Is there a crossroad between infections, genetics, and Henoch–Schönlein purpura?

• Etiology of Henoch–Schönlein purpura (HSp) remains elusive.
• A numerous group of infectious agents may potentially steer HSp pathogenesis.
• Susceptibility to HSp might derive from a peculiar genetic make-up.
• The relationship between infections, genetics and HSp remains blurry.

Henoch–Schönlein purpura is the most common systemic vasculitis in childhood, characterized by the presence of immunoglobulin A deposits in the small vessels of skin, gastrointestinal tube, joints and kidneys. Although there have been great efforts made in elucidating its pathogenic mechanisms, Henoch–Schönlein purpura etiology remains unknown: the basic scene comes across an abnormal inflammatory process deriving from immune reactions to various antigenic stimuli, which might be bacterial, viral, or parasitic agents, in a genetically prone individual. Then, a peculiar immune complex deposition in the vascular walls and overproduction of different proinflammatory molecules elicit different clinical signs, which might be differentiated according to either a specific trigger or a specific genetic make-up. The aim of this review is to make a critical appraisal of the last 15 years' medical literature concerning the relationship between infections, genetics, and Henoch–Schönlein purpura in pediatrics.