Yaws 

Updated: Jan 23, 2017
Author: Hassan I Galadari, MD; Chief Editor: William D James, MD 

Overview

Background

Yaws is the most prevalent infectious, nonvenereal treponemal disease and is caused by Treponema pallidumpertenue. Yaws, endemic syphilis (bejel), and pinta collectively constitute the endemic treponematoses. Yaws is transmitted by direct skin contact and primarily affects children younger than 15 years, with a peak incidence in those aged 6-10 years. Similar to syphilis, yaws can persist for years as a chronic, relapsing disease.[1, 2, 3]

Yaws continues to be endemic along the tropical belt in areas characterized by hot temperatures, high humidity, and heavy rainfall. These conditions, coupled with the persistence of poverty, poor sanitation, overcrowding, and lack of public health surveillance, allow for yaws perpetuation.[4]

Between the years 1952 and 1964, the World Health (WHO) and UNICEF (United Nations Children’s Fund) undertook a major worldwide campaign to eliminate the endemic treponematoses by treating 300 million people in 46 countries with benzathine benzylpenicillin. They achieved a 95% success rate; however, there was a reemergence of yaws in the 1970s. In 1995, the WHO estimated that there were 460,000 infectious cases of yaws throughout the world, with 400,000 in western and central Africa, 50,000 in Southeast Asia, and the remainder in other tropical areas.[3, 5, 6, 7, 8]

A new yaws eradication program was proposed in 2012 by the WHO following a study that showed that oral azithromycin can successfully treat yaws in rural, tropical areas. Compared to benzathine benzylpenicillin, oral azithromycin is a simpler regimen that does not require trained medical personnel for administration.[9] In India, yaws was successfully eradicated through a programm based on providing information to the population at risk, screening, and treatment. The WHO has concluded that this new eradication campaign can completely eliminate yaws worldwide by 2020.[7]

Etiology and Pathophysiology

Yaws is caused by Treponema pallidumpertenue, a slender spirochete that is serologically indistinguishable from the spirochete T pallidum, which causes syphilis. As with the other nonvenereal treponematoses, yaws is not found in urban centers, is not sexually transmitted, and is not congenitally acquired. The major route of infection is through direct person-to-person contact, and the treponemes associated with yaws are located primarily in the epidermis. Children serve as the primary reservoir for yaws, spreading the disease via skin-to-skin and skin-to–mucous membrane contact.

During the incubation period, T pallidum pertenue invades the subcutaneous lymphatics and disseminates hematogenously. The ulcerative skin lesions that develop early in the disease course are teeming with spirochetes, which can be transmitted via direct skin-to-skin contact and via breaks in the skin due to trauma, bites, or excoriations. Agmon-Levin et al suggested that the antitreponemal antibodies that build up in certain populations may also be protective for atherosclerosis while also being pathogenic for yaws.[10]

Yaws, like syphilis, has been classified into the following four stages:

  1. Primary stage, in which the initial yaws lesion develops at the inoculation site

  2. Secondary stage, in which widespread dissemination of treponemes results in multiple skin lesions that are similar to the primary yaws lesion

  3. Latent stage, in which symptoms are usually absent but skin lesions can relapse

  4. Tertiary stage, in which bone, joint, and soft tissue deformities may occur

Cutaneous lesions characterize the primary and secondary stages of yaws. The tertiary stage of yaws may involve the skin, bones, and joints.

Another classification distinguishes early yaws from late yaws. Early yaws includes the primary and secondary stages and is characterized by the presence of contagious skin lesions. Late yaws includes the tertiary stage, when lesions are not contagious.

