Common Errors in Internal Medicine The Trouble with Treponemes

Susan George, MD, CPT, MC, USA and Emil Lesho, DO, LTC, MC, USA

Asking about a patient’s sexual history can mean the difference between a long, costly evaluation and a quick diagnosis when syphilis may be the etiology of the patient’s symptoms.

43-year-old, black man with lymphocytosis. Bone marrow biopsy not assume that a patient participates a history of hepatitis B pres- shows no sign of malignancy. in heterosexual activity exclusively. ents to a primary care clinic Based on these findings, his phy- Men who have sex with men have A with an enlarged lymph sicians explore infectious etiologies. an increased risk of infection with a node in his left groin. He reports that They order an HIV antibody test and quinolone resistant STD. The practi- this swollen lymph node has been Lyme disease, Epstein-Barr virus, and tioner in this case did appropriately present for several weeks. He says he cytomegalovirus titers—all of which discuss constitutional symptoms such has had no fever, chills, weight loss, are negative. as rash, fever, and weight loss, all rash, penile lesions or discharge, or The patient is referred to the infec- of which can be associated with previous episodes of a swollen lymph tious disease clinic. Toxoplasmosis infectious etiologies as well as with node in the groin area. He does not titers conducted there come back neg- malignancy. use tobacco or alcohol and has not ative. A rapid plasma reagin (RPR) Any patient with a history of a po- been taking any medications. test, however, is reactive at 1:64, and tential STD—hepatitis B in this pa- Physical examination reveals a this result is confirmed by a reactive tient’s case—should be screened for soft, 1- to 2-cm, nontender lymph- fluorescent treponemal antibody. other STDs, such as syphilis and HIV. adenopathy in the left groin without After treatment with a total of 7.2 This screening is particularly impor- overlying skin changes. No genital million U of benzathine penicillin IM tant with the increasing frequency of lesions are apparent. Results of the for late latent syphilis, the patient’s HIV and syphilis coinfection.1 In this patient’s complete blood count and RPR titer decreases fourfold and his case, completing a more thorough serum chemistries are normal. His lymphadenopathy resolves. history and STD investigation could provider prescribes levofloxacin PO have avoided a prolonged, expensive, 500 mg/day for suspected reactive CAN YOU IDENTIFY THE and invasive workup. lymphadenopathy. ERRORS? When, after one month, his lymph- The error in this case was the provid- GETTING TO THE ROOT OF THE adenopathy fails to resolve, he is given er’s failure to address the patient’s PROBLEM another two-week course of levoflox- sexual history and then consider sex- Syphilis has long been known as “the acin and is referred to an oncologist ually transmitted diseases (STDs) in great imitator” because of its protean for evaluation of possible lymphoma. the differential diagnosis of inguinal manifestations and diagnostic dilem- Computed tomography and positron lymphadenopathy. mas. It is an STD caused by infection emission tomography scans show cer- Obtaining a sexual history entails with the spirochete Treponema pal- vical, axillary, hilar, abdominal, pel- a discussion of how many sexual lidum, which often passes through vic, and inguinal lymphadenopathy. partners the patient has had, current three overlapping clinical stages. Lymph node biopsy reveals reactive sexual activity, condom use, and any history of genital ulcer disease. If the Primary syphilis

CPT George is an infectious diseases fellow at patient reports previous ulcer disease, Patients with primary syphilis typi- Brooke Army Medical Center, San Antonio, TX. the provider should ask about the na- cally present with a chancre (a pain- LTC Lesho is an investigator in the division of ture of the disease, including whether less, small, round ulcer located at retrovirology at the Walter Reed Army Medical Center, Washington, DC and the National Navy the lesions were painful or recur- the site of infection) an average of 21 Medical Center, Bethesda, MD. rent. In addition, providers should days after exposure (range, 10 to 90

