History

Prurigo nodularis patients are most often middle-aged to elderly. Patients with prurigo nodularis 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 form soon after. Mature nodules rarely increase or decrease in size; spontaneous resolution is even more rare. Prurigo nodularis is usually bilaterally symmetric, with nodules that are either stable or increasing in number.

Umbilicated prurigo has identical clinical and microscopic features of acquired reactive perforating dermatosis and classical components of prurigo nodularis. Umbilicated prurigo meets all the histologic criteria for prurigo nodularis, which increases the consideration of it being a subtype of prurigo nodularis. Umbilicated prurigo is assumed to develop preferentially in the context of metabolic disease, such as diabetes mellitus or uremia, owing to these patients’ reduced wound healing capacities.^[16]

The patient's medical history may be significant for several conditions, as follows:

Hepatic or renal dysfunction
Local trauma or insult to the skin
Infection
HIV/immunodeficiency^[17]
Hypothyroidism^[18]
Hematologic malignancies^[18]
Anxiety or other psychiatric conditions

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 Examination

Prurigo nodularis nodules or papules are 3-20 mm in diameter; they are discrete, scaly, generally symmetric, hyperpigmented or purpuric, and firm. The itchy nodules and papules occur on the extensor surfaces of the arms, the legs, and sometimes the trunk.

Prurigo nodularis 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. Upon 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 prurigo nodularis patients appear very anxious, worried, or even obsessed with the nodules. Note the images below.

Prurigo nodularis. Courtesy of Jeffrey Meffert, MD.

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Prurigo nodularis. Courtesy of Jeffrey Meffert, MD.

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Complications

Some healed lesions show pigmentary changes and scarring.

