When Nothing Stops the Itch

Treatment-Resistant Eczema Pruritus: Conventional, Integrative, and Chinese Herbal Approaches

Yoon Hang Kim, MD, MPH  |  Board-Certified in Preventive Medicine | Integrative & Functional Medicine Physician

For many people living with atopic dermatitis, the defining burden is not the visible rash. It is the itch. Chronic pruritus destroys sleep, fractures concentration, and can persist stubbornly even after conventional therapy has cleared most visible lesions. In treatment-resistant cases, the gap between “your skin looks better” and “I still cannot stop scratching” is the gap between treating inflammation and treating the neurosensory itch circuit itself — related but physiologically separable problems requiring different strategies.

This article examines why itch-dominant eczema resists standard treatment, surveys the conventional itch-specific armamentarium, and then turns to two areas with underappreciated evidence: integrative approaches grounded in the gut-skin and mast cell-neuron axes, and Chinese herbal formulas tested in randomized controlled trials specifically for atopic dermatitis pruritus.

Part I: Why Most Itch Treatment Fails

The non-histaminergic itch problem

The reflexive first move for severe itch — oral antihistamines — is reasonable but frequently disappointing in atopic dermatitis, for mechanistic rather than pharmacologic reasons. Most AD-associated pruritus runs through non-histaminergic pathways. Skin mast cells positioned adjacent to sensory nerve endings release not only histamine but also tryptase, nerve growth factor, and multiple cytokines. These mediators act on neuronal receptors including protease-activated receptors (PAR-1/2), TrkA, and the ATP-gated P2X3 receptor, sensitizing TRPV1 and TRPA1 channels on sensory neurons and producing a state of neuronal hyperexcitability that perpetuates itch independently of the inflammatory signal that first triggered it.¹ Sedating antihistamines may help a client sleep through a flare, but they address a secondary signal rather than the primary circuit.

IL-31: the “itch cytokine”

Among the most important non-histaminergic mediators is interleukin-31 (IL-31), a neuroimmune cytokine produced largely by Th2 cells and mast cells. IL-31 acts directly on sensory neurons through the IL-31 receptor alpha subunit (IL-31RA), forming a bridge between the immune and nervous systems. It drives not only itch but also inflammation, barrier dysfunction, and fibrosis.² This makes IL-31 the mechanistic linchpin connecting the inflammatory and neurogenic components of AD pruritus, and explains why IL-31-targeted treatment tends to produce earlier and more dramatic itch relief than agents aimed at broader inflammatory pathways.

The opioid receptor axis in itch

A parallel itch-modulating circuit runs through the opioid receptor system, where mu-opioid receptor activation is broadly pruritogenic and kappa-opioid receptor activation is broadly antipruritic. A mu/kappa imbalance model has been proposed for chronic pruritus, but it should be understood as a working hypothesis rather than an established mechanism in atopic dermatitis specifically. What is better supported is narrower: reviews of refractory chronic pruritus list mu-opioid receptor antagonists among systemic options once topical measures and identifiable causes have been addressed.³

Part II: The Conventional Itch-Directed Ladder

Nemolizumab — the itch-first biologic

Nemolizumab (marketed as Nemluvio) is a humanized monoclonal antibody targeting IL-31RA. In the pivotal Japanese phase 3 trial, patients with AD and moderate-to-severe pruritus with an inadequate response to topical agents received subcutaneous nemolizumab 60 mg or placebo every 4 weeks alongside topical therapy. Median baseline pruritus VAS was 75. At week 16, mean percent change in VAS was −42.8% with nemolizumab versus −21.4% with placebo (difference −21.5 percentage points; 95% CI −30.2 to −12.7; p<0.001).² The subsequent ARCADIA 1 and ARCADIA 2 replicate phase 3 trials evaluated nemolizumab with concomitant topical therapy in adolescents and adults with moderate-to-severe AD.⁴ Nemolizumab is most rationally selected where pruritus severity is disproportionate to visible lesion extent — the “my skin doesn’t look that bad but I’m clawing all night” phenotype, including prurigo-nodularis-like presentations.

