Yaws, Bejel, and Pinta

Yaws, bejel, and pinta are endemic, nonvenereal treponematoses. The causative organisms are Treponema Treponema Treponema is a gram-negative, microaerophilic spirochete. Owing to its very thin structure, it is not easily seen on Gram stain, but can be visualized using dark-field microscopy. This spirochete contains endoflagella, which allow for a characteristic corkscrew movement. Treponema pallidum pertenue (yaws), T. pallidum endemicum (bejel), and T. carateum (pinta). These treponematoses are generally transmitted by direct skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Structure and Function of the Skin-to- skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Structure and Function of the Skin contact with infected skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Structure and Function of the Skin lesions. Yaws and bejel affect skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Structure and Function of the Skin and bones, resulting in cutaneous plaques and nodules and destructive bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Structure of Bones lesions. Pinta involves only the skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Structure and Function of the Skin. Diagnosis is made with a combination of serology, clinical features, demographics, and geographic distribution. Management includes intramuscular benzathine penicillin G or oral azithromycin.

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Editorial responsibility: Stanley Oiseth, Lindsay Jones, Evelin Maza

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Epidemiology and Etiology

Epidemiology

Yaws (most common):

  • Prevalent in hot, humid areas of: 
    • South Asia
    • Indonesia
    • Pacific Islands
    • Africa
    • South America
  • Children > adults

Bejel:

  • Prevalent in arid regions of:
    • Middle East
    • Central and South Africa
  • Children > adults

Pinta:

  • Very rare
  • Occurrence has declined.
  • May still be endemic in:
    • South America
    • Central America
  • Teenagers and adults > children

Etiology

  • Causative organisms: 
    • Subspecies of Treponema Treponema Treponema is a gram-negative, microaerophilic spirochete. Owing to its very thin structure, it is not easily seen on Gram stain, but can be visualized using dark-field microscopy. This spirochete contains endoflagella, which allow for a characteristic corkscrew movement. Treponema pallidum:
      • Yaws: T. pallidum pertenue (yaws)
      • Bejel: T. pallidum endemicum (bejel)
    • T. carateum (pinta)
  • Basic Treponema Treponema Treponema is a gram-negative, microaerophilic spirochete. Owing to its very thin structure, it is not easily seen on Gram stain, but can be visualized using dark-field microscopy. This spirochete contains endoflagella, which allow for a characteristic corkscrew movement. Treponema characteristics:
    • Spirochete Spirochete Treponema is a gram-negative, microaerophilic spirochete. Owing to its very thin structure, it is not easily seen on Gram stain, but can be visualized using dark-field microscopy. This spirochete contains endoflagella, which allow for a characteristic corkscrew movement. Treponema (spiral shaped)
    • Gram negative

Related videos

Pathogenesis

Reservoir

Humans are the only reservoir.

Transmission

  • Yaws: skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Structure and Function of the Skin-to- skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Structure and Function of the Skin contact with lesions
  • Bejel:
    • Skin-to- skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Structure and Function of the Skin contact with lesions
    • Mouth-to-mouth contact with oral lesions
    • Fomites (e.g., utensils for eating and drinking)
  • Pinta: skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Structure and Function of the Skin-to- skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Structure and Function of the Skin contact with lesions

Pathophysiology

  • Skin contact with an infected lesion → spirochete adheres to the skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Structure and Function of the Skin or mucosal membranes
  • Production of hyaluronidase → allows for tissue invasion
  • Organisms coat themselves in the host’s fibronectin → prevents phagocytosis and recognition by the immune system
  • Travel to lymph nodes → dissemination through the bloodstream
  • Host immune response → disease manifestations
Pathogenesis of treponema infections

Pathogenesis of Treponema Treponema Treponema is a gram-negative, microaerophilic spirochete. Owing to its very thin structure, it is not easily seen on Gram stain, but can be visualized using dark-field microscopy. This spirochete contains endoflagella, which allow for a characteristic corkscrew movement. Treponema infections:
The pathogen adheres to the skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Structure and Function of the Skin or mucosal membranes, leading to the production of hyaluronidase, which allows for tissue invasion. The pathogen coats itself in the host’s fibronectin, which prevents its phagocytosis and recognition by the immune system. Consequently, the pathogen disseminates through the bloodstream. A host immune response ultimately occurs, which causes disease manifestations.

Image by Lecturio.

