Clinical and Laboratory Investigations Dermatology 1992;185:101-103
L. Macheta, L. Vaillanta M. C. Maclietb, E. Estevea C. Muller3, R. Khallouf G. Lorettea
Carpal Tunnel Syndrome and Systemic Sclerosis
Department of Dermatology, and Department of Pathology, CHU Trousseau, Tours. France
Abstract Carpal tunnel syndrome (CTS) was observed in 4 cases of a consecutive series of 16 patients admitted for the initial diagnosis or follow-up of systemic sclero derma from 1986 to 1990. We also observed one case of ulnar nerve compres sion. Neurological involvement was confirmed by electromyogram, and motor and sensory nerve conduction studies. The neurological signs appeared at the beginning of the disease in two cases and preceded the discovery of scleroderma in two. CTS is not rare in scleroderma and must be carefully sought, both clin ically and electrophysiologically. Patients with ‘idiopathic’ CTS might need clin ical follow-up for early diagnosis of scleroderma.
Introduction The occurrence of neurological involvement in systemic scleroderma is rare [1], The frequency of neurological manifestations varies from 5% in a prospective study [2] to 18.5% in a retrospective study [3], Among the different neurological manifestations, trigeminal sensory neuropa thy is the most frequent [4], occurring in 9% of the cases [5], Carpal tunnel syndrome (CTS) occurs in 3% [2], and may occur later in the course of the disease. Moreover, CTS may appear as the initial clinical manifestation of the disease [6-9],
Patients and Methods Sixteen patients (mean age 56.1 years. SD 17.1; sex ratio F/M 1.3; mean follow-up 4.3 years, SD 2.0) were admitted to our dermatology department between January 1986 and December 1990 with the diag nosis of systemic slcerosis. according to the ARA criteria [10]. They were all examined by the same clinician (L.V.). They had routine blood tests, antinuclear anti-SSa. anti-SSb. anti-centromere, and anti-
Received: Decem ber 3, 1991
Accepted: March 26. 1992
Scl 70 antibody determinations, chest X-ray, functional pulmonary tests, oesophageal manometry, skin biopsy, nailfold capillary micros copy, electrocardiography and echocardiography. The minimal crite rion for the clinical diagnosis of CTS was the description of paraesthesia of fingers innervated by the median nerve, aggravated by activity, orT in el'so r Phalen’s sign [11], When peripheral neurological abnor malities were detected at clinical examination, an electromyographic examination (EMG) was performed with a motor and sensory nerve conduction study. Prolongation of the median motor or sensory distal latency was the primary criterion for abnormality [11],
Results Acrosclerosis was present in all 16 patients. Raynaud’s phenomenon was present in 12, oesophageal involvement in 11, cutaneous calcification in 2, telangiectasia in 7 and xerostomia in 8 cases. The diffusing capacity for carbon monoxide was decreased ( 1/400) in 11 cases, with positive anti-Scl 70 antibodies in 3 cases, anti centromere antibodies in 1 case, anti-SSa antibodies in 1 case and anti-mitochondria antibodies in 1 case.
