Skin cancer risk in CHEK2 mutation carriers.

CHEK2 mutations have been linked with an increased risk of breast cancer. A unique challenge for oncodermatologists and oncologists is in the monitoring and counselling of patients regarding skin cancer risk due to CHEK2 mutation carrier status. In this review, we highlight current information in the literature on the risk of melanoma and non-melanoma skin cancers in CHEK2 mutation carriers. On the molecular level, CHEK2 is a cell cycle regulator that has been linked to cancer pathogenesis, though evidence from clinical studies regarding skin cancer risk has been inconsistent and conflicting. For melanoma, one study has demonstrated a statistically significant twofold risk of melanoma in individuals with CHEK2 mutations, particularly the CHEK2*1100delC variant. Five other studies did not show an association. For non-melanoma skin cancer, fewer data exist, with one prevalence study of CHEK2 mutations in a cohort of patients with basal cell carcinomas. Although there are currently no known studies of CHEK2 and cutaneous squamous cell carcinoma (SCC), data from other disciplines associating CHEK2 with head and neck SCCs are emerging. Overall, while there is currently not enough evidence to make conclusive statements regarding increased risk of melanoma and non-melanoma skin cancers in CHEK2 carriers, a molecular mechanism associating the mutation with cutaneous malignancy pathogenesis is evident, and further work is needed. Patient with CHEK2 mutations may benefit from screening dermatologic examinations with particular attention to skin cancers.

Novel application of high-dose rate brachytherapy for severe, recalcitrant palmoplantar pustulosis.

Palmoplantar pustulosis (PPP) is a chronic pustular dermatitis of the palms and soles, which is frequently associated with significant pruritus and pain, often limiting daily activities. We present the case of a 36-year-old man with severe PPP who had treatment failure with multiple medical therapies but showed marked improvement with high-dose rate brachytherapy. Brachytherapy has the advantage of providing a conformal dose distribution over complex curved surfaces, such as the foot and ankle. Our observations suggest that brachytherapy may be a well-tolerated treatment option for patients with severe, refractory PPP.

Successful multimodality treatment of recalcitrant necrobiotic xanthogranuloma using electron beam radiation and intravenous immunoglobulin.

Necrobiotic xanthogranuloma (NXG) is a rare dermatosis with a poorly understood pathophysiology. Studies comparing treatments for such lesions are limited. We present the case of a patient with a 30-year history of NXG refractory to several individual therapeutic interventions [excision, intravenous immunoglobulin (IVIg), systemic chemotherapies and immunosuppressants, cryotherapy and laser therapy], who ultimately responded to a combination of treatment with electron beam radiation therapy (EBRT) in conjunction with IVIg. This combined treatment resulted in flattening of the NXG lesions and a reduction of symptomatic pruritus within the treatment zone. EBRT may represent a potent treatment for NXG, and formal trials evaluating its effectiveness may yield insights into the management of NXG.

Outcome assessment in cellulitis clinical trials: is telephone follow up sufficient?

The US Food and Drug Administration has scrutinized clinical trial methodology in cellulitis, partly because the definition and timing of cure are debatable. We analysed the validity of telephone self-report as a proxy for in-person follow up in a cellulitis treatment trial comparing cephalexin alone with cephalexin-plus-trimethoprim/sulfamethoxazole. Our results demonstrate poor agreement between these two methods of outcome determination and have implications for future cellulitis clinical trial design and clinical management.