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Evaluation and Treatment of Generalized Pruritus

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Evaluation and Treatment of Generalized Pruritus DERMATOLOGY REVIEW Hüll ÍIIIIIS •*™ •••• i i1 HHHJI Evaluation and treatment of generalized pruritus GARY R. KANTOR, MD • Generalized pruritus may be symptomatic of dermatologie disease or it can be a manifestation of a systemic disorder. When the cause of generalized pruritus is not immediately evident, careful clinical and laboratory evaluation and close follow-up are needed to ensure appropriate diagnosis and treatment. 0 INDEX TERM: PRURITUS • CLEVE CLIN J MED 1990; 57:521-526 RURITUS is the most common dermatologic 90% of patients on hemodialysis have either localized or symptom that patients present. It accompanies generalized pruritus.6 These patients complain of severe, a wide range of skin diseases, most of them paroxysmal itching that tends to be most severe in the characterized by primary lesions such as summer. In one study, 25% of patients had discomfort Ppapules, vesicles, and plaques (Table I). soon after hemodialysis and 42% had their most severe Generalized pruritus of undetermined origin (GPUO) is pruritus during hemodialysis.6 continuous itching of at least 3 weeks duration that is The etiology of uremic pruritus is unknown, but unresponsive to 2 weeks of conservative management and several mechanisms have been proposed. Increased unassociated with primary skin lesions. Systemic diseases numbers of mast cells have been found in the spleen and may be associated with generalized pruritus (Table 2); but bone marrow of uremic patients who have no evidence the prevalence of the association ranges from 14% to 50%, of systemic mast cell disease.7 The mast cell proliferation depending on the source of the report.1"* may be related to elevated parathyroid hormone levels. This article discusses the systemic diseases associated Histamine has been implicated, given the increased sen- with generalized pruritus, and provides recommendations sitivity of uremic patients to intradermal histamine.8 for evaluating the patient with generalized pruritus. Calcium hemostasis is defective in uremia, and medical or surgical parathyroidectomy improves the associated SYSTEMIC DISEASES ASSOCIATED WITH PRURITUS pruritus.9'10 Other possibilities include peripheral neuropathy, xerosis, hypermagnesemia, or accumulation Uremia of an unknown pruritogenic substance. Chronic renal failure is the systemic disease most Ultraviolet B phototherapy is the most effective commonly associated with generalized pruritus.5 Up to treatment of pruritus associated with uremia. Most patients improve within six treatments; if a second course of therapy is necessary, the response is more From the Section of Dermatopathology, Division of Dermatology, rapid.11 Ultraviolet A has some advantages because of its Department of Medicine, Hahnemann University School of wider availability and higher safety profile.12 Emollients Medicine, Philadelphia. Address reprint requests to G.R.K., Division of Dermatology, Hah- are useful for associated xerosis. Other effective treat- 13 nemann University School of Medicine, Broad and Vine Streets, ments include topical capsaicin, lidocaine infusion, in- Mail Stop 401, Philadelphia, Pennsylvania 19102-1192. travenous heparin, and oral charcoal. It also helps to SEPTEMBER 1990 CLEVELAND CLINIC JOURNAL OF MEDICINE 521 Downloaded from www.ccjm.org on September 26, 2021. For personal use only. All other uses require permission. GENERALIZED PRURITUS • KANTOR TABLE 1 TABLE 2 SKIN DISEASES ASSOCIATED WITH PRURITUS SYSTEMIC DISEASES ASSOCIATED WITH GENERALIZED PRURITUS Xerosis Urticaria Sunburn System involved Diseases that cause pruritus Dermatitis herpetiformis Contact dermatitis Renal Uremia Fungal infections Hepatic (obstructive Primary biliary cirrhosis Fiberglass dermatitis hepatobiliary disease) Drugs (chlorpropamide, oral contraceptives, Pruritic urticarial papules and plaques of pregnancy anabolic steroids) Pediculosis Extrahepatic biliary obstruction Miliaria Intrahepatic cholestasis of pregnancy Folliculitis Hematologic Polycythemia vera Polymorphous light eruption Iron deficiency anemia Pityriasis rosea Multiple myeloma and paraproteinemia Lichen simplex chronicus Mastocytosis Psoriasis Endocrine Thyrotoxicosis Scabies Hypothyroidism Insect bites Diabetes Atopic dermatitis Neurologic Infarcts Drug reactions Brain abscess Mycosis fungoides Multiple sclerosis Bullous pemphigoid Tumor Pemphigus foliaceus Lymphoreticular Hodgkin's disease Lichen planus neoplasms Lymphoma Internal malignancy Systemic carcinoma Carcinoid syndrome Miscellaneous AIDS Sjogren's syndrome lower the dialysate magnesium concentration for Dumping syndrome Bullous pemphigoid patients undergoing hemodialysis. Hepatobiliary diseases Pruritus may be associated with primary biliary