Neutrophilic Panniculitides.

Neutrophilic panniculitides are a heterogeneous group of inflammatory disorders encompassing many different entities. This review article focuses on the epidemiology, pathogenesis, clinicopathological features, diagnosis, and treatment of selected diseases. Patients often seek care due to systemic involvement, but the variable presentation of panniculitides can present a diagnostic challenge. Most therapeutic modalities for neutrophilic disorders are anecdotal at best with a notable lack of standardization of the responses to medications. There is an urgent need for a larger multi-institutional collaboration to address the unmet needs of these challenging, yet rare conditions.

Pediatric Patch Testing at Mayo Clinic Between 2016 and 2020.

Background: Allergic contact dermatitis (ACD) is a common condition within the pediatric population. Patch testing is an important way to identify relevant allergens. Objective: To provide an update of the common contact allergens seen in children based on patch testing data at our institution from 2016 to 2020. Methods: We performed a retrospective analysis of patch test data from children aged 1-18 years from 2016 to 2020 at Mayo Clinic. Reaction rates were compared to the rates reported by the Pediatric Contact Dermatitis Registry (PCDR). Results: One hundred ninety-two children aged 1-18 were patch tested to various allergens. A total of 15,457 allergens were tested, with 291 positive tests. The top 5 allergens with highest positive reaction rates were hydroperoxides of linalool, hydroperoxides of limonene, methylisothiazolinone, nickel, and cobalt. Seven of the top 38 allergens with the highest reaction rates are not currently included in the Mayo Clinic Pediatric Patch Test Series, and 11 are not currently included in the Pediatric Baseline Series (as developed by the Pediatric Contact Dermatitis Workgroup). Conclusions: Patch testing is a useful tool to diagnose children with ACD. With new products and exposures, there is an opportunity to expand current pediatric patch testing series.

Results of Patch Testing to Botanicals: Review of the Mayo Clinic Experience Over 2 Decades (1997-2017).

Background: Botanicals are increasingly incorporated into skincare products. Although allergic contact dermatitis due to botanicals is recognized, data describing the prevalence of positive patch tests to botanicals are sparse. Objective: To report the Mayo Clinic experience of patch testing to selected botanical products in the standard, extended standard, fragrance, and plant series. Methods: IRB-approved retrospective study of the Mayo Clinic experience with patch testing to botanicals from 1997 to 2017. Results: In total, 12,169 people were patch tested to botanicals in the standard, extended standard, fragrance, and plant series; 4032 were men and 8137 were women. The mean age of the population tested was 54 (standard deviation 17.7) years. Almost 11% (1320/12,169) of the patch-tested population exhibited positive reactions to at least 1 botanical agent. Myroxylon pereirae resin 25% was the most common positive allergen in the series. Patients who had positive reactions to at least 1 botanical agent were more (19.8%) likely to have a positive reaction to at least 1 additional botanical than those patients who did not have any positive tests. Most patients presented with generalized involvement (334) or involvement of the hands (284) or face (232). Conclusion: Physicians should be aware of the high prevalence of allergic contact dermatitis and patch test positivity associated with botanical products.

Systematic Identification of Copositivity Groups in Standard Series Patch Testing Through Hierarchical Clustering.

