8.4 Itching

Purpose: to provoke scratching in order to remove a pruritogen, a response likely to have originated when most pruritogens were parasites. Dedicated neural pathway (pruritoceptors) similar but different compared to those dedicated to pain, including unmyelinated C fibers and small myelinated Aδ fibers.

Primary sensory neurons have cell bodies in the dorsal root ganglions and project primary afferents to the skin, and they send projections to the dorsal horn of the spinal cord, where they synapse with second- or third-order neurons, which come together to form part of the spinothalamic tract projecting through the thalamus to the somatosensory and the anterior cingulate cortex. Second- and third-order neurons in the spinal cord may have either excitatory or inhibitory functions. Itch mediators released by resident skin cells and inflammatory cells include histamine, IL-2, TNF-a, IL-4, IL-13, IL-31, thymic stromal lymphoprotein, proteases, neuropeptides (substance P) and opioid peptides.

Localized pruritus: usually caused by itchy dermatoses, associated with inflamed skin, such as in atopic dermatitis, psoriasis, lichen simplex chronicus, tinea, scabies, insect bite reactions.

Generalized pruritus: can be caused by itchy dermatosis even if the inflamed skin does not show generalized spread, or can be caused by extracutaneous disorders.

Acute or chronic: Itching lasting 6 or more weeks. Localized or generalized.

Pruritus with underlying dermatosis (specific skin lesions): atopic dermatitis, eczema, psoriasis, urticaria, scabies, pemphigoid, drug eruptions, cutaneous T-cell lymphoma, insect bite reactions.

Pruritus associated with excoriated nodules and/or lichenification: prurigo nodularis, lichen simplex chronicus.

Pruritus in patients with normal skin or minimal scratched lesions (pruritus of unknown origin):

• Neurologic diseases: multiple sclerosis, brain tumors, small fiber neuropathies, post-herpetic neuralgia, brachioradial pruritus, nostalgia paresthetica.

• Hematological disorders: polycythemia vera, myeloproliferative disease, lymphoma.

• Endocrine diseases: hyper- and hypothyroidism, hyperparathyroidism, diabetes mellitus.

• Infectious diseases: viral hepatitis, parasitoses including helminthosis, HIV/AIDS.

• Metabolic diseases: chronic kidney disease, iron deficiency/overload, hepatobiliary diseases and/or cholestasis.

• Neoplastic.

• Drug induced.

• Psychiatric diseases: depression, anxiety, delusion disorders, eating disorders.

• Mixed.

Recommended in patients with pruritus of unknown origin: full blood count, ferritin, urea, electrolytes, liver function test, erythrocyte sedimentation rate (ESR), PCR; chest X-ray. Optional screening test: blood loss investigations, serum bile acids, LDH, beta-2 microglobulin, thyroid function test, fasting glucose HbA1c, calcium, potassium, PTH, vitamin D, HIV, HCV, HAV, HBV, malaria, strongyloidiasis, schistosomiasis; CT scan, magnetic resonance, skin biopsy.

Accurate anamnesis, physical examination, assessment of itch severity, screening lab and instrumental tests.

Diagnosis of primary skin disorders. Understanding the etiology of pruritus not associated with specific skin lesions.

Symptomatic therapy and treatment of underlying disease (were present). Topical treatments: local anaesthetics, topical corticosteroids, topical calcineurin inhibitors. Systemic treatments: antihistamines, short term corticosteroids, ciclosporin. Opioid κ receptor agonists (nalfurafine, difelikefalin) and μ receptor antagonists (nalmefene, naltrexone), antiepileptics (gabapentin, pregabalin). Antidepressants (paroxetine, fluvoxamine, sertraline, amitriptiline, mirtazapine), neurokinin antagonists (aprepitant, serlopitant), anti-IL-4/IL-13 antibodies (dupilumab), anti-IL31R (nemolizumab). Ultraviolet phototherapy.