An unusual association with Raynaud's phenomenon

SIR, We read with interest the report by AL-Deiri et al. [1].There is little doubt that the clinical scenario suggests anassociation of possible Raynauds phenomenon (RP) and pituitaryinsufficiency. It again raises     

Increased pulmonary artery pressure in association with Raynaud's phenomenon

Pulmonary artery vasospasm is a hypothesized antecedent and etiologic factor in the pulmonary hypertension associated with progressive systemic sclerosis. Recent clinical data refute the existence of pulmonary vasospasm in a cohort of patients with scleroderma and normal baseline pulmonary artery pressure. A case of episodic pulmonary hypertension associated with a digital Raynaud's response is reported, and a cardiac mechanism is hypothesized.     

Raynaud's phenomenon. An update

The pathogenesis of primary Raynaud's phenomenon remains an enigma. Most evidence favors a local abnormality in the digital arteries as opposed to an increased activity of the sympathetic nervous system. The local fault may involve the alpha 2-adrenergic receptors, which are most important in reflex sympathetic vasoconstriction. Cooling blood vessels increase the sensitivity of alpha 2-adrenergic receptors, increased levels of alpha 2-adrenergic receptors are present in primary Raynaud's disease, and patients show an increased sensitivity to alpha 2-adrenergic receptor agonists on finger blood flow. Serotonin has also been implicated, but the evidence is not compelling. In secondary Raynaud's phenomenon, vasospastic attacks can often be explained by a low arterial distending pressure, a thickened vessel wall, or absence of beta-adrenergic receptor activity. Diagnosis of primary Raynaud's disease relies on a typical history and normal physical examination, laboratory studies, and nailfold capillaroscopy. Finger systolic blood pressures during local cooling with ischemia may be helpful to document vasospastic attacks but does not distinguish primary from secondary Raynaud's phenomenon. The treatment of Raynaud's phenomenon is usually conservative. Pavlovian conditioning or biofeedback may be beneficial. When drug therapy is necessary, the calcium channel entry blocker nifedipine or sympatholytic agents have been shown to decrease the frequency and duration of vasospastic attacks in about two thirds of patients, although subjective improvement does not usually correlate with objective testing. Direct-acting vasodilators have not been shown to be of definite benefit. New therapies include prostaglandins, captopril, and the serotonergic antagonist ketanserin. Surgical sympathectomy has not been beneficial.     

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?     

Raynaud's phenomenon

Raynaud's phenomenon is characterized by repeated daily attacks of ischemia followed by reperfusion at the acrallevel. It is a frequent syndrome found in medical practice; and it can be considered as primary or secondary to other conditions, including rheumatic autoimmune diseases. Current classification had clinical and therapeutic implications. Careful clinical evaluation is the most reliable and reproducible method in the diagnosis of Raynaud's phenomenon. Several risk factors had been associated in the genesis of Raynaud's phenomenon; however, its pathogenesis remains elusive although recently, considerable progress in disease mechanism had been described. Such advances are directing new lines of therapy.     

Raynaud's phenomenon

Raynaud's phenomenon (RP) is a vasospastic disorder characterized by episodic color changes of blanching, cyanosis, and hyperemia in response to cold and/or emotional stress. Although most typically noted in the fingers, the circulation of the toes, ears, nose and tongue is also frequently affected. Population studies have shown that RP in adults is more common in women than men, with prevalence estimates ranging from 4% to 30%. Geographic variations in the prevalence reflect differences in climate. RP may be a primary or a secondary process. LeRoy and Medsger suggested criteria for primary RP: symmetric attacks, the absence of tissue necrosis, ulceration or gangrene, the absence of a secondary cause, negative antinuclear antibodies, normal nailfold capillaroscopy and a normal erythrocyte sedimentation rate. Secondary RP is characterized by an age of onset of more than 30 years, painful and asymmetric attacks, ischemic skin lesions, positive autoantibodies, capillaroscopic abnormalities and/or clinical features suggestive of connective tissue diseases (CTDs). Among the CTDs, systemic sclerosis has the highest frequency of RP. Finding a cause for RP requires a knowledge of the patient's occupational, smoking, drug history, physical examination, nailfold capillaroscopy, routine laboratory tests and autoantibodies. Furthermore, RP should be distinguished from acrocyanosis, a condition characterized by continuous cyanosis of the hands or feet that is aggravated by cold temperature. The most important instruction to the patient is abstinence from any smoking, offending drugs should be discontinued, and abrupt changes in temperature. If these measures are inadequate, calcium-channel blockers are the most widely used (nifedipine 30 mg up to 90 mg daily). Alternatively, sympatholytic agent (prazosin), angiotensin II -receptor type I antagonist (losartan), selective sertonin-reuptake inhibitor (fluoxetine) may be useful. In the severe cases the role of prostaglandins is well established, but standard therapeutic protocols are not jet available.     

