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Briolant, B. Pradines); Aix Marseille Uni- 8. Witkowski B, Iriart X, Soh PN, Menard microbiologically proven versité, Marseille (A. Pascual, N. Wurtz, S, Alvarez M, Naneix-Laroche V, et al. burgdorferi infection. Pfmdr1 amplification associated with E. Baret, S. Briolant, B. Pradines); Centre clinical resistance to mefloquine in West During spring and summer 2009, National de Référence du Paludisme, Mar- Africa: implications for efficacy of - ar a total of 29 patients with classic or seille (A. Pascual, B. Pradines); and Hôpital temisinin combination therapies. J Clin possible EM and suspected Lyme dis- Principal de Dakar, Dakar, Sénégal (B. Fall, Microbiol. 2010;48:3797–9. http://dx.doi. ease were referred by primary care org/10.1128/JCM.01057-10 M. Fall, C. Camara, A. Nakoulima, B Diatta, 9. Fall B, Diawara S, Sow K, Baret E, Dia- physicians for an ongoing prospective B. Wade, B. Pradines) tta B, Fall KB, et al. Ex vivo susceptibil- study. Laboratory methods have been ity of Plasmodium isolates from Dakar, DOI: http://dx.doi.org/10.3201/eid1905.121603 described (8). The patients were >18 Senegal, to seven standard anti-malarial years of age and lived in suburban Bal- drugs. Malar J. 2011;10:310. http://dx.doi. References org/10.1186/1475-2875-10-310 timore, Maryland, USA, where Lyme 10. Sidhu ABS, Uhlmann AC, Valderramos disease is endemic. All patients had 1. Price RN, Uhlemann AC, Brockman SG, Valderramos JC, Krishna S, Fidock extracutaneous manifestations (e.g., A, McReady R, Ashley E, Phaipun L, DA. Decreasing pfmdr1 copy number in virus-like symptoms). Fourteen pa- et al. Mefloquine resistance in Plasmo- Plasmodium falciparum malaria heightens dium falciparum and increased pfmdr1 susceptibility to mefloquine, lumefantrine, tients met laboratory criteria for study gene copy number. Lancet. 2004;364: halofantrine, quinine, and artemisinin. analysis: 1) positive PCR at the initial 438–47. http://dx.doi.org/10.1016/S0140- J Infect Dis. 2006;194:528–35. http:// study visit, detected by a B. burgdor- 6736(04)16767-6 dx.doi.org/10.1086/507115 feri–specific nucleic acid–enhanc- 2. Basco LK, Le Bras J, Rhoades Z, ing PCR method on a 1.25-mL whole Wilson CM. Analysis of pfmdr1 and Address for correspondence: Bruno Pradines, drug susceptibility in fresh isolates blood sample (8), and 2) evidence of Unité de Parasitologie, Unité de Recherche of Plasmodium falciparum from B. burgdorferi exposure by the 2-tiered sur les Maladies Infectieuses et Tropicales Subsaharan Africa. Mol Biochem antibody test at the initial or posttreat- Parasitol. 1995;74:157–66. http://dx.doi. Emergentes, Institut de Recherche Biomédicale ment visit. Other entry criteria were a org/10.1016/0166-6851(95)02492-1 des Armées, GSBdD Marseille-Aubagne, 111 Av 3. Witkowski B, Nicolau ML, Soh PN, >5 cm and symptoms compatible de le Corse, BP 40026, 13568 Marseille Cedex Iriart X, Menard S, Alvarez M, et al. with early (1); exclusion 02, France; email: [email protected] Plasmodium falciparum isolates with criteria were certain preexisting medi- increased pfmdr1 copy number circu- late in West Africa. Antimicrob Agents cal conditions (8). Chemother. 2010;54:3049–51. http:// A panel of experienced special- dx.doi.org/10.1128/AAC.00209-10 ists, including dermatologists, were 4. Gadalla NB, Adam I, Elzaki SE, Bashir shown photographs of the patients’ S, Mukhtar I, Oguike M, et al. Increased Atypical pfmdr1 copy number and sequence Migrans in Patients skin lesions and asked if they would polymorphisms in Plasmodium fal- expect the average primary care phy- ciparum isolates from Sudanese ma- with PCR-Positive sician to diagnose the lesions as EM. laria patients treated with artemether- To avoid bias, PCR and serologic test lumefantrine. Antimicrob Agents Lyme Disease Chemother. 