FEATURE ARTICLE The Clinical Conundrum of Pruritus Victoria Garcia-Albea, Karen Limaye

ABSTRACT: Pruritus is a common complaint for derma- Pruritus is also the most common symptom in derma- tology patients. Diagnosing the cause of pruritus can tological disease and can be a symptom of several sys- be difficult and is often frustrating for patients and pro- temic diseases (Bernhard, 1994). The overall incidence viders. Even after the diagnosis is made, it can be a chal- of pruritus is unknown because there are no epidemio- lenge to manage and relieve pruritus. This article reviews logical databases for pruritus (Norman, 2003). According common and uncommon causes of pruritus and makes to a 2003 study, pruritus and xerosis are the most com- recommendations for proper and thorough evaluation mon dermatological problems encountered in nursing and management. home patients (Norman, 2003). Key words: , Pruritus

INTRODUCTION ETIOLOGY Pruritus (itch) is the most frequent symptom in derma- The skin is equipped with a network of afferent sensory tology (Serling, Leslie, & Maurer, 2011). Itch is the pre- and efferent autonomic nerve branches that respond to dominant symptom associated with acute and chronic various chemical mediators found in the skin (Bernhard, cutaneous disease and is a major symptom in systemic dis- 1994). It is believed that maximal itch production is ease (Elmariah & Lerner, 2011; Steinhoff, Cevikbas, Ikoma, achieved at the basal layer of the , below which & Berger, 2011). It can be a frustration for both the patient pain is perceived (Bernhard, 1994). Autonomic nerves in- and the clinician. This article will attempt to provide an nervate hair follicles, pili erector muscles, blood vessels, overview of pruritus, a method for thorough and com- eccrine, apocrine, and sebaceous glands (Bernhard, 1994). plete evaluation and possible treatment modalities. Afferent sensory nerves transmit noxious stimuli and cold The word pruritus stems from the Latin prurire,which (Stander et al., 2003). Roughly 10% of afferent C fibers means ‘‘to itch’’ (Merriam-Webster, 2009). Itch has been respond to itch and thermal stimuli and not to painful defined as an unpleasant feeling associated with the urge or mechanical stimuli (Stander et al., 2003). Schmelz, to scratch, exclusive to the skin (Stander et al., 2003). Schmidt, Bickel, Handwerker, and Torebjork (1997) showed It can be induced by chemical mediators and by physical that there is one subset of primary afferent C fibers that is and thermal stimuli (Stander et al., 2003). Its biological almost exclusively sensitive and is probably the purpose is likely to have originated from when pruritic primary afferent nerve that carries the itch sensation. agents were mainly parasites (Stander et al., 2003). A mediator of itch is any substance that causes the sensation of itching and the desire to scratch when in- INCIDENCE troduced into the skin (Bernhard, 1994). A number of ‘‘Itching is the most characteristic and distressing symp- chemical mediators have been shown to induce pruritus tom of diseases of the skin’’ (Bernhard, 1994, p. 37). and are, therefore, felt to play a role in various diseases that result in itch. Histamine is the best-known pruritogen. Victoria Garcia-Albea, CPNP, MSN, Mystic Valley , It was first described in the 1920s and is considered the Stoneham, Massachusetts. ‘‘prototypic chemical mediator of itch’’ (Bernhard, 1994, Karen Limaye, FNP, MSN, Department of Dermatology, Lahey p. 26). A biogenic amine, histamine is found in mast Clinic, Burlington, Massachusetts. cells and keratinocytes and is activated by immunoglob- The authors and planners have disclosed that they have no finan- ulin E (IgE), cytokine 5a, substance P, immunoglobulin G cial relationships related to this article. (IgG), and nerve growth factor. Histamine produces itch Correspondence concerning this article should be addressed to Victoria Garcia-Albea, CPNP, MSN, Mystic Valley Dermatology, primarily via the Histamine 1 (H1) receptor, and less so 92 Montvale Ave., Suite 300, Stoneham, MA 02180. via the H2 and H3 receptors. Serotonin, another bio- E-mail: [email protected] genic amine, is a weak pruritogen found in human plate- DOI: 10.1097/JDN.0b013e31824abb10 lets. Serotonin activates mast cells to release histamine.

