Drug Survival in Cyclosporine Treatment for Moderate to Severe Atopic Dermatitis: Analysis of the Spanish Atopic Dermatitis Registry (BIOBADATOP). / Supervivencia de la ciclosporina en el tratamiento de la dermatitis atópica moderada-grave: Registro Español de Dermatitis Atópica (BIOBADATOP).

BACKGROUND: The past 5 years have seen a proliferation of new treatments for atopic dermatitis (AD). We analyzed recent drug survival data for cyclosporine in this setting. Because the Spanish National Healthcare system requires patients with AD to be treated with cyclosporine before they can be prescribed other systemic treatments, drug survival for cyclosporine may be shorter than in other diseases. MATERIAL AND METHOD: Multicenter, observational, prospective cohort study using data from the Spanish Atopic Dermatitis Registry (BIOBADATOP). Data from the Spanish Registry of Systemic Treatments in Psoriasis (BIOBADADERM) were used to create a comparison cohort. RESULTS: We analyzed data for 130 patients with AD treated with cyclosporine (median drug survival, 1 year). Median cyclosporine survival in the psoriasis comparison group (150 patients) was 0.37 years. Drug survival was significantly longer in AD than in psoriasis (P<.001). CONCLUSION: Drug survival of cyclosporine in the BIOBADATOP registry is similar to that described in other series of patients with AD and longer than that observed in the BIOBADADERM psoriasis registry.

Epidemiological, Clinical, and Allergic Profile of Psoriatic Patients. Evaluation of the Spanish Registry of Contact Dermatitis and Cutaneous Allergy (REIDAC). / Perfil epidemiológico, clínico y alérgico en pacientes con psoriasis. Evaluación del Registro Español de Dermatitis de Contacto (REIDAC).

BACKGROUND: Psoriasis is a chronic inflammatory dermatosis whose clinical and topographic distribution requires differential diagnosis, or the possible association with allergic contact dermatitis (ACD), requiring patch testing (PT) as part of the diagnostic procedure. OBJECTIVES: To describe the epidemiological, clinical, and allergic profile of patients with a primary or secondary diagnosis of psoriasis undergoing PT and compare them with patients with a diagnosis of ACD at the end of the diagnostic process. METHODS: Cross-sectional study with data from REIDAC from 2018 through 2023 of selected patients with a diagnosis of psoriasis and/or ACD. RESULTS: A total of 11 502 patients were included, 513 of whom had been diagnosed with primary or secondary psoriasis, 3640 with ACD, and 108 with both diseases. Men were more predominant in the groups of patients with psoriasis, psoriasis+ACD, and lesions were more predominantly seen in the hands with little association with atopic factors vs the ACD group. The rate of positivity in PT to the 2022 Spanish battery of allergens was lower in the group with psoriasis only in 27% of the patients. The most common allergens found in the psoriasis group were also the most common ones found in the overall ACD population. CONCLUSIONS: Overall, 36.2% of psoriatic patients tested positive in PT to the 2022 Spanish battery of allergens, which proved that this association is not uncommon. Overall, psoriatic patients had a higher mean age, were more predominantly men, and showed more hand involvement.

Janus Kinase Inhibitors in Atopic Dermatitis: New Perspectives. / Inhibidores de JAK en dermatitis atópica, nuevas perspectivas.

The JAK/STAT (Janus kinase/signal transducer and activator of transcription) pathway is an essential final step in the signaling process of most interleukins with a critical role in the pathogenesis of atopic dermatitis. By achieving broad, intermittent inhibition of the activity of multiple cytokines, JAK inhibitors help modulate T helper 2 cell-mediated inflammation, epidermal barrier dysfunction, and itch signaling. This comprehensive blockade, however, can result in a wider range of adverse effects. We review a number of JAK inhibitors that have been recently approved for use in atopic dermatitis, such as baricitinib, upadacitinib, and abrocitinib, as well as others that are currently in the pipeline or under development, such as gusacitinib, delgocitinib, ruxolitinib, brepocitinib, tofacitinib, and cerdulatinib. The use of JAK inhibitors to block the signaling of numerous cytokines with a critical role in the pathogenesis of atopic dermatitis has revolutionized the treatment of this pathogenically complex, phenotypically heterogeneous skin disease.

