I. Introduction
Cold hypersensitivity, often referred to as “coldness”, is characterized by an abnormal sensitivity to cold temperatures, particularly affecting specific body parts, and worsening with decreasing ambient temperature1. Common sites of involvement include the hands, feet, lower abdomen, genitals, lumbar region, and back. The prevalence of cold hypersensitivity varies significantly across different populations, with higher rates observed in Asian populations compared to Caucasian populations. Additionally, women are more frequently affected than men, with a reported ratio of 3:22. In Korea, approximately 12% of the general population experiences this condition, primarily affecting the hands or feet3. While cold hypersensitivity is not a life-threatening condition, it can significantly impact quality of life. Further, it may manifest in individuals with conditions such as preterm labor, anemia, chronic gastritis, and degenerative arthritis4,5. The exact etiology of cold hypersensitivity remains unclear, but it is generally believed to be related to vasoconstriction triggered by mental stress, neurovascular disorders, or underlying medical factors6.
In conventional medicine, cold hypersensitivity is often considered a clinical manifestation of Raynaud’s phenomenon, an exaggerated physiological response to cold exposure or emotional stress. However, there are several difficulties to diagnose and treat cold hypersensitivity as Raynaud’s phenomenon in clinical practice. The diagnostic criteria for Raynaud’s phenomenon require the presence of color change in the extremities, while it has been reported that approximately 60% of patients with cold hypersensitivity do not meet the diagnostic criteria7. Moreover, treatments for primary Raynaud’s phenomenon are mostly lifestyle management (avoid coldness, quit smoking) or vasodilatory drugs calcium channel blockers, although the adverse vasodilatory effects such as headache, flushing or hypotension are common for the drug8.
However, in Korean Medicine, cold hypersensitivity has been traditionally recognized as a key symptom for pattern identification, and there were several recent studies to standardize the diagnosis of cold hypersensitivity with digital infrared thermographic imaging (DITI)9,10. Treatment options for cold hypersensitivity in Korean Medicine primarily involve herbal medicine, acupuncture, and moxibustion11. Among various herbal formulas, Ongyeong-tang (溫經湯), Danggwisaeyeok-tang (當歸四逆湯), Gyejibokryeong-hwan (桂枝茯苓丸), and Yijung-tang (理中湯) are commonly recommended for cold hypersensitivity in the hands and feet, according to a recent clinical practice guideline12. There were also several case reports for treating cold hypersensitivity using herbal medicine such as Dojukgangki-tang (導赤降氣湯)13 and Palmijihwang-tang (八味地黃湯)14.
Up to date, one randomized controlled study had analyzed the effect of Ongyeong-tang on cold hypersensitivity in hands and feet, which reported no significant difference between placebo group15. However, the study did not differentiate the clinical pattern of each patient, which might be crucial in the effect of the herbal medicine. In addition, no previous case study has been reported on Ongyeong-tang and cold hypersensitivity, to our knowledge. Therefore, we herein aim to report a case of cold hypersensitivity particularly affecting the lower abdomen, hands, and feet with the pattern of “upper body heat and lower body cold”, which has been clearly improved and well-maintained after treatment with Ongyeong-tang.
II. Report of the case
1. Characteristics of the Patient and Medical History
A 68-year-old woman presented to our hospital with severe cold hypersensitivity, primarily affecting her lower abdomen, hands, and feet. Despite the absence of color changes, palpable coldness was noted in these areas. The patient reported a lifelong history of these symptoms, which worsened during winter months and persisted even in warmer seasons. She often required socks, even in summer, due to cold feet.
In addition to cold hypersensitivity, the patient had a history of breast cancer (pT2N3M0, ER+/ PR+/HER+) treated with mastectomy, chemotherapy, and radiation therapy. She also had comorbidities including diabetes mellitus, hyperlipidemia, non-alcoholic fatty liver disease, osteoporosis, and a history of COVID-19. Her current medications included letrozole, pregabalin, metformin, linagliptin, fenofibrate, pravastatin sodium, calcium carbonate, cholecalciferol, and ibandronate. The patient was a non-smoker and non-drinker. This study adhered to the Case Report Guideline and was approved by the Institutional Review Board of Daejeon University Korean Medical Hospital (DJDSKH-24-E-16) with the patient’s informed consent.
