Prevalence, incidence and treatment patterns of prurigo nodularis in England: a retrospective database analysis.

BACKGROUND: Prurigo nodularis (PN) is a pruritic skin disease characterized by multiple intensely itchy skin nodules in symmetrically distributed areas of the extremities. There are limited studies on the epidemiology and treatment pathways of PN, especially moderate-to-severe PN, from England. OBJECTIVES: To assess the epidemiology and treatment pathways of mild and moderate-to-severe PN in England. METHODS: This retrospective cohort study used data from the Clinical Practice Research Datalink and Hospital Episode Statistics in England. Adult patients (aged ≥ 18 years) with a PN-specific diagnosis code allocated any time between 1 April 2007 and 1 March 2019 (patient identification period) were selected. Patients were included if their first PN diagnostic code (index diagnosis date; IDD) was recorded during the identification period, with data available 6 months before and ≥ 12 months after the IDD. Patients were classified as having moderate-to-severe PN (MSPN) or mild PN (MiPN), based on the presence or absence of a prescription record, post-IDD, for either a systemic immunosuppressant or a gabapentinoid. Patients with MSPN and MiPN were matched 1 : 1 according to age, sex and IDD. Prevalence and incidence were calculated for each year from 2007 to 2019. Drugs prescribed post-IDD were analysed. RESULTS: A total of 8933 patients (MSPN, n = 2498; MiPN, n = 6435) were included in the study; 2462 patients with MiPN and 2462 with MSPN were included for the comparative analysis. The presence of atopic dermatitis, asthma and eosinophilic oesophagitis were significantly higher (all P < 0.001) in patients with MSPN compared with those with MiPN. The overall prevalence of cases of PN increased during the study period. The incidence rate also showed a similar trend. The rates of prescription of potent and super-potent topical corticosteroids (TCS), topical calcineurin inhibitors, first- and second-generation antihistamines, oral and injectable systemic corticosteroids, methotrexate, antidepressants and tacrolimus were significantly higher (all P < 0.001) in patients with MSPN compared with those with MiPN. CONCLUSIONS: The epidemiology of PN was consistent with that found in other European studies. Patients with MSPN received a significantly higher number of prescriptions for potent TCS and systemic drugs compared with patients with MiPN.

Prurigo nodularis is an itchy skin disease that can affect a person's daily life and sleep, and is often accompanied by other diseases. Skin ointments are used to treat the disease. If these are not effective, the disease is treated with oral medicine. The severity of prurigo nodularis is not well established. People with prurigo nodularis and treated with skin ointments are generally considered to have a milder form of the disease. Patients with severe disease most often require oral medicine that target the immune system. In England, there are no estimates of how often prurigo nodularis has affected the population over the last 10 years. In this study, we looked at cases of mild and moderate-to-severe prurigo nodularis in England and the treatments used by patients. We found that cases of prurigo nodularis (both mild and moderate-to-severe) increased during the study period, which was 2007 to 2019. Patients with the more severe form of the disease were more often treated with drugs that were not approved for treating it. Overall, our findings suggest that the number of patients with prurigo nodularis is increasing in England. A new and approved treatment option might be required to manage moderate-to-severe disease.

Increased cardiovascular risks and mortality in prurigo nodularis: a global cohort study.

BACKGROUND: Prurigo nodularis (PN) presents with intensely itchy hard nodules. Despite being limited to the skin, PN was noted to be associated with systemic diseases including diabetes and chronic renal failure. In previous smaller retrospective studies, several cardiac and vascular diseases were found more frequently in patients with PN. However, small cohort sizes, partially discrepant outcomes, missing data, and incomplete risk assessment limit these findings. METHODS: Electronic health records (EHR)s of 64,801 patients (59.44% females) with PN and an equal sized propensity-matched control group were retrieved. In these cohorts, the risks to develop cardiac and vascular diseases and mortality following the diagnosis of PN were determined. Sub-analyses included stratification for sex, ethnicity, and treatments. FINDINGS: PN was associated with a higher risk for a broad range of acute cardiac events including heart failure and myocardial infarction. For example, the hazard ratio of myocardial infarction was 1.11 (95%-CI: 1.041-1.184, p = 0.0015) following PN diagnosis. Also, all-cause mortality was higher in patients with PN. Further, chronic vascular as well as structural heart diseases, e.g., peripheral arterial disease, chronic ischaemic heart disease and valval disorders were found more frequently following a PN diagnosis. Risks were more pronounced in white and female patients. Having established an increased risk for death and cardiovascular disease, we next addressed if dupilumab that has been recently licenced for use in this indication can modulate these risks. The risk of death but not of any cardiovascular disease was slightly reduced in patients with PN treated with dupilumab as opposed to those treated with systemic therapies other than dupilumab. The study is limited by retrospective data collection and reliance on ICD10-disease classification. INTERPRETATION: PN is associated with higher mortality and an increased risk for the development of a wide range of cardiac and vascular diseases. Health care professionals should take this into account when managing patients with PN. FUNDING: This work was supported by the University of Lübeck, the Deutsche Forschungsgemeinschaft and the State of Schleswig-Holstein.

