Dr. Tejesh Patel discusses what’s new and emerging in the diagnosis and treatment of idiopathic pruritus, including screening tips, physical finding insights, and on- and off-label medication use.
Tejesh Patel, MD, Professor and Chair of Dermatology at University of Tennessee Health Science Center, Memphis, Tennessee
“Historically, patients with idiopathic pruritus have been challenging to treat. They’ve experienced significant suffering, faced an extensive workup, and there has been a lack of efficacious treatment options. But things are changing,” said Tejesh Patel, MD, who presented “Diagnostic and Therapeutic Approach to Idiopathic Pruritus” at the 2022 Fall Clinical Conference®.
Pruritus, an unpleasant sensation leading to the desire to scratch, is one of the most common complaints in dermatology, said Dr. Patel.
“It has a profound impact on quality of life. Chronic pruritus can lead to poor sleep as well as impaired memory and attention. For some, the suffering is worse than having a stroke or being on hemodialysis. It also has a tremendous economic burden on both the patient and on society.”
From Symptom to Disease Entity
Acute pruritus has typically been regarded as a symptom—a physiological response to an acute stimulus, such as an insect bite. But when pruritus lasts for more than six weeks, dermatologists should start to take notice, said Dr. Patel.
“It is at this point that it could be said that it has turned from a symptom to a disease entity.”
Recent research on the underlying mechanisms of pruritus shows that it not only involves the skin but also the spinal cord and brain, said Dr. Patel.
“When approaching these patients, one of the key elements is the clinical presentation. This not only includes the physical exam but also the medical history and review of systems, which will help to guide further workup.”
According to Dr. Patel, important questions to ask patients with chronic pruritus include: How long have you been itching? Did the itching start at a time of illness, surgery, or new medication? Did it begin with any skin changes? Are these skin changes localized or generalized? Are any other family members affected?
“I also tend to ask questions about if there are any symptoms associated with malignancy, such as night sweats or unintended weight loss.”
“… I think many of us fear missing an underlying malignancy as a cause of a patient’s chronic pruritus. It has been shown that bile duct and hematologic malignancies are most commonly associated with chronic pruritus. Risk factors that suggest itch is associated with an underlying malignancy include itch less than 12 months of duration, age greater than 60 years old, male sex, and history of liver disease or tobacco use.”
Physical Findings
Patients with chronic pruritus often presents with secondary skin lesions, such as prurigo nodules or excoriations, said Dr. Patel.
“It’s important to look at these patients really closely because you don’t want to miss an underlying primary inflammatory dermatosis that is being masked by secondary skin lesions.”
“I try to check patients all over. I check for dermatographism. I look closely for scabies and sometimes this can be subtle, especially in elderly patients. I look for other signs of systemic diseases also including looking at the nails and look for things such as ichthyosis.”
Initial Therapy, Workup
Dr. Patel said he generally starts patients on bland emollients and suggests they avoid triggers and any harsh detergents.
“I may consider starting them on topical steroids if there are skin lesions like prurigo nodules or lichen simplex chronicus.”
According to Dr. Patel, he screens patients without a primary inflammatory dermatosis with a CBC, renal function, liver function and a thyroid stimulating hormone test. He also recommends checking for diabetes with a fasting blood glucose or hemoglobin A1C.
“These are to screen for an underlying cause of pruritus. I also may consider doing a chest x-ray or serum protein electrophoresis on some patients.”
Further workup can be directed based on physical findings, medical history, and review of systems, said Dr. Patel.
Managing Chronic Idiopathic Pruritus
There have been many recent review articles talking about the management of pruritus, said Dr. Patel.
“My approach has changed in recent years for these patients, and I imagine it’s going to change in the future, given the new and emerging therapies that are coming out.”
Importantly, if an underlying cause is discovered, it should be addressed, he said.
“Some general measures that can be used universally on most patients are things such as soft clothing, low room temperature at night, gentle soaps, lukewarm baths, and bland emollients. I tell patients to put the emollients in the refrigerator and use them as many times as they want.”
Antihistamines really don’t have a role in treating chronic or idiopathic pruritus, said Dr. Patel.
“In fact, there have been reports of pruritus occurring after the discontinuation of antihistamines when they’re used for other things such as allergic rhinitis.”
Topical steroids and topical calcineurin inhibitors have been shown to have antipruritic effects on prurigo nodules. But they should be avoided in skin without skin lesions, he said.
“Phototherapy is a useful tool but is often not a practical option for many patients with patients having to come into the office multiple times in the week.”
Other more traditional medications that have been used such to treat these patients include gabapentin and pregabalin. These can take a few months to work and may cause drowsiness, weight gain, and leg swelling, according to Dr. Patel.
“Consider starting these at lower doses in the elderly, especially in those with decreased renal function.”
Antidepressants—both selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants—have been reported to be useful in the treatment of chronic pruritus, said Dr. Patel.
“I tend to prefer the SSRIs because with the tricyclic antidepressants I have to be cautious of the anticholinergic side effects, especially in the elderly. You may want to consider getting a baseline EKG, especially if they have cardiac risk factors or are on other QT-prolonging medications.”
What’s New and Emerging?
In late September 2022, the FDA approved dupilumab (Dupixent, Regeneron Pharmaceuticals and Sanofi), a monoclonal antibody that targets interleukin (IL)-4 and IL-13, as the first medication approved in the U.S. to treat prurigo nodularis, said Dr. Patel.
“What started as a few case reports, turned into a few case series and this led to the development of two randomized, double blind, placebo-controlled trials on dupilumab for prurigo nodularis. Patients had a significant reduction in worst itch as well as prurigo nodule counts over a 24-week period.”
“The good news doesn’t stop there for the interleukins. New medicines that target IL-13 such as tralokinumab and lebrikizumab have been shown to decrease pruritus in atopic dermatitis patients.”
Another new and exciting treatment is nemolizumab, a monoclonal antibody to the IL-31 receptor, he said.
“A phase 2 randomized, double-blind, placebo-controlled trial of 70 patients with prurigo nodules showed a reduction in mean peak pruritus by 53% in week 4.”
Janus kinase (JAK) inhibitors are also showing promise, said Dr. Patel.
“JAK inhibitors have shown a significant and rapid reduction of pruritus in patients with atopic dermatitis, and this also is true for topical JAK inhibitors. It isn’t surprising that JAK inhibitors have been reported in case reports and case series to reduce chronic pruritus and prurigo nodularis. And there are ongoing clinical trials investigating JAK inhibitors in patients with prurigo nodularis, so be on the lookout for these results. I’m sure they are going to be exciting.”
Finally, there are therapies on the horizon that target opioid receptors, he said.
“Mu-opioid agonists have traditionally been associated with pruritus and this is a well-known side effect of morphine. In contrast, kappa-agonists decrease pruritus and this has led to the opioid receptors being targeted for antipruritic treatments.”
“One drug that has been developed is nalbuphine, which is a kappa-opioid agonist and a mu-opioid antagonist. In a phase 2 randomized controlled trial in patients with prurigo nodularis it has been shown that this medication reduced both mean and worst itch after 10 weeks.”
Disclosure: Dr. Patel reports no relevant conflicts of interest. All of the medication discussed are off-label uses apart from dupilumab which is FDA-approved for the use in adult patients with prurigo nodularis.