Severe Raynaud's Phenomenon Research Articles

Adherence to the Mediterranean Diet in Italian Patients With Systemic Sclerosis: An Epidemiologic Survey.

Systemic sclerosis (SSc) is an orphan disease that can lead to severe involvement of the gastrointestinal tract with a significant impact on patients' quality of life (QoL). The Mediterranean diet (MD) was consistently demonstrated to have beneficial effects on chronic diseases based on biological bases. We aimed to evaluate the adherence to the MD of Italian patients with SSc to preliminarily assess its association with gastrointestinal symptoms and other disease features, mood, and QoL. In this cross-sectional study, adherence to the MD was measured in 387 patients from four SSc Italian referral centers through the 14-item Mediterranean Diet Adherence Screener (14-MEDAS) questionnaire. We also registered patients' reported outcomes related to the QoL and mood. Overall, an optimal adherence to MD was observed in 14.7% of patients with SSc, a moderate adherence in 71.3%, and a low adherence in 14.0%. In univariate analysis, poor adherence to the MD was associated with a more prominent depressive mood, time missed at work, and perception of more severe Raynaud's phenomenon and digital ulcers, whereas the 14-MEDAS score inversely correlated with depression score and reflux. In our cohort of patients with SSc, overall adherence to MD was moderate. Patients with lower adherence to MD also reported worse outcomes related to QoL and mood. Administration of the 14-MEDAS could be a reasonable choice to assess adherence to the MD in patients with SSc. Future initiatives to study the role of MD in the management of patients with SSc are warranted.

ID: 210803 High-Resolution-Doppler-Ultrasound as an Objective Outcome Parameter of ECAP-Controlled Closed-Loop SCS in Patients With Raynaud Phenomenon

Raynaud's phenomenon (RP) is an episodically occurring vasospasm of the peripheral arteries that causes cyanosis, erythema, pain, paresthesia, and sometimes ulceration of the fingers and/or toes [1]. In severe cases, RP patients have physical and functional impairments that substantially affect their ability to work. There are few reports, mostly case series, on the utility of spinal cord stimulation (SCS) to treat RP [2]–[9]. However, there is a lack of objective evidence on the physiological effects (e.g., vasodilation) of SCS in this condition. Here, we present clinical outcomes of severe RP patients treated with evoked compound action potential (ECAP)-controlled closed-loop SCS.

Associations Between Patterns of Esophageal Dysmotility and Extra-Intestinal Features in Patients With Systemic Sclerosis.

The gastrointestinal tract is commonly involved in patients with systemic sclerosis (SSc) with varied manifestations. As our understanding of SSc gastrointestinal disease pathogenesis and risk stratification is limited, we sought to investigate whether patterns of esophageal dysfunction associate with specific clinical phenotypes in SSc. Patients enrolled in the Johns Hopkins Scleroderma Center Research Registry who completed high-resolution esophageal manometry (HREM) studies as part of their clinical care between 2011 and 2020 were identified. Associations between esophageal abnormalities on HREM (absent contractility [AC], ineffective esophageal motility [IEM], hypotensive lower esophageal sphincter [hypoLES]) and patient demographic information, clinical characteristics, and autoantibody profiles were examined. Ninety-five patients with SSc had HREM data. Sixty-five patients (68.4%) had AC (37 patients with only AC, 28 patients with AC and a hypoLES), 9 patients (9.5%) had IEM, and 11 patients (11.6%) had normal studies. AC was significantly associated with diffuse cutaneous disease (38.5% versus 10.0%; P < 0.01), more severe Raynaud's phenomenon, including digital pits, ulcers, or gangrene (56.9% versus 30.0%; P=0.02), and reduced median diffusing capacity of lung for carbon monoxide (50.6% versus 72.2%; P=0.03). AC was observed in most of the patients who died (13 of 14; P=0.06). These findings were not seen in patients with IEM. Among patients with SSc, AC is associated with a significantly more severe clinical phenotype. IEM may associate with a milder phenotype. Further studies are needed to evaluate AC, IEM, and their clinical impact relative to the timing of other end-organ complications in SSc.

