Efficacy and safety of crisaborole ointment, 2%, in participants aged ≥45 years with stasis dermatitis: Results from a fully decentralized, randomized, proof-of-concept phase 2a study.

BACKGROUND: Crisaborole ointment, 2%, is a nonsteroidal topical phosphodiesterase 4 inhibitor approved for the treatment of mild-to-moderate atopic dermatitis. OBJECTIVE: To evaluate the efficacy and safety of crisaborole in stasis dermatitis (SD). METHODS: In this randomized, double-blind, vehicle-controlled, decentralized phase 2a study (NCT04091087), 65 participants aged ≥45 years with SD without active ulceration received crisaborole or vehicle (1:1) twice-daily for 6 weeks. The primary end point was percentage change from baseline in total sign score at week 6 based on in-person assessment. RESULTS: Crisaborole-treated participants had significantly reduced total sign score from baseline versus vehicle based on in-person (nondermatologist) assessment (-32.4% vs -18.1%, P = .0299) and central reader (dermatologists) assessment of photographs (-52.5% vs -10.3%, P = .0004). Efficacy according to success and improvement per Investigator's Global Assessment score and lesional percentage body surface area reached statistical significance based on central reader but not in-person assessments. Skin and subcutaneous tissue disorders were common all-causality treatment-emergent adverse events with crisaborole. LIMITATIONS: Small sample size and short treatment duration were key limitations. In-person assessment was not conducted by dermatologists. CONCLUSION: Crisaborole improved signs and symptoms of SD and was well tolerated. Central reader assessment represents a promising approach for siteless clinical research.

Contact allergy to neomycin in consecutively patch tested Danish eczema patients from 2000 to 2023: A cross-sectional study.

BACKGROUND: Neomycin is an aminoglycoside antibiotic that may cause contact allergy. It was withdrawn as a medicine for human use in Denmark in October 2009 but is still found in some vaccines. OBJECTIVES: To identify time trends in contact allergy to neomycin in the period from 2000 to 2023. METHODS: A cross-section study of patients ≥18 years consecutively patch-tested with neomycin sulfate (20% in pet.) at Gentofte Hospital, Denmark, during the period 2000-2023 was conducted. RESULTS: The overall prevalence of contact allergy to neomycin was 1.4%. The prevalence was significantly lower in the period '2010-2023' (1.2%) than in '2000-2009' (1.8%) (p < 0.005). Contact allergy to neomycin was significantly positively associated with facial dermatitis and age >40 years, and significantly negatively associated with occupational dermatitis and hand dermatitis. No changes in sex, occupational dermatitis, atopic dermatitis, hand dermatitis, leg dermatitis, facial dermatitis, or age > 40/≤40 (the MOAHLFA-index) were identified when comparing neomycin contact allergic-patients in the two periods '2010-2023' and '2001-2009'. CONCLUSION: Neomycin is a rare cause of contact allergy in Denmark with a significantly lower prevalence following its withdrawal as a medicinal product for human use in Denmark in 2009.

Novel teprotumumab treatment of severe thyroid dermopathy; ototoxicity as an adverse side effect.

Pretibial myxedema, more generally thyroid dermopathy, results from mucopolysaccharide accumulation in the dermis, typically between the knee and dorsal foot. Thyroid dermopathy presents in Graves disease, but can occur in Hashimoto thyroiditis, primary hypothyroidism, and euthyroid patients. Treatment of thyroid eye disease with teprotumumab is established in the literature, with few case reports also showing improvement in pretibial myxedema. Reported is a 76-year-old man with thyroid eye disease and pretibial myxedema treated with teprotumumab; improvement was demonstrated in both conditions. He developed "muffled" hearing as an adverse effect, a complication not widely published in the dermatology literature. At 18 months post-treatment, his symptoms are stable without recurrence, but hypoacusis persists. Given the long-term efficacy and side-effects, dermatologists should recognize the potential benefits and risks of using teprotumumab for thyroid dermopathy. A baseline audiogram may be considered prior to therapy. Additionally, longitudinal data is needed to document the benefits and risks of this novel therapy.

Local immune microenvironment of skin may play an important role in the development of pretibial myxedema.

