British Journal of Dermatology Early View Online Version of Record before inclusion in an issue

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How do you determine the optimal biologic treatment for psoriasis?

R. Gardner, A.D. Burden

Version of Record online: 18 July 2019

Thymic stromal lymphopoietin production induced by skin irritation results from concomitant activation of protease‐activated receptor 2 and interleukin 1 pathways

D. Redhu, K. Franke, V. Kumari, W. Francuzik, M. Babina, M. Worm

Version of Record online: 18 July 2019

What's already known about this topic?

• Thymic stromal lymphopoietin (TSLP) is rapidly induced upon skin perturbation and mediates proallergic T helper 2‐type responses by acting on leucocytes.
• Endogenous control of TSLP expression is poorly understood, but interleukin (IL)‐1 is one regulator in the cutaneous environment
• In addition to IL‐1, protease‐activated receptor 2 (PAR‐2) organizes central inflammatory pathways in the skin.

What does this study add?

• IL‐1 and PAR‐2 pathways cooperate in driving TSLP production in mice and humans.
• Pathway integration occurs at the level of the TSLP promoter through enhanced recruitment and transcriptional activation of nuclear factor kappa B.
• When PAR‐2 is co‐stimulated, very low IL‐1 levels (inactive by themselves) can induce biologically meaningful responses in the skin environment.

What is the translational message?

• Physical skin irritation results in robust TSLP production by simultaneous activation of PAR‐2 and IL‐1 pathways.

Gut microbiota dysbiosis in a cohort of patients with psoriasis

C. Hidalgo‐Cantabrana, J. Gómez, S. Delgado, S. Requena‐López, R. Queiro‐Silva, A. Margolles, E. Coto, B. Sánchez, P. Coto‐Segura

Version of Record online: 18 July 2019

What's already known about this topic?

• Psoriasis is a chronic inflammatory immune‐mediated skin disease, the aetiology of which remains unclear.
• The human microbiota is a complex microbial community that inhabits our body and has been related with the maintenance of a healthy status.
• Several studies have focused on the skin microbiome and its connection with psoriasis although less attention has been focused on the potential role of the gut microbiota in psoriatic disease.

What does this study add?

• This study unravels the gut microbiome dysbiosis present in a cohort of patients with psoriasis, compared with a healthy control group from the same geographical location.
• This study shows a lower bacterial diversity and different relative abundance of certain bacterial taxa in patients with psoriasis.
• We gain knowledge and insight into the microbiome alterations in psoriatic disease, opening new avenues for therapeutic approaches to reshape the human microbiome towards a healthy status.

Mosaic abnormalities of the skin: review and guidelines from the European Reference Network for rare skin diseases

V.A. Kinsler, O. Boccara, S. Fraitag, A. Torrelo, P. Vabres, A. Diociaiuti

Version of Record online: 18 July 2019

What's already known about this topic?

• Cutaneous mosaicism is a complex field of dermatology that encompasses most birthmarks, and many rare syndromes.
• Some cutaneous patterns are known to be seen in mosaicism.
• Very few treatment options are available for most mosaic abnormalities of the skin.
• Recent high‐sensitivity genetic techniques have led to an explosion of knowledge about genotype and phenotype in the literature.

What does this study add?

• Expert consensus from the European Reference Network project.
• Review of knowledge of confirmed mosaic abnormalities of the skin, including cutaneous phenotype, extracutaneous associated features and genotype.
• Proposed new classification of mosaic abnormalities of the skin by genetic mechanism and therefore inheritance potential.
• Practical tips on correct sample collection and genetic investigation.
• Review of trials of targeted therapies.
• Guidelines for a practical clinical approach to the patient with suspected mosaicism.

Development of inflammatory arthritis and enthesitis in patients on dupilumab: a case series

Z.N. Willsmore, R.T. Woolf, C. Hughes, B. Menon, B. Kirkham, C.H. Smith, A.E. Pink

Version of Record online: 18 July 2019

Long noncoding RNA single‐nucleotide polymorphisms: a new cause of genetic susceptibility to autoimmune blistering disease

K.T. Amber

Version of Record online: 17 July 2019

Alopecia areata is characterized by dysregulation in systemic type 17 and type 2 cytokines, which may contribute to disease‐associated psychological morbidity

K.A. Bain, E. McDonald, F. Moffat, M. Tutino, M. Castelino, A. Barton, J. Cavanagh, U.Z. Ijaz, S. Siebert, I.B. McInnes, A. Astrand, S. Holmes, S.W.F. Milling

Version of Record online: 17 July 2019

What's already known about this topic?