P26 Challenging Scenario: Scleroderma/Sjogren overlap with dysautonomia

Introduction/BackgroundScleroderma Overlap conditions are well defined and often behave differently than their limited or diffuse counterparts. The treatment for such patients is usually tailored around the organ system involvement and severity. We present a challenging case of Scleroderma/Sjogren overlap with refractory Raynaud's phenomenon who posed treatment challenges due to severe autonomic dysfunction.Description/Method76-year-old Caucasian lady, non-smoker, who presented in 1990’s with dry eyes, dry mouth and severe Raynaud's phenomenon with recurrent digital ulceration which became infected on multiple occasions. ANA was 1:400 with Extractable nuclear antigen Ro and La positive. Anti DsDNA was negative and C4 was low. Antiphospholipid antibodies and cryoglobulins are negative. She failed calcium channels blockers and phosphodiesterase 5 inhibitors and was intolerant to intravenous (IV) Iloprost which was tried on multiple occasions. IV latanoprost was tried as well. This treatment was complicated when she developed postural hypotension and multiple fall episodes during vasodilator use. This was attributed to autonomic dysfunction secondary to her Sjogren syndrome. She was initiated on Injection Fludrocortisone, however her hypotensive episodes continued. She received monthly intravenous immunoglobulins 20gm (over two days) infusion for a few months for autonomic dysfunction with some response. She eventually developed recurrent diarrhoea and abdominal pain and bloating which was attributed to small bowel overgrowth with rapid bowel transit on a gastric emptying scan. She had a blocked bile duct as well which was unblocked using Endoscopic Retrograde Cholangiopancreatography. Over the next 8 years, she continued struggling with refractory Raynaud’s, having failed IV regional guanethidine blocks and digital sympathectomy. Her postural hypotension decompensated on multiple occasions necessitating plasmapheresis which provided some benefit. In 2020, she was detected to have a PET avid slowly progressing left upper lobe lung lesion. She underwent left video assisted thoracoscopy surgery with upper lobectomy. Histology was suggestive of adenocarcinoma. In 2021, she had another fall episode due to an acute/subacute infarct of left pons. She continues having postural hypotension and requires regular plasmapheresis sessions to manage her symptoms. She is also presently on Bosentan for her raynaud’s phenomenon.Discussion/ResultsThis is a case of overlap of Sjogren syndrome with scleroderma features. Management of Refractory Raynaud’s as part of her scleroderma phenotype was challenging. This case gave us the opportunity to explore all the treatment options available for Raynaud’s phenomenon albeit with poor outcome. She also struggled with autonomic dysfunction leading to postural hypotension and gastrointestinal symptoms which can be seen in upto 50% of patients with Sjogren syndrome. Autonomic failure is often thought to be immune mediated in Sjogren syndrome. This makes way for the use of intravenous immunoglobulin and plasmapheresis to treat these conditions as was done in this case. Increased risk of lung carcinoma with scleroderma is well documented. Autonomic dysfunction can also present as paraneoplastic syndrome with lung carcinoma, however it is more common with small cell lung carcinoma and our patient was diagnosed with Adenocarcinoma. We would have to wait and see if the resection of the tumour has any demonstrable effect on her dysautonomia.Key learning points/ConclusionOverlap connective tissue diseases are often difficult to manage in view of extensive disease heterogeneity. Clinicians need to be aware of challenges in managing Difficult Raynaud’s with Autonomic dysfunction. Treating physicians need to be aware of the high risk of lung malignancy and regular close monitoring is required. This case-based conference gives us the opportunity to discuss further management approaches for her.

Osteonecrosis of carpal bones in systemic sclerosis

Background. Systemic sclerosis (SSc) is a rare chronic disease, with unknown aetiology and complex pathogenesis. The hand is often implied in the main clinical findings, being affected primarily by the vascular component (Raynaud phenomenon, digital ulcers). One of the possible complications of the hand vasculopathy is osteonecrosis (ON) of the carpal bones. In these cases, the lunate is the most frequently affected, followed by the scaphoid. In the ON process, not only the vascular supply is important, but the nearby mechanical factors and anatomic variants of the wrist. Our objective was to reveal the most important aspects regarding the ON of the carpal bones in patients with SSc. Methods. A systematic literature review was performed through July 31, 2021 on Pubmed and Cochrane databases. The eligible articles were read in full text and were included in this paper, in the absence of exclusion criteria and after consensus between two reviewers. Results. Ten articles met the inclusion criteria, their main results being described in this review. In all studies, ON of the lunate and the scaphoid is associated with advanced SSc and severe Raynaud phenomenon. Conclusions. In conclusion, carpal ON is a rare complication of SSc, especially of the diffuse type. There is limited data on this condition, its prevalence being difficult to estimate due to the lack of symptoms.