Clinical Presentation

Yaws

Primary phase:

  • Localized papule at the site of inoculation (“mother yaw”):
    • Most commonly occurs on the lower extremities
    • Painless
    • May be pruritic
  • Evolution:
    • Progresses to a large, yellow nodule
    • Possible ulceration with red granulation tissue at the ulcer base
    • Regresses spontaneously into a hyperpigmented scar

Secondary phase:

  • Secondary lesions may be:
    • Solitary, ulcerated nodules resembling primary yaws
    • Multiple smaller nodules
  • Painful palmar and plantar papilloma or plaques
  • Arthralgias
  • Osteoperiostitis:
    • Nocturnal bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Structure of Bones pain Pain Pain has accompanied humans since they first existed, first lamented as the curse of existence and later understood as an adaptive mechanism that ensures survival. Pain is the most common symptomatic complaint and the main reason why people seek medical care. Physiology of Pain
    • Dactylitis

Tertiary phase:

  • Gummatous lesions (destructive, granulomatous lesions) of:
    • Skin
    • Bones
  • Destructive, mutilating lesions can lead to:
    • Long- bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Structure of Bones malformations (e.g., bowed tibia)
    • Juxtaarticular cutaneous or subcutaneous lesions
    • Ulcerations of the nasopharynx and palate Palate The palate is the structure that forms the roof of the mouth and floor of the nasal cavity. This structure is divided into soft and hard palates. Oral Cavity: Palate (“rhinopharyngitis mutilans”)
    • Exostosis of the nasal portion of the maxilla (“goundou”)

Bejel

Primary phase:

  • Small, primary papule, patch, or ulcer on the oral mucosa
  • Not commonly seen due to small size
  • Resolves spontaneously

Secondary stage:

  • Painless ulcers or patches:
    • Can affect:
      • Mucous membranes
      • Skin (particularly warm, moist regions)
    • Become condylomatous before eventually healing
  • Periostitis → bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Structure of Bones pain Pain Pain has accompanied humans since they first existed, first lamented as the curse of existence and later understood as an adaptive mechanism that ensures survival. Pain is the most common symptomatic complaint and the main reason why people seek medical care. Physiology of Pain
  • Laryngitis Laryngitis Laryngitis is an inflammation of the larynx most commonly due to infection or trauma that can be either acute or chronic. In this condition, the 2 folds of mucous membranes that make up the vocal cords become inflamed and irritated. The inflammation results in a distortion of the voice produced, resulting in a hoarse sound or aphonia. Laryngitis → hoarseness 
  • Nasopharyngeal ulcers
  • Possible genital ulcer similar to that seen in syphilis Syphilis Syphilis is a bacterial infection caused by the spirochete Treponema pallidum pallidum (T. p. pallidum), which is usually spread through sexual contact. Syphilis has 4 clinical stages: primary, secondary, latent, and tertiary. Syphilis

Tertiary phase:

  • Gummatous lesions of:
    • Skin
    • Bones
  • Destructive lesions result in:
    • Bone deformities
    • Nasopharyngeal destruction
    • Juxtaarticular nodules

Pinta

Primary phase:

  • Initial red papule or plaque:
    • Pruritic
    • Commonly on lower extremities
    • Satellite lesions may be present.
  • Regional lymphadenopathy Lymphadenopathy Lymphadenopathy is lymph node enlargement (> 1 cm) and is benign and self-limited in most patients. Etiologies include malignancy, infection, and autoimmune disorders, as well as iatrogenic causes such as the use of certain medications. Generalized lymphadenopathy often indicates underlying systemic disease. Lymphadenopathy

Secondary phase: pintids

  • Multiple pruritic plaques undergo a color change from red to gray to black.
  • Similar to the initial skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Structure and Function of the Skin lesion of the primary phase

Tertiary or late phase:

  • Skin discoloration and depigmentation
  • Atrophy
Cutaneous lesions of pinta

Cutaneous lesions of pinta ( Treponema Treponema Treponema is a gram-negative, microaerophilic spirochete. Owing to its very thin structure, it is not easily seen on Gram stain, but can be visualized using dark-field microscopy. This spirochete contains endoflagella, which allow for a characteristic corkscrew movement. Treponema carateum infection)
A: erythematous plaque of early pinta
B: skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Structure and Function of the Skin discoloration of late pinta

Image: “Endemic treponemal diseases” by Marks M, Solomon AW, Mabey DC. License: CC BY 4.0

Diagnosis and Management

Diagnosis

Because these treponemal species are morphologically indistinguishable, the diagnosis is based on the combination of demographics, geographic region, clinical presentation, and laboratory findings.

