Evaluation of primary care physicians' competence in selective skin tumour triage after short versus long dermoscopy training: a randomized non-inferiority trial.

BACKGROUND: Although primary care physicians (PCPs) play a key role in skin cancer screening, their skills in detecting malignant tumours is suboptimal. OBJECTIVES: To determine whether a short dermoscopy e-learning course (4 h) in skin tumour diagnosis for PCPs is non-inferior to a long course (12 h) in selective triage of skin lesions. Secondly, to evaluate whether regular refresher training sessions are necessary to maintain the PCPs' skills in the medium term. METHODS: A randomized 2 × 2 factorial non-inferiority trial was conducted online over an 8-month period among 233 PCPs including 126 certified general practitioners, 94 PCPs in training, and 13 occupational physicians, all without prior advanced dermoscopy training. Participants were randomized 1:1:1:1 to receive short training and mandatory refreshers (n = 58), short training and optional refreshers (n = 59), long training and mandatory refreshers (n = 58), or long training and optional refreshers (n = 58). PCPs' skills were evaluated before training (T0), immediately after training (T1) to test the non-inferiority, and after 5 months (T2) to evaluate the impact of the refreshers. The primary endpoint was the difference in the change of score after short and long training. The non-inferiority margin was set at -28%. RESULTS: Among the 233 randomized participants, 216 (93%) completed T1 and 197 (84.5%) completed T2. For short versus long training, the primary endpoint was 1.392 (95% CI: 0.138; 2.645) in the per-protocol population (p < 0.001) and 1.016 (95% CI: -0.224; 2.256) in the modified intention-to-treat population (p < 0.001). After training, the type of refresher showed no impact on the score (p = 0.840). However, PCPs who completed all refreshers showed the best mean overall score at T2 (p < 0.001). CONCLUSIONS: These findings confirm that short dermoscopy e-learning is non-inferior in training PCPs to triage skin lesions compared to long training. After training, regular refreshers are important to maintain the PCPs' acquired skills over time.

Misleading clinical presentation of carcinoid syndrome.

Rare cases of carcinoid syndromes can develop from either gastrointestinal neuroendocrine tumors (NETs) without liver metastasis or large retroperitoneal involvement. We report a case of a patient with isolated flushing highly suggestive of carcinoid syndrome caused by an ileal NET with adjacent lymph node metastases but with no liver metastases. The final diagnose was delayed for this patient due to a combination of misleading clinical presentation and negative usual screening tests (urinary 5-HIAA and serum chromogranine A). Given its high sensitivity and specificity, 68Ga-DOTATATE PET/CT confirmed the diagnosis of neuroendocrine tumor. Therefore, this case reminds clinicians that carcinoid syndrome may manifest as flushing only and highlights that imaging is a major aspect of the evaluation and diagnosis of patients with suspected gastrointestinal NETs.

Correlations between disease activity, autoimmunity and biological parameters in patients with chronic spontaneous urticaria.

Summary: Background. Biomarkers of disease activity/severity and criteria of autoimmune chronic spontaneous urticaria (CSU) are still a matter of debate. Objective. To investigate possible correlations between clinical and biological markers and their associations with: 1) disease activity, 2) resistance to H1-antihistamines, 3) autoimmunity and 4) autologous serum skin test (ASST) in patients with CSU. To also analyze biological parameter modifications in patients with CSU treated with omalizumab. Materials and methods. Disease activity, H1-antihistamines response and presence of concomitant autoimmune disease were prospectively recorded in 95 patients with CSU. For 60 of them, ASST was performed. Broad biological analysis were performed. Results. C-reactive protein (CRP) serum levels were higher in H1-antihistamines unresponders (p less-than 0.0001) and in more active diseases (p = 0.033). D-dimer plasma levels were higher in H1-antihistamines unresponders (p = 0.008) and in patients with autoimmune status (concomitant autoimmune disease and/or with autoantibodies) (p = 0.016). Total immunoglobuline E (IgE) serum level was lower in patients with positive ASST. Blood basophil counts were lower in patients with CSU and especially in H1-antihistamines unresponders (p = 0.023), in patients with more active disease (p = 0.023), with positive ASST (p = 0.001), and with autoimmune status (p = 0.057). Conversely, under omalizumab, a decrease of CRP (p = 0.0038) and D-dimer serum/plasma levels (p = 0.0002) and an increase of blood basophil counts (p = 0.0023) and total IgE serum levels (p = 0.0007) were observed. Conclusions. This study brings additional evidences of interest to investigate IgE, D-dimer serum/plasma levels and basophil blood counts in patients with CSU as they could be correlated to disease activity, response to treatment and/or autoimmunity.

