New, simplified versus standard photodynamic therapy (PDT) regimen for superficial and nodular basal cell carcinoma (BCC): A single-blind, non-inferiority, randomised controlled multicentre study.

BACKGROUND: Topical photodynamic therapy (PDT) is an approved and widely used treatment for low-risk basal cell carcinoma (BCC), comprising two sessions with an interval of 1 week. Simplification of the treatment course can be cost-effective, easier to organize, and cause less discomfort for the patients. METHODS AND FINDINGS: We performed an investigator-initiated, single-blind, non-inferiority, randomized controlled multicentre study with the objective of investigating whether a simpler and more flexible PDT regimen was not >10% less effective than the standard double PDT in the treatment of primary, superficial, and nodular ≤2 mm-thick BCC and evaluate the cosmetic outcome. With a non-inferiority margin of 0.1 and an expected probability complete response of 0.85, 190 tumours were required in each group. Histologically verified BCCs from seven centres in Norway were randomly assigned (1:1) to either receive a new regimen of single PDT with one possible re-treatment of non-complete responding tumours, or the standard regimen. The primary endpoint was the number of tumours with complete response or treatment failure at 36 months of follow-up, assessed by investigators blinded to the treatment regimen. Intention-to-treat and per-protocol analyses were performed. The cosmetic outcome was recorded. The study was registered with ClinicalTrials.gov, NCT-01482104, and EudraCT, 2011-004797-28. A total of 402 BCCs in 246 patients were included; 209 tumours assigned to the new and 193 to the standard regimen. After 36 months, there were 61 treatment failures with the new and 34 failures with the standard regimen. Complete response rate was 69.5% in the new and 81.1% in the standard treatment group. The difference was 11.6% (upper 97.5% CI 20.3), i.e. > than the non-inferiority margin of 10%. Cosmetic outcomes were excellent or good in 92% and 89% following the new and standard regimens, respectively. CONCLUSIONS: Single PDT with possible re-treatment of primary, superficial, and nodular ≤ 2-mm-thick BCC was significantly less effective than the approved standard double treatment. The cosmetic outcome was favorable and comparable between the two treatment groups.

Clinical consequences of infliximab immunogenicity and the effect of proactive therapeutic drug monitoring: exploratory analyses of the randomised, controlled NOR-DRUM trials.

BACKGROUND: Antidrug antibodies to TNF inhibitors might affect clinical outcomes. Proactive therapeutic drug monitoring allows for early detection of antidrug antibodies and might reduce negative clinical consequences. We aimed to explore how antidrug antibodies to the TNF inhibitor infliximab influence treatment outcomes, and to assess the effect of proactive therapeutic drug monitoring. METHODS: This was a predefined exploratory analysis of data from the randomised, controlled NOR-DRUM trials. The trials were conducted in rheumatology, gastroenterology, and dermatology departments at 21 Norwegian hospitals. Adult patients (aged 18-75 years) with immune-mediated inflammatory diseases were randomly assigned to proactive therapeutic drug monitoring or standard infliximab dosing in the NOR-DRUM A trial (30-week follow-up) and the NOR-DRUM B trial (52-week follow-up). Antidrug antibodies were assessed with a drug-sensitive assay before each infusion. The outcomes of remission (at week 30), disease worsening (during 52 weeks), infusion reactions, and infliximab discontinuation were assessed according to the presence of antidrug antibodies and use of therapeutic drug monitoring. FINDINGS: Between March 1, 2017, and Dec 12, 2019, 616 patients were included in the NOR-DRUM trials, of whom 615 had at least one serum infliximab and antidrug antibody assessment and were included in the present analyses. Mean age was 45 years (IQR 32-56), 305 (50%) patients were women, and 310 (50%) patients were men. Antidrug antibodies were detected in 147 (24%) patients. Remission at week 30 occurred in 25 (35%) of 72 patients with antidrug antibodies and 180 (54%) of 335 without antidrug antibodies (risk ratio 0·62 [95% CI 0·45-0·86]; p=0·0037). In patients with antidrug antibodies compared with patients without antidrug antibodies, higher rates were found for: disease worsening over 52 weeks (0·76 per person-year vs 0· 35 per person-year, hazard ratio [HR] 2·02 [95% CI 1·33-3·07]; p=0·0009), infusion reactions (0·16 per person-year vs 0·03 per person-year, HR 17·02 [6·98-41·47]; p<0·0001), and infliximab discontinuation (1·00 per person-year vs 0·20 per person-year, HR 6·64 [4·84-9·11]; p<0·0001). These associations were more pronounced in patients with high concentrations of antidrug antibodies than in those with low concentrations of antidrug antibodies. Independent of antibody status, therapeutic drug monitoring was associated with a lower risk of disease worsening (HR 0·41 [0·29-0·59]; p=0·0001) or an infusion reaction (HR 0·30 [0·12-0·73]; p=0·0076), and was associated with an increase in the rate of infliximab discontinuation (HR 1·37 [1·02-1·83]; p=0·037). INTERPRETATION: In patients where antidrug antibodies were detected, remission was less likely to be reached and sustained, and infusion reaction or discontinuation of infliximab was more likely. Timely detection of antidrug antibodies by proactive therapeutic drug monitoring facilitated treatment decisions that reduced the negative consequences, both regarding infliximab effectiveness and safety. This highlights the role of proactive therapeutic drug monitoring in optimising infliximab therapy. FUNDING: Inter-regional KLINBEFORSK grants and South-Eastern Norway Regional Health Authority grants.