L. Machct Department of Dermatology CHU Trousseau F-37044 Tours (France)
© 1992 Kargcr AG. Basel 1018-8665/92/1852-0101 $ 2.75/0
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/3/2018 3:43:34 PM
Key Words Systemic sclerosis Carpal tunnel syndrome Neurological manifestations
Table 1. Main clinical and biological features of the 5 patients with scleroderma and neurological involvement
Patients
Time between neural signs and diagnosis of scleroderma Treatment Results
2
3
4
5
51 male + +
60 male + + +
80 female + + +
55 female + + +
-
-
-
-
+ 1:400
-
-
+
-
-
-
1:2,000
1:400 -
-
-
-
-
-
-
75
36
45
100
25
Carpal tunnel syndrome
Carpal tunnel syndrome
Carpal tunnel syndrome
Ulnar nerve compression
2 years before
Carpal tunnel syndrome VI cranial nerve palsy 3 years before
3 months before
0
17 years after
Surgical decompression Complete relief
Surgical decompression Complete relief
Local corticothcrapy Complete relief
Surgical decompression Complete relief
Local corticothcrapy Moderate improvement
Bilateral CTS was diagnosed clinically in 4 cases and confirmed by EMG in 2 of these (table l). For the remain ing 2 cases of CTS, EMG was not performed before surgi cal decompression. In these 2 patients, CTS had preceded the diagnosis of scleroderma by 2-3 years. Peripheral nerve compression occurred at the beginning of scleroderma in the 2 other cases. In another case, diagnosis of right ulnar nerve compression was made 17 years after the onset of scleroderma and confirmed by a decrease in motor and sen sory nerve conduction. The only other neurological com plication encountered in our patients was a paralysis of the Vlth cranial nerve, with normal CT scan and with no other cause than scleroderma. Complete relief of symptoms was obtained by surgical decompression of the median nerve in 3 cases. Pathological examination was possible in 2 cases and revealed synovial fibrosis in one, and a polymorphous inflammatory infiltrate around small vessels with fibrous involvement of the tendinous sheaths in other. In one case of CTS, and in the case of ulnar nerve compression, a clin ical amelioration was obtained by corticosteroid infiltra tion. This was confirmed by the normalisation of the EMG in l case.
102
-
56 female + + + +
-
-
Discussion In this study, neurological involvement is frequent: 5 patients among 16 presented nerve compression of the median or ulnar nerve at some point during the evolution of scleroderma. This high frequency might have been even greater if EMG had been carried out systematically [12], The physiopathology of scleroderma is still debated [ 13, 14], and the numerous proposed mechanisms could explain neurological abnormalities. The vascular hypothesis is sup ported by the frequency of Raynaud’s phenomenon, telan giectasia, and abnormality of the nailfold capillaries. These abnormalities could be due to an endothelial injury [14], There is also strong evidence for abnormal immune func tions. Various auto-antibodies are present in the disease. Deposits of immunoglobulins with a secondary activation of complement fractions could be the first event in endo thelial injury [13, 14], Abnormalities in the cellular response mediated by lymphocytes [14] or mast cells [15, 16] have been described, and may be a cause or a conse quence of the disease activity. Fibroblastic activity is stim ulated as a result of immune activation whatever the pri-
Machct/Vaillant/Machct/Estcvc/Mullcr/ Khallouf/Lorette
Carpal Tunnel Syndrome and Systemic Sclerosis
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/3/2018 3:43:34 PM
Age, years Sex Acrosclerosis Raynaud’s phenomenon Oesophageal involvement Calcinosis Telangiectasia Antinuclear antibodies Anti-centromere antibodies Anti-Scl 70 antibodies Diffusing capacity for carbon monoxyde. % expected value Neurological involvement
1
mary event may be: endothelial injury or immunocompe tent cellular dysregulation. Pathogenesis of neurological involvement in sclero derma may result both from a primary injury of vasa nervo rum or from perineural inflammation [17]. These mech anisms could explain the diffuse sensory neuropathies encountered in scleroderma [7]. However, the pathogen esis of neurological involvement in cases of CTS seems to be directly linked to fibrosis and to soft tissue oedema at the initial oedematous phase of the disease. Neural compres sion may occur more frequently at the carpal tunnel than at other sites because of the large amount of perineural con nective tissue relative to the funicular size of the median nerve [18]. Though trigeminal neuropathy is frequently reported 119], we did not observe this complication. Other reported neurological complications are mononeuritis mul tiplex. peripheral neuropathy, and cranial nerve involve ment [2, 4]. Our data arc consistent with a prospective study of 125 patients suffering from scleroderma: 4 cases of CTS and only 1 trigeminal neuralgia were observed [2], and the onset of CTS had also preceded the discovery of sclero
derma in 3 of the 4 cases, with a time interval of between 12 and 18 months. Some other reports have emphasized the occurrence of CTS in scleroderma [6-9]. In all of these cases, the CTS was discovered before the diagnosis of scle roderma. As in C IS . the trigeminal nerve compression may precede scleroderma by 1-12 months, and is more fre quent in CREST syndrome than in other subsets of scler oderma [11], In toxic oil syndrome, which at a chronic phase of evolution causes a scleroderma-like syndrome, 7% of the patients presented CTS [18]. The onset of mani festation occurred early in the disease, 1-17 months after the initial acute respiratory signs. The early and varied neu rological involvement in scleroderma and scleroderma-like syndromes needs careful examination, since neurological involvement appears to be frequent. This frequency is higher when systematic electrodiagnostic studies are done [12]. Among these complications, CTS is pre-eminent [2, 18], Because the onset of CTS may precede the clinical manifestations of scleroderma, we suggest a clinical follow up of ‘idiopathic’ CTS.
