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Background. Diabetes mellitus (DM) is a current medical and social problem. According to the data from International Diabetes Federation, 415 million people worldwide suffer from DM, and bу 2030, the number of patients is expected to be 552 millions. Diabetic foot syndrome is the most severe form of DM, manifestation of purulent­necrotic complications in the lower extremities, nearly 30–60 % of patients have it. After comparative analysis, the authors of this work noted that in people with diabetic foot syndrome, amputations of lower extremities are being performed 30 times more often than in persons without DM. There are two factors in the pathogenesis of diabetic neuropathy: metabolic and vascular, which may change with time; at early stages, metabolic forms prevail, then — vascular. The use of new examination methods will allow diagnose complications of diabetes mellitus in a timely manner, in particular, diabetic foot syndrome, which will significantly increase the effectiveness of treatment and quality of life. Raynaud’s syndrome manifests itself as a spasm of the large arteries of the distal limb, the tip of the nose. Among non­invasive diagnostic methods, the method of remote infrared thermography is quite informative. The use of thermography allows you to identify an early stage and to monitor the course of this disease. As can be seen from the set forth, Raynaud’s disease and the affection of the lower extremities in patients with DM have much in common. The aim of the study was to use remote infrared therapy for the differential diagnosis of major blood flow disorders in the arteries of the lower extremities of varying severity, which may be the result of Raynaud’s disease or the complication of DM or diabetic foot syndrome. Materials and methods. Patients’ examination was carried out according to the worked out methodology with the use of domestic thermographer with matrix photodetector. Results. A typical thermographic picture is a reduced temperature in the zone of the tip of the nose, hands and feet. Depending on the degree of disease development, the temperature gradient in cold zones may vary from 0.8 to –1.4… –12 °C. The highest temperature gradient is observed when patients are close to so­called thermoamputations of the hand or lower limb. Thermograms in Raynaud’s disease, as a rule, do not have signs of disturbed blood flow in the major vessels of the lower extremities. We observed another thermographic picture of the lower extremities when patients have DM. Patient S. with type 2 diabetes mellitus complained of pain and sensory impairment in the right lower limb. On the thermogram, the disturbance is visualized in the blood supply to the lower limb with the zones of the thermal asymmetry — hypo­ and hyperthermia. The temperature of the front surface of the right foot is 2.03 °C degrees lower than the temperature of the front surface of the left foot. There is a thermal asymmetry of the right and left legs, the temperature difference in the zones marked equals –0.94 °C. Despite the disturbed blood supply to the lower extremities, a sharp decrease in the temperature of the toe bones is not visualized thermograpically. Depending on in­patient and preventive treatment, which is associated with the constant intake of antihyperglycemic drugs, blood sugar levels ranged 19–14–7 mmol/l. Thermographic diagnosis allows non­invasive, easy for the patient dynamic monitoring of the treatment process. Conclusions. The conducted research showed the possibilities of remote infrared therapy in various forms of disturbed blood supply to the lower limbs in patients with DM. Triad of simultaneous thermographic signs, which are characteristic of Raynaud’s disease (violation of blood supply to the nose, hands, feet), is rarely observed when patients have diabetes mellitus, which makes it possible to carry out differential diagnosis of the above­mentioned pathologies. In order to detect the disorders of the micro­ and macrocirculation system in a timely manner, it is expedient to use remote infrared therapy as one of the modern non­invasive methods for determining comprehensive treatment and the prognosis of limb preservation with diabetic foot syndrome.

Objectives Besides cold, emotional distress is the most important trigger of Raynaud's disease (RD) attacks, although little is known about the factors that contribute to the effectiveness of coping with emotional distress. The aim of the present study was to explore alexithymia and emotion regulation and their relationship with depression and quality of life among patients with RD. Methods Total of 110 patients (mean age 53.65; 96 women) with RD completed self-report measures. Results Alexithymia was associated with adverse emotional regulation skills, depression, and quality of life impairment. Detailed analysis revealed that there are significant differences between alexithymic and nonalexithymic patients in emotion regulation. Conclusion Alexithymia is a significant factor affecting health status in RD since it plays a significant role in emotion regulation. A multidisciplinary approach is essential to improve treatment outcome by identifying patients with high alexithymia, and to improve their emotional regulation skills.

Background: Idiopathic Raynaud’s disease is twice common in women than their counterparts, and secondary Raynaud’s disease co-occurs with a variety of medicosurgical conditions. Both diseases are managed by several medications which are invariably associated with various adverse effects. Objective: This study aimed to describe several standardized SPIRIT and PRISMA steps and items that help in the development of research protocol directed towards systematic review and meta-analysis conduction concerning Raynaud’s phenomenon managed by clinical acupuncture. Methods and Results: Statements, guidelines, list of items and processes related to SPIRIT and PRISMA and their extensions and updated versions are ideal methodological tools in framing Raynaud’s disease and acupuncture research protocols for scientifically conducting not only randomized controlled trials but also systematic review and meta-analysis. By extension, these methodological tools could also be applied to develop research protocols for other diseases and nontraditional treatment interventions with some modifications. A total of 53 studies were included in this study protocol. Discussion: In line with Traditional Chinese Medicine, the pattern of Raynaud’s disease and pros and cons of medical acupuncture should make an important component of discussion, besides the details of included randomized clinical interventions in systematic review and meta-analysis, which are but not limited to treatment effects, their strengths and limitations, quality, heterogeneity and endpoints. Conclusion: The development of research protocol for conducting systematic review and meta-analysis is an art and while framing the draft researchers must take into account various SPIRIT and PRISMA statements and guidelines and their latest versions applicable to various diseases including Raynaud’s phenomenon managed by traditional and modern medications across the world.