Epidemiology

Yaws does not occur in the United States. However, according to the last estimate by the World Health Organization (WHO), in 1995, the prevalence of endemic treponematoses, mostly yaws, was 2.5 million, with 460,000 cases being infectious. In 2006, India declared that yaws had been eliminated in that country. According to the WHO, in 2010, yaws continues to be common in areas with the poorest population; the endemic nations included Indonesia, Timor-Leste, Papua New Guinea, the Solomon Islands, Vanuatu, Benin, Cameroon, Central Africa Republic, Congo, Cote d’Ivoire, Democratic Republic of the Congo, Ghana, Sierra Leone, and Togo.[3, 5, 6, 7, 8]

The population at risk of contracting yaws worldwide is estimated to be 34 million, evenly distributed between men and women (17 million each). Children serve as the primary reservoir for yaws, as the condition is transmitted from person to person via direct contact. By age group, the population considered to be at risk includes 23 million who are 14 years of age or younger and 11 million who are between the ages of 16 and 24 years. Approximately 75% of those affected by yaws are children younger than 15 years, with the peak incidence occurring between the ages of 6 and 10 years.[3, 5, 6, 7, 8]

Prognosis

Unless treated, yaws can become a chronic, relapsing disease after 5-15 years, with skin, bone, and joint involvement. In most patients, yaws remains limited to the skin, but early bone and joint involvement can occur. Although yaws lesions disappear spontaneously, secondary bacterial infections and scarring are common complications.

In 10% of yaws cases, patients enter a late stage (tertiary stage) characterized by destructive cutaneous lesions and severely deforming bone and joint lesions. Tissue damage occurring in late yaws is irreversible. Neurologic and ophthalmologic involvement may also occur. Relapses may occur at intervals of up to 5 years after infection.

 

Presentation

History and Physical Examination

Yaws has 3 clinical stages: primary, secondary, and tertiary. Stages are interspersed with asymptomatic latent periods. The typical yaws patient is young and from an endemic area and has been exposed to infected persons with active disease.[11, 12] Primary lesions, also called mother yaw, develop at the site of inoculation. (See the images below depicting yaws lesions).

Initial papilloma, also called mother yaw or prima Initial papilloma, also called mother yaw or primary frambesioma (from Perine PL, Hopkins DR, Niemel PLA, et al. Handbook of Endemic Treponematoses: Yaws, Endemic Syphilis, and Pinta. Geneva, Switzerland: World Health Organization; 1984.).
Plantar papillomata with hyperkeratotic macular pl Plantar papillomata with hyperkeratotic macular plantar early yaws (ie, crab yaws) (from Perine PL, Hopkins DR, Niemel PLA, et al. Handbook of Endemic Treponematoses: Yaws, Endemic Syphilis, and Pinta.Geneva, Switzerland: World Health Organization; 1984.).
Osteoperiostitis of the tibia and fibula in early Osteoperiostitis of the tibia and fibula in early yaws (from Perine PL, Hopkins DR, Niemel PLA, et al. Handbook of Endemic Treponematoses: Yaws, Endemic Syphilis, and Pinta. Geneva, Switzerland: World Health Organization; 1984.).
Early yaws papillomata (from Perine PL, Hopkins DR Early yaws papillomata (from Perine PL, Hopkins DR, Niemel PLA, et al. Handbook of Endemic Treponematoses: Yaws, Endemic Syphilis, and Pinta. Geneva, Switzerland: World Health Organization; 1984.).
Early ulceropapillomatous yaws on the leg (from Pe Early ulceropapillomatous yaws on the leg (from Perine PL, Hopkins DR, Niemel PLA, et al. Handbook of Endemic Treponematoses: Yaws, Endemic Syphilis, and Pinta. Geneva, Switzerland: World Health Organization; 1984.).
Squamous macular palmar yaws (from Perine PL, Hopk Squamous macular palmar yaws (from Perine PL, Hopkins DR, Niemel PLA, et al. Handbook of Endemic Treponematoses: Yaws, Endemic Syphilis, and Pinta. Geneva, Switzerland: World Health Organization; 1984.).

