Clinical and Morphological Diagnostics and Treatment of Sexually Transmitted Infections - Yakimova T. P. 2007
Morphological Diagnostics, Clinical Course, and Treatment of Syphilis
Syphilis is an infectious disease caused by a pathogen belonging to the group of tissue spirochetes, specifically the pale spirochete—Spirochaeta pallidum or Treponema pallidum. The pathogen received its name because it is poorly visible in both native and stained preparations due to its low affinity for laboratory stains. Treponema pallidum is a tissue parasite that invades Cells and Cell nuclei, which accounts for its chronic persistence in Tissues. Being a facultative anaerobe, it readily multiplies in the tissues of Internal Organs in both vegetative forms and long-term persistence forms—cysts, L-forms, and granular forms. These persistence forms of the pale treponema are resistant to Antibodies and pharmacological agents, particularly Antibiotics, which form The basis of the Pathogenetic Treatment of syphilis.
In the Cytology/cytology/16.html">Early stages of the disease, the predominant form of Treponema pallidum is the spiral-shaped form, which is the most contagious form during primary, fresh, and secondary relapsing syphilis.
The disease is primarily transmitted sexually. The pale spirochete penetrates through damaged mucous membranes and abraded Skin, actively proliferating in the nervous, connective, and lymphoid tissues. Non-sexual transmission of a domestic or occupational nature also occurs.
Within 3–4 weeks following infection, a hard chancre appears at the site of entry—an induration that subsequently develops into a painless, rounded ulcer with a smooth, varnished-appearing base and even edges of Cartilage-like density, known as a hard ulcer (ulcus durum).
The localization of the primary ulcer depends on the route of infection. In sexual transmission, the genital organs are affected (the glans Penis, Labia minora and majora). In non-sexual transmission, the oral mucosa or the fingers of healthcare professionals—such as obstetrician-gynecologists and pathologists—are affected. Approximately 10% of patients present with extragenital primary lesions. Lymphatic vessels and regional Lymph Nodes become involved very rapidly. The latter increase in size, become indurated, and, together with the primary affect, form the primary syphilitic complex.
In the hard chancre, along the edges of the ulcer and within the base, the inflammatory infiltrate consists of immunocompetent cells—lymphocytes, plasma cells, a small number of neutrophilic granulocytes, and epithelioid cells. A large number of treponemes are detected within the infiltrate.
The presence of a hard chancre characterizes the primary stage of syphilis. After 2–3 months, an amelanotic scar forms at the site of the primary affect. In the regional lymph nodes, follicular hyperplasia, desquamation and proliferation of sinus endothelium, and sclerotic Changes in the lymph nodes occur. Punctates of the lymph nodes reveal lymphocytes, prolymphocytes, lymphoblasts, macrophages, and endothelial Cells of the lymph node sinuses.
The secondary stage of syphilis lasts from 2–3 months to several years. This is a period of hyperergy and generalization of the process. It develops As a result of the pathogen spreading via lymphatic and Blood Vessels and disseminating throughout the body. During this period, the skin and mucous membranes are affected, where multiple inflammatory lesions known as syphilids appear. In these lesions, inflammatory and necrotic processes coexist, resulting in the appearance of roseolae, papules, or pustules. Syphilids contain a large number of treponemes (col. insert, Figs. 68–69), which are released into the external environment when papules or pustules ulcerate. This stage of syphilis is highly contagious. Enlarged lymph nodes exhibit edema, lymphoid tissue hyperplasia, areas of necrosis, and accumulations of treponemes.
Tertiary syphilis occurs 3–6 years after infection and manifests as a chronic specific productive inflammation with The formation of specific granulomas or gummas. In this stage, infiltrates consisting of accumulations of lymphocytes, plasma cells, epithelioid cells, Langhans-type multinucleated giant cells, fibroblasts, and areas of necrosis appear in internal organs—the Liver, Lungs, and soft tissues. Consequently, punctates from such lesions reveal the aforementioned elements, and occasionally the pale treponema can be detected within the cellular infiltrate using the silver impregnation method.
MICROSCOPIC Diagnosis OF SYPHILIS
Various types of biomaterial are used for the microscopic diagnosis of syphilis. These include blood serum, tissue exudates, smears and scrapings from ulcerated surfaces, erosions, eroded papules, punctates of tumor-like granulomatous formations, lymph nodes, and other biological samples.
The accurate verification of a disease—not only syphilis, but any pathological process—frequently depends on the correct collection of biomaterial.
Prior to collecting material for cytologic examination, the lesion—which may present as an ulcerated surface, erosion, or papule—must be cleaned of purulent or necrotic deposits using a cotton or gauze swab moistened with saline or boiled sterile Water, and then wiped with a dry sterile cotton or gauze swab. If dry or moist crusts are present On the surface of the lesion, they are removed with forceps.
After cleaning the lesion of various exudative-necrotic deposits and crusts, a drop of exudate—which usually has a slightly opalescent appearance—is expressed by gentle pressure near the edge of the lesion using a sterile metal spatula or scalpel. This exudate is then examined by placing it on a coverslip. If bloody content is obtained, it is wiped away, and one waits for a clear, light exudate to appear. The spatula must be thin. If a spatula of the required thickness is unavailable, a drop of exudate from The surface of the lesion is obtained by compressing the tissue edges at the periphery of the lesion from both sides.
Material from tumor-like formations in soft tissues and lymph nodes is obtained via puncture using a syringe. If The amount of biomaterial is negligible (a few drops), it is placed directly onto a Glass slide; if a sufficient amount of punctate is available, it is placed into a Petri dish, and then, using a spatula and a dissecting needle or a Pasteur pipette, a native preparation and smears for staining are prepared on glass slides. In other words, both native and stained micro-preparations must be examined simultaneously. Native preparations for the detection of syphilis are typically examined using dark-field Microscopy, while Romanowsky-Giemsa, Pappenheim, or Shershevsky staining Methods, or the Althhausen staining technique, are used for stained micro-preparations.
EXAMINATION OF NATIVE PREPARATIONS
To study native biomaterial, micro-preparations are prepared, as indicated above, by placing a drop of exudate obtained from the lesion onto a glass slide and covering it with a coverslip. The drop of exudate beneath the coverslip should be free of air bubbles and should not extend beyond the edges of the coverslip. The prepared native preparation is placed in a moist chamber for 5–10 minutes; this can be a Petri dish with a moistened (but not soaking wet, and leak-free) cotton roll placed along its perimeter, or moistened filter paper placed at the bottom of the dish.
Microscopic examination of native preparations under dark-field illumination reveals light, undulating, slender spirochetes characterized by uniform convolutions. One can count from 6 to 14 or more such coils in a single spirochete (col. insert, Fig. 68). The spirochetes in the preparation move by rotating along their longitudinal axis with a very smooth, pendulum-like motion, which distinguishes them from other spirochetes whose movements are much more energetic and whose number of coils is most frequently 3 to 5 (though Treponema denticola has 6–8, and Treponema phagedenis has 10–12).
It should also be emphasized that the pale spirochete is fragile in the external environment, cannot withstand high temperatures, and dies upon heating to 45–48°C, whereas at low temperatures (minus 10°C), its viability persists for up to three days. The most lethal agent for the pale spirochete is a 1:1000 mercuric chloride (sublimate) solution, which inactivates the pale spirochete within minutes, as does a 1–2% phenol solution.
STAINING Methods for the PALE SPIROCHETE
As is well known, due to its poor affinity for stains, the syphilis pathogen is termed the pale spirochete. Consequently, modifications utilizing azure Dyes have been proposed for staining the pale spirochete.
Preparations for staining must be placed on a degreased glass slide, and the biomaterial is distributed on the slide with a gentle rocking motion to produce a thin smear, typically 1–1.5 cm in diameter. Occasionally, 2–3 such rounded smears can be made on a single glass slide. After air-drying, the smears are fixed using methods commonly employed for staining any cytologic preparations: methyl alcohol, Nikiforov’s fixative, or osmium tetroxide vapors.
Romanowsky-Giemsa staining methods.
Fixation with methyl alcohol lasts for 3 minutes. The methyl alcohol used as a fixative must be chemically pure.
Nikiforov’s mixture is a 1:1 solution of equal parts ethyl alcohol and ether. Fixation with Nikiforov’s mixture typically lasts 10–15 minutes. Following fixation, the smears are stained using the Romanowsky-Giemsa method for 2–12 hours. After staining, the preparations are rinsed with running water and air-dried.
Method for accelerated staining of Treponema pallidum. When a rapid diagnosis is required, an accelerated staining method is used. To do this, Romanowsky stain is applied to the fixed smear at a concentration of 2 to 3 drops per 1 ml of distilled water (instead of the usual 1–2 drops per 1 ml of water). The slide is then gently heated over a burner flame until vapors appear and placed on a staining rack. This heating process with the stain is repeated 3 to 4 times, after which the smear is rinsed with water and air-dried.