Differential Diagnoses

Hyde JN, Montgomery FH. A practical treatise on disease of the skin for the use of students and practitioners. 1909. 174-175.
Schuhknecht B, Marziniak M, Wissel A, Phan NQ, Pappai D, Dangelmaier J, et al. Reduced intraepidermal nerve fibre density in lesional and nonlesional prurigo nodularis skin as a potential sign of subclinical cutaneous neuropathy. Br J Dermatol. 2011 Jul. 165(1):85-91. [QxMD MEDLINE Link].
Pereira MP, Pogatzki-Zahn E, Snels C, Vu T, Üçeyler N, Loser K, et al. There is no functional small-fiber neuropathy in prurigo nodularis despite neuroanatomical alterations. Exp Dermatol. 2017 Mar 31. [QxMD MEDLINE Link].
Fukushi S, Yamasaki K, Aiba S. Nuclear localization of activated STAT6 and STAT3 in epidermis of prurigo nodularis. Br J Dermatol. 2011 Nov. 165(5):990-6. [QxMD MEDLINE Link].
Nahass GT, Penneys NS. Merkel cells and prurigo nodularis. J Am Acad Dermatol. 1994 Jul. 31(1):86-8. [QxMD MEDLINE Link].
Vaalasti A, Suomalainen H, Rechardt L. Calcitonin gene-related peptide immunoreactivity in prurigo nodularis: a comparative study with neurodermatitis circumscripta. Br J Dermatol. 1989 May. 120(5):619-23. [QxMD MEDLINE Link].
Mattila JO, Katila ML, Vornanen M. Slowly growing mycobacteria and chronic skin disorders. Clin Infect Dis. 1996 Nov. 23(5):1043-8. [QxMD MEDLINE Link].
Mattila JO, Vornanen M, Vaara J, Katila ML. Mycobacteria in prurigo nodularis: the cause or a consequence?. J Am Acad Dermatol. 1996 Feb. 34(2 Pt 1):224-8. [QxMD MEDLINE Link].
Saporito L, Florena AM, Colomba C, Pampinella D, Di Carlo P. Prurigo nodularis due to Mycobacterium tuberculosis: a case report. J Med Microbiol. 2009 Aug 6. [QxMD MEDLINE Link].
Jacob CI, Patten SF. Strongyloides stercoralis infection presenting as generalized prurigo nodularis and lichen simplex chronicus. J Am Acad Dermatol. 1999 Aug. 41(2 Pt 2):357-61. [QxMD MEDLINE Link].
Sonkoly E, Muller A, Lauerma AI, et al. IL-31: a new link between T cells and pruritus in atopic skin inflammation. J Allergy Clin Immunol. 2006 Feb. 117(2):411-7. [QxMD MEDLINE Link].
Boozalis E, Tang O, Patel S, Semenov YR, Pereira MP, Stander S, et al. Ethnic differences and comorbidities of 909 prurigo nodularis patients. J Am Acad Dermatol. 2018 Oct. 79 (4):714-719.e3. [QxMD MEDLINE Link].
Magand F, Nacher M, Cazorla C, Cambazard F, Marie DS, Couppié P. Predictive values of prurigo nodularis and herpes zoster for HIV infection and immunosuppression requiring HAART in French Guiana. Trans R Soc Trop Med Hyg. 2011 Jul. 105(7):401-4. [QxMD MEDLINE Link].
Seshadri P, Rajan SJ, George IA, George R. A sinister itch: prurigo nodularis in Hodgkin lymphoma. J Assoc Physicians India. 2009 Oct. 57:715-6. [QxMD MEDLINE Link].
Savoia F, Casadio C, Tabanelli M, Gaddoni G, Savoia F, Patrizi A, et al. Prurigo nodularis as the first manifestation of a chronic autoimmune cholestatic hepatitis. Int J Dermatol. 2011 Dec. 50(12):1588-9. [QxMD MEDLINE Link].
Kestner RI, Ständer S, Osada N, Ziegler D, Metze D. Acquired Reactive Perforating Dermatosis is a Variant of Prurigo Nodularis. Acta Derm Venereol. 2017 Feb 8. 97 (2):249-254. [QxMD MEDLINE Link].
Matthews SN, Cockerell CJ. Prurigo nodularis in HIV-infected individuals. Int J Dermatol. 1998 Jun. 37(6):401-9. [QxMD MEDLINE Link].
Lim VM, Maranda EL, Patel V, Simmons BJ, Jimenez JJ. A Review of the Efficacy of Thalidomide and Lenalidomide in the Treatment of Refractory Prurigo Nodularis. Dermatol Ther (Heidelb). 2016 Sep. 6 (3):397-411. [QxMD MEDLINE Link].
Roenigk RK, Dahl MV. Bullous pemphigoid and prurigo nodularis. J Am Acad Dermatol. 1986 May. 14(5 Pt 2):944-7. [QxMD MEDLINE Link].
Tamada Y, Yokochi K, Oshitani Y, et al. Pemphigoid nodularis: a case with 230 kDa hemidesmosomes antigen associated with bullous pemphigoid antigen. J Dermatol. 1995 Mar. 22(3):201-4. [QxMD MEDLINE Link].
Ankad BS, Beergouder SL. Hypertrophic lichen planus versus prurigo nodularis: a dermoscopic perspective. Dermatol Pract Concept. 2016 Apr. 6 (2):9-15. [QxMD MEDLINE Link].
Feuerman EJ, Sandbank M. Prurigo nodularis. Histological and electron microscopical study. Arch Dermatol. 1975 Nov. 111(11):1472-7. [QxMD MEDLINE Link].
Perez GL, Peters MS, Reda AM, Butterfield JH, Peterson EA, Leiferman KM. Mast cells, neutrophils, and eosinophils in prurigo nodularis. Arch Dermatol. 1993 Jul. 129(7):861-5. [QxMD MEDLINE Link].
Sandbank M. Cutaneous nerve lesions in prurigo nodularis. Electron microscopic study of two patients. J Cutan Pathol. 1976. 3(3):125-32. [QxMD MEDLINE Link].
Weigelt N, Metze D, Ständer S. Prurigo nodularis: systematic analysis of 58 histological criteria in 136 patients. J Cutan Pathol. 2009 Nov 30. [QxMD MEDLINE Link].
Grillo M, Long R, Long D. Habit reversal training for the itch-scratch cycle associated with pruritic skin conditions. Dermatol Nurs. 2007 Jun. 19(3):243-8. [QxMD MEDLINE Link].
Ständer HF, Elmariah S, Zeidler C, Spellman M, Ständer S. Diagnostic and treatment algorithm for chronic nodular prurigo. J Am Acad Dermatol. 2020 Feb. 82 (2):460-468. [QxMD MEDLINE Link].