Melanoma Diagnostic Practices of French-Speaking Belgian General Practitioners and the Prospective Study of Their Pigmented Skin Lesion Diagnostic Accuracy and Management.

General practitioners (GPs) are among the main actors involved in early melanoma diagnosis. However, melanoma diagnostic accuracy and management are reported to be insufficient among GPs in Europe. The primary aim of this observational prospective study was to shed light on melanoma diagnostic practices among French-speaking Belgian GPs. The second aim was to specifically analyse these GPs' pigmented skin lesion diagnostic accuracy and management. GPs from the five French-speaking districts of Belgium were asked to complete a questionnaire, before taking part in a melanoma diagnostic training session. First, we assessed the GPs' current melanoma diagnostic practices. Then, their pigmented skin lesion diagnostic accuracy and management were evaluated, through basic theoretical questions and clinical images. These results were subsequently analysed, according to the GPs' sociodemographic characteristics and medical practice type. In total, 89 GPs completed the questionnaire. Almost half of the GPs (43%; CI = [33;54]) were confronted with a suspicious skin lesion as the main reason for consultation once every 3 months, while 33% (CI = [24;43]) were consulted for a suspicious lesion as a secondary reason once a month. Prior to training, one-third of the GPs exhibited suboptimal diagnostic accuracy in at least one of six "life-threatening" clinical cases among two sets of 10 clinical images of pigmented skin lesions, which can lead to inadequate patient management (i.e. incorrect treatment and/or inappropriate reinsurance). This study underlines the need to train GPs in melanoma diagnosis. GPs' pigmented skin lesion diagnostic accuracy and management should be improved to increase early melanoma detection.

A retrospective analysis omalizumab treatment patterns in patients with chronic spontaneous urticaria: a real-world study in Belgium.

BACKGROUND: Chronic spontaneous urticaria (CSU) is characterized by the repeated occurrence of persistent hives and/or angioedema for ≥6 weeks, without specific external stimuli. H1 -antihistamines have long been the standard of care of CSU, but many patients remain uncontrolled even at 4× the approved dose. Add-on therapy with omalizumab has proven effective in clinical trials, but little is known about omalizumab treatment in Belgium. OBJECTIVE: To collect real-world clinical data on omalizumab treatment in adults with CSU in Belgium. METHODS: This was an observational, retrospective chart review of adults with CSU, who initiated omalizumab treatment between August 2014 and December 2016 (maximum 28 months follow-up). RESULTS: In total, 235 patients were included (median time from symptom onset to diagnosis, 5.4 months; median time from diagnosis to commencing omalizumab, 6.7 months). Treatments used before/after commencing omalizumab did not always adhere to guidelines; many patients (26.4%/11.1%) received first-generation H1 -antihistamines, while 20.4% used omalizumab monotherapy after initiating treatment. The mean interval between omalizumab administrations was 4.8 (SD 1.7) weeks; 67.8% of patients had ≥1 interval prolongation and/or shortening. Mean baseline 7-day Urticaria Activity Score (UAS7) was 32.0 (SD 6.05); this improved to 12.6 (SD 11.2) after 1 month of omalizumab. About 67.2% of patients reached UAS7 ≤ 6 (well controlled) during the study. A total of 87 patients stopped omalizumab and never restarted before the end of the observation period; the most prevalent reason was remission of symptoms (49.4% of patients), followed by lack of effect (12.6%), lost to follow-up (6.9%) and adverse events (3.4%). Headache was the most common adverse event (n = 8/82). No anaphylaxis was reported. CONCLUSIONS: This study revealed that patients initiated on omalizumab in Belgium had severe CSU at baseline, and showed substantial improvements after 1 month of treatment. Greater adherence to the prescription of guideline-recommended medications is needed for the treatment of CSU.

