Efficacy of Targeted Mast cell Inhibition Therapy in Chronic Prostatitis/Chronic Pelvic Pain Syndrome.

OBJECTIVE: To identify a subgroup of patients with mast cell dysfunction in chronic prostatitis/chronic pelvic pain syndrome and evaluate efficacy of mast cell directed therapy.

MATERIALS AND METHODS: Men with CP/CPPS were recruited and evaluated in an open label, interventional uncontrolled trial after therapy with cromolyn sodium and cetirizine hydrochloride. The primary endpoint was a change in mast cell tryptase concentrations after treatment while secondary endpoints were changes in the NIH-CPSI and AUA-SI. Isolated cells from post-prostatic massage urine were evaluated for immune changes using mRNA expression analysis.

RESULTS: 31 patients with a diagnoses of Category III CP/CPPS were consented, 25 patients qualified and 20 completed the study after meeting a prespecified threshold for active tryptase in expressed prostatic secretions. After treatment with cromolyn sodium and cetirizine dihydrochloride for 3-weeks, active tryptase concentrations were significantly reduced from 49.03±14.05 ug/ml to 25.49±5.48 ug/ml (p<0.05). The NIH-CPSI total score was reduced with a mean difference of 5.2±1 along with reduction in the pain, urinary and quality of life sub scores (p<0.001). A reduction in the AUA-SI was observed following treatment (p<0.05). NanoString mRNA analysis of isolated cells revealed downregulation of immune related pathways including Th1 and Th17 T cell differentiation and TLR signaling. Marked reduction in CD45+ cells and specifically macrophages and neutrophil abundance was observed.

CONCLUSION: Identification of CP/CPPS patients with mast cell dysfunction may be achieved using tryptase as a discriminating biomarker. Mast cell directed therapy in this targeted subgroup may be effective in reducing symptoms and modulating the immune inflammatory environment.