Verrecchia Elena, Zampetti Anna, Antuzzi Daniela, Ricci Roberta, Ferri Lorenzo, Morrone Amelia, Feliciani Claudio, Dagna Lorenzo, Manna Raffaele
Periodic Fever Research Centre, A. Gemelli Policlinic, Catholic University of the Sacred Heart, Rome, Italy.
Department of Dermatology Saint Mary's Hospital, Imperial College NHS Trust, London, UK.
Eur J Intern Med. 2016 Jul;32:26-30. doi: 10.1016/j.ejim.2016.03.015. Epub 2016 Apr 12.
Fabry disease (FD) is an X-linked lysosomal storage disorder caused by a deficiency of alpha-galactosidase A enzyme, which leads to the accumulation of its substrate, the globotriaosylceramide or Gb3, in many organs and tissues. Main clinical manifestations of FD are neuropathic pain, angiokeratomas, proteinuria and renal failure, left ventricular hypertrophy and stroke. Fever is also a possible symptom at the onset of the disease during childhood and adolescence, but it is frequently misdiagnosed, causing a delay in FD diagnosis.
We retrospectively analysed the medical records in our series of 58 Fabry patients, focusing on the proportion of patients who exhibited fever as the main symptom at the onset of FD in order to evaluate the diagnostic delay in these patients.
In our series, we found a significant proportion of patients with a history of fevers at the beginning of their medical history (20.7%; 12/58). 83% of patients with fever also exhibited acroparesthesias (10/12). Inflammatory markers were elevated in few of those cases (2/12). The mean diagnostic delay was 15.6±SD 12.8years.
Fever emerged to be common as part of the FD clinical spectrum and it significantly contributed to the diagnostic delay encountered with this rare disease. Furthermore, our retrospective analysis indicated that FD patients commonly exhibit episodes of fever in association with other symptoms suggestive of FD (such as episodic pain crisis, acroparesthesias, hypo/anhydrosis, heat intolerance, fatigue and gastrointestinal distress). A careful analysis of the medical history in patients suffering fever could lead to an early and correct FD diagnosis. We believe that fever/hyperthermia, acroparesthesias and angiokeratoma should be considered for inclusion in the algorithm for Intermittent Fever of Unknown Origin (FUO) in order to improve the recognition of FD.
法布里病（FD）是一种X连锁溶酶体贮积病，由α-半乳糖苷酶A缺乏引起，导致其底物Globotriaosylceramide（Gb3）在许多器官和组织中蓄积。FD的主要临床表现为神经性疼痛、血管角质瘤、蛋白尿和肾衰竭、左心室肥厚及中风。发热也是儿童和青少年期疾病发作时的一种可能症状，但常被误诊，导致FD诊断延迟。
我们回顾性分析了我们系列中58例法布里病患者的病历，重点关注以发热为FD发病时主要症状的患者比例，以评估这些患者的诊断延迟情况。
在我们的系列研究中，我们发现相当比例的患者在病史开始时有发热史（20.7%；12/58）。发热患者中有83%也表现出肢端感觉异常（10/12）。少数病例（2/12）炎症标志物升高。平均诊断延迟为15.6±标准差12.8年。
发热是FD临床谱的常见组成部分，显著导致了这种罕见疾病的诊断延迟。此外，我们的回顾性分析表明，FD患者通常表现出发热发作，并伴有其他提示FD的症状（如发作性疼痛危机、肢端感觉异常、少汗/无汗、不耐热、疲劳和胃肠道不适）。对发热患者的病史进行仔细分析可导致早期正确的FD诊断。我们认为，发热/高热、肢端感觉异常和血管角质瘤应考虑纳入不明原因间歇性发热（FUO）的诊断流程，以提高对FD的识别。