Isothiazolinone derivatives and allergic contact dermatitis: a review and update.

Allergic contact dermatitis (ACD) from isothiazolinones has frequently been described in the literature. Following an epidemic of sensitization to methylchloroisothiazolinone/methylisothiazolinone (MCI/MI) in the 1980s, and more recently to MI, the Scientific Committee on Consumer Safety of the European Commission banned their use in leave-on products, while restricting that in rinse-off cosmetics. Despite a decreasing prevalence of ACD from MCI/MI and MI, cases caused by occupational exposure and non-cosmetic isothiazolinone sources are on the rise. Moreover, sensitization to newer and lesser known isothiazolinones has been reported. This paper reviews the epidemiology of contact allergy to different isothiazolinones, clinical presentation of isothiazolinone-induced ACD, most relevant sensitization sources and potential cross-reactions between isothiazolinone derivatives. It also provides an update on recent legislative measures.

A quantum cascade laser-based water vapor isotope analyzer for environmental monitoring.

A field-deployable mid-infrared quantum cascade laser-based spectrometer was designed and developed for measurements of H2(16)O and H2(18)O at 7.12 µm. H2(16)O and H2(18)O absorption features at 1390.52 cm(-1) and 1389.91 cm(-1), respectively, accessible within current tuning range of the laser, were targeted. The target lines were carefully selected to assure similar absorption levels and similar temperature sensitivities of the line strength due to comparable lower state energies. A real-time spectral fitting algorithm was implemented for isotopic concentration retrieval. Detection limits for H2(16)O and H2(18)O of 2.2 ppm and 7.0 ppb, respectively, were achieved at a dew point of 14 °C (volume mixing ratio of 15,766 ppm) in 1 s integration time, which resulted in a δ(18)O isotopic ratio measurement precision of 0.25‰. The ultimate minimum detection limits obtained after 160 s integration time for H2(16)O and H2(18)O, and δ(18)O measurements were 0.6 ppm, 1.7 ppb, and 0.05‰, respectively.

Improvement of psoriasis during glucagon-like peptide-1 analogue therapy in type 2 diabetes is associated with decreasing dermal γδ T-cell number: a prospective case-series study.

BACKGROUND: A few case reports suggest that incretin-based therapies could improve psoriasis in patients with type 2 diabetes, the mechanism(s) of which remain unclear. OBJECTIVES: To determine the effects after 16-20 weeks of treatment with a glucagon-like peptide (GLP)-1 analogue on clinical severity and histopathological aspects of psoriasis in patients with type 2 diabetes, and to examine the presence of γδ T cells and the expression of interleukin (IL)-17 in psoriasis before and after treatment. METHODS: Seven patients with type 2 diabetes and psoriasis were followed. Psoriasis Area and Severity Index (PASI) was measured at baseline (T0) and after 7 ± 1 (T1) and 18 ± 2 (T2) weeks' treatment with exenatide/liraglutide. The histopathological pattern of psoriasis, and flow cytometry and immunological data (γδ T-cell percentage and IL-17 expression) were obtained from psoriatic and control sites. RESULTS: The mean PASI decreased from 12·0 ± 5·9 to 9·2 ± 6·4 (P = 0·04). Histological analysis showed a reduction in epidermal thickness after treatment. The dermal γδ T-cell percentage was higher in psoriatic lesions than in control specimens (P = 0·03), as was IL-17 expression (P = 0·018). A reduction of γδ T cells from 6·7 ± 4·5% to 2·7 ± 3·8% (P = 0·05) was demonstrated in the six patients with improved/unchanged PASI. A correlation between PASI and γδ T-cell percentage evolution during therapy (T2-T0) was noted (r = 0·894, P = 0·007). IL-17 was reduced in the four patients with the highest PASI reductions. CONCLUSIONS: The administration of a GLP-1 analogue improved clinical psoriasis severity in patients with type 2 diabetes. This favourable outcome was associated with a decrease of dermal γδ T-cell number and IL-17 expression. Further studies are needed to establish long-term efficacy in (diabetic) patients with psoriasis.