Primary stage

Early yaws lesions include the following:

  • Papilloma

  • Serpiginous papilloma

  • Ulceropapillomata

  • Squamous macules

  • Maculopapules

  • Nodules

  • Plaques

  • Hyperkeratosis of palms and soles

  • Bone and joint lesions

  • Generalized lymphadenopathy (may occur)

The initial yaws lesion is a papule that enlarges to become a papilloma or frambesioma. The yaws papilloma resolves spontaneously after 3-6 months. Bone and joint involvement may occur in early disease and may cause pain and swelling. Lymphadenopathy, fever, and joint pain may accompany this stage.

After an incubation period of 9-90 days (with an average of 3 weeks), the primary lesion, or the mother yaw, develops at the site of inoculation after a scratch, bite, or abrasion of exposed skin, most commonly on the legs, feet, or buttocks. The primary lesion is a reddish, nontender, and, occasionally, pruritic papulonodule.

The mother yaw ulcer develops a honey-brown crust and enlarges horizontally to 1-5 cm in diameter, sometimes coalescing with satellite lesions. The crust frequently sloughs and reveals a raspberrylike base. On rare occasions, a primary lesion is not seen. Because the exudate of the raspberrylike ulcer is teeming with treponemes, these lesions are considered highly infectious. After the mother yaw heals, an atrophic scar with central hypopigmentation and peripheral hyperpigmentation remains.

Secondary stage

Following a period of latency (about 6-16 weeks after the primary stage), disseminated skin lesions, bone lesions, and constitutional symptoms occur. The cutaneous lesions, or the daughter yaws, resemble the mother yaw but are smaller (up to 2 cm in diameter) and are frequently located adjacent to body orifices, particularly the mouth and the nose. The daughter yaws expand, ulcerate, and exude a fibrinous fluid teeming with treponemes, which dries into a crust. The exudate attracts flies, which are bothersome to the person who is affected.

Secondary yaws lesions may occur near primary lesions or elsewhere on the body and may last for weeks to more than 6 months. Macules, papules, nodules, and hyperkeratotic lesions may appear. Climate influences the morphology and the number of lesions. In the dry season, lesions are fewer and macular in appearance. Secondary lesions heal spontaneously and are generally nonscarring and reversible.

Occasionally, central resolution yields circinate or annular scaly lesions resembling fungal infections. These lesions are referred to as tinea yaws. Papulosquamous patches and plaques that resemble syphilis may be noted on any part of the body. Lesions in the axillae or the groin resemble condylomata lata; lesions on the mucous membranes resemble hypertrophic mucous patches.

Papillomas on the plantar surfaces can form thick, hyperkeratotic plaques that may become fissured or eroded. Lesions are painful and cause a deliberate crablike gait (crab yaws).

Skeletal involvement includes painful osteoperiostitis and fusiform soft tissue swelling of the metatarsals and the metacarpals. Some of the early bone changes can be seen on radiographs. Periosteal thickening can often be palpable.[13]

Piannic onychia is a paronychia caused by papillomas in the nail fold.

Patients may develop relapses at intervals up to 5 years after infection. Relapsing lesions tend to occur in the perioral, perianal, and periaxillary areas. The disease then enters a noninfectious latent period, and patients do not exhibit any signs or symptoms. Most patients remain in a noninfectious latent stage for their lifetime.

Tertiary stage

In about 10% of cases, after 5-15 years of latency, a late stage develops, characterized by destructive skin lesions, bone lesions, and, possibly, neurologic and ophthalmologic involvement. Progressively enlarging, painless, subcutaneous nodules develop, which undergo abscess formation, necrosis, and ulceration. Lesions have well-defined edges and an indurated base with granulation tissue and yellowish slough.

Ulcers may become infected, causing destruction of underlying structures. They may also coalesce, forming serpiginous tracts that heal with keloid formation, which leads to crippling deformities and contractures.

Late skeletal lesions consist of hypertrophic periostitis, gummatous periostitis, osteitis, and osteomyelitis. Chronic osteitis of the tibia can lead to saber shins. In about 1% of patients, there is occurrence of bilateral hypertrophic osteitis of the external aspects of the nasal processes of the maxillae with persistent swelling. This condition is referred to as goundou, which slowly progresses over 5-20 years and eventually may lead to massive destruction and perforation of the nose and the palate (gangosa).

