Treponema pallidum Case File

Treponema pallidum Case File

Eugene C.Toy, MD, Cynthia Debord, PHD, Audrey Wanger, PHD, Gilbert Castro, PHD, James D. Kettering, PHD, Donald Briscoe, MD

CASE 22

A 20-year-old man presents for evaluation of a rash that he thinks is an allergic reaction. For the past 4 or 5 days he has had the “flu,” with fever, chills headache, and body aches. He has been taking an over-the-counter flu medication without any symptomatic relief. Yesterday he developed a diffuse rash made up of red, slightly raised bumps. It covers his whole body, and he says that it must be an allergic reaction to the flu medication. He has no history of allergies and takes no other medications, and his only medical problem in the past was being treated for gonorrhea approximately 2 years ago. On further questioning, he denies dysuria or penile discharge. He denies any genital lesions now, but says that he had a “sore” on his penis a few months ago that never really hurt and went away on its own after a few weeks so he didn’t think much about it. On exam, his vital signs are all normal. He has palpable cervical, axillary, and inguinal adenopathy. His skin has an erythematous, maculopapular eruption covering his whole body including his palms and soles of his feet. No vesicles are noted. His genital examination is normal.

◆ What organism is the likely etiology of this disease?

◆ What disease and stage does this patient have?

◆ What microscopic examination could confirm this diagnosis?

◆ Which serologic tests could assist in his diagnosis?

ANSWERS TO CASE 22: Treponema pallidum

Summary: A 20-year-old man has adenopathy and a macular papular rash affecting his soles and palms. He had a painless penile “sore” that spontaneously resolved.

◆ Most likely causative organism: Treponema pallidum.

◆ Disease and stage: The patient has syphilis, more specifically secondary syphilis.

◆ Microscopic examination to confirm the diagnosis: Examination by darkfield microscopy of exudates from skin lesions could confirm the diagnosis of T. pallidum infection and secondary syphilis.

◆ Serologic tests to assist in the diagnosis: The following serologic examinations are useful in diagnosis: Venereal Disease Research Laboratory (VDRL) and rapid plasmin reagin (RPR) tests are used for initial screening, while the fluorescent treponemal antibody-absorption test (FTA-ABS ), and the microhemagglutination test for T. pallidum (MHA-TP), are the more specific diagnostic tests.

CLINICAL CORRELATION

Treponema pallidum is a gram-negative, microaerophilic spirochete that causes venereal syphilis, the third most common bacterial sexually transmitted disease in the United States. It is transmitted by contact with fluid from an ulcer containing the infectious agent either through sexual contact by penetrating intact mucous membranes or through nonsexual contact with the agent with skin that is broken or abraded. Studies estimate that transmission occurs in over half of sexual encounters where a lesion is present. Treponema pallidum infection results in multiple disease phases with distinctive clinical manifestations. Primary syphilis usually involves the formation of a painless ulcer at the site of entry of the organism, called a chancre. Chancres are highly contagious by contact and can spontaneously heal after a few weeks to a few months. Secondary syphilis develops 2–12 weeks after the primary stage and is characterized by a flu-like illness, followed by a rash that typically starts on the trunk but can spread to any skin or mucous membrane surface. Without treatment, the symptoms generally resolve in 3–12 weeks. This is followed by a relatively asymptomatic period known as latency, which can last for years. Some infected persons have no further symptoms; however, some progress to tertiary syphilis, a diffuse disease with many effects on the dermatologic, musculoskeletal, cardiovascular, and central nervous systems. Currently the population most at risk is heterosexual African Americans living in urban areas.

APPROACH TO SUSPECTED Treponema pallidum INFECTION

Objectives

1. Know the natural history of syphilis infection.
2. Know the methods of diagnosis and treatment of syphilis.

Definitions

Macule: Flat lesion that is not palpable, of a different color from surrounding skin and smaller than 1 cm.

Microaerophilic: Organisms that can tolerate small amounts of oxygen because they contain superoxide dismutase. They use fermentation in the absence of oxygen.

Tabes dorsalis: A condition characterized by diminished vibratory, proprioceptive, pain, and temperature senses, as well as the loss of reflexes.

Argyll Robertson pupil: Constricts during accommodation but does not react to light.

DISCUSSION

Characteristics of Treponema pallidum That Impact Transmission

Treponema pallidum is a thin spirochete and an obligate human pathogen. It consists of three subspecies, each of which causes disease in humans. Treponema pallidum is labile, unable to survive exposure to drying, and is very difficult to grow in culture. Treponema pallidum does not have a capsule and usually contains six axial filaments, located between the outer membrane and the peptidoglycan layer. It produces no toxins that have been currently identified. Treponema pallidum is too thin to be seen with standard microscopy with Gram stain but can be seen with darkfield microscopy or by staining with antitreponemal antibodies labeled with fluorescent dyes. Treponema pallidum is transmitted by direct contact with an infectious lesion, transfusion of infected blood, or congenital transfer. It attaches by one or both ends to host cells, although it rarely penetrates the cell. The resultant disease of syphilis occurring primarily because of the host immune response to the treponemal infection, with both humoral and cell-mediated immune systems playing a role.