Actinic conjunctivitis and its relationship with prurigo in an indigenous population from the Highlands of Chiapas, Mexico.

PURPOSE: Actinic conjunctivitis (AC), along with cheilitis (AChe), is part of the clinical spectrum of actinic prurigo (AP), a rare photo dermatosis that affects high-risk populations. We analyzed the clinical manifestations and onset of actinic conjunctivitis (AC), and its relationship with prurigo (AP) in a susceptible population. METHODS: This prospective observational cohort study was performed on Indigenous populations from the highlands of Chiapas, Mexico. Thorough dermatological and ophthalmological examinations were performed in patients attending a primary health care center. The clinical features, labor and environmental factors, onset timing, and clinical staging of AC and AP were analyzed. RESULTS: Of the 2913 patients studied, 54 patients (108 eyes) (1.8%) had AC, and 14 patients (25.9%) had AP. The mean age at diagnosis was 36.18 ± 18.52 years (6-70 years). The mean residential altitude was 1884 ± 434.2 m above sea level. Mean self-reported sun exposure was 5.14 ± 3.1 h a day (0.5-12 h). A total of 90.7% reported exposure to biomass fuels during cooking, and 50% to farm animals. AC was the sole manifestation in 70% of the cases. All patients had nasal and temporal photo-exposed conjunctiva. Among the eyes, 12.9% were classified as stage-1, 64.8% as stage-2, and 22.2% stage-3. A total of 83.3% of the patients had hyperpigmented lesions, and 35.1% had evaporative dry eye disease. CONCLUSIONS: AC may be the initial or sole manifestation of AP. Most AC cases (87%) were initially observed at the advanced stages of the disease. Although solar exposure was not associated with late AC stages, a positive association was found with farm animal exposure. Evaporative dry eye associated with meibomian gland dysfunction has not been previously reported in patients with AC.

Comorbidities of Chronic Prurigo: A Systematic Review and Meta-Analysis.

BACKGROUND: Chronic prurigo (CPG) is an inflammatory skin disease. Comorbidities including dermatological, cardiovascular, and psychiatric diseases have been reported in patients with CPG; however, the evidence has not been systematically evaluated. We aim to summarize the comorbidities, discuss underlying pathogenesis, and highlight the evaluation of CPG patients. METHODS: We performed a systematic search using PubMed, Embase, and Web of Science databases for all articles reporting possible associated diseases with CPG. Pooled random-effects odds ratios (ORs) with 95% CI were calculated. RESULTS: A total of 17 studies were included in this systematic review. Statistically significant association (p <0.05) with CPG has been demonstrated with atopic diseases: atopic dermatitis (pooled OR, 10.91; 95% CI, 3.65-32.67), allergic rhinitis (2.66; 1.12-6.27), asthma (3.23; 1.55-6.74); infectious diseases: hepatitis B (pooled OR, 2.15; 95% CI, 1.11-4.14); endocrine diseases: diabetes (pooled OR, 4.93; 95% CI, 1.13-21.56), type 1 diabetes (2.46; 2.16-2.81), type 2 diabetes (1.89; 1.34-2.68), hyperlipoproteinemia (2.90; 1.61-5.22); cardiovascular diseases: heart failure (pooled OR, 4.13; 95% CI, 1.15-14.91), hypertension (3.17; 1.56-6.45); respiratory system diseases: chronic obstructive pulmonary disease (pooled OR, 3.19; 95% CI, 1.42-7.16); urinary system diseases: chronic kidney disease (pooled OR, 4.16; 95% CI, 1.79-9.66); digestive system disease: inflammatory bowel disease (pooled OR, 2.06; 95% CI, 1.26-3.36); and others: osteoporosis (pooled OR, 3.08; 95% CI, 1.70-5.59), thyroid disease (1.70; 1.17-2.47). CONCLUSION: CPG is associated with various systemic disorders. Recognition of comorbidities is critical to the appropriate management of affected patients.

INDIVIDUAL ARTICLE: Prurigo Nodularis: Current Clinicopathologic Overview and Psychodermatological Perspectives.