References 9 Ouinonc CA. Perry H. Rushton J: Carpal tun nel syndrome in dermatomyositis and sclero derma. Arch Dermatol 1966:94:21-25. 10 Masi AT. Rodnan GP. Medsger TA. Altman RD. D'Angelo WA. Fries JF. Leroy EC. Kirsncr AB. MacKcnzic H. MacShanc DJ. Myers AR, Sharp GC: Preliminary criteria for the classification of systemic sclerosis (sclero derma). Arthritis Rheum 1980:23:581-590. 11 Stevens JC. Sun S. Beard CM, O'Fallon WM. Kurland LT: Carpal tunnel syndrome in Rochester. Minnesota. 1961 to 1980. Neurol ogy 1988:38:134-138. 12 Christopher RP. Robinson H: Studies of nerve conduction in patients with scleroderma. South Med J 1972:65:668-672. 13 Majewski S. Blaszczyk M. Jablonska S. Rudnika L, Wasik M. Skicndziclewska A. Makiela B: Cytotoxic effects of sera from patients with systemic scleroderma: Comparison of three different in vitro methods. Rheumatol Int 1990:10:64-70. 14 Haustein UF. Herrmann K. Böhme HJ: Pathogenesis of progressive systemic sclerosis. Int J Dermatol 1986:25:286-293. 15 Claman HN: On scleroderma, mast cells, endothelial cells, and fibroblasts. JAMA 1989: 262:1206-1209.
16 Fonseca E. Soll J: Mast cell in the skin. Pro gressive systemic sclerosis and the toxic oil syn drome. Ann Intern Med 1989:102:864-865. 17 Di Trapani G . Tulli A. Lacara A. Lauriezo P. Mazza S. David P: Peripheral neuropathy in course of progressive systemic sclerosis. Acta Neuropathol (Berl) 1986:72:103-110. 18 Alonso-Ruiz A. Lciva-Santana C: Carpal tun nel syndrome in scleroderma-like syndromes. J Rheumatol 1985:12:1030. 19 Pain O. Guillevin !.. Giroux G. Royer I: Neu ropathie sensitive du trijumeau et scléroder mie. Rev Neurol (Paris) 1989:145:236-238.
103
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/3/2018 3:43:34 PM
1 Rocco VK. I lurd ER: Scleroderma and sclero derma-like disorders. Semin Arthritis Rheum 1986:16:22-69. 2 l.ce P. Bruni J: Sukcnik S: Neurological mani festation in systemic sclerosis. J Rheumatol 1984;11:480-483. 3 Gordon RM. Silvcrstcin A: Neurological mani festation in progressive systemic sclerosis. Arch Neurol 1970:22:126-133. 4 Teasdall RD. Fraya RA. Schumann LE: Cra nial involvement in scleroderma. A report of 10 cases. Medicine 1980:59:149-159. 5 Farcll DA. McdsgerTA: Trigeminal neuropa thy in progressive systemic sclerosis. Am J Med 1982:73:57-62. 6 Barr WG. Blair SJ: Carpal tunnel syndrome as the initial manifestation of scleroderma. J Hand Surg [Am] 1988:13a:378-380. 7 Bcrth-Jones J. Coates PA A. Graham-Brown RAC. Burns DA: Neurological complication of systemic sclerosis. A report of three cases and review of the literature. Clin Exp Derma tol 1990:15:91-94. 8 Sukcnik S. Abarbancl JM. Buskila D. Potashnik G. Horowitz J: Impotence, carpal tunnel syndrome and peripheral neuropathy as pre senting symptoms in progressive systemic scle rosis. J Rheumatol 1987:14:641-643.
