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.     

The clinical significance of raynaud's phenomenon in systemic lupus erythematosus

In a prospective study of 226 patients with systemic lupus erythematosus (SLE), 91 patients (40%) had Raynaud's phenomenon. These patients were compared to 135 patients without Raynaud's phenomenon. Patients with Raynaud's phenomenon had a greater incidence of arthritis (P < 0.02), malar rash (P < 0.003), and photosensitivity (P < 0.03), and a lesser incidence of severe renal disease as manifested by serum creatinine over 3.0 mg/dl (P < 0.007) or creatinine clearance below 60 ml/minute. Patients with Raynaud's phenomenon were less likely to have severe, life threatening disease and received a lower average monthly (P < 0.01). and a lower peak daily corticosteroid dose (P < 0.01). Fourteen patients (16%) with Raynaud's phenomenon died, compared to 41 without (30%) (P < 0.03). Raynaud's phenomenon in patients with SLE is associated with milder disease and may be regarded as a favorable prognostic sign.     

A study of headaches and migraine in Sj?gren's syndrome and other rheumatic disorders.

Migraine occurs with increased frequency in patients with systemic lupus erythematosus and in subjects suffering from Raynaud''s phenomenon without any underlying connective tissue disorders. A possible link between migraine and Raynaud''s phenomenon has been suggested. Two rheumatic conditions where Raynaud''s phenomenon occurs very commonly are scleroderma and primary Sjögren''s syndrome. It is possible that migraine is also common in these disorders but has been unrecognised. Therefore, the prevalence of migraine was assessed by a questionnaire in 191 subjects suffering from various connective tissue disorders and control subjects. Migraine was diagnosed in 16/35 (46%) patients with primary Sjögren''s syndrome, 31/97 (32%) patients with scleroderma, 4/33 (12%) patients with rheumatoid arthritis/Sjögren''s syndrome compared with 3/26 (11%) control subjects. A family history of headaches was more common in the patient groups than controls. There was a significant association between occurrence of Raynaud''s phenomenon and migraine. Small vessel pathology may underlie both migraine and Raynaud''s phenomenon in these connective tissue disorders--as has been suggested in systemic lupus erythematosus. The findings stress the need to ask specifically about complaints of headaches/migraines in patients with scleroderma and primary Sjögren''s syndrome for the appropriate total management of these patients.     

Diagnostic potential of in vivo capillary microscopy in scleroderma and related disorders

The prevalence of scleroderma-type capillary abnormalities, as observed by in vivo microscopy, was determined in 173 patients from three rheumatic disease centers. The patients had a variety of connective tissue diseases: scleroderma (systemic sclerosis) 50; systemic lupus erythematosus 60; mixed connective tissue disease 26; Raynaud's disease 11; other rheumatic disorders 26. Enlarged and deformed capillary loops surrounded by relatively avascular areas, most prominently in the nailfolds, were found in 82% of patients with scleroderma and in 54% with mixed connective tissue disease. The rarity of these abnormalities in systemic lupus erythematosus (2%) despite the presence of Raynaud's phenomenon suggests that they are not an expression of the Raynaud's phenomenon frequently associated with scleroderma and mixed connective tissue disease. The single patient with Raynaud's disease and sclerodermatype capillary changes subsequently developed scleroderma.     

Chronic inflammation predicts long‐term mortality in patients with Raynaud's phenomenon

Background

Subclinical chronic inflammation could be the driving force behind the recently revealed association between abnormal nailfold capillaries as well as autoantibodies and long‐term mortality in patients with incipient Raynaud's phenomenon. Whether laboratory markers that reflect a chronic inflammatory process are directly related to mortality in Raynaud's phenomenon is not known.

Methods

In total, 2958 patients with incipient Raynaud's phenomenon without previously known connective tissue disease (CTD ) were enrolled. At their initial presentation, laboratory tests for C‐reactive protein (CRP ), leucocytes, fibrinogen and the haemoglobin concentration were obtained. In addition, nailfold capillaries and antinuclear antibodies (ANA ) were assessed. Patients’ mortality was recorded through a median follow‐up period of 9.3 years.

Results

Baseline CRP , fibrinogen and haemoglobin concentration were associated with long‐term mortality in an individual analysis of patients with incipient Raynaud′s phenomenon. In a multivariable model including patients’ age, nailfold capillaries and ANA , a low haemoglobin concentration remained independently related to future mortality. Amongst potential predictors for mortality in patients with Raynaud's phenomenon, a low haemoglobin concentration was most strongly related to patients’ mortality risk.

Conclusion

In Raynaud's phenomenon, laboratory markers that can be attributed to a chronic inflammatory state independently yield prognostic information in addition to the presence of abnormal nailfold capillaries and ANA . Amongst all prognostic markers, the haemoglobin concentration is most strongly related to patients’ mortality in Raynaud's phenomenon.