Oral JAK inhibitors — faster on itch than on skin

In the JADE COMPARE phase 3 trial, abrocitinib (Cibinqo), an oral JAK1 inhibitor, was compared head-to-head against dupilumab (Dupixent), an anti-IL-4 receptor alpha biologic, and placebo in adults with moderate-to-severe AD on background topical therapy. Both abrocitinib doses produced significantly greater reductions in signs and symptoms than placebo at weeks 12 and 16. Critically, abrocitinib 200 mg — but not 100 mg — was superior to dupilumab on itch response at week 2, while neither dose differed significantly from dupilumab on most other key secondary endpoints at week 16.⁵ A subsequent post-hoc analysis found abrocitinib 200 mg provided significant itch relief compared with dupilumab or placebo as early as 4 days after treatment, and that rapid itch relief within 2 weeks predicted better outcomes at week 12.⁶

The practical implication: abrocitinib’s advantage over dupilumab is concentrated in the speed and depth of early itch relief rather than ultimate skin clearance — a meaningful distinction for clients whose chief complaint is the itch.

Combination biologic + JAK for refractory cases

For clients who have sequentially failed both biologic and JAK monotherapy, an emerging off-label strategy combines dupilumab with a JAK inhibitor. A 2024 real-world study examined dupilumab combined with baricitinib (Olumiant), abrocitinib, or upadacitinib (Rinvoq) in refractory moderate-to-severe AD over 16 weeks.⁷ A separate case series of 6 dupilumab-refractory patients used tofacitinib (Xeljanz) or upadacitinib as rescue therapy; all achieved significant improvement, the JAK inhibitor was successfully discontinued after 2 to 6 months, and durable control was maintained on continued dupilumab monotherapy, with no intolerable adverse events during concomitant use.⁸ This remains an individualized, off-label, time-limited approach reserved for genuinely exhausted monotherapy options.

Neuroactive agents

• Gabapentin (Neurontin) and pregabalin (Lyrica) — used off-label for chronic pruritus, they are promising alternatives particularly for uremic pruritus and neuropathic or neurogenic itch in clients who have failed conservative therapy.⁹
• NK1 receptor antagonists — aprepitant (Emend) — substance P is a major itch mediator binding the neurokinin-1 receptor. In an early open-label study of therapy-refractory pruritus, NK1 blockade produced a high response rate, and the authors concluded the results warranted confirmation in randomized controlled trials.¹⁰ Aprepitant has since shown effect across multiple case series and open-label trials in refractory pruritus of varied etiology.¹¹
• Mu-opioid antagonists — naltrexone (ReVia) — a guideline-recognized systemic option in refractory chronic pruritus.³

Part III: Integrative and Functional Medicine Approaches

The gut-skin axis

Atopic dermatitis is increasingly framed in the literature as a systemic condition involving immune, metabolic, and microbiome dysregulation rather than a purely cutaneous disorder. Multi-omics research has established genetic-level causal links between specific gut microbial taxa and AD. Notably, the genus Sellimonas participates in protein fermentation producing bioactive amines including histamine and tryptamine, which directly activate mast cells and eosinophils and promote Th2-type immune responses. Conversely, the Eubacterium eligens group produces short-chain fatty acids such as butyrate that normally exert anti-inflammatory effects, though excessive proliferation may lower intestinal pH and disrupt microecological balance.¹² This double-edged-sword pattern underscores why individualized microbiome assessment matters more than reflexive broad-spectrum probiotic prescribing.