Shershevsky staining method. A solution of pre-warmed Romanowsky stain in glycerin water is applied to the fixed smear. This solution is prepared by mixing 2 drops of Romanowsky stain with 1 ml of a 0.5% glycerin solution in distilled water, and is left for 5 minutes. The smear is flooded with the hot Romanowsky stain solution three times, after which the slides are rinsed with water and air-dried.
Following staining with Romanowsky stain, Treponema pallidum acquires a pinkish-violet hue with well-defined coils. Other species of spirochetes stain significantly brighter.
A disadvantage of staining Treponema pallidum with azure-eosin mixtures is weak staining and the presence of precipitates that hinder examination. To prevent precipitation, fixation must be performed in a covered vessel with the Microscope slides kept in a vertical position. The actual staining of the fixed smears should be carried out on a staining rack in a horizontal position.
A. Ya. Althausen (1950) proposed his own method for staining Treponema pallidum, which optimizes syphilis Diagnostics. For this purpose, a special stain is prepared using methylene blue dye, sodium carbonate, and distilled water.
The special stain for the Althausen method is prepared as follows: 0.5 g of conventional methylene blue, 0.25 g of sodium carbonate (Na2CO3), and 500 ml of distilled water are combined in a specific manner. First, distilled water is heated to a boil in a flask plugged with cotton to eliminate carbon dioxide. After cooling, sodium carbonate is added to the water, followed by the methylene blue. The prepared solution is transferred to a 500 ml glass container that has been pre-washed, rinsed several times with distilled water, and sterilized. The glassware containing the prepared stain solution must be sealed with a clean stopper and left in a dark cabinet at room Temperature for the stain to "ripen." After 2 to 3 weeks, the stain "ripens," as indicated by the initial blue color turning purple. Methylene azure forms in the ready-made dye, which produces a purple foam upon shaking.
Althausen's method for staining Treponema pallidum. Microscopic smears dried on a slide are fixed by any standard method and stained using the prepared methylene azure and eosin solutions. First, 0.5 ml of an aqueous solution of yellowish eosin (diluted 1:1000) is mixed with 2.5 ml of distilled water and applied to the fixed smear for 10 minutes. After 10 minutes, the stain is drained off without rinsing, and a pre-warmed mixture consisting of 0.8 ml of the prepared methylene azure stain and 2.2 ml of distilled water is applied for 20 minutes. Following this 20-minute staining period, the smear is rinsed in running tap water and air-dried. Syphilis spirochetes stain bright red with multiple fine coils (see color insert, Fig. 69). This staining method clearly distinguishes Treponema pallidum from other spirochetes, which stain blue with sparse, coarse coils.
A significant advantage of this smear staining method is the complete absence of precipitation on the slides.
Detection of Treponema pallidum by dark-field microscopy.
To detect Treponema pallidum using dark-field microscopy, it is essential that the biomaterial is free of erythrocytes and blood contamination, as the presence of red and white Blood Cells complicates the examination. To achieve this, after cleaning the lesion site as described above, a drop of serous exudate is expressed by compressing the Base of the ulcer or erosion from both sides. The exudate is then collected either with a bacteriological loop and transferred to a microscope slide, or by pressing a microscope slide directly against the surface of the lesion. On the slide, the serous discharge is mixed with an equal amount of saline, covered with a coverslip, and examined under a dark-field microscope.
The distinguishing characteristics of Treponema pallidum under dark-field examination include its size, number of coils, and the specific pattern of its motility.
Compared to other commensal treponemes, Treponema pallidum is considerably longer, averaging 10 µm, though its length can range from 6 to 20 µm. This overlap makes it impossible to differentiate it solely by length from other treponeme species such as Treponema refringens, Treponema phagedenis, and Treponema denticola, which measure 5–16 µm, 10–30 µm, and 6–16 µm, respectively. Neither the thickness of commensal treponemes and Treponema pallidum nor the length and number of their coils can serve as absolute differentiating criteria; for instance, both Treponema phagedenis (reiteri) and Treponema pallidum can have up to 10–12 coils, whereas other treponeme species have significantly fewer (2–6–8). The primary distinguishing feature of Treponema pallidum is the depth of its coils, which is the greatest among them at 0.5–0.7 µm, compared to only 0.1–0.4 µm in commensal treponemes.
A hallmark feature of Treponema pallidum is its specific type of movement. It is characterized by slow, free translational motion, which may alternate with rotational movement (ranging from slow to rapid in place), as well as flexing and pendular movements. Flexing and pendular movements are exclusive to Treponema pallidum and are absent in commensal spirochetes. During flexing movements, Treponema pallidum can sharply bend at an angle and straighten out at any point along its body, which serves as an absolute differential diagnostic sign of the syphilis causative agent.
Direct immunofluorescence assay (DFA) developed by Coons—the DFA method—is also a highly informative morphological diagnostic method for syphilis.
To perform this test, the manufacturer's instructions supplied with the commercial fluorochrome-labeled (FITC) immunoglobulin preparation containing antibodies against Treponema pallidum must be followed.
To perform the DFA test, a smear is prepared on a microscope slide using any biomaterial from the surface of the tissue lesion, distributed evenly across the slide, and air-dried. After drying, the smear is fixed with methanol or ethanol, and an immunoglobulin solution containing antibodies against Treponema pallidum (diluted According to the instructions provided with the commercial anti-T. pallidum globulin kits) is applied. The smear is then examined under a fluorescence microscope. If the CAUSATIVE AGENT OF syphilis is present in the biomaterial, bright green Treponema pallidum cells, sometimes with a yellowish tint, are visualized against the dark Background. This reaction is highly specific because the antibodies carried by the immunoglobulin are exclusively anti-T. pallidum antibodies. This method does not detect other non-pathogenic forms of treponemes present on the mucous membranes of the Oral Cavity or rectum.
Morphological methods for diagnosing syphilis are evaluated in conjunction with the results of serological tests that detect antibodies against the antigenic determinants of Treponema pallidum.
Primary syphilis lesions are localized on the skin and genital mucosa.
The primary lesion always resolves spontaneously without treatment. However, the infection spreads throughout the body via hematogenous and lymphatic pathways, giving rise to various clinical manifestations of the disease. After 2 to 10 weeks, secondary lesions appear across the skin of the entire trunk in the form of reddish-brown maculopapular rashes. In intertriginous areas (genital, perianal, and axillary folds), papular syphilids transform into flat, weeping clusters of papules known as broad condylomas (condylomata lata).
The manifestations of syphilis are extremely diverse, which is why venereologists refer to it as the "great imitator."
Both Primary and secondary lesions contain a high concentration of pathogens, making them the most common source of infection.
Secondary lesions also resolve spontaneously. Syphilitic infection can occur in a subclinical form; in some cases, patients go through the primary or secondary stage—or even both—without noticing any signs of the disease. Over time, such patients develop tertiary lesions.
The tertiary stage of syphilis is characterized by The Development of granulomatous lesions (gummas) in the skin, bones, liver, Brain, lungs, Heart, and eyes. Degenerative Changes in the Central Nervous System (paresis, tabes dorsalis) or cardiovascular syphilis (aortitis, aortic aneurysm, aortic valve regurgitation) may also develop.
It is generally accepted that reinfection and superinfection can occur in syphilis. Reinfection is a new infection in an individual who has previously recovered from syphilis, which is possible due to the waning of Immunity after successful treatment. Superinfection is a secondary infection in an active syphilis patient; it occurs rarely because it is prevented by the patient's infection immunity.
Primary syphilis (syphilis I primaria) is a stage of the disease characterized by the appearance of a hard chancre and enlargement of regional lymph nodes. Primary seronegative syphilis (syphilis I seronegativa) is syphilis with persistently negative serological reactions throughout the course of treatment. Primary seropositive syphilis (syphilis I seropositiva) is syphilis with positive serological reactions. Primary latent syphilis (syphilis I latens) is syphilis characterized by the absence of clinical manifestations in patients who started treatment during the primary stage of the disease and received inadequate therapy.
Secondary syphilis (syphilis II) is a stage of the disease caused by the hematogenous spread of pathogens from the primary lesion, characterized by polymorphic rashes (papules, macules, pustules) on the skin and mucous membranes. Early secondary syphilis (syphilis II recens) is a period of syphilis characterized by numerous polymorphic rashes on the skin and mucous membranes and polyadenitis; residual signs of a hard chancre are often observed. Secondary recurrent syphilis (syphilis II recediva) is a period of secondary syphilis that follows early secondary syphilis; it is characterized by sparse, polymorphic, grouped rashes and frequently by nervous system involvement. Secondary latent syphilis (syphilis II latens) is a secondary stage of the disease that proceeds latently.
Tertiary syphilis (syphilis III tertiaria) is the stage that follows secondary syphilis; it is characterized by destructive lesions of the internal organs and nervous system with the formation of gummas within them. Active nodular or gummatous tertiary syphilis (syphilis III activa, seu manifesta, tuberculosa, seu gummosa) is distinguished, characterized by an active process of nodule formation that resolves with necrotic disintegration, ulceration, healing, scarring, and the appearance of uneven pigmentation (mottling), along with latent tertiary syphilis (syphilis III latens), which is a period of the disease in individuals who have experienced active manifestations of tertiary syphilis.
