Patients with positive patch test to formaldehyde can be safely vaccinated with formaldehyde-containing vaccines.

BACKGROUND: Prophylactic vaccination against influenza and other epidemic viruses is recommended for citizens above 65 years. Several vaccines may contain traces of formaldehyde and are contra-indicated in patients hypersensitive (in the broadest possible meaning) to formaldehyde. Thorough knowledge on the various subtypes of hypersensitivity is sparse among non-dermatologists and non-allergists, and therefore many patients are prevented from vaccination based on a positive patch test to formaldehyde. The purpose of this retrospective study was to investigate whether patients with positive patch test to formaldehyde subsequently receiving a formaldehyde-containing vaccine and developed a severe adverse reaction. METHODS/MATERIALS: From January 2000 to June 2021, 169 patients (>50 years) had a positive formaldehyde patch test at the Department of Dermatology and Allergy Center, Odense University Hospital and were included into this retrospective study. The electronic medical record was assessed for receipt of a formaldehyde-containing vaccine after patch test and for subsequent contact with the Acute Ward in the Region of Southern Denmark within 14 days after vaccination. RESULTS: Of the 158 patients residing in the Region of Southern Denmark, 130 patients were vaccinated with one or more formaldehyde-containing vaccines of whom 123 received an influenza vaccine. No contacts to the acute wards were identified. DISCUSSION: Although prospective studies would be beneficial, patients with positive patch test to formaldehyde can be safely vaccinated with formaldehyde-containing vaccines.

Patch Testing With Nickel Sulfate 5.0% Traces Significantly More Contact Allergy Than 2.5%: A Prospective Study Within the International Contact Dermatitis Research Group.

BACKGROUND: Nickel allergy is the most common contact allergy, and a nickel salt is, therefore, included in most baseline patch test series. In the baseline series of the International Contact Dermatitis Research Group and the American Contact Dermatitis Society, nickel sulfate hexahydrate (NSH) in petrolatum at 2.5% is included, whereas NSH at 5.0% is included in many other baseline series, such as the European and Swedish ones. OBJECTIVE: The aim of the study is to investigate whether NSH at 5.0% detects significantly more contact allergy than NSH 2.5% when both preparations are tested simultaneously in consecutive dermatitis patients. PATIENTS AND METHODS: Two thousand two hundred eighty-seven consecutive dermatitis patients were patch tested simultaneously with NSH in petrolatum at 2.5% and 5.0%. The allergy rates were compared for all clinics individually and combined using McNemar test, 2-sided. RESULTS: Contact allergy to NSH 5.0% and 2.5% was found in 20.3% and 16.8%, respectively ( P < 0.0001). In 6 of 11 clinics, significantly more patients tested positive to the higher NSH concentration. For the 2 clinics in North America combined, significantly more patients tested positive to NSH 5.0%. CONCLUSIONS: The NSH preparation in the International Contact Dermatitis Research Group baseline patch test series should be considered to be changed from NSH 2.5% (1 mg NSH/cm 2 ) to 5.0% (2 mg NSH/cm 2 ).

Regular support provided by dermatological nurses improves outcomes in patients with psoriasis treated with topical drugs: a randomized controlled trial.

BACKGROUND: Patient adherence to topical antipsoriatic drugs is often poor, leading to poor efficacy. Use of long-term support delivered by dermatological nurses to patients treated with topical drugs may improve outcome. AIM: To evaluate whether regular support from dermatological nurses improves outcome and treatment adherence in patients with psoriasis receiving topical medications. METHODS: We conducted a randomized controlled trial (RCT) (clinicaltrials.gov registration NCT04220554), in which patients received once-daily topical medications (containing corticosteroids and/or calcipotriol) for as long as their psoriasis was visible. The patients were randomly allocated to standard care by the dermatologist either with (n = 51) or without (n = 52) support from dermatological nurses. The nurse support intervention consisted of a structured dermatological consultation at baseline and Week 1, followed by contact with a nurse each month (in the outpatient clinic or by telephone). The primary outcome was severity of psoriasis, which was measured by the Lattice System Physician's Global Assessment (LS-PGA) and assessed by intention-to-treat analyses using linear mixed regression models for longitudinal data. Secondary outcomes were quality of life (measured by the Dermatology Life Quality Index; DLQI) and good adherence (defined as use of ≥ 80% of recommended doses). RESULTS: In total, 92 patients (89%) completed the 48-week trial period. The intervention group improved more than the nonintervention group from baseline to Week 24 in LS-PGA (2.21 vs. 1.28, P = 0.001) and in DLQI at Week 12 (6.50 vs. 1.55, P < 0.001). Differences between the two groups in favour of the intervention were observed throughout the study period. More participants in the intervention group had good adherence compared with the nonintervention group (36% vs. 14%, P < 0.001). CONCLUSION: Regular, continued patient support from dermatological nurses increased the efficacy of psoriasis treatment, improved quality of life and enhanced long-term adherence to topical antipsoriatic drugs. However, there is still room for more improvement.