Background: Primary Raynaud’s disease preferentially afflicts women with 5% prevalence rate reported in general population, manifests triphasic color phenomenon along with paresthesia involving distal digits and toes and triggered by severe cold and stress. Objective: This review critically describes several perspectives of Raynaud’s diseases with a focus on medical acupuncture. Methods: Electronic searches of relevant data prior to 2019 published in PubMed, MEDLINE, Google Scholar, and ScienceDirect databases were made using the Boolean operators and keywords. Finally, 32 articles that addressed specifically Raynaud’s disease and acupuncture were retained for this minireview. Results: Raynaud’s disease classified into primary and secondary is poorly understood phenomenon, lacks standard care and, hence, needs patient-centered holistic approach. Evidently, medical acupuncture with safe clinical profile has been effectively used as an alternative therapy in Raynaud’s disease. Outcome results with the use of conservative approaches, modern therapies, behavioral interventions and medical acupuncture vary considerably across the board and primary RD carries better prognosis than secondary RD. Conclusion: Both Raynaud's disease phenomena are complex conditions; need individualized treatment approach including surgical in refractory cases and further rigor studies to unravel their pathophysiology pathways and standardized interventions.

INTRODUCTION In primary or refractory cases of Raynaud's Disease (RD), with severe symptoms (pain, ulcers, and disability), minimally invasive surgical treatments such as thoracoscopic sympathectomy have recently been proposed. The objective of this study will be to evaluate the viability, feasibility and results of this therapeutic option in this type of patient. MATERIAL AND METHODS Descriptive prospective study from January 2017 to January 2019 where all patients with a diagnosis of RD, with poor clinical control and disability, and refractory to medical treatment are collected. RESULTS Seven girls (9-15 years old) were collected. All underwent bilateral thoracoscopic sympathectomy, T2-T4, with a mean surgical time of 55 min. No need for pleural drainage. All of them were discharged before 36 hours after surgery (12-36 hours) without any immediate intra or postoperative complications. All reported an immediate postoperative period without incident, without new episodes of pain or intense vasoconstriction. However, 6 months after surgery, 3 of the 7 (42.85%) presented partial reappearance of the symptoms. However, the 7 presented 100% satisfaction with the surgical results. CONCLUSIONS There are currently very few published studies regarding this surgical option. We believe that our series is the first pediatric series to be collected, although it is very limited. However, the results obtained to date, in global terms, are encouraging. We consider that thoracoscopic sympathectomy is a feasible and safe surgical technique to consider in patients with RD refractory to conservative treatment.

Raynaud's phenomenon (RP) is a disease characterized by a transient ischemic process, in an exaggerated vascular response to cold or emotional stress. Thermography is a resource applied to support diagnosis of changes in the circulatory system. The aim of the study was to use the DistalDorsal Thermography Difference (DDD) in thermographic images to assess thermal behavior in individuals with secondary RP. The research was carried out in the period between 2018 and 2019. The sample means of the Distal-consisted of 44 individuals in a control group (Control) and 44 individuals in a pathological group (RP2). The participants, after acclimatization, were submitted to the cold stress protocol. The protocol consisted of immersing hands in a container of water at a temperature of 15°C for 60 seconds. The acquisition of thermographic images was performed at the pre-test moment and at the 1st, 3rd, 5th, 7th, 10th and 15th minute. At each time, the DDD values (of all fingers - minimum, maximum and sum) between the groups were analyzed. For statistical analysis, the independent t test and Cohen's d test were used. Regarding the results, there was a difference in relation to the rate of temperature recovery between the groups. The first group showed a rate of reheating just after the first minute subsequent to the cold stress test, while the RP2 group was unable to recover the temperature over 15 minutes. DDD, regardless of the selected criterion, proved to be a valid index for verifying the temperature gradient in the study with individuals identified with secondary RP.

Using the thermography method, we studied the state of the upper limbs of 43 patients with Raynaud’s disease, 37 of which were operated as a result of dynamic observation in the process of conservative treatment. A directly proportional relationship between the thermal imaging pattern and the treatment method of microcirculatory disorder in the distal sections of the upper limbs has been revealed. It is established that visualization of the contour of fingers at the level of distal phalanges may result in both conservative and surgical treatment – upper thoracic sympathectomy or distal periarterial and thoracic sympathectomy in combination with finger amputation. Taking into account the received data, we confirmed that the use of a thermographic study with computer data processing in the diagnosis of the pathological process of the upper limbs is a method of selecting the principle of treatment (conservative or surgical).

Resumen Introducción: Entre un 15 y un 20% de los pacientes con fenómeno de Raynaud progresarán a una enfermedad autoinmune sistémica. La presencia de autoanticuerpos o alteraciones capilaroscópicas es fundamental para el diagnóstico temprano. Objetivos: Determinar las características de la videocapilaroscopia del lecho ungular y de los anticuerpos antinucleares en una cohorte de pacientes con enfermedad autoinmune sistémica. Materiales y métodos: Se realizó un estudio transversal en sujetos con fenómeno de Raynaud. Estos fueron evaluados con videocapilaroscopia y anticuerpos antinucleares. Las variables cualitativas se describieron con frecuencias absolutas y relativas; las variables cuantitativas, según la distribución de los datos, se reportaron como media o mediana, con desviación estándar y rango intercuartílico, respectivamente. Resultados: Se incluyeron 58 individuos; el 91,4% eran mujeres. La edad promedio fue 40,9 ± 14,1 arios. En 41 sujetos, los anticuerpos antinucleares fueron positivos; el patrón más común fue el moteado (41,5%), con una mediana de dilución de 1:640 (rango inter-cuartílico 1:320-1:1.280). Se encontró enfermedad autoinmune sistémica en 10 individuos (19,2%), 8 de ellos con esclerosis sistémica. Las alteraciones capilares más frecuentes fueron: megacapilares (n = 10), microhemorragias (n = 10) y zonas avasculares (n = 8). Conclusiones: En este grupo de pacientes con fenómeno de Raynaud sometidos a video-capilaroscopia, el diagnóstico de enfermedad autoinmune sistémica fue realizado en un porcentaje similar a lo reportado en la literatura. Se encontró una mayor dilución de anticuerpos antinucleares que la descrita. Abstract Introduction: Between 15 and 20% of patients with Raynaud's phenomenon will progress to a systemic autoimmune disease. The presence of autoantibodies or capillaroscopy alterations are fundamental for early diagnosis. Objectives: To determine the characteristics of nailfold videocapillaroscopy and antinuclear antibodies in a cohort of patients with systemic autoimmune disease. Materials and methods: A cross-sectional study was conducted in subjects with Raynaud s phenomenon. These were evaluated with videocapillaroscopy and antinuclear antibodies. The qualitative variables were described with absolute and relative frequencies. The quantitative variables, according to the distribution of data, were reported as mean or median, with standard deviation and interquartile range, respectively. Results: The study included 58 individuals, of which 91.4% were women. The mean age was 40.9 ± 14.1 years. Antinuclear antibodies were positive in 41 subjects. The most common pattern was speckled (41.5%), with a median dilution of 1:640 (interquartile range 1:3201:1,280). A systemic autoimmune disease was found in 10 (19.2%) patients, 8 of them with systemic sclerosis. The most frequent capillary alterations were: mega-capillaries (n = 10), micro-haemorrhages (n = 10), and avascular zones (n = 8). Conclusions: In this group of patients with Raynaud's phenomenon subjected to videocapillaroscopy, a diagnosis of systemic autoimmune disease was made in a similar percentage to that reported in the literature. A higher dilution of antinuclear antibodies was found than that described.

