Pruritus and Systemic Disease Clinical Presentation

  • Author: David F Butler, MD; Chief Editor: Dirk M Elston, MD   more...
 
Updated: May 21, 2010
 

History

Primary dermatologic disorders can cause pruritus, and these must be excluded before a systemic cause is considered. Therefore, a thorough history, including the onset, duration, severity, location, provoking factors, time relation, and relationship to activities such as bathing should be discussed with the patient who presents with pruritus.

A review of systems is needed to uncover signs and symptoms associated with systemic disease and to direct the physical examination and laboratory evaluation. A detailed drug history is required to exclude medications that can cause itching. A history of alcohol abuse may indicate chronic liver disease. A review of potential emotional stresses and mental health history may reveal a psychiatric cause.

Clues supporting a systemic cause include the insidious onset of generalized pruritus rather than an acute presentation.

Renal pruritus

Symptoms range from paroxysmal discomfort that may remit spontaneously to continuous itching that is present day and night. Approximately 46% of patients have pruritus on a daily basis, whereas 52% report it as appearing weekly or monthly. Pruritus is localized in 56% of patients and is most often seen on the back, abdomen, head, and shunt arms. The remaining patients usually present with generalized pruritus. The vertex of the scalp is a common site of pruritus, and excoriations may be present. Exacerbations are common at night and during or just after HD. The intensity may also increase during summer months.

Cholestatic pruritus

Cholestatic pruritus is characterized by an intermittent, mild, and insidious onset that may be generalized or localized. Pruritus is typically worse on the hands and feet and in areas under tight-fitting clothing. Pruritus and fatigue are commonly the presenting symptoms of patients with primary biliary cirrhosis. Associated symptoms of inflammatory bowel disease may be present in patients with primary sclerosing cholangitis.

Hematologic pruritus

Although hematologic pruritus related to iron deficiency remains controversial, the pattern that has been described is most often generalized; however, it may be localized, especially to the perianal and vulvar regions. Patients with polycythemia vera may have aquagenic pruritus (after a hot bath or shower) with a prickly sensation, but this is not specific. Aquagenic pruritus may occur within minutes of contact with water. However, it may precede the development of the disease by several years. Patients may report headache, visual disturbances, weight loss, night sweats, and vertigo. Other symptoms include redness, warmth, and pain (erythromelalgia) of the digits.

Endocrine pruritus

In most patients, endocrine pruritus is generalized and associated with symptoms of the underlying disease process (eg, hyperthyroidism vs hypothyroidism). Pruritus associated with diabetes mellitus is another controversial association. The described pruritus is often localized to the vulva or anus and usually is due to candidal or dermatophytic infection. However, unrelenting pruritus of the scalp is reported in association with diabetes mellitus.

Pruritus and malignancy

The symptoms of pruritus may differ in patients with lymphoma compared with symptoms in patients with carcinoma. Pruritus due to carcinoma results in moderate-to-severe itching with changes in intensity and location over the course of the disease. Common sites are the extensor surfaces of the upper extremities and the anterior surfaces of the lower legs. Pruritus of the nostrils has been associated with brain tumors.

Pruritus due to lymphoma may precede the diagnosis by 5 years. It is most common in patients with Hodgkin disease (nodular sclerosing subtype). The pruritus is described as intolerable, continuous, and severe and is accompanied by a burning sensation. It may begin on the lower extremities and progress to the whole body. If localized, the pruritus is commonly present in the areas drained by the lymphatics affected in the disease process.

Leukemic pruritus is usually generalized at onset and is less severe than that related to lymphoma.

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Physical

Physical examination assists in differentiating between systemic causes of pruritus and primary dermatologic conditions. When systemic disease underlies pruritus, patients may have normal-appearing skin or secondary lesions, such as excoriations, prurigo nodules, lichen simplex chronicus, or signs of a secondary bacterial infection. Patients may have the butterfly sign, which is an area of relative hypopigmentation or normal skin on the middle of the back in combination with areas of postinflammatory hyperpigmentation in locations accessible to the patient's hands. Other signs of systemic disease are as follows:

  • Renal pruritus: Diffuse xerosis and half-and-half nails may be seen. The patient may have signs of peripheral neuropathy and uremia.
  • Cholestatic pruritus: Signs of liver disease include jaundice, spider angiomata, Dupuytren contractures, white nails, gynecomastia in men, xanthelasma, splenomegaly, and ascites.
  • Endocrine pruritus: Patients with hypothyroidism have brittle nails and dry, course skin and hair. Patients with hyperthyroidism may have warm, smooth, and fine skin. They may also have chronic urticaria and angioedema. Other signs are fever, tachycardia, exophthalmos (associated with Grave disease), and atrial fibrillation.
  • Hematologic pruritus: Patients with iron deficiency may have pallor if they have anemia; they might also have glossitis and angular cheilitis. Polycythemia vera may result in a ruddy complexion around the lips, cheeks, nose, and ears, along with hypertension and splenomegaly.
  • Pruritus and malignancy: Patients with Hodgkin disease may have ill-defined hyperpigmentation of the skin, ichthyosis, nontender lymphadenopathy, and splenomegaly.
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Causes

Renal pruritus occurs in patients with CRF, most often those receiving HD. The exact cause is not known, although toxic substances retained during HD, histamine, opioids, and neural proliferation have been postulated as potential causes.

