Amitriptyline and azathioprine: an effective therapeutic approach in prurigo nodularis resistant to conventional therapies

Briatico, Giulia; Scharf, Camila; Brizzi, Eugenia Veronica Di; Pellerone, Sebastiano; Buononato, Dario; Squadrilli, Francesco; Babino, Graziella; Argenziano, Giuseppe; Giorgio, Caterina Mariarosaria

doi:10.1111/ddg.14975

Cited by 3 publications

(5 citation statements)

References 8 publications

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“…The neural hyperplasia and the concomitant epidermal proliferation can be explained by neurotrophins and the systemic and cutaneous Th2 immune polarization with pronounced STAT 6 expression 6,18 . These findings may help us to use directed therapeutic agents that work on the neural element like nortriptyline, pregabalin, and thalidomide 18,37–39 . As IL‐4, IL‐13, and IL‐31 are the prominent cytokines 6,17,18 which mediate their action via specific JAK receptors (IL‐4=JAK1, JAK3; IL‐13=JAK1 & TYK2 & IL‐31=JAK1), JAK inhibitors would be useful agents in PN, 40 as they can inhibit multiple cytokines, unlike the specific cytokine directed therapeutic agents (nemolizumab, dupilumab, tralokinumab, lebrikizumab, and vixarelimab) 41 …”

Section: Discussionmentioning

confidence: 99%

“…The case–control nature of our study validates the histopathological findings though a drawback in our study is that we did not include the atopic subtype of PN and could not perform cytokine signatures in our biopsy specimens. A larger cohort of patients with the use of directed therapeutic agents towards the salient key “players” of PN with post therapy tissue analysis would help to validate the role of targeted therapeutic agents for PN 37–41 …”

Section: Discussionmentioning

confidence: 99%

“…6,18 These findings may help us to use directed therapeutic agents that work on the neural element like nortriptyline, pregabalin, and thalidomide. 18,[37][38][39] As IL-4, IL-13, and IL-31 are the prominent cytokines 6,17,18 which mediate their action via specific JAK receptors (IL-4=JAK1, JAK3; IL-13=JAK1 & TYK2 & IL-31=JAK1), JAK inhibitors would be useful agents in PN, 40 as they can inhibit multiple cytokines, unlike the specific cytokine directed therapeutic agents (nemolizumab, dupilumab, tralokinumab, lebrikizumab, and vixarelimab). 41 The case-control nature of our study validates the histopathological findings though a drawback in our study is that we did not include the atopic subtype of PN and could not perform cytokine signatures in our biopsy specimens.…”

Section: Discussionmentioning

confidence: 99%

“…A larger cohort of patients with the use of directed therapeutic agents towards the salient key "players" of PN with post therapy tissue analysis would help to validate the role of targeted therapeutic agents for PN. [37][38][39][40][41]…”

Section: Discussionmentioning

confidence: 99%

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A case–control study addressing the population of epidermal and dermal inflammatory infiltrate including neural milieu in primary prurigo nodularis using S‐100 and toluidine blue stain and its therapeutic implications

Agrawal,

Sardana,

Mathachan

et al. 2023

Int J Dermatology

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BackgroundThe pathogenesis of prurigo nodularis (PN) is considered to be multifactorial, with numerous cells and cytokines confabulating to produce an aberrant immune response.MethodsA cross‐sectional observational study was done in cases of untreated primary prurigo nodularis cases with histopathological assessment in 49 cases from lesional and nonlesional skin with assessment of epidermal and dermal changes, dermal infiltrate, S‐100 and toluidine blue staining to assess the expression of nerve and mast cells.ResultsThe most common histological changes seen in lesional skin were hyperkeratosis (98%), irregular hyperplasia (69.4%), hypergranulosis (69.4%), subepidermal clefting (6%), vertical collagen bundles (51.0%), and dermal fibrosis (48.9%). Chronic inflammatory infiltrate was seen in all cases (100%) predominantly of lymphocytes (100%) followed by eosinophils (18.4%), plasma cells (8.2%), and neutrophils (2.0%). There was a marked increase in the expression of S‐100 (6.92 ± 3.40 vs. 3.94 ± 2.15, P < 0.001) and toluidine blue (4.99 ± 4.47 vs. 1.22 ± 1.28, P < 0.001) in the lesional skin as compared to the nonlesional skin.ConclusionWe can infer that the epidermal and dermal pathology in PN is related to the infiltrate of lymphocytes, mast cells, and neural hyperplasia which perpetuate the pathogenesis by triggering the itch‐inflammation cycle. Thus, apart from immunosuppressive agents that target lymphocytes and their cytokines, therapy targeted at mast cells and neural proliferation may be needed to treat prurigo nodularis.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

