Outcomes of invasive melanoma of the head and neck treated with Mohs micrographic surgery - A multicenter study.

BACKGROUND: There are no randomized controlled trials to guide surgical margins for invasive head and neck (H&N) melanoma using conventional excision. Mohs micrographic surgery (MMS) has shown improved local recurrence rates and survival for invasive H&N melanomas. OBJECTIVE: Determine local recurrence (LR), nodal recurrence, and distant recurrence rates, and disease specific survival for invasive melanoma of the H&N treated with MMS. METHODS: A retrospective multicenter study of 785 cases of invasive H&N melanoma treated with MMS using frozen sections with melanoma antigen recognized by T-cells 1 immunohistochemical staining was performed to evaluate long-term outcomes over 12-years. RESULTS: 785 melanomas (thickness: 0.3 mm-8.5 mm) were treated with MMS. LR, nodal recurrence, and distant recurrence rates were 0.51% (4/785), 1.0% (8/785), and 1.1% (9/785) respectively. For T1, T2, T3, and T4 tumors LR was 0.16% (1/636), 1.18% (1/85), 2.22% (1/45), and 5.26% (1/19), respectively. Five and 10-year disease specific survival were 96.8% (95% CI 95.0% to 98.5%) and 93.4% (95% CI 88.5% to 98.3%). LIMITATIONS: A nonrandomized retrospective study. CONCLUSION: MMS achieves significant improvements in LR compared to a meta-analysis of historical cohorts of patients treated with conventional excision. MMS should be considered an important surgical option for invasive H&N melanoma.

Assessment of the American Academy of Dermatology diagnostic criteria for pediatric atopic dermatitis and modification into a checkbox form: A cross-sectional study.

BACKGROUND/OBJECTIVES: Diagnostic criteria for atopic dermatitis (AD) are limited in their performance and/or usability. The American Academy of Dermatology (AAD) consensus criteria include hierarchical categories of disease features to improve these metrics but have not been validated. Our objective was to create and validate a checkbox form of the AAD consensus criteria in the pediatric population. METHODS: We performed a cross-sectional study of 100 pediatric patients with AD (n = 58) and diseases in the differential diagnosis of AD (n = 42). RESULTS: Having three or more "Essential," ≥2 "Important," ≥1 "Associated" features of the AAD criteria was optimal for the diagnosis of AD in children. This combination was 91.4% (95% CI, 84.2%-98.6%) sensitive and 95.2% (88.8%-100%) specific. The UK working party criteria and the Hanifin-Rajka criteria had sensitivities of 96.6% (95% CI 91.9%-100%) and 98.3% (95% CI 94.9%-100%) and specificities of 83.3% (95% CI 72.1%-94.6%) and 71.4% (95% CI 57.8%-85.1%), respectively. The AAD criteria had significantly greater specificity than the Hanifin-Rajka criteria (p = .002). CONCLUSIONS: This study represents an important step in validating the AAD consensus criteria and formulating a useable checkbox form for diagnosing AD in the pediatric population.

Basal cell carcinoma with bone invasion: A systematic review and pooled survival analysis.

BACKGROUND: Although basal cell carcinoma (BCC) tends to follow an indolent course, some tumors can exhibit locally aggressive behavior and invade into bone. OBJECTIVE: To analyze all published demographic, clinical, and treatment data on recurrence patterns, disease progression, disease-specific death, and overall mortality of BCC with bone invasion. METHODS: A systematic review and pooled-survival analysis was performed, including case reports and case series of BCC with bone invasion. RESULTS: The study included 101 patients from 70 publications. BCC tumors invading into bone were most often large, neglected tumors located in high-risk face areas. At 5 years, patients had a 30% risk probability of disease recurrence (after negative margins), a 72.1% risk of disease progression or death (with ambiguous margin status), an 18.2% risk of BCC-related death, and a 20.7% overall probability of death. LIMITATIONS: Limitations include the reliance on case reports and series for individual patient data, which has the potential to introduce selection bias. CONCLUSION: The high rate of disease progression and suboptimal 5-year survival rate highlights the poor prognosis of BCC with bone invasion and further underscores the importance of early detection and treatment.

Cost effectiveness of intermediate-risk squamous cell carcinoma treated with Mohs micrographic surgery compared with wide local excision.

