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Pruritus—it’s more than just “an itch”

Pruritus can be devastating and all-consuming. While it’s defined as an unpleasant sensation that provokes the desire to scratch, we know that it can become a disabling condition for the millions who suffer from it. Certain dermatological and systemic diseases, such as those listed below, have been known to cause a pruritus for which there are few treatment options.

Read on to learn more about the different therapeutic areas we’re investigating to change the treatment landscape.

Chronic Kidney Disease-associated Pruritus (CKD-aP)
According to the National Kidney Foundation, there are over 30 million patients living with chronic kidney disease (CKD).1 It is estimated that nearly 50% suffer from some form of pruritus.2 The pathophysiology of CKD-aP is likely multifactorial, and may involve metabolic disturbances, peripheral neuropathy, a dysregulated immune response, and imbalances in the endogenous opioid system.3-5 Currently most of these patients experience inadequate relief from itching as there are no FDA-approved therapies that have demonstrated efficacy for hemodialysis or non-hemodialysis patients.

Chronic Liver Disease-associated Pruritus (CLD-aP)

Millions of Americans suffer from chronic liver diseases (CLD) of various etiologies ranging from hepatitis to cirrhosis to primary biliary cholangitis (PBC).6 Pruritus is a common, at times debilitating, symptom in patients who suffer from CLD, especially those with chronic cholestatic disease. Although the pathogenesis of CLD-aP remains poorly understood, it is likely multifactorial including evidence for an imbalance in the endogenous opioid system driven by higher mu receptor activation (pruritic) versus kappa receptor activation (anti-pruritic). Currently, there aren’t any FDA-approved therapies to treat CLD-aP.

Pruritus in Atopic Dermatitis (AD)

Atopic dermatitis (AD) is the most common chronic, pruritic inflammatory dermatosis that affects up to 12% of children and 5%-7% of adults.7,8 Chronic pruritus is one of the defining features of AD, so common that AD is often described as “the itch that rashes.” It can lead to sleep disruption, depression, agitation, anxiety, altered eating habits, reduced self-esteem, and difficulty concentrating.

The cause of AD is multifactorial, and many people have trouble controlling it. While there are many medical and non-medical treatments used to manage AD, we are investigating pruritus relief for our patients.

Pruritus in Notalgia Paresthetica (NP)
Notalgia Paresthetica (NP) is a commonly under-recognized chronic sensory neuropathy affecting the upper back. It is estimated that 8% of chronic pruritus patients suffer from neuropathic itch, including NP.9-11 One of the hallmark features of NP is chronic pruritus, which can be significantly burdensome and undermines the affected subject’s quality of life and overall well-being. The exact etiology of NP still has not been fully elucidated; however, it is widely accepted that NP is a sensory neuropathy caused by alteration and damage to thoracic spinal nerves. The management of NP is challenging and is often resistant to multiple therapies. Currently, there aren’t any FDA-approved therapies to treat NP.

References: 1. Centers for Disease Control and Prevention. Chronic kidney disease in the United States, 2021. Atlanta, GA: US Department of Health and Human Services, Centers for Disease Control and Prevention; 2021. 2. Sukul N, Speyer E, Tu Cm Bieber B, et al. Clin J Am Soc Nephrol. 2019;14:673-681. 3. Hiroshige K, Kabashima N, Takasugi M, Kuroiwa A. Optimal dialysis improves uremic pruritus. Am J Kidney Dis. 1995;25:413-419. 4. Kimmel M, Alscher DM, Dunst R, et al. The role of micro-inflammation in the pathogenesis of uraemic pruritus in haemodialysis patients. Nephrol Dial Transplant. 2006;21:749-755. 5. Wang H, Yosipovitch G. New insights into the pathophysiology and treatment of chronic itch in patients with end-stage renal disease, chronic liver disease and lymphoma. Int J Dermatol. 2010;49:1-11. 6. Centers for Disease Control and Prevention. Chronic liver disease and cirrhosis. Atlanta, GA: US Department of Health and Human Services, Centers for Disease Control and Prevention; 2018. 7. Silverberg JI. Public Health Burden and Epidemiology of Atopic Dermatitis. Dermatol Clin. 2017;35(3):283-289. 8. Chiesa Fuxench ZC, Block JK, Boguniewicz M, et al. Atopic Dermatitis in America Study: A Cross-Sectional Study Examining the Prevalence and Disease Burden of Atopic Dermatitis in the US Adult Population. J Invest Dermatol. 2019;139(3):583-590. 9. Pereira MP, Luling H, Dieckhoffer A, Steinke S, Zielder C, and Stander S. Brachioradial pruritus and notalgia parasthetica: A comparative observational study of clinical presentation and morphological pathologies. Acta DV 2018;98:82-88. 10. Mollanazar NK, Koch SD, Yosipovitch G. Epidemiology of chronic pruritus: where have we been and where are we going? Curr Derm Rep. 2015;4:20-29 11. Situm M, Kolic M, Francheschi N, and Pecina M. Acta Clin Croat. 2018;57:721-725.