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Biologic treatments have revolutionised the management of psoriasis in recent years; however, data on their safety profile in large populations and long-term effects are being gathered on an ongoing basis. Ustekinumab is a monoclonal antibody that targets interleukin-12/23 used in the treatment of moderate-to-severe psoriasis. Here, we report the case of a 32-year-old Caucasian gentleman who developed thyrotoxicosis following the commencement of ustekinumab treatment. Following control of thyroid status by the Endocrinology team, this recurred after recommencement of ustekinumab on two further occasions over a 5-year period. This is the second known reported association of this nature. Awareness of these possible adverse effects is imperative in managing patients and informing decision-making, and further long-term studies will help elucidate the precise safety profiles of biologic treatments.

Background The authors sought to compare gray matter changes in First Episode Schizophrenia (FES) compared with Fronto-Temporal Lobar Degeneration (FTLD) using meta-analytic methods applied to neuro-imaging studies. Methods A systematic search was conducted for published, structural voxel-based morphometric MRI studies in patients with FES or FTLD. Data were combined using anatomical likelihood estimation (ALE) to determine the extent of gray matter decreases and analysed to ascertain the degree of overlap in the spatial distribution of brain changes in both diseases. Results Data were extracted from 18 FES studies (including a total of 555 patients and 621 comparison subjects) and 20 studies of FTLD or related disorders (including a total of 311 patients and 431 comparison subjects). The similarity in spatial overlap of brain changes in the two disorders was significant (p = 0.001). Gray matter deficits common to both disorders included bilateral caudate, left insula and bilateral uncus regions. Conclusions There is a significant overlap in the distribution of structural brain changes in First Episode Schizophrenia and Fronto-Temporal Lobar Degeneration. This may reflect overlapping aetiologies, or a common vulnerability of these regions to the distinct aetio-pathological processes in the two disorders.

Polyarteritis nodosa (PAN) is a multisystem, necrotising vasculitis of small- and medium-sized arteries with a predilection for the visceral vessels. Cutaneous PAN is a rare variant with symptomatic vasculitis limited to the skin, typically presenting as nodular lesions on the extremities with a propensity to ulcerate. We describe a rare case of histologically confirmed cutaneous PAN presenting in a 55-year-old Ghanaian woman with severe oropharyngeal ulceration. This was associated with dysphagia and significant weight loss. Oesophagoduodenoscopy showed that the ulceration extended throughout the oropharynx. Systemic polyarteritis nodosa was ruled out with magnetic resonance angiography. Our patient was treated successfully with corticosteroids and methotrexate. This case suggests that cutaneous PAN should be considered in the differential diagnosis of patients with oropharyngeal ulceration and that histological assessment is pivotal in establishing the diagnosis early in order to instigate appropriate therapy.

Biologic treatments have revolutionised the management of psoriasis in recent years; however, data on their safety profile in large populations and long-term effects are being gathered on an ongoing basis. Ustekinumab is a monoclonal antibody that targets interleukin-12/23 used in the treatment of moderate-to-severe psoriasis. Here, we report the case of a 32-year-old Caucasian gentleman who developed thyrotoxicosis following the commencement of ustekinumab treatment. Following control of thyroid status by the Endocrinology team, this recurred after recommencement of ustekinumab on two further occasions over a 5-year period. This is the second known reported association of this nature. Awareness of these possible adverse effects is imperative in managing patients and informing decision-making, and further long-term studies will help elucidate the precise safety profiles of biologic treatments.

The Human Developmental Cell Atlas (HDCA) initiative, which is part of the Human Cell Atlas, aims to create a comprehensive reference map of cells during development. This will be critical to understanding normal organogenesis, the effect of mutations, environmental factors and infectious agents on human development, congenital and childhood disorders, and the cellular basis of ageing, cancer and regenerative medicine. Here we outline the HDCA initiative and the challenges of mapping and modelling human development using state-of-the-art technologies to create a reference atlas across gestation. Similar to the Human Genome Project, the HDCA will integrate the output from a growing community of scientists who are mapping human development into a unified atlas. We describe the early milestones that have been achieved and the use of human stem-cell-derived cultures, organoids and animal models to inform the HDCA, especially for prenatal tissues that are hard to acquire. Finally, we provide a roadmap towards a complete atlas of human development. This Perspective outlines the Human Developmental Cell Atlas initiative, which uses state-of-the-art technologies to map and model human development across gestation, and discusses the early milestones that have been achieved.

Cutaneous T cell lymphoma (CTCL) is a potentially fatal clonal malignancy of T cells primarily affecting the skin. The most common form of CTCL, mycosis fungoides, can be difficult to diagnose, resulting in treatment delay. We performed single-cell and spatial transcriptomics analysis of skin from patients with mycosis fungoides-type CTCL and an integrated comparative analysis with human skin cell atlas datasets from healthy and inflamed skin. We revealed the co-optation of T helper 2 (T H 2) cell-immune gene programs by malignant CTCL cells and modeling of the tumor microenvironment to support their survival. We identified MHC-II + fibroblasts and dendritic cells that can maintain T H 2 cell-like tumor cells. CTCL tumor cells are spatially associated with B cells, forming tertiary lymphoid structure-like aggregates. Finally, we validated the enrichment of B cells in CTCL and its association with disease progression across three independent patient cohorts. Our findings provide diagnostic aids, potential biomarkers for disease staging and therapeutic strategies for CTCL. Haniffa and colleagues provide diagnostic aids, potential biomarkers for disease staging and therapeutic strategies for cutaneous T cell lymphoma.

Cutaneous T cell lymphoma (CTCL) is a potentially fatal clonal malignancy of T cells primarily affecting the skin. The most common form of CTCL, mycosis fungoides, can be difficult to diagnose, resulting in treatment delay. We performed single-cell and spatial transcriptomics analysis of skin from patients with mycosis fungoides-type CTCL and an integrated comparative analysis with human skin cell atlas datasets from healthy and inflamed skin. We revealed the co-optation of T helper 2 (T 2) cell-immune gene programs by malignant CTCL cells and modeling of the tumor microenvironment to support their survival. We identified MHC-II fibroblasts and dendritic cells that can maintain T 2 cell-like tumor cells. CTCL tumor cells are spatially associated with B cells, forming tertiary lymphoid structure-like aggregates. Finally, we validated the enrichment of B cells in CTCL and its association with disease progression across three independent patient cohorts. Our findings provide diagnostic aids, potential biomarkers for disease staging and therapeutic strategies for CTCL.

Graham Thornicroft and colleagues (Jan 31, p 408) address an important health issue. Schizophrenia is highly prevalent and the consequences of stigmatisation are often devastating forthose involved. Although their study was the first to assess systematically the experiences of people with schizophrenia globally, I have some concerns about the interpretation of the findings because of a failure to address two important issues.

May be inaccurate in some ethnic groups, and better tests are needed