Richards RN. Update on intralesional steroid: focus on dermatoses. J Cutan Med Surg. 2010 Jan-Feb. 14(1):19-23. [QxMD MEDLINE Link].
Tupker RA, Coenraads PJ, van der Meer JB. Treatment of prurigo nodularis, chronic prurigo and neurodermatitis circumscripta with topical capsaicin. Acta Derm Venereol. 1992 Nov. 72(6):463. [QxMD MEDLINE Link].
Boyd K, Shea SM, Patterson JW. The role of capsaicin in dermatology. Prog Drug Res. 2014. 68:293-306. [QxMD MEDLINE Link].
Katayama I, Miyazaki Y, Nishioka K. Topical vitamin D3 (tacalcitol) for steroid-resistant prurigo. Br J Dermatol. 1996 Aug. 135(2):237-40. [QxMD MEDLINE Link].
Meyers LN. Use of occlusive membrane in the treatment of prurigo nodularis. Int J Dermatol. 1989 May. 28(4):275-6. [QxMD MEDLINE Link].
Nakamura M, Koo JY. Phototherapy for the treatment of prurigo nodularis: a review. Dermatol Online J. 2016 Apr 18. 22 (4):[QxMD MEDLINE Link].
Saraceno R, Nistico SP, Capriotti E, de Felice C, Rhodes LE, Chimenti S. Monochromatic excimer light (308 nm) in the treatment of prurigo nodularis. Photodermatol Photoimmunol Photomed. 2008 Feb. 24(1):43-5. [QxMD MEDLINE Link].
Wollenschlager I, Hermann J, Ockenfels HM. [Targeted UVB-308 nm (NUVB) therapy with excimer laser in the treatment of atopic dermatitis and other inflammatory dermatoses]. Hautarzt. 2009 Nov. 60(11):898-906. [QxMD MEDLINE Link].
Hammes S, Hermann J, Roos S, Ockenfels HM. UVB 308-nm excimer light and bath PUVA: combination therapy is very effective in the treatment of prurigo nodularis. J Eur Acad Dermatol Venereol. 2011 Jul. 25(7):799-803. [QxMD MEDLINE Link].
Rombold S, Lobisch K, Katzer K, Grazziotin TC, Ring J, Eberlein B. Efficacy of UVA1 phototherapy in 230 patients with various skin diseases. Photodermatol Photoimmunol Photomed. 2008 Feb. 24(1):19-23. [QxMD MEDLINE Link].
Clemmensen OJ, Olsen PZ, Andersen KE. Thalidomide neurotoxicity. Arch Dermatol. 1984 Mar. 120(3):338-41. [QxMD MEDLINE Link].
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. 1996 Dec. 35(6):969-79. [QxMD MEDLINE Link].
Orlando A, Renna S, Cottone M. Prurigo nodularis of Hyde treated with low-dose thalidomide. Eur Rev Med Pharmacol Sci. 2009 Mar-Apr. 13(2):141-5. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
Berger TG, Hoffman C, Thieberg MD. Prurigo nodularis and photosensitivity in AIDS: treatment with thalidomide. J Am Acad Dermatol. 1995 Nov. 33(5 Pt 1):837-8. [QxMD MEDLINE Link].
Andersen TP, Fogh K. Thalidomide in 42 patients with prurigo nodularis Hyde. Dermatology. 2011. 223(2):107-12. [QxMD MEDLINE Link].
Ossorio-García L, Jiménez-Gallo D, Rodríguez-Mateos ME, Arjona-Aguilera C, Linares-Barrios M. Treatment of prurigo nodularis with lenalidomide. Dermatol Ther. 2017 Mar. 30 (2):[QxMD MEDLINE Link].
Bieber AK, Cohen DE, Stein JA. Systemic methotrexate for prurigo nodularis and keratoacanthomas in actinically damaged skin. JAAD Case Rep. 2016 May. 2 (3):269-71. [QxMD MEDLINE Link].
Spring P, Gschwind I, Gilliet M. Prurigo nodularis: retrospective study of 13 cases managed with methotrexate. Clin Exp Dermatol. 2014 Jun. 39 (4):468-73. [QxMD MEDLINE Link].
Qureshi AA, Abate LE, Yosipovitch G, Friedman AJ. A systematic review of evidence-based treatments for prurigo nodularis. J Am Acad Dermatol. 2019 Mar. 80 (3):756-764. [QxMD MEDLINE Link].
Holm JG, Agner T, Sand C, Thomsen SF. Dupilumab for prurigo nodularis: Case series and review of the literature. Dermatol Ther. 2020 Mar. 33 (2):e13222. [QxMD MEDLINE Link].
Beck KM, Yang EJ, Sekhon S, Bhutani T, Liao W. Dupilumab Treatment for Generalized Prurigo Nodularis. JAMA Dermatol. 2019 Jan 1. 155 (1):118-120. [QxMD MEDLINE Link].
Ständer S, Yosipovitch G, Legat FJ, Lacour JP, Paul C, Narbutt J, et al. Trial of Nemolizumab in Moderate-to-Severe Prurigo Nodularis. N Engl J Med. 2020 Feb 20. 382 (8):706-716. [QxMD MEDLINE Link].
Gencoglan G, Inanir I, Gunduz K. Therapeutic hotline: Treatment of prurigo nodularis and lichen simplex chronicus with gabapentin. Dermatol Ther. 2010 Mar-Apr. 23(2):194-8. [QxMD MEDLINE Link].
Dereli T, Karaca N, Inanir I, Ozturk G. Gabapentin for the treatment of recalcitrant chronic prurigo nodularis. Eur J Dermatol. 2008 Jan-Feb. 18(1):85-6. [QxMD MEDLINE Link].
Ständer S, Siepmann D, Herrgott I, Sunderkötter C, Luger TA. Targeting the neurokinin receptor 1 with aprepitant: a novel antipruritic strategy. PLoS One. 2010 Jun 4. 5(6):e10968. [QxMD MEDLINE Link]. [Full Text].
Phan NQ, Lotts T, Antal A, Bernhard JD, Ständer S. Systemic Kappa Opioid Receptor Agonists in the Treatment of Chronic Pruritus: A Literature Review. Acta Derm Venereol. 2012 Apr 16. [QxMD MEDLINE Link].
Stoll DM, Fields JP, King LE Jr. Treatment of prurigo nodularis: use of cryosurgery and intralesional steroids plus lidocaine. J Dermatol Surg Oncol. 1983 Nov. 9(11):922-4. [QxMD MEDLINE Link].
Waldinger TP, Wong RC, Taylor WB, Voorhees JJ. Cryotherapy improves prurigo nodularis. Arch Dermatol. 1984 Dec. 120(12):1598-600. [QxMD MEDLINE Link].
Lotti T, Buggiani G, Prignano F. Prurigo nodularis and lichen simplex chronicus. Dermatol Ther. 2008 Jan-Feb. 21(1):42-6. [QxMD MEDLINE Link].

