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Sylvie M Franken, Carlijn L Vierstra, Thomas RustemeyerDepartment of Dermatology, VU University Medical Centre, Amsterdam, the Netherlands Introduction: Although the treatment burden for phototherapy in the outpatient setting is considerable, prescription of home-based phototherapy has not been instigated. Home-based phototherapy seems more patient friendly in terms of avoiding the thrice-weekly hospital visits. So why are most treatments still given in a hospital setting? Is home-based treatment less effective? Are there financial barriers? Is the treatment not available? To answer these questions, a literature search was done. Methods: A literature search of PubMed, Embase, and Cochrane Library databases was performed, using the search terms “psoriasis” and “phototherapy”. Selection was based on two rounds; the first round involved screening the title and abstract of all records and second involved evaluating the full text of the remaining articles for eligibility according to inclusion and exclusion criteria. Results: In total, 23 publications were included with consensus of both researchers. Overall, the patients reported being very satisfied with home-based phototherapy. Results regarding effectivity in terms of improvement from disease severity and in quality of life were variable but generally positive. Reasons for reluctance varied from medicolegal and social aspects to lack of reimbursement and unfamiliarity on the side of the prescriber. Conclusion: In the treatment for psoriasis, home-based phototherapy is as effective and safe as phototherapy in an outpatient setting. Patients were more satisfied with home-based phototherapy. Factors that negatively influence the prescription of or choice for home-based phototherapy can be summarized in terms of lack of control, lack of knowledge, and lack of a good reimbursement system. Keywords: psoriasis, phototherapy, UVB, home-based, effectiveness, burden, costs, access

Background: While many studies have reported on occupational allergic contact dermatitis amongst dental personnel, studies on the relevance of patch testing in dental patients are scarce., Objectives: To determine the frequency and clinical relevance of contact allergy in patients with intra- and perioral complaints., Methods: A total of 360 patients with intra- and perioral complaints suspected of having a contact allergy were patch-tested with the dental allergen series, European Baseline Series, and extended Amsterdam Baseline Series at Amsterdam University Medical Centers between January 2015 and November 2021., Results: A total of 285 patients (79.2%) had a positive patch test reaction for either one (18.6%) or multiple allergens (60.6%). Sodium tetrachloropalladate was the most sensitising allergen with 98 patients (27.2%) testing positive, followed by nickel sulphate (23.3%), methylisothiazolinone (15.6%), and fragrance mix I (14.2%). Clinical relevance was found in 68 of 208 patients (32.7%), with patients having one (15.4%) or multiple (17.3%) patch test reactions clinically relevant to their (peri)oral complaints., Conclusions: Clinically relevant patch test reactions were frequently seen in dental patients. Although this study provides us with a better understanding on the frequency and clinical relevance of contact allergy in dental patients, further studies are needed to confirm our results., (© 2023 The Authors. Contact Dermatitis published by John Wiley & Sons Ltd.)

Various restorative and prosthetic materials, dental implants, medicines and cosmetic materials, such as toothpaste and denture cleaning products, are used in oral care. In principle, these materials can cause contact allergies, which can manifest as lichenoid reaction, cheilitis and angioedema. It is usually a local reaction of the oral mucosa and surrounding tissues, but a systemic reaction can also occur elsewhere in the body. If a patient develops complaints from dental materials that could be due to an allergy, it makes sense to investigate this allergologically, although these do not yet show full specificity or sensitivity. After a positive allergological examination, it is possible to examine more specifically whether the patient's complaints match the test result and it can be decided whether it is sensible to replace the dental material and, if so, which material could be an alternative. After removal of the causative allergens, the complaints should disappear completely.

Background: Textile dye mix (TDM) is included in the European baseline series (EBS), but it is unknown if TDM identifies all patients with a textile dye allergy., Objectives: To assess the added value of performing patch testing with individual textile dyes in addition to TDM., Methods: Two hundred and nine patients suspected to have a contact allergy to textile dyes were patch tested between January 2015 and December 2021 with the EBS, as well as an individual textile dye test series containing textile dyes part of TDM (TDM-dyes) and outside the scope of TDM (non-TDM dyes)., Results: Fifty-four patients (25.8%) tested positive for TDM or an individual textile dye. Disperse Orange 3 (9.6%) followed by Disperse Blue 106 (4.8%) were the most common individual textile dyes causing a positive patch test reaction. Of the 54 dye positive patients, 28 (51.9%) had a clinically relevant reaction. No clinically relevant reactions were seen in patients that solely tested positive for non-TDM dyes., Conclusions: It is beneficial to test individual textile dyes in addition to TDM in patients suspected of having a textile dye allergy. Otherwise, 46.3% of the dye positive patients and 35.7% of the patients with a clinically relevant reaction would have been missed., (© 2022 The Authors. Contact Dermatitis published by John Wiley & Sons Ltd.)

