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Prurigo Nodularis: Treatment & Medication
Updated: Oct 23, 2009
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
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Treatment
Medical Care
Current available treatments of prurigo nodularis have had mild-to-moderate success at best. Often, combinations of several medications or physical modalities may be used in an attempt to control this process.
- Topical, oral, and intralesional corticosteroids have all been used in prurigo nodularis in attempts to decrease inflammation and sense of itching and to soften and smooth out firm nodules. The improvement with corticosteroids is variable, and corticosteroids are sometimes not helpful.
- Menthol, phenol, pramoxine, capsaicin cream,15 vitamin D-3 ointment,16 and topical anesthetics are some other topical agents used to reduce pruritus. Treatment with DuoDerm or other occlusive therapies has been suggested to flatten lesions while at the same time preventing patients from directly scratching nodules.17
- UV light treatment using UV-B18 or UV-A plus psoralen may be beneficial for severe pruritus. Consider the adverse effects of prolonged UV exposure before such treatment. Monochromatic 308-nm therapy may be helpful for recalcitrant lesions.19 UV-A1 has also been reported to benefit lichen simplex chronicus and prurigo nodularis.20
- Antihistamines, anxiolytics, opiate receptor antagonists, and (most recently) thalidomide are oral medications other than steroids used for prurigo nodularis. Thalidomide21,22,23 has been shown to aid in several severe dermatoses, including prurigo nodularis with or without associated HIV disease.18,24 Severe teratogenic effects are well known and documented, and all women of childbearing age should be on adequate birth control methods. Patients taking thalidomide have an increased risk of peripheral neuropathy.
- For steroid unresponsive patients or those with lesions on thin skin, a few case reports and small studies have shown efficacy of the topical immunomodulators tacrolimus and pimecrolimus.
- Anecdotally, gabapentin has been reported to benefit prurigo nodularis.25 Sedation is the main problem with this generic medication.
- Habit reversal therapy for the itch-scratch cycle associated with prurigo nodularis may be helpful and can be administered by dermatology nurses trained in this therapy.26
Surgical Care
- Cryotherapy with liquid nitrogen helps reduce pruritus and flatten lesions.27,28
- Thirty-second thaw cycles with 2-4 treatments are recommended, depending on the size of the lesion.
- Understanding the risks of scarring and change in pigmentation (especially in darker-skinned individuals) is important.
- Cryotherapy may be combined with other modalities (eg, intralesional corticosteroids).
- Pulsed dye laser therapy may help reduce the vascularity of individual lesions.
Consultations
Pay special attention to patients with prurigo nodularis.
- Take a careful history of immune compromise or other internal disease.
- Refer patients to an internist or a family physician for possible further investigation and examination.
- Some patients benefit from psychiatric referral once underlying dermatologic and medical disorders have been excluded.29
Activity
Instruct prurigo nodularis patients to minimize touching, scratching, and rubbing affected areas.
Medication
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
These agents may control itching by blocking the transmission of nerve impulse.
Pramoxine (Itch-X)
Blocks nerve conduction and impulses by inhibiting depolarization of neurons.
Adult
Apply to affected area q3-4h; not to exceed 200 mg
Pediatric
Not established
None reported
Documented hypersensitivity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Caution in patients with trauma in area to be treated; do not apply over large areas; avoid contact with eyes and nose
Capsaicin (Dolorac, Capsin, Zostrix)
Derived from plants of Solanaceae family. May render skin and joints insensitive to pain by depleting substance P in peripheral sensory neurons.
