Bullous Eruption with Cholestasis in Pregnancy

Sara Al Janahi, Yusra S. Al Ali
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All other investigations were unremarkable. Two 4-mm punch biopsies were taken from the abdomen for histopathology with hematoxylin and eosin (H&amp;E) staining and immunofluorescence studies (Figure 2).</p><p>The clinicopathologic correlation was suggestive of pemphigoid gestationis (PG) with co-existing intrahepatic cholestasis of pregnancy. The patient's obstetrician started treatment with ursodeoxycholic acid (UCDA) 500 IU three times per day. Dermatologic management consisted of oral prednisolone 0.5 mg/kg, antihistamines, topical steroids, and emollients. The patient demonstrated improvement in pruritus and skin lesions, noted at a 2-week follow-up visit where most of the lesions resulted in post-inflammatory hyperpigmentation. The improvement continued throughout her pregnancy. Attempts to taper the dose of oral prednisolone resulted in a flare of disease, marked by the appearance of new bullae. Thus, she remained on the same dose until delivery. The patient delivered a healthy baby girl. There was no noted flare with delivery or in the postpartum period.</p><p>PG is an autoimmune bullous disorder with clinical and histologic overlap with bullous pemphigoid (BP). PG may occur at any stage of pregnancy but tends to favour the third trimester. The aetiology is due to anti-basement membrane zone auto-antibodies to BPAG2 (BP 180, collagen XVII). There is a strong association with HLA-DRs DRB1*0301 (HLA-DR3) and DRB1*0401/040X (HLA-DR4) [<span>1</span>]. Clinically, patients may experience intense pruritus with erythematous urticarial papules and plaques classically on the abdomen that often spread to the rest of the body [<span>2</span>]. Mucosal surfaces are often spared [<span>1</span>]. Histopathology, as in this case, demonstrated eosinophilic spongiosis of the epidermis with oedema of the upper and mid dermis. A perivascular lymphohistiocytic inflammation with abundant eosinophils was noted (Figure 2a). Direct Immunofluorescence (DIF) was significant for linear deposition of C3 (2 + ) and IgG (1 + ) along the basement membrane (Figure 2b).</p><p>Immunofluorescence studies are considered the gold standard for diagnosis of PG, and permit to differentiate PG from other entities. Linear C3 deposition along the BMZ with additional deposition of IgG is characteristic of PG [<span>2</span>]. Foetal risks observed in PG are low birth weight, prematurity, or a transient bullous eruption that resolves in several weeks [<span>1</span>], due to passage of maternal antibodies. There is no risk of stillbirth [<span>2</span>]. PG tends to be exacerbated by delivery, post-delivery use of oral contraceptives and can recur in subsequent pregnancies. When recurrent, it tends to have an earlier and more severe onset and course [<span>1</span>]. The main clinical differential is polymorphic urticarial papules and plaques of pregnancy (PUPPP), which classically involve the striae, carry no risk to the foetus, and do not tend to recur [<span>1</span>]. The suggested cornerstone of treatment of PG consists of topical or systemic corticosteroids. Immunoglobulin therapy, azathioprine, and dapsone have been used for refractory cases, with antihistamines often used as adjuvant therapy [<span>3</span>]. Recently, dupilumab was used successfully for a patient with PG, with improvement in symptoms and skin lesions after 4 weeks of therapy [<span>4</span>].</p><p>Intrahepatic cholestasis of pregnancy (ICP) is characterised by severe pruritus with no primary skin lesions; jaundice may or may not be present. Pruritus is initially confined to the palms and soles and later generalises. Like PG, ICP may recur in future pregnancies. There is no significant risk for the mother, however, prolonged cholestasis may result in Vitamin K deficiency or coagulopathy [<span>5</span>]. Risks to the foetus include preterm delivery or intrapartum foetal distress [<span>2</span>]. Stillbirth is an uncommon complication [<span>2</span>]. A meta-analysis comparing perinatal outcomes in patients with ICP and healthy controls found that stillbirths exceeded the general population rate only when total bile acid levels were 100 μmol/L or higher [<span>6</span>]. A reassuring feature in our case was that the serum bile acids were only mildly elevated and was rapidly corrected with UCDA. UCDA improves pruritus and prognosis by normalisation of impaired hepatobiliary secretion, protection of cholangiocytes against the cytotoxicity of hydrophobic bile acids, and protection of hepatocytes against bile acid-induced apoptosis [<span>7</span>]. As pregnancy advances, bile acids may increase, thus, monitoring of ICP is advisable for the well-being of the foetus.</p><p>Sara Al Janahi and Yusra Al Ali were both directly involved in the care and management of this patient, as well as writing the manuscript.</p><p>The patient in this manuscript has given written informed consent for participation in the study and the use of their deidentified, anonymized, aggregated data and their case details (including photographs) for publication. Ethical approval: not applicable.</p><p>The authors declare no conflicts of interest.</p>","PeriodicalId":94325,"journal":{"name":"JEADV clinical practice","volume":"4 2","pages":"627-629"},"PeriodicalIF":0.0000,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jvc2.623","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"JEADV clinical practice","FirstCategoryId":"1085","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/jvc2.623","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0

