Childhood-onset systemic lupus erythematosus (cSLE) represents a unique phenotype characterized by higher disease activity, earlier multiorgan involvement, and poorer long-term outcomes than adult-onset SLE 1, 2. Lupus nephritis (LN) develops in up to 60%–70% of pediatric patients and remains the leading cause of morbidity and mortality. International cohort data involving 382 children with lupus nephritis demonstrated significant early disease burden and persistent difficulty in achieving sustained renal remission at 24 months 3. These findings underscore the unmet clinical need for adjunctive therapeutic strategies beyond conventional immunosuppression. Although corticosteroids, mycophenolate mofetil (MMF), cyclophosphamide, and biologics such as belimumab have improved survival 4, 5, refractory or overlap features including vasculitis, bullous eruptions, and small-vessel inflammation continue to challenge management. Dapsone, a synthetic sulfone compound (4,4′-diaminodiphenylsulfone) with both antimicrobial and anti-inflammatory activity, has been used for decades in leprosy and dermatitis herpetiformis 6. Owing to its capacity to inhibit neutrophilic inflammation, dapsone has occasionally been employed off-label in autoimmune diseases such as cutaneous lupus erythematosus (CLE) and vasculitic overlap syndromes. Case-based evidence from the International Journal of Rheumatic Diseases and other rheumatology reports suggests its potential role as adjunctive therapy in pediatric SLE, particularly where cutaneous or vasculitic manifestations accompany nephritis. Chinese and Thai populations have been reported to carry a higher risk of dapsone hypersensitivity syndrome (DHS) 7, 8. This article was conducted through a focused literature search of PubMed, Embase, and Web of Science up to January 2026. Search terms included “pediatric systemic lupus erythematosus,” “childhood-onset SLE,” “lupus nephritis,” “dapsone,” and “steroid-sparing therapy.” Case reports, cohort studies, and review articles were included. Articles lacking sufficient clinical data were excluded. This review synthesizes mechanistic rationale and available clinical evidence without performing a quantitative meta-analysis. Dapsone's principal anti-inflammatory mechanism involves inhibition of neutrophil myeloperoxidase and suppression of oxidative burst. By reducing neutrophil chemotaxis and complement activation, it limits endothelial injury and tissue damage in immune-complex–mediated disorders. The mechanism differs from that of corticosteroids or antimetabolites and may complement them in conditions dominated by neutrophilic inflammation, such as bullous lupus or small-vessel vasculitis. Experimental data indicate that dapsone decreases formation of neutrophil extracellular traps (NETs), which contribute to autoantigen exposure and interferon signaling in lupus. It also downregulates adhesion-molecule expression and IL-8-mediated neutrophil recruitment, suggesting an indirect capacity to attenuate vascular injury in lupus nephritis. Although no direct nephroprotective action has been proven, these immunomodulatory effects provide a plausible rationale for its adjunctive use in pediatric LN. However, the human leukocyte antigen HLA-B13:01 was reported as an important risk factor for dapsone hypersensitivity syndrome (DHS) in Chinese and Thai populations 7. It is important to emphasize that dapsone is not indicated for induction or maintenance therapy of active lupus nephritis. Rather, its role is limited to an adjunctive, steroid-sparing option in carefully selected pediatric patients with stable renal disease who present with prominent cutaneous or small-vessel inflammatory manifestations. There is currently no evidence supporting a direct nephroprotective effect. Clinical evidence for dapsone in cSLE remains limited to case reports and small series. In pediatric patients, dapsone is generally initiated at 0.5 mg/kg/day and cautiously titrated to approximately 1 mg/kg/day according to clinical response and tolerability, with a usual maximum dose not exceeding 100 mg per day. Baseline and serial hematologic monitoring are essential, particularly when dapsone is administered concomitantly with mycophenolate mofetil or azathioprine due to the potential risk of additive bone marrow suppression. The decision to initiate dapsone should be individualized and undertaken in consultation with pediatric rheumatology specialists. In previously published pediatric case reports from East Asia 7, 9, children with leukocytoclastic vasculitis, bullous lupus, or ulcerative lesions refractory to corticosteroids or hydroxychloroquine showed significant improvement within weeks of dapsone therapy. Skin healing allowed corticosteroid tapering without renal deterioration. In several cases, dapsone was introduced in patients with stable class III or IV lupus nephritis on MMF or azathioprine, with no worsening of proteinuria or serum creatinine. Specific cases in the