Dr. Hal Scofield
CHICAGO—Neuropathies in patients with Sjögren’s disease are common, but also difficult to diagnose, and no single test for them is available. Sjögren’s disease does not yet have an effective disease-modifying anti-rheumatic drug, although that could change in the future, according to R. Hal Scofield, MD, professor in the Arthritis and Clinical Immunology Research Program at the Oklahoma Medical Research Foundation, Oklahoma City.
In the meantime, both neurologists and rheumatologists must collaborate to identify and treat neuropathies, which are common among patients with Sjögren’s disease.
Dr. Scofield and Arun Varadhachary, MD, PhD, professor of neurology and section chief in the neurohospitalist section, Washington University in St. Louis, brought together their respective specialty expertise during the ACR Convergence 2025 session Tackling the Burning Question of Peripheral Neuropathies in Sjögren’s Disease: New Guidelines.
Dr. Arun Varadhachary
In collaboration with the Sjögren’s Foundation, Dr. Scofield and Dr. Varadhachary have worked with colleagues to publish common nomenclature for peripheral nervous system disorders that affect both rheumatology and neurology.1
Peripheral nervous system involvement with Sjögren’s disease can have several manifestations, including mononeuropathy, polyneuropathy and autonomic neuropathy, the presenters noted.
Although rheumatologists may stick to what they know best when treating patients with Sjögren’s disease, an understanding of the basics with peripheral neuropathy can be useful.
One pearl the presenters shared: The location of symptoms is the key for a neurological diagnosis, and history and physical exams localize the problem the majority of the time. However, electrodiagnostics can further assist with localization.
Mononeuropathy & Sjögren’s
Mononeuropathy involving the facial and trigeminal nerve is one potential type of neuropathy in Sjögren’s patients, with findings usually consistent with fifth or seventh cranial nerve dysfunction. Symptoms may include facial pain and motor function problems in the lower part of the face, such as trouble with biting and chewing. Physicians can offer a contrast-enhanced brain magnetic resonance imaging scan and also consider electrophysiological testing, including a blink reflex.
For dysfunction of the seventh cranial nerve, a 10-day or longer course of glucocorticoid treatment as well as the possible addition of valacyclovir should be considered. For dysfunction of the fifth cranial nerve, treatments may differ for trigeminal neuralgia vs. trigeminal neuropathy. Trigeminal neuralgia can be treated with carbamazepine or oxcarbazepine, along with alternatives or adjuncts, such as gabapentin or pregabalin, Dr. Varadhachary said. For trigeminal neuropathy, specialists can offer a short course of oral glucocorticoids for suspected acute inflammatory etiology.
If the symptoms involve hand pain and weakness and the findings are consistent with median or ulnar neuropathy, electrodiagnostic studies and/or a nerve ultrasound are warranted, Dr. Varadhachary said. If the findings are still consistent for ulnar neuropathy, carpal tunnel syndrome or tenosynovial biopsy for amyloidosis, it’s best to refer to a hand specialist.
Dr. Scofield and Dr. Varadhachary shared a mononeuropathy case example, describing a 65-year-old male with right-hand weakness and numbness that was painful and started about two years earlier. His initial treatment with gabapentin was somewhat helpful but about six months ago, he noticed that his hand appeared to be shrinking. An exam showed loss of muscle bulk of the thenar eminence and a hollowed-out space between the thumb and forefinger. He also had a steppage gait, leading him to lift one of his feet higher than normal.
When discussing the value of an electrodiagnostic study, Dr. Scofield said that would likely be useful. Dr. Varadhachary agreed and said that in this situation, give a precise description to the electromyographer of the type of testing you want. “I’d say to localize for carpal tunnel and for foot drop,” he explained.
Asymmetric & Multifocal Neuropathies
Asymmetric and multifocal neuropathies involve simultaneous or sequential damage to multiple noncontiguous nerves. “It could start with a wrist drop and then there may be a foot drop on the other side a few weeks later,” Dr. Varadhachary said.
Confluent multiple mononeuropathies may simulate a length-dependent polyneuropathy or asymmetric polyneuropathy, the presenters said.
Pain is a significant feature of asymmetric and multifocal neuropathies, particularly for those with an immune-mediated disease, he added. Motor and sensory loss, fever, weight loss and arthralgia also are common.