HLA-DQ2 is associated with anti-drug antibody formation to infliximab in patients with immune-mediated inflammatory diseases.

BACKGROUND: Immunogenicity to tumour necrosis factor inhibitors is a significant clinical problem leading to treatment failure and adverse events. The study aimed to assess human leukocyte antigen (HLA) associations with anti-drug antibody (ADAb) formation to infliximab. METHODS: Immune-mediated inflammatory disease patients on infliximab therapy (n = 612) were included. Neutralising ADAb were assessed with a drug-sensitive assay. Next generation sequencing-based HLA typing was performed. RESULTS: Overall, 147 (24%) patients developed ADAb. Conditional analyses indicated HLA-DQB1 (p = 1.4 × 10-6 ) as a primary risk locus. Highest risk of ADAb was seen when carrying at least one of the HLA-DQ2 haplotypes; DQB1*02:01-DQA1*05:01 or DQB1*02:02-DQA1*02:01 (OR 3.18, 95% CI 2.15-4.69 and p = 5.9 × 10-9 ). Results were consistent across diseases and when adjusting for concomitant immunomodulator. Computational predictions indicated that these HLA-DQ2 haplotypes bind to peptide motifs from infliximab light chain. CONCLUSION: A genome-wide significant association between two HLA-DQ2 haplotypes and the risk of ADAb formation to infliximab was identified, suggesting that HLA-DQ2 testing may facilitate personalised treatment decisions.

Risk factors for anti-drug antibody formation to infliximab: Secondary analyses of a randomised controlled trial.

BACKGROUND: Anti-drug antibodies (ADAb) frequently form early in the treatment course of infliximab and other tumour necrosis factor (TNF) inhibitors, leading to treatment failure and adverse events. OBJECTIVE: To identify risk factors for ADAb in the early phase of infliximab treatment. METHODS: Patients (n = 410) with immune-mediated inflammatory diseases who initiated infliximab treatment were included in the 38-week Norwegian Drug Monitoring Trial (NOR-DRUM) A and randomised 1:1 to therapeutic drug monitoring (TDM) or standard therapy. Serum levels of infliximab and ADAb were measured at each infusion. Possible risk factors for ADAb formation were assessed using logistic regression, adjusting for potential confounders. RESULTS: ADAb were detected in 78 (19%) patients. A diagnosis of rheumatoid arthritis (RA) (odds ratio [OR], 1.9 [95% confidence interval [CI] 1.0-3.6]) and lifetime smoking (OR, 2.0 [CI 1.1-3.6]) were baseline risk factors, while baseline use of concomitant immunosuppressors (OR, 0.4 [CI 0.2-0.8]) and a diagnosis of spondyloarthritis (SpA) (OR, 0.4 [CI 0.2-0.8]) reduced the risk of ADAb. Higher disease activity during follow-up (OR, 1.1 [CI 1.0-1.1]) and "drug holidays" of more than 11 weeks (OR, 4.1 [CI 1.2-13.8]) increased the risk of ADAb, whereas higher infliximab doses (OR, 0.1 [CI 0.0-0.3) and higher serum infliximab concentrations (OR, 0.7 [CI 0.6-0.8]) reduced the risk of immunogenicity. CONCLUSION: Several risk factors for ADAb formation during early-phase infliximab treatment were identified. This knowledge provides a basis for treatment strategies to mitigate the formation of ADAb and identify patients in whom these measures are of particular importance.