Probiotics — strain-specific, not one-size-fits-all

A 2014 meta-analysis of 25 randomized controlled trials (n=1,599) found probiotics significantly reduced SCORAD versus control overall (mean difference −4.51, 95% CI −6.78 to −2.24), in children 1–18 years (−5.74, 95% CI −7.27 to −4.20), and in adults (−8.26, 95% CI −13.28 to −3.25), though effectiveness in infants under 1 year was not established. Mixtures of different bacterial species, or Lactobacillus species, showed greater benefit than Bifidobacterium alone.¹³

Strain selection matters considerably. A 2017 systematic review and meta-analysis found Lactobacillus rhamnosus GG showed no significant effect on SCORAD (MD 3.29, 95% CI −0.30 to 6.88, p=0.07), nor did Lactobacillus plantarum. In contrast, Lactobacillus fermentum (MD −11.42, 95% CI −13.81 to −9.04), Lactobacillus salivarius (MD −7.21, 95% CI −9.63 to −4.78), and multi-strain mixtures (MD −3.52) showed significant effects. The authors cautioned that the evidence base has not robustly established probiotic benefit in children with AD given population heterogeneity.¹⁴ For clients with concurrent histamine intolerance or mast cell activation features, strain selection is doubly important, since certain Lactobacillus species produce rather than degrade histamine.

Vitamin D supplementation

A 2016 systematic review and meta-analysis found serum 25(OH)D was lower in AD patients across all ages (standardized mean difference −2.03 ng/mL, 95% CI −2.52 to −0.78) and predominantly in pediatric patients, and that SCORAD and EASI scores decreased following supplementation (SMD −5.85, 95% CI −7.66 to −4.05).¹⁵ A 2019 meta-analysis found AD patients had lower 25(OH)D than healthy controls by a mean difference of −14 nmol/L (95% CI −25 to −2), and a meta-analysis of three supplementation trials found SCORAD reduced by 11 points (95% CI −13 to −9, p<0.00001), surpassing the minimal clinically important difference.¹⁶ A 2024 systematic review and meta-analysis of 11 RCTs (n=686) again concluded vitamin D supplementation reduces AD severity in children and adults.¹⁷

An important counterweight: a 2023 meta-analysis of 5 RCTs (n=304) applying stricter heterogeneity adjustment and GRADE assessment did not find that vitamin D supplementation decreased AD severity.¹⁸ The honest reading is that the evidence is directionally supportive but not settled. Given that checking and correcting deficiency is low-risk and broadly beneficial, it remains a reasonable component of care, but it should not be oversold as a primary itch intervention.

Quercetin and mast cell stabilization

Quercetin has demonstrated mast cell stabilizing activity that, in several assays, exceeds that of cromolyn. In a comparison using cultured human mast cells, quercetin and cromolyn both inhibited histamine and PGD2 secretion, but quercetin was more effective at inhibiting IL-8 and TNF release from LAD2 mast cells stimulated by substance P — the same neuropeptide targeted by NK1 antagonists. Quercetin also reduced IL-6 release dose-dependently, inhibited cytosolic calcium increase, and inhibited NF-kappaB activation. Notably, quercetin was effective prophylactically, whereas cromolyn had to be added together with the trigger or rapidly lost effect. In two pilot open-label clinical trials, quercetin significantly decreased contact dermatitis and photosensitivity — conditions that do not respond to conventional treatment — and associated pruritus was eliminated in all subjects, including one patient who also had chronic atopic dermatitis.¹⁹

The evidence level here should be stated plainly: pilot open-label trials in contact dermatitis and photosensitivity, with a single incidental AD observation. There is no large AD-specific RCT. What justifies clinical interest is the mechanistic convergence — substance P-triggered mast cell mediator release is precisely the pathway implicated in refractory neurogenic itch.

The MCAS overlap

Mast cells adjacent to sensory nerve endings constitute a neuroimmune interface, and mediators including histamine, tryptase, IL-31, substance P, and NGF participate in AD pruritus.¹ It is tempting to extend this into a clinical pathway — screen refractory AD for mast cell activation syndrome, then treat with low-histamine diet, DAO enzyme support, and gut barrier repair. That extension is not supported by the cited mechanistic literature and should be stated as what it is: a hypothesis. The mast cell-neuron review above describes mediator biology in AD skin; it does not establish that AD clients have systemic mast cell disease, that MCAS testing changes AD outcomes, or that DAO or gut-directed therapy improves AD itch. No randomized trial has tested that pathway in atopic dermatitis. Where a client has independent, objectively documented mast cell activation, treating it on its own merits is reasonable — but AD pruritus alone is not evidence of MCAS, and the gut-histamine treatment cascade should not be presented to clients as established AD therapy.