VOLUME 4 | NUMBER 2 | MARCH/APRIL 2012 97

Copyright © 2012 Dermatology Nurses' Association. Unauthorized reproduction of this article is prohibited. However, when injected into the skin, it causes a pricking, with pruritus report that symptoms get worse at bedtime. painful itch only in some people. Serotonin is involved in Different body parts are disproportionately prone to itch; the central sensation of pruritus and the opioid neuro- ear canals, eyelids, nostrils, perianal and genital areas are transmitter system (Bernhard, 1994). especially susceptible to pruritus (Bernhard, 1994). Because nerves carry the itch sensation, researchers have studied the role of neuropeptides as itch mediators EVALUATION (Bernhard, 1994). Substance P, a neuropeptide, is found A thorough evaluation is necessary in identifying pru- in the cell bodies of C neurons. It is transported toward ritic etiology, because it must be determined whether the the peripheral nerve terminals and released by depolar- patient’s itch is due to a primary dermatological disease, ization to activate dermal mast cells to release histamine, systemic disease, or another cause (Bernhard, 1994). Par- cause vasodilation, and increase vascular permeability. ticular attention must be paid to the onset, nature, du- Substance P is distributed all over the body, including the ration, severity, location, relationship to activities, time and probably the epidermis. It is a potent itch relation, and precipitating, alleviating, and exacerbating inducer, whose pruritic effects can be blocked by proper factors (Table 1). Other pertinent information includes administration of oral antihistamines (Bernhard, 1994). medications, allergies, atopic history, family history of Other chemical mediators involved in itch include ace- or skin disease, occupation, hobbies, social history, tylcholine, bradykinin, tryptase, endothelin, vanilloids, bathing habits, pets, travel history, and prior diagnoses and proteinases (Bernhard, 1994; Stander et al., 2003). (Table 1). Risk factors for human immunodeficiency virus Prostaglandins, interleukins, and nerve growth factor all (HIV) should be assessed, because itch can be an early exaggerate existing itch (Bernhard, 1994; Stander et al., sign of HIV infection. Complaint of interference with 2003). Opioid peptides modify the peripheral and central sleep patterns can be very helpful in making the diagnosis sensations of pruritus (Stander et al., 2003). Antagonizing since some conditions, such as infestation, can be endogenous opioids suppress localized and systemic pru- ritus (Stander et al., 2003). However, morphine, which is a powerful exogenous opioid analgesic, ironically can in- TABLE 1. History of Present Illness and duce intractable itching (Bernhard, 1994). Morphine Pertinent History for Patients With Pruritus induces histamine release from mast cells, but antihis- (Bernhard, 1994) tamines do not prevent or relieve morphine-induced itch (Bernhard, 1994). Description of Itch Pertinent History Cannabinoid receptor agonists have been shown to re- Onset: sudden or gradual Medications: prescription, duce histamine-induced nerve excitation (Stander et al., Nature: continuous, herbal, over the 2003). Two cold receptors that act as desensitizers have intermittent, burning, counter, illicit been found. When skin temperature was reduced, the sen- pricking Allergies: medications, sation of experimentally induced itch was reduced. Sim- Duration:minutes,hours, environmental ilar results, without a decrease in temperature, were days, weeks Atopic history: asthma, achieved when topical menthol was applied to the skin Severity: does it interfere allergies, eczema (Stander et al., 2003). with normal activity Family history of atopy or Time relation: bedtime, skin disease TYPES OF ITCH cyclical Occupation Pruritoceptive itch refers to sensations that arise in af- Location: localized, Hobbies: chemical ferent C nerve fibers and are often due to inflammation, generalized, unilateral or exposures xerosis, or trauma in the dermo-epidermal junction sur- bilateral, scalp Social history: personal rounding the fiber tips (Bernhard, 1994). The sensation Relationship to activities: contacts is then transmitted to the thalamus and sensory cortex worse at work or when via the spinothalamic tract. Neuropathic itch arises when Bathing habits: frequency, doing hobbies temperature of water, a disease process involves the afferent pathway, such as in Provoking factors: heat, type of soap herpes zoster. Central or neurogenic itch is less well un- exercise, water Pets derstood than other types of itch. It arises from a systemic Alleviating factors: distraction, etiology that may involve peripheral cutaneous mediators, Sexual history antihistamines, cool Climate/season such as in severe (Bernhard, 1994). compresses Travel history PATTERNS OF ITCHING Prior diagnoses: by The pattern of itch varies from person to person and healthcare providers or can vary within an individual (Bernhard, 1994). Among patient’s own theories aggravating factors, heat is usually a culprit, as is stress, HIV risk factors absence of distractions, , and fear. Most patients

98 Journal of the Dermatology Nurses’ Association

Copyright © 2012 Dermatology Nurses' Association. Unauthorized reproduction of this article is prohibited. worse at night, whereas psychogenic pruritus rarely inter- Physical examination of the skin should focus on signs feres with sleep. Many medications have a potential to of possible dermatological disease (Bernhard, 1994). Xerosis cause pruritus. Climate and heating systems should be may be present, in addition to primary lesions including taken into account; low humidity and cold weather can wheals, , vesicles, plaques, patches, and nodules cause or exacerbate xerosis, which can trigger itch. Sweat (Figure 1). The presence of secondary changes such as retention caused by high humidity can lead to itch. excoriations, crusts, fissures,ulceration,scarring,andli- Bathing habits and chemical exposures at work or chenification are more commonly found in systemic etiol- through hobbies should be assessed. Patients reporting ogies of pruritus, or long standing dermatological disease severe itch within 30 minutes of water contact without (Figure 2). Involvement of the arms, legs, and anterior visible skin lesions, which is called , trunk with sparing of the upper midback is often asso- should be screened for , myeloprolif- ciated with psychogenic pruritus. The presence of primary erative disease, histioycytic disorders, and physical urti- lesions on the upper midback, where it is difficult for the caria, which usually presents with wheals. Travel history patient to reach, is more characteristic of true dermatol- should be included because parasitic infections can present ogical disease (Bernhard, 1994). A physical examination with pruritus. Patients reporting itch among family mem- that reveals only secondary skin changes, such as excori- bers and patients who are institutionalized should be ations, irregularly shaped ulcers, and hemorrhagic crusts, evaluated for scabies. Recent life stressors or traumatic may indicate a self-induced etiology. In persons with good events may cause patients to experience pruritus; there- hygiene, scabies may be missed. Thus, thorough exami- fore, it is important to include a thorough mental and nation between the digits, in the axillae, waistline, wrists emotional evaluation on every patient. and groin is necessary, as it may reveal subtle papules Systemic signs and symptoms such as weight fluctu- or burrows. Examination of the lymph system and pal- ation, night sweats, fever, chills, lymphadenopathy, ab- pation for liver and spleen should be included to help dominal pain, fatigue, myalgias, and changes in bowel rule out infectious and systemic etiologies. General phy- pattern should prompt further investigation for systemic sical examination may reveal an undiagnosed systemic dis- etiology (Table 2; Bernhard, 1994). The patient’s response ease (Bernhard, 1994). to scratching may provide some information about the Systemic disease has been shown to be associated etiology of the itch. For example, in some diseases, scratch- with generalized pruritus in 16%Y50% of patients ing reduces pain, whereas in others scratching can in- (Bernhard, 1994). ‘‘Most systemic diseases, including crease pain (Bernhard, 1994). underlying malignancy, will be detectedI by history, physical examination, and the screening laboratory tests’’ (Bernhard, 1994, p. 343). Laboratory workup is di- rected by the clinical evaluation and may include complete TABLE 2. Review of Systems blood count with differential, looking for eosinophilia, (Bernhard, 1994) anemia, or evidence of myeloproliferative disease. General health Fever, chills, night sweats, Other relevant studies include measurement of thyroid- weight loss, fatigue, anorexia stimulating hormone and thyroxine, liver and renal Skin , pigmentation, function tests, stool for occult blood, viral B jaundice, xerosis, sweating and C screening, serum glucose level, urinalysis, serum Hair Texture, growth, alopecia protein electrophoresis, and chest X-ray (Table 3). An antitissue transglutaminase antibody level should be Nails Color change, grooves, lines, curvature, onycholysis performed if there is suspicion of herpetifor- mis. A HIV antibody test is needed for patients with Eyes Jaundice, exophthalmos identified risk factors. In select cases, further laboratory Endocrine Temperature intolerance, evaluation is indicated, including serum iron and ferri- polyuria, polydipsia tin, skin biopsy for special stains and direct immuno- Hematopoietic Anemia, bruising, , fluorescence, stool for ova and parasites, and additional lymphadenopathy radiologic studies (Bernhard, 1994). Gastrointestinal , vomiting, , DIFFERENTIAL DIAGNOSIS Genitourinary Frequency, incontinence, The differential diagnosis of an ‘‘itchy ’’ is quite color change lengthy. Included on this list would be , Neurologic Headaches, neuropathy, , scabies, lice, insect bites, allergic or irritant visual disturbances , , urticaria, , Mental status Mood, hallucinations, , drug hypersensitivity, , sleep disturbances Grover’s disease, varicella, pityrosporum, mycosis fun- goides, and many more (Bernhard, 1994). Persistent or