2011;55:5408–11. http:// results were withheld from the spe- dx.doi.org/10.1128/AAC.05102-11 To the Editor: The best diagnos- cialists and they were asked to cate- 5. Akala HM, Eyase FL, Cheruiyot tic sign in patients with early Lyme gorize lesions by characteristics com- AC, Omondi AA, Ogutu BR, Waters disease is a skin lesion, erythema mi- mon to target-like and non–target-like NC, et al. Antimalarial drug sensitiv- grans (EM). However this sign may ity profile of Western Kenya Plasmodium lesions. Lesions with the classic falciparum field isolates determined not occur or be recognized in 30% of bull’s-eye appearance, with central by a SYBR Green I in vitro assay and cases (1). Furthermore, the EM rash clearing and peripheral erythema, molecular analysis. Am J Trop Med Hyg. may not display a classic bull’s-eye were classified as classic EM; those 2011;85:34–41. http://dx.doi.org/10.4269/ (ring-within-a-ring) appearance, a ajtmh.2011.10-0674 with uniform red or red-blue or other 6. Holmgren G, Bjorkman A, Gil JP. fact that may be underappreciated appearance and lacking central clear- Amodiaquine resistance is not re- (2,3). Some studies noted uncharac- ing were classified as possible atypi- lated to rare findings of Pfmdr1 gene teristic variants of EM in 25%–30% cal EM. If any lesion of a multiple le- amplifications in Kenya. Trop Med Int of cases (4–7). One study reported Health. 2006;11:1808–12. http://dx.doi. sion set was classic in appearance, we org/10.1111/j.1365-3156.2006.01742.x the rash to be uniformly red in 60% categorized the rash as classic EM. 7. Wurtz N, Fall B, Pascual A, Diawara of cases (6). Other atypical variants Of the 14 patients with positive PCR, S, Sow K, Baret E, et al. Prevalence of EM are a blue-red appearance 10 had nonclassic EM (Figure) and of molecular markers of Plasmodium and, occasionally, a vesicular central falciparum drug resistance in Dakar, 4 had classic, target-like EM. Atypi- Senegal. Malar J. 2012;11:197. http:// region (4,5). We describe the occur- cal varied from those close dx.doi.org/10.1186/1475-2875-11-197 rence of atypical EM in patients with to classic EM to those resembling

Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 19, No. 5, May 2013 815 LETTERS

systemic and nonsystemic signs and symptoms over multiple seasons and geographic areas and for including PCR analysis of skin lesions in future studies. PCR of skin biopsy samples may provide insight as to whether a negative blood PCR is the result of infection with a skin-restricted strain (10) in patients in whom bacterial dis- semination is not expected or a result of low copy number of B. burgdorferi in the blood sample. Our results serve as a reminder that patients with early Lyme disease may have an atypical rash, not the classic (textbook) bull’s-eye lesion. Close observation and a detailed his- tory of whether the rash is enlarging, has enlarged, or is spreading should be part of the consideration of the diag- Figure. Atypical lesion on a patient with PCR-positive result for Borrelia nosis. Observation for extracutaneous burgdorferi infection. The rash was not considered typical because it lacked central clearing signs of early infection, such as cranial and peripheral erythema. The differential diagnosis included a and seventh nerve palsy (Bell’s palsy) or arthropod bite. At the initial examination, this patient was seronegative for B. burgdorferi , is also essential. by 2-tiered criteria. Three weeks after therapy, the patient had positive results for ELISA In summary, the EM rash of Lyme and IgM Western blot and negative results for IgG Western blot, providing evidence of seroevolution (i.e., increasing antibody titer and/or increase in band intensity or appearance disease can have an atypical appear- of new antigen bands to B. burgdorferi). ance. Thus, clinicians should consider Lyme disease in the differential diagno- sis of patients who have a rash that may lesions more common in other condi- recognition of Lyme disease–associ- not