literature further validate the concept. For instance, a 14-year-old girl with biopsy-proven Class V lupus nephritis and bullous systemic lupus erythematosus (BSLE) achieved rapid clinical remission of skin lesions upon adding dapsone after standard therapies failed 9. In Western pediatric case reports 10 these observations: in juvenile SLE with urticarial vasculitis or bullous overlap, dapsone achieved resolution of rash and mucosal ulceration while maintaining stable renal indices. We noticed a report, an 11-year-old SLE patient with mild proteinuria successfully utilized dapsone at 1 mg/kg/day as a steroid-sparing agent, maintaining long-term control of both cutaneous and articular symptoms 10. Improvement in cutaneous and vasculitic symptoms contributed to overall disease control and reduced cumulative steroid exposure. Prior reviews have emphasized that dapsone functions primarily as a steroid-sparing agent rather than a nephroprotective therapy 8. The safety profile of dapsone requires careful surveillance, particularly in children. The most frequent adverse event is dose-dependent hemolytic anemia due to oxidative stress on erythrocytes. Methemoglobinemia, agranulocytosis, and hypersensitivity reactions are rarer but potentially life-threatening 11. Screening for glucose-6-phosphate dehydrogenase (G6PD) deficiency is essential before initiation. Baseline complete blood count, reticulocyte count, bilirubin, and methemoglobin levels should be obtained and repeated every 2–4 weeks initially. Mild asymptomatic hemolysis can often be tolerated if hemoglobin remains stable. Dapsone hypersensitivity syndrome manifested by fever, rash, lymphadenopathy, and hepatitis usually appears within 6 weeks and warrants immediate discontinuation. Hepatotoxicity and peripheral neuropathy have also been described with chronic use 8. In pediatric SLE, concurrent administration with MMF, azathioprine, or tacrolimus necessitates vigilance to prevent additive myelosuppression. Dose titration and individualized monitoring are imperative to maintain safety. Pharmacogenetic variation in the N-acetyltransferase 2 (NAT2) gene influences dapsone metabolism. Individuals who are slow acetylators, more commonly observed in certain East Asian populations, may experience higher plasma drug levels and an increased risk of hematologic toxicity. In addition, HLA-B13:01 has been strongly associated with dapsone hypersensitivity syndrome (DHS) in several Asian populations. Pre-treatment HLA-B13:01 screening may be considered in regions with high allele prevalence, particularly in East Asia; however, it is not currently mandated by international pediatric rheumatology guidelines and remains a region-specific risk mitigation strategy rather than a universal recommendation. Most available pediatric reports of adjunctive dapsone therapy originate from East Asian countries, particularly Taiwan and South Korea. While the data consist primarily of isolated case reports rather than pooled cohort analyses, the consistency of favorable cutaneous responses without renal deterioration supports cautious consideration in selected patients. However, no aggregated pediatric lupus nephritis dataset currently exists to substantiate a regional treatment effect. The current evidence base is insufficient to define dapsone's precise role in pediatric lupus nephritis, yet accumulated clinical experience suggests potential benefit when neutrophilic inflammation dominates. Its anti-neutrophilic and steroid-sparing effects may enhance control of cutaneous and vasculitic manifestations, contributing indirectly to renal stability and improved quality of life. Future studies should aim to identify biomarkers such as neutrophil activation markers or oxidative-stress indices that predict response to dapsone. Multicenter registries and collaborative case series can provide valuable real-world data on safety and efficacy across diverse ethnic groups. Ultimately, integration of pharmacogenetic testing and standardized monitoring protocols will be essential to maximize benefit and minimize risk. Dapsone remains an uncommon but valuable adjunct in pediatric SLE, particularly when cutaneous vasculitis or bullous lupus overlaps with nephritis. Its benefit in LN is likely indirect, achieved through suppression of neutrophilic inflammation and attenuation of immune-complex–mediated vascular injury. Evidence remains largely anecdotal, yet its clinical utility as a steroid-sparing option deserves recognition. A summary of the clinical role, mechanistic basis, and safety considerations of adjunctive dapsone therapy in pediatric SLE with stable lupus nephritis is provided in Table 1. H.J.C., and S.H.W. writing original draft, review and editing. S.B.Y., X.L.L., and C.Y.W. writing, review and editing. The authors declare no conflicts of interest. Data sharing not applicable to this article as no datasets were generated or analysed during the current study.
Chen et al. (Wed,) studied this question.