Chapter 67 Approaching the pruritic patient
3. Is an itch a separate modality of pain or a submodality of pain?
Cutaneous nerve fibers arranged in an arborizing plexus immediately below the epidermis receive itch impulses. Unmyelinated C fibers conduct itch impulses from the skin to the ipsilateral dorsal root ganglia, ascend in the opposite anterolateral spinothalamic tract (closely associated with pain fibers), continue to the thalamus, and proceed through the internal capsule to the sensory cortex.
4. What causes an itch?
Itch is mediated by a number of local and central substances. Histamine, produced by skin mast cells, is the classical pruritus mediator. Pricking the skin with histamine produces pruritus in most individuals; however, histamine does not account for all pruritus. Other pruritus mediators include prostaglandin, serotonin, tachykinins, cytokines, and opioid receptors. Prostaglandin E1 lowers the threshold of the skin to itching provoked by histamine. Serotonin, 5-hydroxytryptamine (5-HT), may regulate itch by acting on 5-HT3 receptors. Tachykinins, such as the neuropeptide substance P, cause pruritus for reasons attributable to histamine release from mast cells. Cytokine interleukin-2 may be an important peripheral mediator of itching. Opioid receptors in the central nervous system regulate the intensity and quality of perceived itch.
Bernard JD, editor: Itch: mechanisms and management of pruritus, New York, 1994, McGraw-Hill.
Fazio SB: Pruritus, UpToDate 2000, 2005. Available at: http://www.uptodate.com.
Greaves MW, Wall PD: Pathophysiology of itching, Lancet 348:938–940, 1996.
5. Describe the difference between localized and generalized pruritus.
Pruritus occurs with a host of dermatologic conditions, or it can mark systemic disease. Some dermatologic conditions that cause pruritus are inconspicuous or nonspecific. Other dermatologic conditions are apparent on physical exam. A physician must differentiate between localized and generalized pruritus and know a variety of skin diseases that cause pruritus.
6. What is the best approach to evaluation of a patient with localized pruritus?
The most important diagnostic tools are the history and physical exam. After obtaining a thorough history, the best clinical approach is to organize the patient regionally. The physician should ask the patient if there are any lesions associated with pruritus. The patient’s physical exam should focus on identifying a primary skin lesion or disorder in the affected region. After identifying a primary lesion, the physician can categorize the skin disease based on the lesion’s morphology.
8. What is notalgia paresthetica?
Notalgia paresthetica is an acquired unilateral localized form of pruritus that develops near the inferomedial border of either scapula. The skin typically appears normal, although some patients demonstrate subtle hyperpigmentation secondary to repeated rubbing or excoriation. The cause is not understood, although there is substantial evidence to suggest that it is due to spinal nerve impingement. Occasional cases have been familial, and the term “hereditary localized pruritus” has been applied to this variant. The management typically consists of topical capsaicin cream or topical preparations containing lidocaine.
| LOCATION | DISEASES |
|---|---|
| Scalp | Psoriasis, seborrheic dermatitis |
| Trunk | Contact dermatitis (axillae, waistline), erythrasma (axillae), psoriasis (periumbilical), notalgia paresthetica, scabies, seborrheic dermatitis, urticaria |
| Inguinal region | Candida, contact dermatitis, erythrasma, overuse of topical steroids, pediculosis, scabies, tinea cruris |
| Anal region | Candida, contact dermatitis, gonorrhea, hemorrhoids, pinworm, psoriasis, tinea cruris |
| Hands | Contact dermatitis, scabies, eczema |
| Legs | Atopic dermatitis (popliteal fossae), dermatitis herpetiformis (knees), lichen simplex chronicus (malleoli), neurotic excoriations, nummular eczema, stasis dermatitis |
| Feet | Contact dermatitis, pitted keratolysis, tinea pedis |
9. What is the physician’s best approach when seeing a patient with generalized pruritus?
10. After obtaining a complete history and physical examination, what clinically oriented classification scheme should be followed?