Pretibial myxedema (PTM), characterized by the accumulation of glycosaminoglycans in dermis is an autoimmune skin disorder, which is almost always associated with Graves' disease (GD). Although fibroblast stimulated by thyroid-stimulating hormone receptor (TSHR) antibody, cytokines and growth factors have been postulated as target of the autoimmune process in the dermopathy, the pathogenesis of PTM remains unclear. We hypothesize that the local immune microenvironment of the skin including the antigens and antibodies, T cells, B cells, plasma cells and fibroblasts may play an important role in the development of PTM. Results obtained on PTM patients indicate increased thyroid-stimulating hormone receptor antibodies (TRAb) in the blood positively correlate with the dermal thickness of the lesions. Further analysis shows that there were more CD3+ T cells and CD20+ B cells in the skin lesions. These T and B cells are in close contact, indicating that inducible skin-associated lymphoid tissue (iSALT) may be formed in the area. In addition, we found that the infiltrating plasma cells can secrete TRAb, proving that B cells in the skin other than the thyroid are an additional source of TSHR antibodies. Meanwhile, the T and B cells in the skin or skin homogenate of patients can promote the proliferation of pretibial fibroblasts. In conclusion, our results provide evidence that the local immune microenvironment of the skin may play an important role in the development of PTM.

Tofacitinib for the treatment of refractory pyoderma gangrenosum.

Pyoderma gangrenosum (PG) is a rare, debilitating, inflammatory skin disease associated with a variety of systemic diseases. Because of its rarity, PG is treated with miscellaneous immunosuppressive agents as there is no US Food and Drug Administration-approved standardized treatment approach. We present four patients with PG treated with tofacitinib in the context of the six existing cases in the literature. Tofacitinib appeared to be beneficial in the small sample of patients (n = 10) who failed an average of four other systemic therapies. The majority of patients had classic PG located on the legs (80%, 8/10), while 20% of cases (2/10) were peristomal. The most common comorbidity was inflammatory bowel disease (78%, 7/9). There were no negative treatment results and 40% (4/10) of patients had complete healing of their ulcers, while the other 60% (6/10) had marked clinical improvement. From our observation, tofacitinib appears to be a promising steroid-sparing adjuvant treatment in patients with refractory PG who have failed on other systemic therapies.

The chameleon rash: a review of the polyphenotypic dermatoses of dermatomyositis.

Dermatomyositis (DM) is an autoimmune connective tissue disease that is included in the idiopathic inflammatory myopathies. Cutaneous manifestations are a prominent part of the condition: some skin signs in DM are common to most patients, while other signs are encountered infrequently. A number of features are pathognomic for DM. The demonstration of myositis-specific antibodies (MSAs) in DM has extended the ability to define phenotypic subgroups. It appears that the presence of certain MSAs confers susceptibility to specific clinical features, an association which reveals a serotype-phenotype relationship. In this review article we have provided a detailed summary of common and under-recognized cutaneous manifestations of DM.

Frequency of sensitization to the individual fragrances of fragrance mix I and II according to the factors included in the MOAHLFA index.

BACKGROUND: Fragrances constitute the second most frequent cause of allergic contact dermatitis in Spain. OBJECTIVES: To determine the rate of sensitization to the individual fragrances of fragrance mix (FM) I and FM II for each of the demographic and clinical factors included in the MOAHLFA (male, occupational dermatitis, atopic dermatitis, hand dermatitis, leg dermatitis, facial dermatitis, age) index. METHODS: We conducted a 5-year retrospective study in 23 Spanish centres. We identified the patients who had undergone patch testing with a specific fragrance series after reacting positively to fragrance markers in a baseline series. We obtained the MOAHLFA index items in this population, then calculated for each demographic and clinical factor the frequencies of sensitization to the individual fragrances of FM I and FM II. RESULTS: A specific fragrance series was patch tested in 1013 patients. The most frequent allergens in men, women, children, and retired people were Evernia prunastri (16%), geraniol (16.6%), isoeugenol (17.9%), and geraniol (22.4%), respectively. Citral (20.5%) and hydroxyisohexyl 3-cyclohexene carboxaldehyde (HICC) (14.5%) were the most common allergens in occupational eczemas and were also associated with a large proportion of hand and facial dermatitis. CONCLUSIONS: Frequency of sensitization to the individual fragrances of FM I and FM II varies with age, sex, affected body region, and history of occupational or atopic dermatitis.

A negative breakdown test in a fragrance mix I-positive patient does not rule out contact allergy to its fragrance constituents.

