Efficacy of immunotherapy with combination of cryotherapy and topical imiquimod for treatment of Kaposi sarcoma.

Multiple treatment modalities for Kaposi sarcoma (KS) have been reported, including chemotherapy, radiation therapy, surgical excision, electrochemotherapy, and cryotherapy. Common topical treatments include timolol, imiquimod, and alitretinoin. We searched our institutional database for patients with ICD-9 or 10 codes for KS seen by a dermatologist with experience in KS management from July 1, 2004 to January 1, 2022. We screened patient charts to include patients who received combination therapy of cryotherapy followed by topical imiquimod three times a week for 2 months (n = 9). Patients were followed in the clinic every 3 months. Time to resolution was assessed by photographic evidence of resolution as determined by a dermatologist and corroborated with clinical documentation in patient charts. Median age (IQR) at KS diagnosis was 58 (27.5) years. All patients were male (n = 9, 100%). Majority were white (n = 7, 78%) and non-Hispanic (n = 8, 89%). Five (56%) had classic KS, one (11%) had HIV-associated KS, and three (33%) were HIV-negative men who have sex with men. Median time to resolution was 30.5 weeks, with a median of two treatments. In our study, 93% (n = 42/45) of lesions and 89% (n = 8/9) of patients experienced complete resolution during a median (range) duration of follow-up of 58 (13-209) weeks. Side effects were limited to pain during cryotherapy, occasional blister formation after cryotherapy, and mild inflammation due to imiquimod. No infections were observed. Combination therapy of cryotherapy and topical imiquimod may be an efficacious and comparatively low-risk treatment for limited, cutaneous KS.

Suggested methodology for longitudinal evaluation of nevi based on clinical images.

BACKGROUND: Melanoma screening includes the assessment of changes in melanocytic lesions using images. However, previous studies of normal nevus temporal changes showed variable results and the optimal method for evaluating these changes remains unclear. Our aim was to evaluate the reproducibility of (a) nevus count done at a single time point (method I) versus two time points (method II); and (b) manual and automated nevus diameter measurements. MATERIALS AND METHODS: In a first experiment, participants used either a single time point or a two time point annotation method to evaluate the total number and size of nevi on the back of an atypical mole syndrome patient. A Monte Carlo simulation was used to calculate the variance observed. In a second experiment, manual measurements of nevi on 2D images were compared to an automated measurement on 3D images. Percent difference in the paired manual and automated measurements was calculated. RESULTS: Mean nevus count was 137 in method I and 115.5 in method II. The standard deviation was greater in method I (38.80) than in method II (4.65) (p = 0.0025). Manual diameter measurements had intraclass correlation coefficient of 0.88. The observed mean percent difference between manual and automated diameter measurements was 1.5%. Lightly pigmented and laterally located nevi had a higher percent difference. CONCLUSIONS: Comparison of nevi from two different time points is more consistent than nevus count performed separately at each time point. In addition, except for selected cases, automated measurements of nevus diameter on 3D images can be used as a time-saving reproducible substitute for manual measurement on 2D images.

Association of interleukin-6 and tumor necrosis factor-α with mortality in hospitalized patients with cancer.

BACKGROUND: Severe cutaneous adverse reactions (SCARs) are associated with high morbidity and mortality in patients with cancer. Early identification and treatment of SCARs may improve outcomes. OBJECTIVE: To identify biomarkers to predict outcomes in hospitalized patients with cancer who developed SCARs. METHODS: Retrospective review of 144 hospitalized patients with cancer with a morbilliform rash, recorded testing for serum cytokines (interleukin [IL]-6, IL-10, and tumor necrosis factor [TNF]-α) or elafin, and a dermatology consultation. Rashes were categorized as simple morbilliform rash without systemic involvement or complex morbilliform rash with systemic involvement. RESULTS: Fifty-four of 144 (37.5%) patients died during follow-up. Elevated levels of IL-6, IL-10, and TNF-α were associated with decreased survival. Overall survivals in patients with elevated levels of IL-6, IL-10, and TNF-α were 53.7%, 56.6%, 53.6%, respectively, compared with 85.7%, 82.5% and 83.6%, respectively, in those with lower levels. Patients with increased levels of both IL-6 and TNF-α had a nearly 6-fold increase in mortality (hazard ratio, 5.82) compared with patients with lower levels. LIMITATIONS: Retrospective design, limited sample size, and high-risk population. CONCLUSIONS: Hospitalized patients with cancer with rash and elevated IL-6 and TNF-α were nearly 6 times more likely to die over the course of follow-up. These biomarkers may serve as prognostic biomarkers and therapeutic targets for this high-risk population.