Uremia, cholestasis, primary biliary cirrhosis, chronic renal failure, HIV infection, dermatophysis, drugs, polycythemia rubra vera, Hodgkin’s lymphoma, iron-deficiency anemia, carcinoid syndrome, drug-induced pruritus, solid tumor (such as colon, prostate), perimenopausal pruritus
New diagnostic tools are evolving to better evaluate patients with pruritus. The International Forum for the Study of Itch has published a clinical classification utilizing the physician exam to provide physicians with a framework for improving the care of the pruritic patient.
Xerosis (dry skin), atopic dermatitis, contact dermatitis, urticaria, bullous pemphigoid, dermatitis herpetiformis, lichen planus, mastocytosis, polymorphic eruption of pregnancy, prurigo gestationis, cutaneous T-cell lymphoma, other leukemic infiltrates
Patient can be classified as group I, patient with pruritus on diseased inflamed skin; group II, patients with pruritus on normal noninflamed skin; and group III, patients with pruritus on chronic secondary reactive lesions such as scratching/rubbing (Table 67-2).
| CATEGORY | DISEASES |
|---|---|
Diagnostic tests for group I include a skin biopsy and laboratory investigation, such as IgE or indirect immunofluorescence. Diagnostic tests for group II include a laboratory and radiologic investigation based on the patient’s history. Diagnostic tests for group III include a skin biopsy and laboratory and radiologic investigation based on patient’s history.
11. What are common causes of generalized pruritus?
12. How prevalent is an underlying systemic disease in a patient who seeks medical attention for pruritus?
Medical literature reports suggest that the prevalence of an underlying systemic disease in a patient who seeks medical attention for pruritus has been reported to be between 10% and 50%. Therefore, most causes of pruritus are secondary to a dermatologic disease. The following dermatoses are among the most severely pruritic: xerosis, atopic dermatitis, contact dermatitis, urticaria, pediculosis, scabies, bullous pemphigoid, and dermatitis herpetiformis.
13. What is “winter itch”? In which patient population is it common?
Winter itch is the term applied to xerosis (dry skin), which is aggravated by the low ambient humidity that occurs in many homes during the winter months. Xerosis occurs with great frequency in elderly patients and is the most common cause of pruritus for this age group. Xerosis is also aggravated by repeated water exposure due to excessive bathing, swimming, or hot tub use, and strong soaps. The physical exam often shows dry, cracked, scaly skin on the lower legs. Treatment includes limiting frequency, duration, and water temperature of bathing; use of superfatted soaps; and use of emollients immediately after bath or shower. Use of oral antihistamines may help treat “winter itch.”
14. The patient complains that “wool makes me itch” or “I am allergic to wool.” What disease does this patient probably have?
Pruritus is such an integral part of atopic dermatitis that no diagnosis of active atopic dermatitis can be made without a history of itching. External factors, such as irritating clothing (e.g., wool), dry air, and emotional stress, exacerbate atopic dermatitis. Patients tend to have a personal or family history of asthma, rhinitis, and various allergies. Primary skin lesions are not typically seen, but lichenification (an exaggeration of the skin folds) is common because of constant rubbing by the patient. Therapy involves avoiding wool or other irritating clothing. Antihistamines are used to treat pruritus in atopic dermatitis, although some physicians attribute their beneficial effects to their sedative properties.
15. What treatment should the physician consider if a patient presents with pruritus and “hives”?
Urticaria occurs as a consequence of histamine release. A history of wheals is usually associated with pruritus. A physical exam may reveal dermatographism, even if wheals are not present. Therapy includes antihistamines that have a peripheral antipruritic action when itch is due to histamine release.
16. What disease should the physician consider if the patient volunteers that his spouse also suffers from itching?
This history suggests an arthropod reaction, such as scabies or pediculosis pubis. Scabies commonly infects the entire family, especially if young children are present. The characteristic primary lesion is a burrow. Burrows may be difficult to visualize but are most commonly located on the flexor wrists, fingerwebs, and glans penis. Vesicles, papules, pustules, and excoriations are other skin lesions that may be present. Women often complain of pruritus about the nipples. Nocturnal itching is also characteristic of scabies.
