What Caused This Eruption?

Patient Presentation A 33-year-old pregnant woman, gravida one, para zero, presented at 34 weeks of gestation complaining of a progressively worsening pruritic eruption. The lesions began around her umbilicus, and over a few days, extended to involve her whole abdomen with extension to her lower extremities. She was otherwise healthy with no personal or family history of any skin diseases. Her current list of medications included only iron supplements and prenatal vitamins. On physical examination, multiple erythematous papules and plaques were noted on her abdomen and upper thighs. The lesions were slightly edematous and had a predilection for striae; no blisters were noted. She had no mucosal involvement and a review of her systems was unremarkable. Her complete blood count and liver function tests were within normal limits. What is Your Diagnosis? Diagnosis: Pruritic Urticarial Papules and Plaques of Pregnancy (PUPPP) Pruritic urticarial papules and plaques of pregnancy (PUPPP) is the most common of the pregnancy-specific dermatoses.1 It was initially reported as a “toxemic rash of pregnancy,”2 and the term PUPPP was introduced by Lawley and colleagues in 1979.2 In Great Britain the condition is known as polymorphic eruption of pregnancy. Epidemiology PUPPP is an inflammatory dermatosis associated solely with pregnancy, with an incidence ranging from 1 in 130 to 1 in 300 pregnancies.3 The majority (75% to 85%) of patients are primigravidas.4 The reason why it primarily develops in the first pregnancy is unclear.5 PUPPP typically occurs within the last 5 weeks of pregnancy, but lesions have been reported to develop as early as 17 weeks gestation,6 and rarely in the immediate post-partum period.7,8 A male:female ratio of 2:1 has been found in the offspring of affected women, but the relevance of this is not currently clear.9 No associations have been found with atopy, pre-eclampsia or autoimmune phenomena,10 but 11% of patients are noted to have asthma.11 Pathogenesis The cause of PUPPP is unknown. Several theories including abdominal distension, deposition of fetal DNA in the skin, an autoimmune hypothesis and a hormonal etiology have been implicated.5 The common clinical localization to abdominal striae suggests that abdominal distension may be an important factor. This theory is consistent with the findings of PUPPP being associated with an increased incidence of twins,12,13,14 multiple pregnancies9 and excess maternal weight gain.12 The immunohistologic profile may imply a delayed hypersensitivity reaction to an unknown antigen. In a study by Aractingi et al, fetal DNA was found in skin lesions of PUPPP, and the authors suggested that fetal cells migrating to maternal skin may be an etiological factor.15 No definitive evidence has been found to implicate autoimmune mechanisms, and the frequency of human leukocyte antigens is normal.16 Zurn et al17 reported circulating IgM anti-basement membrane zone (BMZ) antibodies in five patients with PUPPP; however, the specificity of this observation has been debated.18 A recent prospective study of 44 patients with PUPPP also showed low serum cortisol levels compared with controls, suggesting a potential hormonal influence.9 Clinical Features The clinical morphology of PUPPP is variable. Aronson et al have categorized the clinical features into three types.11 The typical lesions of PUPPP are pruritic, red, urticarial papules and plaques appearing on the trunk and proximal regions of the extremities. These lesions usually develop in abdominal striae and spread centrifugally, with sparing of the periumbilical region.19 Other commonly affected sites include the thighs, back, buttocks and the extensor surfaces of the arms.8 Sparing of the face is characteristic, even though facial involvement has been reported in a few cases.20 The palms and soles are also usually spared, and approximately 40% of patients develop vesicles.8 Laboratory Investigations The diagnosis of PUPPP is often made clinically. There is no specific laboratory abnormality found in PUPPP. Investigations serve to exclude concurrent diseases.11,21 Skin biopsy findings are non-specific. In early PUPPP there is epidermal and upper dermal edema, accompanied by a superficial perivascular lymphohistiocytic infiltrate.10 In approximately one-third of cases, eosinophils can be numerous, and occasionally eosinophilic spongiosis occurs.10 When small vesicles are present clinically, the histopathology usually reveals intense focal spongiosis, and occasionally subepidermal vesicles. In the resolving stage of the eruption, there are foci of parakeratosis and acanthosis.5 A biopsy for direct immunofluorescence (DIF) may be done when necessary to differentiate PUPPP from the urticarial form of gestational pemphigoid (herpes gestationis).22 DIF is negative in the great majority of cases. Differential Diagnosis The most important differential diagnosis to consider is urticarial gestational pemphigoid. Clinically, patients with gestational pemphigoid have systemic symptoms, involvement of the palms and soles, and periumbilical lesions are common. In addition, laboratory tests indicate leukocytosis with eosinophilia, and histology reveals subepidermal bullae.23 This is an immune-mediated condition, which characteristically shows linear deposits of C3 along the BMZ. Pruritic folliculitis of pregnancy is distinguished on the basis of the follicular nature of the lesions and histopathologic features of folliculitis.24 Prurigo of pregnancy begins earlier in pregnancy, lacks urticarial lesions, persists throughout pregnancy, and may recur with subsequent pregnancies.24 Other conditions to consider in the differential diagnosis include drug eruptions, viral exanthems, scabies, urticaria, contact dermatitis and erythema multiforme. Treatment Because PUPPP is a self-limiting disorder without serious consequences for the mother or the fetus, a conservative approach is justified in most cases.5 Patients should be reassured that the eruption will resolve after delivery.24 General measures, such as cool soothing baths, frequent application of emollients, wet soak applied to the skin and light cotton clothing may provide symptomatic relief.5 Symptomatic treatment may involve using an antipruritic topical medication such as topical corticosteroids (for example, betamethasone valerate 0.1% applied twice daily).24 Most cases respond to this regimen within 24 to 72 hours with clearing of the rash and resolution of the pruritus.19 Systemic antihistamines such as hydroxyzine (Atarax) and diphenhydramine (Benadryl) may also provide some symptomatic relief.19 Of note, these drugs are both pregnancy category C. In severe cases, a short course of prednisone in doses ranging from 40 mg to 60 mg daily usually induces a prompt resolution of symptoms and the eruptions.9,24 The use of oral corticosteroids in the latter part of the third trimester of pregnancy appears to have little adverse effect on the pregnancy. However, their use is rarely necessary, and should be limited to symptoms of intractable pruritus persisting in spite of intensive topical therapy.5 Early delivery in cases of intractable pruritus has been debated, but has not gained support.14,25,26 Prognosis The mean duration of the eruptions is 6 weeks, but in general it is not severe for more than 1 week.10 Resolution typically occurs within 10 to 14 days of delivery.27 On resolution, there is no post-inflammatory pigment change or scarring of the skin.5 PUPPP does not appear to be associated with adverse perinatal outcomes,28 and to our knowledge, only one possible case of transient neonatal PUPPP involvement has been described.29 Recurrence in subsequent pregnancies, with menses or oral contraceptives, is uncommon.14 Our patient was treated successfully with topical corticosteroids, and her lesions resolved in 2 weeks. Call For Cases If you have a case you’d like to see published, send a write-up (1,200 to 1,500 words) and an image of the patient’s condition to: Dr. Amor Khachemoune, Wellman Center for Photomedicine (BAR314) Department of Dermatology, Massachusetts General Hospital Harvard Medical School 40 Blossom Street Boston, MA 02114 Or, e-mail them to amorkh@pol.net.