Primary period of syphilis: hard chancre

Primary syphilis is characterized by the development of a hard chancre (ulcus durum, primary syphiloma) at the site of the introduction of pale treponemas and regional lymphangitis and lymphadenitis. Primary syphiloma begins with the formation of a red spot, which then turns into a limited infiltrate (papule). Due to the disruption of the nutrition of the epidermis caused by the vascular lesion characteristic of syphilis, necrosis occurs in the center of the infiltrate and erosion or ulceration is formed.

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Pathogenesis

Histologically, a typical hard chancre has a number of pathohistological signs: absence of epidermis (and part of the dermis) in the central zone due to the formation of foci and zones of necrosis; in the dermis - a dense perivascular infiltrate consisting of lymphocytes and plasma cells. Changes in the blood and lymphatic vessels of the dermis are noted in the form of proliferation and infiltration of all membranes (panvasculitis) with obliteration and thrombosis of some vessels; numerous pale trepopemata in all areas (especially in the walls of vessels and their circumference).

Regional lymphadenitis (concomitant bubo, regional scleradenitis) develops 5-7 days after the appearance of hard chancre and is the second obligatory clinical symptom of primary syphilis. Clinically, scleradenitis is characterized by a peculiar enlargement and compaction of the lymph nodes closest to the chancre. When hard chancre is localized on the genitals, the inguinal lymph nodes undergo characteristic changes. If primary syphiloma is localized on the lips and oral mucosa, the submental and submandibular lymph nodes enlarge. When chancre is localized on the upper lip, the parotid glands enlarge.

The lymph nodes are enlarged to the size of a bean, a small plum, sometimes a pigeon's egg, dense, not fused together or with the surrounding tissues, mobile, ovoid in shape and completely painless. The skin above them is unchanged. When a secondary infection occurs, the lymph nodes may become painful. It is typical that not one lymph node enlarges, but a group ("pleiad") of nodes, with one of them appearing to be the largest. Scleradenitis can be both bilateral and unilateral, and almost never suppurates or opens. After 3-4 weeks of the hard chancre, all the lymph nodes gradually begin to enlarge and become dense - a specific polyadenitis occurs - an important accompanying symptom of the end of primary and the beginning of secondary syphilis.

Regional lymphangitis is a lesion of the lymphatic vessels along the length from the hard chancre to the nearby lymph nodes. In this case, the lymphatic vessel is palpated as a dense, elastic, painless cord, sometimes having thickenings along its course.

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Symptoms primary syphilis

The main clinical signs of a typical hard chancre are: erosion (ulcer) with the absence of acute inflammatory phenomena; solitary or singular; regular (round or oval) outlines; clear boundaries; the size of a small coin; the element is raised above the surrounding healthy skin (mucous membrane); smooth, shiny ("varnished") bottom; sloping (saucer-shaped) edges; bluish-red color of the bottom; scanty serous discharge; dense-elastic ("cartilaginous") infiltrate at the base (nodular, lamellar, leaf-shaped); painlessness; resistance to local disinfectant and anti-inflammatory therapy.

At the end of the primary period, general flu-like disorders are sometimes observed: headache, bone-joint and muscle pain, general weakness, insomnia, and increased body temperature.

Hard chancre usually persists until the onset of the secondary period and soon heals, rarely exists for several weeks and after the appearance of a generalized rash, even more rarely - heals before the onset of secondary manifestations. This depends mainly on its size.

Hard chancre can be single or multiple. In case of simultaneous penetration of infection through several portals of entry, the resulting hard chancres are at the same stage of development. These are the so-called twin chancres. If the infection occurred at different times (for example, as a result of repeated sexual contacts with an interval of several days), then the chancres will appear at different times and differ from each other in the degree of maturity. These are the so-called sequential chancres. The localization of the hard chancre depends on the route of infection. In case of sexual infection, hard chancre usually appears on the genitals or on adjacent areas (skirts, abdomen, inner thighs, perineum, anus). In case of non-sexual infection, hard chancre is located extragenitally (for example, on the lips, tongue, mammary glands, fingers). The second place after the genitals in terms of the frequency of localization of primary syphiloma is the oral mucosa (lips, gums, tongue, soft palate, tonsils). Other localizations of hard chancre are rare.

Forms

Atypical forms of hard chancre include indurative edema, chancre-amygdalitis and chancre-panaritium.

In indurative edema is characterized by painless, dense swelling of the labia or foreskin. The absence of acute inflammatory phenomena is characteristic, which distinguishes indurative edema from processes such as bartholinitis or inflammatory phimosis. The skin in the lesion acquires a stagnant bluish color or retains its normal color.

Chancre-amygdalitis is characterized only by a sharp, usually unilateral enlargement of the tonsils. The tonsil is dense, acute inflammatory phenomena are absent. Chancre-amygdalitis is very similar to indurative edema. This atypical chancre is often mistaken for common tonsillitis.

Chancre-paparicium is the most atypical of all chancres. It really does simulate panaritium: the distal phalanx is edematous, bluish-red in color, accompanied by sharp, "shooting" pains, covered with purulent-necrotic plaque. Then erosions and ulcers appear.

