These guidelines were developed by the psoriasis research group of the French Society of Dermatology with the aim of providing updated decision‐making algorithms for the systemic treatment of adult patients with moderate‐to‐severe psoriasis. Our algorithms were generated after rigorous evaluation of existing guidelines on the treatment of psoriasis and of publications concerning new systemic treatments, not yet incorporated into existing guidelines. A total of nine existing guidelines and 53 publications related to new systemic treatments were found to meet our criteria for use in the generation of the algorithms. We have proposed two new algorithms to assess therapeutic responses, both of which incorporate emerging criteria for evaluating treatment goals. Updated therapeutic strategy algorithms, incorporating both established and new systemic therapies, were also generated for the treatment of plaque psoriasis and psoriatic arthritis, together with recommendations for the treatment of particular forms of psoriasis and treatment of patients with comorbidities.

Summary This article is a report of the fourth meeting of the Harmonising Outcome Measures for Eczema (HOME) initiative held in Malmö, Sweden on 23–24 April 2015 (HOME IV). The aim of the meeting was to achieve consensus over the preferred outcome instruments for measuring patient‐reported symptoms and quality of life for the HOME core outcome set for atopic eczema (AE). Following presentations, which included data from systematic reviews, consensus discussions were held in a mixture of whole group and small group discussions. Small groups were allocated a priori to ensure representation of different stakeholders and countries. Decisions were voted on using electronic keypads. For the patient‐reported symptoms, the group agreed by vote that itch, sleep loss, dryness, redness/inflamed skin and irritated skin were all considered essential aspects of AE symptoms. Many instruments for capturing patient‐reported symptoms were discussed [including the Patient‐Oriented SCOring Atopic Dermatitis index, Patient‐Oriented Eczema Measure (POEM), Self‐Administered Eczema Area and Severity Index, Itch Severity Scale, Atopic Dermatitis Quickscore and the Nottingham Eczema Severity Score] and, by consensus, POEM was selected as the preferred instrument to measure patient‐reported symptoms. Further work is needed to determine the reliability and measurement error of POEM. Further work is also required to establish the importance of pain/soreness and the importance of collecting information regarding the intensity of symptoms in addition to their frequency. Much of the discussion on quality of life concerned the Dermatology Life Quality Index and Quality of Life Index for Atopic Dermatitis; however, consensus on a preferred instrument for measuring this domain could not be reached. In summary, POEM is recommended as the HOME core outcome instrument for measuring AE symptoms.

Sciences (grant no. UL1TR000039), and Arkansas Biosciences Institute (to R.C.K.). S.S.A has salary support from CEGIR (U54 AI117804) which is part of the Rare Diseases Clinical Research Network (RDCRN), an initiative of the Office of Rare Diseases Research (ORDR), NCATS, and is funded through collaboration between NIAID, NIDDK, and NCATS, funded by AI114585 (to T.A.D.). Disclosure of potential conflict of interest: E. Tkachenko owns stock in MuWells Inc (supplier of elastic cell substrates

Summary This is the report from the fifth meeting of the Harmonising Outcome Measures for Eczema initiative (HOME V). The meeting was held on 12–14 June 2017 in Nantes, France, with 81 participants. The main aims of the meeting were (i) to achieve consensus over the definition of the core domain of long‐term control and how to measure it and (ii) to prioritize future areas of research for the measurement of the core domain of quality of life (QoL) in children. Moderated whole‐group and small‐group consensus discussions were informed by presentations of qualitative studies, systematic reviews and validation studies. Small‐group allocations were performed a priori to ensure that each group included different stakeholders from a variety of geographical regions. Anonymous whole‐group voting was carried out using handheld electronic voting pads according to predefined consensus rules. It was agreed by consensus that the long‐term control domain should include signs, symptoms, quality of life and a patient global instrument. The group agreed that itch intensity should be measured when assessing long‐term control of eczema in addition to the frequency of itch captured by the symptoms domain. There was no recommendation of an instrument for the core outcome domain of quality of life in children, but existing instruments were assessed for face validity and feasibility, and future work that will facilitate the recommendation of an instrument was agreed upon.

Homozygous or compound heterozygous IL36RN gene mutations underlie the pathogenesis of psoriasis-related pustular eruptions including generalized pustular psoriasis, palmoplantar pustular psoriasis, acrodermatitis continua of Hallopeau, and acute generalized exanthematous pustular eruption. We identified two unreported IL36RN homozygous mutations (c.41C>A/p.Ser14X and c.420_426del/p.Gly141MetfsX29) in patients with familial generalized pustular psoriasis. We analyzed the impact of a spectrum of IL36RN mutations on IL-36 receptor antagonist protein by using site-directed mutagenesis and expression in HEK293T cells. This enabled us to differentiate null mutations with complete absence of IL-36 receptor antagonist (the two previously unreported mutations, c.80T>C/p.Leu27Pro, c.28C>T/p.Arg10X, c.280G>T/p.Glu94X, c.368C>G/p.Thr123Arg, c.368C>T/p.Thr123Met, and c.227C>T/p.Pro76Leu) from mutations with decreased (c.95A>G/p.His32Arg, c.142C>T/p.Arg48Trp, and c.308C>T/p.Ser113Leu) or unchanged (c.304C>T/p.Arg102Trp and c.104A>G/p.Lys35Arg) protein expression. Functional assays measuring the impact of mutations on the capacity to repress IL-36-dependent activation of the NF-κB pathway showed complete functional impairment for null mutations, whereas partial or no impairment was observed for other mutations considered as hypomorphic. Finally, null mutations were associated with severe clinical phenotypes (generalized pustular psoriasis, acute generalized exanthematous pustular eruption), whereas hypomorphic mutations were identified in both localized (palmoplantar pustular psoriasis, acrodermatitis continua of Hallopeau) and generalized variants. These results provide a preliminary basis for genotype-phenotype correlation in patients with deficiency of the IL-36Ra (DITRA), and suggest the involvement of other factors in the modulation of clinical expression.

