AUTHOR AND EDITOR INFORMATION

Section 1 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

INTRODUCTION

Section 2 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Background

In 1909, Hyde and Montgomery first described prurigo nodularis (PN) as pruritic nodules on the extensor surfaces of the lower extremities in middle-aged women. PN can be a bothersome-to-debilitating disease, usually seen as multiple, intensely pruritic, excoriated nodules erupting on the extensor surfaces of the limbs secondary to itching or rubbing. Today, PN is still a condition of unknown etiology. Many conditions have been reported to induce PN, from internal malignancy to renal failure to psychiatric conditions.

Pathophysiology

Chronic mechanical trauma to the skin causes thickening of the skin proportionate to the trauma. Repetitive rubbing, scratching, and touching (induced by a foreign body or self-induced) results in plaque or nodular lichenification and hyperkeratosis. Pigmentary changes often result from such repetitive trauma to the skin.

With PN, a person feels intense pruritus at discrete points and cannot control the urge to rub or scratch these points on the body. Any abnormality or explanation for the pruritus is unknown; scratching by the individuals who are affected is obvious. The results are discrete, nodular, hyperpigmented/purpuric lesions with surfaces that are scaly, excoriated, and possibly crusted.

Mortality/Morbidity

PN is benign and does not increase mortality; however, severe morbidity can occur in untreated and even in some treated persons who are affected. Pruritus and the extent of body surface area involved become so great for some patients that they no longer feel functional for work or other everyday activities.

Some conditions associated with PN may cause mortality. PN has been documented to be much more common in immunocompromised and HIV populations. Some associations have been made of PN with internal malignancy and severely decreased kidney function.

Race

No racial disparity is known.

Sex

Women were formerly believed to have a disproportionate amount of PN compared to men; however, no documented difference exists in frequency between the sexes.

Age

PN can occur at any age, but it most often occurs in middle-aged and older persons.

CLINICAL

Section 3 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

History

• Patients are most often middle-aged to elderly.
• Patients with PN invariably complain of a long-standing history of severe, unremitting pruritus.
• Patients can point out specific sites where they began feeling itchy and where dark-colored nodules formed soon after.
• Mature nodules rarely increase or decrease in size; spontaneous resolution is even more rare.
• PN is usually bilaterally symmetric, with nodules that are either stable or increasing in number.
• The patient's medical history may be significant for several conditions.
• • Hepatic or renal dysfunction
  • Local trauma or insult to the skin
  • Infection
  • HIV/immunodeficiency
  • Anxiety or other psychiatric condition

• Patients may have no significant medical or psychiatric history.
• The patient's history often reveals a long list of over-the-counter and/or prescribed medications (topical and oral), which usually have produced little or no relief of symptoms.
• Up to 80% of patients have a personal or family history of atopic dermatitis, asthma, or hay fever (compared with approximately 25% of the normal population).

Physical

• Nodules or papules are 3-20 mm in diameter; they are discrete, scaly, generally symmetric, hyperpigmented or purpuric, and firm.
• Nodules and papules occur on the extensor surfaces of the arms, the legs, and sometimes the trunk.
• Lesions may show signs of excoriation with flat, umbilicated, or crusted top.
• Lesions may number from 1-2 to hundreds.
• The nodule pattern may be follicular.
• Nodule pattern may be follicular.
• On entering the examination room and while patients' describe the locations of the lesions, patients may scratch or rub the lesions rather than pointing to them.
• Many patients appear very anxious, worried, or even obsessed with the nodules.

Causes

The cause of PN is still unknown. Many associated conditions are known, but their roles as coexisting or preexisting conditions have not been established in causing PN. Notable changes in papules and nodules are increased in certain inflammatory cell types, inflammatory products, and neural hyperplasia.

