Low-Dose Naltrexone in the Management of Grover's Disease
- Yoon Hang "John" Kim MD
- Sep 20
- 4 min read
Introduction
Grover's disease, also known as transient acantholytic dermatosis, is an acquired pruritic skin disorder characterized by papulovesicular eruptions, usually on the trunk. While the condition is often self-limiting, chronic or recalcitrant cases present significant therapeutic challenges. This has led clinicians to explore off-label therapies, including low-dose naltrexone (LDN), which has gained attention for its immunomodulatory and antipruritic properties in dermatology.
This article reviews the potential role of LDN in Grover’s disease, with a focus on pathophysiology, mechanisms of action, available evidence, and treatment considerations.
Overview of Grover's Disease
Grover’s disease predominantly affects adults over the age of 50, with a higher prevalence in men and in individuals with lighter skin. Clinical presentation includes erythematous papules and vesicles associated with intense pruritus, often worsened by heat, sweating, or UV exposure.
Histologically, Grover’s disease demonstrates focal acantholysis, which helps differentiate it from other acantholytic dermatoses such as Hailey-Hailey disease and pemphigus.
Standard Management
First-line therapies: topical corticosteroids, emollients, and avoidance of known triggers.
Refractory cases: systemic retinoids, phototherapy, or immunomodulators may be considered.
Despite these interventions, some patients continue to experience refractory symptoms, which has prompted investigation into alternative treatments such as LDN.
Introduction to Low-Dose Naltrexone
Naltrexone, originally approved at 50–100 mg daily for opioid and alcohol dependence, is repurposed at 1–5 mg daily for immunomodulatory benefits.
At low doses, naltrexone produces transient opioid receptor blockade, leading to immune regulation without the sustained antagonism seen at higher doses. Its off-label applications extend to autoimmune and inflammatory dermatologic conditions, where pruritus and dysregulated keratinocyte activity are central features.
Mechanisms of Action in Dermatology
LDN’s potential benefits in Grover’s disease may be explained by several mechanisms:
TLR4 antagonism: reduces pro-inflammatory cytokine release.
OGFR blockade: modulates keratinocyte proliferation and differentiation, relevant in acantholytic conditions.
Endorphin release: enhances anti-inflammatory and antipruritic effects.
These pathways have demonstrated promise in other skin conditions such as systemic sclerosis, lichen planopilaris, guttate psoriasis, and Hailey-Hailey disease.
Clinical Evidence for LDN in Grover’s Disease
Evidence for LDN in Grover’s disease is limited and largely anecdotal. While case reports suggest symptomatic improvement, robust clinical trials are lacking.
Pruritus relief: LDN’s antipruritic effects may provide benefit in Grover’s disease, where itching is often the most distressing symptom.
Mechanistic parallels: Success in Hailey-Hailey disease, another acantholytic disorder, supports its theoretical application in Grover’s disease.
Expert opinion: Some dermatologists consider LDN as an adjunct for refractory disease, particularly when standard therapies fail.
Case Reports and Outcomes
One reported case described a 45-year-old woman with biopsy-confirmed Grover’s disease who had failed multiple therapies, including oral acitretin. She was started on LDN at 1.5 mg daily, titrated to 4.5 mg. While LDN alone provided only minimal benefit, dupilumab was added, leading to significant improvement and eventual sustained clearance on dupilumab monotherapy.
This case highlights:
LDN’s limited efficacy as monotherapy.
Its potential adjunctive role in complex, treatment-resistant cases.
The need for more systematic research.
Anecdotal reports from patients also describe subjective improvement in pruritus and inflammation, though these accounts lack validation in controlled studies.
Treatment Considerations
LDN is generally safe, inexpensive, and well tolerated.
Common side effects: vivid dreams, headaches, anxiety, or sleep disturbances.
Dosing: usually initiated at 1.5 mg daily and titrated to 3–4.5 mg as tolerated.
Cost: approximately $35 per month via compounding pharmacies.
Contraindications: concurrent opioid use due to receptor blockade.
In Grover’s disease, LDN may be considered:
As an adjunctive therapy for refractory cases.
When pruritus predominates and impacts quality of life.
After first-line options have been exhausted.
Conclusion
Low-dose naltrexone offers a promising, low-cost, and well-tolerated adjunctive option in the management of Grover’s disease, particularly for patients with persistent pruritus unresponsive to standard therapies. However, current evidence remains limited to case reports and anecdotal experience. Well-designed clinical studies are urgently needed to determine its true efficacy, optimal dosing, and long-term safety in this patient population.
Until such data are available, clinicians may consider LDN on a case-by-case basis, integrating it into a broader, individualized management plan.
Dr. Yoon Hang Kim is a distinguished physician, expert in Low Dose Naltrexone (LDN) therapy, and a published author dedicated to advancing integrative medicine. With a deep commitment to patient-centered care, Dr. Kim combines his extensive medical expertise with innovative approaches to help individuals achieve optimal health and wellness. His work in LDN therapy has positioned him as a trusted authority in the field, and his published writings reflect his passion for empowering patients and healthcare professionals alike. To learn more about Dr. Kim's work and insights, visit yoonhangkim.com.
References
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