Dr Neda AdibiDermatologist and researcher of Isfahan university of medical sciences

Pruritus The most common (10-50%) complaint in

dermatologyWith or without skin lesion With or without systemic problemsElicit desire to scratch Primary or secondary

What is pruritus a sensation that causes the desire or reflex

to scratch. • has many similarities to pain, and while both

are unpleasant sensory experiences, their behavioral response patterns are different.

• Pain creates a withdrawal reflex, while itch leads to a scratch reflex

EpidemiologyPruritus occurs in approximately 20% of

adults. It is present in approximately 25% of patients with jaundice and in 50% of patients receiving renal dialysis.

An underlying systemic disease is reported in 10-50% of patients who seek medical attention for pruritus.

Pruritus is more common in elderly people

Pathophysiology

• The sensation of pruritus is transmitted through

slow-conducting unmyelinated C-polymodal and possibly type A delta nociceptive neurons with free nerve endings located near the dermoepidermal junction or in the epidermis.

• These neurons appear to be located more superficially and are more sensitive to pruritogenic substances than pain receptors. Activators of these nerves include histamine, neuropeptide substance P,[1] serotonin, bradykinin, opioid peptides .[2]

Complication • Debilitating sleep deprivation and

suicidal ideation • Women with untreated intrahepatic

cholestasis of pregnancy that begins before 33 weeks of gestation have increased rates of preterm deliveries and stillbirths.

• lichen simplex chronicus, prurigo nodules, and excoriations

complicationRenal pruritus is an independent marker for

mortality at 3 years for patients on HD. Patients with severe generalized pruritus and

Hodgkin disease have a poor prognosis. Pruritus that recurs after treatment is useful

in detecting recurrence of the cancer.

Many of the therapeutic modalities listed in the Treatment and Medication sections offer only symptomatic control. Only cure of the underlying condition results in complete resolution of pruritus. During treatment to relieve symptoms, every effort should be made to treat the underlying systemic disease.

management• The management of pruritus is challenging

especially when an underlying etiology cannot be identified. Due to the poorly understood pathophysiology, the development of effective treatment modalities for pruritus has proven to be particularly difficult.

. General Principles in the Treatment of Pruritus

• There are a number of possible underlying etiologies for pruritus .

• Detailed Hx and physical exam • If an underlying cause is discovered it should

be treated

• . Topical therapies are the mainstay

of therapy for mild and localized itch while systemic therapies should be considered for severe and generalized itch.

Topical emolient and moisturizer

Improving the barrier function

Corticosteroid Not having the direct anti pruritus effect but can decrease the inflamation

Topical calcineurin inhibitors

Tacrolimus 0.03 -0.1 % specially effective in atopic dermatitis pruritus and anogenital pruritus

Doxepin 5% Not should be used in children because of risk of sedation

Capsaicin 0.025%–0.1% cream Particularly useful in neuropathic itch, mayexperience initial transient burning

Lidocaine patch 5% Useful in neuropathic pruritus

• . The possible causes for itchiness range from internal illnesses, such as kidney or liver disease, to skin rashes, allergies, and dermatitis.

• categories on the basis of the underlying causative disease: renal pruritus, cholestatic pruritus, hematologic pruritus, endocrine pruritus, pruritus related to malignancy, and idiopathic generalized pruritus

What is dermatitissymptoms of dermatitis may include a red

rash, blisters, and dry, cracked skin. Itchy skin is also common and can become severe. The skin may become painful, with stinging or burning.

What Are the Risk Factors For Dermatitis

a family history of dermatitis . a family history of asthma or hay fever

increases the risk of atopic dermatitis. People who work with or near strong

chemical substances

How Is Dermatitis Prevented• Dermatitis often runs in families, so it is not

always preventable. But it is possible to prevent symptom flare-ups.

• People with allergies should avoid skin contact with allergens. Frequently moisturizing the skin can also help.

• Avoid excess drying of the skin by reducing bath time to 15 minutes or less, and use warm water instead of hot water. Use mild soaps and detergents, which are less likely to irritate the skin.

• Home care for dermatitis may include applying cool, wet cloths to the skin. Covering the skin with a dressing or bandage prevents scratching or infection if the skin is broken. 

