432

症例

Simultaneous Development of Japanese in a Married Couple in Kagoshima Prefecture

Takaaki KUBOZONO１） & Toshiro HONDA２） 1）Department of Internal Medicine, Morizono Hospital 2）Izumi Public Health Center （Received：October 19, 2005） （Accepted：March 6, 2006）

Key words : Japanese spotted fever, japonica

Introduction

Japanese spotted fever is a rickettsial infection of the spotted fever group. Since Mahara et al．１） reported the initial clinical case in Tokushima Prefecture in 1984, patients have been confirmed in various regions south of the Kanto district in Japan. This is an acute febrile disease with 3 signs-fever, exanthema, and eschar. Differen- tiation from Tsutsugamushi disease, which develops similar clinical symptoms, is not always easy, but cases more fulminant than Tsutsugamushi disease were noted in southwest Japan, and the first case of death from Japanese spotted fever was reported in 2001２）. In many incidences in 2004, high temperature continued from spring, and severe cases including death occurred in southwest Japan. Japanese spotted fever was specified for surveillance of the total number of incidences in Group 4 infectious diseases by the new Infectious Disease Law in April 1999, and is considered an emerging disease requiring monitoring. General clinicians may not, however, yet fully recognize the disease． We report a rare case of simultaneous development of Japanese spotted fever in a married couple．

Case report

Patients：65-year-old husband and 59-year-old wife Chief complaint：Fever and erythema in both patients Medical and activity histories：Nothing remarkable in either patient Present illness：Patients stayed overnight at a campsite in Tarumizu, Kagoshima, on July 26, 2003. They de- veloped fever above 38℃ from August 5 and headache and chill on August 7. They visited a physician, who prescribed Chinese medicine（Kampoyaku）． Erythema appeared mainly in the extremities on the evening on this day. Since symptoms worsened, and the wife suffered severe anorexia and systemic malaise, they were re- ferred to the Department of Internal Medicine of Morizono Hospital and admitted on August 10． Physical findings on admission：Erythema was noted over almost the entire body in both patients, but super- ficial lymph nodes were not palpable, and no swelling of the liver or spleen was noted. The husband had a tem- perature of 39.0℃, and an eschar possibly due to a tick was noted on the right thigh.Thewifehadatempera- ture of 39.2℃, and an eschar was noted on the left thigh. Both noticed the eschars in the morning after camp. The wife could not walk or eat and her symptoms were markedly severer than those of her husband． Skin findings on admission (Fig. 1) : Regarding exanthema, many adzuki bean-sized erythemas with irregular margins were noted over almost the entire body, including the palms. Erythemas were not itchy or painful, and were withdrawn by diascopy. The color of exanthemas was relatively thin without bleeding． A 15×13mm eschar was noted on the right thigh of the husband and a 14×9mm eschar on the left thigh

Correspondence to：Takaaki KUBOZONO Department of Internal Medicine, Morizono Hospital, 19―38 Ohshoji-cho, Satsumasendai-shi, Kagoshima 895―0076, Japan

感染症学雑誌 第80巻 第 4 号 Japanese spotted fever in a married couple 433

Fig. 1 Exanthema and eschar in husband (left) and wife (right)

Table 1 Laboratory data on admission

Husband WBC 7,800 /μL（stab 17%， seg 62%， lymph 17%， mono 4%） RBC 389×104 /μL，Hb 12.4 g/dL，Plt 10.2×104 /μL AST 48 IU/L，ALT 39 IU/L，LD 598 IU/L，TB 0.8 mg/dL，Cr 1.2 mg/dL CRP 15.0 mg/dL，PT 81.8%， fibringen 346.6 mg/dL urine protein（＋）urine occult blood（－）