Effect of Therapeutic Drug Monitoring vs Standard Therapy During Maintenance Infliximab Therapy on Disease Control in Patients With Immune-Mediated Inflammatory Diseases: A Randomized Clinical Trial.

Importance: Proactive therapeutic drug monitoring (TDM), consisting of individualized treatment based on scheduled assessments of serum drug levels, has been proposed as an alternative to standard therapy to optimize efficacy and safety of infliximab and other biologic drugs. However, it remains unclear whether proactive TDM improves clinical outcomes during maintenance therapy. Objective: To assess whether proactive TDM during maintenance therapy with infliximab improves treatment efficacy by preventing disease worsening compared with standard infliximab therapy without TDM. Design, Setting, and Participants: Randomized, parallel-group, open-label clinical trial including 458 adults with rheumatoid arthritis, spondyloarthritis, psoriatic arthritis, ulcerative colitis, Crohn disease, or psoriasis undergoing maintenance therapy with infliximab in 20 Norwegian hospitals. Patients were recruited from June 7, 2017, to December 12, 2019. Final follow-up took place on December 14, 2020. Interventions: Patients were randomized 1:1 to proactive TDM with dose and interval adjustments based on scheduled monitoring of serum drug levels and antidrug antibodies (TDM group; n = 228) or to standard infliximab therapy without drug and antibody level monitoring (standard therapy group; n = 230). Main Outcome and Measures: The primary outcome was sustained disease control without disease worsening, defined by disease-specific composite scores or consensus about disease worsening between patient and physician leading to a major change in treatment (switching to another biologic drug, adding an immunosuppressive drug including glucocorticoids, or increasing the infliximab dose), during the 52-week study period. Results: Among 458 randomized patients (mean age, 44.8 [SD, 14.3] years; 216 women [49.8%]), 454 received their randomly allocated intervention and were included in the full analysis set. The primary outcome of sustained disease control without disease worsening was observed in 167 patients (73.6%) in the TDM group and 127 patients (55.9%) in the standard therapy group. The estimated adjusted difference was 17.6% (95% CI, 9.0%-26.2%; P < .001) favoring TDM. Adverse events were reported in 137 patients (60%) and 142 patients (63%) in the TDM and standard therapy groups, respectively. Conclusions and Relevance: Among patients with immune-mediated inflammatory diseases undergoing maintenance therapy with infliximab, proactive TDM was more effective than treatment without TDM in sustaining disease control without disease worsening. Further research is needed to compare proactive TDM with reactive TDM, to assess the effects on long-term disease complications, and to evaluate the cost-effectiveness of this approach. Trial Registration: ClinicalTrials.gov Identifier: NCT03074656.

Effect of Therapeutic Drug Monitoring vs Standard Therapy During Infliximab Induction on Disease Remission in Patients With Chronic Immune-Mediated Inflammatory Diseases: A Randomized Clinical Trial.

