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].