CASE REPORT

Polyneuropathy as Initial Manifestation of Systemic Sclerosis(Scleroderma)

S. Knupp-Oliveira1 and M. Matucci Cerinic2

1Department of Pediatrics, Division of Pediatric Rheumatology, Universidade Federal do Rio de Janeiro, Brasil, 2Department of Medicine,Division of Rheumatology, University of Florence, Italy

We report the ®rst case of a young female patient who developed a sensory-motor polyneuropathy, without any skin or internal involvement

characteristic of SSc, but with a serological positivity of antitopoisomerase I antibodies. After 4 years she developed a rapid skin tightening

with lung involvement, in a full blown picture of the diffuse subset of SSc. The case suggests that the peripheral nervous system deserves

more attention, in particular in the earliest phase of SSc.

Key words: systemic sclerosis, polyneuropathy

The clinical features of the involvement of theperipheral nervous system (PNS) in systemic sclero-sis (SSc) are well known (1) and have been recentlydescribed as subclinical in the early phase of thedisease (2, 3). In some cases, the onset of the diseasehas been characterized by a trigeminal neuropathy ora carpal tunnel syndrome entrapment (see Table I).We report, for the ®rst time, an overt polyneuro-pathy as the onset symptom of SSc.

Case report

A 21 year old female patient came to our observa-tion in June 1993 for numbness, swelling, and pain inthe feet. Her hematological analyses were all normal,serum cobalamine included. Pain was controlledwith NSAIDs and analgesics, but swelling was stillpresent after 45 days from the beginning of thetherapy. In September, she experienced itch andnumbness in her right hand followed by total loss ofsensitivity in her ®ngertips. In addition she com-plained about symptoms of a mild depression andfor this reason she was put on bromazepan(benzodiazepine, tranquilizer, and hypnotic) andamitryptilin (tryciclic antidepressant). Electromyo-graphy showed a reduction of Sensory NeuralAction Potentials of the median, ulnar, and suralnerves and a sensory polyneuropathy of unknowncause was diagnosed. The liquoral ¯uid analysis andthe whole hematologic pro®le were normal butantinuclear autoantibodies proved positive 1 : 100(speckled) and anti topoisomerase I were positive.The patient refused esophageal manometry and

nerve biopsy. Barium enhanced x-ray, lung highresolution tomography, and pulmonary functiontests were normal. After 4 months she started tocomplain of Raynaud's phenomenon (RP) attacks inher hands and feet and for hand tremors. Scler-oderma was suspected even if no skin and lunginvolvement was evident. She was put on prednisone30 mg/day and bu¯omedil (300 mg/day) (increaseintracellular cAMP secondary to adenyl-cyclasestimulation, vasodilator) and a reduction of RPattacks was obtained in a few days. The tremorswere treated with biperiden (atropine-like action,usually effective in controlling Parkinson, spasticityand muscular incoordination) without any realimprovement. Prednisone was progressively taperedto 5 mg/day until withdrawal. In January 94 shedeveloped a numbness of the chins: the blink re¯exwas positive and a diagnosis of trigeminal involve-ment was made. This event was followed by a totalloss of acral sensitivity of both upper and lowerlimbs with dif®culty in writing, working, andwalking. Prednisone was increased to 20 mg/dayand in February her ®ngertip sensitivity improved.In April she partially recovered her handwriting,walking up to 200 meters but the numbness of thetrigeminal nerve was still present. She was then notseen until September 1997 when she came backbecause she had experienced in the previous monthsan abrupt and rapid tightening of the skin that brokeout diffusely over the extremities and trunk.According to LeRoy et al, a diagnosis of diffusecutaneous scleroderma was made (4). This time, theprevious symptoms of polyneuropathy were absent,HRCT of the lung showed a mild ground glass at thelower lobes of both lungs while the pulmonaryfunction tests were normal. Unfortunately, after thisvisit she had not been see by us.

Marco Matucci Cerinic, via P. Thouar 18, I-50122 Firenze, Italy

Received 22 December 1998

Accepted 3 March 1999

Scand J Rheumatol 1999;28:260±1

260 # 1999 Scandinavian University Press on license from Scandinavian Rheumatology Research Foundation

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Discussion

Peripheral neuropathy with mixed sensory and

motor involvement has been described in a few

cases during the disease evolution (1). This is the ®rst

report of polyneuropathy as the opening symptom of

a diffuse SSc. Previously, the carpal tunnel syndrome

and sensory neuropathy of the trigeminal nerve have

been described as the starting symptoms, in parti-

cular in the limited form of the disease (1). Our

patient developed a trigeminal neuropathy over-

lapping the full blown clinical picture of polyneuro-

pathy. The patient developed also depressive

symptoms that may sometimes accompany the overt

clinical picture of SSc (5) but which has never been

described as an initial feature of the disease.