Primary cutaneous T-cell lymphomas other than mycosis fungoides and Sézary syndrome. Part II: Prognosis and management.

Primary cutaneous T-cell lymphomas (CTCLs) other than mycosis fungoides (MF) and Sézary syndrome (SS) encompass a heterogenous group of non-Hodgkin lymphomas with variable clinical courses, prognoses, and management approaches. Given the morphologic and histologic overlap among the CTCL subtypes and other T-cell lymphomas with cutaneous manifestations, thorough evaluation with clinicopathologic correlation and exclusion of systemic involvement are essential prior to initiating therapy. Staging and treatment recommendations vary, depending on the subtype, clinical behavior, and treatment response. Generally, for subtypes in which staging is recommended, Ann Arbor or tumor, node, metastasis staging specific to CTCL other than MF or SS are used. For many subtypes, there is no standard treatment to date. Available recommended treatments range widely, from no active or minimal intervention with skin-directed therapy to aggressive systemic therapies that include multi-agent chemotherapy with consideration for hematopoietic stem cell transplant. Emerging targeted therapies, such as brentuximab, a chimeric antibody targeting CD30, show promise in altering the disease course of non-MF/SS CTCLs.

Primary cutaneous T-cell lymphomas other than mycosis fungoides and Sézary syndrome. Part I: Clinical and histologic features and diagnosis.

Primary cutaneous T-cell lymphomas (CTCLs) are defined as lymphomas with a T-cell phenotype that present in the skin without evidence of systemic or extracutaneous disease at initial presentation. CTCLs other than mycosis fungoides and Sézary syndrome (SS) account for approximately one third of CTCLs and encompass a heterogenous group of non-Hodgkin lymphomas, ranging from indolent lymphoproliferative disorders to aggressive malignancies with a poor prognosis. The spectrum of CTCLs continues to broaden as new provisional entities are classified. Given the morphologic and histologic overlap among CTCLs and other diagnoses, a thorough clinical history, physical evaluation, and clinicopathologic correlation are essential in the work up and diagnosis of these rare entities. This article will summarize the epidemiologic, clinical, pathologic, and diagnostic features of CTCLs other than mycosis fungoides and SS.

A Randomized, Double-Blind, Placebo-Controlled, Split-Face Study of the Efficacy of Topical Epidermal Growth Factor for the Treatment of Melasma.

INTRODUCTION: Melasma is a condition in which patients develop symmetric, reticulated, hyperpigmented macules and patches on the face which is thought to be the result of ultraviolet (UV) exposure and hormonal influences, although the pathogenesis is not completely understood. The topical application of epidermal growth factor has been used as a whitening agent, moisturizer, and an aid for wound healing. In this study, we explore the efficacy of topical EGF in the treatment of melasma. MATERIALS AND METHODS: This was a randomized, double-blind, placebo-controlled, split-face study to determine the efficacy of a topical EGF serum in the treatment of melasma. Fifteen women with a mean age of 44 were randomized to treatment side of the face and applied a topical EGF serum and a placebo twice daily to each designated side of the face for eight weeks. Patient satisfaction was assessed by use of the MelasQoL Questionnaire as well as a patient outcome survey. Subjects were evaluated using the Physician Global Aesthetic Improvement Scale (GAIS) by two board-certified dermatologists. RESULTS: GAIS scores showed an improvement in the melasma in 73.4% of subjects vs 13% improvement for the placebo side. The average MelasQoL questionnaire score decreased from 42 to 33 with 73% of subjects having an improvement in their score. In addition, 73% of subjects reported an improvement in their melasma. No adverse events or side effects were reported with use of the topical serum or placebo. CONCLUSIONS: This study suggests that topical EGF is a safe, noninvasive, and effective treatment for melasma. J Drugs Dermatol. 2018;17(6):970-973.

Management of immune-related cutaneous adverse events with dupilumab.

