Small fiber neuropathy (SFN), a type of peripheral neuropathy, has been linked to several conditions and diseases, the most common being diabetes. Despite extensive workup, pinpointing etiology can be difficult especially when the potential cause is regarded as speculative, as is the case with vaccine-associated SFN. A case published in the Journal of Clinical Neuromuscular Disease describes this type of neuropathy in a patient following human papillomavirus (HPV) vaccination.

The patient, a 14-year-old girl, had been experiencing intractable generalized burning and tingling sensations for approximately 1.5 years; this began 9 days after receiving the HPV vaccine. Despite the use of various analgesics, the patient’s pain continued to persist, however no gait impairment, weakness, or autonomic symptoms were noted; medical history was found to be nonsignificant. Her medication and vaccination history included a prescription for valacyclovir (for the past 3 years), MMR, TdaP, DTap, varicella, meningococcus, Hep A and B, flu (intranasal), and polio vaccination; none of these vaccines were tied to any subsequent complications. 

Physical examination showed significant allodynia of her right scapula and reduced pinprick sensation in her feet. A battery of tests (including nerve conduction/electromyogram studies, MRI, skin biopsy, lab work [to rule out other causes of neuropathy]) were unremarkable apart from an abnormally low intraepidermal nerve fiber density (INFD) in the skin biopsy leading clinicians to suspect the patient had small fiber neuropathy associated with HPV vaccine. Other differentialswere considered (herpes neuralgia, thoracic syrinx), however these did not completely explain the sensations she was feeling. 

There are several possible pathophysiologic mechanisms that may explain vaccine-associated polyneuropathies including including immune-mediated hypersensitivity to the adjuvants or solvents in the vaccine, as well as nervous system invasion caused by prolonged, less virulent, viral infection. Based on available literature, there have been similar cases involving other vaccines (Lyme, hepatitis B, HPV, rabies), however the relationship is not well-defined due to a lack of epidemiological data supporting the association. At this time, no conclusive evidence points to an association between influenza or varicella vaccine and SFN. In addition, relying on self-reports may make it difficult to quantify the incidence of SFN after vaccination, since sensory symptoms are predominantly subjective.

Sensory symptoms following vaccination can have multiple causes, including local inflammation or transient immune-mediated phenomena, leading clinicians to only a possible diagnosis of SFN. While additional studies are needed to gain more insight into this association, the authors conclude “objective evidence from INFD is likely required before determination between SFN and vaccination.”


1. Kafaie, J. Kim, M. Krause, E. Journal of Clinical Neuromuscular Disease. Small Fiber Neuropathy Following Vaccination. 2016. (1):37-40.