• NKG2D⁺CD8⁺ T cells cause hair loss in alopecia areata (AA) but the immunological mechanisms underlying the disease are not fully understood.
• AA is associated with changes in levels of interleukin (IL)‐6, tumour necrosis factor‐α, IL‐1β and type 17 cytokines.
• Psychiatric comorbidity is common among people with AA.

What does this study add?

• People with AA have increased plasma levels of the type 2 cytokines IL‐33, IL‐31 and IL‐17E (IL‐25), in addition to the type 17 cytokines IL‐17A, IL‐21, IL‐23 and IL‐17F.
• Levels of IL‐17E and IL‐22 positively predict depression score.

What is the translational message?

• AA is associated with increased levels of multiple inflammatory cytokines, implicating both type 17‐ and type 2 immune pathways.
• Our data indicate that therapeutic strategies for treating AA may need to address the underlying type 17‐ and type 2 immune dysregulation, rather than focusing narrowly on the CD8⁺ T‐cell response.
• An immunological mechanism might contribute directly to the depression observed in people with AA.

Why use an allergy‐based quality of life measure in childhood atopic eczema?

L. Manolache, A.Y. Finlay

Version of Record online: 17 July 2019

Continued treatment with secukinumab is associated with high retention or regain of response

M. Augustin, D. Thaci, K. Eyerich, A. Pinter, M. Radtke, F. Lauffer, U. Mrowietz, S. Gerdes, D. Pariser, M. Lebwohl, C. Sieder, N. Melzer, K. Reich

Version of Record online: 17 July 2019

What's already known about this topic?

• Secukinumab, a fully human monoclonal antibody that selectively neutralizes interleukin (IL)‐17A, shows significant and sustained efficacy in the treatment of moderate‐to‐severe psoriasis.
• Secondary loss of response may be experienced by a minority of patients treated with secukinumab, as with other biologics, but the extent of this and the potential for regain of efficacy with continued treatment is not well understood.

What does this study add?

• To determine stability of response to secukinumab and inform clinical practice, changes in efficacy were assessed at individual patient level using response categories.
• Efficacy with secukinumab was stable over 52 weeks of treatment in most patients, and continued treatment with secukinumab resulted in efficacy regain after loss in some patients. Persistent loss of response was uncommon.
• Patient factors such as body weight may affect the likelihood of loss of efficacy.

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The conchal bowl donor site for full‐thickness skin graft reconstruction of nasal ala surgical defects: a comprehensive review, approach and outcomes of 81 cases over 10 years

R.H. El‐khayat, P.J. Salmon, N.J. Mortimer

Version of Record online: 15 July 2019

 Open Access

Sunscreen photoprotection and vitamin D status

T. Passeron, R. Bouillon, V. Callender, T. Cestari, T.L. Diepgen, A.C. Green, J.C. van der Pols, B.A. Bernard, F. Ly, F. Bernerd, L. Marrot, M. Nielsen, M. Verschoore, N.G. Jablonski, A.R. Young

Version of Record online: 15 July 2019

What's already known about this topic?

• Knowledge of the relationship between solar exposure behaviour, sunscreen use and vitamin D is important for public health but there is confusion about optimal vitamin D status and the safest way to achieve this.
• Practical recommendations on the potential impact of daily and/or recreational sunscreens on vitamin D status are lacking for healthy people.

What does this study add?

• Judicious use of daily broad‐spectrum sunscreens with high ultraviolet (UV) A protection will not compromise vitamin D status in healthy people.
• However, photoprotection strategies for patients with photosensitivity disorders that include high sun‐protection factor sunscreens with high UVA protection, along with protective clothing and shade‐seeking behaviour are likely to compromise vitamin D status.
• Screening for vitamin D status and supplementation are recommended in patients with photosensitivity disorders.

Primary paediatric cutaneous mucinoses

F. Rongioletti

Version of Record online: 15 July 2019

What's already known about this topic?

• The nosography of primary cutaneous mucinoses occurring in childhood is confusing because of the very limited number of cases and overlaps in their clinicopathological features in the absence of homogeneous case series.
• The diagnosis and management of paediatric patients with cutaneous mucinoses are also difficult as these diseases are rarely seen in children.

What does this study add?

