Allergic contact dermatitis in adults with and without atopic dermatitis: Evaluation of the Spanish Contact Dermatitis Registry (REIDAC).

BACKGROUND: Atopic dermatitis (AD) and allergic contact dermatitis (ACD) are inflammatory skin conditions whose association is not clearly defined. OBJECTIVES: To identify differences in ACD profile between patients with and without AD among those referred for patch testing. Additionally, to determine the prevalence of sensitisation to standard Spanish contact allergens in both groups. METHODS: We analysed two groups (AD and non-AD) within the Spanish Registry of Research in Contact Dermatitis and Cutaneous Allergy (REIDAC). Contact allergy, clinical relevance and epidemiological data were compared between them. RESULTS: A total of 5055 patients were included. Among them, 23% (1168) had a history or final diagnosis of AD. At least one positive reaction was seen in 468 (40%) of AD patients and 1864 (48%) of non-AD patients. In both groups, the most common positive reactions were to nickel sulphate, methylchloroisothiazolinone/methylisothiazolinone and cobalt chloride. Age-adjusted OR for sensitisation to nickel sulphate was 0.72 (95% CI: 0.61-0.86), indicating a decreased likelihood of sensitisation in AD patients compared to non-AD individuals. CONCLUSIONS: We did not find an increased presence of ACD in patients with AD referred for patch testing, exhibiting similar profiles to non-AD population, except for a negative relationship between AD and sensitisation to nickel sulphate.

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.

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.

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

La vía Janus Kinase/Signal Transducer and Activator of Transcription (JAK/STAT) es esencial en la señalización final de una gran mayoría de interleucinas (IL) fundamentales en la patogénesis de la dermatitis atópica (DA). El bloqueo transversal que consiguen los inhibidores de JAK a través de la inhibición intermitente de las acciones de múltiples citoquinas, permite modular la inflamación Th2, la disfunción de barrera epidérmica y la señalización del prurito. Sin embargo, esa inhibición amplia también puede asociarse con una mayor variedad de efectos adversos. En este artículo se revisan los inhibidores de JAK recientemente aprobados en la DA —baricitinib, upadacitinib y abrocitinib—, así como otros emergentes o en desarrollo como gusacitinib, delgocitinib, ruxolitinib, brepocitinib, tofacitinib y cerdulatinib. El bloqueo de la señalización de diversas citoquinas relevantes en esta dermatosis, compleja patogénicamente y con una expresión fenotípica heterogénea, a través de los inhibidores de JAK, ha supuesto una revolución en el tratamiento de la DA (AU)

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 (AU)

[Translated article] 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 (AU)

La vía Janus Kinase/Signal Transducer and Activator of Transcription (JAK/STAT) es esencial en la señalización final de una gran mayoría de interleucinas (IL) fundamentales en la patogénesis de la dermatitis atópica (DA). El bloqueo transversal que consiguen los inhibidores de JAK a través de la inhibición intermitente de las acciones de múltiples citoquinas, permite modular la inflamación Th2, la disfunción de barrera epidérmica y la señalización del prurito. Sin embargo, esa inhibición amplia también puede asociarse con una mayor variedad de efectos adversos. En este artículo se revisan los inhibidores de JAK recientemente aprobados en la DA —baricitinib, upadacitinib y abrocitinib—, así como otros emergentes o en desarrollo como gusacitinib, delgocitinib, ruxolitinib, brepocitinib, tofacitinib y cerdulatinib. El bloqueo de la señalización de diversas citoquinas relevantes en esta dermatosis, compleja patogénicamente y con una expresión fenotípica heterogénea, a través de los inhibidores de JAK, ha supuesto una revolución en el tratamiento de la DA (AU)

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.

