Unexpected drug-induced Raynaud phenomenon: Analysis from the French national pharmacovigilance database.

OBJECTIVE: To estimate the association between exposure to medicinal products and Raynaud phenomenon. METHODS: The study used the data of all adverse drug reactions notified to the French national pharmacovigilance database. All cases reported between 1st January 1995 and 10th December 2012 were selected. A case/non-case method was used to measure disproportionality of the association between drug exposure and Raynaud phenomenon. The cases concerned all observations involving Raynaud phenomenon. Non-cases comprised all other reports of adverse drug reactions over the same period. RESULTS/DISCUSSION: Among the 307,128 adverse drug reaction reports selected from the French national pharmacovigilance database, 175 involved Raynaud phenomenon, most of them affecting women (61.1%). The mean age was 50.1 years, and 8% had a past medical history of Raynaud phenomenon. According to the summaries of product characteristics, 42.3% of these cases were exposed to drugs known to induce Raynaud phenomenon. Unexpected Raynaud phenomenons (unlisted in the summaries of product characteristics) were associated with exposure to drugs for which Raynaud phenomenons are published (interferons, ribavirin, gemcitabine) or for which Raynaud phenomenons are not published (hepatitis B vaccine, isotretinoin, leflunomide, hydroxycarbamide, rofecoxib, telmisartan, zolmitriptan). CONCLUSION: The case/non-case method is usually used to generate signals. Further epidemiological studies are now necessary to confirm these findings.

[Comparative evaluation of dermoscopy and capillaroscopy in Raynaud's phenomenon]. / Évaluation comparative de la dermatoscopie et de la capillaroscopie dans le phénomène de Raynaud.

OBJECTIVE: Raynaud's phenomenon (RP) is a common cause for consultation. Capillaroscopy is a well-established technique to detect capillary abnormalities suggestive of a connective tissue disease, but it is sometimes unavailable. The aim of this study was to compare dermoscopy and capillaroscopy in the assessment of RP. METHODS: This was a prospective single-centre observational study in adult patients consulting for RP at the Hôpital Nord Franche-Comté between January 2014 and June 2015. Dermoscopy was performed at dermatological consultations and capillaroscopy was prescribed. For each capillaroscopy and dermoscopy, the following parameters were examined: normal appearance, giant capillaries, avascular areas, dystrophic capillaries or tortuosity and haemorrhages. Kappa coefficients were calculated. RESULTS: Twenty-six patients participated in this study. The kappa coefficient was 0.76 for "normal" status, 0.78 for tortuosity, 0.70 for giant capillaries, 0.48 for haemorrhage and 0.62 for avascular areas. The global kappa coefficient was 0.33. Detection of these abnormalities with capillaroscopy was significantly associated with abnormal dermoscopic status (P<0.05). The sensitivity of dermoscopy for the detection of "abnormal" capillaroscopic status was 0.87. CONCLUSION: The correlation coefficients were good. Despite poor global concordance, 80% of patients had the same status, normal or abnormal, for both capillaroscopy and dermoscopy, which resulted in the same clinical management. Dermoscopy is thus a valuable tool screening for periungual anomalies and provides support for clinical examination by the dermatologist, although the reference method continues to be capillaroscopy.

[Diagnosis of vascular acrosyndromes]. / Diagnostic des acrosyndromes vasculaires.

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.

[Clinical and capillaroscopic regression of CD30 anaplastic lymphoma associated with limited cutaneous systemic sclerosis following autologous bone marrow transplantation]. / Régression clinique et capillaroscopique après autogreffe de moelle d'une sclérodermie systémique cutanée limitée associée à un lymphome anaplasique CD30.

BACKGROUND: In rare cases, tumors are associated with secondary Raynaud's phenomenon in systemic sclerosis (SSc). We report the case of a patient presenting cutaneous limited SSc associated with CD30 anaplastic lymphoma with cutaneous and lymph node involvement in whom the capillaroscopic scleroderma pattern regressed completely after autologous bone marrow transplantation, with complete remission of the lymphoma. CASE REPORT: A 37-year-old man presented bilateral Raynaud's phenomenon associated with digital ulcers contracted one year earlier but subsequently neglected. Right axillary lymph nodes and regional cutaneous tumors were present, leading to the diagnosis of CD30+ anaplastic lymphoma with cutaneous and lymph node involvement. Chemotherapy containing cyclophosphamide achieved only partial remission of the lymphoma. Clinical examination showed bilateral Raynaud's phenomenon, sclerodactyly, a right axillary subcutaneous nodule and a pathological Allen's test for the right hand. Antinuclear antibodies were positive without any other immunological abnormalities, and capillaroscopy showed an SSc pattern with numerous megacapillaries. Digital blood pressure was reduced in the right index and the left middle fingers, in which ulcers of the pulp were observed. Bone marrow transplantation was performed, resulting in complete remission of the lymphoma and disappearance of the sclerodactyly, with no recurrence of the pulp ulcers and complete normalization of capillaroscopic appearance and digital pressure. DISCUSSION: This case raises the question of authentic SSc and neoplasia and highlights the importance of capillaroscopy in the follow-up of SSc. The complete regression of SSc and of capillaroscopic abnormalities could be explained by the paraneoplastic nature of SSc or by the direct action of the chemotherapy and bone marrow transplantation.

