Woman Presents With Severe Pruritus on Both Arms

How to relieve severe bilateral itching of the arms that has affected a woman for the past 4 years? That's the clinical challenge facing Shawn G. Kwatra, MD, of Johns Hopkins University School of Medicine in Baltimore, and colleagues.

On presentation, the woman, who was in her 50s, rated the itch as a 10 on the Worst Itch Numeric Rating Scale (range 0-10), Kwatra and colleagues reported in JAMA Dermatology.

She told clinicians that the itch had been uncontrolled for the previous 11 months and had an increasingly deleterious effect on her quality of life. Over that time, she received numerous topical and systemic treatments.

On an MRI of her cervical spine, the team observed moderate stenosis at C4 to C6. Given the patient's growing state of despair, they prescribed a regimen of ketamine 125 mg and lidocaine 100 mg, which was delivered intravenously over 50 minutes, along with 25 mL of bupivacaine 0.25%, which they injected as a field block in her forearms and posterior neck.

Within an hour, the patient reported that her itchiness had improved significantly, to 1 out of 10 on the Worst Itch Numeric Rating Scale. This positive response continued for 5 weeks without any additional treatments.

However, the patient reported having some gastrointestinal side effects with the therapy. Clinicians provided treatment with ondansetron via intravenous infusion, which improved these symptoms without further complications.

Unfortunately, over the subsequent 4 weeks, the itchiness in her arms returned, and her itch score rebounded to 10 out of 10.

Thus, 2 months later, the patient was given a similar IV regimen of ketamine 100 mg and lidocaine 100 mg, with 28 mL of bupivacaine injected in the same distribution. After this modification of the regimen with a lower ketamine dose and preventive therapy, the patient did not experience adverse effects. The second round of treatment also reduced her itchiness, providing relief that was sustained for 30 weeks.

Discussion

"Neuropathic pruritus (NP) is characterized by severe itch that is secondary to dysregulation of the somatosensory nervous system," Kwatra and team wrote. It is frequently treatment-resistant and can have a significant negative impact on the quality of life of those affected.

"To our knowledge, there are currently no approved therapeutics for NP," the authors noted. Furthermore, the condition is often unresponsive to off-label therapies. As a subtype of NP, brachioradial pruritus (BRP) is related to abnormalities in the C5 to C6 region of the cervical spine.

It is not possible to anatomically distinguish between fibers that transmit itch from those that transmit pain, Kwatra and colleagues explained, suggesting that the term "neuropathic itch," coined almost 50 years ago "should perhaps more appropriately be referred to as nociplastic itch," since nociplastic pain was described in 2016 as "pain arising from abnormal somatosensory processing in the absence of biomarkers."

They said that ketamine is a noncompetitive antagonist at the N-methyl-D-aspartate receptor most commonly studied for treating depression and chronic pain. Its effectiveness in managing chronic pain may occur via suppression of central sensitization, they added.

"This patient may also have benefited from a bupivacaine field block, which inhibits neural transmission, and a lidocaine infusion, which suppresses ectopic discharges and hyperalgesia," they pointed out.

Kwatra and colleagues explained that due to the adverse effects this patient experienced after the initial treatment, it was important to further assess the risk-benefit ratio associated with use of ketamine infusions in the treatment of neuropathic itch.

"Consensus guidelines on ketamine infusions for chronic pain have established that across clinical trials, adverse effects were few and the rate of serious adverse effects was similar to placebo, with higher dosages (and possibly faster administration and higher peak blood levels) associated with greater risks and benefits," they wrote. "These adverse effects included psychomimetic, cardiovascular, and gastrointestinal effects."

They suggested several explanations for this patient's prolonged relief from pruritus. "For pain, a morphological and teleological cousin to itch, the most commonly cited reason for relief that outlasts the pharmacological duration of action for ketamine is the reversal of central sensitization," they noted.

In addition, anecdotal accounts have described extended effects of local anesthetic blockade, and Kwatra and team suggested that this may be related to reversal of both peripheral and central sensitization.

They acknowledged that the generalizability of conclusions regarding individual therapies is limited by the use of three treatments at high doses, an approach that was used to prioritize treatment effectiveness and practicality, since "the patient was from out of state and infusions are rarely covered by payers."

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