BACKGROUND: In about half of the patients reacting positive to fragrance mix I (FM I), breakdown testing remains negative. This raises the question of whether the reaction to FM I is false-positive, or the breakdown test is false-negative. OBJECTIVES: To identify characteristics and sensitization patterns of patients positive to FM I, but not to its fragrance constituents. PATIENTS AND METHODS: Retrospective analysis of data from the Information Network of Departments of Dermatology (IVDK) between 2005 and 2019. Three patient groups were defined according to their reaction pattern: Group I, FM I positive and ≥1 single fragrance positive in the breakdown test (n = 1912); Group II, FM I positive and breakdown test negative (n = 1318); Group III, FM I negative (n = 19 790). RESULTS: Regarding the pattern of concomitant reactions to other fragrances, Group II had an intermediate position between Group I and Group III. In other respects (age and sex distribution, frequency of sensitization to non-fragrance baseline series allergens), Group II rather resembled Group I. CONCLUSIONS: Not every positive reaction to FM I in patients with negative breakdown tests is false-positive. There may be false-negative reactions to the single fragrance components when patch tested at 1% pet. Raising patch concentrations of some single fragrances is recommended.

The epidemic of contact allergy to methylisothiazolinone-An analysis of Danish consecutive patients patch tested between 2005 and 2019.

BACKGROUND: In 2005, methylisothiazolinone (MI) was allowed as a stand-alone preservative in cosmetics. This resulted in an epidemic of allergic contact dermatitis to MI, mainly affecting women exposed to leave-on cosmetics. Consequently, a regulation of Annex V in the European Union in 2017 banned the use of MI in leave-on cosmetics and reduced the allowed concentration in rinse-off products. OBJECTIVE: To analyze the temporal trends in contact allergy to MI in Danish patients in relation to key events including European regulations over time. METHODS: A retrospective study of consecutive patients patch tested with methylisothiazolinone from 2005 to 2019. Demographics and clinical characteristics in terms of MOAHLFA (male, occupational, atopic dermatitis, hand dermatitis, leg dermatitis, facial dermatitis and age >40 years), sources of exposure, and clinical relevance were analyzed in relation to key historical events. RESULTS: Three hundred eighty of 12 494 patients (3.0%, 95CI: 2.7-3.4%) tested from 2005 to 2019 were sensitized to MI. An increasing trend in the prevalence of MI contact allergy from 2005 to 2019 (P < .01) was observed, although a decline in the absolute number of patch-test positive patients was seen from 2013 and onward. A reduction in leave-on cosmetics as a source of exposure was observed following the legislative ban in 2017, from 24.8% from in 2010 to 2013 to 6.2% in 2017 to 2019 (P < .01). CONCLUSION: The epidemic of MI contact allergy is declining in absolute terms, although the prevalence in the patch-tested population has not returned to its pre-epidemic levels. The legislative regulation of MI in 2017 has been effective in terms of leave-on cosmetics as a source of exposure in MI allergic patients. The process of post-marketing risk assessment of contact allergens in the European Union needs improvement.

Occupational contact dermatitis in Triveneto: Analysis of patch test data of the North Eastern Italian Database from 1996 to 2016.

BACKGROUND: Occupational contact dermatitis (OCD) is frequent in the workplace. OBJECTIVES: To provide recent data on the epidemiology of OCD in Italy. METHODS: This multicenter retrospective study, conducted from 1996 to 2016, included patients with suspected allergic contact dermatitis (ACD) patch tested in the departments comprising the North-East Italy Contact Dermatitis Group. RESULTS: We studied 18 859 workers with a diagnosis of contact dermatitis (CD), of which 10.4% were recognized as being of professional origin. OCD declined from 1996 to 2011-2013 and increased in 2014-2016. The overall prevalence of both CD and OCD was higher in women compared to men, but the share of OCD of the total CD was greater for men compared to women. A history of atopic dermatitis was less frequent in workers with OCD than in non-OCD patients (5.8% vs 8.6%). Hairdressers were the youngest profession (27.1 ± 11.7 years). Hands were the primary site of involvement in patients with OCD (76.6%). The five highest risk occupations for OCD were hairdressers, cooks, metalworkers, chemical industry workers, and construction workers. CONCLUSIONS: OCDs have a relevant impact in our region, mainly for five job categories, and the increase in the last 3 years suggests the need to improve preventive measures.

Lower limb cellulitis: low diagnostic accuracy and underdiagnosis of risk factors.

Accurate diagnosis and recognition of predisposing factors has been shown to be challenging in lower limb cellulitis (LLC). Assessment of 1746 consecutive patients with cellulitis presenting to a UK university hospital showed increasing overdiagnosis, with only 31.9% of patients referred during the period 2015-2018 having the diagnosis of LLC confirmed. Recognition of at least one predisposing factor increased from 61% to 89% following introduction of more specific screening questions. This identified a need for better primary care dermatology education and the benefit of a proforma with specific screening questions for reversible predisposing factors for LLC.

Distribution of atopic dermatitis lesions in United States adults.

