Triggers, clinical manifestations and assessment of paediatric fixed drug eruptions: A systematic review of the literature.

Fixed drug eruption (FDE) is a cutaneous drug reaction characterised by recurrent skin lesions occurring at the same site after each exposure to a causative agent. There is currently limited evidence in the paediatric population. The objective of this systematic review is to investigate the clinical features, causative agents and management of paediatric FDE. A systematic search of the English and French literature on paediatric FDE was conducted using the Medline and Embase databases. After full-text article review, 92 articles were included, representing a total of 233 patients. Antibiotics were the most frequent triggering agents, mainly sulfonamides (65.0% of antibiotics). Systemic symptoms were rare, and most patients only received supportive therapy. One hundred and six patients (106) performed a test to confirm the causative agent. Of these, 72.6% had oral provocation tests (OPTs) and 28.3% had patch tests. The patient's age, presence of bullous lesions and mucosal lesions were similar between tested and untested patients. It did not seem to influence the decision to perform OPTs. Paediatric FDE is a non-severe skin drug reaction. Antibiotics were the most reported triggering agents. Drug testing, including oral provocation test, was safely performed in the paediatric population.

The contribution of metal allergy to the failure of metal alloy implants, with special reference to titanium: Current knowledge and controversies.

After almost three-quarters of a century during which contact dermatologists have often struggled to comprehend the relationship between metal allergy and failure of metal-alloy containing implant, it is possible to say that a relationship does exist, particularly for cobalt and chromium, but also for nickel. There is still debate as to whether allergy develops as a consequent of failure but thenceforth contributes to it, or whether sensitisation starts first and induces failure secondarily-opinion probably favours the first. Metal-on-polypropylene articulations were associated with few metal allergic problems but now are less favoured by orthopaedists due to plastic wear products causing osteolysis and pseudotumour formation through local inflammation. New metal alloys are regularly being introduced such that interested dermatologists need to stay on top of the situation. The jury is still out as to whether the recent favouring of titanium-containing alloys will confirm them to be more inert allergenically. Case reports do show some clinical reactions to titanium-containing implants and patch test series have inferred sometimes quite a high background rate of allergy, but interpretation must be tempered by the awareness that titanium salts on patch testing have a tendency to cause irritant reactions. Blood monitoring of metal ion values is now recommended in certain situations after joint replacement and increasing levels may be an indication that allergy with joint failure can develop, in which case patch testing is indicated, and suggested series are available. Predictive patch testing, whilst generally not recommended in the past, has been introduced into some protocols often by non-dermatologists, such that it is now needed for temporo-mandibular joint and Nuss bar insertion, and it can be anticipated that this may become more commonplace in the future. One of the major current deficits for patch testers is standardised guidance on which preparation or preparations to use for suspected titanium allergy. One suggestion is 0.5% titanium sulphate in petrolatum, though experience in at least one centre suggests the use of a battery of titanium salts might be desirable.

Delayed-type allergic reaction to furazolidone: A case report and review of the literature.

BACKGROUND: Furazolidone is a nitrofuran antimicrobial agent used in the treatment of bacterial and protozoal infections. Hypersensitivity to furazolidone is rarely reported and only eight cases have been documented in English since 1967. OBJECTIVES: To report a 24-year-old man who developed exanthematous drug eruptions in general and swelling sensation of the hands after first dose of oral administration of medicines for Helicobacter pylori infection 7 h later, who was finally confirmed with delayed-type IV allergic reaction to furazolidone by provocation tests. And to review the existing literature. METHODS: Thorough clinical examination, prick, intradermal, and patch tests, drug provocation tests were performed in the patient. RESULTS: Skin tests of all used drugs were negative. Drug provocation tests to furazolidone resulted to be positive. CONCLUSIONS: Clinicians should be aware that furazolidone may induce delayed-type allergic reactions; diagnostic approaches should be taken to identify the responsible drug when multiple medications were used concurrently.

Anxiety and depression in patients with hand eczema: A population-based study among 853 middle-aged subjects.

