Where Does Relapse Reside? The Healed-Looking Skin of Atopic Dermatitis and Psoriasis and the Korean Medical Doctrines of Nobok (勞復) and Gojil (痼疾)

1. Abstract

In the clinical management of atopic dermatitis and psoriasis, one experience recurs: the skin improves, and then a single food, a cosmetic product, or a period of stress overturns it and the course seems to start again from the beginning. This paper asks whether there is literature that explains that experience. The modern literature reports that atopic skin which has returned to an apparently normal state retains microinflammation (Wollenberg 2018), and that healed psoriatic sites retain tissue-resident memory T cells involved in relapse at the same location, together with a transcriptome that has not normalized—a "molecular scar" (Benezeder 2019; Emmanuel 2024; Peng 2024). Among the classical sources of Korean medicine, the 脈義簡摩, Maiyi jianmo, distinguished 痼疾, gojil—an intractable, recurrent illness, which "although healed, has a root that is not clean, so that it recurs from time to time"—from 宿疾, sukjil—an injury that does not recur but is not restored. The passages on 勞復, nobok—relapse brought on by exertion during convalescence—and 食復, sikbok—relapse brought on by diet during convalescence—in the literature on 傷寒, sanghan—"cold damage," the classical category of acute febrile disease—state that in the vulnerable interval immediately after an illness resolves, exertion, food, and worry cause the illness to return. The objects of observation and the explanatory systems of the two traditions differ, and there is no evidence that the residual heat (餘熱) of convalescence from cold damage and the memory T cells of psoriasis are the same pathology. What this paper compares is an explanatory structure in which vulnerability persists after recovery and becomes manifest again under certain conditions, and it uses this comparison to shift the way relapse management is conceived, from avoidance of causes to the design of a maintenance phase.

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2. Context of the Question

Atopic dermatitis is the skin disease with the greatest global burden and is described as a condition that, at present, can be neither prevented nor cured (Lax 2024, Cochrane). The German S2k guideline defines it as a "chronic or chronically relapsing" inflammatory skin disease and states that both the first manifestation and subsequent exacerbations arise when multiple triggers are superimposed on a genetic predisposition (Werfel 2016). The textbook describes most atopic dermatitis as provoked not by interaction with allergens but by "environmental stress applied to genetically vulnerable skin" (Habif, Clinical Dermatology, 5th ed., p.165).

The clinician's sense of starting "again from the beginning" is contained within this definition. A definition, however, is not an explanation. Why a healed site collapses again under the same stimulus, what remains at that site, and how the remnant should be managed are separate questions.

Korean medicine has treated this question as a problem of the period after an illness has resolved. This paper does not judge the relative merit of treatments. It reads side by side how each of the two traditions described the criterion that distinguishes "healed" from "finished."

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3. What the Literature Says

3-1. What remains in skin that looks healed: microinflammation and the molecular scar

Non-lesional skin of patients with atopic dermatitis shows histological signs of microinflammation and a pro-inflammatory cytokine milieu; because this microinflammation is present even in apparently healed skin, it should be taken into account in treatment. — Wollenberg et al., 2018, Journal of the European Academy of Dermatology and Venereology (PMID 29533490)

In psoriasis, the residual changes have been characterized in greater detail. Even when lesions have disappeared to the naked eye after biologics or phototherapy, they tend to recur within months at the same sites, and cytokine reservoirs together with tissue-resident memory T cells (TRM, T cells that remain in the skin and retain memory of the same antigen) left at those sites have been proposed as the clue to relapse (Benezeder & Wolf, 2019, Seminars in Immunopathology, PMID 31673756).

Both secukinumab and Dead Sea climatotherapy normalized lesional skin histologically to the level of non-lesional skin, but neither treatment normalized the transcriptome. At the end of treatment, 479 differentially expressed genes were observed between the two groups. — Emmanuel et al., 2024, International Journal of Molecular Sciences (PMID 38892277)

A single-cell sequencing study reported that IL-17A/F double-producing T cells, unstable regulatory T cells, and quiescent TRM remain within clinically healed psoriatic lesions as candidates for relapse (Peng et al., 2024, Clinical Immunology, PMID 39067676). Histological normalization and molecular normalization are not the same event. Cellular and transcriptomic evidence at this level is concentrated in psoriasis; in atopic dermatitis it remains at the level of histological description of microinflammation.