2. Diagnosis
Regarding the patients’ long history of symptoms (since childhood), localized coldness (lower abdomen, both hands and feet), and normal blood test results (Appendix 1), we ruled out systemic diseases (such as autoimmune disorders) or medication side effects that may cause cold hypersensitivity. In addition, given the absence of color changes in the skin, the patient’s condition could not meet the diagnostic criteria for Raynaud’s phenomenon.
However, digital infrared thermographic imaging (DITI) revealed noticeably lower surface temperatures in the lower abdomen, hands, and feet. To objectively assess these temperature differences, specific acupoints were selected as assessment and reference points, as presented: PC8 (勞宮) and LU4 (俠白) for the hands, LR3 (太衝) and ST32 (伏兎) for the feet, and CV6 (氣海) and CV17 (膻中) for the lower abdomen, according to previous studies9,10,12. Considerably different surface temperatures were observed between the assessment and reference points: -1.5 ℃ in the lower abdomen (CV6-CV17), -2.6 ℃ in the hands (PC8-LU4), and -2.0 ℃ in the feet (LR3-ST32). These findings followed the previously established diagnostic criteria for cold hypersensitivity; which cut-off values were -0.3 ℃ in the hands (PC-LU4, sensitivity 94.0%, specificity 90.0%) and -2.0 ℃ in the feet (LR3-ST32, sensitivity 94.0%, specificity 76.0%)9,10,12. While there are no established diagnostic criteria for cold hypersensitivity in the lower abdomen, a previous study had selected CV17 and CV6 as assessment and reference acupoints13. DITI examinations were conducted using an IRIS-XP device (Medicoa, Hanam, South Korea) in a controlled environment.
Subjective assessment of overall coldness using a numeric rating scale (NRS) yielded a score of 8 at baseline. While the patient experienced cold sensitivity in the lower extremities, warmth was noted in the face and neck. She also reported frequent hot flashes, particularly during stress. Tongue examination revealed a mild pinkish-red color and a weak, rapid pulse. Abdominal examination was unremarkable, with coldness confined to the lower abdomen. Based on these clinical findings, the patient was diagnosed with an imbalance characterized by “upper body heat and lower body cold (上熱下寒)”.
3. Intervention
Based on the pattern diagnosis of “upper body heat and lower body cold”, a modified formulation of Ongyeong-tang was prescribed to alleviate the cold hypersensitivity of the patient, which was administrated orally three times daily for approximately 12 weeks. Detailed compositions of the herbal formula and its daily dose is presented in Table 1. Concurrently, the patient received regular acupuncture with dry needling and indirect moxibustion sessions, twice weekly for 30 minutes each (using 0.20×30 needles and Hwangto moxibustion from DongBang Co., Seoul, South Korea). Specific acupoints used are presented in Fig. 2.