L. Macheta, L. Vaillanta M. C. Maclietb, E. Estevea C. Muller3, R. Khallouf G. Lorettea
Carpal Tunnel Syndrome and Systemic Sclerosis
Department of Dermatology, and Department of Pathology, CHU Trousseau, Tours. France
Abstract Carpal tunnel syndrome (CTS) was observed in 4 cases of a consecutive series of 16 patients admitted for the initial diagnosis or follow-up of systemic sclero derma from 1986 to 1990. We also observed one case of ulnar nerve compres sion. Neurological involvement was confirmed by electromyogram, and motor and sensory nerve conduction studies. The neurological signs appeared at the beginning of the disease in two cases and preceded the discovery of scleroderma in two. CTS is not rare in scleroderma and must be carefully sought, both clin ically and electrophysiologically. Patients with ‘idiopathic’ CTS might need clin ical follow-up for early diagnosis of scleroderma.
Introduction The occurrence of neurological involvement in systemic scleroderma is rare [1], The frequency of neurological manifestations varies from 5% in a prospective study [2] to 18.5% in a retrospective study [3], Among the different neurological manifestations, trigeminal sensory neuropa thy is the most frequent [4], occurring in 9% of the cases [5], Carpal tunnel syndrome (CTS) occurs in 3% [2], and may occur later in the course of the disease. Moreover, CTS may appear as the initial clinical manifestation of the disease [6-9],
Patients and Methods Sixteen patients (mean age 56.1 years. SD 17.1; sex ratio F/M 1.3; mean follow-up 4.3 years, SD 2.0) were admitted to our dermatology department between January 1986 and December 1990 with the diag nosis of systemic slcerosis. according to the ARA criteria [10]. They were all examined by the same clinician (L.V.). They had routine blood tests, antinuclear anti-SSa. anti-SSb. anti-centromere, and anti-
Received: Decem ber 3, 1991
Accepted: March 26. 1992
Scl 70 antibody determinations, chest X-ray, functional pulmonary tests, oesophageal manometry, skin biopsy, nailfold capillary micros copy, electrocardiography and echocardiography. The minimal crite rion for the clinical diagnosis of CTS was the description of paraesthesia of fingers innervated by the median nerve, aggravated by activity, orT in el'so r Phalen’s sign [11], When peripheral neurological abnor malities were detected at clinical examination, an electromyographic examination (EMG) was performed with a motor and sensory nerve conduction study. Prolongation of the median motor or sensory distal latency was the primary criterion for abnormality [11],
Results Acrosclerosis was present in all 16 patients. Raynaud’s phenomenon was present in 12, oesophageal involvement in 11, cutaneous calcification in 2, telangiectasia in 7 and xerostomia in 8 cases. The diffusing capacity for carbon monoxide was decreased ( 1/400) in 11 cases, with positive anti-Scl 70 antibodies in 3 cases, anti centromere antibodies in 1 case, anti-SSa antibodies in 1 case and anti-mitochondria antibodies in 1 case.