     

Possible adverse effect of phenoxybenzamine therapy in a patient with progressive systemic sclerosis

A 52-year-old male was observed with the recent development of progressive systemic sclerosis (PSS). The most prominent symptoms of the PSS were circulatory, with pain in the digits, severe Raynaud's phenomenon and associated atrophic changes and ulcerations of the fingertips. Therapy with phenoxybenzamine was instituted in an attempt to improve digital blood flow. Rapid development of dry gangrene of several digits was observed over the following month. A possible association between phenoxybenzamine therapy and decreased digital circulation is discussed.     

Studies of endogenous catecholamines in patients with Raynaud's phenomenon secondary to progressive systemic sclerosis (scleroderma)

Studies of the resting venous plasma catecholamine concentration and the urinary catecholamine excretion patterns of patients with Raynaud's phenomenon secondary to progressive systemic sclerosis (scleroderma) failed to support the hypothesis that norepinephrine and/or epinephrine are neurohumors of excess in this particular form of Raynaud's phenomenon.     

Anticentromere antibody as a predictor of digital ischemic loss in patients with systemic sclerosis

Objective. To determine the clinical and serologic risk factors for digital ischemic events in patients with systemic sclerosis (SSc). Methods. Retrospective review of clinical and laboratory data and review of current clinical status of 98 patients with SSc, seen between 1985 and 1990. Results. Amputation of 1 or more digits due to ischemia occurred in 20.4% of the patients; 9.2% had multiple digit loss. Sclerodactyly alone and anticentromere antibody (ACA) were associated with loss of 1 or more digits. Age, smoking status, duration of disease, or duration of Raynaud's phenomenon were not predictive for loss of digits. Conclusion. Patients with limited SSc who are positive for ACA have an increased risk of major peripheral vascular occlusive disease.     

A double blind, randomised, multicentre comparison of two doses of intravenous iloprost in the treatment of Raynaud''s phenomenon secondary to connective tissue diseases.

OBJECTIVE--To compare low (0.5 ng/kg/min) and standard dose (2 ng/kg/min) iloprost (a stable carbacyclin analogue of prostacyclin) in patients with Raynaud''s phenomenon secondary to connective tissue disorders. DESIGN--Double blind, random allocation, three six hour infusions on consecutive days. Follow up period eight weeks. SETTING--Rheumatology units, five teaching hospitals. PATIENTS--55 Patients with Raynaud''s phenomenon (greater than seven attacks per week), 32 secondary to well documented classical progressive systemic sclerosis (American Rheumatism Association criteria), 11 CREST syndrome, 5 mixed connective tissue disease, 1 rheumatoid arthritis, 1 Sjögren''s syndrome, 1 childhood dermatomyositis, and 4 abnormal nailfold capillaroscopy and antibody profiles but no definite diagnosis. INTERVENTIONS--All other treatment for Raynaud''s phenomenon was discontinued two weeks before entry. 28 Patients were randomly allocated to receive the low dose, 27 the standard dose. Differing dilutions allowed infusion rates to be started at 10 ml/h with increments of 10 ml/h every 15 minutes until infusion rates reached 0.5 ng/kg/min and 2 ng/kg/min respectively. MAIN OUTCOME MEASURE(s)--Reduction in frequency, duration, and severity of attacks of Raynaud''s phenomenon. Assessment of ulcer and ischaemic lesion healing. RESULTS--Both dosage regimens were equally effective in reducing severity, frequency, and duration of Raynaud''s attacks. Ulcer healing occurred to similar degree in both treatment groups (standard dose 44%, low dose 39%). Low dose was associated with significantly fewer side effects. CONCLUSIONS--Both dosage regimens reduce severity of Raynaud''s phenomenon and encourage ulcer healing. Low dose was associated with fewer side effects and was better tolerated by the patients.     

Time to diagnosis in systemic sclerosis: Is sex a factor?

Objective

To determine whether sex plays a role in the time to diagnosis of systemic sclerosis (SSc).

Methods

In the Canadian Scleroderma Research Group registry, dates of onset of Raynaud's phenomenon, the first non–Raynaud's disease symptom, and diagnosis were recorded based on patient reports. Association between sex and time to diagnosis was assessed for the group as a whole and stratified based on extent of skin involvement, either limited or diffuse.

Results

Of the 408 patients studied (347 women, 61 men, 44% with diffuse cutaneous SSc), the time to diagnosis after the onset of Raynaud's phenomenon was significantly longer for women than men (log rank P = 0.001), but not significantly different after the onset of the first non–Raynaud's disease manifestation. In an analysis stratified by limited or diffuse status, the time to diagnosis from onset of Raynaud's phenomenon was also significantly longer for women than men with diffuse cutaneous SSc (log rank P = 0.008). A trend toward a longer period between onset of Raynaud's phenomenon and SSc diagnosis was observed in women compared with men with limited cutaneous SSc (median 4.6 years in women versus 2.1 years in men; P = 0.085), and there was no sex difference in time to diagnosis after the onset of the first non–Raynaud's disease manifestation.

Conclusion

In SSc, the time to diagnosis is longer for women than men after the onset of Raynaud's phenomenon, suggesting that there may be possible biologic differences in the progression of disease or in the health care trajectories of men and women with early SSc.     

