Summary
These guidelines for the management of congenital ichthyoses have been developed by a multidisciplinary group of European experts following a systematic review of the current literature, an ...expert conference held in Toulouse in 2016, and a consensus on the discussions. These guidelines summarize evidence and expert‐based recommendations and intend to help clinicians with the management of these rare and often complex diseases. These guidelines comprise two sections. This is part two, covering the management of complications and the particularities of some forms of congenital ichthyosis.
What's already known about this topic?
Various symptomatic treatment options exist for congenital ichthyoses, but there are no European guidelines.
What does this study add?
These European guidelines for the management of congenital ichthyosis may help to improve outcomes and quality of life for patients.
Linked Comment: Akiyama. Br J Dermatol 2019; 180:449–450.
Plain language summary available online
Summary
These guidelines for the management of congenital ichthyoses have been developed by a multidisciplinary group of European experts following a systematic review of the current literature, an ...expert conference held in Toulouse in 2016 and a consensus on the discussions. They summarize evidence and expert‐based recommendations and are intended to help clinicians with the management of these rare and often complex diseases. These guidelines comprise two sections. This is part one, covering topical therapies, systemic therapies, psychosocial management, communicating the diagnosis and genetic counselling.
Linked Comment: Levy. Br J Dermatol 2019; 180:253.
Abstract
Objective:
A systematic review and meta-analysis was conducted to determine the efficacy and tolerability of tacrolimus ointment for the treatment of atopic dermatitis (AD) compared with ...topical corticosteroids.
Methods:
Electronic searches were performed in Medline, Embase and the Cochrane Library, as well as relevant conference proceedings. Two researchers independently selected trials investigating the efficacy and/or safety of tacrolimus ointment in the treatment of AD. No language restrictions were applied. Relevant outcome data from included trials were extracted by two independent reviewers. Direct meta-analysis to calculate relative risks (RR) (95% confidence intervals (CIs)) was conducted on dichotomous efficacy/safety outcomes of interest.
Results:
Seventeen trials comparing tacrolimus ointment with topical corticosteroids in both paediatric (n = 2328) and adult (n = 2849) patients were identified. No studies comparing tacrolimus ointment with class IV topical corticosteroids were identified. Tacrolimus 0.1% ointment was found to be of similar efficacy to class I/II and class III topical corticosteroids. In three individual trials (comparing tacrolimus 0.1% ointment to a topical corticosteroid), evaluation of the Physician's Global Evaluation of Clinical Response (PGECR) resulted in RRs of 0.95 (95% CI 0.78-1.16), 3.09 (95% CI 2.14-4.45) and 1.35 (95% CI 0.86-2.12), where values above one favour tacrolimus ointment. With the exception that tacrolimus ointment caused more skin burning than comparator treatments (tacrolimus 0.03% versus a class III topical corticosteroid, the RR was 3.00 (95% CI 1.21-7.43) in favour of the corticosteroid), no significant differences with regards to side-effects and withdrawals due to AEs were found. Quality of life data were reported in two studies. While one study reported greater improvements in tacrolimus-treated adult patients compared with topical steroids, the second reported greater improvements in paediatric patients treated with steroids compared with tacrolimus ointment.
Conclusions:
The current review and meta-analysis showed tacrolimus ointment to be of similar efficacy to corticosteroids. The interpretation of available data is limited by heterogeneity in outcome measures between trials. Further trials are needed to assess the impact of treatments on patient reported outcomes.
Summary
Background Assessment of hand eczema in a clinical study has been achieved using a scoring system which documents extent of eczema on different areas of the hand.
Objectives To investigate ...whether the same scoring system could be used by patients to communicate current status of hand eczema.
Methods In a study of 62 patients (36 women and 26 men, age range 19–75 years), the patient’s own assessment was compared with the assessment by a dermatologist and a dermatological nurse. Standardized information was given to the patient and the form was filled in independently by the patient, the nurse and the dermatologist, during the patient’s visit to the clinic. Individual area scores were summed to a total score.
