Dermatology Department, Hospital Federal de Bonsucesso, Rio de Janeiro, Brazil ; and.
ID- Investigação em Dermatologia, Rio de Janeiro, Brazil .
Am J Dermatopathol. 2021 Jul 1;43(7):497-505. doi: 10.1097/DAD.0000000000001787.
Heparin-induced bullous hemorrhagic dermatosis (HBHD) is an unusual cutaneous adverse reaction to heparin characterized by acute onset of hemorrhagic bullae.
An exuberant case of HBHD is reported, and a revision of previously reported cases indexed on PubMed is provided. Cases were tabulated to the following parameters: sex, age, type of heparin and route of administration, associated medical procedure, number of days between heparin start and onset of lesions, site of the lesions, level of blister on histopathology, inflammatory infiltrate on histopathology, direct immunofluorescence findings, heparin-related intervention, number of days to resolution of skin lesions, associated hemorrhagic event, and outcome.
A 21-year-old woman with end-stage renal disease was receiving intravenous unfractioned heparin (UFH) during hemodialysis section for the past 3 months. Four hours after using for the first time an arteriovenous fistula punctured on her right wrist, the patient noticed the onset of vesicles and blisters on the right forearm containing citrus or serohemorrhagic exudate, which became overt hemorrhagic in 24 hours. Histopathology depicted a nonacantholytic subcorneal blister containing erythrocytes and plasma without any significant dermal inflammatory infiltrate.
Sixty cases of HBHD were included. HBHD affected predominantly men, with a male/female rate of 2.75. The age range was from 21 to 94 years, with an average of 70.8 and a median of 72 years. Nine patients used UFH, and 54 patients used low molecular weight heparins (3 patients used both). The lapse of time between the start of heparin and the onset of skin lesion varied from 6 hours to 240 days, with an average of 17.3 days and a median of 7 days. Limbs were affected in most of the cases. The level of the blister was subcorneal in 10 patients, intraepidermal in 30, subepidermal in 8, and both intraepidermal and subepidermal in 1. In 33 cases, there was no significant dermal inflammatory infiltrate. Pure lymphocytic inflammatory infiltrate was present in 10 cases. Eosinophils were found within the dermal inflammatory infiltrate in 2 cases, neutrophils in 2, and a mixture of eosinophils and neutrophils in other 2. Direct immunofluorescence was performed in 18 cases, all of them with negative results.
We hypothesize that mechanical trauma, skin fragility, and the anticoagulation effect of heparin might contribute concomitantly to the development of the lesions and speculate that subepidermal blisters in HBHD could be formed by rupture of the floor of a former intraepidermal blister.
肝素诱导的大疱性出血性皮肤病（HBHD）是肝素引起的一种罕见的皮肤不良反应，其特征为急性出血性大疱。
报告了一例过度活跃的 HBHD 病例，并对 PubMed 索引的先前报道的病例进行了修订。病例按以下参数进行列表：性别、年龄、肝素类型和给药途径、相关医疗程序、肝素开始使用和皮损出现之间的天数、皮损部位、组织病理学上的水疱水平、组织病理学上的炎症浸润、直接免疫荧光检查结果、与肝素相关的干预措施、皮损消退所需的天数、相关出血事件和结局。
一名 21 岁女性，患有终末期肾病，在过去 3 个月的血液透析期间接受静脉普通肝素（UFH）治疗。在她的右腕部首次使用动静脉瘘后 4 小时，患者注意到右前臂出现水疱和大疱，其中含有柑橘或血清血性渗出物，24 小时后变为明显出血。组织病理学显示，一个非棘层松解性的表皮下水疱，其中含有红细胞和血浆，没有任何明显的真皮炎症浸润。
共纳入 60 例 HBHD 病例。HBHD 主要影响男性，男女比例为 2.75。年龄范围为 21 至 94 岁，平均年龄为 70.8 岁，中位数为 72 岁。9 例患者使用 UFH，54 例患者使用低分子量肝素（3 例患者同时使用）。从肝素开始使用到皮肤病变出现的时间间隔从 6 小时到 240 天不等，平均为 17.3 天，中位数为 7 天。大多数病例累及四肢。10 例水疱位于表皮下，30 例位于表皮内，8 例位于表皮下，1 例同时位于表皮内和表皮下。33 例无明显真皮炎症浸润。10 例存在单纯淋巴细胞炎症浸润。2 例真皮炎症浸润中有嗜酸性粒细胞，2 例有中性粒细胞，2 例有嗜酸性粒细胞和中性粒细胞混合物。18 例行直接免疫荧光检查，均为阴性。
我们假设机械性创伤、皮肤脆弱和肝素的抗凝作用可能共同导致病变的发生，并推测 HBHD 中的表皮下水疱可能是由于先前表皮内水疱的底部破裂形成的。
