Sjögren’s syndrome (SS) is a systemic autoimmune disease known for causing dryness in the eyes and mouth. However, its effects extend beyond the moisture-producing glands, as the immune system mistakenly attacks healthy cells throughout the body. A significant complication is peripheral neuropathy, which is damage to the nerves outside the brain and spinal cord. Neuropathy is a confirmed manifestation of Sjögren’s syndrome, affecting many patients and causing symptoms like chronic pain, numbness, and weakness.
The Confirmed Link and Autoimmune Pathology
The underlying cause of nerve damage is the misguided immune response that attacks the glands, promoting systemic inflammation. Immune cells (B-cells and T-cells) infiltrate and damage the nerve tissue or the blood vessels supplying the nerves. This cellular attack disrupts peripheral nerve function, leading to neurological issues.
A major mechanism involves vasculitis, the inflammation of the small blood vessels (vasa nervorum) that nourish the nerves. When these vessels narrow, the nerves are starved of oxygen and nutrients, often resulting in axonal neuropathy. The systemic inflammatory environment, marked by autoantibodies, creates a toxic environment for nerve fibers.
Neurological involvement can appear before the characteristic dry eyes and dry mouth symptoms are recognized, complicating diagnosis. Patients with primary Sjögren’s syndrome (existing without an accompanying autoimmune condition) show distinct neurological complications. Generalized systemic inflammation drives this severe extra-glandular manifestation.
Distinct Types of Neuropathy Associated with Sjögren’s
Sjögren’s syndrome causes nerve damage that manifests in several distinct ways, depending on which nerve fibers are affected.
Small Fiber Neuropathy (SFN)
SFN is the most common form, damaging the thin, unmyelinated nerve fibers responsible for transmitting pain, temperature, and autonomic functions. Patients frequently experience burning, tingling, and lancinating pain, often starting in the feet and hands. SFN can also disrupt the autonomic nervous system, causing issues with heart rate, blood pressure regulation, and abnormal sweating.
Large Fiber Neuropathy (LFN)
LFN is a less frequent but often more disabling manifestation, affecting the thicker, myelinated nerves responsible for movement and positional sense. This can present as a sensorimotor polyneuropathy, causing weakness and numbness.
Sensory Ganglionopathy
This specific form occurs when the immune system attacks the dorsal root ganglia, the nerve cell clusters that relay sensory information. Damage results in a severe loss of proprioception (the sense of where the body is in space), leading to unsteadiness and difficulty with balance, known as sensory ataxia.
Sjögren’s can also cause mononeuropathy (damage to a single nerve) or mononeuropathy multiplex. Cranial nerves, which control facial movement and sensation, are vulnerable. Trigeminal neuralgia, characterized by intense, stabbing facial pain, is a common cranial nerve issue.
Diagnostic Procedures and Assessment
Diagnosis requires a coordinated approach between a rheumatologist and a neurologist. Initial assessment includes a neurological exam, Nerve Conduction Studies (NCS), and electromyography (EMG). Since Small Fiber Neuropathy (SFN) affects fibers too small for standard NCS, specialized tests are necessary.
The gold standard for diagnosing SFN is a skin punch biopsy, which involves taking a small skin sample to count the density of intraepidermal nerve fibers. A reduced number confirms small fiber damage. The Quantitative Sudomotor Axon Reflex Test (QSART) assesses the function of autonomic small nerve fibers that control sweating.
To confirm the neuropathy is caused by Sjögren’s, doctors rely on specific blood tests and biopsies. Blood work looks for autoantibodies like anti-Ro/SSA and anti-La/SSB. A minor salivary gland biopsy can reveal characteristic clusters of inflammatory cells, confirming Sjögren’s syndrome and helping differentiate it from other causes of nerve damage.
Therapeutic Management Approaches
Treatment focuses on managing painful symptoms and suppressing the underlying autoimmune inflammation. For symptomatic relief of neuropathic pain, first-line medications include anticonvulsants (gabapentin and pregabalin) which calm overactive nerve signals. Antidepressants, such as tricyclic antidepressants and SNRIs, are also used for their independent pain-relieving effects.
Targeting systemic inflammation is paramount, especially for severe forms like vasculitic neuropathies. These typically require aggressive treatment with high-dose corticosteroids or powerful immunosuppressive drugs like cyclophosphamide. For non-vasculitic or refractory cases, therapies aimed at modulating the immune response are considered.
Immune-modulating therapies include intravenous immunoglobulin (IVIg) and B-cell targeted biologic therapies, such as rituximab. Rituximab works by reducing B-cells, which are central to the autoimmune attack. Conventional disease-modifying antirheumatic drugs (DMARDs), like methotrexate or azathioprine, may also be used to reduce the need for long-term steroid use.