VOLUME 4 | NUMBER 2 | MARCH/APRIL 2012 99

Copyright © 2012 Dermatology Nurses' Association. Unauthorized reproduction of this article is prohibited. FIGURE 1. Evaluation of the patient with pruritus caused by a primary dermatitis (Bernhard, 1994). recurrent pruritus of such severity to cause scratching apy for other dermatoses fails to bring improvement. Ef- and bleeding, with or without primary cutaneous man- fective treatment is dependent on the etiology of the itch. ifestations is most often associated with lichen simplex Itch secondary to irritation from fecal matter is amelio- chronicus, atopic dermatitis, nummular eczema, derma- ratedwithproperskinhygieneandskinprotectionwith titis herpetiformis, neurotic excoriations, eosinophilic barrier creams such as white petrolatum (Bernhard, 1994). folliculitis, , subacute , prurigo and vulvae are similar in clinical pre- nodularis, and scabies. History and physical examina- sentation, etiology, and treatment (James, Berger, & tion can provide a variety of clues as to the diagnosis. Elston, 2011). Genital itch induces psychosomatic overlay and vice versa (Bernhard, 1994). A report of sudden onset LOCALIZED PRURITUS of genital itching and burning generates a differential Localized pruritus is not usually due to a systemic eti- diagnosis including candida infection, irritant contact ology (Bernhard, 1994). is the term used for dermatitis and allergic contact dermatitis, urinary tract in- perianal itch, although it can also involve the anogenital fection, , and pinworms (Bernhard, 1994). area. Pruritus ani affects 1% to 5% of the population, with is a common complaint, especially in men being affected four times more frequently than women. older people. The most common cause is buildup of Manifestations mimic ; the itch is scale and hair products in people who do not wash their characterized by intense bouts of burning pruritus, caus- scalps often. Seborrheic dermatitis, folliculitis, atopic ing the patient to scratch until the skin bleeds. The most dermatitis, psoriasis, lichen planus, , dermatomyo- common causes are allergic contact dermatitis; irritant sitis, and some forms of alopecia can present with scalp contact dermatitis due to fecal matter coming in contact itch. However, these skin conditions usually have char- with the skin, due to poor hygiene; episodic diarrhea, in- acteristics accompanying dermatological manifestations flammatory bowel disease, or dietary causes, such as spicy that assist in diagnosis. It is important to recognize cic- foods; infectious etiologies such as gonorrhea, streptococ- atricial (scarring) alopecia as a potential cause of scalp cus, erythrasma, mycotic infections, parasites, or scabies; itch when it is accompanied by inflammation, indicating or skin diseases such as psoriasis, seborrheic dermatitis, that it is new and, therefore, more responsive to treat- lichen planus, or lichen sclerosis. Bowen disease or squa- ment. Biopsy of refractory inflammatory scalp pruritus, mous cell carcinoma in situ is less likely to be intensely pru- leading to diagnosis and treatment, can be key to pre- ritic but is easily overlooked (Muehlbauer & McGowan, venting permanent scarring alopecia. When no cutane- 2009). Squamous cell carcinomainsituisdiagnosedwith ous findings are present, diagnosis and treatment can be a skin biopsy and should be considered if traditional ther- especially challenging. Topical tar shampoos, salicylic

FIGURE 2. Evaluation of the patient with pruritus not caused by a primary dermatitis (Bernhard, 1994).

