Infectious : The Return of the Great Imitator To Rhode Island Gail Skowron, MD, Xiaodan Wang, MD, and Ekta Gupta, MD  Si n c e 2010, Rh o d e Is l a n d h a s s e e n a Asia. In the United States, syphilis cases Clinical Ma n i f e s t a t i o n s precipitous increase in the number of reached a peak during World War II, and Primary Syphilis cases of infectious syphilis, particularly declined steadily with the use of serologic The classic syphilitic chancre occurs at among HIV+ men who have sex with men testing and penicillin therapy until the late the site of inoculation of the spirochete, and (MSM). As clinicians, we are charged with 1980s and early 1990s, when an increase in may be seen as single or multiple genital, recognizing the protean manifestations of cases in heterosexual women and neonates perianal, or oral lesions.5 The chancre is this ancient , often called “the Great was linked to exchange of sex for drugs, characteristically indurated with a rolled Imitator,” a task made difficult by the low particularly crack cocaine.2 After declining edge and clean base, painless, and accompa- prevalence of syphilis during our training once again by 2000, a more recent rise in nied by regional lymphadenopathy. Lesions and practice. Entire textbooks have been cases has been noted in men who have sex may be inapparent to the patient. The me- devoted to the topic of syphilis; this article with men. In Rhode Island, the number of dian incubation period before appearance is designed as a clinical primer on infec- infectious syphilis cases per year rose from of the chancre is 21 days, with a range from tious syphilis for the practicing clinician 25 in 2008 to 61 in 2010. In 2010, 93% three to 90 days after acquisition.6 Syphilitic in primary care, emergency medicine, of cases were in MSM and half of those chancres are not reliably diagnosed by any dermatology, neurology, hepatology, and were HIV-infected. Factors associated with serologic test and, given the lack of ready nephrology. In order to contribute to syphilis included engagement in availability of dark-field microscopy, these public health efforts to reduce the spread anonymous sex and finding sexual partners must be diagnosed clinically and man- of syphilis (see accompanying article on the internet.3 This epidemiology neces- aged presumptively (treatment, reporting, “Interrupting Transmission of HIV and sitates all physicians to complete a com- follow-up and partner management).5 Other Sexually Transmitted in prehensive assessment of sexual practices, Rhode Island”), emphasis is placed on the and testing for HIV infection and other Secondary Syphilis diagnosis of infectious syphilis (primary, sexually transmitted .4 The clinical presentation of secondary secondary and early latent) in adults. Syphilis can be acquired by sexual syphilis is protean, as one would expect contact, transplacental transfer, kissing or from the wide dissemination of treponemes Et i o l o g y other close contact with an active lesion, throughout the body during the spiroche- Syphilis is caused by Treponema pal- transfusion of contaminated fresh human temia of early infection. (Table 1) The lidum, a slender, tightly coiled bacterium blood, or accidental direct inoculation presentation most easily remembered from that cannot be cultivated in vitro. The (needlestick).1 medical school is a rash with the classic genome of T. pallidum lacks apparent “palms and soles” distribution. (Figure 1) transposable elements, sug- gesting that the genome is Table 1. Multi-organ system manifestations of Secondary Syphilis extremely conserved and ������� ���������������������������������������������������������������������������������� !�" (modified from Mandell PPID)1 stable. This is the likely �#�� explanation of why T. pal- ���������$�������%������� � ������������������#&����������������������� lidum has remained exqui- � ��������������������&�������������&���������������� � ��������������'��'���������(������ sitely sensitive to penicillin ���������)��������������� � ����������������� for more than 70 years and � ��������&������&������&������*������������������������+��� that there are few differ- � ���������*���&������������ ����������������������� � ����������������� ences in DNA sequences � ���'��������&���������������������*������������������� among subspecies.1 � �������������&��������&����������������������� )���������������������� � ��*���������'��&��������&������������&�����������&������,��&�*����������&� ����������� Hi s t o r y & ��������������� � ��������%��������������������������� � ����������������������������������������������������+����������������������� Ep i d e m i o l o g y ��*������������������������������������� Syphilis has a long -��������� � )-����'��'���������������./0������������ � and storied past. Histori- � 1���������������������������������� 