British Journal of Oral Surgery 14 (1976) 137-142
THE
CRST
SYNDROME
(CALCINOSIS,
SCLERODACTYLY A. E. BROWN,
RAYNAUD’S
AND TELANGIECTASIA)
M.B., B.S., B.D.S., F.D.S.R.C.S.(Eng.)., M.R.C.S., L.R.C.P.l
Eastman
Dental IIospital,
PHENOMENON,
F.D.S.R.C.P.S.(Glasg.).,
Gray’s Inn Road, London
WCIX
8LD
Summary. The CRST syndrome is defined, and its relation to systemic sclerosis described. The literature referring to the condition is reviewed and a further case reported. Clinical and diagnostic features of the telangiectasia are emphasised, particularly in comparison with those of the similar condition, hereditary haemorrhagic telangiectasia.
Introduction The CRST syndrome (calcinosis, Raynaud’s phenomenon, sclerodactyly and telangiectasia) is considered to be a comparatively benign variant of the group of conditions which constitute the disease spectrum known as scleroderma. Although uncommon, it is of interest to dental surgeons because of the multiple telangiectases which affect the lips and oral mucous membrane.
Relationship
of scleroderma
(systemic
sclerosis) to the CRST syndrome
Scleroderma is a chronic disease of unknown aetiology, characterised by a diffuse sclerosis of the connective tissue of the skin, gastrointestinal tract and other organs. In view of the possible widespread nature of the pathological process, which is rarely confined to the skin alone, many authorities prefer to group all varieties of the condition under the more precise name of systemic sclerosis. The disease is relatively uncommon, usually begins in middle age and is occasionally familial, although not exhibiting any definite pattern of inheritance. Between three and four females are affected for every male (Rowell, 1972). It is important to realise that, although systemic sclerosis is a diffuse condition, it need not affect every organ in any one patient. The process is best thought of as a spectrum of disease which manifests itself in various forms (Tumulty, 1970; British Medical Journal, 1973). At one end of this spectrum are the relatively benign variants which mainly involve the skin in a localised or generalised manner, otherwise referred to as morphoea and scleroderma respectively; and at the other end is the rapidly fatal condition, progressive systemic sclerosis. This latter variety is marked by widespread visceral involvement. Patients with so-called scleroderma may well have latent visceral involvement as well, and this can either manifest itself later in the course of the disease or remain sub-clinical as far as symptoms are concerned. Furthermore, although cutaneous lesions usually precede visceral lesions in most cases of progressive systemic sclerosis, occasionally the reverse may be true. In a minority of cases the skin is spared altogether. A possible classification of systemic sclerosis is therefore: (Received 1 March 1976; accepted 22 March 1976)
1 Present address: Queen Victoria Hospital, East Grinstead,
Sussex.
138
BRITISH
JOURNAL
OF ORAL
SURGERY
CUTANEOUS
1. Localised Morphoea Linear streaks Plaques Sclerodactyly 2. Generalised Scleroderma
VISCERAL 1.
Localised
t 2. Generalised Progressive
systemic
sclerosis
The extreme variation in the presentation, distribution and progression of the disease, coupled with the fact that the aetiology remains obscure, inevitably makes such a classification of limited value. The distinct clinical features of the CRST syndrome were first delineated by Winterbauer (1964). He proposed that it should be recognised as a separate entity within the spectrum of systemic sclerosis, although he acknowledged that several authors had previously described typical cases of the condition without suggesting this fact. (e.g. Netherton & Curtis, 1942; Verel, 1956) The association of calcinosis with systemic sclerosis has been known for some time. Thibierge and Weissenbach (1911) published a series of patients with this combination, and the condition has since been referred to as the Thibierge-Weissenbach syndrome, although Weber (1878) described the relationship over 30 years before these authors. Similarly, telangiectasia are often seen in all forms of systemic sclerosis, the reported incidence varying from 14 per cent to 70 per cent (Tuffanelli & Winkelman, 1961; Rowell, 1972). Nevertheless, the combination of telangiectasia and calcinosis with a particularly localised, non-progressive form of the disease, namely sclerodactyly, resulted in the definition of this new syndrome by Winterbauer. Rowe11 (1972) suggests that such a distinction is not valid, bearing in mind the protean manifestations of systemic sclerosis but other authorities agree that the CRST syndrome is a definite entity (Tumulty, 1970; Harris, 1975). Following Winterbauer’s (1964) original description and presentation of seven patients, a further three cases were reported by Schimke et al. (1967).