[Nail-fold capillaroscopy in dermatology]. / La capillaroscopie péri-unguéale en dermatologie.

Nail-fold capillaroscopy is a non-invasive tool to study the microcirculation and is increasingly being used in dermatology, angiology and rheumatology. More recently, the use of video-capillaroscopy has allowed computer storage of capillaroscopic images (video-capillaroscopy), enabling evaluation of changes in capillaroscopic abnormalities during the follow-up of patients with systemic sclerosis or mixed connective tissue disease. Qualitative and quantitative assessment of the nail-fold dermal capillaries and of their organization can readily distinguish between a normal capillaroscopic pattern in primary Raynaud phenomenon and a specific sclerodermic pattern in secondary Raynaud phenomenon carrying a very high risk of systemic sclerosis. Apart from its important role as a diagnostic tool for distinguishing between primary and secondary Raynaud phenomenon, capillaroscopy is now used to predict the risk of development of digital ulcers and of future visceral complications in patients with systemic sclerosis. Moreover, nail-fold capillaroscopy is essential for differential diagnosis between connective tissue diseases, for the etiologic diagnosis of digital necrosis and diffuse interstitial lung disease, and in sclerodermiform syndromes.

[Minimal work-up for Raynaud syndrome: a consensus report. Microcirculation working group of the Société française de médecine vasculaire]. / Bilan étiologique minimal du phénomène de Raynaud : un consensus d'experts.

About ten to fifteen percent of the French population suffer from Raynaud's phenomenon. Most of the time, it is considered as primary Raynaud's phenomenon, without underlying disease. The aim of this expert consensus from the "microcirculation group" for the French Society of Vascular Medicine and the French Society for Microcirculation, was to define clinical guidelines in patients consulting for Raynaud's phenomenon. The recommended minimal screening includes clinical examination, nailfold capillaroscopy and antinuclear antibodies. In particular, the aim of this screening is to identify patients with a significant risk for scleroderma, who would need a careful follow up.

[Paroxysmal vascular acrosyndromes: Practical approach to diagnosis and management]. / Acrosyndromes vasculaires paroxystiques : démarche pratique de diagnostic et de prise en charge.

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.

[Raynaud phenomenon with arterial thromboses and IgG4-related disease]. / Phénomène de Raynaud avec thromboses artérielles au cours d'une maladie associée aux IgG4.

INTRODUCTION: This is a clinical case illustrating a diagnosis of an IgG4 related-disease (IgG4-RD) diagnosed in a vascular context. CASE REPORT: A 47-year-old man with no past medical history consulted for a recent and disabling Raynaud phenomenon without trophic disorder. Vascular examinations revealed multiple arterial thromboses with no abnormal finger and toe pressures. Secondly, weight loss and submandibular glands enlargement appeared, leading to the diagnosis of IgG4-RD without a link being able to be established with vascular involvement. This is the second observation of this association. A French translation of the new classification criteria for IgG4-RD published in 2019 by the American College of Rheumatology and European Ligue Against Rhumatism (ACR/EULAR) is offered with direct application to the clinical case. CONCLUSION: A Raynaud phenomenon with distal arterial thrombosis is rarely observed in the IgG4-RD.

[Hypothenar hammer syndrome: A recurrent case report after surgery]. / Syndrome du marteau hypothénarien : à propos d'un cas de récidive après traitement chirurgical.