Importance: Proactive therapeutic drug monitoring (TDM), defined as individualized drug dosing based on scheduled monitoring of serum drug levels, has been proposed as an alternative to standard therapy to maximize efficacy and safety of infliximab and other biological drugs. However, whether proactive TDM improves clinical outcomes when implemented at the time of drug initiation, compared with standard therapy, remains unclear. Objective: To assess whether TDM during initiation of infliximab therapy improves treatment efficacy compared with standard infliximab therapy without TDM. Design, Setting, and Participants: Randomized, parallel-group, open-label clinical trial of 411 adults with rheumatoid arthritis, spondyloarthritis, psoriatic arthritis, ulcerative colitis, Crohn disease, or psoriasis initiating infliximab therapy in 21 hospitals in Norway. Patients were recruited from March 1, 2017, to January 10, 2019. Final follow-up occurred on November 5, 2019. Interventions: Patients were randomized 1:1 to receive proactive TDM with dose and interval adjustments based on scheduled monitoring of serum drug levels and antidrug antibodies (TDM group; n = 207) or standard infliximab therapy without drug and antibody level monitoring (standard therapy group; n = 204). Main Outcomes and Measures: The primary end point was clinical remission at week 30. Results: Among 411 randomized patients (mean age, 44.7 [SD, 14.9] years; 209 women [51%]), 398 (198 in the TDM group and 200 in the standard therapy group) received their randomized intervention and were included in the full analysis set. Clinical remission at week 30 was achieved in 100 (50.5%) of 198 and 106 (53.0%) of 200 patients in the TDM and standard therapy groups, respectively (adjusted difference, 1.5%; 95% CI, -8.2% to 11.1%; P = .78). Adverse events were reported in 135 patients (68%) and 139 patients (70%) in the TDM and standard therapy groups, respectively. Conclusions and Relevance: Among patients with immune-mediated inflammatory diseases initiating treatment with infliximab, proactive therapeutic drug monitoring, compared with standard therapy, did not significantly improve clinical remission rates over 30 weeks. These findings do not support routine use of therapeutic drug monitoring during infliximab induction for improving disease remission rates. Trial Registration: ClinicalTrials.gov Identifier: NCT03074656.

Therapeutic drug monitoring of infliximab compared to standard clinical treatment with infliximab: study protocol for a randomised, controlled, open, parallel-group, phase IV study (the NOR-DRUM study).

BACKGROUND: Infliximab (INX) and other tumour necrosis factor inhibitors (TNFi) have revolutionised the treatment of several immune mediated inflammatory diseases. Still, many patients do not respond sufficiently to therapy or lose efficacy over time. The large interindividual variation in serum drug concentrations on standard doses and the development of anti-drug antibodies are thought to be major reasons for treatment failures. Therapeutic drug monitoring (TDM), an individualised treatment strategy based on systematic assessments of serum drug concentrations, has been proposed as a clinical tool to optimise efficacy of INX treatment. TDM seems reasonable both from a clinical and an economical point of view, but the effectiveness of this treatment strategy has not yet been demonstrated in randomised clinical trials. The NORwegian DRUg Monitoring study (NOR-DRUM) aims to assess the effectiveness of TDM, both with regard to the achievement of remission in patients starting INX treatment (part A) as well as to maintain disease control in patients on INX treatment (part B). METHODS: The NOR-DRUM study is a randomised, open, controlled, parallel-group, comparative, multi-centre, national, superiority, phase IV study with two separate parts, NOR-DRUM A and NOR-DRUM B. Patients with rheumatoid arthritis, psoriatic arthritis, spondyloarthritis, ulcerative colitis, Crohn's disease and psoriasis are included. In both study parts participants are randomised 1:1 to either TDM of infliximab (intervention group) or to standard treatment with infliximab without knowledge of drug levels or ADAb status (control group). NOR-DRUM A will include 400 patients starting INX therapy. The primary outcome is remission at 30 weeks. In NOR-DRUM B, 450 patients on maintenance treatment with INX will be included. The primary endpoint is occurrence of disease worsening during the 52-week study period. DISCUSSION: As the first trial to assess the effectiveness, safety and cost-effectiveness of TDM in patients receiving TNFi for a range of immune mediated inflammatory diseases, we hope that the NOR-DRUM study will contribute to the advancement of evidence based personalised treatment with biological medicines. TRIAL REGISTRATION: Clinicaltrials.gov, NCT03074656. Registered on 090317.

Infectious Pseudochromhidrosis: A Case Report and Literature Review.

