Prurigo nodularis explained

Prurigo nodularis (PN), also known as nodular prurigo, is a skin disorder characterized by pruritic (itchy), nodular lesions, which commonly appear on the trunk, arms and legs.^[1] Patients often present with multiple excoriated nodules caused by chronic scratching. Although the exact cause of PN is unknown, PN is associated with other dermatologic conditions such as untreated or severe atopic dermatitis and systemic causes of pruritus including liver disease and end stage kidney disease.^[2] The goal of treatment in PN is to decrease itching. PN is also known as Hyde prurigo nodularis, or Picker's nodules.^[3]

Signs and symptoms

• Nodules are discrete, generally symmetric, hyperpigmented and firm. They are greater than 0.5 cm in both width and depth (as opposed to papules which are less than 0.5 cm).
• The nodules of PN can appear on any part of the body, but generally are found in areas where patients are able to reach to scratch. Patients can exhibit a 'butterfly sign' in which nodules are absent in the mid upper back.^{[1] [4]}
• Nodular lesions are often excoriated from persistent scratching.
• The nodules in PN are extremely itchy, this sensation can have an impact on patients perceived quality of life^[5]
• Nodule pattern can be follicular.

Causes

The exact cause of prurigo nodularis is unknown, however, it is thought to be induced by other dermatologic conditions such as severe atopic dermatitis, Becker's nevus,^[6] and linear IgA disease.^[7] PN is also associated with systemic causes of pruritus such as liver disease,^[8] cholestasis, thyroid disease, polycythemia vera, uremia, Hodgkins lymphoma, HIV and kidney failure diseases.^{[9] [10]} Psychiatric illnesses have been considered to induce PN, although later research refuted a psychiatric cause for PN. Patients report an ongoing battle to distinguish themselves from those with psychiatric disorders, such as delusions of parasitosis and other psychiatric conditions.^{[11] [12]}

Pathophysiology

Chronic and repetitive scratching, picking, or rubbing of the nodules may result in permanent changes to the skin, including nodular lichenification, hyperkeratosis, hyperpigmentation, and skin thickening. Unhealed, excoriated lesions are often scaly, crusted or scabbed. Many patients report a lack of wound healing even when medications relieve the itching and consequent scratching.

Patients often:

• seek treatment during middle-age, although PN can occur at any age.
• have a history of chronic severe pruritus.
• have a significant medical history for unrelated conditions.
• develop liver or kidney dysfunctions.
• develop secondary skin infections.
• have a personal or family history of atopic dermatitis.
• have other autoimmune disorders.
• have low vitamin D levels.

Diagnosis

Diagnosis is based on visual examination and the presence of itching for greater than 6 weeks duration.

^[13] A skin biopsy is often performed to exclude other diseases. Lesion biopsies usually show light inflammation, sometimes with increased numbers of eosinophils.^[14] A culture of at least one lesion will rule out staphylococcus infection, which has been significantly linked to atopic dermatitis.^{[15] [16] [17]}

Treatment

Prurigo nodularis is hard to treat and therapies include steroids, dupilumab, vitamins, cryosurgery, thalidomide, and UVB light. In the event that staphylococcus or other infection is present, antibiotics have proven effective, but tend to cause more harm than good for this particular disease. A physician may administer a strong dose of prednisone, which will almost immediately stop the itch/scratch cycle. However, cessation of steroids allows relapse to occur, usually within a few weeks. A 2006 study reported improvement in prurigo nodularis with antibiotic therapy.^[18]

Azathioprine, an immunosuppressive drug used in organ transplantation and autoimmune diseases belonging to the chemical class of purine analogues, also known by the brand name Imuran, has been reported to be effective.^{[19] [20]}

Dupilumab (Dupixent) was approved for medical use in the United States in September 2022.^[21] Dupilumab is the first medication approved for the treatment of prurigo nodularis by the US Food and Drug Administration.

Nemolizumab (Nemluvio) was approved for medical use in the United States in August 2024.^[22]

History

Prurigo nodularis was first described by Hyde and Montgomery in 1909.^[23]

