Polymorphic Eruption of Pregnancy Presented with Targetoid Lesions: A Report of Two Cases

Polymorphic eruption of pregnancy (PEP) and herpes gestationis (HG) are pregnancy-related dermatoses of unknown aetiology with eosinophil infiltration which, at early stages, may show similar clinical and histopathological features. To determine the relative contributions of eosinophils, neutrophils and mast cells to the pathogenesis of PEP and HG through deposition of granule proteins, we studied tissue and serum from 15 patients with PEP and 10 with HG. Using indirect immunofluorescence with antibodies to human eosinophil granule major basic protein (MBP), eosinophil-derived neurotoxin (EDN), eosinophil cationic protein (ECP), neutrophil elastase and mast cell tryptase, we determined and compared cellular and extracellular staining patterns in lesional skin biopsy specimens and, using immunoassay, measured MBP, EDN, and ECP in patients' sera. Eosinophil infiltration and extracellular protein deposition of all three eosinophil granule proteins were present in both PEP and HG indicating a pathogenic role for eosinophils in both diseases. Staining for eosinophil granule proteins was especially prominent in urticarial lesions and around blisters in HG. EDN and ECP serum levels in PEP and ECP serum levels in HG were significantly increased compared with those in normal pregnant and normal nonpregnant serum. Neutrophils were more prominent in HG specimens than in PEP specimens; extracellular neutrophil elastase was minimally present and similar in both diseases. Mast cell numbers and extracellular tryptase deposition did not differ between the two diseases and did not differ from mast cell counts in skin of normal pregnant women. This study shows that eosinophil granule proteins are deposited extracellularly in tissue and are increased in serum in both PEP and HG. Moreover, eosinophil involvement in the two diseases is more consistent than neutrophil and mast cell involvement. Comparatively, tissue eosinophil infiltration and extracellular protein deposition is more extensive in HG than in PEP, suggesting that eosinophil involvement is greater in the pathogenesis of HG than PEP and similar to that found in bullous pemphigoid.

Pruritic Urticarial Papules and Plaques of Pregnancy

The specific dermatoses of pregnancy represent a heterogeneous group of pruritic skin diseases that have been recently reclassified and include pemphigoid (herpes) gestationis, polymorphic eruption of pregnancy (syn. pruritic urticarial papules and plaques of pregnancy), intrahepatic cholestasis of pregnancy, and atopic eruption of pregnancy. They are associated with severe pruritus that should never be neglected in pregnancy but always lead to an exact work-up of the patient. Clinical characteristics, in particular timing of onset, morphology and localization of skin lesions are crucial for diagnosis which, in case of pemphigoid gestationis and intrahepatic cholestasis of pregnancy, will be confirmed by specific immunofluorescence and laboratory findings. While polymorphic and atopic eruptions of pregnancy are distressing only to the mother because of pruritus, pemphigoid gestationis may be associated with prematurity and small-for-date babies and intrahepatic cholestasis of pregnancy poses an increased risk for fetal distress, prematurity, and stillbirth. Corticosteroids and antihistamines control pemphigoid gestationis, polymorphic and atopic eruptions of pregnancy; intrahepatic cholestasis of pregnancy, in contrast, should be treated with ursodeoxycholic acid. This review will focus on the new classification of pregnancy dermatoses, discuss them in detail, and present a practical algorithm to facilitate the management of the pregnant patient with skin lesions.

Pruritic urticarial papules and plaques of pregnancy (PUPPP) is among the most common dermatoses of pregnancy. Most reports of the effective treatment of PUPPP involve high potency topical corticosteroids or oral steroids. Many authorities have noted cases of PUPPP whose resolution followed parturition. A few have noted that PUPPP can arise and resolve the third trimester. A 36-year-old prima gravida at 38 weeks of gestation presented with a 2-week history of a pruritic papular abdominal eruption. She used fluticasone propionate 0.05 percent lotion twice a day. One week after starting this medication, the pruritus had resolved and the erythema/urticaria had abated; the pigmentary alteration had improved, but still remained. The PUPPP did not return after parturition. PUPPP can abate entirely during pregnancy. Fluticasone propionate 0.05 percent lotion, a class 5 (low-medium potency) corticosteroid, has a benign side effect profile and should be considered for the treatment of PUPPP during pregnancy.