• Mast cells and neutrophils are seen in higher-than-normal levels in PN; however, their degranulation products are not increased. Eosinophils are not seen in higher numbers; however, the protein granule products (ie, major basic protein, eosinophil cationic protein, eosinophil-derived neurotoxin) are seen in significantly higher levels.
• Papillary dermal nerves and Merkel cells are sensory nerves found in the dermis and the epidermis, respectively. They are both found in increased numbers in PN. These are neural receptors that sense touch, temperature, pain, and itch. These increases in sensory nerves are not seen in lichen simplex chronicus, another pruritic disease that causes epidermal hyperplasia but in a plaquelike morphology (see Lichen Simplex Chronicus).
• Calcitonin gene–related peptide and substance P immunoreactive nerves are markedly increased in PN skin compared with normal skin. These neuropeptides may mediate the cutaneous neurogenic inflammation and pruritus in PN. In addition, the capsaicin-binding nonselective cation channel known as vanilloid receptor subtype 1 has highly increased expression in epidermal keratinocytes and nerve fibers in PN lesions, but these can be normalized with capsaicin application.
• Hepatitis C, mycobacteria, Helicobacter pylori, Strongyloides stercoralis, and HIV have been reported as infectious etiologies of PN or as associated with PN in case reports or from single-center studies.
• Interleukin 31, a T-cell–derived cytokine that causes severe pruritus and dermatitis in transgenic mice, is elevated in individuals with PN. Interleukin 31 expression in atopic individuals is also rapidly induced by staphylococcal superantigen; however, the link between these findings has not been extensively researched.

DIFFERENTIALS

Section 4 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Other Problems to be Considered

Mastocytosis (urticaria pigmentosa)
Pemphigoid nodularis
Pilomatrixoma (benign calcifying epithelioma, calcifying epithelium of Malherbe)

WORKUP

Section 5 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Lab Studies

• Perform a CBC count and a chemistry panel, including liver function tests (LFTs), to help exclude underlying hematologic malignancies, renal failure, and hepatic diseases.

Procedures

• Obtaining skin biopsy samples for histologic examination and/or cultures may be indicated to exclude squamous cell carcinoma (particularly the keratoacanthoma type) and infections (especially deep fungal, atypical mycobacterial).
• Patch testing to exclude contact sensitivity may be considered, particularly with coexisting dermatitis.

Histologic Findings

The histologic features of prurigo nodularis include a hyperkeratotic epidermis with acanthosis and parakeratosis. Rete ridges are elongated and irregular with a dense dermal infiltrate consisting of neutrophils, eosinophils, histiocytes, and monocytes. Also notable in the dermis are thickened nerve fibers and fibrosis with thickened collagen bundles.

Thickened nerve fibers are dilated on electron microscopy. Schwann cells show vacuolization and degeneration with no detectable mitochondria. Axons and Schwann cells both show hyperproliferation.

TREATMENT

Section 6 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Medical Care

Current available treatments of PN 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 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, vitamin D-3 ointment, 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.
• UV light treatment using UV-B or UV-A plus psoralen may be beneficial for severe pruritus. Consider the adverse effects of prolonged UV exposure before such treatment.
• Antihistamines, anxiolytics, opiate receptor antagonists, and (most recently) thalidomide are oral medications other than steroids used for PN. Thalidomide has been shown to aid in several severe dermatoses, including PN with or without associated HIV disease. 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.

Surgical Care

• Cryotherapy with liquid nitrogen helps reduce pruritus and flatten lesions.
• • 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 PN.

• 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.
• A minority of patients benefit from psychiatric referral once underlying dermatologic and medical disorders have been excluded.

Activity

Instruct patients to minimize touching, scratching, and rubbing affected areas.

MEDICATION

Section 7 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

The goal of pharmacotherapy 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.

Drug Category: Antipruritics

These agents may control itching by blocking the transmission of nerve impulse.

Drug Name	Capsaicin (Dolorac, Capsin, Zostrix)
Description	Derived from plants of Solanaceae family. May render skin and joints insensitive to pain by depleting substance P in peripheral sensory neurons.
Adult Dose	Apply to skin tid/qid for 3-4 consecutive wk and evaluate efficacy; not to exceed 4 applications/d
Pediatric Dose	Apply as in adults
Contraindications	Documented hypersensitivity; broken or irritated skin
Interactions	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)
Pregnancy	C - Safety for use during pregnancy has not been established.
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

Drug Category: Vitamin D analog

These agents regulate skin cell production and development.

Drug Category: Psoralens

These agents may be beneficial for patients with severe pruritus.