Infectious pseudochromhidrosis is a rare dermatological disorder, characterized by a change in colour of the sweat from normal skin, caused by pigments from microorganisms. Such pigments are a result of evolutionary competition among microorganisms, which appears to be a decisive factor in their survival, patho-genicity, and virulence. Four bacteria are known to be involved in infectious pseudochromhidrosis: Bacillus spp. (blue colour), Corynebacterium spp. (brown/black colour), Serratia marcescens (red/pink colour), and Pseudomonas aeruginosa (blue-green colour). Infectious pseudochromhidrosis seems to be triggered by certain drugs and conditions causing physiological alterations and/or changes in microflora on the skin surface. The condition can be treated by addressing potential triggers and/or prescribing antibiotic/antiseptic therapies. We report here a case of blue infectious pseudochromhidrosis caused by pigment-producing Bacillus cereus and the results of a literature review.

Switching from originator infliximab to biosimilar CT-P13 compared with maintained treatment with originator infliximab (NOR-SWITCH): a 52-week, randomised, double-blind, non-inferiority trial.

BACKGROUND: TNF inhibitors have improved treatment of Crohn's disease, ulcerative colitis, spondyloarthritis, rheumatoid arthritis, psoriatic arthritis, and chronic plaque psoriasis, but are expensive therapies. The aim of NOR-SWITCH was to examine switching from originator infliximab to the less expensive biosimilar CT-P13 regarding efficacy, safety, and immunogenicity. METHODS: The study is a randomised, non-inferiority, double-blind, phase 4 trial with 52 weeks of follow-up. Adult patients on stable treatment with infliximab originator treated in a hospital setting for at least 6 months were eligible for participation. Patients with informed consent were randomised in a 1:1 ratio to either continued infliximab originator or to switch to CT-P13 treatment, with unchanged dosing regimen. Data were collected at infusion visits in 40 Norwegian study centres. Patients, assessors, and patient care providers were masked to treatment allocation. The primary endpoint was disease worsening during 52-week follow-up. 394 patients in the primary per-protocol set were needed to show a non-inferiority margin of 15%, assuming 30% disease worsening in each group. This trial is registered with ClinicalTrials.gov, number NCT02148640. FINDINGS: Between Oct 24, 2014, and July 8, 2015, 482 patients were enrolled and randomised (241 to infliximab originator, 241 to CT-P13 group; one patient was excluded from the full analysis and safety set for CT-P13) and 408 were included in the per-protocol set (202 in the infliximab originator group and 206 in the CT-P13 group). 155 (32%) patients in the full analysis set had Crohn's disease, 93 (19%) had ulcerative colitis, 91 (19%) had spondyloarthritis, 77 (16%) had rheumatoid arthritis, 30 (6%) had psoriatic arthritis, and 35 (7%) had chronic plaque psoriasis. Disease worsening occurred in 53 (26%) patients in the infliximab originator group and 61 (30%) patients in the CT-P13 group (per-protocol set; adjusted treatment difference -4·4%, 95% CI -12·7 to 3·9). The frequency of adverse events was similar between groups (for serious adverse events, 24 [10%] for infliximab originator vs 21 [9%] for CT-P13; for overall adverse events, 168 [70%] vs 164 [68%]; and for adverse events leading to discontinuation, nine [4%] vs eight [3%], respectively). INTERPRETATION: The NOR-SWITCH trial showed that switching from infliximab originator to CT-P13 was not inferior to continued treatment with infliximab originator according to a prespecified non-inferiority margin of 15%. The study was not powered to show non-inferiority in individual diseases. FUNDING: Norwegian Ministry of Health and Care Services.

Specific changes in conduction velocity recovery cycles of single nociceptors in a patient with erythromelalgia with the I848T gain-of-function mutation of Nav1.7.

Seven patients diagnosed with erythromelalgia (EM) were investigated by microneurography to record from unmyelinated nerve fibers in the peroneal nerve. Two patients had characterized variants of sodium channel Nav1.7 (I848T, I228M), whereas no mutations of coding regions of Navs were found in 5 patients with EM. Irrespective of Nav1.7 mutations, more than 50% of the silent nociceptors in the patients with EM showed spontaneous activity. In the patient with mutation I848T, all nociceptors, but not sympathetic efferents, displayed enhanced early subnormal conduction in the velocity recovery cycles and the expected late subnormality was reversed to supranormal conduction. The larger hyperpolarizing shift of activation might explain the difference to the I228M mutation. Sympathetic fibers that lack Nav1.8 did not show supranormal conduction in the patient carrying the I848T mutation, confirming in human subjects that the presence of Nav1.8 crucially modulates conduction in cells expressing EM mutant channels. The characteristic pattern of changes in conduction velocity observed in the patient with the I848T gain-of function mutation in Nav1.7 could be explained by axonal depolarization and concomitant inactivation of Nav1.7. If this were true, activity-dependent hyperpolarization would reverse inactivation of Nav1.7 and account for the supranormal CV. This mechanism might explain normal pain thresholds under resting conditions.