Guidelines for diagnosis, prevention, and treatment of hand eczema.

BACKGROUND: Hand eczema is a common inflammatory skin disorder. Health care providers need continuously updated information about the management of hand eczema to ensure best treatment for their patients. OBJECTIVES: To update the European Society of Contact Dermatitis guideline on the diagnosis, prevention, and treatment on of hand eczema. METHOD: The Guideline Development Group (GDG) was established on behalf of the ESCD. A call for interest was launched via the ESCD website and via the ESCD members' mailing list. Appraisal of the evidence for therapeutic and preventive interventions was applied and a structured method of developing consensus was used and moderated by an external methodologist. The final guideline was approved by the ESCD executive committee and was in external review on the ESCD webpage for 1 month. RESULTS: Consensus was achieved for several statements and management strategies. CONCLUSION: The updated guideline should improve management of hand eczema.

Patch Testing With a New Composition of the Mercapto Mix-A Multicenter Study from the International Contact Dermatitis Research Group.

BACKGROUND: Mercaptobenzothiazole compounds are associated with allergic contact dermatitis caused by rubber products. Several screening substances have been used for patch testing. OBJECTIVE: To compare the frequency of positive test reactions to a mercapto mix containing a higher concentration of 2-mercaptobenzothiazole with reactions to the combination of 2-mercaptobenzothiazole 2.0% and mercapto mix 2.0%. METHODS: There were 7103 dermatitis patients in 12 International Contact Dermatitis Research Group dermatology departments who were patch tested with 2-mercaptobenzothiazole 2.0% petrolatum (pet.), mercapto mix 2.0% pet., and mercapto mix 3.5% pet. RESULTS: Contact allergy to the 3 test preparations varied among the 12 centers: 2-mercaptobenzothiazole 2.0% pet. (0-2.4%), mercapto mix 2.0% pet. (0-4.9%), and mercapto mix 3.5% pet. (0-1.4%). 2-Mercaptobenzothiazole 2.0% and mercapto mix 2.0% detected a few more positive patients compared with mercapto mix 3.5%, but the difference was statistically insignificant (mercapto mix 2.0% pet., P = 1.0; 2-mercapto-benzothiazole 2.0% pet., P = 0.66). CONCLUSIONS: Mercapto mix 3.5% pet. is not better than 2-mercaptobenzothiazole 2.0% and mercapto mix 2.0% by a difference that is significant. By using only 1 test preparation (mercapto mix 3.5%), an additional hapten could be tested. No cases of suspected/proven patch test sensitization were registered.

Patch Testing With Methylchloroisothiazolinone/Methylisothiazolinone Using a New Diagnostic Mix-A Multicenter Study From the International Contact Dermatitis Research Group.

