EADV Task Force Pruritus White Paper on chronic pruritus and chronic prurigo: Current challenges and future solutions.

Chronic pruritus (CP) is frequent in general medicine and the most common complaint in general dermatology. The prevalence of CP is expected to rise in the future due to the ageing population. The clinical presentation, underlying aetiology and treatment strategy of CP are heterogeneous. Also, individual treatment aims and physical, psychic and economic burdens of patients might vary. Chronic prurigo (CPG) is the most severe disease in the chronic pruritus spectrum, being associated with long-standing scratch-induced skin lesions and a therapy refractory itch-scratch-cycle. It is thus important to raise disease awareness for CP and CPG in the general public and among decision-makers in the health system. Further, there is a need to support a rational clinical framework to optimize both diagnostics and therapeutics. Currently, there is still a shortcoming regarding approved therapies and understanding CP/CPG as severe medical conditions. Therefore, the EADV Task Force Pruritus decided to publish this white paper based on several consensus meetings. The group consented on the following goals: (a) ensure that CP is recognized as a serious condition, (b) increase public awareness and understanding of CP and CPG as chronic and burdensome diseases that can greatly affect a person's quality of life, (c) clarify that in most cases CP and CPG are non-communicable and not caused by a psychiatric disease, (d) improve the support and treatment given to patients with CP to help them manage their disease and (e) publicize existing therapies including current guidelines. We aim to point to necessary improvements in access and quality of care directed to decision-makers in health policy, among payers and administrations as well as in practical care.

Prurigo Nodularis: Pathogenesis and the Horizon of Potential Therapeutics.

Chronic pruritus that lasts for over 6 weeks can present in various forms, like papules, nodules, and plaque types, with prurigo nodularis (PN) being the most prevalent. The pathogenesis of PN involves the dysregulation of immune cell-neural circuits and is associated with peripheral neuropathies, possibly due to chronic scratching. PN is a persistent and challenging condition, involving complex interactions among the skin, immune system, and nervous system. Lesional skin in PN exhibits the infiltration of diverse immune cells like T cells, eosinophils, macrophages, and mast cells, leading to the release of inflammatory cytokines and itch-inducing substances. Activated sensory nerve fibers aggravate pruritus by releasing neurotransmitters, perpetuating a vicious cycle of itching and scratching. Traditional treatments often fail, but recent advancements in understanding the inflammatory and itch transmission mechanisms of PN have paved the way for innovative therapeutic approaches, which are explored in this review.

The blood proteomic signature of prurigo nodularis reveals distinct inflammatory and neuropathic endotypes: A cluster analysis.

BACKGROUND: Prurigo nodularis (PN) is an extremely pruritic, chronic inflammatory skin disease. Little is known about systemic inflammation in PN. OBJECTIVE: To characterize plasma inflammatory biomarkers in patients with PN and investigate the presence of disease endotypes. METHODS: In this cross-sectional study, Olink proteomic analysis was performed on plasma samples from patients with PN (n = 29) and healthy controls (n = 18). RESULTS: Patients with PN had increased levels of 8 circulating biomarkers compared to controls, including tumor necrosis factor, C-X-C Motif Chemokine Ligand 9, interleukin-12B, and tumor necrosis factor receptor superfamily member 9 (P < .05). Two PN clusters were identified in cluster 1 (n = 13) and cluster 2 (n = 16). Cluster 2 had higher levels of 25 inflammatory markers than cluster 1. Cluster 1 had a greater percentage of patients with a history of myelopathy and spinal disc disease compared with cluster 2 (69% vs 25%, P = .03). Patients in cluster 2 were more likely to have a history of atopy (38% in cluster 2 vs 8% in cluster 1, P = .09). LIMITATIONS: Small sample size precludes robust subgroup analyses. CONCLUSION: This study provides evidence of neuroimmune-biased endotypes in PN and can aid clinicians in managing patients with PN that are nonresponsive to traditional therapies.

Healthcare Utilization and Treatment Patterns in Patients with Chronic Prurigo and Chronic Pruritus in Germany.

