Paroxysmal Dysarthria and Raynaud's Phenomenon in the Tongue

Abstract Three patients suffering from systemic scleroderma and Raynaud's phenomenon in the digits as well as the tongue are reported. Following exposure to cold, a vasospasm was observed in the digits and the tongue accompanied by severe dysarthria. These striking oral symptoms had been overlooked for years in the medical ward. It is recommended to question all patients with Raynaud's phenomenon about visceral manifestations during the digital attacks.     

Skin Capillary Abnormalities in Patients with Raynaud's Phenomenon

ABSTRACT The digital skin microcirculation was studied by vital capillaroscopy in 32 consecutive patients with Raynaud's phenomenon. A detailed classification (stages 0–6) of the capillary abnormalities based upon observations of the capillaries in many different sites of the fingers was used. Associated diseases were searched for by an extensive clinical and immunological investigation. Seventeen (53%) of the patients had distinct structural changes in the capillaries but only 6 of them showed a restricted total digital circulation. Fifteen (88%) of these 17 patients displayed an underlying disease and/or immunological abnormalities. The corresponding figure for patients with mild or no capillary changes was 40% (p<0.01). Thus, the presence of marked (≥stage 3) skin capillary abnormalities seems to be a good indicator of an associated systemic disease. The majority of patients in this category improved their capillary status during successful treatment of the underlying disease. We conclude that the form of capillaroscopy used in this study is a sensitive method for evaluating disturbances of the skin microcirculation in patients with Raynaud's phenomenon. The method may also contribute to the clinical evaluation of patients with this syndrome by identifying those with an underlying systemic disease.     

Raynaud's Phenomenon Progressing to Gangrene after Vincristine and Bleomycin Therapy

Abstract Vascular symptoms after vinca-alcaloids and bleomycin are known. We report a 50-year-old woman who was cigarette smoker and who had had the syndrome of Raynaud's phenomenon for two years before she developed non-Hodgkin lymphoma. She was treated with chemotherapy including vincristine and bleomycin. Immediately after the second course of chemotherapy she had severe vertigo, nystagmus, dysarthria and dysphagia. The fingers remained cyanotic and became extremely painful despite stellatum blockade, intra-arterial vasodilators and thoracic sympathectomy. Two digits of the left hand were partially amputated because of gangrenous areas on the fingertips. The cerebral symptoms disappeared.     

Hypothyroidism,Raynaud's phenomenon,and acute myocardial infarction in a young woman

We describe an acute inferior myocardial infarction in a 29-year-old woman with normal coronary arteries. She has suffered from Raynaud's phenomenon in the fingers for several years. Manifest thyroid deficiency was discovered during hospitalization. A functional-type link between hypothyroidism and myocardial infarction via vasospasm manifested as Raynaud's phenomenon is proposed as one possible etiology for the syndrome of myocardial infarction in young women.     

Symptoms and esophageal motility based on phenotypic findings of scleroderma

Scleroderma esophagus is characterized by ineffective peristalsis and reduced esophageal sphincter pressure. Esophageal disease in scleroderma can precede cutaneous manifestations and has been associated with Raynaud's phenomenon (RP) and pulmonary fibrosis (PF). The objective of the study is to evaluate the impact of cutaneous findings, RP, and PF on demographics, symptoms, and esophageal motility in patients with scleroderma. Scleroderma patients with esophageal involvement were included after review of esophageal manometries and charts over a 6‐year period. High‐resolution esophageal manometry was performed. Patients completed a symptom questionnaire. The study enrolled 28 patients (22 females; mean age 50.3 ± 12.8 years) with scleroderma esophagus. Patients without skin involvement (n= 12) reported more severe heartburn (P= 0.02), while those with cutaneous findings (n= 16) had more frequent dysphagia with solids (P= 0.02). Patients with RP (n= 22) had lower amplitude of distal esophageal contractions (P= 0.01) than those without RP (n= 6). Patients with PF (n= 11) reported more severe coughing and wheezing (both P= 0.03) than those without lung disease (n= 17). This study highlights subgroups of patients with scleroderma esophagus according to phenotypic findings of dermatologic changes, RP, and PF. Heartburn and dysphagia are important symptoms that may be associated with different stages of disease progression based on skin changes in scleroderma. RP was associated with greater esophageal dysmotility. Coughing and wheezing were more severe in patients with PF.     