Adult
Apply to skin tid/qid for 3-4 consecutive wk and evaluate efficacy; not to exceed 4 applications/d
Pediatric
Apply as in adults
Concurrent use with antiplatelet agents, thrombolytics, and heparin, including low molecular weight heparins, may increase risk of bleeding; may cause or exacerbate coughing associated with ACEI treatment; acute use may cause inhibition of cytochrome P450 enzymes; chronic use may cause induction of cytochrome P450 enzymes (avoid concomitant use of capsaicin and barbiturates until clinical significance of interaction defined); may increase mesenteric blood flow due to cholinergic action and thereby increase bioavailability of theophylline (monitor theophylline levels and signs and symptoms of theophylline toxicity)
Documented hypersensitivity; broken or irritated skin
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
For external use only; avoid contact with eyes; do not use tight bandage; discontinue use if condition worsens or symptoms persist for 14-28 d
Vitamin D Analogs
These agents regulate skin cell production and development.
Calcipotriene (Dovonex)
Synthetic vitamin D-3 analog. Used in the treatment of moderate plaque psoriasis.
Adult
Apply thin film to affected skin bid to response; 120 g/wk (if greater doses used, monitor 24 h urinary calcium excretion and serum calcium levels; urinary calcium is more sensitive parameter)
Pediatric
Not established
None reported
Documented hypersensitivity; hypercalcemia; vitamin D toxicity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Discontinue treatment if skin becomes irritated; discontinue if serum calcium level is increased outside reference range; avoid applying over >10% of TBSA
Psoralens
These agents may be beneficial for patients with severe pruritus.
Methoxsalen (8-MOP, Oxsoralen)
Inhibits mitosis by binding covalently to pyrimidine bases in DNA when photoactivated by UV-A.
Adult
0.57 mg/kg PO or 10-70 mg PO 1.5-2 h before exposure to UV light bid/tid at least 48 h apart
Pediatric
Not established
Toxicity increases with phenothiazines, griseofulvin, nalidixic acid, tetracyclines, thiazides, and sulfanilamide
Documented hypersensitivity; squamous cell cancer; cataract; light-sensitive diseases such as lupus or porphyria; ingestion of photosensitizing drugs; hepatitic disease; arsenic therapy; history of melanoma; patients with aphakia
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Severe burns may occur from sunlight or UV-A if dose or treatment frequency exceeded; use only if response to other forms of therapy is inadequate; long-term use may increase risk of skin cancer; ocular changes may occur
Trioxsalen (Trisoralen)
Inhibits mitosis by covalently binding, in presence of UV-A radiation, to pyrimidine bases in DNA.
Adult
10 mg/d PO once 2-4 h before controlled exposure to UV-A or sunlight; not to exceed 14 d
Pediatric
<12 years: Not established
>12 years: Administer as in adults
Toxicity increases with phenothiazines, griseofulvin, nalidixic acid, tetracyclines, thiazides, and sulfanilamide
Documented hypersensitivity; squamous cell cancer; cataract; light-sensitive diseases such as lupus or porphyria; ingestion of photosensitizing drugs; hepatitic disease; arsenic therapy; history of melanoma; patients with aphakia
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Severe burns may occur from sunlight or UV-A if dose or treatment frequency exceeded; use only if response to other forms of therapy is inadequate; long-term use may increase risk of skin cancer; ocular changes may occur
Antihistamines
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)
First-line treatment. For symptomatic relief of pruritus caused by release of histamine.
Adult
25-50 mg PO q6-8h prn; not to exceed 400 mg/d
10-50 mg IV/IM q6-8h prn; not to exceed 400 mg/d
Pediatric
12.5-25 mg PO tid/qid or 5 mg/kg/d PO/IV/IM or 150 mg/m2/d PO/IV/IM divided tid/qid; not to exceed 300 mg/d
Potentiates effect of CNS depressants; because of alcohol content, do not give syr dosage form to patient taking medications that can cause disulfiramlike reactions; concomitant alkaloids present in belladonna, antidepressants with strong anticholinergic effects (eg, amitriptyline, trimipramine, amoxapine, doxepin, imipramine, nortriptyline, maprotiline), or phenothiazines with strong anticholinergic effects (eg, chlorpromazine, triflupromazine, thioridazine) and antihistamines may increase possibility of adynamic ileus, urinary retention, or chronic glaucoma (more prominent in elderly patients)
Documented hypersensitivity; acute asthma; newborns; breastfeeding; MAOIs
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
May exacerbate angle-closure glaucoma, hyperthyroidism, peptic ulcer, and urinary tract obstruction; elderly more susceptible to side effects; caution in history of bronchial asthma, cardiovascular disease or hypertension; may cause excitation in young children
Chlorpheniramine (Chlor-Trimeton)
First-line treatment. Competes with histamine or H1 receptor sites on effector cells in blood vessels and respiratory tract.
