Understanding Prurigo Nodularis Through the Ages
1660
Itch is defined as the unpleasant sensation that provokes the desire to scratch.1
1808
Skin diseases are categorized based on primary lesion morphology.2,3
1860
Prurigo Nodularis is first described in the Atlas der Hautkrankheiten (Atlas of Skin Diseases).
Hebra described “constitutional prurigo” as a difficult-to-treat, chronic, recurrent skin disorder characterized by intensely pruritic papules and nodules on the trunk and limbs. This definition was controversial due to its dogmatic nature and continued to be so until the 1930s. However, it formed the conceptual and clinical framework for prurigo diseases.4
1879
Additional description of skin nodules with intense itch appears.
William Hardaway describes a disease characterized by “multiple tumors (nodules) of the skin accompanied by itching” in the Archives of Dermatology.5
1891
Disseminated neurodermatitis is described.
The definition consists of constant itch, plaque formation restricted to areas where the itch started, distribution of skin lesions indicating dermatosis with nervous system origin, skin dryness, hypertrophy, and pigmentation.6
1909
Dermatologist James Hyde introduces the term “Prurigo Nodularis.”
“PN Hyde” is established as a distinct disease until it becomes known in modern times as “Prurigo Nodularis.”5
1934
Dr Pautrier describes neuronal hyperplasia in the skin of patients with PN.
Dermal neuronal abnormalities, including neuronal hyperplasia, were observed in the skin of patients with PN.7
2000
Interaction between inflammatory cells and peripheral nerve fibers contributes to PN pathophysiology.
PN pathophysiology is evolved to include immune and nervous system interactions in addition to itch.7,8
2015
A code for prurigo nodularis was added to the ICD-10 (L-28.1).9
2018
Prurigo nomenclature is evolved to chronic prurigo (CPG), which includes PN.
The European Academy of Dermatology and Venereology initiative suggested the use of the term chronic prurigo (CPG) for prurigo, including PN.10
2019
Recommendations emerged for an evidence-based, standardized approach to the diagnostic evaluation of PN (to differentiate PN from other chronic skin conditions).
The recommended diagnostic work-up includes lab testing, skin biopsy for histology and immunohistochemistry, and other tests as needed to rule out other causes.11
2020
Diagnostic criteria for CPG and PN were clearly defined.
CPG was defined as chronic pruritis of at least 6 weeks with signs of constant scratching and localized or generalized pruriginous lesions. PN was defined as the most common of 5 subtypes of CPR, characterized by itchy, dome-shaped nodules over 1 cm diameter.5
April 2022
Mouse transcriptome studies show multiple axes involved in PN.
Transcription studies in mice show convergence in the expression of molecules such as neurotransmitters, neuropeptides, leukotrienes, and cytokines that activate itch receptors, including IL-4RA, IL-13RA1, and IL-31RA.12
December 2022
Human transcriptomic data show differences in gene expression between lesional skin in PN and AD Increases in neurotrophic and extracellular matrix remodeling gene signatures in PN lesions compared with AD lesions provide evidence that PN and AD are unique and distinct diseases.13
- Siemens W, Xander C, Meerpohl JJ, et al. Pharmacological interventions for pruritus in adult palliative care patients. Cochrane Database Syst Rev.2016;11(11):CD008320. doi:10.1002/14651858.CD008320.pub3
- Kramer ON, Strom MA, Ladizinski B, Lio PA. The history of atopic dermatitis. Clin Dermatol. 2017;35(4):344-348. doi:10.1016/j.clindermatol.2017.03.005
- Grzybowski A, Parish LC. Robert Willan: pioneer in morphology. Clin Dermatol. 2011;29(2):125–129. doi:10.1016/j.clindermatol.2010.09.005
- Taïeb A, Wallach D, Tilles G. The history of atopic eczema/dermatitis. In: Ring J, Przybilla B, Ruzicka T, eds. Handbook of Atopic Eczema. Springer; 2006.
- Ständer S, Pereira MP, Berger T, et al. IFSI-guideline on chronic prurigo including prurigo nodularis. Itch. 2020;5(4):e42. doi:10.1097/itx.0000000000000042
- Murota H, Katayama I. Exacerbating factors of itch in atopic dermatitis. Allergol Int. 2017;66(1):8–13. doi:10.1016/j.alit.2016.10.005
- Williams KA, Roh YS, Brown I, et al. Pathophysiology, diagnosis, and pharmacological treatment of prurigo nodularis. Expert Rev Clin Pharmacol.2021;14(1):67-77. doi:10.1080/17512433.2021.1852080
- Johansson O, et al. Eosinophil cationic protein- and eosinophil-derived neurotoxin/eosinophil protein X-immunoreactive eosinophils in prurigo nodularis. Arch Dermatol Res. 2000;292(8):371-378. doi:10.1007/s004030000142
- 2023 ICD-10-CM Diagnosis Code L28.1: Prurigo nodularis. Accessed July 29, 2023. https://www.icd10data.com
- Pereira MP, Steinke S, Zeidler C, et al. European academy of dermatology and venereology European prurigo project: expert consensus on the definition, classification and terminology of chronic prurigo. J Eur Acad Dermatol Venereol. 2018;32(7):1059-1065. doi:10.1111/jdv.14570
- Kwon CD, Khanna R, Williams KA, Kwatra MM, Kwatra SG. Diagnostic workup and evaluation of patients with prurigo nodularis. Medicines (Basel). 2019;6(4):97. doi:10.3390/medicines6040097
- Kim BS. The translational revolution of itch. Neuron. 2022;110(14):2209-2214. doi: 10.1016/j.neuron.2022.03.031
- Deng J, Parthasarathy V, Marani M, et al. Extracellular matrix and dermal nerve growth factor dysregulation in prurigo nodularis compared to atopic dermatitis. Front Med (Lausanne). 2022;9:1022889. doi: 10.3389/fmed.2022.1022889