Hypothenar hammer syndrome is a rare entity secondary to ulnar artery damage in the wrist, affecting mainly those exposed to repeated hand-palm trauma. Surgery is discussed in case of severe symptoms, resistant to medical treatment, and/or when anatomical lesions with emboligenic potential are demonstrated in the radiological exams. In this case, resection of the pathological zone with revascularization by autologous vein graft is the best option. We report the case of a 60-year-old patient who had a recurrence of symptoms more than 10 years after the completion of a surgical treatment. There was an aneurysmal thrombosed vein graft with extensive thrombus extending from the ulnar artery upstream of the Guyon's canal to the superficial palmar arch. The digital revascularization was provided by the radial superficial palmar arch and the presence of a collateral vascular supply. This late complication was responsible for compression of the ulnar nerve in Guyon's canal. A new surgery was performed consisting of the resection of the thrombosed zone, including the vein graft, without vascular reconstruction given the good vascularization of all the fingers, and release of the ulnar nerve to the wrist. The operative follow-up was uneventful with the disappearance of pain and sensory-motor deficits. Good digital vascularization was confirmed by imaging at 3 months postoperatively; nerve recovery by electromyogram at 6 months with normal conduction.

Hypothenar hammer syndrome: A case of a late complication after surgery.

Hypothenar hammer syndrome is a rare condition secondary to ulnar artery damage in Guyon's canal, affecting mainly those exposed to repeated palm trauma. Surgery is discussed in cases of severe symptoms that are resistant to conservative treatment, and/or when anatomical lesions with high embolism potential are discovered during imaging exams. Resection of the pathological zone with revascularization by autologous vein graft is the best option. We report the case of a 60-year-old patient who had a recurrence of symptoms more than 10 years after this type of surgical treatment was performed. There was an aneurysmal thrombosed vein graft with extensive thrombus from the ulnar artery upstream to Guyon's canal to the superficial palmar arch. Finger revascularization was provided by the superficial branch of the radial artery and the presence of a collateral vascular supply. This late complication was responsible for compression of the ulnar nerve in Guyon's canal. A new surgery was performed to resect the thrombosed zone, including the vein graft, without vascular reconstruction due to the good vascularization of all the fingers, and to release the ulnar nerve at the wrist. The postoperative course was uneventful with the disappearance of pain and sensory-motor deficits. Good finger vascularization was confirmed by imaging at 3 months postoperative; nerve conduction was normal at 6 months on electroneuromyography.

[Etiological profile of secondary Raynaud's phenomenon in an internal medicine department. About 121 patients]. / Profil étiologique d'un phénomène de Raynaud secondaire dans un service de médecine interne. À propos de 121 patients.

INTRODUCTION: Raynaud's phenomenon is a reversible episodic vasospastic disorder triggered by cold or emotion. Two types of Raynaud's phenomenon were distinguished: Raynaud's disease and secondary Raynaud's phenomenon. The purpose of this study was to determine the etiologic profile of secondary Raynaud's phenomenon in an internal medicine department. METHODS: A descriptive retrospective study including patients with secondary Raynaud's phenomenon followed in a tertiary internal medicine department between 2000 and 2013. RESULTS: We included 121 patients. The sex ratio M/F was 0.16. The mean age at the onset of Raynaud's phenomenon was 41.7 years. The average age of patients at the time of the etiologic diagnosis was 47.3 years. The mean delay between Raynaud's phenomenon onset and the first consultation was 41.33 months. Raynaud's phenomenon involved hands in all cases and feet in 16.10% of cases with a typical form in most cases (41.4%). Complications (digital ulcers and scars) were noted in 32.23% of cases. Nail fold capillaroscopy showed scleroderma pattern in 49.52% of patients. Antinuclear antibodies were positive in 88.49% of patients. Interstitial lung disease was reported in 54.04% of cases. Connective tissue diseases were diagnosed in 86.77% of patients. Other secondary Raynaud's phenomenon causes were vasculitis (6.61%), atherosclerosis (1.65%) and medical or professional causes (1.65%). The most frequent one cause systemic sclerosis (n=61, 98%) followed by systemic lupus erythematosus (11.57%) and primary Sjögren syndrome (6.61%). CONCLUSION: In our study, the Raynaud's phenomenon was most frequently secondary to connective tissue diseases. This may be a selection bias because our department is a third-line unit where patients are often referred for systemic disease suspicion.

[Periungueal capillaroscopy: an easy and reliable method to evaluate all microcirculation diseases]. / Capillaroscopie périunguéale : une évaluation simple et fiable de toute pathologie de la microcirculation.

Periungueal capillaroscopy is a simple and reliable non-invasive technique allowing evaluation of cutaneous microcirculation. It was promoted for decades in patients with Raynaud's phenomenon in order to differentiate between the benign primary Raynaud's phenomenon and the secondary form in connective tissue diseases, especially systemic sclerosis. Nevertheless, the value of this procedure has also been shown in numerous pathologies such as diabetes or cardiovascular diseases. This literature review points to the versatility of this useful exam and its results in a large spectrum of diseases with microvascular involvement.

