Severely compromised supply of patch test allergens in Europe hampers adequate diagnosis of occupational and non-occupational contact allergy. A European Society of Contact Dermatitis (ESCD), European Academy of Allergy and Clinical Immunology (EAACI), European Academy of Dermatology and Venereology (EADV) task forces 'Contact Dermatitis' and 'Occupational Skin Disease' position paper.

Patch testing is the only clinically applicable diagnostic method for Type IV allergy. The availability of Type IV patch test (PT) allergens in Europe, however, is currently scarce. This severely compromises adequate diagnostics of contact allergy, leading to serious consequences for the affected patients. Against this background, the European Society of Contact Dermatitis (ESCD) has created a task force (TF) (i) to explore the current availability of PT substances in different member states, (ii) to highlight some of the unique characteristics of Type IV vs. other allergens and (iii) to suggest ways forward to promote and ensure availability of high-quality patch testing substances for the diagnosis of Type IV allergies throughout Europe. The suggestions of the TF on how to improve the availability of PT allergens are supported by the ESCD, the European Academy of Allergy and Clinical Immunology, and the European Academy of Dermatology and Venereology and intend to provide potential means to resolve the present medical crisis.

Patterns of positive patch test reactions to formaldehyde and formaldehyde releasers at the Finnish Institute of Occupational Health from 2007 to 2020.

BACKGROUND: Formaldehyde is an important contact sensitizer. Formaldehyde releasing substances induce positive reactions in formaldehyde-allergic patients, but there are also reactions independent of formaldehyde allergy. In an earlier study, stronger formaldehyde reactions led to more positive reactions to quaternium-15. OBJECTIVES: To analyze patterns of positive patch test reactions to formaldehyde and different formaldehyde releasers. METHODS: Patch test files of 1497 patients investigated during the period November 2007-August 2020 were retrospectively reviewed for positive reactions to formaldehyde and its releasers. During the study period, almost all (≥99.3%) patients were tested with a formaldehyde dilution series and six formaldehyde releasers. RESULTS: Ninety-three patients tested positive to formaldehyde; 80% of these had positive reactions to at least one formaldehyde releaser, most often benzylhemiformal. There were only nine independent contact allergies to formaldehyde releasers. There were only two reactions to 2-bromo-2-nitropropane-1,3-diol and they occurred in formaldehyde-negative patients. In patients with extreme (+++) reactions to formaldehyde, concomitant positive reactions to any of the other 11 investigated formaldehyde releasers were more common than in patients with milder formaldehyde reactions. CONCLUSIONS: Strong formaldehyde reactions were associated with positive reactions to formaldehyde releasers.

Formaldehyde 2% is not a useful means of detecting allergy to formaldehyde releasers- results of the ESSCA network, 2015-2018.

BACKGROUND: Studies suggest that patch testing with formaldehyde releasers (FRs) gives significant additional information to formaldehyde 1% aq. and should be considered for addition to the European baseline series (EBS). It is not known if this is also true for formaldehyde 2% aq. OBJECTIVES: To determine the frequency of sensitization to formaldehyde 2% aq. and co-reactivity with FRs. To establish whether there is justification for including FRs in the EBS. MATERIALS AND METHODS: A 4-year, multi-center retrospective analysis of patients with positive patch test reactions to formaldehyde 2% aq. and five FRs. RESULTS: A maximum of 15 067 patients were tested to formaldehyde 2% aq. and at least one FR. The percentage of isolated reactions to FR, without co-reactivity to, formaldehyde 2% aq. for each FR were: 46.8% for quarternium-15 1% pet.; 67.4% imidazolidinyl urea 2% pet.; 64% diazolidinyl urea 2% pet.; 83.3% 1,3-dimethylol-5, 5-dimethyl hydantoin (DMDM) hydantoin 2% pet. and 96.3% 2-bromo-2-nitropropane-1,3-diol 0.5% pet. This demonstrates that co-reactivity varies between FRs and formaldehyde, from being virtually non-existent in 2-bromo-2-nitropropane-1,3-diol 0.5% pet. (Cohen's kappa: 0, 95% confidence interval [CI] -0.02 to 0.02)], to only weak concordance for quaternium-15 [Cohen's kappa: 0.22, 95%CI 0.16 to 0.28)], where Cohen's kappa value of 1 would indicate full concordance. CONCLUSIONS: Formaldehyde 2% aq. is an inadequate screen for contact allergy to the formaldehyde releasers, which should be considered for inclusion in any series dependant on the frequency of reactions to and relevance of each individual allergen.

Hairdressers' occupational skin diseases in the Finnish Register of Occupational Diseases in a period of 14 years.