Objective: A 57-year-old female with a 33-year history of constant hand discoloration and paronychia had undergone multiple evaluations with a failure to find a diagnosis. She continues to undergo an evolving treatment regimen and diagnostic workup in an effort to find a long-eluded diagnosis. Clinical Presentation: She began to develop superficial ulcerations over the proximal phalanx of her fingers, often pruritic and erythematous, with pain and edema. Intervention: She has since been managed with nifedipine and sildenafil and intermittent stellate ganglion blocks. Conclusion: Despite still lacking a formal diagnosis, her constellation of symptoms is most likely the result of an atypical presentation of Raynaud’s disease.

β-Blockers are a widely utilised class of medication. They have been in use for a variety of systemic disorders including hypertension, heart failure and intention tremors. Their use in dermatology has garnered growing interest with the discovery of their therapeutic effects in the treatment of haemangiomas, their potential positive effects in wound healing, Kaposi sarcoma, melanoma and pyogenic granuloma, and, more recently, pemphigus. Since β-blockers are deployed in a variety of disorders, which have cutaneous co-morbidities such as psoriasis, their pertinence to dermatologists cannot be overstated. Likewise, β-blockers, like any other drug category, carry risks of side effects, some of which are dermatologic. These include triggering and exacerbation of psoriasis, psoriatic and rheumatoid arthritis, anaphylaxis, contact dermatitis, occupational contact dermatitis, Raynaud's disease, alopecia, lichen planus-like drug eruption, hyperhydrosis and vitiligo. While recent articles have focussed on the positive uses of β-blockers, it may also be wise to call our attention to the potential dermatologic adverse effects that may follow β-blocker use, as well as possible therapeutic approaches to these. This short review will focus on those dermatoses resulting from β-blocker use, which have an immunologic basis.

Raynaud’s phenomenon is one of the most common disorders of the blood vessels, which usually affects fingers and toes. Raynaud’s disease, also called primary Raynaud’s phenomenon, is diagnosed when the cause is unknown, whereas Raynaud’s syndrome or secondary Raynaud’s phenomenon occurs as a skin manifestation of concomitant disease. The most common trigger is exposure to cold. Specific clinical features allow a quick diagnosis. Raynaud’s phenomenon usually does not require pharmacologic treatment, but in some cases symptoms are severe and pharmacotherapy is necessary. Calcium channel blockers are usually used as a first-line treatment. Alternative forms of therapy include angiotensin-converting-enzyme inhibitors, 1-adrenergic blockers, phosphodiesterase-5 inhibitors, endothelin antagonists, nitrates, antioxidants, statins, botulinum toxin, and even autologous fat grafting.

We present a case of Raynaud’s disease with digital ulcers that was successfully treated with hyperbaric oxygen therapy. Hyperbaric oxygen therapy can be considered as a safe and useful adjunct treatment for intractable digital ulcers in patients with Raynaud’s disease.

β-Blockers are a widely utilised class of medication. They have been in use for a variety of systemic disorders including hypertension, heart failure and intention tremors. Their use in dermatology has garnered growing interest with the discovery of their therapeutic effects in the treatment of haemangiomas, their potential positive effects in wound healing, Kaposi sarcoma, melanoma and pyogenic granuloma, and, more recently, pemphigus. Since β-blockers are deployed in a variety of disorders, which have cutaneous co-morbidities such as psoriasis, their pertinence to dermatologists cannot be overstated. Likewise, β-blockers, like any other drug category, carry risks of side effects, some of which are dermatologic. These include triggering and exacerbation of psoriasis, psoriatic and rheumatoid arthritis, anaphylaxis, contact dermatitis, occupational contact dermatitis, Raynaud's disease, alopecia, lichen planus-like drug eruption, hyperhydrosis and vitiligo. While recent articles have focussed on the positive uses of β-blockers, it may also be wise to call our attention to the potential dermatologic adverse effects that may follow β-blocker use, as well as possible therapeutic approaches to these. This short review will focus on those dermatoses resulting from β-blocker use, which have an immunologic basis.

Raynaud's disease is a medical condition in which arterial spasm causes episodes of reduced blood flow, in the setting of certain triggers such as cold weather. Patients with this condition are at risk of adverse reactions if they receive medications with vasoactive properties. Methylergonovine maleate is one drug used during cesarean delivery to treat postpartum hemorrhage due to uterine atony. By acting directly on uterine and vascular smooth muscle, it produces cardiovascular responses such as coronary vasospasm, myocardial infarction, and even cardiac arrest. However, pulmonary events have rarely been reported. We report our anesthetic management of a 36-year-old patient, with undiagnosed Raynaud's disease and undergoing cesarean delivery, who experienced new onset acute pulmonary edema after methylergonovine administration to manage postpartum hemorrhage.