Systemic contact dermatitis to corticosteroids.

BACKGROUND: Although unexpected and paradoxical, allergic hypersensitivity to corticosteroids is a common finding, delayed-type reactions being much more frequently encountered than the immediate-type ones. Although the skin is the main sensitization and elicitation route, other routes, amongst them systemic administration of corticosteroids may exceptionally be involved. OBJECTIVE: To determine the frequency, clinical presentation and cross-reactivity patterns for allergic reactions following systemic administration of corticosteroids amongst patients with identified and investigated 'contact allergy' to corticosteroids. METHODS: We reviewed clinical data, patch test results and sensitization sources in patients who reacted positively to corticosteroids tested in the K.U. Leuven Dermatology department during an 18-year period. RESULTS: Sixteen subjects (out of 315 with CS delayed-type hypersensitivity) presented with allergic manifestations due to systemic administration of corticosteroids. Most patients reacted to molecules from the three groups of the recently reappraised classification. CONCLUSION: The reactions observed seem to be in most cases 'systemic contact dermatitis' due to oral or parenteral re-exposure of sensitized individuals with the respective corticosteroids previously applied topically. Moreover, most patients seem to be able to react to any corticosteroid molecules and therefore need a systematic individualized evaluation of their sensitization/tolerance profile.

New insights about delayed allergic hypersensitivity to corticosteroids.

Corticosteroids are among the most commonly used drugs, both topically and systemically. Although unexpected and paradoxical, allergic hypersensitivity to corticosteroids is a common finding, delayed-type reactions being much more frequently encountered than the immediate-type ones. With regard to cross-reactions between corticosteroids, based on patch-test results and molecular modelling, we were recently able to simplify the previous classification into 3 different groups, i.e., Group 1: the non-methylated, most often non-halogenated molecules (Group A, D2 and budesonide), which produce most of the allergic reactions; Group 2: the halogenated molecules with a C16/C17 cis ketal/diol structure (acetonide Group B); and Group 3: the halogenated and C16-methylated molecules (Group C and D1) that only rarely produce allergy.

Corticosteroid cross-reactivity: clinical and molecular modelling tools.

BACKGROUND: Corticosteroids have been classified into following four cross-reacting groups in function of their contact-allergenic properties: A, B, C and D, the last subdivided into D1 and D2. Recent data indicate that C(16)-methylated and nonmethylated molecules need to be distinguished, the latter selectively binding with arginine to form stable cyclic adducts and producing considerably more positive reactions than the former. This study compares molecular modelling and patch-test results to determine cross-reactivity patterns. METHODS: The patch-test results obtained with 66 corticosteroid molecules in 315 previously sensitized subjects were analysed and correlated with modelling and clustering in function of the electrostatic and steric fields of these molecules. RESULTS: The classification obtained after in silico hydrolysis of C(21) and C(17) esters was selected with an optimal cut into three clusters: the patients who reacted positively to cluster 2 (halogenated molecules from group B, with C(16)/C(17) cis ketal or diol structure) and cluster 3 (halogenated molecules from groups C and D1, C(16)-methylated) also reacted to cluster 1 (molecules mostly from groups A and D2, without C(16)-methyl substitution or halogenation and budesonide). The reverse, however, was not the case. CONCLUSION: Two patient profiles with probably different areas of immune recognition are identified as follows: the profile 1 patients were allergic to the frequently positively reacting cluster 1 only, for whom electrostatic fields (molecular charge) seem important; the profile 2 patients reacted to clusters 1 and 2 and/or 3, for whom steric fields (structure) are determinant and who probably presented a global recognition of the corticosteroid skeleton. A modified classification is thus proposed.

Allergic hypersensitivity to topical and systemic corticosteroids: a review.

Corticosteroids, which are potent anti-inflammatory and immunomodulator agents used in the treatment of various inflammatory diseases including allergic diseases, can in some cases produce immediate or delayed hypersensitivity reactions. This review summarizes the epidemiological and clinical characteristics of such reactions, including related diagnostic issues. It also presents a detailed analysis of the proposed immunological mechanisms including underlying cross-reactions.