Adult
4 mg PO q4-6h; not to exceed 24 mg/d
8-12 mg SR q8-12h; not to exceed 24 mg/d
Pediatric
2-6 years: 1 mg PO divided q4-6h; not to exceed 6 mg/d
6-12 years: 2 mg PO q4-6h; not to exceed 12 mg/d
8 mg SR hs
Potentiates effect of CNS depressants; because of alcohol content, do not give syr dosage form to patient taking medications that can cause disulfiramlike reactions; concomitant alkaloids present in belladonna, antidepressants with strong anticholinergic effects (eg, amitriptyline, trimipramine, amoxapine, doxepin, imipramine, nortriptyline, maprotiline), or phenothiazines with strong anticholinergic effects (eg, chlorpromazine, triflupromazine, thioridazine) and antihistamines may increase possibility of adynamic ileus, urinary retention, or chronic glaucoma (more prominent in elderly patients)
Documented hypersensitivity; asthma; narrow-angle glaucoma; symptomatic prostate hypertrophy; bladder-neck obstruction; stenosing peptic ulcer
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
May exacerbate angle-closure glaucoma, hyperthyroidism, peptic ulcer, and urinary tract obstruction; elderly more susceptible to side effects; caution in history of bronchial asthma, cardiovascular disease or hypertension; may cause excitation in young children
Hydroxyzine (Anxanil, Atarax, Atozine, Durrax, Vistaril)
First-line treatment. Antagonizes H1 receptors in periphery. May suppress histamine activity in subcortical region of CNS and can be used as an anxiolytic.
Adult
50-100 mg PO/IM qid
Pediatric
0.6 mg/kg/dose PO q6h
CNS depression may increase with alcohol or other CNS depressants, nonnarcotic analgesics, barbiturates, and alcohol
Documented hypersensitivity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Associated with clinical exacerbations of porphyria (may not be safe for patients with porphyria); ECG abnormalities (alterations in T waves) may occur; may cause drowsiness
Corticosteroids
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)
First-line treatment if few lesions (for intralesional use).
For inflammatory dermatosis responsive to steroids; decreases inflammation by suppressing migration of polymorphonuclear leukocytes and reversing capillary permeability.
Intramuscular injection may be used for widespread skin disorder, or intralesional injections may be used for localized skin disorder. Consider limiting total monthly dose to 20 mg to ensure HPA axis will not be suppressed.
Adult
5-10 mg/mL to mid dermis of each nodule q4-6wk as individual nodules resolve
Pediatric
<12 years: Not established
>12 years: Administer as in adults
Coadministration with barbiturates, phenytoin, and rifampin decreases effects
Documented hypersensitivity; fungal, viral, and bacterial skin infections
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Intralesional use may result in localized lipoatrophy, epidermal atrophy, and hypopigmentation; abrupt discontinuation of systemic glucocorticoids may cause adrenal crisis; hyperglycemia, edema, osteonecrosis, myopathy, peptic ulcer disease, hypokalemia, osteoporosis, euphoria, psychosis, myasthenia gravis, growth suppression, and infections may occur with glucocorticoid use
Clobetasol (Temovate)
First-line treatment (for topical use). Class I superpotent topical steroid; suppresses mitosis and increases synthesis of proteins that decrease inflammation and cause vasoconstriction. Ointment may be more efficacious than cream secondary to the former's occlusive properties.