BACKGROUND: The efficacy of Mohs micrographic surgery (MMS) in treating cutaneous squamous cell carcinoma has been demonstrated. The cost effectiveness of MMS has rarely been studied to support the perceived higher cost. OBJECTIVE: Perform a cost-effectiveness analysis to determine whether MMS is cost effective over wide local excision (WLE) for Brigham and Women's Hospital tumor stage T2a cutaneous squamous cell carcinoma over a 5-year period. METHODS: A Markov model with a 5-year time horizon was created using variables from published data. Costs in United States dollars and quality-adjusted life-years (QALY) were calculated. RESULTS: MMS was $333.83 less expensive ($4365.57 [95% CI, $3664.68-$6901.66] vs $4699.41 [95% CI, $3782.94-$10,019.31]) than WLE. MMS gained 2.22 weeks of perfect health (3.776 QALY [95% CI, 3.774-3.777] for MMS and 3.733 QALY [95% CI, 3.728-3.777]) over 5 years. The incremental cost-effectiveness ratio was -$7,822.19. MMS had a 99.9% probability of being more cost effective than WLE. Annualized savings of choosing MMS over WLE would be $200 million and over 25,000 QALY. MMS could cost 3.1 times its current rate and remain cost effective. LIMITATIONS: Relied on data from external retrospective sources. CONCLUSION: MMS is less costly and more effective than WLE and should be strongly considered for stage T2a cSCC, given improvements in costs and QALY.

Squamous Cell Carcinoma With Bone Invasion: A Systematic Review and Pooled Survival Analysis.

BACKGROUND: Bone invasion has long been recognized as a poor prognostic indicator for cutaneous squamous cell carcinoma (SCC). Survival analyses of factors associated with SCC with bone invasion have not been published. OBJECTIVE: To analyze all published demographic, clinical, and treatment data for SCC with bone invasion and assess the impact of prognostic variables on disease progression, disease-specific death, and overall mortality. MATERIALS AND METHODS: A systematic review and pooled-survival analysis was performed using individual patient data from case reports. Progression-free survival (PFS), disease-specific survival (DSS), and overall survival (OS) were estimated by Kaplan-Meier analysis. RESULTS: The study included 76 cases of SCC with bone invasion from 49 publications. Recurrent tumors and nonsurgical treatment modality were predictors of disease progression in univariable analysis and tumors of the trunk, head, and neck were predictors of disease progression in multivariable analysis. At 5 years from bone invasion diagnosis, patients had a PFS, DSS, and OS rate of 66.7%, 71.7%, and 66.2%, respectively. CONCLUSION: Cases of SCC with bone invasion had poor DFS, DSS, and OS rates, with worse outcomes imparted to tumors of the trunk, head, and neck.

Current guidelines for the evaluation and management of atopic dermatitis: A comparison of the Joint Task Force Practice Parameter and American Academy of Dermatology guidelines.

Atopic dermatitis (AD) is a chronic pruritic inflammatory disease that commonly presents in the pediatric population. Although definitions and diagnosis of AD have largely been agreed upon, allergists and dermatologists have similar and divergent approaches to the management of AD. This review facilitated integration of the American Academy of Allergy, Asthma & Immunology/American College of Allergy, Asthma & Immunology Joint Task Force 2012 AD Practice Parameter and the 2014 American Academy of Dermatology guidelines to highlight the basic principles of AD management and discuss therapies and management of AD from the distinct perspectives of the allergist and dermatologist.

Cost-Effectiveness Analysis of Ixekizumab vs Etanercept and Their Manufacturer-Recommended Dosing Regimens in Moderate to Severe Plaque Psoriasis.

INTRODUCTION: Biologic therapies have revolutionized the treatment of psoriasis; however, their use is limited by costs. Ixekizumab was more effective than etanercept in the UNCOVER trials, and the Food and Drug Administration (FDA) approved ixekizumab for treating psoriasis. Evaluating the cost-effectiveness of these therapies is crucial for medical decision making and our objective was to determine the cost-effectiveness of various ixekizumab dosing frequencies compared with etanercept. METHODS: We utilized published data from the UNCOVER comparative efficacy trials, including transitional probabilities and treatment response rates, to create a Markov model simulating the clinical course and cost-effectiveness of three treatment algorithms for patients with moderate to severe plaque psoriasis over 60-weeks: (1) ixekizumab every 2 weeks for 12 weeks then every 4 weeks, (2) ixekizumab every 4 weeks throughout the treatment period, (3) biweekly etanercept for 12 weeks then once weekly. We utilized a standard willingness-to-pay (WTP) threshold of $150,000 per quality adjusted life year (QALY) and Medicaid drug acquisition costs for our calculations. RESULTS: Ixekizumab every 4 weeks was $28,681 (USD) less expensive than biweekly etanercept, and $21,375 less expensive, and 0.006 QALY less effective, than ixekizumab every 2 weeks-- a savings of $28.7 and $21.4 million, respectively, per 1,000 patients. A 95.6% cost reduction to $197.83 per dose is required for ixekizumab every 2 weeks to be more cost-effective than every 4 weeks. Biweekly etanercept requires a 29.5% cost reduction ($743.82 per dose) to be competitive with ixekizumab every 4 weeks. DISCUSSION: This cost-effectiveness model utilizes strong input data but is a limited approximation of real-life scenarios. Treatment with ixekizumab every 2 weeks is unlikely to be cost-effective compared with ixekizumab every 4 weeks at current U.S. market prices. Yet, the U.S. FDA approval and manufacturer's recommendation are for ixekizumab every 2 weeks. Accordingly, we suggested selecting biologic therapies using cost-effectiveness analyses.

