Summary
Pyoderma gangrenosum (PG) and Sweet's syndrome (SS) are two inflammatory skin diseases presenting with painful ulcers and erythematous plaques, respectively; both disorders have a ...debilitating clinical behaviour and PG is potentially life‐threatening. Recently, PG and SS have been included among the autoinflammatory diseases, which are characterized by recurrent episodes of sterile inflammation, without circulating autoantibodies and autoreactive T cells. However, an autoinflammatory pattern clearly supporting this inclusion has never been demonstrated. We studied 16 patients with PG, six with SS and six controls, evaluating, using a sandwich‐based protein antibody array method, the expression profile of inflammatory effector molecules in PG, SS and normal skin. The expressions of interleukin (IL)‐1 beta and its receptor I were significantly higher in PG (P = 0·0001 for both) and SS (P = 0·004–0·040) than in controls. In PG, chemokines such as IL‐8 (P = 0·0001), chemokine (C‐X‐C motif) ligand (CXCL) 1/2/3 (P = 0·002), CXCL 16 (P = 0·003) and regulated upon activation normal T cell expressed and secreted (RANTES) (P = 0·005) were over‐expressed. In SS, IL‐8 (P = 0·018), CXCL 1/2/3 (P = 0·006) and CXCL 16 (P = 0·036) but not RANTES were over‐expressed, suggesting that chemokine‐mediated signals are lower than in PG. Fas/Fas ligand and CD40/CD40 ligand systems were over‐expressed in PG (P = 0·0001 for Fas, P = 0·009 for Fas ligand, P = 0·012 for CD40, P = 0·0001 for CD40 ligand), contributing to tissue damage and inflammation, while their role seems to be less significant in SS. Over‐expression of cytokines/chemokines and molecules amplifying the inflammatory network supports the view that PG and SS are autoinflammatory diseases. The differences in expression profile of inflammatory effectors between these two disorders may explain the stronger local aggressiveness in PG than SS.
Summary
Mycosis fungoides is the most prevalent form of primary cutaneous T‐cell lymphoma. Patients frequently present with early‐stage disease typically associated with a favourable prognosis and ...survival of 10–35 years, but over 25% may progress to advanced disease with a median survival < 4 years, and just 13 months in those with nodal involvement. Sézary syndrome presents in advanced disease with erythroderma, blood involvement and lymphadenopathy. The Bunn and Lamberg staging system (1979) includes stages IA–IIA (early‐stage disease) and IIB–IVB (advanced‐stage disease) and provides prognostic information, but some patients with tumour‐stage disease (IIB) have a worse prognosis than those with erythrodermic‐stage (III). Conversely, patients with plaque‐stage (IB) folliculotropic mycosis fungoides may have a worse outcome than those with tumour‐stage (IIB). The more recent staging system of the European Organisation for the Research and Treatment of Cancer/International Society for Cutaneous Lymphoma has been designed to reflect tumour burden at different sites. However, this staging system has not been validated prospectively for prognosis. Furthermore, this staging system does not include a detailed measurement of skin tumour burden, as indicated by the modified skin weighted severity assessment tool. This assessment measures body surface area of disease and is weighted to record patch, plaque and tumour to produce a numerical value from 0·5 to 400 and is an established endpoint for clinical studies. Nor does this staging include clinicopathological features associated with a poor prognosis such as folliculotropism. Here we review the clinical, haematological, pathological and genotypic parameters outside the staging system, which may affect survival in mycosis fungoides and Sézary syndrome. Most studies are retrospective and single centre. The identification of poor prognostic factors may be used to develop a prognostic index to use alongside staging, which may be of benefit in mycosis fungoides/Sézary syndrome to identify patients with a potentially poor prognosis.
What's already known about topic?
The European Organization for the Research and Treatment of Cancer/International Society for Cutaneous Lymphoma published a revised staging system for mycosis fungoides/Sézary syndrome (MF/SS) in 2007 to include tumour, node, metastasis and blood involvement at diagnosis.
Survival in MF/SS is diverse and ranges from months to decades.
Factors outside staging affect survival.
What does this study add?
This is a review of clinical, haematological, pathological and genotypic changes affecting survival in MF/SS.
The development of an international prognostic index to be adopted alongside staging may aid the management of patients.
Background
Sentinel lymph node biopsy (SLNB) is currently recommended for patients with intermediate-thickness melanomas (T2–T3). Historically, T4 melanoma patients have not been considered good ...candidates for SLNB because of the high risk of distant progression. However, some authors suggest that T4 melanoma patients could be considered as a heterogeneous group that could benefit from SLNB.
Methods
We retrospectively analyzed 350 patients with thick (>4 mm) melanomas between 1999 and 2011. Patients were stratified into three groups depending on the results of SLNB: (1) 94 SLNB-negative; (2) 84 SLNB-positive; and (3) 172 SLNB not performed (observation group). The associations of clinical-pathologic features with the result of SLNB, disease-free interval (DFI), and disease-specific survival (DSS) were analyzed.
Results
Multivariate analyses confirmed a better prognosis for SLN-negative patients compared with patients in the observation group (DSS hazard ratio HR 0.62,
p
= 0.03; DFI HR 0.47,
p
< 0.001). The observation group was shown to have the same prognosis as the positive-sentinel lymph node group, when adjusted for principal confounders in the model.
Conclusions
We confirmed that thick-melanoma patients are a heterogeneous group with different prognosis. In our experience, SLNB allowed for an appropriate stratification of patients in different survival groups. On the basis of our results, we strongly recommend the routine execution of SLNB in cases of primary melanoma thicker than 4 mm.
Background
Many national guidelines at the European level recommend first‐line therapy based on the anti‐TNF‐alpha adalimumab for treatment of psoriasis and psoriatic arthritis, mainly for economic ...reasons. Consequently, patients being treated with newer IL‐17 and IL‐23 inhibitors underwent previous unsuccessful first‐line adalimumab‐based therapy.
Objectives
Evaluate the efficacy and safety of IL‐17 and IL‐23 inhibitors after treatment with adalimumab compared to adalimumab‐naive psoriatic patients.
Methods
We retrospectively analysed 1053 psoriatic patients treated with anti‐IL17 and anti‐IL23 agents, which included 68 and 24 adalimumab‐experienced and 399 and 260 bio‐naive patients. Efficacy was assessed with mean PASI, PASI90, PASI100, and <3.
Results
Concerning the achieving of PASI100, PASI90 and PASI < 3 in patients treated with anti‐IL17 agents, no significant differences were observed between adalimumab‐experienced and bio‐naive patients. In patients treated with an anti‐IL‐23 agent, a faster response was observed in bio‐naive patients, with PASI < 3 significantly higher than ADA‐experienced patients at 16 weeks (77% vs. 58% p = 0.048). In a sub‐analysis that evaluated the performance of anti‐IL17 and anti‐IL23 agents in adalimumab‐experienced patients with a history of secondary failure, no significant differences were found. In multivariate analysis of PASI100, only anti‐IL‐17 therapy appeared to have a negative impact at 52 weeks (OR: 0.54 p = 0.04) independently of previous treatment. For PASI90, type of treatment and bio‐naïve status did not seem to have an impact at any time point.
Conclusions
Anti‐IL 23 and anti‐IL 17 agents are not significantly different in terms of efficacy in bio‐naive patients or as second‐line therapy after failure with a biosimilar or originator adalimumab.