Case report A 51-year-old lady was referred by her general dental practitioner complaining of mobility and loss of teeth due to periodontal disease. On examination, she had several obvious telangiectases on both lips (Fig. 1) and thickened, immobile fingers with loss of the skin creases over the proximal and distal interphalangeal joints. There were further telangiectases on the palmar surface of both hands and a few small scattered lesions on the trunk. Intra-orally, both the tongue and hard palate were affected by the telangiectasia (Fig. 2) and all standing teeth exhibited varying degrees of mobility with marked periodontal pocketing. Further questioning eliminated any family history of the condition. The patient did not admit to any unusual haemorrhagic episodes and there was no difficulty in swallowing. The first symptom of the disease was Raynaud’s phenomenon, which was noticed at approximately 20 years of age. Progressive sclerodactyly had been occurring since then, and the telangiectasia had been present for most of her adult life. A small piece of calcareous material had been extruded from a finger tip two months prior to her attendance. The patient was under the care of a consultant rheumatologist and had been informed that she was suffering from scleroderma and mild hypertension. The only therapy she was receiving was penicillamine, possibly with some effect as far as the mobility of the fingers was concerned. An earlier barium swallow had revealed
THE CRST
SYNDROME
FIGS 1 and 2. Telangiectasia
139
on lips and tongue.
mild oesophageal abnormalities of no functional significance. An important aspect of the past medical history was that a right mastectomy had been performed seven years previously, with subsequent radiotherapy. Radiographic examination confirmed the presence of calcific deposits in some of the digits of both hands (Fig. 3) and intra-oral views showed evidence of widespread periodontal disease with a periodontal membrane of normal width. Other investigations were as follows, Hb, 13.8 g per 100 ml, ESR 29 mm in the first hour, the blood
140
FIG. 3.
BRITISH
JOURNAL
OF
ORAL
SURGERY
Calcific deposits, (left) adjacent to proximal phalanx of right little finger (right) at tip of left index and middle finger.
film was normal (no L.E. cells seen), rheumatoid factor, negative, antinuclear positive 1 :lO, and tests for clotting function were normal.
antibodies,
Treatment and progress Two extremely mobile teeth were extracted using local analgesia, with no untoward after-effects. A gingival biopsy taken at the time revealed normal tissue. Whilst awaiting further treatment for her periodontal condition, the patient unfortunately suffered an acute myocardial infarction and died shortly thereaftw. Discussion Systemic sclerosis is known to affect the oro-facial tissues in a large number of cases, resulting in an expressionless face with possible limitation in opening (Gores, 1957; Smith, 1958). Localised plaques of sclerodermatous tissue can result in facial asymmetry (Hoggins, 1969). The so-called characteristic finding of a widened periodontal membrane is thought to occur in less than 10 per cent of cases of scleroderma according to Stafne and Austin (1944), and has never been reported in the CRST syndrome. There was no evidence of oro-facial involvement in the disease process in the patient reported above, but the history of carcinoma of the breast is of interest in view of the increased tendency to malignancy reported in patients with systemic sclerosis (Turn&y, 1970; Rowe& 1972). The obvious clinical importance of the CRST syndrome, as far as the oral surgeon is concerned, is the presence of multiple telangiectases involving the lips and mouth. The differential diagnosis will naturally include a condition with very similar lesions, hereditary haemorrhagic telangiectasia (HHT). Although the angiomatous lesions
THE
CRST
SYNDROME
141
Table I A Comparison of the Clinical Features in HHT and the CRST Syndrome
of the Telangiectasia
Clinical features
