The diverse landscape of dermatologic toxicities of non-immune checkpoint inhibitor monoclonal antibody-based cancer therapy.

BACKGROUND: Since their first approval 25 years ago, monoclonal antibodies (mAbs) have become important targeted cancer therapeutics. However, dermatologic toxicities associated with non-immune checkpoint inhibitor (non-ICI) mAbs may complicate the course of cancer treatment. Data on the incidence and types of these reactions are limited. METHODS: A comprehensive review was conducted on dermatologic toxicities associated with different classes of non-ICI mAbs approved for treatment of solid tumors and hematologic malignancies. The review included prospective Phase 1, 2, and 3 clinical trials; retrospective literature reviews; systematic reviews/meta-analyses; and case series/reports. RESULTS: Dermatologic toxicities were associated with several types of non-ICI mAbs. Inflammatory reactions were the most common dermatologic toxicities, manifesting as maculopapular, urticarial, papulopustular/acneiform, and lichenoid/interface cutaneous adverse events (cAEs) with non-ICI mAbs. Immunobullous reactions were rare and a subset of non-ICI mAbs were associated with the development of vitiligo cAEs. CONCLUSION: Dermatologic toxicities of non-ICI mAbs are diverse and mostly limited to inflammatory reactions. Awareness of the spectrum of the histopathologic patterns of cAE from non-ICI mAbs therapy is critical in the era of oncodermatology and oncodermatopathology.

Periorbital edema associated with alpelisib.

Alpelisib is an alpha isoform-specific phosphatidylinositol 3-kinase (PI3K) inhibitor approved for use in the treatment of hormone receptor (HR)-positive, human epidermal growth factor receptor (HER2)-negative metastatic breast cancer in combination with fulvestrant. Hyperglycemia, rash, and gastrointestinal upset are the most commonly reported adverse events associated with alpelisib. Although rash is a known on-target effect of alpelisib, patients typically present with a morbilliform rash. We describe two cases of periorbital edema associated with alpelisib. We discuss the clinical findings, management, and prognosis of this unique reaction. These cases highlight the importance of early involvement of dermatology to manage adverse cutaneous events associated with alpelisib.

Actinobacillus actinomycetemcomitans isolated from a case of cutaneous botryomycosis.

Cutaneous botryomycosis is an uncommon chronic suppurative bacterial skin infection that can mimic a fungal infection both clinically and histopathologically. Causative bacteria, most commonly Staphylococcus aureus, aggregate to form characteristic granules. We report the case of a 52-year-old black man who developed cutaneous botryomycosis of the hand following trauma. Routine bacterial cultures grew S aureus and Actinobacillus actinomycetemcomitans, a fastidious gram-negative bacillus known to cause periodontal disease, endocarditis, and actinomycosislike soft tissue infections. Despite culture-proven eradication of S aureus with long-term appropriate antibiotic therapy, the lesion, resolved only after fluoroquinolone treatment directed against A. actinomycetemcomitans, suggesting that A. actinomycetemcomitans was of etiologic significance.

Celecoxib, a cyclooxygenase 2 inhibitor as a potential chemopreventive to UV-induced skin cancer: a study in the hairless mouse model.

OBJECTIVE: To assess the preventive effect of a cyclooxygenase 2 inhibitor, celecoxib (Celebrex; G.D. Searle & Co, Skokie, Ill), in UV-induced skin cancer in hairless mice. DESIGN: Randomized dose-response study. A total of 75 SKH-HR-1 female hairless mice, aged 2 months, were randomized into control, low-dose (200 mg twice daily human dose equivalent), and high-dose (400 mg twice daily human dose equivalent) celecoxib treatment groups. Animals received 1 J/cm(2) daily (5 d/wk) total irradiation. The animals were evaluated weekly for appearance of tumors, and the data were analyzed with respect to tumor latency period and tumor multiplicity using statistical software and Wilcoxon rank sum analyses, respectively. Prostaglandin E(2) levels in the blood and skin were assessed in each group. SETTING: Veterans Affairs Medical Center, Research and Dermatology Services. INTERVENTION: Animals received restricted diets containing the Food and Drug Administration-approved human equivalent doses of 200 mg (low dose) and 400 mg (high dose) of celecoxib twice daily. Controls received no drug. Tumors were induced in all animals with an equivalent UV dose. MAIN OUTCOME MEASURES: Animals were evaluated weekly for the appearance of tumors, and data were analyzed with regard to tumor latency period and tumor multiplicity. Constitutive prostaglandin E(2) levels in blood and epidermis were assessed in each group. RESULTS: Low doses and high doses of celecoxib significantly lengthened the tumor latency period (P<.03 and P<.003, respectively) and reduced tumor multiplicity (P<.005 and P<.001, respectively) compared with controls. There were no differences in the constitutive levels of blood or epidermal prostaglandin E(2) in the low- or high-dose treated animals compared with controls when analyzed at study termination. CONCLUSIONS: Celecoxib is an effective and safe chemopreventive agent in UV carcinogenesis. The epidemiologic, laboratory, and animal studies of the influence of celecoxib on cancer incidence and its low association with systemic adverse effects have led to a potentially new therapeutic approach for the prevention of skin cancer.