Citations

Abstract Background Immune checkpoint inhibitors (ICIs) directed against PD-1, PD-L1, and CTLA-4 augment antitumor immune responses but may also induce unintended immune activation, resulting in immune-related adverse events (irAEs). Cutaneous manifestations of irAEs are among the most common, ranging from mild eruptions to severe autoimmune blistering disorders (AIBDs). Although bullous pemphigoid (BP) is the most reported ICI-related autoimmune bullous disorder (irAIBD), data on the spectrum, and management of other ICI-associated AIBDs remain limited. Understanding these reactions is crucial to managing treatment interruptions and influencing oncologic outcomes. Objective This study aims to comprehensively characterize ICI-associated irAIBDs by examining demographics, clinical presentation, disease severity, therapeutic approaches, treatment responses, clinical outcomes, and mortality. Methods A single-institution retrospective chart review was conducted, using a text-based database search from 2011–2023. Adult patients (≥18 years) with biopsy-confirmed AIBDs attributed to ICIs were included. Demographic, oncologic, and immunotherapy details, as well as clinical, histopathologic, and immunofluorescence characteristics of AIBDs, were reviewed. Treatment approaches, outcomes, and mortality data were analyzed. Results Forty-four patients with irAIBDs were identified, predominantly representing males (29, 65.9%) with a mean age of 70.4 years (range: 62-80 years). Lung carcinoma (12, 27.2%) and melanoma (9, 20.4%) were the most frequent underlying malignancies, and pembrolizumab (25, 56.8%) was the most common agent. Bullous pemphigoid (BP) accounted for most cases (36, 81.8%), followed by lichen planus pemphigoides (LPP) (6, 13.6%), with one case each of mucous membrane pemphigoid (MMP) and linear IgA bullous dermatosis (LABD). Pruritus was reported in most (42, 9%) patients, and upper (36, 81.8%), lower (32, 72.2%) extremities and the chest (34, 77.2%) were most often involved. Eosinophilic infiltration was present in most (23, 81.8%) of BP cases, and linear IgG and C3 deposition were the predominant immunofluorescence patterns in BP. Most patients received topical (34, 77.2%) and/or systemic corticosteroids (32, 72.7%), while 16 required at least temporary ICI discontinuation. Four BP (4, 9.1%) patients were treated with dupilumab. Other systemic agents used included doxycycline (22, 50%), intravenous immunoglobulin (IVIG) (5, 11.3%), rituximab (6, 13.6%), dapsone (1, 2.2%), mycophenolate mofetil (1, 2.2%), methotrexate (1, 2.2%), and colchicine (1, 2.2%). Three cases with Grade 3 severity necessitated permanent ICI discontinuation. Clinical stabilization (24, 54.5%) or remission of the irAIBD (16, 36.3%) was achieved in most cases. One death (2.2%) was attributed to sepsis in a patient with severe irAIBD. Conclusion ICI-associated AIBDs are uncommon but clinically significant complications. Most patients in our cohort continued ICI therapy during management of their irAIBD, while others required temporary or permanent interruption. These findings highlight the importance of prompt recognition and multidisciplinary management of these uncommon toxicities.

BACKGROUND The use of Mohs micrographic surgery with melanocytic immunostains (MMS-I) for cutaneous melanoma is increasing. OBJECTIVE To assess local recurrence, melanoma-specific death rates in patients with invasive melanoma treated with MMS-I. MATERIALS AND METHODS A single-center retrospective review of patients with invasive melanoma treated with MMS-I from January 2008 to December 2018. RESULTS Three hundred fifty-two patients (359 melanomas) were included. The median age was 71 years; most patients were male (252%; 71.6%). Most tumors were T1a/b (341, 95%), H/N (322; 89.7%), and lentigo maligna subtype (281, 78.3%). At a median follow-up of 4.3 years, local recurrence rates were 1.4% (5) and 0.9% (3) among all-stage and T1a/b tumors, respectively. There were 3 melanoma-related deaths (0.9%). CONCLUSION MMS-I is associated with <1% risk of local recurrence and disease-specific mortality for T1a/b melanomas.

BACKGROUND While increasing evidence supports the safety and effectiveness of immunohistochemistry-assisted Mohs micrographic surgery (MMS) for superficially invasive melanoma, there is a paucity of the literature investigating its effect on final defect size. OBJECTIVE To evaluate the tissue sparing effect of MMS for melanoma. MATERIALS AND METHODS Three hundred and twenty-eight patients with early-stage (T1a/T1b) cutaneous melanomas treated with MMS from January 2008 to December 2018 were evaluated. Measured defect sizes after Mohs tumor extirpation were compared with anticipated defect size that would result from standard-margin wide local excision (WLE). Average actual versus anticipated defect areas were compared using a paired t-test (95% confidence intervals). RESULTS The following groups demonstrated a significantly smaller defect area for MMS-treated tumors when compared with anticipated standard-margin WLE defect: All tumors combined (13.8 cm2 vs 10.4 cm2, p < .001), tumors requiring 1 stage (13.6 cm2 vs 10.1 cm2, p < .001), and tumors requiring 2 stages (13.2 cm2 vs 10.5 cm2, p = .004). The majority of patients (83.5%, n = 274) achieved clear margins with 1 stage. CONCLUSION Immunohistochemistry-assisted MMS for early-stage invasive melanoma is associated with smaller final defect size and overall tissue sparing effect compared with standard WLE margins.

