Bejel is an infectious disease non-venereal tropical infectious disease caused by the organism Treponema pertenue that is rare in the United States but common in certain parts of the world. The infection is very similar to syphilis but is not sexually transmitted. Most frequently, transmission is by means of non-sexual skin contact or by the common use of eating and drinking utensils. Primary lesions are rare, probably occurring undetected in the oropharyngeal mucosa. The most common presentation is with secondary oral lesions resembling mucous patches. These are shallow, relatively painless ulcerations, occasionally accompanied by laryngitis. Split papules, angular cheilitis, condylomatous lesions of the moist folds of the axillae and groin, and a nonpruritic generalized papular eruption may be seen. Generalized lymphadenopathy is common. Osteoperiostitis of the long bones may occur, causing nocturnal leg pains.
The organism that causes bejel belongs to the same family as the bacterium that causes syphilis, pinta and yaws and is known as treponema. Treponemas are spiral-shaped bacteria (spirochetes). Also known as endemic syphilis, bejel is characterized by lesions of the skin and bones that begin in the mouth and progress in gradual stages. The late stages are the most severe.
Bejel is very common in dry, hot climates especially in the countries of the eastern Mediterranean region and in Saharan West Africa.
Symptoms
At the outset, children with bejel have patchy, slimy, ulcerations (lesions) on the mucous membranes, particularly in or near the mouth. Later, blisters appear on the back, arms, and legs. Further disease progression is indicated by infections of the bones, especially those of the legs. In these later stages, soft, gummy lumps (gummas) appear on the roof of the mouth and in the nasal passages.
Other symptoms may include swollen glands or lymph nodes (lymphadenopathy), and/or skin ulcerations under the arms or around the rectum and groin.
Causes
Bejel is a Bedouin term for this nonvenereal treponematosis, which occurs primarily in the semi-nomadic tribes who live in the arid regions of North Africa, Southwest Asia, and the eastern Mediterranean. The etiologic agent of bejel is treponema pallidum subsp.endemicum. It occurs primarily in childhood and is spread by skin contact or from mouth to mouth by kissing or the use of contaminated drinking vessels. The skin, oral mucosa, and skeletal system are primarily involved.
The genus of Treponema includes several uncultivable spirochete pathogens notably including but not limited to T. pallidum, the causative agent of syphilis, Treponema endemicum, the causative agent of bejel, related Treponema carateum, the causative agent of pinta, and Treponema pertenue, the causative agent of yaws. The first genome mapping of T. pallidum in 1998 led to the further genomic sequencing of twelve treponemal pathogens and this notably revealed minimal variability between sub-species.[rx] Despite this T. pertenue and its associated disease, yaws present with a distinct history and clinical features.
Bejel is a rare infectious disease caused by a spiral-shaped bacterium (spirochete), known as Treponema pallidum endemicum. Under a microscope, T. p. endemicum is virtually indistinguishable from Treponema pallidum, the bacterium that causes syphilis. The disease is not sexually transmitted.
Diagnosis
The diagnosis of bejel is based on the geographic history of the patient as well as laboratory testing of material from the lesions (darkfield examination). The responsible bacterium is readily identifiable on sight in a microscope as a treponema. Samples of the fluid that surrounds the lesions yield a positive VDRL (Venereal Disease Research Laboratory) and FTA-ABS (fluorescent treponemal antibody-absorption) test. However, additional history may be required to differentiate bejel from venereal syphilis.
T. pallidum, as a group, are not viable ex vivo, and therefore, diagnostic methods are limited. Darkfield microscopy does allow direct visualization of spirochetes; however, equipment is often not available in endemic areas. Combinations of serologic assays and nucleic acid amplification tests have been used as the primary mode of identification.[rx]
History and Physical
The disease is characterized by primary, secondary, and tertiary stages.
