INTRODUCTION
Nummular eczema (NE) or discoid eczema is an idiopathic chronic dermatitis characterized by pruritic, coin-shaped lesions often affecting the extremities.1 NE frequently follows a relapsing course, is intensely pruritic, and can substantially impair quality of life.2 NE is the third most common noncommunicable inflammatory skin disease, after atopic dermatitis (AD) and psoriasis, with an estimated prevalence of 0.1-9.1%.1,2 Potential triggers of NE have been identified as cutaneous microbial colonization, long-standing contact dermatitis, systemic retinoid therapy, and excessive alcohol use.1
Although previously classified as a variant of AD, NE is characterized by unique clinical and histological markers.3 Unlike AD, which is predominantly mediated by a Th2 immune response, NE displays a Th2/Th17 immunologic profile and closely aligns with psoriasis, as evidenced by its well-demarcated erythematous plaques and scaling.3,4 Histologically, NE exhibits increased eosinophils and spongiosis similar to AD, as well as epidermal hyperplasia, parakeratosis, and neutrophilic infiltration similar to psoriasis.1,5 One study demonstrated that NE shares 16% of differentially expressed genes with psoriasis, while only 4.3% with AD.1 NE’s immunologic, histologic, and genetic profiles suggest that the dermatitis may respond to existing targeted psoriasis and atopic dermatitis therapies, which have shown efficacy in real-world practice.6
The current first-line treatment for NE is topical corticosteroids.7 Corticosteroids are associated with side effects, including skin atrophy and telangiectasia.8 Achieving remission remains challenging; patients frequently relapse and suffer from severe pruritus.7 Therefore, new therapeutic strategies are warranted.
Despite NE's high prevalence and patient burden, the condition has been poorly researched, making its etiology and pathophysiology largely unknown. There is no FDA-approved treatment for NE, leaving a clear unmet need that demands urgent attention. Emerging research has demonstrated that biologics and small-molecule inhibitors, including Janus kinase (JAK) inhibitors and phosphodiesterase 4 (PDE4) inhibitors, represent promising therapeutics in the treatment of NE.6,9 Herein, we summarize the safety and efficacy of biologics and small-molecule inhibitors evaluated in studies for the treatment of NE, describe their mechanisms of action, and identify gaps to inform future trial design and clinical implementation.
Although previously classified as a variant of AD, NE is characterized by unique clinical and histological markers.3 Unlike AD, which is predominantly mediated by a Th2 immune response, NE displays a Th2/Th17 immunologic profile and closely aligns with psoriasis, as evidenced by its well-demarcated erythematous plaques and scaling.3,4 Histologically, NE exhibits increased eosinophils and spongiosis similar to AD, as well as epidermal hyperplasia, parakeratosis, and neutrophilic infiltration similar to psoriasis.1,5 One study demonstrated that NE shares 16% of differentially expressed genes with psoriasis, while only 4.3% with AD.1 NE’s immunologic, histologic, and genetic profiles suggest that the dermatitis may respond to existing targeted psoriasis and atopic dermatitis therapies, which have shown efficacy in real-world practice.6
The current first-line treatment for NE is topical corticosteroids.7 Corticosteroids are associated with side effects, including skin atrophy and telangiectasia.8 Achieving remission remains challenging; patients frequently relapse and suffer from severe pruritus.7 Therefore, new therapeutic strategies are warranted.
Despite NE's high prevalence and patient burden, the condition has been poorly researched, making its etiology and pathophysiology largely unknown. There is no FDA-approved treatment for NE, leaving a clear unmet need that demands urgent attention. Emerging research has demonstrated that biologics and small-molecule inhibitors, including Janus kinase (JAK) inhibitors and phosphodiesterase 4 (PDE4) inhibitors, represent promising therapeutics in the treatment of NE.6,9 Herein, we summarize the safety and efficacy of biologics and small-molecule inhibitors evaluated in studies for the treatment of NE, describe their mechanisms of action, and identify gaps to inform future trial design and clinical implementation.
MATERIALS AND METHODS
A systematic search of PubMed, Embase, and Cochrane Library was conducted on October 29, 2025, according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses [PRISMA] guidelines (Figure 1).