Hereditary haemorrhagic telangiectasia
The CRST syndrome
Age of onset
10-40 (usually 30-40) yrs
20-70 (often 40+) yrs
Sex
Ml :Fl
Predominantly females
Family history
Positive (autosomal dominant inheritance)
Negative
Distribution lesions
Face, oral mucosa, trunk and upper limbs. Widespread internal and visceral involvement
Predominantly face, oral mucosa and upper extremities. Visceral lesions uncommon
of
Haemorrhagic
diathesis
(a) Epistaxis
Common (75 %). Often severe and may precede appearance of telangiectases
Less common (40%) Never severe
(b) Melaena and haematuria
Common
Uncommon
(c) Oral and cutaneous bleeding
Common
Not reported
are macroscopically and microscopically identical in both conditions, the presence of Raynaud’s phenomenon and an absolute lack of a positive family history will aid diagnosis. Winterbauer (1964) made a detailed comparison of the clinical picture in the two conditions, and his findings are summarised in Table I. An interesting feature of practical importance is that there appears to be a lesser tendency for haemorrhagic episodes to occur in patients with the CRST syndrome. This may be related to the lack of visceral and internal involvement in the telangiectasia, in contrast to the widespread distribution of the lesions in HHT. However, it seems that although the lesions are histologically identical in both conditions, they may react differently to physiological stimuli. Verel (1956) showed that the angiomatous vessels in patients presenting with telangiectasia and Raynaud’s phenomenon constricted normally following light tactile stimulation or the perivascular introduction of histamine. Similarly introduced adrenaline caused the expected profound vasoconstriction. In contrast to this, Macfarlane (1941) noted that the angiomatous vessels in HHT failed to constrict after puncture with a fine needle, although other capillaries in the same patient reacted normally. Despite the suggestion from these studies that haemorrhage is less of a problem in the CRST syndrome compared to HHT, the dental surgeon is well advised to operate with caution on any patient who has multiple intra-oral telangiectases (Killey & Kay, 1970). However, mucosal and facial involvement in the sclerodermatous process is notably absent in this benign localised variant of systemic sclerosis, and the lack of progression of the disease is especially welcome in view of the absence of any effective treatment to date.
142
BRITISH
JOURNAL
OF
ORAL
SURGERY
Acknowledgement I would like to thank Dr J. D. Manson for permission to report a case referred under his care. References British Medical Journal (1973). Leading Article, 4, 249. Gores, R. J. (1957). Journal of the American Dental Association, 54, 755. Harris, E. D. (1975). Textbook of Medicine, Edit. P. B. Beeson & W. McDermott, 14th Ed., p. 126 Philadelphia: Saunders. Hoggins, G. S. (1969). Oral Surgery, Oral Medicine and Oral Pathology, 27, 734. Killey, H. C. & Kay, L. W. (1970). British Journal of Oral Surgery, 7, 161. Macfarlane, R. G. (1941). Quarterly Journal of Medicine, 10, 1. Netherton, E. W. & Curtis, G. H. (1942). Archives of Dermatology and Syphilology, 46, 579. Rowell, N. R. (1972). Textbook of Dermatology, Edit. A. Rook, D. S. Wilkinson & F. D. Ebling, 2nd Ed., p. 1096. Oxford: Blackwell. Schimke, M. D. Kirkpatrick, C. H. & Delp, M. H. (1967). Archives of Internal Medicine, 119, 365. Smith, D. B. (1958). Oral Surgery, Oral Medicine and Oral Pathology, 11, 865. Stafne, E. C. & Austin, L. T. (1944). American Journal of Orthodontics (Oral Surgery Section), 30,25. Thibierge, G. & Wiessenbach, R. J. (1911). A nnales de Dermatologie et de Syphiligraphie, 2,129. Tuffanelli, D. L. & Winkelmann, R. K. (1961). Archives of Dermatology, 84, 359. Turn&y, P. A. (1970). Harrison’s Principles of Internal Medicine, Edit. M. M. Wintrobe, 6th Ed., p. 1968. New York: McGraw-Hill. Verel, D. (1956). Lance& 2, 914. Weber, H. (1878). Korrespondenzblattfiir Schweizer Artze, 8, 623. Winterbauer, R. H. (1964). Bulletin of the Johns Hopkins Hospital, 114, 361.
