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Raynaud's Phenomenon: Its Relevance to Scleroderma

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Raynaud's Phenomenon: Its Relevance to Scleroderma Annals ofthe Rheumatic Diseases 1991; 50: 839-845 839 Ann Rheum Dis: first published as 10.1136/ard.50.Suppl_4.839 on 1 November 1991. Downloaded from Raynaud's phenomenon: its relevance to scleroderma Jill J F Belch It is now over 125 years since Maurice Raynaud Raynaud's phenomenon as a precursor of first described his clinical syndrome.' By systemic sclerosis definition, it is episodic digital ischaemia Based on various studies,7 the prevalence of provoked by cold and emotion. It is classically systemic sclerosis ranges from 0-1 to 13-8 per manifest by pallor of the affected part followed 100 000 population. This is far lower than the by cyanosis and rubor. The pallor reflects prevalence of Raynaud's phenomenon, and thus vasospasm, the cyanosis results from removal of only a proportion of patients presenting with oxygen from the static venous blood, and rubor Raynaud's phenomenonwill progress to systemic is caused by reactive hyperaemia following sclerosis. One of the earliest studies of disease return of flow. Raynaud's phenomenon has an progression was carried out by Gifford and overall prevalence of about 10%,2 though it may Hines,8 In a study of629 female patients over 28 affect as many as 20-30% of younger women.3 years of age they found progression to a Although it can be a benign condition (primary connective tissue disease in 24%. Another early Raynaud's disease), it may be associated with an study suggested a figure of 50%.6 Both these underlying disorder (Raynaud's syndrome). It studies, however, were published before 1970 is particularly associated with the connective and since then there has been an increasing tissue diseases (table 1). Raynaud's syndrome awareness that Raynaud's syndrome may be occurs in between 90 and 98% of patients with much more common than previously thought. systemic sclerosis,4 and more importantly At the present time the frequency with which proves to be the first symptom in 700/o of secondary conditions are recognised varies patients with this disease4 5 and may precede its widely in reported studies and may depend in development by up to 20 years.6 part on doctors' referral patterns, duration of In this review it is proposed to evaluate the Raynaud's phenomenon at the time seen, and relevance ofRaynaud's phenomenon to systemic the thoroughness with which a search for an sclerosis in two ways. Firstly, by reporting the associated disorder is undertaken.9 '0Moreover, Department ofMedicine, evidence supporting Raynaud's phenomenon as the development of more sophisticated labora- Nineweils Hospital, a precursor of systemic sclerosis and, secondly, tory tests has produced a shrinkage in the group indee DD1 9SY by discussing its importance as a complicating with Raynaud's disease and an expansion in the http://ard.bmj.com/ J J F Belch symptom in fully established systemic sclerosis. numbers of patients with Raynaud's phenom- enon and one or more features of systemic sclerosis. These patients are sometimes referred to as suspected secondary Raynaud's syndrome. It should be noted, however, that the above Table I Conditions associated with Raynaud's phenomenon applies to patients referred to hospital because Immunological disorders Obstructive vasular disease of their Raynaud's phenomenon and should not on September 26, 2021 by guest. Protected copyright. Systemic sclerosis Thoracic outlet syndrome (eg cervical rib) be applied to patients with Raynaud's phenom- Systemic lupus erythematosus Atherosclerosis (especially Beurger's disease) Mixed connective tissue disease enon in the general population. This is clearly Dermatomyositis Drugs shown by the low incidence or absence of Rheumatoid arthritis Ergotamines Cryoglobulinaemia i Blockers connective tissue disease in a group of patients Sj6gren's syndrome Cytotoxic drugs with Raynaud's phenomenon in the general Occupational population followed up by questionnaire."1 Vinyl chloride disease Others Both from a clinical and prognostic point of Vibration induced white finger Malignancy Nitrate workers (outside work) Endocrine disorders (eg hypothyroidism) view, however, it is important to be able to Frozen food packers Uraemia detect, ifpossible, those patients with Raynaud's phenomenon who will develop a connective tissue disease. Furthermore, the study of the pathophysiology of systemic sclerosis might be enhanced by identifying patients at risk or those Table 2 Features associated with progression ofRaynaud's disease to Raynaud's syndrome presenting early in the disease. This early detection of a connective tissue disease in a Clinical symptoms and signs c Detection of antibodies Any features of connective tissue disease Antinuclear patients with Raynaud's