Background: Allergic contact dermatitis (ACD) in paediatric patients is on the rise. Continuous identification of emerging allergens is of great importance to ensure accurate patch testing., Objectives: To assess the frequency and relevance of contact sensitivity in children and adolescents and evaluate changes in sensitization rates in the last decade., Methods: All patients with suspected ACD who underwent patch testing at the Amsterdam University Medical Centers between 2015 and 2021 were included., Results: Of 439 patients tested with the European Baseline Series (EBS) and additional series, 334 (76%) patients had at least 1 positive reaction and 172 patients (39%) had 1 or more relevant positive reactions. If additional series would have been omitted, 20% of patients would have been underdiagnosed. Compared to patients tested between 1996 and 2013, reactions to metal allergens, isothiazolinones, methyldibromo glutaronitrile, carba mix, amerchol L-101, and benzophenone-4 were more frequently observed., Conclusions: This study confirms the need for patch testing in paediatric patients suspected of having ACD. For accurate patch testing, it is advised to include additional series., (© 2022 The Authors. Contact Dermatitis published by John Wiley & Sons Ltd.)

Background: Low-dose UV treatment has been shown to be effective in mild psoriasis. However, the prolonged use of this treatment modality may raise concerns about its safety. These concerns are mainly focused on potential carcinogenic risks and overuse of this treatment modality., Objectives: This study was set out to evaluate possible carcinogenic risks of prolonged low-dose phototherapy., Methods: Three groups of psoriasis patients were evaluated: patients with local treatment only (n = 15); low-dose UV treatment at home for at least 18 months (n = 39); and patients with conventional NB-UVB (n = 8). Patients underwent visual inspection for signs of photoageing, and p53, CPDs and γH2AX were measured in skin biopsies. Patients undergoing low-dose phototherapy answered a survey about their recent patterns of use in a survey., Results: In the skin biopsies, low-dose UV treatment caused a lower amount of CPDs (p = .016) and p53 (p = .015) than NB-UVB. γH2AX did not show a significant difference. Self-report in patients undergoing low-dose phototherapy showed only one case of overuse (2.7%). Visual skin inspection showed no difference in signs of photoageing in the three groups., Conclusion: Prolonged treatment with low-dose UV for 18 months appears at least as safe as a course of conventional NB-UVB., (© 2021 The Authors. Photodermatology, Photoimmunology & Photomedicine published by John Wiley & Sons Ltd.)

Background: Patch testing with the fragrance allergy markers in the European baseline series (EBS) does not identify all patients with fragrance allergy. Hydroperoxides of linalool and limonene have been shown to be useful allergens in detecting fragrance sensitization., Objectives: To evaluate the added value of testing with 30 fragrance allergens in addition to the EBS., Methods: All patients with suspected fragrance allergy who underwent patch testing at the Amsterdam University Medical Centers between November 2019 and January 2021 to the EBS and fragrance series were included., Results: Of 323 patients tested, 162 (50.2%) were found to be fragrance sensitized. The most sensitizing single allergens were the hydroperoxides of linalool (1.0 and 0.5% pet.) and limonene (0.3 and 0.2% pet.). Testing with the hydroperoxides of linalool and limonene identified 62 fragrance-sensitized patients (38.3%) who could not be detected by the common fragrance markers. Of all fragrance-sensitized patients, 21 (13.0%) would have been missed when not testing with the fragrance series., Conclusions: Patch testing with the fragrance series in addition to the EBS is valuable. To reduce the risk of false-negative reactions, it is advisable to test the hydroperoxides of linalool and limonene., (© 2022 The Authors. Contact Dermatitis published by John Wiley & Sons Ltd.)