100 Journal of the Dermatology Nurses’ Association

Copyright © 2012 Dermatology Nurses' Association. Unauthorized reproduction of this article is prohibited. students, people who are incarcerated, or those living in TABLE 3. Laboratory Evaluation for assisted living facilities. The major symptom is severe Patients With Pruritus (Bernhard, 1994) pruritus, worse at night, accompanied by small, nonde- Suggested initial screening Further laboratory script papules and eczematous changes found in the in- to evaluate pruritus evaluation for terdigital spaces, wrists, axillae, ankles, waistline, and Complete blood count selected cases genitalia. When correctly identified, the presence of bur- with differential Serum iron, ferritin rows is pathognomonic for scabies, although well-formed Blood urea nitrogen, Serum protein burrows are not always present. The scabetic itch can creatinine electrophoresis, serum persist for 2 to 4 weeks after successful treatment because Alkaline phosphatase, immunoelectrophoresis mite parts, eggs, and feces remain in the skin. Pedicu- bilirubin Skin biopsy for special losis (lice infestation) is accompanied by itching of body regions with dense hair follicles. In pediculosis, itch is Thyroxine, thyroid-stimulating stains (to exclude hormone mastocytosis) due to a delayed hypersensitivity reaction to the louse’s saliva. Itch subsides with treatment (Bernhard, 1994). Serum glucose Skin biopsy for direct immunofluorescence Many inflammatory skin conditions present with pru- Stool for occult blood (to exclude bullous ritus (Bernhard, 1994). A review of all of them is beyond Urinalysis pemphigoid, dermatitis the scope of this article. Atopic dermatitis or eczema, the Chest X-ray herpetiformis) most common of these inflammatory skin conditions, Stool for ova and is usually a clinical diagnosis, characterized by chronic parasites recurrent courses of pruritic dermatitis with an early age Additional radiologic of onset and a personal and/or family history of atopy studies (Bernhard, 1994). Contact dermatitis refers to both irritant contact der- matitis and allergic contact dermatitis (Bernhard, 1994). Irritant contact dermatitis results when irritants, such acid preparations, and topical corticosteroid prepara- as fragrances, chemicals, or harsh soaps directly cause tions usually provide some relief. Unfortunately, this relief damage to the skin, leading to the release of histamine is often temporary. In the case of scalp folliculitis, oral and inflammatory mediators, resulting in itch. Allergic tetracyclines are often helpful (Bernhard, 1994). contact dermatitis is induced by an immune response (Bernhard, 1994). Psoriasis is an autoimmune disease, characterized by ITCH DUE TO CUTANEOUS DISEASE a T-cell-mediated inflammatory response, with expres- The most common cause of pruritus is xerosis or dry sion of multiple chemical mediators, including interleu- skin. It can be present with or without a rash and is kin 2 (IL2), which is known to play a role in pruritus most common in winter; it is also called ‘‘winter itch’’ (Bernhard, 1994). Eighty percent of patients with psoriasis (Bernhard, 1994, p. 56). It can be widespread but usually report itch. The best treatment for psoriatic itch is to treat involves bilateral upper and lower extremities. Associated and control the underlying psoriasis itself (Bernhard, 1994). factors include a history of atopy, advanced age, hypo- Lichen simplex chronicus is a chronic, localized derma- thyroidism, anticholinergic medications, oral retinoids, tological disorder characterized by intense itch (Bernhard, frequent bathing with hot water and harsh soaps, forced 1994). The patient repeatedly scratches the affected areas, hot air heating, and low humidity. Treatment consists of causing thickened, lichenified plaques that may develop repairing the skin barrier totrapandretainmoisturein into nodules, termed as or prurigo nod- skin with emollients and use of barrier creams. In severe ules. These prurigo nodules are itchy, so the patient con- cases, use of the ‘‘soak and seal’’ technique, which is often tinues to scratch, and the nodules persist. The primary used in patients with atopic dermatitis, is helpful. In this etiology of lichen simplex chronicus can vary and may be method, the patient will soak the affected area in luke- associated with an underlying inflammatory disorder or warm water for 10 to 15 minutes. Before drying the area, psychogenic pruritus. Treatment focuses on breaking the an emollient or topical corticosteroid ointment is applied itchYscratch cycle. Intralesional triamcinolone, topical to the wet skin, locking in the moisture and providing a fluorandrenolide tape, high-potency topical corticoste- barrier at the same time (Bingham, Noble & Davis, 2007). roids under occlusion, and Unna boots are effective. In patients who have a parasitic infestation, pruritus Urticaria()isarelatively common, transient, in- is a common complaint (Bernhard, 1994). The outstand- tensely pruritic dermatosis (Bernhard, 1994). Acute ur- ing clinical feature of scabetic infestation is itching, pri- ticaria is usually allergic in nature. Chronic urticaria, marily due to the dermal hypersensitivity reaction produced defined as regular outbreaks of urticaria lasting for more by the host. Any person can contract scabies, but it is most than 6 weeks, may be the presentingfeatureinasystemic common in persons living in close quarters, such as college disease but is usually idiopathic (Bernhard, 1994).

