Chapter 16: Neuropathies Associated with Systemic Disease

INTRODUCTION

Neuropathies are associated with a number of systemic disorders (Table 16-1). Neuropathies related to vasculitis, infection, endocrinopathies, cancer, and medications are discussed in other chapters. The neuropathies discussed in this chapter may be directly or indirectly related to the systemic disorder (e.g., nutritional deficiency due to malabsorption in gastrointestinal disease).

NEUROPATHIES ASSOCIATED WITH CONNECTIVE TISSUE DISEASES

SJÖGREN SYNDROME

Clinical Features

Sjögren syndrome is characterized by the sicca complex: xerophthalmia (dry eyes), xerostomia (dry mouth), and dryness of other mucous membranes. It is more common in women and typically presents in middle adult life. Sjögren syndrome can be complicated by central nervous system (CNS) and peripheral nervous system (PNS) involvement. The CNS manifestations can mimic transverse myelitis or multiple sclerosis. Peripheral neuropathy occurs in 2–22% of patients with Sjögren syndrome.^1–13 Furthermore, peripheral neuropathy can be the presenting feature of Sjögren syndrome and develop in patients without the typical sicca symptoms.

The most common form of peripheral neuropathy is a length-dependent axonal sensorimotor neuropathy characterized by numbness and tingling in the distal portions of the limbs.^{1,2,6,7,9–11} Mild distal muscle weakness may also be seen. A pure small fiber neuropathy characterized by burning discomfort and tingling is also common.^14,15 Signs of autonomic nervous system dysfunction involving the cardiovascular system are often evident.^16,17 Necrotizing vasculitis may be responsible for as many as one-third of the cases of neuropathy associated with Sjögren syndrome.⁸ Vasculitis should be suspected in patients with an asymmetric, multiple mononeuropathy pattern of involvement. Cranial neuropathies, particularly involving the trigeminal nerve, can also be seen.¹⁸

Sjögren syndrome is also associated with sensory neuronopathy/ganglionopathy.^{1–3,7,10,19–21} Patients with sensory ganglionopathies develop progressive numbness and tingling of the limbs, trunk, and face. Although the symptoms may seem length-dependent, a careful history and examination typically uncovers a non–length-dependent pattern. Symptoms can involve the arms more than the legs, and involvement can be quite asymmetric or even unilateral. Patches of numbness may occur in unusual locations like the perioral regions, back of the head, or the ...