Introduction: Pruritic urticarial papules and plaques of pregnancy (PUPPP), also known as polymorphic eruption of pregnancy (PEP), is a common, self-limiting dermatosis of pregnancy. However, its specific characteristics and management outcomes in Indonesia, a diverse and populous nation, remain understudied. This study aimed to comprehensively assess the clinical features, risk factors, and management outcomes of PUPPP in an Indonesian population. Methods: A retrospective cohort study was conducted at Private Hospital in Jakarta, Indonesia, between January 2019 and December 2023. Medical records of pregnant women diagnosed with PUPPP were reviewed. Data collected included demographics, gestational age at onset, clinical presentation (lesion morphology, distribution, pruritus severity), associated symptoms, parity, pre-pregnancy BMI, weight gain during pregnancy, smoking history, presence of comorbidities, treatment modalities, and treatment outcomes (symptom resolution time, recurrence). Statistical analysis was performed using SPSS version 28. Results: A total of 285 pregnant women were included in the study. The mean age was 29.5 years (SD ± 4.8). The majority (72.3%) were primigravida. Onset was most common in the third trimester (88.4%). The most frequent presenting symptom was severe pruritus (94.7%), followed by erythematous papules (98.2%) and urticarial plaques (91.6%). Lesions predominantly affected the abdomen (96.5%), particularly the striae distensae (89.1%), with frequent involvement of the thighs (75.4%) and buttocks (62.1%). Higher pre-pregnancy BMI (p=0.012) and excessive gestational weight gain (p=0.003) were significantly associated with PUPPP development. Topical corticosteroids (85.6%) were the most commonly used treatment, followed by oral antihistamines (68.4%). Symptom resolution occurred within a mean of 10.2 days (SD ± 3.5) after treatment initiation. Recurrence was observed in 8.4% of cases. Conclusion: PUPPP in Indonesian women predominantly affects primigravida in the third trimester, presenting with severe pruritus and characteristic lesions on the abdomen, thighs, and buttocks. Higher pre-pregnancy BMI and excessive gestational weight gain appear to be significant risk factors. Topical corticosteroids and oral antihistamines are effective in achieving symptom resolution. These findings highlight the need for increased awareness and appropriate management of PUPPP in Indonesia.

Dear Editor: Pruritic urticarial papules and plaques of pregnancy (PUPPP) is one of the most common diseases associated with pregnancy, and is characterized by urticarial papules and plaques with pruritus on the abdomen, buttocks and thighs1. In most cases, the skin lesions develop in the third trimester of primigravida and disappear within 7 to 10 days after labor1. Lesions mostly appear first on the abdomen, and then spread to the proximal extremities. Therefore, the abdomen is involved in most cases, especially the stria distensae. A 30-year-old female patient visited our department due to pruritic erythematous papules and plaques on both arms and both legs (Fig. 1 A~C). She complained that the erythematous skin lesions had first developed on both legs and were very pruritic. The lesions then spread to both arms. The patient's abdomen was spared. She went through labor seven days before the lesions developed in both thighs. She was in a postpartum period, which is the period beginning immediately after the birth of a child and extending for about six weeks. It was her first labor and a single pregnancy. She had no specific medical or dermatological history. We did laboratory studies including complete blood counts, liver function tests, renal function tests, thyroid function tests urinalysis and autoimmune study. She has no specific abnormal findings during these studies. We performed a biopsy of the lower leg for an exact diagnosis. Histopathological findings showed spongiosis of the epidermis, edema of the papillary dermis and perivascular infiltration of lymphocytes and eosinophils (Fig. 1D, E). The results of direct immunofluorescence were negative. The patient began to take prednisolone 20 mg daily for 4 days and then tapered to 5 mg per week. She was also treated with an oral antihistamine and a topical corticosteroid. After two weeks of treatment, the patient's symptoms of pruritus and erythematous skin rash were improved. In most cases, this disorder develops in the third trimester of pregnancy. Tiny pruritic erythematous papules first appear in the striae distensae of the abdomen, and then spread to the buttocks and legs. In our case, multiple pruritic erythematous papules and plaques occurred after labor, and the lesions were limited to the legs and arms, sparing the abdomen. Postpartum PUPPP is very rare (Table 1)2-5. In previous cases, the lesions first developed on the abdomen, and then spread to other parts of the body. In our patient, the pruritic skin lesions were limited to the extremities, while the abdomen was spared. Some previous cases also exhibited unique distributions. In contrast to all these cases, our case spared the abdomen and involved only the extremities. Generally, histological findings of PUPPP showed dyskeratosis, spongiosis of the epidermis, edema of the papillary dermis and perivascular lymphocytic infiltrations1. Direct immunofluorescence studies are negative. We also noted these histological features in our case. Based on these histopathological and clinical findings, we diagnosed the case as PUPPP developed in postpartum-period. Although our case was similar to urticarial vasculitis, clinically, the specimen did not show findings of leukocytoclastic vasculitis, and she improved without hyperpigmentation. Thus, we can rule out the urticarial vasculitis. Our case characterized itself by postpartumperiod developments which simultaneously show unique distributions of the disease that only limits the lesions to the extremities and sparing abdomen. This pattern of the disease has never been reported, and thus, display the strength of our case report. In conclusion, we report a case of PUPPP in which the lesions developed after labor and were limited to both the legs and arms. Fig. 1 Multiple itchy erythematous papules and plaques were observed on both the arms and legs. (A) Lesions on the lower extremities. (B, C) Lesions on the upper extremity. Histopathology of the skin lesions. (D) There were mild epidermal spongiosis and perivascular ... Table 1 Summary of postpartum pruritic urticarial papules and plaques of pregnancy cases