be classic EM and who have been tions (e.g., insect or spider bites) and, ated EM is essential because current in areas where Lyme disease occurs. consequently, prone to misdiagnosis. approved laboratory tests may not Funding for this study was provided Depending on the appearance of identify B. burgdorferi in the first few by a grant (AI077156) from the National an atypical rash, the differential di- weeks of infection (8), when an accu- Institute of Allergy and Infectious Diseas- agnosis could include contact derma- rate diagnosis can lead to early cura- es, National Institutes of Health. titis, arthropod bite, or, in cases with tive therapy. annular lesions, fixed drug eruptions, Separate studies found different , , derma- percentages of atypical Lyme disease– Steven E. Schutzer, tophytosis, or systemic erythe- associated rashes (3,4,9); each was Bernard W. Berger, matosus (5). In addition, a diagnosis lower than the percentage found in our James G. Krueger, can be more challenging when there study. Our study has several limita- Mark W. Eshoo, David J. Ecker, are multiple skin lesions rather than a tions: it encompassed only 1 recruit- and John N. Aucott single lesion and in a pattern unfamil- ment season, 1 geographic site, and University of Medicine and Dentistry of New iar to a general practitioner. a small number of patients. The sen- Jersey–New Jersey Medical School, New- Multiple textbooks and websites sitivity of PCR for blood specimens ark, New Jersey, USA (S.E. Schutzer); Pri- have featured pictures of EM as a is improving (8); however, PCR may vate Dermatology Practice, Southampton, bull’s-eye lesion (online Technical Ap- have missed some acute cases in our New York, USA (B.W. Berger); Rockefeller pendix, wwwnc.cdc.gov/EID/pdfs/12- study for reasons cited below. There- University, New York, New York, USA (J.G. 0796-Techapp.pdf). This emphasis on fore, these patients should not obliga- Krueger); Ibis Biosciences Inc., Carlsbad, target-like lesions may have inadver- torily be considered as representative California, USA (M.W. Eshoo, D.J. Ecker); tently contributed to an underapprecia- of all acute Lyme disease patients. and Johns Hopkins School of Medicine, tion for atypical skin lesions caused by Our study results serve as an im- Baltimore, Maryland, USA (J.N. Aucott) Lyme disease. Nevertheless, physician petus for studying more patients with DOI: http://dx.doi.org/10.3201/eid1905.120796

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References Brucellosis chills, and weakness; some cases were associated with encephalitis, 1. Centers for Disease Control and Preven- in Guangdong tion. Lyme disease [cited 2012 Oct 23]. meningitis, and arthritis. Of the 112 http://www.cdc.gov/lyme Province, People’s reported cases during 2005–2010, 2. Feder HM Jr, Whitaker DL. Misdiag- Republic of China, 105 were laboratory confirmed: 61 nosis of erythema migrans. Am J Med. by culture (55 from blood culture, 3 1995;99:412–9. http://dx.doi.org/10.1016/ 2005–2010 S0002-9343(99)80190-9 from bone marrow, and 1 each from 3. Berger BW. Erythema migrans. Clin Der- To the Editor: Brucellosis is joint fluid, cerebrospinal fluid, and matol. 1993;11:359–62. http://dx.doi. one of the most prevalent zoonotic a vertebrae disc ); and 44 by org/10.1016/0738-081X(93)90090-Y diseases in the world. It is principally serum agglutination test (SAT; single 4. Steere AC, Sikand VK, Meurice F, Parenti DL, Fikrig E, Schoen RT, et al. Vaccina- an animal disease, but globally, titer >400). The male:female ratio tion against Lyme disease with recombi- >500,000 human cases are reported among these patients was 66:46. The nant outer-surface each year (1). Transmission to humans age ranges were similar by sex; male lipoprotein A with adjuvant. N Engl J occurs primarily through contact with patients were 18–71 (median 47) Med. 1998;339:209–15. http://dx.doi. org/10.1056/NEJM199807233390401 infected animals and consumption of years of age, and female patients were 5. Berger BW, Johnson RC, Kodner C, contaminated food (2,3). Persons with 20–70 (median 43) years of age. Coleman L. Cultivation of Borrelia burg- occupational exposure are at highest The first 3 cases of brucellosis dorferi from erythema migrans lesions risk for brucellosis, in particular those in 2005 were reported in Shenzhen and perilesional skin. J Clin Microbiol. 