Paroxysmal vascular acrosyndromes are related to a peripheral vasomotor disorder and presented as paroxysmal color changes of the fingers. They include primary Raynaud's phenomenon (RP), which is the most common, secondary RP and erythermalgia. They are to be distinguished from non-paroxysmal acrosyndromes such as acrocyanosis and chilblains, which are very frequent and often associated with RP, digital ischemia and necrosis, spontaneous digital hematoma and acrocholosis. The challenge of a consultation for a vascular acrosyndrome is to make positive diagnosis through history and clinical examination, and to specify its nature, to prescribe complementary exams. In any patient consulting for RP, assessment includes at least an antinuclear antibody test and capillaroscopy. For erythermalgia, a blood count and even a search for JAK2 mutation are required. A thryoid-stimulating hormon assay, a test for antinuclear antibodies, and a search for small fiber neuropathy are also performed. The treatment of RP is essentially documented for secondary RP where calcium channel blockers are indicated in first line, and iloprost in severe cases. The treatment of primitive erythermalgia is based on sodium channel blockers such as mexiletine or lidocaine infusions, and on drugs effective on neuropathic pain, such as gabapentin or amitryptiline, in case of erythermalgia associated with small fiber neuropathy. The treatment of erythermalgia associated with myeloproliferative syndromes is based on etiological treatment and aspirin.
Lidove O, Zeller V, Chicheportiche V, Meyssonnier V, Sené T , et al.
Joint bone spine •
Fabry disease is a rare X-linked metabolic disorder characterized by a deficiency in the enzyme alpha-galactosidase A. Both males and females can be affected. The main presenting symptom is pain in the extremities, whereas at a more advanced stage, the manifestations include hypertrophic cardiomyopathy, cardiac dysrhythmia, proteinuria, chronic kidney dysfunction, stroke, and hearing loss. When not diagnosed and treated, Fabry disease causes early death. No studies specifically designed to describe the musculoskeletal manifestations of Fabry disease are available. We conducted a single-center retrospective study of patients receiving follow-up at a Fabry disease referral center. We described the musculoskeletal manifestations and analyzed the differential diagnoses. Our study included 40 patients belonging to 20 families, including 25 females with a mean age of 44.2 years (range, 20-76 years) and 15 males with a mean age of 40.1 years (range, 16-61 years). Mean age at the diagnosis of Fabry disease was 37.2 years (range, 7-71 years) in the females and 26.9 years (range, 9-51 years) in the males. Specific enzyme replacement therapy was given to 10 (40%) females and 12 (80%) males. Musculoskeletal manifestations were as follows: past or present pain in the extremities (13 females and 10 males), combined in some patients with vasomotor disorders in the extremities and telangiectasia; exercise intolerance (12 females and 12 males); osteoporotic fractures (2 brothers aged 45 and 44 years, respectively); osteoporosis (3 females, aged 57, 63, and 75 years, respectively), which contributed to death in the oldest patient; osteopenia (2 females aged 38 and 47 years, respectively; and 1 male aged 43 years); Charcot foot and lymphedema with serious infectious complications (4 males older than 40 years), with avascular osteonecrosis of the lower limbs in 2 cases; toe amputations (3 cases); bilateral lower-limb amputation (1 case); abnormally slender lower limbs (5 females and 8 males); acute gout (3 males with severe chronic kidney failure); and carpal tunnel syndrome (1 female and 1 male, both younger than 40 years). Mistaken diagnoses that were made at an early stage, contributing to delay the identification of Fabry disease, included rheumatic fever (2 females and 2 males), growing pains (2 males), pain with paralysis (1 female), chilblains of the lower limbs (1 female), and erythermalgia (1 female). In adulthood, the following mistaken diagnoses were made: Sjögren's syndrome and/or sicca syndrome (6 females), systemic sclerosis (1 male), dysautonomia (1 female), and familial Mediterranean fever (1 female). The diagnosis of Fabry disease is usually delayed, due to confusion with more common disorders. Musculoskeletal manifestations may constitute the presenting symptoms. Past or present pain in the extremities is typical. Osteoporosis may develop early and become severe. Together with the family history, the presence of musculoskeletal manifestations can lead to the correct diagnosis by prompting alpha-galactosidase assays in males and genetic testing in females. Fabry disease is often responsible for musculoskeletal manifestations, of which the most common are pain in the extremities and osteoporosis. These manifestations can be inaugural and lead to diagnostic wanderings. They require specific treatment strategies.
Vascular acrosyndromes are associated with vasomotor disorders. They may be paroxysmal, like Raynaud's phenomenon, whitening of the fingers on exposure to cold, or erythromelalgia, a painful form of erythema induced by exposure to heat. Others are permanent or semi-permanent, such as acrocyanosis, chilblains, spontaneous haematoma of the fingers, acrocholose and digital ischaemia or necrosis. Diagnosis of the type of acrosyndrome at issue is based primarily on clinical examination and history-taking. Capillaroscopy and antinuclear antibody assay are key examinations essential for distinguishing between primary and secondary Raynaud's phenomenon and connective tissue disorders. Complete blood counts, screening for thyroid dysthyroidism, and antinuclear antibody assay can help distinguish between primary erythromelalgia and erythromelalgia secondary to a systemic disease, principally myeloproliferative syndrome. In the case of acrocyanosis, spontaneous digital haematomas and typical bilateral chilblains, examinations are of no value. For the other permanent and semi-permanent acrosyndromes such as digital ischaemia and purpuric or livedoid lesions, screening for arterial or thrombotic disease is necessary.
Congenital insensitivity to pain (CIP) is a rare syndrome with various clinical expressions, characterized by a dramatic impairment of pain perception since birth. In the 1980s, progress in nerve histopathology allowed to demonstrate that CIP was almost always a manifestation of hereditary sensory and autonomic neuropathies (HSAN) involving the small-calibre (A-delta and C) nerve fibres which normally transmit nociceptive inputs along sensory nerves. Identification of the genetic basis of several clinical subtypes has led to a better understanding of the mechanisms involved, emphasizing in particular the crucial role of nerve growth factor (NGF) in the development and survival of nociceptors. Recently, mutations of the gene coding for the sodium channel Nav1.7--a voltage-dependent sodium channel expressed preferentially on peripheral nociceptors and sympathetic ganglia--have been found to be the cause of CIP in patients showing a normal nerve biopsy. This radical impairment of nociception mirrors the hereditary pain syndromes associated with "gain of function" mutations of the same ion channel, such as familial erythromelalgia and paroxysmal extreme pain disorder. Future research with CIP patients may identify other proteins specifically involved in nociception, which might represent potential targets for chronic pain treatment. Moreover, this rare clinical syndrome offers the opportunity to address interesting neuropsychological issues, such as the role of pain experience in the construction of body image and in the empathic representation of others' pain.