Introduction: The COVID-19 pandemic dramatically disrupts health care around the globe. The impact of the pandemic on chronic urticaria (CU) and its management are largely unknown., Aim: To understand how CU patients are affected by the COVID-19 pandemic; how specialists alter CU patient management; and the course of CU in patients with COVID-19., Materials and Methods: Our cross-sectional, international, questionnaire-based, multicenter UCARE COVID-CU study assessed the impact of the pandemic on patient consultations, remote treatment, changes in medications, and clinical consequences., Results: The COVID-19 pandemic severely impairs CU patient care, with less than 50% of the weekly numbers of patients treated as compared to before the pandemic. Reduced patient referrals and clinic hours were the major reasons. Almost half of responding UCARE physicians were involved in COVID-19 patient care, which negatively impacted on the care of urticaria patients. The rate of face-to-face consultations decreased by 62%, from 90% to less than half, whereas the rate of remote consultations increased by more than 600%, from one in 10 to more than two thirds. Cyclosporine and systemic corticosteroids, but not antihistamines or omalizumab, are used less during the pandemic. CU does not affect the course of COVID-19, but COVID-19 results in CU exacerbation in one of three patients, with higher rates in patients with severe COVID-19., Conclusions: The COVID-19 pandemic brings major changes and challenges for CU patients and their physicians. The long-term consequences of these changes, especially the increased use of remote consultations, require careful evaluation., (© 2020 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Background/purpose: Hospital-based phototherapy is a widely accepted treatment modality in psoriasis patients. It, however, requires several hospital visits weekly, interfering with (school)work. Home ultraviolet (UV) treatment has been proven effective before but is only available in certain countries, and safety aspects play a part in reluctancy to prescribe this treatment. Patients, however, are usually keen on the use of phototherapy as it is effective and gives them the possibility of reducing the amount of topical treatment needed. In this study, we assess the effectivity of a low-emission UV device used daily., Methods: Sixty-two patients were treated for 6 months either with daily low-emission UV treatment and mometasone ointment 0.1% or with mometasone ointment 0.1% alone. Psoriasis severity scores, quality of life, vitamin D level, and blood pressure were monitored every 2 months during the study., Results: Patients treated with daily low-emission UV treatment showed a significant improvement in psoriasis severity, quality of life, amount of steroid ointment used, and vitamin D levels., Conclusion: Daily low-emission UV therapy is an effective treatment for psoriasis patients, diminishing the amount of steroid ointment needed and improving disease activity, quality of life, and vitamin D scores. Further investigation, however, is necessary., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: An effective prophylactic treatment of patients with polymorphic light eruption (PLE) consists of repeated low, gradually increasing exposures to UVB radiation. This so-called UV(B) hardening induces better tolerance of the skin to sunlight., Objective: SunshowerMedical company (Amsterdam) has developed an UV (B) source that can be used during taking shower. The low UV fluence of this apparatus makes it an interesting device for UV hardening. In a group of PLE patients, we compared the effectiveness of the irradiation with SunshowerMedical at home with that of the UVB treatment in the hospital., Methods: The PLE patients were randomized for one of the treatments. The hospital treatment consisted of irradiations with broad-band UVB (Waldmann 85/UV21 lamps) twice a week during 6 weeks. The home UV-device was used each day with the maximal irradiation time of 6 min. The outcome assessment was based on the information obtained from patients' dermatological quality of life (DLQI) questionnaires, the ability of both phototherapies to reduce the provocation reaction and from the patients' evaluation of the long-term benefits of their phototherapies., Results: Sixteen patients completed treatment with SunshowerMedical and thirteen completed treatment in hospital. Both types of phototherapy were effective. There was a highly significant improvement in DLQI with either treatment. In most cases, the hardening reduced or even completely suppressed clinical UV provocation of PLE. The patients using SunshowerMedical at home were, however, much more content with the treatment procedure than the patients visiting the dermatological units., Conclusions: Both treatments were equally effective in the induction of skin tolerance to sunlight in PLE patients. However, the home treatment was much better accepted than the treatment in the hospital., (© 2011 The Authors. Journal of the European Academy of Dermatology and Venereology © 2011 European Academy of Dermatology and Venereology.)