BACKGROUND: To date, there have been no large studies describing real-world treatment of chronic prurigo (CPG) and pruritus (CPR) in Germany. OBJECTIVE: To determine the healthcare utilization, treatment patterns, and costs associated with CPG and CPR in Germany. METHODS: Retrospective analysis using anonymized claims data (German DAK-Gesundheit), based on a 40% sample of all insured adults of the DAK-Gesundheit on December 31, 2010 (N = 2,006,003). RESULTS: Patients with CPR (prevalence 2.2%) most commonly visited general medicine/general practitioners (GPs, 80.1%), followed by gynecologists (66.1%) and dermatologists (51.1%). Patients with CPG (prevalence 0.2%) most commonly visited dermatologists (85.7%), GPs (78.1%), and ophthalmologists (47.2%). Of adult patients, 44% received at least one drug prescription. Two thirds of patients with a drug prescription received ≥1 topical drug (66.2%), and 54.3% ≥1 systemic drug (total costs of approximately EUR 550,000 and 2,500,000, respectively). Of patients with CPG, 33.8% received ≥1 systemic and 45.1% ≥1 topical drug prescription (costs of approximately EUR 360,000 vs. 105,000). Of patients with CPR, 23.5% received ≥1 systemic and 28.6% ≥1 topical drug prescription (costs of approximately EUR 2,000,000 vs. 500,000). Of patients with CPG, 5.8% received ≥1 phototherapy application vs. 1.2% of patients with CPR. CONCLUSIONS: These findings reflect the reality of care and can form a basis for the identification of overuse, underuse, and misuse in order to design CPG and CPR healthcare more effectively and efficiently.

Chronic Nodular Prurigo: An Update on the Pathogenesis and Treatment.

Chronic nodular prurigo (CNPG) is a recalcitrant chronic itchy disorder that affects the quality of life. It can be triggered by multiple etiologies, such as atopic dermatitis, diabetes, and chronic renal diseases. The mechanisms of CNPG are complicated and involved the interaction of the cutaneous, immune, and nervous systems. Diverse immune cells, including eosinophils, neutrophils, T cells, macrophages, and mast cells infiltrated the lesional skin of CNPG, which initiated the inflammatory cytokines and pruritogens release. In addition, the interaction between the immune cells and activated peripheral sensory nerve fibers by neurotransmitters caused neuroinflammation in the skin and intractable itch. This itch-scratch vicious cycle of CNPG results in disease exacerbation. CNPG is difficult to treat with traditional therapies. Recently, great advances have been made in the pathophysiology of both inflammation and pruritus transmission in CNPG. In this review, we summarize the updated mechanisms and novel therapies for CNPG.

Prurigo nodularis comparative treatment outcome in patients attending a tertiary hospital in northern Tanzania.

Prurigo nodularis (PN) is a chronic, benign neurodermatitis of unclear etiology characterized by excoriated, intensely pruritic nodules secondary to an intense itch-scratch cycle. PN treatment is still a challenge, and it is frustrating for both dermatologists and patients. The evidence for the effectiveness of a readily available treatment like cryotherapy is limited. To compare the efficacy of cryotherapy vs 0.05% clobetasol propionate in PN patients attending the RDTC, Northern Tanzania, from October 2018 to July 2019. Based on previous year data, it was expected to enroll nine patients. Assent and consent were obtained. Fourteen patients were enrolled, 11 analyzed; intra-subject control done each one-half of the body received either intervention randomly. The cryotherapy was given in two cycles from 5 to 10 s in one session and clobetasol propionate was applied twice daily for 4 weeks. The patients were followed-up weekly by telephone reminded them to apply clobetasol. Data entry and analysis was done in SPSS version 20. Ethical considerations were observed. Eleven patients were analyzed; four (36%) males and seven (64%) females. Cryotherapy had nodule clearance in the 11 patients of 75% to 100% in 11 (100%) and clobetasol propionate only in three of the patients. Seven patients (63.6%) preferred cryotherapy. Cryotherapy preferred above clobetasol propionate.

Prurigo Pigmentosa: Demographics and Characteristics in 14 Caucasian Patients.

BACKGROUND: Prurigo pigmentosa (PP) is an inflammatory dermatosis typically reported in young Asian women and characterized by recurrent papulovesicular lesions resolving with a postinflammatory reticulated hyperpigmentation. METHODS: We have included all consecutive patients with PP diagnosed in our tertiary center between 2013 and 2020. The clinical information was retrospectively collected from medical records. RESULTS: We identified 14 patients with PP. The median age at the time of diagnosis was 29.5 years (range 17-43 years), while the female-to-male ratio was 13:1. Diagnostic delay varied from 10 days to 10 years (mean of 25 months). Light microscopy studies consistently showed presence of a lymphohistiocytic infiltrate in combination in 40% of cases with neutrophils. Interface changes were found in 60% of cases. In 6 (43%) of 14 cases, there was a chronological relationship between the starting of a new diet and the development of the first flares. Treatment with doxycycline in 9 patients resulted in a complete regression of the lesions. LIMITATION: This was a retrospective study in a tertiary referral hospital. CONCLUSIONS: Our observations indicate that PP is not so rare in Europe as previously thought and is often diagnosed after a long delay. Demographics, clinical characteristics and triggering factors in Caucasian patients are similar to those described in the Asian population. Diagnosis is based on the peculiar recurrent course and distinctive clinicopathological features. Tetracyclines represent the first-line therapy in PP.