17. Is pruritus in HIV-infected patients common? What are the common causes of pruritus in these patients?
Pruritus is common in HIV-infected patients and is experienced with increasing frequency as the disease progresses. Occult HIV infection can present with generalized pruritus. Causes of pruritus secondary to skin disease in HIV-infected patients include 1) xerosis; 2) infectious etiologies, such as scabies; and 3) noninfectious etiologies, such as photoeruptions, eosinophilic pustular folliculitis, or pruritic papular eruption. Pruritus unassociated with skin disease is probably secondary to immune dysregulation of HIV disease. The physical exam will help identify specific causes of skin disease, but a significant number of HIV-infected patients have no demonstrable skin lesions.
18. Which psychiatric disorder often presents with intractable pruritus?
Delusions of parasitosis is the fixed belief that a patient is infested with living organisms in the absence of evidence of such infestation. Delusions of parasitosis often occurs as a sole psychological disturbance, but it may be associated with an underlying personality disorder, such as the obsessive-compulsive type. A physician must take care not to miss a true infestation. A careful history, thorough examination of the skin, microscopic review of “bugs” brought in by the patient, and, occasionally, a biopsy of the “bite” sites is needed. Establishing a dermatology-psychiatry liaison is helpful in establishing a diagnosis and selecting therapy. The neuroleptic pimozide, a blocker of dopamine receptors, is considered an effective treatment but requires careful monitoring because of several potentially serious side effects.
19. Which patients with renal failure experience “renal itch”?
Pruritus reportedly affects 50% to 90% of patients undergoing peritoneal dialysis or hemodialysis. Pruritus usually starts 6 months after the start of dialysis and can be episodic, mild, and localized; or generalized, intractable, and severe. The etiology of uremic pruritus is poorly understood. Possibilities include secondary hyperparathyroidism, histamine release by mast cells, hypervitaminosis A, iron deficiency anemia, or some combination of these. The cornerstone of treatment is regular, intensive, efficient dialysis. Dietary restrictions, phosphate-binding therapy, and phototherapy (UVB) are alternative therapies.
Robertson KB, Meuller BA: Uremic pruritus, Am J Health Syst Pharm 53:2159–2170, 1996.
20. Which patients with liver disease are most likely to experience pruritus? What is the best screening laboratory test?
21. What are the common causes of cholestic pruritus?
The three most common causes of cholestic pruritus are primary biliary cirrhosis, cholestasis of pregnancy, and cholestasis from drugs. Pruritus affects virtually 100% of all patients with primary biliary cirrhosis (PBC) and is the initial symptom in 50%. PBC is a disease of unknown etiology characterized by the destruction of small intrahepatic bile ducts by a granulomatous reaction. Approximately 90% of the patients are female. The serum antimitochondrial antibody test against M2, a component of the pyruvate dehydrogenase complex of mitochondrial enzymes, is 88% sensitive and 96% specific for PBC. Treatment is hepatic transplantation, and it completely eliminates the pruritus. Benign cholestatic jaundice of pregnancy is a frequent cause of pruritus in pregnancy. The pruritus is most severe in the third trimester. The pruritus disappears and elevated liver function tests return to normal after delivery. Pruritus secondary to cholestasis frequently occurs with drug therapy. Common culprits include oral contraceptives, anabolic steroids, cephalosporins, chlorpropamide, cimetidine, erythromycin estolate, gold, nonsteroidal antiinflammatory drugs, nicotinic acid, penicillin, phenothiazine, phenytoin, progestin, and tolbutamide. Removal of the offending drug usually leads to resolution of symptoms. Other causes of cholestatic pruritus include primary sclerosing cholangitis, obstructive choledocholithiasis, carcinoma blocking the biliary tree, or chronic hepatitis C.
Key Points: Pruritus
1. The initial approach in treating the pruritic patient should focus on identifying and treating a primary skin disorder.