Raynaud's disease is a disorder that is characterized by attacks of pain, cyanosis, redness, and numbness in the upper extremities caused by vasospasm of digital arteries due to cold or emotional stress. We aimed at demonstrating our experiences with endoscopic thoracic sympathectomy (ETS) in the treatment of Raynaud's disease.From 48 patients who underwent ETS for various reasons at our department between January 2014 and January 2015, we reviewed 9 patients with Raynaud's disease (18.7%) with respect to their demographic characteristics such as gender and age, postoperative complications, short-term results, side effects, recurrence of symptoms, and long-terms results.The symptoms and findings reappeared and the number and dosage of the drugs used returned to their preoperative levels in 66.6% of the patients at month 6, and in all patients except 1 at the end of the 1st year.ETS should be considered an ultimate choice for patients with Raynaud's disease who have treatment-resistant severe symptoms and serious complications, disturbed social and daily lives, and impaired quality of life, and all patients should be properly informed before the surgery about the possibility of a high rate of recurrence.

Objective: To review the evidence for using intravenous (IV) epoprostenol to treat Raynaud’s phenomenon (RP). Data Sources: The databases MEDLINE (1946 to March 2016), PubMed, and International Pharmaceutical Abstracts were searched using the terms epoprostenol, Flolan, Raynaud’s disease, and CREST syndrome. Further literature sources were identified by reviewing article citations. Study Selection and Data Extraction: All English-language, clinical trials and case series evaluating IV epoprostenol for the management or treatment of RP were included. Lower-quality evidence were incorporated due to limited information. Data Synthesis: Seven small uncontrolled studies/case series, 1 small placebo controlled study, and 1 larger randomized trial were identified and included. There was no consistent measurement of efficacy utilized, but improvements in hand temperature, RP attack duration and frequency were commonly associated with IV epoprostenol treatment (5 trials). There were conflicting data regarding effect sustainability, with 5 trials showing long-term effects and 3 showing immediate effects. Fewer ischemic ulcers developed during treatment with IV epoprostenol in 1 trial compared to conventional treatment. Ulcer healing ocurred in 2 trials. Common adverse effects included hypotension, headache, flushing, gastrointestinal symptoms, and jaw pain. Conclusions: Available evidence supports the use of IV epoprostenol for treatment of severe RP in patients refractory or intolerant to standard therapies. The dose, titration schedule, and duration of IV epoprostenol utilized in studies varied, but a conservative approach to initiation should be considered. Patients who do not respond to intermittent infusions and have severe digital ischemia may require more aggressive regimens.

Ischemia of the extremities is a fairly common clinical entity most commonly caused by occlusive arteriosclerotic disease with secondary thrombosis or embolization. The resultant ischemic extremity will present with progressive pain syndromes and pregangrenous or gangrenous tissue. When the disease progresses beyond survivability and the symptomatology is unbearable, amputation is necessitated. The pathologist then receives the premorbid or neurotic tissue after removal.

Objective: To report a case of Raynaud disease and its successful treatment with spinal cord stimulation utilizing the newly designed five-column Penta™ lead paddle. Specific electrode design, programming characteristics, and surgical technique are also discussed in this case. Design: Case Report. Setting: University pain management center. Background: A 65-year-old man with Raynaud disease presented with neck and upper extremity pain. The patient also had herniation and spondylosis of the lumbar spine and intervertebral disc disease of the cervical spine. An examination revealed venous changes, chronic ulceration, and digit discoloration in upper and lower extremities. Method: Conservative management and pharmacological treatment were ineffective. Sympathetic block produced significant but limited improvement. Treatment with spinal cord stimulation was tried after a successful 7-day trial. Results: Initial stimulation of the cervical spine with two octapolar leads at the C2 level produced greater than 75% pain improvement. However, the patient lost coverage shortly after discharge due to lead migration which could not be regained with reprogramming. A revision with Penta™ lead paddles produced sustainable and significant paresthesia coverage. Limitations: A case report. Conclusion: We report the successful application of spinal cord stimulation utilizing a five-column paddle lead in an individual with severe refractory Raynaud disease. Key words: Keywords: Spinal cord stimulation, Penta lead, five-column lead, electrode, paresthesia, Raynaud disease, cervical pain, programming.

Summary Accurate diagnosis and timely management are crucial to avoid an ischaemic consequence in Raynaud's disease. There is, however, no objective classification of this disorder which guides surgical planning in refractory cases. We propose a new classification system to achieve this. From 2003 to 2009, we treated 178 patients (351 hands) who underwent surgical intervention due to an ischaemic consequence. We analysed the angiographic features of the arterial supply of the hand at three levels: (1) radial or ulnar, (2) palmar arch and common digital and (3) digital vessels. Subsequent surgical interventions were tailored according to disease types, and these included combinations of: digital sympathectomy, balloon angioplasty and end-to-end interposition venous or arterial grafting. We classified Raynaud's disease into six types: type I and II involve the radial or ulnar arteries. Type I (27.3%) showed complete occlusion, while type II (26.2%) involved partial occlusion. Type IIIa (27.1%) showed tortuous, narrowed or stenosed common digital and digital vessels. Type IIIb (1.4%) is a subset which involved the digital vessel of the index finger related to exposure to prolonged vibration. Type IV and V showed global involvement from the main to digital vessels. Type IV (13.7%) showed diffused tortuosity, narrowing and stenosis. Type V (4.3%) is the most severe, with paucity of vessels and very scant flow. Nearly half (47%) of the patients had associated systemic disease. This new classification provides objective and valuable information for decision making regarding choice of surgical procedures for the treatment of patients with Raynaud's disease which had failed conservative therapy.

The aim of this study was to assess nailfold capillaroscopic (NC) findings in patients with primary Sjogren's syndrome (PSS) with and without Raynaud's phenomenon (RP) as well as in the presence of positive anti-SSA/Ro and anti-SSB/La antibodies. Videocapillaroscopy was performed in 150 patients with PSS. Data collected included demographics, presence of RP, PSS symptoms, antinuclear antibodies, rheumatoid factor, anti-Ro, anti-La, anti-CCP, salivary scintigraphy, labial biopsy, and NC findings. RP was present in 32 % of PSS, keratoconjunctivitis sicca in 91 %, oral xerosis in 93 %, and skin or genital xerosis in 53 %. In patients with positive anti-SSA/Ro (75 %) and positive anti-SSB/La (40 %), NC showed normal findings in 53 % of cases and nonspecific in 36 %. In patients with PSS, NC was normal in 51 % of cases and non-specific in 34 %. Scleroderma pattern was found in 14 patients. RP associated with PSS had non-specific capillaroscopy in 40 % of cases (p = 0.1). Pericapillary haemorrhages (p = 0.06) and capillary thrombosis (p = 0.2) were not increased, but more dilated capillaries were detected in 48 % of cases. Patients with positive anti-Ro and/or anti-La have not a distinct NC profile. Patients with RP associated with PSS had more dilated capillaries, but neither pericapillary haemorrhages nor capillary thrombosis was observed.

