Most of these syndromes are invariably marked by episodes of high spiking fever (often >40°C) accompanied by chills and sweating. For example, in Blau syndrome and PAPA syndrome, fever is not a major symptom. One of the hallmarks, common to all autoinflammatory syndromes, is the accompanying acute phase response with elevated C-reactive protein (CRP) (often 10–30 mg/dL), erythrocyte sedimentation rate, serum amyloid A and leukocytosis (often 15–30 × 109/L) usually caused by neutrophilia. Parents and patients often describe a short but recognizable prodromal phase with aspecific symptoms like fatigue, irritability, headache, and malaise before the onset of fever. Recurrent inflammation can cause general symptoms such as normocytic anemia, fatigue, weight loss, or growth retardation. With the exception of PFAPA syndrome, all other syndromes are associated with a positive family history for comparable symptoms. A negative family history does not exclude an autoinflammatory syndrome since sporadic cases have been described in all hereditary autoinflammatory syndromes except PAPA and Majeed syndrome. Symptoms resolve spontaneously, and in between inflammatory attacks patients are asymptomatic although also in asymptomatic periods an acute phase response can be present. In the more severe syndromes (mevalonic aciduria, NOMID, Muckle-Wells syndrome), there is usually a fluctuating degree of inflammation without complete resolution between episodes.2