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 Table of Contents 
Year : 2020  |  Volume : 9  |  Issue : 7  |  Page : 3773-3775  

Herbal medicine-induced multiple pulmonary pseudotumors

1 Department of Education and Support for Regional Medicine; Department of Kampo Medicine; Department of Kampo and Integrative Medicine, Tohoku University School of Medicine, Sendai, Japan
2 Department of Education and Support for Regional Medicine, Tohoku University School of Medicine, Sendai, Japan
3 Department of Respiratory Medicine, Red Cross Ishinimaki Hospital, Ishinomaki, Japan
4 Department of Pathology, Red Cross Ishinimaki Hospital, Ishinomaki, Japan
5 Department of Education and Support for Regional Medicine; Department of Kampo Medicine, Tohoku University School of Medicine, Sendai, Japan

Date of Submission19-Mar-2020
Date of Decision25-Apr-2020
Date of Acceptance08-May-2020
Date of Web Publication30-Jul-2020

Correspondence Address:
Prof. Shin Takayama
Department of Integrative and Kampo Medicine, Tohoku University Graduate School of Medicine, Seiryo-machi 1-2, Aoba-ku, Sendai, Miyagi 980-8575
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jfmpc.jfmpc_420_20

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Japanese herbal medicines (HMs) cause adverse drug reactions (ADRs); however, solid nodule formation is uncommon. In this report, we aimed to show that ADRs with HM can mimic lung cancer. A 63-year-old man complained of back pain. His physician prescribed a traditional Japanese HM, Keishikajutsubuto, which alleviated his symptoms. After 4 weeks, a chest radiograph showed multiple lung nodules that were absent 6 months earlier; the patient did not have cough, fever, or dyspnea. Computed tomography (CT) showed multiple, bilateral lung nodules; however, blood tests and lung biopsy showed no abnormalities, ruling out interstitial pneumonia and lung cancer. Three months after the HM was discontinued, CT showed resolution of the lesions. Interstitial pneumonia was reported as a side effect of HM; however, no such side effect was reported for Keishikajutsubuto. When a patient presents with multiple lung nodules, a side effect of HM should be considered as a differential diagnosis.

Keywords: Adverse reaction, herbal medicine, lung nodule, pseudotumor

How to cite this article:
Takayama S, Akaishi T, Hanagama M, Itakura Y, Arita R, Kikuchi A, Ishii T. Herbal medicine-induced multiple pulmonary pseudotumors. J Family Med Prim Care 2020;9:3773-5

How to cite this URL:
Takayama S, Akaishi T, Hanagama M, Itakura Y, Arita R, Kikuchi A, Ishii T. Herbal medicine-induced multiple pulmonary pseudotumors. J Family Med Prim Care [serial online] 2020 [cited 2021 Jul 29];9:3773-5. Available from: https://www.jfmpc.com/text.asp?2020/9/7/3773/290812

  Introduction Top

Approximately 90% of Japanese physicians use traditional Japanese herbal medicines (HMs) with approval from the Japanese Ministry of Health, Labour and Welfare. Clinical practice guidelines published by medical societies in Japan recommend HM for several conditions.[1] Adverse drug reactions (ADRs) associated with HM have been reported and vary in terms of clinical manifestations. The incidence of liver disorders is 0.16%[2] and that of interstitial pneumonia is 0.08%.[3] However, the formation of solid nodules, which can be misdiagnosed as end-stage metastatic cancer, is uncommon. This case report aims to inform clinicians that ADRs with HM can mimic end-stage metastatic lung cancer. Ethical and institutional permission: This case report was approved by the Institutional Review Board of Tohoku University School of Medicine (No. 19272).

  Case Report Top

A healthy 63-year-old man presented with spontaneous back pain. He was prescribed a traditional Japanese HM, Keishikajutsubuto, which is usually prescribed for neuralgia and arthralgia.[4] Keishikajutsubuto contains the following crude drugs: JP Cinnamon Bark, JP Peony Root, JP Atractylodes lancea Rhizome, JP Jujube, JP Glycyrrhiza, JP Ginger, and JP Powdered Processed Aconite Root (JP: The Japanese Pharmacopoeia). His back pain was alleviated by HM. After 4 weeks, during a medical checkup of the patient, his chest X-ray revealed multiple solid nodules in both lungs. In a retrospective review of a chest X-ray 6 months earlier, no lung nodules were observed. During the entire treatment period, the patient did not have cough, fever, or dyspnea.