Neurologic and ophthalmologic involvement is debated in the literature. Some reports suggest that disc atrophy, optic atrophy, and myeloneuropathies may occur.

Attenuated yaws

Some reports have described an attenuated, less contagious form of yaws in areas of low disease prevalence. A solitary patch or a few dry, flat, gray patches confined to the skin folds have been noted to characterize attenuated yaws.[14, 15]

 

DDx

Diagnostic Considerations

The differential diagnosis of skin lesions includes the following:

  • Idiopathic keratoderma

  • Calluses

  • Arthropod bites

  • Vitamin deficiencies

The differential diagnosis of nasopharyngeal lesions includes the following:

  • Rhinosporidiosis

  • Rhinoscleroma

  • Tuberculosis

  • South American blastomycosis

  • Mucocutaneous leishmaniasis

  • Nasopharyngeal carcinoma

  • Noma

The differential diagnosis of bone lesions includes the following:

  • Venereal syphilisor endemic syphilis

  • Tuberculosis

  • Osteomyelitis

  • Sickle cell anemia

Other problems to be considered include tinea versicolor, lichen planus, and tropical ulcer.

Differential Diagnoses

 

Workup

Approach Considerations

The diagnosis of yaws is made by clinical evaluation of lesions and is confirmed by the detection of treponemes on dark-field microscopy of serum obtained by squeezing the bases of the lesions.

Radiologic studies are nonspecific but can include any of the following findings:

  • Surface striations (periostitis)

  • Cortical thickening with bowing (saber shin deformity)

  • Spiculated periosteal reaction

  • General osseous expansion

  • Gummatous destruction

  • Draining sinuses

  • Epiphyseal separation

  • Stellate frontal bone scans

Serologic Tests

Serologic tests for yaws are identical to those for venereal syphilis, including rapid plasma reagent (RPR) test, Venereal Disease Research Laboratory (VDRL) test, fluorescent treponemal antibody absorption (FTA-ABS) test, T pallidum immobilization (TPI) test, and T pallidum hemagglutination assay (TPHA). RPR and VDRL tests are reactive 2-3 weeks after the onset of the primary lesion, and they generally remain reactive throughout all stages.

No serologic test can distinguish yaws from other nonvenereal treponematoses; therefore, diagnosis is ultimately based on correlation of the clinical findings, epidemiologic history, and positive serologic results that are suggestive of yaws. Biopsy of late lesions may be needed to show characteristic histopathology.[16]

Histologic Findings

Histologic findings in early yaws include acanthosis, papillomatosis, and spongiosis. Treponemes are found in the epidermidis. Neutrophilic exocytosis with intraepidermal microabscess formation is the most characteristic finding. The dermis has a moderate to dense granulomatous infiltrate that is mainly composed of plasma cells and lymphocytes, with few histiocytes, neutrophils, and eosinophils. Unlike syphilis, endothelial proliferation is absent or low.

Late yaws has histologic findings similar to those of tertiary syphilis, including an intense dermal infiltrate composed of epithelioid cells, giant cells, lymphocytes, and fibroblasts. Caseation necrosis can also be observed. Plasma cells and histiocytes, in contrast to early yaws, are scarce.

Silver stains (Steiner) can be used to identify numerous treponemes between keratinocytes in early yaws. They are seen in a bandlike pattern or in clusters in the epidermis. Unlike T pallidum, which is found in both the epidermis and the dermis, T pallidumpertenue is almost entirely epidermotropic.

Electron microscopy of early lesions demonstrates scarce treponemes in clusters in the intercellular spaces of the epidermis among inflammatory cells, within the cytoplasm of macrophages, and in the dermis.