AbstractBackgroundBier anemic spots, cyanosis with urticaria‐like eruption (BASCULE) syndrome is a recently described entity with episodic urticarial lesions and white anemic halos on a background of erythrocyanosis, commonly affecting the lower extremities. Possible association with autonomic dysfunction remains poorly understood. Existing publications are limited, but the condition is suggested as highly underrecognized.ObjectiveTo further characterize clinical and epidemiologic data for BASCULE syndrome.MethodsWe performed an IRB‐approved retrospective chart review on patients with BASCULE syndrome evaluated at Mayo Clinic from April 2021 to November 2022.ResultsA total of 17 patients were identified (13 female, 4 male). Median age of onset was 12 years (range 9–17). Lower extremities were involved in all patients (17). Most patients were symptomatic with pruritus (8) or burning pain (8); three were asymptomatic. Triggers were standing (11), hot showers or hot environments (7), or no clear trigger (4). Autonomic dysfunction was present in 10 patients. Treatment responses were observed from propranolol (3) and high‐dose cetirizine (1).ConclusionNovel epidemiologic data from 17 pediatric and young adult patients with BASCULE syndrome further supports an association with autonomic dysfunction and suggests a higher prevalence than previously acknowledged.

Abstract: 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.

Abstract Background Reactive granulomatous dermatitis (RGD) is an umbrella term used to describe interstitial granulomatous dermatitis (IGD), palisaded neutrophilic and granulomatous dermatitis (PNGD), and interstitial granulomatous drug eruption (IGDR). Objective The aim of this study was to describe systemic associations of RGD, explore possible associations between histopathologic findings and systemic RGD associations and determine clinical relevance of RGD subtypes. Methods We retrospectively studied clinical and histopathologic characteristics of patients with RGD from 1990 through 2020. Results Of 65 patients with RGD (41 women, 24 men; median age at diagnosis, 62 years), 37 had IGD, 26 had PNGD, and 2 had IGDR. Fifty patients (76.9%) had an associated systemic condition; rheumatologic conditions were identified for 34 (52.3%) patients. The associated systemic condition occurred before RGD in approximately 75% of patients. Statistical analyses did not show significant associations between specific subtypes of RGD and systemic diseases or treatment response, and specific histopathologic findings were not predictive of an associated systemic disease. Conclusions Although most patients with RGD had an associated systemic condition, subtypes of RGD did not correlate with systemic associations, lending support to the use of the umbrella term RGD .

Management of PD-1 blockade resistance in metastatic melanoma (MM) remains challenging. Immunotherapy or chemotherapy alone provides limited benefit in this setting. Chemo-immunotherapy (CIT) has demonstrated favorable efficacy and safety profiles in lung cancer. Our pre-clinical study showed that in MM patients who have failed PD-1 blockade, the addition of chemotherapy increases CX3CR1+ therapy-responsive CD8+ T-cells with enhanced anti-tumor activity, resulting in improved clinical response. Here, we examined the clinical outcomes of CIT in MM patients after PD-1 blockade failure and the treatment-related changes in CX3CR1+ therapy-responsive CD8+ T-cells. We reviewed MM patients seen between January 2012 and June 2018 who failed anti-PD-1-based therapy and received subsequent CIT, immune checkpoint inhibitors (ICI) or chemotherapy alone. Overall survival (OS), objective response rate (ORR), event-free survival (EFS), and toxicities were assessed. Among 60 patients, 33 received CIT upon disease progression on PD-1 blockade. At a median follow-up of 3.9 years, the CIT group had a median OS of 3.5 years [95% confidence interval (CI) 1.7–NR] vs. 1.8 years (95% CI 0.9–2; P = 0.002) for those who received subsequent ICI (n = 9) or chemotherapy alone (n = 18), with ORR of 59% vs. 15% (P = 0.0003), respectively. The median EFS was 7.6 months (95% CI 6–10) following CIT vs. 3.4 months (95% CI 2.8–4.1; P = 0.0005) following ICI or chemotherapy alone. Therapy-responsive CX3CR1+CD8+ T-cells showed dynamic increase with successful CIT. CIT showed favorable clinical outcomes and acceptable safety profile in PD-1 blockade-resistant patients. CX3CR1+CD8+ therapy-responsive T-cells can be potentially used for monitoring disease response to CIT.