2�������������� � 3����������������������'�������������'�����&�������������&�'��������&����������&�����������&� ans have speculated that �������������#��������&�����������������������&����������������������� Columbus brought syphi- � ��������������������������������������������&���������������������&������������&� ��,����������&���������������&������������������������ ������������ lis back to Europe from 2������������ � �������������������'����������������������������&���������&�'������&����� the New World, perhaps ����+��������� 1������ � �������������#��������������������'��&���������������������������'����������� leading to the “Great Pox” ����������������������� epidemic in Europe and 4����� � �������������,�������������������&�*����������������������������������������� 245 Volume 95 No. 8 Au g u s t 2012 ������� ��������������5��������!�������������������� ������&���������������5�����������"

6����������7 � !��8��%������� ����������$�� .��9�,�� ���� ���������������������������� � ��,����������//�������8!��,��.����� � )������,��������!�����!:�;��,��/��.������� � 3%����������������������,��< �� �������������'�����������������������������������'�����������������(����������������*��� �� ����������������������� ��2������������(��������������������� ������������������������������� �� �����������������������*����������� ��)����������������������������������������������������� �

��#��1���� ����� � ����������������������������������������������������������������� � ��*������������������������=�1!:&����������&���������� � ����������������������������������������������1( �������������������������� � ����������������������������,�����������������&�)����,����������������������������������� � ��*����������������������������6 6������ � ��,������������������������������������������������������*����������������������<�������" skin, though the use of gloves is solved), or 3) a sex partner documented recommended when examining to have primary, secondary, or early latent any potentially infectious rash. syphilis.6 Late Latent syphilis is defined as Vesicular lesions occur only in asymptomatic seroreactivity in the absence congenital syphilis.1 of these conditions. Early latent syphilis is Two highly infectious skin considered “early” or “infectious” syphilis lesions are condylomata lata and and treatment recommendations are iden- mucous patches. Condylomata tical to primary and secondary syphilis. lata occur on warm, moist, in- tertriginous areas (perianal area, To LP or not to LP? vulva, scrotum, inner aspects of A common clinical dilemma is wheth- the thighs, skin under pendulous er to perform an LP on a patient presenting breasts, nasolabial folds, cleft of with early syphilis.8 This is particularly the chin, axillary and antecubital true for HIV-infected patients, in whom folds, webs of the fingers and an increased likelihood of progression toes) as painless, broad, moist, to symptomatic neurosyphilis has been grey-white to erythematous described.9 In HIV+ individuals, clinical plaques.1 Mucous membrane and CSF abnormalities consistent with lesions, termed mucous patches, neurosyphilis are associated with an RPR are silvery gray, superficial ero- titer > 1:32 and/or a CD4 cell count < sion with a red periphery, and 350 cells/µL.11-13 However, no studies have may occur on lips, mouth, phar- demonstrated a change in clinical outcome Figure 1. Lesions of secondary syphilis on the ynx, tonsils, vulva, vagina, glans if a lumbar puncture is performed and soles of the feet. penis, inner prepuce, cervix, and neurosyphilis is documented and treated.8,14 anal canal.1 Therefore, CDC does not recommend CSF Patients may ascribe the rash to another eti- Constitutional symptoms examination in HIV-infected or -unin- ology, and, though classically non-pruritic, may be prominent (or the presenting com- fected patients who lack neurologic signs or they may present with the common “gen- plaint), including fever, malaise, pharyngi- symptoms suggestive of neurosyphilis.6 In eralized pruritic rash” to their primary care tis, anorexia, weight loss, and arthralgias. clinical practice, therefore, a detailed history provider. (Figure 2) The lesions typically Generalized lymphadenopathy (particularly and physical examination to detect symp- begin as three to ten mm macules, sym- epitrochlear), hepatitis, and glomerulone- tomatic neurosyphilis must be performed metrically distributed first on the trunk and phritis may accompany other manifesta- in all patients diagnosed with syphilis. If upper extremities, that may progress to pap- tions. Seeding of the central nervous system clinical evidence of neurologic involvement ules, and less commonly, to pustules.1 A fine may occur at any stage of syphilis, and early is observed (e.g., cognitive dysfunction, scaly appearance is seen in papulosquamous neurologic disease (syphilitic