THE
CRST
SYNDROME
(CALCINOSIS,
SCLERODACTYLY A. E. BROWN,
RAYNAUD’S
AND TELANGIECTASIA)
M.B., B.S., B.D.S., F.D.S.R.C.S.(Eng.)., M.R.C.S., L.R.C.P.l
Eastman
Dental IIospital,
PHENOMENON,
F.D.S.R.C.P.S.(Glasg.).,
Gray’s Inn Road, London
WCIX
8LD
Summary. The CRST syndrome is defined, and its relation to systemic sclerosis described. The literature referring to the condition is reviewed and a further case reported. Clinical and diagnostic features of the telangiectasia are emphasised, particularly in comparison with those of the similar condition, hereditary haemorrhagic telangiectasia.
Introduction The CRST syndrome (calcinosis, Raynaud’s phenomenon, sclerodactyly and telangiectasia) is considered to be a comparatively benign variant of the group of conditions which constitute the disease spectrum known as scleroderma. Although uncommon, it is of interest to dental surgeons because of the multiple telangiectases which affect the lips and oral mucous membrane.
Relationship
of scleroderma
(systemic
sclerosis) to the CRST syndrome
Scleroderma is a chronic disease of unknown aetiology, characterised by a diffuse sclerosis of the connective tissue of the skin, gastrointestinal tract and other organs. In view of the possible widespread nature of the pathological process, which is rarely confined to the skin alone, many authorities prefer to group all varieties of the condition under the more precise name of systemic sclerosis. The disease is relatively uncommon, usually begins in middle age and is occasionally familial, although not exhibiting any definite pattern of inheritance. Between three and four females are affected for every male (Rowell, 1972). It is important to realise that, although systemic sclerosis is a diffuse condition, it need not affect every organ in any one patient. The process is best thought of as a spectrum of disease which manifests itself in various forms (Tumulty, 1970; British Medical Journal, 1973). At one end of this spectrum are the relatively benign variants which mainly involve the skin in a localised or generalised manner, otherwise referred to as morphoea and scleroderma respectively; and at the other end is the rapidly fatal condition, progressive systemic sclerosis. This latter variety is marked by widespread visceral involvement. Patients with so-called scleroderma may well have latent visceral involvement as well, and this can either manifest itself later in the course of the disease or remain sub-clinical as far as symptoms are concerned. Furthermore, although cutaneous lesions usually precede visceral lesions in most cases of progressive systemic sclerosis, occasionally the reverse may be true. In a minority of cases the skin is spared altogether. A possible classification of systemic sclerosis is therefore: (Received 1 March 1976; accepted 22 March 1976)
1 Present address: Queen Victoria Hospital, East Grinstead,
Sussex.
138
BRITISH
JOURNAL
OF ORAL
SURGERY
CUTANEOUS
1. Localised Morphoea Linear streaks Plaques Sclerodactyly 2. Generalised Scleroderma
VISCERAL 1.
Localised
t 2. Generalised Progressive
systemic
sclerosis
The extreme variation in the presentation, distribution and progression of the disease, coupled with the fact that the aetiology remains obscure, inevitably makes such a classification of limited value. The distinct clinical features of the CRST syndrome were first delineated by Winterbauer (1964). He proposed that it should be recognised as a separate entity within the spectrum of systemic sclerosis, although he acknowledged that several authors had previously described typical cases of the condition without suggesting this fact. (e.g. Netherton & Curtis, 1942; Verel, 1956) The association of calcinosis with systemic sclerosis has been known for some time. Thibierge and Weissenbach (1911) published a series of patients with this combination, and the condition has since been referred to as the Thibierge-Weissenbach syndrome, although Weber (1878) described the relationship over 30 years before these authors. Similarly, telangiectasia are often seen in all forms of systemic sclerosis, the reported incidence varying from 14 per cent to 70 per cent (Tuffanelli & Winkelman, 1961; Rowell, 1972). Nevertheless, the combination of telangiectasia and calcinosis with a particularly localised, non-progressive form of the disease, namely sclerodactyly, resulted in the definition of this new syndrome by Winterbauer. Rowe11 (1972) suggests that such a distinction is not valid, bearing in mind the protean manifestations of systemic sclerosis but other authorities agree that the CRST syndrome is a definite entity (Tumulty, 1970; Harris, 1975). Following Winterbauer’s (1964) original description and presentation of seven patients, a further three cases were reported by Schimke et al. (1967).