BACKGROUND: In the early 1980s, a preservative containing a mixture of methylchloroisothiazolinone (MCI) and methylisothiazolinone (MI) in a ratio of 3:1 was introduced. This mixture (mix) has been patch tested at 100 ppm (0.01%) worldwide and at 200 ppm (0.02%) in Sweden since 1986 and also in the European baseline series since 2014. OBJECTIVE: A new aqueous mix of MCI 0.015% and MI 0.2% was compared with patch testing with the 2 aqueous baseline preparations of MCI/MI 0.02% and MI 0.2%. METHODS: Four thousand three hundred ninety-seven patients with dermatitis in 12 International Contact Dermatitis Research Group dermatology departments from 3 continents were patch tested simultaneously with the 3 preparations. RESULTS: The frequency of positive patch tests to the allergens varied between 0% and 26.7% in the 12 test centers. The new mixture MCI/MI 0.215% in aqua (aq) detected significantly more patients with MCI/MI allergy than both MCI/MI 0.02% aq (P < 0.001) and MI 0.2% aq (P < 0.001) alone and combined. CONCLUSIONS: The results favor replacing the preparations MCI/MI 0.02% aq and MI 0.2% aq with the mixture MCI/MI 0.215% aq in the International Contact Dermatitis Research Group baseline series.

Compositae sensitization in Danish children and adolescents.

BACKGROUND: Compositae plant sensitization in children is relatively frequent. From 1995-2006, we found a prevalence of 1.8% sesquiterpene lactone (SL) mix/parthenolide patch test positives among consecutive eczema patients <18 years. OBJECTIVES: To report the results of patch test screening for Compositae sensitization in patients <18 years in the last 13 years. METHODS: Children and adolescents <18 years, diagnosed with Compositae sensitization between 2007 and 2019, were included. RESULTS: Among 388 children tested, 12 (3%) were Compositae-sensitized, and 11 (2.8%) had positive reactions to SL mix. Compositae mix 5% pet. elicited positive reactions in six of seven patients tested, and dandelion extract 2.5% pet. in six of 10 patients tested. The mean age of the five girls and seven boys was 9.4 years and 11.7 years, respectively. Eleven children had a personal and one a family history of atopy, and 11 children had hand eczema. Only two were mono-sensitized to Compositae. CONCLUSIONS: SL mix is a suitable screening agent among children and adolescents in our area, well supplemented with Compositae mix 5% and dandelion extract. The study emphasizes the importance of Compositae screening in children with a personal and/or family history of atopy, hand eczema or widespread airborne dermatitis, summer exacerbation, and plant exposure.

Contact Allergy to Fragrance Mix II and Hydroxyisohexyl 3-Cyclohexene Carboxaldehyde: A Retrospective Study by International Contact Dermatitis Research Group.

BACKGROUND: Fragrance mix II (FM II) is included in the baseline patch test series recommended by the International Contact Dermatitis Research Group (ICDRG). Hydroxyisohexyl 3-cyclohexene carboxaldehyde (HICC) is the most important sensitizer of the 6 fragrance materials included in FM II. Besides being a part of FM II, HICC is also tested separately in the ICDRG baseline series. OBJECTIVES: The aim of the study was to investigate the prevalence of contact allergy to FM II and HICC in 2012-2016 with a focus on simultaneous reactions and the percentage of missed contact allergy to HICC provided that only FM II had been tested. PATIENTS AND METHODS: A total of 25,019 consecutive dermatitis patients in 13 dermatology clinics representing 12 countries in 5 continents were patch tested with FM II and HICC in the baseline series. RESULTS: Contact allergy to FM II and HICC was found in 3.9% and 1.6%, respectively. For FM II, the frequency varied from 1.5% to 7.6% in different centers. The corresponding range for HICC was 0.2% to 3.6%. Simultaneous contact allergy to FM II and HICC was noted in 1.4% with the range 0.2% to 2.6%. Seventy-seven patients (0.31%) with contact allergy to HICC did not test positively to FM II. The range for missed HICC allergy by testing only FM II in the different centers would be 0.04% to 0.74%. The ratio between the contact allergy rates for FM II and HICC was similar for all centers, except for Montreal having significantly more contact allergy to FM II than to HICC. CONCLUSIONS: The frequency of missed contact allergy to HICC when testing only with FM II was less than 0.5%, therefore questioning the need to test HICC separately in the ICDRG baseline series.

Contact sensitization to florists' chrysanthemums and marguerite daisies in Denmark: A 21-year experience.