Prurigo nodularis (PN) is a quintessential neurocutaneous condition characterized by neural sensitization and intractable itch leading to intense scratching. This causes the formation of nodules with epidermal thickening and further release of pro-inflammatory mediators that recruit immune cells and increase dermal nerve proliferation and hypertrophy perpetuating the itch-scratch cycle. Those with PN have a significant quality-of-life (QoL) burden due to itch, anxiety, and sleep disturbance. In addition, PN exhibits psychiatric comorbidities that affect mental wellbeing such as depression, mood disorders, and substance abuse. This paper serves as an overview of the clinicopathologic aspects of PN, the burden of PN on QoL, and the psychodermatological aspects of the disease state.  J Drugs Dermatol. 2023;22:12(Suppl 2):s6-11.

INDIVIDUAL ARTICLE: Patient Journey and the Burden of Systemic Comorbidities and Sequalae in Prurigo Nodularis.

BACKGROUND: Prurigo Nodularis (PN) is a relatively rare chronic inflammatory skin disease characterized by firm pruritic nodules. PN is associated with significantly increased rates of many systemic and non-systemic comorbidities. This results in a higher burden of disease and utilization of specialty care compared to non-PN United States (US) adults. Psychiatric comorbidities associated with PN include depression and anxiety. In this article, we describe the burden of comorbidities. sequelae of disease, inflammatory disease signatures, and the impact of PN in African American and Asian patients. Furthermore, we explore challenges in the recognition and diagnosis of PN and describe methods to increase awareness of PN among dermatologists. J Drugs Dermatol. 2023;22:12(Suppl 2):s12-14.

A review of the current management and burden of prurigo nodularis in the United States.

Prurigo nodularis (PN) is a chronic neural- and immune-mediated disease that is characterized by intense itch, history of skin scratching, and development of papulonodular lesions. These lesions can develop consequent to a cycle of itching and scratching associated with inflammation and changes in skin cells and nerve fibers (eg, pathogenic skin fibrosis, tissue remodeling, and chronic neuronal sensitization). Diagnosis of PN involves individual evaluation of clinical characteristics to identify disease and symptom severity. In the United States, adult patients with PN (estimated, < 90,000) are more likely to be older (age, 50-60 years); in addition, this disease is detected at higher rates in women and Black individuals relative to other demographic subgroups. Still, the small population of patients with PN exhibits considerably high use of health care resources and experiences considerable symptom burden and negatively impacted quality of life. Further, PN is associated with increased rates of a range of comorbid diseases compared with other inflammatory dermatoses (eg, atopic dermatitis, psoriasis). Adequate treatment must address both the neural and immunological component of the disease; there remains a great unmet need for safe and effective therapies that can reduce the burden of disease.

Impact of Chronic Kidney Disease Severity on the Risk of Prurigo Nodularis: A Population-Based Cohort Study.

While dialysis is linked with prurigo nodularis, little is known about the impact of non-dialysis chronic kidney disease on prurigo nodularis. The influence of chronic kidney disease on development of prurigo nodularis was measured using the Korean National Health Insurance and National Health Screening Program data, identifying 17,295,576 individuals without prior prurigo nodularis. Chronic kidney disease severity was determined by the estimated glomerular filtration rate (in ml/min/1.73 m2) calculated from serum creatinine, and proteinuria detected with urine dipstick. Prurigo nodularis incidence during follow-up was determined. Over a median follow-up period of 9.72 years, 58,599 individuals developed prurigo nodularis, with an incidence rate of 3.59 per 10,000 person-years. Among different variables, estimated glomerular filtration rate was the strongest risk factor for prurigo nodularis. Compared with estimated glomerular filtration rate ≥ 90, estimat-ed glomerular filtration rate 15-29 (hazard ratio 1.31, 95% confidence interval 1.05-1.62) and end-stage renal disease (hazard ratio 1.46, 95% confidence interval 1.25-1.69) were associated with higher risks. The presence of proteinuria independently increased the risk of prurigo nodularis, increased risks associated with estimated glomerular filtration rate 15-29 and end-stage renal disease, and caused risk associated with estimated glomerular filtration rate 30-59 to become significant. With differential impact of chronic kidney disease severity on the risk of prurigo nodularis, preservation of renal function would potentially translate into lower risk of prurigo nodularis.

Chronic Nodular Prurigo: A Retrospective Study of 74 Cases. / Prurigo crónico nodular: Estudio retrospectivo de 74 casos.