BACKGROUND: The distribution of atopic dermatitis (AD) lesions and its impact on quality of life (QOL) is not well established in the US adult population. OBJECTIVE: To elucidate the distribution of AD lesions and its impact on QOL in US adults with AD. METHODS: A cross-sectional, population-based study of 602 adults was performed. AD was determined using modified UK Diagnostic Criteria, and its lesional distribution was assessed. QOL was assessed using Dermatology Life Quality Index (DLQI). Latent class analysis (LCA) was used to determine distinct phenotypes of AD lesional distribution. Multivariable logistic regression was used to determine the relationship between DLQI and distinct phenotypes. RESULTS: The most common sites of skin lesions were reported to be the popliteal fossae, lower legs, dorsal feet and antecubital fossae. Most persons reported partial (19.0%) or complete (63.0%) symmetry of lesions on the extremities. Lesions on the trunk were significantly more common in blacks and Hispanics. Age ≥ 60 years was associated with significantly lower proportions of active lesions on the face and scalp, and significantly higher proportion of lesions on the buttocks or genitals. LCA identified 5 classes of lesional distribution: 1. lower probabilities of lesions affecting any sites; 2. Higher probability of lesions involving the anterior and posterior neck and trunk; 3. lesions involving the antecubital fossae and upper extremities; 4. lesions involving the arms, posterior hands, genitals and buttocks, and to a lesser extent face, palms and legs; 5. lesions affecting all sites. Class-2 (multivariable logistic regression; adjusted odds ratio [95% confidence interval]: 7.19 [3.21-16.07], class-3 (7.11 [3.20-15.80]), class-4 (6.90 [3.07-15.50]) and class-5 (7.92 [3.54-17.71]) were all significantly associated with higher DLQI scores compared to class 1. CONCLUSION: AD is associated with heterogeneous distribution of AD lesions, and distinct phenotypes that are associated with QOL impact.

Erosive Pustular Dermatosis of the Leg Successfully Treated With an Oral Retinoid and a Bi-layered Skin Substitute

Erosive pustular dermatosis is a rare inflammatory skin disorder characterized by crusted erosions, sterile pustules, skin atrophy, and scarring alopecia. Cases of involvement of lower extremities, with or without scalp lesions, have been scarcely reported in the literature, and have been denominated Erosive Pustular Dermatosis of the Legs. The disorder usually affects elderly patients associated with chronic venous insufficiency and venous dermatitis. Topical corticosteroids and topical calcineurin inhibitors have been reported to be effective. On the other hand, several treatments have also failed to achieve appropriate results; hence we present a case of erosive pustular dermatosis of the leg, who was unresponsive to compression and antibacterial ointments, but successfully treated systemically with an oral retinoid and locally with the application of a bioengineered bi-layered skin substitute. This condition may be overlooked, which represents its low prevalence in literature. J Drugs Dermatol. 2019;18(3):301-302.

European Surveillance System on Contact Allergies (ESSCA): Contact allergies in relation to body sites in patients with allergic contact dermatitis.

BACKGROUND: Analyses of the European Surveillance System on Contact Allergies (ESSCA) database have focused primarily on the prevalence of contact allergies to the European baseline series, both overall and in subgroups of patients. However, affected body sites have hitherto not been addressed. OBJECTIVE: To determine the prevalence of contact allergies for distinct body sites in patients with allergic contact dermatitis (ACD). METHODS: Analysis of data collected by the ESSCA (www.essca-dc.org) in consecutively patch tested patients, from 2009 to 2014, in eight European countries was performed. Cases were selected on the basis of the presence of minimally one positive patch test reaction to the baseline series, and a final diagnosis of ACD attributed to only one body site. RESULTS: Six thousand two hundred and fifty-five cases were analysed. The head and hand were the most common single sites that ACD was attributed to. Differences between countries were seen for several body sites. Nickel, fragrance mix I, cobalt and methylchloroisothiazolinone/methylisothiazolinone were the most frequent allergens reported for various body sites. CONCLUSIONS: Distinct allergen patterns per body site were observed. However, contact allergies were probably not always relevant for the dermatitis that patients presented with. The possibility of linking positive patch test reactions to relevance, along with affected body sites, should be a useful addition to patch test documentation systems.

The preservative 2-(thiocyanomethylthio)benzothiazole: A potential allergen in leather products.