L. Machct Department of Dermatology CHU Trousseau F-37044 Tours (France)
© 1992 Kargcr AG. Basel 1018-8665/92/1852-0101 $ 2.75/0
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/3/2018 3:43:34 PM
Key Words Systemic sclerosis Carpal tunnel syndrome Neurological manifestations
Table 1. Main clinical and biological features of the 5 patients with scleroderma and neurological involvement
Patients
Time between neural signs and diagnosis of scleroderma Treatment Results
2
3
4
5
51 male + +
60 male + + +
80 female + + +
55 female + + +
-
-
-
-
+ 1:400
-
-
+
-
-
-
1:2,000
1:400 -
-
-
-
-
-
-
75
36
45
100
25
Carpal tunnel syndrome
Carpal tunnel syndrome
Carpal tunnel syndrome
Ulnar nerve compression
2 years before
Carpal tunnel syndrome VI cranial nerve palsy 3 years before
3 months before
0
17 years after
Surgical decompression Complete relief
Surgical decompression Complete relief
Local corticothcrapy Complete relief
Surgical decompression Complete relief
Local corticothcrapy Moderate improvement
Bilateral CTS was diagnosed clinically in 4 cases and confirmed by EMG in 2 of these (table l). For the remain ing 2 cases of CTS, EMG was not performed before surgi cal decompression. In these 2 patients, CTS had preceded the diagnosis of scleroderma by 2-3 years. Peripheral nerve compression occurred at the beginning of scleroderma in the 2 other cases. In another case, diagnosis of right ulnar nerve compression was made 17 years after the onset of scleroderma and confirmed by a decrease in motor and sen sory nerve conduction. The only other neurological com plication encountered in our patients was a paralysis of the Vlth cranial nerve, with normal CT scan and with no other cause than scleroderma. Complete relief of symptoms was obtained by surgical decompression of the median nerve in 3 cases. Pathological examination was possible in 2 cases and revealed synovial fibrosis in one, and a polymorphous inflammatory infiltrate around small vessels with fibrous involvement of the tendinous sheaths in other. In one case of CTS, and in the case of ulnar nerve compression, a clin ical amelioration was obtained by corticosteroid infiltra tion. This was confirmed by the normalisation of the EMG in l case.
102
-
56 female + + + +
-
-
Discussion In this study, neurological involvement is frequent: 5 patients among 16 presented nerve compression of the median or ulnar nerve at some point during the evolution of scleroderma. This high frequency might have been even greater if EMG had been carried out systematically [12], The physiopathology of scleroderma is still debated [ 13, 14], and the numerous proposed mechanisms could explain neurological abnormalities. The vascular hypothesis is sup ported by the frequency of Raynaud’s phenomenon, telan giectasia, and abnormality of the nailfold capillaries. These abnormalities could be due to an endothelial injury [14], There is also strong evidence for abnormal immune func tions. Various auto-antibodies are present in the disease. Deposits of immunoglobulins with a secondary activation of complement fractions could be the first event in endo thelial injury [13, 14], Abnormalities in the cellular response mediated by lymphocytes [14] or mast cells [15, 16] have been described, and may be a cause or a conse quence of the disease activity. Fibroblastic activity is stim ulated as a result of immune activation whatever the pri-
Machct/Vaillant/Machct/Estcvc/Mullcr/ Khallouf/Lorette
Carpal Tunnel Syndrome and Systemic Sclerosis
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/3/2018 3:43:34 PM
Age, years Sex Acrosclerosis Raynaud’s phenomenon Oesophageal involvement Calcinosis Telangiectasia Antinuclear antibodies Anti-centromere antibodies Anti-Scl 70 antibodies Diffusing capacity for carbon monoxyde. % expected value Neurological involvement
1
mary event may be: endothelial injury or immunocompe tent cellular dysregulation. Pathogenesis of neurological involvement in sclero derma may result both from a primary injury of vasa nervo rum or from perineural inflammation [17]. These mech anisms could explain the diffuse sensory neuropathies encountered in scleroderma [7]. However, the pathogen esis of neurological involvement in cases of CTS seems to be directly linked to fibrosis and to soft tissue oedema at the initial oedematous phase of the disease. Neural compres sion may occur more frequently at the carpal tunnel than at other sites because of the large amount of perineural con nective tissue relative to the funicular size of the median nerve [18]. Though trigeminal neuropathy is frequently reported 119], we did not observe this complication. Other reported neurological complications are mononeuritis mul tiplex. peripheral neuropathy, and cranial nerve involve ment [2, 4]. Our data arc consistent with a prospective study of 125 patients suffering from scleroderma: 4 cases of CTS and only 1 trigeminal neuralgia were observed [2], and the onset of CTS had also preceded the discovery of sclero
derma in 3 of the 4 cases, with a time interval of between 12 and 18 months. Some other reports have emphasized the occurrence of CTS in scleroderma [6-9]. In all of these cases, the CTS was discovered before the diagnosis of scle roderma. As in C IS . the trigeminal nerve compression may precede scleroderma by 1-12 months, and is more fre quent in CREST syndrome than in other subsets of scler oderma [11], In toxic oil syndrome, which at a chronic phase of evolution causes a scleroderma-like syndrome, 7% of the patients presented CTS [18]. The onset of mani festation occurred early in the disease, 1-17 months after the initial acute respiratory signs. The early and varied neu rological involvement in scleroderma and scleroderma-like syndromes needs careful examination, since neurological involvement appears to be frequent. This frequency is higher when systematic electrodiagnostic studies are done [12]. Among these complications, CTS is pre-eminent [2, 18], Because the onset of CTS may precede the clinical manifestations of scleroderma, we suggest a clinical follow up of ‘idiopathic’ CTS.