Pathogenic mutations in CYLD can be identified in patients affected with Brooke-Spiegler syndrome, (Familial) Cylindromatosis or multiple familial trichoepithelioma. To date, only technologies which are able to identify small point mutations in CYLD, such as sequence and WAVE analysis, were used. Here we describe the identification of a larger rearrangement identified by Quantitative PCR analysis of CYLD, indicating that a combination of these technologies is necessary when searching for pathogenic mutations in CYLD.

The X-ray structures of the 1:1 complexes formed between p21H-ras (residues 1 to 166) and the nucleotides P3-1-(2-nitrophenyl)ethyl guanosine triphosphate ("caged GTP"; pure R- and S-diastereomers) and 3'-O-(N-methylanthraniloyl)-2'-deoxyguanosine 5'-(beta, gamma-imido)-triphosphate ("mant dG-ppNHp"), have been refined to an R-factor of 21.4% (R-caged GTP, 1.85 A resolution), 18.9% (S-caged GTP, 2.5 A resolution) and 17.6% (mant dGppNHp, 2.7 A resolution), respectively. Details of the structure determination, refinement and the structures themselves are presented. The overall structures of the complexes are identical in terms of the general organization of their secondary structure elements and are also identical to that reported for the analogous complex of p21H-ras with GppNHp. The binding of the GTP part is not significantly affected by the additional aromatic group (cage and mant, respectively) in contrast to the original observation on p21:caged GTP using the racemic mixture of R- and S-caged GTP. The main differences in the structures are observed in the region of loop L2 (residues Glu31 to Thr35) where the additional aromatic group attached to the nucleotide comes very close to the side-chain of Tyr32, including backbone displacements of 2.6 A, 2.2 A and 0.3 A for the residues from Glu31 to Thr35 for R-caged, S-caged GTP and mant dGppNHp, respectively. The refined structures provide additional data for the design of new nucleotide analogs and the importance of their stereochemistry as well as for the design of new mutant forms of p21H-ras for further biochemical investigations. The binding mode of mant dGppNHp reveals significant features for the understanding of the fluorescence signals observed in solution.

The three-dimensional structures and biochemical properties of two mutants of the G-domain (residues 1-166) of p21H-ras, p21 (G12D) and p21 (G12P), have been determined in the triphosphate-bound form using guanosine 5'-(beta,gamma-imido)triphosphate (GppNHp). They correspond to the most frequent oncogenic and the only nononcogenic mutation of Gly-12, respectively. The G12D mutation is the only mutant analyzed so far that crystallizes in a space group different from wild type, and the atomic model of the protein shows the most drastic changes of structure around the active site as compared to wild-type p21. This is due to the interactions of the aspartic acid side chain with Tyr-32, Gln-61, and the gamma-phosphate, which result in reduced mobility of these structural elements. The interaction between the carboxylate group of Asp-12 and the gamma-phosphate is mediated by a shared proton, which we show by 31P NMR measurements to exist in solution as well. The structure of p21 (G12P) is remarkably similar to that of wild-type p21 in the active site, including the position of the nucleophilic water. The pyrrolidine ring of Pro-12 points outward and seems to be responsible for the weaker affinity toward GAP (GTPase-activating protein) and the failure of GAP to stimulate GTP hydrolysis.

The crystal structure of haloalkane dehalogenase from Xanthobacter autotrophicus GJ10 has been refined at 1.9 A resolution at two different pH values, the pH of crystallization (pH 6.2) and the pH of optimal activity (pH 8.2), to final R-factors of 16.8% and 16.4%, respectively. Both models show good stereochemical quality. Two non-glycine residues have main-chain torsion angles that are located outside the "allowed" regions in a Ramachandran plot. One of them is the nucleophilic residue Asp124, which, together with the two other active site residues His289 and Asp260, is situated in an internal, predominantly hydrophobic cavity. The other residue, Asn148, helps stabilize the conformations of two of these active-site residues, Asp124 and Asp260. Comparison of the models at pH 6.2 and pH 8.2 revealed one major structural difference. At pH 6.2, a salt-bridge is present between the N epsilon 2 atom of His289 and the O delta 1 atom of Asp124, while at pH 8.2, this salt-bridge is absent, indicating that the N epsilon 2 atom of the histidine residue is mostly deprotonated at the pH of optimum activity. This is in agreement with the putative reaction mechanism in which the O delta 1 atom of Asp124 performs a nucleophilic attack on the substrate, resulting in an intermediate ester. This ester is subsequently cleaved by a hydrolytic water molecule. The high-resolution data sets clearly show the exact position of this water molecule. It is in an ideal position for donating a proton to the N epsilon 2 atom of His289 and subsequently cleaving the covalently bound intermediate ester, releasing the alcohol product. Detailed investigation of both refined models showed a number of unusual structural features. Four out of 11 helices contain an internal proline residue other than in the first turn. Two other alpha-helices have adopted in their central part a 3(10) conformation. A novel four-residue turn between a helix and a strand, the alpha beta 4 turn, is located at the site of the bend in the central eight-stranded beta-sheet of the dehalogenase structure.