 

Treatment

Approach Considerations

Penicillin is the drug of choice for yaws. After a single penicillin injection, early lesions become noninfectious after 24 hours and heal within 1-2 weeks. Tetracycline, erythromycin, or doxycycline should be considered for patients allergic to penicillin.[17]

In one study in children in Papua New Guinea, oral azithromycin was found to be a reasonable alternative for treating yaws; in addition, it is a simpler regimen that does not require trained medical personnel for administration. In this study, children aged 6 months to 15 years who were diagnosed with yaws were randomly assigned to receive either one 30 mg/kg oral dose of azithromycin or an intramuscular (IM) injection of 50,000 units/kg of benzathine benzylpenicillin. After 6 months of follow-up, 96% of patients in the azithromycin group were cured, compared with 93% in the benzathine benzylpenicillin group.[9]

A new yaws eradication program was proposed in 2012 as the result of the azithromycin study conducted in Papua New Guinea.[9] The World Health Organization (WHO) has concluded that this new eradication campaign can completely eliminate yaws worldwide by 2020.[7]

Epidemiologic treatment recommendations for yaws are as follows:

  • If greater than 50% of children are seropositive (hyperendemic), treat the entire population

  • If 10-50% of children are seropositive (mesoendemic), treat active cases, contacts, and all children aged 15 years or younger

  • If less than 10 of children are seropositive (hypoendemic), treat active cases, household members, and other obvious contacts

 

Medication

Medication Summary

Empirical antimicrobial therapy must be comprehensive and should cover all likely pathogens in the context of the clinical setting.[18, 19] Penicillin remains the drug of choice for yaws. No resistant strains of T pallidum have been reported. Benzathine benzylpenicillin is the drug of choice for treating yaws. In remote areas where benzathine benzylpenicillin is unavailable, oral penicillin V for 7-10 days can reduce the prevalence of yaws and is effective in treating individual children with active lesions.[20]

Antibiotics

Class Summary

Empirical antimicrobial therapy must be comprehensive and should cover all likely pathogens in the context of the clinical setting. Benzathine benzylpenicillin should be avoided in patients who are allergic to penicillin; tetracycline, azithromycin, or erythromycin are alternative therapies.

Penicillin G benzathine (Bicillin LA)

Penicillin G benzathine interferes with synthesis of cell wall mucopeptides during active multiplication, which results in bactericidal activity. It is given as a single injection, which kills the treponemes within minutes, and lesions become noninfectious after 18-24 hours.

Azithromycin (Zithromax, Zmax)

Azithromycin is a semisynthetic antibiotic that is structurally similar to erythromycin. It inhibits protein synthesis in bacterial cells by binding to the 50S subunit of bacterial ribosomes. In a study in children in Papua New Guinea,[20] oral azithromycin was found to be a reasonable alternative for treating yaws; 96% of patients in the azithromycin group were cured, compared with 93% in the benzathine benzylpenicillin group.

Tetracycline

Tetracycline treats gram-positive and gram-negative organisms, as well as mycoplasmal, chlamydial, and rickettsial infections. It inhibits bacterial protein synthesis by binding with 30S and, possibly, 50S ribosomal subunits. Tetracycline may be used in adults and in children who are older than 8 years and are allergic to penicillin.

Erythromycin (E.E.S., Erythrocin, Ery-Tab)

Erythromycin inhibits bacterial growth, possibly by blocking dissociation of peptidyl tRNA from ribosomes, causing RNA-dependent protein synthesis to arrest. It is used for the treatment of staphylococcal and streptococcal infections. In children, the proper dosage is determined by age, weight, and severity of infection. When twice-daily dosing is desired, half of the total daily dose may be taken every 12 hours. For more severe infections, the dose can be doubled.

Erythromycin may be used in adults and children who are allergic to penicillin.

Doxycycline (Adoxa, Alodox, Doryx, Vibramycin)

Doxycycline may be used in adults with a penicillin allergy. It inhibits protein synthesis and, thus, bacterial growth by binding to 30S and, possibly, 50S ribosomal subunits of susceptible bacteria.