P019 Audit of prostanoid use in severe Raynaud’s and adherence to treatment of digital ulcers in patients with SSc NHSE pathway: commissioning policy cost analysis and alternative therapeutic pathway proposed

Background/Aims Severe Raynaud’s phenomenon (RP) can lead to digital ulcers (DU), ischaemia, infection and gangrene. In 2015, NHS England published a commissioning policy enabling the use of bosentan for digital ulceration in SSc in patients refractory to intravenous 6-8 weekly prostanoid in combination with sildenafil following standard therapy (including calcium channel blockers (CCB), ACE inhibitors, losartan and fluoxetine). Bosentan is licensed to prevent new DUs in SSc. Specialist MDT ratification and Blueteq registration is required. RCTs showed bosentan reduced the formation of new DU by 30-50% in at risk individuals. It is a well-tolerated drug. It is now off-patent so its cost has reduced from £22,000 to £650 per year. Aim To audit current departmental practice in patients receiving prostanoid (epoprostenol) for severe RP from any cause and check adherence to the patient pathway for treatment escalation prior to prostanoid therapy. To determine approximate costs of alternative therapeutic approaches. Methods We retrospectively audited patients attending our day unit for epoprostenol infusions over a 12-month period between 2018 and 2019. Using our centre’s admissions database and electronic patient records, we identified which oral medications patients were currently co-prescribed or had previously trialled. Using pharmacy data and tariff costings, we calculated the cost of epoprostenol infusions and oral medications with blood monitoring. Results Between 2018 and 2019, 73 patients attended for epoprostenol infusions: 31 SSc, 25 RP, 17 other diagnoses (mixed/undifferentiated CTD, SLE, vasculitis). The mean number of epoprostenol infusions per patient per year was 5.92 days (range 1-25). The percentage of patients who had first been trialled on the following medications include: CCB 77.4%, ACEi/ARB 41.1%, fluoxetine 9.59%, sildenafil 87.1% and tadalafil 25.8%. In the SSc group 22.6% had also trialled bosentan. Only 2 SSc patients (6.45%) had trialled all of the drugs on the pathway prior to prostanoid reflecting the relative lack of efficacy of some first line therapies. The departmental tariff per prostanoid infusion is £450, resulting in an estimated average annual cost of £2700 per patient. The annual cost of supplying bosentan 125mg twice daily plus blood monitoring for the first year is approximately £1350. Conclusion Epoprostenol is used in our unit for patients with severe RP from a range of conditions. Sildenafil and CCB have been trialled in the majority of our patients prior to escalation. Only a minority of patients have received bosentan according to current guidelines and licensing. Given the reduction in cost, combined with the importance of avoiding hospital admissions with COVID-19, we would suggest that bosentan could be used earlier in the treatment pathway for a broader range of indications. NHSE is revising the SSc commissioning policy. Disclosure A. Young: None. B. Griffiths: None. J. Vila: None.

Drug Treatment of Raynaud's Phenomenon of the Nipple.

Drug Treatment of Raynaud's Phenomenon of the Nipple.

AB0574 BENEFITS OF ILOPROST IN LONG – TERM STABILIZATION OR IMPROVEMENT IN NEOANGIOGENESIS IN SYSTEMIC SCLEROSIS: A 15 YEARS OBSERVATION COHORT

Background:In Systemic Sclerosis (SSc) fibrosis is due to microcirculation damage with capillary necrosis, arteriolar intimal proliferation and local ischemia. loprost (ILO) is used IV for the treatment of severe Raynaud phenomenon (RP) and digital ulcers (DU) in (SSc). We have already described (1) an improvement of peripheral vascularization with ILO, observed after 3 years treatment by capillaroscopy with an increase in the capillary number and mild regression of avascular areas and pericapillar oedemaObjectives:Our aim was to observe capillaroscopic changes in a cohort of 26 patients treated with ILO, once a month (25 – 50 ng each infusion) for an average time of 15 yearsMethods:We evaluated the initial and 2019 capillaroscopic picture of 26 SSc patients (24 W,2 M; median age 63.8Y) in continuous treatment with monthly infusion of ILO from 2004 to today. 6/26 were SCL70 positive;the remainder was positive for anticentromere AbResults:We documented stability of capillaroscopic picture in 62% of patients,an improvement in 19% and a worsening (mainly from early to active pattern) in 19%. Low adherence to therapy was observed among the worsened patients. Out of 8 patients with onset ulcers, only 3 patients still have skin ulcers, all with late stable capillaroscopic picture from onset.We have not documented serious adverse eventsConclusion:Our observations confirm the efficacy and safety of ILO in the treatment of SSc even after many years of treatment, resulting in a stabilization of microvascular damage, independent of disease severity.

