Assessing Health-Related Quality of Life in Mycosis Fungoides and Sézary Syndrome: Unmet Needs.

Mycosis fungoides (MF) and Sézary syndrome (SS) can impair multiple dimensions of health-related quality of life (HRQoL). Currently, there is no standardized assessment tool for measuring HRQoL in patients with MF/SS. Here, we describe the existing literature on multiple dimensions of HRQoL in MF/SS with a special focus on the gaps in the current knowledge and identify future directions necessary to assess the HRQoL of patients with this disease.

Assessing T-cell receptor clonality by next-generation sequencing in atypical cutaneous lymphoid infiltrates and cutaneous T-cell lymphoma: A scoping review.

The diagnosis of cutaneous T-cell lymphoma (CTCL) remains challenging. Demonstration of a clonal T-cell population using T-cell receptor (TCR) gene rearrangement studies by next-generation sequencing (NGS) has been explored in several studies. This review summarizes the current literature on NGS-based sequencing methods for the assessment of TCR clonality in the evaluation of atypical cutaneous lymphoid infiltrates and CTCL on behalf of the American Society of Dermatopathology Appropriate Use Criteria Committee (lymphoproliferative subgroup). PubMed was searched for relevant articles, including CTCL and NGS, for clonality from 1967 to 2022. Thirteen studies were included in the analysis. The skin was the most commonly assayed compartment with TCR NGS. Sensitivity for TCR NGS in the skin ranged between 69% and 100%, compared to 44%-72% for polymerase chain reaction (PCR)-capillary electrophoresis. Specificity for TCR NGS in the skin ranged from 86% to 100%, compared to 77%-88% for PCR capillary electrophoresis. TCR NGS was also reported to have potential prognostic value in CTCL and can also be used to detect relapse and/or minimal residual disease after treatment.

Development and psychometric properties of the Functional Assessment of Cancer Therapy-Cutaneous T-Cell Lymphoma (FACT-CTCL).

BACKGROUND: Patients with Mycosis Fungoides (MF)/Sézary Syndrome (SS) can experience impacted health-related quality of life (HRQoL). OBJECTIVES: To validate the CTCL-S, a novel subscale of the Functional Assessment of Cancer Therapy - General (FACT-G), in patients with MF/SS. METHODS: Qualitative interviews were conducted with expert clinicians and MF/SS patients. Thematic analysis identified the most common concerns, and 19 items were selected.MF/SS patients were recruited from a single center. FACT-G, CTCL-S (collectively "FACT-CTCL"), Skindex29, and Visual Analogue Scale-Pruritis (VAS itch) were administered. A subset repeated FACT-CTCL and VAS itch after ≈2 weeks. Patient demographics and clinical characteristics were obtained via review of the electronic medical record.Psychometric properties were assessed. Internal consistency was estimated using Cronbach's alpha (α). Convergent and discriminant validity were assessed by comparing CTCL-S to disease stage, age, VAS itch, FACT-G, and SkinDex29. Exploratory factor analysis (EFA) was used to preliminarily assess CTCL-S dimensionality. Test-retest repeatability was summarized using intraclass correlation coefficient (ICC), within-subject standard deviation (wSD), and within-subject coefficient of variation. RESULTS: Seventy-two patients completed the initial survey, and 35 repeated the FACT-CTCL and VAS itch after ≈2 weeks. Two-thirds were male, most were white (78%). The majority (85%) had MF, 15% SS, and 75% early (stage IA-IIA) and 25% advanced (≥ stage IIB) disease. Preliminary EFA found a single predominant factor, supporting a hypothesis of unidimensionality of the CTCL-S. Internal consistency of the CTCL-S was high (α: 0.95 [95% CI: 0.93-0.96]). There was no significant change in CTCL-S average test-retest scores (ICC of 0.93 (p = 0.63)). CTCL-S was significantly lower in advanced vs early stage disease (median[IQR]: 34[26, 48] vs. 59[44, 68], p < 0.001) and strongly correlated with VAS itch (Spearman's r (rs): -0.70, 95% CI: -0.81, -0.55), FACT-G (rs: 0.77, 95% CI: 0.65, 0.85), and Skindex29 (rs: -0.90, 95% CI: -0.94, -0.84), supporting convergent validity. CTCL-S scores had little correlation with age (rs: 0.19, 95% CI: -0.05, 0.41, p = 0.12), supporting discriminant validity. CONCLUSIONS: The FACT-CTCL is a disease specific instrument for assessing HRQoL with high reproducibility and good performance in a cohort of patients with MF/SS.