aseptic men- motor or sensory deficits, ophthalmic or rashes. The lesions on the palms and soles ingitis, ocular and otic syphilis) may occur.1 auditory symptoms, cranial nerve palsies, are typically reddish brown, flat or with a Acute HIV infection is in the differential and symptoms or signs of meningitis), scaly appearance. A patchy alopecia or loss diagnosis of secondary syphilis, both due to an evaluation that includes CSF analysis, of eyebrows and beard may occur.1,7 These overlapping clinical presentation and shared ocular slit-lamp ophthalmologic examina- skin lesions are not infectious to intact modes of transmission, and all patients tion, and otologic examination should be diagnosed with syphilis performed. Treatment should be guided by should have HIV test- the results of this evaluation.6 ing performed. Laboratory Diagnosis Early Latent The serologic diagnosis of syphilis Syphilis relies on the use of non-treponemal (RPR, Latent syphilis is VDRL) and treponemal tests (FTA-ABS, by definition serore- EIA). In Rhode Island, an RPR/VDRL activity without other screening test can be performed rapidly evidence of disease. in the clinical laboratory. All samples Early Latent syphilis testing positive by the non-treponemal is defined as 1) docu- RPR/VDRL assay are confirmed by the mented seroconversion treponemal FTA-ABS test. or fourfold rise in titer The RPR/VDRL tests are subject to a in the past year, or 2) false-negative “prozone effect,” due to high unequivocal symptoms antibody titers, particularly in secondary Figure 2. Diffuse macules and papules of secondary of primary or second- syphilis. In cases where syphilis is highly syphilis on the upper arm ary syphilis (now re- suspected, the lab should be asked to repeat 246 Medicine & Health/Rhode Island ������� ���������������������������������������������������������������������������������� !�"

�#�� ���������$�������%������� � ������������������#&����������������������� � ��������������������&�������������&���������������� � ��������������'��'���������(������ ���������)��������������� � ����������������� � ��������&������&������&������*������������������������+��� � ���������*���&������������ ����������������������� � ����������������� � ���'��������&���������������������*������������������� � �������������&��������&����������������������� )���������������������� � ��*���������'��&��������&������������&�����������&������,��&�*����������&� ����������� ��������������� � ��������%��������������������������� � ����������������������������������������������������+����������������������� ��*������������������������������������� -��������� � )-����'��'���������������./0������������ � � 1���������������������������������� 2�������������� � 3����������������������'�������������'�����&�������������&�'��������&����������&�����������&� �������������#��������&�����������������������&����������������������� � ��������������������������������������������&���������������������&������������&� ��,����������&���������������&������������������������ ������������ 2������������ � �������������������'����������������������������&���������&�'������&����� ����+��������� 1������ � �������������#��������������������'��&���������������������������'����������� ����������������������� 4����� � �������������,�������������������&�*�����������������������������������������

the test using higher dilutions Table 2. Therapy for Early or Infectious Syphilis (Primary, Secondary and of serum. False positive RPR/ Early������� ��������������5��������!�������������������� Latent) ������&���������������5�����������" VDRL tests may occur in colla- gen vascular disease, pregnancy, 6����������7 � !��8��%������� ����������$�� .��9�,�� intravenous drug use, advanced ���� ���������������������������� malignancy, , ma- � ��,����������//�������8!��,��.����� laria, viral and rickettsial dis- � )������,��������!�����!:�;��,��/��.������� < eases, and advanced age. A � 3%����������������������,�� �� �������������'�����������������������������������'�����������������(����������������*��� false positive FTA may result �� ����������������������� ��2������������(��������������������� ������������������������������� from cross-reactivity with other �� �����������������������*����������� ��)����������������������������������������������������� � spirochetes, such as Borrelia burgdorferi, the etiologic agent 1 ��#��1���� ����� of . � �����������������������������������������������������������������rial vaginosis/cervical gonorrhea and chla- of these regimens have reduced efficacy, New rapid treponemal tests,� such��*������������������������=�1!:&����������&���������� mydia (vaginal receptive women). Patients increasing resistance and/or a paucity as the Syphilis EIA or chemilumines� ����������������������������������������������1(- may state they “always practice safe