To further investigate the lesions, computed tomography (CT) scanning of the chest was performed; this revealed multiple irregular tumors in the bilateral lung. An irregular tumor with a diameter of 53 mm was observed in the S2 area of the right upper lung lobe. The tumor, with spicule formation, was connected to the interlobar pleura. Furthermore, right hilar lymph node enlargement indicated lymph node metastasis. The findings of the CT scan suggested stage-IV metastatic lung cancer [Figure 1]a. Based on bronchoscopic biopsy, the extracted specimen revealed no remarkable findings suggestive of malignancy; it only showed the infiltration of inflammatory cells [Figure 1]b, [Figure 1]c, [Figure 1]d. Other laboratory tests presented no findings suggestive of systemic inflammation (assessed using white blood cell count and analyses of serum amyloid A and C-reactive protein) or connective tissue diseases (assessed based on antinuclear antibody, rheumatoid factor, antineutrophil cytoplasmic antibody, and sialylated carbohydrate antigen KL-6). Based on the findings of the CT scan, the man was presumptively diagnosed with stage-IV metastatic lung cancer. However, the bronchoscopic biopsy revealed no malignancy, and the laboratory tests presented no findings of systemic inflammation or connective tissue diseases. At this point, an association with the HM was suspected.
Figure 1: Computed tomography (CT) scans and stained histopathological sections of the chest before and after discontinuation of the suspected medicine. (a) CT scan during treatment with herbal medicine (HM). (b, c, and d) Hematoxylin and eosin-stained tissue from the bronchoscopic biopsy. (e) CT scan, 3 months after discontinuing HM. (f) CT scan, 6 months after discontinuing HM

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The HM was discontinued; subsequently, the multiple nodules gradually decreased in size and some disappeared. The chest CT scan 3 months after the discontinuation of the HM revealed shrinkage of multiple nodular lesions [Figure 1]e. All the lesions fully disappeared, as observed in the latest CT scan of the chest 6 months after the discontinuation of HM [Figure 1]f. The definitive diagnosis was HM-induced multiple lung pseudotumor.

  Discussion Top

Japanese physicians can prescribe 148 types of HM, which are covered under the National Health Insurance System. HMs cause a variety of clinical ADRs, although severe ADRs are not frequent. The most common ADR of HM is hypokalemia, caused by medicines containing licorice.[5],[6],[7] The most severe ADR associated with HM is interstitial pneumonia, caused by the combination therapy of interferon-β and Shosaikoto (which contains the following crude drugs: JP Bupleurum Root, JP Pinellia Tuber, JP Scutellaria root, JP Jujube, JP Ginseng, JP Glycyrrhiza, and JP Ginger).[4],[8] A crude drug of Scutellaria root is suspected as a cause of HM-induced pneumonitis;[9] however, Keishikajutsubuto does not contain Scutellaria root. Furthermore, HM-induced pneumonitis manifests as interstitial pneumonia, and there are no reports of multiple lung nodular lesions caused by HM. In this case, the histopathological evaluation of the bronchoscopically extracted specimen revealed no cellular dysplasia. The multiple lesions completely disappeared after discontinuing the suspected medicine, and nodular lesions were confirmed not to be metastatic lung cancer.

Primary care physicians have many opportunities to treat patients with lung nodules. They also have opportunities to prescribe HMs or treat patients who have taken HMs in clinical practice.[10],[11],[12],[13],[14] If the patient started new drugs such as HMs before the appearance of lung lesions, an ADR should be one of the differential diagnoses. If physicians incidentally identify such multiple nodular lesions without clinical symptoms, systemic inflammation, or signs of malignancy in a patient, the history of drug use should be reviewed. In such cases, before considering surgical interventions, the suspected drugs should be discontinued. Based on this case report, we alert physicians to the fact that ADRs caused by HM can mimic end-stage metastatic lung cancer. When a patient presents with multiple lung nodules, a side effect of HM should be considered as a differential diagnosis.

