View metadata, citation and similar papers at core.ac.uk brought to you by CORE

provided by Elsevier - Publisher Connector

CASE REPORT

African Bite Fever Yi-Shan Tsai,1 Yu-Hung Wu,1,2* Pao-Tsuan Kao,3 Yang-Chih Lin1,2,4

Physicians may encounter unfamiliar diseases as a result of international travel. Fever with rash is an impor- tant sign that usually represents initial manifestation of infectious disorders. A 62-year-old Taiwanese woman presented with multiple , a papulovesicular rash, and fever 5 days after returning from South Africa. A biopsy specimen of an had wedge-shaped tissue , hemorrhage, necrotizing vasculitis of the small venules and arterioles, and a dense perivascular lymphocytic infiltrate in the dermis. Serologically, there was cross reaction with both conorii and R. rickettsii. DNA sequencing demonstrated R. africae, confirming the diagnosis of African tick bite fever. The patient responded well to minocycline. Recognition of the symptoms and signs, and diagnostic tools for different types of are essential for correct diagnosis and treatment. [J Formos Med Assoc 2008;107(1):73–76]

Key Words: African tick bite fever,

Many physicians are unfamiliar with African tick She also had a low-grade fever but no myalgias bite fever (ATBF), a rickettsiosis caused by Rickettsia or . africae1 and transmitted by in rural sub- Histologically, an eschar specimen had wedge- Saharan Africa. We report the case of a patient who shaped tissue necrosis and diffuse was infected with ATBF whilst in South Africa. extending to the subcutis (Figure 2A). There was necrotizing vasculitis of small venules and arteri- oles with a dense perivascular lymphocytic in- Case Report filtrate and hemorrhage (Figure 2B). Gram and periodic acid-Schiff stains were negative for bac- A 62-year-old Taiwanese woman presented with teria and fungi. Serial indirect fever and two mild tender skin nodules 5 days serology for rickettsiae by the Taiwan Centers for after returning from a 2-week trip to South Africa. Disease Control found a four-fold increase (160− She denied a history of insect bites or close con- 1280×) in immunoglobulin G titers for both tact with animals. There were two erythematous R. rickettsii and R. conorii, but was negative for pustular nodules on her left inner thigh and left other rickettsioses. shoulder. Oral cephalexin was prescribed for pre- Nested polymerase chain reaction (PCR) of sumed furunculosis. However, 10 days later, the eschar material was performed as previously de- nodules became two black eschars, about 1 cm in scribed.1 The first suicide PCR assay used the diameter (Figures 1A and 1B), and with scattered primers AF3F, AF3R, AF4F and AF4R for nested 2–3-mm asymptomatic erythematous papules and amplification (Figure 3). The PCR product was vesicles near the eschars (Figures 1C and 1D). then amplified by using AF5F, AF5R, AF6F and

©2008 Elsevier & Formosan Medical Association ...... 1Department of Dermatology, Mackay Memorial Hospital, 2Mackay Medicine, Nursing and Management College, Taipei, 3Department of Medicine, Cardinal Tien Hospital, Yungho, and 4Lee-Ming Institute of Technology, Taipei, Taiwan.

Received: March 15, 2007 *Correspondence to: Dr Yu-Hung Wu, Department of Dermatology, Mackay Memorial Revised: April 14, 2007 Hospital, 92, Section 2, Chung-Shan North Road, Taipei 104, Taiwan. Accepted: July 3, 2007 E-mail: [email protected]

J Formos Med Assoc | 2008 • Vol 107 • No 1 73 Y.S. Tsai, et al

A B

C D

Figure 1. Black eschars on the (A) left shoulder and (B) left thigh, with a few surrounding red papules. (C) Erythematous papule on dorsal foot. (D) Vesicle in the axilla.

A B

Figure 2. (A) Histopathologic examination shows wedge-shaped tissue necrosis deep in the subcutis (hematoxylin & eosin, 40×). (B) Necrotizing vasculitis of small venules with perivascular lymphocytic infiltration with some leukocytes, nuclear dust and hemorrhage (hematoxylin & eosin, 400×).