BACKGROUND: Both florists' chrysanthemums (Chrysanthemum cultivars) and marguerite daisies (Argyranthemum frutescens [L.] Sch.Bip. and its varieties and cultivars) are popular ornamental plants in Denmark. OBJECTIVES: To present results of aimed patch testing with chrysanthemum and marguerite daisy extracts in Danish patients with Compositae sensitization. METHODS: The results of patch testing with chrysanthemum extract 3% petrolatum (pet.) and marguerite daisy extract 3% pet. (and possibly 1% pet.) from 1998 to 2019 were analyzed. RESULTS: Altogether, 111/191 (58%) patients tested positive to chrysanthemum extract and 104/179 (58%) tested positive to marguerite daisy. The majority was recreationally exposed, and most reactions were considered relevant. Feverfew extract 1% pet., Compositae mix 5% or 6% pet., or parthenolide 0.1% pet. may cross-react with chrysanthemum; Compositae mix seems to be best at detecting sensitization to marguerite daisy. CONCLUSIONS: In areas where exposure to chrysanthemum or marguerite daisies is prevalent, it is suggested to include extracts of these plants in the plant series to improve diagnosis of, and advice to, Compositae-allergic patients.

Patch Testing With Formaldehyde 2.0% (0.60 mg/cm2) Detects More Contact Allergy to Formaldehyde Than 1.0.

BACKGROUND: The International Contact Dermatitis Research Group increased the patch test concentration of formaldehyde from 1.0% aqueous (aq) to 2.0% aq (in 2011). OBJECTIVE: This study was designed to investigate the outcome of the decision. METHODS: Consecutive dermatitis patients in 8 different clinics were patch tested with formaldehyde 1.0% aq and 2.0% aq. The test solutions were applied with a micropipette to the filter paper discs in the respective chamber. RESULTS: A total of 2778 patients were tested with 1.0% aq and 2766 to 2.0% aq. Sixty-five patients (2.3%, calculated from 2766 tested, to 2.0% aq) had positive patch test reactions interpreted as contact allergy to formaldehyde. This is a rather low frequency. Of these 65, 46 were women (46/1703 [2.7%]) and 19 were men (19/1063 [1.8%]). Thirty-six reacted only to 2.0% aq, 21 patients reacted to both concentrations, and 8 patients reacted only to 1.0% aq. Significantly, more patients reacted to 2.0% aq compared with 1.0% aq (P < 0.001). There was no significant sex difference. A total of 0.8% irritant reactions were recorded to formaldehyde 2.0% aq and 0.1% to 1.0% aq. CONCLUSIONS: The increased formaldehyde patch test concentration to 2.0% aq revealed more formaldehyde contact allergy.

Screening for Compositae contact sensitization with sesquiterpene lactones and Compositae mix 2.5% pet.

BACKGROUND: Compositae contact sensitization may be difficult to diagnose, because of a lack of reliable screening allergens. OBJECTIVES: To assess the suitability of Compositae mix II 2.5% pet. (CM2.5) as a screening mix in the baseline series combined with sesquiterpene lactone (SL) mix and parthenolide (PTH). METHODS: CM2.5 was added to the baseline series, which included SL mix and PTH 0.1% pet., in January 2015, and PTH was included in TRUE Test Panel 3 in October 2015. All Compositae-sensitive patients diagnosed or tested in the next 4 years were assessed. RESULTS: Altogether, 57 patients (2.7%) presented with Compositae allergy. On primary testing in 53 newly diagnosed patients, SL mix elicited positive reactions most frequently (53% positive), followed by CM2.5 (47% positive), and PTH (45% positive). CM2.5 and PTH pet. elicited a few irritant reactions. Three patients had late reactions. Altogether, 16 patients (28%) were not detected by any of the three screening agents. CONCLUSIONS: SL mix is an indispensable, although insufficient, screening mixture in Denmark. It may be relatively safely supplemented with CM2.5 and PTH in the TRUE Test system for screening, but, when Compositae sensitization is suspected, further extracts should be tested on the basis of the history.

Screening for Gold Sensitization in Consecutive Eczema Patients: Prevalence, Relevance, and Sources of Exposure.