BACKGROUND AND OBJECTIVE: Chronic nodular prurigo (CNPG) is a recently defined and currently underdiagnosed disease with a variety of causes. It is associated with multiple comorbidities, and its management and treatment have improved with a better understanding of its pathogenesis. The aim of this study was to describe our experience with a series of patients with CNPG. MATERIAL AND METHODS: Single-center, observational, retrospective study of the sociodemographic and clinical characteristics of patients with CNPG seen at the dermatology department of a tertiary care hospital between 2009 and 2021. RESULTS: We included 74 patients, mostly women (63.5%), with a mean age of 57 years. Overall, 39.2% of patients had a concomitant skin condition, mainly atopic dermatitis (62%). Other comorbidities included endocrine disorders (54.1%), cardiovascular disease (44.4%), and psychiatric disorders (36.5%). Skin biopsy helped confirm the clinical diagnosis in 70% of cases. The mean immunoglobulin E level was higher than normal (516 IU/mL), regardless of atopic predisposition. On average, patients received 3 treatments, the most common choices being methotrexate, antihistamines, and topical and oral corticosteroids. Methotrexate was among the most effective options. CONCLUSIONS: CNPG is a complex disease associated with multiple comorbidities. It requires a multidisciplinary approach, with the dermatologist at the center. Classical treatment approaches are probably insufficient.

Epidemiology of prurigo nodularis in England: a retrospective database analysis.

BACKGROUND: Prurigo nodularis is a debilitating skin condition that is classified as rare by the Genetic and Rare Diseases Information Center (GARD) and the National Organization for Rare Diseases (NORD). There are currently no estimates of the prevalence of prurigo nodularis in England. OBJECTIVES: We aimed to address this data gap by describing the epidemiology of prurigo nodularis in a representative dataset derived from the English National Health Service. METHODS: The study utilized data from the Clinical Practice Research Datalink linked to Hospital Episode Statistics inpatient data. Patients with a diagnosis of prurigo nodularis were selected by clinical code in the primary care or inpatient datasets. Case definition was based on a minimum of two distinct diagnoses to maximize specificity. Point prevalence was calculated for the midpoint of 2018 and incidence rates from 2008 to 2018 were presented. For those classified as incident cases, demographic and clinical characteristics were reported. In sensitivity analyses the case definition was modified to relax the multiple diagnosis criteria and to restrict cases to those diagnosed within a maximum of 4 or 10 years of the midpoint prevalence date. RESULTS: Overall, 11 656 patients within the dataset had at least one prurigo nodularis diagnosis. Following application of the relevant inclusion criteria, 2743 patients formed the point prevalent cohort; the estimated prevalence was 3·27 patients per 10 000 population [95% confidence interval (CI) 3·15-3·40]. In sensitivity analyses the estimated prevalence ranged from 2·24 (95% CI 2·14-2·34) to 6·98 (95% CI 6·80-7·16). Incidence over the study period was 2·88 per 100 000 patient-years. Comorbidity was relatively high in this population, notably for atopic dermatitis (52·2%), depression (41·1%) and anxiety (35·4%). CONCLUSIONS: This study supports the NORD/GARD classification of prurigo nodularis as a rare disease with a prevalence of 3·27 patients per 10 000 population, which equates to 18 471 patients living with the disease in England in 2018. The relatively high prevalence of comorbidity observed for these patients may increase the complexity of management.

Cognitive Impairment in Inpatients with Prurigo Nodularis and Psychiatric Comorbidities.

BACKGROUND: Prurigo nodularis (PN) is a chronic refractory itchy dermatosis. Although psychiatric comorbidity is known, research in cognitive impairment is lacking. We evaluated the occurrence and types of cognitive impairment in a series of inpatients with PN. METHODS: This was a retrospective chart review of all the patients with PN admitted to a referral neurological institute from September 2018 to March 2021. Any neurological and psychiatric disorder, along with neuroactive drugs taken, were concomitantly assessed. RESULTS: A total of 16 patients with PN (median age: 70 years, two males) were selected from a total of 1806 hospital admissions. Most of them had a neurodegenerative cognitive disorder, from mild cognitive impairment (8) to Alzheimer's disease (1), followed by mixed disorder (degenerative and vascular) in six and vascular dementia in one. Comorbid psychiatric diseases (anxiety and depression) were more common than either individual condition, followed by bipolar disorder, whereas two patients did not show psychiatric manifestations. Most patients were on combined treatment with benzodiazepines and antidepressants. CONCLUSION: Cognitive impairment can be observed in PN. In addition to screening for psychiatric comorbidity and initiating appropriate treatment or referral, clinicians may also consider the presence of cognitive impairment in PN of both degenerative and vascular origin.