In herpes zoster, 29%–46% of patients in the acute phase and 38%–62% of patients in the chronic phase develop itch [2,3,4]. However, pain is the main symptom rather than itch in 88% of patients, and pain reduces quality of life [2,3,4]. Therefore, itch is often left unattended in such cases, whereas pain is frequently treated. Conversely, severe cases wherein itch was the main symptom and threatened quality of life have been rarely reported . The rarity of our case was that the patient had no pain but had itching, which was severe enough to cause ulcers.
The pathophysiology of chronic pruritus can be classified under neurogenic, psychogenic, or neuropathic etiologies . In this case, we diagnosed the itch as neuropathic based on the findings of alloknesis, which appeared in the same distribution of hypoesthesia confined to two adjacent dermatomes. We considered the likely involvement of neurogenic itch to be low because the rash had disappeared. Furthermore, while the patient had a medical history of dysthymia, psychogenic itch was unlikely based on the findings of the Hospital Anxiety and Depression Scale.
There are two mechanisms of itching in herpes zoster depending on the time course. The first mechanism is a neurogenic itch mediated due to histamine in the acute phase when the rash appears . The second mechanism of itching is neuropathic itch or PHI caused by neural injury in the chronic phase of herpes zoster after the rash has disappeared [10, 12]. In neuropathic itch, varicella-zoster virus alleviates and demyelination of nerve fibers in the skin that transmit itch occurs , which is similar to neuropathic pain [13, 14]. Demyelination of nerve fibers could cause ectopic discharges due to changes in ion channels [15, 16], and overexcitation of primary neurons increases the transmission of itch, resulting in intractable neuropathic itch.
Our patient had no pain and only neuropathic itch. We believe that itch without pain may promote more severe symptoms than itch with pain. Skin damage due to scratching normally induces the pain, which serves as a protective mechanism against scratching. However, when itch occurs in painless areas, these protective mechanisms would not work. As a result, a patient who has painless itch would continue to scratch despite the resulting skin damage becoming severe . Therefore, neuropathic itch in painless areas may lead to dangerous symptoms.
In theory, antihistamines are not effective for such neuropathic itch [1, 6, 8], as observed in our patient. The treatment for intractable neuropathic itch is difficult, and several treatments have been attempted, including gabapentin , carbamazepine , nerve block , stellate ganglion block , and pulsed radiofrequency . Nalfurafine, which serves as a kappa opioid agonist, may also be effective for the treatment of PHI. We believe that several drugs that alleviate neuropathic pain are effective for relief of PHI, given the mechanism of neuropathic itch noted above [1, 10, 12]. We selected pregabalin for our patient. Although serotonin norepinephrine reuptake inhibitors and tricyclic antidepressants were other options, their use in our patient was difficult because she was already using a selective serotonin reuptake inhibitor. Pregabalin is a γ-amino acid analog that binds to the α2δ-subunit of voltage-dependent calcium channels in the dorsal root ganglion, suppressing the release of neurotransmitters and thus relieves neuropathic pain . Taken together, we infer that pregabalin suppresses neuropathic itch in PHI with similar mechanisms in neuropathic pain .
Many studies on chronic pruritus have reported that pregabalin is effective at a dose of 75 mg/day or more . In the present case, we started pregabalin at a small dose of 25 mg/day to prevent side effects, such as dizziness. This low dose was satisfactory for this patient, despite another study reporting a case in which 150 mg/day of pregabalin was ineffective for PHI treatment . The reason for the effectiveness of a small amount of pregabalin in this case could be that the patient had a poor physique with poor general condition after cerebral infarction. Pregabalin was effective for our PHI patient, and could therefore also be a useful treatment for other PHI cases.