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Importance Sezary syndrome (SS) is an advanced form of cutaneous T-cell lymphoma with few long-term remissions observed. Objective To profile 3 patients with SS who have experienced long-term remission following the addition of low-dose total skin electron beam therapy (TSEBT) to systemic regimens of extracorporeal photopheresis, bexarotene, and interferon-γ. Design, setting, and participants This is a retrospective case series with additional investigations of patient-donated samples to assess therapeutic response. The study was conducted at the University of Pennsylvania Cutaneous Lymphoma Clinic and follows 3 patients with stage IVA1 CD4+ SS who presented to the clinic between November 1, 2009, and November 1, 2017, and who had a history of SS that was refractory to multimodality systemic therapy prior to receiving low-dose TSEBT. Interventions Patients were treated in a multimodality fashion with combined extracorporeal photopheresis, bexarotene, interferon-γ, and low-dose TSEBT. Main outcomes and measures To characterize treatment responses in these patients, the extent of skin disease was measured with the modified severity weighted assessment tool. Blood disease was measured with flow cytometric assessments of Sezary cell count, CD4:CD8 ratio, and high throughput sequencing of the T-cell receptors. To assess for restoration of immune function, we measured markers of immune exhaustion, including PD-1 (programmed cell death 1), TIGIT (T-cell immunoreceptor with immunoglobulin and ITIM domains), CTLA4 (cytotoxic T-lymphocyte-associated protein 4), TOX (thymocyte selection-associated high mobility group box protein), and Foxp3 (forkhead box P3) on circulating CD4 and CD8 T cells, along with production capacity of interferon-γ by lymphocytes following activation stimuli. Results Following administration of low-dose TSEBT and maintenance of the other therapies, remissions ranged from 24 to 30 months, with complete responses in 2 patients ongoing. Markers of immune exhaustion including PD-1, TIGIT, CTLA4, TOX, and Foxp3 were significantly reduced from baseline following TSEBT, along with enhanced production capacity of interferon-γ by lymphocytes following activation stimuli. High throughput sequencing demonstrated near-complete eradication of the circulating clone among 2 of 3 patients with stable levels in 1. Conclusions and relevance We describe 3 patients who achieved long-term clinical and molecular remissions following low-dose TSEBT as part of a multimodality regimen for treatment of SS. As long-term remissions in SS are uncommon, this approach demonstrates promise, and clinical trials should be considered.

Stephen Richardson, MD; Jeanne B. Budgin, DVM; Jacqueline M. Junkins-Hopkins, MD; Carmela C. Vittorio, MD; Jason Lee, MD; Wallace T. Miller, Jr, MD; Alain H. Rook, MD; Ellen J. Kim, MD; Departments of Dermatology (Drs Richardson, Junkins-Hopkins, Vittorio, Rook, and Kim) and Radiology (Dr Miller), University of Pennsylvania Health System; Department of Dermatology, University of Pennsylvania School of Veterinary Medicine (Dr Budgin); Department of Dermatology, Thomas Jefferson Medical College (Dr Lee), Philadelphia

Importance A validated scoring system is essential to assess the effect of therapeutic interventions on a disease. The instrument introduced here captures sarcoidosis disease activity in a reliable, reproducible manner, which will help standardize clinical trial outcomes and allow comparative efficacy studies in the future and may help lead to more robust data regarding the effect of different treatments on cutaneous sarcoidosis. Objective To assess the reliability and convergent validity of the Cutaneous Sarcoidosis Activity and Morphology Instrument (CSAMI) and Sarcoidosis Activity and Severity Index (SASI) for evaluating cutaneous sarcoidosis outcomes. Design and Setting Cross-sectional study evaluating cutaneous sarcoidosis disease severity using CSAMI, SASI, and Physician's Global Assessment (PGA) as reference in the dedicated cutaneous sarcoidosis clinic of a teaching hospital. Participants Eight dermatologists evaluating cutaneous sarcoidosis in 11 patients. Intervention Evaluation using the study instruments. Main Outcomes and Measures Primary outcomes included interrater and intrarater reliability and convergent validity; secondary outcomes, correlation with quality-of-life measures and time required for completion. Results All instruments demonstrated good to excellent intrarater reliability. Interrater reliability was excellent for CSAMI Activity scores (intraclass correlation coefficient, 0.82 [95% CI, 0.66-0.94]) and fair to poor for CSAMI Damage scores (0.42 [0.21-0.72]), modified Facial SASI (0.40 [0.17-0.72]), and PGA scores (0.40 [0.18-0.70]). CSAMI Activity and Damage scores and modified Facial SASI all demonstrated convergent validity with statistically significant correlations with PGA scores. Trends for correlations were seen between CSAMI scores and specific Skindex-29 quality-of-life domains. Although CSAMI required longer time to complete than SASI, both were scored within adequate time for use in clinical trials. Conclusions and Relevance CSAMI appears to be a reliable and valid outcome instrument to measure cutaneous sarcoidosis and may capture a wide range of body surface and cutaneous morphologic types. This instrument can be adopted into clinical practice and clinical trials to allow physicians to assess the intensity of their patients' cutaneous sarcoidosis disease activity. Widespread use of one metric for disease severity assessment can help standardize the evaluation of the effect of various treatments on the disease. Future research is necessary to demonstrate its sensitivity to change and to confirm its correlation with quality-of-life measures.

An 83-year-old man with a history of diabetes and chronic obstructive pulmonary disorder (COPD) (taking prednisone, 5 mg/d) was admitted to our facility with a monthlong history of persistent right arm swelling, erythema, and pain. He had multiple prior admissions for this issue and was treated with oral and intravenous antibiotics for a suspected “cellulitis.” His skin symptoms worsened despite treatment, and he developed an extensive superimposed pustular eruption with sinus tracts involving the entire forearm and a portion of the upper arm (Figure 1). Workup included ultrasonography, which showed no fluid collection, and magnetic resonance imaging, which showed soft-tissue swelling without evidence of any underlying myositis or osteomyelitis. A Tzanck smear failed to show multinucleated giant cells. Punch biopsy specimens for culture and histopathologic analysis were obtained (Figure 2 and Figure 3). What is your diagnosis?