Case report A 51-year-old lady was referred by her general dental practitioner complaining of mobility and loss of teeth due to periodontal disease. On examination, she had several obvious telangiectases on both lips (Fig. 1) and thickened, immobile fingers with loss of the skin creases over the proximal and distal interphalangeal joints. There were further telangiectases on the palmar surface of both hands and a few small scattered lesions on the trunk. Intra-orally, both the tongue and hard palate were affected by the telangiectasia (Fig. 2) and all standing teeth exhibited varying degrees of mobility with marked periodontal pocketing. Further questioning eliminated any family history of the condition. The patient did not admit to any unusual haemorrhagic episodes and there was no difficulty in swallowing. The first symptom of the disease was Raynaud’s phenomenon, which was noticed at approximately 20 years of age. Progressive sclerodactyly had been occurring since then, and the telangiectasia had been present for most of her adult life. A small piece of calcareous material had been extruded from a finger tip two months prior to her attendance. The patient was under the care of a consultant rheumatologist and had been informed that she was suffering from scleroderma and mild hypertension. The only therapy she was receiving was penicillamine, possibly with some effect as far as the mobility of the fingers was concerned. An earlier barium swallow had revealed
THE CRST
SYNDROME
FIGS 1 and 2. Telangiectasia
139
on lips and tongue.
mild oesophageal abnormalities of no functional significance. An important aspect of the past medical history was that a right mastectomy had been performed seven years previously, with subsequent radiotherapy. Radiographic examination confirmed the presence of calcific deposits in some of the digits of both hands (Fig. 3) and intra-oral views showed evidence of widespread periodontal disease with a periodontal membrane of normal width. Other investigations were as follows, Hb, 13.8 g per 100 ml, ESR 29 mm in the first hour, the blood
140
FIG. 3.
BRITISH
JOURNAL
OF
ORAL
SURGERY
Calcific deposits, (left) adjacent to proximal phalanx of right little finger (right) at tip of left index and middle finger.
film was normal (no L.E. cells seen), rheumatoid factor, negative, antinuclear positive 1 :lO, and tests for clotting function were normal.
antibodies,
Treatment and progress Two extremely mobile teeth were extracted using local analgesia, with no untoward after-effects. A gingival biopsy taken at the time revealed normal tissue. Whilst awaiting further treatment for her periodontal condition, the patient unfortunately suffered an acute myocardial infarction and died shortly thereaftw. Discussion Systemic sclerosis is known to affect the oro-facial tissues in a large number of cases, resulting in an expressionless face with possible limitation in opening (Gores, 1957; Smith, 1958). Localised plaques of sclerodermatous tissue can result in facial asymmetry (Hoggins, 1969). The so-called characteristic finding of a widened periodontal membrane is thought to occur in less than 10 per cent of cases of scleroderma according to Stafne and Austin (1944), and has never been reported in the CRST syndrome. There was no evidence of oro-facial involvement in the disease process in the patient reported above, but the history of carcinoma of the breast is of interest in view of the increased tendency to malignancy reported in patients with systemic sclerosis (Turn&y, 1970; Rowe& 1972). The obvious clinical importance of the CRST syndrome, as far as the oral surgeon is concerned, is the presence of multiple telangiectases involving the lips and mouth. The differential diagnosis will naturally include a condition with very similar lesions, hereditary haemorrhagic telangiectasia (HHT). Although the angiomatous lesions
THE
CRST
SYNDROME
141
Table I A Comparison of the Clinical Features in HHT and the CRST Syndrome
of the Telangiectasia
Clinical features
