Associations between tobacco smoking status and patch test results-A cross-sectional pilot study from the Information Network of Departments of Dermatology (IVDK).

BACKGROUND: Earlier studies suggested a potential association between tobacco smoking and nickel sensitization, but little is known about other contact allergens. OBJECTIVES: To investigate the association of smoking status and contact sensitizations as well as subtypes of dermatitis, and to analyse the sensitization profiles of tobacco smokers. PATIENTS AND METHODS: Within the Information Network of Departments of Dermatology (IVDK), we performed a cross-sectional multicentre pilot study comprising 1091 patch-tested patients from 9 departments, comparing 541 patients with a history of cigarette smoking (281 current and 260 former smokers) with 550 never-smokers. RESULTS: We could not confirm the previously reported association between nickel sensitization and tobacco smoking. Moreover, sensitizations to other allergens, including colophony, fragrance mix I, Myroxylon pereirae and formaldehyde, were not increased in cigarette smokers compared with never smokers. Hand dermatitis (50.6% vs. 33.6%) and occupational cause (36.2% vs. 22.5%) were significantly more frequent among cigarette smokers compared with never-smokers as shown by non-overlapping 95% confidence intervals. CONCLUSIONS: Although our study does not allow a firm conclusion on whether smoking status contributes to certain contact sensitizations, it confirms an association of smoking with hand dermatitis and occupational cause.

The benefit of late readings in patch testing depends both on allergen and patient characteristics.

BACKGROUND: Patch test (PT) readings are recommended after 48 h and 72 h (D3). An additional day 7 (D7) reading has been suggested by some, although data on efficient patient selection are scarce. We investigated positive D7 reactions regarding (i) allergens in the baseline series and additional PT series of the German Contact Dermatitis Research Group (DKG) and (ii) characteristics of the patients tested. METHODS: Retrospective, multicentre analysis of 190 allergens derived from 17 DKG test series in 4687 patients with an additional D7 reading. Patients were patch tested with the baseline series and additional series, if required. Occurrence of novel D7 reactions as well as increasing skin reactions from D3 to D7 was analysed separately. RESULTS: Depending on the allergen tested, waiving D7 readings would have missed 4.4-26.8% of positive PT results. Patch test series with the highest number of novel D7 reactions were baseline series, metal series, and leather/shoe series. New positive reactions on D7 were associated with age over 50 years and with a negative irritant control containing sodium lauryl sulphate. Of note, application of the PT allergens for 48 h instead of 24 h was positively associated with late PT reactions. CONCLUSION: Within the most frequently tested allergens, without late readings, on average 11.7% of sensitizations would have been missed. Novel late reacting allergens were identified. This study comprehensively dissects patient-, allergen- and test-dependent parameters in support for D7 readings. We propose to always consider late readings individually based on effort-benefit considerations.

Ocular syphilis - a case series of four patients.

Ocular manifestations of syphilis with visual impairment symptoms may occur already at the stage of secondary syphilis. They may also be the only manifestation of syphilis and mimic other diseases of the eye. Therefore, in all patients with uveitis, optic neuritis, optic atrophy, acute ocular muscle paresis, or loss of visual acuity, syphilis infection should be ruled out, even if the medical history does not initially raise suspicion. Ocular involvement should be treated as neurosyphilis. Delayed diagnosis and inadequate therapy are often associated with irreversible consequences for the affected patient. As with any syphilis infection, HIV infection should be considered and excluded, especially in the case of ocular manifestations.

Contact urticaria: Frequency, elicitors and cofactors in three cohorts (Information Network of Departments of Dermatology; Network of Anaphylaxis; and Department of Dermatology, University Hospital Erlangen, Germany).

