Mariam B. Totonchy

Nivolumab-associated vitiligo-like depigmentation in a patient with acute myeloid leukemia: A novel finding

Programmed cell death–1 receptor (PD-1) inhibitors enhance the antitumoral immune response via immune checkpoint inhibition. In a healthy immune system, the binding of ligands to PD-1 induces T-cell inactivation and prevents overactive immune responses. However, PD-1 ligands are also expressed by a variety of tumors, including melanomas, renal cell carcinomas, and brain tumors, in an effort to evade the host immune response. Although immune checkpoint inhibitors have revolutionized care for cancer patients, new cutaneous and systemic toxicities are still being discovered. Nivolumab is a humanized IgG4 anti–PD-1 monoclonal antibody that is currently approved by the US Food and Drug Administration for the treatment of melanoma, non–small cell lung cancer, renal cancer, and classical Hodgkin lymphoma.1 Several adverse effects of immune-targeting therapies are described and are referred to as immune-related adverse events (irAEs). Systemic irAEs include enterocolitis, pneumonitis, hepatitis, nephritis, hypophysitis, and autoimmune thyroid disease. In addition, dermatologic toxicity is the most common irAE of checkpoint inhibitors and ranges from pruritus and mild dermatoses to severe reactions including Stevens-Johnson syndrome and toxic epidermal necrolysis.2 Vitiligo-like depigmentation is well described in melanoma patients receiving immunotherapy with PD-1 inhibitors and may be associated with favorable outcomes.3 Here we report a case of vitiligo-like depigmentation in a patient with acute myeloid leukemia (AML) receiving nivolumab as part of a phase II clinical trial. To our knowledge, this is the first reported case of vitiligo-like depigmentation associated with PD-1 inhibitor treatment in a patient with a nonmelanoma malignancy. Previous reports of PD-1 inhibitor–associated vitiligo-like depigmentation have been exclusively described in patients being treated for melanoma.

UV-Based Therapy

UV phototherapy has a long history of use for the treatment of select diseases in dermatology. Its use has evolved into more effective and targeted modalities, including psoralen + UV-A photochemotherapy, narrowband UV-B, excimer laser, and UV-A1 phototherapy. With its proven record of efficacy and safety, UV phototherapy is an excellent option in the treatment of an ever-growing number of skin conditions.

Sirolimus-Associated Rapid Progression of Leg Ulcers in a Renal Transplant Recipient

Sirolimus-Associated Rapid Progression of Leg Ulcers in a Renal Transplant Recipient Sirolimus is a mammalian target of rapamycin (mTOR) inhibitor indicated for therapeutic immunosuppression following solid organ transplantation. It has also been shown to decrease skin cancer risk in transplant recipients. We present a case of rapid progression and de novo formation of leg ulcers in a renal transplant recipient coincident with sirolimus therapy.

Koebnerization of Hailey–Hailey disease into a cutaneous drug eruption of acute generalized exanthematous pustulosis associated with systemic symptoms

We describe a 65‐year‐old Caucasian female with well‐controlled Hailey–Hailey disease (HHD) who developed acute generalized exanthematous pustulosis (AGEP) with severe systemic symptoms. Despite sparing of the patients intertriginous skin, histopathologic evidence of HHD was observed in all biopsies, suggestive of a unique koebernization phenomenon of HHD to areas of cutaneous drug eruption. While internal organ involvement is less commonly reported in AGEP, there are an increasing number of patients with signs and symptoms suggestive of an AGEP/drug reaction with eosinophilia and systemic symptoms (DRESS) spectrum of cutaneous drug disorders. Early diagnosis of patients with AGEP and systemic symptoms is critical so that these patients may receive prompt and aggressive systemic therapy to decrease the risk of end organ damage and improve overall morbidity and mortality.

Bullous disorders associated with anti-PD-1 and anti-PD-L1 therapy: A retrospective analysis evaluating the clinical and histopathologic features, frequency, and impact on cancer therapy

Background: Bullous disorders associated with anti–programmed cell death 1 (PD‐1)/programmed cell death ligand 1 (PD‐L1) therapy are increasingly reported and may pose distinct therapeutic challenges. Their frequency and impact on cancer therapy are not well established. Objective: To evaluate the clinical and histopathologic findings, frequency, and impact on cancer therapy of bullous eruptions due to anti–PD‐1/PD‐L1 therapy. Methods: We retrospectively reviewed the medical records of patients evaluated by the oncodermatology clinic and consultative service of Yale New Haven Hospital from 2016 to 2018. Results: We identified 9 of 853 patients who developed bullous eruptions (˜1%) that were treated with an–PD‐1/PD‐L1 therapy at our institution during the study period: 7 presented with bullous pemphigoid, 1 presented with bullous lichenoid dermatitis, and 1 presented with linear IgA bullous dermatosis in the context of vancomycin therapy. In all, 8 patients required systemic steroids, 5 required maintenance therapy, and 8 required interruption of immunotherapy. All 9 patients had an initial positive tumor response or stable disease, but 4 went on to develop disease progression. Limitations: This was a retrospective study from a single tertiary care center. Conclusions: Bullous disorders developed in approximately 1% of patients treated with anti–PD‐1/PD‐L1 therapy at our institution and frequently resulted in interruption of immune therapy and management with systemic corticosteroids and occasionally steroid‐sparing agents.

A case of subungual tumors of incontinentia pigmenti: A rare manifestation and association with bipolar disease

IP: incontinentia pigmenti NF-kB: nuclear factor-kB STIPs: subungual tumors of incontinentia pigment

Emerging concepts and recent advances in basal cell carcinoma

Basal cell carcinoma (BCC) is the most common malignancy worldwide, arising from non-keratinizing cells within the basal layer of the epidermis. The incidence of BCC continues to rise annually, increasing the burden of management of these carcinomas and the morbidity associated with their treatment. While surgical interventions such as Mohs micrographic surgery and surgical excision are the standard of care and yield the highest cure rates, the number of non-surgical interventions approved for the treatment of BCC continues to expand. We review various surgical and non-surgical approaches to the treatment of BCC, focusing on targeted molecular therapies that are approved for locally advanced or recurrent disease.