Prurigo nodularis (PN) is a chronic inflammatory skin disease characterized oftentimes by symmetrically distributed, severely pruritic nodules. Currently, the pathophysiology of PN remains to be fully elucidated, but emerging evidence suggests that neuroimmune alterations play principal roles in the pathogenesis of PN. There are several associated etiologic factors thought to be associated with PN, including dermatoses, systemic, infectious, psychiatric, and neurologic conditions. We conducted a systematic literature review to evaluate the clinical presentation, diagnosis, and etiologic factors of PN. In this review, we discuss common differential diagnoses of PN and recommend an evidence-based, standardized diagnostic evaluation for those with suspected PN.

Background: Prurigo nodularis (PN) is an intensely pruritic skin condition of considerable morbidity. However, the pathogenesis of PN and its association with underlying neuropathy is unclear. Objective: We sought to investigate the association between PN and etiologies of peripheral neuropathy. Methods: A cross-sectional analysis of adult patients (≥18-year-old) with PN, AD, and Psoriasis at the Johns Hopkins Health System over a six-year period (January 2013–January 2019) was performed. The strength of association with etiologies of peripheral neuropathy were compared to a control cohort of individuals without PN, as well as those with AD or psoriasis. Results: A total of 1122 patients with PN were compared to 10,390 AD patients, 15,056 patients with psoriasis, and a control cohort of 4,949,017 individuals without PN, with respect to 25 comorbidities associated with peripheral neuropathies. Limitations: Comparisons between peripheral neuropathies and PN represent associations but are not causal relationships. Conclusion: Prurigo nodularis is strongly associated with peripheral neuropathies, suggesting a role for neural dysregulation in pathogenesis.

Background: Mycosis fungoides (MF) is a cutaneous T-cell lymphoma. Previous reports have suggested MF is associated with inflammatory conditions such as psoriasis, increased cardiovascular risk factors as well as secondary neoplasms. Methods: A cross-sectional study of MF patients seen from 2013 to 2019 was performed. Comorbidities were selected based on the 2015 Medicare report highlighting the most common chronic medical illnesses in the United States. Lifetime comorbidity occurrence in patients with MF were compared with that in patients with atopic dermatitis, psoriasis and patients without MF. Additional analyses were performed with patients sub-stratified by race. Results: Compared to control groups, MF was strongly associated with lymphomatoid papulosis and Hodgkin’s disease, but not significantly associated with lung, breast or colon cancer. Interestingly, the association with lymphomatoid papulosis was observed in Caucasians (CI 1062-4338; p < 0.001) and not African Americans (p = 0.9). Patients with MF had a greater association with congestive heart failure, hypertension (HT) and hyperlipidemia (HLD) compared with the general population. However, they were significantly less likely to have HT and HLD when compared with psoriasis patients (HT CI: 0.6–0.9; p < 0.001, and HLD CI: 0.05–0.07; p < 0.001). MF patients were also significantly less likely to have concomitant vitamin D deficiency compared with atopic dermatitis (AD) and psoriasis (p < 0.001). Conclusions: Our results suggest that the association of MF with lymphomatoid papulosis varies by race. Compared to the general population, hypertension and hyperlipidemia were positively associated with MF, however, these were significantly less likely on comparison to psoriasis. Unlike previously described, vitamin D deficiency was found to be significantly less in patients with MF.

Background: Pruritus is a well-recognized paraneoplastic phenomenon. Previous studies have examined the association of itch with a variety of malignancies in adults. However, no large study has examined this association in a pediatric population. Methods: A retrospective study was conducted of patients age 18 or less seen at Johns Hopkins Health System between 2012 and 2019. Results: A pediatric hospital population of 1,042,976 patients was reviewed. Pruritus was observed in 3836 pediatric patients of whom 130 also had cancer. Pediatric patients with pruritus were significantly more likely to have concomitant malignancy compared to pediatric patients without pruritus (OR 12.84; 95% CI 10.73–15.35, p < 0.001). Malignancies most strongly associated with pruritus included neoplasms of the blood (OR 14.38; 95% CI 11.30–18.29, p < 0.001), bone (OR 29.02, 95% CI 18.28–46.06, p < 0.001) and skin (OR 22.76, 95% CI 9.14–56.72, p < 0.001. Conclusions: Pruritus is significantly associated with malignancy in the pediatric hospital population. Clinicians should also be aware of the high burden of itch in pediatric malignancies and the variation in pruritus across malignancies.

Background: Epidermal growth factor receptor (EGFR) inhibitors can cause serious cutaneous toxicities, including pruritus and papulopustular acneiform skin eruptions. Increasingly, the neurokinin-1 receptor (NK1R) antagonist aprepitant is being utilized as an anti-pruritic agent in the treatment of EGFR-inhibitor induced pruritus. Aprepitant is believed to reduce itching by blocking NK1R on the surface of dermal mast cells. However, the effects of aprepitant on human keratinocytes remains unexplored. Methods: Herein, we examine the effects of aprepitant on EGFR stimulation in HaCaT cells using a phosphoproteomic approach including reverse phase protein arrays and Ingenuity Pathway Analysis. Changes in EGFR phosphorylation were visualized using Western blotting and the effect of EGF and aprepitant on the growth of HaCaT cells was determined using the WST-1 Cell Proliferation Assay System. Results: We found that aprepitant increased the phosphorylation of EGFR, as well as 10 of the 23 intracellular proteins phosphorylated by EGF. Analysis of phosphoproteomic data using Ingenuity Pathway Analysis software revealed that 5 of the top 10 pathways activated by EGF and aprepitant are shared. Conclusions: We propose that aprepitant produces its antipruritic effects by partially activating EGFR. Activation of EGFR by aprepitant was also seen in primary human keratinocytes. In addition to itch reduction through partial activation of shared EGFR pathways, aprepitant exerts a dose-dependent cytotoxicity to epithelial cells, which may contribute to its antitumor effects.