• Dermatitis is sometimes associated with an increase in stress. Alternative therapies may help reduce stress. These include acupuncture, massage, and medications.

• Other alternative therapies, such as herbs and dietary supplements, may be used to treat dermatitis. Some studies indicate that children under the age of 13 may reduce eczema by taking probiotics

Types of Dermatitis

• , the two most common types are contact dermatitis and atopic dermatitis.

• Contact dermatitis skin comes in direct contact with an allergen. This causes an allergic reaction.like poison oak, poison ivy, detergent, perfume, cosmetics, and nickel.

• Atopic dermatitis is also called eczema. It can be chronic and may first start in infancy. It tends to run in families with a history of allergies

• Treatments for dermatitis depend on the severity of symptoms and the cause. Medication is often the main treatment.

• Topical creams containing hydrocortisone can reduce inflammation, redness, and itching.

• Antihistamines are sometimes recommended in order to reduce allergic reactions, which can cause dermatitis.

• Antibiotics are usually given only if an infection has developed. Infections can occur when the skin is broken due to intense scratching.

Other causes of dermatitis 1)thromboflebitis2)dermatomyosistis3)cellulitis4)graft versus host 5)candida skin infectionkwashiocor

. How Is Contact Dermatitis Treated?

• Avoid scratching• clean skin with soap and lukewarm water to

remove any irritants. Soak a washcloth in the cool water, wring it out, and apply it to the skin. 

• calamine lotion or hydrocortisone cream. • Taking an antihistamine drug such as

diphenhydramine • Most cases of contact dermatitis will go away

on their own and aren’t cause for concern.

Moisturizers, Emollients and Barrier Creams

• improved barrier function• Transepidermal water loss (TEWL) is

associated with itch intensity in patients with atopic dermatitis. This observation may be explained by the suboptimal epidermal barrier function facilitating the entry of irritants and itch-causing agents.

Topical Corticosteroids• Topical corticosteroids should only be used to

provide relief of itching associated with inflammatory skin diseases such as atopic dermatitis or psoriasis.

• should not be used to treat generalized chronic itch or for prolonged periods. Corticosteroids are not directly antipruritic and it is believed they exert a beneficial effect on pruritus through their reduction in skin inflammation.

Topical Immunomodulators

• The topical calcineurin inhibitors (TCI), tacrolimus and pimecrolimus, have been shown to be effective in reducing pruritus in atopic dermatitis , chronic irritative hand dermatitis, graft-versus host disease, lichen sclerosis, anogenital pruritus and prurigo nodularis.

• Common side effects of these agents are transient burning and stinging sensations

Pimecrolimus is indicated only after other treatment options have failed. Use short-term and for intermittent use only.

Topical Antihistamines

• Doxepin, a tricyclic antidepressant, is a potent H1 and H2 antagonist.

• Doxepin 5% cream has been shown to significantly reduce pruritus in patients with atopic dermatitis, lichen simplex chronicus, contact dermatitis and nummular dermatitis.

• drowsiness, through systemic absorption of doxepin, occurs in approximately 20 -25% of patients, limiting its use especially in children. Other common side effects of this treatment include localized cutaneous burning and allergic contact dermatitis.

Menthol

• Menthol has been used alone or in combination as a topical antipruritic for centuries.

• Menthol at concentrations of 1 – 3 % being commonly used to relieve pruritus while higher doses can induce irritation.

• Of note, patients who report a reduction in pruritus with cold sensation may especially benefit from topical therapies containing menthol.

Capsaicin

• Beneficial effects in chronic, localized pruritic disorders, particularly those of neuropathic origin, such as notalgia paresthetica and brachioradial pruritus as well as other pruritic conditions (e.g. prurigo nodularis, aquagenic pruritus and pruritus associated with chronic kidney disease).

• Initial application causes an intense transient burning sensation at the application site which may lead to poor compliance or premature cessation of treatment; however, this side effect usually resolves after using the medication for a few days or with application of a topical anesthetic.

Local anesthetics

• Topical local anesthetics such as pramoxine 1 percent, lidocaine 5 percent and the eutectic mixture of lidocaine 2.5 percent and prilocaine 2.5 percent, have all been shown to have antipruritic properties.