VOLUME 4 | NUMBER 2 | MARCH/APRIL 2012 101

Copyright © 2012 Dermatology Nurses' Association. Unauthorized reproduction of this article is prohibited. Cutaneous diseases due to infectious etiologies can biliary initially present with pruritus; 100% also present with itch as a symptom. The most common report pruritus at some point (James, Berger, & Elston, of these are (fungal) infections, which com- 2011). Pruritus is reported in 20% of patients with He- monly present with annular red rings with active scaly patitis C (Mazoff, 2008). Pruritus from may borders and central clearing. A potassium hydroxide (KOH) be localized to a specific body part, such as hands and mount or fungal culture will confirm the diagnosis. Itch will feet, or generalized, involving the entire body (Mazoff, resolve when the infection is treated, usually with topical 2008). Some patients with Hepatitis C complain that antifungal creams (Bernhard, 1994). their internal organs feel itchy (Mazoff, 2008). Etiology Other infectious etiologies include , pity- is related to the increased level of bile salts, elevated rosporum or bacterial folliculitis, and streptococcal skin plasma and tissue levels of opioid peptides, and down infections, such as scarlet fever. Viral are not regulation of opioid peptide receptors (James, Berger, & usually pruritic; those that are include varicella and par- Elston, 2011). Hence, opioid receptor antagonists have vovirus B19 (fifth disease). Patients with HIV are prone to been effective in many patients (James, Berger, & many cutaneous problems, and pruritus is one of them. Elston, 2011). Cholestyramine and colchicines have also Patients with HIV may develop any cutaneous disorder been effective in some cases (James, Berger, & Elston, that affects patients with an intact immune system. How- 2011). Liver transplantation provides immediate and ever, HIV patients have elevated IgE levels. Elevated IgE dramatic relief (James, Berger, & Elston, 2011). ‘‘Severe levels have been found in many pruritic conditions, in- pruritus resistant to therapy has been accepted by the cluding atopic dermatitis (Bernhard, 1994). This will be National Institutes of Health Consensus Conference on discussed further in the next section. Liver Transplantation as a valid indication for the pro- cedure’’ of liver transplantation (Bernhard, 1994, p. 239). ITCH DUE TO SYSTEMIC DISEASE Pruritus has been reported as the presenting symp- Chronic renal failure is the most common internal sys- tom of HIV infection; therefore, at risk individuals with temic etiology of pruritus; this is termed uremic pruritus pruritus should be screened. Persons with HIV are also (Bernhard, 1994). Itch is not a symptom of acute renal at higher risk of pruritic disease secondary to immuno- failure (Bernhard, 1994). Uremic pruritus is usually general- suppression and other complications of HIV. The most ized and is especially bothersome on the back (Bernhard, common causes of itch in patients with HIV are scabies, 1994). It primarily affects patients on hemodialysis and pediculosis, candidiasis, renal and/or hepatic dysfunc- continuous ambulatory peritoneal dialysis (Bernhard, 1994). tion, and eosinophilic folliculitis (Bernhard, 1994). The etiology of the pruritus is multifactorial. The multiple Hypothyroidism is commonly associated with pruri- side effects of renal failure, including xerosis, hyperphos- tus, as it causes the skin to be ‘‘cold, dry, pale, rough, phatemia due to secondary hyperparathyroidism, in- and scaly’’ (Bernhard, 1994, p. 253). Xerosis is seen in creased serum histamine levels, hypervitaminosis A, iron 80% to 90% of patients with hypothyroidism. Correct- deficiency anemia, and neuropathy, likely contribute to ing thyroid level imbalances and using topical emol- the problem (Bernhard, 1994). The incidence of pruritus lients and dry skin care can treat this xerosis. Severe itch increases as renal function deteriorates (Bernhard, 1994). can be a presenting symptom of hypothyroidism. Thyroid Treatment is often frustrating, with poor response rates hormones influence skin maturation, oxygen consump- to oral and topical medications (Bernhard, 1994; James, tion, protein synthesis, skin thickness, hair formation, Berger, & Elston, 2011). Some success has been reported and sebum secretion. Itch in hyperthyroidism is possibly from narrow band Ultraviolet B (NB UVB) phototherapy, due to a reduction in the itch threshold caused by warmth but recurrence is common with discontinuation. Renal and vasodilatation (Bernhard, 1994). transplantation is effective (Bernhard, 1994). Variable re- Pruritus in diabetic patients is less common now than sponse rates have been reported with activated charcoal, in decades past, now occurring in about 3% of patients. cholestyramine, thalidomide, oral naltrexone, and oral on- The cause is not known, but it is thought to be related dansetron (James, Berger, & Elston, 2011). to diabetic neuropathy and autonomic dysfunction, re- Chronic , including , cir- sulting in anhidrosis and xerosis. It is possible that dia- rhosis, pruritus gravidarum (cholestasis of pregnancy), betic renal failure accounts for some cases. Pruritus ani and drug-induced cholestasis, can be accompanied by and vulvae have been associated with poorly controlled obstructive jaundice and pruritus, termed as cholestatic (Bernhard, 1994). pruritus (Bernhard, 1994). It is most commonly localized Mastocytosis, in which the skin and internal organs to the palms and soles, and around tight-fitting clothing exhibit an excessive number of mast cells, causes a variety (Bernhard, 1994; James, Berger, & Elston, 2011). Pruritus of systemic and local cutaneous symptoms, including pru- associated with liver disease spreads proximally, becomes ritus. Extreme temperatures, certain medications, and generalized in 20% to 50% of patients with jaundice or alcohol can exacerbate symptoms. Oral antihistamines impaired bile secretion, and is usually worse at night decrease pruritus, flushing, bullae, and urticaria, which (Bernhard, 1994). Fifty percent of patients with primary are often seen in mastocytosis (Alto & Clarcq, 1999).

