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Autonomic Failure and Proximal Skeletal Myopathy in a Patient With Primary Sjögren Syndrome

      Autonomic failure and proximal skeletal myopathy are rare features of the Sjögren syndrome (SS). We describe a 51-year-old woman with primary SS who had development of esophageal dysmotiIity, urinary retention, severe orthostatism, and skeletal myopathy during a 3-month period after the diagnosis of SS. Her symptoms and signs responded well to corticosteroid therapy. Although dysfunction of the peripheral nervous system has a prevalence rate of 20% in patients with SS, most commonly the nerve dysfunction is a sensory deficit, and autonomic neuropathy is less frequent. Autonomic neuropathy due to SS may be underreported. The cause of our patient's myopathy remains undetermined. We speculate that the myopathy was due to either a form of polymyositis or an immunemediated neuropathy with muscle involvement.
      SS (Sjögren syndrome)
      Peripheral nervous system involvement is well recognized in patients with the Sjögren syndrome (SS). The deficit is usually neurosensory, and documentation of auto nomic neuropathy is rare. We describe a case of primary SS associated with generalized autonomic failure and proximal skeletal myopathy. Our report highlights the systemic nature of SS and emphasizes the importance of considering this syndrome in evaluations of idiopathic autonomic neuropathy.

      Report Of A Case

      Nine months before hospital admission, a previously healthy 51-year-old woman began to experience dysphagia when eating solid foods; this impairment progressed in severity and was associated with intermittent symptoms of dry eyes and dry mouth. On hospital admission, she was suffering from persistent postprandial nausea and vomiting and had a 27 -kg weight loss. One month before admission, pronounced proximal muscular weakness had progressed until she was unable to raise her head or arise from bed without assistance. This weakness was associated with progressive dysarthria and dyspnea.
      Videoesophagography demonstrated a collection of contrast medium in the oropharynx, which was aspirated without progression to peristalsis. Findings on an endoscopic evaluation of the esophagus and stomach were normal. A percutaneous endoscopic gastric tube was placed for enteral nutrition. By this time, the patient also had severe urinary retention, with postvoid residual urine volumes ranging from 300 to 900 mL. Quantitative sudomotor axon reflex testing demonstrated completely absent sudomotor responses, as well as poor variability in heart rate with respiration and the Val salva maneuver; after the patient had been on the tilt table for 2 minutes, her blood pressure decreased from 130/80 mm Hg to 50/36 mm Hg without compensatory tachycardia. Laboratory tests yielded the following results (reference ranges shown par enthetically): rheumatoid factor, 185 IU/mL (0-39 IU/mL); antinuclear antibody, 1:320, speckled pattern; anti-SSA antibody, 205.8 U (<26 U); and anti-SSB antibody, 233.5 U (<26 U). A polyclonal gammopathy was present; the γ globulin value was 3.05 g/dL (0.7-1.7 g/dL). Rose bengal corneal staining was positive. A lip biopsy specimen showed plasma cell and lymphocytic infiltration of salivary glands, with a focus score of 2, characteristic of SS. Electromyography revealed proximal fibrillation potentials consistent with myositis and findings of modest denervation atrophy. Nerve conduction studies demonstrated low action potential amplitude of the right ulnar compound muscle. Repetitive stimulation of the right peroneal and ulnar nerves disclosed normal findings. A muscle biopsy specimen of the left triceps revealed changes suggestive of a denervating process without evidence of inflammation or necrosis. Special staining for enzyme activity showed no evidence of an abnormality other than extremely rare cytochromic c oxidase-negative fibers, which were too infrequent to diagnose a mitochondrial myopathy. Results of the following tests were normal: complete blood cell count;
      electrolyte, thyroid-stimulating hormone, angiotensin-converting enzyme, aldolase, hemoglobin Ale’ creatine kinase, vitamin B12, and complement levels; and erythrocyte sedimentation rate. Results of tests for antineuronal, antiacetylcholine receptor, striated muscle, and anticalcium channel antibodies were all negative, as were anti-UI-RNP, anti Jo1, anti-Scl-70, and anti-Sm.
      After a videotaped functional assessment, methylprednisolone sodium succinate (1 g/d for 3 days) was given, followed by prednisone (60 mg/d). Within 2 days, the dysarthria, dyspnea, orthostatism, and muscular weakness had dramatically improved. After 6 weeks of treatment, the patient was able to sit and stand without assistance. Symptoms of dysarthria and sicca syndrome resolved. At 2-year follow-up, the patient felt well except for symptoms of dry mouth and dry eyes. She was taking prednisone, 6 mg/d, and hydroxychloroquine, 200 mg twice a day. Her muscle strength, swallowing, appetite, bladder function, and blood pressure were normal.