Antihistamin Oral antihistamines have traditionally been

the cornerstone of pruritus treatment. With the exception of urticaria, antihistamines have little effect on conditions associated pruritus.

sedating (first-generation) antihistamines may have a role in patients where pruritus is exacerbated at night probably via their soporific

effects.In cases of urticaria, sedative antihistamines, such as hydroxyzine, may be particularly valuable with pruritus during the night while non-sedating (second-generation) antihistamines such as loratadine, desloratadine, cetirizine and levocetirizine may be suitable in the daytime for relief of pruritus.

Antidepressants

Mirtazapine, has been reported to relieve itch in patients with advanced cancer, leukemia, lymphoma (including cutaneous lymphoma), chronic kidney disease, cholestasis and atopic dermatitis.

• Mirtazapine is a relatively safe for the treatment of nocturnal pruritus.

• venlafaxine and duloxetine do not seem to have significant antipruritic effects in our experience.

paroxetine and fluvoxamine, were shown to reduce chronic pruritus, with the most favourable responses being seen in patients with pruritus due to atopic dermatitis, systemic lymphoma and solid carcinoma.

Sertraline, another SSRI, has also been shown to an effective, well-tolerated treatment for pruritus due to chronic liver disease.

• Several studies have shown the antipuritic effects of μ-opioid receptor antagonists such as naltrexone and nalmefene. Natrexone has been reported to reduce pruritus in patients with cholestasis, end-stage renal disease, burns and atopic dermatitis.

• butorphanol and nalfurafine appear to be beneficial in pruritic conditions.

. Gabapentin may be particularly useful in forms of neuropathic pruritus related to nerve entrapment disorders such as brachioradial pruritus and notalgia paresthetica

100-300 mg / day specially after hemodyalysis and cutaneus T cell lymphoma

, cyclosporine and azothioprine, have demonstrated antipruritic effects in patients with atopic dermatitis most likely through their anti-inflammatory effects. It is recommended that oral cyclosporine and azathioprine, only be used in the short-term for patients with atopic dermatitis who have failed conventional therapy and with appropriate monitoring.

Renal pruritusIn CRF specially in those with HDNot related to uremiaelevated levels of circulating histamine in

patients receiving HD. increased numbers of mast cells in various

organ systems. antihistamines are, at best, marginal in the treatment of renal pruritus

• Elevated levels of divalent ions, such as calcium, magnesium, and phosphate, are thought to play a role.

• Marked improvement of pruritus resulting from low dialysate calcium and magnesium concentrations has been reported

• Decreased transepidermal elimination of pruritogenic substances, xerosis, elevated levels of serum bile acids, and increased epidermal vitamin A levels all may contribute to the condition. Elevated

. In patients with CRF, a systemic inflammatory response involving overexpression of activated type 1 helper T lymphocytes (which secrete interleukin 2) may induce pruritus. UV-B, thalidomide, and tacrolimus all target mediators of this inflammation. Elevated ferritin and low transferrin and albumin levels have been correlated with the severity of pruritus.

Cholestatic pruritus

some combination of the pruritogenic substances mentioned above (ie, bile salts, histamine, opioids) induces cholestatic pruritus.

Hematologic pruritus

Patients with pruritus and iron deficiency may not be anemic; this observation suggests that pruritus may be related to iron and not hemoglobin.

Polycytemia Vera Hodgkin lymphoma

Endocrine pruritus

Hyper and hypotyroidismDiabetes mellitus

• 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.

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.

Laboratory Studies• When a primary dermatologic condition is excluded and a systemic

cause is suspected, certain laboratory tests may aid diagnosis. If suspicion is low concerning a systemic disease, a 2-week trial of therapy with oilated soap for bathing, emollients for after the bath, and oral antihistamines may be attempted. If this fails, a laboratory evaluation is indicated.

• The following screening laboratory tests are recommended:• CBC count with differential: This test assists in uncovering

polycythemia vera, in which the hemoglobin level, hematocrit value, WBC count (including absolute neutrophil count; see the Absolute Neutrophil Count calculator), and platelet count are elevated. Abnormalities are also seen in persons with hematologic malignancies. Patients with iron deficiency may have microcytosis and low hemoglobin levels. However, those with pruritus and iron deficiency may not be anemic; tests of and serum iron, ferritin, and total iron-binding capacity may be ordered to confirm or exclude the diagnosis.