Latent syphilis (syphilis latens) is syphilis in which serological reactions are positive, but signs of skin, mucous membrane, and internal organ lesions are absent. Early latent syphilis (syphilis latens praecox) is syphilis in which less than 2 years have passed since infection. Late latent syphilis (syphilis latens tarda) is when 2 years or more have passed since infection. Unspecified latent syphilis (syphilis ignorata) is a disease whose duration cannot be established.
Congenital syphilis (syphilis congenita) is syphilis transmitted from an infected mother during intrauterine development. Early congenital syphilis (syphilis congenita praecox) is congenital syphilis in a fetus and in children under 2 years of age, manifested by syphilitic Pemphigus, diffuse papular infiltration of the skin, lesions of the mucous membranes, internal organs, Bone tissue, nervous system, and eyes. Late congenital syphilis (syphilis congenita tarda) is congenital syphilis in children over 2 years of age, manifested by Hutchinson's triad, as well as skin, internal organ, and bone lesions resembling tertiary syphilis. Latent congenital syphilis (syphilis congenita latens) is congenital syphilis with no clinical manifestations and normal CEREBROSPINAL FLUID laboratory parameters.
Nervous system syphilis (neurosyphilis): early (neurosyphilis praecox) with a disease duration of up to 5 years, and late (neurosyphilis tarda) exceeding 5 years.
Visceral syphilis (syphilis visceralis) is syphilis affecting the internal organs (heart, brain and/or Spinal Cord, lungs, liver, Stomach, Kidneys).
Endemic (or household) syphilis is syphilis contracted through non-sexual transmission.
Syphilis decapitata (syphilis decapitata) occurs when the pathogen enters the bloodstream directly (through a wound or during blood examination); it is characterized by the absence of a hard chancre.
Transfusion syphilis (syphilis transfusionalis) is infection resulting from the transfusion of blood from an infected person.
Malignant syphilis is syphilis with massive involvement of the internal organs and nervous system, characteristic of tertiary syphilis within the first year of the disease.
Experimental syphilis is syphilis that occurs in laboratory animals (monkeys, rabbits) as a result of their artificial infection.
PRIMARY SYPHILIS
Primary syphilis begins with the appearance of a hard chancre and lasts 6–7 weeks until multiple rashes appear on the skin and mucous membranes. 5–8 days after the appearance of the hard chancre, nearby lymph nodes begin to enlarge (regional syphilitic scleradenitis), and inflammation of the lymphatic vessels (specific lymphangitis) may develop. Clinically, the lymph nodes are characterized by a firm-elastic consistency and are painless. Furthermore, they are not inflamed, never fuse with each other or with the surrounding tissue, and remain mobile; each of them can be easily palpated individually.
During the 3–4 weeks of the primary stage of the disease, standard blood serological tests for syphilis are negative (primary seronegative syphilis). Thereafter, the course of primary syphilis is characterized by positive standard serological reactions (primary seropositive syphilis).
In most cases, the primary syphiloma is located in the area of the external genitalia; however, hard chancres can be situated on any area of the skin or visible mucous membranes. At the site of *Treponema pallidum* inoculation, a well-demarcated, rounded erythema first appears, which does not cause discomfort to the patient and rapidly (within 2–3 days) transforms into a flat papule with slight scaling and minor induration at the base. After some time, an erosion or ulcer with an indurated base forms on the surface of the papule.
An erosive hard chancre is usually round or oval in shape. Its diameter is 0.7–1.5 cm, the base is bright red (the color of fresh meat) or grayish-yellow (the color of spoiled lard), the edges are not undermined, are clearly demarcated, and lie on the same level as the skin. Signs of acute inflammation at the periphery are absent. The discharge from the erosion surface is serous, transparent, or opalescent, and in small amounts. A clearly demarcated leaf-like or laminar induration can be palpated at the base of the chancre. The base of the erosion is smooth, glossy, and seemingly varnished. A characteristic feature of the primary syphiloma is its painlessness. Following epithelialization, a pigmented spot remains, which soon disappears without a trace. The infiltrate at the base of the erosion persists for a longer period (several weeks, and sometimes months), but then completely resolves.
An ulcerative hard chancre is less common than the erosive type, although in recent years it has been observed with increasing frequency. Unlike the erosive variant, the skin defect is deeper (within the dermis), the ulcer is saucer-shaped, and the base is more often of a dingy yellow color, sometimes with small hemorrhages. The discharge is more abundant than in an erosive hard chancre. The induration at the base of the ulcer is more pronounced and nodular. The lesion is painless, without an inflammatory border at the periphery. The ulcer heals by scarring (without treatment, 6–9 weeks after onset), leaving a smooth surface and a rounded, hypopigmented or narrow hyperpigmented border at the periphery.
The size of the primary syphiloma varies widely, most often reaching 0.7–1.5 cm in diameter, sometimes the size of a coin or larger (giant chancres), while in some patients dwarf chancres measuring 0.2–0.3 cm are observed. The latter are particularly dangerous from an epidemiological standpoint because they remain unnoticed and patients can serve as a source of infection for a long time.
The second important symptom of primary syphilis is the bubo—regional lymphadenitis. It usually appears by the end of the first week following The Emergence of the hard chancre. When the bubo is localized in the genital area, the inguinal lymph nodes enlarge; on the lower lip or chin—submandibular lymph nodes; under the Tongue—submental lymph nodes; on the fingers—cubital and axillary lymph nodes; on the lower extremities—popliteal and femoral lymph nodes; and in the area of the Mammary Glands—axillary lymph nodes. The inguinal lymph nodes most often change on the ipsilateral side, less frequently on the contralateral side, and quite often on both sides (with the dimensions of the lymph nodes located on the opposite side being smaller).
Regional scleradenitis manifests as an enlargement of the lymph nodes (sometimes to the size of a hazelnut). In this condition, signs of acute inflammation, pain, and skin discoloration are absent. The nodes have a firm-elastic consistency, are mobile, not fused with each other or with adjacent tissues, and show no signs of periadenitis. Several lymph nodes usually enlarge in the zone close to the lesion site; one of them, located closest to the hard chancre, is the largest in size.
Regional scleradenitis resolves significantly more slowly than the hard chancre regresses, which is why it is also present in patients with manifestations of early secondary syphilis.
The third symptom of primary syphilis is positive standard serological reactions. The Wassermann reaction usually becomes positive in the 7th week after infection, i.e., 3–4 weeks after the appearance of the hard chancre, at which point primary seronegative syphilis transitions into the primary seropositive stage. The immunofluorescence test becomes positive slightly earlier than standard reactions, but its readings are not taken into account when determining whether a patient has seronegative or seropositive primary syphilis.
Subsequently, 5–6 weeks after the appearance of the hard chancre, symptoms appear that indicate the generalization of treponemal infection. All lymph nodes enlarge, i.e., polyscleradenitis develops. The nodes have a firm-elastic consistency, are ovoid in shape, painless, not fused with each other or with adjacent tissues, and show no signs of acute inflammation. Their dimensions are significantly smaller than those of the concomitant regional scleradenitis. The closer the lymph nodes are located to the primary syphiloma, the larger they are. Like the concomitant bubo, they resolve slowly, even with intensive treatment.
The primary period of syphilis ends not with the disappearance of the hard chancre, but with the emergence of secondary syphilids. Therefore, in some patients, the healing of the hard chancre, particularly the ulcerative type, is completed already in the secondary period, while in others the erosive chancre manages to disappear even in the middle of the primary period, 3–4 weeks after its appearance.
SECONDARY SYPHILIS
During the secondary stage of syphilis, roseolous, papular, and pustular rashes appear on the skin and mucous membranes, accompanied by pigmentation and pronounced Hair loss. Internal organs (such as The Liver and kidneys), as well as the nervous, endocrine, and skeletal systems, may be affected. These lesions are functional in nature and rapidly regress with specific treatment. General systemic symptoms are also occasionally observed. As a rule, the secondary stage of the disease follows a benign course. Patients report no subjective Complaints, and destructive changes are absent. Clinical signs regress even without treatment, and blood serological reactions remain positive.
Typically, the onset of the secondary stage features an abundant, often polymorphic, fine rash that does not tend to coalesce. The exanthems of secondary syphilis are referred to as syphilids (or syphilides). They are distributed haphazardly yet symmetrically. In some patients, clinical signs of primary syphilis persist, notably an unhealed hard chancre or residual traces of the primary syphiloma (such as a pigmented secondary spot or a fresh scar) along with regional scleradenitis. The most common finding is polyadenitis. The clinical course of the disease is variable. Most commonly, within 2–2.5 months, the rashes gradually disappear, leaving behind only positive serological reactions and residual signs of polyscleradenitis. This marks the beginning of the secondary latent period. In the later phase, a relapse of the disease occurs, characterized by a rather diverse clinical course.