Drug Name	Trioxsalen (Trisoralen)
Description	Inhibits mitosis by covalently binding, in presence of UV-A radiation, to pyrimidine bases in DNA.
Adult Dose	10 mg/d PO once 2-4 h before controlled exposure to UV-A or sunlight; not to exceed 14 d
Pediatric Dose	<12 years: Not established >12 years: Administer as in adults
Contraindications	Documented hypersensitivity; squamous cell cancer; cataract; light sensitive diseases (eg, lupus erythematosus, porphyria cutanea tarda, erythropoietic protoporphyria, variegate porphyria, xeroderma pigmentosum, albinism); history of melanoma; invasive squamous cell carcinoma; ingestion of photosensitizing drugs; hepatitic disease; arsenic therapy; patients with aphakia (increase risk of retinal damage due to the absence of lenses)
Interactions	Furocoumarin-containing food increases UV sensitivity
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Severe burns may occur from sunlight or UV-A exposure if dose or frequency is exceeded; observe patients, with previous history of arsenic exposure, for signs of carcinoma; observe patients, with previous history of radiation therapy or Grenz ray therapy, for signs of carcinoma; special care needed with concomitant administration of photosensitizing agents; use only if response to other forms of therapy is inadequate

Drug Category: 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.

Drug Name	Chlorpheniramine (Chlor-Trimeton)
Description	First-line treatment. Competes with histamine or H1 receptor sites on effector cells in blood vessels and respiratory tract.
Adult Dose	4 mg PO q4-6h; not to exceed 24 mg/d 8-12 mg SR q8-12h; not to exceed 24 mg/d
Pediatric Dose	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
Contraindications	Documented hypersensitivity; asthma; narrow-angle glaucoma; symptomatic prostate hypertrophy; bladder-neck obstruction; stenosing peptic ulcer
Interactions	CNS toxicity increases with coadministration of other CNS depressants, TCAs, MAOIs, and phenothiazines
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	May cause significant confusional symptoms; not for administration to premature or full-term neonates; may exacerbate narrow-angle closure glaucoma, hyperthyroidism, peptic ulcer, and urinary tract obstruction; avoid concurrent MAOI therapy and/or CNS depressants; decreases mental alertness and psychomotor performance; topical form, nor for use on eyes or eye lids; elderly persons more susceptible to adverse effects; caution in history of bronchial asthma, increased intraocular pressure, cardiovascular disease or hypertension; may cause excitation in young children; caution in pyloroduodenal obstruction, stenosing peptic ulcer, symptomatic prostatic hypertrophy

Drug Name	Hydroxyzine (Anxanil, Atarax, Atozine, Durrax, Vistaril)
Description	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 Dose	50-100 mg PO/IM qid
Pediatric Dose	0.6 mg/kg/dose PO q6h
Contraindications	Documented hypersensitivity
Interactions	CNS depression may increase with alcohol or other CNS depressants
Pregnancy	C - Safety for use during pregnancy has not been established.
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

Drug Category: 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.

Drug Name	Clobetasol (Temovate)
Description	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 Dose	Apply thinly to nodules only bid/qid for up to 2 wk; not to exceed 50 g/wk
Pediatric Dose	<12 years: Not recommended >12 years: Apply as in adults
Contraindications	Documented hypersensitivity; viral or fungal skin infections
Interactions	None reported
Pregnancy	C - Safety for use during pregnancy has not been established.
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

Drug Name	Flurandrenolide (Cordran Tape)
Description	First-line treatment (for topical use). Also helps protect nodule from continued trauma if tape is left in place.
Adult Dose	Apply over lesion and leave in place until changed qd
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity; fungal, viral, and bacterial skin infections
Interactions	None reported
Pregnancy	C - Safety for use during pregnancy has not been established.
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

Drug Category: Immunologic agents

These agents have immunomodulatory effects.

FOLLOW-UP

Section 8 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Further Outpatient Care

• Monitor patients with PN for the following:
• • Signs of improvement
  • Resistance to treatment
  • Development of symptoms or signs of underlying medical or psychiatric conditions
  • Atypical lesions meriting skin biopsy
  • Use of alternative therapies that may actually worsen atopic dermatoses

Complications

• Some healed lesions show pigmentary changes and scarring.