102 Journal of the Dermatology Nurses’ Association

Copyright © 2012 Dermatology Nurses' Association. Unauthorized reproduction of this article is prohibited. Postmenopausal pruritus may be generalized or lo- psoriasis and eczema are also itchy, calized; the localized form usually affects the anogenital patches, plaques, and tumors usually do not follow the area (Bernhard, 1994). Generalized pruritus is frequently patterns of distribution of psoriasis or eczema. In addi- associated with hot flashes, which tend to be persistent tion, mycosis fungoides tumors do not have the over- but are not usually described as severe. Premenstrual pru- lying micaceous scale of psoriasis and are usually more ritus can be caused by recurrent cholestasis. Pruritus due infiltrated and thicker than the characteristic plaques of to cholestasis induced by oral contraceptives has also been eczema. It can be the ‘‘exasperating’’ nature of the itch reported. There are documented cases of recurrent pre- that first awakens suspicion for CTCL (Bernhard, 1994, menstrual urticaria related to estrogen sensitivity. Autoim- p. 300). Sezary syndrome, the leukemic variant of CTCL, mune progesterone dermatitis can cause eczema, is often characterized by significant generalized pruritus multiforme (EM), and urticaria. This improves with ad- (Booher, McCann, & Tawa, 2011). ministration of oral contraceptives (Bernhard, 1994). Iron deficiency anemia is rarely associated with pru- PSYCHODERMATOLOGY ritus. Itch can be generalized or localized, especially in the Psychodermatoses can cause itch. However, this is a perianal and vulvar areas. Complete relief is achieved more difficult diagnosis to make, because it tends to be once normal iron levels are restored (Bernhard, 1994). diagnoses of exclusion. Psychodermatoses may manifest clinically in many forms. Patients demonstrate second- PRURITUS-ASSOCIATED MALIGNANCIES ary skin changes, with scattered excoriations and lichen- The most common malignancies associated with pruri- ified papules. Skin lesions usually occur on the extremities tus are Hodgkin’s lymphoma, polycythemia vera, he- and always spare areas that are out of the patient’s reach, matologic malignancies, gastric carcinomas, and mycosis such as the central back. Often a major life stressor or fungoides. It is important to remember that the associa- trauma precedes the onset of this condition (Bernhard, 1994). tion of malignancy and generalized pruritus is rare, with Neurotic excoriations are self-induced, as an uncon- the exception of Hodgkin’s lymphoma and polycythemia scious habit of picking, scratching, or rubbing. Most vera. Pruritus is the presenting symptom of Hodgkin’s patients are aware that they are responsible for the le- lymphoma in 30% of patients and can precede develop- sions, but they cannot control their behavior. Patients ment of other symptoms by several months or up to 5 years. cannot tolerate any imperfection in the smooth surface The itch is described as burning and usually involves the of the skin. The patient picks off the raised or altered lower extremities. Itch intensity increases with age and skin, which results in more crusting, ‘‘and so the process disease severity. Pruritus in Hodgkin’s disease is resis- become progressive’’ (Bernhard, 1994, p. 355). In some tant to all therapy, except treatment of the lymphoma cases, pruritus is not a significant factor. For others, pru- (Bernhard, 1994), ritic lesions such as papular urticaria or folliculitis attract Polycythemia vera, a disease of the bone marrow result- attention, and therefore, the patient picks and scratches. ing in increased numbers of red blood cells, often presents Another scenario involves pruritic papules, which cause with itch induced by a drop in temperature, such as after a uncontrollable focal itch, leading to scratching, which hot bath or shower. This type of itch can last up to an causes prurigo nodules (Bernhard, 1994). hour. The etiology of this phenomenon is not understood, Lesions in patients with neurotic excoriations are but the pruritus is intractable. As with the pruritus asso- polymorphous, with ulcers, excoriations, and licheni- ciated with many malignancies, itch can precede diagnosis fied papules and nodules. There will be evidence of older, by many years. Low-dose aspirin may provide immediate healed lesions, with scarring and pigmentary alteration. relief. Psoralen plus Ultraviolet A (PUVA), NB UVB, and The upper extremities and face are common sites of in- oral paroxetine can also be helpful. Interferon alpha-2 has volvement; excoriee is a form of this condition. Most been shown to effectively treat the underlying disease and, patients are normal, healthy adults. The most common therefore, reduce itch (James, Berger, & Elston, 2011). psychopathologies seen in association with neurotic ex- Pruritus has been documented in approximately 2 to 3% coriations are depression, obsessive compulsive disorder, of patients with non-Hodgkin’s lymphoma at presenta- and anxiety. Treatment is difficult, often requiring col- tion. About 10% of non-Hodgkin’s lymphoma patients laboration with a therapist. Treatment with and will develop itch at some time during the course of dis- various selective serotonin reuptake inhibitors has been ease. Pruritus is not common but has been described effective (James, Berger, & Elston, 2011). in chronic leukocytic leukemia and multiple myeloma Delusions of parasitosis are firm beliefs in an indi- (Bernhard, 1994). vidual’s mind that he or she experiences an infestation Mycosis fungoides, the most common type of cuta- (James, Berger, & Elston, 2011). Patients may also ex- neous T-cell lymphoma (CTCL), can present with pru- perience delusions that they can retrieve or express for- ritus before the onset of cutaneous findings. Early skin eign material out of their skin (Bernhard, 1994). The lesions are often subtle. Mycosis fungoides is commonly patient will often bring pieces of skin, fibers, threads of initially misdiagnosed as psoriasis or eczema. Whereas clothing, and other materials to show the provider the