[Unilateral isolated Raynaud's phenomenon leading to diagnosis of multifocal giant-cell arteritis complicated with renal ischemia]. / Phénomène de Raynaud unilatéral isolé révélateur d'une artérite à cellules géantes multifocale (maladie de Horton) compliquée d'ischémie rénale.

We report a case of a 76-year-old woman with isolated unilateral Raynaud phenomenon revealing giant-cell arteritis with diffuse arterial lesions and bilateral renal artery stenosis. Doppler ultrasonography showed bilateral stenosis of the subclavian and axillary arteries. Angio-CT PET enlightened diffuse arterial lesions, mainly involving the aorta and the brachial and femoral arteries as well as bilateral renal ostial stenosis with right kidney ischemia. Diagnosis of giant-cell arteritis was made on the temporal artery biopsy. Corticosteroid therapy led to rapid clinical and radiological improvement. Clinical manifestations of giant-cell arteritis may be atypical. Diffuse arterial disease may exist in the absence of cephalic symptoms or significant inflammatory biological features. Ostial renal artery stenosis may induce potentially threatening renal ischemia.

[Hypothenar hammer syndrome: case report and review of the literature]. / Syndrome du marteau hypothénarien : cas clinique et revue de la littérature.

INTRODUCTION: Hypothenar hammer syndrome is a rare cause of upper extremity digital ischemia or Raynaud phenomenon, a diagnosis which should be considered in cases of iterative palmar trauma. Its treatment can be medical or surgical and should not suffer any delay. The best options remain controversial. METHODS: A 65-year-old patient presented with an ischemia of the last three fingers of the left hand. A partially thrombosed aneurysm of the left ulnar artery was diagnosed at imaging. After a partially effective medical treatment, a surgical treatment was performed with resection of the aneurysm and a vascular reconstruction with an autologous vein graft. The postoperative course was uneventful with disappearance of the symptoms and revascularization of the hypothenar area. CONCLUSION: Appropriate treatment for hypothenar hammer syndrome is controversial but whould always begin with medical care. The decision to perform surgery should be based on evidence of ulnar artery lesions and the associated symptoms.

[Raynaud's phenomenon and other circulatory disorders of the fingers]. / Das Raynaud-Phänomen und andere Durchblutungsstörungen der Finger.

Raynaud's phenomenon (RP) is defined as attacks of blanking, subsequent cyanosis and rubeosis of fingers due to vasospasms in response to cold or emotional stimuli. Primary RP has no known underlying cause and occurs mainly in young and otherwise healthy women. Secondary RP goes along with various causes such as connective tissue diseases, toxic substances, drugs, physical trauma or organic finger artery occlusions, and occurs at any age and in both genders. Related affections are acrocyanosis and finger artery occlusions either due to arteriosclerosis or vasculitis. Also spontaneous finger hematoma may provoke an episode of RP. Therapeutically strict cold protection and avoidance of possible noxa is recommended besides the treatment of underlying diseases. No standard vasoactive drug has proven ideal for RP due to side effects. In cases with rest pain or ulcerations the same principles are applied as in ischemic diseases with no possibility for revascularization.

Le phénomène de Raynaud(PR) est défini comme des attaques de blancheur suivie d'une cyanose et d'une rougeur des doigts dues à un vasospasme en réponse au froid ou à un stimulus émotionnel. Le PR primaire n'a pas de cause connue et atteint surtout des jeunes femmes qui sont par ailleurs en bonne santé. Le PR secondaire se rencontre avec des causes variées comme la sclérodermie, des substances toxiques, des médicaments, des traumatismes physiques ou des occlusions artérielles au niveau des doigts. Cette forme de PR peut survenir à tout âge, tant chez l'homme que chez la femme. Des affections relatées au PR sont l'acrocyanose et les occlusions des artères digitales dues à l'artériosclérose ou une vasculite. Enfin, un hématome spontané au niveau d'un doigt peut provoquer un PR. Une protection stricte contre le froid et l'évitement autant que possible des facteurs favorisants est recommandé, ceci en plus du traitement de la maladie sous-jacente. Il n'y a pas de médicament vasoactif standard idéal pour traiter le PR, particulièrement en raison de leurs effets secondaires. En cas de douleur au repos ou en présence d'ulcérations les mêmes principes de traitement sont appliqués que lors d'affections ischémiques, avec cependant l'impossibilité d'effectuer une revascularisation.