What are the causes of chronic itching?

Causes of Chronic Itching

Chronic itching (pruritus) is most commonly caused by inflammatory skin diseases, systemic disorders, neuropathic conditions, and psychogenic factors, with iron deficiency being the most frequent systemic cause that responds well to iron replacement therapy. 1, 2

Classification of Pruritus

Pruritus can be classified into two main categories:

1. Pruritus with associated underlying dermatosis 1, 2

   • Inflammatory skin conditions (eczema, psoriasis, seborrheic dermatitis) account for approximately 60% of chronic pruritus cases 3

2. Pruritus with no underlying dermatosis 1

   • Secondary pruritus due to underlying systemic disorder 1
   • Generalized pruritus of unknown origin (GPUO) - approximately 8% of all pruritus cases 1, 2

Systemic Causes of Chronic Itching

• Disorders of iron metabolism 1, 2

  • Iron deficiency - most common cause of generalized pruritus in patients with underlying systemic disease (25% of cases) 1
  • Iron overload (hemochromatosis, hyperferritinemia) 1

• Renal disorders 2, 3

  • Uremia/chronic renal failure 2
  • Uremic pruritus 3

• Hepatic disease 2, 3

  • Especially cholestasis 2
  • Cholestatic pruritus 3

• Malignancy 2, 4

  • Hodgkin's lymphoma 2
  • Polycythemia vera 2
  • Solid tumors 2
  • Heightened concern for underlying malignancy in individuals >60 years with liver disease and diffuse itch <12 months duration 4

• Other hematological disorders 2, 5

  • Polycythemia vera 2
  • Hematologic malignancies 3

• Endocrine disorders 2, 3

  • Thyroid dysfunction 2, 3
  • Diabetes 2

• Infections 2, 3

  • HIV 2
  • Parasitic infections 3
  • Tinea corporis, scabies 3

• Neurological disorders 2, 3

  • Postherpetic neuralgia 3
  • Notalgia paresthetica 3

• Psychological and emotional factors 2, 5

  • Stress 2
  • Anxiety 5
  • Depression 5

• Adverse drug reactions 2, 3

  • Opioid-induced pruritus 2
  • Immunotherapy-related pruritus 3

• Other causes 2

  • Heart failure 2
  • Pregnancy 2
  • Pruritus of elderly skin 2

Diagnostic Approach

For chronic generalized pruritus without rash, the following tests should be performed:

• First-line laboratory evaluation 4, 3

  • Complete blood count with differential 4, 3
  • Liver function tests 4, 3
  • Renal function tests 4, 3
  • Thyroid function tests 4, 3
  • Ferritin levels (iron studies) - essential in all patients with chronic generalized pruritus without rash 1
  • Diabetes screening 4

• Additional testing based on history and physical examination findings 4

  • For suspected iron deficiency with "normal" ferritin, check serum iron and total iron binding capacity 1
  • For unexplained iron deficiency, test for tissue transglutaminase (TTG) antibodies 1
  • Blood eosinophil levels may serve as a biomarker for T helper cell type 2 polarization and response to immunomodulator therapies in chronic pruritus of unknown origin 4

Clinical Pearls and Pitfalls

• Duration definition: Chronic pruritus is defined as itch lasting more than 6 weeks 6, 3

• Prevalence: Chronic pruritus affects approximately 22% of people in their lifetime and accounts for about 1% of physician visits 3

• Quality of life impact: Chronic pruritus significantly impairs quality of life similar to chronic pain, causing sleep disturbances and psychological distress 2, 6, 3

• Iron deficiency pitfall: Ferritin is an acute-phase protein and may appear "normal" even in iron deficiency states 1

• Diagnostic challenge: Approximately 15% of people with chronic pruritus have systemic diseases with secondary itch, requiring thorough investigation 3

• Treatment resistance: About 10% of patients do not respond to topical therapies and may require referral to dermatology for systemic treatments 3

• Multiple etiologies: In some patients, more than one cause may account for pruritus, requiring a comprehensive diagnostic approach 7