Investigator's Global Assessment of Chronic Prurigo: A New Instrument for Use in Clinical Trials.

Chronic prurigo is a pruritic disease characterized by the development of pruriginous lesions due to scratching. The number of lesions is representative of the stage of the disease, while the presence of excoriations reflects the scratching activity. Aim of this study was to validate a new developed tool for the objective assessment of chronic prurigo. Investigator's Global Assessment scales for stage and activity were completed for 187 patients with chronic prurigo, who also reported patient-reported outcomes for itch intensity and quality of life. To assess the reliability and objectivity of the Investigator's Global Assessment, 5 independent raters completed the Investigator's Global Assessment scales for 8 patients twice. The scores increased with increased intensity of pruritus. The Investigator's Global Assessment stage scales correlated strongly with each other (Kendall's-tau-b 0.62) and moderately with the Investigator's Global Assessment activity scale (Kendall's-tau-b 0.47). Intra-rater test-retest reliability was excellent for all items, while the congruence among raters was very good for Investigator's Global Assessment - chronic prurigo activity (Kendall's W 0.84) and good for Investigator's Global Assessment stage scales (Kendall's W 0.747). Investigator's Global Assessment - chronic prurigo stage and activity are thus the best Investigator's Global Assessment instruments for use in assessing chronic prurigo.

Prurigo nodularis: Pathogenesis and management.

Prurigo nodularis is a chronic skin condition characterized by severely pruritic nodules that cause a profound negative impact on quality of life. The second article in this 2-part continuing medical education series focuses on reviewing the pathogenesis of prurigo nodularis and exploring management algorithms for this condition. In addition, we discuss some emerging and novel therapies for treating prurigo nodularis. The first article in this 2-part series describes the broader epidemiology, patient demographics, physical examination findings, and symptoms to aid in the timely recognition and diagnosis of prurigo nodularis.

Treatment and Burden of Disease in a Cohort of Patients with Prurigo Nodularis: A Survey-based Study.

Prurigo nodularis is a pruritic dermatosis with poor treatment options. To describe treatment patterns, comorbidities, pruritus, and quality of life a survey was administered to 92 patients with prurigo nodularis. A total of 52 patients completed the survey. The most frequently used treatments were topical corticosteroids, which were prescribed to 49/52 patients, with positive effect in 13/49. A total of 46/52 patients were treated with ultraviolet B, and 9/46 reported a positive effect. A positive effect was reported for topical corticosteroids under occlusion in 21/40, for zinc dressing treatment in 17/37, for steroid injection in 9/14, for methotrexate in 5/16, and for thalidomide in 4/12 of treated patients. Thirty-six patients reported a Pittsburgh Sleep Quality Index >5, indicating poor sleep. Patients with prurigo nodularis are severely bothered by pruritus negatively affecting quality of life. Various treatments are prescribed; most frequently topical corticosteroids and ultraviolet B. Surprisingly, patients reported topical corticosteroids under occlusion, zinc-dressing treatment and steroid injection as the most effective.

How to define chronic prurigo?

Chronic prurigo impairs quality of life and is immensely challenging to treat. Until recently, no clear definition or classification system was available for this disease. A European task force specialized in pruritus defined chronic prurigo as a distinct disease characterized by chronic pruritus, a lengthy scratching behaviour and the presence of pruriginous lesions. Papular, nodular, plaque, umbilicated and linear prurigo were identified as clinical subtypes according to the most prominent lesion type observed in the physical examination. Various clinical and pathophysiological aspects, which are common across the range of clinical manifestations of chronic prurigo, argue for chronic prurigo as a disease in its own right. Chronic prurigo should be clearly demarcated from other conditions such as so-called acute or subacute prurigo forms as well as from psychogenic self-inflicted skin lesions, since different diagnostic criteria apply for these diseases. This viewpoint essay provides a detailed definition and classification of chronic prurigo including its obligatory and associated diagnostic criteria and discusses chronic prurigo as a distinct disease as well as the demarcation to other relevant conditions.

A systematic review of evidence-based treatments for prurigo nodularis.

