Rhein, An Anthraquinone Drug, Suppresses the NLRP3 Inflammasome and Macrophage Activation in Urate Crystal-Induced Gouty Inflammation.

Rhein, an anthraquinone drug, is a widely used traditional Chinese medicine. Rhein is a major bioactive metabolite of diacerein which has been approved for treating osteoarthritis with a good safety profile in humans. Gouty arthritis is an inflammatory disease characterized by urate crystal-induced NLRP3 inflammasome activation with up-regulated caspase-1 protease and IL-1 ß in macrophages. Inhibition of the NLRP3 inflammasome formation has been considered as a potential therapeutic avenue for treating or preventing many inflammatory diseases. This study aimed to evaluate the anti-inflammatory effects of rhein on gouty arthritis. Rhein within the physiological levels of humans showed no toxicity on the cell viability and differentiation, but significantly decreased the production of IL-1 ß , TNF- α and caspase-1 protease in urate crystal-activated macrophages. Compared to medium controls, rhein at the therapeutic concentration (2.5 µ g/mL) effectively inhibited IL-1 ß production by 47% ( P=0.002 ). Rhein did not affect the mRNA levels of CASP1, NLRP3 and ASC, but suppressed the protein expression and enzyme activity of caspase-1. Immunofluorescence confocal microscopy further revealed that rhein suppressed the aggregation of ASC speck and inhibited the formation of NLRP3 inflammasome. Rhein of 5 µ g/mL significantly decreased the ASC speck to 36% ( P=0.0011 ), and reduced the NLRP3 aggregates to 37.5% ( P=0.014 ). Our data demonstrate that rhein possesses pharmacological activity to suppress caspase-1 protease activity and IL-1 ß production by interfering with the formation of NLRP3 multiprotein complex. These results suggest that rhein has therapeutic potential for treating NLRP3 inflammasome-mediated diseases such as gouty arthritis.

Methotrexate-induced epidermal necrosis: A case series of 24 patients.

BACKGROUND: Methotrexate-induced epidermal necrosis (MEN) is a rare but life-threatening cutaneous reaction that mimics Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). OBJECTIVES: To investigate the clinicopathology, risk factors, and prognostic factors of MEN. METHODS: We enrolled 24 patients with MEN and 150 controls and analyzed the demographics, pathology, and plasma concentrations of methotrexate (MTX). RESULTS: Patients with MEN showed extensive skin necrosis (mean, 33.2% total body surface area) but no target lesions. The histopathology displayed keratinocyte dystrophy. Early signs of MEN included painful skin erosions, oral ulcers, and leukopenia/thrombocytopenia. Although 79.2% patients received leucovorin treatment, there was 16.7% mortality. Risk factors for MEN included older age (>60 years), chronic kidney disease, and high initial dosage of MTX without folic acid supplementation. Renal insufficiency delayed MTX clearance. Severe renal disease and leukopenia predicted poor prognosis in MEN, but none of the SCORe of Toxic Epidermal Necrosis criteria were associated with mortality of MEN. LIMITATIONS: The study was limited by the small sample size. CONCLUSION: MEN exhibited distinct clinicopathologic features from SJS/TEN. Recognition of the early signs and prognostic factors is important, because the rapid institution of leucovorin may be helpful. To reduce the risk of MEN, physicians should avoid prescribing MTX to high-risk patients and titrate the dosage slowly upward with folic acid supplementation.

Early application of low-level laser may reduce the incidence of postherpetic neuralgia (PHN).

BACKGROUND: Postherpetic neuralgia (PHN) is difficult to treat, and currently there are no available treatments that effectively reduce its incidence. Low-level laser therapy (LLLT) has been proposed for indirect virus deactivation in treating recurrent herpes simplex infections. OBJECTIVE: This study seeks to investigate whether LLLT could reduce the incidence of PHN. METHODS: We retrospectively reviewed the incidence of PHN at the first, third, and sixth months after rash outbreak in 3 groups: the acute group of patients who received LLLT during the first 5 days; the subacute group of patients who received LLLT during days 6 to 14 of the eruption; and the control group of patients who did not receive LLLT. RESULTS: There were 48, 48, and 154 patients in the acute, subacute, and control groups, respectively. After adjusting for confounding factors, including age, sex, and use of famciclovir, the incidence of PHN was significantly lower in the acute group versus the control group after 1 month (odds ratio [OR] 0.21, P = .006, 95% confidence interval [CI] 0.068-0.632), 3 months (OR 0.112, P = .038, 95% CI 0.014-0.886), and 6 months (OR 0.123, P = .021, 95% CI 0-0.606). The subacute group only had a lower incidence (OR 0.187, P = .032, 95% CI 0.041-0.865) after 3 months when compared with the control group. LIMITATIONS: This is a retrospective study lacking double-blind randomization, and the placebo effect may be a major concern. Lack of standardized and prospective evaluation measures is also a limitation of this study. CONCLUSION: Applying LLLT within the first 5 days of herpes zoster eruption significantly reduced the incidence of PHN. LLLT may have the potential to prevent PHN, but further well-designed randomized controlled trials are required.