<p class="abstract"><strong>Background:</strong> Pregnancy being a complex state, the interactions of multiple factors result in a number of cutaneous findings that can be separated into physiologic changes, pre-existing dermatoses that can be aggravated or improved during pregnancy and dermatoses that are specific to pregnancy. Dermatoses specific to pregnancy are important to recognise because they may be pruritic or painful to the mother and may pose significant risk to mother, her fetus or both. Early identification of the condition may go a long way in preventing morbidity and mortality<span lang="EN-IN">.</span></p><p class="abstract"><strong>Methods:</strong> Antenatal women attending dermatology outpatient for dermatologic problems or referred from Obstetrics and Gynaecology, department for skin conditions in a tertiary care hospital in Kottayam, Kerala state were taken up for the study. Pregnancy related dermatoses or physiologic changes due to pregnancy if present were noted. The patients were followed up till delivery and the pregnancy outcome recorded. The results were analyzed using SPSS.<strong></strong></p><p class="abstract"><strong>Results:</strong> 94.3% of the patients had physiological changes, hyperpigmentation being the commonest. Specific pregnancy dermatoses were present in 38.3%. 94% of pregnancy dermatoses occurred during third trimester. The most common specific dermatoses observed was pruritic urticarial papules and plaques of pregnancy (PUPPP)-63.6%. It is more common in primi gravida (30/42), in twin pregnancies, in mothers of babies with more birth weight, male babies and those with gestational diabetes mellitus. None of the specific dermatoses produced adverse fetal outcome<span lang="EN-IN">. </span></p><p class="abstract"><strong>Conclusions:</strong> Pregnancy dermatoses usually manifest in the third trimester. PUPPP is the commonest pregnancy dermatosis. PUPPP is more common among mothers with increased body weight, gestational diabetes, in twin pregnancy and in mothers with male babies. Most of the common pregnancy dermatoses have no adverse effect on the fetus<span lang="EN-IN">.</span></p>

<p class="abstract">Polymorphic eruption of pregnancy (PEP), also known as pruritic urticarial papules and plaques of pregnancy [PUPPP] is the most common of all the specific dermatoses of pregnancy. It is a benign, self-resolving, pruritic disorder of pregnancy, usually affecting primigravida during the last trimester of pregnancy or immediately postpartum. Its exact pathogenesis is still unknown, and its clinical presentations are variable. It may mimic many common dermatoses. In PEP, the histological findings are non-contributory and the laboratory results, including direct and indirect immunofluorescence are negative. Diagnosis mainly depends on clinical findings. Significant diagnostic confusion may occur with early lesions of pemphigoid gestationis, which needs to be differentiated from PEP as the former may have a bad fetal outcome. PEP is not associated with any fetal or maternal risk, and symptomatic treatment is all that is usually required. The awareness of this condition helps the physician recognize this entity, reassure the patient, and avoid unnecessary investigations. This review focuses on etiology, various clinical presentations, differential diagnosis, and management of PEP.</p>

