Lecture 8

General course of the syphilis. Primary syphilis.

Definition
Syphilis, a chronic systemic infection caused by Treponema pallidum subspecies pallidum, is usually sexually transmitted and is characterized by episodes of active disease interrupted by periods of latency. After an incubation period averaging 2 to 6 weeks, a primary lesion appears, often associated with regional lymphadenopathy. A secondary bacteremic stage, associated with generalized mucocutaneous lesions and generalized lymphadenopathy, is followed by a latent period of subclinical infection lasting many years. In about one-third of untreated cases, the tertiary stage is characterized by progressive destructive mucocutaneous, musculoskeletal, or parenchymal lesions; aortitis; or symptomatic central nervous system (CNS) disease.

Etiology
The Spirochaetales include three genera that are pathogenic for humans and for a variety of other animals: Leptospira, which causes human leptospirosis; Borrelia, which causes relapsing fever and Lyme disease; and Treponema, which causes the diseases known as treponematoses. The genus Treponema includes T. pallidum subspecies pallidum, which causes venereal syphilis; T. pallidum subspecies pertenue, which causes yaws; T. pallidum subspecies endemicum, which causes endemic syphilis or bejel; and T. carateum, which causes pinta. Other Treponema species found in the human mouth, genital mucosa, and gastrointestinal tract have no proven pathogenic role in human disease. These spirochetes can be confused with T. pallidum on dark-field examination.

Etiology

An oral treponeme that is very closely related to T. pallidum antigenically has been found to be significantly associated with periodontitis and acute necrotizing ulcerative gingivitis; its etiologic role in these gum diseases is unknown. None of the four pathogenic treponemes has yet been cultured in quantity. Until recently, the subspecies were distinguished primarily by the clinical syndromes they produce. Recent studies have identified molecular signatures that can differentiate T. pallidum subspecies pallidum from the other pathogenic T. pallidum subspecies by culture-independent, polymerase chain reaction (PCR)-based methods.

Etiology
The T. Pallidum has three forms of existence: 1. Spiral (protoplasmic cylinder with fibrils, nuclides, cytoplasm with ribosomes, cytoplasmic membrane, lysosomes, outside-cell wall and capsule-like cover). 2. Encysted - curtaining treponemas in a mass and covering them with a mucin-like membrane, which hinders penetration of medical substances. Spirohaetas can exist in the form of cyst for a long time, do not affecting mans organism pathologically. There is a condition of a balance between macro- and micro-organism. Weakening of protective forces of the organism leads to the cyst reversion. 3. L-forms-partial or complete loss of the cell wall, reduction of metabolism, infringement of cell division at intensive synthesis of DNA.

Classification of syphilis
There is a standard classification for registration and record of patients with syphilis in our country. The following forms are distinguished after the incubation period. 1.Primary, seronegative syphilis syphilis I seronegativa. 2.Primary, seropositive syphilis syphilis I seropositiva. 3.Primary latent syphilis syphilis I latens. This diagnosis is made when the treatment is begun in the primary period of the disease in the absence of subsequent clinical manifestations of syphilis.

Classification of syphilis
4. Secondary fresh syphilis syphilis II recens. 5. Secondary recurrent syphilis syphilis II recidiva. 6. Secondary latent syphilis syphilis II latens. It is diagnosed in patients whose treatment was begun in the secondary fresh or recurrent period in the absence of clinical manifestations of syphilis at the given time.

Classification of syphilis
7. Tertiary active syphilis syphilis III activa. 8. Tertiary latent syphilis syphilis III latens. This diagnosis is made in patients who have no clinical manifestations of the disease but revealed active manifestations of the tertiary period in the past. 9. Latent syphilis syphilis latens: a)Early latent syphilis syphilis latens praecox; b)Late latent syphilis syphilis latens tarda. This diagnosis is made in cases with no clinical manifestations of the disease, but with positive serological tests.

Classification of syphilis
10. Early congenital syphilis syphilis congenita praecox: congenital syphilis of infants (under 1 year of age) and in very young children (from 1 to 4 years old). 11. Late congenital syphilis syphilis congenita tarda. 12. Late congenital syphilis syphilis congenita latens. 13. Visceral syphilis (indicating the involved organ). 14. Syphilis of the nervous system. 15. Tabes dorsalis. 16. General paresis paralysis progressiva.

General Course

T. pallidum rapidly penetrates intact mucous membranes or microscopic abrasions in skin and within a few hours enters the lymphatics and blood to produce systemic infection and metastatic foci long before the appearance of a primary lesion. Blood from a patient with incubating or early syphilis is infectious. The generation time of T. pallidum during early active disease in vivo is estimated to be 30 to 33 h, and the incubation period of syphilis is inversely proportional to the number of organisms inoculated. The concentration of treponemes generally reaches at least 107 per gram of tissue before the appearance of a clinical lesion.

General Course
The median incubation period in humans (about 21 days) suggests an average inoculum of 500 to 1000 infectious organisms for naturally acquired disease. The incubation period (from inoculation until the primary lesion becomes discernible) rarely exceeds 6 weeks. Subcurative therapy during the incubation period may delay the onset of the primary lesion, but it is not certain that such treatment reduces the probability that symptomatic disease will ultimately develop.