BACKGROUND: Contact urticaria (CU) is an infrequent, mostly occupational disease that may be life-threatening (CU syndrome stage 4). OBJECTIVES: To identify the current frequency, elicitors and cofactors of CU. PATIENTS: Three cohorts were retrospectively analysed for CU: (a) patients from the Information Network of Departments of Dermatology (IVDK) database (2000-2014; n = 159 947); (b) patients from an allergy unit (Department of Dermatology, University Hospital Erlangen, 2000-2015; n = 4741); and (c) patients from the Anaphylaxis Registry (2007-2015: 6365 reported cases, including 2473 patients with Ring and Messmer grade III-IV reactions) for severe cases with skin/mucosal manifestations occurring at the workplace vs cases not occurring at the workplace (n = 68 vs n = 1821). RESULTS: Four hundred and forty-eight CU patients (0.28%) were diagnosed in the IVDK cohort, and 16 (0.34%) (10 of immunological aetiology, and 6 of non-immunological aetiology) in the Erlangen cohort. The most frequent elicitors in the IVDK cohort were cosmetics, creams, sun protection agents (although these were less frequent in CU patients than in controls without CU; 26.8% vs 35.6%, P < .0001), and gloves (significantly more frequent in CU patients than in controls; 18.1% vs 6.5%, P < .0001). The most frequent elicitors in the Erlangen cohort were natural rubber latex and sorbic acid. Among the MOAHLFA index characteristics, in both cohorts occupational disease was more common in CU patients than in patients without CU. CU was significantly associated with allergic rhinitis and allergic asthma. Wet work was a relevant cofactor. In the Anaphylaxis Registry, 19 cases (0.3%) were identified with severe reactions including skin symptoms at the workplace linked to common occupational elicitors. CONCLUSIONS: CU is a rare occupational skin manifestation with a frequency of <0.4% in the examined patients; it may, however, progress to anaphylaxis. Preventive measures are important, and should take into account the identified elicitors and cofactors.

S3 Guidelines: Epicutaneous patch testing with contact allergens and drugs - Short version, Part 2.

Epicutaneous patch testing is the diagnostic standard for the detection of allergic contact dermatitis. The present guidelines are aimed at residents and board-certified physicians in the fields of dermatology and allergology as well as other medical specialties involved in establishing the indication for patch testing and its execution in patients with contact dermatitis and other forms of delayed-type hypersensitivity. The target audience also includes other health care providers and insurance funds. Based on a systematic literature search and a formal consensus process (S3), the guidelines were developed by dermatologists in collaboration with pediatricians, occupational medicine physicians, nursing staff as well as patient representatives. The systematic methodological approach and appraisal of evidence upon which the recommendations are based are outlined in a separate method report that also contains evidence tables. The guidelines address general aspects of patch testing as well as medicolegal issues. The recommendations given relate to topics such as the indication for patch testing, informed patient consent, as well as the choice of test substances, test chambers and test site, duration of exposure, reading times and interpretation of test reactions. Furthermore, recommendations are provided with respect to endogenous and exogenous factors, specific patient groups (children, pregnant women, immunosuppressed individuals) as well as possible risks and adverse events associated with patch testing using contact allergens.

S3 guidelines: Epicutaneous patch testing with contact allergens and drugs - Short version, Part 1.

Epicutaneous patch testing is the diagnostic standard for the detection of allergic contact dermatitis. The present guidelines are aimed at residents and board-certified physicians in the fields of dermatology and allergology as well as other medical specialties involved in establishing the indication for patch testing and its execution in patients with contact dermatitis and other forms of delayed-type hypersensitivity. The target audience also includes other health care providers and insurance funds. Based on a systematic literature search and a formal consensus process (S3), the guidelines were developed by dermatologists in collaboration with pediatricians, occupational medicine physicians, nursing staff as well as patient representatives. The systematic methodological approach and appraisal of evidence upon which the recommendations are based are outlined in a separate method report that also contains evidence tables. The guidelines address general aspects of patch testing as well as medicolegal issues. The recommendations given relate to topics such as the indication for patch testing, informed patient consent, as well as the choice of test substances, test chambers and test site, duration of exposure, reading times and interpretation of test reactions. Furthermore, recommendations are provided with respect to endogenous and exogenous factors, specific patient groups (children, pregnant women, immunosuppressed individuals) as well as possible risks and adverse events associated with patch testing using contact allergens. Note: This publication is part 1 of the short version of the S3 guidelines for "Epicutaneous patch testing using contact allergens and drugs" (registry no. 013 - 018; date: March 20, 2019; valid until December 31, 2021). Part 2 of the short version will be published in the next issue. The long version of these guidelines can be accessed at www.awmf.org. The method report is available as online publication (https://www.awmf.org/leitlinien/detail/ll/013-018.html) and contains the evidence tables in its appendix.

Comparing reliabilities of strip and conventional patch testing.

BACKGROUND: The standardized protocol for performing the strip patch test has proven to be valid, but evidence on its reliability is still missing. OBJECTIVE: To estimate the parallel-test reliability of the strip patch test as compared with the conventional patch test. METHODS: In this multicentre, prospective, randomized, investigator-blinded reliability study, 132 subjects were enrolled. Simultaneous duplicate strip and conventional patch tests were performed with the Finn Chambers® on Scanpor® tape test system and the patch test preparations nickel sulfate 5% pet., potassium dichromate 0.5% pet., and lanolin alcohol 30% pet. Reliability was estimated by the use of Cohen's kappa coefficient. RESULTS: Parallel-test reliability values of the three standard patch test preparations turned out to be acceptable, with slight advantages for the strip patch test. The differences in reliability were 9% (95%CI: -8% to 26%) for nickel sulfate and 23% (95%CI: -16% to 63%) for potassium dichromate, both favouring the strip patch test. CONCLUSIONS: The standardized strip patch test method for the detection of allergic contact sensitization in patients with suspected allergic contact dermatitis is reliable. Its application in routine clinical practice can be recommended, especially if the conventional patch test result is presumably false negative.

