AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Background

Treponematosis traditionally refers to the group of nonvenereal diseases that are caused by Treponema species that are morphologically and serologically identical to each other and to Treponema pallidum subspecies pallidum, the cause of syphilis. They differ only in their clinical manifestations. All the nonvenereal Treponema species are transmitted, chiefly by direct contact, among children living in tropical and subtropical climates. In humans, the pathogenic treponemes are T pallidum pallidum, Treponema pertenue (yaws), Treponema endemicum (bejel or endemic syphilis), and Treponema carateum (pinta).

Pathophysiology

These organisms usually invade traumatized cutaneous or mucosal surfaces that come in contact with a draining open sore of the index case. A primary cutaneous lesion appears at the site of inoculation following an incubation period of a few weeks. Treponema may be spread from this site either topically (by scratching) or hematogenously. These lesions often heal. The disease can remain latent or it may recur. The secondary stage of any of these diseases follows the dissemination of the treponemes. It may begin while the primary lesion is still present or after a variable latent period. It may also resolve spontaneously, recur, or persist. The long-term effects of these infections include multiple cutaneous lesions and destruction of bones or cartilage.

Frequency

United States

Although infection with the endemic treponemes does not occur in the United States, imported cases have been documented.

International

In 1997, the World Health Organization (WHO) estimated that 460,000 new cases of endemic treponematoses occurred worldwide.

Endemic syphilis (bejel) (T pallidum endemicum) is typically spread among children, most commonly in the Middle East and the southern Sahara desert regions. In Europe, cases have been diagnosed in children who have moved from endemic areas. In one study, 12% of children younger than 5 years in Niger were seropositive. High rates of seropositivity are also observed in Mali, Burkina Faso, and Senegal. Pinta (T carateum), which occurs in the Caribbean and in Central and South America, is more common in young adults.

Yaws (T pallidum pertenue) occurs mainly in equatorial regions and can be found in South America, Central America, the Caribbean, Africa, and Southeast Asia. It is associated with high humidity and rainfall. Fifty years ago, the WHO recognized that endemic treponematoses—yaws in particular—were a major cause of disfigurement and disability and a significant economic burden in poor countries.

In Haiti and the Dominican Republic, a pilot project was initiated to eradicate the disease with mass applications of penicillin. This project was so successful that it was extended to 46 other countries. Overall, the incidence of yaws was reduced to isolated foci of endemicity. As public health priorities changed and support for the eradication programs lapsed, the disease has undergone a resurgence in the 1970s and 1980s. The introduction of mass treatment has been necessary in some areas.

Mortality/Morbidity

If untreated, treponematosis may cause disfiguring cutaneous lesions as well as deformities of the bone and cartilage. If left untreated, any of these pathogens may cause significant disfigurement, pain, and disability. These infections can extract a significant economic toll on already disadvantaged populations. Fortunately, with penicillin therapy, cure rates of 95-97% are possible.

Race

Differences in frequency or severity of infection between races have not been described.

Sex

Differences in frequency or severity of infection between the sexes have not been described.

Age

Although individuals of any age can be infected, endemic syphilis and yaws are more common in children younger than 10 years, whereas pinta is observed more frequently in young adults. Yaws most often infects children and peaks from ages 2-10 years. Of new cases, 75% arise in children younger than 15 years. Congenital infections with the endemic treponemes are unusual because most primary infections occur in children. Primary infection during pregnancy is rare.

CLINICAL

Section 3 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

History

• Patients may present with a characteristic rash or lesions that either do not heal or that continue to spread.
• Patients often have a history of living in or extended travel to endemic areas.
• Patients in later stages may present with a variety of skin, bone, and joint manifestations.