VOLUME 4 | NUMBER 2 | MARCH/APRIL 2012 103

Copyright © 2012 Dermatology Nurses' Association. Unauthorized reproduction of this article is prohibited. alleged insect, parasite, or expressed foreign material. effect. Aloe vera, a popular favorite, may have bacteri- Patients complain of pruritus, stinging, and the sensa- cidal and antifungal effects but has been shown to cause tion of being bitten or of bugs crawling on the skin (James, allergic contact dermatitis. Vitamin E can also cause al- Berger, & Elston, 2011). There is often a psychiatric his- lergic contact dermatitis but is a popular home remedy tory, most commonly depression, schizophrenia, bipolar (Bernhard, 1994). disorder, or obsessive compulsive disorder (Bernhard, Topical antipruritics include ‘‘caine’’ preparations, such 1994). However, the absence of a pre-existing mental as lidocaine, pramoxine, and prilocaine. These antipru- health problem does not rule out this condition (Bernhard, ritics may be useful for localized conditions. Capsaicin 1994). Development of delusions of parasitosis can pre- cream, which contains the naturally occurring alkaloid cede the onset of other symptoms of mental illness (James, present in hot peppers, causes the release of neuropep- Berger, & Elston, 2011). Women are afflicted by this tides, including substance P. Repeated application of cap- disorder twice as often as men, and patients are usually saicin cream causes progressive depletion of substance P, middle age or older (James, Berger, & Elston, 2011). Eval- which interferes with transmission of certain painful and uation of these patients should focus on ruling out a true itchy stimuli from the periphery to the central nervous infestation and looking for systemic or drug-induced causes system. Therefore, results are best in localized, chronic, of itch (James, Berger, & Elston, 2011). Cocaine and am- pruritic disorders. Topical antihistamines, like doxepin phetamine abuse are well-documented causes of delusions 5% cream, block H1 and H2 receptors. These are useful of parasitosis (James, Berger, & Elston, 2011). Referral antipruritics; however, percutaneous absorption leads to to a psychiatrist is recommended; haloperidol, pimozide, somnolence and limits widespread use (Bernhard, 1994). or other antipsychotic medication is the recommended Topical corticosteroids decrease itch by reducing in- treatment (James, Berger, & Elston, 2011). flammation and chemotaxis and by causing vasocon- striction. Therefore, they are most effective in pruritus caused by diseases of inflammation. Crotamiton is an TREATMENT older antiscabetic lotion that has been relaunched as an The first step in treating any type of pruritus is to first make antipruritic. It is most useful for postscabetic itch and the correct diagnosis. However, symptomatic treatment is has shown mixed results in patients with other forms of often required, regardless of the diagnosis. Bernhard pruritus (Bernhard, 1994). (1994) identifies six main categories for symptomatic Antihistamines are most frequently utilized by non- treatment: patient education; elimination of provocative dermatologists. H1 first generation antihistamines, such factors; nonspecific topical preparations and skin hydra- as diphenhydramine and hydroxyzine, may be helpful tion; chemical treatments, both topical and oral; physical in nocturnal pruritus, primarily due to their side effect modalities, such as phototherapy or counterstimulation; of somnolence (Bernhard, 1994). Unfortunately, their drastic measures, such as plasmapheresis; and under- use as antipruritics has been disappointing. Oral doxe- standing and support from healthcare providers, family, pin is one exception. Doxepin is a more effective antipru- and friends. ritic, at doses of 10 to 25 mg up to four times daily, possibly Patient education should involve a clear explanation because at higher doses it acts as an antidepressant of the diagnosis, including exacerbating and triggering (Bernhard, 1994). There is some evidence that selective factors. Teaching about breaking the itchYscratch cycle serotonin reuptake inhibitor antidepressants, including is critical. Stress, fear, loss of sleep, and anxiety can make paroxetine, fluvoxamine, fluoxetine, and sertraline, itch worse; therefore, every effort to alleviate stress is may ameliorate itch of a variety of causes (Hundley & helpful. Psychiatrists, social workers, and counselors can Yosipovitch, 2004). There are anecdotal case reports of help address stress at home and at work and can provide gabapentin decreasing itch in patients with liver disease, coping mechanisms for the patient (Bernhard, 1994). patients on hemodialysis, and patients with pruritus of Eliminating exacerbating factors includes avoiding unknown origin, but conclusive evidence is not pub- dry skin, excessive bathing, low humidity, irritating lished in the literature (James, Berger, & Elston, 2011). fabrics and chemicals, contact allergens or irritants, al- Nonsedating H2 antihistamines have been especially cohol ingestion, hot foods and liquids, stress and anx- disappointing as antipruritics and are only effective in iety, excessive ambient temperature, dust and dust mites, urticaria (James, Berger, & Elston, 2011). The opiate fiberglass, and certain animal products (Bernhard, 1994). antagonists naloxone and naltrexone and the serotonin Patients should be encouraged to bathe in moderation, antagonist ondansetron have shown mixed efficacy in which will help maintain adequate skin hydration. Col- various studies (James, Berger, & Elston, 2011). loidal oatmeal products can be soothing when added to PUVA and NB UVB phototherapy have been shown bath water. Bland emollients or bath oils applied after to be efficacious in a wide variety of dermatological dis- bathing can help hydrate the skin. Nonsteroidal topical eases and systemic etiologies of pruritus, including pso- emollients, such as menthol, tar, and salicylic acid, act riasis, atopic dermatitis, pityriasis rosea, mastocytosis, as counterirritants to relieve itch through their cooling renal itch, and polycythemia vera (Bernhard, 1994).