3-2. Gojil and sukjil: the illness that recurs and the injury that is not restored

The classical source that defines recurrent illness most explicitly is the Maiyi jianmo by Zhou Xuehai (周學海) of the late Qing.

凡病證遷延不愈, 或雖愈而病根不淨, 時時復發者, 謂之痼疾. 病愈不復發, 而本經血氣受傷, 終不能復者, 謂之宿疾. Whenever a pattern of illness drags on without healing, or, although healed, its root is not clean so that it recurs from time to time, it is called gojil. When the illness is healed and does not recur, yet the blood and qi of the channel concerned have been injured and in the end cannot be restored, it is called sukjil. — Maiyi jianmo (脈義簡摩), vol. 3, "Pulses of Gojil and Sukjil" (痼疾宿疾脈) (https://mediclassics.kr/books/285/volume/3#content_86; no Korean translation available; translation by the author)

This definition divides the course of illness into two branches. Gojil is an illness in which the root of the illness (病根, byeonggeun) remains and flares again; sukjil is an illness that does not flare again but leaves injury behind. The distinction can serve directly as a framework for thinking separately about the residual immune changes that the modern literature identifies as the source of relapse and the tissue changes that remain after repeated inflammation.

The same passage states that "goiter, scaling eruptions, hemorrhoids, and fistulae are external gojil" (癭癬痔瘻, 外痼疾也), placing scaling skin eruptions (癬, seon) within gojil, and it describes the conditions under which the residual state becomes manifest as follows.

又以年壯體强, 境遇豐順, 心情舒暢, 血氣流通, 亦有不見脈者, 稍或飮食勞倦, 思慮憂鬱, 卽見矣. Moreover, when a person is young and strong in body, fortunate in circumstance, and at ease in mind, so that blood and qi flow freely, it may not show in the pulse at all; yet with even slight food or fatigue, deliberation or worry, it at once appears. — Maiyi jianmo, vol. 3, "Pulses of Gojil and Sukjil" (same location; translation by the author)

The description of a residual state that remains hidden in ordinary circumstances and becomes manifest when conditions are added resembles, in its explanatory structure, the way the modern literature describes microinflammation in apparently normal skin. The object of observation in the "manifestation" of which the source speaks is the pulse.

Classical descriptions of skin disorders also record recurrence and a slow course.

四彎風生腿脚彎, 每月一發最纏綿, 形如風癬風邪襲, 搔破成瘡癢難堪. … 其癢即止, 緩緩取效. Four-bend wind arises in the bends of the legs; it flares once each month and is the most lingering of conditions. In form it resembles wind tinea (風癬) and is an invasion of wind pathogen; scratched open, it turns into sores, and the itching is hard to bear. … The itching then stops, but the effect is obtained only slowly. — 醫宗金鑑·外科心法要訣, Yizong jinjian: Waike xinfa yaojue, vol. 71, "Four-Bend Wind" (四彎風, samanpung) (https://mediclassics.kr/books/100/volume/11#content_119)

Of 白疕, baekbi, the classical condition corresponding to psoriasis, the same work states that "it is indeed caused by wind pathogen lodging in the skin, yet it also arises from blood dryness that cannot nourish the exterior" (固由風邪客皮膚, 亦由血燥難榮外) (same work, vol. 74, "Baekbi" (白疕), #content_185), naming both the external pathogen and the internal insufficiency as causes.

3-3. Vulnerability during convalescence: nobok and sikbok

If gojil concerns the course of illness as a whole, the passages on nobok and sikbok set apart the interval in which an illness has only just receded. Their subject is convalescence from sanghan, an acute febrile disease; although this differs from chronic skin disease, the passages provide material for comparing how vulnerability immediately after recovery was described.