1992;30:359–61. performing husbandry activities, in Guangdong Province. One 6. Smith RP, Schoen RT, Rahn DW, Sikand butchering, and livestock trading (4,5). case was culture confirmed VK, Nowakowski J, Parenti DL, et al. Although brucellosis has been by clinical laboratory, and the Clinical characteristics and treatment eradicated from many industrialized isolate was identified as Brucella outcome of early Lyme disease in pa- tients with microbiologically confirmed countries, new foci of disease melitensis biovar 3 by SAT and erythema migrans. Ann Intern Med. continually appear, particularly in phage biotyping. The other 2 2002;136:421–8. parts of Asia (6–8). In China, 160,214 cases were in dairy farm workers; 7. Nadelman RB, Wormser GP. Recogni- brucellosis cases were reported during their infections were laboratory tion and treatment of erythema migrans: are we off target? Ann Intern Med. 2005–2010; 90% of them occurred confirmed by SAT but could not be 2002;136:477–9. in 6 northern agricultural provinces: identified by biovar. Since 2005, 8. Eshoo MW, Crowder CC, Rebman AW, Neimenggu, Shanxi, Heilongjiang, more cities in Guangdong have Rounds MA, Matthews HE, Picuri JM, Hebei, Jilin, and Shaanxi. Livestock, reported brucellosis cases (Figure, et al. Direct molecular detection and geno- typing of Borrelia burgdorferi from whole such as goats, cattle, and pigs, are Appendix, wwwnc.cdc.gov/EID/ blood of patients with early Lyme disease. the main infectious source. However, article/19/5/12-0146-F1.htm). The PLoS ONE. 2012;7:e36825. http://dx.doi. factors such as the rapid movement Pearl River Delta region reported org/10.1371/journal.pone.0036825 of people from northern to southern 100 cases: 48 in Guangzhou, 27 9. Berger BW, Lesser RL. Lyme disease. Dermatol Clin. 1992;10:763–75. China, increased livestock trading, in Shenzhen, 7 in Zhongshan, 6 in 10. Seinost G, Dykhuizen DE, Dattwyler and lack of livestock quarantine Foshan, 6 in Jiangmen, 4 in Zhuhai, RJ, Golde WT, Dunn JJ, Wang IN, et al. mean that infected livestock or their and 2 in Dongguan. Only 12 cases Four clones of Borrelia burgdorferi sensu products readily traverse provincial were reported from undeveloped stricto cause invasive infection in humans. Infect Immun. 1999;67:3518–24. borders and transmit disease to rural areas in Guangdong: 5 in persons who have no direct contact Zhaoqing, 2 in Yangjiang, and 1 each Address for correspondence: Steven E. with livestock. in Huizhou, Qingyuan, Meizhou, Schutzer, University of Medicine and Dentistry- With an illness rate of <0.01 Maoming, and Yunfu. New Jersey Medical School, Newark, NJ 07103, cases/100,000 population, Guangdong A total of 42 Brucella isolates USA; email: [email protected] Province in southern China is one of were cultured during 2005–2009, and the areas in China with the lowest all were identified as B. melitensis incidence of brucellosis (9), but biovar 3. However, of 19 Brucella incidence is increasing. During 1955– isolates cultured during 2010, a total 2004, Guangdong Province recorded of 13 were identified as B. melitensis 51 confirmed cases of brucellosis; biovar 3, 4 as B. melitensis biovar however, during 2005–2010, 112 1, and 2 as B. suis biovar 3. These cases were reported. All reported cases results indicate a shift in species and had typical clinical characteristics, biovar for Brucella spp. circulating including undulant fever, night sweats, in China.

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