Chronic nodular prurigo – What it is and how to treat it


Chronic nodular prurigo, also known as prurigo nodularis, is a dermatological condition characterized by the presence of intensely itchy nodules or papules on the skin. It is considered a chronic pruritic disorder and is often associated with significant discomfort and impaired quality of life for affected individuals.

In this research, we will delve into the details of chronic nodular prurigo, including its clinical presentation, etiology, pathogenesis, diagnosis, and treatment options.

  • Clinical Presentation: Chronic nodular prurigo typically presents as multiple, firm, hyperkeratotic nodules or papules on the skin. The lesions are often intensely itchy and may be symmetrically distributed on extensor surfaces of the limbs, such as the elbows and knees. Scratching or picking at the nodules can lead to excoriation, ulceration, and secondary infection. The condition can persist for months to years, causing significant distress and frustration for affected individuals.
  • Etiology and Risk Factors: The exact cause of chronic nodular prurigo remains unknown, but it is believed to result from a combination of genetic, immunological, and neurogenic factors. It is considered a multifactorial disorder, and various triggers or predisposing factors may contribute to its development. These include atopic diathesis, chronic pruritus, neurogenic inflammation, and psychosocial factors such as stress and anxiety. In some cases, chronic nodular prurigo can be associated with underlying conditions like atopic dermatitis, psoriasis, or chronic renal or liver diseases.
  • Pathogenesis: The pathogenesis of chronic nodular prurigo involves a complex interplay of immune dysregulation, neurogenic inflammation, and skin barrier dysfunction. Persistent scratching or rubbing of the skin leads to a cycle of itch-scratch-itch, perpetuating the development and persistence of nodules. Histopathological examination of the lesions reveals epidermal hyperplasia, dermal fibrosis, and inflammatory infiltrates consisting of T cells, eosinophils, and mast cells.
  • Diagnosis: Diagnosing chronic nodular prurigo is primarily based on the characteristic clinical presentation and exclusion of other underlying skin disorders. A thorough medical history and physical examination are essential for diagnosis. Additional tests, such as skin biopsies, may be performed to rule out other possible causes of nodular skin lesions. The diagnosis may be challenging, and it often requires the expertise of a dermatologist.
  • Treatment Options: The management of chronic nodular prurigo focuses on alleviating pruritus, reducing inflammation, and preventing further damage to the skin. Treatment approaches may include a combination of topical therapies, systemic medications, and behavioral interventions. Topical treatments may involve potent corticosteroids, calcineurin inhibitors, or local anesthetics to relieve itching and reduce inflammation. Systemic therapies, such as oral antihistamines, oral corticosteroids, or immunosuppressive agents, may be prescribed for more severe or refractory cases. Behavioral interventions, including counseling, cognitive-behavioral therapy, or habit-reversal techniques, can help break the itch-scratch cycle and improve symptoms.
  • Emerging Therapies: Research into novel treatment options for chronic nodular prurigo is ongoing. Several emerging therapies show promise in managing the condition, including targeted biologic agents, such as dupilumab, which has demonstrated efficacy in prurigo nodularis associated with atopic dermatitis. Other potential therapeutic options being explored include neurokinin-1 receptor antagonists, opioid receptor antagonists, and therapies targeting specific pathways involved in pruritus and inflammation.
  • Patient Education and Support: Living with chronic nodular prurigo can be challenging, both physically and emotionally. Providing patients with education about the condition, its triggers, and management strategies is crucial. Patients should be advised to avoid scratching or picking at the nodules to prevent exacerbation of symptoms and potential complications. They should also be educated about proper skin care techniques, including gentle cleansing and moisturization, to maintain the skin barrier function.Support groups and patient communities can play a valuable role in providing emotional support and sharing experiences with others facing similar challenges. Connecting patients with these resources can help reduce feelings of isolation and provide a platform for sharing coping strategies and success stories.
  • Prognosis: The prognosis of chronic nodular prurigo can vary among individuals. Some patients may experience periods of remission, while others may have persistent symptoms despite treatment. The condition is chronic and tends to have a relapsing and remitting course. The long-term outlook often depends on the severity of symptoms, response to treatment, and the presence of any underlying conditions or triggers.
  • Importance of Multidisciplinary Approach: Given the complex nature of chronic nodular prurigo, a multidisciplinary approach involving dermatologists, allergists, psychiatrists, and other healthcare professionals may be necessary for optimal management. Collaboration between specialists allows for comprehensive assessment, individualized treatment plans, and addressing both the physical and psychological aspects of the condition.
  • Genetic Factors: There is evidence to suggest a genetic predisposition to chronic nodular prurigo. Studies have shown an increased prevalence of the condition among individuals with a family history of atopic dermatitis, allergic rhinitis, or asthma. Specific genetic variations related to immune dysfunction and skin barrier function have also been implicated in the pathogenesis.
  • Immunological Factors: Immunological abnormalities play a significant role in chronic nodular prurigo. The condition is associated with chronic inflammation, characterized by an increased presence of immune cells, such as T cells, mast cells, and eosinophils, in the skin lesions. These immune cells release various inflammatory mediators and cytokines, contributing to pruritus and perpetuating the inflammatory response.
  • Neurogenic Factors: Neurogenic factors, including altered sensory perception and neuronal hypersensitivity, are believed to contribute to the intense pruritus experienced in chronic nodular prurigo. Abnormalities in the peripheral and central nervous systems may amplify itch signals and decrease the threshold for itch perception. Neurotransmitters and neuropeptides, such as substance P and calcitonin gene-related peptide, have been implicated in mediating itch sensation.
  • Itch-Scratch Cycle: The itch-scratch cycle is a fundamental component of chronic nodular prurigo. Persistent pruritus leads to scratching and picking at the skin, resulting in the formation of nodules and excoriations. Scratching further exacerbates the inflammatory response and triggers the release of more pruritogenic mediators, perpetuating the cycle of itch and skin damage.
  • Skin Barrier Dysfunction: Impairment of the skin barrier function is thought to contribute to the development of chronic nodular prurigo. Disruption of the skin barrier allows allergens, irritants, and microbial agents to penetrate the skin, triggering an immune response and inflammatory cascade. Additionally, the compromised skin barrier may lead to increased transepidermal water loss, dryness, and further pruritus.
  • Psychological Factors: Psychological factors, including stress, anxiety, and depression, can significantly influence the course and severity of chronic nodular prurigo. Itch and scratching can cause emotional distress and impact quality of life. Psychological stressors can also exacerbate the itch-scratch cycle and contribute to the chronicity of the condition.

