Pruritus is seen in almost all conditions associated with inflammation, tumors, or metabolic abnormalities. In rare cases, it may be idiopathic, but investigations are necessary to rule out other possible causes before attributing itch to idiopathic causes. Pruritus may be described as burning, tingling, tickling, deep or superficial. It may be localized or generalized and may occur on any part of the skin.

Localized itching usually indicates specific local causes such as:

• Atopic, contact, or seborrheic dermatitis
• Photodermatitis
• Eczema
• Psoriasis
• Lichen planus
• Dermatophytosis (ringworm)
• Scabies
• Pediculosis (lice infestation)
• Freshwater and saltwater schistosomes, jellyfish, and anemones.

In addition to local causes, anal or vulvar pruritus may be secondary to the underlying condition. Anal itching may be caused by hemorrhoids, anal fissures, proctitis due to inflammatory bowel disease, or tumors. Vulvar itching may be caused by cystitis, cervicitis, or rectal malignancy.

Persistent itching in the medial scapular border is called notalgia paresthetica and is probably a distinct sensory neuropathy.

Generalized pruritus

Generalized pruritus is a characteristic feature of many skin conditions and may also be a symptom of various systemic diseases. In most cases, this pruritus is caused by the following systemic factors

• Pregnancy
• Medication reactions: barbiturates, antibiotics, contraceptives, psoralen and ultraviolet A (PUVA) therapy, etc.
• Parasitic infestations: trichinellosis, onchocerciasis, echinococcosis, etc.
• Infectious diseases: chickenpox, rubella, etc.
• Chronic kidney failure/uremic pruritus
• Bile duct obstruction
• Hematological disorders: leukemia, myeloproliferative disorders, paraproteinemia/myeloma, eosinophilia syndrome, iron deficiency
• Endocrine disorders: hyperthyroidism, hypothyroidism, diabetes, hyperparathyroidism, hypoparathyroidism
• Neurological disorders: cerebrovascular disorders, multiple sclerosis, neurosis, psychosis, peripheral nerve injuries, postherpetic neuralgia
• Sjögren's syndrome
• Mastocytosis
• HIV infection
• Malignant tumors of internal organs
• Aquagenic urticaria
• Psychological factors

A clinical approach to a patient with pruritus includes a thorough physical examination and a detailed medical history. In some cases, laboratory data may be helpful. During the physical examination, it's important to distinguish primary skin lesions, which indicate a skin disorder, from secondary lesions caused by scratching. Lymphadenopathy, hepatomegaly, or splenomegaly may indicate systemic disease.

The history of pruritus plays a crucial role in the diagnosis. It's useful to determine:

1. Whether the itch is localized or generalized
2. How long it has been present
3. If it's acute or chronic
4. Any connection with the patient's activities (occupation, hobbies)
5. When it occurs (at night or not)
6. Provoking factors (water, physical exertion, pets, etc.)
7. Allergies and/or atopy
8. Which medications have been taken orally or topically
9. The patient's travel history and sexual history
10. Getting the patient's perspective on the condition is essential.

The proposed screening may include:

1. Complete blood count
2. Hematocrit
3. Hemoglobin
4. Serum iron
5. Erythrocyte sedimentation rate (ESR)
6. Glucose level
7. Alkaline phosphatase and bilirubin
8. Blood urea nitrogen (BUN) and creatinine
9. T3, T4, and thyroid-stimulating hormone
10. Stool analysis for occult blood, worm eggs, and parasites.

General therapeutic recommendations

Once the underlying disease has been diagnosed and treatment initiated, pruritus may resolve spontaneously. Negative test results and assessments do not necessarily rule out an associated systemic disorder. In such patients, repeated testing and re-evaluation of the condition is essential.

If the pruritus is localized, local therapy is prescribed. Typically, therapy progresses from local to systemic.

It is important to explain the diagnosis and the factors influencing the itch in detail to the patient. Breaking the "itch-scratch" cycle is critical, especially in conditions such as atopic dermatitis.