General Course
The time period of primary syphilis from the moment of appearance of primary syphiloma is 6 weeks, during which the serologic reaction is negative within the first 2-3 weeks, and seropositive later on. Taking into account the importance of correct treatment of the case in the possibility of transmission of seronegative period into seropositive, the patients with the seronegative primary syphilis are examined for serologic reactions every 5-7 days.

Ulcer By lesions Erosion Genital By an arrangement Extragenital Paragenital Common 10-20 mm Dwarf 2 -5 mm By size Giant 40 -50 mm Chancre-amygdalitis

Typical course (Non-pain) (Regional lymphoadenit) Atypical course

Hard chancre

Chancre panaritium

Primary lesion

Indurative swelling

Chancre cervical part of the uterus

Clinical features of primary syphilis

After the incubation period, the primary syphiloma (hard chancre) forms at the site of entry of T. pallidum into the skin or mucous membranes. The hard chancre is usually localized on the skin and mucous membranes of the genitals (glans penis, preputial sac, the anus in homosexuals, labia majora and minora, posterior commissure, cervix uteri), less frequently on the thighs, pubis or abdomen.

Clinical features of primary syphilis

The extragenital chancre, which is a less frequent occurrence, forms on the lips, tongue, tonsils, eyelids, fingers and on any other area of the skin or mucous membranes which the treponemas have penetrated. This concerns extragenital localization of the primary syphiloma. In such cases as well as in localization on the neck of the uterus (found in 11 to 12 per cent of cases, according to the different authors) the primary syphiloma remains unnoticed, which some authors claim to occur in 95 per cent of female patients.

Erosion chancre
The clinical picture of hard chancre as a rule is very characteristic. It is usually manifested by single, strictly rounded or oval, saucer-like erosion with discrete boundaries, and the size of the little fingernail. The erosion has the colour of raw meat or spoiled fat, its edges are slightly elevated and sloping towards the floor (saucershaped). It produces serous sparse secretions, which lend the chancre a shiny ('polished') appearance. The most characteristic sign of the hard chancre is an infiltrate of dense-elastic consistency palpated in the base of the erosion (hence the name 'hard' chancre, primary 'sclerosis'). The edges of an ulcerous hard chancre are elevated even more, while the infiltrate is more pronounced.

Ulcer chancre

On healing an ulcerous hard chancre leaves a scar while an erosive chancre heals without a trace. The course of the primary syphiloma is characterized by mild tenderness or total absence of subjective disturbances. T. pallidum is easily detected in secretions of the primary syphiloma in dark-field illumination.

Hard chancre
The clinical picture of hard chancre has considerably changed over the years. One of the substantial features of primary syphiloma was that it was always single (in 80-90 per cent of cases), whereas in the last decade, in contrast, the number of patients with two or more chancres has markedly increased. A considerable increase in the specific share of ulcerous chancres and their complication by pyogenic infection is also observed. The number of patients with chancre of the anogenital region has grown. A definite number of chancres of oral and anal localization is associated with sex perversions. The specific share of chancres in the mouth, for instance, is considerably higher among females. The anus is the most frequent localization of an extragenital chancre in males. The absence, in some cases, of an obvious induration in the base of a primary syphiloma (in 5 per cent of patients) is among the peculiarities of the course of primary syphilis today.

Regional lymphadenopathy

R L usually accompanies the primary syphilitic lesion, appearing within 1 week of the onset of the lesion. The nodes are firm, nonsuppurative, and painless. Inguinal lymphadenopathy is bilateral and may occur with anal as well as with external genital chancres. Rectal chancres result in perirectal lymphadenopathy, while chancres of the cervix and vagina result in iliac or perirectal adenopathy. The chancre generally heals within 4 to 6 weeks (range, 2 to 12 weeks), but lymphadenopathy may persist for months.

Atypical Chancres
The atypical chancres are not divided by an arrangement. In case of atypical chancres we can supervise absence or presence of one of clinical signs. There are several variants of atypical chancre: chancre-amygdalitis, chancre-panaritium; indurative swelling; chancre cervical part of the uterus.

Chancre amygdalitis
Chancre amygdalitis is characterized by enlargement and hardening of one tonsil with no erosion or ulcer on it (if an erosion or ulcer of the primary period of syphilis is found on the tonsil, it is called primary syphiloma localized on the tonsil). There is no evidence of marked inflammation around the tonsil, temperature reaction or painful swallowing, while the tonsil is sharply demarcated. Its resilience is felt on palpation with a spatula. A large number of treponemas are easily found on the surface of the tonsil in such cases after it has been lightly stroked with a platinum loop. The presence of regional scleradenitis on the neck at the mandibular angle, typical of the primary period of syphilis (lymph nodes ranging in size from a large bean to a hazelnut, mobile, of dense, elastic consistency, not fused with the surrounding tissues, painless), and positive serological blood tests help in making the diagnosis.

