English
Polski
Español
українська
Causes and PathogenesisTop
Pruritus (itching) is an unpleasant sensation that triggers the need to scratch. It occurs in the superficial layers of the skin, mucous membranes, upper respiratory tract, and conjunctiva. The pathogenesis of pruritus is not well understood and most likely multifactorial.
Causes of generalized pruritus:
1) Generalized pruritus with primary skin lesions (dermatologic causes):
a) Inflammatory conditions, such as atopic dermatitis, allergic or irritant contact dermatitis, lichen planus, urticaria, bullous pemphigoid, dermatitis herpetiformis, and prurigo nodularis.
b) Infestations and bites, such as scabies and insect and arthropod bites.
c) Neoplastic skin conditions, such as primary cutaneous T-cell lymphoma.
d) Drug eruptions, such as exanthematous drug reactions and drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome.
e) Other causes, such as severe xerosis.
2) Generalized pruritus without primary skin lesions:
a) Renal pruritus in patients with chronic kidney disease, particularly end-stage renal disease (ESRD).
b) Hepatobiliary pruritus: Primary sclerosing cholangitis, extrahepatic cholestasis (eg, chronic pancreatitis with obstruction of the biliary system), drug-induced cholestasis, cholestasis of pregnancy, hepatitis C and B.
c) Hematologic: Iron deficiency, chronic anemia, hypereosinophilic syndrome, mastocytosis, polycythemia vera, Hodgkin lymphoma, other lymphoproliferative and myeloproliferative diseases.
d) Endocrine and metabolic disorders: Hyperthyroidism, hypothyroidism, diabetes mellitus, carcinoid syndrome, hyperparathyroidism and hypercalcemia.
e) Infectious: HIV, hepatitis C and B, parasitic diseases (eg, giardiasis, onchocerciasis, schistosomiasis, ascariasis).
f) Central neuropathic pruritus (tumors and abscesses of the brain, stroke, aneurysm, multiple sclerosis) and peripheral neuropathic pruritus (herpes zoster, Guillain-Barré syndrome, diabetes mellitus, amyloidosis, drug induced [mainly due to epidural or subarachnoid opioids, monoclonal antibodies to the epidermal growth factor receptor, tyrosine kinase inhibitors]).
g) Paraneoplastic pruritus: Solid and more commonly hematologic malignancies can induce pruritus as a paraneoplastic phenomenon.
h) Psychogenic pruritus: Anxiety-related pruritus and delusions of parasitosis.
i) Drug induced: Several groups of medications can induce pruritus in the absence of skin eruptions, such as opioids, angiotensin-converting enzyme inhibitors (ACEIs) (due to the increase in bradykinin levels), antimalarial agents, and programmed cell death 1 (PD-1) or programmed cell death ligand 1 (PD-L1) checkpoint inhibitors.
DiagnosisTop
1. Recommended screening tests in patients with generalized pruritus and no primary skin lesions: Complete blood cell count (CBC) with differential count, erythrocyte sedimentation rate (ESR), aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), bilirubin, lactate dehydrogenase (LDH), blood urea nitrogen (BUN) and creatinine, thyroid-stimulating hormone (TSH) and thyroxine (T4), ferritin, chest radiography, hepatitis C and B serology.
2. Optional additional tests based on clinical suspicion:
1) Fasting glucose and glycated hemoglobin (HbA1c) levels.
2) Stool examination for ova and parasites.
3) HIV serology.
4) Serum tryptase and 24-hour urine collection for methylimidazoleacetic acid (MIAA) (for systemic mastocytosis).
5) 24-hour urine collection for 5-hydroxyindoleacetic acid (5-HIAA) (for carcinoid syndrome).
6) Serum free calcium, phosphate, and parathyroid hormone levels.
7) Antimitochondrial antibodies and serum bile acids (for primary biliary cholangitis and anti–smooth muscle antibodies for autoimmune hepatitis).
8) Serum immunoglobulin levels, especially IgE.
9) Serum protein electrophoresis.
10) Magnetic resonance imaging (MRI) of the brain and spinal cord (for brain and spinal cord tumors or related causes).
Pruritus without skin lesions may precede disease onset even by several years.
TreatmentTop
Generalized pruritus is complex and can pose a challenge. Treatment should be directed at the underlying cause, if known. It should be an individualized approach combining both topical and systemic therapy. Recommended treatment options for selected clinical conditions: Table 1.
1) Topical therapy: Emollients and moisturizing creams, cooling creams (eg, menthol- or camphor-based creams), creams containing local anesthetics (eg, polidocanol and pramoxine 1% cream), topical glucocorticoids, topical calcineurin inhibitors (eg, tacrolimus ointment, pimecrolimus cream), topical phosphodiesterase-5 (PDE-5) inhibitors (eg, crisaborole), topical capsaicin.
2) Systemic therapy: H1 antihistamines (sedating, eg, hydroxyzine, diphenhydramine; and nonsedating, eg, cetirizine, levocetirizine, rupatadine, bilastine), oral glucocorticoids, gamma-aminobutyric acid (GABA) analogues and anticonvulsants (eg, gabapentin, pregabalin), antidepressants (selective serotonin reuptake inhibitors [SSRIs], eg, sertraline, paroxetine; tricyclic antidepressants [TCAs], eg, amitriptyline, doxepin; mirtazapine), mu-opioid receptor antagonists (eg, naltrexone, naloxone, nalmefene), kappa-opioid receptor agonists (eg, nalfurafine, difelikefalin), others (cholestyramine, ursodiol [INN ursodeoxycholic acid], rifampin [INN rifampicin], thalidomide, activated charcoal).
