| Systemic |
| Endocrine and metabolic disorders |
| Renal failure | Occurs in 15%-48% of patients with end-stage renal failure, up to 90% on hemodialysis4 Etiology poorly understood | Generalized more common than localized Peaks at night Resolves with transplantation5 |
| Hepatic disorders | Common—in up to 80% of patients with primary biliary cirrhosis Seen more in intrahepatic than extrahepatic obstruction: primary biliary cirrhosis, primary sclerosing cholangitis, obstructive choledochlolithiasis, carcinoma of the bile duct, cholestasis, and hepatitis Pruritus of pregnancy (pruritus gravidarum) occurs in 1%-8% of pregnancies | Generalized, migratory Worse on the hands, feet, and areas constricted by clothing Worse at night May precede other manifestations of liver disease such as chronic cholestasis6 Pruritus of pregnancy presents with pruritus of the hands and feet, may generalize. Usually presents in the 3rd trimester and resolves with delivery7 |
| Thyroid disease | More common with hyperthyroidism Pruritus with hypothyroidism, hypoparathyroidism, and pseudohypoparathyroidism may be due to xerosis8 | Usually more severe and generalized with hyperthyroidism Generalized or localized with hypothyroidism8 |
| Diabetes mellitus | Approximately 7% of diabetics are affected Reported with poor glycemic control, mechanism unknown8 | May be localized, especially in genital and perianal areas (may be due to neuropathy or infection) |
| Infections |
| Human immunodeficiency virus (HIV)/Acquired immunodeficiency syndrome (AIDS) | May be presenting symptom of HIV infection HIV-infected patients develop several pruritic dermatoses, but may develop pruritus without other cutaneous findings9 | Local or generalized Intractable pruritus may correlate with HIV viral loads Elevated serum IgE, peripheral hypereosinophilia, and altered TH1/TH2 profile are associated with poor prognosis9 |
| Hepatitis C | Present in approximately 15% of patients with chronic hepatitis C10 | Generalized or localized (See cholestasis, above) |
| Parasites | Several, including ancylostoma, tungiasis, schistosomiasis, myiasis, helminthosis, toxicosis, trypanosomiasis10 | Local or generalized Often with other skin findings |
| Hematologic disorders |
| Myelodysplasia | Prevalence unknown | Generalized or localized May present as aquagenic pruritus |
| Iron deficiency | May be a sign of malignancy10 | Generalized or localized Perianal or vulvar regions may be involved |
| Polycythemia vera (PCV) | 30%-50% experience pruritus | Generalized Aquagenic pruritus may precede development of PCV by years11 |
| Hodgkin's disease | 30% have pruritus Severe persistent pruritus associated with poor prognosis May predict recurrence Less prevalent in non-Hodgkin's lymphoma and leukemia12 | Persistent, generalized Mild to intractable |
| Tumors |
| Solid-organ tumors | May precede a cancer diagnosis Occurs in 5%-27% of patients in palliative care Unknown whether or not rates of malignancy are increased in patients with unexplained pruritus | Often generalized Mild to intractable Intensity or extent of pruritus not correlated with extent of tumor involvement12 |
| Carcinoid | Flushing and gyrate (wave-like) erythema common May experience pruritus during flushing episode | Upper half of body more commonly affected Other symptoms are often present |
| Drug induced: virtually any drug may be associated with pruritus |
| Common: antihypertensives, antiarrhythmics, anticoagulants, antidiabetic drugs, hypolipidemics, antimicrobials and chemotherapy agents, psychotropics, antiepileptics, cytostatic agents, cytokines, growth factors, monoclonal antibodies, plasma volume expanders, nonsteroidal anti-inflammatory drugs (NSAIDs)10 | Generalized pruritus is more common Mechanisms include cholestasis, hepatotoxicity, sebostasis/xerosis, phototoxicity, neurologic, histamine release, deposition, idiopathic |
| Neurologic (Neurogenic/Neuropathic) |
| Diverse etiology: brachioradial pruritus, multiple sclerosis, spinal or cerebral neoplasms, abscess, or infarcts; phantom itch, postherpetic neuralgia, notalgia (Figure 26-3) or meralgia paresthetica, conditions associated with nerve damage, compression, or irritation (including diabetes mellitus or vitamin B12 deficiency)10 | Usually localized Occurs due to dysfunction of signaling, synthesis, or sensation at any level of afferent pathway from skin to brain |
| Psychogenic/Psychosomatic |
| Delusions of parasitosis, psychogenic excoriations, and somatoform pruritus Associated with psychiatric disorders10 | Generalized or localized Important to rule out other causes |
| Mixed |
| Combination, such as uremic itch with xerosis, or neurologic and dermatologic itch in HIV/AIDS | |
| Other (of Unknown Origin) |
| Pruritus of the elderly | Many causes: chronic disease, polypharmacy, xerosis, institutionalized care, age-related alterations of skin including atrophy, decreased cutaneous vascular supply, altered lipid composition, altered peripheral nerve innervations, and compromised moisture retention13 | Generalized or localized |
| Aquagenic pruritus | Generally secondary to systemic disease or other skin disorders There are strict criteria for true idiopathic aquagenic pruritus | Prickling, stinging, burning, and tingling sensation occur within 30 min of water exposure and lasts up to 2 h Begins on lower extremities and generalizes Spares head, palms, soles, and mucosa14 |
| Pruritus in anorexia nervosa | Etiology unknown Not related to other behaviors or internal abnormalities Resolves with weight restoration15 | Intermittent or constant May also experience burning or tingling Often localized: neck, thighs, forearms, buttocks, ankles, and upper arm |