Syphilis disease presents in three different stages with characteristics specific to each stage. Primary syphilis presents with a hard, painless, broadbased chancre. The chancre has a punched-out base and rolled-up edges, sometimes expelling a serous exudate. This primary lesion presents 3–6 weeks after the initial contact with the infectious agent. It typically resolves in 4–6 weeks and does not leave scar tissue. Secondary syphilis presents with a symmetrical widely distributed macular rash. The rash can infect the mucous membranes including the cervix, throat, and mouth. It may also appear on the palms and soles of the patient, an important clinical finding because there are few diseases that present with a rash on palms and soles. Patchy hair loss is also seen, typically causing the eyebrows to fall out. There is usually a lowgrade fever, weight loss, and general malaise. Condyloma latum is a painless, wart-like lesion on the scrotum or vulva that may also be present during this stage (Figure 22-1). Secondary syphilis occurs several weeks after the lesion of primary syphilis has healed. It is during the secondary stage where syphilis is considered to be most infectious.

After secondary syphilis, there is a latent period where the disease is not infectious, although the patient is still seropositive. This stage can range from 2 years to several decades. Tertiary syphilis can present with personality changes, blindness, paresis, gummas, Argyll Robertson pupils and tabes

dorsalis. Gummas are granulomatous lesions of the skin and bone which are necrotic and fibrotic. Tabes dorsalis is characterized by diminished vibratory, proprioceptive, pain, and temperature sense, as well as the loss of deep tendon reflexes. It is the damage to the dorsal roots and ganglia which cause the loss of reflexes, pain, and temperature sense, while the loss of proprioception and vibratory sense are because of the posterior column involvement. The Argyll Robertson pupil constricts during accommodation but does not react to light.

Figure 22-1. Genital condylomata lata of secondary syphilis. (Reproduced, with permission, from Cunningham FG et al. William’s Obstetrics, 21st ed. New York: McGraw-Hill, 2001:1487.)

Diagnosis

The diagnosis of syphilis can be made by identification of spirochetes by darkfield microscopy of a chancre or skin lesion sample of the primary and secondary stages, respectively; however, most syphilis is diagnosed by serologic studies.

There are several serologic laboratory tests that may be used to detect syphilis. The VDRL and RPR are nonspecific tests of host production of anticardiolipin antibody. These will be positive in approximately 80 percent of cases of primary and all secondary stages of syphilis. False-positive VDRLs may be encountered in patients with lupus, infectious mononucleosis, hepatitis A, the antiphospholipid antibody syndrome, leprosy, malaria, and occasionally pregnancy. False-negative RPR and VDRLs may be obtained early in the disease. The more specific treponemal tests, the FTA-ABS and the TP-PA, are used for confirmation of infection. They detect the presence of antibodies specific to T. pallidum.

Treatment and Prevention

The drug of choice for the treatment of syphilis is benzathine penicillin. One injection is given when the infection is less than 1 year duration, whereas injections each week for 3 weeks is administered for infection longer than 1 year. Patients who are allergic to penicillin are treated with erythromycin and doxycycline. However, doxycycline is contraindicated in patients who are pregnant, because it can cross the placenta and is toxic to the fetus. Universal precautions used in the clinical setting are adequate to prevent the transmission of syphilis. Outside of the clinical setting, safe sex should be practiced to prevent the transmission through sexual contact. Currently, there is no vaccine available for the prevention of T. pallidum infection.

COMPREHENSION QUESTIONS

[22.1] A 21-year-old Asian woman visits her obstetrician and is later diagnosed with secondary syphilis. On further questioning, it is determined she is allergic to penicillin. Because T. pallidum is known to cross the placenta, treatment is started immediately. Which antibiotic would be most appropriate in this situation?

A. Tetracycline

B. Ceftriaxone

C. Penicillin G

D. Doxycycline

E. Erythromycin

[22.2] A 27-year-old white man presents to his family doctor complaining of being tired all the time and having a slight fever for the past 2 weeks. He recently returned from a trip to Las Vegas, where he indulged in some of the infamous nightlife. His physical exam is unremarkable except for a macular rash over his trunk and on the palms of his hands. There are no lesions or ulcers on the penis. What organism is causing this man’s illness?

A. Chlamydia trachomatis

B. Neisseria gonorrhea

C. Treponema pallidum

D. Borrelia burgdorferi

E. Rickettsia rickettsii

[22.3] A sample is taken from a vulvar ulcer in a 25-year-old sexually active African American female. The organism is a weakly staining gramnegative, microaerophilic organism. When attempting to view a smear under a microscope, no organisms are seen. Which method of visualization is most appropriate in this setting?