cirrhosis, beneficial despite the associated increase in serum bile drug-induced cholestasis (as occurs with chlorpropamide, acid concentration.21 oral contraceptives, and anabolic steroids), biliary obstruc- The general consensus is that pruritus with hepatobiliary tion from intrahepatic or extrahepatic sources, and choles- disease is an effect of bile salts on the liver, not the skin. The tasis of pregnancy. Cyclic premenstrual pruritus due to pruritus is related to the release of an unknown pruritogenic recurrent cholestasis has also been reported.14 substance that binds to cholestyramine and is photolabile.22 Pruritus may develop weeks or months before other signs Supporting this theory is the beneficial effect of rifampin on and symptoms of hepatic disease. Itching often begins on pruritus associated with primary biliary cirrhosis; this drug the hands, feet, and other pressure areas of the skin and is inhibits bile acid uptake in the liver and stimulates hepatic especially severe at night. The presence of the "butterfly enzymatic degradation of bile salts.23 sign" suggests chronic obstructive hepatobiliary disease.15 Pruritus associated with hepatobiliary disease can be The butterfly sign is characterized by the relative hypopig- severe and can interfere with quality of life. Cholestyr- mentation of the skin on the mid- to upper back, sur- amine is the first treatment of choice; in resistant cases, the rounded by postinflammatory hyperpigmentation. drug may be combined with phototherapy.24 UVA or UVB Although accumulated bile salts have been impli- phototherapy alone is less useful than in the treatment of cated as the cause of pruritus in hepatobiliary disease, pruritus associated with uremia. Naloxone, a central opioid this notion is controversial.16 Factors that support the antagonist, is beneficial for intractable itching related to role of bile salts include relief of pruritus with bile salt- primary biliary cirrhosis.25 Besides rifampin,23 other treat- binding resins such as cholestyramine17 and the produc- ments include surgical external diversion of bile26 and plas- tion of pruritus when bile salts are applied to the skin.18 ma perfusion through charcoal coated glass beads.27 Nevertheless, other studies on the correlation of itching with serum and skin bile salt concentrations have had Hematologic diseases conflicting results.19,20 Furthermore, in some patients Patients with polycythemia vera may present with phenobarbital relieves pruritus without a decrease in generalized pruritus. The itching is described as "prick- serum bile acids, while in others, androgen therapy is ing" in quality and lasts from minutes to hours. It starts 522 CLEVELAND CLINIC JOURNAL OF MEDICINE VOLUME 57 NUMBER 6 Downloaded from www.ccjm.org on September 26, 2021. For personal use only. All other uses require permission. GENERALIZED PRURITUS • KANTOR after the patient emerges from a shower or bath as the Patient presents skin begins to cool—hence with pruritus the term "bath pruritus." The cause of the pruritus is unknown, although elevated History and cutaneous plasma and urine histamine •YES -« signs suggest primary levels were detected in one ( skin disease study and correlated with an Diagnosis and treat increase in circulating according to standard i basophils.28 Earlier reports tests and therapies NO claimed that cimetidine was beneficial for these I 2930 patients, but subsequent Surveillance skin POSITIVE controlled studies did not scraping for mites confirm efficacy.31 Aspirin and cyproheptadine (Periac- Treat scabies tin) have also been used for 1 treatment. NEGATIVE Generalized pruritus has been reported in association 4 Examine for with iron deficiency PRESENT lymphadenopathy, anemia.32 Although small organomegaly studies have described relief of pruritus with iron I 3334 therapy, the relationship ABSENT between generalized pruritus • and iron deficiency is ques- tionable. A large series of Treat symptomatically Begin NOT patients needs to be inves- for 2 weeks and laboratory workup IMPROVED tigated before any con- evaluate response clusions can be made. Rarely, benign gam- 35 mopathy and multiple J IMPROVED myeloma36 are associated ABNORMAL with pruritus. Systemic mas- NORMAL J tocytosis has also been Follow patient reported in a patient Treatment, additional i laboratory studies Continue symptomatic presenting with generalized as indicated treatment; re-evaluate pruritus and no observable laboratory tests in 3 months skin lesions.37 FIGURE 1. Flow chart for evaluating patients with generalized pruritus of unknown origin. Endocrine disorders Pruritus may occur in up to 5% of patients with thyrotoxicosis and subside with sitivity to catecholamines, activation of kalli-krein- treatment of the thyroid disorder.38 Some patients with kinin system, and prostaglandin mediation.40 hyperthyroidism
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