Cost-effectiveness of patch testing allergens within the same group - a computational approach to optimize formaldehyde-related allergen selection.

BACKGROUND: Patch testing to multiple cross reactive allergens for allergic contact dermatitis (ACD) may not be necessary due to copositivity. OBJECTIVE: We evaluated the formaldehyde group allergens to determine the optimal, most cost-effective allergens to test. METHODS: A retrospective analysis of Mayo Clinic (1997-2022) examined the well-established copositive formaldehyde group: Formaldehyde, Quaternium 15, Hexahydro-1,3,5-tris(2-hydroxyethyl)triazine, Diazolidinyl urea, Imidazolidinyl urea, Toluenesulphonamide formaldehyde resin, DMDM hydantoin, and Ethyleneurea melamine formaldehyde mix. Patch Optimization Platform (POP) identified which single formaldehyde-related allergen optimally captures patients with clinically relevant ACD. Next, POP determined the optimal additional 1, 2, 3, etc. allergens. Cost per patch test was $5.19 (Medicare 2022). RESULTS: 9832 patients were tested to all listed allergens, with 830 having positive patch tests. POP determined that Quaternium 15 alone captures 53% of patients with ACD to the formaldehyde group; adding the optimal second allergen (Formaldehyde 1%) captures 78%; the optimal five top allergens capture over 94% of patients. The incremental cost-per-additional-diagnosis increased up to 44-fold as the number of allergens tested increased. LIMITATIONS: Data is from a single institution, and the cost-per-test was fixed to Medicare Part B in 2022. CONCLUSIONS: For diagnosing ACD, we recommend considering an optimized allergen selection algorithm.

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.

Antibiotics online: digital pharmacy marketplaces and pastiche medicine.

The internet enables access to information and the purchasing of medical products of various quality and legality. Research and regulatory attention have focused on the trafficking of illicit substances, potential physical harms of pharmaceuticals, and possibilities like financial fraud. However, there is far less attention paid to antibiotics and other antimicrobials used to treat infections. With online pharmacies affording greater access, caution around antibiotic use is needed due to the increasing health risks of antimicrobial resistance (AMR). The COVID-19 pandemic has helped to normalise digital healthcare and contactless prescribing, amplifying the need for caution. Little is known of how antibiotics are consumed via digital pharmacy and implications for AMR prevention. To expand insight for AMR prevention policy in Australia and internationally, we use digital ethnographic methods to explore how digital pharmacies function in the context of health advice and policy related to AMR, commonly described as antimicrobial stewardship. We find that digital pharmacy marketplaces constitute 'pastiche medicine'. They curate access to pharmaceutical and information products that emulate biomedical authority combined with emphasis on the 'self-assembly' of healthcare. Pastiche medicine empowers the consumer but borrows biomedical expertise about antibiotics, untethering these goods from critical medicine information, and from AMR prevention strategies. We reflect on the implications of pastiche medicine for AMR policy, what the antibiotics case contributes to wider critical scholarship on digital pharmacy, and how medical humanities research might consider researching online consumption in future.

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.

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.

Skin-directed radiation therapy for cutaneous lymphoma: The Mayo Clinic experience.

BACKGROUND: Focal or total skin radiation therapy can be used to treat mild to refractory cutaneous T-cell lymphoma. OBJECTIVE: To report the broad therapeutic benefit of radiation therapy for cutaneous T-cell lymphoma. METHODS: Retrospective, single-institution review of outcomes for skin-directed radiation therapy. RESULTS: Skin-directed radiation therapy showed a 99% response rate and 80% complete response rate after treatment regardless of involvement, severity, histopathologic subtype, dose, or fractionation. The overall in-field recurrence rate was 15%, and median time to recurrence was 296 days (range, 1-1884 days). Focal and hypofractionated regimens were similarly associated with disease response and rare toxicity. Short-term rates of secondary skin cancer after treatment were comparable to expected incidence in a patient population without radiation. LIMITATIONS: Large total number of treatments courses compared with overall number of patients. Heterogenous mix of treatment regimens (no standardization of dose or fraction number). CONCLUSIONS: Radiation therapy is a well-tolerated treatment option for properly selected patients with cutaneous T-cell lymphoma.

Society of Dermatology Hospitalists supportive care guidelines for the management of Stevens-Johnson syndrome/toxic epidermal necrolysis in adults.