Notes and References

1. Leis . Maria . Fleming . Patrick . Lynde . Charles W. . May 2021 . Prurigo Nodularis: Review and Emerging Treatments . Skin Therapy Letter . 26 . 3 . 5–8 . 1201-5989 . 34077168.
2. Web site: Prurigo nodularis: Causes . 13 February 2024 . www.aad.org . en.
3. Frølunde . Anne Sofie . Wiis . Malthe Alexander Knudsgaard . Ben Abdallah . Hakim . Elsgaard . Stine . Danielsen . Anna Kathrine . Deleuran . Mette . Vestergaard . Christian . 13 April 2022 . Non-Atopic Chronic Nodular Prurigo (Prurigo Nodularis Hyde): A Systematic Review of Best-Evidenced Treatment Options . Dermatology . 238 . 5 . 950–960 . 10.1159/000523700 . 35417906 . 1018-8665.
4. Huang . Amy H. . Williams . Kyle A. . Kwatra . Shawn G. . December 2020 . Prurigo nodularis . Journal of the American Academy of Dermatology . en . 83 . 6 . 1559–1565 . 10.1016/j.jaad.2020.04.183. 32454098 . 218910999 .
5. Ingrasci . Giuseppe . El-Kashlan . Nour . Alexis . Andrew . Yosipovitch . Gil . 1 July 2022 . Chronic itch in African Americans: an unmet need . Archives of Dermatological Research . en . 314 . 5 . 405–415 . 10.1007/s00403-021-02255-6 . 34129098 . 235429367 . 1432-069X.
6. Lockshin BN, Brogan B, Billings S, Billings S . Eczematous dermatitis and prurigo nodularis confined to a Becker's nevus . International Journal of Dermatology . 45 . 12 . 1465–1466 . December 2006 . 17184268 . 10.1111/j.1365-4632.2006.02971.x . 32658695 .
7. Torchia D, Caproni M, Del Bianco E, Cozzani E, Ketabchi S, Fabbri P . Linear IgA disease presenting as prurigo nodularis . The British Journal of Dermatology . 155 . 2 . 479–480 . August 2006 . 16882196 . 10.1111/j.1365-2133.2006.07315.x . 28166468 .
8. Hazin R, Abu-Rajab Tamimi TI, Abuzetun JY, Zein NN . Recognizing and treating cutaneous signs of liver disease . Cleveland Clinic Journal of Medicine . 76 . 10 . 599–606 . October 2009 . 19797460 . 10.3949/ccjm.76A.08113 . free .
9. Hiramanek N . Itch: a symptom of occult disease . Australian Family Physician . 33 . 7 . 495–499 . July 2004 . 15301165 .
10. Berger TG, Hoffman C, Thieberg MD . Prurigo nodularis and photosensitivity in AIDS: treatment with thalidomide . Journal of the American Academy of Dermatology . 33 . 5 Pt 1 . 837–838 . November 1995 . 7593791 . 10.1016/0190-9622(95)91846-9 .
11. Kieć-Swierczyńska M, Dudek B, Krecisz B, Swierczyńska-Machura D, Dudek W, Garnczarek A, Turczyn K . [The role of psychological factors and psychiatric disorders in skin diseases] . pl . Medycyna Pracy . 57 . 6 . 551–555 . 2006 . 17533993 . The role of psychological factors and psychiatric disorders in skin diseases .
12. Vargas Laguna E, Peña Payero ML, Vargas Márquez A . [Influence of anxiety in diverse cutaneous diseases] . es . Actas Dermo-Sifiliograficas . 97 . 10 . 637–643 . December 2006 . 17173825 . 10.1016/s0001-7310(06)73484-6 . Influence of anxiety in diverse cutaneous diseases .
13. Kwon . Christina D. . Khanna . Raveena . Williams . Kyle A. . Kwatra . Madan M. . Kwatra . Shawn G. . 26 September 2019 . Diagnostic Workup and Evaluation of Patients with Prurigo Nodularis . Medicines . en . 6 . 4 . 97 . 10.3390/medicines6040097 . free . 2305-6320 . 6963711 . 31561504.
14. Johansson O, Liang Y, Marcusson JA, Reimert CM . Eosinophil cationic protein- and eosinophil-derived neurotoxin/eosinophil protein X-immunoreactive eosinophils in prurigo nodularis . Archives of Dermatological Research . 292 . 8 . 371–378 . August 2000 . 10994770 . 10.1007/s004030000142 . 9095256 .
15. Gong JQ, Lin L, Lin T, Hao F, Zeng FQ, Bi ZG, Yi D, Zhao B . Skin colonization by Staphylococcus aureus in patients with eczema and atopic dermatitis and relevant combined topical therapy: a double-blind multicentre randomized controlled trial . The British Journal of Dermatology . 155 . 4 . 680–687 . October 2006 . 16965415 . 10.1111/j.1365-2133.2006.07410.x . 27948096 .
16. Lin YT, Wang CT, Chiang BL . Role of bacterial pathogens in atopic dermatitis . Clinical Reviews in Allergy & Immunology . 33 . 3 . 167–177 . December 2007 . 18163223 . 10.1007/s12016-007-0044-5 . 25203471 .
17. Guzik TJ, Bzowska M, Kasprowicz A, Czerniawska-Mysik G, Wójcik K, Szmyd D, Adamek-Guzik T, Pryjma J . Persistent skin colonization with Staphylococcus aureus in atopic dermatitis: relationship to clinical and immunological parameters . Clinical and Experimental Allergy . 35 . 4 . 448–455 . April 2005 . 15836752 . 10.1111/j.1365-2222.2005.02210.x . 38030209 .
18. Horiuchi Y, Bae S, Katayama I . Uncontrollable prurigo nodularis effectively treated by roxithromycin and tranilast . Journal of Drugs in Dermatology . 5 . 4 . 363–365 . April 2006 . 16673805 .
19. Briatico . Giulia . Scharf . Camila . Di Brizzi . Eugenia Veronica . Pellerone . Sebastiano . Buononato . Dario . Squadrilli . Francesco . Babino . Graziella . Argenziano . Giuseppe . Giorgio . Caterina Mariarosaria . Amitriptyline and azathioprine: an effective therapeutic approach in prurigo nodularis resistant to conventional therapies . JDDG: Journal der Deutschen Dermatologischen Gesellschaft . 21 . 3 . 2023 . 1610-0379 . 10.1111/ddg.14975 . 291–293.
20. Lear . J.T. . English . J.S.C. . Smith . A.G. . Nodular prurigo responsive to azathioprine (letter). British Journal of Dermatology . 134 . 6 . 1996 . 10.1111/j.1365-2133.1996.tb07964.x . 1151–1151.
21. Web site: FDA approves first treatment for prurigo nodularis . U.S. Food and Drug Administration (FDA) . 29 September 2022 .
22. Galderma Receives U.S. FDA Approval for Nemluvio (nemolizumab) for Adult Patients Living With Prurigo Nodularis . Galderma . Business Wire . 13 August 2024 . 14 August 2024.
23. Hyde JN, Montgomery FH: A practical treatise on disease of the skin for the use of students and practitioners. 1909; 174–175.