Importance: Patients are frequently copositive for multiple allergens simultaneously, either due to chemical similarity or simultaneous sensitization. A better understanding of copositivity groups would help guide contact avoidance. Objective: To use patient data to systematically determine copositivity groups in the Mayo Clinic Standard Series. Design, Setting, and Participants: In this retrospective cross-sectional analysis, the Mayo Clinic patch test database was queried for pairwise copositivity rates in the 80 allergen Mayo Clinic Standard Series between 2012 and 2021. Data were collected from 3 tertiary care sites of the Mayo Clinic Contact Dermatitis Group and a total of 5943 patients were included, comprising all patients undergoing patch testing to the Mayo Clinic Standard Series allergens. Main Outcomes and Measures: Copositivity rates between every 2 allergens in the 80-allergen Mayo Clinic Standard Series were estimated. After background correction, copositivity rates were analyzed using unsupervised hierarchical clustering to systematically identify copositivity groups in an unbiased manner. Results: Overall, 394 921 total patches were applied to 5943 patients (4164 [70.1%] women, 1776 [29.9%] men, with a mean [SD] age of 52.3 [18.8] years ), comprising 9545 positive reactions. After background correction based on overall positivity rates, hierarchical clustering revealed distinct copositivity groups. Many were supported by prior literature, including formaldehyde releasers, cobalt-nickel-potassium dichromate, acrylates, 3-dimethylaminopropylamine-amidoamine-oleamidopropyl dimethylamine, alkyl glucosides, budesonide-hydrocortisone-17-butyrate, certain fragrances, compositae-sesquiterpene lactone mix, mercapto mix-mercaptobenzothiazole, carba mix-thiuram mix, and disperse orange-p-phenylenediamine. However, novel associations were also found, including glutaraldehyde-sorbitan sesquioleate, benzalkonium chloride-neomycin-bacitracin, bronopol-methylchloroisothiazolinone-methylisothiazolinone, and benzoic acid-iodopropynyl butylcarbamate. Conclusions and Relevance: This retrospective cross-sectional analysis found that copositivity rates varied between allergens; allergens with extremely high positivity rates demonstrated nonspecific copositivity to multiple other allergens. Background correction based on positivity rates followed by hierarchical clustering confirmed prior known copositivity groups, contaminants and/or excipients leading to copositivity, and novel associations to guide contact avoidance.

Differential proteomic expression profiles in vulvar lichen planus as compared to normal vulvar tissue, vulvar lichen sclerosus, or oral lichen planus: An exploratory study.

Vulvar lichen planus (VLP) is a chronic inflammatory disease which adversely affects patients' quality of life. The pathogenesis of VLP is unknown although Th1 immune response has been implicated. We aimed to discover specific tissue-based protein biomarkers in VLP compared to normal vulvar tissue (NVT), vulvar lichen sclerosus (VLS) and oral lichen planus (OLP). We used laser capture microdissection-liquid chromatography- tandem mass spectrometry to assess protein expression in fixed lesional mucosal specimens from patients with VLP (n = 5). We then compared proteomic profiles against those of NVT (n = 4), VLS (n = 5), OLP (n = 6) and normal oral mucosa (n = 5), previously published by our group. IL16, PTPRC, PTPRCAP, TAP1 and ITGB2 and were significantly overexpressed in VLP compared to NVT. Ingenuity pathway analysis identified antigen presentation and integrin signalling pathways. Proteins overexpressed in both VLP versus NVT and OLP versus NOM included IL16, PTPRC, PTPRCAP, TAP1, HLA-DPB1, HLA-B and HLA-DRA. This proteomic analysis revealed several overexpressed proteins in VLP that relate to Th1 autoimmunity, including IL16. Overlapping pathways, including those involving IFNγ and Th1 signalling, were observed between VLP, VLS, and OLP.

Trends in Patch Testing With the Mayo Clinic Standard Series, 2017-2021.

Background: Patch testing to a standard series is used to identify culprit allergens in patients with contact dermatitis. The reaction rates evolve over time based on trends in cutaneous exposures by the general population. Objective: The aim of this study was to analyze the patch test results of the Mayo Clinic standard series in patients tested from 2017 to 2021. Methods: The patch test reactions of standard series allergens tested from 2017 to 2021 were retrospectively reviewed and compared with the results of our prior report from 2011 to 2015 as well as the North American Contact Dermatitis Group (NACDG) report from 2017 to 2018. Results: Of 2667 patients tested, 1683 (63.1%) had at least 1 positive reaction. The 15 allergens with the highest reaction rates were hydroperoxides of linalool 1%, nickel (II) sulfate hexahydrate, methylisothiazolinone, Myroxylon pereirae resin, hydroperoxides of linalool 0.5%, methyldibromo glutaronitrile, neomycin sulfate, cobalt (II) chloride hexahydrate, fragrance mix I, benzalkonium chloride, bacitracin, hydroperoxides of limonene, methylchloroisothiazolinone/methylisothiazolinone, p-phenylenediamine, and textile dye mix. Twelve (80%) of these allergens were also in the top 15 of the most recent NACDG report. Conclusions: Hydroperoxides of linalool and hydroperoxides of limonene are new allergens that have been added to our standard series. These are associated with high reaction rates.