      Discussion

      SS is an autoimmune disorder of the exocrine glands that is classically linked to symptoms of keratoconjunctivitis sicca and xerostomia. In patients with SS, peripheral neuropathy, most commonly manifesting as paresthesias, has a prevalence rate of 21.7%.
      • Gemignani F
      • Marbini A
      • Pavesi G
      • et al.
      Peripheral neuropathy associated with primary Sjögren's syndrome.
      Peripheral neuropathy is more common than the sicca syndrome as the initial symptom in patients with neuropathic involvement.
      • Gemignani F
      • Marbini A
      • Pavesi G
      • et al.
      Peripheral neuropathy associated with primary Sjögren's syndrome.
      In fact, neuropathic dysfunction may precede sicca symptoms by a median interval of 24 months
      • MeUgren SI
      • Conn DL
      • Sievcns JC
      • Dyck PJ
      Peripheral neuropathy in primary Sjögren's syndrome.
      and may dominate the clinical picture.
      • Kaplan JG
      • Rosenberg R
      • Reinitz E
      • Buchbinder S
      • Schaumberg HH
      Invited review; peripheral neuropathy in Sjögren's syndrome.
      • Andonopoulos AP
      • Ballas C
      Autonomie cardiovascular neuropathy in primary Sjögren's syndrome.
      In patients with peripheral neuropathy of SS, autonomic involvement has a prevalence rate of 6.3%,
      • MeUgren SI
      • Conn DL
      • Sievcns JC
      • Dyck PJ
      Peripheral neuropathy in primary Sjögren's syndrome.
      although the prevalence of subclinical autonomic insufficiency may be much higher. Testing for nerve dysfunction in small nerve fibers (autonomic nerves) may be more sensitive than in large nerve fibers in patients with this syndrome.
      • Denislic M
      • Meh D
      Neurophysiological assessment of peripheral neuropathy in primary Sjögren's syndrome.
      • Denislic M
      • Meh D
      • Popovic M
      • Kos-Golja M
      Small nerve fibre dysfunction in a patient with Sjögren's syndrome: neurophysiological and morphological confirmation.
      The current case clearly supports this possibility and emphasizes the importance of considering SS in cases of idiopathic autonomic neuropathy.
      The cause of SS is poorly understood, although autoimmune T cells are central to the pathogenesis.
      • Fox RI
      Sjögren's syndrome: controversies and progress.
      Electron microscopy of the sural nerve in patients with SS has revealed severe damage of unmyelinated fibers consistent with small nerve fiber damage.
      • Denislic M
      • Meh D
      • Popovic M
      • Kos-Golja M
      Small nerve fibre dysfunction in a patient with Sjögren's syndrome: neurophysiological and morphological confirmation.
      Investigators have suggested that the neuropathy, including the autonomic cardiovascular neuropathy with orthostasis, is due to a vasculitic mechanism.
      • Andonopoulos AP
      • Ballas C
      Autonomie cardiovascular neuropathy in primary Sjögren's syndrome.
      The most common manifestations of autonomic dysfunction in SS are anhidrosis, cardiac parasympathetic dysfunction, and the Adie syndrome.
      • Kaplan JG
      • Rosenberg R
      • Reinitz E
      • Buchbinder S
      • Schaumberg HH
      Invited review; peripheral neuropathy in Sjögren's syndrome.
      Autonomic failure without sensory or peripheral motor deficits predominated in our patient. Other than the dysarthria, cranial nerve function was normal. She had no evidence of central nervous system disease or family history of similar neurologic disease. Physical examination revealed no sensory or trophic changes, and electromyography demonstrated no selective involvement of sensory pathways. No secondary causes of autonomic neuropathy were detected, such as diabetes mellitus, in which low tear production has been associated with autonomic neuropathy.
      • Ramos-Remus C
      • Suarez-Almazor M
      • Russell AS
      Low tear production in patients with diabetes mellitus is not due to Sjögren's syndrome.
      The pathophysiology of the myopathy in our patient remains undefined. Despite extensive investigation, no evidence of malignancy, myasthenia gravis, inclusion body myositis, dermatomyositis, immunodeficiency, or other suspected abnormalities was found. We speculate that the myopathy was due to either a form of polymyositis, which has a prevalence rate of 3% in patients with SS,
      • Kraus A
      • Cifucnlcs M
      • Villa AR
      • Jakez J
      • Reyes E
      • Alarcon-Segovia D
      Myositis in primary Sjögren's syndrome: report of 3 cases.
      or an immune-mediated neuropathy with muscle involvement. In 10% of patients with polymyositis, findings on a muscle biopsy are normal.
      • Tandan R
      • Bradley WG
      Dermatomyositis and polymyositis.
      A review of 26 patients with concomitant SS and polymyositis revealed several features resembling those of our patient: mean age of onset was 51.4 years for both disorders, the onset of each disorder occurred within 8 months of the other, creatine kinase levels were low or only moderately increased, and all patients had proximal muscle weakness that responded to corticosteroids.
      • Gran JT
      • Myklebust G
      The concomitant occurrence of Sjögren's syndrome and polymyositis.
      Possibly, our patient had only primary SS with secondary muscle involvement. Certainly, the electromyographic and muscle biopsy findings were consistent with this hypothesis. A similar case report suggested that lymphocytic infiltration of the pulmonary stretch receptors in the nodose ganglion can lead to dyspnea.
      • McCombe PA
      • Shcean GL
      • McLaughlin DB
      • Pender MP
      Vestibu-lar and ventilatory dysfunction in sensory and autonomie neuropathy associated with primary Sjögren's syndrome [letter].
      Because the causes of both SS and polymyositis are undetermined, drawing conclusions based on either model is difficult.
      Extraglandular involvement in SS may overshadow the classic symptoms of the sicca complex, particularly if neuropathic abnormalities coexist. Autonomic dysfunction is a rare feature of SS; however, it may be underreported. SS should be considered in patients with idiopathic autonomic neuropathy. Early treatment with corticosteroids may be of benefit, as in our patient, and other therapies including cytotoxic agents and immunoglobulin may also be useful.
      • Molina JA
      • Bcnito-Lcon J
      • Bermejo F
      • Jimenez-Jimenez FJ
      • Olivan J
      Intravenous immunoglobulin therapy in sensory neuropathy associated with Sjögren's syndrome [letter].
      Further investigation of the pathophysiology, natural history, and treatment of this condition is needed.