The initial lesion typifying primary yaws infection are solitary nodules[rx] or multiple ulcerative non-tender papules.[rx] They classically are yellow, 2 to 5 cm in diameter, and have a distinct red base of granulation tissue with elevated borders.[rx] This occurs at the site of inoculation on average 21 days after exposure. Time to onset ranges from 9 to 90 days. This lesion is termed the “Mother Yaw” and is an exudative papillomatous lesion that may degenerate into a single crusted non-tender ulcer. The most common location is the lower extremity, but any site of exposure may be involved. Untreated lesions heal spontaneously over 3 to 6 months leaving hyperpigmentation.[rx]
Dissemination of the organism through lymphatic or hematogenous spread is responsible for the progression of the disease.[rx] Arthralgias manifest during this period, and the primary and secondary stages may overlap. Secondary lesions can occur in the presence of primary findings. One to 2 months after inoculation, (up to 2 years), patients develops disseminated papillomatous or ulcerative lesions with macular or hyperkeratotic palmoplantar involvement. The term “crab-yaws” describes a crab-like gait change secondary to painful fissuring of hyperkeratotic pedal plaques and secondary infection.[rx][rx] Generalized lymphadenopathy and constitutional malaise are present during this stage. During the secondary stage of yaws, the specific bony disease begins to manifest.[rx] Osteoperiostitis presents as a bilateral polyostotic disorder with an average of 3 bones involved. Radius, ulna, and phalanges are the most frequent. Radiologic abnormalities reveal dactylitis and osteoperiostitis.
In between primary and secondary or secondary and tertiary stages, a latent period occurs. The latent period is defined as a positive serology with no clinical signs. This is due to the host immune response against the organism. During this relapse of clinical disease can occur and characteristically manifests around axillae, anus, and mouth.[rx]
Tertiary disease historically occurred in 10% of untreated patients; however, due to surveillance and available antibiotics, it is now rarely seen. Late lesions may occur 5 to 10 years after inoculation. Cutaneous manifestations are the most common and are typically near joints with ulcerative necrotic nodules. Facial destruction historically has been a marked manifestation[rx] with other classic late findings including juxta-articular nodules (gummas), bowed tibia (saber shins), and nasal cartilage destruction (gangosa), or exostosis of the paranasal maxilla (gondou).[rx]
Diagnosis is based on the combined clinical picture and serologic testing. The latter requires the presence of antibodies with one being a non-treponemal antigen and the other a treponemal antigen. The non-treponemal antibodies are the same as used in syphilitic disease: the venereal disease research laboratory (VDRL) and rapid plasma reagin (RPR). These have a chance of false-positive results but good sensitivity and are useful as markers to confirm cure with falling titers following treatment. The treponema-specific antibodies include Treponema pallidum particle agglutination (TPPA) and haemagglutination (TPHA) assays. Once positive, these latter 2 tests are positive for life.[rx]
Additionally, as the treponemes are indistinguishable serologically and early clinical features may overlap accurate diagnosis may be difficult. A combination of epidemiology, clinical signs and symptoms, direct visualization, and serologic data are required to establish the diagnosis.[rx]
Treatment
The standard treatment for bejel is the antimicrobial drug benzathine penicillin G. Those individuals who are allergic to penicillin may be given doxycycline or tetracycline. The lesions caused by this disease typically heal after treatment. However, scarring may be permanent.
Treatment in the 1950s, during the initial eradication of T. pertenue and yaws, began with penicillin aluminum monostearate. Benzathine penicillin subsequently supplanted this as it was found to have prolonged treponemicidal levels and convenient dosing. Treatment dosing was determined by age with 600,000 units for ages younger than 6 years old, 1.2 million units for children 6 to 14 years,[rx] and some sources reporting similar dosing of 1.2 million units for adults. This dosing is lower than used in venereal syphilis.[rx]
Prolonged oral penicillin and tetracyclines may be effective; however, azithromycin 30 mg/kg became the primary alternative after it was shown to be non-inferior when compared to penicillins maintaining a 96% cure rate at 6 months.[rx] In 2012, the WHO re-duplicated efforts for eradication and implemented single mass dosing of oral azithromycin in endemic areas and case detection monitoring with subsequent treatment. It is through this they hope to eradicate the disease by the target date of 2020, as stated above.[rx]
Resistance to macrolides is a concern, however, as T. pallidum is notoriously resistant, and concerns about the similar organism of yaws have been discussed.[rx]
References
Behçet’s Syndrome