Hereditary haemorrhagic telangiectasia
The CRST syndrome
Age of onset
10-40 (usually 30-40) yrs
20-70 (often 40+) yrs
Sex
Ml :Fl
Predominantly females
Family history
Positive (autosomal dominant inheritance)
Negative
Distribution lesions
Face, oral mucosa, trunk and upper limbs. Widespread internal and visceral involvement
Predominantly face, oral mucosa and upper extremities. Visceral lesions uncommon
of
Haemorrhagic
diathesis
(a) Epistaxis
Common (75 %). Often severe and may precede appearance of telangiectases
Less common (40%) Never severe
(b) Melaena and haematuria
Common
Uncommon
(c) Oral and cutaneous bleeding
Common
Not reported
are macroscopically and microscopically identical in both conditions, the presence of Raynaud’s phenomenon and an absolute lack of a positive family history will aid diagnosis. Winterbauer (1964) made a detailed comparison of the clinical picture in the two conditions, and his findings are summarised in Table I. An interesting feature of practical importance is that there appears to be a lesser tendency for haemorrhagic episodes to occur in patients with the CRST syndrome. This may be related to the lack of visceral and internal involvement in the telangiectasia, in contrast to the widespread distribution of the lesions in HHT. However, it seems that although the lesions are histologically identical in both conditions, they may react differently to physiological stimuli. Verel (1956) showed that the angiomatous vessels in patients presenting with telangiectasia and Raynaud’s phenomenon constricted normally following light tactile stimulation or the perivascular introduction of histamine. Similarly introduced adrenaline caused the expected profound vasoconstriction. In contrast to this, Macfarlane (1941) noted that the angiomatous vessels in HHT failed to constrict after puncture with a fine needle, although other capillaries in the same patient reacted normally. Despite the suggestion from these studies that haemorrhage is less of a problem in the CRST syndrome compared to HHT, the dental surgeon is well advised to operate with caution on any patient who has multiple intra-oral telangiectases (Killey & Kay, 1970). However, mucosal and facial involvement in the sclerodermatous process is notably absent in this benign localised variant of systemic sclerosis, and the lack of progression of the disease is especially welcome in view of the absence of any effective treatment to date.
142
BRITISH
JOURNAL
OF
ORAL
SURGERY
Acknowledgement I would like to thank Dr J. D. Manson for permission to report a case referred under his care. References British Medical Journal (1973). Leading Article, 4, 249. Gores, R. J. (1957). Journal of the American Dental Association, 54, 755. Harris, E. D. (1975). Textbook of Medicine, Edit. P. B. Beeson & W. McDermott, 14th Ed., p. 126 Philadelphia: Saunders. Hoggins, G. S. (1969). Oral Surgery, Oral Medicine and Oral Pathology, 27, 734. Killey, H. C. & Kay, L. W. (1970). British Journal of Oral Surgery, 7, 161. Macfarlane, R. G. (1941). Quarterly Journal of Medicine, 10, 1. Netherton, E. W. & Curtis, G. H. (1942). Archives of Dermatology and Syphilology, 46, 579. Rowell, N. R. (1972). Textbook of Dermatology, Edit. A. Rook, D. S. Wilkinson & F. D. Ebling, 2nd Ed., p. 1096. Oxford: Blackwell. Schimke, M. D. Kirkpatrick, C. H. & Delp, M. H. (1967). Archives of Internal Medicine, 119, 365. Smith, D. B. (1958). Oral Surgery, Oral Medicine and Oral Pathology, 11, 865. Stafne, E. C. & Austin, L. T. (1944). American Journal of Orthodontics (Oral Surgery Section), 30,25. Thibierge, G. & Wiessenbach, R. J. (1911). A nnales de Dermatologie et de Syphiligraphie, 2,129. Tuffanelli, D. L. & Winkelmann, R. K. (1961). Archives of Dermatology, 84, 359. Turn&y, P. A. (1970). Harrison’s Principles of Internal Medicine, Edit. M. M. Wintrobe, 6th Ed., p. 1968. New York: McGraw-Hill. Verel, D. (1956). Lance& 2, 914. Weber, H. (1878). Korrespondenzblattfiir Schweizer Artze, 8, 623. Winterbauer, R. H. (1964). Bulletin of the Johns Hopkins Hospital, 114, 361.