Improvement in Psoriasis Area and Severity Index score predicts improvement in skin pain over time in patients with psoriasis.

Pain and discomfort are common and often severe skin symptoms in patients with psoriasis. However, no studies have investigated skin pain and discomfort over time, or factors that explain changes in these symptoms. The aims of the present study were to describe the changes in skin pain, skin discomfort and Psoriasis Area and Severity Index (PASI) over time, and to investigate whether change in PASI predicted change in skin pain intensity. A total of 129 patients participated in this exploratory, longitudinal study. Data were obtained through interviews and questionnaires. The results indicated reduction in skin symptoms and psoriasis severity over a period of 3 months. However, a majority of patients with skin pain at baseline reported also skin pain at follow-up. Furthermore, changes in PASI predicted changes in skin pain intensity. In conclusion, improvement in psoriasis severity predicts improvement in skin pain.

Pre-treatment deep curettage can significantly reduce tumour thickness in thick Basal cell carcinoma while maintaining a favourable cosmetic outcome when used in combination with topical photodynamic therapy.

Topical photodynamic therapy (PDT) has limitations in the treatment of thick skin tumours. The aim of the study was to evaluate the effect of pre-PDT deep curettage on tumour thickness in thick (≥2 mm) basal cell carcinoma (BCC). Additionally, 3-month treatment outcome and change of tumour thickness from diagnosis to treatment were investigated. At diagnosis, mean tumour thickness was 2.3 mm (range 2.0-4.0). Pre- and post-curettage biopsies were taken from each tumour prior to PDT. Of 32 verified BCCs, tumour thickness was reduced by 50% after deep curettage (P ≤ 0.001). Mean tumour thickness was also reduced from diagnosis to treatment. At 3-month followup, complete tumour response was found in 93% and the cosmetic outcome was rated excellent or good in 100% of cases. In conclusion, deep curettage significantly reduces BCC thickness and may with topical PDT provide a favourable clinical and cosmetic short-term outcome.

Periodontitis in psoriasis patients: a blinded, case-controlled study.

OBJECTIVE: Destructive periodontitis is one of the most frequent and widespread bacterial infections in humans. Psoriasis is a common condition in the general population. Since both psoriasis and periodontal diseases are characterized by an exaggerated response of the immune system to the epithelial surface microbiota, there may possibly be an association between these two conditions. The aim of the present pilot study was to investigate the prevalence of periodontal disease in psoriasis patients compared to healthy controls. MATERIAL AND METHODS: Dental bite-wing X-rays were obtained from 155 psoriasis patients aged 45-60 years, as well as from 155 age- and gender-matched controls. All X-rays were examined by the same investigator for accumulated destructive periodontitis using bone level and loss of teeth as endpoints. RESULTS: A significantly lower radiographic bone level (p < 0.001) and a significantly higher number of missing teeth (p < 0.001) were observed in the psoriasis cases compared to the controls. CONCLUSION: Our study indicates that psoriasis patients experience more bone loss than age- and gender-matched controls.

Skin pain and discomfort in psoriasis: an exploratory study of symptom prevalence and characteristics.

Few studies have investigated subjective sensory skin symptoms in patients with psoriasis. The aim of this study was to investigate prevalence and characteristics of psoriasis-related skin pain and discomfort, and evaluate differences in demographic/clinical characteristics among patients with or without skin symptoms. A total of 139 patients was recruited for this exploratory, descriptive, cross-sectional study. Data were obtained through interviews and questionnaires. While 42.6% reported skin pain, 36.7% reported skin discomfort. Mean average symptom intensity score (0-10 numeric rating scale) was 4.4 for pain and 3.5 for discomfort. Unpleasant, surface, sensitive, itchy, and hot/burning were the most common symptom qualities. Sleep was the most severely affected function. No differences were found in demographic characteristics. However, larger proportions of patients with skin symptoms had more severe psoriasis (p < 0.05). In conclusion, pain and discomfort are more common and more severe in patients with psoriasis than previously estimated.