A variant of the CXCL11 gene may influence susceptibility to contact allergy, particularly in polysensitized patients.

BACKGROUND: Hereditary factors may influence individual susceptibility to contact allergy. OBJECTIVES: To investigate genetic variants with impacts on early inflammatory reactions and T cell functions that possibly increase the risk of contact allergy. PATIENTS AND METHODS: Three hundred and seventy two patients undergoing patch testing were recruited from the Information Network of Departments of Dermatology (IVDK). Of these, 133 were monosensitized and 239 were polysensitized, defined as reacting to three or more unrelated sensitizers. Within the polysensitized individuals, a subgroup with at least one particularly strong patch test reaction (strong reactors; n = 194) was considered. Three hundred and forty-seven blood bank donors served as controls. Fifteen genetic variants in 13 genes were analysed. RESULTS: The homozygous variant CXCL11 AA genotype (rs6817952) was significantly more frequent among polysensitized patients (10 of 239 = 4.2%; p = 0.0048; odds ratio 7.49; 95%CI: 1.7-36.1) than among monosensitized patients (2.2%) and in the control group (0.6%). None of the remaining genetic variants investigated were characterized by similarly strong associations. However, the significance was lost after correction for multiple comparisons. CONCLUSIONS: The homozygous variant CXCL11 genotype is associated with an increased risk of contact allergy. To confirm this exploratory finding, further independent studies are needed.

Strip patch testing does not affect reaction profiles of standard allergens.

BACKGROUND: It has been hypothesized that positive reactions in the strip patch test are irritant rather than allergic. OBJECTIVE: To study reaction profiles of the baseline series patch test substances applied routinely on tape-stripped skin according to the reaction index (RI) and the positivity ratio (PR). PATIENTS AND METHODS: One thousand two hundred and twenty-eight consecutive patients were routinely strip patch tested with the baseline series between January 2011 and June 2013 (intervention group). On the basis of test reactions at D3/D4, the RI, and the PR, 25 standard allergens were analysed, and the results were compared with those obtained in 1161 patients patch tested conventionally from July 2008 to December 2010 (historical control group). RESULTS: Nickel sulfate, fragrance mix I, cobalt chloride, Myroxylon pereirae (balsam of Peru) and colophonium showed the highest frequencies of positive reactions in both groups, without any significant differences. Of 25 patch test substances of the baseline series, 18 showed good reaction profiles in the intervention group, and 16 in the historical control group. CONCLUSIONS: Reaction profiles of baseline series patch test substances remained largely unaffected by tape stripping the skin prior to patch testing. Thus, if conventional patch test results are presumed to be false-negative, performance of the strip patch test can be recommended independently of the standard allergen.

DKG statement on the use of metal alloy discs for patch testing in suspected intolerance to metal implants.

Intolerance reactions to metal implants may be caused by metal allergy. However, prior to implantation, 'prophetic'/prophylactic patch testing should not be performed. Pre-implant patch testing should only be done to verify or exclude metal allergy in patients with a corresponding history. In case of implant-related complications - in particular following replacement arthroplasty - such as pain, effusion, skin lesions, reduced range of motion or implant loosening, orthopedic causes should be ruled out first. Workup of suspected metal implant allergy should then be done using the DKG standard series, which includes nickel, cobalt, and chromium preparations. Various studies assessing the usefulness of metal alloy discs for patch testing have shown this particular approach to be ineffective with respect to providing reliable information on metal allergy. Any positive reaction in such tests cannot be assigned to a specific metal contained within the alloy. Furthermore, there is a risk of broad and indiscriminate use of these readily available discs. Accordingly, given the lack of additional benefit compared to patch testing with standardized metal salt preparations, we do not recommend patch testing with metal alloy discs.

Extensive hypertrophic scarring after toxic epidermal necrolysis in a child.

Stevens-Johnson syndrome and toxic epidermal necrolysis are some of the most serious, usually drug-induced, skin reactions. We report a case of severe toxic epidermal necrolysis in a child, which in addition to ophthalmic sequelae, caused extensive hypertrophic scarring of the skin. Such a course is uncommon and has rarely been described in the literature.