INVITED RE VIEW
Our experience and review of the literature reveal that Sjogren’s syndrome (SS) is an important, poorly recognized cause of peripheral neuropathy. Several forms of peripheral nerve dysfunction occur in SS including trigeminal sensory neuropathy, mononeuropathy multiplex, distal sensory neuropathy, distal sensorimotor peripheral neuropathy and a pure sensory neuronopathy syndrome. Rarely, chronic relapsing inflammatory polyneuropathy and multiple cranial neuropathies appear. Clinical evidence of glandular involvement is often minimal or absent when patients with SS develop peripheral neuropathy; and the diagnosis of the underlying condition is elusive. We review clinical and laboratory features of this disorder and suggest appropriate evaluation of patients with neuropathy and suspected SS. Key words: peripheral neuropathy Sjogren’s syndrome mononeuropathy multiplex distal polyneuropathy subacute sensory neuropathy MUSCLE 81 NERVE 13570-579 1990
INVITED REVIEW:
PERIPHERAL NEUROPATHY IN SJOGREN’S SYNDROME JERRY G. KAPLAN, MD, RICHARD ROSENBERG, MD, ELIZABETH REINITZ, MD, SHALOM BUCHBINDER, MD, and HERBERT H. SCHAUMBURG, MD
Peripheral nerve involvement is an important, underrecognized complication of Sjogren’s syndrome (SS). The peripheral nervous manifestations of SS are varied; minimal or no systemic or glandular abnormalities may accompany the neuropathy, and the diagnosis of the underlying condition is often missed. Our experience with 4 patients and review of the literature delineate the clinical spectrum of neuropathy in SS patients and suggest the clinical and laboratory evaluations appropriate for patients with neuropathy and suspected SS. CASE REPORTS
A 56-year-old women developed numbness and tingling of the left palm and first 3 digits in 1984. Left carpal tunnel release in 1985 failed to relieve the symp-
Case 1 (Yononeuropathy Multlplex).
From the Departments of Neurology, (Drs. Kaplan, Rosenberg, and Schaurnberg) Rheurnatology (Dr. Reinitz), and Radiology (Dr. Buchbinder), Albert Einstein College of Medicine, Bronx, New York. Address reprint requests to Dr. Schaurnburg, Department of Neurology, Albert Einstein College of Medicine of Yeshiva University, 1300 Morris Park Avenue, Bronx, NY 10461. Accepted for publication October 5, 1989 CCC 0148-639W90/070570-010 $04.00 0 1990 John Wiley & Sons, Inc.
570
Peripheral Neuropathy in Sjogren’s Syndrome
toms, and unpleasant paresthesias progressed to involve all the fingers on both hands accompanied by loss of dexterity. The symptoms remained more severe in the left hand but never involved the lower limbs. Because of these symptoms and a 35-pound weight loss associated with chronic diarrhea, she was seen by numerous medical and neurological consultants over the ensuing two years. Gastrointestinal investigations including upper and lower tract contrast studies revealed only a rectal polyp, which, on biopsy, was found to be benign without evidence of amyloid. Rheumatological evaluation disclosed a positive fluorescent antinuclear antibody (FANA) and positive rheumatoid factor by latex fixation. On our examination in September 1987, she complained of some mouth soreness and dryness on directed questioning but denied dry eyes. Physical examination revealed a thin woman without parotid gland enlargement or deforming arthritis. Neurological examination was remarkable for bilateral pupillary unresponsiveness to light with brisk response to the near reflex. There was minimal bilateral intrinsic hand muscle and tibialis anterior weakness. Sensory examination showed moderate distal loss to all modalities in the hands and a lesser degree of shading in the feet. All tendon reflexes were depressed, and the Romberg sign was absent.
