Pain is defined as an unpleasant sensory and emotional experience associated with or resembling that associated with actual or potential tissue damage.¹ Chronic pain is commonly defined as any pain that lasts more than 12 weeks. Typically, pain is a feature of many infectious processes such as abscess, urinary tract infection, or any bacterial infection that causes an inflammatory process. The main scope of this chapter is focused on neuralgia, such as postherpetic neuralgia (PHN), where the pain is a result of the involvement of the neurological pathways resulting in neuropathic pain. Neuropathic pain is different from nociceptive pain. Nociceptive pain is a result of tissue damage that results in secondary activation of the neural pathways. Neuropathic pain or neuralgia is related to nervous system lesions or dysfunction and could be due to different mechanisms such as peripheral nervous system sensitization, deafferentation, or neurogenic inflammation.²,³

Postherpetic neuralgia is one of the commonly encountered neuralgia related to infections in clinical practice. The incidence of herpes zoster (HZ) is ˜4 cases per 1000 population, with a total burden of about 1 million cases annually in the United States. About 15% of adults with HZ develops PHN, and there are ˜150 000 new cases in the United States annually.⁴ After the initial varicella infection, the virus persists in the dorsal root ganglia and cranial ganglia, such as geniculate ganglion. Reactivation of the virus can occur through reduced cell-mediated immunity due to stress, illness, medication, aging, or idiopathic cause’s results in shingles.⁵

The clinical hallmark of PHN includes a rash consisting of erythematous papules in a dermatomal distribution followed by lancinating or burning pain in the dermatomal distribution. Thoracic and lumbar dermatomes are commonly affected. Usually, the pain persists for 3 months or more following HZ.⁶ In immunocompromised patients, multidermatomal involvement is seen.⁷ Reactivation of the varicella-zoster virus (VZV) at geniculate ganglion presents with a vesicular rash on the ear accompanied by facial nerve paralysis,⁸ which is referred to as Ramsay Hunt syndrome. Reactivation of the latent virus in the trigeminal ganglion with involvement of the ophthalmic division of the trigeminal nerve leads to ocular zoster, which may causes keratitis, scleritis, uveitis, retinitis, and choroiditis.⁹ Rarely involvement of the other cranial nerves such as the abducens and vagus nerve without typical skin rash has been described.¹⁰ Other neurological complication of HZ infection includes encephalitis, motor neuropathy,¹¹ myelitis,¹² stroke,¹³ and Guillain-Barré syndrome.¹⁴ This chapter focuses on chronic and acute infection diseases, their evaluation, diagnosis, and differential diagnosis.

One in every three persons develops HZ during their lifetime.²² It is estimated that 5%-20% of those with HZ can develop PHN.²³ The frequency and severity of PHN increase with advancing age, occurring in 20% of people aged 60-65 years who have had acute HZ and in more than 30% of people aged >80 years.²⁴ In addition to age, risk factors for developing PHN after HZ include the presence of a prodrome (defined as pain and/or abnormal sensations before rash onset), severe rash (defined as >50 lesions: papules, vesicles, or crusted vesicles), and severe pain during the acute phase.²⁵ A recent meta-analysis also identified ophthalmic involvement as a risk factor. Additional possible risk factors included systemic lupus erythematosus, diabetes, and recent trauma.²⁶ Immunocompromised patients are at increased risk of VZV reactivation as well as neurological complications.¹²

Lai and Yew²⁷ identified five studies (N = 4169) for meta-analysis and demonstrated that family history is a significant risk factor for HZ infection (OR = 3.03; 95% CI, 1.86-4.94). One proposed genetic mechanism involves human leukocyte antigens (HLAs), specifically HLA-A, which are responsible for presenting peptides to CD8⁺ receptors to elicit an immune response. IE6862 is a VZV transcription factor protein and is responsible for eliciting CD8⁺ response. A study conducted by Meysman et al.²⁸ found that patients who had lower HLA-A presentation ability of IE62 protein had a 60% greater risk of HZ.