Prurigo nodularis is a chronic dermatologic condition involving the development of multiple cutaneous nodules in the setting of intractable pruritus. Given emerging treatment options for this difficult-to-treat condition, a current review of therapeutics is needed. A systematic review was performed for clinical studies investigating prurigo nodularis treatment published from 1990 to present including ≥5 subjects. A total of 35 articles were assigned a level of evidence according to the Oxford Center for Evidence-based Medicine. All 5 studies investigating topical agents, including corticosteroids, calcineurin inhibitors, calcipotriol, and capsaicin, conveyed some beneficial effect with level of evidence 2b or higher. Six of 8 reports investigating photo- and photochemotherapy achieved levels of evidence 2b or greater and showed good partial response rates. Thalidomide was studied by 6 reports providing evidence of good symptom response, only 2 of which were rated level 2b or greater. Cyclosporine and methotrexate have demonstrated benefit in 4 combined studies, albeit with level 4 evidence. Pregabalin, amitriptyline, paroxetine, fluvoxamine, and neurokinin-1 receptor antagonists have demonstrated promising evidence in 5 level 2b studies. Higher-powered studies and additional randomized controlled trials are needed for the evaluation of safe and efficacious systemic treatment options for prurigo nodularis.

Ethnic differences and comorbidities of 909 prurigo nodularis patients.

BACKGROUND: Prurigo nodularis (PN) is a poorly understood, understudied pruritic dermatosis that reduces quality of life. OBJECTIVE: To characterize the demographics and comorbidities associated with PN. METHODS: Cross-sectional study of patients 18 years and older who were seen at the Johns Hopkins Health System between December 6, 2012, and December 6, 2017. RESULTS: Over the past 5 years, 909 patients with PN were seen at Johns Hopkins Health System. African American patients were 3.4 times more likely to have PN than white patients were (odds ratio [OR], 3.4; 95% confidence interval [CI], 2.9-3.9; P < .001). A comparison of the study patients and race-matched controls revealed that PN was significantly associated with a variety of systemic, cardiovascular, and psychiatric comorbidities, including chronic kidney disease, chronic hepatitis C, chronic obstructive pulmonary disease, congestive heart failure, depression, and atopic dermatitis. Black patients with PN were 10.5 times more likely (OR, 10.5; 95% CI, 7.9-13.9; P < .001) to have HIV than were race-matched controls with atopic dermatitis, and 8 times more likely (OR, 8.0; 95% CI, 5.7-11.1; P < .001) to have HIV than were African American patients with psoriasis. LIMITATIONS: Our data describe patients seen by 1 hospital system. Our data identify associated conditions and comorbidities but are unable to support a causal relationship. CONCLUSION: PN disproportionately affects African Americans and is associated with several systemic conditions, including HIV, chronic kidney disease, and diabetes.

Chronic Prurigo of Nodular Type: A Review.

Prurigo nodularis (PN) is a subtype of chronic prurigo presenting single to multiple symmetrically distributed, hyperkeratotic and intensively itching papules and nodules. PN evolves along with chronic pruritus in the context of diverse dermatological, systemic, neurological or psychiatric conditions. Permanent scratching is possibly a major trigger of PN, although its exact pathophysiology remains unclear. Current state-of-the-art therapy for PN consists of topical steroids, capsaicin, calcineurin inhibitors, ultraviolet (UV) therapy, systemic administration of gabapentinoids, µ-opioid receptor antagonists, antidepressants or immunosuppressants. Novel treatment concepts, such as inhibitors of neurokinin-1, opioid and interleukin-31 receptors, have been developed and are currently being clinically tested.

[Chronic prurigo]. / Chronische Prurigo.

Chronic prurigo is a disease characterized by the presence of chronic pruritus and singular or multiple usually hyperkeratotic symmetrically distributed itchy papules, nodules, and/or plaques. This condition is difficult to treat and leads to a substantial impairment of the quality of life. It may originate from dermatological, systemic, neurological, psychiatric/psychosomatic, multifactorial or unknown conditions causing itch, which lead to prolonged scratching behavior and sensitization mechanisms and ultimately to the development of pruriginous lesions. Thorough diagnostic efforts, including a detailed clinical history and physical examination, as well as targeted complementary examinations should be initiated as soon as possible. The German guideline recommends topical steroids and phototherapy as first-choice options. Pimecrolimus and capsaicin (topical), as well as antihistamines, anticonvulsants, and immunosuppressive drugs (systemic) should be considered as valid alternatives.

[Dyspnea, itching and depression in palliative medicine]. / Luftnot, Jucken und Depression in der Palliativmedizin.

Palliative medicine focuses on relieving burdening symptoms to improve quality of life. The most common symptoms are physical weakness, pain, loss of appetite, nausea as well as dyspnea, itching and depression. Frequently, good symptom control can be achieved using the most effective drug combination therapy or non-medicinal interventions. This article specifically addresses the physical symptoms dyspnea, itching and the psychological symptom depression.