Wife WBC 7,600 /μL（stab 66%， seg 23%， lymph 11%） RBC 469×104 /μL，Hb 14.0 g/dL，Plt 10.2×104 /μL AST 175 IU/L，ALT 127 IU/L，LD 1,028 IU/L，TB 0.6 mg/dL，Cr 1.1 mg/dL CRP 18.1 mg/dL，PT 105.9%， fibringen 476.6 mg/dL urine protein（3＋），urine occult blood（＋）

of the wife. These were ulcers with brown crust formed in the center. No tick bodies were noted． Laboratory data on admission (Table 1) : Left shift of leukocyte maturation within the normal range of the to- tal WBC number was noted in both patients, and the platelet count was slightly decreased. CRP was 15.0mg!dL in the husband and 18.1mg!dL in the wife. AST, ALT, and LD were increased especially in the wife． Serological findings (Table 2) : In paired sera collected on August 12 and 21, the antibody titer（IgM）against Japanese spotted fever Rickettsia (, YH strain）was significantly increased from less than 20 times to 320 times in the husband and from less than 20 times to more than 2,560 times in the wife. No in- creases were noted in antibody titer against murine or Tsutsugamushi disease Rickettsia. Based on the above findings, the patients were serologically diagnosed as having Japanese spotted fever that simultaneously

平成18年 7 月20日 434 Takaaki KUBOZONO et al

Table 2 Antibody titers measured by indirect immunofluorescence assay and Weil-Felix tests

Japanese Murine Tsutsugamushi Weil-Felix Day of spotted fever typhus disease Date YH Wilmington standard straina） illness OX2 OX19 OX K IgG IgM IgG IgM IgG IgM

Husband Aug. 12 8 ＜20b） ＜20 ＜20 ＜20 ＜20 ＜20 ＜20 ＜20 ＜20 Aug. 21 17 60 320 ＜20 ＜20 ＜20 ＜20 ＜20 80 ＜20

Wife Aug. 12 8 ＜20 ＜20 ＜20 ＜20 ＜20 ＜20 ＜20 ＜20 ＜20 Aug. 21 17 1,280 ≧2,560 ＜20 ＜20 ＜20 ＜20 ＜20 ＜20 ＜20

a）Kato，Karp，Gilliam， Kawasaki，Kuroki b）Reciprocal of serum dilution

Fig. 2 Clinical course

developed in the couple. In the Weil-Felix reaction used for assistive diagnosis of , OX2 antigen, which is reported to be reactive in many cases of Japanese spotted fever, was negative． Clinical course (Fig. 2) : The latent period may have been 10 days. Rickettsiosis was suspected at admission on August 10, and minocycline was administered by intravenous drip infusion at 200mg!day. Fever was resolved in the husband and wife on August 13 and 14, and subjective symptoms slowly disappeared. No DIC was noted throughout the course. AST, 249IU!L；ALT, 159IU!L；and LD, 1290IU!L were detected in the wife on August 12, but improved thereafter. The clinical course was uneventful. The disease remitted with disappearance of most erythemas on August 26 and patients were discharged．

Discussion

Japanese spotted fever is a febrile exanthematous disease caused by R. japonica. Fever generally, accompanied by headache and chill develops after 2-8 days of incubation, and erythemas appear mainly in the extremities. Differentiation from Tsutsugamushi disease with similar clinical symptoms is not always easy, but cases more fulminant than Tsutsugamushi disease have been noted regionally, and cases developing convulsion and con- sciousness disturbance２）～４）, DIC, and multiorgan failure２）４）have been reported． Since rickettsiosis was suspected in the couple at admission, treatment was initiated before definitive diagno- sis. Since Tsutsugamushi disease occurs mostly in April-June and October-December, while many cases of Japa- nese spotted fever occurs in July-September (these cases developed in August), fever is resolved within 1-2 days

