Pain In Fabry Disease Research Articles

Characterization of Pain in Fabry Disease

To give a detailed characterization of pain in a large cohort of patients with Fabry disease. In this single-center, retrospective study we performed a detailed analysis of pain prevalence and characteristics of 132 patients with Fabry disease. Data were obtained by screening all medical records and using standardized extraction forms. Missing data were completed by telephone interviews. We show that men and women with Fabry disease frequently experience pain, mostly starting in early childhood. Pain is typically episodic with pain attacks being the predominant phenotype. The most frequent localization is in the distal extremities, the most often named pain quality is "burning." Fabry pain is triggerable by physical activity and thermal stimuli and improves over time. Frequently used acute pain medication consists of nonsteroidal antirheumatics and nonopioid analgesics. Long-term medications such as drugs used to treat neuropathic pain syndromes are rarely taken by Fabry patients. Pain in Fabry disease affects both sexes and has a complex phenotype that requires comprehensive assessment. Current pain questionnaires fail to cover the entire scope of Fabry pain. Although basically neuropathic, some types of Fabry pain may respond to nonsteroidal antirheumatics and nonopioid analgesics.

The relation between small nerve fibre function, age, disease severity and pain in Fabry disease

Background Small fibre neuropathy supposedly causes pain in Fabry patients, but the relationship between small nerve fibre function and pain severity is unclear. Methods A cohort of 15 male and 33 female Fabry patients was studied making use of a quantitative sensory testing protocol, disease severity measures and pain scales to investigate the relationship between nerve fibre function, age, disease severity and pain intensity. Results Male Fabry patients exhibited an abnormal cold detection threshold and thermal sensory limen at the upper and lower limb, indicating Aδ-fibre hypofunction. Female patients showed Z-scores within normal range for all modalities. Nerve fibre function was worse at older age and with more severe disease. The overall severity of pain was mild, without significant differences between males and females. No linear relationship between pain severity and small nerve fibre function was identified. Conclusions In Fabry disease, no linear relationship exists between pain and small nerve fibre function. With older age and more severe disease pain may abate as nerve fibre function further deteriorates.

Nature and Prevalence of Pain in Fabry Disease and Its Response to Enzyme Replacement Therapy—A Retrospective Analysis From the Fabry Outcome Survey

Fabry disease is a multisystemic life-threatening lysosomal storage disorder caused by deficiency of alpha-galactosidase A. Symptoms of the disease may occur in different organs including kidney, heart, and the nervous system. To evaluate the nature and prevalence of pain in a large cohort of patients with Fabry disease and to assess the effect of enzyme replacement therapy (ERT) with agalsidase alfa. Retrospective analysis of the data of 752 patients with Fabry disease (393 females, 353 males) enrolled in the Fabry Outcome Survey, a multicentre database. The prevalence of pain in male patients was 81.4% (females 65.3%). Mean age at onset of pain was 14.8+/-1.0 year in males (females 19.8+/-1.4 y). Pain was most frequently reported in the hands (males 76%, females 60%) and feet (males 73%, females 52%), but often affected the whole body. Interference of pain with daily life was higher in females than in males, and was observed predominantly for general activities, mood, and normal work. Fifty-eight percent of the patients were on ERT with agalsidase alfa. At 24 and 36 months after commencement of ERT, pain severity classification shifted towards lower severity (P<0.05). Moreover, after 36 months, "average pain" and "pain now" were significantly reduced (P<0.05). Pain is one of the most prevalent symptoms in Fabry disease with onset early in childhood. ERT with agalsidase alfa significantly reduces pain in this debilitating disorder.