Prognosis

• The prognosis for spontaneous remission of PN is not good. Once PN lesions occur, complete resolution of lesions is rare. Most lesions remain present in some form even after long-term treatment. At this time, treating more than just the most symptomatic lesions is difficult. Considerable time is usually required to slow or stop the itch/scratch cycle so that the lesions resolve.
• Ultimately, a strong therapeutic alliance is the best outcome predictor because the course of the disease is long, with waxing and waning symptoms, making the patient prone to being subjected to excessive diagnostic procedures and to seek alternative therapies.

MISCELLANEOUS

Section 9 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Medical/Legal Pitfalls

• In the diagnosis of PN, proving that the observed lesions are PN rather than skin cancers is important, especially in patients who express this concern. Performing a biopsy is important, especially when the lesion is solitary.
• When treating PN with intralesional steroids or topical steroids under occlusion, overaggressively treating the condition is not necessary because this may potentially cause local cutaneous atrophy.

MULTIMEDIA

Section 10 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Media file 1:  Prurigo nodularis. Courtesy of Jeffrey Meffert, MD.
	View Full Size Image
Media type:  Photo

Media file 2:  Prurigo nodularis. Courtesy of Jeffrey Meffert, MD.
	View Full Size Image
Media type:  Photo

REFERENCES

Section 11 of 11

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

• Berger TG, Hoffman C, Thieberg MD. Prurigo nodularis and photosensitivity in AIDS: treatment with thalidomide. J Am Acad Dermatol. Nov 1995;33(5 Pt 1):837-8. [Medline].
• Casey GA, Hunt HM, Paddon AC, Wilcock PM. Paired associates: a workshop model for effecting change. Child Care Health Dev. May-Jun 1983;9(3):137-44. [Medline].
• Cheng YC, Grill SP, Dutschman GE, Frank KB, Chiou JF, Bastow KF, et al. Effects of 9-(1,3-dihydroxy-2-propoxymethyl)guanine, a new antiherpesvirus compound, on synthesis of macromolecules in herpes simplex virus-infected cells. Antimicrob Agents Chemother. Sep 1984;26(3):283-8. [Medline].
• Clemmensen OJ, Olsen PZ, Andersen KE. Thalidomide neurotoxicity. Arch Dermatol. Mar 1984;120(3):338-41. [Medline].
• Ferrándiz C, Carrascosa JM, Just M, Bielsa I, Ribera M. Sequential combined therapy with thalidomide and narrow-band (TL01) UVB in the treatment of prurigo nodularis. Dermatology. 1997;195(4):359-61. [Medline].
• Feuerman EJ, Sandbank M. Prurigo nodularis. Histological and electron microscopical study. Arch Dermatol. Nov 1975;111(11):1472-7. [Medline].
• Hann SK, Cho MY, Park YK. UV treatment of generalized prurigo nodularis. Int J Dermatol. Jul-Aug 1990;29(6):436-7. [Medline].
• Harris B, Harris K, Penneys NS. Demonstration by S-100 protein staining of increased numbers of nerves in the papillary dermis of patients with prurigo nodularis. J Am Acad Dermatol. Jan 1992;26(1):56-8. [Medline].
• Hyde JN, Montgomery FH. A practical treatise on disease of the skin for the use of students and practitioners. 1909;174-175.
• Jacob CI, Patten SF. Strongyloides stercoralis infection presenting as generalized prurigo nodularis and lichen simplex chronicus. J Am Acad Dermatol. Aug 1999;41(2 Pt 2):357-61. [Medline].
• Katayama I, Miyazaki Y, Nishioka K. Topical vitamin D3 (tacalcitol) for steroid-resistant prurigo. Br J Dermatol. Aug 1996;135(2):237-40. [Medline].
• Lee MR, Shumack S. Prurigo nodularis: a review. Australas J Dermatol. Nov 2005;46(4):211-18; quiz 219-20. [Medline].