Immune checkpoint inhibitors (ICI) target the PD-1/PD-L1 and CTLA-4 pathways and allows the immune system to deliver antitumor effects. However, it is also associated with well-documented immune-related cutaneous adverse events (ircAEs), affecting up to 70-90% of patients on ICI. In this study, we describe the characteristics of and patient outcomes with ICI-associated steroid-refractory or steroid-dependent ircAEs treated with dupilumab. Patients with ircAEs treated with dupilumab between March 28, 2017, and October 1, 2021, at Memorial Sloan Kettering Cancer Center were included in this retrospective study, which assessed the rate of clinical response of the ircAE to dupilumab and any associated adverse events (AEs). Laboratory values were compared before and after dupilumab. All available biopsies of the ircAEs were reviewed by a dermatopathologist. Thirty-four of 39 patients (87%, 95% CI: 73% to 96%) responded to dupilumab. Among these 34 responders, 15 (44.1%) were complete responders with total ircAE resolution and 19 (55.9%) were partial responders with significant clinical improvement or reduction in severity. Only 1 patient (2.6%) discontinued therapy due to AEs, specifically, injection site reaction. Average eosinophil counts decreased by 0.2 K/mcL (p=0.0086). Relative eosinophils decreased by a mean of 2.6% (p=0.0152). Total serum immunoglobulin E levels decreased by an average of 372.1 kU/L (p=0.0728). The most common primary inflammatory patterns identified on histopathological examination were spongiotic dermatitis (n=13, 33.3%) and interface dermatitis (n=5, 12.8%). Dupilumab is a promising option for steroid-refractory or steroid-dependent immune-related cutaneous adverse events, particularly those that are eczematous, maculopapular, or pruritic. Among this cohort, dupilumab was well-tolerated with a high overall response rate. Nonetheless, prospective, randomized, controlled trials are warranted to confirm these observations and confirm its long-term safety.

Dermatologic adverse events associated with IDH inhibitors ivosidenib and enasidenib for the treatment of acute myeloid leukemia.

Two novel inhibitors of isocitrate dehydrogenase (IDHi), ivosidenib and enasidenib, significantly improve survival for AML patients with an IDH1 or IDH2 mutation, respectively; however, rash has been reported as a toxicity of IDHi. The objective of our study is to determine the incidence, grade, clinical, and histopathologic features of dermatologic adverse events (DAEs) secondary to IDHi. This study is a retrospective analysis of 169 patients who were treated with either ivosidenib or enasidenib as single agent or in combination with induction chemotherapy at Memorial Sloan Kettering Cancer Center from January 1, 2013 to April 1, 2021. DAEs thought to be possibly, probably, or definitely related to IDHi occurred in 55 of 169 patients [0.32, 95 % CI: 0.25 - 0.40]. Of a total 81 DAEs observed, the most common DAE types were inflammatory dermatoses (27 %); cutaneous vascular manifestations (8%); cutaneous infections (7%); and pruritus (2%). Notably, 50% of infections and 15.5% of rashes were high grade. Knowledge of these findings is critical to optimize the treatment and quality of life of patients with AML on IDHi.

Real-Time Reflectance Confocal Microscopy of Cutaneous Graft-versus-Host Disease Correlates with Histopathology.

Reflectance confocal microscopy (RCM) allows noninvasive, real-time evaluation of the skin at a resolution akin to histopathology (HP), but its application in cutaneous graft-versus-host disease (GVHD) has not been extensively assessed. We describe RCM features of cutaneous GVHD including acute (aGVHD), late acute, chronic (cGVHD; sclerotic and nonsclerotic subtypes), and inactive GVHD and correlate RCM with same-site HP for a subset of patients. Thirty-two adult and pediatric allogeneic hematopoietic cell transplantation (allo-HCT) recipients with cutaneous GVHD received RCM imaging of ≥1 lesions (n = 44), 13 of which necessitated skin biopsy. RCM images were deidentified and assessed by 2 RCM experts blinded to clinical and HP findings to reach a consensus on the features and patterns of the inflammatory dermatoses. Major RCM features (present in ≥65% of lesional sites) and patterns were reported. To determine the correlation between RCM and HP, detection of cellular features and patterns of inflammatory dermatoses were compared using percent agreement and prevalence-adjusted, bias-adjusted kappa estimates. Seven patients with early or late aGVHD (7 lesions) had irregular honeycombing, spongiosis, dermoepidermal junction (DEJ) and dermal inflammation, and melanophages; those with early aGVHD also had hyperkeratosis, dilated vessels, and coarse connective tissue. Both groups had an interface dermatitis pattern. Eighteen patients with nonsclerotic cGVHD (24 lesions) had irregular honeycombing, spongiosis, DEJ and dermal inflammation, dilated vessels, coarse connective tissue, and interface and spongiotic dermatitis patterns. Three sclerotic patients with cGVHD (7 lesions) had irregular honeycombing, DEJ and dermal inflammation with an interface dermatitis pattern. Four patients with inactive GVHD (6 lesions) showed minimal inflammation. RCM and HP had similar detection rates for 6 of 13 features and overall patterns important for diagnosis in 2 patients with late aGVHD (2 lesions; 15%) and 10 with nonsclerotic cGVHD (11 lesions; 85%) necessitating skin biopsy. RCM can detect features commonly reported in cutaneous GVHD and is comparable to HP. Additional characterization of cutaneous GVHD by RCM may enable future use in diagnosing, monitoring, or predicting disease in real time.