Results The overall agreement was good, with an interclass correlation (ICC) of 0·61 between patient and dermatologist for the total score. The ICC between nurse and dermatologist was 0·78. Differences between observers were more pronounced for the more severe cases – those with higher numerical scores as assessed by the dermatologist. There was a tendency for women and for patients over the median age of 44 years to set a lower point score than the dermatologist. The concordance of observations from individual anatomical areas was higher for fingertips and nails and lower for the palm and dorsum of the hand.
Conclusions Patients are able to report the extent of hand eczema with good accuracy. Self‐assessment protocols for hand eczema may well have a place in the monitoring of hand eczema extent over time.
See also the Commentary by English
Background: Autosomal recessive congenital ichthyosis (ARCI) is a heterogeneous group of skin disorders. Several mutant genes have been identified in ARCI, but the association between genotype and ...phenotype is poorly understood. Methods: To investigate genotype–phenotype correlations in ARCI, we selected 27 patients from 18 families with specific ultrastructural features of the epidermis. The characteristic findings using electron microscopy (EM) were abnormal lamellar bodies and elongated membranes in the stratum granulosum, classified as ARCI EM type III. DNA samples from a subset of affected individuals were screened for homozygous genomic regions, and a candidate gene region was identified on chromosome 5q33. The region coincides with the ichthyin gene, previously reported as mutated in ARCI. Results: Mutation screening of ichthyin revealed missense or splice-site mutations in affected members from 16 of 18 (89%) families with characteristics of ARCI EM type III. In a control group of 18 patients with ARCI without EM findings consistent with type III, we identified one patient homozygous for a missense mutation in ichthyin. Discussion: Our findings indicate a strong association between ultrastructural abnormalities in the granular layer of epidermis and ichthyin mutations. The results also suggest that EM provides a tool for specific diagnosis in a genetically homogenous subgroup of patients with ARCI.
Summary
Ichthyosis is the term used to describe continual and widespread scaling of the skin. There are several genetic types which are present from birth and persist life‐long – the “congenital ...ichthyoses”. There is no agreed treatment ‐ different doctors use different approaches, so this group of experts from all over Europe worked together to develop guidelines. They reviewed the medical literature and met to discuss the evidence and to make recommendations. A separate paper (Part 1) covered treatments for the skin condition itself. This paper, Part 2, provides guidelines for managing complications of the congenital ichthyoses. Itch, pain and infections are common, particularly fungal infection, and cancers sometimes occur. Tight skin often prevents eyelids from shutting properly so the eye surface must be protected with lubricant; eyelid massage may help and retinoid medicine may soften tight skin but can dry the eyes further. Surgical options include injecting filler or grafting extra skin to the eyelid: if the patient's own ichthyotic skin is used the problem eventually recurs and mucous membrane from inside the mouth is a promising alternative. Hearing is commonly affected: blockage of ears by a build‐up of skin may be prevented by regular oil drops but syringing or suction may be necessary. In children, growth may be affected and vitamin D supplements are usually recommended. There are special considerations for newborn babies and those with complex ichthyotic disorders such as Netherton Syndrome, epidermolytic ichthyosis and Ichthyosis Prematurity Syndrome. These treatment guidelines should help to improve outcomes and quality of life for patients with congenital ichthyoses.
Linked Article: Mazereeuw‐Hautier et al. Br J Dermatol 2019; 180:484–495
Simple, validated eczema severity scores are required for the evaluation of interventions. The Rajka & Langeland (R&L) scale is based on 3 domains (extent, course, and intensity); however, its ...validity is not yet confirmed. The aim of this study was to investigate the quality aspects of the R&L scale in clinical practice. In the first part of the study, experts and consumers judged the content validity of the scale. The second part of the study was performed with 87 children during a 4-month eczema school. Construct validity, internal consistency, sensitivity to change, time consumption and health-related quality of life variables were investigated. The content of the R&L scale was considered valid by 45 panellists. Inter- and intra-observer reliability was very good. Divergent construct validity was adequate, while convergent construct validity and internal consistency were inadequate. The R&L scale was able to define a significant improvement in eczema during the eczema school. The time required for completing the R&L assessment was significantly shorter than for objective Severity Scoring of Atopic Dermatitis (SCORAD). The R&L scale is a simple, fast, valid, reliable and sensitive tool for scoring of atopic dermatitis in everyday clinical practice.
