940

A Case of Oral Lichen Planus with Chronic Hepatitis C

Successfully Treated by Glycyrrhizin

Yumiko NAGAO'), Michio SATA2), Kyuichi TANIKAWA2)

and Tadamitsu KAMEYAMA1)"Department of Oral Surgery, 2'Second Department of Medicine,

Kurume University School of Medicine, Fukuoka, Japan

(Received: April 21, 1995)(Accepted: June 8, 1995)

Key words: oral lichen planus, chronic hepatitis C, glycyrrhizin

Introduction

Oral lichen planus (OLP) is an inflammatory and intractable disease with a long course associat-

ed with chronic hyperkeratosis. Although many causative factors have been mentioned1>-13>, the

pathogenesis of OLP is as yet unknown and a treatment for the disease has not been established.Because of reports pointing out the relation between lichen planus and chronic liver disease, we

studied the possible relation between OLP and hepatitis B virus (HBV) or hepatitis C virus (HCV) as

well as liver dysfunction, and found that patients with OLP were frequently infected with HCV").This finding implies that HCV infection by itself plays an important role in the development of OLP .We experienced a patient with chronic hepatitis C accompanied by OLP whose oral mucosal lesion

was greatly improved by administration of glycyrrhizin (SNMC®) which has been widely used intreatment for liver disease. The patient is interesting for investigating the causes of OLP and

therapeutics for OLP.

Case Report

Patient: A 49-year-old women.

First medical examination: 23 February 1994.

Chief complaint: Pain in the oral cavity on eating or drinking.Past history: She had acute hepatitis at the age of 30 years and was treated with therapy for

chronic hepatitis non A, non B by a local doctor.

Family history: Her elder sister has chronic hepatitis.Life history: No history of smoking or drinking.

Present illness: From about November 1993 the patient has had white papular lesions from the

bilateral lower gingivae to the buccal mucosae causing pain in the oral cavity on eating or drinking .Because of enlargement of the lesions and exacerbation of subjective symptoms,the patient consulted

a local medical doctor, who administrated an external drug and vitamins and observed her course.However, no improvement was seen and the patient was referred to the outpatient of oral surgery

clinic.

Physical examination: Among her physical findings, characteristic observations were: reticular

type of white papules on her bilateral buccal mucosae, upper and lower gingivae and floor of themouth; a specific finding of widespread erosions on her buccal mucosae (Fig . 1); and small white

Correspondence to : Yumiko NAGAO, D.D.S.

Department of Oral Surgery, Kurume University School of Medicine, 67 Asahi-machi, Kurume 830 , Japan

感染症学雑誌 第69巻 第8号

Treatment of Lichen Planus in Patient with HCV 941

Fig. 1 Lichen planus of the right buccal mucosa

before SNMC. White lesions of the bilateral

buccal mucosa accompanied by erosion.

Fig. 2 Photomicrograph illustrating the charac-

teristic features of the disease.

papules on the hard palate. All of the lesions caused severe contact pain. These lesions in the oralcavity were similar to those of lichen planus.

Other findings: Blood pressure, 120/80 mmHg; pulse, 60/min; no anemia in the palpable con-

juctiva; no jaundice in the bulbus conjunctiva; no findings such as palmar erythema, vascular spiderand pitting edema of either leg or foot; no abnormalities in heart and breath sounds; and no distentionor fluctuation of the abdomen. The liver was palpable by one finger breadth below the right costal

margin, the liver edge was blunt and, smooth, and its consistency was soft. The spleen was not

palpable and the area of spleen dullness was widened.Clinical examination: The results of peripheral blood examination included RBC, 508 x 104(/

mm3); Hb, 14.4 (g/dl); Ht, 43.6 (%); WBC, 7,000 (/mm3) (St, 6%; Seg, 38%; Ba, 1%; Lym, 47%; and

Mo, 8%); and platelets, 20.4 x 10' (/mm3). Blood chemical tests on serum showed AST, 53 (IU/1);ALT, 59 (IU/1); y-GTP, 28 (IU/1); LDH, 307 (IU/1); ZTT, 21.1 (U); total bililubin, 0.66 (mg/dl); total

protein, 8.8 (g/dl); albumin, 4.3 (g/dl); and y-globulin, 20.9 (%). HCV antibody was positive by thePHA method and serum HCVRNA was detected by the RT-"nested" PCR. The serum HCV RNA

level measured by branched DNA signal amplification assay (bDNA, Quantiplex a, Chiron Corp.,Emeryville, CA, USA) was 13.0 Meq/ml. The serum was negative for HBsAg and anti-nuclear

antibody. The serum levels of IgA, IgM and IgG were 276, 149, and 2658 mg/dl, respectively.