MUSCLE & NERVE
July 1990
Electromyography and nerve conduction studies (EMG/NCS) were consistent with mononeuritis multiplex. Subsequent evaluation included a positive Schirmer test and a positive anti-R, antibody. Sialography was considered diagnostic of SS. Biopsy of a minor salivary gland revealed moderate lymphoplasmacytic interstitial infiltration. Serum levels of vitamin B, B,,, folic acid, and pyridoxine were normal. Sural nerve biopsy showed a mild axonopathy, as evidenced by clusters of thinly myelinated nerve fibers and a single nerve fiber on teased preparation containing myelin ovoids. Right quadriceps biopsy showed an inflammatory myopathy with type I1 fiber atrophy suggestive of a collagen vascular disease. There was no arteritis. Diarrhea responded well to oral pancreatin (microencapsulated pancreatic enzymes) and Synergyne (ox bile salts and enzymes). She refused treatment with corticosteroids. The paresthesias in the hands have stabilized and there has been no progression of weakness for the last 6 months. A 56-year-old woman slowly developed numbness and paresthesias of the feet which gradually spread to involve the legs and hands over several years. Xerostomia and xerophthalmia occurred 18 months after the onset of neuropathic symptoms. Neurologic examination was remarkable for impaired sensation of the hands and feet in a glove and stocking distribution involving all sensory modalities. There was mild gait ataxia and a mild sway on Rhomberg maneuver. Distal weakness was present in the feet. Test for rheumatoid factor, cryoglobulins, and antinuclear antibodies were negative. The patient refused therapy. Anti-R,, was positive. Nerve conduction and late response studies were consistent with distal axonopathy. Sural nerve biopsy showed severL loss of myelinated fibers. There was no evidence of demyelination or vasculitis.
Case 2 (Distal Polyneuropathy).
Case 3 (Subacute Sensory Neuronopathy Syndrome).
A 54-year-old woman developed profound sensory loss involving the left arm and both lower extremities over 6 months. Initial symptoms of lancinating extremity pain and paresthesias were rapidly followed by numbness, unsteady gait, poor balance and inability to use the left arm despite normal strength. Examination revealed anesthesia in the left arm and leg, profound sensory loss in
Peripheral Neuropathy in Sjogren's Syndrome
the right leg, and sparing of all sensory modalities in the right arm. Strength was normal throughout, there was severe pseudoathetosis in the left arm and leg and diffuse areflexia. Mental status and cranial nerve function were normal. Laboratory studies demonstrated positive antinuclear antibody and elevated sedimentation rate. The patient was treated with high-dose prednisone and plasmapheresis, and the neurologic status stabilized. The patient subsequently developed arthritis. When re-evaluated 6 years later, she was unchanged. Work-up at that time revealed positive antinuclear antibody, elevated sedimentation rate and positive anti-SSA. Case 4 (Mononeuropathy Multiplex). A 62-year-old woman experienced ocular and oral dryness over 3 years. A purpuric skin rash appeared over a 6week period. Skin biopsy revealed perivascular lymphocytic cuffing with necrosis of the arterial wall. The patient subsequently developed numbness of the hands which began in the median nerve distribution on the right and progressed to involve the hands and forearms to the elbows. Subsequently, she developed numbness of the toes. Examination revealed moderate sensory loss to all modalities in the upper limbs and mild shading in the feet. Weakness was mild and confined to the intrinsic hand muscles. Deep tendon reflexes were present throughout. Mental status, cranial nerves, and cerebellar functions were normal and no pathological reflexes were present. Clinical laboratory testing, including antinuclear antibody, rheumatoid factor, SMA-6 and SMA-12, immunoprotein electrophoresis, and levels of vitamins B,, and E were normal. The sedimentation rate was moderately elevated (45). AntiENA was negative. Salivary gland biopsy displayed glandular destruction and peri-acinar lymphocytic infiltration. Sural nerve biopsy revealed loss of myelinated fibers; a teased fiber preparation demonstrated secondary degeneration of myelin. Muscle biopsy showed changes of inflammatory myopathy with perivascular infiltration and muscle fiber degeneration. Treatment with prednisone resulted in amelioration of the rash; the'neuropathy is unchanged. DISCUSSION