BACKGROUND: Since the 1990s, gold has been recognized as an important contact allergen. OBJECTIVES: Based on our results with gold sodium thiosulfate (GST) in the TRUE Test patch test system in the baseline series, the aims of the study were to evaluate baseline testing with gold salts worldwide and to discuss relevance. METHODS: Patients with positive patch test reactions to GST were questioned on exposure at day 7 reading. RESULTS: In a 1-year period, 89 (18.5%) of 480 patients tested positive to GST, making this the most frequent contact allergy. The 89 patients comprised 18 males and 71 females. The reaction was considered relevant in 21%; this is a minimum figure because 2 patients were withdrawn because of unknown relevance and because clinical features suggestive of gold contact allergy at distant sites, such as the face, were not taken into account. Altogether, 88% had been exposed. Worldwide, the prevalence of gold sensitization ranges between 0.78% and 30.7%, and relevance, in larger studies, has been between 15% and 20% of patients. The use of earrings and the presence of dental gold were important sources of exposure. CONCLUSIONS: Because it may be difficult to diagnose gold allergy, screening may be recommended when history taken suggests gold exposure.

Twenty-eight-day follow-up of patch test reactions to p-phenylenediamine and p-phenylenediamine dihydrochloride: A multicentre study on behalf of the European Environmental and Contact Dermatitis Research Group.

BACKGROUND: There is an ongoing discussion on whether routinely patch testing with p-phenylenediamine (PPD) 1.0% pet. is safe, owing to the risk of patch test sensitization. Late-appearing patch test reactions may reflect patch test sensitization, but may also be attributable to a low degree of pre-existing sensitization. OBJECTIVES: To follow the positive patch test reactions to PPD and its salt PPD dihydrochloride (PPD-DHC) in order to characterize reaction patterns concerning time and dose in PPD-sensitized individuals. METHODS: Volunteers with previous reactions to PPD 1.0% were included and patch tested with PPD and PPD-DHC in equimolar dilution series. There were then seven follow-up visits over a period of 28 days. RESULTS: Twenty-six volunteers completed the study, of whom 23 of 26 (88%) reacted to PPD 1.0%, and 69% reacted to PPD 0.32%. Altogether, 42% and 27% reacted to the corresponding equimolar concentrations of PPD-DHC. After day 7, no new reactions were observed to any concentration tested, either of PPD or of PPD-DHC. CONCLUSION: No late-appearing reactions to PPD or PPD-DHC were observed at any dose. There is a risk of missing contact allergy when the dose is decreased.

Atopic diseases and type I sensitization from adolescence to adulthood in an unselected population (TOACS) with focus on predictors for allergic rhinitis.

BACKGROUND: While much is known on childhood atopic diseases, knowledge about persistence of atopic diseases from childhood to adulthood is limited. We therefore aimed to study the clinical course of atopic diseases and type I sensitization prospectively in an unselected cohort of adolescents followed into adulthood. METHODS: A cohort of unselected 8th-grade school children (mean age 14 years) established in 1995 and followed up in 2010 were evaluated with questionnaire, clinical examination, skin prick tests and measurements of specific IgE. RESULTS: The lifetime prevalence of atopic diseases was high and increased significantly from adolescence (31%) to adulthood (57%); particularly allergic rhinitis increased with an incidence rate of 17.5/1000 person-years. Childhood predictors for adult allergic rhinitis were atopic dermatitis, asthma and asymptomatic sensitization to pollen and house dust mite. Among those with asymptomatic sensitization in adolescence, 53%-78% developed allergic rhinitis in adulthood. Furthermore, type I sensitization increased significantly from adolescence to adulthood mostly due to increased sensitization to pollen. Type I sensitization was found mainly in those with allergic rhinitis. A high number of adults had oral allergy symptoms due to the high number of birch pollen allergic individuals. CONCLUSION: Persistence of atopic diseases in adulthood is common, and a high proportion of the adult population is sensitized giving a high prevalence of allergic rhinitis. Many with asymptomatic sensitization in adolescence will develop allergic rhinitis in adult life. The focus should be on prevention of atopic diseases and sensitization already in childhood.

Excipient and Dose per Unit Area Affect Sensitivity When Patch Testing With Gold Sodium Thiosulfate.

