The analysis of an unparalleled resource revealed key clinical and genetic differences between patients with PPP and those with GPP.

Prominent skin involvement is a defining characteristic of autoinflammatory disorders caused by abnormal IL-1 signaling. However, the pathways and cell types that drive cutaneous autoinflammatory features remain poorly understood. We sought to address this issue by investigating the pathogenesis of pustular psoriasis, a model of autoinflammatory disorders with predominant cutaneous manifestations. We specifically characterized the impact of mutations affecting AP1S3, a disease gene previously identified by our group and validated here in a newly ascertained patient resource. We first showed that AP1S3 expression is distinctively elevated in keratinocytes. Because AP1S3 encodes a protein implicated in autophagosome formation, we next investigated the effects of gene silencing on this pathway. We found that AP1S3 knockout disrupts keratinocyte autophagy, causing abnormal accumulation of p62, an adaptor protein mediating NF-κB activation. We showed that as a consequence, AP1S3-deficient cells up-regulate IL-1 signaling and overexpress IL-36α, a cytokine that is emerging as an important mediator of skin inflammation. These abnormal immune profiles were recapitulated by pharmacological inhibition of autophagy and verified in patient keratinocytes, where they were reversed by IL-36 blockade. These findings show that keratinocytes play a key role in skin autoinflammation and identify autophagy modulation of IL-36 signaling as a therapeutic target.

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Introduction: Psoriasis is a chronic inflammatory disease with a global prevalence of approximately 2% and significant psychiatric comorbidity. There is a great deal of existing literature assessing different aspects of psychology in psoriasis. We aimed to conduct an in-depth review of current evidence linking psoriasis to personality traits and psychiatric comorbidities, as well as factors that put these patients at risk of psychopathology. Materials and Methods: A search of the PubMed database identified 1632 articles. We included articles studying psychological comorbidity in patients with psoriasis, looking especially at personality characteristics, and data linking psoriasis with increased risks of psychological distress, depression, anxiety and suicidality. In particular, we also evaluated subgroups in psoriasis found to be at risk. Results: Patients with psoriasis are more likely to be alexithymic, lack body awareness and possess a Type D personality. Alcohol, but not illicit drug use, disorders are also more common in patients with psoriasis. Patient groups who are especially at risk of psychological distress include women, younger patients, patients with a younger age of disease onset, those who self-assess their psoriasis to be severe, and those with lesions on visible or sensitive areas. Adopting motivational interviewing skills and incorporating the use of learning materials during consultations have been found to be useful. Conclusion: The knowledge of personality characteristics, “at-risk” groups, and early recognition of psychological distress among patients with psoriasis can help clinicians provide better holistic care and encourage a change in patients’ behaviour. Key words: Alexithymia, Personality, Psychopathology, Suicidality

The ASPSG recommends a patient-centered approach to scalp psoriasis management, consistent with the international consensus statements. Asian physicians should also consider patient QoL, prior treatment response, formulation preferences, likely adherence, cost, time available for self-management, and potential adverse events.