Understanding Delusional Infestation: from pattern recognition to pathogenesis

Delusional infestation (DI) is a psychocutaneous disorder marked by sensations of crawling and perceived fibers or foreign materials on the skin. Traditionally viewed as psychiatric, evidence now suggests a multifactorial pathogenesis involving dermatologic, neurologic, endocrine, psychosocial, and pharmacologic factors-most notably, striatal dopamine dysregulation. This review explores DI through a multidimensional lens, highlighting elevated striatal dopamine as a mechanism influenced by factors such as medication (e.g., amphetamines, dopamine agonists), iron deficiency, estrogen status, substance use, and psychosocial stressors. Radioligand neuroimaging supports aberrant striatal dopamine activity as central to pathogenesis. It is also possible that genetic predispositions may intersect with these factors, implicating polymorphisms in dopamine transporter/receptor genes and, iron regulation pathways. Central and peripheral nervous system dysfunction-seen in spinal cord injury, fibromyalgia, and neuropathic itch-may contribute, as can dermatologic conditions like prurigo nodularis that share inflammatory and sensory processing pathways with DI. We propose a model of DI that extends beyond psychiatric classification, emphasizing integrated care. Addressing nutritional deficiencies, medication effects, hormonal status, neuroinflammation, and social determinants may improve patient outcomes. Such a multidisciplinary approach targets underlying biological and environmental contributors.