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Conflicts of interest

S. T., A. K., and T. I. belong to the Department of Kampo and Integrative Medicine, Tohoku University School of Medicine. The department received a grant from Tsumura & Co, a Japanese manufacturer of Kampo medicine which was used as per Tohoku University rules.

  References Top

Takayama S, Arita R, Kikuchi A, Ohsawa M, Kaneko S, Ishii T. Clinical practice guidelines and evidence for the efficacy of traditional Japanese herbal medicine (Kampo) in treating geriatric patients. Front Nutr 2018;5:66.  Back to cited text no. 1
Arai I, Hagiwara Y, Motoo Y. Estimated incidence of adverse reactions to Kampo medicines in randomized controlled clinical trials. Traditional Kampo Med 2018;5:106-12.  Back to cited text no. 2
Nogami T, Fujimoto M, Shimada Y, Watari H, Kitahara H, Kimbara Y, et al. Incidence of kampo medicine-induced interstitial pneumonia: 10 year retrospective study at a university hospital kampo medicine department. Traditional Kampo Med 2019;6:26-31.  Back to cited text no. 3
STORK [homepage on the Internet] Department of Pharmacognosy, Phytochemistry and Narcotics (DPPN), National Institute of Health Sciences (NIHS) of Japan and National Institutes of Biomedical Innovation, Health and Nutrition (NIBIOHN) c2001-10 [updated 2018 Oct 23; cited]. Available from: http://mpdb.nibiohn.go.jp/stork/.  Back to cited text no. 4
Mumoli N, Cei M. Licorice-induced hypokalemia. Int J Cardiol 2008;124:e42-4.  Back to cited text no. 5
Meltem AC, Figen C, Nalan MA, Mahir K, Sebnem B, Mehlika I, et al. A hypokalemic muscular weakness after licorice ingestion: A case report. Cases J 2009;2:8053.  Back to cited text no. 6
Shintani S, Murase H, Tsukagoshi H, Shiigai T. Glycyrrhizin (licorice)-induced hypokalemic myopathy. Report of 2 cases and review of the literature. Eur Neurol 1992;32:44-51.  Back to cited text no. 7
Ji FP, Li ZX, Deng H, Xue HA, Liu Y. Diagnosis and management of interstitial pneumonitis associated with interferon therapy for chronic hepatitis C. World J Gastroenterol 2010;16:4394-9.  Back to cited text no. 8
Enomoto Y, Nakamura Y, Enomoto N, Fujisawa T, Inui N, Suda T. Japanese herbal medicine-induced pneumonitis: A review of 73 patients. Respir Investig 2017;55:138-44.  Back to cited text no. 9
Takayama S, Akaishi T, Nozaki H, Suzuki S, Arita R, Saito N, et al. Characteristics and course of patients treated with Kampo medicine in the department of general medicine. J Gen Fam Med. 2020;00:1-8.  Back to cited text no. 10
Numata T, Miura K, Akaishi T, Arita R, Ishizawa K, Saito N, et al. Successful treatment of myalgic encephalomyelitis/chronic fatigue syndrome with chronic febricula using the traditional Japanese medicine Shosaikoto. Intern Med 2020;59:297-300.  Back to cited text no. 11
Iwasaki K, Kurachi M, Nogami T, Takayama S. Traditional Chinese therapy initiates oral feeding in a stroked woman after three years of nasogastric tube feeding. J Family Med Prim Care 2019;8:3059-60.  Back to cited text no. 12
[PUBMED]  [Full text]  
Iwasaki K, Takayama S. Hemp seed pill may improve chronic constipation of the elderly and reduce the burden of helpers. J Family Med Prim Care 2019;8:2150.  Back to cited text no. 13
[PUBMED]  [Full text]  
Akaishi T, Takayama S, Ohsawa M, Kikuchi A, Arita R, Nakashima I, et al. Successful treatment of intractable menstrual migraine with the traditional herbal medicine tokishakuyakusan. J Gen Fam Med 2019;20:118-21.  Back to cited text no. 14


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