J Drugs Dermatol. 2017;16(10):964-970.

Atopic dermatitis: therapeutic care delivery: therapeutic education, shared decision-making, and access to care.

Atopic dermatitis (AD) is a chronic skin condition affecting children and adults, with a significant negative impact on patient and caregiver quality of life (QOL). Although effective treatments for AD are available, outcomes are often limited by poor adherence to treatment plans. Effective patient and caregiver education about the disease and its management is a necessary and important component of AD care. Therapeutic patient education (TPE) is a patient-centered process that aims to transfer information and skills necessary to manage and cope with a disease from health care professionals to patients and caregivers. Shared decision making between the health care provider and the patient/caregiver is an integral component of the TPE process and recognizes the importance of both the medical provider's clinical expertise, as well as the patient/caregiver's preferences and experiences regarding their own medical condition and its treatment. TPE programs for patients with AD and their caregivers are typically provided by multidisciplinary teams and utilize a number of different methods and tools to facilitate the transfer of knowledge and skills through both individual care and group-based educational sessions. TPE has been demonstrated to improve outcomes such as AD disease severity, treatment adherence, QOL, and coping with itch. It is important to consider strategies to reduce barriers to cost-effective accessible AD education and treatment.

Atopic dermatitis: phototherapy and systemic therapy.

The majority of atopic dermatitis (AD) patients respond satisfactorily to gentle bathing, frequent moisturizing, and topical medications. Second-line therapies for AD should be used in recalcitrant cases or in patients with uncontrolled disease despite compliance with first-line measures and avoidance of allergens. Recommended advanced therapies include phototherapy, especially narrowband ultraviolet B, systemic immunosuppressants, and a new biologic agent. Few studies have compared head-to-head efficacy of the different immunosuppressant therapies such as cyclosporine, methotrexate, azathioprine and mycophenolate mofetil. Therefore, the agent used is based on provider and patient preferences and can be decided on a case-by-case basis.

Atopic dermatitis: emerging therapies.

Crisaborole and dupilumab represent the first 2 Food and Drug Administration (FDA)-approved therapies for atopic dermatitis (AD) in more than 15 years, and there are many promising drugs currently in development. This new wave of therapeutics capitalizes on the large body of work clarifying the pathogenesis of AD over the last several decades. In particular, type 2 cytokine-driven inflammation and skin barrier dysfunction are key processes underlying AD pathogenesis.

Atopic dermatitis: skin care and topical therapies.

Atopic dermatitis (AD) pathogenesis is strongly influenced by Type 2 innate lymphoid cell and T-helper cell type 2 lymphocyte-driven inflammation and skin barrier dysfunction. AD therapies attempt to correct this pathology, and guidelines suggest suggest basics of AD therapy, which include repair of the skin barrier through bathing practices and moisturizers, infection control, and further lifestyle modifications to avoid and reduce AD triggers.While some patients' AD may be controlled using these measures, inflammatory eczema including acute flares and maintenance therapy in more severe patients are treated with topical pharmacologic agents such as topical corticosteroids, topical calcineurin inhibitors, and, more recently, topical PDE-4 inhibitors. This model of basic skin therapy and, as needed, topical pharmacologic agents may be used to treat the vast majority of patients with AD and remains the staple of AD therapy.

Tumor necrosis factor-induced alopecia: alternative pathology and therapy.

