Dupilumab treatment in paediatric atopic dermatitis (2 to 18 years): Spanish multicentre retrospective real-life study.

BACKGROUND: Moderate-to-severe atopic dermatitis (AD) can be difficult to manage in paediatric patients, with few licensed treatments in this age group. Dupilumab is approved for AD in children older than 6 months. OBJECTIVES: To assess the effectiveness and safety of dupilumab in a real-life cohort of paediatric AD patients in Spain. METHODS: A multicentre, retrospective real-life study on the effectiveness and safety of dupilumab in patients aged 2 to 18 years old with moderate-to-severe AD was conducted. Demographic and clinical characteristics were analysed, and effectiveness (EASI, IGA, DLQI, NRS itch), safety, and drug survival measures were assessed. A comparison of our results with other real-world outcomes and with clinical trials was made. RESULTS: Data from 243 patients from 19 centres was collected, with a mean follow-up of 85 weeks. Dupilumab exhibited significant effectiveness, with marked reductions in severity scores from week 4. By week 16, 79.4% of patients reached EASI75 and 40.5% reached EASI90. Mean percentage reduction in EASI was 79.7%. Increasing improvements were observed until week 52, with 85.8% and 49.6% achieving EASI75 and EASI90, respectively. Forty-three patients developed adverse events (AE) (43/243, 17.7%), being the most frequent ocular surface diseases (20/243, 8.2%), injection site reactions (8/243, 3.3%) and facial redness (7/243, 2.9%). Drug survival was high (96.9% and 93.1% after 1 and 2 years of follow-up, respectively), with only 19 (19/243, 7.8%) patients interrupting treatment: 7 (7/243, 2.9%) due to AE, 2 (2/243, 0.82%) due to secondary failure, 5 (5/243, 2.1%) were lost to follow-up and 5 (5/243, 2.1%) entered remission and stopped treatment. CONCLUSION: Real-life use of dupilumab in paediatric AD showcased sustained effectiveness, high drug survival, and acceptable safety profiles. Longer-term studies are crucial for AE surveillance and how to manage disease remission.

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.

Inflammatory linear verrucous epidermal nevus associated with erosive monoarthritis.

Inflammatory linear verrucous epidermal nevus and linear psoriasis are different entities with clinical and histopathologic similarities. Isolated reports of inflammatory linear verrucous epidermal nevus with concomitant psoriasis or a positive family history of psoriasis have been described, and the possibility that inflammatory linear verrucous epidermal nevus may be a mosaic form of cutaneous psoriasis has been postulated. We report a 17-year-old boy with a congenital, linear, erythematous, keratotic plaque on the dorsum of the fifth finger of the left hand with ipsilateral nail dystrophy. Histopathologic examination showed epidermal hyperplasia with alternating orthokeratosis and parakeratosis. During follow-up, he developed erosive monoarthritis of the distal interphalangeal joint. This case seems to confirm the association between inflammatory linear verrucous epidermal nevus and arthritis and supports a possible relationship between inflammatory linear verrucous epidermal nevus and psoriasis.

Basophil FcεRI Expression in Chronic Spontaneous Urticaria: A Potential Immunological Predictor of Response to Omalizumab Therapy.

Although the efficacy of omalizumab has been clearly demonstrated in the treatment of chronic spontaneous urticaria (CSU), its mechanism of action, which results in improvement in CSU symptoms, is not entirely understood. This study investigated the effect of omalizumab on expression of the high-affinity IgE receptor (FcεRI) on blood basophils from patients with active CSU, and its association with the clinical response. Patients exhibiting significant clinical improvement showed a sharp reduction in the levels of basophil FcεRI after 4 weeks, which was maintained throughout the total duration of the treatment. Such evolution was not observed in non-responder patients. Furthermore, non-responders showed significantly lower baseline levels of FcεRI than responders. Baseline basophil FcεRI expression was found to be a potential immunological predictor of response to omalizumab (100% sensitivity and 73.2% specificity). The results of this study contribute to our knowledge of the therapeutic benefit and mechanism of action of anti-IgE therapy in CSU.

Acquired cold urticaria: Clinical features, particular phenotypes, and disease course in a tertiary care center cohort.

BACKGROUND: Data about special phenotypes, natural course, and prognostic variables of patients with acquired cold urticaria (ACU) are scarce. OBJECTIVES: We sought to describe the clinical features and disease course of patients with ACU, with special attention paid to particular phenotypes, and to examine possible parameters that could predict the evolution of the disease. METHODS: This study was a retrospective chart review of 74 patients with ACU who visited a tertiary referral center of urticaria between 2005 and 2015. RESULTS: Fourteen patients (18.9%) presented with life-threatening reactions after cold exposure, and 21 (28.4%) showed negative results after cold stimulation tests (classified as atypical ACU). Nineteen patients (25.7%) achieved complete symptoms resolution at the end of the surveillance period and had no subsequent recurrences. Higher rates of atypical ACU along with a lower likelihood of achieving complete symptom resolution was observed in patients who had an onset of symptoms during childhood (P < .05). In patients with atypical ACU, shorter disease duration and lower doses of antihistamines required for achieving disease control were detected (P < .05). Age at disease onset, symptom severity, and cold urticaria threshold values were found to be related to disease evolution (P < .05). LIMITATIONS: This study was limited by its retrospective nature. CONCLUSIONS: The knowledge of the clinical predictors of the disease evolution along with the clinical features of ACU phenotypes would allow for the establishment of an early and proper therapeutic strategy.

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.

A concept for integrated care pathways for atopic dermatitis-A GA2 LEN ADCARE initiative.

INTRODUCTION: The integrated care pathways for atopic dermatitis (AD-ICPs) aim to bridge the gap between existing AD treatment evidence-based guidelines and expert opinion based on daily practice by offering a structured multidisciplinary plan for patient management of AD. ICPs have the potential to enhance guideline recommendations by combining interventions and aspects from different guidelines, integrating quality assurance, and describing co-ordination of care. Most importantly, patients can enter the ICPs at any level depending on AD severity, resources available in their country, and economic factors such as differences in insurance reimbursement systems. METHODS: The GA2 LEN ADCARE network and partners as well as all stakeholders, abbreviated as the AD-ICPs working group, were involved in the discussion and preparation of the AD ICPs during a series of subgroup workshops and meetings in years 2020 and 2021, after which the document was circulated within all GAL2 EN ADCARE centres. RESULTS: The AD-ICPs outline the diagnostic procedures, possible co-morbidities, different available treatment options including differential approaches for the pediatric population, and the role of the pharmacists and other stakeholders, as well as remaining unmet needs in the management of AD. CONCLUSION: The AD-ICPs provide a multidisciplinary plan for improved diagnosis, treatment, and patient feedback in AD management, as well as addressing critical unmet needs, including improved access to care, training specialists, implementation of educational programs, assessment on the impact of climate change, and fostering a personalised treatment approach. By focusing on these key areas, the initiative aims to pave the way for a brighter future in the management of AD.

Pruritic nodular secondary syphilis in a 61-year-old man with HIV infection.

The typical finding in secondary syphilis stage is a generalized non-pruritic maculopapular eruption. We report a case of secondary syphilis in an HIV-infected patient presenting with pruritic crusted nodules showing numerous eosinophils on the histopathological examination.