Dapsone as a potential treatment option for Henoch-Schönlein Purpura (HSP)

Lee, Keum Hwa; Park, Jae Hyon; Kim, Dong Hyun; Hwang, Jimin; Lee, Go-Eun; Hyun, Jae Seok; Heo, Sung Taik; Choi, Ji Hoon; Kim, Minwoo; Kim, Minhye; Kim, Seong Il; Eisenhut, Michael; Kronbichler, Andreas; Smıth, Lee

doi:10.1016/j.mehy.2017.07.018

Cited by 19 publications

(10 citation statements)

References 35 publications

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“…This in silico study further revealed that DDS binds to the AT-rich region of the minor groove of DNA, having a relative binding energy of −6.22 kcal mol −1 [ 57 ]. The currently available evidence indicates that DDS can exert various anti-inflammatory effects by inhibiting the generation of toxic free radicals, myeloperoxidase-mediated halogenation that converts H 2 O 2 to HOCl − , leukocyte chemotaxis, the production of tumor necrosis factor, and other anti-inflammatory molecules [ 58 ].…”

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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“…The use of dapsone in IgA vasculitis appears rela tively unfamiliar to clinicians compared to that of steroids, although the first case of IgA vasculitis treated with dapsone was reported in 1983. 29) Dapsone is an antileprosy drug that can be used for dermatological diseases associated with the deposition of antibodies and accumulation of neutrophils. 30) Dapsone is an alter native, especially in relapsed IgA vasculitis, considering that IgA vasculitis is an IgA-mediated vasculitis and that the IgA-neutrophil interaction could be inhibited by dapsone.…”

Section: F)mentioning

confidence: 99%

Treatment of refractory IgA vasculitis with dapsone: a systematic review

et al. 2020

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IgA vasculitis, formerly known as Henoch-Schönlein purpura, is a systemic IgA-mediated vasculitis of the small vessels commonly seen in children. The natural history of IgA vasculitis is generally self-limiting; however, one-third of patients experience symptom recurrence and a refractory course. This systematic review examined the use of dapsone in refractory IgA vasculitis cases. A literature search of PubMed databases retrieved 13 articles published until June 14, 2018. The most common clinical feature was a palpable rash (100% of patients), followed by joint pain (69.2%). Treatment response within 1–2 days was observed in 6 of 26 patients (23.1%) versus within 3–7 days in 17 patients (65.4%). Relapse after treatment discontinuation was reported in 17 patients (65.4%) but not in 3 patients (11.5 %). Four of the 26 patients (15.4%) reported adverse effects of dapsone including arthralgia (7.7%), rash (7.7%), and dapsone hypersensitivity syndrome (3.8%). Our findings suggest that dapsone may affect refractory IgA vasculitis. Multicenter randomized placebo-controlled trials are necessary to determine the standard dosage of dapsone at initial or tapering of treatment in IgA vasculitis patients and evaluate whether dapsone has a significant benefit versus steroids or other medications.

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“…Blood puri cation is invasive and expensive, which is not applicable for the treatment of non-life-threatening HSP. In recent years, several immunosuppressants and biological products such as methotrexate, azathioprine, dapsone, colchicine, and rituximab, have also been reported with some successes [9][10][11][12][13].…”

Section: Discussionmentioning

confidence: 99%

Preliminary experience with tacrolimus in managing Henoch-Schönlein purpura featuring extrarenal symptoms refractory to conventional therapy

Chen¹,

Yang²,

Lian³

2020

Preprint

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Background Henoch-Schönlein purpura (HSP) is the commonest vasculitis of childhood, affecting multiple organ systems. The extrarenal manifestations are prominent in some HSP cases, for which no standard treatment is available. It is interesting to examine the value of tacrolimus in such cases. Findings Seventeen children received tacrolimus to manage their refractory extrarenal symptoms of HSP in an open-label prospective study. Tacrolimus was administered at daily dose of 0.05–0.15 mg/kg. Tacrolimus was effective in all cases after treatment for 7–21 days. Tacrolimus treatment resulted in complete resolution of extrarenal symptoms in 15 cases, and partial resolution in the remaining 2 cases. During follow-up, skin purpura reoccurred in 2 cases, abdominal pain and loss of follow-up in 1 case each. Drug-related adverse reaction was not observed in any case. Abnormal renal function test was identified in 7 patients by urinary screening tests before tacrolimus therapy, 4 of them received renal biopsy. Only one patient showed evidence of renal impairment during follow-up. Conclusions Tacrolimus works quickly without drug-related adverse reaction in managing the HSP patients featuring recurrent extrarenal symptoms. Our preliminary experience suggests good clinical efficacy and safety of tacrolimus in such off-label use.

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Dapsone as a potential treatment option for Henoch-Schönlein Purpura (HSP)

Cited by 19 publications

References 35 publications

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

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

Treatment of refractory IgA vasculitis with dapsone: a systematic review

Preliminary experience with tacrolimus in managing Henoch-Schönlein purpura featuring extrarenal symptoms refractory to conventional therapy

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