感染症学雑誌 第80巻 第 4 号 Japanese spotted fever in a married couple 435 after initiation of minocycline treatment in many cases of Tsutsugamushi disease (fever was resolved on day 3 and 4 in the husband and wife), and exanthemas developed on the palm, Japanese spotted fever was considered and the course carefully observed. In general clinical practice, Japanese spotted fever cannot be definitively di- agnosed before observation of an increase in the antibody titer against R. japonica in paired sera collected at the initial examination and after 10-14 days. Suitable treatment may thus be delayed. In some opinions, treatment should be initiated with effective antibiotics immediately after rickettsiosis is suspected. New quinolone antibac- terial agents with minocycline are recommended for treatment of severe cases. While we also considered its ap- plication, minocycline administration alone was sufficient because clinical symptoms improved early． Honda et al．５） attempted early diagnosis and isolation of the etiologic agent by PCR in 23 patients serologically diagnosed with Japanese spotted fever between 2000 and 2002, but detection and isolation of R. japonica DNA were difficult because many samples were blood collected, stored, and transported to determine serum antibody titer. Although cryopreservation of whole blood immediately after sampling is necessary for isolation of R. japon- ica, it is not practically possible in many cases． Early diagnosis of Japanese spotted fever by immunohistological demonstration of Rickettsia antigen in skin biopsy specimens of the eschar and exanthema has recently been investigated (personal communication from Mahara, F．), and definite diagnosis can be made 3-4 days after skin biopsy. Wide recognition of the presence of quite a number of severe cases of Japanese spotted fever and the development of an early diagnosis method and suitable therapy are expected． Despite the paucity of reports, an outbreak of Japanese spotted fever was confirmed in Awajishima. It is therefore important in diagnosis to keep in mind that multiple cases of the infection may occur at the same time andspottedasinthesetwocases．

Acknowledgments

We thank Dr. Hiromi Fujita of Ohara Research Laboratory, Ohara General Hospital, for providing us with serological test results and Dr. Fumihiko Mahara (Mahara Clinic) for his invaluable advice．

References

1）Mahara F, Koga K, Sawada S, Taniguchi T, Shigemi F, Suto T, et al.：The first report of the rickettsial infections of spotted fever group in Japan : three clinical cases. J J A Inf D 1985；59：1165―71. 2）Kodama K, Senba T, Yamauchi H, Chikahara Y, Katayama T, Furuya Y, et al.：Fulminant Japanese spotted fe- ver definitively diagnosed by the polymerase chain reaction method. J Infect Chemother 2002；8：266―8. 3）Kodama K, Senba T, Yamauchi H, Chikahara Y, Fujita H：A patient with Japanese spotted fever complicated by meningoencephalitis. J J A Inf D 2001；75：812―4. 4）Araki M, Taketsuka K, Kawamura J, Kanno Y：Japanese spotted fever involving the central nervous system : two case reports and a literature review. J Clin Microbiol 2002；40：3874―6. 5）Honda T, Nakayama K, Yoshikuni K, Shinkawa N, Arima T, Yumata Y, et al.：Survey of Japanese spotted fever- positive cases. Annual Report of Kagoshima Prefectural Institute for Environmental Research and Public Health 2004；4：58―61.

鹿児島県で発生した日本紅斑熱の夫婦同時発症例

森園病院内科1），出水保健所2） 久保園 高 明 １） 本田 俊郎２）

症例は夫 65 歳，妻 59 歳．2003 年 7 月鹿児島県内のキャンプ場に 1 泊し，10 日後に発熱，その後頭痛，紅 斑が出現した．15 日後に夫婦共に森園病院内科に入院となった．共に全身に紅斑を認めたが，表在リンパ節 を触知せず，夫は右大腿部に，妻は左大腿部に刺し口があり，白血球数は正常範囲で，CRP は著明に上昇し ていた．リケッチア症を疑い，直ちに MINO 点滴静注にて治療を開始し，DIC などの重篤な状態に陥らずに 軽快した．夫婦共に，日本紅斑熱リケッチアに対する抗体価の有意な上昇が認められ，日本紅斑熱の夫婦同時 発症例と診断した． 本症は，同時に同地点で複数の感染が起こり得る疾患であることにも注意する必要がある． 〔感染症誌 80：432～435，2006〕

平成18年 7 月20日