A primiparous patient, 30 days postpartum, presented to the clinic with a chief complaint of an itchy red rash on her mid to lower abdomen. It started 2 days ago. The rash had spread to her upper thighs. Past medical history was negative for skin disease or atopy. Her examination exposed pruritic erythematous polymorphous papules, with subsequent coalescence of larger urticarial plaques on the mid to lower abdomen and upper thighs. The patient was diagnosed with pruritic urticarial papules and plaques of pregnancy (PUPPP). PUPPP is the most common dermatosis affecting about one in 200 pregnant women. It has no tendency to recur in subsequent pregnancies. The elevated differential diagnosis included pemphigoid gestationis and eczema. Drug eruptions, urticaria, and viral exanthems were also considered. The primary goal of PUPPP treatment is to alleviate pruritus and discomfort. Antihistamines and topical corticosteroids are often prescribed along with skin care recommendations. Patients frequently have limited relief from topical treatments or skin care strategies. The extent of patient discomfort mandates competent evaluation because treatment is symptomatic and PUPPP can be difficult to manage. Despite the discomfort related to severe pruritus, PUPPP is not harmful to the mother or baby.

Fetal DNA in skin of polymorphic eruptions of pregnancy

Pruritic urticarial papules and plaques of pregnancy (PUPPP) is one of the most common diseases associated with pregnancy. In most cases, the skin lesions develop in the third trimester of primigravidas. There are no systemic alterations seen in PUPPP; however, most patients report severe pruritus. A 34-year-old woman presented 1 week postpartum with typical clinical features of PUPPP. The patient showed good response to intramuscular injection of autologous whole blood with no adverse effects to the patient or her baby. Presentation of PUPPP in the postpartum period is rare. Conservative management with topical corticosteroids and oral antihistamines is commonly used to relieve pruritus. In severe cases, skin lesions and symptoms are controlled with a brief course of systemic corticosteroids. Investigation of new treatment options has been limited by patient concerns about the negative effects of medication on the fetus or breastfeeding. Intramuscular injection of autologous whole blood could be an alternative treatment option for PUPPP, especially for women who worry about the use of medications during pregnancy or breastfeeding.

The specific dermatoses of pregnancy represent a recently reclassified heterogeneous group of pruritic inflammatory skin diseases unique to pregnancy that include pemphigoid gestationis, polymorphic eruption of pregnancy (PEP), intrahepatic cholestasis of pregnancy, and atopic eruption of pregnancy (AEP). Among them, PEP and AEP are the most frequent ones. We performed a histopathological study of a series of PEP and AEP patients (n = 41). Twenty-two patients had PEP that started in the third trimester in 16 (73%) patients and postpartum in 6 (27%) patients. Histopathology revealed a superficial or superficial and deep perivascular dermatitis with eosinophils in all biopsies and signs of a lymphocytic vasculitis in 5 (23%) cases. Epidermal changes, including epidermal hyperplasia, spongiosis, and parakeratosis, occurred in 8 cases, in particular in elder lesions. Nineteen patients had AEP that started earlier [less than third trimester, 14 (74%) patients; third trimester, 5 (26%) patients]. Clinically, 5 (26%) patients showed eczematous lesions, 7 (37%) papular lesions, 3 (16%) presented both eczematous and prurigo lesions, and 4 (21%) experienced exacerbation of preexisting atopic dermatitis. Histopathologically, AEP was characterized by a perivascular lymphohistiocytic infiltrate with frequent eosinophils (74%) and epidermal changes in all but most of P-type biopsies. No definitive differential histopathological criteria between PEP and AEP were found. Only lymphocytic vasculitis with a mixed infiltrate with eosinophils was more frequent in PEP patients. Timing of onset, morphology of skin lesions, and a detailed clinicopathologic correlation are essential for diagnosis.