Part IV: Chinese Herbal Medicine — Where Tradition Has Trial Data

Chinese herbal medicine for skin disease is rarely subjected to rigorous placebo-controlled methodology. Atopic dermatitis is an important exception.

Xiao Feng San (消风散) — the strongest evidence base

 [RCT, double-blind, human] In a prospective, randomized, double-blind, placebo-controlled trial, 71 patients with severe intractable atopic dermatitis received 8 weeks of oral Xiao-Feng-San (n=47) or placebo (n=24), with total lesion, erythema, surface damage, pruritus, and sleep scores measured at 4-week intervals. Fifty-six completed treatment and follow-up. Total lesion score decreased 79.7% (±5.8%) in the treatment group versus 13.5% (±7.64%) in placebo (p<0.001), with statistically significant differences in erythema, surface damage, pruritus, and sleep scores. At 12-week follow-up (4 weeks after treatment ended) the between-group difference remained significant for all measures except erythema. No side effects were reported, though some patients commented on the medication’s unpalatability. The authors concluded XFS may be an alternative for severe, refractory, extensive, nonexudative atopic dermatitis.²⁰

That last qualifier matters clinically and is often dropped when this trial is cited: the population studied was nonexudative disease.

The formula’s four “king” herbs (Jing Jie, Fang Feng, Niu Bang Zi, Chan Tui) are understood to vent wind outward and address itching directly. Cang Zhu, Ku Shen, and Mu Tong drain dampness associated with oozing. Shi Gao and Zhi Mu clear heat associated with redness and burning. Dang Gui, Sheng Di Huang, and Hei Zhi Ma nourish blood and yin specifically to prevent the formula’s drying components from worsening skin dryness — an internal check-and-balance that Western-trained clinicians often do not expect from a traditional formula.

 [RCT, sham-controlled, human] A multi-center, participant- and assessor-blinded, randomized, sham-controlled trial enrolled 156 adults with non-severe AD and a wind-dampness-heat pattern, then randomized to auricular acupuncture (n=78) or sham auricular acupuncture (n=78) for four weeks. The acupuncture group showed a significantly greater SCORAD reduction at week 4 (mean difference −9.1, p<0.0001), exceeding the minimal clinically important difference.²¹ This trial is frequently miscited — including in an earlier draft of this article — as supporting Xiao Feng San. It does not. Every participant in both arms received XFS decoction; the only randomized variable was auricular acupuncture versus sham. The trial therefore provides evidence for the added benefit of auricular acupuncture on a background of XFS, and provides no independent evidence of XFS efficacy. The Cheng 2011 trial above remains the only randomized placebo-controlled evidence for the formula itself.

Angelica Yinzi (当归饮子) — preclinical only, mechanism unresolved

 [Preclinical, mouse model only] Angelica Yinzi is a classical formula traditionally used for nourishing blood, moistening dryness, dispelling wind, and relieving itch. In a mouse model of DNCB-induced atopic dermatitis, Angelica Yinzi reduced scratching behavior and attenuated dermatitis; the authors reported accompanying changes in skin barrier markers, oxidative stress markers, and peripheral mu- and kappa-opioid receptor expression.²² A related study from the same group demonstrated inhibition of NLRP3 inflammasome activation and downregulation of MAPKs/NF-kappaB signaling in the same model.²³

This must be framed accurately, and my earlier framing of it overreached. Both studies are preclinical murine work; neither is a human trial. More importantly, the opioid receptor findings are correlative expression changes accompanying an antipruritic effect — the studies did not establish that receptor modulation causes the benefit, and no receptor-blockade or knockout experiment was done to test it. Nor does this make Angelica Yinzi mechanistically equivalent to naltrexone or low-dose naltrexone: naltrexone is a competitive mu antagonist, LDN is thought to act through intermittent blockade with receptor upregulation and glial/TLR4 effects, and a multi-herb formula shifting receptor expression in mouse skin is a different phenomenon from any of these. The formulas share a vocabulary, not a demonstrated mechanism. Angelica Yinzi has no human efficacy data in atopic dermatitis and should not be offered to clients as an itch treatment.