傷寒新差後, 血氣未平, 餘熱未盡, 勞動其熱, 熱氣還經絡, 遂復發也. 此有二種, 一者因勞動外傷, 二者因飮食內傷. 其勞動外傷者, 非止强力搖體, 持重遠行之勞, 至於梳頭洗面則動氣, 憂悲思慮則勞神, 皆能復也. When cold damage has only just been cured, while blood and qi have not yet regained balance and residual heat has not yet been exhausted, exertion that stirs that heat sends the heat qi back into the channels, and the illness at last recurs. There are two kinds: injury of the exterior through bodily exertion and injury of the interior through food and drink. Bodily exertion is not limited to forcing one's strength, or to carrying heavy loads and traveling far; even combing the hair and washing the face stir the qi, and grief and worry tax the spirit (神)—all of these can bring about relapse. — 傷寒明理論, Shanghan mingli lun, vol. 3, "Nobok," ch. 50 (勞復 第五十) (https://mediclassics.kr/books/198/volume/3#content_60)

This passage describes relapse as divided into an underlying residual state—血氣未平, 餘熱未盡, hyeolgi mipyeong, yeoyeol mijin, "blood and qi not yet balanced, residual heat not yet exhausted"—and the triggers that act upon it, and among the triggers it explicitly names "worry that taxes the spirit" (憂悲思慮則勞神).

帝曰, 熱病已愈, 時有所遺者, 何也. 岐伯曰, 諸遺者, 熱甚而强食之, 故有所遺也. 帝曰, 治遺柰何. 岐伯曰, 視其虛實, 調其逆從, 可使必已矣. 帝曰, 病熱當何禁之. 岐伯曰, 病熱少愈, 食肉則復, 多食則遺, 此其禁也. The Emperor asked: When a febrile disease has already healed, yet at times something remains, why is this? Qibo answered: Whatever remains, remains because food was forced on the patient while the heat was intense. The Emperor asked: How is what remains to be treated? Qibo answered: Examine its deficiency and excess and regulate its counterflow and compliance, and it can surely be brought to an end. The Emperor asked: What should be prohibited in febrile disease? Qibo answered: When a febrile disease has slightly abated, eating meat brings relapse, and eating much leaves a remnant. These are its prohibitions. — 東醫寶鑑, Dongui Bogam, Japbyeong pyeon, vol. 3, "Residual Patterns of Cold Damage" (傷寒遺證), quoting the Huangdi Neijing (內經) (https://mediclassics.kr/books/8/volume/11#content_195)

The prohibition is paired with a therapeutic principle: "examine its deficiency and excess and regulate" (視其虛實, 調其逆從). The source treats the dietary prohibition as a defense that keeps the residual state from being disturbed, and regards the persisting imbalance of deficiency and excess as the object of treatment.

3-4. Modern evidence on triggers: food, contact, and stress

The evidence on triggers must be read with a distinction between "has an effect" and "is resolved by avoidance."

Food. This evidence does not address whether food is involved in exacerbation; it examines the average effect of uniform dietary elimination used as treatment. In a meta-analysis of 10 randomized controlled trials (599 participants, median participant age 1.5 years), 50% of the elimination group and 41% of the non-elimination group showed clinically meaningful improvement in SCORAD (risk difference 9%, 95% CI 0–17%). The certainty of evidence was low; the authors concluded that the improvement was "slight and may be unimportant," and noted that, on indirect evidence, dietary elimination may increase the risk of IgE-mediated food allergy (Oykhman et al., 2022, J Allergy Clin Immunol Pract, PMID 35987995).

Contact allergens. In a population referred for patch testing, 39.0% of patients positive to glucosides, surfactants used in personal hygiene products, had a history of atopic dermatitis, higher than the 28.6% of the negative group (P<0.0001), and 83.9% of positive reactions were of current clinical relevance (Warshaw et al., 2022, J Am Acad Dermatol, PMID 35551968). Among patients positive to benzophenone, a UV-filter ingredient, the proportion with a history of atopic dermatitis was likewise higher, at 39.8% versus 30.7% in the negative group (Warshaw et al., 2023, Dermatitis, PMID 36917534). Reactions to cosmetics fall within a domain that can be confirmed by individual testing.

Stress. In a mouse study, a subtype of sympathetic neurons (Pdyn+) distributed in hairy skin recruited and activated eosinophils and mediated stress-induced exacerbation in a model of atopic-like dermatitis. Genetic ablation of these neurons or of eosinophils reduced stress-induced exacerbation (Tian et al., 2026, Science, PMID 41855337). For psoriasis, a review holds that dysregulation of the hypothalamic–pituitary–adrenal axis and the sympathetic–adrenomedullary axis, together with the skin's own local stress-hormone system, participates in exacerbation (Marek-Jozefowicz et al., 2022, Int J Mol Sci, PMID 35054853). The textbook adds a clinical point. Because patients readily believe that stress caused their disease and tend to blame themselves, it reassures them to explain that atopic dermatitis is a genetic disease that is not "caused" by stress but "aggravated" by it (Habif, Clinical Dermatology, 5th ed., p.182).