Tratamiento con oxígeno hiperbárico en el fenómeno de Raynaud y las úlceras digitales asociadas a esclerosis sistémicas

We describe 4 patients with Raynaud's phenomenon associated with systemic sclerosis, 3 with ischaemic ulcers, successfully treated with hyperbaric oxygen. This therapy has been useful in the treatment of chronic wounds due to its anti-inflammatory, antimicrobial and angiogenic effects. Hyperbaric oxygen treatment could be a therapeutic option in patients with Raynaud's phenomenon refractory to conventional treatment.     

Reversible cerebral vasoconstriction syndrome (RCVS) in antiphospholipid antibody syndrome (APLA): the role of centrally acting vasodilators. Case series and review of literature

Reversible cerebral vasoconstriction syndrome (RCVS) is Raynaud's phenomenon of the brain. Changes in neurological function are dependent upon which areas of the brain are deprived of normal blood flow. Antiphospholipid antibody syndrome (APLA) is a common cause of Raynaud's phenomenon that can occur anywhere in the body, including the brain. Management of CNS vasospasm generally involves the use of centrally acting calcium channel blockers, which have been shown to relieve the associated headaches and transient neurological symptoms associated with it. Three patients with APLA and RCVS from our clinics are illustrated. It is demonstrated that the use of centrally acting calcium channel-blocking drugs, such as nimodipine, which prevent and reverse CNS vasospasm, led to clinical improvement in our patients over the course of 5–9 years. All of them had MRIs done at the initiation of therapy and 5–9 years after being on therapy. MRI measures of T2 lesion volumes (LVs) and number were obtained. All three patients had a good response in controlling clinical symptoms related to CNS vasospasm, Raynaud's phenomenon, visual disturbances, confusion, headaches, and hearing loss. There was also a resolution in the MRI findings of these patients. This case series of three patients shows a clinical improvement and decrease in T2 LV and number in patients with APLA and Raynaud's syndrome on centrally acting calcium channel blockers. RCVS is much more common than that currently appreciated. APLA is the common cause of RCVS. Further studies are needed to determine the optimal methods to diagnose RCVS and optimal therapies to treat it.     

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.     

A long-term longitudinal study of anticentromere antibodies

A longitudinal retrospective study of 37 patients previously tested for anticentromere antibodies (ACA) in 1982 was carried out. No ACA were found in stored sera from 22 ACA-negative patients including 1 patient with CREST (calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly, telangiectasia). All ACA-positive patients, with 1 exception, were found to have ACA in their sera over prolonged periods of time. One patient developed ACA for the first time when the third feature of the CREST syndrome (Raynaud's phenomenon) was noted. Anticentromere antibodies were IgG, and no consistent change in titer over time was found.     

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.     

Nicardipine in the treatment of raynaud's phenomenon

A new calcium channel blocker, nicardipine, was studied for treatment of Raynaud's phenomenon in a double-blind, placebo-controlled, crossover trial during the winter months. Clinical response was assessed by a patient-kept diary of symptoms and finger systolic pressure that was measured at room temperature and during cold challenge. In vivo platelet activation was determined by measuring plasma levels of the platelet-specific proteins, beta-thromboglobulin and platelet factor 4. When treatment with placebo was compared with treatment with nicardipine, no significant differences were found in the number of Raynaud's attacks per day, the severity of attacks, change in character in Raynaud's phenomenon, use of hands in winter months, patient assessment of medication or objective measurements of finger systolic pressure, and critical closing temperature. There was a reduction of plasma levels of beta-thromboglobulin and platelet factor 4 in the overall study group while taking nicardipine compared with that during the placebo period (mean change 5.0 ± 2.4 ng/ml, P = 0.054, and 1.4 ± 0.6 ng/ml, P < 0.01, respectively). These results demonstrate that while nicardipine was not effective in reducing the episodes of Raynaud's phenomenon, it did inhibit in vivo platelet activation. These findings suggest that platelet activation is not the primary event in the pathogenesis of acute vasospasm in Raynaud's phenomenon, since reduction of platelet activation by the drug did not change the severity of vasospasm.     

Deforming arthritis of the hands in polymyositis

Arthritis of the hands with erosions, periosteal calcification, and interphalangeal thumb joint instability was seen in 6 patients with polymyositis. “Overlap” features such as Raynaud's phenomenon, positive LE clot test, and positive antinuclear antibody test were present, but clinically the primary disease was clearly polymyositis. This rather unusual constellation of roentgenographic findings strongly suggests the possibility of polymyositis.     

Familial aggregation of primary Raynaud's disease

Objective. To determine the occurrence of familial aggregation of primary Raynaud's disease. Methods. Twenty-three patients with primary Raynaud's disease and their first-degree relatives were assessed by questionnaire and, when possible, by physical examination. The same procedures were performed on the patients' spouses and the spouses' first-degree relatives, who served as the control group. Results. The prevalence of Raynaud's disease was significantly higher in the families of the probands than in the control families when assessed by questionnaire (26.1% versus 5.5%; P < 10₋₅), and by physical examination (11.2% versus 2.8%; P = 0.015). Conclusion. These findings demonstrate that there is significant familial aggregation of primary Raynaud's disease.     

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

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?