Pain in Fabry Disease: Practical Recommendations for Diagnosis and Treatment

Abstract

SummaryAimsPatients with Fabry disease (FD) characteristically develop peripheral neuropathy at an early age, with pain being a crucial symptom of underlying pathology. However, the diagnosis of pain is challenging due to the heterogeneous and nonspecific symptoms. Practical guidance on the diagnosis and management of pain in FD is needed.MethodsIn 2014, experts met to discuss recent advances on this topic and update clinical guidance.ResultsEmerging disease‐specific tools, including FabryScan, Fabry‐specific Pediatric Health and Pain Questionnaire, and Würzburg Fabry Pain Questionnaire, and more general tools like the Total Symptom Score can aid diagnosis, characterization, and monitoring of pain in patients with FD. These tools can be complemented by more objective and quantifiable sensory testing. In male and female patients of any age, pain related to FD can be an early indication to start disease‐specific enzyme replacement therapy before potentially irreversible organ damage to the kidneys, heart, or brain occurs.ConclusionTo improve treatment outcomes, pain should be diagnosed early in unrecognized or newly identified FD patients. Treatment should include: (a) enzyme replacement therapy controlling the progression of underlying pathology; (b) adjunctive, symptomatic pain management with analgesics for chronic neuropathic and acute nociceptive, and inflammatory or mixed pain; and (c) lifestyle modifications.

A novel GLA mutation in a Korean boy with an early cardiac manifestation of Fabry disease

“…As in the present patient, pain is one of the earliest and predominant clinical symptoms of FD, affecting 60-70% of male and 40-60% of female patients [3,4]. Neuropathic pain and heat and cold intolerance often begin at an average age of 6 to 8 years in males and, generally, a few years later in females than in males [6,11].…”

“…Neuropathic pain and heat and cold intolerance often begin at an average age of 6 to 8 years in males and, generally, a few years later in females than in males [6,11]. Typically, pain in FD manifests as episodes of burning, stabbing, or shooting pain that begins in the distal extremities with various triggering factors such as physical exercise, thermal stimuli, and fever [4]. Therefore, unexplained neuropathic pain in pediatric patients should alert the physician to the possibility of FD.…”

Consensus recommendations for diagnosis, management and treatment of Fabry disease in paediatric patients

“…49 Neuropathic pain has been reported by up to 72.3% of patients with FD 4,14,47 and is more frequently present in boys. 49,50 The mean age of onset of pain has been reported as 10.1 years in boys 3 and 15 years in heterozygote girls 2 although one study reported median onset of neuropathic pain as 7 years in boys and 9 years in girls. 49 Patients can experience crises of excruciating pain that radiate proximally to the entire body and that can last up to several days, with no respite offered by analgesics.…”

“…49 Patients can experience crises of excruciating pain that radiate proximally to the entire body and that can last up to several days, with no respite offered by analgesics. 49,50 The mean age of onset of pain has been reported as 10.1 years in boys 3 and 15 years in heterozygote girls 2 although one study reported median onset of neuropathic pain as 7 years in boys and 9 years in girls. 14 However, pain in children can also arise from diverse conditions such as growing pains.…”

“…Ala143Thr, 75 central analgesics and topical agents. 50 No randomised controlled trial has compared the efficacy of different agents or optimal dosing for the management of Fabry pain in children. Nonetheless, recent US paediatric guidelines suggest an algorithm for starting dose, uptitration and maximum doses of pain medication by age group.…”