• Serum creatinine and blood urea nitrogen values: Persons with CRF have elevated levels.

• Serum alkaline phosphatase and bilirubin, direct and indirect: Elevated levels may suggest cholestasis. If elevated, antimitochondrial antibody and serum anti–hepatitis C tests may be ordered to confirm primary biliary cirrhosis and hepatitis C, respectively, if these are suspected. Other tests may be needed to confirm other causes of cholestasis. A positive antimitochondrial antibody finding has 98% specificity for primary biliary cirrhosis.

• Thyrotropin and thyroxine: The results assist in ruling out hypothyroidism and hyperthyroidism.

• Fasting glucose value, if prompted by signs or symptoms• Stool for occult blood in patients aged 40 years or older: A

positive result suggests possible malignancy in the GI tract.• HIV antibody test, if risk factors are present• Skin biopsy for routine pathology and immunofluorescence to

exclude subacute occult autoimmune conditions such as pemphigoid and dermatitis herpetiformis

Imaging Studies

In patients with Hodgkin disease, chest radiography may help in detecting lymphadenopathy in the mediastinum. If cholestasis is present, abdominal ultrasonography may be performed to evaluate the biliary tract.

• When the results of initial laboratory screening are negative and when the physician still suspects a systemic cause, tests of the following may be ordered:

• Serum protein electrophoresis• Stool for ova and parasites• Stool for occult blood (may reveal source for

anemia)• Urine for hydroxy indole acetic acid (5-HIAA) and

mast cell metabolites• Negative findings from the initial evaluation do

not necessarily exclude systemic disease, and follow-up screening may be repeated every 3-6 months if clinical suspicion continues

Skin biopsy for direct immunofluorescence and special stains may help exclude a primary dermatologic condition, such as dermatitis herpetiformis or bullous pemphigoid (ie, pruritic pemphigoid), or confirm a systemic cause, such as in mastocytosis. Medical Care

Renal pruritus therapy• Narrow band 6-8 session have response is

choice and after• Gabapanthin• Cholestiramin• Nalteroxane• Capsaicin 0.025% • Tacrolimus 0.03% . Tacrolimus is a calcineurin

inhibitor, it decreases the differentiation of type 1 helper T lymphocytes, and it reduces the production of interleukin 2.[13]

• Topical gabapentin cream (3-6%) • Oral zinc sulfat 440 mg /day

Cholestatic pruritus• Cholestiramin• Rifampin• Ursodeoxycholic acid and S-adenosyl-L-methionine

have both been reported to decrease pruritus in women with cholestasis of pregnancy, but ursodeoxycholic acid may improve fetal outcomes and biochemical serum markers.[39, 40]

• Extracorporeal albumin dialysis may be considered when severe pruritus is refractory to other therapies.[41, 42]

• Thalidomide

• uvb

• Iron deficiency responds to treatment with iron, which should be continued until ferritin levels are normalized

• Patients with pruritus due to polycythemia vera may benefit from aspirin, which is considered the first-line therapy. Cimetidine, danazol, cholestyramine, UV-B light therapy, and psoralen with UV-A therapy have all been shown to help.[43, 44]

Endocrine pruritusThe pruritus of hypothyroidism is secondary

to xerosis and should be treated with emollients and thyroid hormone replacement. Pruritus secondary to hyperthyroidism improves with the correction of thyroid function.

Patient Education

. Instructions should include keeping the skin well moisturized and avoiding excessive bathing in hot water, low ambient humidity, use of alkaline soaps, and exposure to irritating fabrics. For severe cases, the patient can perform the soak and smear technique, which is the process of hydrating the skin for 20 minutes prior to bedtime, followed by the application of ointment to the wet skin.

• The itch-scratch cycle should be discussed, and patients should be encouraged to apply cool washcloths or gentle pressure to the areas and to resist the urge the scratch. Reduction or elimination of stressful factors should be discussed because stress appears to worsen itching.