Autonomic Neuropathy Phenotypes
Yes, autonomic neuropathy does occur in three distinct phenotypes: as a component of generalized polyneuropathy, as a distinct autonomic neuropathy, and as part of small fiber sensory polyneuropathy. 1, 2
Phenotype 1: Component of Generalized Polyneuropathy
- Autonomic nervous system dysfunction commonly occurs as one component of a generalized polyneuropathy, such as diabetic distal symmetric polyneuropathy (DSP) 1
- In this phenotype, large fiber sensory and motor involvement typically predominates, with autonomic symptoms as an additional feature 1, 3
- The most common clinical findings of autonomic involvement in this phenotype are abnormalities of sweating and circulatory instability in the feet 1
- Cardiovascular symptoms, gastrointestinal dysfunction, and urogenital problems may also be present 2
Phenotype 2: Distinct Autonomic Neuropathy
- In this phenotype, autonomic nerves are affected disproportionately relative to somatic nerves, as seen in conditions like amyloidosis and autoimmune autonomic neuropathy 1
- Autonomic fibers can be affected in isolation, and their involvement may precede somatic fiber involvement 1, 2
- This phenotype often presents with prominent cardiovascular, gastrointestinal, urogenital, sudomotor, and pupillomotor dysfunction 4, 5
- Symptoms may include orthostatic hypotension, alternating diarrhea and constipation, urinary retention, and sexual dysfunction 3
Phenotype 3: Part of Small Fiber Sensory Polyneuropathy
- Small fiber sensory polyneuropathy (SFSN) commonly manifests as burning pain affecting the feet, often with allodynia and sometimes with erythromelalgia (red hot and painful skin) 1
- In this phenotype, involvement of autonomic and somatic C fibers usually occurs concurrently 1, 6
- Small fiber neuropathy affects small myelinated Aδ-fibers and unmyelinated C-fibers, which can affect both sensory and autonomic function 6
- This phenotype typically presents with prominent pain and autonomic symptoms with minimal or absent motor findings 7, 8
Diagnostic Considerations
- Autonomic testing should be considered to document autonomic nervous system dysfunction in patients with suspected polyneuropathy 2, 3
- A battery of validated autonomic tests rather than a single test is recommended to achieve the highest diagnostic accuracy 2
- Heart rate variability testing is a simple and reliable test of cardiovagal function that detects diabetic polyneuropathy with nearly the same sensitivity as nerve conduction studies 1, 2
- For small fiber polyneuropathy, skin biopsy with intraepidermal nerve fiber density assessment is a validated diagnostic technique 3, 8
Clinical Implications
- Recognition of the specific autonomic neuropathy phenotype is important for determining the underlying etiology and guiding appropriate management 2, 5
- Treatment approaches may differ based on the phenotype, with some requiring treatment of the underlying cause while others focus on symptomatic management 3
- Optimizing glucose control is particularly important in diabetic patients to prevent or delay the development of autonomic neuropathy 2
- Early recognition and treatment of autonomic neuropathy may improve symptoms, reduce sequelae, and improve quality of life 2