Mortality and Autopsy Findings in Patients with Pyoderma Gangrenosum: A Multi-Institutional Series.

INTRODUCTION: Pyoderma gangrenosum (PG) is a rare ulcerative skin condition with an increased risk of mortality compared to the general population. The causes of this increased risk are not well understood. Misdiagnosis is common in PG, and many studies are limited by the inclusion of misdiagnosed cases. The goal of this study was to review autopsy findings, identify causes of death, and identify factors that may worsen outcomes among deceased patients confirmed to have PG. METHODS: Data was retrospectively reviewed from the electronic medical records at five academic hospitals. A search was conducted for deceased patients with a diagnosis of PG who had an autopsy performed between 2010 and 2020. We report a descriptive analysis of 11 patients and their clinical characteristics, causes of death, and autopsy findings. RESULTS: The average age of death was 62.9 years. Seven patients had at least one underlying condition known to be associated with PG including inflammatory bowel disease, inflammatory arthritis, or a hematologic disorder. The most common cause of death was infection (n = 6, 54.5%), followed by pulmonary embolism (n = 3, 27.3%), and myelodysplastic syndrome (n = 2, 18.2%). Six patients (54.5%) were taking systemic steroids at the time of death. CONCLUSION: The development of PG may shorten life expectancy among those with underlying conditions associated with PG, and common treatments for PG may contribute to the risk of fatal complications. Awareness of the risk of infection, thrombosis, and malignancy among those with PG is necessary for proper management. Further research is needed to explore the relationship between PG and thromboembolism.

Desmoplakin I/II immunohistochemical staining may be a helpful tool in differentiating cutaneous graft versus host disease from the erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis spectrum disorders.

Cutaneous graft versus host disease (cGVHD) has substantial clinical and histopathologic overlap with erythema multiforme (EM), Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN). This overlap can make it difficult to distinguish these disorders in patients who have received hematopoietic transplants. We sought to evaluate the utility of Dp I/II immunohistochemical stain in differentiating EM/SJS/TEN and cGVHD in a large cohort. Skin biopsy specimens from patients with cGVHD (n = 58) and EM/SJS/TEN (n = 60) were evaluated for Dp I/II expression by immunohistochemistry. We found a statistically significant difference in Dp I/II staining between cGVHD (all grades) and EM/SJS/TEN (mean scores 1.62 and 2.14, respectively; p < 0.005), as well as between Grades 2 + 3 cGVHD and EM/SJS/TEN (mean scores 2.26 and 1.62, respectively; p < 0.005), while we did not find a significant difference between Grade 4 cGVHD and EM/SJS/TEN (mean scores 1.69 and 1.62, respectively; p = 0.71). Dp I/II immunostain may be useful for differentiating EM/SJS/TEN from Grade 2 and Grade 3 cGVHD, especially in clinically ambiguous cases without extracutaneous GVHD.

International Dermatology Outcome Measures (IDEOM) - Report from the 2022 Annual Meeting.

BACKGROUND: The International Dermatology Outcome Measures (IDEOM) is a non-profit organization dedicated to the advancement of evidence-based, consensus-driven outcome measures in dermatological diseases. Researchers and stakeholders from various backgrounds collaborate to develop these objective benchmark metrics to further advance treatment and management of dermatological conditions. SUMMARY: The 2022 IDEOM Annual Meeting was held on June 17-18, 2022. Leaders and stakeholders from the hidradenitis suppurativa, acne, vitiligo, actinic keratosis, alopecia areata, itch, cutaneous lymphoma, and psoriatic disease workgroups discussed the progress of their respective outcome-measures research. This report summarizes each workgroup's updates from 2022 and their next steps as established during the 2022 IDEOM Annual Meeting. J Drugs Dermatol. 2023;22(12):1153-1159 doi:10.36849/JDD.7615.

