E-Case #8-B

Jane Yeh, M.D.

August 6-10, 2001

32 year-old female with a history of Graves disease presents with 6 months of intense generalized pruritus. The pruritus is located on her back, abdomen, arms, and legs. Her face is relatively spared. The pruritus is worse at night but occurs throughout the day. She reports episodes of rashes associated with the itching but the majority of her rashes occur only after scratching. She occasionally is unable to sleep due to intense itching and often awakens from sleep due to it. She has no previous history of pruritus or rashes. She has no history of atopic dermatitis or asthma.

She has been treated with Allegra and Claritin in the past without much benefit. She was then switched to Zyrtec, which gives her a few hours of relief. In addition, she has used both Benadryl and hydroxyzine on an as needed basis. She also has been using Dove soap to bathe and uses Eucerin lotion 2-3 times a day.

Past Medical History:

1. Graves disease - previously on PTU then methimazole, but currently in remission x 6 months with normal TFTs

2. Oligomenorrhea

Meds: none

Family history is unremarkable and is notably without a history of atopic dermatitis, rashes or generalized pruritus.

Physical examination

• General: petite Asian female looking younger than stated age, in mild distress

• VS normal

• HEENT- NC/AT, PERRL, sclera not injected, anicteric

• neck-supple, no LAN, thyroid mildly enlarged/smooth

• CV- RRR, no m/r/g

• lungs- clear

• abdomen- soft, nontender, liver/spleen nonpalpable

• extrem- no edema

• skin- smooth, not dry, no burrows/papules; areas of erythema on arm, upper chest with some excoriations; no areas of hypo/hyperpigmentation (this can be seen with chronic scratching)

QUESTIONS:

1. What are the causes of generalized pruritus without urticaria or rash?
   Generalized pruritus is often due to dry skin. This is especially the case in the elderly. In addition, generalized pruritus can be a result of multiple systemic diseases: uremia, obstructive liver disease (of note, primary biliary cirrhosis can present with pruritus that precedes any LFT abnormalities), malignancy (lymphoma especially Hodgkin's, leukemia, GI cancers, CNS cancers). The list also includes polycythemia vera, hyperthyroidism, diabetes, Sjogren's, dermatomyositis, and iron deficiency.
   
   Infestations such as scabies and parasitic diseases can also cause itching.
   Also multiple drugs can cause pruritus. Opiates can cause mast cell degranulation and many drugs such as estrogen can cause cholestasis.

2. What are the tests that one should get?
   Stool parasite evaluation, hematocrit, white count with differential (for eosinophils), liver function testing, BUN/creatinine, glucose, TSH.  CXR and stool hemoccult if age >40 may be worthwhile to search for malignancy.
   
   Skin biopsy is usually unhelpful as it is often reveals changes consistent only with scratching.
   
   In the patient above, her studies included:

   • normal chest X-ray

   • normal CBC, normal Chem-7 with glucose 78, normal LFTs

   • ESR 32 (sl high)

   • ANA negative, RF negative

   • TSH 0.61, normal free T4

3. What substances other than histamine have been implicated in itching?
   
   opiates (elicit histamine), serotonin, prostaglandins, kallikrein, IL-2, substance P, VIP, trypsin.

4. What are possible therapies?
   Prevention of scratching is the most important as scratching elicits the secretion of inflammatory mediators. Keeping the skin moist is important. A moisturizing soap such as Dove is recommended; deodorant soaps and Ivory are very drying. A good moisturizer such as Eucerin is important as well as avoiding heat and hot water as they can increase histamine secretion. Topical agents that can be used include coolants such as menthol, eucalyptus oil, camphor, and calamine lotion. Anesthetic agents such as EMLA ointment can be used. Other possible topical agents include topical aspirin, topical doxepin, and capsaicin.  A good hand out describing sensitive skin care is available in the exam rooms or with other patient information handouts in the clinic.
   
   Systemic antihistamines are helpful. Of the nonsedating agents, Zyrtec is often the most efficacious for itching. The sedating antihistamines may help with sleep as well (hydroxyzine).  Doxepin is often used as well perhaps for its sedating power or the antidepressive action.

References:

Greaves MW & Wall PD. Pathophysiology of itching. The Lancet 1996, 348, 938-40.

Yosipovitch G & David M. The diagnostic and therapeutic approach to idiopathic generalized pruritus. International Journal of Dermatology 1999, 38, 881-7.