Purpose of review
Over the past decade many previously poorly understood vascular malformation disorders have been linked to somatic activating mutations in PIK3CA, which regulates cell survival and growth via activation of the mTOR1-AKT pathway. The goal of this article is to describe and provide an update on the clinical features, complications, and management strategies for the PIK3CA-related overgrowth spectrum (PROS).
Recent findings
PROS encompasses a heterogenous group of disorders with complications related to the tissues harboring the mutation. Vascular malformation syndromes, such as Klippel–Trenaunay syndrome and Congenital Lipomatous Overgrowth Vascular malformations Epidermal nevi and Skeletal abnormalities, have an increased risk of thromboembolic complications, which is accentuated postprocedurally. Asymmetric overgrowth, particularly of limbs, results in a high rate of orthopedic complications. Hypoglycemia screening in the neonatal period and ongoing monitoring for growth failure is recommended in megalencephaly capillary malformation due to its association with multiple endocrinopathies. Recently, sirolimus, an mTOR1 inhibitor, has shown promise in vascular anomalies and now PROS. PIK3CA direct inhibitor, Alpelisib (BYL719), was recently trialed with significant clinical benefit.
Summary
As the pathogenesis of these conditions is better elucidated and targeted treatments are developed, recognizing the clinical features, comorbidities, and evolving therapeutic landscape across the PROS spectrum becomes more crucial for optimization of care.
A papulopustular rash occurs in 45-100% of patients undergoing anti-cancer treatment with epidermal growth factor (EGFR) inhibitors. Although the majority of cases involve the face and upper trunk, ultraviolet radiation has not yet been documented to play a major role in inducing or exacerbating symptoms. We describe a 75-year-old man who was being treated with the EGFR inhibitor erlotinib and developed the characteristic rash on unprotected areas of the trunk after photoexposure, while the protected areas (face and neck) remained uninvolved. This case underscores the importance of sun protection in patients treated with EGFR inhibitors and supports in vitro data showing that EGFR blockade results in altered keratinocyte survival and proliferation in response to ultraviolet radiation.
The genodermatoses encompass a range of inheritable skin diseases that may be associated with significant mortality and long-term morbidity. In the past, options for prenatal diagnosis of these diseases were limited to fetal skin biopsy. As a result of recent leaps made in genetics and molecular biology, DNA-based prenatal diagnosis is now available for an increasing number of genodermatoses, and newer non-invasive methods are being developed that have the potential for tremendous future impact in dermatology. Dermatologists caring for patients with genodermatoses should be aware of the options for screening and prenatal testing and partake in a multi-disciplinary approach to patient care.
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