BACKGROUND: Allergic contact dermatitis caused by leather is common, and several responsible allergens, such as tanning agents, glues, mercaptobenzothiazole derivatives, and dyes, but also antimicrobials and antifungals, are involved. MATERIAL AND METHODS: Three female patients were referred to the Departments of Dermatology in a Belgian university hospital following skin reactions caused by leather products (shoes, belt, and car seats). They were patch tested with the European baseline series and samples of suspected leather products, and additionally with 2-(thiocyanomethylthio)benzothiazole (TCMTB), an antifungal agent previously reported to be a contact allergen in footwear. Chromatographic analyses of samples of all the leather materials tested were performed at the Department of Occupational and Environmental Dermatology in Malmö, Sweden. RESULTS: The patients reacting to the leather samples were shown to be sensitized to TCMTB, the presence of which could be confirmed by chemical analyses of samples obtained from the patients. CONCLUSION: Patch tests with TCMTB should be considered in patients with contact dermatitis caused by leather items.

Contact dermatitis and sensitization in professional musicians.

BACKGROUND: Professional musicians have prolonged and intense physical contact with their instruments. This can lead to occupational skin diseases, particularly irritant and allergic contact dermatitis. OBJECTIVES: To assess the skin diseases and sensitization patterns common among professional musicians. METHODS: A retrospective analysis of the data of the Information Network of Departments of Dermatology (IVDK) was performed, including data from 1997 to 2017. RESULTS: We identified 236 professional musicians. In this group, male sex (58.6%) and younger age (60.6% aged < 40 years) were common. The musicians suffered more frequently from facial dermatitis (23.7% vs 15.7%) and less often from leg dermatitis (5.1% vs 10.7%) than the control group (the non-musicians in the IVDK database). The most frequent diagnoses were allergic contact dermatitis, atopic dermatitis, and irritant contact dermatitis. The sensitization profile of the professional musicians was similar to that of the control group. In 8.9% of cases, an occupational background of skin disease was confirmed. CONCLUSIONS: Severe occupational skin diseases among professional musicians are not as common as in classic "skin-damaging" professions. However, as these skin conditions can mostly be controlled with simple preventive measures, we recommend that this group should be patch tested and treated by a specialist.

Sensitization to fragrances in Spain: A 5-year multicentre study (2011-2015).

BACKGROUND: Fragrance chemicals constitute the second most frequent cause of contact allergy in Spain. There are no data available concerning the individual fragrances that are most frequently involved. OBJECTIVES: To describe the diagnostic contribution provided by specific fragrance series to the results obtained with baseline series fragrance markers by correlating the results of both series. MATERIALS AND METHODS: We performed a 5-year retrospective study of fragrance marker-positive patients tested with specific fragrance series in 23 Spanish centres. We collected the demographic and clinical characteristics, and compared the results of patch tests obtained from different suppliers. RESULTS: Of 19 588 patients patch tested with the Spanish baseline series, 1590 (8.1%) reacted positively to a fragrance marker. Of these, 1013 (63.7%) were patch tested with a fragrance series, and 664 patients reacted positively to at least one individual fragrance other than hydroxyisohexyl 3-cyclohexene carboxaldehyde. Geraniol was the most frequent allergen. Positive reactions to substances not included in fragrance mix (FM) I or FM II were found in 230 patients. Of the 436 FM I-positive patients and the 419 FM II-positive patients, 184 (42%) and 64 (39.1%), respectively, had no positive reactions to fragrance series. In the case of FM I, negative results were more common when individual fragrances were patch tested at low concentrations. CONCLUSIONS: We recommend patch testing all patients positive for any fragrance marker with a specific fragrance series. The correlation between the results of baseline series and fragrance series could be improved by increasing the concentrations of individual fragrances.

Linear amyopathic dermatomyositis with calcinosis cutis responsive to topical sodium thiosulfate.

A case of a 15-year-old male patient with a 3-year history of linear, segmental amyopathic dermatomyositis with calcinosis cutis is presented. The calcinosis was recalcitrant to treatment with topical steroids and hydroxychloroquine. Topical 10% sodium thiosulfate use for 8 weeks resulted in improvement. The use of topical sodium thiosulfate for patients in whom surgical extraction is not an option is detailed.

Linear morphea overlying site of previous lichen aureus in a pediatric patient.

Lichen aureus is a pigmented purpuric dermatosis that tends to occur on the lower extremities, and linear morphea is an inflammatory disease of the dermis and subcutaneous fat that leads to a scarlike induration. We present a pediatric case of linear morphea developing in the same anatomic distribution as prior lichen aureus. Due to the possible progression of lichen aureus to morphea described herein and the difficulty in diagnosing early morphea, close follow-up may be considered for pediatric patients who present with this pigmented purpuric dermatosis.