Department of Dermatology, Hospital Clinic, University of Barcelona, Barcelona, Spain.
Orphanet J Rare Dis. 2009 Sep 10;4:19. doi: 10.1186/1750-1172-4-19.
Erythropoietic protoporphyria (EPP) is an inherited disorder of the haem metabolic pathway characterised by accumulation of protoporphyrin in blood, erythrocytes and tissues, and cutaneous manifestations of photosensitivity. EPP has been reported worldwide, with prevalence between 1:75,000 and 1:200,000. It usually manifests in early infancy upon the first sun exposures. EPP is characterised by cutaneous manifestations of acute painful photosensitivity with erythema and oedema, sometimes with petechiae, together with stinging and burning sensations upon exposure to sunlight, without blisters. These episodes have a variable severity depending on the exposure duration and may result in chronic permanent lesions on exposed skin. As protoporphyrin is a lipophilic molecule that is excreted by the liver, EPP patients are at risk of cholelithiasis with obstructive episodes, and chronic liver disease that might evolve to rapid acute liver failure. In most patients, EPP results from a partial deficiency of the last enzyme of the haem biosynthetic pathway, ferrochelatase, EC 4.99.1.1/FECH (encoded by the FECH gene). EPP appears to be inherited as an autosomal dominant disease, the clinical expression of which is modulated by the presence of the hypomorphic FECH IVS3-48C allele trans, but recessive inheritance with two mutated FECH alleles has also been described. In about 2% of patients, overt disease was recently shown to be caused by gain-of-function mutations in the erythroid-specific aminolevulinic acid synthase 2 (ALAS2/ALAS, EC 2.3.1.27) gene and named X-linked dominant protoporphyria. Diagnosis is established by finding increased levels of protoporphyrin in plasma and red blood cells, and detection of a plasma fluorescence peak at 634 nm. Investigations for hepatic involvement, ferrochelatase activity level, genetic analysis (FECH mutations, presence of the hypomorphic FECH IVS3-48C allele trans and ALAS2 mutations) and family studies are advisable. Differential diagnosis includes phototoxic drug reactions, hydroa vacciniforme, solar urticaria, contact dermatitis, angio-oedema and, in some cases, other types of porphyria. Management includes avoidance of exposure to light, reduction of protoporphyrin levels and prevention of progression of possible liver disease to liver failure. As the major risk in EPP patients is liver disease, a regular follow-up of hepatic involvement is essential. Sequential hepatic and bone marrow transplantation should be considered as a suitable treatment for most severe cases of EPP with hepatic involvement. EPP is a lifelong disorder whose prognosis depends on the evolution of the hepatic disease. However, photosensitivity may have a significant impact on quality of life of EPP patients.
红细胞生成性原卟啉症（EPP）是一种血红素代谢途径的遗传性疾病，其特征是原卟啉在血液、红细胞和组织中蓄积，并伴有皮肤光敏性表现。EPP 已在全球范围内报道，患病率为 1/75000 至 1/200000。它通常在婴儿首次暴露于阳光下时出现。EPP 的特征是皮肤出现急性疼痛性光敏性表现，伴有红斑和水肿，有时伴有瘀点，同时在暴露于阳光下时会出现刺痛和烧灼感，但没有水疱。这些发作的严重程度取决于暴露持续时间，可能导致暴露皮肤出现慢性永久性损伤。由于原卟啉是一种亲脂性分子，通过肝脏排出，因此 EPP 患者有胆石症和阻塞性发作的风险，并且可能发展为快速急性肝功能衰竭的慢性肝病。在大多数患者中，EPP 是由于血红素生物合成途径的最后一种酶，亚铁螯合酶（EC 4.99.1.1/FECH）部分缺乏引起的，该酶由 FECH 基因编码。EPP 似乎作为一种常染色体显性遗传疾病遗传，其临床表达受隐性等位基因 FECH IVS3-48C trans 的存在所调节，但也有报道称其为两个 FECH 基因突变等位基因的隐性遗传。最近发现，大约 2%的患者显性疾病是由红细胞特异性氨基酮戊酸合酶 2（ALAS2/ALAS，EC 2.3.1.27）基因的功能获得性突变引起的，并被命名为 X 连锁显性原卟啉症。通过发现血浆和红细胞中原卟啉水平升高，以及在 634nm 处检测到血浆荧光峰来确诊。建议进行肝脏受累、亚铁螯合酶活性水平、基因分析（FECH 突变、隐性等位基因 FECH IVS3-48C trans 和 ALAS2 突变的存在）和家族研究。鉴别诊断包括光毒性药物反应、水疱性红斑狼疮样疹、光线性荨麻疹、接触性皮炎、血管性水肿，在某些情况下还包括其他类型的卟啉症。治疗包括避免暴露于光线下、降低原卟啉水平以及预防可能的肝脏疾病进展为肝功能衰竭。由于 EPP 患者的主要风险是肝脏疾病，因此对肝脏受累情况进行定期随访至关重要。对于大多数有肝脏受累的严重 EPP 病例，应考虑序贯肝和骨髓移植作为一种合适的治疗方法。EPP 是一种终身疾病，其预后取决于肝脏疾病的发展。然而，光敏性可能会对 EPP 患者的生活质量产生重大影响。