BIOBADATOP Spanish Atopic Dermatitis Registry: Description and Early Findings. / BIOBADATOP: Registro Español de Dermatitis Atópica. Descripción y primeros resultados.

BACKGROUND: In recent years, remarkable improvements in our understanding of atopic dermatitis (AD) have revolutionized treatment perspectives, but access to reliable data from clinical practice is essential. MATERIALS AND METHOD: The Spanish Atopic Dermatitis Registry, BIOBADATOP, is a prospective, multicenter database that collects information on patients of all ages with AD requiring systemic therapy with conventional or novel drugs. We analyzed the registry to describe patient characteristics, diagnoses, treatments, and adverse events (AEs). RESULTS: We studied data entries for 258 patients who had received 347 systemic treatments for AD. Treatment was discontinued in 29.4% of cases, mostly due to a lack of effectiveness (in 10.7% of cases). A total of 132 AEs were described during follow-up. Eighty-six AEs (65%) were linked to a systemic treatment, most commonly dupilumab (39AEs) and cyclosporine (38AEs). The most common AEs were conjunctivitis (11patients), headache (6), hypertrichosis (5), and nausea (4). There was 1severe AE (acute mastoiditis) associated with cyclosporine. CONCLUSIONS: Initial findings on AEs from the Spanish BIOBADATOP registry are limited by short follow-up times precluding comparisons or calculation of crude and adjusted incidence rates. At the time of our analysis, no severe AEs had been reported for novel systemic therapies. BIOBADATOP will help answer questions on the effectiveness and safety of conventional and novel systemic therapies in AD.

Skin lesions in neurofibromatosis type 2: diagnostic and prognostic significance of cutaneous (plexiform) schwannomas.

BACKGROUND: Neurofibromatosis type 2 (NF2) is a genetic disease characterized by the appearance of multiple tumours in the nervous system. Cutaneous lesions are common and may provide useful diagnostic and prognostic information, but they have not been widely studied. OBJECTIVES: To characterize cutaneous lesions in a Spanish cohort of patients with NF2 and investigate associations with clinical and genetic severity. METHODS: We studied the clinical and histologic characteristics of cutaneous lesions in 49 patients with NF2 and analysed correlations with phenotype- and genotype-based severity scores. We collected information on the presence/absence of cutaneous lesions, location, age at onset, type of lesion, and histologic features. We also studied level of systemic involvement and genetic mutations involved. RESULTS: Forty-nine patients (31 women [63.3%] and 18 men [36.7%]) were analysed, and 33 (67.3%) had cutaneous lesions presumed to be schwannomas. According to their clinical form, they were distributed as follows: 24 patients (48%) had deep tumours, 21 (42%) had plaque-like lesions, and 3 (6%) had superficial tumours. Histologic examination from 27 lesions analysed out 23 patients showed classic schwannoma or hybrid schwannoma-neurofibroma features in the 8 deep tumours biopsied and plexiform schwannoma features in the 17 plaque-like lesions and the 2 superficial tumours analysed. Early onset (first 2 decades of life) was reported by all patients with plaques and superficial tumours. In our cohort, 100% of the patients with plaque-like lesions and superficial tumours with microscopic features of plexiform schwannoma were in the 2 groups with the most severe clinical phenotypes, and 82.6% of them were in the 3 most severe genotype-based classes. CONCLUSIONS AND RELEVANCE: Cutaneous lesions, specially plexiform schwannomas, are common in NF2, and they usually appear at an early age providing useful diagnostic and prognostic information. These tumours are part of the spectrum of cutaneous manifestations in this disease. Although its diagnostic and prognostic value has been pointed out, there are few studies focussed on their analysis.

Current treatment goals are achieved by the majority of patients with atopic dermatitis treated with tralokinumab: results from a multicentric, multinational, retrospective, cohort study.

