Ruxolitinib (a JAK2 inhibitor) as an emerging therapy for refractory pruritis in a patient with low-risk polycythemia vera

Abstract

Introduction: Polycythemia vera (PV) is a Philadelphia-negative myeloproliferative neoplasm (MPN) characterized by the overproduction of red blood cells. The presence of JAK2 mutation is detected in up to 99% of patients with PV. Pruritis is commonly encountered in patients with PV and is considered the most troublesome symptom. Multiple treatment modalities are used for treatment; however, their efficacy is variable. Sometimes, pruritis will not improve even by the use of combined therapies. Recently, Ruxolitinib (a JAK2 inhibitor) has been shown to be very effective, especially in patients with refractory pruritis in the setting of other treatment modalities failure.Patient concern: We describe a 55-year-old male with history of low risk PV presented with severe itching despite using different therapies, including phlebotomy and hydroxyurea. His laboratory results on presentation were significant for red blood cells (RBC) of 8.2 Â 10 6 /uL (normal = 4.5-5.5), hematocrit (Hct) of 52.8% (normal = 40-50%), platelet count of 519 Â 10 3 /uL (normal = 150-400), white blood cells count of 12.3 Â 10 3 /uL (normal = 4-10), and basophils count of 0.22 Â 10 3 /uL (normal < 0.1).

Itch and Janus Kinase Inhibitors

“…Wang et al ( 30 ) reported that 5 rheumatoid arthritis patients with chronic pruritus who had not responded at all to prior anti-itch therapies, including gabapentin and prednisone, were successfully treated with oral tofacitinib. A 55-year-old male patient with polycythemia vera was completely relieved of itching after 2 months of treatment with oral ruxolitinib ( 4 ).…”

“…The Janus kinase and signal transducer and activator of transcription (JAK-STAT) pathway is an important signalling mechanism that regulates intracellular gene expression through cytokines and cell growth factors, such as interleukin (IL) and interferon (IFN) ( 2 ). The importance of the JAK-STAT pathway began to be elucidated through the association between gene mutations and haematological and immunological diseases, including gain-of-function mutations in JAK2 in polycythemia vera, essential thrombocytosis, and myelofibrosis, and loss-of-function mutation in STAT3 of autosomal dominant hyperimmunoglobulin E syndrome ( 3 , 4 ). It is now known that JAK-dependent cytokines play an important role in the development of a number of inflammatory and autoimmune diseases ( 2 ).…”

Effect of Ruxolitinb in refractory pruritus in a patient with high-risk polycythemia vera A Case Report

“…Also, it was found that in patients with Philadelphia-negative MPN, mast cells released greater levels of pruritogenic factors like histamine, leukotrienes, and interleukin-31. It was also found that in a patient with JAK2V617F mutation, basophil count was increased, and this mutation is also known to induce cytokine hypersensitivity in cell lines [3,5].…”

“…Other PV-associated pruritus treatment options include cytoreduction, phototherapy, interferonalpha, SSRIs (e.g., paroxetine), pregabalin, and naltrexone. All were tried with different results [3,6].…”

“…Patients with PV may experience a broad symptom burden that include constitutional symptoms such as fatigue, weight loss, night sweats and pruritus, mild-to moderate degree of splenomegaly, symptoms of hyperviscosity, microvascular symptoms (e.g., headaches, lightheadedness, visual disturbances, atypical chest pain, erythromelalgia, paresthesia), and thrombotic and bleeding complications [3,4].…”