Influence of narrowband UVB phototherapy on vitamin D and folate status.

BACKGROUND: A variety of studies have shown beneficial effects of different types of phototherapy in skin disorders. Such therapy leads to enhanced cutaneous vitamin D synthesis, which may be one of the mechanisms of action. Furthermore, another nutrient, folate, can probably also be influenced by UV radiation. OBJECTIVE: The aim of our study was to investigate the influence of low-dose narrowband UVB (nUVB) phototherapy of patients with psoriasis, atopic eczema and other skin disorders on serum levels of 25(OH) vitamin D (the serum marker for vitamin D status) and on serum and erythrocyte-folate. METHODS: 25(OH) vitamin D (25(OH)D), serum and erythrocyte-folate levels were measured before and after low-dose nUVB (TL-01 tubes) phototherapy of these patients. The spectrum of the TL-01 tube was compared with the solar spectrum, and the efficiency spectra of vitamin D photosynthesis were calculated. RESULTS: For patients with a high initial 25(OH)D serum level (> 80 nmol/l), no significant (P = 0.36) increase in 25(OH)D levels was seen, in contrast to patients with a low initial level (< 80 nmol/l) where a significant increase (P < 0.001) was observed. The increase was 30-60%, depending on the UVB dose (2.35-13.4 J/cm(2)). No significant nUVB-effect was found on the erythrocyte and serum-folate level. CONCLUSION: Low-dose nUVB treatment gives a significant increase (P < 0.001) of the vitamin D status in persons with low initial levels of 25(OH)D, but no effect on the folate level.

[A 62-year-old woman with non-pitting leg oedema]. / En kvinne med leggødem og arrforandringer.

A patient presented with non-pitting lymphoedema of the legs and finger clubbing. A skin biopsy showed epidermal hyperkeratosis and abundant mucinous material (Alcian blue positive) in reticular dermis. Treatment (radioactive iodine) for Grave's disease (with exophthalmus) 20 years ago, raised suspicion of thyroid dermopathy. Together, these three extrathyroidal manifestations of Graves' disease are typical of the EMO syndrome. In addition, the patient had elevated serum concentrations of thyroid-stimulating hormone receptor autoantibodies. Autoimmune mechanisms are involved in the stimulation of fibroblasts and the production of large amounts of mucin. Pretibial myxoedema relates to scars, mechanical factors, and dependent position. Lack of steroid treatment during radioactive iodine therapy and smoking, may have exacerbated the thyroid dermopathy in this case. Awareness of pretibial myxoedema as a late autoimmune manifestation of Graves' disease, may contribute to earlier diagnosis and correct treatment.

Photodynamic therapy with methyl aminolevulinate for prevention of new skin lesions in transplant recipients: a randomized study.

BACKGROUND: Organ transplant recipients on long-term immunosuppressive therapy are at increased risk of non-melanoma skin lesions. Repeated field photodynamic therapy using topical methyl aminolevulinate (MAL) may have potential as a preventive treatment. METHODS: This open randomized, intrapatient, comparative, multicenter study included 81 transplant recipients with 889 lesions (90% actinic keratoses (AK)]. In each patient, the study treatment was initially administered to one 50 cm area on the face, scalp, neck, trunk, or extremities (n=476 lesions) twice (1 week apart), with additional single treatments at 3, 9, and 15 months. On each occasion, the area was debrided gently and MAL cream (160 mg/g) applied for 3 hr, before illumination with noncoherent red light (630 nm, 37 J/cm2). The control, 50 cm2 area (n=413 lesions) received lesion-specific treatment (83% cryotherapy) at baseline and 3, 9, and 15 months. Additionally, all visible lesions were given lesion-specific treatment 21 and 27 months in both treatment and control areas. RESULTS: At 3 months, MAL photodynamic therapy significantly reduced the occurrence of new lesions (65 vs. 103 lesions in the control area; P=0.01), mainly AK (46% reduction; 43 vs. 80; P=0.006). This effect was not significant at 27 months (253 vs. 312; P=0.06). Hypopigmentation, as assessed by the investigator, was less evident in the treatment than control areas (16% vs. 51% of patients; P<0.001) at 27 months. CONCLUSION: Our results suggest that repeated field photodynamic therapy using topical MAL may prevent new AK in transplant recipients although further studies are needed.