Unlike early secondary syphilis, the cutaneous manifestations in this later stage are fewer in number, larger, prone to grouping, and paler. They are more frequently located in major skin folds, areas subject to mechanical trauma, and regions with increased sweating; polyadenitis is less pronounced. Changes in the oral mucosa occur more often in patients who abuse alcohol or hot food, as well as in individuals with untreated dental caries. Serological tests in the blood are positive in 98% of patients, though the titer of the Wassermann reaction is lower than in early secondary syphilis. Additionally, cases involving damage to internal organs, the nervous and endocrine systems, Sensory Organs, bones, and joints may be encountered, which are detected through specialized diagnostic Procedures.
The clinical manifestations of secondary syphilis are exceptionally diverse. Syphilids in this stage of the disease may be macula-like (roseola), papular, vesicular, or pustular. Other notable presentations include syphilitic leukoderma, alopecia, and lesions affecting the Larynx, vocal cords, oral mucosa, Nasal cavity, as well as erosive and ulcerative syphilids on the mucous membranes.
The macula-like (roseolous) syphilid is the most frequent eruption during the initial phase of early secondary syphilis. The rash appears on the lateral surfaces of the chest, abdomen, and back, the anterior surfaces of the upper extremities, and occasionally on the thighs. Notably, it is rarely found on the face, hands, and feet. The eruptions develop gradually—at a rate of 10–20 roseola spots per day—and reach full development within 7–10 days. In early secondary syphilis, the rash is dense, irregularly yet symmetrically distributed, focal, and rarely coalesces. Immature elements are pink, mature ones are red, and older ones take on a yellowish-brown hue. The roseola spot is round, 8–12 mm in diameter, typically flush with the skin surface, non-scaling, and causes no subjective sensations; it disappears upon diascopy (only in rare cases does it scale or cause itching).
In secondary recurrent syphilis, the roseola spots are larger, less vivid, frequently annular in shape, and tend to cluster in groups.
Papular syphilids typically develop 7–14 days after the appearance of roseola. They can vary in size—resembling a lentil (lenticular), a millet seed (milliary), or a coin (nummular)—and rise above the skin level, usually within major skin folds (where they form hypertrophic broad condylomas). As a result of surface maceration, serous fluid may ooze from them (moist papules). Erosive and ulcerated papules are also encountered. When covered with dense scales resembling psoriasis, they are termed psoriasiform, or seborrheic if the scales are greasy (particularly in the scalp and nasolabial folds).
Lenticular papules are most commonly observed in patients with early secondary syphilis, and less frequently in the recurrent form. New elements appear daily over the course of several days. In the early secondary stage, they are frequently accompanied by roseola spots, presenting as a polymorphic rash.
A lenticular papula is firm, rounded, about the size of a lentil, and clearly demarcated from the surrounding tissue without an inflammatory halo; it exhibits a copper-red color with a bluish undertone and a lustrous surface. During regression (1–2 months after onset), a small scale forms on the papule; subsequently, its central part detaches, leaving a visible peripheral collar of undermined stratum corneum (Biett's collar). Following the resorption of the papule, a pigmented spot remains, which eventually fades. Syphilitic papules do not cause subjective sensations. In early secondary syphilis, papules are numerous and distributed haphazardly yet symmetrically, whereas in recurrent syphilis, they are fewer in number and tend to group together.
Nummular papules share the same characteristics as lenticular ones. They are larger (up to 2.5 cm in diameter) and are more commonly observed in recurrent syphilis. Milliary syphilitic papules are small (resembling a millet seed), hemispherical, firm, reddish-blue in color, multiple, tend to cluster, resolve slowly, and leave behind minor scar atrophy.
Hypertrophic (vegetative, or broad) condylomas typically localize in major skin folds, the Perineum, the genitalia, and around the anus, developing as a result of chronic, sustained irritation. They are large, rise significantly above the skin level, and coalesce to form plaques with scalloped borders. These are most frequently seen in patients with secondary recurrent syphilis. Their surface is often macerated and moist, and in some patients, it becomes eroded or ulcerated.
Psoriasiform papules are typically localized on the palms and soles, feature pronounced scaling, and are more frequently encountered in secondary recurrent syphilis. Seborrheic papules are covered with greasy, yellowish scales and appear in areas rich in Sebaceous Glands. Cracks—known as ragadiform syphilids—frequently develop on papules located at the corners of the Mouth, near the eyes, and in the interdigital folds.
The vesicular syphilid is extremely rare and develops during a severe course of secondary syphilis accompanied by reduced body resistance. Against the background of copper-red papules (typically large in size), small, serous, clustered vesicles appear, which rapidly dry into thin crusts. Following their regression, small superficial scars remain upon a secondary pigmented spot.
Pustular syphilids typically arise in secondary syphilis as a result of papular breakdown, forming yellowish-brown crusts that resemble Pyoderma. Unlike regular pustules, their periphery features an un-decayed infiltration rim rather than an acute inflammatory halo. Pustular syphilids are most frequently observed in individuals with compromised immune defenses suffering from severe concurrent illnesses (such as tuberculosis, malaria, or chronic alcoholism). The onset of the rash is occasionally accompanied by fever, malaise, and weight loss, and is often preceded by prominent signs of primary syphilis. Pustular syphilids (including acneiform, impetiginous, varioliform, rupioid, and ecthymatous forms) are rare. Their specific subtype depends on the localization of the rash, the size of the elements, and the degree of tissue breakdown.
The impetiginous pustular syphilid, or syphilitic impetigo, manifests as eruptions of rounded papules 0.6–1 cm in diameter with superficial epidermal breakdown, which subsequently dries into a dirty-yellow crust bordered by a reddish-blue, firm rim of un-decayed infiltrate. It is localized predominantly on the HEAD, chest, back, and anterior surfaces of the upper extremities. Deeper tissue breakdown accompanied by a central umbilicated depression gives rise to the varioliform (smallpox-like) syphilid. All three subtypes of pustular syphilids are most commonly observed in patients with early secondary syphilis.
Syphilitic ecthyma (the ecthymatous pustular syphilid) develops as a result of deep breakdown in large nummular papules. In the event of a sharp decline in the patient's immune resistance, tissue destruction beneath the formed crust may continue, progressing both deeper and peripherally. This leads to the formation of a layered, shell-like crust known as the rupioid pustular syphilid, or syphilitic rupia. Syphilitic ecthyma and rupia are most frequently seen in secondary recurrent syphilis, typically in patients experiencing a severe clinical course, often accompanied by negative serological tests for syphilis. Without treatment, they persist for long periods and regress very slowly under therapy, leaving scars behind.
Pigmented syphilid (syphilitic leukoderma) develops on otherwise unaltered skin, usually 5–7 months after infection—that is, during the secondary recurrent stage. In recent years, it has become slightly more common in women and in cases of early secondary syphilis. It is frequently associated with nervous system involvement, which may manifest solely as pathological changes in the cerebrospinal fluid.
Syphilitic leukoderma is located predominantly on the lateral and posterior surfaces of the neck, and less frequently on the skin of the upper
extremities, abdomen, and lumbar region. Against a background of moderately hyperpigmented skin, hypopigmented spots of various sizes—usually rounded—appear. Depending on the width of the hyperpigmentation zone around the spots and the color contrast between the hyper- and hypopigmented areas, leukoderma is classified as spotted (featuring a clear color contrast and wide hyperpigmentation zones), lacelike (narrow strips of hyperpigmentation intercalated between hypopigmented spots), or marbled (slight color difference between the zones). Side lighting makes the color contrast more apparent. The spots cause no discomfort or scaling, and signs of inflammation are absent. Leukoderma is persistent, disappearing within 6–12 months—and occasionally 1.5–2 years—even with full and proper treatment. It is frequently associated with syphilitic alopecia.
Syphilitic alopecia is observed in a proportion of patients with secondary recurrent syphilis. Nowadays, it is also noted slightly more frequently in early secondary syphilis. Hair loss occurs (predominantly in men) as a result of impaired ROOT Nutrition caused by vasculitis and perivascular infiltration. Alopecia in secondary syphilis is primary in nature (and is best visualized when the hair is cut short).
There are three clinical varieties of alopecia: small-patch (focal), diffuse, and mixed. It develops abruptly and progresses rapidly. The temporoparietal and occipital regions are most commonly affected; however, in severe cases of the disease, hair loss may also occur in other areas of the scalp, as well as the axillae, beard, mustache, eyebrows, and eyelashes. Notably, the skin in the affected areas remains unchanged—there is no redness, scaling, or scarring—only a portion of the hair is shed, and subjective sensations are absent. Hair growth typically recovers 1–2 months after the infiltrate resolves. This is particularly noticeable in the eyelash region, where recovering hairs of varying lengths create a stepped appearance (known as Pinkus' sign).
