Abstract
The itch associated with cutaneous T-cell lymphoma (CTCL), including Mycosis Fungoides (MF) and Sézary syndrome (SS), is often severe and poorly responsive to treatment with antihistamines. Recent studies have highlighted the possible role of interleukins in nonhistaminergic itch. We investigated the role of IL-31 and IL-8 in CTCL, concerning disease severity and associated itch. Serum samples of 27 patients with CTCL (17 MF and 10 SS) and 29 controls (blood donors) were analyzed for interleukin- (IL-) 31 and IL-8; correlations with disease and itch severity were evaluated. IL-31 serum levels were higher in CTCL patients than in controls and higher in SS than in MF. Also, serum IL-31 levels were higher in patients with advanced disease compared to those with early disease, and they correlated positively with lactate dehydrogenase and beta 2-microglobulin levels, as well as with the Sézary cell count. Itch affected 67% of CTCL patients (MF: 47%; SS: 100%). Serum IL-31 levels were higher in itching patients than in controls and in patients without itching. There was no association between serum IL-8 and disease severity, nor with itching. Serum IL-8 levels correlated positively with peripheral blood leukocyte and neutrophil counts in CTCL patients. Our study suggests a role for IL-31 in CTCL-associated itch, especially in advanced disease and SS, offering a rational target for new therapeutic approaches. Increased serum IL-8 observed in some patients may be related to concomitant infections, and its role in exacerbating itch by recruiting neutrophils and promoting the release of neutrophil proteases deserves further investigation.
Highlights
Cutaneous T-cell lymphomas (CTCLs), classically represented by Mycosis Fungoides (MF) and Sezary Syndrome (SS), account for 70% of cutaneous lymphomas and 10% of extranodal non-Hodgkins lymphomas [1]. ese chronic pathologies reduce the patients quality of life [2], and the prognosis depends on the cutaneous T-cell lymphoma (CTCL) type and stage [3]
11 patients (40.7%) had SC in the peripheral blood (PB); the percentage of SC among total lymphocytes was >5% in 10 cases (37.0%), and the SC count exceeded 1000 cells/μl in 5 cases (18.5%), given blood involvement to be classified as B0b in 1 case, B1b in 5 cases, and B2b in another 5 cases
With respect to disease severity, we found sIL-31 to be higher in advanced CTCL cases and to correlate significantly with lactate dehydrogenase (LDH) and beta 2 microglobulin (B2MG), which reflect tumor burden [75]
Summary
Cutaneous T-cell lymphomas (CTCLs), classically represented by Mycosis Fungoides (MF) and Sezary Syndrome (SS), account for 70% of cutaneous lymphomas and 10% of extranodal non-Hodgkins lymphomas [1]. ese chronic pathologies reduce the patients quality of life [2], and the prognosis depends on the CTCL type and stage [3].Pruritus, or itch, a frequent feature in CTCL, is severe in patients with SS [4, 5], being often recalcitrant and refractory to treatment [6, 7], motivating the study of the pathways involved [8].Histamine has been shown to cause itching [9], and antihistamines are the most prescribed medications for itch [10]. Itch, a frequent feature in CTCL, is severe in patients with SS [4, 5], being often recalcitrant and refractory to treatment [6, 7], motivating the study of the pathways involved [8]. IL-31 signals through a heterodimeric receptor [24] and stimulates the JAK-STAT, RAS/ERK, and PI3K/AKT pathways [25]. It does not induce itch immediately after skin challenge [26] but has receptors in the dorsal root ganglia [27] and is a likely mediator in nonhistaminergic itch [28, 29]
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