Resident Editor: John Landefeld, M.D.

Faculty Editor: Ryan Arakaki, M.D.

Background

• Pruritus is a symptom of a primary dermatologic or systemic disease. At times it is idiopathic.
• History, physical, and workup aim to distinguish primary dermatologic from systemic etiologies.
• Chronic pruritus refers to a subset of pruritus that lasts longer than 6 weeks
• Many patients report that itching is more intolerable than pain

Signs and Symptoms

History:

• Time course and distribution of itch
• Precipitating and alleviating factors
• Past medical/surgical history
• Prescription and OTC medications (esp. new)
• New cosmetics or creams
• Drug allergies
• Living and work conditions, including pets
• Recent exposures/travel
• Contacts with similar symptoms
• Review of systems

Physical exam:

• Focus on finding a primary skin lesion; pay attention to the scalp, finger/toe web spaces, genitalia, clothing. Itching of any type can cause secondary changes, therefore, skin findings do not rule out a systemic disease
  • Consider distribution – interdigital spaces for scabies, for instance, or in photo distributed area
• Secondary changes can camouflage both cutaneous and noncutaneous causes of itch. These include excoriations, non-specific dermatitis, prurigo nodules, lichen simplex chronicus.
• Organomegaly or lymphadenopathy may suggest a systemic process
• The absence of primary lesions may suggest systemic or psychogenic/neurogenic process

Differential diagnosis: pruritus with primary skin lesion

• If a primary skin lesion is present on physical exam, use the morphology and distribution of these lesions to guide differential diagnosis
• Some dermatologic diseases that commonly present with pruritus:
  • Atopic dermatitis, contact dermatitis, xerotic dermatitis, urticaria, dermatophyte infection, arthropod infestation (scabies, lice, etc), lichen sclerosus, lichen planus, pityriasis rosea, bullous pemphigoid, dermatitis herpetiformis, pemphigus gestationis, drug eruption, cutaneous lymphoma

Differential diagnosis: pruritus without primary skin lesion

• Malignancy: Hodgkin’s lymphoma (30% of patients, can precede lymphoma by years), NHL, CLL, multiple myeloma, gastric carcinoid, brain tumor
• Hematologic: Hemochromatosis, iron deficiency anemia, polycythemia vera (aquagenic pruritis), mastocytosis, plasma cell dyscrasias
• Renal: Pruritis experienced by 50% with CKD and 80% on dialysis (rarely caused by acute kidney injury)
• Liver: Primary biliary cirrhosis, primary sclerosing cholangitis, chronic biliary obstruction, drug-induced cholestasis, viral hepatitis (especially HCV) (serum bilirubin level does not correlate with severity of pruritus)
• Endocrine: Hyperthyroidism, hypothyroidism, diabetes, hyperparathyroidism
• Autoimmune: Dermatomyositis, Sjogren's syndrome, Dermatitis herpetiformis
• Neurologic: Multiple sclerosis, neuropathy, nerve compression (notalgia paresthestica, brachioradialis pruritis), postherpetic neuralgia. CVAs, tumors, and abscesses can also contribute to chronic neuropathic itch.
• Infectious: AIDS, parasitic infections, infectious hepatitis
• Medications: Opioids, antimalarials, NSAIDs, cholestatic agents
• Psychogenic: OCD, delusions of parasitosis, substance abuse
• Other: pregnancy-related dermatoses, rapid weight loss

Evaluation

Dermatologic workup:

• Skin biopsy of primary skin lesions
• Scraping for arthropod infestations
• KOH and/or fungal culture for dermatophyte infection

Systemic workup:

• Pursue if no primary skin lesion and/or the patient has concerning systemic signs/symptoms
• CBC with diff, Chem-7, liver enzymes, HBV/HCV serologies, TSH, HIV, CXR, iron studies, fasting glucose.
• Consider stool O&P and SPEP/UPEP if concerning signs/symptoms

Treatment

• Treat any primary dermatologic or systemic disease
• Counsel on principles of gentle skincare:
  • Skin moisturizer and occlusive emollients (e.g. Vaseline, Aquaphor)
  • Humidifier
  • Short showers avoiding hot water
  • Limited soap to oily areas
  • Avoidance of wool clothing
  • Clean towel every few days
• Topical agents to treat itch:
  • Sarna lotion acts as a coolant to reduce the itch
  • Topical capsaicin (neuropathic itch particularly responsive) is an anesthetic that desensitizes peripheral nerve fibers
• Antihistamines: most useful for urticarial or other Type I hypersensitivity disorders
  • First-generation (sedating) antihistamines: Use with caution in the elderly (anti-cholinergic effects can be life-threatening)
    • Doxepin (be especially careful in elderly patients)
    • Hydroxyzine (Atarax), most commonly used oral agent for itching
    • Diphenhydramine (Benadryl)
  • Second generation (nonsedating) antihistamines:
    • Fexofenadine (Allegra)
    • Loratidine (Claritin)
    • Cetirizine (Zyrtec)
• Opioid-mediated agents
  • Nalfurafine: Kappa receptor agonist and mu receptor antagonist
    • May blunt analgesia of morphine and other mu agonists
• Neuropathic agents:
  • Gabapentin (agent of choice for neurogenic itch)
  • Antidepressants (duloxetine, sertraline, paroxetine, mirtazapine especially for nocturnal itch)
•  
• Healing touch, a holistic approach, has been used effectively as an adjunct to pharmacologic therapy in chronic neuropathic itch

When to Refer

• Consider referral to dermatology for assistance in diagnosing primary skin conditions or for intractable pruritus.

References

Reamy BV, et a;. A Diagnostic Approach to Pruritus. Am Fam Physician. 2011;84(2):195-202.

Greco PJ, Ende J. Pruritus: a practical approach. J Gen Intern Med. 1992;7(3):340-9.

Yosipovitch G, Bernhard JD. Clinical practice. Chronic pruritus. N Engl J Med. 2013;368(17):1625-34.

Habif TP. Clinical Dermatology: A Color Guide to Diagnosis and Therapy - Chronic Pruritus. 6^th Edition, Saunders. 2015: p215-217.