Pathogenesis evolution of "deficiency-turbidity-toxin-wang" in rheumatoid arthritis: a staged strategy based on pathogenic factor-targeted treatment

Rheumatoid arthritis (RA) belongs to the category of "Bi Zheng" (impediment syndrome) in traditional Chinese medicine (TCM). It is characterized by high disability and complex pathological mechanisms. Its pathogenesis evolves according to the pattern of "deficiency leading to turbidity, turbidity condensing into toxin, and toxin causing damage resulting in Wang-Bi," which is summarized as the "deficiency-turbidity-toxin-wang" pathogenesis evolution. Guided by ZHANG Zhongjing′s theory of "treatment according to pathogenic factors involved," this study systematically elucidates the evolution pattern of RA′s "deficiency-turbidity-toxin-wang" pathogenesis, and identifies the "obtained pathogen" as the aggregation of pathogenic factors with tangible evils such as phlegm, stasis, turbidity, and toxin during pathological evolution. We establish a three-stage treatment system: the initial stage (the onset of evolution), the active stage (the peak of evolution), and the remission stage (the deep stage of evolution). In the initial stage, we focus on "turbidity accumulating in the meridians" as the obtained pathogen. Due to healthy qi deficiency and weakened defensive qi, wind-cold-dampness-heat pathogens invade the superficies and meridians, causing qi and blood stagnation that condenses into turbidity. The treatment uses modified Mahuang Xingren Yiyi Gancao Decoction combined with Guizhi Fuzi Decoction to dispel wind-cold, transform turbidity, unblock collaterals, and expel superficial pathogens, thereby preventing transmission from meridians to zang-fu organs. In the active stage, the pathogen obtained is "toxin and stasis interbinding in the bones and joints." At this stage, turbidity accumulates and condenses into toxin, with phlegm and stasis intertwining, damaging collaterals and consuming yin. The joints become red, swollen, burning, painful, and deformed. The treatment uses modified Simiao Xiaobi Decoction to clear heat and resolve toxin, activate blood and unblock collaterals, soften hardness and dissipate masses, while also nourishing yin to prevent toxin from penetrating into the nutrient level. In the remission stage, the condition is identified as "deficiency of healthy qi with lurking turbidity," presenting a pattern of root deficiency and branch excess after prolonged bi. Although the intense toxicity has subsided, turbidity and toxin lurk uncleanly, and the liver, spleen, and kidney are deficient, leading to malnutrition of sinews and bones and failure of qi and blood generation. The treatment uses modified Wubi Shanyao Pill combined with Huangqi Guizhi Wuwu Decoction to nourish liver and kidney, strengthen spleen and supplement qi, harmonize nutrient and defensive qi, and combine attack with supplementation to unblock the zang-fu organs and network vessels. By clarifying the pathogenesis and therapeutic targets ("obtained" pathogens) at each stage, the treatment principle of "determining the obtained pathogen based on pathogenesis and determining the treatment method based on the obtained pathogen" is established. This approach inherits ZHANG Zhongjing′s principle of attacking pathogens, and highlights the advantage of dynamic intervention under the model of integration of disease and syndrome, providing a theoretical foundation and practical guidance for the diagnosis and treatment of RA in TCM.