Sjogren's syndrome (SS) is a chronic inflammatory disorder of exocrine glands which primarily affects middle-aged women; it is defined as a triad of keratoconjunctivitis sicca (dry eyes), xerostomia
MUSCLE & NERVE
July 1990
571
(dry mouth) and arthritis. Two of these features The are required to establish the sicca complex of ocular and oral dryness is the result of an autoimmune exocrinopathy characterized by lymphocytic and plasma cell infiltration of glandular structures; symptoms depend on the site of involvement. Ocular dryness, redness, pain, grittiness, or more rarely, decreased tearing are clinical features of keratoconjunctivitis sicca, the result of lacrimal gland involvement. Xerostomia, diminished saliva, difficulty with chewing and swallowing, oral fissures and dental caries is secondary to involvement of the major salivary glands. Primary or secondary forms exist, depending on the presence of other connective tissue diseases, especially rheumatoid arthritis (RA). Extraglandular involvement is common in SS and may overshadow the sicca syndrome or occur in the absence of glandular dysfunction. Frequently, there are signs and symptoms of reduced secretion in other mucosal surfaces including the respiratory, gastrointestinal, and genitourinary tracts. Patients may develop urinary tract infections, bronchitis or pneumonia (Asbury). Pancreatic involvement may result in malabsorption which responds to pancreatic enzymes (case 1). Many forms of peripheral nerve involvement may accompany SS, These are summarized in Table 1. Symmetric sensorimotor polyneuropathy is common,22(Tables 1 and 2), characterized by paresthesia and pain. Motor and autonomic complaints are infrequent; when present, they are mild12.22 (Tables 1 and 2). A distal, purely sensory neuropathy22 has also been defined in patients with Sjogren's syndrome. This may resemble distal sensorimotor neuropathy when clinical evidence of motor dysfunction is mild or absent; electrophysiological studies are usually required to make this distinction.22Both of these neuropathies are frequently accompanied by serologic abnormalities; approximately half will have elevated sedimentation rate, positive rheumatoid factor, or antinuclear antibody.22 Anti-SSB (La) or SSA (R,) antibodies are present in 29% to 46%, respectively.22 Sicca symptoms follow or occur simultaneously with the onset of neuropathy in about half of these Peripheral electrodiagnostic studies are quite sensitive; 88% show abnormalities of at least one nerve conduction study, usually decreased amplitude of a sensory nerve action potential. Electromyography shows neurogenic changes in 70%.22Nerve biopsy evidence of vasculitis is frequently present in these patients.6,22-2427 The sensory motor polyneuropa-
572
Peripheral Neuropathy in Sjogren's Syndrome
thy of Sjo ren's resembles other connective tissue diseases?. 2p27 Recently, a pure sensory neuronopathy syndrome (PSN) has been described in SS patient^.^^^^'^^'^^'^ PSN is characterized by paresthesias, and severe, global sensory loss.Y%i Sensory ataxia and pseudoathetosis are prominent and disablin features while motor function is Involvement may begin in the hands or feet, but frequently s reads to involve the extremities, trunk and face.'98,15 This differs from distal sensory neuropathy in its diffuse sensory loss with prominent proximal dermatomal involvement. Pure sensory neuronopathy displays great variability in its clinical course, from abrupt onset to indolent progression; approximately 40% of patients improve spontaneously. The pure sensory neuronopathy of Sjogren's syndrome can be differentiated from the idiopathic and paraneoplastic sensory neuronopathies that occur with ovarian and small cell lung carcinoma. As in other neuropathies associated with SS, the majority of patients are women. Pure sensory neuronopathy may be associated with prominent autonomic dysfuncti~n.~.'~ The recently described immune-mediated sensory neuropathy in patients with Sjogren's syndrome is most likely a variant of pure sensory neuronopathy." Pure sensory neuropathy in SS may be asymmetrical and patchy, in contrast with other PSN syndromes, which are usually diffuse. Carcinomatous sensory ganglionitis differs from the pure sensory neuronopathy of Sjogren's syndrome in its relentlessly progressive course, prominence of small fiber sensory loss, CSF pleocytosis, association with ocular motor and cerebellar involvement and b the presence of specific antiganglion antibodies.7 5
.5:
pa red.^^^*'^,''