Adult
Apply thinly to nodules only bid/qid for up to 2 wk; not to exceed 50 g/wk
Pediatric
<12 years: Not recommended
>12 years: Apply as in adults
None reported
Documented hypersensitivity; viral or fungal skin infections
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Caution in children because they are more susceptible to adverse effects of topical steroids and are more likely to have systemic complications secondary to absorption; caution use on occluded areas and face because these areas increase potency and adverse effects of an already ultrapotent steroid; cutaneous adverse effects include striae distensae, acneiform eruptions, cutaneous atrophy, purpura, systemic complications, and irritant or allergic contact dermatitis; may suppress adrenal function in prolonged therapy
Flurandrenolide (Cordran Tape)
First-line treatment (for topical use). Also helps protect nodule from continued trauma if tape is left in place.
Adult
Apply over lesion and leave in place until changed qd
Pediatric
Not established
None reported
Documented hypersensitivity; fungal, viral, and bacterial skin infections
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Caution in children because they are more susceptible to adverse effects of topical steroids and are more likely to have systemic complications secondary to absorption; caution use on occluded areas and face because these areas increase potency and adverse effects of an already ultrapotent steroid; cutaneous adverse effects include striae distensae, acneiform eruptions, cutaneous atrophy, purpura, systemic complications, and irritant or allergic contact dermatitis; may suppress adrenal function in prolonged therapy
Immunologic Agents
These agents have immunomodulatory effects.
Thalidomide (Thalomid)
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 <50 kg (110 lb), start at low end of dose regimen.
Can cause severe, life-threatening birth defects and is contraindicated in pregnant women. Also contraindicated in women of childbearing potential unless using 2 forms of reliable contraception and complying with serial pregnancy testing while on therapy.
Also contraindicated in sexually active men not using latex condom as barrier contraception. Drug available only under 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.
Adult
100-300 mg/d with water, preferably hs and at least 1 h pc; may be combined with narrowband UV-B (TL-01) irradiation
Pediatric
Not established
May increase sedation effects of alcohol, barbiturates, chlorpromazine, and reserpine; increases thromboembolic risk of erythropoietic proteins such as Darbepoetin Alfa in myelodysplastic syndrome (MDS) patients
Coadministration with dexamethasone increases risk of developing toxic epidermal necrolysis;
risk of renal dysfunction may be increased when zoledronic acid used in combination with thalidomide in multiple myeloma patients
Documented hypersensitivity; pregnancy
Pregnancy
X - Contraindicated; benefit does not outweigh risk
Precautions
Perform pregnancy test within 24 h prior to initiating therapy (weekly during first mo, followed by monthly tests in women with regular menstrual cycles or q2wk with irregular menstrual cycles); bradycardia may occur; use protective measures (eg, sunscreens, protective clothing) against exposure to sunlight or UV light (eg, tanning beds); as result of teratogenic effects, women must use 2 additional methods of contraception or abstain from intercourse
Immunosuppressant Agents
Tacrolimus (Protopic)
Mechanism of action in prurigo nodularis not known. Reduces itching and inflammation by suppressing release of cytokines from T cells. Also inhibits transcription for genes that encode IL-3, IL-4, IL-5, GM-CSF, and TNF-alpha, all of which are involved in early stages of T-cell activation. Additionally, may inhibit release of preformed mediators from skin mast cells and basophils and down-regulate expression of FCeRI on Langerhans cells. Can be used in patients as young as 2 y. Drugs of this class are more expensive than topical corticosteroids. Available as ointment in concentrations of 0.03 and 0.1%. Indicated only after other treatment options have failed.