BACKGROUND: Hand eczema (HE) is a common dermatological disorder with considerable effect on the health-related quality of life (HRQoL). The data on mental comorbidities of HE is sparse and mostly studied among selected patient groups. OBJECTIVES: We aimed to investigate symptoms of depression and anxiety in patients with HE in general population. METHODS: Study subjects (n = 6695) belonging to the Northern Finland Birth Cohort 1966 Study (NFBC1966) responded to an extensive health questionnaire including questions about HE. Depression and anxiety symptoms were evaluated according to the Hopkins Symptom Checklist-25 (HSCL-25). RESULTS: Having ever suffered from HE was reported by 853 (12.8%) study subjects. Symptoms scores of depression were significantly higher among (n = 172, 20.3%) HE subjects compared with (n = 884, 15.4%) subjects without HE (Odds ratio [OR] 1.40, 95% confidence interval [CI]: 1.17-1.68, P < 0.001). Correspondingly, symptoms scores of anxiety were also more common among (n = 90, 10.6%) HE subjects than among (n = 448, 7.8%) subjects without HE (OR 1.40, 95% CI: 1.10-1.78, P = 0.007). In an adjusted model, the associations remained statistically significant (OR 1.30, 95% CI: 1.08-1.57, P = 0.007 and OR 1.34, 95% CI: 1.04-1.72, P = 0.021, respectively). CONCLUSIONS: Symptoms associated with mental health should be taken into account when managing patients with HE.

Epidermal biomarkers of the skin barrier in atopic and contact dermatitis.

Dysfunction of the skin barrier plays a critical role in the initiation and progression of inflammatory skin diseases, such as atopic dermatitis and contact dermatitis. Epidermal biomarkers can aid in evaluating the functionality of the skin barrier and understanding the mechanisms that underlay its impairment. This narrative review provides an overview of recent studies on epidermal biomarkers associated with the function and integrity of the skin barrier, and their application in research on atopic dermatitis and contact dermatitis. The reviewed studies encompass a wide spectrum of molecular, morphological and biophysical biomarkers, mainly obtained from stratum corneum tape strips and biopsies. Lipids, natural moisturizing factors, and structural proteins are the most frequently reported molecular biomarkers. Additionally, corneocyte surface topography and elasticity show potential as biomarkers for assessing the physical barrier of the skin. In contact dermatitis studies, biomarkers are commonly employed to evaluate skin irritation and differentiate between irritant and allergic contact dermatitis. In atopic dermatitis, biomarkers are primarily utilized to identify differences between atopic and healthy skin, for predictive purposes, and monitoring response to therapies. While this overview identifies potential biomarkers for the skin barrier, their validation as epidermal biomarkers for atopic dermatitis and contact dermatitis has yet to be established.

Delayed hypersensitivity reactions to iodinated contrast media: A diagnostic approach by skin tests.

BACKGROUND: Adverse drug reactions to iodinated contrast media (ICM) have risen due to their increasing use in x-ray-based imaging modalities. Delayed hypersensitivity reactions are mainly caused by nonionic monomeric compounds and represent an issue impacting the diagnostic-therapeutic pathways of cancer, cardiology and surgery patients. OBJECTIVES: To prospectively evaluate the usefulness of skin tests in delayed hypersensitivity reactions to ICM and to evaluate the tolerability of iobitridol, a monomeric nonionic low osmolality compound, as a possible safe alternative. METHODS: Patients with delayed hypersensitivity reactions to ICM referred to us from 2020 to 2022 were prospectively enrolled in the study. All patients underwent patch test and, if negative, intradermal test with the culprit ICM and iobitridol as alternative. RESULTS: A total of 37 patients (females 24, 64.9%) were enrolled in the study. Iodixanol and iomeprol were the most frequently involved ICM (48.5% and 35.2%, respectively); 62.2% of patients presented maculopapular eruption, while 37.8% reported delayed urticaria-like rash. Skin tests resulted positive to the culprit ICM in 19 patients (51.4%), 16 to patch test and 3 to intradermal test. Skin tests with iobitridol, tested as alternative, resulted positive in 3/19 patients (15.8%). All 16 patients with negative results to iobitridol were administered this ICM and tolerated it. CONCLUSIONS: In at least half of patients, delayed-type hypersensitivity was demonstrated by skin tests, particularly by patch test. This diagnostic approach resulted simple, cost-effective and safe, not only to confirm the culprit ICM but also to identify iobitridol as feasible alternative.

Irritant potential of different washing procedures used for heavy-duty soiling: Short and intense or longer and mild?

