Update on the use of dapsone in dermatology

Ghaoui, Nohra; Hanna, Edith; Abbas, Ossama; Kibbi, Abdul‐Ghani; Kurban, Mazen

doi:10.1111/ijd.14761

Cited by 67 publications

(52 citation statements)

References 83 publications

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“…Data are lacking to determine which of these features were due to critical illness-related encephalopathy, cytokines, the effect or withdrawal of medication, and which features were specific to SARS-CoV-2 infection [ 35 , 36 ]. To date, clinical studies have shown that DDS can block disease progression due to critical illness (inflammation)-related encephalopathy or immune-related diseases [ 36 , 37 , 62 , 63 ].…”

Section: Resultsmentioning

confidence: 99%

4,4′-Diaminodiphenyl Sulfone (DDS) as an Inflammasome Competitor

Lee

Sohn

et al. 2020

IJMS

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The aim of this study is to examine the use of an inflammasome competitor as a preventative agent. Coronaviruses have zoonotic potential due to the adaptability of their S protein to bind receptors of other species, most notably demonstrated by SARS-CoV. The binding of SARS-CoV-2 to TLR (Toll-like receptor) causes the release of pro-IL-1β, which is cleaved by caspase-1, followed by the formation and activation of the inflammasome, which is a mediator of lung inflammation, fever, and fibrosis. The NLRP3 (NACHT, LRR and PYD domains-containing protein 3) inflammasome is implicated in a variety of human diseases including Alzheimer’s disease (AD), prion diseases, type 2 diabetes, and numerous infectious diseases. By examining the use of 4,4′-diaminodiphenyl sulfone (DDS) in the treatment of patients with Hansen’s disease, also diagnosed as Alzheimer’s disease, this study demonstrates the diverse mechanisms involved in the activation of inflammasomes. TLRs, due to genetic polymorphisms, can alter the immune response to a wide variety of microbial ligands, including viruses. In particular, TLR2Arg677Trp was reported to be exclusively present in Korean patients with lepromatous leprosy (LL). Previously, mutation of the intracellular domain of TLR2 has demonstrated its role in determining the susceptibility to LL, though LL was successfully treated using a combination of DDS with rifampicin and clofazimine. Of the three tested antibiotics, DDS was effective in the molecular regulation of NLRP3 inflammasome activators that are important in mild cognitive impairment (MCI), Parkinson’s disease (PD), and AD. The specific targeting of NLRP3 itself or up-/downstream factors of the NLRP3 inflammasome by DDS may be responsible for its observed preventive effects, functioning as a competitor.

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Section: Resultsmentioning

confidence: 99%

4,4′-Diaminodiphenyl Sulfone (DDS) as an Inflammasome Competitor

Lee

Sohn

et al. 2020

IJMS

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“…Further data on dapsone, relevant to GB and accruing since 2014, is reviewed here. As a sulfone antibiotic, dapsone is used in general medicine to treat various infections-Hansen's disease, Plasmodia, Pneumocystis, Toxoplasmodia, and others [7]. In dermatological practice, dapsone is used to treat a variety of neutrophilic dermatoses of non-microbial origin like bullous pemphigoid, dermatitis herpetiformis, urticarial dermatoses, cutaneous lupus, and others [7][8][9][10].…”

Section: Dapsonementioning

confidence: 99%

Research Supporting a Pilot Study of Metronomic Dapsone during Glioblastoma Chemoirradiation

Kast¹

2021

Medical Sciences

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This short note presents previous research data supporting a pilot study of metronomic dapsone during the entire course of glioblastoma treatment. The reviewed data indicate that neutrophils are an integral part of human glioblastoma pathophysiology, contributing to or facilitating glioblastoma growth and treatment resistance. Neutrophils collect within glioblastoma by chemotaxis along several chemokine/cytokine gradients, prominently among which is interleukin-8. Old data from dermatology research has shown that the old and inexpensive generic drug dapsone inhibits neutrophils’ chemotaxis along interleukin-8 gradients. It is on that basis that dapsone is used to treat neutrophilic dermatoses, for example, dermatitis herpetiformis, bullous pemphigoid, erlotinib-related rash, and others. The hypothesis of this paper is that dapsone will reduce glioblastomas’ neutrophil accumulations by the same mechanisms by which it reduces dermal neutrophil accumulations in the neutrophilic dermatoses. Dapsone would thereby reduce neutrophils’ contributions to glioblastoma growth. Dapsone is not an ideal drug, however. It generates methemoglobinemia that occasionally is symptomatic. This generation is reduced by concomitant use of the antacid drug cimetidine. Given the uniform lethality of glioblastoma as of 2020, the risks of dapsone 100 mg twice daily and cimetidine 400 mg twice daily is low enough to warrant a judicious pilot study.

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“…Dapsone is a drug from the sulfone group, which has an antimicrobial and anti‐inflammatory effects 65 . Its side effects do not include risk of infections.…”

Section: Infection Risk In Immunomodulators and Immunosuppressants Usmentioning

confidence: 99%

Immunosuppressive and immunomodulator therapy for rare or uncommon skin disorders in pandemic days

Karadağ

Kayıran

Lotti

et al. 2020

Dermatologic Therapy

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Immunosuppressive and immunomodulatory therapies are important in dermatology, but indications are influenced by SARS-CoV-2. We will focus on skin disorders such as autoimmune connective tissue disorders, neutrophilic dermatoses, and vasculitis. Immunomodulators such as colchicine and antimalarials can easily be preferred taking their beneficial effects on COVID-19 into consideration and also given their wide spectrum of action. Among the conventional therapies, methotrexate, azathioprine, and mycophenolate mofetil increase the risk of infection, and thus their use is recommended only when necessary and at low doses. On the other hand, use of cyclosporine is also not recommended as it increases the risk of hypertension, which is susceptible to COVID-19. Anti-TNF agents from among the biological therapies appear to be slightly risky in terms of susceptibility to infection. However, there are ongoing studies which suggest that some biological treatments may reduce cytokine storm impeding the COVID-19 progression as a result, in spite of their susceptibilities to COVID-19. Patients, who will be started on immunosuppressive therapy, should be tested for COVID-19 prior to the therapy, and in the event that COVID-19 is suspected, the therapy should be discontinued.

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Update on the use of dapsone in dermatology

Cited by 67 publications

References 83 publications

4,4′-Diaminodiphenyl Sulfone (DDS) as an Inflammasome Competitor

4,4′-Diaminodiphenyl Sulfone (DDS) as an Inflammasome Competitor

Research Supporting a Pilot Study of Metronomic Dapsone during Glioblastoma Chemoirradiation

Immunosuppressive and immunomodulator therapy for rare or uncommon skin disorders in pandemic days

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