Huoxiang Zhengqi (薿香正气) — dampness-pattern specific

 [RCT, double-blind, human] The CHARM trial has now completed and been published. In this multi-center, double-blind, randomized placebo-controlled trial, 218 adults with mild AD or eczema received HXZQ oral liquid (n=110) or placebo (n=108) for 4 weeks, with change in EASI score from baseline to end of treatment as the primary outcome. Greater improvement was reported with HXZQ than placebo at 4 and 8 weeks, with no treatment-related or severe adverse events.²⁴ The published protocol is cited separately.²⁵ Two limitations bear on how far this can be carried: the population was mild disease, and the primary endpoint was EASI (a lesion severity measure), not a pruritus-specific endpoint — so this trial supports HXZQ for mild AD generally, and does not by itself establish an antipruritic effect.

Pattern differentiation: why “the eczema herb” does not exist

Formula selection in Chinese herbal medicine is guided by pattern differentiation, not Western diagnosis alone. Red, weeping, intensely itchy lesions (wind-damp-heat) call for a different formula than dry, lichenified, chronic itch (blood-yin deficiency). Prescribing Xiao Feng San for a dry blood-deficiency itch pattern would be mechanistically mismatched even though the surface complaint sounds identical — and note that the XFS trial itself specified a nonexudative population.

Part V: An Integrated Framework

Refractory itch typically reflects multiple parallel pathways rather than one insufficiently suppressed pathway. A reasonable clinical framework:

1. Characterize the itch phenotype. Is pruritus disproportionate to lesion extent (IL-31-dominant)? Does it have neuropathic qualities — burning, stinging, paresthesia? Or classically histaminergic features with multisystem mast cell symptoms?
2. Select the itch-forward systemic agent. Nemolizumab for itch-dominant, lesion-light phenotypes; abrocitinib where rapid itch onset matters most; combination therapy as off-label rescue.
3. Optimize modifiable drivers. Correct vitamin D deficiency (acknowledging mixed meta-analytic evidence). Assess gut barrier and dysbiosis. Select probiotic strains deliberately rather than generically. Evaluate for mast cell activation as an upstream contributor.
4. Consider herbal adjuncts only where trial evidence matches the client. Xiao Feng San has one placebo-controlled RCT, in severe nonexudative disease. HXZQ has one, in mild disease with a lesion endpoint. Quercetin's human data are two small open-label trials in other dermatoses. Angelica Yinzi has no human data at all. None of these has been tested against, or alongside, modern systemic therapy, and none should displace it.
5. Interrupt the itch-scratch cycle behaviorally. Habit reversal training, stress-related mast cell degranulation reduction, and sleep protection address the cycle at a level no drug reaches.

The organizing idea is that refractory itch often involves more than one pathway, so a single escalating drug class may not reach all of it. That is a reasonable clinical heuristic, not a validated treatment algorithm: no trial has tested this layered approach as a strategy. The individual components differ enormously in evidentiary strength — nemolizumab and abrocitinib rest on phase 3 trials, while several integrative components rest on mechanism, small open-label studies, or animal work. Those tiers should not be blurred when discussing options with a client.