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

Antecedentes En los últimos años se ha producido una revolución en el conocimiento de la dermatitis atópica (DA) que ha revertido en un salto cualitativo en las expectativas terapéuticas. En este contexto, resulta fundamental disponer de datos de práctica clínica de calidad. Material y método BIOBADATOP es el Registro Español de Dermatitis Atópica, un estudio observacional, prospectivo y multicéntrico, con una cohorte de pacientes de cualquier edad con DA que requieren el empleo de tratamiento sistémico (convencional o innovador). Se registraron los datos demográficos, de diagnóstico, los tratamientos y los acontecimientos adversos (AA). Resultados Se incluyeron 258 pacientes, con 347 tratamientos sistémicos iniciados para la DA. Se suspendieron el 29,4% de los tratamientos, principalmente por falta de eficacia (10,7%). Durante el período de seguimiento se registraron 132AA. Del total, el 65% (86) relacionaron con el tratamiento sistémico iniciado, siendo los más frecuentes dupilumab (39AA) y ciclosporina (38AA). Los AA más frecuentes fueron: conjuntivitis (11pacientes), cefalea (6), hipertricosis (5) y náuseas (4). Se registró un AA grave (mastoiditis aguda) relacionado con ciclosporina. Conclusiones En este primer informe, la descripción de AA está limitada por los cortos períodos de seguimiento, que no permiten el cálculo de tasas de incidencias crudas ni ajustadas y no se han realizado comparaciones. Hasta la fecha del análisis no se han registrado AA graves en relación a las nuevas terapias. BIOBADATOP permitirá generar conocimiento en términos de efectividad y seguridad de los tratamientos sistémicos clásicos y las nuevas terapias en DA (AU)

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 (AU)

[Translated article] 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 (AU)

Antecedentes En los últimos años se ha producido una revolución en el conocimiento de la dermatitis atópica (DA) que ha revertido en un salto cualitativo en las expectativas terapéuticas. En este contexto, resulta fundamental disponer de datos de práctica clínica de calidad. Material y método BIOBADATOP es el Registro Español de Dermatitis Atópica, un estudio observacional, prospectivo y multicéntrico, con una cohorte de pacientes de cualquier edad con DA que requieren el empleo de tratamiento sistémico (convencional o innovador). Se registraron los datos demográficos, de diagnóstico, los tratamientos y los acontecimientos adversos (AA). Resultados Se incluyeron 258 pacientes, con 347 tratamientos sistémicos iniciados para la DA. Se suspendieron el 29,4% de los tratamientos, principalmente por falta de eficacia (10,7%). Durante el período de seguimiento se registraron 132AA. Del total, el 65% (86) relacionaron con el tratamiento sistémico iniciado, siendo los más frecuentes dupilumab (39AA) y ciclosporina (38AA). Los AA más frecuentes fueron: conjuntivitis (11pacientes), cefalea (6), hipertricosis (5) y náuseas (4). Se registró un AA grave (mastoiditis aguda) relacionado con ciclosporina. Conclusiones En este primer informe, la descripción de AA está limitada por los cortos períodos de seguimiento, que no permiten el cálculo de tasas de incidencias crudas ni ajustadas y no se han realizado comparaciones. Hasta la fecha del análisis no se han registrado AA graves en relación a las nuevas terapias. BIOBADATOP permitirá generar conocimiento en términos de efectividad y seguridad de los tratamientos sistémicos clásicos y las nuevas terapias en DA (AU)

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

La pandemia por SARS-CoV-2 ha causado un gran impacto desde el punto de vista sanitario, económico y social. La semiología dermatológica se ha demostrado heterogénea y compleja. En la actualidad se han definido cinco grupos principales de manifestaciones cutáneas asociadas a la COVID-19: lesiones acrales, exantemas vesiculares, erupciones urticariales, exantemas maculopapulares y lesiones livedoides/necróticas. Sin embargo, es probable que esta clasificación se modifique en el futuro. La clínica cutánea es probablemente el reflejo de distintas vías patogénicas con implicación variable de la infección vírica, del proceso inflamatorio, de las complicaciones vasculares o sistémicas de la enfermedad o incluso de los tratamientos administrados. El conocimiento de las manifestaciones cutáneas puede permitir un diagnóstico precoz o incluso servir como marcador pronóstico

The coronavirus 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (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 5 main 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