Table 1
Composition of Ongyeong-tang
| Scientific name | Herbal name | Chinese name | Daily dose* |
|---|---|---|---|
| Liriope platyphylla Wang et Tang | Liriopis Tuber | 麥門冬 | 27.0 g |
| Pinellia ternata Breitenbach | Pinelliae Tuber | 半 夏 | 27.0 g |
| Cinnamomum cassia (L.) C. Presl. | Cinnamomi Ramulus | 桂 枝 | 13.5 g |
| Angelica gigas Nakai | Angelicae Gigantis Radix | 當 歸 | 9.0 g |
| Ligusticum officinale (Makino) Kitag | Ligustici Chuanxiong Rhizoma | 川 芎 | 9.0 g |
| Paeonia lactiflora Pall. | Paeoniae Radix Alba | 白芍藥 | 9.0 g |
| Panax ginseng C.A. Mey. | Ginseng Radix | 人 參 | 9.0 g |
| Equus africanus asinus Linnaeus | Asini Corii Colla | 阿 膠 | 9.0 g |
| Paeonia suffruticosa Andrews | Moutan Cortex | 牧丹皮 | 9.0 g |
| Zingiber officinale Roscoe | Zingiberis Rhizoma | 生 薑 | 9.0 g |
| Glycyrrhiza uralensis Fischer | Glycyrrhizae Radix et Rhizoma | 甘 草 | 9.0 g |
| Evodia rutaecarpa Bentham | Evodiae Fructus | 吳茱萸 | 9.0 g |
4. Outcomes
After approximately 12 weeks of treatment (week 13), the patient’s subjective feeling on cold hypersensitivity has noticeably improved, with the NRS score decreased from 8 to 1 and DITI analysis revealed a clear improvement in surface temperature across all affected areas (Fig. 1). Specific temperature difference in each region was -1.4 ℃ for the lower abdomen (CV6-CV17), -0.3 ℃ for the hands (PC8-LU4), and -1.0 ℃ for the feet (LR3-ST32) (Fig. 2B). Detailed surface temperature for each acupoints are presented in Table 2. Additionally, the severity of hot flashes has diminished.
Fig. 2
Acupoints used for treatments and assessments.
(A) Acupoints used for acupuncture (yellow) and moxibustion (red). No acupuncture was applied to the patients’ left arm considering the history of mastectomy with lymph nodes dissection. (B) Acupoints used for assessment (▲) and reference points (●) in each region. The difference of surface temperature between assessment and reference points were measured.
Table 2
Surface Temperature for Each Acupoint
| Date\Region | Lower abdomen | Hands | Feet | ||||||
|---|---|---|---|---|---|---|---|---|---|
|
|
|||||||||
| CV6 | CV17 | CV6-CV17 | PC8* | LU4* | PC8-LU4 | LR3* | ST32* | LR3-ST32 | |
| Week 1 | 28.9 | 30.4 | -1.5 | 25.8±0.2 | 28.5±0.2 | -2.6 | 24.6±0.3 | 26.6±0.2 | -2.00 |
| Week 13 | 29.0 | 30.4 | -1.4 | 28.0±0.2 | 28.4±0.1 | -0.3 | 26.5±0.5 | 27.6±0.0 | -1.0 |
| Week 30 | 30.9 | 30.8 | +0.1 | 29.8±0.0 | 29.2±0.1 | +0.6 | 29.8±0.1 | 29.2±0.5 | +0.5 |
Given the significant improvement in symptoms, we did not further prescribed Ongyeong-tang but maintained acupuncture and moxibustion. A follow-up assessment conducted about 17 weeks after discontinuation of Ongyeong-tang (week 30) demonstrated sustained improvement; +0.1 ℃ for the lower abdomen, +0.6 ℃ for the hands, and +0.5 ℃ for the feet. The NRS score remained at 1, and the patients no longer complained of the cold hypersensitivity. No adverse effects or abnormal laboratory findings were observed during the treatment period, and there were no signs of breast cancer recurrence (Appendix 1).
III. Discussion and Conclusion
This case report presents a 68-year-old woman with severe cold hypersensitivity affecting the lower abdomen, hands, and feet. After approximately 12 weeks of treatment with Ongyeong-tang, the improvement was clearly observed in both subjective symptoms, as assessed by the Numeric Rating Scale (NRS), and objective measures, such as digital infrared thermographic imaging (DITI). Importantly, these improvements were sustained even after discontinuation of the herbal formula. No adverse effects or abnormal laboratory findings were reported throughout the treatment and follow-up periods.