sex” ��������������������������of supporting clinical data, and should cence immunoassay, have been utilized� ����������������������������,�����������������&�)����,����������������������������������� only be used when patients are unable to � ��*����������������������������6but on specific questioning, 6������ may admit to to accomplish low-cost, automated,� ��,������������������������������������������������������*����������������������<�������" unprotected oral sex; while this is less risky be treated with penicillin. HIV-negative high-volume syphilis screening. If the for transmission of HIV infection, the lo- patients should have follow-up RPR titers rapid treponemal test is positive, an RPR/ calization of syphilis organisms on external at six and twelve months post-treatment. VDRL with titer must be performed������� ����������������������������������������������������������� to genitalia during primary and secondary HIV-infected����������������������� persons should have !�"clinical 15 and serologic follow-up at three, six, nine, distinguish active from past infection.�#�� syphilis provides ample opportunity for 6 The laboratory diagnosis of neuro���������$�������%�������- transmission during� ������������������#&�����������������������oral sex. This under- 12, and 24 months post-treatment. syphilis is made difficult by the lack of scores the need to� look��������������������&�������������&���������������� for the lesions of � 8 ��������������'��'���������(������ a standard definition. A positive���������)��������������� CSF primary syphilis in� and����������������� around the mouth. Jarisch-Herxheimer reaction VDRL, in the absence of substantial Patients testing negative� ��������&������&������&������*������������������������+��� for HIV on this The Jarisch-Herxheimer reaction is an � ���������*���&������������ contamination of CSF with blood,����������������������� is initial evaluation� should����������������� be considered for acute febrile reaction frequently accompa- 16 considered diagnostic of neurosyphilis. re-testing in three� months.���'��������&���������������������*�������������������nied by headache, myalgia, fever, and other However, this test is relatively insensitive, � �������������&��������&�����������������������symptoms that usually occur within the first )���������������������� � ��*���������'��&��������&������������&�����������&������,��&�*����������&� thus a negative CSF VDRL does not rule Tr e a t m e n t o f Ea�����������r l y 24 hours after the initiation of any therapy out neurosyphilis (i.e., helpful only if��������������� posi- (In f e c t i o u s ) S� yph��������%���������������������������ilis for syphilis. It occurs most frequently � ����������������������������������������������������+����������������������� tive). Other diagnostic criteria include CSF Early or Infectious��*������������������������������������� syphilis includes among patients who have secondary syphi- pleocytosis (> 5 cells/mm3 in HIV -���������unin- primary syphilis,� secondary)-����'��'���������������./0������������ � syphilis and lis, due to high bacterial burden. Patients fected, >10-20 cells/mm3 in HIV-infected) � 1����������������������������������should be informed about this possible 2��������������early latent syphilis,� 3����������������������'�������������'�����&�������������&�'��������&����������&�����������& all of which are � and elevated CSF protein.17,18 In HIV pa- treated with the same�������������#��������&�����������������������&����������������������� regimen of one adverse reaction. Many clinicians pre-treat tients who are not on antiretroviral therapy, � ��������������������������������������������&���������������������&������������&with 1 g acetominophen two hours prior� injection of Benzathine��,����������&���������������&������������ Penicillin G 2.4 ������������ ������������ these abnormalities are common, making2������������ MU intramuscularly.� �������������������'����������������������������&���������&�'������&���� (Table 2) The CDC to IM PCN, although this is not proven� to it difficult to ascribe CSF abnormalities to and RI Department����+��������� of Health strongly prevent Jarisch-Herxheimer reaction. 1������ � �������������#��������������������'��&���������������������������'����������� neurosyphilis in the absence of a positive recommend that clinicians����������������������� always use Ben- CSF VDRL.14,17 The CSF FTA-ABS4����� is zathine Penicillin� whenever�������������,�������������������&�*����������������������������������������� possible. In Treatment of Exposed Partners highly sensitive but not specific, thus, if practice, this may require some investiga- The CDC 2010 STD guidelines rec- negative, neurosyphilis is highly unlikely tion into the details of reported penicillin ommend that persons who were exposed (i.e., helpful only if negative).6,14,19 ������� ��������������5��������!