Pure sensory neuropathy is accompanied by characteristic laboratory studies. Absent cranial and peripheral sensory evoked potentials are accompanied by normal motor nerve conduction, F response, and EMG studies (Table 3). Peripheral nerve biopsy shows severe fiber loss, frequently with perivascular inflammatory cell infiltrates, usually without evidence of vasc~litis.~,~ There is a mononuclear cell infiltration of the dorsal root ganglia (DRG), similar to that seen on salivary gland biopsy." Pure sensory neuropathy tends to occur early in the course of SS, may antedate clinical glandular involvement and serologic abnormalities may be absent.6 Patients with progressive sensory neuronopathy often demonstrate mild and subtle manifestations of the sicca syndrome. These fea-
MUSCLE & NERVE
July 1990
I cn
Y
c
c
rn
Our experience and review of the literature reveal that Sjogren’s syndrome (SS) is an important, poorly recognized cause of peripheral neuropathy. Several forms of peripheral nerve dysfunction occur in SS including trigeminal sensory neuropathy, mononeuropathy multiplex, distal sensory neuropathy, distal sensorimotor peripheral neuropathy and a pure sensory neuronopathy syndrome. Rarely, chronic relapsing inflammatory polyneuropathy and multiple cranial neuropathies appear. Clinical evidence of glandular involvement is often minimal or absent when patients with SS develop peripheral neuropathy; and the diagnosis of the underlying condition is elusive. We review clinical and laboratory features of this disorder and suggest appropriate evaluation of patients with neuropathy and suspected SS. Key words: peripheral neuropathy Sjogren’s syndrome mononeuropathy multiplex distal polyneuropathy subacute sensory neuropathy MUSCLE 81 NERVE 13570-579 1990
INVITED REVIEW:
PERIPHERAL NEUROPATHY IN SJOGREN’S SYNDROME JERRY G. KAPLAN, MD, RICHARD ROSENBERG, MD, ELIZABETH REINITZ, MD, SHALOM BUCHBINDER, MD, and HERBERT H. SCHAUMBURG, MD
Peripheral nerve involvement is an important, underrecognized complication of Sjogren’s syndrome (SS). The peripheral nervous manifestations of SS are varied; minimal or no systemic or glandular abnormalities may accompany the neuropathy, and the diagnosis of the underlying condition is often missed. Our experience with 4 patients and review of the literature delineate the clinical spectrum of neuropathy in SS patients and suggest the clinical and laboratory evaluations appropriate for patients with neuropathy and suspected SS. CASE REPORTS
A 56-year-old women developed numbness and tingling of the left palm and first 3 digits in 1984. Left carpal tunnel release in 1985 failed to relieve the symp-
Case 1 (Yononeuropathy Multlplex).
From the Departments of Neurology, (Drs. Kaplan, Rosenberg, and Schaurnberg) Rheurnatology (Dr. Reinitz), and Radiology (Dr. Buchbinder), Albert Einstein College of Medicine, Bronx, New York. Address reprint requests to Dr. Schaurnburg, Department of Neurology, Albert Einstein College of Medicine of Yeshiva University, 1300 Morris Park Avenue, Bronx, NY 10461. Accepted for publication October 5, 1989 CCC 0148-639W90/070570-010 $04.00 0 1990 John Wiley & Sons, Inc.
570
Peripheral Neuropathy in Sjogren’s Syndrome
toms, and unpleasant paresthesias progressed to involve all the fingers on both hands accompanied by loss of dexterity. The symptoms remained more severe in the left hand but never involved the lower limbs. Because of these symptoms and a 35-pound weight loss associated with chronic diarrhea, she was seen by numerous medical and neurological consultants over the ensuing two years. Gastrointestinal investigations including upper and lower tract contrast studies revealed only a rectal polyp, which, on biopsy, was found to be benign without evidence of amyloid. Rheumatological evaluation disclosed a positive fluorescent antinuclear antibody (FANA) and positive rheumatoid factor by latex fixation. On our examination in September 1987, she complained of some mouth soreness and dryness on directed questioning but denied dry eyes. Physical examination revealed a thin woman without parotid gland enlargement or deforming arthritis. Neurological examination was remarkable for bilateral pupillary unresponsiveness to light with brisk response to the near reflex. There was minimal bilateral intrinsic hand muscle and tibialis anterior weakness. Sensory examination showed moderate distal loss to all modalities in the hands and a lesser degree of shading in the feet. All tendon reflexes were depressed, and the Romberg sign was absent.