AUGUST 2006 • FEDERAL PRACTITIONER • 29 COMMON ERRORS IN INTERNAL MEDICINE

days). This stage is often associated or condyloma lata, can be scraped GOOD NEWS IN TREATMENT with inguinal lymphadenopathy. and examined under a dark-field Fortunately, syphilis has not yet dem- microscope. This test is particularly onstrated any clinically significant Secondary syphilis important for patients with primary resistance to penicillin—its thera- Symptoms of secondary syphilis typi- syphilis, in whom an antibody re- peutic mainstay3 and drug of choice cally develop four to 10 weeks after sponse may not yet be positive. The for treatment. Primary, secondary, or the initial chancre. A rash occurs spirochete has a classic corkscrew early latent syphilis can be treated most often during this stage, usually or folding motion that is detectable with benzathine penicillin G 2.4 mil- described as macular or maculopapu- using this method of examination— lion U IM in a one-time dose. Patients lar. This rash commonly is found on provided the slides are examined with late latent syphilis, syphilis of the patient’s trunk, arms, palms of the immediately. In addition, the exam- unknown duration, or tertiary syphi- hands, or soles of the feet—but also ination’s sensitivity varies with the lis should be treated with benzathine may affect the face. The papules of skill of the technician. penicillin G 2.4 million U IM each secondary syphilis can coalesce in in- Scrapings should be examined on week for three weeks.5 Neurosyphi- tertriginous areas, causing highly in- three different days before a lesion is lis should be treated with benzathine fectious lesions known as condyloma determined to be free of T. pallidum.2 penicillin 3 to 4 million U IV every lata. The lesions may be accompanied Direct fluorescent antibody assays, four hours or as a continuous infu- by constitutional symptoms, such as such as the fluorescent treponemal an- sion for 10 to 14 days.5 low-grade fever, arthralgias, and gen- tibody-absorbed (FTA-abs) test, can Second-line agents, such as doxy- eralized lymphadenopathy. be used to detect treponemal antigens cycline, can be used in penicillin- Another manifestation of second- from scrapings. These tests are advan- allergic patients who are not pregnant ary syphilis is the appearance of su- tageous because they can be performed and do not have neurosyphilis. Peni- perficial, painless, mucosal erosions on dried specimens and, therefore, do cillin-allergic patients who are preg- in the mouth or genital regions. Cen- not require immediate evaluation by a nant or have neurosyphilis, however, tral nervous system (CNS) involve- specially trained microscopist. should undergo penicillin desensiti- ment during this stage can manifest Patients suspected of having syph- zation.5 as aseptic meningitis, cranial neurop- ilis are evaluated initially with a non- Follow-up with a nontreponemal athy, or anterior uveitis. treponemal serology test, such as RPR serology test (such as RPR) at six or venereal disease research labora- months and 12 months is recom- Latent syphilis tory tests, both of which measure an- mended. Treatment failure is defined Latent syphilis is defined as the pe- tibody response to lipoidal antigen. as either the failure of titers to decline riod after the manifestations of sec- Positive nontreponemal tests are fourfold within six months or a four- ondary syphilis resolve. Patients confirmed with a treponemal test, fold increase in titers after treatment become asymptomatic at this time, such as the FTA-abs, that measures is completed.5 which can be divided further into treponemal-specific antibodies by The RPR may not be available early and late stages. immunofluorescence. False-positive as a primary diagnostic modality in About one third of individuals nontreponemal results may be seen some settings with limited resources, with untreated latent syphilis de- with various conditions, including where targeted test-and-treat eradi- velop tertiary syphilis, characterized autoimmune diseases, tuberculosis, cation strategies are performed, be- by gumma—which are inflamma- pregnancy, infectious mononucleosis, cause cold storage is required for tory lesions of the skin, the CNS, or HIV, rickettsial infections, and other reagents and electricity is needed to bone. General pareses from cerebral spirochete infections (such as lepto- operate a rotator. To alleviate these involvement and tabes dorsalis from spirosis).3 Nontreponemal serology drawbacks, new RPRs that are stable posterior column demyelination tests are 78% to 86% sensitive during at room temperature are becoming characterize CNS involvement in ter- the primary syphilis stage, 100% sen- more readily available, as are solar tiary syphilis. sitive in secondary syphilis, and 95% powered rotators.6 to 98% sensitive in latent syphilis.4 Similarly, confirmatory assays usu- Diagnosis FTA-abs is 84% sensitive in primary ally are not available outside of ref- To make a syphilis diagnosis, muco- syphilis and 100% sensitive in sec- erence laboratories in these limited cutaneous lesions, such as chancre ondary and latent syphilis.4 settings, but the availability of confir-