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Complications and consequences

If chancre becomes complicated, phimosis, paraphimosis, gangrenization of the primary syphilis, and in women, vulvitis and vulvovaginitis may develop.

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Treatment primary syphilis

Four decades of clinical use show that parenteral penicillin G is effective in resolving local lesions (lesion healing and prevention of sexual transmission) and in preventing long-term sequelae. However, adequate comparative trials to determine the optimal penicillin regimen (dose, duration of treatment, drug) have not been conducted. Even less data are available for the use of other drugs.

Recommended regimen for adults

Patients with primary or secondary syphilis should be treated according to the following regimen:

Benzathine penicillin G 2.4 million units intramuscularly once

NOTE: Recommendations for the treatment of syphilis in pregnant women and HIV-infected patients are discussed in the appropriate sections.

Recommended scheme for children

After the neonatal period, children diagnosed with syphilis should have CSF examination to exclude neurosyphilis, and a careful history of both the child and mother should be taken to determine whether syphilis is congenital or acquired (see Congenital Syphilis). Children with acquired primary or secondary syphilis should be evaluated (including consultation with Child Protective Services) and treated according to the treatment regimen for syphilis in children (see Child Sexual Abuse or Rape).

Benzathine penicillin G, from 50,000 U/kg IM to an adult dose of 2.4 million U IM in a single dose

Other considerations for patient management

All patients with syphilis should be tested for HIV. In areas with a high prevalence of HIV infection, patients with primary syphilis should be retested for HIV after 3 months if the initial reaction was negative. In case of seroconversion, intensive antiviral therapy should be started immediately.

Syphilitic patients who also have lesions of the nervous system or eye should be carefully examined (including CSF examination and slit-lamp examination of the eyes). These patients should be treated according to the examination results.

Penetration of T. pallidum into the CSF, accompanied by pathological changes in the CSF, occurs in adults with primary or secondary syphilis. However, only a small number of patients develop neurosyphilis after treatment with the regimens presented in this review. Therefore, despite the presence of clinical symptoms and signs suggestive of nervous system and ocular involvement, lumbar puncture is not recommended for the routine evaluation of patients with primary or secondary syphilis.

Follow-up observation

Failure to respond to treatment may occur with any regimen. However, evaluation of response to treatment is often difficult, and there are no definitive criteria for its effectiveness. Serological test titers may decline more slowly in patients with a previous syphilitic infection. Repeat clinical and serological testing is performed after 3 months and again after 6 months; if results are inconclusive, testing may be performed more frequently.

In patients with persistent or recurrent symptoms and signs, or in patients who maintain a 4-fold increase in titers over baseline or the titer obtained in a previous study, these features indicate either treatment failure or reinfection. These patients should be retreated after testing for HIV infection. A lumbar puncture is necessary despite the possibility of reinfection.

If patients with primary or secondary syphilis do not show a fourfold reduction in nontreponemal test titers after 6 months of treatment, the treatment is considered ineffective. Such patients should be retested for HIV infection. The optimal management of such patients is unclear. At a minimum, such patients should undergo additional clinical and serologic monitoring. HIV-infected patients should be monitored more frequently (i.e., after 3 months instead of 6). If there is no guarantee that follow-up will be carried out, retreatment is recommended. Some experts recommend CSF testing in such situations.

For retreatment, most experts recommend 3 weekly injections of benzathine penicillin G 2.4 million units IM unless CSF examination indicates neurosyphilis.

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Special Notes

• Allergy to penicillin

In men and non-pregnant women with penicillin allergy and primary or secondary syphilis, treatment should be carried out according to one of the following regimens, and it is very important to monitor the cure.

Recommended schemes

Doxycycline 100 mg orally 2 times daily for 2 weeks

Or Tetracycline 500 mg orally 4 times a day for 2 weeks.

There are fewer data on the clinical use of doxycycline compared with tetracycline, but doxycycline is better tolerated. When treating patients who are intolerant to doxycycline or tetracycline, it is important to ensure that they complete the course of treatment and return for follow-up evaluation.

The pharmacologic and antimicrobial properties of ceftriaxone and limited studies suggest that ceftriaxone is effective, but these data are insufficient to assess the long-term effects of its use. The optimal dose and duration of treatment for ceftriaxone have not been established, but the suggested regimen of 1 g daily may be used if treponemocidal blood levels are maintained for 8 to 10 days. Single-dose ceftriaxone is ineffective for the treatment of syphilis.

In men and non-pregnant women in whom the full course of treatment and follow-up can be guaranteed, orally administered erythromycin 4 times daily for 2 weeks may be an alternative regimen if tolerated. However, erythromycin is less effective than other recommended agents.

If the above drugs are intolerable and follow-up monitoring is not possible, patients should undergo desensitization and be given penicillin. If possible, penicillin skin allergy tests are recommended (see Management of patients with penicillin allergy).

Pregnancy

Pregnant patients with penicillin allergy should be desensitized if necessary and then treated with penicillin (see Management of Patients with Penicillin Allergy and Syphilis in Pregnancy).