AF6R as second primers. The PCR product was once ATBF was diagnosed. The patient had al- then sequenced by restriction fragment length ready received a total of 14 days of polymorphism and found to be homologous to and minocycline before the diagnosis was made. R. africae DNA. She recovered without sequelae other than hy- Initial treatment before confirmation of the perpigmented scars at the eschar sites. None of the diagnosis included ceftazidime, ciprofloxacin and other members in her tour group had a similar minocycline, but ceftazidime was discontinued disease.

74 J Formos Med Assoc | 2008 • Vol 107 • No 1 African tick bite fever

A 1 2 3 4 5B 678910

445 bp 256 bp

209 bp 140 bp

AF3F/R AF5F/R AF4F/R AF6F/R Figure 3. Agarose gel electrophoresis of the DNA fragments obtained by nested polymerase chain reaction of the eschar specimen. Lanes 1, 3, 6, 8 = eschar specimens; lanes 2, 4, 7, 9 = negative control; lanes 5, 10 = DNA ladder.

Discussion aggressive. In contrast to other rickettsioses, there- fore, about one quarter to one half of patients Rickettsioses can be transmitted by ticks, , with ABTF have multiple eschars,2 a pathog- or lice. ATBF, caused by R. africae, and Medi- nomonic sign. The rash in ATBF is usually more terranean , caused by R. conorii, are the papular and vesicular than purpuric. With this most common tick-born rickettsioses associated constellation of skin signs, therefore, it is possible with international travel over the last decade.1 for physicians to tentatively diagnose ATBF even ATBF is transmitted by Amblyomma hebraeum and before the serology results are available, espe- A. variegatum.2 The risk of this infection is partic- cially if it occurs in a cluster of people who have ularly high from November to April in rural sub- traveled from an endemic area such as South Saharan Africa.2–4 Africa, Botswana and Zimbabwe.4,7–9 All physicians need to be familiar with rick- The diagnosis can be made without difficulty ettsioses because patients may present with vari- with serologic tests for R. africae. The specific an- ous symptoms. Rashes are common and may tibody is usually not accessible in non-endemic be recognized first; they are usually characterized areas, however. The organism is antigenically sim- by diffuse or scattered blanching erythematous ilar to R. conorii and may show cross reactivity to macules, papules, vesicles, petechiae or purpura. different species in the spotted fever group, such A cigarette burn-like eschar at the site of the vec- as R. rickettsii (which causes Rocky Mountain spot- tor bite may be present in some. Very similar ted fever) and R. conorii. Our patient had this clinical manifestations are present in the spotted cross-reactivity. This possibility should be kept fever group of rickettsioses (including both Rocky in mind, therefore, and ATBF should be included Mountain and Mediterranean spotted fever) and in the differential diagnosis when there is a history the group, such as .5,6 Scrub consistent with exposure. Suggested diagnostic typhus, endemic in Eastern Taiwan and caused criteria for patients with a flu-like illness com- by , may also present with mencing no later than 10 days after leaving rural eschar, scattered erythematous macules, papules, sub-Saharan Africa include: (1) direct evidence vesicles or patches.6 However, ATBF is somewhat of R. africae infection by culture and/or PCR; (2) unusual in that the ticks that transmit it are quite specific antibody against R. africae detected by