Pathophysiology and assessment of neuropathic pain in Fabry disease

Severe neuropathic pain and hypohidrosis are important symptoms of Fabry disease, particularly in the first three decades of life. The pain is associated with a length-dependent small-fibre neuropathy that also causes a selective deficiency of cold perception. Cold exposure often accentuates the pain and worsens thermal perception. The hypohidrosis leads to poor exercise and heat tolerance. The mechanisms by which α-galactosidase A deficiency causes these physiological abnormalities are poorly understood. The stored glycolipid (globotriaosylceramide) may interfere with the function of cellular membrane proteins, such as ion channels, or may lead to cytotoxicity. The characteristic neuropathic pain can be symptomatically treated with various types of anticonvulsant drugs, such as carbamazepine. Improvement in neuropathic pain as a primary outcome measure has been useful in demonstrating that enzyme replacement therapy is effective in improving pain-related quality of life in Fabry disease. Conclusions: The dysfunction of the peripheral nervous system is easily assessable and more readily reversible with specific therapy than the destructive processes that occur in organs such as the kidney. In future, therefore, it is likely that neuropathic pain, quantitative sensory testing and hypohidrosis will serve as clinical outcome measures for studies of specific and effective therapies for Fabry disease.

Pathophysiology of neuropathic pain in Fabry disease: evidence of C fibre sensitization

Pathophysiology of neuropathic pain in Fabry disease: evidence of C fibre sensitization

Pathophysiology and assessment of neuropathic pain in Fabry disease.

Severe neuropathic pain and hypohidrosis are important symptoms of Fabry disease, particularly in the first three decades of life. The pain is associated with a length-dependent small-fibre neuropathy that also causes a selective deficiency of cold perception. Cold exposure often accentuates the pain and worsens thermal perception. The hypohidrosis leads to poor exercise and heat tolerance. The mechanisms by which alpha-galactosidase A deficiency causes these physiological abnormalities are poorly understood. The stored glycolipid (globotriaosylceramide) may interfere with the function of cellular membrane proteins, such as ion channels, or may lead to cytotoxicity. The characteristic neuropathic pain can be symptomatically treated with various types of anticonvulsant drugs, such as carbamazepine. Improvement in neuropathic pain as a primary outcome measure has been useful in demonstrating that enzyme replacement therapy is effective in improving pain-related quality of life in Fabry disease. The dysfunction of the peripheral nervous system is easily assessable and more readily reversible with specific therapy than the destructive processes that occur in organs such as the kidney. In future, therefore, it is likely that neuropathic pain, quantitative sensory testing and hypohidrosis will serve as clinical outcome measures for studies of specific and effective therapies for Fabry disease.

Relative hypoxia of the extremities in fabry disease

A purine degradation study, thermography and near infrared spectroscopy of the extremities were performed on 2 young males with Fabry disease and 2 healthy controls. Two-minute semi-ischemic forearm exercise caused a distinct increase in lactate in all subjects, but venous hypoxanthine and ammonia were greatly increased only in the Fabry patients, suggesting a relatively hypoxic state of the extremities. Limb thermograms of the patients revealed glove and stocking type disturbance at rest. Poor recovery of the skin temperature of the hands and forearms after exercise was observed in the patients, but the sharp increase in oxygenated hemoglobin after total ischemia was found to be normal or near infrared spectroscopy. Neurotropin showed an analgesic effect, i.e. a strong and selective heat-productive action on the painful lesions, and suppressed the hypoxanthine level after exercise in 1 patient. Although the pathophysiology of the pain in Fabry disease has not been clearly elucidated, a relatively hypoxic state with peripheral hypothermia might play an important role in triggering of a painful attack or chronic burning paresthesia.

Relief of chronic burning pain in Fabry disease with neurotropin

Neurotropin, an extract from the inflamed skin of vaccinia virus-inoculated rabbits, was effective in the relief of sharp or burning pain induced by pyrexia, hot weather, bathing, or exercise in 2 siblings with Fabry disease. Neither neurotropin nor carbamazepine monotherapy relieved the episodic colicky pain in 1 patient; however, therapy with both drugs eliminated the pain completely. This result suggests that the mechanisms underlying the analgesic actions of both drugs may be complementary in ameliorating the pain of Fabry disease, even though the mechanism underlying the pain has not been clearly elucidated.