP) is always causally linked with a personal and/or family atopic background.

Intrahepatic cholestasis of pregnancy (ICP): Geographic pattern: South America (10-30%), Scandinavian countries (2.4%), USA, Europe: 0.1-1.5%. Positive family history > 50% of cases.

Pustular psoriasis of pregnancy: Very Rare. No more than 200 reported cases.

Polymorphic eruption of pregnancy (PEP): Pathogenesis unknown, but there are multiple theories: hormonal factors, autoimmune factors, fetal cell microchimerism and atopic background.

Pemphigus gestationis: Autoimmune response against a placental matrix antigen. Possible cross reactivity between placental tissues and skin. Autoantibodies against BP180 (bullous pemphigoid) antigen. Circulating complement-fixing IgG antibodies of the subclass IgG1 (‘pemphigoid gestationis factor’). Immune complex deposition, complement activation, chemo-attraction of eosinophils and blister formation. PG is associated with other autoimmune disorders (Graves’ disease, pernicious anemia and Hashimoto thyroiditis). Possible occurrence of the disease when using oral contraceptives or during the premenstrual period.

Atopic eruption of pregnancy: May occur in atopic subjects or others without atopy. Etiology: unknown. Possible role of dominant Th2 cytokine production during pregnancy.

Intrahepatic cholestasis of pregnancy: Not a primary dermatosis but a pregnancy-related liver disorder with secondary cutaneous lesions in particular induced by scratching. Pathogenesis: Multifactorial - hormonal (estrogen and progesterone metabolites), genetic and exogenous (environmental).

Pustular psoriasis of pregnancy: Possible peculiar form of ordinary pustular psoriasis.

Depends on disorder. Skin eruptions usually appear in the third trimester of pregnancy and tend to resolve after delivery.

The severity of symptoms and signs are variable. The lesions may manifest as papules/plaques (PEP, AEP), blisters (PG, PEP), urticarial lesions (PEP, PG), pustules (PPP, PEP), lichenified plaques (AEP, ICP) or eczematous lesions. Sometimes scars may be present (ICP).

Polymorphic eruption of pregnancy (PEP): Benign, self-limited, pruritic, papulo-urticarial inflammatory disorder that usually affects the primigravida in the last trimester of pregnancy or in the immediate post-partum period. Clinically polymorphous intensely itchy erythematous papules and plaques develop within and/or adjacent to striae gravidarum, occasionally macules, papulo-vesicles (eczematous), urticarial, targetoid lesions similar to erythema multiforme; annular or polycyclic wheals may also be present; and rarely, small bullae excoriations and crusts. During the evolution of the disease, other body sites may be involved such as buttocks, proximal thighs, or back.

Pemphigoid gestationis (PG): Autoimmune vesiculobullous disorder. Intensely pruritic. Late pregnancy (second or third trimester) or puerperium. Clinically, erythematous urticarial papules and plaques mostly on the abdomen (peri-umbilical), also limbs, palms, or soles. The lesions progress to tense blisters and bullae. Distribution: Abdomen, trunk and extremities. Face, palms, soles, and mucous membranes usually spared.

Atopic eruption of pregnancy (AEP): Generalized pruritic skin condition. Exacerbation or the first occurrence of eczematous and/or papular skin changes during pregnancy in patients with an atopic diathesis. Most common presentation: Eczematous dermatitis in the classic atopic sites: antecubital and popliteal fossae, face, eyelids, and neck. Non-specific pruritic papules on the neck, trunk, and extremities.

Xerosis, excoriations, and prurigo lesions. Prurigo of pregnancy: Excoriated papules and nodules on the limbs and/or trunk and typical onset in mid-pregnancy. Pruritic folliculitis of pregnancy: Follicular/pustular and papular lesions on the trunk or generalized.

Intrahepatic cholestasis of pregnancy (ICP): Widespread pruritus. No primary skin lesions, Onset: Last trimester of pregnancy. Secondary skin changes due to scratching (excoriations, scratch marks and/or prurigo nodules). Jaundice (10%) due to concomitant extra-hepatic cholestasis.

Pustular psoriasis of pregnancy (PPP): Second half of pregnancy with widespread, tiny, superficial, pustules arranged in herpetiform distribution. Extension with a centrifugal pattern. The eruption is usually associated pain, fever, chills, vomiting, nausea, and malaise.

Polymorphic eruption of pregnancy (PEP): striae gravidarum, abdomen, trunk. Pemphigoid gestationis: abdomen (peri-umbilical), trunk, extremities.

Atopic eruption of pregnancy: antecubital popliteal folds.

Intrahepatic cholestasis of pregnancy: shins and lower arms, buttocks or abdomen. Pustular psoriasis of pregnancy: trunk, extremities.