Abstract

A 26-year-old female, 27 weeks pregnant (G2P1) presented to our clinic with a 2-week history of a progressively worsening, urticarial and bullous eruption that started on the abdomen and subsequently spread to the trunk and extremities. She reported significant nocturnal pruritus, disrupting her sleep andpredominately affecting her palms and soles. Her previous pregnancy had been uneventful. She was also not known to have atopy or any preceding dermatologic conditions. Clinical examination revealed pink to erythematous urticarial papules and plaques, with bullae at the periphery, distributed over the extremities and trunk, involving the umbilicus and sparing the peri-umbilical striae (Figure 1). Laboratory investigations were significant for elevated bile salts 16.5 μmol/L (normal < 10 μmol/L in pregnant women). All other investigations were unremarkable. Two 4-mm punch biopsies were taken from the abdomen for histopathology with hematoxylin and eosin (H&E) staining and immunofluorescence studies (Figure 2).

The clinicopathologic correlation was suggestive of pemphigoid gestationis (PG) with co-existing intrahepatic cholestasis of pregnancy. The patient's obstetrician started treatment with ursodeoxycholic acid (UCDA) 500 IU three times per day. Dermatologic management consisted of oral prednisolone 0.5 mg/kg, antihistamines, topical steroids, and emollients. The patient demonstrated improvement in pruritus and skin lesions, noted at a 2-week follow-up visit where most of the lesions resulted in post-inflammatory hyperpigmentation. The improvement continued throughout her pregnancy. Attempts to taper the dose of oral prednisolone resulted in a flare of disease, marked by the appearance of new bullae. Thus, she remained on the same dose until delivery. The patient delivered a healthy baby girl. There was no noted flare with delivery or in the postpartum period.

PG is an autoimmune bullous disorder with clinical and histologic overlap with bullous pemphigoid (BP). PG may occur at any stage of pregnancy but tends to favour the third trimester. The aetiology is due to anti-basement membrane zone auto-antibodies to BPAG2 (BP 180, collagen XVII). There is a strong association with HLA-DRs DRB1*0301 (HLA-DR3) and DRB1*0401/040X (HLA-DR4) [1]. Clinically, patients may experience intense pruritus with erythematous urticarial papules and plaques classically on the abdomen that often spread to the rest of the body [2]. Mucosal surfaces are often spared [1]. Histopathology, as in this case, demonstrated eosinophilic spongiosis of the epidermis with oedema of the upper and mid dermis. A perivascular lymphohistiocytic inflammation with abundant eosinophils was noted (Figure 2a). Direct Immunofluorescence (DIF) was significant for linear deposition of C3 (2 + ) and IgG (1 + ) along the basement membrane (Figure 2b).

Immunofluorescence studies are considered the gold standard for diagnosis of PG, and permit to differentiate PG from other entities. Linear C3 deposition along the BMZ with additional deposition of IgG is characteristic of PG [2]. Foetal risks observed in PG are low birth weight, prematurity, or a transient bullous eruption that resolves in several weeks [1], due to passage of maternal antibodies. There is no risk of stillbirth [2]. PG tends to be exacerbated by delivery, post-delivery use of oral contraceptives and can recur in subsequent pregnancies. When recurrent, it tends to have an earlier and more severe onset and course [1]. The main clinical differential is polymorphic urticarial papules and plaques of pregnancy (PUPPP), which classically involve the striae, carry no risk to the foetus, and do not tend to recur [1]. The suggested cornerstone of treatment of PG consists of topical or systemic corticosteroids. Immunoglobulin therapy, azathioprine, and dapsone have been used for refractory cases, with antihistamines often used as adjuvant therapy [3]. Recently, dupilumab was used successfully for a patient with PG, with improvement in symptoms and skin lesions after 4 weeks of therapy [4].

Intrahepatic cholestasis of pregnancy (ICP) is characterised by severe pruritus with no primary skin lesions; jaundice may or may not be present. Pruritus is initially confined to the palms and soles and later generalises. Like PG, ICP may recur in future pregnancies. There is no significant risk for the mother, however, prolonged cholestasis may result in Vitamin K deficiency or coagulopathy [5]. Risks to the foetus include preterm delivery or intrapartum foetal distress [2]. Stillbirth is an uncommon complication [2]. A meta-analysis comparing perinatal outcomes in patients with ICP and healthy controls found that stillbirths exceeded the general population rate only when total bile acid levels were 100 μmol/L or higher [6]. A reassuring feature in our case was that the serum bile acids were only mildly elevated and was rapidly corrected with UCDA. UCDA improves pruritus and prognosis by normalisation of impaired hepatobiliary secretion, protection of cholangiocytes against the cytotoxicity of hydrophobic bile acids, and protection of hepatocytes against bile acid-induced apoptosis [7]. As pregnancy advances, bile acids may increase, thus, monitoring of ICP is advisable for the well-being of the foetus.

Sara Al Janahi and Yusra Al Ali were both directly involved in the care and management of this patient, as well as writing the manuscript.