• New investigations have yielded significant insights into a classification of paediatric cutaneous mucinoses.
• The current update tries to offer a more meaningful guide to diagnosis and treatment of these rare diseases in patients of paediatric age.

Benefits to patient care of electronically capturing patient‐reported outcomes in dermatology

A.M. Secrest, M.‐M. Chren, Z.H. Hopkins, S.C. Chen, L.K. Ferris, R. Hess

Version of Record online: 15 July 2019

Eczema apps conformance with clinical guidelines: a systematic assessment of functions, tools and content

L.S. van Galen, X. Xu, M.J.A. Koh, S. Thng, J. Car

Version of Record online: 15 July 2019

What's already known about this topic?

• There is limited information about the quality of eczema self‐management smartphone apps on the global market.

What does this study add?

• This systematic assessment evaluated all English, Chinese and Spanish language apps that support eczema self‐management.
• The majority did not conform with information in guidelines and insufficiently support evidence‐based self‐management.
• The large variance in the quality of eczema apps highlights the need for mechanisms to ensure app quality and to guide personalized app selection for patients, caregivers and doctors.

Naegeli–Franceschetti–Jadassohn syndrome and dermatopathia pigmentosa reticularis: intrafamilial overlap of phenotypes in patients with the same KRT14 frameshift variant

B. Burger, I. Spoerri, E. Imahorn, H. Wariwoda, T. Leeb, P. H. Itin

Version of Record online: 15 July 2019

The optimal oral biopsy site for diagnosis of mucous membrane pemphigoid and pemphigus vulgaris

B. Carey, S. Joshi, A. Abdelghani, J. Mee, M. Andiappan, J. Setterfield

Version of Record online: 15 July 2019

What's already known about this topic?

• The variation in sensitivity of oral biopsy sites for direct immunofluorescence (DIF) in the diagnosis of oral MMP and PV has not been studied in detail in large series of patients.
• Biopsy can be challenging due to difficult access and fragility of the oral mucosa. The diagnostic biopsy technique is therefore critical.

What does this study add?

• We have shown that a normal buccal punch biopsy (NBPB) from uninvolved oral mucosa is as sensitive as a perilesional biopsy (PLB) for diagnosis of oral PV, and superior to serology and histology.
• For multisite MMP, NBPB is equivalent to PLB and is more sensitive than serology and histology.
• The oral punch biopsy technique on uninvolved buccal mucosa tissue is a simple and safe practical method for diagnosing oral PV and MMP.

Topical calcineurin inhibitors in the treatment of oral lichen planus: a systematic review and meta‐analysis

S.‐L. Sun, J.‐J. Liu, B. Zhong, J.‐K. Wang, X. Jin, H. Xu, F.‐Y. Yin, T.‐N. Liu, Q.‐M. Chen, X. Zeng

Version of Record online: 15 July 2019

What's already known about this topic?

• The main topical drug for oral lichen planus (OLP) is topical corticosteroids (TCS).
• Patients with OLP who are not responsive to TCS or are at risk of adverse events from TCS need other alternative drugs.
• Topical calcineurin inhibitors (TCI), including tacrolimus, pimecrolimus and ciclosporin, have become a hot topic in a variety of mucocutaneous immune‐mediated diseases.

What does this study add?

• TCI including tacrolimus, pimecrolimus and ciclosporin were similar to TCS in efficacy for the short‐term treatment of OLP.
• The local adverse events of tacrolimus were higher than with TCS. A few systemic adverse events were reported with TCI, but they were all tolerable and not serious.
• The limited evidence for pimecrolimus (three trials) and ciclosporin (six trials) requires further studies to evaluate the short‐term and long‐term efficacy and safety of TCI compared with TCS.

Single‐agent taxane is useful in palliative chemotherapy for advanced extramammary Paget disease: a case series

M. Kato, K. Yoshino, T. Maeda, K. Nagai, S. Oaku, A. Hiura, Y. Fujisawa

Version of Record online: 15 July 2019

Concurrent mucous membrane pemphigoid and membranous glomerulonephritis in a patient with autoantibodies targeting the 1080 region of collagen XVII

M. Stump, K.N. Messingham, J.A. Fairley

Version of Record online: 15 July 2019

Features of cutaneous acute graft‐versus‐host disease by reflectance confocal microscopy

I. Saknite, M. Gill, C. Alessi‐Fox, M. Byrne, M. Jagasia, S. Gonzalez, M. Ardigo, E.R. Tkaczyk

Version of Record online: 15 July 2019