3-5. Modern evidence on the design of the maintenance phase

The evidence below concerns mainly atopic dermatitis (eczema). The representative approach is proactive maintenance therapy (proactive therapy): after the acute phase has been brought under control, anti-inflammatory agents are applied intermittently twice a week to previously affected sites and emollients are used daily.

Twice-weekly (weekend) proactive topical corticosteroid therapy substantially reduces the likelihood of relapse, from 58% to 25% (RR 0.43, 95% CI 0.32–0.57; 7 trials, 1,149 participants; moderate certainty). No cases of abnormal skin thinning were identified with this regimen. — Lax et al., 2022, Cochrane Database of Systematic Reviews (PMID 35275399)

A twice-weekly regimen of tacrolimus, a non-steroidal anti-inflammatory agent, also reduced relapse compared with placebo (RR 0.78, 95% CI 0.60–1.00; Schmitt et al., 2011, Br J Dermatol, PMID 20819086). In a small trial (45 participants) of maintenance with emollients alone, relapse over six months occurred in 21% of the daily emollient group and 65% of the control group (Weber et al., 2015, J Drugs Dermatol, PMID 25942666).

The literature also records differences according to mode of use. With short-term use (median 3 weeks) there was no evidence of increased skin thinning. In 3 trials comparing long-term use over 6–60 months, skin thinning occurred in 6 of 2,044 participants (0.3%) in the topical corticosteroid groups and in 0 of 2,025 in the calcineurin inhibitor groups (p=0.031; Lax et al., 2024, Clinical and Experimental Allergy, PMID 39219446). In a retrospective cohort of 55 patients reporting withdrawal symptoms after prolonged overuse, 60% had used high-potency preparations on the face for extended periods and 42% had a history of oral corticosteroid use (Sheary, 2018, Dermatitis, PMID 29923852). The variable to which these data point is the mode of use—site, potency, and duration.

3-6. Clinical evidence for herbal medicine

In a multicenter, double-blind, randomized controlled trial, 91 patients with atopic dermatitis selected for a weak, easily fatigued, or hypersensitive constitution (體質, chejil—an individual's inherent physiological disposition; here the Japanese concept Kikyo, determined by questionnaire score) received 補中益氣湯, Bojungikgi-tang (Japanese: Hochu-ekki-to), or placebo for 24 weeks while continuing their existing treatment. Total skin severity scores did not differ between the two groups. The total amount of topical anti-inflammatory agents used was significantly lower in the Bojungikgi-tang group (P<0.05), and the proportion of patients whose topical agent use increased by more than 50% from baseline was 3% (1/37) in the Bojungikgi-tang group and 18% (7/39) in the placebo group (P<0.05). — Kobayashi et al., 2010, Evid Based Complement Alternat Med (PMID 18955318)

The figures of 3% versus 18% represent an aggravation index defined by increased topical agent use, and this trial did not measure the number of relapses or the time to relapse. Kikyo is a Japanese concept of delicate constitution determined by questionnaire and is a different classification from the Sasang constitution (四象體質, Sasang chejil—the four-type constitutional classification of Sasang medicine).

The conclusions of systematic reviews are cautious. A Cochrane review of 28 studies with 2,306 participants found no conclusive evidence that oral or topical herbal medicine reduces the severity of eczema, and most of the studies carried a high risk of bias (Gu et al., 2013, PMID 24018636). A systematic review in JAAD reported that in 7 studies herbal medicine combined with conventional treatment was superior to conventional treatment alone and that in 2 the use of concomitant medication decreased, but stated that, because of the low quality of the studies, no conclusion supporting routine use could be drawn (Tan et al., 2013, PMID 23759835). A review in American Family Physician judged the evidence for integrative medicine in the treatment of atopic dermatitis to be insufficient (Frazier & Bhardwaj, 2020, PMID 32412211).