Lymphaticovenular anastomosis and venous arterialization in coexisting Raynaud's phenomenon and lymphedema: A case report

Raynaud's phenomenon is highly prevalent in the general population. The optimal medical management for patients with severe Raynaud's phenomenon remains unclear. Venous arterialization (VA) may be considered as a salvage procedure when no distal vessels are available for vascular reconstruction. Surgical treatments for lymphedema, including lymphovenous anastomosis (LVA), are becoming popular alternatives to conservative therapy. Here, we report on a patient with comorbid primary Raynaud's phenomenon and lymphedema in whom both VA and LVA were performed. The patient was a 60-year-old woman with an edematous right upper limb and pain and cold sensitivity in the middle, ring, and small fingers that was refractory to medication. Indocyanine green lymphography and computed tomography angiography suggested coexistence of lymphedema and primary Raynaud's phenomenon. VA and LVA were performed to reduce the risks of cellulitis and amputation. Computed tomography angiography was performed regularly after surgery to examine the arterialized venous system and Doppler echography to search for developing branches. Five months later, three branches of the arterialized veins that flowed proximally at the level of the hand and wrist were ligated. By around 1 year after surgery, the lymphedema index in the affected upper limb had improved from 116 to 103 and the patient's numerical rating scale score for intractable pain and cold sensitivity had improved from 6-7 to 1-2. We believe that the combination of VA and LVA in the early stages of primary Raynaud's phenomenon and lymphedema was effective in this case.

Iloprost use and medical management of systemic sclerosis-related vasculopathy in Italian tertiary referral centers: results from the PROSIT study.

Vasculopathy is a crucial feature of systemic sclerosis (SSc), and Raynaud's phenomenon (RP) and digital ulcers (DU) have a deep impact on the quality of patients' life. The management of vascular disease can be challenging for the clinician because of the suboptimal tolerability of the treatments and lack of consensus on the best therapeutic approach. Intravenous iloprost, a synthetic analogue of prostacyclin, is broadly used for the treatment of RP and ischemic ulcers secondary to SSc. However, no standardized protocol on iloprost use is currently available and, consequently, the management of this treatment is largely based on the experience of each single center. The PROSIT project is an observational, multicenter study aiming to investigate the current treatments for SSc vasculopathy, the use of prostanoids, with special regard to iloprost, and the perception of the treatment from a patient's perspective. The study was conducted on a cohort of 346 patients from eight Italian centers and included a structured survey addressed to physicians, data collected from patient's medical records and two patient-administered questionnaires assessing the level of satisfaction, tolerability and perception of the efficacy of Iloprost. PROSIT data confirmed that in the contest of SSc iloprost represents the first-line choice for the management of severe RP and DU. Moreover, it is a well-tolerated treatment as reported by patients' experience. Although a standard protocol for the treatment of SSc-related vasculopathy is lacking, PROSIT study identified different therapeutic approaches largely supported by tertiary Italian centers. Further studies are needed in order to optimize the best treatment for SSc vascular diseases, in particular to improve the best iloprost schedule management.

Botulinum toxin type A in the treatment of Raynaud's phenomenon: A three-year follow-up study.