Physical

• Endemic syphilis (bejel) (T pallidum endemicum)
• • The primary lesions are painless, white, mucinous ulcers within the oral cavity, where they may be overlooked.
  • Secondary lesions may be in the mouth or widely disseminated. The secondary lesions may be papules, macules, or a variety of other rashes.
  • The organism may infect the periosteal space, which leads to bone deformities.
  • A condition known as gangosa may occur late in the disease because the nasopharyngeal cartilage is destroyed.
  • Ocular manifestations include uveitis, optic atrophy, and chorioretinitis.
• Pinta (T carateum)
• • Pinta, which occurs in the Caribbean and Central and South America, is more common in young adults. It is favored by an arid rather than humid climate. A marked reduction to only several hundred reported cases has occurred over the past 2 decades.
  • The primary lesions appear 1-3 weeks after inoculation as slowly enlarging copper-colored papules, which may become hyperkeratotic and blue. Smaller satellite lesions may be observed and may coalesce with the larger ones. The lymph draining this area may be swollen. Lesions may persist for years and may heal, leaving hypopigmentation.
  • Secondary lesions may develop within 3-12 months as small papules, which are often located at the site of primary lesions. The lesions may be numerous and are called pintids. They are initially red but can become pigmented and appear blue over time. Lesions may later become depigmented to varying degrees, leading to a mottled appearance. Later manifestations are limited to cutaneous involvement. The deeper tissues or viscera are not involved.
• Yaws (T pallidum pertenue)
• • The primary lesion occurs 2 weeks to 6 months after inoculation. It begins as a papule that typically becomes a large papilloma. This may persist for several months and then resolve spontaneously, often with scarring. During this stage, the treponeme may disseminate by means of the bloodstream or the lymphatics or topically through excoriation by the individual.
  • Secondary disease can involve multiple cutaneous lesions, including macules, papules, nodules, hyperkeratoses, and ulcerations. Lymphadenitis with swollen and tender lymph nodes may occur proximal to lesions. Periosteal infection and destruction of cartilage occur later in the course of the disease.
  • The initial lesions characteristically resolve spontaneously by 6 months but then recur after a latent period. Relapses often occur for up to 5 years, after which they diminish in severity and frequency.
  • Approximately 10% of untreated patients develop late disease, including periosteal lesions that damage bone.
  • Deformities are also observed, including saber shins caused by chronic periosteal infection of the tibia and gangosa as well as destruction of the cartilage in the nose.
  • Other late-stage manifestations include hyperkeratoses of the palms and soles and gummas of the skull, sternum tibia, and other bones.

Causes

Direct contact with lesions, or in the case of endemic syphilis, fomites, spreads the diseases.

• Endemic syphilis (bejel) (T pallidum endemicum)
• • The organism can be indirectly transmitted on objects as well as by direct contact with lesions.
  • Much of the transmission is thought to be from mouth-to-mouth contact or from shared eating utensils or drinking cups.
• Yaws is transmitted by direct exposure to skin lesions that shed the treponemes.

DIFFERENTIALS

Section 4 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Other Problems to be Considered

Pyoderma
Cutaneous leishmaniasis
Tropical ulcer
Neurodermatitis
Tinea versicolor
Chloasma
Vitiligo

WORKUP

Section 5 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Lab Studies

• Endemic syphilis should be suspected in persons with chronic skin or bone lesions who live in endemic areas.
• • As with other treponeme diseases, confirmation of the diagnosis depends on dark-field examination and serologic testing.
  • The epidemiologic setting is vital because laboratory studies cannot distinguish the nonvenereal treponemes from T pallidum pallidum (the cause of venereal syphilis).
• Because treponemes cannot be easily and readily cultured, use other laboratory methods of identifying infection. The current tests for syphilis fall into the following 3 categories: direct microscopic identification when lesions are present, nontreponemal tests used for screening, and treponemal tests used for confirmation.
• • Direct microscopy
  • • Direct microscopic identification of treponemes from lesion fluids by either dark-field microscopy or direct fluorescent antibody should be the initial step in diagnosing a treponemal infection. This is most helpful during the primary stage of infection because treponemal antibodies do not usually appear until 1-4 weeks after the lesion has formed.
    • A negative dark-field finding does not exclude the diagnosis of treponematosis because the organisms may be too few if the lesion is in the healing stage or if the infection has been altered by treatment.
  • Nontreponemal tests
  • • These include the nontreponemal rapid plasma reagin (RPR) test and the VDRL test.
    • RPR is inexpensive and rapid and is convenient for screening large numbers of sera specimens.
    • The standard nontreponemal test is the VDRL slide test in which serum is tested for its ability to flocculate a suspension of cardiolipin-cholesterol-lecithin antigen. This test is based on the observation that antibodies elicited against treponemal surface antigens cross-react with cardiolipin.
  • Treponemal tests
  • • The principal confirmatory treponemal antibody test is the fluorescent treponemal antibody absorption (FTA-ABS) test. This is an indirect immunofluorescent antibody test that uses T pallidum organisms as the antigen. The patient's serum is first absorbed to remove any naturally occurring cross-reacting antibody; it is then reacted with the organism.
    • Because of the nonstandardized, qualitative, and subjective nature of this test, its principal use is to confirm any positive VDRL or RPR test result.

Imaging Studies

• Imaging studies are generally not used in the diagnosis or treatment of endemic treponematosis, although changes to bone periosteum and cartilage may be observed on x-ray film in late-stage yaws or endemic syphilis.

Histologic Findings

Dark-field microscopy of material from cutaneous lesions often yields treponemes. However, this technique may not be available in endemic areas, and pathologic diagnosis is not considered necessary. In yaws and pinta, granulomatous inflammation resembles that of syphilis. Endarteritis is a feature of late yaws lesions.

TREATMENT

Section 6 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical Care

Treatment is based on single-dose antibiotic therapy with benzathine penicillin.