Development of a Skin-Directed Scoring System for Stevens-Johnson Syndrome and Epidermal Necrolysis: A Delphi Consensus Exercise.

Importance: Scoring systems for Stevens-Johnson syndrome and epidermal necrolysis (EN) only estimate patient prognosis and are weighted toward comorbidities and systemic features; morphologic terminology for EN lesions is inconsistent. Objectives: To establish consensus among expert dermatologists on EN terminology, morphologic progression, and most-affected sites, and to build a framework for developing a skin-directed scoring system for EN. Evidence Review: A Delphi consensus using the RAND/UCLA appropriateness criteria was initiated with a core group from the Society of Dermatology Hospitalists to establish agreement on the optimal design for an EN cutaneous scoring instrument, terminology, morphologic traits, and sites of involvement. Findings: In round 1, the 54 participating dermatology hospitalists reached consensus on all 49 statements (30 appropriate, 3 inappropriate, 16 uncertain). In round 2, they agreed on another 15 statements (8 appropriate, 7 uncertain). There was consistent agreement on the need for a skin-specific instrument; on the most-often affected skin sites (head and neck, chest, upper back, ocular mucosa, oral mucosa); and that blanching erythema, dusky erythema, targetoid erythema, vesicles/bullae, desquamation, and erosions comprise the morphologic traits of EN and can be consistently differentiated. Conclusions and Relevance: This consensus exercise confirmed the need for an EN skin-directed scoring system, nomenclature, and differentiation of specific morphologic traits, and identified the sites most affected. It also established a baseline consensus for a standardized EN instrument with consistent terminology.

Trends in Patch Testing of Black Patients: The Mayo Clinic Decade Experience (January 1, 2011, to December 31, 2020).

Background: Trends in patch testing for allergic contact dermatitis (ACD) have not been well characterized in Black patients. Despite similar incidence of ACD in Black and White patients, there are differences in allergen profiles. Understanding patch testing trends in Black patients furthers knowledge that has considerable impact on the management of ACD in the Black population. Objective: The purpose of this study was to review the results of patch testing in Black patients at Mayo Clinic over a decade. Methods: We retrospectively reviewed the results of patch testing to the standard, extended standard, or hairdresser series in 149 Black patients seen at Mayo Clinic (Rochester, MN; Scottsdale, AZ; and Jacksonville, FL) from January 1, 2011, to December 31, 2020. Results: During the 10-year period, 149 Black patients (mean age, 49.2 years [SD, 17.1 years]; female 67.1%) were patch tested at Mayo Clinic to the standard, extended standard, or hairdresser series. Most common sites of dermatitis were generalized (30.9%), hands (18.8%), leg (16.8%), trunk (16.1%), and arm (14.8%). Overall, 109 patients (73.2%) had at least 1 positive reaction and 74 patients (50%) had 2 or more positive reactions. Overall, the 10 allergens with the highest reaction rates (from highest to lowest) identified in our study population were 4-amino-2-hyroxytoluene (33.3%), thimerosal (20.4%), nickel sulfate (18.9%), methylisothiazolinone (16.5%), methyldibromo glutaronitrile (13.4%), methyldibromo glutaronitrile/phenoxyethanol (12.5%), captan (12.5%), carmine (12.5%), methylchloroisothiazolinone/methylisothiazolinone (11.5%), and hydroperoxide of linalool 1% (11.3%). Conclusions: We describe patch test results in Black patients over a decade at Mayo Clinic. The top 10 allergens were preservatives, hair dyes, and fragrances. Differing patterns of allergens may occur in Black patients due to different patterns of exposures related to cultural practices.

Long-term risk of death in patients with hidradenitis suppurativa.

