Highlights
- •Fever is an early symptom of Fabry disease.
- •Fabry disease may be a cause of Recurrent Fever of Unknown Origin.
- •Fever in Fabry disease can also be encountered in adults.
- •The inclusion of FD in the differential diagnosis of recurrent fever of unknown origin should be mandatory.
Abstract
Background
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.
Methods
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.
Findings
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 12.8 years.
Interpretation
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.
Keywords
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Article info
Publication history
Published online: April 12, 2016
Accepted:
March 18,
2016
Received in revised form:
March 9,
2016
Received:
November 18,
2015
Identification
Copyright
© 2016 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.