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are life-threatening conditions with high morbidity and mortality. Supportive care management of SJS/TEN is highly variable. A systematic review of the literature was performed by dermatologists, ophthalmologists, intensivists, and gynecologists with expertise in SJS/TEN to generate statements for supportive care guideline development. Members of the Society of Dermatology Hospitalists with expertise in SJS/TEN were invited to participate in a modified, online Delphi-consensus. Participants were administered 9-point Likert scale questionnaires regarding 135 statements. The RAND/UCLA Appropriateness Method was used to evaluate and select proposed statements for guideline inclusion; statements with median ratings of 6.5 to 9 and a disagreement index of ≤1 were included in the guideline. For the final round, the guidelines were appraised by all of the participants. Included are an evidence-based discussion and recommendations for hospital setting and care team, wound care, ocular care, oral care, urogenital care, pain management, infection surveillance, fluid and electrolyte management, nutrition and stress ulcer prophylaxis, airway management, and anticoagulation in adult patients with SJS/TEN.

'Willy nilly' doctors, bad patients, and resistant bodies in general public explanations of antimicrobial resistance.

Increased public engagement is a feature of policy and communications focussed on the reduction of antimicrobial resistance. Explaining antimicrobial resistance for general publics has proven difficult and they continue to endorse apparently mistaken knowledge, including the conflation of antimicrobial resistance with the notion of the resistant body. We interviewed members of the general public in Melbourne, Australia, to explore explanatory models for antimicrobial resistance and shed light on the persistence of the resistant body assumption and related concepts. In the face of AMR's complexity and the portended antibiotic apocalypse, publics rely on a heavily inscribed understanding of the body defending itself against microbes. Publics also read antibiotic misuse and overuse messages as the responsibility of other patients and medical practitioners, and not themselves. Significantly, the scientific world view that has created expert knowledge about AMR hails publics in ways that discredits them and limits their capacity to take action. Increased engagement with publics will be required to ensure that collaborative and sustainable AMR approaches are fashioned for the future.

Squamous Cell Carcinoma in Perineal, Perianal, and Gluteal Hidradenitis Suppurativa: Experience in 12 Patients.

BACKGROUND: Few reports describe squamous cell carcinoma (SCC) arising in hidradenitis suppurativa (HS). OBJECTIVE: The 2 objectives were (1) to describe the clinical characteristics, pathologic findings, and postoperative outcomes of SCC in HS and (2) to assess whether human papillomavirus (HPV) is involved in the pathogenesis. MATERIALS AND METHODS: Cases of SCC in HS were identified through institutional medical records (1976-2013) and the Rochester Epidemiology Project. Tumor specimens were assessed for HPV DNA/RNA with in situ hybridization. RESULTS: Twelve patients were identified (11 Caucasians and 9 men). All SCCs involved gluteal, perianal, or perineal skin; 1 patient had, in addition, involvement of the vagina. Surgical excision was performed on all 12 patients, 4 of whom had a colostomy. Mean duration of HS before SCC development was 28.5 years (range, 15-53 years). Mean follow-up was 4.3 years after surgical excision. Seven of 12 patients followed had postoperative SCC recurrence. Squamous cell carcinoma caused death despite wide surgical excision in these 7 patients. Of the remaining 5 patients, 4 are unknown and 1 who did not recur had an in situ SCC (Bowen disease carcinoma). Squamous cell carcinoma was not associated with high-risk or low-risk HPV. CONCLUSION: Invasive SCC arising in HS carries a high risk of death.

Primary Cutaneous Acral CD8+ T-Cell Lymphoma-A Single Center Review of 3 Cases and Recent Literature Review.

The recently published 2016 revision of the WHO classification of lymphoid neoplasms includes primary cutaneous acral CD8-positive T-cell lymphoma (PCATCL) as a provisional entity. This is a rare indolent lymphoma characterized by papules or nodules on the ear and a dermal infiltrate of CD8-positive T-lymphocytes with cytotoxic marker expression. A retrospective review of a single institutional experience with PCATCL identified 3 patients (mean age 54; range 49-62) with papules or nodules on the ear. Lesional biopsies demonstrated a dense diffuse dermal infiltrate of atypical lymphocytes with a Grenz zone in 2 cases and focal epidermotropism in 1 case. The atypical lymphocytes were predominantly CD3 and CD8 positive with expression of cytotoxic marker TIA1. Staging evaluation failed to reveal systemic disease. Two patients underwent local excision, and the third received local radiation therapy all with complete response and no disease recurrence at last follow-up 3 months (range 2-5 months). Our cases add to the existing limited literature on the clinical and histopathological features of PCATCL. We also performed an updated systematic literature view of the entity.

Dermatologic manifestations of solid organ transplantation-associated graft-versus-host disease: A systematic review.