Cryosurgery is used commonly to treat both benign and malignant skin lesions: the medical professional treating the condition must select the best method from among the many available today. This chapter deals with selection of lesions that are best suited for cryosurgery. Though there are hardly strict confines to what can or cannot be treated this chapter will discuss lesions commonly treated by cryosurgery and general contraindications as well as some lesions where cryosurgery is not the best recommendation.

Systemic sclerosis (SSC) is sometimes associated with the appearance of Raynaud’s disease due to diffuse vasculopathy associated with SSC. Low reactive-level laser therapy (LLLT) has been reported in the past to have beneficial effects in various vasculopathies, including Buerger’s and Raynaud’s diseases. The authors surmised that LLLT might therefore be of some assistance in the treatment of the Raynaud’s component of SSC. A 30-yr old male patient with SSC was treated with a combination of bosentan and LLLT (GaAlAs diode laser, 60 mW, continuous wave, incident power density 3 W/cm2) in 35 treatment sessions over 24 weeks. After the final treatment session, both skin tightness and Raynaud’s phenomenon had improved, whereas no progression was seen in the pulmonary fibrosis and pulmonary function did not get any worse. The results suggest that bosentan with complementary LLLT was effective for not only improving the dermal blood circulation but also preventing progression of the overall disease status in this case.

The aim of this study was to assess nailfold capillaroscopic (NC) findings in patients with primary Sjogren's syndrome (PSS) with and without Raynaud's phenomenon (RP) as well as in the presence of positive anti-SSA/Ro and anti-SSB/La antibodies. Videocapillaroscopy was performed in 150 patients with PSS. Data collected included demographics, presence of RP, PSS symptoms, antinuclear antibodies, rheumatoid factor, anti-Ro, anti-La, anti-CCP, salivary scintigraphy, labial biopsy, and NC findings. RP was present in 32% of PSS, keratoconjunctivitis sicca in 91%, oral xerosis in 93%, and skin or genital xerosis in 53%. In patients with positive anti-SSA/Ro (75%) and positive anti-SSB/La (40%), NC showed normal findings in 53% of cases and non-specific in 36%. In patients with PSS, NC was normal in 51% of cases and non-specific in 34%. Scleroderma pattern was found in 14 patients. RP associated with PSS had non-specific capillaroscopy in 40% of cases (p = 0.1). Pericapillary haemorrhages (p = 0.06) and capillary thrombosis (p = 0.2) were not increased, but more dilated capillaries were detected in 48% of cases. Patients with positive anti-Ro and/or anti-La have not a distinct NC profile. Patients with RP associated with PSS had more dilated capillaries, but neither pericapillary haemorrhages nor capillary thrombosis was observed.

The pathophysiology of primary Raynaud's phenomenon (Raynaud's disease) remains uncertain but the transmission of this primary microcirculatory dysregulation seems strongly influenced by genetic factors. For a long time, physicians have found that the hereditary factor plays an important role in the genesis of Raynaud's disease. Familial analysis and twin studies have confirmed the role of an hereditary factor. It seems heterogeneous but pedigree analysis indicates the possibility of an autosomal dominant transmission influenced by sex, in some families, allowing an approach called "reverse genetic" based on linkage analysis. Such an approach has focused on few loci but sequencing of candidate genes for genetic mutations remains negative. Given the supposed heterogeneity of the genetic transmission of Raynaud's disease, diversification of strategies in molecular genetics is suitable with reference to techniques applied to multifactorial heredity.

Raynaud's phenomenon is due to transient cessation of blood flow to the digits of the hands or feet. An attack of Raynaud’s phenomenon is classically manifested as triphasic color changes. The white phase is due to excessive vasoconstriction and cessation of regional blood flow. This phase is followed by a cyanotic phase, as the residual blood in the finger desaturates. The red phase is due to hyperemia as the attack subsides and blood flow is restored. An attack is frequently associated with pain and/or paresthesia due to sensory nerve ischemia. Variants of Raynaud’s phenomenon include acrocyanosis and primary livedo reticularis, each of which is associated with reduced skin blood flow, exacerbated by cold or emotional upset. Raynaud’s phenomenon in the absence of other disorders is primary Raynaud’s phenomenon, or Raynaud’s disease. The mechanisms of Raynaud’s disease include increased activation of the sympathetic nerves, in response to cold or emotion; an impaired habituation of the cardiovascular response to stress may contribute. In addition, there appears to be a local fault, which is likely multifactorial. This local fault is due to an alteration in vascular function rather than vascular structure. The alteration in vascular function may be related to increased sensitivity to cold of the adrenergic receptors on the digital artery vascular smooth muscle. In some cases, locally released or systemically circulating vasoconstrictors may participate, including endothelin, 5-hydroxytryptamine and thromboxane. A deficiency or increased degradation of nitric oxide, possibly due to increased oxidative stress, may be involved in some cases. These recent pathophysiological insights may lead to new therapeutic options.