ObjectiveRaynaud’s phenomenon consists of vasospastic disease of the digital arteries after exposure to cold or stress. It causes an important reduction in the patient’s quality of life when severe. The available treatments do not always offer favorable results.MethodsA 3-year retrospective study was presented. A total of 15 patients with severe Raynaud’s phenomenon who required infiltration with botulinum toxin type A participated in the study. In the first and follow-up visits (30 min, 7 days, 3 months, 6 months, and annual), the overall response by the patient was assessed as was the reduction in the number of weekly episodes of Raynaud’s phenomenon, improvement in pain by means of the Visual Analogue Scale, and resolution of ulcers and necrosis as efficacy variables.ResultsA total of 15 patients were included in the study. After 30 min of infiltration, the immediate results showed a very good perception of response in four patients. After 1 month of treatment, eight patients had obtained and maintained a very good response, persisting throughout the study. A statistically significant reduction in pain was obtained, as well as the number of weekly episodes of Raynaud’s phenomenon. Of the seven patients with basal ulcers, five were completely healed at 3 months. Of the patients, 64.3% showed an overall satisfaction level of >8 at the end of treatment. No serious adverse events were observed.ConclusionBotulinum toxin is a useful treatment for severe Raynaud’s phenomenon that is generally well tolerated. Its mechanism of action is not based exclusively on vasodilation. Further studies are necessary to define the ideal patient for this treatment, the most appropriate method of administration, and the number of units and frequency of the infiltrations.

The clinical effects of l-arginine and asymmetric dimethylarginine: implications for treatment in secondary Raynaud's phenomenon.

Secondary Raynaud's phenomenon (RP) is often the sentinel clinical finding in systemic sclerosis and may precede systemic disease by several years. Altered nitric oxide metabolism plays a critical role in both fibrosis and severe secondary RP phenotypes in these patients. Increased flux through inducible nitric oxide synthase (iNOS) drives cutaneous fibrosis. Failure of flux through endothelial nitric oxide synthase (eNOS) contributes to increased vasoconstriction and decreased vasorelaxation. The underproduction of nitric oxide by eNOS is in part due to increased levels of asymmetric dimethylarginine (ADMA), an endogenous competitive inhibitor of nitric oxide synthase. The inhibitory effects of increased ADMA levels may be counteracted increasing serum l‐arginine, which is often an effective treatment strategy in these patients. As such, l‐arginine‐based therapies should be considered in managing secondary RP, particularly given their favourable safety and tolerability profile. While there is no established dosing regimen, studies of oral l‐arginine in secondary RP suggest that divided dosing may begin at 1–2 g/day and may be titrated up to 10 g/day. Conversely, primary RP is not associated with increased ADMA production which likely accounts for the failure of l‐arginine trials to show benefit in primary RP.

The safety of iloprost in systemic sclerosis in a real-life experience.

Iloprost (ILO) is employed intravenously for the treatment of severe Raynaud phenomenon (RP) and digital ulcers (DU) in systemic sclerosis (SSc). The aim of this study was to evaluate the safety and tolerability of the intravenous treatment with ILO in different phases of SSc. Eighty-one consecutive non-selected SSc patients, all on nifedipine, with moderate RP, treated with ILO infusion, were retrospectively evaluated. Patients were sub classified according to the edematous or fibrotic/atrophic cutaneous phase of the disease. ILO was infused with a progressive increase of the dosage up to the achievement of patient's tolerance, 1day/week. In cases of slower infusion regimen due to adverse events (AE) at the beginning of the administration, patients received a lower dose of the drug (not possible to quantify precisely the final cumulative dosage). 16/81 SSc patients presented digital edema, 5 developed diarrhea, and 9 developed transient hypotension during the infusion at 20ml/h that ameliorated when the drug was withdrawn. Moreover, 10/16 edematous patients experienced significant and painful digital swelling, unlike patients in the fibrotic group (p < 0.0001); 11/16 patients reported flushing and 7/16 headache, always controlled with dose tapering below 10ml/h. In the atrophic/fibrotic phase patients (65/81), 10 developed diarrhea and 24 hypotension at infusion rate of 20ml/h that led to temporary withdrawal of the drug. When ILO was restarted and kept below 10ml/h, no side effects were experienced. 23/65 patients experienced flushing and 8/65 headache, all controlled with infusion reduction below 10ml/h. In these patients, adverse events were significantly less frequent than in the edematous group (p = 0.023 and p = 0.008, respectively). Our data suggest that calcium channel blockers should be transitorily stopped while using ILO and that a pre-treatment approach might reduce or control adverse events. In patients with digital edema, ILO infusion should be carefully employed after the evaluation of patient's drug tolerance.

Stem cell transplant in systemic sclerosis: An Indian experience.

