Assessment of potential predictive factors of dupilumab response in patients with moderate-to-severe atopic dermatitis.

BACKGROUND: Dupilumab has shown to be an effective and safe treatment for patients with moderate-to-severe atopic dermatitis (AD). OBJECTIVE: To evaluate the predictive factors of response (PRF) in patients with moderate-to-severe AD treated with dupilumab. METHODS: Observational, retrospective and multicentre study conducted on adult patients diagnosed with moderate-to-severe AD treated with dupilumab, with a post-treatment follow-up of at least 16 weeks. The primary endpoints were EASI-75 and the IGA scale at week 52. RESULTS: A total of 198 patients were included in the analysis. Mean age was 38 ± 15.1 years and 116 (58.6%) were men. The most prevalent AD-predominant phenotypes were flexural eczema (45.3%), head-and-neck eczema (18.2%) and erythroderma (17.7%). At week 52, 140 (86.4%) patients achieved EASI-75 and 119 (93.0%) achieved an improvement in ≥2 points from baseline in IGA score. Women were 3.6 times more likely to achieve EASI-75 response than men (Odds ratio: 3.58; p = 0.020). While increased body mass index significantly reduced the probability of obtaining an improvement of ≥2 points in the IGA scale at week 52 (odds ratio: 0.88; p = 0.049). CONCLUSIONS: Dupilumab was an effective treatment in patients with moderate-to-severe AD. Additionally, sex and body mass index were significantly associated with achieving EASI-75 and an improvement of ≥2 points in the IGA scale, respectively, at week 52.

Heterogeneous IL-9 Production by Circulating Skin-Tropic and Extracutaneous Memory T Cells in Atopic Dermatitis Patients.

Interleukin (IL)-9 is present in atopic dermatitis (AD) lesions and is considered to be mainly produced by skin-homing T cells expressing the cutaneous lymphocyte-associated antigen (CLA). However, its induction by AD-associated triggers remains unexplored. Circulating skin-tropic CLA+ and extracutaneous/systemic CLA- memory T cells cocultured with autologous lesional epidermal cells from AD patients were activated with house dust mite (HDM) and staphylococcal enterotoxin B (SEB). Levels of AD-related mediators in response to both stimuli were measured in supernatants, and the cytokine response was associated with different clinical characteristics. Both HDM and SEB triggered heterogeneous IL-9 production by CLA+ and CLA- T cells in a clinically homogenous group of AD patients, which enabled patient stratification into IL-9 producers and non-producers, with the former group exhibiting heightened HDM-specific and total IgE levels. Upon allergen exposure, IL-9 production depended on the contribution of epidermal cells and class II-mediated presentation; it was the greatest cytokine produced and correlated with HDM-specific IgE levels, whereas SEB mildly induced its release. This study demonstrates that both skin-tropic and extracutaneous memory T cells produce IL-9 and suggests that the degree of allergen sensitization reflects the varied IL-9 responses in vitro, which may allow for patient stratification in a clinically homogenous population.

Real-World Experience with Vismodegib on Advanced and Multiple BCCs: Data from the RELIVIS Study.

BACKGROUND: Vismodegib is approved for advanced cases of basal cell carcinomas not amenable to surgery or radiotherapy. Large studies on the use of vismodegib in clinical practice are scarce. OBJECTIVES: The main objective of the study was to analyse the evolution and therapeutic management of relapses and lack of response in patients who had received vismodegib for locally advanced and/or multiple basal cell carcinomas in a real-life multicentre setting. METHODS: This nationwide retrospective study collected data on patients treated with vismodegib in 15 specialized centres. We included patients who first received vismodegib until intolerable toxicity, maximum response, or progressive disease. Exploratory research variables referred to patient and tumour characteristics, vismodegib effectiveness and safety, relapse rate and management, and mortality. A multivariable logistic regression model was used to identify predictors of complete clinical response. RESULTS: 133 patients with advanced BCC were included in the registry. The objective response rate (ORR) was 77.5% and nearly half of the patients (45.9%) achieved complete remission. Long-term information and detailed information of subsequent treatments after a regime of vismodegib was available for 115 patients. Only 34% of the patients in this group were subsequently treated with other therapies or vismodegib rechallenge. Sixty-nine percent of the patients who had shown a complete remission with vismodegib remained free of recurrence while 30.7% relapsed. Almost half of the patients who received additional therapies after the first course of vismodegib achieved complete tumour remission. Three and 2 out of 9 patients who were rechallenged with vismodegib achieved complete and partial responses, respectively, with an ORR of 55.5%. CONCLUSION: Our study confirms efficacy of vismodegib in routine clinical practice. The risk of recurrence after achieving complete response with vismodegib was lower than previous reports. Rechallenge with vismodegib is feasible and most patients responded to re-treatment.

Cutaneous Neoplasms in Myotonic Dystrophy Type 1.