BACKGROUND: Hidradenitis suppurativa (HS) is associated with substantial morbidity. Few studies have addressed the natural history and mortality rates associated with HS. A higher risk of cardiovascular death in patients with HS has been reported. We investigated whether patients with HS have an increased overall risk of death compared with age- and gender-matched referents. METHODS: We performed a retrospective cohort study of residents of Olmsted County, Minnesota, with incident HS between January 1, 1980, and December 31, 2008, and age- and gender-matched referents. The main outcomes and measures were the overall and cause-specific risks of death. RESULTS: We identified 226 incident cases of HS and 678 age- and gender-matched referents among Olmsted County residents during the study period. Compared to referents, patients with HS had a significantly higher risk of all-cause death (hazard ratio [HR, 2.48; 95% CI, 1.53-4.03, P < 0.001) and cardiovascular- or cerebrovascular-related death (HR, 2.85; 95% CI, 1.10-7.40, P = 0.03). However, these risks were attenuated by adjusting for smoking history: all-cause HR, 1.65 (95% CI, 0.97-2.82, P = 0.07) and cardiovascular- or cerebrovascular-related HR, 2.03 (95% CI, 0.71-5.81, P = 0.18). The 71% of patients were former or current smokers at the time of HS diagnosis. CONCLUSIONS: Hidradenitis suppurativa patients have a substantially increased risk of death from any cause, including cardiovascular or cerebrovascular causes; the risk is especially dependent on smoking history.

Characteristics of ulcerated and non-ulcerated necrobiosis lipoidica.

BACKGROUND: Necrobiosis lipoidica (NL) is complicated by ulceration in up to 35% of cases. METHODS: Retrospective study of patients with NL seen at our institution between January 1, 1992, and May 25, 2021, was conducted. Ulcerated NL (UNL, n = 83) and non-ulcerated NL (NUNL, n = 233) groups were compared. RESULTS: Twenty-six percent (83/316) of patients with NL experienced ulceration. UNL was significantly more likely to be painful (52% vs. 36%, P = 0.01), was more likely to have a lesion-associated cutaneous malignancy (7% vs. 0%, P < 0.001), and had a larger median size (7 vs. 5 cm, P = 0.004) compared to NUNL. Vascular studies were performed on a subset of patients and revealed transcutaneous oxygen pressure (TcPO2) < 40 mm Hg in 53% and venous insufficiency in 62% with no significant differences between UNL and NUNL groups. In patients with unilateral ulceration, mean TcPO2 values (39.7 vs. 46.6 mm Hg), regional perfusion index <0.6 (29% vs. 14%), and TcPO2 < 40 mm Hg (43% vs. 14%) were worse in the ulcerated leg compared to the non-ulcerated leg, but these differences were not statistically significant. CONCLUSIONS: UNL was more likely to be painful, develop lesion-associated malignancy, and be larger in size compared to NUNL. There were no statistically significant differences in venous insufficiency, arterial Doppler/ankle brachial index, or TcPO2 values between UNL and NUNL patients, however, a significant portion of the cohort demonstrated abnormal vascular studies, particularly on TcPO2 and venous insufficiency testing.

Erythromelalgia: A Review of Medical Management Options and Our Approach to Management.

Erythromelalgia (EM) is a rare disorder characterized by episodic, burning pain associated with erythema and warmth of the extremities. The feet and hands are most commonly affected. The pain can be so severe that patients may engage in behaviors, sometimes extreme, to cool the affected areas and change their lifestyle to avoid precipitating factors, such as exercise and increased ambient heat. A literature search was performed with PubMed and MEDLINE with the search term erythromelalgia. Inclusion criteria were studies on EM published after 1985 until January 1, 2022, in the English language and studies that provided information on medical treatment of EM. Studies were excluded if they were duplicates or did not include treatment data. No guidelines exist for the treatment of this complex disorder. Lifestyle modifications and pharmacologic treatments (topical and systemic) are discussed in this article, which provides a comprehensive review of published medical management options for erythromelalgia and a proposed approach to management.

Reevaluating Corticosteroid Classification Models in Patient Patch Testing.