BACKGROUND: Hairdressers have a high risk of occupational contact dermatitis caused by exposure to wet work and allergens in hairdressing chemicals. OBJECTIVES: To examine the distribution of diagnoses of occupational skin diseases (OSDs) and their main causes in hairdressers based on a national register data on occupational diseases. METHODS: We retrieved cases of recognized OSDs in hairdressers from the Finnish Register of Occupational Diseases (FROD) in years 2005-2018. RESULTS: During the 14-year period, a total of 290 cases of recognized OSD in hairdressers were registered in the FROD. Allergic contact dermatitis (ACD) was diagnosed in 54%, irritant contact dermatitis in 44%, and contact urticaria (CU) in 5% of them. ACD was most commonly caused by hair dye products and their ingredients (N = 57), persulfates (N = 35), and preservatives (N = 35; mainly isothiazolinones). Acrylates emerged as hairdressers' occupational contact allergens (N = 8) probably due to introduction of structure nails into hair salons. Persulfates was the most common cause of CU. CONCLUSIONS: ACD was the most common OSD in hairdressers. Our analysis confirms that preservatives are important causes of ACD in hairdressers in addition to hair dye products and persulfates. Acrylates emerged as hairdressers' occupational contact allergens, but contact allergy to perming agents remained rare.

Allergic contact dermatitis and other occupational skin diseases in health care workers in the Finnish Register of Occupational Diseases in 2005-2016.

BACKGROUND: Health care workers are an important risk group for occupational skin disease (OSD). AIMS: To study diagnoses and causes of OSDs in health care workers in the Finnish Register of Occupational Diseases (FROD) in 2005-2016. METHODS: We searched the FROD for dermatological cases (a) in health care-related occupations defined by ISCO-08 and (b) in the industrial branch of health care defined by European industry standard classification system (NACE rev. 2). RESULTS: Health care workers comprised 19% of all OSD cases in the FROD, and irritant contact dermatitis dominated the diagnoses. Nurses and assistant nurses were the largest occupational groups with incidence rates of 3.3 and 2.7/10 000 person years, respectively. Rubber chemicals were by far the most common causative agents of allergic contact dermatitis (ACD) followed by preservatives, the latter mainly comprising isothiazolinones and formaldehyde. Acrylates were important allergens in dental professions. Metals and coconut fatty acid derivatives were the next largest causative groups for ACD. Drugs caused only 1% of the ACD cases. CONCLUSIONS: Workers in different health care occupations do not have a uniform risk for OSD, but they share the risk for ACD due to rubber chemicals and various preservatives.

Construction workers' skin disorders in the Finnish Register of Occupational Diseases 2005-2016.

BACKGROUND: Construction workers are a known risk group for occupational skin disease (OSD). OBJECTIVES: To study diagnoses and causes of OSD in construction workers in the Finnish Register of Occupational Diseases (FROD) 2005-2016. MATERIALS AND METHODS: We searched the FROD for dermatological cases in (a) construction-related occupations defined by the International Standard Classification of Occupations (ISCO-08) and (b) in the industrial branch of construction defined by the Statistical Classification of Economic Activities in the European Community (NACE Rev. 2). RESULTS: The two searches yielded the same number of cases, 329, although they were not identical subgroups. The number of allergic contact dermatitis (ACD) cases was 235 (71%) in construction-related occupations and 228 (69%) in the industrial branch of construction. In the latter analysis, synthetic resin systems caused 66% of ACD cases and 46% of all OSDs, epoxy compounds being the leading cause (122 cases; 54% of ACD cases; 37% of all OSDs). Metals were the second most common group of causes of ACD with 31 cases (chrome 22 cases; cobalt 8 cases). Isothiazolinones caused ACD in 21 cases, many of whom were painters. CONCLUSIONS: ACD dominated the OSDs of construction workers and epoxy products were by far the leading cause comprising 37% of all OSDs. Chrome and isothiazolinones were also prominent causes of ACD.

Contact urticaria and protein contact dermatitis in the Finnish Register of Occupational Diseases in a period of 12 years.