2. Patients who do not have an obvious explanation for pruritus should undergo a physical examination and a laboratory evaluation to look for evidence of systemic disease.
3. All patients should be advised about appropriate skin care, which includes adequate nutrition and daily fluid intake, protection from the environment, and cleansing practices that do not dry the skin. In addition to the skin care factors, medications applied to the skin or taken by mouth may be necessary to treat pruritus.
22. Which hematologic disorders are known to present with pruritus?
Polycythemia rubra vera and Hodgkin’s lymphoma are the two most common hematologic disorders known to cause pruritus. Between 14% and 52% of patients with polycythemia rubra vera suffer from pruritus. Pruritus is classically triggered by a sudden decrease in temperature (i.e., sudden cooling off after emerging from a warm bath). Treatment of the underlying disease is necessary to treat this symptom. A patient suffering from Hodgkin’s lymphoma may present with a pruritus that precedes the diagnosis by as many as 5 years. The pruritus can be intolerably severe and continuous, or, less commonly, the patient may complain of a burning sensation. A review of 10 studies on Hodgkin’s disease noted that 35% of patients suffered from pruritus sometime during the disease course, 15% presented with pruritus along with other symptoms, and 7% presented only with the symptom of pruritus. The significance of pruritus as a prognostic sign in Hodgkin’s disease is unknown. Treatment of the lymphoma is the best therapy for pruritus of Hodgkin’s disease.
23. Is generalized pruritus a common symptom of endocrine disorders?
Generalized pruritus occurs in 4% to 11% of patients with thyrotoxicosis and occurs more commonly in patients with long-standing disease. No recent publications on the incidence of pruritus in patients with diabetes mellitus exist. Notwithstanding, patients are more likely to experience pruritus vulvae and pruritus ani secondary to candidiasis, dermatophyte infection, and bacterial infection.
24. Can itching cause skin disease?
Tissue damage caused by scratching may lead to chronic skin conditions such as lichen simplex chronicus or prurigo nodularis. Lichen simplex chronicus results from repeated scratching, which leads to a patch of chronic dermatitis that subsequently becomes lichenified, later becomes intensely pruritic, and leads to a perpetuation of the itch-scratch-itch cycle. Lichen simplex chronicus seems to be precipitated by stress, depression, and frustration. Prurigo nodularis, rather than lichenification, may result from persistent localized itching and scratching. Postinflammatory hypopigmentation and hyperpigmentation is often seen with chronic skin conditions and is a result of repeated scratching and associated inflammation.
25. What is the best symptomatic treatment for a patient with pruritus?
The best treatment for a patient with pruritus involves identifying an underlying dermatosis or systemic disorder responsible for the pruritus and treating that disease. All patients should be advised about appropriate skin care, which includes adequate nutrition and daily fluid intake, protection from the environment, and cleansing practices that do not dry the skin. In addition to the skin care factors, medications applied to the skin or taken by mouth may be necessary to treat pruritus. Topical agents containing menthol produce a cooling sensation. Topical agents containing phenol or camphor have local anesthetic effects. Pramoxine, another topical anesthetic, can provide relief. If appropriate, topical corticosteroids can be used for local control. Oral antihistamines, such as hydroxyzine or doxepin, are commonly used and often provide the first-line treatment for pruritus with no identifiable cause. Other less traditional therapies and techniques are reserved for refractory cases and are best reserved for the practicing clinical dermatologist to address (Table 67-3).
Table 67-3. Treatment of Pruritus
| Topical | Cooling agents, emollients, topical corticosteroids, anesthetics |
| Systemic | Antihistamines, systemic corticosteroids, opioid receptor antagonists |
| Phototherapy | Ultraviolet B (UVB), narrowband UVB (NBUVB) |
| Miscellaneous | Transcutaneous electrical nerve stimulation (TENS), acupuncture, capsaicin |
Greece PJ, Ende J: Pruritus: a practical approach, J Gen Intern Med 7:340–349, 1992.