To prospectively evaluate long term outcomes in a cohort of patients with Systemic sclerosis treated with Hematopoietic stem cell transplant (HSCT). This is a prospective observational study of four SSc patients who underwent HSCT at a tertiary care center in India between 2008-2012. The selection criteria included young individuals with rapidly progressive disease and at least one major organ involvement. We used granulocyte colony-stimulating factor for peripheral blood stem cell mobilization, pre-transplant conditioning with fludarabine, cyclophosphamide and rabbit anti-thymocyte globulin followed by re-infusion of autologous stem cells as per standard institute protocol. A total of four patients (one male and three females) underwent autologous HSCT for SSc. Patients had heterogeneous disease manifestations including severe Raynaud's phenomenon with vasculopathic ulcers, gastrointestinal problems and mild interstitial lung disease (ILD). Patients were followed up for a mean duration of 7years. There was significant sustained improvement in skin score, vasculopathy and gastrointestinal manifestations. Interstitial lung disease did not show any deterioration. The quality of life indices showed remarkable improvement in all subjects. No complications related to transplant were noted. In absence of an effective pharmacotherapy for SSc, autologous HSCT has a huge potential in management of cutaneous and internal organ manifestations.

Risk of Digital Vascular Events in Scleroderma Patients Who Have Both Anticentromere and Anti-Interferon-Inducible Protein 16 Antibodies.

To evaluate whether scleroderma patients who are double-positive for anti-interferon-inducible protein 16 (anti-IFI-16) antibodies and anticentromere (anti-CENP) antibodies are at increased risk for significant digital vascular events relative to patients positive for anti-CENP antibodies alone. Sera from 165 scleroderma patients who tested positive for anti-CENP antibodies upon clinical evaluation were reassayed for both anti-CENP and anti-IFI-16 antibodies using enzyme-linked immunosorbent assay testing. Patients who were positive for anti-CENP antibodies alone were then compared to patients who were double-positive for both anti-IFI-16 and anti-CENP antibodies. The association between a history of significant digital vascular events (digital pits, ischemic digital ulcers, and/or gangrene) and double-positive antibody status was examined using chi-square tests. After completion of univariate analysis, multivariable analyses were done to adjust for clinically relevant covariates. Of the 165 anti-CENP antibody positive patients, 21 (12.7%) also had anti-IFI-16 antibodies. Patients who were double-positive for anti-CENP and anti-IFI-16 antibodies were more likely to have had digital pits, ischemic digital ulcers, and/or gangrene (P = 0.03). After adjustment for clinically relevant covariates (age, cutaneous subtype, disease duration, and smoking), double-positive patients remained at significantly higher odds of having severe Raynaud's phenomenon (odds ratio 3.5 [95% confidence interval 1.1-11.1]; P = 0.03). Scleroderma patients who are double-positive for antibodies recognizing CENP and IFI-16 are significantly more likely to have significant digital vascular events during the course of their disease. This study provides further evidence that anti-CENP and anti-IFI-16 antibodies are disease biomarkers that may be used for risk stratification of vascular events in scleroderma.

Ulnar artery vasculopathy: a common but nonspecific feature of systemic sclerosis

Introduction Systemic sclerosis (SSc) is characterized by microvascular abnormalities and fibrosis. Several studies have reported that large vessel disease is also common in SSc. The aim of this case series was to investigate whether ulnar artery involvement in patients with SSc is a disease-specific phenomenon, as compared to other connective tissue diseases (CTD). Methods A total of 28 patients, including 7 with SSc and 12 with systemic lupus erythematosus (SLE), underwent brachial arteriography due to severe Raynaud's phenomenon and/or digital ulcerations and were enrolled in the study. They were divided into two groups: an SSc/SSc-overlap group and a non-SSc group. The collection of the clinical parameters was conducted to investigate the associations between clinical factors and the ulnar artery vasculopathy. Results The SSc/SSc-overlap group (n = 10) consisted of 7 patients with SSc and 3 with features overlapping SSc. In the non-SSc group (n = 18), 12 cases of SLE, 2 of mixed connective tissue disease, 1 of dermatomyositis + SLE, 1 of rheumatoid arthritis, 1 of Sjogren's syndrome, and 1 case of skin vasculitis, were included. The relative frequencies of ulnar artery involvement were not significantly different between the SSc/SSc-overlap and non-SSc groups, respectively (n = 6, 60% vs. n = 9, 50%, p = 0.611). Conclusions Although ulnar artery involvement was frequently detected in patients with SSc/SSc-overlap, it was also a common finding in other CTDs; therefore, it is not specific to SSc or SSc-overlap diseases.

