BRAF inhibitor (BRAFi) therapy is associated with the induction of neoplasia, most commonly cutaneous squamous cell carcinoma (cuSCC). This toxicity is explained in part by “paradoxical ERK activation,” or the hyperactivation of ERK signaling by BRAFi in BRAF wild-type cells. However, the rate of cuSCC induction varies widely among BRAFi. To explore this mechanistically, we profiled paradoxical ERK activation by vemurafenib, dabrafenib, encorafenib (LGX818), and PLX8394, demonstrating that vemurafenib induces ERK activation the greatest, while dabrafenib and encorafenib have higher “paradox indices”, defined as the pERK activation EC80 divided by the IC80 against A375, corresponding to wider therapeutic windows for achieving tumor inhibition without paradoxical ERK activation. Our results identify differences in the paradox indices of these compounds as a potential mechanism for the differences in cuSCC induction rates and highlight the utility of using ERK activity as a biomarker for maximizing the clinical utility of BRAFi.

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Atopic dermatitis (AD) is a chronic, pruritic skin disease often complicated by bacterial superinfection affecting 10.7% of American children. The pathogenesis involves a skin barrier breakdown in addition to dysfunctional innate and adaptive immune response, including an unbalanced increase in T-helper 2 cells and hyperimmunoglobulinemia E. The increased numbers of T-helper 2 cells are involved in stimulating the production of immunoglobulin E and eosinophilia by releasing interleukin-4, -5, and -13 as well as in decreasing protection against bacterial superinfection by releasing interleukin-10. The current Food and Drug Administration-approved symptomatic treatment for AD includes topical ointments, topical and systemic corticosteroids, topical immunomodulant therapy, antibiotics, and phototherapy, but there are not approved targeted therapies or cures. By presenting a case of an 8-year-old African-American boy, this case report supports novel therapy of moderate-to-severe AD with apremilast, a phosphodiesterase type 4 inhibitor. Apremilast has recently completed the phase 2 clinical trial (NCT02087943) for treatment of AD in adults. This case report illustrates the potential for apremilast as a treatment for AD in children, where there is a great need for safe and effective medications.

“Skin popping” is a method of injecting illicit drugs into the skin. There are numerous acute and chronic complications associated with skin popping. We present a case of a 48-year-old, African-American female patient with 40 - 60 hyperpigmented, fibrotic, depressed, round papules and plaques on the extremities, which were incidentally noticed during a clinic visit for her acne vulgaris. Skin popping scars are important clues for possible drug abuse. Healthcare practitioners should be aware of and recognize the lesions associated with this practice so further testing can be performed if clinically indicated. Recognition of the lesions and thus earlier treatment of the complications could prevent the complications of skin popping in the skin and other organs.

Bilateral infarction of the superior cerebellar arteries with sparing of the rest of the posterior circulation, particularly the posterior cerebral arteries, is an uncommon finding in neurological practice. Most commonly, the deficits of the superior cerebellar arteries and posterior cerebral arteries occur together due to the close proximity of their origins at the top of the basilar artery. A patient was transferred to the neurological intensive care unit with a history of recent-onset falls from standing, profound hypertension, dizziness, and headaches. The neurological exam revealed cerebellar signs, including dysmetria of the right upper extremity and a decreased level of consciousness. Computed tomography of the head and neck revealed decreased attenuation throughout most of the cerebellar hemispheres suggestive of ischemic injury with sparing of the rest of the brain. Further investigation with a computed tomography angiogram revealed a fetal-type posterior cerebral artery on the right side that was providing collateral circulation to the posterior brain. Due to this embryological anomaly, the patient was spared significant morbidity and mortality that would have likely occurred had the circulation been more typical of an adult male.