BACKGROUND: To prevent irritant contact eczema even in occupational fields with heavy-duty soiling, it is generally recommended to use 'mild' hand cleansers (mild detergent without grits, MC). On the other hand, since grit-containing cleansers (GC) show a higher washing power that minimizes washing time, their usage is generally preferred in specific occupational fields. OBJECTIVES: To compare whether a shorter, intense washing period might cause less skin damage than a longer washing period with an MC. METHODS: Differences in cleaning time were first verified in a pilot study using standardized model dirt. In the main study, the forearms of 35 healthy volunteers were washed with three standardized procedures over a period of 3 days, either using 2 min of MC with/without hand brush or 1-min GC. Clinical scoring, transepidermal water loss (TEWL), corneometry, colourimetry and scaliness/roughness (Visioscan) were used to evaluate the epidermal barrier, topography and irritation. RESULTS: The pre-study showed that washing time doubled when using MC vs. GC. Using GC resulted in stronger barrier disruption, even after a shorter washing period - median ΔT4-T1 TEWL 0.96 g/m2 /h vs. 4.91 g/m2 /h respectively, p < 0.0001. The most harmful procedure for the skin was the additional application of a hand brush (18.86 g/m2 /h). CONCLUSIONS: Short-time washing with GC damages the skin barrier more significantly in comparison to a longer application of an MC. When washing with MC, the strongest irritant reaction occurred when accompanied with hand brushing.

Shedding a light on the importance of photopatch testing: A 12-year experience in a dermatology unit.

BACKGROUND: Photopatch testing has been standardized for diagnosing photoallergic contact dermatitis but is still infrequently used. OBJECTIVES: To characterize photopatch test (PPT) results and their clinical relevance. METHODS: We collected retrospective data from patients photopatch tested in our Dermatology Unit (2010-2021), using the European PPT 'baseline' series, other allergens, and patient's own products, when appropriate. RESULTS: Out of 223 patients, 75 patients (33.6%) were reactive with 124 positive PPT reactions, considered relevant in 56/223 patients (25.1%) and in 72/124 reactions (58.1%). Most reactions were caused by topical drugs (n = 33; 45.8%), such as ketoprofen or promethazine, and 7 (9.8%) by systemic drugs, such as hydrochlorothiazide and fenofibrate. 'Classical' ultraviolet filters were responsible for six positive PPT reactions whereas there was only three relevant PPT to the 'newer' UV filters. Patients' sunscreens/cosmetics or plant extracts caused 10 positive PPT each. Additional patch test reactions were observed, mostly to Tinosorb® M. CONCLUSION: Contrary to the trend in ACD, most positive PPT reactions were caused by topical drugs, outweighing ultraviolet filters and cosmetics. We stress the low reactivity to the 'newer' UV filters included in the PPT series. PPT was occasionally positive in systemic drug photosensitivity, but overall PPT reactivity was low.

Experiences from daily practice of upadacitinib treatment on atopic dermatitis with a focus on hand eczema: Results from the BioDay registry.

BACKGROUND: Real-world data on the effectiveness of upadacitinib on atopic dermatitis (AD), hand eczema (HE) and HE in the context of AD are limited. OBJECTIVES: To evaluate the effectiveness and safety of upadacitinib on AD and on HE in patients with AD. METHODS: This prospective observational cohort study includes clinical outcomes: Eczema Area and Severity Index (EASI), Investigator's Global Assessment (IGA), Hand Eczema Severity Index (HECSI), Photographic guide; and PROMs: average pruritus and pain Numeric Rating Scale (NRS) score of the past week, Patient-Oriented Eczema Measure (POEM), Patient-Oriented Eczema, Dermatology Life Quality Index (DLQI), Atopic Dermatitis Control Tool (ADCT), Patient Global Assessment of Disease (PGAD), Quality Of Life Hand Eczema Questionnaire (QOLHEQ) at baseline, Week 4, and Week 16 of upadacitinib-treated patients. Adverse events were monitored during each visit. RESULTS: Thirty-eight patients were included, of which 32 patients had HE. At Week 16, EASI-75 was achieved by 50.0%. Absolute cutoff score NRS-pruritus ≤4 was reached by 62.5%, POEM ≤7 by 37.5%, DLQI ≤5 by 59.4%, ADCT <7 by 68.8%, and PGAD rating of at least 'good' by 53.1%. HECSI-75 was achieved by 59.3% and (almost) clear on the Photographic guide by 74.1%. The minimally important change in QOLHEQ was achieved by 57.9%. Sub-analysis in patients with concomitant irritant contact dermatitis showed no differences. Safety analysis showed no new findings compared to clinical trials. CONCLUSIONS: Upadacitinib can be an effective treatment for patients with AD and concomitant HE in daily practice. Future studies should focus on the effectiveness of upadacitinib on chronic HE, especially on the different etiological subtypes of HE, including HE in non-atopic individuals.