BACKGROUND: Although occupational contact urticaria (CU) and protein contact dermatitis (PCD) are considered frequent among workers with exposure to proteinaceous materials, data on occupations at risk and the main causes of these occupational skin diseases are relatively limited. OBJECTIVES: To report the causative agents and risk occupations for CU and PCD in the Finnish Register of Occupational Diseases (FROD). METHODS: We retrieved from the FROD all recognized cases of CU/PCD in the years 2005-2016. RESULTS: With 570 cases, CU and PCD constituted 11% of all recognized cases of occupational skin diseases in the study period. Occupations with the highest incidence of CU/PCD included bakers, chefs and cooks, farmers and farm workers, veterinarians, gardeners, and hairdressers. The most common causative agents were cow dander and flour and grain, followed by natural rubber latex (NRL) and other food. In food-related occupations, wheat and other flours were by far the most common cause of CU/PCD, with 76 cases, whereas fish and other animal-derived food caused 33 and other plant-derived food caused 23 cases. CONCLUSIONS: Apart from the Finnish peculiarity of cow dander allergy, a striking finding was a large share of CU/PCD caused by flours in food handlers as compared to other food.

12-year data on skin diseases in the Finnish Register of Occupational Diseases II: Risk occupations with special reference to allergic contact dermatitis.

BACKGROUND: Detailed epidemiological studies on occupational skin diseases (OSDs) are scarce. OBJECTIVES: To analyze risk occupations for OSDs in the Finnish Register of Occupational Diseases (FROD). METHODS: We retrieved numbers of OSD cases (excluding skin infections) for different occupations from the FROD in 2005-2016. In the FROD, Finnish ISCO-08-based classification of occupations was used since 2011, and the preceding ISCO-88-based version until 2010. We combined cases from the earlier and the later period using conversion tables provided by Statistics Finland. We included occupations with at least five cases and analyzed them in detail. We calculated incidence rates for OSDs and separately for allergic contact dermatitis (ACD) in different risk occupations using national labor force statistics. We also studied causes of ACD in these occupations. RESULTS: Risk occupations with the largest number of OSD cases included farmers, hairdressers, assistant nurses, cooks, cleaners, machinists, and nurses. Occupations with the highest incidences of OSDs comprised spray painters (23.8/10 000 person years), bakers (20.4), and dental technicians (19.0). Epoxy compounds and acrylates were prominent causes of ACD in occupations with the highest incidences of ACD. CONCLUSIONS: Uniform use of International Standard Classification of Occupations (ISCO) would facilitate comparisons of OSD figures in different countries.

12-year data on dermatologic cases in the Finnish Register of Occupational Diseases I: Distribution of different diagnoses and main causes of allergic contact dermatitis.

BACKGROUND: Skin diseases are among the most common occupational diseases, but detailed analyses on their epidemiology, diagnoses, and causes are relatively scarce. OBJECTIVES: To analyze data on skin disease in the Finnish Register of Occupational Diseases (FROD) for (1) different diagnoses and (2) main causes of allergic contact dermatitis (ACD). METHODS: We retrieved data on recognized cases with occupational skin disease (OSD) in the FROD from a 12-year-period 2005-2016 and used national official labor force data of the year 2012. RESULTS: We analyzed a total of 5265 cases, of which 42% had irritant contact dermatitis (ICD), 35% ACD, 11% contact urticaria/protein contact dermatitis (CU/PCD), and 9% skin infections. The incidence rate of OSD in the total labor force was 18.8 cases/100 000 person years. Skin infections concerned mainly scabies in health care personnel. Twenty-nine per cent of the ACD cases were caused by plastics/resins-related allergens, mainly epoxy chemicals. Other important causes for ACD were rubber, preservatives, metals, acrylates, and hairdressing chemicals. Cases of occupational ACD due to isothiazolinones reached a peak in 2014. CONCLUSION: Our analysis confirms that epoxy products are gaining importance as causes of OSD and the isothiazolinone contact allergy epidemic has started to wane.

Allergic reactions to lower concentrations of nickel sulfate and formaldehyde often appear later than reactions to higher concentrations.

BACKGROUND: A late-appearing patch test reaction may be a sign of active sensitization or represent a delayed elicitation reaction. OBJECTIVES: To retrospectively study the effect of concentration on the time course of allergic reactions to routine concentration dilution series of formaldehyde and nickel sulfate. METHODS: We tested concentration dilution series of 2%, 1%, 0.32% and 0.1% formaldehyde and 5%, 1.6%, 0.5% and 0.16% nickel sulfate, respectively. The last readings were performed on day 4 to day 6. We included patients with allergic reactions to either of the two lowest concentrations in each dilution series and whose tests had been read three times. RESULTS: Forty-two nickel-allergic and 23 formaldehyde-allergic patients fulfilled the inclusion criteria. In 26 (62%) of the nickel-sensitive patients, reactions to lower concentrations appeared later than reactions to the highest concentration. Of the formaldehyde-sensitive patients, 17 (74%) developed one or two allergic reactions to lower concentrations later than reactions to the highest concentration, and one (4%) patient developed allergic reactions to lower concentrations sooner than a reaction to the highest concentration. The remaining patients showed all allergic reactions at the same reading. CONCLUSIONS: In these selected, relatively strongly sensitized patients, allergic reactions to lower concentrations quite regularly appeared later than reactions to higher concentrations.