Tertiary syphilis of the Bones and joints manifests as osteoperiostitis or Osteomyelitis. Osteoperiostitis may be either localized or diffuse. Localized osteoperiostitis presents as a gumma, which in the course of its development either undergoes ossification or breaks down to form a typical gummatous ulcer.
LATENT SYPHILIS
This term denotes a clinical variety of syphilis that follows a latent course from the moment of infection, lacking clinical signs of the disease while presenting positive blood serological reactions. Early and late latent syphilis are distinguished. Early latent syphilis refers to acquired forms of syphilis with a duration of infection of up to two years, whereas late latent syphilis refers to those exceeding two years.
Standard serological reactions in patients with early latent syphilis are typically positive across the full complex and at high titers (1:160). However, it must be taken into account that in some patients who have previously been treated for Gonorrhea or have practiced self-medication, these reactions may be positive only in an incomplete complex or exhibit a low reagin titer (1:10-1:20). Usually, such cases present with positive Wassermann reactions using treponemal or cardiolipin Antigens, or those performed in the cold, alongside a negative Wassermann reaction with lipoidal antigens. A low reagin titer may also occur in patients in the initial stage of early latent syphilis, which corresponds in terms of infection duration to primary seropositive syphilis. FTA-ABS (fluorescent treponemal antibody absorption) tests in patients with early latent syphilis are generally positive. TPI results, depending on the duration of the infection, may be either positive or negative. The diagnosis of early latent syphilis is confirmed by the appearance of a Herxheimer reaction (aggravation reaction) at THE START OF treatment and a relatively rapid negative conversion of standard serological reactions, similar to that observed in patients with primary and secondary syphilis.
CONGENITAL SYPHILIS
Congenital syphilis refers to the presence of a treponemal infection in a child dating from the period of intrauterine development.
Pale treponemes penetrate the fetus's body via the umbilical vein, the lymphatic clefts of the umbilical vessels, and through maternal blood across a damaged Placenta, starting from the 10th week of Pregnancy. Typically, intrauterine transmission of syphilis occurs in the 5th month of pregnancy. In pregnant women with secondary syphilis, fetal infection occurs in virtually 100% of cases; intrauterine infection is less frequent in patients with late forms of syphilis and very rare in patients with primary syphilis.
At this stage, congenital syphilis is characterized by mild symptoms, usually proceeding with minor, "blurred" manifestations or latently. Infants are frequently born premature (25–30%), featuring dry, wrinkled skin of an earthy-pale hue.
Early congenital syphilis. This period encompasses The concepts of "fetal syphilis," "syphilis in infants," and "syphilis of early childhood."
Fetal syphilis culminates in fetal demise during the 6th or 7th month of pregnancy, or less commonly prior to the 5th month, due to the Toxic effects of the pale treponeme. The stillborn fetus is delivered on the 4th day and consequently undergoes maceration in the Amniotic Fluid.
Infants born with active manifestations of syphilis prove non-viable and rapidly succumb. Clinical signs of syphilis developing after birth within the child's first months of life (up to one year of age) are classified as secondary syphilids. However, aside from the typical secondary syphilids characteristic of acquired syphilis, infants with syphilis exhibit unique forms of syphilids peculiar solely to this condition. For instance, the roseola differs by its reddish-brown hue, slight infiltration, and desquamation into furfuraceous scales upon resolution. Papular syphilid may manifest as a diffuse papular infiltration of the skin and mucous membranes.
A specific symptom of infantile syphilis is syphilitic pemphigus. The bullae appear at birth or During the first days, and more rarely the first weeks, of the infant's life. They are predominantly localized on the palms and soles, and very rarely on other PARTS OF THE body. Arising on an infiltrated base, they are initially filled with clear fluid which subsequently turns turbid; they rupture easily, leaving erosions in their place. Their characteristic localization, the absence of an inflammatory halo, and the detection of pale treponemes allow for a Differential diagnosis between syphilitic pemphigus and epidemic pemphigus of the newborn.
Diffuse syphilitic infiltration of the skin is somewhat less common (occurring in 20% of patients), develops during the first three months of life, and is generally absent In the second half of the year. The skin on the palms, soles, buttocks, and in the region of the chin, Lips, and forehead becomes infiltrated, indurated, thick, glossy, and as if varnished. Subsequently, desquamation, maceration, and wrinkling appear on the palms and soles ("washerwoman's hands"). When the process localizes on the lips and chin, fissures develop that heal with the formation of characteristic Robinson-Fournier scars, which persist for a lifetime and allow congenital syphilis to be diagnosed many years later. In the area of the forehead and scalp, diffuse infiltration resembles seborrheic dermatitis. Vertically oriented scars remain at the sites of deep folds and fissures.
Syphilitic rhinitis occurs exclusively in congenital syphilis in infants. It arises immediately after birth or during the first month of life. It is characterized by infiltration of the mucous membrane of the nasal passages, the appearance of mucopurulent discharge, and blood-tinged purulent crusts that "block" the nasal passages. Breathing becomes labored and acquires a distinct whistling, snorting character, making breastfeeding impossible. In some cases, deep infiltration involves the cartilage tissue and destroys the bones, resulting in nasal deformities ("saddle Nose", "pug nose", or "opera-glass" nose).
Congenital syphilis of early childhood (from 1 to 2 years of age) does not differ in its clinical manifestations from secondary recurrent syphilis. During the child's 2nd year of life, the clinical symptomatology of congenital syphilis is less diverse. Papular elements are observed on the skin and mucous membranes, while roseola is rare. Robinson-Fournier scars, periostitis, phalangitis, bone gummata, orchitis, chorioretinitis, lesions of the liver, Spleen, and the central nervous system (in the form of meningitis, meningoencephalitis, or cerebral vascular syphilis) may also be noted.
Late congenital syphilis. The clinical symptomatology of the disease is quite variable. Pathognomonic, absolute, and probable symptoms of late congenital syphilis are distinguished. Pathognomonic symptoms include Hutchinson's triad: parenchymatous keratitis, specific labyrinthitis, and alterations of the permanent upper central incisors (Hutchinson's Teeth).
Parenchymatous keratitis presents with redness and opacity of the cornea, photophobia, and lacrimation. The process is typically bilateral: one eye is affected first, and after some time, the second eye becomes involved as well. Vascular forms of keratitis also occur, in which corneal opacity develops without ocular redness or photophobia.
Syphilitic labyrinthitis and the consequent deafness are caused by the development of periostitis in the osseous portion of the labyrinth and damage to the auditory nerve. The process is usually bilateral. Deafness develops suddenly, sometimes preceded by dizziness and tinnitus (ringing and buzzing in the ears). It typically manifests between the ages of 7 and 15. If it occurs early, by the time speech is developing in the child, deaf-mutism may be observed. Labyrinthine deafness is resistant to administered treatment.
Syphilitic lesions of the mucous membranes in patients with secondary syphilis are frequent and are sometimes the sole symptom of the disease. The eruptions are frequently macerated, eroded, and weeping; they are highly contagious and represent an epidemiological hazard. They regress slowly because they are often subjected to chronic irritation when localized in the oral cavity (spicy or hot food, smoking, decayed teeth, etc.) or on the external genitalia. Morphologically and histologically, they resemble certain cutaneous manifestations of secondary syphilis. Macular and papular syphilids, often eroded and even ulcerated, are observed on the mucous membranes. The mucous membranes of the lips, oral cavity, tongue, Pharynx, vocal cords, female genitalia, and rectum are typically affected.
Roseolous syphilids on the oral mucosa present as rounded, red-bluish, clearly demarcated roseolas of small size (0.5–0.7 cm in diameter) that do not rise above the level of the surrounding tissues. Gradually, they coalesce to form erythematous patches. They cause no subjective sensations and disappear without a trace. The Tonsils, anterior and posterior pillars, uvula, and soft palate frequently become inflamed (syphilitic erythematous angina), which may be accompanied by a sensation of tickling in the throat, while pain is absent. Syphilitic erythematous laryngitis may be finely spotted or diffuse (accompanied by slight hoarseness). In syphilitic macular (catarrhal) rhinitis, dryness of the mucous membranes is noted, and crusts sometimes appear due to the drying of mucous secretions.
TERTIARY SYPHILIS
Typically 5 to 10 years, and occasionally later, after the initial syphilis infection, the tertiary period of the disease begins. However, it is not an inevitable outcome of the infection, even in cases where the patient received inadequate treatment or no treatment at all. Research data indicate that the frequency of progression of syphilis to the tertiary stage varies within significant limits (from 5% to 40%).
In the tertiary period, the skin, mucous membranes, nervous and endocrine systems, bones, joints, internal organs (heart, aorta, lungs, liver), eyes, and Sense Organs may be affected.
A distinction is made between the manifest (active) stage of tertiary syphilis and the hidden (latent) stage. The manifest stage is accompanied by clear signs of syphilis, whereas the hidden stage is characterized by the presence of residual signs (scars, bone alterations, etc.) of prior active manifestations of the disease.