Prevalence, risk factors, and prevention of occupational contact dermatitis among professional cleaners: a systematic review.

OBJECTIVE: The aim of this study was to investigate the prevalence, risk factors, and prevention of occupational contact dermatitis (OCD), as well as risk factors and consequences of OCD among professional cleaners. METHODS: A systematic review following PRISMA guidelines was performed using Medline, EMBASE, and Cochrane Library. RESULTS: Thirty-nine studies containing over 109.000 participants were included in the review. The prevalence of OCD varied between 2.2% and 30.1%. Main occupational risk factors for developing OCD among cleaners included wet work and irritants in cleaning products (bleach, chlorine, ammonia, multi-use-cleaning) and skin contact to metal. The most common contact allergies included rubber, biocides, nickel/cobalt, and perfumes. Other risk factors were inconsistent use of protective gloves and low educational level. Consequences associated with OCD included significant impairment in quality of life, tendency to have unscheduled absence from work, sick leave, increased rate of disability, and recognized degree of injury. Only one prevention study has been published investigating the effect of an educative course in skin-protective behavior in cleaners. The study reported a higher degree of knowledge of skin protection, a decrease in the severity of hand eczema, and a shift toward fewer daily hand washings at follow-up after 3 months. CONCLUSION: Our study proves that OCD is common in cleaners, and the main risk factors included wet work, irritants, and contact allergies, as well as inconsistent use of protective gloves and low educational level. More focus and a greater number of studies are needed on skin protection in this population.

Risk factors of hand eczema: A population-based study among 900 subjects.

BACKGROUND: Many risk factors such as atopic dermatitis (AD) have shown to associate with hand eczema (HE). However, studies concerning other atopic diseases, parental or longitudinal risk factors of HE are scarce. OBJECTIVES: To examine the association between HE and atopic diseases, parental factors, environmental factors (keeping animals, exposure to moulds) and lifestyle factors (obesity, tobacco smoking, alcohol consumption and physical activity) at population level. METHODS: Subjects belonging to the Northern Finland Birth Cohort 1966 Study (NFBC1966) (n = 6830) answered a comprehensive health questionnaire. The data was completed with parental information. RESULTS: HE was reported in 900 (13.3%) individuals. All atopic diseases, parental allergy, female gender and obesity increased the risk of HE whereas physical activity decreased the risk of HE. A statistically significant association was not found between HE and tobacco smoking or alcohol consumption. CONCLUSIONS: All atopic diseases, not only AD, seem to have influence on the presence of HE. In addition, parental and environmental factors associated with HE.

Patch testing in drug reaction with eosinophilia and systemic symptoms (DRESS): A literature review.

The literature on positive patch test results in drug reaction with eosinophilia and systemic symptoms (DRESS) is reviewed. One hundred and five drugs were identified that have together caused 536 positive patch tests in 437 DRESS patients. By far, the most reactions (n = 145) were caused by carbamazepine, followed by amoxicillin, isoniazid, phenytoin, ethambutol, fluindione, phenobarbital, rifampicin, and ceftriaxone; 43 drugs each caused a single case only. The drug classes causing the highest number of reactions were anticonvulsants (39%), beta-lactam antibiotics (20%), antituberculosis agents (11%), non-beta-lactam antibiotics (6%), and iodinated contrast media (5%). The sensitivity of patch testing (percentage of positive reactions) is high for anticonvulsants (notably carbamazepine), beta-lactam antibiotics (notably amoxicillin), and, possibly, iodinated contrast media. Allopurinol and sulfasalazine frequently cause DRESS but never give positive patch tests. Patch testing in DRESS appears to be safe, although mild recurrence of DRESS symptoms, mostly skin reactions, may not be rare. Multiple drug hypersensitivity was found to occur in 16% of all patients, but it is argued that the true frequency is higher. Clinical aspects of DRESS, including diagnosing the disease and identifying culprit drugs (patch tests, intradermal tests, in vitro tests, challenge tests) are also provided, emphasizing the role of patch testing.