Lamellar ichthyosis (LI) is characterized by generalized scaling of the skin and is often resistant to ordinary emollients. Recently, Locobase® fatty cream containing a mixture of 5% lactic acid and ...20% propylene glycol (LPL) was found to be markedly effective in a pilot study. To consolidate this finding, a double‐blind study comparing LPL with the corresponding mixture in Essex® (Diprobase®) cream (LPE) and Locobase® fatty cream containing either 5% urea or 20% propylene glycol was conducted in 20 patients with LI. Before and after applying the creams twice daily on each of the four extremities for 4 weeks, the following investigations were performed: scoring of xerosis, scaling and erythema, measurements of skin hydration (capacitance) and transepidermal water loss (TEWL), and moulding of the skin surface (replicas). Xerosis was reduced by all four creams, but significantly more so by LPL (P < 0·001) and LPE (P < 0·01). Scaling was only reduced by LPL (P < 0·001) and LPE (P < 0·01), which also caused a slight increase in the erythema score (P < 0·05 for both). The patients’ weekly evaluation of symptoms showed that LPL produced the most rapid effect: the response rate after 4 weeks was 63%. Skin hydration and TEWL were both significantly increased by LPL and LPE, whereas skin roughness was reduced most by LPL. Fourteen patients preferred LPL over the other cream formulations. Ten patients continued using LPL for up to 8 weeks with good results and no side‐effects other than occasional irritation in the skin folds. LPL is a major advance in the topical treatment of LI that suits most patients. Some patients, however, seem to prefer the more hydrophilic LPE formulation. Both formulations effectively reduce hyperkeratosis and xerosis, but may cause slight irritation and adversely affect the epidermal barrier function.
Autosomal recessive congenital ichthyosis (ARCI) represents a heterogeneous group of rare disorders of cornification with 3 major subtypes: harlequin ichthyosis (HI), lamellar ichthyosis (LI) and ...congenital ichthyosiform erythroderma (CIE). A 4th subtype has also been proposed: pleomorphic ichthyosis (PI), characterized by marked skin changes at birth and subsequently mild symptoms. In nationwide screenings of suspected cases of ARCI in Denmark and Sweden, we identified 132 patients (age range 0.1-86 years) classified as HI (n = 7), LI (n = 70), CIE (n = 17) and PI (n = 38). At birth, a collodion membrane or similar severe hyperkeratosis was reported in almost all patients with HI and LI, and in nearly half of patients with CIE and PI. Persistent ectropion was more common in HI (85%) and LI (57%), than in CIE (35%) and PI (5%). Anhidrosis was a frequent problem in all 4 groups (58-100%). A scoring (0-4) of ichthyosis/ery-thema past infancy showed widely different mean values in the subgroups: HI (3.2/3.1), LI (2.4/0.6), CIE (1.8/1.6), PI (1.1/0.3). Novel or recurrent mutations were found in 113 patients: TGM1 (n = 56), NIPAL4 (n = 15), ALOX12B (n = 15), ABCA12 (n = 8), ALOXE3 (n = 9), SLC27A4 (n = 5), CYP4F22 (n = 3), PNPLA1 (n = 1) and ABHD5 (n = 1). In conclusion, by performing a deep phenotyping and gene screening, ARCI can be definitely diagnosed in 85% of cases in Scandinavia, with a prevalence of 1:100,000 and > 8 different aetiologies.
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