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4. Cross-Reading

When the two traditions are placed side by side, their explanatory structures overlap at several points. The microinflammation and molecular scar of the modern literature and the "root of the illness is not clean" (病根不淨, byeonggeun bujeong) and hyeolgi mipyeong, yeoyeol mijin of the classical sources all hold that a gap exists between healing on the surface and recovery beneath it. The triggers overlap in part. Food and worry (stress) appear on both lists, but the classical "bodily exertion" and the modern "contact allergens" do not correspond to each other.

The relation between avoidance and maintenance is something the author has drawn from reading the two bodies of evidence together. In the modern literature, the average effect of uniform dietary elimination was small, and, separately, twice-weekly proactive therapy and daily emollient use reduced relapse. The Neijing set the regulation of deficiency and excess as a therapeutic principle alongside its dietary prohibitions. Placing these results side by side permits the interpretation that avoiding triggers alone is insufficient and that the interval after healing must be managed separately.

The account of Yi Je-ma (李濟馬) adds one follow-up question to this comparison.

太陽人, 小便旺多, 則完實而無病. 太陰人, 汗液通暢, 則完實而無病. 少陽人, 大便善通, 則完實而無病. 少陰人, 飮食善化, 則完實而無病. The Taeyang person (太陽人), when urine is abundant; the Taeeum person (太陰人), when sweat flows freely; the Soyang person (少陽人), when the bowels move well; and the Soeum person (少陰人), when food is well digested—each is healthy and free of illness. — 東醫壽世保元, Dongui Suse Bowon, Sinchuk edition [17-16] (https://mediclassics.kr/books/182/volume/4#content_241)

Yi Je-ma presented urination, sweating, defecation, and digestion as the constitution-specific signs of health. In the same book, [2-17] states that when one "frequently rouses anger and frequently suppresses it" (頻起怒, 而頻伏怒), the place where that qi resides cannot remain stable, and the organs are injured (#content_57). Whether recovery of the constitution-specific signs of 完實, wansil—being whole and replete—could serve as an indicator predicting subsequent relapse risk is left as a research question for Section 5.

What can be carried into clinical practice is a way of explaining and observing. Relapse is not immediately judged to be treatment failure; the residual vulnerability and the triggers are examined together; triggers are identified individually through food diaries and patch testing rather than by uniform restriction; and the point at which the surface of the skin normalizes is presented as the beginning of the maintenance phase.

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5. What Needs to Be Verified

To carry the comparison in this paper over into clinical evidence, the following must be established.

1. The molecular scar in atopic dermatitis. Analyze tissue-resident memory T cells and the transcriptome of clinically healed atopic skin by the same methods as the psoriasis studies (single-cell sequencing; comparison of healed lesions, relapsed lesions, and adjacent normal skin).
2. Relapse outcomes of add-on herbal medicine. In randomized controlled trials adding herbal medicine to proactive maintenance therapy, measure the time to relapse and the number of relapses as primary outcomes.
3. The effect of constitutional selection. Compare whether the results of item 2 differ between a patient group selected by Sasang constitutional diagnostic criteria and an unselected group.
4. The predictive value of the signs of wansil. At the point when the skin normalizes, record the constitution-specific signs of wansil (urination, sweating, defecation, digestion) and prospectively follow their association with subsequent relapse risk.
5. The effect of individual trigger identification. Compare relapse rates between a group in which triggers are identified individually through food diaries and patch testing and a group given uniform avoidance education.

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Appendix. Source Cards

Three items are recorded separately on each card. Source verification is the level at which the author checked the quoted passage against the original material; study type is the form of the material; and certainty of evidence for the result is the strength with which that material supports the claims of this paper.

Source 1 [KM] Maiyi jianmo (脈義簡摩), vol. 3, "Pulses of Gojil and Sukjil" (痼疾宿疾脈) — Zhou Xuehai (周學海), Qing (淸)

• MEDICLASSICS: https://mediclassics.kr/books/285/volume/3#content_86
• Source verification: original text checked directly; translation by the author (no Korean translation available) | Study type: classical source (pulse-diagnosis literature) | Certainty of evidence for the result: not applicable (material for conceptual comparison)
• Key point: Distinction between gojil and sukjil; classification of scaling eruptions as external gojil; a residual state that appears when conditions are added.