Media Gallery

Prurigo nodularis. Courtesy of Jeffrey Meffert, MD.
Prurigo nodularis. Courtesy of Jeffrey Meffert, MD.

of 2

Author

Amarateedha Prak LeCourt, MD Resident Physician, Department of Anesthesiology, Naval Medical Center San Diego; Naval Flight Surgeon/Fleet Marine Force Qualified Officer, US Navy

Amarateedha Prak LeCourt, MD is a member of the following medical societies: Aerospace Medical Association, Association of Military Surgeons of the US

Disclosure: Nothing to disclose.

Coauthor(s)

Kristina Marie Dela Rosa, MD Dermatologist, Insight Dermatology, San Diego, CA

Kristina Marie Dela Rosa, MD is a member of the following medical societies: American Academy of Dermatology, American Medical Association

Disclosure: Nothing to disclose.

Specialty Editor Board

Michael J Wells, MD, FAAD Dermatologic/Mohs Surgeon, The Surgery Center at Plano Dermatology

Michael J Wells, MD, FAAD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, Texas Medical Association

Disclosure: Nothing to disclose.

Chief Editor

William D James, MD Paul R Gross Professor of Dermatology, Vice-Chairman, Residency Program Director, Department of Dermatology, University of Pennsylvania School of Medicine

William D James, MD is a member of the following medical societies: American Academy of Dermatology, Society for Investigative Dermatology

Disclosure: Received income in an amount equal to or greater than $250 from: Elsevier; WebMD<br/>Served as a speaker for various universities, dermatology societies, and dermatology departments.

Additional Contributors

Daniel J Hogan, MD Clinical Professor of Internal Medicine (Dermatology), Nova Southeastern University College of Osteopathic Medicine; Investigator, Hill Top Research, Florida Research Center

Daniel J Hogan, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Contact Dermatitis Society, Canadian Dermatology Association

Disclosure: Nothing to disclose.

Franklin Flowers, MD Professor Emeritus, Department of Dermatology, Affiliate Associate Professor of Pathology, University of Florida College of Medicine

Franklin Flowers, MD is a member of the following medical societies: American College of Mohs Surgery

Disclosure: Nothing to disclose.

Stephen H Mason, MD

Stephen H Mason, MD is a member of the following medical societies: American Academy of Dermatology, American College of Mohs Surgery, American Society for Dermatologic Surgery, Women's Dermatologic Society, Skin Cancer Foundation

Disclosure: Nothing to disclose.

Siobahn M Hruby, MD Internal Medicine Physician, Boys Town National Research Hospital

Siobahn M Hruby, MD is a member of the following medical societies: American College of Physicians, American Medical Association

Disclosure: Nothing to disclose.

Sharron M Mason, MD Staff Physician, Department of Internal Medicine, University of Kansas School of Medicine

Disclosure: Nothing to disclose.