BACKGROUND: Dose/area and reading paradigms for gold patch testing are controversial and not standardized worldwide. OBJECTIVES: The aims of this study were to determine the optimum patch test dose of gold sodium thiosulfate (GST) in a hydrogel (HYD) and to establish GST HYD safety/efficacy and further characterize normal morphology and time course of GST reactions. METHODS: Twenty gold-allergic patients were patch tested with a dilution series of GST HYD and with GST 2% petrolatum (pet). Furthermore, this previously determined optimal dose was compared with GST 0.5% pet in 19 known-allergic and 216 consecutive subjects. RESULTS: The optimal GST HYD dose was 0.075 mg/cm, not statistically different from GST 2% pet (P = 0.4795). Gold sodium thiosulfate HYD outperformed GST 0.5% pet in both known-allergic subjects (79% vs 63%, P = 0.2482) and consecutive subjects (30% vs 9%, P < 0.0001). Late reactions were common in consecutive patients with both HYD and pet. Significantly more persistent reactions were associated with GST HYD than with GST 0.5% pet. CONCLUSIONS: Gold sodium thiosulfate HYD 0.075 mg/cm is the optimal dose for diagnosis of gold contact allergy with GST. Gold sodium thiosulfate 0.5% pet yielded false-negatives in some patients, suggesting inadequate dose per centimeter squared. Late reads are normal, expected, and necessary for diagnosis of gold contact allergy in this cohort.

Parthenolide in Danish biodynamic and organic milk: A new source of exposure to an allergenic sesquiterpene lactone.

BACKGROUND: The sunflower family of plants (Compositae = Asteraceae) is currently the most allergenic plant family worldwide, according to the number of sensitizing species. Secondary plant metabolites, including the allergenic sesquiterpene lactones present in Compositae plants, may occur in food items either through their presence in, or through contamination of, plant-based raw materials, or through their occurrence in products of non-plant origin. OBJECTIVE: To analyse biodynamic, organic and conventional milk for the presence of the sesquiterpene lactone parthenolide. METHODS: The content of parthenolide in the milk samples was investigated in dichloromethane extracts obtained by liquid-liquid extraction, followed by gas chromatography-mass spectrometry analyses. RESULTS: The concentration of parthenolide was 0.07 ±0.004 ppm in biodynamic milk, 0.05 ±0.002 ppm in organic milk, and not detectable (<0.002 ppm) in conventional milk. CONCLUSIONS: This is the first report of a potent contact allergen in milk. There seems to be an association between the time that the dairy cattle spend grazing and the amount of parthenolide detected. Although the concentration is low, it is estimated to be high enough to elicit dermatitis in the most sensitive persons by direct contact with the milk.

Anti-inflammatory potency testing of topical corticosteroids and calcineurin inhibitors in human volunteers sensitized to diphenylcyclopropenone.

AIMS: To quantify the anti-inflammatory potency of topical corticosteroids and topical calcineurin inhibitors by measuring the contact allergic response to a diphenylcyclopropenone (DPCP) challenge in de novo sensitized human volunteers. METHODS: Two randomized, double-blind, vehicle-controlled studies were performed encompassing 76 volunteers: 29 in the first and 47 in the second study. Topical drugs were applied pre- and/or post-treatment in block designs. The compounds were tested simultaneously under occluded patch tests covering DPCP-induced dermatitis. Inhibitory responses were assessed by visual scoring and measurements of the oedema thickness with ultrasound. RESULTS: When applied both before and after the DPCP challenge, significant anti-inflammatory effects were seen in descending order for tacrolimus 0.1% ointment, clobetasol propionate ointment, betamethasone valerate ointment and hydrocortisone butyrate ointment, while pimecrolimus cream, hydrocortisone ointment and vehicles had no significant effect. Only tacrolimus ointment (P < 0.01) demonstrated a consistent significant pre-treatment inhibitory effect compared with an untreated DPCP control. CONCLUSIONS: This human testing method in which the inflammation of experimentally induced allergic patch test reactions is quantified by objective measurement allows an analysis of the anti-inflammatory potency of not only topical corticosteroids, but also of drugs that have no effect on vasoconstriction. The method allowed comparison of the potencies of four topical corticosteroids and two calcineurin inhibitors.