Serology:

  • Nontreponemal tests:
    • Options:
      • Rapid plasma reagin
      • VDRL
    • Titers should decline after treatment. 
  • Treponemal tests:
    • Options:
      • Fluorescent treponemal antibody absorption Absorption Absorption involves the uptake of nutrient molecules and their transfer from the lumen of the GI tract across the enterocytes and into the interstitial space, where they can be taken up in the venous or lymphatic circulation. Digestion and Absorption test (FTA-ABS)
      • Microhemagglutination test for antibodies Antibodies Immunoglobulins (Igs), also known as antibodies, are glycoprotein molecules produced by plasma cells that act in immune responses by recognizing and binding particular antigens. The various Ig classes are IgG (the most abundant), IgM, IgE, IgD, and IgA, which differ in their biologic features, structure, target specificity, and distribution. Immunoglobulins to T. pallidum (MHA-TP)
      • T. pallidum particle agglutination test
      • T. pallidum enzyme immunoassay
      • Chemiluminescence immunoassay
    • Cannot differentiate between current and previous infection (titers stay positive after treatment)

Direct methods:

  • PCR PCR Polymerase chain reaction (PCR) is a technique that amplifies DNA fragments exponentially for analysis. The process is highly specific, allowing for the targeting of specific genomic sequences, even with minuscule sample amounts. The PCR cycles multiple times through 3 phases: denaturation of the template DNA, annealing of a specific primer to the individual DNA strands, and synthesis/elongation of new DNA molecules. Polymerase Chain Reaction (PCR):
    • Detect Treponema Treponema Treponema is a gram-negative, microaerophilic spirochete. Owing to its very thin structure, it is not easily seen on Gram stain, but can be visualized using dark-field microscopy. This spirochete contains endoflagella, which allow for a characteristic corkscrew movement. Treponema DNA DNA The molecule DNA is the repository of heritable genetic information. In humans, DNA is contained in 23 chromosome pairs within the nucleus. The molecule provides the basic template for replication of genetic information, RNA transcription, and protein biosynthesis to promote cellular function and survival. DNA Types and Structure
    • Specimen: swabs of an ulcer
  • Dark-field microscopy:
    • A microscopy technique that illuminates specimens against a dark background
    • Motile spirochetes will be seen.

Management

Treatment is the same for all of these infections. Options include:

  • Intramuscular benzathine penicillin G (preferred with bejel and pinta)
  • Oral azithromycin