BACKGROUND Large-scale epidemiological studies have demonstrated that both anaemia and polycytaemia are independent cardiovascular risk factors. This was substantiated by the Framingham study, which demonstrated a U-shaped relation between haemoglobin concentration and mortality. It was previously noted that delineating the corresponding haematocrit/blood viscosity ratios in the function of haematocrit provided a distribution of an inverted U-shaped curve. The peak appeared physiologically important because it denotes a healthy balance between a relatively high oxygen binding capacity and a moderately low blood viscosity. It was the aim of this study to examine the mathematical relationship between the haematocrit and haematocrit/blood viscosity ratio. MATERIALS AND METHODS In a retrospective study, the haemorheological data of 32 healthy controls, 52 outpatients with hyperlipidaemia and 120 outpatients with Raynaud's disease were analyzed. Whole blood viscosity was measured with Hevimet 40 capillary viscometer at 37.0 degrees C and at shear rates of 10 s(-1), 90 s(-1) and 200 s(-1). RESULTS Haematocrit/blood viscosity ratios in the function of haematocrit values showed a Gaussian association in the healthy subjects, hyperlipidaemic and Raynaud's disease outpatient groups. Peak values (i.e. the rheologically optimal haematocrit) were shear-rate and group dependent and were found at 44.3%, 43.5% and 38.3% in controls, hyperlipidaemic and Raynaud's disease patients, respectively, at a shear rate of 90 s(-1). CONCLUSIONS This is one of the first reports in which a theoretically optimal haematocrit value was determined using the haematocrit/blood viscosity ratio. Further studies are needed to examine the potential clinical usefulness of this approach.

Background Raynaud's phenomenon (RP) is a frequent vascular paroxysmal syndrome of the extremities. Generally benign, the condition is called Raynaud's disease (RD), which may reveal a connective tIssue disease, particularly systemic sclerosis (SS). We evaluated digital blood flow in patients with RD and SS using color Doppler ultrasound. Patients and methods Ultrasound examination was performed with a newly developed multi-D linear array transducer (VFX 13-5 Siemens), which allows better resolution. We first measured the diameters of the digital arteries (appendix 1) then epidermal, dermal, and hypodermal thickness for each patient (appendix 3) and performed a qualitative and quantitative analysis of pulpar microcirculation (appendix 4 & 5). All measures were made at 25 degrees C, 45 degrees C, 11 degrees C and after recovery. Thirty-three patients were included: 14 with primary RD and 19 with SS as assessed by American College of Rheumatology criteria. Results The diameters of the digital arteries showed significant discrepancies allowed to distinguish primary RP from SS. At 11 degrees C, diameters were 0.6 +/- 0.2 mm for primary RP versus 0.2 +/- 0.3 mm for SS on lateral digital arteries (LDA) [p=0.005]; 0.7 +/- 0.2 mm for primary RP versus 0.4 +/- 0.3 mm for SS on medial digital arteries (MDA) [p=0.004]. After recovery, these diameters were respectively 1 +/- 0.2 mm versus 0.5 +/- 0.4 mm for LDA [p=0.000] and 1 +/- 0.2 mm versus 0.6 +/- 0.3 mm for MDA [p=0.000] (tables 1, 2, 3, 4). Similarly, pulpar vascularization was significantly higher in primary RP than in SS (tables 6, 7, 8). No difference was found in skin thickness nor in the epidermal aspect between the two groups (table 5). Conclusion Color Doppler ultrasound shows morphological and dynamic differences between RD and SS.

Although certain broad principles of treatment apply to all patients with Raynaud's phenomenon, the exact approach will vary depending on the nature and severity of the underlying digital vascular problem. Advances in the understanding of the pathophysiology of Raynaud's phenomenon are directing new lines of therapy. This review considers general (nonpharmacologic) measures, the different types of drug therapy, and the role of surgery. Recent advances in the use of more conventional treatments, such as calcium channel blockers, are discussed and also newer agents that are currently being researched, for example, endothelin-1 receptor antagonists and nitric oxide donors. The necessity of prompt assessment and treatment of acute digital ischemia, which is a medical emergency, is highlighted.

Introduction: primary Raynaud's disease may be difficult to differentiate clinically from the secondary form with an underlying connective tissue, haematological, neurovascular or drug-induced disorder. We undertook a study to determine the elastic carotid and muscular femoral arterial biomechanical properties and intima-media thickness (IMT) in subjects with primary and secondary Raynaud's disease, to assess whether these parameters could differentiate the two conditions. Methods: twenty patients with primary Raynaud's disease and 53 subjects with secondary Raynaud's associated with scleroderma (systemic sclerosis, SSc) had measurements of their carotid and femoral wall mechanics with a duplex scanner coupled to a Wall Track system. Their age, gender, body mass index, heart rate, systolic and diastolic blood pressures, presumed cardiovascular load, plasma creatinine, fasting cholesterol, triglyceride and glucose concentrations were also measured. Results: the carotid elastic properties [mean (SD): elastic modulus: 560 (180) vs 1204 (558) mmHg, p < 0.001 and stiffness index: 5.69 (1.35) vs 11.92 (6.4), p < 0.001 for primary and secondary Raynaud's respectively] were significantly impaired in patients with secondary Raynaud's disease even after adjustment for potentially influencing physiological and biochemical variables. There were no statistical differences in the femoral elastic properties or the carotid and femoral IMTs between the two groups. Conclusion: Duplex determination of the carotid elasticity or stiffness is different in primary Raynaud's phenomenon compared with secondary Raynaud's associated with SSc. This may be a useful non-invasive tool, in addition to auto-antibody markers and nail-fold capillaroscopy, to differentiate between the two forms of Raynaud's phenomenon.Eur J Vasc Endovasc Surg 25, 336-341 (2003)