Botulinum toxin in the management of primary and secondary Raynaud's phenomenon

Raynaud's phenomenon (RP) is common in rheumatic diseases. In the setting of systemic sclerosis (SSc), it can be complicated by digital ischemia that includes ulceration and gangrene. Systemic adverse effects may preclude the use of oral or topical vasodilators for the treatment of RP and its complications. In this article, we review effectiveness/efficacy of botulinum toxin injection in primary and secondary RP. We discuss botulinum toxin formulations, dosage, sites of administration, and adverse effects. The evidence for botulinum toxin in the treatment of primary and SSc-associated RP is promising. Consistency across patient populations, treatment options (botulinum serotype, dose, and injection site), and outcome measures will be essential for further research.     

Increased mean platelet volume in primary Raynaud's phenomenon

We hypothesized that mean platelet volume (MPV), a reliable marker of platelet activation, might be elevated in primary Raynaud's phenomenon (PRP) even if there was no thrombotic complication in our subjects. In this retrospective-cohort study, we examined the clinical value of MPV in 200 patients with PRP and 116 clinical controls, and measured MPV and platelet P-selectin (CD62P) in all study participants. We also evaluated the effect of age, gender, and disease duration on these platelet activation markers in PRP. MPV and CD62 positivities were significantly (p?<?0.001) elevated in patients with PRP compared with controls. These differences retained when patients and controls were analyzed according to age, gender, and the disease duration. In logistic regression analysis, MPV (OR: 15.8, 95% CI: 8.14–30.64, p?<?0.001) and CD62P (OR: 11.3, 95% CI: 4.85–26.12, p?<?0.001) were found to be independently associated with PRP. In conclusion, increased MPV is independently related to PRP, and its level was not influenced by age, gender, and the duration of PRP.     

Raynaud's phenomenon

Raynaud's phenomenon (RP) is a major cause of pain and disability in patients with autoimmune connective tissue diseases (CTDs), particularly systemic sclerosis (SSc). The clinician must perform a comprehensive clinical assessment in patients with RP to differentiate between primary (idiopathic) and secondary RP, in particular (for rheumatologists), secondary to an autoimmune CTD, as both the prognosis and treatment may differ significantly. Key investigations are nailfold capillaroscopy and testing for autoantibodies (in particular, those associated with SSc). Patients with RP and either abnormal nailfold capillaroscopy or an SSc-specific antibody (and especially with both) have a high risk of transitioning to an autoimmune CTD. Both nailfold capillaroscopy and autoantibody specificity may help the clinician in predicting organ-based complications. The management of CTD-associated RP requires a multifaceted approach to treatment, including patient education and conservative (‘non-drug’) measures. Patients with CTD-associated RP often require pharmacological treatment, which in the first instance is usually a calcium channel blocker, although other agents can be used. There is an increasing tendency to use phosphodiesterase type 5 inhibitors early in the treatment of CTD-associated RP. Oral therapies are commonly associated with side effects (often due to systemic vasodilation) that may result in failure of dose escalation and/or permanent discontinuation. Intravenous prostanoid therapy and surgery (e.g., botulinum toxin injection and digital sympathectomy) can be considered in severe RP. Patients with CTD-associated RP can develop a number of ischaemic digital complications (primarily ulcers and critical ischaemia), which may be associated with significant tissue loss. Future research is required to increase the understanding of the pathogenesis and natural history of RP (to drive therapeutic advances), and to explore/develop drug therapies, including those that target the mechanisms mediating cold-induced vasoconstriction, and locally acting therapies free of systemic side effects.     

Raynaud's phenomenon

Raynaud's phenomenon (RP) is common, affecting approximately 5% of the population, and is important to the rheumatologist because it is often the presenting symptom of connective tissue disease, especially of systemic sclerosis (SSc)-spectrum disorders. RP therefore provides a window of opportunity for early diagnosis. When RP is associated with SSc it is particularly challenging to treat.This review begins with a discussion of some of the recent advances in our understanding of the pathogenesis of RP: it is through increased understanding of the complex pathophysiology of RP that we are most likely to develop new therapies. The following questions are then addressed (with three clinical scenarios demonstrating key principles of assessment and management):1. How can we predict underlying connective tissue disease in the patient presenting with Raynaud's?2. How can we measure severity of Raynaud's?3. What are the latest advances in treatment of connective tissue disease-related digital vasculopathy?     

Lower serum magnesium level after exposure to cold in women with primary Raynaud's phenomenon

Serum levels of magnesium (s-Mg), calcium (s-Ca), potassium (s-K) and sodium (s-Na) were measured in 80 women with primary Raynaud's phenomenon (RP) and in 24 age-matched female controls recruited from a population survey. The blood samples were taken after a 40-min standardized whole body cooling test. The mean s-Mg level in the group with RP was significantly lower than in the controls (0.81 +/- 0.05 vs. 0.86 +/- 0.07 mmol l-1, P less than 0.05). One year later, 66 members of the RP group and 22 members of the control group were investigated further, but without any exposure to cold. No differences in mean s-Mg values were found between the groups. The mean s-Mg level was significantly higher in the blood samples taken later without cold exposure than at the initial examinations after exposure to cold in the RP group, but not in the controls. The s-Mg level was lower after exposure to cold in 82% of the women with RP, compared to 45% of the controls (P less than 0.001). No differences in the other electrolytes were found. It is concluded that exposure to cold under standardized conditions may decrease the s-Mg level in women with primary RP. Further studies of the role of magnesium in patients with RP are required.     