References 9 Ouinonc CA. Perry H. Rushton J: Carpal tun nel syndrome in dermatomyositis and sclero derma. Arch Dermatol 1966:94:21-25. 10 Masi AT. Rodnan GP. Medsger TA. Altman RD. D'Angelo WA. Fries JF. Leroy EC. Kirsncr AB. MacKcnzic H. MacShanc DJ. Myers AR, Sharp GC: Preliminary criteria for the classification of systemic sclerosis (sclero derma). Arthritis Rheum 1980:23:581-590. 11 Stevens JC. Sun S. Beard CM, O'Fallon WM. Kurland LT: Carpal tunnel syndrome in Rochester. Minnesota. 1961 to 1980. Neurol ogy 1988:38:134-138. 12 Christopher RP. Robinson H: Studies of nerve conduction in patients with scleroderma. South Med J 1972:65:668-672. 13 Majewski S. Blaszczyk M. Jablonska S. Rudnika L, Wasik M. Skicndziclewska A. Makiela B: Cytotoxic effects of sera from patients with systemic scleroderma: Comparison of three different in vitro methods. Rheumatol Int 1990:10:64-70. 14 Haustein UF. Herrmann K. Böhme HJ: Pathogenesis of progressive systemic sclerosis. Int J Dermatol 1986:25:286-293. 15 Claman HN: On scleroderma, mast cells, endothelial cells, and fibroblasts. JAMA 1989: 262:1206-1209.
16 Fonseca E. Soll J: Mast cell in the skin. Pro gressive systemic sclerosis and the toxic oil syn drome. Ann Intern Med 1989:102:864-865. 17 Di Trapani G . Tulli A. Lacara A. Lauriezo P. Mazza S. David P: Peripheral neuropathy in course of progressive systemic sclerosis. Acta Neuropathol (Berl) 1986:72:103-110. 18 Alonso-Ruiz A. Lciva-Santana C: Carpal tun nel syndrome in scleroderma-like syndromes. J Rheumatol 1985:12:1030. 19 Pain O. Guillevin !.. Giroux G. Royer I: Neu ropathie sensitive du trijumeau et scléroder mie. Rev Neurol (Paris) 1989:145:236-238.
103
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/3/2018 3:43:34 PM
1 Rocco VK. I lurd ER: Scleroderma and sclero derma-like disorders. Semin Arthritis Rheum 1986:16:22-69. 2 l.ce P. Bruni J: Sukcnik S: Neurological mani festation in systemic sclerosis. J Rheumatol 1984;11:480-483. 3 Gordon RM. Silvcrstcin A: Neurological mani festation in progressive systemic sclerosis. Arch Neurol 1970:22:126-133. 4 Teasdall RD. Fraya RA. Schumann LE: Cra nial involvement in scleroderma. A report of 10 cases. Medicine 1980:59:149-159. 5 Farcll DA. McdsgerTA: Trigeminal neuropa thy in progressive systemic sclerosis. Am J Med 1982:73:57-62. 6 Barr WG. Blair SJ: Carpal tunnel syndrome as the initial manifestation of scleroderma. J Hand Surg [Am] 1988:13a:378-380. 7 Bcrth-Jones J. Coates PA A. Graham-Brown RAC. Burns DA: Neurological complication of systemic sclerosis. A report of three cases and review of the literature. Clin Exp Derma tol 1990:15:91-94. 8 Sukcnik S. Abarbancl JM. Buskila D. Potashnik G. Horowitz J: Impotence, carpal tunnel syndrome and peripheral neuropathy as pre senting symptoms in progressive systemic scle rosis. J Rheumatol 1987:14:641-643.