OBJETIVO: Avaliar a ação do medicamento inibidor do receptor de leucotrieno CysLT1 (montelucaste) nas alterações vasculares das mãos em pacientes com fenômeno de Raynaud. MÉTODOS: Foram selecionadas pacientes com fenômeno de Raynaud secundário à doença inflamatória do tecido conjuntivo, excluindo tabagismo, hipertensão arterial e diabetes mellitus. As pacientes mantiveram a medicação prévia e iniciaram o uso de montelucaste 10 mg/dia por 60 dias. Foi realizada capilaroscopia periungueal dos dedos das mãos antes do uso da medicação e após 30 e 60 dias. A análise estatística foi feita por meio de porcentagem, média, desvio-padrão e teste exato de Fisher, com intervalo de confiança de 95%. RESULTADOS: Foram estudadas cinco pacientes mulheres, brancas, com fenômeno de Raynaud secundário a doenças do tecido conjuntivo, das quais três apresentavam esclerodermia e duas apresentavam doença mista do tecido conjuntivo. A média de idade foi de 42,4 ± 12,4 anos, e a média de tempo de doença foi de 9,6 ± 4,8 anos. As pacientes estavam em uso de até 20 mg/dia de prednisona (pacientes com doença mista do tecido conjuntivo), nifedipina, pentoxifilina. As medicações foram mantidas. Após o uso de inibidor de receptor de leucotrieno por dois meses, o controle com capilaroscopia ungueal demonstrou diminuição do edema e da palidez e normalização do número, tamanho e distribuição dos capilares. CONCLUSÃO: O uso do montelucaste modificou as alterações capilares observadas na capilaroscopia periungueal de pacientes com fenômeno de Raynaud OBJECTIVE: To assess the effect of the leukotriene receptor inhibitor (montelukast) on vascular alterations in fingers of patients with Raynaud's phenomenon. METHODS: Patients with Raynaud's phenomenon of the hands secondary to inflammatory connective tissue disease were selected, and those with the following characteristics were excluded: smokers, arterial hypertension, and diabetes mellitus. All patients maintained their previous medications and started the use of montelukast, 10 mg/day, for 60 days. Naifold capillaroscopy of fingers was performed before the use of medication and after 30 and 60 days. Statistical analysis was performed with percentage, media, standard deviation, Fisher exact test, with 95% of confidence interval. RESULTS: The study assessed five Caucasian, female patients with Raynaud's phenomenon secondary to inflammatory connective tissue disease (three with scleroderma and two with mixed connective tissue disease), aged 42.4 ± 11.5 years, and with 9.6 ± 4.8 years of disease duration. Patients were on nifedipine and pentoxifylline, and those with mixed connective tissue disease were also on prednisone. The medications were maintained. After using montelukast for two months, nailfold capillaroscopy showed a reduction in edema and pallor, and normalization of capillary number, size, and distribution. CONCLUSION: The use of montelukast modified the capillary abnormalities observed on nailfold capillaroscopy of patients with Raynaud's phenomenon

Adventitial stripping of the palmar arch, the palmar common digital arteries, or the proper digital arteries is a last resort in the treatment of refractory primary or secondary Raynaud's phenomenon. Seven patients who had adventitial stripping of the ulnar and radial arteries proximal to the wrist and resection of the nerve of Henle, if identifiable, are presented. All of them were evaluated by telethermography, acral rheography, and a questionnaire before and after surgery. All were asymptomatic after surgery with satisfactory healing of the ulcers at the fingertips. None of them relapsed during the follow-up time of 1.5 years.

Resume Objectif de l’etude. – Analyser les donnees epidemiologiques du syndrome de Raynaud chez l’enfant. Patients et methodes. – Nous avons mene une etude retrospective sur une periode de neuf ans, des enfants de moins de 17 ans ayant consulte pour un syndrome de Raynaud. Les dossiers ont ete retrouves a partir des consultations de pediatrie, de dermatologie et egalement a partir du registre des capillaroscopies. Un questionnaire type a ete etabli et les donnees manquantes ont ete completees apres entretien telephonique avec les parents. Resultats. – Un diagnostic definitif de syndrome de Raynaud a ete retenu chez 23 enfants avec une nette predominance feminine ( sex-ratio : 0,27). Les facteurs declenchant essentiels etaient le froid et les emotions. L’âge moyen au moment du diagnostic etait de 11 ans (cinq a 16 ans) avec un debut apres l’âge de dix ans dans 65 % des cas. Onze de ces syndromes de Raynaud se sont reveles secondaires dont dix a une connectivite, huit sont restes apparemment primaires et quatre ont ete juges comme suspects d’etre secondaires. Discussion. – Cette serie de syndromes de Raynaud pediatriques etait consequente compte tenu des donnees actuelles de la litterature sur le sujet. Elle a mis en evidence les difficultes du diagnostic qui reste exclusivement clinique et la forte representation des causes secondaires notamment des connectivites. Une enquete etiologique est donc imperative devant tout syndrome de Raynaud chez un enfant. Le caractere sensible (78 %) et specifique (80 %) de la capillaroscopie pour le diagnostic des connectivites dans le cadre de notre etude, a retenu notre attention ; sa valeur pronostique merite d’etre evaluee sur un plus grand echantillon de patients.

Objective. To investigate digital microvascular responses to topical glyceryl trinitrate (GTN) in patients with primary Raynaud's phenomenon (PRP), limited cutaneous systemic sclerosis (LCSSc) and healthy control subjects, using laser Doppler imaging. Methods. Ten patients with PRP, 13 with LCSSc and 10 control subjects were studied. Baseline skin microvascular blood flow of the dorsum of the index, middle and ring fingers of the non-dominant hand was measured using scanning laser Doppler imaging. After the initial image, 2% GTN ointment was rubbed on the dorsum of one finger for 1 min; placebo ointment was rubbed on the dorsum of a second finger for 1 min, and the third finger remained untreated. Further laser Doppler scanning of these three fingers was conducted immediately, 10 and 20 min after ointment application. Results. There was increased blood flow response to placebo compared with no treatment (P

A test procedure for evaluating vasospasm in hand digits using cold water immersion at 15°C for a period of 10 minutes is described, and the result of initial and repeat tests on 25 subjects who volunteered for a control group study are reported. Digit skin temperatures were continuously recorded and the recovery temperatures were noted while the hands were immersed and for a further 10 minutes afterwards in air. Five from their history and test results were determined to have Raynaud's disease or Constitutional White Finger, and a further 5 subjects with no history of cold hands or Raynaud's phenomenon had non-repeatable test results indicative of an asymptomatic sub-clinical state. A statistical analysis of the results from the 15 normal control subjects provides reference data (means and standard deviations) for the maximum skin temperature at 10 minutes immersion, and the skin recovery temperatures post-cold stress at 1 minute intervals in air. This objective test is frequently used for evaluating cold induced vasospasm in hand digits, and the normative data provided will enable abnormal subjects to be identified. Additional reference data is provided for use with vibration exposed workers to permit the severity of the vasospasm to be graded in accordance with the Stockholm vascular scale for Hand-arm Vibration Syndrome (HAVS).