Source 2 [KM] Shanghan mingli lun (傷寒明理論), vol. 3, "Nobok," ch. 50 (勞復 第五十) — Cheng Wuji (成無己), Jin dynasty (金)

• MEDICLASSICS: https://mediclassics.kr/books/198/volume/3#content_60
• Source verification: original text and Korean translation checked directly | Study type: classical source (convalescence from acute febrile disease) | Certainty of evidence for the result: not applicable (comparative material)
• Key point: In the chahu state of hyeolgi mipyeong, yeoyeol mijin, exertion, food, and worry bring about relapse.

Source 3 [KM] Dongui Bogam (東醫寶鑑), Japbyeong pyeon, vol. 3, "Residual Patterns of Cold Damage" (傷寒遺證) (quoting Neijing, "Re lun" 熱論) — Heo Jun (許浚), Joseon (1613)

• MEDICLASSICS: https://mediclassics.kr/books/8/volume/11#content_195
• Source verification: original text checked directly | Study type: classical source (febrile disease) | Certainty of evidence for the result: not applicable (comparative material)
• Key point: The prohibitions of sikbok are paired with the therapeutic principle of regulating deficiency and excess.

Source 4 [KM] Yizong jinjian: Waike xinfa yaojue (醫宗金鑑·外科心法要訣), vol. 71, "Four-Bend Wind" (四彎風); vol. 74, "Baekbi" (白疕) — Wu Qian (吳謙) et al., Qing (1742)

• MEDICLASSICS: https://mediclassics.kr/books/100/volume/11#content_119 ; https://mediclassics.kr/books/100/volume/14#content_185
• Source verification: original text and Korean translation checked directly | Study type: classical source (external medicine) | Certainty of evidence for the result: not applicable (description of disease patterns)
• Key point: The recurrence and slow response of samanpung; the dual cause of baekbi—external pathogen and internal blood dryness.

Source 5 [KM] Dongui Suse Bowon (東醫壽世保元), Sinchuk edition [2-17], [17-16] — Yi Je-ma (李濟馬), Joseon (1901)

• MEDICLASSICS: https://mediclassics.kr/books/182/volume/1#content_57 ; https://mediclassics.kr/books/182/volume/4#content_241
• Source verification: original text and Korean translation checked directly | Study type: classical source | Certainty of evidence for the result: not applicable (starting point for a research hypothesis)
• Key point: Repeated arousal and suppression of anger injures the organs; constitution-specific signs of 完實無病, wansil mubyeong (whole and replete, free of illness).

Source 6 [WM] Wollenberg A et al., 2018, J Eur Acad Dermatol Venereol, PMID 29533490

• Source verification: abstract | Study type: review | Certainty of evidence for the result: moderate
• Key point: Microinflammation and a pro-inflammatory cytokine milieu in apparently healed skin.

Source 7 [WM] Benezeder T, Wolf P, 2019, Semin Immunopathol, PMID 31673756

• Source verification: abstract | Study type: review | Certainty of evidence for the result: moderate
• Key point: The molecular scar of resolved psoriatic sites; cytokine reservoirs and TRM.

Source 8 [WM] Emmanuel T et al., 2024, Int J Mol Sci, PMID 38892277

• Source verification: abstract | Study type: original study (biopsy tissue and transcriptomic analysis) | Certainty of evidence for the result: moderate (small scale)
• Key point: Transcriptome not normalized despite histological normalization; 479 differentially expressed genes.

Source 9 [WM] Peng L et al., 2024, Clin Immunol, PMID 39067676

• Source verification: abstract | Study type: original study (single-cell sequencing) | Certainty of evidence for the result: moderate (small scale)
• Key point: Three candidate cell types for relapse within healed lesions.

Source 10 [WM] Oykhman P et al., 2022, J Allergy Clin Immunol Pract, PMID 35987995

• Source verification: abstract | Study type: systematic review and meta-analysis | Certainty of evidence for the result: low (GRADE)
• Key point: Slight average improvement from uniform dietary elimination (50% vs 41%).

Source 11 [WM] Warshaw EM et al., 2022, J Am Acad Dermatol, PMID 35551968; 2023, Dermatitis, PMID 36917534

• Source verification: abstract | Study type: retrospective analysis (patients referred for patch testing) | Certainty of evidence for the result: moderate (association)
• Key point: Higher proportion with a history of atopic dermatitis among patients positive to personal hygiene product ingredients.

