Medication Summary
The goal of pharmacotherapy for prurigo nodularis is to break the itch-scratch-itch cycle by reducing pruritus, rubbing, picking, and scratching. One should always consider and rule out treatable endogenous and exogenous causes of pruritus.
Antipruritics
Class Summary
These agents may control itching by blocking the transmission of nerve impulse.
Pramoxine topical (Itch-X)
Pramoxine topical blocks nerve conduction and impulses by inhibiting depolarization of neurons.
Capsaicin topical (Dolorac, Capsin, Zostrix)
Capsaicin topical is derived from plants of the Solanaceae family. It may render skin and joints insensitive to pain by depleting substance P in peripheral sensory neurons.
Vitamin D Analogs
Class Summary
These agents regulate skin cell production and development.
Calcipotriene (Dovonex)
Calcipotriene is a synthetic vitamin D-3 analog used in the treatment of moderate plaque psoriasis.
Psoralens
Class Summary
These agents may be beneficial for patients with severe pruritus.
Methoxsalen (8-MOP, Oxsoralen)
Methoxsalen inhibits mitosis by binding covalently to pyrimidine bases in DNA when photoactivated by UV-A.
Antihistamines
Class Summary
These agents may control itching by blocking effects of endogenously released histamine but probably best used as a sedative to control pruritus, especially at night.
Diphenhydramine (Benadryl, Belix Oral)
Diphenhydramine is first-line treatment for symptomatic relief of pruritus caused by the release of histamine.
Chlorpheniramine (Chlor-Trimeton)
Chlorpheniramine is first-line treatment. It competes with histamine or H1 receptor sites on effector cells in blood vessels and the respiratory tract.
Hydroxyzine (Anxanil, Atarax, Atozine, Durrax, Vistaril)
Hydroxyzine is a first-line treatment. It antagonizes H1 receptors in the periphery. Hydroxyzine may suppress histamine activity in the subcortical region of the CNS and can be used as an anxiolytic.
Corticosteroids
Class Summary
These agents have anti-inflammatory properties and cause profound and varied metabolic effects. These agents also modify the body's immune response to diverse stimuli.
Triamcinolone (Kenalog)
Triamcinolone is first-line treatment if few lesions (for intralesional use) are present. It is for inflammatory dermatosis responsive to steroids; triamcinolone decreases inflammation by suppressing the migration of polymorphonuclear leukocytes and reversing capillary permeability.
Intramuscular injection may be used for widespread skin disorders, or intralesional injections may be used for localized skin disorders. Consider limiting the total monthly dose to 20 mg to ensure the HPA axis will not be suppressed.
Clobetasol (Temovate)
Clobetasol is first-line treatment (for topical use). It is a class I superpotent topical steroid; it suppresses mitosis and increases the synthesis of proteins that decrease inflammation and cause vasoconstriction. Ointment may be more efficacious than cream secondary to the former's occlusive properties.
Flurandrenolide (Cordran Tape)
Flurandrenolide is first-line treatment (for topical use). It also helps protect nodules from continued trauma if tape is left in place.
Immunologic Agents
Class Summary
These agents have immunomodulatory effects.
Thalidomide (Thalomid)
Thalidomide may suppress excessive production of tumor necrosis factor alpha (TNF-alpha) and may down-regulate selected cell-surface adhesion molecules involved in leukocyte migration.
If the patient is less than 50 kg (110 lb), start at the low end of the dose regimen.
Thalidomide can cause severe, life-threatening birth defects and is contraindicated in pregnant women. It is also contraindicated in women of childbearing potential unless using 2 forms of reliable contraception and complying with serial pregnancy testing while on therapy.
Thalidomide is also contraindicated in sexually active men not using latex condom as barrier contraception. The drug is available only under a special restricted distribution program called STEPS (System for Thalidomide Education and Prescribing Safety) Program; only prescribers and pharmacists registered with this program may prescribe and dispense thalidomide. For more information, contact the Celgene Corporation at 1-888-423-5436.
Immunosuppressant Agents
Tacrolimus ointment (Protopic)
The mechanism of action of tacrolimus in prurigo nodularis not known. Tacrolimus reduces itching and inflammation by suppressing the release of cytokines from T cells. It also inhibits transcription for genes that encode IL-3, IL-4, IL-5, GM-CSF, and TNF-alpha, all of which are involved in the early stages of T-cell activation. Additionally, it may inhibit the release of preformed mediators from skin mast cells and basophils and down-regulate the expression of FCeRI on Langerhans cells. Tacrolimus can be used in patients as young as 2 years. Drugs of this class are more expensive than topical corticosteroids. Tacrolimus is available as ointment in concentrations of 0.03 and 0.1%. It is indicated only after other treatment options have failed.
Immune Modulators
Pimecrolimus (Elidel)
Pimecrolimus is derived from ascomycin, a natural substance produced by the fungus Streptomyces hygroscopicus var ascomyceticus. It selectively inhibits the production and release of inflammatory cytokines from activated T-cells by binding to the cytosolic immunophilin receptor macrophilin-12. The resulting complex inhibits phosphatase calcineurin, thus blocking T-cell activation and cytokine release. Cutaneous atrophy was not observed in clinical trials, a potential advantage over topical corticosteroids. It is indicated only after other treatment options have failed.
Neuromuscular Blocker Agents, Toxin
OnabotulinumtoxinA (BOTOX®)
OnabotulinumtoxinA is one of several toxins produced by Clostridium botulinum. It blocks neuromuscular transmission through a 3-step process, as follows: (1) blockade of neuromuscular transmission; onabotulinumtoxinA binds to the motor nerve terminal. The binding domain of the type A molecule appears to be the heavy chain, which is selective for cholinergic nerve terminals. (2) OnabotulinumtoxinA is internalized via receptor-mediated endocytosis, a process in which the plasma membrane of the nerve cell invaginates around the toxin-receptor complex, forming a toxin-containing vesicle inside the nerve terminal. After internalization, the light chain of the toxin molecule, which has been demonstrated to contain the transmission-blocking domain, is released into the cytoplasm of the nerve terminal. (3) OnabotulinumtoxinA blocks acetylcholine release by cleaving SNAP-25, a cytoplasmic protein that is located on the cell membrane and that is required for the release of this transmitter. The affected terminals are inhibited from stimulating muscle contraction. The toxin does not affect the synthesis or storage of acetylcholine or the conduction of electrical signals along the nerve fiber. OnabotulinumtoxinA prevents calcium-dependent release of acetylcholine and produces a state of denervation at the neuromuscular junction and postganglionic sympathetic cholinergic nerves in the sweat glands.
Typically, a 24-72 hour delay between administration of toxin and onset of clinical effects exists, which terminate in 2-6 months.
This purified neurotoxin complex is a vacuum-dried form of purified onabotulinumtoxinA , which contains 5 ng of neurotoxin complex protein per 100 U.
OnabotulinumtoxinA has to be reconstituted with 2 mL of 0.9% sodium chloride diluent. With this solution, each 0.1 mL results in 5 U dose. The patient should receive 5-10 injections per visit.
It must be reconstituted from vacuum-dried toxin into 0.9% sterile saline without preservative using manufacturer's instructions to provide injection volume of 0.1 mL; it must be used within 4 hours of storage in the refrigerator at 2-8°C.
Preconstituted dry powder must be stored in a freezer at less than 5°C.
Injections of botulinum toxin must be repeated at varying intervals to maintain long-term results.
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Prurigo nodularis. Courtesy of Jeffrey Meffert, MD.
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Prurigo nodularis. Courtesy of Jeffrey Meffert, MD.