BACKGROUND: Tralokinumab is a human monoclonal antibody targeting interleukin-13 that is approved for the treatment of moderate-severe atopic dermatitis. Studies analyzing the efficacy and safety of tralokinumab in a real-world setting are scarce. RESEARCH DESIGN AND METHODS: A European, multicentric, real-world, retrospective cohort study was defined to assess the effectiveness and safeness profile of tralokinumab, investigating the achievement of pre-specified treatment goals; and to detect potential differences in terms of effectiveness and safeness across some selected patient subcohorts. RESULTS: A total of 194 adult patients were included in this study. A significant improvement in physician-assessed disease severity was detected at each follow-up visit as compared with baseline and similar trend was observed for patient-reported outcomes and quality of life. No meaningful difference in effectiveness was found when considering patient age (<65 versus ≥65 years), neither dissecting patient cohort in dupilumab-naive vs dupilumab-treated subjects. Among tralokinumab-treated patients, 88% achieved at least one currently identified real-world therapeutic goal at week 16. CONCLUSIONS: This retrospective multicenter study confirmed the effectiveness and safeness of tralokinumab throughout 32 weeks of observation, showing the achievement of therapeutic goals identified in both trial and real-world settings in a large proportion of tralokinumab-treated patients.

Innovation in Atopic Dermatitis: From Pathogenesis to Treatment. / Innovación en dermatitis atópica: de la patogenia a la terapéutica.

Atopic dermatitis is the most common inflammatory skin disease and up to 20% of cases can be classified as moderate to severe. Our understanding of the pathogenesis of this disease has improved in recent years. The process is primarily driven by the Th2 pathway, but with significant contributions from the Th22 pathway, the Th1 and Th17 axes, epidermal barrier dysfunction, pruritus, and JAK/STAT signaling. Advances in our understanding of the pathogenesis of atopic dermatitis have led to the development of new systemic treatments. Of particular note are biologic agents targeting IL-4 and IL-13 (e. g., dupilumab, tralokinumab, and lebrikizumab) and small molecules, such as JAK inhibitors (e. g., baricitinib, upadacitinib, and abrocitinib). Novel topical treatments include phosphodiesterase 4 and JAK/STAT inhibitors. In this article, we review the main advances in the treatment of atopic dermatitis. Characterization of clinical and molecular phenotypes with a key pathogenic role is essential for driving these advances.

Cutaneous Manifestations in the Context of SARS-CoV-2 Infection (COVID-19). / Manifestaciones cutáneas en el contexto de la infección por SARS-CoV-2 (COVID-19).

The coronavirus 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus2 (SARS-CoV-2), has had enormous health, economic, and social consequences. The clinical spectrum of cutaneous manifestations observed in patients with COVID-19 is both heterogeneous and complex. To date, reports have identified 5main categories: acral lesions, vesicular rashes, urticarial rashes, maculopapular rashes, and livedoid and necrotic lesions. However, these will probably be modified as new information comes to light. Cutaneous manifestations associated with COVID-19 probably reflect the activation of pathogenic pathways by the virus or a response to inflammatory processes, vascular or systemic complications, or even treatments. Familiarity with the cutaneous manifestations of COVID-19 may enable early diagnosis or help guide prognosis.

Paradoxical Reactions to Biologic Therapy in Psoriasis: A Review of the Literature. / Reacciones paradójicas de los tratamientos biológicos utilizados en psoriasis: revisión de la literatura.

Biologic drugs, which are molecules designed to act on specific immune system targets, have been shown to be very effective in treating various dermatological, rheumatological, and systemic diseases. As a group, they have an acceptable safety profile, but their use has been associated with the onset of both systemic and organ-specific inflammatory conditions. True paradoxical reactions are immune-mediated disorders that would usually respond to the biologic agent that causes them. There is still debate about whether certain other adverse reactions can be said to be paradoxical. The hypotheses proposed to explain the pathogenesis of such reactions include an imbalance in cytokine production, with an overproduction of IFN-α and altered lymphocyte recruitment and migration (mediated in part by CXCR3), and the production of autoantibodies. Some biologic therapies favor granulomatous reactions. While most of the paradoxical reactions reported have been associated with the use of TNF-α inhibitors, cases associated with more recently introduced biologic therapies -such as ustekinumab, secukinumab, and ixekizumab- are increasingly common. The study of paradoxical adverse events not only favors better management of these reactions in patients receiving biologic therapy, but also improves our knowledge of the pathogenesis of chronic inflammatory diseases and helps to identify potential therapeutic targets.