Low plasma insulin-like growth factor (IGF)-I despite high circulating growth hormone (GH) in insulin-dependent diabetes mellitus (IDDM) indicate a hepatic GH resistance. This state may be reflected by the reduction of the circulating GH binding protein (GHBP), corresponding to the extracellular domain of the GH receptor, and the reduction of insulin-like growth factor binding protein (IGFBP)-3, major IGF-I binding protein, upregulated by GH. We carried out two studies. In the first, plasma GHBP activity was compared in patients with IDDM on continuous subcutaneous insulin infusion (CSII) or on conventional therapy and in healthy subjects. In the second study, the 18 patients on CSII at baseline were then treated by continuous intraperitoneal insulin infusion with an implantable pump (CPII) and prospectively studied for GH-IGF-I axis. Although HbA1c was lower in patients on CSII than in those on conventional therapy, GHBP was similarly reduced in both when compared to control subjects (10.2 +/- 0.8 and 11.6 +/- 0.9% vs 21.0 +/- 1.3, p < 0.01). CPII for 12 months resulted in: a slight and transient improvement in HbA1c (Time (T)0: 7.6 +/- 0.2%, T3: 7.1 +/- 0.2%, T12: 7.5 +/- 0.2%, p < 0.02), improvement in GHBP (T0: 10.2 +/- 0.8%, T12: 15.5 +/- 1.5, p < 0.0001), near-normalization of IGF-I (T0: 89.4 +/- 8.8 ng/ml, T12: 146.9 +/- 15.6, p < 0.002) and normalization of IGFBP-3 (T0: 1974 +/- 121 ng/ml, T12: 3534 +/- 305, p < 0.0001). The hepatic GH resistance profile in IDDM does not seem to be related to glycaemic control, but partly to insufficient portal insulinization. Intraperitoneal insulin delivery, allowing primary portal venous absorption, may influence GH sensitivity, and improve hepatic IGF-I and IGFBP-3 generation.

BackgroundDupilumab is approved for use in moderate‐to‐severe atopic dermatitis (AD) and as an add‐on maintenance treatment in patients suffering from severe asthma with type 2 inflammation. Ocular adverse events (OAEs) have been reported with dupilumab almost exclusively in patients treated for AD.ObjectivesThe objectives of this study were to describe the incidence and nature of dupilumab‐induced OAEs and to assess the potential predisposing factors.Patients and methodsWe conducted a prospective, single‐centre, real‐life study in adult AD patients treated with dupilumab, who were systematically examined by an ophthalmologist before and during treatment.ResultsForty‐six patients were included prospectively with a median age of 41.1 years and a median initial SCOring Atopic Dermatitis of 46.0 (IQR: 34.5–55.5). OAEs concerned 34.8% of patients and were mostly of mild to moderate severity. Two patients had to discontinue treatment due to OAE. The majority of patients developed or aggravated dry eye disease, with superficial punctate keratitis (SPK). Six patients developed conjunctivitis. Dupilumab‐induced OAEs were associated with the following pre‐existing parameters: dry eye disease with SPK (Odds ratio (OR); 6.3 [95% confidence interval (CI): 1.3–31.6]), eyelid eczema (OR: 8.7 [95%CI: 1.8–40.6]), history of food allergy (OR 3.8 (95% CI: 1.002–14,070) and IgE serum level> 1000 kU/L (OR:10.6 [CI 95%: 1.2–91.3]).ConclusionAtopic dermatitis patients with eyelid eczema or dry eye disease symptoms may be referred to an ophthalmologist before starting dupilumab to consider initiating preventive eye hydration measures. Further multicentric and translational studies are warranted to better explain OAEs pathophysiology.

The notion that it is related to M. lepromatosis may be true according to some authors. However, others showed that the correlation is not that strong, looking at leprosy clinical types in different countries 6 ; M. lepromatosis may resemble M. leprae in causing different manifestations depending on the host immunity. 2 From the group around Rea and Modlin, Maria Achoa reported at the World Congress Dermatology in Milano that of their Mexican patients with lepra bonita, the majority was indeed infected with M. lepromatosis, while some had a single M. leprae infection or a mixed infection. Whether M. lepromatosis affects the internal organs more than M. leprae is yet to be proven. The difference in the type of infection may in part account for clinical and geographical variabilities associated with leprosy infection; however, according to our opinion, the survival of the bacilli in the environment and the socioeconomic factors are relatively more important. For the practising dermatologist, the bacilli causing leprosy are of academic interest only. The treatment is the same, and it is the resistance to therapy that counts. As far as the role of physical medicine is concerned, she is right, but to direct this requires publishing of another article.