Dry skin should be avoided as it can trigger itching. Excessive watering and low humidity in winter in heated rooms or in summer due to air conditioning can dry out the skin.

Other factors should also be considered, such as exposure to fur and animal products, alcohol consumption, and other causes of vasodilatation, such as hot foods.

Local Treatment

Emollients and Cooling Agents

It is recommended that all patients with generalized or localized pruritus apply emollients after a bath or shower. Emollients include a wide range of products, starting with petroleum jelly. It is better to advise the patient to try different emollients and choose the one that is most comfortable.

Cold compresses can be applied locally with water, milk, Burow's solution or potassium permanganate solution (0.1 g per 1 liter of water). Medicinal baths are prescribed for generalized pruritus. It is recommended to use baths with oatmeal or potassium permanganate (6-8 g per full bathtub), which are very helpful for patients, especially those with uremic pruritus. The tub surface can be cleaned with a solution of sodium thiosulfate or vinegar, and nail stains can be removed with 3% hydrogen peroxide. Oil baths are not recommended as frequently because they make the tub slippery and increase the risk of injury. Baths with tar and baking soda may also help relieve itching.

Lotions or creams containing 0.5-2% menthol, 0.2-5% camphor, 0.2-5% phenol (use cautiously in children, avoid in pregnant women), 1-2% salicylic acid, 3-10% tar, 2-5% resorcinol, 5-10% urea, 6-20% ammonium lactate, lactic acid and other alpha-hydroxy acids, and 5-10% precipitated sulfur have soothing and antipruritic effects and may be used in combination with wet compresses or baths. Castellani's solution (0.5% menthol and 5% salicylic acid in 70% alcohol) is effective for intertriginous and anal itching.

Corticosteroids

Topical steroids are prescribed only for localized pruritus and in cases where the cause is a dermatosis that justifies the use of corticosteroids. For children and for the face, genitalia, and intertriginous areas in adults, start with low-potency steroids. For other areas of the body, you may prescribe a high-potency steroid for 1-2 weeks and then switch to a medium-potency preparation.

Chronic use of topical corticosteroids may be combined with the prescription of 0.0025-0.005% tretinoin or 12% ammonium lactate to counteract atrophy that may result from continuous steroid use.

Corticosteroid creams or lotions may be added to emollients or preparations containing other anti-itch agents. However, be aware that the strength of the corticosteroid is not diminished when combined with other substances, and the stability of the corticosteroid molecule may be compromised when mixed with other substances.

Antihistamines and Anesthetics

The use of topical antihistamines is limited because of their relative ineffectiveness and the risk of allergic sensitization. New preparations are expected to overcome these shortcomings.

Doxepin, a tricyclic compound in a 5% cream, significantly reduces pruritus in patients with atopic dermatitis, lichen simplex chronicus, nummular eczema and contact dermatitis.

Local anesthetics do not provide effective pruritus relief and may cause allergic reactions. EMLA, a slow-acting anesthetic containing 2.5% lidocaine and 2.5% prilocaine, pramoxine, or capsaicin cream are effective for localized pruritus such as nodular prurigo, notalgia paresthetica, or hemodialysis-induced pruritus. Capsaicin dissolved in topical steroids may also be effective for anal pruritus.

A recently developed liquid aspirin preparation significantly reduces pruritus compared with placebo. Tacrolimus ointment is a nonsteroidal topical immunomodulator that is considered safe and effective for long-term treatment of atopic dermatitis in children.

Systemic Therapy

Antihistamines, Tricyclic Antidepressants

Antihistamines are among the most widely used drugs in the world. They can be helpful in pruritic dermatoses that are directly dependent on histamine release, such as urticaria. These substances can be divided into classical sedative histamine blockers and more modern non-sedative histamine blockers and tricyclic antidepressants.

In general, among the traditional H1 antihistamines, substances of the ethanolamine class, including diphenhydramine, have stronger sedative effects than substances of the piperazine class, such as hydroxyzine and cyproheptadine. New-generation antihistamines have additional effects that allow them to block the release of various inflammatory mediators from mast cells without causing greater sedation than a placebo. Among these antihistamines, cetirizine and acrivastine are more likely to cause sedation than loratadine and fexofenadine. The new antihistamines also have a longer duration of action than the classic H1 blockers.