Adult
Apply thin layer to affected skin areas bid and rub in gently and completely; continue treatment for 1 wk after clearing of signs and symptoms
Short-term and intermittent use only
Pediatric
<2 years: Not recommended
2-15 years: Apply 0.03% ointment bid to affected area(s)
>15 years: Administer as adults
Short-term and intermittent use only
None reported
Documented hypersensitivity to tacrolimus or components of ointment
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Patients may experience a burning sensation during first few days of application; skin can become photosensitive and patients should be cautioned about exposure to direct or artificial sunlight and to use sunscreen; safety and efficacy in infected atopic dermatitis is not known; application under occlusion, which may promote systemic exposure, has not been evaluated (do not use ointment with occlusive dressings); absorption following topical applications is minimal (relative to systemic administration), but tacrolimus is excreted in human milk and, thus, a decision should be made whether to discontinue nursing or to discontinue drug, taking into account importance of drug to mother (potential for serious adverse reactions in nursing infants from tacrolimus should also be a concern); caution with conditions that suppress the immune system (eg, AIDS, cancer) ; possible risk of lymph node or skin cancer based on animal studies and a small number of patients; may increase risk of viral infections; other adverse effects include headache, sore throat, flulike symptoms, fever, and cough
Immune Modulators
Pimecrolimus (Elidel)
Derived from ascomycin, a natural substance produced by fungus Streptomyces hygroscopicus var ascomyceticus. Selectively inhibits production and release of inflammatory cytokines from activated T-cells by binding to 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. Indicated only after other treatment options have failed.
Adult
Apply topically to affected areas bid
Short-term and intermittent use only
Pediatric
<2 years: Not established
>2 years: Administer as in adults
Short-term and intermittent use only
None reported
Documented hypersensitivity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Potential exacerbation of existing infection at site of application; may cause burning and irritation; caution with conditions that suppress the immune system (eg, AIDS, cancer); possible risk of lymph node or skin cancer based on animal studies and a small number of patients; may increase risk of viral infections; other adverse effects include headache, sore throat, flulike symptoms, fever, and cough
Neuromuscular Blocker Agents, Toxin
Botulinum Toxin Type A (BOTOX ®)
One of several toxins produced by Clostridium botulinum. Blocks neuromuscular transmission through a 3-step process, as follows: (1) blockade of neuromuscular transmission; botulinum toxin type A (BTA) 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) BTA 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) BTA 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. Toxin does not affect synthesis or storage of acetylcholine or conduction of electrical signals along the nerve fiber. 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 h delay between administration of toxin and onset of clinical effects exists, which terminate in 2-6 mo.
This purified neurotoxin complex is a vacuum-dried form of purified BTA, which contains 5 ng of neurotoxin complex protein per 100 U.
BTA 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. Patient should receive 5-10 injections per visit.
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; must be used within 4 h of storage in refrigerator at 2-8°C.
Preconstituted dry powder must be stored in freezer at <5°C.
Injections of botulinum toxin must be repeated at varying intervals to maintain long-term results.
Adult
Varies by size and number of lesions, injections should be evenly distributed into multiple sites (5-10), administered in 0.1- to 0.2-mL aliquots, ~1-2 cm apart
Pediatric
Not established
Aminoglycosides or drugs that interfere with neuromuscular transmission may potentiate effects
Documented hypersensitivity; infection present at injection site
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Do not exceed recommended dosages and frequencies of administration; presence of antibodies to BTA may reduce effects of therapy; mild transient thumb weakness and muscle weakness at toxin-treated sites may occur but resolve within 2-5 wk
Units of biological activity of BTA cannot be compared to nor converted into units of any other botulinum toxin; relative potencies of botulinum A toxin preparations available in United Kingdom and North American differ significantly; reduced blinking as a result of administration of BOTOX ® cosmetic may lead to corneal exposure, persistent epithelial defect and corneal ulceration; epinephrine should be available or other precautions taken as necessary should an anaphylactic reaction occur
More on Prurigo Nodularis |
| Overview: Prurigo Nodularis |
| Differential Diagnoses & Workup: Prurigo Nodularis |
 Treatment & Medication: Prurigo Nodularis |
| Follow-up: Prurigo Nodularis |
| Multimedia: Prurigo Nodularis |
| References |
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Further Reading
Keywords
prurigo nodularis, Hyde prurigo nodularis, picker’s nodules, lichen simplex chronicus, prurigo nodularis type, atypical nodular form of neurodermatitis circumscripta, lichen corneus obtusus, PN