References

1. Li D, Han Y, Zhou J, Yang H, Chen J, Tey HL, Tan TTY. Mast cell–neuron axis as a core mechanism in chronic pruritus of atopic dermatitis: from mechanistic insights to therapeutic targets. Front Immunol. 2025;16:1645095. doi:10.3389/fimmu.2025.1645095
2. Kabashima K, Matsumura T, Komazaki H, Kawashima M; Nemolizumab-JP01 Study Group. Trial of nemolizumab and topical agents for atopic dermatitis with pruritus. N Engl J Med. 2020;383(2):141–150. doi:10.1056/NEJMoa1917006. PMID: 32640132
3. Pereira MP, Mittal A, Ständer S. Current treatment strategies in refractory chronic pruritus. Curr Opin Pharmacol. 2019;46:1–6. doi:10.1016/j.coph.2018.11.007. PMID: 30530232
4. Silverberg JI, Wollenberg A, Reich A, et al. Nemolizumab with concomitant topical therapy in adolescents and adults with moderate-to-severe atopic dermatitis (ARCADIA 1 and ARCADIA 2): results from two replicate, double-blind, randomised controlled phase 3 trials. Lancet. 2024;404:445–460.
5. Bieber T, Simpson EL, Silverberg JI, Thaçi D, Paul C, Pink AE, Kataoka Y, Chu CY, DiBonaventura M, et al. Abrocitinib versus placebo or dupilumab for atopic dermatitis. N Engl J Med. 2021;384(12):1101–1112. doi:10.1056/NEJMoa2019380. PMID: 33761207 (JADE COMPARE, NCT03720470)
6. Ständer S, Kwatra SG, Silverberg JI, Simpson EL, Thyssen JP, Yosipovitch G, Zhang F, Cameron MC, Rojo Cella R, Valdez H, DiBonaventura M, Feeney C. Early itch response with abrocitinib is associated with later efficacy outcomes in patients with moderate-to-severe atopic dermatitis: subgroup analysis of the randomized phase III JADE COMPARE trial. Am J Clin Dermatol. 2023;24(1):97–107. doi:10.1007/s40257-022-00738-4. PMID: 36512175
7. Song X, Liu B, Peng C, Tan Y, Zuotao Z. Dupilumab in combination with JAK inhibitor for refractory moderate-to-severe atopic dermatitis. Dermatol Ther. 2024;2024:9515524. doi:10.1155/dth/9515524
8. Shahriari N, Strober B, Shahriari M. JAK-inhibitors as rescue therapy in dupilumab-refractory severe atopic dermatitis: a case series of 6 patients. JAAD Case Rep. 2023;33:81–83. doi:10.1016/j.jdcr.2023.01.020. PMID: 36873051
9. Matsuda KM, Sharma D, Schonfeld AR, Kwatra SG. Gabapentin and pregabalin for the treatment of chronic pruritus. J Am Acad Dermatol. 2016;75(3):619–625.e6. PMID: 27206757
10. Ständer S, Siepmann D, Herrgott I, Sunderkötter C, Luger TA. Targeting the neurokinin receptor 1 with aprepitant: a novel antipruritic strategy. PLoS ONE. 2010;5(6):e10968. doi:10.1371/journal.pone.0010968
11. He A, Alhariri JM, Sweren RJ, Kwatra MM, Kwatra SG. Aprepitant for the treatment of chronic refractory pruritus. Biomed Res Int. 2017;2017:4790810. doi:10.1155/2017/4790810
12. Cao F, Liu A, Tong J, Guo C, Zhang H, Pang Y, Tang K, Yu Q, Guo J. Integrative multi-omics analysis reveals gut-skin axis mechanisms and novel therapeutic target GALE in atopic dermatitis. mSystems. 2026;11(1):e01403-25. doi:10.1128/msystems.01403-25 (published online 5 December 2025)
13. Kim SO, Ah YM, Yu YM, Choi KH, Shin WG, Lee JY. Effects of probiotics for the treatment of atopic dermatitis: a meta-analysis of randomized controlled trials. Ann Allergy Asthma Immunol. 2014;113(2):217–226. doi:10.1016/j.anai.2014.05.021. PMID: 24954372
14. Huang R, Ning H, Shen M, Li J, Zhang J, Chen X. Probiotics for the treatment of atopic dermatitis in children: a systematic review and meta-analysis of randomized controlled trials. Front Cell Infect Microbiol. 2017;7:392. doi:10.3389/fcimb.2017.00392
15. Kim MJ, Kim SN, Lee YW, Choe YB, Ahn KJ. Vitamin D status and efficacy of vitamin D supplementation in atopic dermatitis: a systematic review and meta-analysis. Nutrients. 2016;8(12):789. doi:10.3390/nu8120789. PMID: 27918470