Importance: Individuals with allergic contact dermatitis to one topical corticosteroid may also react to other corticosteroids. Corticosteroid classification models have been proposed to predict such copositivity, recommend representative screening corticosteroids, and guide allergen avoidance. Objective: To use patient data to determine copositivity patterns between corticosteroids and evaluate against previous corticosteroid classification models. Design, Setting, and Participants: This qualitative study included a retrospective analysis of the Mayo Clinic Contact Dermatitis Group corticosteroid patch test data from 2010 to 2019. Among patients undergoing patch testing with the Mayo Clinic's standard or steroid series who consented to research participation, 5637 patients were included in the analysis. Copositivity rates were determined between corticosteroids and analyzed by hierarchical clustering for comparison to previous classification models. Main Outcomes and Measures: The frequency of patch test positivity to each of the analyzed corticosteroids was noted and compared with previously published patch test positivity rates. Copositivity rates between each pair of corticosteroids were determined, and overall copositivity patterns were analyzed and evaluated against known steroid classes. Results: A total of 49 472 individual patches were applied to 5637 patients, testing 18 corticosteroids. Patch test positivity rates ranged between 0.3% and 4.7%. The fluocinonide positivity rate corresponded to the highest copositivity rate with other corticosteroids (mean [SD], 50.7% [26.1%]). Tixocortol-21-pivalate, 0.1%, and tixocortol-21-pivalate, 1%, positivity rates corresponded to the lowest copositivity rates (mean [SD], 4.1% [1.7%] and 3.6% [1.4%], respectively). Hierarchical clustering elucidated patterns that did not support previous corticosteroid classification models. Conclusions and Relevance: In this qualitative study, copositivity rates were variable between corticosteroids, and overall patch test positivity for allergy to topical corticosteroids was rare. Previously published corticosteroid classifications are not supported by real patient-derived data and may not be accurate in predicting corticosteroid copositivity.

Differential proteomic expression in indolent vulvar lichen sclerosus, transforming vulvar lichen sclerosus and normal vulvar tissue.

Vulvar lichen sclerosus (VLS) confers approximately 3% risk of malignant transformation to vulvar squamous cell carcinoma (VSCC). We used unbiased proteomic methods to identify differentially expressed proteins in tissue of patients with VLS who developed VSCC compared to those who did not. We used laser capture microdissection- and nanoLC-tandem mass spectrometry to assess protein expression in individuals in normal vulvar tissue (NVT, n = 4), indolent VLS (no VSCC after at least 5 years follow-up, n = 5) or transforming VSCC (preceding VSCC, n = 5). Interferon-γ and antigen-presenting pathways are overexpressed in indolent and transforming VLS compared to NVT. There was differential expression of malignancy-related proteins in transforming VLS compared to indolent VLS (CAV1 overexpression, AKAP12 underexpression), particularly in the EIF2 translation pathway, which has been previously implicated in carcinogenesis. Results of this study provide additional molecular evidence supporting the concept that VLS is a risk factor for VSCC and highlights possible future biomarkers and/or therapeutic targets.

Suggestions for a New Clinical Classification Approach to Panniculitis Based on a Mayo Clinic Experience of 207 Cases.

BACKGROUND: Panniculitis, or inflammation of adipose tissue, includes a heterogeneous group of disorders with similar morphologic presentations. Currently, panniculitides are classified based on histopathologic findings only. OBJECTIVE: In this retrospective study of 207 cases of biopsy-proven panniculitis over 20 years at Mayo Clinic, we aimed to propose a new classification that integrates the clinical morphologic features with the histopathology of panniculitis. METHODS: We collected patient demographic and lesion morphologic characteristics using lesion photographs and physician notes for each of our 207 cases, including location, ulceration, scale, pattern (unilateral versus circumferential), atrophy/sclerosis (cicatricial), redness, and swelling. RESULTS: The panniculitides most likely to ulcerate were calciphylaxis (85.7% ulcerating), pancreatic panniculitis (66.6%), and α1-antitrypsin deficiency-associated panniculitis (100%). The panniculitides least likely to ulcerate were erythema nodosum and medication-induced and granulomatous panniculitis. This retrospective study used only descriptions in clinical notes and available medical photographs. CONCLUSION: We present an updated classification schema of panniculitides based on clinical findings. The primary distinctions are based on ulceration, location, and number of lesions. Although complete distinction of all panniculitides based on clinical examination alone is not possible, we hope the proposed schema allows clinicians to tailor differential diagnoses.

