How much sweating is enough? Predicting thermoregulatory capacity in patients with ectodermal dysplasia based on a minimal pilocarpine-induced sweat volume.

BACKGROUND: Pathogenic EDA gene variants underlying X-linked hypohidrotic ectodermal dysplasia cause either anhidrosis (null mutations) or hypohidrosis (hypomorphic mutations). Due to their inability to sweat, heat-stressed individuals with EDA null mutations are unable to regulate their body temperature without external cooling and are thus vulnerable to heat-induced injury. For the purpose of developing a therapeutic intervention it would be necessary to know what sweat production is sufficient for normal thermoregulation, e.g., by correlating perspiration in a standard test with thermoregulatory ability, so that a certain sweat volume can be used as an endpoint in clinical trials of drug candidates. METHODS: In patients with hypomorphic EDA mutations, perspiration in response to pilocarpine iontophoresis was determined with the Macroduct sweat collector and volumetry after 30 minutes. Parental- or self-reported heat intolerance and clinical signs of overheating were recorded. If sweat production was borderline, exercise-induced and thermal sweating were assessed by infrared thermography of the skin and core temperature monitoring. In addition, a systematic review of the literature reporting sweat volumes obtained after pilocarpine iontophoresis and thermoregulatory ability of patients with hypomorphic EDA mutations was performed. RESULTS: We studied a rare cohort of individuals with hypomorphic EDA mutations (n = 14) managed at the German national centre for ectodermal dysplasias. Subjects who produced more than 15 µL of sweat upon stimulation with pilocarpine did not show heat intolerance or signs of overheating. Pilocarpine-induced sweating of 16 µL/30 min in early childhood was found to correlate with normal thermoregulation at the age of 10 years. The literature review suggested that a pilocarpine-induced sweat production of 15 µL/30 min in boys indeed represents the bottom of the normal range. CONCLUSION: A sweat volume ≥15 µL, measured in a standard test on male infants using the Macroduct system, appears to indicate normal thermoregulatory capacity in the European climate.