104 Journal of the Dermatology Nurses’ Association

Copyright © 2012 Dermatology Nurses' Association. Unauthorized reproduction of this article is prohibited. Recently, NB UVB has been shown to be as effective as which are not well understood or identified. The initial PUVA in treating psoriasis (Amer, Tosson, Al Mokadem, approach to the pruritic patient should focus on trying & Nofal, 2007). Phototherapy can be used in conjunction to identify or rule out primary dermatological disease. with other agents, including oral antihistamines and top- In patients without cutaneous findings, a thorough phys- ical corticosteroids (Borzova, Rutherford, Konstantinou, ical examination should be performed, looking for sys- Leslie, & Grattan, 2008). However, use of phototherapy temic disease. In the absence of skin findings, first-line is limited by the frequency of visits required, potential side therapy should include a short course of oral antihis- effects of oral psoralens, increased risk for skin cancer, tamines, proper dry skin care education, and topical and because symptoms frequently recur after therapy has emollients and antipruritics. The patient should have a been discontinued (James, Berger, & Elston, 2011). follow-up evaluation in 2 to 4 weeks. If there is no im- Pruritus is reduced with thermal counterstimulation provement or worsening of symptoms, consider labora- with heat or cold. This has been known for generations. tory evaluation for systemic disease. h The effects of heating the skin are less consistent than cooling the itchy skin. Heating can aggravate itch in REFERENCES about one third of patients (Bernhard, 1994). Alto, W. A., & Clarcq, L. (1999). Cutaneous and systemic manifestations Acupuncture, transcutaneous electrical nerve stimu- of mastocytosis. Retrieved on September 3, 2011, from http:// lation, and vibration provide counterstimulation and www.aafp.org/afp/990600ap/3047.html Amer, M., Tosson, Z., Al Mokadem, S., & Nofal, A. (2007). Controversial may reduce itch (Bernhard, 1994). In some studies, trans- results of phototherapy in the treatment of psoriasis. Egyptian cutaneous electrical nerve stimulation loses efficacy with Dermatology Online Journal, 3(1), 6. continued use. However, these modalities have been Bernhard, J. D. (1994). Itch: Mechanisms and management of pruritus. shown to be effective beyond the placebo effect. ‘‘Drastic New York, NY: McGraw-Hill. Bingham, L. G., Noble, J. W., & Davis, M. D. (2007). Wet dressings used measures’’areusedinseverecases,whenitchiscausing with topical corticosteroids for pruritic dermatoses: A retrospective significant reduction in quality of life (Bernhard, 1994, study. Journal of the American Academy of Dermatology, 60(5), 792Y800. p. 376). These measures, including plasmapheresis, have Booher, S., McCann, S. A., & Tawa, M. C. (2011). Cutaneous T-cell been effective in specific situations. Providing understand- lymphoma: Mycosis fungoides/Sezary syndrome: Part 1. Journal of the Y ing for an itchy patient makes that person more likely to Dermatology Nurses’ Association, 3(1), 18 32. Borzova, E., Rutherford, A., Konstantinou, G. N., Leslie, K. S., & Grattan, comply with treatments and helps to reduce stress. Con- C. E. H. (2008). Narrowband Ultraviolet B phototherapy is beneficial versely, lack of understanding can further isolate the pa- in antihistamine-resistant symptomatic dermatographism: A pilot study. Journal of the American Academy of Dermatology, 59(5), tient, causing more stress and self-aggression toward the 752Y757. skin. It is important to collaborate with the patient’s fam- Desai, N. S., Poindexter, M. D., Monthrope, Y. M., Bendeck, S. E., ily and friends to create a positive and supportive environ- Swerlick, R. A., & Chen, S. C. (2008). A pilot quality-of-life instrument for pruritus. Journal of the American Academy of ment (Bernhard, 1994). Dermatology, 59(2), 234Y244. The difficulty in treating pruritus stems from the fact Elmariah, S. B., & Lerner, E. A. (2011). Topical therapies for pruritus. Y that pruritus, like pain, is a stimulus that cannot be mea- Seminars in Cutaneous Medicine and Surgery, 30(2), 118 126. Hundley, J. L., & Yosipovitch, G. (2004). Mirtazapine for reducing sured directly and affects individuals differently. Most nocturnal itch in patients with chronic pruritus: A pilot study. Journal assessments measure pruritus by direct observation of of the American Academy of Dermatology, 50(6), 889Y891. James, W. D., Berger, T. G., & Elston, D. M. (Eds.) (2011). Andrews’ scratching or by having patients rate itch on a severity diseases of the skin: Clinical dermatology (11th ed.). xxx, PA: Elsevier. scale, similar to a pain scale. A study by Desai et al. (2008) Mazoff, C. D. (2008). Extrahepatic manifestations: Pruritus (itching). developed a pruritus-specific quality of life instrument that Retrieved on November 20, 2011, from http://www.hcvadvocate.org/ showed validity, reproducibility, and reliability with inter- hepatitis/factsheets_pdf/pruritus.pdf Merriam-Webster. (2011). Itch. Retrieved from http://www.merriam-webster nal consistency. Hopefully, instruments such as these will .com/dictionary/itch assist in studying pruritus and lead to more effective Muehlbauer, P., & McGowan, C. (2009). Skin cancer. Pittsburgh, PA: treatment options. Oncology Nursing Society. Norman, R. A. (2003). Xerosis and pruritus in the elderly: Recognition Nursing implications for the pruritic patient include and management. Dermatologic Therapy, 16(3), 254Y259. encouraging the patient to avoid triggering or exacer- Schmelz, M., Schmidt, R., Bickel, A., Handwerker, H. O., & Torebjork, bating factors, maintaining proper skin hydration, using H. E. (1997). Specific C-receptors for itch in human skin. Journal of Neuroscience, 17(20), 8003Y8008. cool compresses on the skin, keeping the fingernails Serling, S. L., Leslie, K., & Maurer, T. (2011). Approach to pruritus in the trimmed, and adequate adherence to the established adult HIV-positive patient. Seminars in Cutaneous Medicine and Y treatment plan. Surgery, 30(2), 101 106. Stander, S., Steinhoff, M., Schmelz, M., Weisshaar, E., Metze, D., & Luger, T. (2003). Neurophysiology of pruritus: Cutaneous elicitation of itch. CONCLUSION Archives of Dermatology, 139(11), 1463Y1470. Steinhoff, M., Cevikbas, F., Ikoma, A., & Berger, T. G. (2011). Pruritus: In summary, pruritus is a complex mechanism with nu- Management algorithms and experimental therapies. Seminars in merous psychological and chemical mediators, many of Cutaneous Medicine and Surgery, 30(2), 127Y137.

For more than 70 additional articles related to skin/wound care, go to NursingCenter.com\CE.

VOLUME 4 | NUMBER 2 | MARCH/APRIL 2012 105

Copyright © 2012 Dermatology Nurses' Association. Unauthorized reproduction of this article is prohibited.