A case–control study addressing the population of epidermal and dermal inflammatory infiltrate including neural milieu in primary prurigo nodularis using S‐100 and toluidine blue stain and its therapeutic implications

Agrawal,

Sardana,

Mathachan

et al. 2023

Int J Dermatology

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show abstract

“…Systemic therapeutic options include gabapentinoids, conventional immunosuppressants (for example, ciclosporin, methotrexate, azathioprine), neuromodulating therapies (especially opioid modulators like naloxone, naltrexone, nalbuphine), and immunomodulating therapies including biologics (for example, dupilumab, nemolizumab) and oral Janus kinase inhibitors 20,39 . In some cases, a combination of drugs may be considered, while taking potential interactions into account 41 Systemic therapies are indicated in moderate to severe chronic prurigo.…”

Section: Therapymentioning

confidence: 99%

Chronic Prurigo

Thünemann,

Müller,

Steinbrink

et al. 2024

J Deutsche Derma Gesell

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SummaryChronic prurigo (CPG) is a neuroinflammatory dermatosis characterized by prolonged pruritus lasting more than 6 weeks, pruriginous skin lesions, and repeated scratching.Patients with CPG suffer significantly from psychological distress and a marked impairment in their quality of life. The most common subtype of CPG is chronic nodular prurigo (CNPG, also called prurigo nodularis).In addition to the clinical features of CPG and the burden of disease, this CME article provides an overview of the significant advances in understanding the pathophysiology, including the associated therapeutic options for CPG. Dupilumab is the first approved therapy for moderate and severe CNPG to date from the European Medicines Agency (EMA) and the US Food & Drug Administration (FDA). It also highlights other agents currently being studied in Phase II and Phase III clinical, randomized, placebo‐controlled trials. These include biologics such as nemolizumab (anti‐IL‐31‐RA‐mAb), vixarelimab/KPL‐716 (anti‐Oncostatin‐M receptor β‐mAb), and barzolvolimab/CDX‐0159 (anti‐KIT‐mAb), as well as Janus kinase inhibitors such as povorcitinib/INCB054707 and abrocitinib, and opioid modulators such as nalbuphine.

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A case control study examining the population of epidermal and dermal pathology, inflammatory infiltrate and neural milieu of primary prurigo nodularis using S-100 and Toluidine blue stain and its therapeutic implications

Agrawal¹,

Sardana

Mathachan³

et al. 2023

Preprint

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A cross-sectional observational study was in cases of untreated primary prurigo nodularis cases with histopathological assessment in 49 cases of prurigo from lesional and non lesional uninvolved skin with assessment of epidermal and dermal changes, composition of dermal infiltrate and S-100 & toluidine blue staining to assess the role of nerve and mast cells. The most common histological changes seen in lesional skin were hyperkeratosis( 98%), irregular hyperplasis (69.4%) hypergranulosis (69.4%), sub epidermal clefting( 6%), vertical collagen bundles (51.0%) & dermal fibrosis (48.9%). Chronic inflammatory infiltrate was seen in all cases (100%) and the most common inflammatory cells seen being found were lymphocytes (100%) followed by, eosinophils (18.4%), plasma cells (8.2%) patients neutrophils. (2.0%). There was a marked increase in the expression of S-100 (6.92 ± 3.40 Vs 3.94 ± 2.15, p < 0.001) and toludidine blue (4.99 ± 4.47 Vs 1.22 ± 1.28, p < 0.001) in the lesional skin as compared to the non lesional skin. Thus we can infer that the epidermal and dermal pathology is dependent on lymphocytes, mast cells and neural hyperplasia which perpetuate the pathology of PN by triggering the itch-inflammation cycle. Thus apart from immunosuppressive agents that target lymphocytes and their cytokines therapy targeted at mast cells and neural proliferation may be needed to treat prurigo nodularis.

show abstract

Amitriptyline and azathioprine: an effective therapeutic approach in prurigo nodularis resistant to conventional therapies

Cited by 3 publications

References 8 publications

A case–control study addressing the population of epidermal and dermal inflammatory infiltrate including neural milieu in primary prurigo nodularis using S‐100 and toluidine blue stain and its therapeutic implications

A case–control study addressing the population of epidermal and dermal inflammatory infiltrate including neural milieu in primary prurigo nodularis using S‐100 and toluidine blue stain and its therapeutic implications

Chronic Prurigo

A case control study examining the population of epidermal and dermal pathology, inflammatory infiltrate and neural milieu of primary prurigo nodularis using S-100 and Toluidine blue stain and its therapeutic implications

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