Discussion: -
Pruritus is a common presentation in PV. It is characterized by the development of intense itching, stinging, tingling, or burning sensations without visible skin lesions.
It is commonly triggered by contact with water. However, its severity is variable and can be the most bothersome symptom in PV.
The underlying pathophysiology of PV-associated pruritus is poorly understood.
Most patients with PV patient found to have significantly increased mast cells in their skin. 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].
One theory mentioned that PV pruritus is due to the probable involvement of platelets (PLT) and prostaglandin. For example, platelet-rich plasma serotonin level is variably decreased in patients with PV, and PV-associated pruritus is sometimes controlled by treatment with selective serotonin reuptake inhibitors [6,7].
Treatment of PV-associated pruritus is a constant challenge.
The most frequently prescribed drugs are antihistamines; however, their effectiveness in reducing pruritus is variable. Other PV-associated pruritus treatment options include cytoreduction, phototherapy, interferon-alpha, SSRIs (e.g., paroxetine), pregabalin, and naltrexone. All were tried with different results [3,6].
As the target of HCT in the management of PV is less than 45%, reducing hematological parameters often improves PV symptoms, including pruritus. Phlebotomy showed mixed results. Also, hydroxyurea causes cytoreduction and can improve pruritus in some patients; it was found that 25% of the patient couldn’t tolerate hydroxyurea. Interferon alfa (IFN-a) was found to be effective against PV-associated pruritus in some patients, but in the long term, it was found to have side effects that led to discontinuation of IFN-a in about 15% of patient [5,8].
Our patient was on INF-a for a long time. Her hematological indices were within the normal range, but pruritus was not controlled.
Ruxolitinib was approved for treating patients with PV who have an inadequate response to or are intolerant of hydroxyurea. Ruxolitinib is a JAK1/JAK2 inhibitor that leads to suppression of JAK-STAT signaling and reduction of cytokines and plasma levels of inflammatory markers, and this explains the improvement in PV-associated symptoms, including pruritus [9]. In 2017 the RELIEF study concluded that ruxolitinib showed beneficial results in controlling PV-associated itchiness [10]. The RESPONSE-2 study showed that ruxolitinib has good hematocrit control, and improvement in disease-related symptoms, including pruritus, in comparison to hydroxyurea [11].
In our case, the use of ruxolitinib showed significant improvement in pruritus with complete resolution of the symptom.
Furthermore, our patient tolerated ruxolitinib treatment and reported no side effects over several months of follow-up.
Addressing the quality of life and trying to improve it [12,13],as well as answering the unanswered questions and unmet needs in MPNs are patient and hematologist necessity [14,15,16].