Ultrasonographic examination of the abdomen performed in the outpatient clinic revealed a hepatic

shape similar to that in chronic hepatitis while no intrahepatic spaceoccupying lesion was observed.The spleen was enlarged. The pathohistological findings in a specimen biopsy of the oral mucosal

lesion obtained when she visited outpatient clinic were similar to those of lichen planus (Fig. 2).

Clinical course and treatments: Since patients with chronic hepatitis C in general show only a

slightly abnormal ALT level without reduction of liver function, we decided to observe her coursewithout giving any specific treatment. For the OLP, we scaled her teeth and instructed her in tooth

brushing. And we prescribed Cepharanthir powder daily at a dose of 20 mg/day in two divided doses

after morning and evening meals. Simultaneously, a steroid for external use [Salcoat®] was used

to treat the site showing severe inflammation. These treatments were continued for 7 months,resulting in slight improvement of the oral mucosal lesion, recurrence of the erosion, enlargement of

the erosion in the bilateral buccal mucosa observed in October 1994, and ingestive disturbance due to

the intensive contact pain. Then, considering her chronic hepatitis C, SNMC® was administered daily

from October 1994 at a dose of 40 ml/day by intravenous injection. Two months after the therapy,erosion of the bilateral buccal mucosae had almost disappeared, the white papules observed over a

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942 Yumilco NAGAO et al

Fig. 3 Lichen planos of the right buccal mucosa

after SNMC.The size of the erosion is decreased.

Fig. 4 illustrates the result of liver function tests and the clinical course of the

patient.

wide range showed a tendency to disappear , and the pain was relieved (Fig. 3). During this period, nochanges were observed in serum levels of AST and ALT from those before SNMC administration .

Discussion

Erosive or bullous types of OLP generally cause intensive contact pains . OLP is generally treatedby systemic administration of various vitamins , adrenocortical hormones and tranquilizing agents, orlocal application of an ointment containing adrenocortical hormones''"' . Howerver, there is noestablished treatment for OLP at present. Among reports indicating the causes of lichen planus (LP) ,a number of them suggest a relationship between LP and chronic hepatitis5)-15) . Recently LP ac-companying HCV infection has been reported at a high incidence14•16'-L8' Furthermore , it has becomeevident that HCV infection is associated with various immunological disorders , including cryog-lobulinemia, autoimmune thyroiditis and Sjogren syndrome19)

Based on our finding that HCV infection is closely relates to a cause of OLP14), we think that

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Treatment of Lichen Planus in Patient with HCV 943

patients with OLP will possibly be improved by administrating SNMC® which has been used to treat

patients with viral hepatitis.SNMC(R) containing glycyrrhizin as a main ingredient is a drug to improve liver function and is

widely used for treating viral hepatitis. The efficacy of the drug has been established but its activity

has not been as yet. It has been reported that the drug has such effects as antiinflamatory activity

by glycyrretin, a metabolite of glycyrrhizin; interferon-derived antiviral activity; and activation of

natural killer cells. SNMC® was intravenously injected at a daily dose of 40 mg to the present patient.Two weeks after the administration, contact pain at the buccal mucosae had decreased and, two and

a half months after the treatment, the extent, color and pain of the OLP lesions were greatly

improved as shown in Fig. 3 . Serum levels of AST and ALT, which in the normal range before

administration of SNMC®, remained within normal limits during the treatment. This suggests that

OLP had improved because of the direct effect of SNMC® on OLP, not because of the secondary

effect of improvement in liver function by SNMC®. The results observed in the present study suggestthat SNMC® is effective for treatment of OLP associated with HCV infection. The effect of the drug

on the pathology should be clarified by further case studies.

References

1) Scully, C.& Kom, E. L.: Lichen planus. review and update on pathogenesis. J. Oral. Pathol. 14: 431-458, 1985.2) Brody, L.: Electron microscopic demonstration of bacteria in the skin of patients with lichen ruber planus. Nature.

207: 96, 1965.3) Neumann, J. B., Holmstrup, P.& Pindborg, J. J.: Smoking habits of 611 patiens with oral lichen planus. Oral. Surg.

43: 410, 1977.4) Jolly, M.: Lichen planus and its association with diabetes mellitus. Med. J. Aust. 1: 990, 1972.5) Rebora, A., Patri, P., Rampini E., et al.: Erosive lichen planus and cirrhotic hepoatis. It. Gen. Rev. Dermatol. 15:

123-131, 1978.6) Rebora, A.: Lichen planus and the liver. Lancet. 1: 805, 1981.7) Rebora, A.& Rongioletti, F.: Lichen planus and chronic active hepatitis. J. Am. Acard. Dermatol. 10: 840-841,

1984.8) Rebora, A.& Rongioletti, F.: Lichen planus and chronic active hepatitis. Acta. Germ. Venereol. 64: 52-56, 1984.9) Rebora, A.: Lichen planus and the liver. Acta. Derm. Venereol. 64: 365, 1984.