• Polymorphic eruption of pregnancy (PEP).

• Pemphigoid gestationis (PG).

• Atopic eruption of pregnancy (AEP): encompasses atopic eczema in pregnancy, prurigo of pregnancy, as well as pruritic folliculitis of pregnancy.

• Intra-hepatic cholestasis of pregnancy (ICP).

• Pustular psoriasis of pregnancy (PPP).

Polymorphic eruption of pregnancy (PEP): Non-specific histologic features: Spongiosis papillary dermal edema; superficial, mid-dermal perivascular lymphohistiocytic infiltrate with occasional eosinophils, DIF (direct immunofluorescence) and IIF (indirect immunofluorescence) are negative.

Pemphigoid gestations: Pre-bullous stage: Perivascular inflammatory infiltrate, composed of lymphocytes, histiocytes, and eosinophils. Spongiosis and focal epidermal necrosis. Bullous stage: Subepidermal blister, Eosinophils are seen along the BMZ (basal membrane zone) and in the bullous spaces.

Direct immunofluorescence (IF): Linear deposition of C3 and occasionally IgG along the BMZ. Indirect immunofluorescence/ELISA: Circulating IgG antibodies anti BP180.

Intra-hepatic cholestasis of pregnancy: Skin biopsy: Non-specific changes. DIF and IIF: Negative.

Atopic eruption of pregnancy: Histopathology is non-specific (spongiosis) and direct immunofluorescence: negative.

Pustular psoriasis of pregnancy: Subcorneal spongiform pustules similar to pustular psoriasis.

Polymorphic eruption of pregnancy (PEP): The lesions usually resolve within 4-6 weeks.

Pemphigoid gestationis: Self-limiting. Spontaneous remission in weeks to months after delivery. Alternating exacerbations and remissions during pregnancy. Improvement in the third trimester. Flare- up at the time of delivery. Tends to recur in all subsequent pregnancies, usually with an earlier onset and increased severity. Possible exacerbations or recurrences during the premenstrual period or oral contraceptives use.

Resolution after delivery and possible recurrences with subsequent pregnancies in atopic eruption of pregnancy, intrahepatic cholestasis of pregnancy and pustular psoriasis of pregnancy.

In many instances should be established with other specific dermatoses of pregnancy and/or different dermatoses appearing during pregnancy.

Polymorphic eruption of pregnancy (PEP): Pemphigoid gestationis (pre-bullous) or different papular/ plaque/urticarial dermatoses appearing during pregnancy: Drug eruptions, allergic contact dermatitis, scabies, erythema multiforme.

Pemphigoid gestationis: Pre-blistering stage: PEP, Blistering stage: Other autoimmune bullous diseases: bullous pemphigoid, dermatitis herpetiformis, linear IgA disease, bullous systemic lupus erythematosus, erythema multiforme, bullous drug eruptions, or contact dermatitis coincident with pregnancy.

Atopic eruption of pregnancy: Pruritic dermatoses unrelated to and coinciding with gestation (e.g. atopic dermatitis, scabies, drug eruptions, and arthropod bites).

Intra-hepatic cholestasis of pregnancy: Different dermatologic and/or internal conditions that cause pruritus in the absence of primary skin lesions.

Pustular psoriasis of pregnancy: Autoimmune bullous dermatoses that coincide with pregnancy, acute generalized exanthematous pustulosis.

• Polymorphic eruption of pregnancy (PEP): Symptomatic treatment: topical corticosteroids, topical antipruritic or emollient treatments; Systemic antihistamines (loratadine or cetirizine).

• Pemphigoid gestationis: Dependent on the stage and severity of the disease. Potent topical corticosteroids. Systemic corticosteroids (prednisone, 0.5–2 mg/kg/day), to control blister formation, tapered and maintained at the lowest effective dose. Immunosuppressive treatments only used after delivery.

• Atopic eruption of pregnancy: Moderately potent topical corticosteroids and oral antihistamines. Emollients or anti-pruritic additives such as menthol or polidocanol.

• Intrahepatic cholestasis of pregnancy: Antipruritic treatments: ursodeoxycholic acid, cholestyramine, antihistamines (non-sedative), anion exchange resins.

• Pustular psoriasis of pregnancy: Systemic corticosteroids, ciclosporin. After pregnancy, other agents used in psoriasis could be prescribed: PUVA, or other systemic agents. If secondary skin infection, antibacterials can be used.

Fetal prognosis:

Pemphigoid gestationis: Increased risk of prematurity and developing small-for-gestational-age babies.

Intrahepatic cholestasis of pregnancy: Risk of premature birth (19-60%), fetal distress (22-33%) and stillbirth (1-2%).

Pustular psoriasis of pregnancy: Increased fetal risk such as stillbirth, neonatal death, and fetal abnormalities.