      References

        • Gemignani F
        • Marbini A
        • Pavesi G
        • et al.
        Peripheral neuropathy associated with primary Sjögren's syndrome.
        J Neurol Neurosurg Psychiatry. 1994; 57: 983-986
        • MeUgren SI
        • Conn DL
        • Sievcns JC
        • Dyck PJ
        Peripheral neuropathy in primary Sjögren's syndrome.
        Neurology. 1989; 39: 390-394
        • Kaplan JG
        • Rosenberg R
        • Reinitz E
        • Buchbinder S
        • Schaumberg HH
        Invited review; peripheral neuropathy in Sjögren's syndrome.
        Muscle Nerve. 1990; 13: 570-579
        • Andonopoulos AP
        • Ballas C
        Autonomie cardiovascular neuropathy in primary Sjögren's syndrome.
        Rheumatnl Int. 1995; 15: 127-129
        • Denislic M
        • Meh D
        Neurophysiological assessment of peripheral neuropathy in primary Sjögren's syndrome.
        Clin Investig. 1994; 72: 822-829
        • Denislic M
        • Meh D
        • Popovic M
        • Kos-Golja M
        Small nerve fibre dysfunction in a patient with Sjögren's syndrome: neurophysiological and morphological confirmation.
        Scand J Rheumatol. 1995; 24: 257-259
        • Fox RI
        Sjögren's syndrome: controversies and progress.
        Clin Lab Med. 1997; 17: 431-444
        • Ramos-Remus C
        • Suarez-Almazor M
        • Russell AS
        Low tear production in patients with diabetes mellitus is not due to Sjögren's syndrome.
        Clin Exp Rheumatol. 1994; 12: 375-380
        • Kraus A
        • Cifucnlcs M
        • Villa AR
        • Jakez J
        • Reyes E
        • Alarcon-Segovia D
        Myositis in primary Sjögren's syndrome: report of 3 cases.
        J Rheumatol. 1994; 21: 649-653
        • Tandan R
        • Bradley WG
        Dermatomyositis and polymyositis.
        in: Issclbacher KJ Braunwald E Wilson JD Martin JB Fauci AS Kasper DL Harrison's Principles of Internal Medicine. 13th ed. McGraw-Hill, New York, NY1994: 2379-2383
        • Gran JT
        • Myklebust G
        The concomitant occurrence of Sjögren's syndrome and polymyositis.
        Scand J Rheumatnl. 1992; 21: 150-154
        • McCombe PA
        • Shcean GL
        • McLaughlin DB
        • Pender MP
        Vestibu-lar and ventilatory dysfunction in sensory and autonomie neuropathy associated with primary Sjögren's syndrome [letter].
        J Neurol Neurosurg Psychiatry. 1992; 55: 1211-1212
        • Molina JA
        • Bcnito-Lcon J
        • Bermejo F
        • Jimenez-Jimenez FJ
        • Olivan J
        Intravenous immunoglobulin therapy in sensory neuropathy associated with Sjögren's syndrome [letter].
        J Neurol Neurosurg Psychiatry. 1996; 60: 699