Evaluation of Insulin Pump Infusion Sites in Type 1 Diabetes: The DERMIS Study.

OBJECTIVE: Continuous subcutaneous insulin infusion (CSII) for type 1 diabetes is increasing in use. Pump site failures are common, but little is known about skin changes from pump use. Using noninvasive optical coherence tomography (OCT), OCT angiography (OCTA), and skin biopsies, we evaluated skin changes from chronic insulin infusion. RESEARCH DESIGN AND METHODS: In this cross-sectional study, OCT operating at a 1,310-nm central wavelength with a bandwidth of 100 nm was performed immediately before skin punch biopsies were collected at three sites: the current site, with the infusion set removed at time of OCT and biopsy; the recovery site, with the infusion set removed 3 days before biopsy; and the control site, which was never used for any insulin infusion or injection. RESULTS: OCT and OCTA identified characteristics of increased inflammation and vessel density at pump sites compared with control sites. Histologic analysis of pump sites showed differences in skin architecture, including fibrosis, inflammation (including increased tissue eosinophils), and fat necrosis. Immunohistochemical staining showed differences between infusion and control sites regarding staining of ILGF-I and transforming growth factor-ß3. CONCLUSIONS: These findings support allergic sensitization as a potentially common reaction at CSII sites. The leading candidates causing this include insulin preservatives, plastic materials, and adhesive glue used in device manufacturing. The inflammatory response caused by these common allergic responses may result in tissue changes responsible for the infusion site failures seen frequently in clinical practice.

Gender disparities in health-related quality of life (HRQoL) in patients with cutaneous T-cell lymphoma.

Patients with cutaneous T-cell lymphoma (CTCL) often experience debilitating symptoms that impair health-related quality of life (HRQoL). Existing evidence for HRQoL differences with respect to gender is conflicting. Objective: To investigate potential gender differences in HRQoL for patients with CTCL. Methods: We performed a cross-sectional study to assess HRQoL in patients with CTCL by partnering with the Cutaneous Lymphoma Foundation to distribute an electronic survey from February to April 2019. Results: A total of 292 patient responses (66% women, mean age 57 years) were included in the analysis. Most of the cohort had early-stage (IA-IIA) (74%; 162/203) mycosis fungoides (MFs) (87%; 241/279), followed by Sézary syndrome (SS) (12%; 33/279). Women with CTCL experienced significantly worse HRQoL compared with men (Skindex-16: 51±26 vs. 36±26, P ≤ 0.001; FACT-G: 69±21 vs. 77±16, P = 0.005). This gender difference was present even when controlling for stage of disease. Women experienced worse HRQoL in all three of the Skindex-16 subscales (symptoms: ß = 14.0, P ≤ 0.001; emotions: ß = 15.1, P ≤ 0.001; functioning: ß = 11.3, P = 0.006), but only two of the four FACT-G subscales (physical: ß =-2.8, P ≤ 0.001; emotional: ß = -2.0, P = 0.004). Limitations: Due to the method of distribution of the survey, we were unable to estimate a participant response rate. Participants' diagnosis and stage were self-reported. Conclusion: In this cohort women with CTCL experienced significantly worse HRQoL when compared to men. Additional studies are necessary to determine what factors contribute to this gender disparity.

New Molecular and Biological Markers in Cutaneous T Cell Lymphoma: Therapeutic Implications.