Source 12 [WM] Tian J et al., 2026, Science, PMID 41855337 (commentary: Gaudenzio N, Basso L, PMID 41855349)

• Source verification: abstract | Study type: original study (mechanistic study in a mouse model) | Certainty of evidence for the result: clinical application in humans not established
• Key point: A Pdyn+ sympathetic–eosinophil axis mediates stress-induced exacerbation of dermatitis.

Source 13 [WM] Marek-Jozefowicz L et al., 2022, Int J Mol Sci, PMID 35054853

• Source verification: abstract | Study type: review | Certainty of evidence for the result: moderate
• Key point: The brain–skin axis in psoriasis; the HPA axis and the local stress system.

Source 14 [WM] Lax SJ et al., 2022, Cochrane Database Syst Rev, PMID 35275399

• Source verification: abstract | Study type: systematic review and meta-analysis | Certainty of evidence for the result: moderate (relapse outcome of proactive therapy, GRADE)
• Key point: Twice-weekly proactive therapy RR 0.43 (58%→25%).

Source 15 [WM] Lax SJ et al., 2024, Cochrane Database Syst Rev, PMID 39105474; Clin Exp Allergy, PMID 39219446 (PMC11629051)

• Source verification: abstract and full text of the Clin Exp Allergy version | Study type: systematic review and network meta-analysis | Certainty of evidence for the result: low for the short-term atrophy outcome; long-term atrophy from pairwise comparisons in 3 trials
• Key point: No evidence of increased atrophy with short-term use; long-term atrophy 6/2,044 in the corticosteroid groups vs 0/2,025 in the calcineurin inhibitor groups (p=0.031).

Source 16 [WM] Schmitt J et al., 2011, Br J Dermatol, PMID 20819086

• Source verification: abstract | Study type: systematic review and meta-analysis | Certainty of evidence for the result: not reported (based on the abstract)
• Key point: Twice-weekly tacrolimus regimen RR 0.78.

Source 17 [WM] Weber TM et al., 2015, J Drugs Dermatol, PMID 25942666

• Source verification: abstract | Study type: randomized controlled trial (45 participants) | Certainty of evidence for the result: low (small scale)
• Key point: Relapse 21% in the daily emollient group vs 65% in the control group.

Source 18 [WM] Sheary B, 2018, Dermatitis, PMID 29923852

• Source verification: abstract | Study type: retrospective cohort (55 patients) | Certainty of evidence for the result: low
• Key point: In the withdrawal-symptom group, 60% had long-term use of high-potency preparations on the face and 42% a history of oral corticosteroid use.

Source 19 [KM-JP] Kobayashi H et al., 2010, Evid Based Complement Alternat Med, PMID 18955318

• Source verification: abstract | Study type: randomized controlled trial (91 enrolled, 77 completed) | Certainty of evidence for the result: low (single trial, no direct measurement of relapse)
• Key point: No difference in skin scores; reduced topical agent use; aggravation index defined by increased topical agent use 3% vs 18%.
• Formula mapping: Hochu-ekki-to = Bojungikgi-tang (補中益氣湯)

Source 20 [WM] Gu S et al., 2013, Cochrane, PMID 24018636; Tan HY et al., 2013, J Am Acad Dermatol, PMID 23759835; Frazier W, Bhardwaj N, 2020, Am Fam Physician, PMID 32412211

• Source verification: abstract | Study type: two systematic reviews and one clinical review | Certainty of evidence for the result: low (high risk of bias in included studies)
• Key point: Lack of conclusive evidence for the effect of herbal medicine; evidence for integrative medicine judged insufficient.

Source 21 [WM] Werfel T et al., 2016, J Dtsch Dermatol Ges, PMID 26713654

• Source verification: abstract | Study type: consensus-based guideline (S2k) | Certainty of evidence for the result: expert consensus
• Key point: Definition as chronic relapsing; genetic predisposition and triggers.

Source 22 [WM] Habif TP, Clinical Dermatology, 5th ed., pp.165, 182

• Source verification: checked against the textbook original in the author's library | Study type: textbook | Certainty of evidence for the result: not applicable (clinical description)
• Key point: Environmental stress applied to vulnerable skin; the clinical value of explaining stress as an aggravating factor rather than a cause.

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Choi Jang-hyuk | Doctor of Korean Medicine · Director, Dongjedang Korean Medicine Clinic · Method: DJD multi-literature cross-research