During this period of syphilis, the lesions practically lack the causative agent, and therefore they are not contagious. Tubercles (gummas) or gummata typically arise, which are prone to breakdown and ulceration. They leave behind scars or cicatricial atrophy. Tertiary syphilids are arranged in groups within a single area and are not accompanied by lymphadenitis. Tubercles located superficially in the skin may group in the shape of arcs, rings, or garlands and, upon regression, leave behind characteristic atrophic scars (brownish spots with atrophic changes) featuring a bizarre pattern resembling a mosaic. Deeply situated tubercles (gummata) originating from the subcutaneous tissue reach a large size. They may resolve, but more frequently they break down, turning into deep ulcers of irregular shape. Gummata can appear in any organ.
Classical serological reactions are positive in the majority of cases, with fluctuating titers. They may be negative in 35% of patients with tertiary syphilis. Specific serological reactions are almost always positive.
Tubercular syphilids are characterized by eruptions on limited areas of the skin consisting of dense, bluish-red, painless, grouped tubercles ranging in size from a lentil to a pea, which lie at varying depths within the dermis and do not coalesce with one another.
Eruptions appear in waves. Consequently, upon examination of the patient, one can observe fresh, mature elements, tubercles in a state of breakdown, ulcers, and in some cases, scars. A marked tendency toward grouping is noted: in some patients, they are arranged densely, while in others they appear as incomplete rings, semi-arcs, or garlands that merge to form continuous foci of lesions. Several clinical variants of tubercular syphilis are distinguished: grouped, diffuse, serpiginous, and dwarf.
Gummatous syphilids are currently rare. They manifest as discrete nodes or diffuse gummatous infiltration, originating in the subcutaneous tissue or deeper tissue layers. At this stage, they present as well-demarcated, firm, painless formations devoid of inflammatory signs that easily glide beneath the skin. Gradually, the node enlarges to the size of a walnut, or occasionally a chicken egg, and becomes adherent to the surrounding tissues and the overlying skin, which progressively reddens. This is followed by softening of the gumma and discernible fluctuation. A small amount of viscous, dirty-yellow fluid discharges from a small fistula formed as a result of skin thinning and rupture. Over time, the fistulous opening enlarges, transforming into a deep ulcer with firm, ridge-like margins that slope down to the base, where the gummatous core (dirty-yellow necrotic tissue) resides. Following its sloughing, the base of the ulcer fills with granulation tissue, which is subsequently followed by scarring. Initially reddish-brown, the scar later acquires a brownish hue and gradually depigments; it is deep, retracted, stellate, and firm. The evolution of a gumma spans from several weeks to several months. Typically, a gumma causes no subjective sensations, except when located directly over bone, near joints, the angle of the mouth, the tongue, or external genitalia.
Gummatous ulcers may be complicated by secondary infection or erysipelas.
Standard serological tests for syphilitic gummata are positive in 60–70% of patients, while TPI and IFA are positive slightly more often.
A characteristic manifestation of this disease stage is tertiary syphilitic erythema, appearing as large reddish-bluish macules arranged in arciform patterns, predominantly on the lateral trunk. It causes no subjective sensations and persists for a long time (a year or more).
Mucosal lesions in the tertiary stage of the disease are relatively common. On the lips, particularly the upper lip, circumscribed nodes (gummata) or diffuse gummatous infiltrations are observed. Similar lesions are noted in the region of the tongue. In gummatous glossitis, two to three gummata the size of a small walnut develop within the substance of the tongue, which undergo ulceration if left untreated.
Tubercular and gummatous eruptions may occur on the soft and hard palate. They ulcerate, leading to tissue destruction, occasionally causing the sloughing of the uvula, and—following scarring—deformity of the soft palate. Small gummatous nodes or diffuse gummatous infiltration sometimes develop in the pharynx, resulting in pain and functional disorders. Tertiary syphilids of the larynx may provoke perichondritis, vocal cord lesions (hoarseness, huskiness, aphonia), and a cough productive of thick, dirty-yellow mucus. As the ulcers scar, incomplete closure of the vocal cords occurs, leaving the voice permanently hoarse. Persistent respiratory impairment may also develop.
Gummatous lesions of the nasal mucosa are most frequently located in the region of the nasal septum, at the border of the cartilaginous and bony parts, though they may also arise elsewhere. In some patients, the process begins directly within the nose, occasionally extending from adjacent areas (skin, cartilage, bone), and manifests as circumscribed nodes or diffuse gummatous infiltration. Subjective sensations are usually absent. Once ulceration occurs, the nasal discharge becomes purulent. A probe at the base of the ulcer frequently detects necrotic bone. When the process extends to the bone of the nasal septum, destruction may ensue, resulting in nasal deformity (saddle nose).
Dystrophy of the two permanent upper central incisors is observed (Hutchinson's teeth). The principal sign is Atrophy of the crown, causing the tooth to be wider at the neck than at the cutting edge. The teeth typically have a chisel or screwdriver shape with a semilunar notch on the incisal edge. Prior to the eruption of permanent teeth, these alterations can be detected on radiographs. Hutchinson's triad is rarely observed; more commonly, parenchymatous keratitis and Hutchinson's teeth, or one of these symptoms, are present. In addition to pathognomonic—that is, absolute—signs, the identification of even a single one allows for the unequivocal diagnosis of late congenital syphilis. There are also possible signs that warrant a suspicion of congenital syphilis, though confirmation requires supplementary data: concurrent clinical manifestations or the results of family screening.
In late congenital syphilis, standard serological tests are positive in 70–80% of patients and in nearly 100% of patients with parenchymatous keratitis. TPI and IFA are positive in 92–100% of cases. Following adequate treatment, standard serological tests (particularly TPI and IFA) remain positive for many years, which does not, however, indicate The Need for additional treatment.
VISCERAL SYPHILIS
This term denotes syphilis characterized by involvement of the internal organs. Syphilitic lesions can develop in any organ, but they most frequently arise in internal organs carrying the heaviest functional load (heart, brain, spinal cord, lungs, liver, stomach).
Early and late forms of visceral syphilis are distinguished.
Early visceral syphilis. The results of modern research indicate that cardiac involvement, particularly of the myocardium, is observed even in the early stages of syphilis. Myocardial changes are accompanied by toxic-infectious dystrophy. Functional cardiac disorders (palpitations, muffled heart sounds) are noted.
Alterations in various liver function tests are detected in 21–68% of patients with infectious syphilis. Prothrombin- and protein-forming Functions of the liver are most frequently enhanced, while pigmentary function is affected less often. Anicteric, latent forms of syphilitic hepatitis may occur, the clinical sign of which is an enlarged and firm liver accompanied, in nearly half of the cases, by Splenomegaly. Acute hepatitis accompanied by jaundice and marked liver dysfunction is very rarely observed.
Recently, gastric involvement in early visceral syphilis (syphilitic gastritis, specific gastric ulcer) has been registered more frequently. Syphilis may complicate the course of a concomitant gastric disease.
In clinical practice, Glomerulonephritis is observed in patients with early visceral syphilis. As a rule, it follows a benign course, unaccompanied by edema or elevated blood pressure. Impairment of the renal filtration capacity may manifest as albuminuria or Hematuria, which resolve rapidly under specific treatment.
Late visceral syphilis. Based on statistical data and clinical experience, it can be stated that within The Structure of visceral syphilis, 90–94% of cases represent cardiovascular syphilis, 4–6% hepatic syphilis, and 1–2% syphilis of other internal organs: lungs, kidneys, spleen, and stomach.
The symptomatology of visceral syphilis is extremely diverse, depending on the localization of the process, its specific features, intensity of development, duration, and other factors. Syphilitic involvement of a given organ frequently triggers a chain of pathogenetically related secondary disorders in other organs. Collectively, these conditions can produce a complex and variegated clinical picture in which symptoms of the secondary disorders come to the forefront, while the primary syphilitic process often remains obscured.
SYPHILIS OF The Nervous System (NEUROSYPHILIS)
This concept encompasses a wide range of diseases that differ pathogenetically, morphologically, and in their clinical course. The primary roles in the development of neurosyphilis are played by the absence or inadequacy of prior antisyphilitic treatment, trauma (especially craniocerebral), intoxication, chronic infections, and impaired immune status in patients. From a clinical perspective, it is practical to distinguish: syphilis of the central nervous system, syphilis of the Peripheral Nervous System, and functional nervous and mental manifestations in syphilis.
Syphilis of the central nervous system. This condition is closely linked to various syphilitic processes (localized or diffuse) within the brain or spinal cord. These may be either vascular or localized within the neural parenchyma. A combination of such processes is frequently observed, often without clear demarcation and with scattered symptoms.
Clinically, CNS syphilis may present with the picture of meningitis, meningoencephalitis, meningomyelitis, endarteritis, or gummatous processes that produce tumor-like symptoms in the cerebrum or Brainstem.
Nervous system syphilis is categorized into early, or early neurosyphilis (up to 5 years from the moment of infection, predominantly within the first 2–3 years), and late, or late neurosyphilis (no earlier than 6–8 years post-infection).