MUSCLE & NERVE
July 1990
Electromyography and nerve conduction studies (EMG/NCS) were consistent with mononeuritis multiplex. Subsequent evaluation included a positive Schirmer test and a positive anti-R, antibody. Sialography was considered diagnostic of SS. Biopsy of a minor salivary gland revealed moderate lymphoplasmacytic interstitial infiltration. Serum levels of vitamin B, B,,, folic acid, and pyridoxine were normal. Sural nerve biopsy showed a mild axonopathy, as evidenced by clusters of thinly myelinated nerve fibers and a single nerve fiber on teased preparation containing myelin ovoids. Right quadriceps biopsy showed an inflammatory myopathy with type I1 fiber atrophy suggestive of a collagen vascular disease. There was no arteritis. Diarrhea responded well to oral pancreatin (microencapsulated pancreatic enzymes) and Synergyne (ox bile salts and enzymes). She refused treatment with corticosteroids. The paresthesias in the hands have stabilized and there has been no progression of weakness for the last 6 months. A 56-year-old woman slowly developed numbness and paresthesias of the feet which gradually spread to involve the legs and hands over several years. Xerostomia and xerophthalmia occurred 18 months after the onset of neuropathic symptoms. Neurologic examination was remarkable for impaired sensation of the hands and feet in a glove and stocking distribution involving all sensory modalities. There was mild gait ataxia and a mild sway on Rhomberg maneuver. Distal weakness was present in the feet. Test for rheumatoid factor, cryoglobulins, and antinuclear antibodies were negative. The patient refused therapy. Anti-R,, was positive. Nerve conduction and late response studies were consistent with distal axonopathy. Sural nerve biopsy showed severL loss of myelinated fibers. There was no evidence of demyelination or vasculitis.
Case 2 (Distal Polyneuropathy).
Case 3 (Subacute Sensory Neuronopathy Syndrome).
A 54-year-old woman developed profound sensory loss involving the left arm and both lower extremities over 6 months. Initial symptoms of lancinating extremity pain and paresthesias were rapidly followed by numbness, unsteady gait, poor balance and inability to use the left arm despite normal strength. Examination revealed anesthesia in the left arm and leg, profound sensory loss in
Peripheral Neuropathy in Sjogren's Syndrome
the right leg, and sparing of all sensory modalities in the right arm. Strength was normal throughout, there was severe pseudoathetosis in the left arm and leg and diffuse areflexia. Mental status and cranial nerve function were normal. Laboratory studies demonstrated positive antinuclear antibody and elevated sedimentation rate. The patient was treated with high-dose prednisone and plasmapheresis, and the neurologic status stabilized. The patient subsequently developed arthritis. When re-evaluated 6 years later, she was unchanged. Work-up at that time revealed positive antinuclear antibody, elevated sedimentation rate and positive anti-SSA. Case 4 (Mononeuropathy Multiplex). A 62-year-old woman experienced ocular and oral dryness over 3 years. A purpuric skin rash appeared over a 6week period. Skin biopsy revealed perivascular lymphocytic cuffing with necrosis of the arterial wall. The patient subsequently developed numbness of the hands which began in the median nerve distribution on the right and progressed to involve the hands and forearms to the elbows. Subsequently, she developed numbness of the toes. Examination revealed moderate sensory loss to all modalities in the upper limbs and mild shading in the feet. Weakness was mild and confined to the intrinsic hand muscles. Deep tendon reflexes were present throughout. Mental status, cranial nerves, and cerebellar functions were normal and no pathological reflexes were present. Clinical laboratory testing, including antinuclear antibody, rheumatoid factor, SMA-6 and SMA-12, immunoprotein electrophoresis, and levels of vitamins B,, and E were normal. The sedimentation rate was moderately elevated (45). AntiENA was negative. Salivary gland biopsy displayed glandular destruction and peri-acinar lymphocytic infiltration. Sural nerve biopsy revealed loss of myelinated fibers; a teased fiber preparation demonstrated secondary degeneration of myelin. Muscle biopsy showed changes of inflammatory myopathy with perivascular infiltration and muscle fiber degeneration. Treatment with prednisone resulted in amelioration of the rash; the'neuropathy is unchanged. DISCUSSION
Sjogren's syndrome (SS) is a chronic inflammatory disorder of exocrine glands which primarily affects middle-aged women; it is defined as a triad of keratoconjunctivitis sicca (dry eyes), xerostomia
MUSCLE & NERVE
July 1990
571