Ongyeong-tang was originally described in the “Synopsis of Prescriptions of the Golden Chamber (金匱要略)” written by Zhang Zhongjing in the early third century, and also introduced as Chokyungsan in Heo Jun’s “Treasured Mirror of Eastern Medicine (東醫寶鑑)”16. This herbal formula is primarily used to treat lower abdominal coldness and improves gynecologic conditions such as menstrual disorders, abnormal uterine bleeding, and infertility, with its efficacy supported by several clinical studies17,18. While relatively few studies have been specifically investigated Ongyeong-tang for cold hypersensitivity, a randomized study on postmenopausal women highlighted its benefits on improving cold sensation by increasing the blood flow in the lower extremities19. Interestingly, the study also showed that Ongyeong-tang reduced excessive heat in the upper half of the body, suggesting its potential use for patients with hypogastric cold hypersensitivity and upper body hot flashes. Similarly, another randomized controlled study observed Ongyeong-tang significantly improved cold hypersensitivity in feet but not in hands15. These findings align with the observed effects of Liriope Platyphylline and Pinellia ternata, the primary components of Ongyeong-tang, which extracts have been shown to ameliorate vascular dysfunction in animal models20. These clinical and pre-clinical studies may support the description in the “Synopsis of Prescriptions of the Golden Chamber (金匱要略)” that Ongyeong-tang “cures heat of the upper half of the body and the chilly sensation of the lower half of the body”21. Currently, other commonly used herbal medicine for cold hypersensitivity such as Gyejibokryeong-hwan (桂枝茯苓丸) and Danggwisaeyeok-tang (當歸四逆湯) lacks evidence on improving the clinical condition mentioned above.
The patient herein presented with cold hypersensitivity along hot flashes in the face, leading us to identify the pattern as “upper body heat and lower body cold (上熱下寒)” and prescribe Ongyeong-tang. To address the heat sensation in the upper body, we increased the dosage of Cinnamomi Ramulus, based on the principles of Yoshimasu Nangai (吉益南涯)22. As these symptoms had been present since childhood and were not exacerbated by specific events, we attributed the case of cold hypersensitivity to constitutional factors rather than menopause or various breast cancer treatments (total mastectomy, radiotherapy, chemotherapy, and anti-hormonal therapy).
We were somewhat concerned about long-term administration of Ongyeong-tang due to the potential estrogen-like effects of the herbal medicine and its component (glycyrrhizae radix, cinnamomi cortex, evodiae fructus, and zingiberis rhizoma)23, which could potentially interact with letrozole. However, there were also studies reporting that glycyrrhiza radix may prevent estrogen-related carcinogenesis and that cinnamon cortex exhibits anti-estrogenic properties24,25. Therefore, we closely monitored CEA and CA15-3 levels as markers for breast cancer recurrence, which remained within the normal range (Appendix 1). Additionally, regular CT scans did not reveal any signs of cancer recurrence.
Alongside Ongyeong-tang, the patient was also received acupuncture and moxibustion (Fig. 2A). However, we primarily attribute the improvement in cold hypersensitivity to Ongyeong-tang, as the patient had previously undergone acupuncture and moxibustion for CIPN and cancer-related fatigue at our hospital, using the same acupoints. Nonetheless, we observed that the surface temperatures in each body region further improved after discontinuing Ongyeong-tang, suggesting a potential synergetic effect of acupuncture and moxibustion. This is evidenced by another study which reported that acupoints used in this study (LI4, ST36, and SP6) are commonly used for cold hypersensitivity in Korean medicine26, while the underlying mechanisms are yet unclear.
Although Ongyeong-tang is a widely prescribed herbal medicine for cold hypersensitivity in Korean medicine, no case reports have been published using DITI assessment. This case study is unique due to the dramatic symptom improvement, relatively long-term prescription period, follow-up assessment using objective tools, and regular blood tests for safety monitoring. We recommend Ongyeong-tang as a treatment option for patients with cold hypersensitivity, especially those who features clinical pattern of “upper body heat and lower body cold”. We hope this study may provide an evidence in decision-making process in clinical fields for treating cold hypersensitivity.
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