• Treponemes are highly sensitive to penicillin, which remains the drug of choice.
• • Yaws, pinta, and endemic syphilis are treated with benzathine penicillin G. Children younger than 10 years should receive 600,000 U intramuscularly, and children older than 10 years should receive 1.2 million U intramuscularly.
  • Alternatives are appropriate only if benzathine penicillins cannot be used. Tetracycline (25 mg/kg/d for 10-14 d) and chloramphenicol (25 mg/kg/d for 10-14 d) have been used successfully, as has a 10-day course of doxycycline. Other penicillins, cephalosporins, and macrolides are probably active against the treponemes; however, quinolones, aminoglycosides, and sulfa antibiotics are ineffective.
  • Treatment failures with penicillin have been reported, but reinfection could not be ruled out.
• Other important measures from the perspective of the individual patient and for public health include avoiding contact to others with cutaneous lesions and careful follow-up care to identify and to re-treat initial treatment failures.

MEDICATION

Section 7 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

The goals of pharmacotherapy are to eradicate the infection, reduce morbidity, and prevent complications.

Drug Category: Antibiotics

Treponemes are highly sensitive to penicillin, which remains the DOC. Yaws, pinta, and endemic syphilis are treated with penicillin G benzathine. Alternatives are appropriate only if penicillin cannot be used. Tetracyclines or chloramphenicol have been used. Treatment failures with penicillin have been reported, but reinfection could not be ruled out.

FOLLOW-UP

Section 8 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Further Inpatient Care

• Conscientious follow-up care to detect treatment failures and reinfection is recommended. Treatment failures or reinfections should be treated again. If penicillin was initially used, one of the alternative antibiotics listed might be considered.

Patient Education

• For excellent patient education resources, visit eMedicine's Sexually Transmitted Diseases Center. Also, see eMedicine's patient education article Syphilis.

MISCELLANEOUS

Section 9 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical/Legal Pitfalls

• Failure to diagnose is the greatest pitfall for clinicians presented with cases of the endemic treponematosis. Although treatment failures are unusual, a follow-up examination several months after completion of treatment may be useful to detect recurrence or inadequate treatment.

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

• Agadzi VK, Aboagye-Atta Y, Nelson JW. Resurgence of yaws in Ghana. Lancet. Aug 13 1983;2(8346):389-90. [Medline].
• Anselmi M, Araujo E, Narvaez A. Yaws in Ecuador: impact of control measures on the disease in the Province of Esmeraldas. Genitourin Med. Dec 1995;71(6):343-6. [Medline].
• Backhouse JL, Hudson BJ, Hamilton PA. Failure of penicillin treatment of yaws on Karkar Island, Papua New Guinea. Am J Trop Med Hyg. Sep 1998;59(3):388-92. [Medline].
• Chulay JD. Treponema species (Yaws, Pinta, Bejel). In: Long SS, Pickering LK, Prober CG, eds. Principles and Practice of Infectious Diseases. New York, NY. Churchill Livingston;2000:2490-94.
• Engelkens HJ, Judanarso J, Oranje AP. Endemic treponematoses. Part I. Yaws. Int J Dermatol. Feb 1991;30(2):77-83. [Medline].
• Julvez J, Michault A, Kerdelhue V. [Serologic studies of non-venereal treponematoses in infants in Niamey, Niger]. Med Trop (Mars). 1998;58(1):38-40. [Medline].
• Kim SC, Guerrero R, Gonzalez R. A 23-year-old pregnant woman with left-foot and left-ankle ulceration. Clin Infect Dis. Jul 1 2004;39(1):81-2, 136-7. [Medline].
• Koff AB, Rosen T. Nonvenereal treponematoses: yaws, endemic syphilis, and pinta. J Am Acad Dermatol. Oct 1993;29(4):519-35; quiz 536-8. [Medline].
• Perine PL, Hopkins DR, Niemel PLA. Handbook of Endemic Treponematoses: Yaws, Endemic Syphilis, and Pinta. WHO Publications Centre, USA. World Health Organization;1984.
• Second International Conference on Control of Yaws. Report of the Second International Conference on Control of Yaws: Nigeria 1955. J Trop Med Hyg. 1957;60:2638.
• Tabbara KF, al Kaff AS, Fadel T. Ocular manifestations of endemic syphilis (bejel). Ophthalmology. Jul 1989;96(7):1087-91. [Medline].
• Vabres P, Roose B, Berdah S. [Bejel: an unusual cause of stomatitis in the child]. Ann Dermatol Venereol. Jan 1999;126(1):49-50. [Medline].
• Walker DH, Guerrant RL, Weller PF. Treponemal infections. In: Guerrant RL, Walker DH, Weller PF, eds. Tropical Infectious Diseases: Principles, Pathogens, and Practice. New York, NY. Churchill Livingstone;1999:527-34.
• Walker SL, Hay RJ. Yaws-a review of the last 50 years. Int J Dermatol. Apr 2000;39(4):258-60. [Medline].
• World Health Organization. WHO Expert Committee on Venereal Infections. Report on the third session. Vol 13. 1950.
• World Health Organization. 1998 World Health Report: Health in the 21st Century: A Vision for All. 1998.

Article Last Updated: Mar 24, 2006