(dry mouth) and arthritis. Two of these features The are required to establish the sicca complex of ocular and oral dryness is the result of an autoimmune exocrinopathy characterized by lymphocytic and plasma cell infiltration of glandular structures; symptoms depend on the site of involvement. Ocular dryness, redness, pain, grittiness, or more rarely, decreased tearing are clinical features of keratoconjunctivitis sicca, the result of lacrimal gland involvement. Xerostomia, diminished saliva, difficulty with chewing and swallowing, oral fissures and dental caries is secondary to involvement of the major salivary glands. Primary or secondary forms exist, depending on the presence of other connective tissue diseases, especially rheumatoid arthritis (RA). Extraglandular involvement is common in SS and may overshadow the sicca syndrome or occur in the absence of glandular dysfunction. Frequently, there are signs and symptoms of reduced secretion in other mucosal surfaces including the respiratory, gastrointestinal, and genitourinary tracts. Patients may develop urinary tract infections, bronchitis or pneumonia (Asbury). Pancreatic involvement may result in malabsorption which responds to pancreatic enzymes (case 1). Many forms of peripheral nerve involvement may accompany SS, These are summarized in Table 1. Symmetric sensorimotor polyneuropathy is common,22(Tables 1 and 2), characterized by paresthesia and pain. Motor and autonomic complaints are infrequent; when present, they are mild12.22 (Tables 1 and 2). A distal, purely sensory neuropathy22 has also been defined in patients with Sjogren's syndrome. This may resemble distal sensorimotor neuropathy when clinical evidence of motor dysfunction is mild or absent; electrophysiological studies are usually required to make this distinction.22Both of these neuropathies are frequently accompanied by serologic abnormalities; approximately half will have elevated sedimentation rate, positive rheumatoid factor, or antinuclear antibody.22 Anti-SSB (La) or SSA (R,) antibodies are present in 29% to 46%, respectively.22 Sicca symptoms follow or occur simultaneously with the onset of neuropathy in about half of these Peripheral electrodiagnostic studies are quite sensitive; 88% show abnormalities of at least one nerve conduction study, usually decreased amplitude of a sensory nerve action potential. Electromyography shows neurogenic changes in 70%.22Nerve biopsy evidence of vasculitis is frequently present in these patients.6,22-2427 The sensory motor polyneuropa-
572
Peripheral Neuropathy in Sjogren's Syndrome
thy of Sjo ren's resembles other connective tissue diseases?. 2p27 Recently, a pure sensory neuronopathy syndrome (PSN) has been described in SS patient^.^^^^'^^'^^'^ PSN is characterized by paresthesias, and severe, global sensory loss.Y%i Sensory ataxia and pseudoathetosis are prominent and disablin features while motor function is Involvement may begin in the hands or feet, but frequently s reads to involve the extremities, trunk and face.'98,15 This differs from distal sensory neuropathy in its diffuse sensory loss with prominent proximal dermatomal involvement. Pure sensory neuronopathy displays great variability in its clinical course, from abrupt onset to indolent progression; approximately 40% of patients improve spontaneously. The pure sensory neuronopathy of Sjogren's syndrome can be differentiated from the idiopathic and paraneoplastic sensory neuronopathies that occur with ovarian and small cell lung carcinoma. As in other neuropathies associated with SS, the majority of patients are women. Pure sensory neuronopathy may be associated with prominent autonomic dysfuncti~n.~.'~ The recently described immune-mediated sensory neuropathy in patients with Sjogren's syndrome is most likely a variant of pure sensory neuronopathy." Pure sensory neuropathy in SS may be asymmetrical and patchy, in contrast with other PSN syndromes, which are usually diffuse. Carcinomatous sensory ganglionitis differs from the pure sensory neuronopathy of Sjogren's syndrome in its relentlessly progressive course, prominence of small fiber sensory loss, CSF pleocytosis, association with ocular motor and cerebellar involvement and b the presence of specific antiganglion antibodies.7 5
.5:
pa red.^^^*'^,''
Pure sensory neuropathy is accompanied by characteristic laboratory studies. Absent cranial and peripheral sensory evoked potentials are accompanied by normal motor nerve conduction, F response, and EMG studies (Table 3). Peripheral nerve biopsy shows severe fiber loss, frequently with perivascular inflammatory cell infiltrates, usually without evidence of vasc~litis.~,~ There is a mononuclear cell infiltration of the dorsal root ganglia (DRG), similar to that seen on salivary gland biopsy." Pure sensory neuropathy tends to occur early in the course of SS, may antedate clinical glandular involvement and serologic abnormalities may be absent.6 Patients with progressive sensory neuronopathy often demonstrate mild and subtle manifestations of the sicca syndrome. These fea-
MUSCLE & NERVE
July 1990
I cn
Y
c
c
rn