Changes in quality of life in persons with eczema and psoriasis after treatment in departments of dermatology.

The objective of this study was to assess the impact of chronic dermatological diseases on quality of life (QoL) of Norwegian patients following in-patient management. QoL was measured by the Norwegian version of the Dermatology Life Quality Index, a validated, self-administered questionnaire. Adult in-patients with psoriasis and eczema were selected for one year from the dermatological departments in Norway. A total of 212 patients were included, and 126 patients (50% men, 85 with psoriasis and 41 with eczema, mean age 46 years) completed the questionnaires at time of hospital admission and one week after discharge. The patients reported adverse impact on QoL, but no differences between the psoriasis and eczema groups could be demonstrated. Patients with psoriasis improved from 18.3 (7.6) (mean (SD)) to 12.1 (8.2) (p < 0.01), and those with eczema improved from 20.0 (6.0) to 14.4 (7.8) (p < 0.01). Seventy percent of the patients showed improvement, 20% remained unchanged and 10% worsened. The parameters for which the most improvement was seen were those that were of most concern to the patients, i.e. their symptoms and embarrassment. In conclusion, the results are consistent with previous international studies.

18S rDNA polymerase chain reaction and sequencing in onychomycosis diagnostics.

Diagnostic approaches to onychomycosis have traditionally been based on a combination of culture and microscopy. In the present study clinical specimens from 346 patients with suspected onychomycosis were analysed by 18S polymerase chain reaction (detection) followed by sequencing and subsequent database search (identification) in parallel with routine culture on agar (detection and identification). In 49 samples Trichophyton rubrum was identified by culture and sequencing. In 67 additional culture negative samples, a positive dermatophyte sequence was obtained (T. rubrum in 54, T. mentagrophytes in 5, and T. species in 8 samples). Fifteen samples cultured positive while no sequence was obtained. Two hundred and seven samples were negative by culture as well as by sequencing. Nails from 10 healthy controls were negative by culture and sequencing. In conclusion, the number of specimens that were positive by polymerase chain reaction was more than double the number that were positive by culture alone.

Lifestyle of Nordic people with psoriasis.

AIM: The Nordic Quality of Life Study was undertaken to assess the relationship between psoriasis and the quality of life in Nordic countries. The intention was also to determine whether there was a relationship between drinking, smoking, and the use of psychotherapeutic agents on the one hand, and psoriasis severity and quality of life on the other. MATERIALS AND METHODS: A questionnaire was mailed to 11,300 members of the Nordic Psoriasis Associations. Additional psoriasis patients were recruited by dermatologists (387) or admitted to dermatologic wards (385). These patients also underwent a physical examination, and their Psoriasis Area and Severity Index (PASI) was determined. The questionnaire included the Psoriasis Disability Index (PDI), Psoriasis Life Stress Inventory (PLSI), and additional questions on disease severity, treatment, and psoriasis arthritis. It also included questions regarding lifestyle issues, such as smoking, alcohol use, and the use of tranquilizers, antidepressants, and sleeping medications. RESULTS: The response rate for members was 50.2%. Included in the evaluation were 6497 patients. Men drank significantly more beer and liquor than women. The number of beers per day had a weak correlation with the PDI. Wine consumption, however, showed a weak, but significant, negative correlation with both PDI and PLSI. Patients admitted to dermatologic wards smoked more cigarettes and drank less wine than the other two groups. Significant differences were found between countries with regard to total alcohol consumption and cigarette smoking. The number of cigarettes and the use of tranquilizers, sleeping medications, and antidepressants showed small, but significant, positive correlations with psoriasis quality of life measures. CONCLUSIONS: Cigarette smoking and the use of tranquilizers, sleeping medications, and antidepressants are statistically correlated with impaired psoriasis-related quality of life.