J Formos Med Assoc | 2008 • Vol 107 • No 1 75 Y.S. Tsai, et al

Western blot with or without cross-adsorption References assays; or (3) serology specific for recent spotted fever group rickettsial infection plus clinical and 1. Jensenius M, Fournier PE, Raoult D. Tick-borne rick- epidemiologic features consistent with ATBF, such ettsioses in international travellers. Int J Infect Dis 2004; as multiple inoculation eschars, eschar plus a vesic- 8:139–46. 2. Jensenius M, Fournier PE, Kelly P, et al. African tick bite ular cutaneous rash, or clustering of cases.10 fever. Lancet Infect Dis 2003;3:557–64. Histologic examination is helpful but not 3. Jensenius M, Fournier PE, Vene Sirkka, et al. African diagnostic. Papular lesions in ATBF often have tick bite fever in traveler to rural sub-equatorial Africa. necrotizing vasculitis with perivascular infiltrates Clin Infect Dis 2003;36:1411–7. composed mostly of lymphocytes and macro- 4. Caruso G, Zasio C, Guzzo F, et al. Outbreak of African tick-bite fever in six Italian tourists returning from South phages, luminal thrombosis, and microinfarcts.11 Africa. Eur J Clin Microbiol Infect Dis 2002;21:133–6. The eschars are characterized by wedge-shaped epi- 5. Jensenius M, Fournier PE, Raoult D. Rickettsioses and the dermal and dermal necrosis. It has been reported international traveler. Clin Infect Dis 2004;39:1493–9. that the vasculitis in ATBF contains significantly 6. Wu YH, Su HY. Cutaneous manifestations of scrub typhus. more polymorphonuclear leukocytes than that of Dermatol Sinica 1998;16:251–60. Mediterranean spotted fever,12 although we did 7. Consigny PH, Rolain JM, Mizzi D, et al. African tick- bite fever in French travelers. Emer Inf Dis 2005;11: not find this to be true in our patient. The eschar 1804–6. contains the most organisms and is therefore the 8. Fournier PE, Roux V, Caumes E, et al. Outbreak of Rickettsia best specimen for PCR.2 Identification of R. africae africae infections in participants of an adventure race in by this method yields a definitive diagnosis. South Africa. Clin Infect Dis 1998;27:316–23. ATBF usually has a benign clinical course, 9. McQuiston JH, Paddock CD, Singleton J Jr, et al. Imported spotted fever rickettsioses in United States travelers with no deaths reported as yet,5 compared to returning from Africa: a summary of cases confirmed by scrub typhus that may have severe systemic symp- laboratory testing at the Centers for Disease Control and toms or complications, such as meningitis, hepa- Prevention, 1999–2002. Am J Trop Med Hyg 2004;70: titis or renal failure.6 Rare complications have, 98–101. however, occurred in ATBF, including acute myo- 10. Jensenius M, Fournier PE, Hellum KB, et al. Sequential changes in hematologic and biochemical parameters in carditis,13 subacute neuropathy,14 temporary neu- African tick bite fever. Clin Microbiol Infect 2003;9: 15 3 ropsychiatric symptoms, and . 678–83. Treatment is similar to that for other rickettsial 11. Toutous-Trellu L, Peter O, Chavaz P, et al. African tick bite infections, i.e. with tetracycline, quinolones or fever: not a spotless rickettsiosis J Am Acad Dermatol .11 2003;48:S18–9. In conclusion, physicians should be aware of 12. Lepidi H, Fournier PE, Raoult D. Histologic features and immunodetection of African tick-bite fever eschar. Emerg ATBF. A careful search should be made for the Inf Dis 2006;12:1332–7. characteristic eschars in patients with a history of 13. Bellini C, Monti M, Potin M, et al. Cardiac involvement in travel to endemic areas. a patient with clinical and serological evidence of African tick-bite fever. BMC Infect Dis 2005;5:90. 14. Jensenius M, Fournier PE, Fladby T, et al. Sub-acute Acknowledgments neuropathy in patients with African tick bite fever. Scand J Infect Dis 2006;38:114–8. 15. Jackson Y, Chappuis F, Loutan L. African tick-bite fever: This work was supported by a grant (MMH-9150- four cases among Swiss travelers returning from South 66) from Mackay Memorial Hospital, Taiwan. Africa. J Travel Med 2004;11:225–8.

76 J Formos Med Assoc | 2008 • Vol 107 • No 1