BACKGROUND: Graft-versus-host-disease (GVHD) after solid organ transplantation (SOT) is extremely rare. OBJECTIVE: To investigate the dermatologic manifestations and clinical outcomes of SOT GVHD. METHODS: Systematic literature review of SOT GVHD. RESULTS: After full-text article review, we included 61 articles, representing 115 patients and 126 transplanted organs. The most commonly transplanted organ was the liver (n = 81). Among 115 patients, 101 (87.8%) developed skin involvement. The eruption appeared an average of 48.3 days (range, 3-243 days) posttransplant and was pruritic in 5 of 101 (4.9%) cases. The eruption was described as morbilliform in 2 patients (1.9%), confluent in 6 (5.9%), and desquamative in 4 (3.9%) cases. In many cases, specific dermatologic descriptions were lacking. The mortality rate was 72.2%. Relative time of death was reported in 23 patients who died during the follow-up period. These patients died an average of 99.2 days (range, 22-270 days) posttransplant, or 50.9 days after the appearance of dermatologic symptoms. Frequent causes of death were sepsis and multiorgan failure. LIMITATIONS: Incomplete descriptions of skin findings and potential publication bias resulting in publication of only the most severe cases. CONCLUSIONS: GVHD is a potentially fatal condition that can occur after SOT and often presents with a skin rash. We recommend that dermatologists have a low threshold to consider and pursue this diagnosis in the setting of post-SOT skin eruption.

Clinical and histopathologic manifestations of solid organ transplantation-associated graft-versus-host disease involving the skin: A single-center retrospective study.

BACKGROUND: Graft-versus-host disease (GVHD) following solid organ transplantation (SOT) is extremely rare and infrequently described in the dermatologic literature. METHODS: We performed a retrospective clinicopathologic review of our institution's experience with patients diagnosed with SOT-associated GVHD (SOT GVHD) (May 1, 1996 to September 1, 2017). RESULTS: Of nine patients with SOT GVHD, seven had undergone liver transplantation, while two had undergone lung transplantation. All presented initially with a skin eruption, which developed an average of 63 days (range: 11-162 days) post transplant. The average time to diagnosis following the onset of the skin eruption was 12 days (range: 0-54 days). Diagnosis was often delayed because of a competing diagnosis of drug reaction. Frequent skin findings included pruritic erythematous to violaceous macules and papules with desquamation. Histopathology showed vacuolar interface dermatitis in 12 of 15 cases (80.0%). Of the 11 specimens in which a hair follicle was present for evaluation, vacuolar interface changes around the hair follicle were present in eight (72.7%) cases. Seven patients (77.8%) died from complications during the follow-up period. CONCLUSIONS: SOT GVHD presents initially with skin involvement, is associated with vacuolar interface changes on skin biopsy, and is associated with a high mortality rate. Clinicopathologic correlation is required for accurate diagnosis.

Crusted (Norwegian) Scabies: Nine-Month Course With Iatrogenic Immunosuppression.

Crusted scabies (CS) is a highly infectious hyperinfestation variant of scabies with up to millions of Sarcoptes scabiei mites present on the skin surface. Diagnostic clues include intense itching and thick crusting especially on the face, groin, and buttocks, although variable presentations may mimic other dermatoses. CS has been associated with immunosuppression including the human immunodeficiency virus (HIV) and lymphoreticular malignancies.1-3 A long latency period from symptom onset to diagnosis and appropriate treatment is often reported. Clinical suspicion is required to obtain a mineral oil preparation or biopsy. We report a patient treated for eczema with 9 months of progressive immunosuppression who was found to have crusted scabies. J Drugs Dermatol. 2018;17(10):1131-1133.

Lichen planus affecting the female genitalia: A retrospective review of patients at Mayo Clinic.

BACKGROUND: Genital or vulval lichen planus (VLP) may have a disabling effect on a patient's quality of life. Evidence-based management guidelines are lacking for VLP. OBJECTIVE: We sought to review clinical presentation and treatment of patients who received a diagnosis of VLP. METHODS: The 100 consecutive patients who received a diagnosis of VLP at Mayo Clinic between January 1, 1997, and December 31, 2015, were reviewed retrospectively. Descriptive statistics were used for data analysis. Fisher's exact test and the Wilcoxon rank sum test were used for analysis of categorical and continuous variables, respectively. All statistical tests were 2 sided, with the α level set at .05 for statistical significance. RESULTS: The time to diagnosis for 49% of patients was more than 1 year. Three patients (3%) had vulval dysplasia, including invasive squamous cell carcinoma. Sixty-eight patients (68%) had multisite lichen planus disease. Eleven patients (11%) had disease remission. Dermatology was the lead specialty for 9 of these cases of remission. LIMITATIONS: This was a retrospective, small-cohort study. CONCLUSION: A low frequency of disease remission was seen in patients with VLP. Patients with lichen planus benefit considerably from dermatology consultation. Further research is warranted to establish high-quality, evidence-based guidelines for multidisciplinary management of this challenging disease.