��������������������allergy and mandates penicillin desensiti ������&���������������5�����������"- within the 90 days preceding the diagnosis zation for pregnant women and patients of primary, secondary, or early latent 6����������7 a b o r a t o r y t e s t i n g f o r o t h e r syphilis in a sex partner might be infected L � !��8��%�������diagnosed with ����������$�� .��9�,�� neurosyphilis. Alternative STDs ���� ���������������������������regimens for treatment� of early syphilis in even if seronegative; therefore, such persons Syphilis, HIV, gonorrhea and chla- � patients��,����������//�������8!��,��.����� with a history of severe penicillin should be treated presumptively. Persons � mydia are transmitted person-to-person � allergy)������,��������!�����!:�;��,��/��.������ are: Doxycyline 100 mg po BID x who were exposed >90 days before the di- � 3%����������������������,��< by similar sexual practices.20,21 Individu- 14 days; Ceftriaxone 1 g IM or IV QD x agnosis of primary, secondary, or early latent �� �������������'�����������������������������������'�����������������(����������������*��� als testing positive for syphilis, therefore, syphilis in a sex partner should be treated �� ����������������������� ��2������������(��������������������� ������������������������������� 10-14 days; Azithromycin 2 g po x 1. All should be screened for other �� �����������������������*����������� ��)����������������������������������������������������� � STDs. Testing should target Table 3. Take Home Points areas of exposure, i.e., urine ��#��1���� ����� gonorrhea and chlamydia � ����������������������������������������������������������������� (all patients), rectal gonorhea � ��*������������������������=�1!:&����������&���������� and chlamydia (anal receptive � ����������������������������������������������1( �������������������������� patients), pharyngeal gonor- � ����������������������������,�����������������&�)����,����������������������������������� � ��*����������������������������6 6������ rhea (oral receptive patients), � ��,������������������������������������������������������*����������������������<�������" vaginal trichomonas and bacte- 247 Volume 95 No. 8 Au g u s t 2012 presumptively if serologic test results are not fast.” It is unknown whether a serofast 15. Syphilis Testing Algorithms Using Treponemal available immediately and the opportunity high titer has different clinical implication Tests for Initial Screening – Four Laboratories, New York City, 2005 – 2006. MMWR. August 6 8 for follow-up is uncertain. from a low titer. 15, 2008;57(32);872–5. 16. CDC surveillance case definitions for syphilis. Reporting and follow-up Co n c l u s i o n s http://www.cdc.gov/osels/ph_surveillance/ nndss/casedef/syphilis1990.htm. All stages of syphilis are reportable Rising rates of infectious syphilis in 17. Marra CM, Maxwell CL, Collier AC, et al. diseases in RI, and laboratories report posi- Rhode Island, particularly among men Interpreting cerebrospinal fluid pleocytosis in tive results directly to the RI Department of who have sex with men, compels all physi- HIV in the era of potent antiretroviral therapy. BMC Infect Dis. 2007;7:37. Health. Physicians are required to complete cians to be aware of the varied manifesta- 18. Marra CM. Update on Neurosyphilis. Current the RIDOH STD case report form (http:// tion of this disease, and the management Infectious Disease Reports. 2009;11:127–34. www.health.ri.gov/forms/reporting/cases/ of the infected patient and contacts. Physi- 19. Marra CM, Tantalo LC, Maxwell CL, et al. Alternative cerebrospinal fluid tests to diagnose SexuallyTransmittedDiseases.pdf), and cians must be mindful of the superiority of neurosyphilis in HIV-infected individuals. Disease Intervention Specialists from the benzathine penicillin as the drug of choice Neurology. 2004;63;85–8. RI Dept of Health will interview index for infectious syphilis, and the need for 20. Kent CK, Chaw JK, Wong W, et al. Prevalence cases. Many index cases will decline to give careful evaluation and follow-up for coex- of rectal, urethral, and pharyngeal chlamydia and gonorrhea detected in 2 clinical settings among names of sexual contacts, preferring to no- isting sexually acquired diseases. men who have sex with men: San Francisco, Cali- tify their contacts to be tested by their own fornia, 2003. Clin Infect Dis. 2005; 41:67–74. physician. Importantly, RPR testing may Re f e r e n c e s 21. Rieg G, Lewis RJ, Miller LG, et al. Asymptomatic sexually transmitted infections in HIV-infected be negative in incubating or early syphilis, 1. Tramont, EC. “Treponema pallidum (Syphi- lis).” In Principles and Practice of Infectious men who have sex with men: Prevalence, inci- therefore, contacts testing negative initially Diseases, 7th Edition. ed. Gerald L Mandell, dence, predictors, and screening strategies. AIDS must be re-tested three months after their MD, John E. Bennett, MD, Raphael Dolin, Patient Care and STDs. 2008;22:947–54. last exposure. Preferably, however, CDC MD, Churchill, Livingston, Elsevier, 2010. 