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 is episodic digital ischemia provoked by cold and emotion; it is associated with other disorders, such as Raynaud's syndrome, especially the connective tissue diseases. Recent information suggests links with Sj?gren's syndrome, malignancy, and obstructive vascular disease. The vasospasm can affect areas outside the periphery such as the inner ear in vibration white finger syndrome and the placental vessels in pregnancy. The initial presence of autoantibodies increases the chance by 63-fold of developing connective tissue diseases, and such immunologic testing can be usefully combined with nailfold vessel microscopy. Several factors are considered to be of etiologic importance in Raynaud's phenomenon, such as the augmenting effect of cold on the responsiveness of alpha 2-adrenoceptors to agonists. Deficiency in the vasodilator neuropeptide calcitonin gene-related peptide has been detected, as have excess amounts of the vasoconstrictor endothelin. Treatment of vasospasm remains symptomatic, and directed towards the vasospasm and altered blood constituents.     

Raynaud's phenomenon.

Much has been learned about the complexity of the local, humoral and nervous factors regulating the normal behavior of the skin blood vessels, and many studies have addressed how this knowledge might relate to the causation of primary Raynaud's disease. Despite this, the mechanism(s) responsible for the attacks of digital vasospasm remain an enigma. A key question is whether these attacks represent an exaggeration of the normal mechanisms causing constriction of the digital vessels with local cooling, or are due to a specific abnormality. In this article it is suggested that multiple factors are responsible, including the possibility of co-transmitters released with norepinephrine from the sympathetic nerves, increased activation of beta 2-adrenoceptors on the nerve endings, a shift in the balance of alpha 1 and alpha 2 adrenoceptors on the vascular smooth muscle and in endothelium-derived relaxing and contracting factors, and altered interactions of the endothelium with the blood elements including the effects of increased platelet serotonin.     

Paraneoplastic Raynaud's phenomenon

Summary A testicular tumour could be diagnosed by the occurrence of a Raynaud's phenomenon complicated by severe digital arteritis. The arteritis rapidly regressed under prostacyclin therapy. Such vascular manifestations are frequent in testicular carcinoma, but they usually develop after chemotherapy. To our knowledge, this is the first case where they preceded the diagnosis and specific treatment of a tumour of the testis.     

Raynaud's phenomenon in a female population: prevalence and association with other conditions

In a random sample of 3000 women of ages eighteen to fifty-nine years in the city of V?ster?s, Sweden, 19% of the 2705 responders to a questionnaire complained of cold and white fingers with or without numbness. On the basis of interview and examination, 79% of these women were diagnosed as having Raynaud's phenomenon (RP), giving a prevalence of 15.6%. A significantly higher rate of family members with cold, white fingers was found only in the group of women with pronounced RP (p less than 0.001). A significantly higher frequency of women with pronounced RP than of the control group had a history of recurrent muscle/joint pain (p less than 0.05). Laboratory tests that might indicate an active connective tissue disease did not, however, confirm a diagnosis of rheumatoid arthritis. All three subgroups differed significantly from the control group in terms of recurrent chest pains; subgroups 2 and N differed significantly from controls in terms of recurrent headaches.     

Raynaud's phenomenon.

Raynaud's phenomenon occurs in about 5% of the adult population, and most individuals do not seek medical attention for the condition. In symptomatic patients with Raynaud's phenomenon, it is useful to categorize the condition as primary or secondary. In addition to providing a framework for epidemiologic and therapeutic protocols, such classification may reflect basic pathophysiologic differences. Occupation-related Raynaud's phenomenon has been recognized recently as a major cause of lost wages and productivity. Neurogenic and "local fault" hypotheses to explain primary Raynaud's phenomenon are still being studied. In secondary Raynaud's phenomenon, obliterative arteriopathy and the role of endothelial-derived products have been the focus of intense research interest. Under some circumstances, the combination of nailfold capillary microscopy and autoantibody analysis can identify patients with primary Raynaud's phenomenon that is likely to evolve into a secondary form of Raynaud's phenomenon. Although information from this type of analysis may be overinterpreted, the prognostic yield is highest for patients destined to develop systemic sclerosis-related disorders. Newer vasodilating agents and antithrombotic drugs may offer benefit for patients with both primary and secondary Raynaud's phenomenon.