Deep learning for dermatologists: Part II. Current applications.

Because of a convergence of the availability of large data sets, graphics-specific computer hardware, and important theoretical advancements, artificial intelligence has recently contributed to dramatic progress in medicine. One type of artificial intelligence known as deep learning has been particularly impactful for medical image analysis. Deep learning applications have shown promising results in dermatology and other specialties, including radiology, cardiology, and ophthalmology. The modern clinician will benefit from an understanding of the basic features of deep learning to effectively use new applications and to better gauge their utility and limitations. In this second article of a 2-part series, we review the existing and emerging clinical applications of deep learning in dermatology and discuss future opportunities and limitations. Part 1 of this series offered an introduction to the basic concepts of deep learning to facilitate effective communication between clinicians and technical experts.

Deep learning for dermatologists: Part I. Fundamental concepts.

Artificial intelligence is generating substantial interest in the field of medicine. One form of artificial intelligence, deep learning, has led to rapid advances in automated image analysis. In 2017, an algorithm demonstrated the ability to diagnose certain skin cancers from clinical photographs with the accuracy of an expert dermatologist. Subsequently, deep learning has been applied to a range of dermatology applications. Although experts will never be replaced by artificial intelligence, it will certainly affect the specialty of dermatology. In this first article of a 2-part series, the basic concepts of deep learning will be reviewed with the goal of laying the groundwork for effective communication between clinicians and technical colleagues. In part 2 of the series, the clinical applications of deep learning in dermatology will be reviewed and limitations and opportunities will be considered.

Incidence, prevalence, and predictors of inflammatory arthritis in patients with hidradenitis suppurativa: a systematic review and meta-analysis.

An increasing amount of evidence has emerged suggesting that hidradenitis suppurativa (HS) is associated with inflammatory arthritis. This study reviewed the incidence, prevalence, and predictors of inflammatory arthritis in patients with HS. A comprehensive literature search was conducted in CINAHL, Embase, and Medline from inception to February 14, 2020. Articles were included in the review if they provided data on disease epidemiology or predictors of adult or pediatric HS patients with comorbid inflammatory arthritis. There are no validated diagnostic criteria for HS, thus we considered patients as having HS if they had at least one diagnostic code in a hospital or claims database or a diagnosis of HS/inflammatory arthritis in a medical record. The same criteria were used to confirm presence of inflammatory arthritis. We identified an increased incidence of rheumatoid arthritis (RA), ankylosing spondylitis (AS), and psoriatic arthritis (PsA) in HS patients when compared with estimates in the general population. We identified a relatively high prevalence of RA, spondyloarthritis (SpA), and PsA in HS patients when compared with estimates in the general population. There was evidence to suggest that patients who are younger than 30, male, have severe HS, or are taking infliximab or adalimumab (which may also be confounded by HS disease severity) may be at greater risk for specific subtypes of inflammatory arthritis. However, further data are needed to confirm these associations. The increased incidence and prevalence of inflammatory arthritis within HS patients underscore the need for increased awareness and interdisciplinary partnership within rheumatology and dermatology.

Cutaneous Manifestations of Diabetes.

Diabetes mellitus is a significant worldwide health concern and cutaneous manifestations are common. This review describes characteristic skin findings of diabetes, general skin findings related to diabetes, and findings related to diabetes treatment with a focus on clinical presentation, diagnosis, pathophysiology, epidemiology, and treatment. As the prevalence of diabetes continues to rise, cutaneous manifestations of diabetes mellitus likely will be encountered more frequently by physicians in all disciplines including dermatologists and primary care physicians. Accordingly, knowledge regarding the prevention, diagnosis, and management of cutaneous manifestations is an important aspect in the care of patients with diabetes.