OBJECTIVE: To identify chromosomal regions containing genes involved in the susceptibility to primary Raynaud's phenomenon (RP). METHODS: Six extended families with multiple individuals affected with primary RP (n = 37) were examined for linkage in a 2-stage, whole-genome screen, using a total of 298 microsatellite markers. RESULTS: Multipoint, nonparametric linkage analysis identified 5 areas of possible linkage, with a nominal level of significance of P < or = 0.05. Analysis of a finer map of markers in these regions defined the regions of linkage as 21.4 cM on 6q13-6q23.3 (D6S261; P = 0.0004), 10.2 cM on 7p22-7p15 (D7S664; P = 0.014), 1.6 cM on 9p23-9p22 (D9S156; P = 0.0075), 5.1 cM on 17p13.1-17p12 (D17S1791; P = 0.036), and 11.8 cM on Xp11.4-Xp11.23 (DXS8054; P = 0.006). Three potential candidate genes map to these regions: the beta subunit of the muscle acetylcholine receptor and the serotonin 1B and 1E receptors. CONCLUSION: These results provide evidence of the presence and location of genes that are involved in the genetic susceptibility to primary RP

The study was aimed at choosing an appropriate characteristic of laser-Doppler flux (LDF) data for (1) distinguishing patients with Raynauds disease from normal controls and (2) evaluating the effect of nifedipine under different thermal conditions. We checked the reliability of three characteristics of nonlinear dynamics as statistical dimension D_s, correlation dimension D_2 and power-law index PLI. Their values depended heavily on the thermal condition. The most reliable characteristics that enabled us to distinguish the patients from normal controls and the effect of nifedipine under definite thermal condition proved to be D_s and PLI. The latter is simple for computation and is thus recommendable for clinical practice. D_s and PLI were higher in patients with Raynauds compared to normal controls and diminished during the transitions from low to high temperature. However, the characteristics used were unable to distinguish significantly Raynauds I from Raynauds II patients.

Aims We examined the effect of cooling on the response to the endothelium-dependent and -independent dilators, acetylcholine (ACh) and sodium nitroprusside (SNP), respectively, in human microvessels in vitro, and compared the responses between Raynaud’s disease (RD) patients and controls, in order to assess the pathogenic role of the endothelium in RD. Methods Subcutaneous resistance arteries were dissected from gluteal fat biopsies taken from patients with RD (n=18) and from age-and sex-matched control subjects (n=17). Vessels were cannulated in a small vessel arteriograph, in which a pressure of 50 mmHg was maintained across the vessel wall. Cumulative concentration-response curves for ACh (10−10–10−4 m ) and SNP (10−10–10−3 m ) were generated in vessels at either 37° C or 24° C, with endothelium intact for ACh and removed for SNP (n=6 per group). Results Neither dilator showed significant differences in sensitivity when comparing responses between vessels from RD patients and controls, at either temperature, but the maximal relaxation to ACh was depressed in vessels from RD patients compared with controls at 37° C (Emax=45±13 in RD vs 89±4 in controls; P=0.004). Conclusions These results support the hypothesis that impaired endothelium-dependent vasodilatation is involved in the pathophysiology of RD.

Objective. Reactive oxygen species have been implicated in the pathogenesis of inflammatory and vascular disease. We have undertaken a controlled trial to evaluate probucol, a synthetic antioxidant, as a potential therapy for Raynaud’s phenomenon. Methods. The study cohort included patients with systemic sclerosis (SSc; n= 20), primary Raynaud’s phenomenon (n= 15) or ‘autoimmune Raynaud’s’ (n= 5). Patients were allocated to receive either probucol (500 mg daily) or nifedipine (20 mg daily) for 12 weeks. Clinical and biochemical variables at baseline were compared with those at completion of treatment. Evaluation included assessment of Raynaud’s attack frequency and severity by visual analogue scale, measurement of low-density lipoprotein (LDL) oxidation lag time, and plasma concentrations of cholesterol, triglyceride, vitamin E and vitamin C. Results. There was a significant reduction of both the frequency and severity of Raynaud’s attacks in the patients who received probucol, but not in the control group. LDL oxidation lag time, reflecting in vitro susceptibility to oxidation, was also increased by probucol therapy and serum cholesterol levels were significantly reduced. Similar changes were observed in both SSc- and non-SSc-associated Raynaud’s cases. Conclusion. These data suggest that probucol may be useful for the symptomatic treatment of Raynaud’s phenomenon and also reduces LDL oxidation susceptibility. Since oxidized lipoproteins may mediate vascular damage in SSc, the use of probucol could have additional disease-modifying benefits. Based upon the results of this pilot study, further evaluation of this novel form of therapy is warranted.

Anticentromere autoantibodies (ACA) are associated with Raynaud's disease and systemic sclerosis (SSc). ACA usually bind at least one of three major centromere proteins (CENPs), particularly CENP-B. We identified 16 patients with ACA who do not have Raynaud's disease or SSc. The objective of this study was to determine whether these 16 ACA differ in antigenic specificity from the ACA found in patients with Raynaud's disease or SSc. Binding of these serum ACA was tested using competition experiments with recombinant CENP-B, and native centromere proteins from HEp-2 cells and HeLa nuclear extracts in ELISAs, immunoblots, and indirect immunofluorescence assays. The ACA from these 16 patients are strikingly different from those obtained from patients who have Raynaud's disease or SSc. Only 5 of the 16 index sera (31.25%) bound CENP-B from two or more different sources by at least two methods. Six of these 16 sera (37.5%) did not bind CENP-B on ELISA, and 8 of 16 (43.75%) did not bind CENP-B on immunoblots. Three sera did not bind CENP-B either by ELISA or immunoblots. Of the 13 sera that bound CENP-B, their patterns of binding to CENP-B strongly suggested that they bind different epitopes within the CENP-B antigen. Independently of their binding to CENP-B, these sera reacted mainly with minor CENP antigens detected by HeLa nuclear extracts. We have identified unusual ACA not associated with Raynaud's disease or SSc.