Dissipation of body heat, essential to human life, is largely achieved through sweating. If sweating does not occur normally-as in patients with hypohidrosis (reduced sweating) or anhidrosis (lack of sweating)-the ability to dissipate heat via evaporative mechanisms is overwhelmed. Body temperature may rise, leading to heat-related illness, including heat intolerance, hyperthermia, heat exhaustion, heat stroke, and even death. In patients seen by a dermatologist, anhidrosis may underly and contribute to their symptoms and signs but may be difficult to detect given a limited availability of tools to measure anhidrosis. An association between anhidrosis and skin symptoms including flushing syndromes (eg, facial flushing and erythromelalgia) and widespread skin symptoms (eg, itching, burning, numbness, or tingling, and paresthesias) has recently been described. This review explores the existing dermatologic literature on anhidrosis including clues to the pathophysiology of these disorders, its relationship to skin diseases and symptoms, the tests currently available, and approaches to management. Recognition of an underlying anhidrosis by dermatologists may be important for providing optimal management for patients with heat-related symptoms.
In this case report, we describe the difficulty in finding a suitable treatment for a nine-year-old girl with erythromelalgia. Initially, she could only find pain relief through immersion of her hands and feet in buckets of cool water. Her pain did not respond to outpatient treatments, and she was ultimately admitted to the hospital for pain management. Many different medications and modalities were tried over the course of several weeks in the hospital. Finally, she received the most benefit from 10% compounded capsaicin cream administered under general anesthesia with regional analgesia for post-application pain. Over the course of several years, exacerbations of her pain were treated with additional applications of 10% capsaicin cream, with each application providing relief for an increased duration. Her severe pain flares eventually went into remission after several years. Today, after more than a decade following her initial presentation, she is a successful college student and is taking no medications for her erythromelalgia.
Sheets PL, Jackson JO, Waxman SG, Dib-Hajj SD, Cummins TR
The Journal of physiology •
Mutations in the TTX-sensitive voltage-gated sodium channel subtype Nav1.7 have been implicated in the painful inherited neuropathy, hereditary erythromelalgia. Hereditary erythromelalgia can be difficult to treat and, although sodium channels are targeted by local anaesthetics such as lidocaine (lignocaine), some patients do not respond to treatment with local anaesthetics. This study examined electrophysiological differences in Nav1.7 caused by a hereditary erythromelalgia mutation (N395K) that lies within the local anaesthetic binding site of the channel. The N395K mutation produced a hyperpolarized voltage dependence of activation, slower kinetics of deactivation, and impaired steady-state slow inactivation. Computer simulations indicate that the shift in activation is the major determinant of the hyperexcitability induced by erythromelalgia mutations in sensory neurons, but that changes in slow inactivation can modulate the overall impact on excitability. This study also investigated lidocaine inhibition of the Nav1.7-N395K channel. We show that the N395K mutation attenuates the inhibitory effects of lidocaine on both resting and inactivated Nav1.7. The IC50 for lidocaine was estimated at 500 microM for inactivated wild-type Nav1.7 and 2.8 mM for inactivated Nav1.7-N395K. The N395K mutation also significantly reduced use-dependent inhibition of lidocaine on Nav1.7 current. In contrast, a different hereditary erythromelalgia mutation (F216S), not located in the local anaesthetic binding site, had no effect on lidocaine inhibition of Nav1.7 current. Our observation of reduced lidocaine inhibition on Nav1.7-N395K shows that the residue N395 is critical for lidocaine binding to Nav1.7 and suggests that the response of individuals with hereditary erythromelalgia to lidocaine treatment may be determined, at least in part, by their specific genotype.