• Liang Y, Marcusson JA, Jacobi HH, Haak-Frendscho M, Johansson O. Histamine-containing mast cells and their relationship to NGFr-immunoreactive nerves in prurigo nodularis: a reappraisal. J Cutan Pathol. Apr 1998;25(4):189-98. [Medline].
• Matthews SN, Cockerell CJ. Prurigo nodularis in HIV-infected individuals. Int J Dermatol. Jun 1998;37(6):401-9. [Medline].
• Mattila JO, Katila ML, Vornanen M. Slowly growing mycobacteria and chronic skin disorders. Clin Infect Dis. Nov 1996;23(5):1043-8. [Medline].
• Mattila JO, Vornanen M, Vaara J, Katila ML. Mycobacteria in prurigo nodularis: the cause or a consequence?. J Am Acad Dermatol. Feb 1996;34(2 Pt 1):224-8. [Medline].
• Meyers LN. Use of occlusive membrane in the treatment of prurigo nodularis. Int J Dermatol. May 1989;28(4):275-6. [Medline].
• Miyauchi H, Uehara M. Follicular occurrence of prurigo nodularis. J Cutan Pathol. Aug 1988;15(4):208-11. [Medline].
• Nahass GT, Penneys NS. Merkel cells and prurigo nodularis. J Am Acad Dermatol. Jul 1994;31(1):86-8. [Medline].
• Noppakun N, Apisarnthanarax P. Multiple cutaneous granular cell tumors simulating prurigo nodularis. Int J Dermatol. Mar 1981;20(2):126-9. [Medline].
• Perez GL, Peters MS, Reda AM, Butterfield JH, Peterson EA, Leiferman KM. Mast cells, neutrophils, and eosinophils in prurigo nodularis. Arch Dermatol. Jul 1993;129(7):861-5. [Medline].
• Roenigk RK, Dahl MV. Bullous pemphigoid and prurigo nodularis. J Am Acad Dermatol. May 1986;14(5 Pt 2):944-7. [Medline].
• Sandbank M. Cutaneous nerve lesions in prurigo nodularis. Electron microscopic study of two patients. J Cutan Pathol. 1976;3(3):125-32. [Medline].
• Seeburger J, Anderson-Wilms N, Jacobs R. Lennert's lymphoma presenting as prurigo nodularis. Cutis. May 1993;51(5):355-8. [Medline].
• Sonkoly E, Muller A, Lauerma AI, Pivarcsi A, Soto H, Kemeny L, et al. IL-31: a new link between T cells and pruritus in atopic skin inflammation. J Allergy Clin Immunol. Feb 2006;117(2):411-7. [Medline].
• Stoll DM, Fields JP, King LE Jr. Treatment of prurigo nodularis: use of cryosurgery and intralesional steroids plus lidocaine. J Dermatol Surg Oncol. Nov 1983;9(11):922-4. [Medline].
• Ständer S, Moormann C, Schumacher M, Buddenkotte J, Artuc M, Shpacovitch V, et al. Expression of vanilloid receptor subtype 1 in cutaneous sensory nerve fibers, mast cells, and epithelial cells of appendage structures. Exp Dermatol. Mar 2004;13(3):129-39. [Medline].
• Szeidemann Z, Shanabrough M, Leranth C. Hypothalamic Leu-enkephalin-immunoreactive fibers terminate on calbindin-containing somatospiny cells in the lateral septal area of the rat. J Comp Neurol. Aug 7 1995;358(4):573-83. [Medline].
• Tamada Y, Yokochi K, Oshitani Y, Nitta Y, Ikeya T, Hara K, et al. Pemphigoid nodularis: a case with 230 kDa hemidesmosomes antigen associated with bullous pemphigoid antigen. J Dermatol. Mar 1995;22(3):201-4. [Medline].
• Tseng S, Pak G, Washenik K, Pomeranz MK, Shupack JL. Rediscovering thalidomide: a review of its mechanism of action, side effects, and potential uses. J Am Acad Dermatol. Dec 1996;35(6):969-79. [Medline].
• Tupker RA, Coenraads PJ, van der Meer JB. Treatment of prurigo nodularis, chronic prurigo and neurodermatitis circumscripta with topical capsaicin. Acta Derm Venereol. Nov 1992;72(6):463. [Medline].
• Vaalasti A, Suomalainen H, Rechardt L. Calcitonin gene-related peptide immunoreactivity in prurigo nodularis: a comparative study with neurodermatitis circumscripta. Br J Dermatol. May 1989;120(5):619-23. [Medline].
• Waldinger TP, Wong RC, Taylor WB, Voorhees JJ. Cryotherapy improves prurigo nodularis. Arch Dermatol. Dec 1984;120(12):1598-600. [Medline].

Article Last Updated: May 2, 2006