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30 • FEDERAL PRACTITIONER • AUGUST 2006 NOTES FROM THE FIELD

ing, and rescue services for the flight MWSS 372 corpsmen built cabinets formulary”—that usually are handled line and served as first responders to for field sinks, which have tanks of by support staff stateside. This tour any aviation mishaps. Corpsmen ac- water that are pumped to faucets and helped me to grow as a physician and companied each convoy and response drain into other containers. Other improve my diagnostic skills without team that left the base in case any in- projects—such as the remodeling of the benefit of many technological juries or illnesses occurred during the living areas and routing of cables for tools available at home. By forcing us trip. To keep our base healthy, preven- computer networks, electricity, and to adapt from practice in a sophisti- tive medicine technicians inspected American Forces Network televi- cated, tertiary care center one month and exterminated insects from the liv- sion—improved the appearance and to a level-one aid station in a remote ing quarters of hundreds of marines. organizational capacity of the base. combat zone the next, deployment Corpsmen also shared their first aid presents military physicians with a knowledge with everyone on the BACK TO BASICS unique opportunity as well as a chal- battlefield through combat lifesaver My experience in Iraq, though worlds lenging responsibility. ● classes. Moreover, we all learned from away, reminded me of my step- one another in informal ways—about grandfather’s and great-grandfather’s The opinions expressed herein are those medicine, the marine corps, and our stories about practicing medicine of the author and do not necessarily own hobbies and interests. in rural Wisconsin. In treating their reflect those of Federal Practitioner, During our deployment, the patients, they made due with the lim- Quadrant HealthCom Inc., the U.S. corpsmen of MWSS 372 made a tre- ited tools and medications available government, or any of its agencies. This mendous effort to improve the clinic. in their offices, which were an hour’s article may discuss unlabeled or inves- They built countless plywood shelves drive away from the nearest hospital. tigational use of certain drugs. Please to organize supplies and records, I found it refreshing to participate in review complete prescribing information painted whole rooms, converted an tasks—such as positioning patients for specific drugs or drug combina- unusable shower room into an of- for x-ray imaging, casting fractures, tions—including indications, contra- fice, and even built a charcoal grill viewing laboratory samples under the indications, warnings, and adverse from a 40-gallon drum. Though microscope, and browsing the phar- effects—before administering pharma- the building has no running water, macy shelves to see what was “on cologic therapy to patients.

COMMON ERRORS IN INTERNAL MEDICINE

Continued from page 30 matory testing platforms that do not obtain a comprehensive sexual his- contraindications, warnings, and ad- require electricity also is increasing.6 tory, as the patient’s previous hepatitis verse effects—before administering New platforms for predicting clini- B infection represents a history of a pharmacologic therapy to patients. cal phenotypes of infected strains of potential STD. ● T. pallidum are under development. REFERENCES 1. Lynn WA, Lightman S. Syphilis and HIV: A danger- These may help identify patients who The authors wish to thank Dr. Kather- ous combination. Lancet Infect Dis. 2004;4:456–466. are at risk for developing neurosyphi- ine Spooner for her input on this manu- 2. Brown DL, Frank JE. Diagnosis and management of syphilis. Am Fam Physician. 2003;68:283–290. lis and, therefore, would benefit from script. 3. Fantry L, Tramont EC. Treponema pallidum (syphi- more extensive evaluations, such as lis). In: Yu VL, Webber R, Raoult D, eds. Antimicro- bial Therapy and Vaccines. 2nd ed. New York, NY: lumbar puncture or empiric therapy The opinions expressed herein are Apple Trees Productions, LLC;2002:749–757. targeted at the CNS.7 those of the authors and do not neces- 4. Larsen SA, Steiner BM, Rudolph AH. Laboratory di- agnosis and interpretation of tests for syphilis. Clin The case presented here empha- sarily reflect those of Federal Practi- Microbiol Rev. 1995;8:1–21. sizes the importance of primary care tioner, Quadrant HealthCom Inc., the 5. Centers for Disease Control and Prevention. Sexu- ally transmitted diseases treatment guidelines 2002. providers obtaining a thorough pa- U.S. government, or any of its agencies. MMWR Recomm Rep. 2002;51(RR-6):1–78. tient history and performing a com- This article may discuss unlabeled or 6. Peeling RW, Mabey DC. Syphilis. Nature Rev: Mi- crobiol. 2004;2:448–449. Available at: www.who.int plete physical examination in order to investigational use of certain drugs. /trd/dw/pdf/dw6_2004.pdf. Accessed July 20, 2006. prevent unnecessary, time consuming, Please review complete prescribing in- 7. Tantalo LC, Lukehart SA, Marra CM. Treponema pallidum strain-specific differences in neuroinvasion and costly evaluations. It also demon- formation for specific drugs or drug and clinical phenotype in a rabbit model. J Infect strates the consequences of failing to combinations—including indications, Dis. 2005;191:75–80.

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