However, in our case, depression might more likely

be a reactive condition to the distress provoked by

the loss of daily and working capabilities.Swelling and itching, present at the beginning of

the disease, may be due to the early skin involvement

and in particular to mastcells activation. In the skin,

mast cells are responsible for itching (6) through the

release of substances that is induced by neuropep-

tides- derived from activated sensory nerve terminals

(7) ± and that mainly contributes to in¯ammatory

processes (8). In our case, swelling and itching in the

early phase of the disease might be dependent upon

both skin involvement and the involvement of the

sensory system, respectively.

In SSc, it has been suggested that the vasomotorinstability of RP may be due to a nerve dysfunctionthat may thus in¯uence the disease development (9).It is noteworthy that, in this case, neuropathy startednot only before skin and internal involvement butalso before RP. Usually, in the limited form of thedisease, the ®rst sentinel symptom is RP which maypreceed with several years the disease onset, while, inthe diffuse subset, RP onset and the disease startalmost simultaneously. Therefore, our case indicatesthat polyneuropathy may be one of the startingsymptoms of a diffuse SSc, preceeding both RP andthe disease development.

In this case, amytriptiline was unsuccessful incontrol of neuropathy despite the previous report ofits ef®cacy in the management of polyneuropathy inSSc (10). Only steroids induced a partial remission ofthe symptoms. In the future, a treatment targetingthe nervous system, in the early phase of the disease,may become a pivotal need in order to modify theprogression of the involvement of the sensory andautonomic nervous system.

Further studies are needed to understand the rolethat the involvement of the nervous system plays inthe development, progression, and maintenance ofSSc.

References

1. Matucci-Cerinic M, Generini S, Pignone A, Casale R. The

nervous system in systemic sclerosis: clinical and pathogene-

tical features. Rheum Dis Clin North Am 1996;22:789 ± 96.

2. Mondelli M, Romano C, Della Porta PD, Rossi A.

Electrophysiological evidence of nerve entrapment syndromes

and subclinical peripheral neuropathy in progressive systemic

sclerosis. J Neurol 1995;242:185 ± 94.

3. Lori S, Matucci-Cerinic M, Casale R, et al. Canalicolar

syndromes in systemic sclerosis (scleroderma): the wrist as a

target structure. Clin Exp Rheumatol 1996;14:601 ± 5.

4. LeRoy EC, Black CM, Fleischmajer R, Jablonska S, Krieg T,

Medsger TA Jr, et al. Scleroderma (systemic sclerosis):

Classi®cation, subsets and pathogenesis. J Rheumatol

1988;15:202 ± 5.

5. Roca RP, Wigley FM, White B. Depressive symptoms

associated with scleroderma. Arthritis Rheum

1996;39:1035 ± 40.

6. Greaves MW, Wall PD. Pathophysiology of itch. Lancet

1996;348:938 ± 40.

7. Hagermark O, Hokfelt T, Pernow B. Flare and itch induced

by substance P in human skin. J Invest Dermatol

1978;71:233 ± 5.

8. Bienenstock J, Tomioka M, Matsuda H, Stead HR, Quinonez

G, Simon GT, et al. The role of mast cells in in¯ammatory

processes: evidence for nerve/mast cell interaction, Int Archs

Allergy Appl Immun 1987;82:238 ± 43.

9. Kahaleh BM, Matucci-Cerinic M. Raynaud's phenomenon

and scleroderma: dysregulated neuroendothelial control of

vascular tone. Arthritis Rheum 1995;38:1 ± 4.

10. Bondavalli P, Parodi A, Rebora A. Peripheral neuropathy in

scleroderma successfully treated with amitryptiline. Int J

Dermatol 1997;36:234 ± 5.

Table I. Literature describing median nerve involvement as theonset symptom of SSc.

author cases reference

Grossman LA 1 JAMA 1961;176:259 ± 261Barr WG, et al 2. J Hand Surg (Am)

1988;13a:378 ± 381.Machet L, et al 2 Dermatology 185: 101, 1992.Gonzalez-Alvaro I, 1 Ann Rheum Dis

et al 1995;54:782 ± 783Sukenik S, et al 1 J Rheumatol 1987;14:641 ± 642.Quinones CA, et al 1 Arch Dermatol 1996;94:21 ± 23.

Literature describing trigeminal neuropathy as the onsetsymptom of SSc

author cases reference

Beighton P, et al 1 Ann Rheum Dis1968;27:367 ± 369.

Casey EB et al 1 Rheumatol Phys Med1971,11,131 ± 3

Thompson PD, et al 1 J Maine Med Assoc1973;64:123 ± 4

Burke MJ, et al 3 Postgrad Med J 1979;55:423 ± 427.Ferroir JP 1 Presse Med 1984,13,2153Heald A 1 J Neurol Neurosurg Psychiatr

1989;52:918 ± 22.

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