Kathryn Ciccolini

Autoimmune Bullous Skin Disorders with Immune Checkpoint Inhibitors Targeting PD-1 and PD-L1

Bullous pemphigoid is a rare immune-related adverse event after anti–PD-1/PD-L1 immune checkpoint treatment and may be mediated by both T-cell and B-cell responses. Early referral to dermatology for accurate diagnosis and management is recommended. Monoclonal antibodies (mAb) targeting immune checkpoint pathways such as cytotoxic T-lymphocyte–associated protein 4 (CTLA-4) and programmed death 1 (PD-1) may confer durable disease control in several malignancies. In some patients, immune checkpoint mAbs cause cutaneous immune-related adverse events. Although the most commonly reported cutaneous toxicities are mild, a subset may persist despite therapy and can lead to severe or life-threatening toxicity. Autoimmune blistering disorders are not commonly associated with immune checkpoint mAb therapy. We report a case series of patients who developed bullous pemphigoid (BP), an autoimmune process classically attributed to pathologic autoantibody formation and complement deposition. Three patients were identified. Two patients developed BP while receiving the anti–PD-1 mAb nivolumab, and one while receiving the anti–PD-L1 mAb durvalumab. The clinicopathologic features of each patient and rash, and corresponding radiologic findings at the development of the rash and after its treatment, are described. Patients receiving an anti–PD-1/PD-L1 mAb may develop immune-related BP. This may be related to both T-cell– and B-cell–mediated responses. Referral to a dermatologist for accurate diagnosis and management is recommended. Cancer Immunol Res; 4(5); 383–9. ©2016 AACR.

Overview and Management of Dermatologic Events Associated with Targeted Therapies for Medullary Thyroid Cancer

BACKGROUND Treatment options for patients with advanced or metastatic medullary thyroid cancer (MTC) have, in recent years, expanded with the approval of two tyrosine kinase inhibitors (TKIs): vandetanib and cabozantinib. Other agents, including TKIs, are under clinical investigation for MTC. Although patients treated with TKIs are at risk of developing dermatologic adverse events (AE), these untoward events may be mitigated through AE-driven algorithms. SUMMARY AE-driven algorithms combine effective nonpharmaceutical and pharmaceutical treatment modalities implemented by a multidisciplinary effort that incorporates nursing interventions, patient education, and referrals to pain-management specialists, podiatrists, and dermatologists, as appropriate. Effective AE prevention and management reduce the need for dose interruptions and modifications, allowing patients the opportunity to derive the maximal benefit from TKI therapy, while maintaining quality of life. CONCLUSIONS Optimal use of targeted therapies in the treatment of MTC depends on careful patient selection, interdisciplinary communication, and patient education and encouragement to enhance compliance and safety, optimize consistent dosing, and maximize the use of effective therapies.

Incidence and risk of xerosis with targeted anticancer therapies

BACKGROUND Many targeted therapies used in the treatment of cancer can lead to the development of xerosis, but the incidence and relative risk of xerosis have not been ascertained. OBJECTIVE We conducted a systematic review and metaanalysis of clinical trials, to ascertain the incidence and risk of developing xerosis after taking anticancer drugs. METHODS The PubMed (1966-October 2013), Web of Science (January 1998-October 2013), and American Society of Clinical Oncology abstracts (2004-2013) databases were searched for clinical trials of 58 targeted agents. Results were calculated using random or fixed effects models. RESULTS The incidences of all- and high-grade xerosis were 17.9% (95% confidence interval [CI]: 15.6-20.4%) and 1.0% (95% CI: 0.9-1.5%), respectively. The risk of developing all-grade xerosis was 2.99 (95% CI: 2.0-4.3), and it varied across different drugs (P < .001). LIMITATIONS The reporting of xerosis may vary among clinicians and institutions, and the incidence may be affected by age, concomitant medications, comorbidities, and underlying malignancies or skin conditions. CONCLUSION Patients receiving targeted therapies have a significant risk of developing xerosis. Patients should be counseled and treated early for this symptom to prevent suboptimal dosing and quality of life impairment.

Dermatologic Reactions to Targeted Therapy: A Focus on Epidermal Growth Factor Receptor Inhibitors and Nursing Care

Cancer treatments usually have side effects of bone marrow depression, mucositis, hair loss, and gastrointestinal issues. Rarely do we think of skin side effects until patients have been treated successfully with epidermal growth factor receptor inhibitors (EGFRi). Those reactions include papulopustular rash, hair changes, radiation dermatitis enhancement, pruritus, mucositis, xerosis, fissures, and paronychia. This article discusses the common skin reactions seen when using EGFRi and presents an overview of skin as the largest and important organ of the body, including an overview of skin assessment, pathophysiology of the skin reactions, nursing care involved, and introduction to oncodermatology.

Inflammatory dermatoses, infections, and drug eruptions are the most common skin conditions in hospitalized cancer patients

Background: Dermatologic conditions cause morbidity and mortality among hospitalized cancer patients. An improved understanding is critical for implementing clinical and research programs in inpatient oncodermatology. Objective: To characterize inpatient dermatology consultations at a large comprehensive cancer center. Methods: Retrospective database query of new admissions and medical record review of initial inpatient dermatology consultations comparing inpatients consulted and not consulted during January‐December 2015. Results: In total, 412 of 11,533 inpatients received 471 dermatology consultations (54% male, median age 59.5 years). Patients with hematologic cancers were 6 times more likely to receive dermatologic consultations compared with nonhematologic cancers (odds ratio 6.56, 95% confidence interval 5.35–8.05, P < .0001). Patients consulted by a dermatologist had a significantly longer length of stay than inpatients not consulted by dermatology (median 11 vs 5 days, P < .0001). Among the 645 dermatologic conditions diagnosed, the most common categories were inflammatory diseases, infections, and drug reactions; the most frequent conditions were contact dermatitis, herpes zoster, and chemotherapy‐induced drug eruptions. Limitations: The studys retrospective nature and single‐institution setting are potential limitations. Conclusion: Hematologic malignancies are a significant risk factor for dermatology inpatient consultations. A significantly longer length of stay was associated with dermatology consultations, suggesting high comorbidities in these patients. Increased dermatologic care of these inpatients might improve quality of life, dermatologic health, and ability to receive anticancer agents.