Raynaud's Phenomenon Caused by β-Receptor Blocking Drugs

ABSTRACT Twenty-four hypertensive patients reported vasospastic symptoms in their hands during treatment with β-blocking drugs with different pharmacological properties. Twenty patients had symptoms when staying indoors and 11 did not always experience complete relief of symptoms following active rewarming attempts. Finger systolic blood pressures were measured after standardized local cooling. In 15 patients, blood pressure decreased to a pathological level during this procedure. Previous β-blockade was changed to combined α- and β-blockade with labetalol given twice daily in a mean dose of 259 mg/day for 3 months. After this period, most patients showed a decreased temperature sensitivity both objectively and subjectively. Blood pressure control was maintained at the previous level. Heart rate increased significantly during treatment with labetalol. Labetalol offers an alternative treatment to patients suffering from vasospastic side-effects of β-blockers.     

Cold exposure increases cyclic guanosine monophosphate in healthy women but not in women with Raynaud's phenomenon

Abstract. Objective. To investigate influence of whole-body cooling on cyclic GMP (cGMP) in women with Raynaud's phenomenon and in healthy women. Design. The study was performed as an open, parallel-group comparison between women with Raynaud's phenomenon and healthy women during the winter month of February. Setting. The municipality of Västerås (Sweden). Participants. The Raynaud group comprised 24 female patients. The control group consisted of 21 healthy females. Main outcome measure. The venous levels of cGMP were measured on three different occasions: just before and after 40 min of whole-body cooling and after 20 min rest at room temperature (21°C). Results. Venous cGMP increased significantly in the control group after cold exposure (mean difference 0.43 pmol ml^?1; 95% CI, 0.018–0.848; t = 2.18; df = 20; P = 0.02) and remained at a high level after 20 min rest (mean difference 0.58 pmol mL^?1; 95% CI, 0.063–1.108; t = 2.34; df = 20; P = 0.015). In contrast, the levels of venous cGMP in the Raynaud group did not change significantly. The difference in increase between the two groups was significant (P < 0.02). The diastolic blood pressure in the Raynaud group increased after 40 min of whole-body cooling and was still significantly increased (P < 0.001) after 20 min rest at room temperature (21 °C). Conclusion. These results indicate that women suffering from Raynaud's phenomenon lack the physiological response of cGMP to cold exposure, which may explain their increased vasospastic response.     

Warfarin-associated multiple digital necrosis complicating heparin-induced thrombocytopenia and Raynaud's phenomenon after aortic valve replacement for adenocarcinoma-associated thrombotic endocarditis

Necrosis of the digits is a rare complication of warfarin therapy of obscure pathogenesis. We report a 61-year-old woman with a 12-month history of Raynaud's phenomenon who developed multiple digital necrosis following aortic valve replacement with mechanical prosthesis for aortic insufficiency caused by nonbacterial thrombotic endocarditis. Exacerbation of Raynaud's phenomenon occurred during the postoperative period, with daily episodes of ischemia of the fingers and toes that improved with local warming. However, coincident with the occurrence of immune heparin-induced thrombocytopenia, and while undergoing routine warfarin anticoagulation because of the mechanical valve prosthesis, the patient abruptly developed progression of digital ischemia to multiple digital necrosis on postoperative day 8, at the time the international normalized ratio reached its peak value of 4.3. All limb pulses were readily palpable, and vascular imaging studies showed thrombosis only in the superficial femoral and popliteal veins of the right leg. Coagulation studies showed greatly elevated levels of thrombin-antithrombin complexes and prothrombin fragment F1.2 levels, consistent with uncontrolled thrombin generation. After vitamin K administration, no abnormalities of the protein C anticoagulant pathway were identified, consistent with previous studies of other patients with warfarin-induced necrosis complicating heparin-induced thrombocytopenia. Subsequently, the patient was shown to have metastatic breast adenocarcinoma, which explained the patient's initial presentation with nonbacterial thrombotic endocarditis. This patient case suggests that multiple digital gangrene can result from the interaction of various localizing and systemic factors, including compromised microvascular blood flow (Raynaud's phenomenon), increased thrombin generation (heparin-induced thrombocytopenia, adenocarcinoma), and warfarin-induced failure of the protein C natural anticoagulant pathway.