A. Ziehl-Neelsen stain

B. India ink preparation

C. Congo red stain

D. Darkfield microscopy

E. Giemsa stain

[22.4] A third-year medical student is on his first rotation in internal medicine. His attending physician points out that there are several tests that are used to diagnose syphilis. Which test is most specific for the detection of syphilis?

A. Rapid plasmin reagin (RPR)

B. Fluorescent treponemal antibody-absorption (FTA-ABS)

C. Venereal Disease Research Laboratory (VDRL)

D. Ziehl-Neelsen stain

E. Aerobic and anaerobic blood cultures

[22.5] A 28-year-old sexually active woman presents for her annual wellwoman exam. She at times has a low-grade fever and lately has noticed a rash on her face, mainly on the cheeks. She is saddened to learn she has a positive VDRL test for syphilis. However, she is asymptomatic for syphilis and is in a monogamous relationship with her husband who has not had any other sexual contacts. Which of the following is the most likely reason for the positive syphilis test?

A. She has secondary syphilis.

B. She has HIV, altering her immune reaction.

C. She had exposure to syphilis earlier this week.

D. She has systemic lupus erythematosus (SLE).

E. She has Chlamydia.

Answers

[22.1] E. Erythromycin and doxycycline are used when allergy to penicillin is present. Doxycycline is contraindicated in pregnant women because it crosses the placenta and is toxic to the fetus. Ceftriaxone and tetracycline are not used for the treatment of syphilis. Penicillin is contraindicated because of the patient’s allergies.

[22.2] C. Treponema pallidum is usually transmitted through unprotected sexual activity with an infected individual. This man presents with the symptoms of secondary syphilis, which includes malaise, mild fever, and rash on the palms or soles of the feet. The primary lesion (chancre) may go unnoticed because it is painless and subsides in a few weeks. Neisseria gonorrhea is associated with a serous exudate. Chlamydia is associated with painful urination. Rickettsia rickettsii and Borrelia burgdorferi are associated with arthropod vectors.

[22.3] D. The organism present is T. pallidum, a spirochete. No organisms are seen under light microscopy because spirochetes are too small to be visualized by this technique. Use of darkfield microscope allows for visualization of the corkscrew morphology. The Ziehl-Neelsen stain is used to detect acid-fast bacteria such as mycobacteria. India ink preparations are used to visualize a capsule that is present in Cryptococcus neoformans but that spirochetes do not have. Giemsa stain is used to detect Borrelia, Plasmodium, Trypanosomes, and Chlamydia species.

[22.4] B. There are two classes of test used to detect the presence of an infection. The nontreponemal tests detect the presence of antibodies against lipids present on the organism. The nontreponemal tests include RPR and VDRL. Specific tests that detect antibodies against the organism itself, include TP-PA and FTA-ABS. Aerobic and anaerobic cultures are not specific tests used to identify syphilis. The Ziehl-Neelsen stain is used to identify acid fast bacteria.

[22.5] D. In the presence of a woman with no known contacts with syphilis and a low-grade fever and rash, it is most likely that she had a falsepositive reaction to the VDRL test because of lupus (SLE). This is often a common finding in lupus patients, and may be the first sign that they have lupus. In contrast, the VDRL test would be positive in secondary syphilis, often in high titer (greater than 1:32). Her being positive for HIV, while she may also have a false-positive reaction to the VDRL test if HIV positive, is not the most likely answer choice for this patient. The presence of the malar rash makes SLE more likely. Recent exposure to syphilis would lead to a false-negative test result; antibodies form between 4 and 8 weeks from exposure. Chlamydia trachomatis infection would not lead to a positive test result for syphilis.

MICROBIOLOGY PEARLS ❖ Some of the nontreponemal nonspecific tests are the VDRL and RPR. ❖ The specific treponemal tests include the FTA-ABS and TP-PA. ❖ Primary syphilis generally consists of a painless chancre. ❖ Secondary syphilis consists of a generalized macular popular rash especially affecting the palms or soles, or condyloma latum. ❖ Tertiary syphilis is typified by gummas, neurosyphilis, tabes dorsalis, Argyll Robertson pupil. ❖ The best treatment for syphilis is penicillin.

REFERENCES

Murray PR, Rosenthal KS, Pfaller MA. Medical Microbiology, 5th ed. St. Louis, MO: Mosby, 2005:339–45. 

Ryan JR, Ray CG. Sherris Medical Microbiology, 4th ed. New York: McGraw-Hill, 2004:422–30. 

Schneider AS, Szanto PA. Pathology: Board Review Sseries, 2nd ed. Philadelphia, PA: Lippincott Williams & Wilkins, 2001:272, 278, 281.

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