Differential Diagnosis

  • Syphilis: a sexually transmitted bacterial infection caused by T. pallidum pallidum. Syphilis has 3 stages. Primary syphilis Syphilis Syphilis is a bacterial infection caused by the spirochete Treponema pallidum pallidum (T. p. pallidum), which is usually spread through sexual contact. Syphilis has 4 clinical stages: primary, secondary, latent, and tertiary. Syphilis presents with a painless genital ulcer called a chancre. Secondary syphilis Syphilis Syphilis is a bacterial infection caused by the spirochete Treponema pallidum pallidum (T. p. pallidum), which is usually spread through sexual contact. Syphilis has 4 clinical stages: primary, secondary, latent, and tertiary. Syphilis presents with diffuse rash, condylomata lata, and flu-like symptoms. Tertiary syphilis Syphilis Syphilis is a bacterial infection caused by the spirochete Treponema pallidum pallidum (T. p. pallidum), which is usually spread through sexual contact. Syphilis has 4 clinical stages: primary, secondary, latent, and tertiary. Syphilis presents with neurological and cardiac involvement. Diagnosis is with nontreponemal and treponemal serological tests. The mainstay of treatment is intramuscular benzathine penicillin G.
  • Chancroid Chancroid Chancroid is a highly transmissible STD caused by Haemophilus ducreyi. The disease presents with painful ulcer(s) on the genital tract (termed chancroid or "soft chancre"). Up to 50% of patients will develop painful inguinal lymphadenopathy. Chancroid: a sexually transmitted infection Sexually Transmitted Infection Sexually transmitted infections (STIs) are infections that spread either by vaginal intercourse, anal sex, or oral sex. Symptoms and signs may include vaginal discharge, penile discharge, dysuria, skin lesions (e.g., warts, ulcers) on or around the genitals, and pelvic pain. Some infections can lead to infertility and chronic debilitating disease. Overview: Sexually Transmitted Infections caused by Haemophilus Haemophilus Haemophilus is a genus of Gram-negative coccobacilli, all of whose strains require at least 1 of 2 factors for growth (factor V [NAD] and factor X [heme]); therefore, it is most often isolated on chocolate agar, which can supply both factors. The pathogenic species are H. influenzae and H. ducreyi. Haemophilus ducreyi. Chancroid Chancroid Chancroid is a highly transmissible STD caused by Haemophilus ducreyi. The disease presents with painful ulcer(s) on the genital tract (termed chancroid or "soft chancre"). Up to 50% of patients will develop painful inguinal lymphadenopathy. Chancroid presents with painful genital ulcers and suppurative inguinal lymphadenopathy Lymphadenopathy Lymphadenopathy is lymph node enlargement (> 1 cm) and is benign and self-limited in most patients. Etiologies include malignancy, infection, and autoimmune disorders, as well as iatrogenic causes such as the use of certain medications. Generalized lymphadenopathy often indicates underlying systemic disease. Lymphadenopathy (buboes). Diagnosis is usually clinical, though PCR PCR Polymerase chain reaction (PCR) is a technique that amplifies DNA fragments exponentially for analysis. The process is highly specific, allowing for the targeting of specific genomic sequences, even with minuscule sample amounts. The PCR cycles multiple times through 3 phases: denaturation of the template DNA, annealing of a specific primer to the individual DNA strands, and synthesis/elongation of new DNA molecules. Polymerase Chain Reaction (PCR) and cultures can help (if available). Treatment is with macrolide antibiotics.
  • Leishmaniasis Leishmaniasis Leishmania species are obligate intracellular parasites that are transmitted by an infected sandfly. The mildest form is cutaneous leishmaniasis (CL), characterized by painless skin ulcers. The mucocutaneous type involves more tissue destruction, causing deformities. Visceral leishmaniasis (VL), the most severe form, presents with hepatosplenomegaly, anemia, thrombocytopenia, and fever. Leishmania/Leishmaniasis: an infection caused by Leishmania Leishmania Leishmania species are obligate intracellular parasites that are transmitted by an infected sandfly. The disease is endemic to Asia, the Middle East, Africa, the Mediterranean, and South and Central America. Clinical presentation varies, dependent on the pathogenicity of the species and the host's immune response. Leishmania/Leishmaniasis species, which are obligate intracellular parasites transmitted by the sandfly. The mildest form is cutaneous leishmaniasis, which is characterized by painless skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Structure and Function of the Skin ulcers. The mucocutaneous type involves more tissue destruction and deformities. Visceral leishmaniasis (VL) presents with hepatosplenomegaly, anemia Anemia Anemia is a condition in which individuals have low Hb levels, which can arise from various causes. Anemia is accompanied by a reduced number of RBCs and may manifest with fatigue, shortness of breath, pallor, and weakness. Subtypes are classified by the size of RBCs, chronicity, and etiology. Anemia: Overview, thrombocytopenia Thrombocytopenia Thrombocytopenia occurs when the platelet count is < 150,000 per microliter. The normal range for platelets is usually 150,000-450,000/µL of whole blood. Thrombocytopenia can be a result of decreased production, increased destruction, or splenic sequestration of platelets. Patients are often asymptomatic until platelet counts are < 50,000/µL. Thrombocytopenia, and fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever. Management is based on the clinical severity. Systemic treatment (amphotericin B) is needed for VL. 
  • Leprosy Leprosy Leprosy, also known as Hansen's disease, is a chronic bacterial infection caused by Mycobacterium leprae complex bacteria. Symptoms primarily affect the skin and peripheral nerves, resulting in cutaneous manifestations (e.g., hypopigmented macules) and neurologic manifestations (e.g., loss of sensation). Leprosy: a chronic bacterial infection caused by Mycobacterium Mycobacterium Mycobacterium is a genus of the family Mycobacteriaceae in the phylum Actinobacteria. Mycobacteria comprise more than 150 species of facultative intracellular bacilli that are mostly obligate aerobes. Mycobacteria are responsible for multiple human infections including serious diseases, such as tuberculosis (M. tuberculosis), leprosy (M. leprae), and M. avium complex infections. Mycobacterium leprae complex. Symptoms primarily affect the skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Structure and Function of the Skin and peripheral nerves, resulting in cutaneous manifestations (e.g., hypopigmented macules) and neurologic manifestations (e.g., loss of sensation). Diagnosis is established clinically and supported with skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Structure and Function of the Skin biopsy. Management includes long-term multidrug antibiotic combinations.

References

  1. Mitjà, O., Mabey, D. (2019). Yaws, bejel, and pinta. Uptodate. Retrieved May 9, 2021, from https://www.uptodate.com/contents/yaws-bejel-and-pinta
  2. Galadari, H. (2021). Yaws: Background, etiology and pathophysiology, epidemiology. Medscape. Retrieved May 9, 2021, from https://emedicine.medscape.com/article/1053612-overview
  3. Fine, S.M. (2021). Treponematosis (Endemic syphilis, yaws, and pinta): Background, pathophysiology, epidemiology. Medscape. Retrieved May 10, 2021, from https://emedicine.medscape.com/article/230403-overview
  4.  Maxfield, L. Crane, J.S. (2020). Yaws. Stat Pearls. https://pubmed.ncbi.nlm.nih.gov/30252269/
  5.  Torok, E. (2009). Oxford Handbook of Infectious Diseases and Microbiology (1st ed.). Oxford University Press. p. 388. ISBN 978-0-19-856925-1
  6. Bush, L.M., Vazquez-Pertejo, M.T. (2020). Bejel, pinta, and yaws. MSD Manual Professional Version. Retrieved May 18, 2021, from https://www.msdmanuals.com/professional/infectious-diseases/spirochetes/bejel,-pinta,-and-yaws

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