Mechanisms by which clofazimine and dapsone inhibit the myeloperoxidase system

Zyl, Johann M. van; Basson, Karen; Kriegler, A.; Walt, B. J. Van Der

doi:10.1016/0006-2952(91)90323-w

Cited by 55 publications

(26 citation statements)

References 22 publications

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“…Several other mechanisms regarding dapsone's anti-inflammatory properties have been previously proposed. These include its propensity to interfere with neutrophil chemotactic migration [36,37] , integrin-mediated adherence [38] , leukocyte myeloperoxidase (MPO) and eosinophil peroxidase (EPO) activity [39][40][41] , leukotriene B 4 (LTB 4 ) stimulated inflammation and chemotactic response [42] , 5-lipoxygenase (5-LOX) metabolite production [43] , and the inhibition of lysosomal enzymes [44,45] . Perhaps the combination of dapsone's various antiinflammatory mechanisms, which mainly target the effector mechanisms of the inflammatory process, may lead to its efficacy in treating a variety of inflammatory dermatoses.…”

Section: Discussionmentioning

confidence: 99%

Efficacy of Dapsone in the Treatment of Pemphigus Vulgaris: A Single-Center Case Study

Baum¹,

Debby²,

Gilboa³

et al. 2016

Dermatology

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Background: Pemphigus vulgaris (PV) is a chronic autoimmune blistering disease. Most patients require long-term therapy with systemic steroids, and a steroid-sparing agent is usually also utilized. Dapsone is a chemotherapeutic agent with anti-inflammatory properties that is used as a steroid-sparing agent in PV. Objective: The aim of the present study was to evaluate the efficacy of dapsone as an adjuvant therapy in patients with PV. Methods: A retrospective analysis of patients' files was performed. All 26 patients included in the study group were treated with dapsone as an adjuvant to systemic steroids for at least 3 consecutive months and were followed up during their dapsone treatment period. Results: After 3 months of treatment with dapsone, 13 patients were in the consolidation phase, 4 patients demonstrated partial remission on minimal therapy, 7 patients demonstrated complete remission on minimal therapy, and 2 patients were defined as treatment failures. The trend of clinical improvement continued after 6 months of treatment and at the study end point. Conclusion: This retrospective case series, one of the largest reported, indicates that dapsone is efficacious and safe for patients with PV in whom it is well tolerated soon after the initiation of treatment.

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Section: Discussionmentioning

confidence: 99%

Efficacy of Dapsone in the Treatment of Pemphigus Vulgaris: A Single-Center Case Study

Baum¹,

Debby²,

Gilboa³

et al. 2016

Dermatology

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“…This is then converted by myeloperoxidase to hypochlorous acid, a potent cytotoxic molecule which can cause significant tissue damage. Through direct myeloperoxidase inhibition, dapsone prevents local tissue injury [21,22]. Dapsone's metabolites, dapsonehydroxylamine and monoacetyl dapsone, have also been studied in vitro and in vivo and found to have anti-inflammatory effects.…”

Section: Discussionmentioning

confidence: 99%

Dapsone Therapy for Pustular Psoriasis: Case Series and Review of the Literature

Sheu¹,

Divito²,

Enamandram³

et al. 2015

Dermatology

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Background: Pustular psoriasis is an uncommon psoriasis variant, clinically characterized as small sterile pustules on an erythematous base. Evidence for therapy is lacking, and many currently employed systemic therapeutics carry risks of significant side effects, without specifically targeting disease etiology which includes the aggregation of neutrophils. Observations: We report therapy with the anti-neutrophil agent dapsone in 5 patients with pustular psoriasis and provide a brief review of the literature. Four patients responded to oral dapsone and 1 to topical dapsone therapy. All 5 patients had previously failed multiple topical and systemic treatments. In 2 cases, oral dapsone allowed for the discontinuation of other systemic agents. One patient stopped oral dapsone due to a side effect of sleep disturbance. Conclusion: Dapsone has a much safer side effect profile and may target the pathophysiology of pustular psoriasis more directly than many other systemic agents. As such, dapsone should be considered for the treatment of patients with pustular psoriasis.

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“…Various in vitro experiments suggest, for instance, that some ␤-lactams may play a cytoprotective role (241,288) or prevent antiprotease inactivation by activated neutrophils (65). The anti-inflammatory potential of dapsone, isoniazid clofazimine, and cyclines may be due to their impact on HOCl generation (132,394), and various anti-inflammatory drugs also impair HOCl generation by the MPO-H 2 O 2 -halide system. However, the clinical relevance of these results has been questioned recently, since superoxide anion limits the potency of dapsone and various anti-inflammatory drugs (175).…”

Section: Effects With a Potential Clinical Impact (I) Modulation Of mentioning

confidence: 99%

Interference of Antibacterial Agents with Phagocyte Functions: Immunomodulation or "Immuno-Fairy Tales"?

Labro¹

2000

Clinical Microbiology Reviews

151

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Mechanisms by which clofazimine and dapsone inhibit the myeloperoxidase system

Cited by 55 publications

References 22 publications

Efficacy of Dapsone in the Treatment of Pemphigus Vulgaris: A Single-Center Case Study

Efficacy of Dapsone in the Treatment of Pemphigus Vulgaris: A Single-Center Case Study

Dapsone Therapy for Pustular Psoriasis: Case Series and Review of the Literature

Interference of Antibacterial Agents with Phagocyte Functions: Immunomodulation or "Immuno-Fairy Tales"?

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