Analysis of the IL-31 pathway in Mycosis fungoides and Sézary syndrome

Möbs, Markus; Gryzik, Stefanie; Haidar, A; Humme, Daniel; Beyer, Marc; Vandersee, Staffan

doi:10.1007/s00403-014-1527-x

Cited by 22 publications

(40 citation statements)

References 32 publications

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“…Although several recent studies have found increased levels of IL-31 in CTCL, these studies largely focus on serum analysis and do not address the crucial question of IL-31's role in the skin (13,14,18). This is the first study to show the expression levels and patterns of IL-31 and both of its receptors within the skin of CTCL subjects with pruritus.…”

Section: Discussionmentioning

confidence: 98%

Cutaneous T-cell Lymphoma and Pruritus: The Expression of IL-31 and its Receptors in the Skin

Nattkemper¹,

Martínez-Escala²,

Gelman³

et al. 2016

Acta Derm Venerol

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Approximately 88% of cutaneous T-cell lymphoma (CTCL) patients are affected by pruritus that responds poorly to current antipruritic therapies. Interleukin (IL)-31, a Th2 cytokine, has been found to be increased in the serum of CTCL patients and to correlate with itch severity. This study investigated the role of IL-31 and its receptors (IL-31 receptor-alpha [IL-31RA] and OSMRβ) in the skin of CTCL patients with mild versus moderate/severe pruritus. Expression levels of IL-31, IL-31RA, and OSMRβ in the skin were measured using immunohistochemistry and correlated to pruritus severity and disease stage. In CTCL patients with moderate/severe pruritus, IL-31 was significantly elevated in the epidermis and dermal infiltrate, while IL-31RA and OSMRβ were significantly elevated only in the epidermis. Furthermore, epidermal IL-31 levels correlated to itch severity. These results show that IL-31 may play a role in CTCL pruritus by exerting indirect effects on sensory nerves through epidermal neoplastic T cells and keratinocytes to transmit itch.

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Section: Discussionmentioning

confidence: 98%

Cutaneous T-cell Lymphoma and Pruritus: The Expression of IL-31 and its Receptors in the Skin

Nattkemper¹,

Martínez-Escala²,

Gelman³

et al. 2016

Acta Derm Venerol

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“…Subsequent findings contradicted those from early studies. Möbs et al . found no difference in IL‐31, IL‐31RA, and OSMRβ expression among various stages of MF/SS.…”

Section: Resultsmentioning

confidence: 97%

“…These studies, although, only analysed IL‐31 and IL‐31 receptor levels in the serum . These interleukins are also quantifiable within the skin, and IL‐31RA and OSMRβ are present in keratinocytes .…”

Section: Resultsmentioning

confidence: 99%

“…44 Subsequent findings contradicted those from early studies. M€ obs et al 45 found no difference in IL-31, IL-31RA, and OSMRb expression among various stages of MF/SS. In addition, although Malek et al 46 identified higher serum IL-31 levels in CTCL patients than in healthy controls, they found no association between IL-31 and severity of pruritus.…”

Section: Opioidsmentioning

confidence: 94%

“…These studies, although, only analysed IL-31 and IL-31 receptor levels in the serum. [43][44][45][46] These interleukins are also quantifiable within the skin, and IL-31RA and OSMRb are present in keratinocytes. 47 Nattkemper et al 48 demonstrated increased expression of IL-31, IL-31RA and OSMRb in the epidermis of CTCLinfiltrated skin.…”

Section: Opioidsmentioning

confidence: 99%

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Inflammatory cytokines and peripheral mediators in the pathophysiology of pruritus in cutaneous T‐cell lymphoma

Lewis

Huang

Duvic

2018

Acad Dermatol Venereol

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Cutaneous T-cell lymphoma (CTCL) includes a diverse group of neoplasms, including mycosis fungoides and Sézary syndrome. One of the earliest and most common symptoms of CTCL is pruritus, which affects up to 88% of patients. The severity of pruritus can range from mild to very debilitating, producing tremendous discomfort and a significant decrease in quality of life. Patients with advanced disease, in particular, may experience a more chronic, intractable pruritus. However, the underlying mechanism of pruritus in CTCL remains unknown. Conventional antipruritic agents, such as antihistamines, gamma-aminobutyric acid analogs and antidepressants, are only partially effective in relieving symptoms, suggesting a more complex, unique pathophysiology. In this review, we summarize the current research on cytokines and peripheral mediators implicated in pruritus in CTCL.

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Clinical Staging and Prognostic Factors in Folliculotropic Mycosis Fungoides

et al. 2016

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IMPORTANCE Large case series suggest that patients with folliculotropic mycosis fungoides (FMF) have a worse prognosis than patients with classic mycosis fungoides (MF). However, recent studies described a subgroup of patients with FMF with a more favorable prognosis. Distinction between indolent and aggressive FMF may have important therapeutic consequences but is hampered by the inability of the current tumor-node-metastasis-blood (TNMB) staging system to classify patients with FMF in a clinically meaningful way. OBJECTIVE To differentiate between indolent and aggressive FMF using clinicopathological criteria and to define prognostic factors in patients with FMF. DESIGN, SETTING, AND PARTICIPANTS In this prospective cohort study, we followed 203 patients with FMF, included in the Dutch Cutaneous Lymphoma Registry between October 1985 and May 2014 at a tertiary referral center hosting the Dutch Cutaneous Lymphoma Registry. Overall, 220 patients with FMF had been registered, but 17 patients with incomplete follow-up data or a history of classic MF were excluded. MAIN OUTCOMES AND MEASURES Main outcomes included clinical and histological characteristics, disease progression, and survival. Prognostic factors were investigated using Cox proportional hazard regression analysis. Distinction between early plaque-stage FMF and advanced plaque-stage FMF was made by a blinded review of skin biopsy specimens from patients presenting with plaques. RESULTS In a cohort of 147 men and 56 women (median [range] age, 59 [15-93] years), patients with histologically early plaque-stage FMF had a very similar overall survival (OS) rate to patients with only patches and/or follicular papules (10-year OS, 71% vs 80%), while the survival rate of patients with histologically advanced plaque-stage FMF was almost identical to that of patients presenting with tumors (10-year OS, 25% vs 27%). Subsequently, 3 clinical subgroups with significantly different survival data were distinguished: early skin-limited FMF (group A; n = 84; 5-year and 10-year OS, 92% and 72%); advanced skin-limited FMF (group B; n = 102; 5-year and 10-year OS, 55% and 28%); and FMF presenting with extracutaneous disease (group C; n = 17; 5-year and 10-year OS, 23% and 2%). Age at diagnosis, large cell transformation and secondary bacterial infection were independent risk factors for disease progression and/or poor survival. CONCLUSIONS AND RELEVANCE The results of this study provide useful criteria to differentiate between indolent and aggressive FMF and confirm the existence of a subgroup of FMF with a favorable prognosis.

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Analysis of the IL-31 pathway in Mycosis fungoides and Sézary syndrome

Cited by 22 publications

References 32 publications

Cutaneous T-cell Lymphoma and Pruritus: The Expression of IL-31 and its Receptors in the Skin

Cutaneous T-cell Lymphoma and Pruritus: The Expression of IL-31 and its Receptors in the Skin

Inflammatory cytokines and peripheral mediators in the pathophysiology of pruritus in cutaneous T‐cell lymphoma

Clinical Staging and Prognostic Factors in Folliculotropic Mycosis Fungoides

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