Tumor necrosis factor (TNF) inhibitors are used to treat Crohn disease and psoriasis. Although they are typically well tolerated, adverse effects include the development of alopecia, and paradoxically, psoriatic lesions. We recently described a woman with Crohn disease who developed alopecia and scalp psoriasis during infliximab therapy. After discontinuing infliximab and beginning oral and topical therapies, her alopecia completely resolved. We compared our experience with that of the Craddock et al. who described a woman with Crohn disease and alopecia secondary to adalimumab therapy. Although the authors described typical histopathologic features of TNF inhibitor-induced alopecia, including decreased sebaceous glands, psoriasiform changes, superficial and deep perifollicular infiltrate of peribulbar lymphocytes, prominent plasma cells, and variable eosinophils, we observed atypical findings that included chronic folliculitis and perifolliculitis with dermal scarring and naked hair shafts in the dermis - reminiscent of folliculitis decalvans. Both patients experienced a complete recovery; however, Craddock et al. described continuing adalimumab therapy and using intralesional triamcinolone acetonide whereas our patient discontinued infliximab therapy, used a combination of topical scalp therapies including betamethasone lotion and mineral oil overnight under occlusion, and began oral minocycline. In conclusion, various histopathologies are observed with TNF-inhibitor induced alopecia and multiple, effective, therapeutic avenues exist for this affliction.

CD30+ lymphoproliferative disorder in a patient with metastatic papillary thyroid carcinoma.

Background CD30+ lymphoproliferative disorders are rare and may feature a wide variety of presentations that mimic other conditions. Purpose A man with metastatic papillary thyroid carcinoma to skin who subsequently developed cutaneous anaplastic large cell lymphoma is described. Methods The PubMed medical database was used to search the following terms separately and in combination: ALCL, anaplastic large cell lymphoma ALCL, cutaneous anaplastic large cell lymphoma CALCL, cutaneous t-cell lymphoma CTCL, large t-cell lymphoma LTCL, lymphoproliferative, lymphomatoid papulosis LyP, mimic, papillary, thyroid cancer. Results CD30+ cutaneous anaplastic large cell lymphoma was diagnosed in a man with metastatic papillary thyroid carcinoma based on the temporal, histologic, and immunochemical features of an enlarging lesion. To the best of our knowledge, this is the initial description of a CD30+ lymphoproliferative disorder occurring in a patient with primary carcinoma of the thyroid. Conclusion Cutaneous lesions may present with various morphologies. Our patient had a previous history of metastatic papillary thyroid carcinoma to skin. His new chest lesion was originally suspected to be either an infection or a cutaneous metastasis. Multiple biopsies, not only for microscopic evaluation but also cultures for infectious organisms, were performed. Unexpectedly, a CD30+ lymphoproliferative disorder was diagnosed; subsequently the tumor spontaneously resolved. Therefore, when skin lesions appear that have more than one clinical presentation, it may be prudent for the clinician to collect representative samples of each distinct morphology to assure that an accurate diagnosis is established.

Adenocarcinoma of the colon presenting with scrotal metastasis: case report and review of the literature.

BACKGROUND: The scrotum is an uncommon site for cutaneous metastases from visceral malignancies. PURPOSE: A man with colon cancer, which subsequently developed cutaneous metastasis to the scrotum is described. MATERIALS AND METHODS: PubMed medical database was used to search the following terms separately and in combination: cutaneous metastasis, skin metastasis, scrotal metastasis, scrotum, rectal cancer, and colon cancer. RESULTS: Cutaneous metastasis most frequently occur in the vicinity of the primary tumor. Skin sites of metastatic cancer may include the abdomen, back, chest, face, scalp, and genitalia. The reported patient developed metastatic cutaneous lesions of his colon cancer not only on the abdomen but also on the scrotum. Including our patient, 9 men have been described with metastatic colon or rectal carcinoma localized to the scrotum. The lesions were the presenting sign of malignancy in one man and in the others, the lesions appeared within 24 months of their initial diagnosis of cancer. The skin metastases were pleomorphic; they appeared as papules, nodules and/or cutaneous induration. Survival data was only reported in five of the patients.  However, colon or rectal metastases to the scrotum is a poor prognostic sign with a mean survival time of 11 months. CONCLUSION: Scrotal metastases from carcinoma of the colon or rectum may be the initial presentation of malignancy or herald the discovery of recurrent disease. The morphology of the metastatic tumor is variable: papules, nodules and/or sclerosis. The development of scrotal metastases from colon or rectal carcinoma portends a poor prognosis. Most of the patients succumb to theirmetastatic disease within a year.