PURPOSE OF REVIEW: Cutaneous T cell lymphomas (CTCLs) exhibit a wide variety of clinical features, histologic characteristics, and genetic drivers. We review novel molecular findings that inform our understanding of the pathogenesis of CTCL, with a focus on the tumor microenvironment (TME). RECENT FINDINGS: There is increasing evidence challenging the model of TCM:mycosis fungoides (MF) and TEM:Sézary syndrome (SS) phenotype. Phylogenetic analysis performed using whole-exome sequencing (WES) raises the possibility that MF can arise without a common ancestral T cell clone. The detection of ultraviolet (UV) marker signature 7 mutations in the blood of patients with SS raises questions about the role of UV exposure in CTCL pathogenesis. There is also increasing interest on the role of the TME in CTCL. Existing therapies such as the RXR retinoid bexarotene and the anti-CCR4 monoclonal antibody mogamulizumab may act through the CTCL TME by impacting the CCL22:CCR4 axis, while cancer-associated fibroblasts (CAFs) in the CTCL TME contribute to drug resistance, as well as a Th2 milieu and tumor growth via secretion of pro-tumorigenic cytokines. Staphylococcus aureus (SA) is a frequent cause of morbidity among CTCL patients. SA may positively select for malignant T cells through adaptive downregulation of alpha-toxin surface receptors and promotion of tumor growth via upregulation of the JAK/STAT pathway. Recent molecular advancements have contributed to our understanding of the pathogenesis of CTCL and shed light into the potential mechanisms of existing therapies. Further understanding of the CTCL TME may fuel the discovery of novel therapies for CTCL.

Characteristics and Outcomes for Hospitalized Patients With Cutaneous T-Cell Lymphoma.

Importance: Cutaneous T-cell lymphoma (CTCL) is a group of rare, complex cutaneous malignant neoplasms associated with significant disease burden on patients and the health care system. Currently, the population of patients with CTCL admitted to the hospital remains largely uncharacterized and poorly understood. Objective: To characterize the clinical characteristics, course of hospitalization, and mortality outcomes of an inpatient CTCL cohort. Design, Setting, and Participants: This multicenter retrospective cohort study reviewed medical records for adult patients (age ≥18 years) with a CTCL diagnosis per National Comprehensive Cancer Network guidelines admitted for inpatient hospitalization at 5 US academic medical centers with inpatient dermatology consult services and CTCL clinics between August 2016 and August 2020. Main Outcomes and Measures: Patient demographics, clinical history and findings, hospitalization courses, and mortality outcomes. Results: A total of 79 hospitalized patients with CTCL were identified, including 52 (70.3%) men and 22 (29.7%) women, with a median (IQR) age at hospitalization of 62.9 (27-92) years. The majority of admitted patients with CTCL were White (65 patients [82.3%]), had disease classified as mycosis fungoides (48 patients [61.5%]), and had advanced-stage disease (≥IIB, 70 patients [89.7%]). Most hospitalizations were complicated by infection (45 patients [57.0%]) and required intravenous antibiotic therapy (45 patients [57.0%]). In-hospital mortality occurred in 6 patients (7.6%) and was associated with higher body mass index (36.5 vs 25.3), history of thromboembolic disease (50.0% vs 12.3%), and diagnosis of sepsis on admission (66.7% vs 20.5%). At 1-year postdischarge, 36 patients (49.3%) patients had died, and mortality was associated with history of solid organ cancers (27.8% vs 10.8%), wound care as the reason for dermatology consultation (58.3% vs 24.3%), and presence of large cell transformation (58.3% vs 22.9%). Conclusions and Relevance: The findings of this cohort study improve the understanding of hospitalized patients with CTCL and lend valuable insight into identifying factors associated with both in-hospital and long-term mortality outcomes. This refined understanding of the inpatient CTCL population provides a foundation for larger, more robust studies to identify causal risk factors associated with mortality, development of prognostic scoring systems to estimate the probability of hospital mortality. Overall, the findings may prompt physicians caring for patients with CTCL to implement preventive strategies to diminish hospitalization and improve clinical management across this unique disease spectrum.

Differences in nomenclature usage and preference among dermatopathologists for "dysplastic" nevi: A national survey.