10) Cottoni, F., Solonas, A., Piga, M. R., Tocco, A., Lissia, M.& Cerimele, D.: Lichen planus, chronic liver disease andimmunologic involvement. Arch. Dermatol. Res. 280: 55-60, 1988.

11) Rebora, A.: Lichen planus and the liver. Int. J. Dermatol. 31: 392-395, 1992.12) Gandolfo, S., Carbone, M., Zulian, P., Brocoletti, R. Carrozzo, M.: Lichen planus orale e patoloia epatica. Parte

II-Correlazioni clinico-statistiche tra manifestazioni orali e danno etatico. Minerva. Stomatol. 41: 209-213, 1992.13) EL, Kabir, M., Sully, C., Porter, S., Porter, K.& Macnamara, E.: Liver function in UK patients with oral lichen

planus. Clin. Exp. Dermatol. 18: 12-16, 1993.14) Nagao, Y., Sata, M., Tanikawa, K., Itho, K.& Kameyama, T.: Lichen planus and Hepatitis C virus in the Northern

Kyushu region of Japan. Eur. J. Clin. (in press)15) Okamoto, H., Okada, S., Sugiyama, Y., Tanaka, T., Sugai, Y., Akahane, Y., et al.: Detection of hepatitis C virus

RNA by a two-stage polymerase chain reaction with two pairs of primers deduced from the 5'-non cording region.Japan. J. Exp. Med. 60: 215-222, 1990.

16) Ferguson, M.M., Simpson, N.B.& Hammersley, N.: The treatment of erosive lichen planus with a retinoid-etretinate. Oral. Surg. 58: 283-287, 1984.

17) Agner, T., Fogh, H.& Weismann, K.: The relation between lichen planus and hepatitis C. A case report. Acta.Derm. Venereol. 72: 380, 1992.

18) Jubert, C., Pawlotsky, J. M., Pouget, F., Andre, C., Deforges, L., Bretagne, S., et al.: Lichen planus and hepatitis Cvirus-related chronic active hepatitis. Arch. Dermatol. 130: 73-76, 1994.

19) Gandolfo, S., Carbome, M., Carrozzo, M.& Gallo, V.: Oral lichen planus and hepatitis C virus (HCV) infection: isthere a relationship? a report of 10 cases. J. Oral. Pathol. Med. 23: 119-122, 1994.

20) Takahara, T., Watanabe, A.& Shiraki, K.: Effects of glycyrrhizin on hepatitis B surface antigen: a biochemicaland morphological study. J. Hepatol. 21: 601-609, 1994.

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944 Yumiko NAGAO et al

グ リチル リチ ンの静注 治療 が 著効 を示 したC型 慢 性肝 炎 を

有 す る 口腔 扁 平苔 癬 の1例

久留米大学医学部口腔外科1),第2内 科2)

長尾由実子1)佐 田 通夫2)谷 川 久一2)亀 山 忠光1)

要 旨

口腔扁平苔癬(orallichenplanus:OLP)は,

慢性の角化異常 を伴う難治性の炎症性疾患である

が,そ の経過は長 く完全治癒が困難な疾患の一つ

である.OLPの 発症原因については種々のものが

あるとされているが,今 だ明らかにされておらず,

根治的治療法は,確 立されていない.そ こで今回,

従来慢性肝炎に対する有効な治療法の一つとして

広 く使われているグリチル リチン(SNMC(R))を,

OLP患 者に投与 してその経過 を観察 した.

症例は49歳 の女性で,主 訴は口腔内粘膜全体の

i接触痛であった.既 往歴にC型 慢性肝炎があり現

在経過観察中である.現 病歴 は,1994年11月 頃 よ

り両側下顎歯肉部か ら頬粘膜 にかけて白斑を認め

近医での加療を続 けていたが,改 善ないため久留

米大学医学部口腔外科を受診 した.扁 平苔癬(両

側頬粘膜,全 顎に及ぶ歯肉並びに歯肉頬移行部,

口底,口 蓋粘膜部)の 診断で,セ ファランチン(R)末

の内服投与及び外用ステロイ ド剤 を使用 した.同

治療を7カ 月続けたが,口 腔粘膜病変の若干の改

善 と再発を繰 り返すだけで,同 年10月 には両側頬

粘膜のびらん面の拡大 を認 め,強 い接触痛のため

に摂食障害が出現した.そ こで,軽 度の血清AST

値,ALT値 の異常があることを考慮 し,SNMC

の連 日投与(40ml/dayiv)を 行った.治 療後2カ

月で両側頬粘膜のびらん面 はほぼ消失 しまた広範

囲に認められていた白斑病変 は消失傾向を示 し,

疹痛 も軽減した.

感染症学雑誌 第69巻 第8号