BACKGROUND: The most frequent skin features associated with myotonic dystrophy type 1 (DM1) are frontal alopecia and pilomatrixomas. Several reports suggest that the incidence of basal cell carcinoma is increased in DM1. However, two recently published studies examining this topic have contradictory results. OBJECTIVE: To retrospectively study the incidence of cutaneous tumours in patients with DM1. METHODS: The clinical features of 102 Caucasian patients diagnosed with DM1 at Bellvitge Hospital in Barcelona, Spain, were retrospectively analysed. Clinical charts of the patients were reviewed, and cutaneous tumours diagnosed in our hospital were recorded. A group of 103 Caucasian patients matched for age and sex were used as the control group. RESULTS: A total of 56 male and 46 female patients with DM1 were included in the study (mean age 49.07 years, SD 13.02). At least 1 basal cell carcinoma was diagnosed in 6 patients in the DM1 group versus 3 patients in the control group (p = 0.332). The mean age at diagnosis of the first basal cell carcinoma was 51 years compared with 66 years in the control group (p = 0.035). Five patients with DM1 presented pilomatrixomas versus none in the control group (p = 0.029). We did not detect any melanoma in our DM1 patients. CONCLUSION: Basal cell carcinomas appeared at a significantly younger age in our DM1 patients than in the general population, and this suggests that, at least in some patients, DM1 may predispose to the development of basal cell carcinomas.

Allergen sensitization stratifies IL-31 production by memory T cells in atopic dermatitis patients.

Background: The role of allergen sensitization in IL-31 production by T cells and specifically in the clinical context of atopic dermatitis (AD) has not been characterized. Methods: The response to house dust mite (HDM) in purified memory T cells cocultured with epidermal cells from AD patients (n=58) and control subjects (n=11) was evaluated. AD-associated cytokines from culture supernatants, plasma proteins and mRNA expression from cutaneous lesions were assessed and related with the clinical features of the patients. Results: HDM-induced IL-31 production by memory T cells defined two subsets of AD patients according to the presence or absence of IL-31 response. Patients in the IL-31 producing group showed a more inflammatory profile, and increased HDM-specific (sp) and total IgE levels compared to the IL-31 non-producing group. A correlation between IL-31 production and patient's pruritus intensity, plasma CCL27 and periostin was detected. When the same patients were analyzed based on sp IgE and total IgE levels, an increased IL-31 in vitro response, as well as type 2 markers in plasma and cutaneous lesions, was found in patients with sp IgE levels > 100 kUA/L and total IgE levels > 1000 kU/L. The IL-31 response by memory T cells was restricted to the cutaneous lymphocyte-associated antigen (CLA)+ T-cell subset. Conclusion: IgE sensitization to HDM allows stratifying IL-31 production by memory T cells in AD patients and relating it to particular clinical phenotypes of the disease.

Are antihistamines still used during omalizumab treatment for chronic spontaneous urticaria?

Background: The guidelines for the treatment of chronic spontaneous urticaria (CSU) recommend adding omalizumab to the treatment of patients with uncontrolled disease despite four-fold doses of second-generation antihistamines (AH). On the contrary, some studies revealed that omalizumab was effective without concomitant AH and several authors suggest tapering off AH when CSU is controlled with omalizumab. Objectives: The aim of our study was to evaluate the use of AH during treatment with omalizumab in patients with CSU in real clinical practice. Materials & Methods: This was a multicentre cross-sectional and observational study conducted by the Catalan and Balearic Chronic Urticaria Network (XUrCB) based on a cohort of 298 CSU patients treated with omalizumab. Results: In total, 23.5% of our patients decided themselves to stop taking AH during omalizumab treatment. The ratio of patients with CSU without concomitant inducible urticaria and the percentage of patients with a good response to omalizumab (UAS7≤6 and/or UCT ≥12) were higher in those who stopped taking AH. Conclusion: More studies are required to identify the phenotypic characteristics of patients responding to omalizumab as monotherapy in order to avoid overtreating with AH. Our study suggests that patients with CSU without concomitant inducible urticaria and those who achieve a good response to omalizumab tend to be controlled by omalizumab without AH. In order to establish guidelines on how to stop AH, further evidenced-based studies are required.

"Clown nose" as first manifestation of squamous cell carcinoma of the lung.

BACKGROUND: Skin metastases occur in 0.7% to 9% of all patients with cancer and are usually considered a late event in the evolution of most visceral carcinomas. The development of a nodular metastatic lesion on the nasal tip is known as clown nose sign. MAIN OBSERVATION: We report a 64-year-old man that developed a nodular lesion on his nasal tip as first manifestation of squamous lung carcinoma. CONCLUSION: The biopsy of the cutaneous metastasis may be helpful to histopathologically confirm the suspected primary tumour avoiding invasive diagnostic procedures.