What is Pruritus?
Pruritus is the sensation that is relieved by scratching the skin—commonly known as itching—and represents one of the most common presenting symptoms in dermatology, significantly impairing quality of life in a manner comparable to chronic pain. 1, 2
Pathophysiology
Pruritus arises from activation of somatosensory neurons that carry sensations of touch, pain, and itch, triggered by tissue damage or inflammation. 1, 2 The key mechanistic features include:
Distinct neural pathways: Pain and itch sensations are transduced by separate subpopulations of sensory neurons and spinal afferent pathways, though "cross-talk" between these circuits exists. 1, 2
Central processing: Multiple brain centers are involved in chronic pruritus perception, including signal transducer and activator of transcription 3 (STAT3), lipocalin-2-mediated signaling in astrocytes, and GABA-A receptor activation in the central nucleus of the amygdala. 1, 2
Mediators: Various pruritogenic substances can trigger itch, including histamine, proteases, lipid mediators, neuropeptides (VIP, CGRP, substance P), opioids, and cytokines. 3
Clinical Classification
Pruritus is categorized based on the presence or absence of underlying skin disease: 1, 2
Type 1: Pruritus with Associated Underlying Dermatosis
Type 2: Pruritus Without Underlying Dermatosis
Type 2a - Secondary Pruritus (Systemic Causes): 1, 2
- Iron metabolism disorders: Both iron deficiency (most common systemic cause, accounting for 25% of cases) and iron overload/hemochromatosis. 1, 2
- Renal disease: Uremia and end-stage renal disease (42% incidence in hemodialysis patients). 1, 2
- Hepatic disease: Especially cholestasis. 2, 4
- Hematological disorders: Polycythemia vera (often with aquagenic pruritus), Hodgkin lymphoma, rarely non-Hodgkin lymphoma or myeloma. 1, 2
- Malignancy: Solid tumors can present with pruritus. 2, 6
- Endocrine/metabolic: Thyroid disorders, diabetes mellitus (can cause diabetic neuropathy with regional trunk pruritus). 1, 2
- Infections: HIV and other systemic infections. 2, 4
- Neurological disorders: Neuropathic pruritus from nerve compression, small fiber neuropathy, multiple sclerosis, or spinal cord tumors. 1, 7
- Drug-induced: Particularly opioid-induced pruritus and other adverse drug reactions. 2
- Cardiac: Heart failure. 2
- Pregnancy-related pruritus. 2
Type 2b - Generalized Pruritus of Unknown Origin (GPUO): 1, 2
- Chronic itch (>6 weeks) for which no underlying cause is identified despite comprehensive diagnostic workup. 6
- Accounts for approximately 8% of all pruritus cases. 1, 2
Psychogenic Pruritus (Functional Itch Disorder)
This diagnosis requires three compulsory criteria plus three of seven optional criteria: 1
Compulsory:
- Chronic pruritus (>6 weeks)
- No somatic cause (cutaneous or systemic)
- Chronological relationship with psychologically significant life events
Optional (need 3 of 7):
- Variations in intensity with stress
- Worse at night
- Predominance during rest/inaction
- Associated psychological disorder
- Improvement with psychotropic drugs
- Improvement with psychological therapy
- Generalized distribution
Clinical Impact
Quality of life impairment from chronic pruritus equals that of chronic pain. 1, 2 Consequences include:
- Deranged sleep patterns contributing to itch exacerbation and impaired coping. 1
- Psychosocial morbidity develops in up to one-third of individuals with chronic pruritus, including anxiety and depressive disorders. 1
- Psychological factors (stress, emotional excitation, viewing itch-related images, or verbal suggestion) can trigger or worsen pruritus. 1, 2
Common Pitfalls
- Assuming all pruritus has a visible rash: Approximately 8% of pruritus cases have no underlying dermatosis, and systemic disease must be excluded. 1
- Missing iron deficiency: This is the most common systemic cause (25% of systemic cases), and ferritin is an acute-phase protein that may appear falsely normal despite true iron deficiency. 1
- Labeling as psychogenic prematurely: Exhaustive physical investigation must be completed before diagnosing functional itch disorder. 1
- Overlooking neuropathic causes: Small fiber neuropathy may produce no clinical or electrophysiological changes, requiring skin biopsy for diagnosis. 1