The exact mechanism of cholestatic pruritus is not known. However, bile salts, histamine, opioids, and an unknown pruritogen from damaged hepatocytes are postulated as potential causes. Cholestatic pruritus is particularly common with cholestasis caused by primary biliary cirrhosis, primary sclerosing cholangitis, chronic hepatitis C, choledocholithiasis, obstructive carcinoma of the pancreas/biliary system, cholestasis of pregnancy, and end-stage liver disease of any cause. Drug-induced cholestasis may be caused by chlorpropamide, tolbutamide, phenothiazines, erythromycin, anabolic steroids, and oral contraceptives.

Hematologic pruritus may be seen in association with the following conditions:

  • Iron deficiency
  • Polycythemia rubra vera
  • Hypereosinophilic syndrome
  • Essential thrombocythemia
  • Myelodysplastic syndrome

Endocrine pruritus may be seen in association with the following disorders:

  • Hyperthyroidism
  • Hypothyroidism
  • Diabetes mellitus
  • Hyperparathyroidism
  • Hypoparathyroidism

The following malignancies are known to have the potential to cause itching:

  • Hodgkin disease
  • Non-Hodgkin lymphoma
  • Leukemias
  • Paraproteinemias and myeloma
  • Carcinoid syndrome
  • Sipple syndrome (multiple endocrine neoplasia)
  • Solid tumors, including GI malignancies, CNS tumors, and lung cancer

A variety of other systemic disorders are associated with pruritus, including the following:

  • Drug-induced pruritus without a rash
  • Mastocytosis
  • HIV infection and AIDS
  • Sarcoidosis
  • Eosinophilia-myalgia syndrome
  • Dermatomyositis
  • Scleroderma
  • Systemic lupus erythematosus
  • Sjögren syndrome
  • Neurofibromatosis
  • Hemochromatosis
  • Multiple sclerosis
  • Brain abscess
  • Parasitic infections, including those due to hookworms, pinworms, Trichinella spiralis (trichinosis), Gnathostoma spinigerum (gnathostomiasis), Giardia species, Ascaris species (ascariasis), or Onchocerca species (onchocerciasis)
  • Parvoviral infection
  • Leptospirosis
  • Chemical intoxication with mercury or diamino diphenylmethane
  • Primary cutaneous amyloidosis
  • Starvation
  • Fibromyalgia
  • Chronic fatigue syndrome
  • Dumping syndrome
  • Notalgia paresthetica
  • Adrenergic conditions (adrenergic pruritus)
  • Cholinergic conditions (cholinergic pruritus)
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Contributor Information and Disclosures
Author

David F Butler, MD  Professor of Dermatology, Texas A&M University College of Medicine; Chair, Department of Dermatology, Director, Dermatology Residency Training Program, Scott and White Clinic, Northside Clinic

David F Butler, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, American Society for Dermatologic Surgery, American Society for MOHS Surgery, Association of Military Dermatologists, and Phi Beta Kappa

Disclosure: Nothing to disclose.

Coauthor(s)

Jared J Lund, MD  Dermatology Resident, Department of Dermatology, Marshfield Clinic, St Joseph's Hospital

Disclosure: Nothing to disclose.

Specialty Editor Board

Franklin Flowers, MD  Chief, Division of Dermatology, Professor, Department of Medicine and Otolaryngology, Affiliate Associate Professor of Pediatrics and Pathology, University of Florida College of Medicine

Franklin Flowers, MD, is a member of the following medical societies: American College of Mohs Micrographic Surgery and Cutaneous Oncology

Disclosure: Nothing to disclose.

Michael J Wells, MD  Associate Professor, Department of Dermatology, Texas Tech University Health Sciences Center

Michael J Wells, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, and Texas Medical Association

Disclosure: Nothing to disclose.

Jeffrey J Miller, MD  Associate Professor of Dermatology, Penn State University College of Medicine; Staff Dermatologist, Penn State Milton S Hershey Medical Center

Jeffrey J Miller, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, Association of Professors of Dermatology, North American Hair Research Society, and Society for Investigative Dermatology

Disclosure: Nothing to disclose.

Joel M Gelfand, MD, MSCE  Medical Director, Clinical Studies Unit, Assistant Professor, Department of Dermatology, Associate Scholar, Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania

Joel M Gelfand, MD, MSCE is a member of the following medical societies: Society for Investigative Dermatology

Disclosure: AMGEN Consulting fee Consulting; AMGEN Grant/research funds Investigator; Genentech Grant/research funds investigator; Centocor Consulting fee Consulting; Abbott Grant/research funds investigator; Abbott Consulting fee Consulting; Novartis investigator; Pfizer Grant/research funds investigator; Celgene Consulting fee DMC Chair; NIAMS and NHLBI Grant/research funds investigator

Chief Editor

Dirk M Elston, MD  Director, Department of Dermatology, Geisinger Medical Center

Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

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