The Role of Oncodermatology in the Care of Patients Receiving Cancer Therapy

OBJECTIVE To review the emerging sub-specialty of oncodermatology and the role of oncodermatology nurses as facilitators of interprofessional collaboration between the oncology team and the dermatology team. DATA SOURCES Journal articles indexed on the National Library of Medicine database. CONCLUSION The complexity of cancer care with new cancer therapies and their associated dermatologic adverse events profiles benefit from a collaborative, interprofessional approach between dermatology and oncology in the care of the patient with cancer. IMPLICATIONS FOR NURSING PRACTICE Oncodermatology nurses are in roles that can facilitate interprofessional collaboration, optimizing the care of patients with cancer.

Checkpoint Inhibitors: Common Immune-Related Adverse Events and Their Management

BACKGROUND: Immunotherapy, specifically the use of checkpoint inhibitors, offers patients with cancer an alternative to chemotherapy, targeting different pathways to destroy cancer cells. The side effects of immunotherapies, as well as their impact on normal tissue, need to be assessed and managed based on their mechanisms of action. OBJECTIVES: This article presents an overview of immune‐related adverse events (AEs). METHODS: Common immune‐related toxicities, as well as rare and refractory toxicities, are reviewed. FINDINGS: Immunotherapy treatment is an option for many patients with cancer, and nurses must understand the distinct side effect profile of these agents. Prompt identification and expert management are the cornerstones of success when dealing with immune‐related AEs, and oncology nurses play a key role in improving patient care.

Nursing Best Practice Referral Algorithm for the Early Detection of Mycosis Fungoides

Background Mycosis fungoides is the most common type of cutaneous T-cell lymphoma (CTCL), yet is frequently misdiagnosed and perplexing to those who may not be familiar with the disease process and management. Therefore, nursing involvement in the interdisciplinary referral process from a generalist to a specialist is key to improving patient outcomes in the early detection of mycosis fungoides. Purpose of Study/Inquiry This manuscript elucidates the nursing role in the referral process of patients with CTCL, the importance of clinical grasp in the interdisciplinary approach for referrals, and factors to consider when customizing patient care plans. Methodology/Methods and Analytical Approach In effort to elucidate the nursing role in the obscure referral process in this unique patient population, an evidence-based approach is utilized to create a standardized method of care coordination to improve patient outcomes. Harvesting this method improves clinical care coordination and can result in a powerful tool to streamline the referral process. Findings/Implications An evidence-based standardized algorithm has been created for the nurse in the generalist office referring to patients with cutaneous lymphoma to dermatology specialists. Furthermore, this manuscript will strengthen nursing clinical knowledge, define the referral process, and improve patient outcomes in the transfer of care for patients with CTCL.

Reply to: “Skin moisturization for xerosis related to targeted anticancer therapies”

To the Editor: We would like to thank Drs Gisondi and Girolomoni for their comments regarding the treatment of xerosis. We agree that salicylic acid and ammonium lactate should be used judiciously, and only on areas of hyperkeratosis without evident dermatitis, as is commonly seen in patients treated with targeted therapies. Indeed, targeted therapies lead to aberrant keratinocyte proliferation, migration, differentiation, and adhesion, all of which result in xerotic skin with retention hyperkeratosis. Patients receiving targeted therapies who develop xerosis and hyperkeratosis require rapid resolution of findings, because progression into a grade 3 adverse event dictates interruption, dose decrease, or discontinuation of life-prolonging anticancer treatments. Therefore, according to the treatment algorithm in Fig 4 of our manuscript, salicylic acid or ammonium lactate is to be used in conjunction with emollients and topical steroids to eczematous areas. These treatment recommendations are based on clinical experience at a dermatology referral clinic for patients on targeted therapies started in 2006. While emollients and humectants are essential to treatment of xerosis, keratolytics also play an important role, especially in this patient population. It is critical to understand that targeted anticancer treatments uniquely alter skin integrity. Xerosis as a consequence of a targeted therapy is distinct from atopic skin. For example, epidermal growth factor inhibitors impede normal keratinocyte differentiation, leading to accelerated differentiation and cornification, as evidenced by increased keratin 1 and STAT3 in basal keratinocytes and loss of the basket-weave arrangement in the stratum corneum. Furthermore, these therapies increase cell-to-cell attachments via increased desmosome assembly and upregulate adhesion molecules such as cadherins, all of which result in skin barrier alterations, with consequent recruitment of inflammatory cells and clinical findings of dermatitis and pruritus. Consequently, the keratolytic effect of salicylic acid and ammonium lactate to resultant hyperkeratotic lesions can suppress excessive corneocyte adhesion and facilitate the delivery of emollients and topical steroids. Regarding the authors’ recommendation to discuss clinical criteria to discern eczema from xerosis, we concur that the distinction is significant. The goal of our paper was to assess the incidence of xerosis with targeted therapies. Abundant clinical and experimental data on the diagnosis and treatment of xerosis and dermatitis are published