Mast cells and tryptase are linked to itch and disease severity in mycosis fungoides: Results of a pilot study

Abstract

IntroductionIn mycosis fungoides (MF), the most common cutaneous T-cell lymphoma, itch is a frequent clinical symptom. Whether mast cells (MCs), eosinophils (Eos) or their mediators play a role in MF-associated itch or disease severity is controversially discussed. Here, we explored the role of MC and Eo numbers in the skin as well as blood levels of their mediators in disease severity and itch.MethodsIn 10 patients with MF and 10 matched control subjects we assessed disease severity, itch, and quality of life impairment using dedicated tools such as the mSWAT, ItchyQoL and DLQI. We analyzed skin biopsies and measured serum levels of tryptase, a mast cell mediator, as well as of the eosinophil products eosinophil cationic protein (ECP) and major basic protein (MBP).ResultsThe presence of chronic itch, in four of 10 patients, was associated with significantly higher disease severity (mSwat), larger body surface area affected, and stronger QoL impairment (Itchy-Qol, DLQI). Serum levels of tryptase, but not ECP and MBP, were linked with patient-reported disease severity, body surface area affected, and the presence of itch. Three of the four patients with chronic itch, but none of the six patients without, had tryptase levels above >6µg/l. Numbers of MCs in the papillary dermis were higher in MF skin lesions then in non-lesional skin of MF patients and skin of healthy controls.DiscussionThe MC-mediator tryptase, in MF, is linked to disease activity and impact, most prominently to itch. Our findings call for larger studies that explore the role of MCs, tryptase and other MC mediators as drivers of itch and their role in MF pathogenesis.

Systemic inflammation and its relationship with pruritus in early‐stage mycosis fungoides

“…In a study, disease severity scores on the mSWAT scale were significantly higher in MF patients who experienced itching, indicating a more severe condition 23 . In our study, the mSWAT score was significantly higher in MS patients with pruritus compared to those without pruritus.…”

Pruritogens in pemphigoid diseases: Possible therapeutic targets for a burdensome symptom

“…Tryptase induces pruritus via a PAR‐2 activated pathway, which was confirmed by inhibition of tryptase‐induced scratch behavior in mice using PAR‐2 antibodies or a PAR‐2 antagonist 114 . Clinically, the link between pruritus severity and serum tryptase was established in mycosis fungoides 115 . Several tryptase inhibitors were evaluated in early clinical trials for allergy, asthma, colitis, and psoriasis; but none of them were approved for clinical use 116 .…”

“… 114 Clinically, the link between pruritus severity and serum tryptase was established in mycosis fungoides. 115 Several tryptase inhibitors were evaluated in early clinical trials for allergy, asthma, colitis, and psoriasis; but none of them were approved for clinical use. 116 Nafamostat, a serine protease inhibitor and potential tryptase inhibitor used for anticoagulation and the treatment of pancreatitis, had efficacy in addressing pruritus in NC mice, which mimics atopic dermatitis.…”

An update on mechanisms of pruritus and their potential treatment in primary cutaneous T-cell lymphoma

“…However, although there is strong evidence in support of a direct connection between tryptase and itch from various diseases, there is currently only one study that involved a small group of patients with MF. This study observed numerically higher serum levels of tryptase in MF patients with pruritus compared to those without pruritus [ 204 ]. Furthermore, since tryptase is a marker of mast cell activation, any association between pruritus and tryptase may reflect the role of mast cell activation and the consecutive release of other pruritus associated mediators.…”