Astemizole and terfenadine have long been discontinued because of serious side effects that can be caused by their use. Old drugs such as chlorpheniramine, tripelennamine, and diphenhydramine are safe during pregnancy. Hydroxyzine, cyproheptadine, and tripolidine require further evaluation. Brompheniramine is teratogenic. The effects of modern non-sedative antihistamines during pregnancy have not been adequately studied.

One of the new-generation antihistamines is usually prescribed for morning use to avoid sedative effects. If these medications do not control itching adequately, hydroxyzine is added for nighttime use. Hydroxyzine seems to be more effective than other sedating antihistamines at controlling itching. However, it's worth trying several antihistamines and different combinations, as patients often respond differently.

Cyproheptadine is a serotonin antagonist and has been used for polycythemia vera and cholinergic urticaria. Ketotifen has been used successfully in mastocytosis. Finally, the addition of an H2 antagonist, cimetidine or ranitidine, may be helpful in some cases of generalized pruritus.

Corticosteroids

Steroids are rarely prescribed and their use is limited to cases where a dermatosis or other condition warrants their use. I usually start with a dose equivalent to 20-40 mg of prednisone per day until the pruritus subsides, and then reduce the dose by 25% every 3 days. Antihistamines may also be prescribed.

Phototherapy

Phototherapy with UVB, UVA, combinations of UVB and UVA, and PUVA (psoralen plus UVA) has been used successfully for the treatment of generalized pruritus. Patients usually respond within 7 sessions of suberythemogenic doses. If there is no response within 15 sessions, therapy is discontinued. This treatment regimen is primarily used for uremic pruritus associated with biliary cirrhosis, atopic dermatitis, photosensitivity disorders, pityriasis lichenoides, and aquagenic urticaria. However, it has also been used for several other pruritic conditions. Idiopathic pruritus is more resistant to treatment than symptomatic pruritus. It should be noted that PUVA therapy itself may cause pruritus in the early stages of treatment.

Other Medications with Antipruritic Effects

Cholestyramine, administered orally at a dose of 4 grams 1-3 times a day, helps reduce pruritus caused by renal insufficiency, cholestasis, and polycythemia vera.

Phenobarbital (3-4 mg/kg per day per os), rifampicin (10 mg/kg per day), oral hydroxyethylrutosides, and ondansetron, a serotonin receptor antagonist, may reduce cholestatic pruritus.

Erythropoietin and ondansetron may be useful in patients with uremia undergoing hemodialysis.

Tranquilizers such as haloperidol, alprazolam, buspirone, and other neurotropic and psychotropic agents such as pimozide and gabapentin have been used to treat pruritus with variable results.

Opiate antagonists, naloxone, naltrexone, nalmefene, nalbuphine, and injectable and oral droperidol have shown efficacy in cholestasis, atopic dermatitis, and urticaria.

Cyclosporine effectively controls severe pruritus caused by psoriasis, prurigo, and various types of dermatitis.

Ascomycin derivatives, a new class of substances with immunomodulatory properties that can penetrate only damaged skin, have been used in the treatment of inflammatory skin conditions, particularly atopic dermatitis. An association between skin disease and Helicobacter pylori infection has been suggested. Recent research has shown the feasibility of testing patients with generalized pruritus for H. pylori infection and eradicating the infection in those who test positive.

Aspirin has been successfully prescribed for patients with polycythemia vera, and cromolyn has been given orally to patients with systemic mastocytosis and Hodgkin's disease. Promising results have been obtained with thalidomide treatment for generalized pruritus.

Resinferatoxin, an ultra-potent analog of capsaicin, is currently being studied as a systemic treatment for generalized pruritus.

Intravenous administration of propofol, a new hypnotic used in anesthesia, has proven effective in alleviating both the motor and sensory components of itching.