The patient in this manuscript has given written informed consent for participation in the study and the use of their deidentified, anonymized, aggregated data and their case details (including photographs) for publication. Ethical approval: not applicable.

The authors declare no conflicts of interest.

妊娠期大疱性皮疹伴胆汁淤积
一名26岁女性,怀孕27周(G2P1),以2周的进行性恶化,荨麻疹和大疱性皮疹病史就诊于我们的诊所,该病史始于腹部,随后扩散到躯干和四肢。她报告有明显的夜间瘙痒,扰乱了她的睡眠,主要影响她的手掌和脚底。她之前的怀孕平安无事。她也不知道有特应性或任何先前的皮肤病。临床检查显示粉红色至红斑性荨麻疹丘疹和斑块,周围有大泡,分布于四肢和躯干,累及脐,保留脐周纹(图1)。实验室检查显示胆盐升高16.5 μmol/L(孕妇正常10 μmol/L)。所有其他的调查都不引人注目。采用苏木精和伊红(H&amp;E)染色和免疫荧光研究(图2),从腹部取2个4毫米穿孔活检进行组织病理学检查。临床病理相关性提示类天疱疮妊娠(PG)合并妊娠肝内胆汁淤积。患者的产科医生开始使用熊去氧胆酸(UCDA) 500 IU,每天三次。皮肤治疗包括口服强的松龙0.5 mg/kg,抗组胺药,局部类固醇和润肤剂。在2周的随访中,患者表现出瘙痒和皮肤病变的改善,其中大多数病变导致炎症后色素沉着。这种改善在她怀孕期间一直持续。试图逐渐减少口服强的松龙的剂量导致疾病发作,其特征是出现新的大泡。因此,她一直服用相同的剂量直到分娩。病人生了一个健康的女婴。在分娩或产后期间没有明显的耀斑。PG是一种自身免疫性大疱性疾病,临床和组织学上与大疱性类天疱疮(BP)有重叠。PG可能发生在妊娠的任何阶段,但倾向于发生在妊娠晚期。病因是由于抗基底膜区自身抗体BPAG2 (BP 180,胶原XVII)。与HLA-DRs DRB1*0301 (HLA-DR3)和DRB1*0401/040X (HLA-DR4)[1]有很强的相关性。临床上,患者可能会出现强烈的瘙痒,伴有红斑性荨麻疹丘疹和斑块,通常在腹部,并经常扩散到身体的其他部位。粘膜表面常不受影响。组织病理学,如本例,显示表皮嗜酸性海绵状病变伴真皮上部和中部水肿。可见血管周围淋巴组织细胞炎症伴大量嗜酸性粒细胞(图2a)。直接免疫荧光(DIF)显示C3(2 +)和IgG(1 +)沿基底膜呈线性沉积(图2b)。免疫荧光研究被认为是诊断PG的金标准,并允许将PG与其他实体区分开来。C3沿BMZ呈线性沉积,并伴有IgG的沉积,这是PG[2]的特征。在PG中观察到的胎儿风险是低出生体重,早产,或由于母体抗体通过而在几周内消退的短暂大疱性皮疹。没有死产的风险。分娩和产后口服避孕药可加重PG,并可在随后的妊娠中复发。当复发时,它往往有更早和更严重的发作和病程[1]。主要的临床区别是妊娠期多形荨麻疹丘疹和斑块(PUPPP),通常包括斑纹,对胎儿没有风险,并且不容易复发。建议的治疗PG的基石包括局部或全身皮质类固醇。免疫球蛋白治疗、硫唑嘌呤和氨苯砜已被用于难治性病例,抗组胺药常被用作辅助治疗bbb。最近,dupilumab成功用于一名PG患者,治疗4周后症状和皮肤病变得到改善。妊娠肝内胆汁淤积症(ICP)的特征是严重瘙痒,无原发性皮肤病变;黄疸可能存在,也可能不存在。瘙痒症最初局限于手掌和脚底,后来普遍化。像PG一样,ICP也可能在以后的妊娠中复发。对母亲没有明显的风险,然而,长期的胆汁淤积可能导致维生素K缺乏或凝血功能障碍。对胎儿的风险包括早产或产时胎儿窘迫。死产是一种罕见的并发症。一项比较ICP患者和健康对照组围产期结局的荟萃分析发现,只有当总胆汁酸水平为100 μmol/L或更高时,死产率才超过一般人群。在我们的病例中,一个令人放心的特征是血清胆汁酸仅轻度升高,并通过UCDA迅速纠正。 UCDA通过使受损的肝胆分泌正常化、保护胆管细胞免受疏水胆汁酸的细胞毒性、保护肝细胞免受胆汁酸诱导的细胞凋亡[7],改善瘙痒和预后。随着妊娠的进展,胆汁酸可能增加,因此,监测ICP对胎儿的健康是可取的。Sara Al Janahi和Yusra Al Ali都直接参与了该患者的护理和管理,并撰写了手稿。本文中的患者已书面同意参与研究,并同意使用其未识别、匿名、汇总的数据和病例详细信息(包括照片)进行发表。伦理批准:不适用。作者声明无利益冲突。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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