Erythromelalgia: Identification of a corticosteroid-responsive subset.

BACKGROUND: Corticosteroids (CS) may benefit certain patients with erythromelalgia. OBJECTIVES: Our objective was to determine clinical predictors of corticosteroid-responsive erythromelalgia. METHODS: Patients with erythromelalgia who received CS were identified and stratified into corticosteroid nonresponders (NRs), partial corticosteroid responders (PSRs), complete corticosteroid responders (CSRs), and steroid responders (SRs = PSRs + CSRs). In the study variable analysis, P < .05 was considered statistically significant. RESULTS: The median (interquartile range) age of the 31-patient cohort was 47 years (26-57 years), and 22 (71%) were female. Fourteen (45%) were NRs, 17 (55%) SRs, 8 (26%) PSRs, and 9 (29%) CSRs. A subacute temporal profile to disease zenith (<21 days) was described in 15 (48%) patients, of whom 13 (87%) were SRs (P = .003; odds ratio [OR] = 0.069 [95% confidence interval {CI}, 0.011-0.431]). Six (67%) CSRs reported a disease precipitant (eg, surgery, trauma, or infection; P = .007; OR = 12.667 [95% CI, 2-80.142]). SR patients received CS sooner than NR at 3 (3-12) versus 24 (17-45) months (P = .003). A high-dose CS trial (≥200 mg prednisone cumulatively) was administered to 17 (55%) patients, of whom 13 (76%) were SRs (P = .012; OR = 8.125 [95% CI, 1.612-40.752]). LIMITATIONS: This was a retrospective case series. CONCLUSION: An infectious, traumatic, or surgical precipitant and subacute presentation may portend CR erythromelalgia. A transient "golden window" where CS intervention is useful may exist before irreversible nociceptive remodeling and central sensitization occurs.

Sézary syndrome without erythroderma: A review of 16 cases at Mayo Clinic.

BACKGROUND: Sézary syndrome (SS) is characterized by erythroderma with leukemic involvement. In atypical SS, leukemic involvement is present without erythroderma. Little is known about the presentation, prognosis, and outcome in these patients. OBJECTIVE: We sought to describe our experience with patients with SS without erythroderma. METHODS: We retrospectively identified patients with SS, but without erythroderma, at Mayo Clinic from 1976 to 2010. Patients all met criteria for high blood tumor burden. Their clinical characteristics, disease course, and prognosis were reviewed and compared with a previously described cohort of 176 patients with SS from this institution. RESULTS: Among 16 patients identified, all had cutaneous findings consistent with cutaneous T-cell lymphoma, most commonly erythematous patches (n = 6) and plaques (n = 12). All 16 patients were deceased at the time of the study. Median time from diagnosis of SS without erythroderma to the date of death was 3.6 years (range, 0.5-8.7 years). Survival was not different between patients with SS with and without erythroderma (hazard ratio 1.58; 95% confidence interval 0.94-2.66; P = .08). LIMITATIONS: This was a single-institution retrospective study. CONCLUSION: Leukemic involvement may confer shortened survival in patients with SS, because the presence of erythroderma did not affect survival. These atypical cases could potentially be more accurately described using the TNMB classification.

Early clinical manifestations of Sézary syndrome: A multicenter retrospective cohort study.

BACKGROUND: Classic Sézary syndrome (SS) is defined by erythroderma, generalized lymphadenopathy, and leukemic blood involvement. Clinical observations suggest that SS begins as a nonerythrodermic disease. OBJECTIVE: To describe the early clinical characteristics of patients with SS. METHODS: A retrospective, multicenter chart review was performed for 263 confirmed cases of SS diagnosed during 1976-2015. RESULTS: Erythroderma was the earliest recorded skin sign of SS in only 25.5% of cases, although most patients (86.3%) eventually developed erythroderma. In patients without erythroderma during their initial visit, the first cutaneous signs of SS were nonspecific dermatitis (49%), atopic dermatitis-like eruption (4.9%), or patches and plaques of mycosis fungoides (10.6%). The mean diagnostic delay was 4.2 years overall, 2.2 years for cases involving erythroderma at the initial presentation, and 5.0 years for cases not involving erythroderma at the initial presentation. LIMITATIONS: This study is retrospective. CONCLUSION: Erythroderma is uncommon as an initial sign of SS. Early SS should be considered in cases of nonerythrodermic dermatitis that is refractory to conventional treatments. In these cases, examination of the blood by PCR for monoclonal T-cell receptor rearrangement and by flow cytometry to identify an expanded or aberrant T-cell population should be considered.