Tabes dorsalis (locomotor ataxia). For diagnosing the disease, the following clinical symptoms are of key importance: pupillary disorders (miosis, mydriasis, anisocoria, and particularly the pathognomonic Argyll Robertson pupil), loss of knee and ankle Reflexes, unsteadiness in Romberg's position, bone-air dissociation, trophic disturbances, cold hyperesthesia in the back, and pain hypesthesia in the chest region (in Hitzig's zone). Tabetic arthropathies and primary optic atrophy are now rarely noted, subjective signs (tabetic pain, crises, paresthesias) are frequently absent, and pelvic organ dysfunctions are either absent or mild; consequently, such patients rarely seek medical attention independently. As a rule, they are discovered incidentally during a neurological examination while hospitalized for another condition.
General paresis may develop 15–20 or even 40 years after infection, predominantly in individuals who received insufficient treatment or none at all for early forms of syphilis.
During the acute stage of the disease, personality disintegration, severe progressive dementia, Various Forms of daydreaming, hallucinations, and cachexia are observed, among other symptoms. In the fully developed phase of the process, four Clinical forms of progressive paralysis are distinguished: demented, expansive, agitated, and depressive.
Gumma of the brain or spinal cord is currently rare. It is typically localized on the convex surface or at the base of the cerebral hemispheres. The neurological picture is characterized by focal symptoms combined with headache and elevated intracranial pressure. Spinal cord gummas may lead to symptoms of complete transverse myelopathy. Cerebrospinal fluid analysis reveals cytoalbuminologic dissociation (elevated protein levels with a low lymphocyte count), as well as positive Wassermann, TPI, and IFA reactions (the latter are also positive in blood serum). Gumma must be differentiated from a brain tumor. The absence of a response to antisyphilitic therapy over 3 to 4 weeks, or the progression of neurological symptoms despite treatment, indicates a brain tumor. Mental status alterations in cerebral gumma depend on its size and localization.
Syphilis of the peripheral nervous system.
This refers to conditions affecting various peripheral nerves. This disorder, with its typical Clinical presentation, is essentially a secondary neuritis that develops as the inflammatory process spreads to the tissues surrounding the nerve. In A number of cases, syphilitic lesions of the peripheral nerves result from a compressive mechanical effect. For example, in syphilitic arteritis, neuritis occurs due to the nerve being compressed by gummas or specifically affected lymph nodes.
There are two forms of syphilitic involvement of the peripheral nerves: mononeuritis and multiple nerve and root involvement—polyneuritis and polyradiculoneuritis.
Functional nervous and mental manifestations in syphilis. In certain cases of nervous system involvement by syphilis, various symptom complexes occur that are purely functional in nature. These include neurasthenia and certain psychoses.
Neurasthenia. The psychological trauma of contracting syphilis almost always impacts the patients' mental state. Neurasthenic psychiatric disorders are diverse and exhibit individualized manifestations.
Syphilophobia. In its manifestations, it is partly similar to neurasthenia. It represents a specific type of fixed psychopathy and is found in individuals who do not actually have syphilis. This disorder is characterized by a wide array of complaints. Unlike neurasthenia, patients with syphilophobia experience a constant, persistent fear of having contracted syphilis, continually going from one doctor to another. Such patients present diagnostic and therapeutic challenges (similar to Other forms of phobias) and require psychiatric supervision. Occasionally, such cases may be of differential diagnostic interest regarding certain forms of neurosyphilis.
Other psychoses in acquired or congenital syphilis may manifest as manic-depressive states, catatonic phenomena, Korsakoff's syndrome, etc. Such states indicate their direct connection with the syphilitic infection.
In certain forms of organic syphilitic diseases, such as progressive paralysis, congenital syphilis, and others, distinct functional manifestations may occur whose organic Pathogenesis remains controversial. These include epileptiform phenomena, convulsions, neurological disorders, neuritis, and others.
TREATMENT
General Principles. Penicillins are the primary therapeutic agents for combating syphilis. These antibiotics readily penetrate lymph and lymph nodes, which serve as a reservoir for T. pallidum. Modern penicillin therapy is based on the premise that penicillin, starting at a concentration of 0.018 mcg/mL (0.03 IU/mL), exhibits high activity against Treponema pallidum. It is a generally accepted view that to achieve a reliable therapeutic effect, a penicillin concentration of at least 0.3 IU/mL must be maintained in all Body Fluids, including cerebrospinal fluid and amniotic fluid, to cover 10–15 development cycles of T. pallidum.
In the clinical practice of treating syphilis in Ukraine, the following biosynthetic penicillin preparations are used:
✵ benzylpenicillin sodium salt (Borshchahivka CPP, Kyivmedpreparat, penicillin G)
✵ benzylpenicillin procaine salt (Kyivmedpreparat, procaine penicillin G mega)
✵ benzathine benzylpenicillin preparations (Kyivmedpreparat, bicillin-1, extencillin, retarpen)
✵ combined penicillin preparations (bicillin-3: benzathine benzylpenicillin + benzylpenicillin + benzylpenicillin procaine salt; bicillin-5: benzathine benzylpenicillin + benzylpenicillin procaine salt).
In cases of hypersensitivity to the penicillin series, reserve antibiotics are used: Tetracyclines, macrolides, and Cephalosporins. Their therapeutic efficacy is significantly lower than that of penicillin, and therefore they are used only when treatment with penicillin-Class drugs is absolutely impossible.
Preventive treatment. A course of treatment is prescribed to individuals who have had sexual or close household contact with a patient suffering from an infectious form of syphilis, provided that no more than 3 months have passed since the contact. Individuals who have had contact with a syphilis patient for more than 3 months undergo a complete serological evaluation (VDRL, ELISA, FTA-ABS, TPI), and if the result is negative, treatment is not required.
Benzathine benzylpenicillin is prescribed (once daily at a dose of 2.4 million IU intramuscularly) or procaine penicillin G (1.5 million IU once daily for 7 days). Bicillin-1, -3, or -5 can be used at 1.2, 1.8, and 1.5 million IU respectively, 3 times a week, with an interval of 3–4 days. Preventive treatment is carried out on an outpatient basis. In an inpatient Setting, benzylpenicillin sodium salt may be prescribed at 500,000 to 1 million IU every 3 hours, or benzylpenicillin procaine salt at 600,000 IU twice daily for 7 days.
Preventive treatment for a recipient who has received a blood transfusion from a syphilis patient is administered similarly, but the course doses (duration of treatment) are increased twofold.
Acquired syphilis with a reliably established infection duration of up to 3 months (primary, early secondary, latent):
✵ benzylpenicillin sodium salt — 500,000 to 1 million IU every 3 hours for 14 days. In cases of a malignant course (giant chancres, alopecia, early visceral and neurological manifestations) or in the presence of comorbid pathology, the treatment duration is extended to 21–28 days;
✵ penicillin G (sodium salt) — intramuscularly at 1 million IU 3 times daily for 14 days;
✵ benzylpenicillin procaine salt — 1.2 million IU twice daily for 14 days;
✵ procaine penicillin G: 3 million IU for 14 days;
✵ benzathine benzylpenicillin: 2.4 million IU once weekly, two injections. For patients weighing over 90 kg, 3 injections are prescribed once every 5 days;
✵ bicillin-1, 3, 5: 1.2, 1.8, and 1.5 million IU respectively, twice a week for two weeks.
Acquired syphilis with a precisely determined infection period of 3 to 6 months (fresh secondary, relapsing, latent):
✵ benzylpenicillin sodium salt: 500,000 to 1 million IU every 3 hours for 16 days.
✵ penicillin G (sodium salt): intramuscularly, 1 million IU 3 times a day for 16 days;
✵ benzylpenicillin procaine salt: 1.2 million IU twice a day for 16 days;
✵ procaine penicillin G: 3 million IU once a day for 14 days;
✵ benzathine benzylpenicillin: 2.4 million IU, 3 injections once a week. For patients weighing over 90 kg, 4 injections are prescribed once every 5 days;
✵ bicillin-1, 3, 5: 1.2, 1.8, and 1.5 million IU respectively, once every 3 days, 7 injections.
Acquired syphilis with a precisely determined infection period of 6 months to 1 year (relapsing secondary, latent):
✵ benzylpenicillin sodium salt: 1 million IU. For patients weighing less than 50 kg, a dose of 500,000 IU may be prescribed every 3 hours for 21 days;
✵ day 1: procaine penicillin G, 3 million IU twice a day, or penicillin sodium salt intramuscularly, 2 million IU 3 times; from day 2: benzathine benzylpenicillin, 2.4 million IU, 4 injections once a week. For patients weighing over 90 kg, 5 injections of benzathine penicillin are prescribed once every 5 days;
✵ benzylpenicillin procaine salt: 1.2 million IU twice a day for 21 days;
✵ procaine penicillin G: 3 million IU once a day for 21 days;
✵ day 1: penicillin procaine salt, 1.2 million IU twice a day; from the second day: bicillin-1, 3, 5, 1.2, 1.8, and 1.5 million IU respectively, twice a week, 4 weeks;
✵ penicillin G (sodium salt): 2 million IU intramuscularly every 8 hours for 21 days.