It is important to note that these factors are interconnected, and the pathogenesis of chronic nodular prurigo likely involves a complex interplay between genetic, immunological, neurogenic, and psychosocial factors. Further research is needed to gain a comprehensive understanding of the underlying mechanisms and to identify potential targets for more effective treatments.

Emerging treatments for chronic nodular prurigo are focused on targeting interleukin-31 (IL-31), a cytokine that has been implicated in the pathogenesis of pruritus in various skin conditions, including chronic nodular prurigo. IL-31 is predominantly produced by activated T helper 2 (Th2) cells and mast cells and plays a role in mediating itch sensation and promoting inflammation in the skin.

  • IL-31 Antibodies: Monoclonal antibodies targeting IL-31 or its receptor have shown promise in clinical trials for the treatment of pruritic skin conditions. Nemolizumab, a monoclonal antibody against the IL-31 receptor alpha subunit, has demonstrated efficacy in reducing pruritus and improving skin lesions in patients with atopic dermatitis. Clinical trials evaluating the use of nemolizumab in chronic nodular prurigo are ongoing, and early results are encouraging.
  • JAK Inhibitors: Janus kinase (JAK) inhibitors are a class of drugs that block signaling pathways involved in inflammation and immune responses. They have shown efficacy in various inflammatory skin conditions, and their potential in treating pruritus associated with chronic nodular prurigo is being investigated. JAK inhibitors, such as tofacitinib and baricitinib, have shown promising results in reducing itch and improving skin lesions in prurigo nodularis and atopic dermatitis.
  • Dupilumab: Dupilumab is a monoclonal antibody targeting the IL-4 receptor alpha subunit, which is involved in signaling pathways associated with Th2 inflammation. While not directly targeting IL-31, dupilumab has demonstrated efficacy in reducing pruritus and improving skin lesions in atopic dermatitis, a condition that shares similarities with chronic nodular prurigo. Studies exploring the use of dupilumab in chronic nodular prurigo are underway to evaluate its potential benefits.
  • Neurokinin-1 Receptor Antagonists: Neurokinin-1 (NK-1) receptor antagonists block the binding of substance P, a neuropeptide involved in mediating itch, to its receptor. Preliminary studies have shown that NK-1 receptor antagonists, such as serlopitant and tradipitant, can reduce pruritus in prurigo nodularis and other pruritic skin conditions. These agents hold potential for targeting pruritus associated with chronic nodular prurigo.

It is important to note that these emerging treatments are still undergoing clinical trials and further research is needed to establish their safety and efficacy specifically in the context of chronic nodular prurigo. Additionally, combination therapies targeting multiple pathways involved in the pathogenesis of chronic nodular prurigo may hold promise for enhanced therapeutic outcomes. As research progresses, these targeted therapies have the potential to provide novel and effective treatment options for individuals suffering from chronic nodular prurigo.

Conclusion: Chronic nodular prurigo is a distressing and chronic pruritic disorder characterized by the presence of itchy nodules or papules on the skin. While the exact cause and pathogenesis remain unclear, a combination of genetic, immunological, and neurogenic factors likely contribute to its development. Diagnosis requires careful evaluation and exclusion of other skin conditions. Treatment options focus on relieving pruritus, reducing inflammation, and breaking the itch-scratch cycle. Ongoing research and emerging therapies offer hope for improved management in the future. Comprehensive patient education, support, and a multidisciplinary approach are vital for addressing the physical and emotional aspects of living with chronic nodular prurigo.

reference link :

Dermatol Ther (Heidelb). 2022 Sep; 12(9): 2039–2048.

Published online 2022 Aug 20. doi: 10.1007/s13555-022-00782-2

PMCID: PMC9464280

PMID: 35986886

Prurigo Nodularis: A Review of IL-31RA Blockade and Other Potential Treatments


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