Occupational contact allergy to cocamidopropyl betaine and its impurities.

BACKGROUND: Contact allergy to cocamidopropyl betaine has been attributed to its impurities dimethylaminopropylamine and cocamidopropyl dimethylamine. OBJECTIVES: To describe patients with positive patch test reactions to cocamidopropyl betaine-related compounds in an occupational dermatology clinic. METHODS: We reviewed the 2002-2009 patch test records at the Finnish Institute of Occupational Health for allergic reactions to cocamidopropyl betaine, dimethylaminopropylamine, cocamidopropyl dimethylamine, and oleamidopropyl dimethylamine. Results. Irritant reactions to at least one of the test substances were seen in 39% of the 1092 patients tested. Fifteen (1.3%) patients showed allergic reactions: 13 to cocamidopropyl dimethylamine, 11 to dimethylaminopropylamine, 8 to oleamidopropyl dimethylamine, and 2 to cocamidopropyl betaine. Concomitant reactions to cocamidopropyl dimethylamine, dimethylaminopropylamine and oleamidopropyl dimethylamine were common. Ten of the 15 patients were diagnosed with occupational allergic contact dermatitis caused by cocamidopropyl betaine-related compounds. The sources of occupational exposure included hair care products, hair colours, perm wave solutions, and liquid soaps. Multiple contact allergies and exposure to several irritant factors were common, and all patients had hand eczema. CONCLUSIONS: Patch test reactions to cocamidopropyl betaine-related compounds are difficult to interpret, owing to extremely common irritant reactions. Cocamidopropyl betaine itself is probably not an allergen. Occupational allergic contact dermatitis caused by cocamidopropyl betaine-related compounds is relatively rare and, unlike non-occupational cocamidopropyl betaine-related allergy, typically manifests as hand dermatitis.

Primary cutaneous T-cell lymphomas show a deletion or translocation affecting NAV3, the human UNC-53 homologue.

Multicolor fluorescent in situ hybridization (FISH) was used to identify acquired chromosomal aberrations in 12 patients with mycosis fungoides or Sézary syndrome, the most common forms of primary cutaneous T-cell lymphoma (CTCL). The most frequently affected chromosome was 12, which showed clonal deletions or translocations with a break point in 12q21 or 12q22 in five of seven consecutive Sézary syndrome patients and a clonal monosomy in the sixth patient. The break point of a balanced translocation t(12;18)(q21;q21.2), mapped in the minimal common region of two deletions, fine mapped to 12q2. By locus-specific FISH, the translocation disrupted one gene, NAV3 (POMFIL1), a human homologue of unc-53 in Caenorhabditis elegans. A missense mutation in the remaining NAV3 allele was found in one of six cases with a deletion or translocation. With locus-specific FISH, NAV3 deletions were found in the skin lesions of four of eight (50%) patients with early mycosis fungoides (stages IA-IIA) and in the skin or lymph node of 11 of 13 (85%) patients with advanced mycosis fungoides or Sézary syndrome. Preliminary functional studies with lentiviral small interfering RNA-based NAV3 silencing in Jurkat cells and in primary lymphocytes showed enhanced interleukin 2 expression (but not CD25 expression). Thus, NAV3 may contribute to the growth, differentiation, and apoptosis of CTCL cells as well as to the skewing from Th1-type to Th2-type phenotype during disease progression. NAV3, a novel putative haploinsufficient tumor suppressor gene, is disrupted in most cases of the commonest types of CTCL and may thus provide a new diagnostic tool.

A new parvovirus genotype persistent in human skin.

Parvovirus B19 is the exclusive human pathogen of the Erythrovirus genus. In classical view, the B19 DNA sequence shows little variability, with no disease-specific or tissue type specific associations. We examined skin biopsies from patients with B19-unrelated skin disease or from constitutionally healthy adults by polymerase chain reaction assays for four different genomic regions of the B19 virus. Sequencing showed that the skin-derived viral DNA differed within the protein-coding region from the B19 reference sequences by 10.8% and from the V9 variant by 8.6% and within the noncoding region (covering nucleotides 189-435 of the promoter region) by 26.5 and 17.2%, respectively. Despite this sequence difference, the promoter region was shown by a luciferase gene expression assay to be biologically active. We have detected a new B19 virus genotype, K71, which differs extensively from the known B19-virus genotypes and is persistently carried in human skin.