Polymorphic eruption of pregnancy (PEP), formerly known as pruritic urticarial papules and plaques of pregnancy, is a dermatosis of pregnancy that must be distinguished from pemphigoid gestationis (PG). Although this differential diagnosis may be possible on routine histology, an additional biopsy for direct immunofluorescence (DIF) is often needed. Recent studies have demonstrated the utility of anti-C4d or anti-C3d antibodies in the diagnosis of bullous pemphigoid (BP) in formalin-fixed paraffin-embedded tissue (FFPE). We investigated the utility of routine immunohistochemistry (IHC) for anti-C4d in FFPE tissue in the specific differential diagnosis of PEP versus PG in known, DIF-proven cases. We performed C4d IHC on PEP (n = 11), PG (n = 8), DIF-proven BP (n = 12), and other common dermatoses (n = 12) that are typically DIF negative. None of the PEP cases (0/11) or the other common dermatoses (0/12) demonstrated C4d positivity at the basement membrane zone. In comparison, 100% of PG cases (8/8) and 83.3% of BP cases (10/12) showed linear C4d immunoreactant deposition along the basement membrane zone. The results demonstrate the potential utility of C4d IHC in FFPE tissue for distinguishing PEP from PG, thus potentially obviating the need of a repeat biopsy for DIF, particularly in C4d-negative cases where there is a low suspicion of PG on both clinical and histological grounds. Also, patients with positive C4d-positive immunoreactivity may also potentially proceed directly to less invasive serological confirmatory testing, such as BP180 NC16a enzyme-linked immunoabsorbent assay.

Introdução: Além da morbilidade relacionada às lesões cutâneas e prurido, as dermatoses da gravidez causam preocupação psicológica e algumas formas implicam riscos fetais. Objectivo: Avaliação do tipo, frequência e características clínicas das dermatoses nas grávidas e puérperas que recorreram ao Serviço de Urgência. Métodos: Estudo retrospectivo das dermatoses nas grávidas e puérperas observadas por Dermatologia no Serviço de Urgência entre Setembro de 2006 e Setembro de 2010. Resultados: O estudo incluiu 79 grávidas e 7 puérperas, com idade mediana de 33 anos. Foram diagnosticadas dermatoses específicas de gravidez em 42 doentes (48,8%). A forma mais comum foi a erupção polimorfa da gravidez (n=16), seguida por eczema da gravidez (n=12), prurigo da gra- videz (n=8), penfigóide gestacional (n=5) e foliculite pruriginosa da gravidez (n=1). Observamos outras dermatoses em 44 doentes (51,2%), incluindo: pitiríase rósea (n=11), infecções e infestações, eczema desidrótico, dermatite de contacto, lúpus eritematoso e pustulose exantemática aguda. Nas dermatoses com apresentação atípica a biópsia ajudou na caracterização da doença. Em 43 casos analisou-se o estado dos recém-nascidos, com registo de parto pré-termo em 3 casos. Discussão: As dermatoses específicas de gravidez têm maior tendência de ocorrer na segunda parte da gravidez, especialmente durante o terceiro trimestre. Nas grávidas com lesões cutâneas exuberantes ou atípicas, o estudo laboratorial e histológico é imprescindível para o diagnóstico específico, permitindo abordagem terapêutica adequada e avaliação dos riscos fetais.PALAVRAS-CHAVE – Doenças da Pele; Prurido; Complicações da Gravidez.

Polymorphic Eruption of Pregnancy (PEP) is one of the most common dermatosis related to pregnancy. PEP usually consists of pruritic papules and plaques appearing in the third trimester of pregnancy. It is more common in primigravidae and twin pregnancies. Although not associated with poorer foetal or maternal outcomes, it may be hard for pregnant women to endure. The diagnosis is easy if suspected, though sometimes it may be hard to distinguish from other dermatosis such as atopic eczema of pregnancy, pemphigoid gestationis or dermatitis. Topical treatment with emollients and low-medium potency steroids is usually effective but systemic steroid treatment may be required. PEP is self-limiting and resolves days or weeks after the first appearance or after delivery. In this article, the authors aim to review the literature published from 2000 onwards regarding the subject, either in English or Portuguese.