BACKGROUND: Ongoing controversy exists regarding terminology used to describe atypical melanocytic nevi. Efforts to standardize nomenclature, including the 1992 NIH consensus conference, have been largely unsuccessful. Significant advances have revealed an increasingly detailed genetic picture of melanocytic neoplasms, including strong evidence for the existence of those with "intermediate" behavior. METHODS: We sent an electronic survey to dermatopathologists (n = 846) to assess trends in nomenclature usage and attitudes toward developing new consensus nomenclature for atypical melanocytic nevi. RESULTS: There were 229 complete responses (27.1% response rate). The most used/preferred nomenclature was "dysplastic nevus" (43%/39%, respectively), followed by the NIH-recommended terminology (28%/26%). Three-tier grading systems were most heavily used/preferred (79%/63%). Dermatopathologists based in New England were most likely to use the NIH terminology; on the other hand, "dysplastic nevus" or "other" were most used elsewhere (p = 0.029). Most (76%) expressed at least "moderate" enthusiasm for developing consensus nomenclature, with 47% "very" or "extremely" enthusiastic. CONCLUSION: Little has changed with the wide variation in terminology for atypical melanocytic nevi. There continues to be no one dominant terminology in use. However, there is enthusiasm for standardization. A new attempt at updated consensus nomenclature may be fruitful.

Limb amputation in patients with pyoderma gangrenosum: a multi-institutional case series.

INTRODUCTION: Pyoderma gangrenosum (PG) can represent a diagnostic challenge, leading to missed or delayed diagnosis. With prolonged immunosuppressive therapy, the risk of infections is elevated, predisposing patients to receive anti-infective treatments and, in serious cases, amputations. Limb amputations have been reported as complication of PG misdiagnosis but can also occur as a complication of long-standing PG ulcers. METHODS: We aimed to describe the clinical characteristics of patients with PG leading to limb amputation through a multicenter retrospective case series between 2010 and 2020 including patients with PG who underwent limb amputation. We report a descriptive analysis of these patients' clinical course and outcome. RESULTS: Ten patients with PG who underwent at least one limb amputation were identified. Six were male (60%). Mean age was 65 years. All patients had ulcerative PG on the lower extremities, with a mean PG ulcer duration of 30.6 months. Six patients had PG-related comorbidities such as ulcerative colitis, myelodysplasia, and inflammatory arthritis. Other significant comorbidities included diabetes mellitus (DM) (five patients), coronary artery disease (five patients), and chronic kidney disease (two patients). The majority of patients (8/10) were correctly diagnosed with PG prior to amputation, whereas two patients were misdiagnosed with necrotizing soft tissue infections (NSTIs). All patients received intravenous antibiotics without substantial improvement. Eight patients developed sepsis and shock-like symptoms and the diagnosis of NSTIs was considered. Below-knee amputation was performed in six patients and above-knee amputation in four. Four patients had amputation performed twice because of recurrent NSTIs. Conclusion This multicenter case series sheds light on practice gaps for physician assessing patients with PG, in that limb amputation may result from PG misdiagnosis or complications thereof. Elderly patients (above 65 years) with coexisting lower extremity PG, DM, and/or chronic cardiac or renal disease should be managed with particular care toward preventing infection/NSTIs to prevent further complications such as limb amputations.

Management and Prognosis of Cardiac Metastatic Merkel Cell Carcinoma: A Case-Control Study and Literature Review.

Merkel cell carcinoma (MCC), an aggressive neuroendocrine skin cancer, has a high rate (20%) of distant metastasis. Within a prospective registry of 582 patients with metastatic MCC (mMCC) diagnosed between 2003-2021, we identified 9 (1.5%) patients who developed cardiac metastatic MCC (mMCC). We compared overall survival (OS) between patients with cardiac and non-cardiac metastases in a matched case-control study. Cardiac metastasis was a late event (median 925 days from initial MCC diagnosis). The right heart was predominantly involved (8 of 9; 89%). Among 7 patients treated with immunotherapy, 6 achieved a complete or partial response of the cardiac lesion. Among these 6 responders, 5 received concurrent cardiac radiotherapy (median 20 Gray) with immunotherapy; 4 of 5 did not have local disease progression or recurrence in the treated cardiac lesion. One-year OS was 44%, which was not significantly different from non-cardiac mMCC patients (45%, p = 0.96). Though it occurs relatively late in the disease course, cardiac mMCC responded to immunotherapy and/or radiotherapy and was not associated with worse prognosis compared to mMCC at other anatomic sites. These results are timely as cardiac mMCC may be increasingly encountered in the era of immunotherapy as patients with metastatic MCC live longer.

