Consider further differential diagnoses.

Abstract

Unfortunately the certified CME article (1) makes only passing reference to the fact that mere heat accumulation can result in body temperatures above 38 °C, and that not every fever is caused by pyrogenics. I especially missed any mention of thirst fever owing to exsiccosis and hypohidrotic forms of ectodermal dysplasia, which are important differential diagnoses in childhood fever of unclear origin and can lead to fatalities (2, 3). Thirst fever develops when a body has less water available than would be needed to regulate the body temperature through perspiration. Due to their more sensitive fluid balance, this is particularly common in infants. By contrast, most children with hypohidrotic ectodermal dysplasia are not capable of releasing surplus body heat through perspiration as they do not have sweat glands (4). In such cases, infant mortality—depending on the climate zone and healthcare provision—is between 2% and 20% (3). Antipyretic drugs are ineffective in this setting, in contrast to physical measures to lower the body temperature. In fever of unknown origin, what also needs to be identified is whether the affected person is actually physically capable of sweating. The medical history and physical examination serve this purpose. For the most common form of hypohidrotic ectodermal dysplasia, there is a causal treatment approach that requires a diagnosis as early on as possible, and which is currently being evaluated in clinical studies (www.clinicaltrials.gov NCT01775462 und NCT01992289).