The Na[Au(CN)2] heavy atom derivative contributed considerably to the successful elucidation of the crystal structure of haloalkane dehalogenase isolated from Xanthobacter autotrophicus GJ10. The gold cyanide was located in an internal cavity of the enzyme, which also contains the catalytic residues. Refinement of the dehalogenase-gold cyanide complex at 0.25 nm to an R-factor of 16.7% demonstrates that the heavy atom molecule binds non-covalently between two tryptophan residues pointing into the active site cavity. At this same site also chloride ions can be bound. Therefore, inhibition of dehalogenase activity by the Au(CN)-2 presumably occurs by competition for the same binding site as substrates.

Ras (or p21) is the product of the ras proto-oncogene and is believed to be involved in growth-promoting signal transduction. The structure of the guanine nucleotide-binding domain of H-Ras (or p21H-ras) in the triphosphate conformation was determined at very high resolution (1.4 A). All the binding interactions between protein and Gpp[NH]p and Mg2+ can be resolved in great detail. The region around amino acids 61-65 is flexible and exists in two conformations, one of which seems to be important for catalysis. The properties and structures of several oncogenic and non-oncogenic mutant forms of Ras have also been determined. Since the structure of the GDP-bound form is also known, the nature of the conformational change from the GTP-bound to the GDP-bound form can be inferred from the 3-D structure. A mechanism for the intrinsic GTP hydrolysis has been proposed. Its implications for the GAP-stimulated GTPase reaction is discussed in the light of recent kinetic and mutational experiments.

We have identified a new protein fold--the alpha/beta hydrolase fold--that is common to several hydrolytic enzymes of widely differing phylogenetic origin and catalytic function. The core of each enzyme is similar: an alpha/beta sheet, not barrel, of eight beta-sheets connected by alpha-helices. These enzymes have diverged from a common ancestor so as to preserve the arrangement of the catalytic residues, not the binding site. They all have a catalytic triad, the elements of which are borne on loops which are the best-conserved structural features in the fold. Only the histidine in the nucleophile-histidine-acid catalytic triad is completely conserved, with the nucleophile and acid loops accommodating more than one type of amino acid. The unique topological and sequence arrangement of the triad residues produces a catalytic triad which is, in a sense, a mirror-image of the serine protease catalytic triad. There are now four groups of enzymes which contain catalytic triads and which are related by convergent evolution towards a stable, useful active site: the eukaryotic serine proteases, the cysteine proteases, subtilisins and the alpha/beta hydrolase fold enzymes.

Haloalkane dehalogenase from Xanthobacter autotrophicus GJ10 converts 1-haloalkanes to the corresponding alcohols and halide ions with water as the sole cosubstrate and without any need for oxygen or cofactors. The three-dimensional structure has been determined by multiple isomorphous replacement techniques using three heavy atom derivatives. The structure has been refined at 2.4 A resolution to an R-factor of 17.9%. The monomeric enzyme is a spherical molecule and is composed to two domains: domain I has an alpha/beta type structure with a central eight-stranded mainly parallel beta-sheet. Domain II lies like a cap on top of domain I and consists of alpha-helices connected by loops. Except for the cap domain the structure resembles that of the dienelactone hydrolase in spite of any significant sequence homology. The putative active site is completely buried in an internal hydrophobic cavity which is located between the two domains. From the analysis of the structure it is suggested that Asp124 is the nucleophilic residue essential for the catalysis. It interacts with His289 which is hydrogen-bonded to Asp260.