Acquired syphilis with an infection duration exceeding 1 year (relapsing secondary, unspecified, or late latent), as well as early syphilis (under 1 year) with a malignant course and visceral or neurological impairments, and congenital syphilis in adults (treatment is carried out in a hospital setting):
✵ benzylpenicillin sodium salt: 1 million IU every 3 hours for 18 days – two courses with a 1-month interval. If necessary, a third course can be administered;
✵ penicillin G (sodium salt): intramuscularly, 2 million IU three times a day for 16 days – two courses with a 1-month interval;
✵ penicillin G (sodium salt): 2 to 4 million IU intravenously twice a day for 14 days – two courses with a 1-month interval:
✵ benzylpenicillin procaine salt: 1.2 million IU twice a day for 18 days – two courses with a 1-month interval;
✵ procaine penicillin G: 3 million IU once a day for 18 days – two courses with a 1-month interval.
Patients with latent syphilis and active syphilis with an infection duration of more than 1 year or an undetermined duration are referred for cerebrospinal fluid examination. In cases of early neurosyphilis, intravenous penicillin administration is preferred. Alongside specific treatment, non-specific Pathogenetic Therapy must be administered taking into account the recommendations of a general practitioner, neurologist, ophthalmologist, etc.
TREATMENT OF CHILDREN
All children under the age of 3 who have been in contact with a patient suffering from infectious syphilis must undergo treatment if no more than 3 months have passed since the last exposure. The decision to treat children over 3 years of age is made on a case-by-case basis. Syphilis treatment in children follows the same fundamental principles as in adults, while taking into account body weight and physiological characteristics. The treatment regimens for children with acquired or congenital syphilis depend on the stage of the disease, the child's age, and the Specifics of the case.
Prophylactic treatment
Infants (under 7 weeks of age):
✵ Benzylpenicillin sodium salt or penicillin G (sodium salt) — single dose of 50,000 IU/kg, intramuscularly, every 12 hours for 8 weeks.
Aged 7 to 30 weeks:
✵ Benzylpenicillin sodium salt or penicillin G (sodium salt) — single dose of 50,000 IU/kg, intramuscularly, every 8 hours for 8 weeks.
Preventive treatment
Aged 1 to 6 months:
✵ Benzylpenicillin sodium salt — single dose of 50,000 IU/kg, intramuscularly, every 6 hours (4 times daily) for 8 weeks;
✵ Penicillin G (sodium salt) — dose of 50,000 IU/kg, intramuscularly, every 8 hours (3 times daily) for 8 weeks.
✵ Benzathine benzylpenicillin — 100,000 IU/kg, intramuscularly, as a single dose (divided into two equal parts and injected into both buttocks).
Aged over 6 months:
✵ Benzylpenicillin sodium salt — single dose of 25,000 IU/kg, intramuscularly, every 4 hours for 8 weeks;
✵ Penicillin G (sodium salt) — dose of 50,000 IU/kg, intramuscularly, every 8 hours for 8 weeks.
✵ Benzathine benzylpenicillin — single dose of 60,000 IU/kg, intramuscularly, once (divided into two equal parts and injected into both buttocks);
✵ Bicillin-1, 3, 5 at 60,000 IU/kg, every 2 days, 4 injections (divided into two equal parts and injected into both buttocks);
✵ Benzylpenicillin procaine salt 60,000 IU/kg, intramuscularly twice daily for 8 days;
✵ Procaine penicillin G — dose of 100,000 IU/kg, intramuscularly, once daily for 8 weeks.
Specific treatment
Infants (under 7 weeks of age):
✵ Benzylpenicillin sodium salt or penicillin G (sodium salt) — single dose of 50,000 IU/kg, intramuscularly, every 12 hours for the 1st week, followed by 50,000 IU/kg every 8 hours for two weeks;
✵ Penicillin G (sodium salt) — single dose of 50,000 IU/kg, intravenously, every 12 hours for the 1st week, followed by every 8 hours for two weeks.
Aged 7 to 30 weeks:
✵ Benzylpenicillin sodium salt or penicillin G (sodium salt) — single dose of 50,000 IU/kg, intramuscularly, every 8 hours;
✵ Penicillin G (sodium salt) — single dose of 50,000 IU/kg, intravenously, every 12 hours.
Ages 1 to 6 months:
✵ benzylpenicillin sodium salt or penicillin G (sodium salt) - single dose 50,000 IU/kg, intramuscularly, every 6 hours;
✵ penicillin G (sodium salt) - single dose 50,000 IU/kg, intravenously, every 8 hours.
TREATMENT OF PREGNANT WOMEN
Penicillins are not only the drugs of choice, but also the sole adequate treatment for pregnant women with syphilis. The only alternatives are macrolides, The Use of which is justified solely by penicillin intolerance, provided specific hypersensitization is not feasible. Erythromycin penetrates the placenta poorly and should not be prescribed for treating pregnant women after 18 weeks. Clarithromycin and spiramycin exhibit high bioavailability and readily cross the placental barrier.
For women in the second half of pregnancy, effective and practical syphilis treatment regimens are required that meet the following criteria:
✵ Prevention of congenital syphilis with timely initiation of treatment;
✵ guarantee of treponemicidal (treponemostatic) concentrations in all maternal and fetal tissues for 2 to 4 weeks (depending on the form of the disease);
✵ Minimization of hospital stay, with the option of outpatient day-care treatment;
✵ good tolerability and absence of adverse effects on the fetus.
Core Methods. Treatment regimens for syphilis in pregnant women depend not only on the stage of the disease, but also on the gestational age. Preventive treatment for pregnant women in the first half of pregnancy (up to 19–20 weeks) is administered using one of the following methods:
✵ benzylpenicillin sodium salt - 500,000 IU every 3 hours for 15 days;
✵ benzathine benzylpenicillin - 2.4 million IU once weekly, two to three injections;
✵ bicillin-1, 3, 5 at 1.2, 1.8, and 1.5 million IU respectively, twice a week, course consisting of 7 injections;
✵ procaine penicillin G - 1.5 million IU once daily for 15 days;
✵ penicillin novocain salt - 600,000 IU twice daily for 15 days;
✵ penicillin G (sodium salt) - intramuscularly, 1 million IU 3 times daily for 15 days.
Preventive and specific treatment for women in the first half of pregnancy (up to 19–20 weeks) is carried out using methods similar to those applied in the treatment of non-pregnant adults.
Treatment for women in the second half of pregnancy is based on a combination of water-soluble penicillin G (sodium salt) administered intravenously and benzathine benzylpenicillin administered intramuscularly. To prevent the Jarisch-Herxheimer reaction, which may cause toxic damage to the fetus, a single dose of 30 mg of prednisolone is administered prior to the start of treatment. Treatment is performed in a hospital setting.
Specific treatment regimens for various forms of syphilis in women in the second half of pregnancy
Penicillin G (sodium salt) - 2 million IU, intravenously twice daily, every 12 hours (1st injection - 500,000 IU, 2nd - 1 million IU):
✵ preventive and prophylactic treatment - 8 days (16 injections);
✵ primary syphilis - 10 days (20 injections);
✵ fresh secondary syphilis and early latent syphilis with an infection duration of up to 6 months - 12 days (24 injections);
✵ recurrent secondary syphilis and early latent syphilis with an infection duration from 6 months to 1 year - 14 days (24 injections).
In all forms of syphilis, 12 hours after the last intravenous injection, a single dose of 2.4 million IU of benzathine benzylpenicillin is administered (1.2 million IU into each buttock). For latent syphilis of unspecified type, treatment consists of two 14-day courses: penicillin G at 2 million IU intravenously twice daily, combined with a single dose of 2.4 million IU of benzathine benzylpenicillin. The second course is administered 3–4 weeks after the first.
Alternative antibiotic regimens for the treatment of patients with syphilis:
✵ doxycycline (vibramycin, doxybene, dox) 0.3 g daily for 14–28 days;
✵ erythromycin 2.0–2.5 g daily for 14–28 days;
✵ azithromycin (sumamed) 1.0 g daily for 10–21 days;
✵ clarithromycin (fromilid, klacid) 0.5 g daily for 10–21 days;
✵ ceftriaxone (rocephin, oframax, ificef) 1.0 g daily for 8–14 days;
✵ cefotaxime (claforan) 2.0 g daily for 8–14 days;
✵ cefuroxime (zinacef, zinnat) 3.0 g daily for 8–14 days;
✵ cefixime 0.4 g daily for 8–14 days.
In the event of a severe Herxheimer reaction, penicillin therapy should not be discontinued; instead, prednisolone is administered at a dose of 0.5 mg per kg of the patient's body weight. If the reaction does not subside within 6 hours, the prednisolone injection is repeated.
Last update: 13/08/2026
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