Sexual harassment from patient to medical student: a cross-sectional survey.

BACKGROUND: There is little existing research investigating SH/SA specifically from patients to students. This study aims to assess the prevalence and impact of SH and SA from patient to medical student. METHODS: A cross-sectional survey study was administered via electronic email list to all current medical students at the University of Washington School of Medicine (n = 1183) over a two-week period in 2019. The survey questions addressed respondents' experiences with SH/SA from patients, frequency of reporting, and impact on feelings of burnout. RESULTS: Three hundred eleven responses were received for a response rate of 26%; 268 complete responses were included in the final analysis. Overall, 56% of respondents reported ever experiencing SH from a patient. SH from a patient was reported by significantly more of those who identify as female compared to male (66% vs 31%; p < .001). Similar frequency of experiencing SH within the last year were reported by females and males (90% vs 88%; p = .96). Clinical students were more likely to have ever experienced SH compared to preclinical students (61% vs 39%; p < .001). The majority (86%) of respondents who experienced SH/SA did not report it in an official capacity. Those who identify as female were more likely to report that SH from a patient contributed to feelings of burnout (21% vs 5% for male; p = .02). Behaviors consistent with SA were experienced by 16% of respondents, with similar frequency between females and males. CONCLUSIONS: This study demonstrates that patient to medical student SH/SA is a common occurrence, particularly among students identifying as female. It also highlights the significant impact of SH/SA incidents on feelings of burnout.

Mechlorethamine Hydrochloride Gel in the Treatment of Mycosis Fungoides-Type Cutaneous T-Cell Lymphoma (MF-CTCL): A Focus on Patient Selection and Special Considerations.

Mycosis fungoides (MF) is the most common type of cutaneous T-cell lymphoma (CTCL) and often has an indolent course, particularly for patients presenting with early-stage (patch/plaque) disease. Early-stage MF is primarily managed with skin-directed therapies. Topical mechlorethamine hydrochloride (nitrogen mustard [NM]) gel has increased tolerability compared to prior NM formulations, though contact dermatitis remains a common side effect. The addition of topical steroids can improve tolerability while maintaining the efficacy of NM gel. Real-world experience supports that NM gel also has a role in combination therapy and as adjunctive therapy in advanced-stage disease. Here we review factors that may influence patient selection for use of NM gel, including MF variants, special patient populations, cost effectiveness, and impact on quality of life for patients with MF.

Novel Diagnostic Educational Resource: Use of a web-based adaptive learning module to teach inflammatory reaction patterns in dermatopathology to medical students, residents, and fellows.

Background: Perceptual and adaptive learning modules (PALM's) provide a large number of visual examples for evaluation and accommodate to learner performance by actively adjusting the module parameters. Methods: We developed a module for discriminating 5 inflammatory reaction patterns using the Novel Diagnostic Educational Resource (NDER) platform. The module included a 20 question pre-test, a 200 question training section, and a 20 question post-test. During the pre-test and post-test, images were displayed for an indefinite period of time with no feedback given. In the training section, images were displayed for a duration inverse to learner performance, and after submitting their response learners were immediately shown the correct answer. The performance of module participants was compared to a control group who completed pre-test and post-test only. Results: 26 pathology and dermatology residents completed the module and were included in analysis. Pre-test and post-test scores showed an average increase of 17.1 percentage points (95% CI 13.0 to 21.2, P < 0.001). When performance on pre-test and post-test was compared between the module and control groups, module group performance increased more than control group performance by an average of 10.1 percentage points (95% CI -2.5 to 17.8, P = 0.0119). 84% (37) of participants found the module somewhat useful or very useful and 68% (30) of participants would be pretty likely or very likely to recommend to another trainee. Conclusions: Our findings validate the use of NDER for teaching inflammatory reaction patterns. Participants generally had favorable feedback regarding the interface and teaching potential of the module. Including a late re-test as part of the module would be beneficial in further validating future iterations. Next steps include optimizing module performance and developing module content for more advanced learners.