22. Syphilis CDC Fact Sheet and Patient Handouts. 2. Jones DL, Irwin K, Inciardi J, et al. The high- http://www.cdc.gov/std/syphilis/STDFact- recommends empiric therapy of all recent risk sexual practices of crack-smoking sex work- Syphilis.htm. http://www.cdc.gov/std/syphilis/ contacts, as noted above. Counseling Syphi- ers recruited from the streets of three American syphilis-Fact-Sheet.pdf. http://www.cdc.gov/ lis Fact Sheets for patients and contacts are cities. Sex Transm Dis. 1998;25:187–93. std/syphilis/syphilis-MSM-Fact-Sheet.pdf. 23. Brown ST, Akbar Z, Larsen SA, et al. Serologi- available on the CDC website.22 3. Primary, Secondary and Early Latent Syphilis Surveil- lance Data. Rhode Island Department of Health. cal response to syphilis treatment. JAMA. 1985; http://www.health.ri.gov/data/diseases/Syphilis.pdf. 253:1296–9. Tr e a t m e n t Fai l u r e o r 4. Zetola NM, Klausner JD. Syphilis and HIV infec- Re i n f e c t i o n tion: An update. Clin Infect Dis. 2007; 44:1222–8. Gail Skowron, MD, is Chief of the Divi- 5. Diagnosis algorithm for Primary Syphilis. Signs or symptoms that persist or California STD/HIV Prevention Training sion of Infectious Diseases at Roger Williams recur may suggest treatment failure or Center. http://www.stdhivtraining.net/pdf/ Medical Center and a Professor of Medicine at reinfection. The serologic definition of std-primerPDFBsae_Letter.pdf. the Boston University School of Medicine. 6. CDC. Sexually Transmitted Diseases Treat- failure/reinfection is a sustained fourfold ment Guidelines, 2010. Centers for Disease Xiaodan Wang, MD, was an Infec- increase in RPR titer compared to the Control and Prevention. MMWR. December tious Disease Fellow at Roger Williams maximum or day of treatment titer. For 17, 2010; 59(RR-12):26–36. http://www.cdc. Medical Center at the time that this article this reason, it is imperative that a day of gov/std/treatment/2010/default.htm. was written. She is currently an Infectious 7. Diagnosis algorithm for Secondary Syphilis. treatment titer be drawn, in addition to the California STD/HIV Prevention Training Disease practitioner and hospitalist in Fall initial blood draw that made the diagnosis. Center. http://www.stdhivtraining.net/pdf/ River, MA. For treatment failure or reinfection, HIV std-secondPDFBsae_Letter.pdf. Ekta Gupta, MD, is an Infectious 8. Ghanem K, Workowski KA. Manage- testing should be repeated, and an evalu- ment of adult syphilis. Clin Infect Dis. Disease Fellow at Roger Williams Medical ation for neurosyphilis, including lumbar 2011;53(S3):S110–28. Center. puncture, should be performed. 9. Flood JM, Weinstock HS, Guroy ME, Bayne L, Simon RP, Bolan G. Neurosyphilis during The quantitative RPR/VDRL test the AIDS epidemic, San Francisco, 1985–1992. Disclosure of Financial Interests should become nonreactive one year after J Infect Dis. 1998;177:931–40 The authors and/or their spouses/ successful therapy in primary syphilis 10. CDC. Symptomatic early neurosyphilis among significant others have no financial inter- HIV-positive men who have sex with men: four ests to disclose. and two years after successful therapy in cities, United States, January 2002–June 2004. secondary syphilis; most patients with late MMWR. 2007;56:625–8. syphilis will be nonreactive by the fifth 11. Marra CM, Maxwell CL, Smith SL, et al. Ce- Discussion of Off-Label Usage year after successful therapy.23 The RPR ti- rebrospinal fluid abnormalities in patients with Ceftriaxone, Azithromycin syphilis: Association with clinical and laboratory ter may fail to decline fourfold by one year features. J Infect Dis. 2004;189:369–76. post-treatment in 15-20% of patients. For 12. Libois A, De Wit S, Poll B, et al. HIV and Corresponden c e these patients, CDC recommends repeat syphilis: when to perform a lumbar puncture. Gail Skowron, MD Sex Transm Dis. 2007; 34:141–4. HIV testing, close clinical and serologic 13. Ghanem KG, Moore RD, Rompalo AM, Er- Division of Infectious Diseases follow-up, and consideration of lumbar belding EJ, Zenilman JM, Gebo KA. Lumbar Roger Williams Medical Center puncture to rule out inadequately treated puncture in HIV-infected patients with syphilis 825 Chalkstone Ave and no neurologic symptoms. Clin Infect Dis. Providence, RI 02908 neurosyphilis. If conversion to negative 2009; 48:816–21. does not occur, and active syphilis is ruled 14. Sparling PF. Diagnosis of neurosyphilis: New tools. phone: (401) 456-2437 out, the test result is said to be be “sero- Sexually Transmitted Diseases. 2010; 37(5):288–9. e-mail: [email protected] 248 Medicine & Health/Rhode Island