16. Hattangdi-Haridas SR, Lanham-New SA, Wong WHS, Ho MHK, Darling AL. Vitamin D deficiency and effects of vitamin D supplementation on disease severity in patients with atopic dermatitis: a systematic review and meta-analysis in adults and children. Nutrients. 2019;11(8):1854. doi:10.3390/nu11081854. PMID: 31405041
17. Nielsen AY, Høj S, Thomsen SF, Meteran H. Vitamin D supplementation for treating atopic dermatitis in children and adults: a systematic review and meta-analysis. Nutrients. 2024;16(23):4128. doi:10.3390/nu16234128. PMID: 39683522. PROSPERO CRD42024535014
18. Park JS, Kim M, Sol IS, Lee KS, Park S, Yang HJ, Lee E. Effect of vitamin D on the treatment of atopic dermatitis with consideration of heterogeneities: meta-analysis of randomized controlled trials. Allergy Asthma Immunol Res. 2023;15(2):262–270. doi:10.4168/aair.2023.15.2.262. PMID: 37021510
19. Weng Z, Zhang B, Asadi S, Sismanopoulos N, Butcher A, Fu X, Katsarou-Katsari A, Antoniou C, Theoharides TC. Quercetin is more effective than cromolyn in blocking human mast cell cytokine release and inhibits contact dermatitis and photosensitivity in humans. PLoS ONE. 2012;7(3):e33805. doi:10.1371/journal.pone.0033805
20. Cheng HM, Chiang LC, Jan YM, Chen GW, Li TC. The efficacy and safety of a Chinese herbal product (Xiao-Feng-San) for the treatment of refractory atopic dermatitis: a randomized, double-blind, placebo-controlled trial. Int Arch Allergy Immunol. 2011;155(2):141–148. doi:10.1159/000318861. PMID: 21196758
21. Tran NT, et al. Efficacy of herbal medicine Xiao-Feng-San combined with auricular acupuncture for atopic dermatitis: a randomized controlled trial. Integr Med Res. 2026;15:101256. ClinicalTrials.gov NCT06492902
22. Liu W, Luo Y, Song W, Dan H, Li L, Zhou D, You P. Angelica Yinzi alleviates pruritus-related atopic dermatitis through skin repair, antioxidation, and balancing peripheral mu- and kappa-opioid receptors. Evid Based Complement Alternat Med. 2023;2023:6058951. PMC10545464 [preclinical, mouse model]
23. Liu W, Song W, Luo Y, Dan H, Li L, Zhang Z, Zhou D, You P. Angelica Yinzi alleviates 1-chloro-2,4-dinitrobenzene-induced atopic dermatitis by inhibiting activation of NLRP3 inflammasome and down-regulating the MAPKs/NF-kB signaling pathway. Saudi Pharm J. 2022;30(10):1426–1434. PMC9649345 [preclinical, mouse model]
24. Xuan M, et al. Chinese herbal formula Huoxiang Zhengqi oral liquid for atopic dermatitis: the CHARM randomized controlled trial. Phytomedicine. 2025. doi:10.1016/j.phymed.2025.157180 [volume/pages not yet confirmed at publisher — verify before submission]
25. Xuan M, Guo X, Li H, Xie T, Mo X, Wen Z. The Chinese herbal formula Huoxiang Zhengqi for atopic dermatitis with dampness pattern (CHARM): a study protocol for a double-blinded randomized controlled trial. Trials. 2021;22(1):67. doi:10.1186/s13063-020-05014-6. PMID: 33468222. ChiCTR1900026700

In health,

Yoon Hang Kim, MD, MPH

Dr. Kim is a board-certified physician with over 20 years of clinical experience, trained through the University of Arizona/Dr. Andrew Weil Integrative Medicine Fellowship, with certifications in preventive medicine, medical acupuncture, and integrative and holistic medicine. His clinical focus includes low-dose naltrexone therapy, autoimmune disease, chronic pain, integrative oncology, fibromyalgia, chronic fatigue syndrome, mast cell activation syndrome, and mold toxicity. He is the author of three books and more than 20 peer-reviewed articles.

Professional: www.yoonhangkim.com  | 

Clinical: www.directintegrativecare.com