phenomenon can be Asymmetry of vasospastic attacks Anticentromere difficult, but, recently, more clearly defined Digital ulceration Scleroderma 70 Return of chilblains in older age group Type IV collagen abnormalities have been detected which have a Older age at onset of Raynaud's phenomenon Laminin strong link with disease progression (table 2). Very young children d Blood coagulation These are: (a) certain clinical features; (b) b Abnormal nailfold vessels Raised factor VIII von Willebrand abnormal nailfold vessels; (c) some immuno- factor antigen Raised ,3 thromboglobulin logical tests; and (d) test of blood coagulation and rheology. Each will be dealt with in turn. 840 Belch Ann Rheum Dis: first published as 10.1136/ard.50.Suppl_4.839 on 1 November 1991. Downloaded from Clinical features associated with connective blains in an adult may also raise suspicions, as tissue disease development should the occurrence of severe attacks persist- The American Rheumatism Association (ARA) ing throughout the summer.'8 Furthermore, criteria for systemic sclerosis'2 have a high asymmetrical colour change with few digits specificity but low sensitivity for the disease. affected suggests Raynaud's syndrome rather Thus patients who quite clearly have a sclero- than Raynaud's disease.'9 It is also of interest derma spectrum disorder presenting with iso- that those patients who do develop systemic lated features such as sclerodactyly, or pitting sclerosis are much more likely to develop scars and digital ulceration do not fulfil the limited cutaneous systemic sclerosis (CREST ARA criteria. It is reasonable to suspect on (calcinosis, Raynaud's phenomenon, oeso- clinical grounds that the disease in such patients phageal dysmotility, sclerodactyly, telangiec- will evolve with time into fully established tasia)) if the history of the preceding Raynaud's systemic sclerosis, and indeed this impression is phenomenon is over many years or decades. supported by prospective clinical studies.'3" Those presenting with systemic sclerosis within Thus isolated features of connective tissue one year of onset of Raynaud's phenomenon disease occurring in association with Raynaud's tend to have diffuse systemic sclerosis (progres- phenomenon should alert clinical suspicion. sive systemic sclerosis). 20 The age of onset of Raynaud's phenomenon The above clinical symptoms, however, can may also be important. As stated, Raynaud's only act as a guide to the clinician as age and phenomenon is common in young women and symptomatology vary widely at presentation. A most of these patients probably have primary more reliable guide is the finding of abnormal Raynaud's disease. When Raynaud's phenom- nailfold vessels on capillary microscopy. enon develops in older subjects the likelihood of an underlying connective tissue disease is increased. Kallenberg reports a study of 90 Nailfold capillary microscopy patients, in whom the median age of onset of A more reliable indication of systemic sclerosis vasospastic symptoms in Raynaud's disease was is the microvascular involvement by the disease, 14 years, and 36 years in patients with a definite which results in characteristic patterns of capil- connective tissue disease.'" Eighty per cent of lary abnormalities in the skin of the fingers, patients presenting with onset of Raynaud's especially at the nail fold, that can be seen by in phenomenon at the age of 60 years or above will vivo microscopy." Direct observations of capil- have an associated condition,'6 but the incidence laries in human skin date back to 1912, but the of connective tissue disease remains the same as best known early description ofnailfold capillary in the general population. The higher number abnormalities in systemic sclerosis was published of secondary cases reflects a larger proportion of by Brown and O'Leary in 1926.22 Recent patients with atherosclerosis (29% v 5% in the refinements have permitted photographic total Raynaud's population) and to a lesser recordings of the row of horizontal capillary extent, hyperviscosity syndromes secondary to a loops at the nail fold just proximal to the cuticle, malignancy. Conversely, Raynaud's phenom- but less sophisticated apparatus allows a clinician enon occurring in very young children, though to examine the nailfold vessels as part of his or http://ard.bmj.com/ rare, is usually due to an underlying connective her routine clinical procedure. tissue disease.'7 Nailfold capillary abnormalities have been Other suspicious but, as yet, unvalidated seen in many diseases, but their most character- symptoms which perhaps should alert the istic pattern is found in the scleroderma clinician are those such as the presence ofdigital spectrum disorders; systemic sclerosis, mixed ulceration. Digital ulceration does not occur in connective tissue disease, overlap syndromes, Raynaud's
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