A comprehensive neurological exam and electrodiagnostic studies can dig deeper to find a cause. For example, for findings consistent with small fiber neuropathy and the nerve conduction and electromyography are normal, epidermal nerve fiber density with punch skin biopsy may be warranted. For findings consistent with vasculitis, neoplasm, amyloid or another infiltrative process, the presenters recommended a nerve and muscle biopsy. If the findings are still consistent with vasculitis, assess serum cryoglobulins or surrogate markers, such as positive rheumatoid factor or low C4, Dr. Scofield said.
The polyneuropathies can vary, but a few treatment recommendations include:
- For vasculitic neuropathy: immediately start high-dose systemic glucocorticoids with rituximab along with cyclophosphamide
- For immune-mediated non-vasculitic large fiber polyneuropathy: intravenous immunoglobulin (IVIG)
- For persistent pain: gabapentin, pregabalin or serotonin and norepinephrine reuptake inhibitors; also add sodium channel-blocking agents or tricyclic antidepressants
The presenters shared the case of a 36-year-old female who came to clinic complaining of two months of diffuse joint pains, myalgias and distal dysesthesias. Her initial lab tests and joint exam were normal, although her ankles were mildly swollen. Her general exam showed stocking-glove dry, warm, red skin. Her sensory exam showed normal vibration sensation but abnormal pin-prick and temperature perception. Her reflexes at the biceps and knees were easily elicitable but indeterminate at the ankles.
Dr. Scofield said that nerve conduction study would be warranted with this patient. If the results come back normal, a skin biopsy would be a reasonable next step.
Autonomic Nervous System Neuropathies
Autonomic nervous system neuropathies are common in people with Sjögren’s disease, Dr. Varadhachary said.
“Because autonomic nerves are widely distributed cutaneously and viscerally, manifestations can be all over the place,” Dr. Varadhachary said. “People with lots of complaints may have autonomic nervous system neuropathy.”
Some of the symptoms include orthostatic intolerance, vasomotor dysfunction, gastrointestinal (GI) disturbances and bladder dysfunction.
Use of the Composite Autonomic Symptom Score-31 (COMPASS-31) and measurement of orthostatic blood pressure and pulse are useful when autonomic neuropathy is suspected. If findings are abnormal, refer to a specialist or to an autonomic testing center for further evaluation.
For autonomic failure, sensory neuropathy and sensory ataxia, make an urgent neurologist referral. For symptoms of orthostatic intolerance, refer to an autonomic testing center. For other symptoms, such as genitourinary or GI dysfunction, refer to the appropriate specialist.
Although testing is critical, keep in mind that tests are sometimes overly sensitive. “It’s easy to overinterpret a test where someone is still taking a beta blocker and then goes to an autonomics lab and the data is uninterpretable, Dr. Varadhachary said.
Therapy will depend on the exact symptoms. For example, immune-mediated autonomic dysfunction that is severe and progressive may require IVIG and rituximab. Orthostatic tachycardia that causes low blood pressure may require vasopressors or fluid expansion.
“A lot of autonomic neuropathy is patient education and having a multidisciplinary team to educate the patient about lifestyle,” Dr. Scofield said.
The presenters shared the case example of a 31-year-old female with both Sjögren’s and diabetes who came to clinic with positional dizziness, chronic constipation and pain behind her shoulder blades. Her vital signs showed a resting tachycardia and orthostatic hypotension as well as sluggish pupils, stocking-glove dry skin and non-length dependent loss of pin-prick sensation. Her gait was mildly antalgic, and she preferred to travel in a manual wheelchair.
Dr. Scofield said the determination of what tests to do next may depend on how fast the symptoms started.
“Trying to figure out if this is due to diabetes or Sjögren’s is a very difficult task, but clarifying the timeline can inform what you can offer the patient,” Dr. Varadhachary said.
Ordering a tilt test is reasonable, Dr. Scofield said.
This is the type of situation where staying open-minded to other disorders beyond what is already diagnosed may be useful, Dr. Varadhachary added.
Vanessa Caceres is a medical writer in Bradenton, Florida.
Reference
- Noaiseh G, Deboo A, King JK, et al. Recommendations for aligned nomenclature of peripheral nervous system disorders across rheumatology and neurology. Arthritis Rheumatol. 2025 Apr;77(4):383–389.