3) Phototherapy (eg, ultraviolet B [UVB] and psoralen and ultraviolet A [PUVA]).
TablesTop
|
Clinical condition |
Most frequently used treatments |
Other available treatments |
|
Renal pruritusa |
– Emollients ± menthol 0.25% + camphor 0.25% tid – Optimization of RRT and increasing dialysis dose – Activated charcoal 6 g/d – UVB phototherapy – Topical 0.03% tacrolimus ointment bid – Capsaicin cream 0.025%-0.075% up to tid – Oral antihistamines (eg, hydroxyzine 10-25 mg PO qid as needed or diphenhydramine 25 mg PO qid as needed) – Gabapentin (eg, 100-300 mg after hemodialysis or at bedtime) – Pregabalin (eg, 25-50 mg after dialysis or at bedtime) |
– Sertraline 25-200 mg/d – Thalidomide 100 mg at night – Naltrexone 50 mg/d – Cholestyramine 5 g bid – Montelukast 10 mg/d PO – Ondansetron 4-8 mg PO, once daily to bid – Doxepin 25-50 mg at bedtime – Nalfurafineb 5 microg IV after hemodialysis |
|
Cholestasis |
– Bile duct stenting – Bile acid sequestrants (eg, cholestyramine [4-16 g/d PO; advise patients to take other drugs ≥1 h before or 4-6 h after each cholestyramine dose] or colesevelam (1875 mg bid in case of intolerable adverse effects secondary to cholestyramine) – UDCA 12-15 mg/kg/d PO in 3 divided doses – Rifampin 150-300 PO bid (monitor LFTs regularly due to risk of hepatitis) – SSRIs (eg, sertraline 50-100 mg/d, paroxetine 5-20 mg/d, fluvoxamine 25-100 mg/d) – Mu-opioid receptor antagonists (eg, naltrexone 12.5-50 mg/d PO or naloxone 0.4 mg IV bolus followed by 0.2 microg/kg/min for 24 h) |
– UVB phototherapy – Transdermal buprenorphine 5-10 microg/h (if patient has received another opioid for pain, try switching to buprenorphine using dose conversion for opioid rotation; see Pain Management: Basic Principles) – Androgens – Tropisetronb – Propofol
|
|
Polycythemia vera |
– Emollients – Low-dose aspirin – Phototherapy (eg, narrow-band UVB or PUVA) |
– SSRIs (eg, sertraline 25-100 mg/d) – Paroxetine 5-20 mg/d, fluvoxamine 25-100 mg/d, or fluoxetine – Sedative H1 antihistamines (hydroxyzine) – H2 antihistamines (cimetidine) – Hydroxyurea or interferon alpha (if cytoreduction is indicated) – JAK inhibitors (ruxolitinib) – Thalidomide |
|
Hodgkin lymphoma |
– Topical and systemic glucocorticoids – H1 antihistamines (eg, cetirizine up to 20 mg bid) |
– Cimetidine 800 mg/d – Mirtazapine 7.5-30 mg at bedtime – Sertraline 25-100 mg/d – Carbamazepine 200 mg bid |
|
Paraneoplastic pruritus in patients with solid tumors |
Paroxetine 5-20 mg/d, sertraline 25-100 mg/d, or fluvoxamine 25-100 mg/d |
Mirtazapine 7.5-30 mg at bedtime |
|
Epidural or subarachnoid opioids |
Intrathecal bupivacaine, prophylactic ondansetron 4 mg IV, gabapentin, mirtazapine |
NSAIDs, antihistamines, ondansetron 4-8 mg IV, nalbuphine hydrochloride, butorphanol, naloxone or naltrexone, propofol, promethazine |
|
Systemic morphine or other opioids |
Emollients, lowering ambient temperature, benzodiazepines, first-generation H1-receptor antagonists |
Switching to another opioid (especially in the case of morphine) if pruritus does not resolve within a few days and is very uncomfortable; ondansetron, paroxetine |
|
Neuropathic pruritus |
– Topical capsaicin – TCAs (eg, amitriptyline 10-50 mg PO at bedtime) – Antiepileptic drugs (eg, gabapentin 300-900 mg/d divided in 2-3 doses and pregabalin 75-150 mg/d PO) – Mirtazapine 15-30 mg PO at bedtime |
NSAIDs |
|
Other causes or idiopathic pruritus |
Sertraline or paroxetine |
Mirtazapine, gabapentin, aprepitant |
|
a Exclude hyperparathyroidism. b Not available in Canada. |
||
|
bid, 2 times a day; IV, intravenous administration; JAK, Janus kinase; LFT, liver function test; NSAID, nonsteroidal anti-inflammatory drug; PO, oral administration; PUVA, psoralen and ultraviolet A; qid, 4 times a day; RRT, renal replacement therapy; SSRI, selective serotonin reuptake inhibitor; TCA, tricyclic antidepressant; tid, 3 times a day; UDCA, ursodeoxycholic acid; UVB, ultraviolet B. |
||