Difficulties in diagnosis and treatment of severe secondary Raynaud’s phenomenon in a Cameroonian woman: a case report

BackgroundRaynaud’s phenomenon is a microvascular disorder that results in exaggerated vasoconstriction over vasodilatation secondary to an alteration in autonomic control. Though benign, it can result in severe ulceration and ultimately gangrene associated with disfiguration and permanent deformity. We present a case of severe secondary Raynaud’s phenomenon in a black-African patient from a resource-limited setting, with focus on the difficulties encountered in the diagnosis and treatment.Case presentationA 43-year-old female Cameroonian farmer with a 7-year history of episodic paresthesia in her fingers and toes (when exposed to cold) presented to our emergency department with severe pain, ulceration, and “darkening” of her fingertips over a period of 2 days. An examination revealed bilateral ulceration and dry gangrene of her fingers and toes, based on which a diagnosis of secondary Raynaud’s phenomenon due to a connective tissue disease was proposed. Results of paraclinical investigations were normal. Lifestyle modification along with a calcium channel blocker and phosphodiesterase type 5 inhibitor provided significant relief.ConclusionsAn early diagnosis and knowledge on appropriate treatment of Raynaud’s phenomenon is of vital importance to prevent permanent tissue damage and disability. Relying on biphasic color change for the diagnosis of Raynaud’s phenomenon in black Africans can be potentially misleading.

Recent advances in the pathogenesis and management of Raynaud's phenomenon and digital ulcers.

Systemic sclerosis (SSc)-related digital vasculopathy can progress from severe Raynaud's phenomenon to digital ulceration, is a major cause of pain and disability, and impacts negatively on quality of life. Current treatments are often ineffective and poorly tolerated. This review summarises some of the progress which has been made in the last 12 to 18 months in terms of our understanding of disease process, measurement and treatment. The most important findings include that we can now better predict which patients with SSc are most likely to develop digital ulcers. In terms of treatment, a multicentre trial showed that the phosphodiesterase inhibitor sildenafil confers some benefit in SSc-related digital ulceration. Topical therapies are being explored: iontophoresis of vasodilators increases local blood flow, and in an avian model, VEGF121 fibrin applied in a gel matrix improved wound healing. Progress is being made. Advances in our understanding of SSc-related vasculopathy continue to lead to exploration of new treatment approaches. Clinical trials and observational studies are challenging, but are being facilitated by developments in outcome measures and improved infrastructures and networking, allowing trials in much larger numbers of patients than have previously been possible.

Efficacité de l’oxygénothérapie hyperbare dans le traitement d’un ulcère nécrotique d’orteil au cours d’une sclérodermie systémique

The medical treatment of ischemic ulcers in patients with systemic sclerosis remains difficult. Despite the major help provided by vasodilator treatments, the risk of spontaneous or surgical amputation remains high. A 48-year-old female patient from Guadeloupe was treated in our department for diffuse systemic sclerosis present for 15years complicated by lung, joint and digestive involvement, and associated with severe Raynaud's phenomenon. The clinical course was marked by the occurrence of multiple ischemic ulcers, which were resistant to conventional medical treatment and resulted in two surgical amputations (to the 2nd and 3rd interphalangeal joints of the toes of the left foot). Treatment with an endothelin-receptor antagonist and a calcium inhibitor was then introduced for secondary prevention. Two years later, the patient consulted for a further ischemic ulcer of the left 4th toe. She refused the proposed treatment with iloprost. Because of the unfavorable outcome and the absence of therapeutic alternative to amputation, hyperbaric oxygen therapy was initiated. Thirty 90-minutes sessions of pure oxygen at 2.5 ATA were conducted over a 10-week period. Complete healing was obtained after 8 months. We report herein a clinical case illustrating the efficacy of hyperbaric oxygen therapy for the treatment of ischemic ulcers of the toes in systemic sclerosis. It could offer an alternative therapeutic option, in particular for patients presenting resistant ischemic ulcers and a contraindication for or intolerance to the conventional medical treatment.

Evidence for the Use of Epoprostenol to Treat Raynaud's Phenomenon With or Without Digital Ulcers.

To review the evidence for using intravenous (IV) epoprostenol to treat Raynaud's phenomenon (RP). 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. 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. 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. 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.