Chancre panaritium
The hard chancre may be found on the fingers in the usual clinical form, or in an atypical form (chancre panaritium). This localization is mostly characteristic of medical personnel (laboratory workers, gynecologists, stomatologists, etc.). In clinical picture chancre-panaritium resembles the common panaritium of streptococcal etiology (club-shaped swelling and sharp tenderness of the distal phalange), but the presence of a hard infiltrate, the absence of an acute inflammatory erythema and, which is most important, the presence of characteristic regional (cubital lymph nodes) scleradenitis make its recognition easier. Despite the differential signs, the diagnosis of chancre-panaritium may be very difficult. If it is suspected, the results of the Wassermann test should be borne in mind in making the diagnosis. The recognition of such cases is sometimes delayed until eruptions of the secondary period of syphilis appear.

Indurative swelling

I S as a manifestation of the primary period of syphilis is found in the region of labia majora, scrotum or prepuce, i.e. in places richly supplied with lymph vessels. These areas become swollen. Induration of the tissues with no pitting while compressing is distinctive. Characteristic regional scleradenitis, medical history, results of examination of the sex partner, and the positive results of serological blood test for syphilis (in the second half of the primary period) also help in the diagnosis of atypical hard chancre manifested as indurative swelling.

Chancre cervical part of the uterus

It cannot be revealed in very weak patients and in localization of the chancre on the posterior vault of the vagina, cervical part of the uterus, rectum behind the sphincter. In this situation the deep mesenteric lymphatic nodes cannot be palpated.

Complications
In some patients primary syphiloma is complicated by secondary bacterial infection. This condition is called complicated hard chancre: Balanitis; Balanoposthitis; Phimosis; Paraphimosis The development of gangrene; Phagedena

Balanitis
Balanitis is the commonest complication. It develops as a result of attendant coccal or trichomonadal infection. In such cases swelling, bright erythema, and maceration of the epithelium develop around the chancre. The secretion on the surface of the chancre becomes seropurulent, which makes detection of T. pallidum and, consequently, the diagnosis much more difficult. Lotions with isotonic sodium chloride solution are applied for one or two days to relieve the inflammation, which in most cases makes it possible to establish the correct diagnosis in repeated tests.

Balanoposthitis

Balanoposthitis The swelling of the prepuce in phimosis looks as an enlarged penis, which is red and painful. The hard chancre localized in such cases in the corona glandis or on the inner surface of the prepuce cannot be examined for T. pallidum. The diagnosis of syphilis is made easier by the characteristic regional lymph nodes whose aspirate is examined for the causative agent.

Phimosis

Balanoposthitis may lead to constriction of the prepuce so that the foreskin cannot be retracted. This condition is called phimosis. The swelling of the prepuce in phimosis looks as an enlarged penis, which is red and painful.

Paraphimosis

An attempt to retract the prepuce in phimosis with force may lead to another complication called paraphimosis, in which the edematous and infiltrated preputial ring strangulates the glans. As a result of mechanical disorders of blood and lymph circulation, the swelling increases. Necrosis of the tissues of the glans penis and prepuce may occur if appropriate measures are not applied in time. In the initial stages of paraphimosis the physician removes the serous fluid from the swollen prepuce (by puncturing the thin skin with a sterile needle repeatedly) and attempts to 'reduce' the glans. If the manipulation proves ineffective, the prepuce must be cut.

The development of gangrene and phagedena

The development of gangrene and phagedena are more severe but less frequent complications of hard chancre. They occur in weakened patients and alcoholics as a result of attendant fusospirillary infection. A dirty-black or black scab (gangrene) forms on the surface of the chancre and may spread beyond it (phagedena). The scab covers an extensive ulcer and the process may be attended with elevated body temperature, chill, headache and other general symptoms. A coarse scar remains after the gangrenous ulcer heals. Treatment consists in immediate prescription of penicillin.

The development of gangrene and phagedena

Gangrene

Fagedena

Immunity
Congenital immunity to syphilis is absent. A person cured of syphilis does not acquire immunity either and repeated infection (reinfection) is possible. Non-sterile infectious immunity develops in the patients body in 10-14 days after a hard chancre appears. At the same time there is a number of scientific works (T. V. Vasiljev, Sazonova, I. I. Domushin, N. N. Saveljeva, etc.), that prove that 20% of healthy people can be unreceptive to syphilis because of thermolabile, thermostatic and treponemacide substances in the serum of blood. It was considered that the number of these substances increased after sexual contact with patients with active form of syphilis, 20-hour incubation of t. Pallidum in such a serum leads to its immobility and even to a complete lysis.

Immunity
These data require further study nevertheless immunity to syphilis exists as long as the causative agent remains in the body and disappears as soon as the patient recovers. Non-sterile immunity is followed by allergic reaction. With disappearance of infectious immunity the infectious allergy vanishes. So reactivity of the organism varies in 2 directions: increased (allergy) and decreased (immunity). The major factor of immunity is phagocytosis. The process of absorption of treponema by mononuclear phagocytes is divided into 4 stages: 1. rapprochement of phagocyte and treponema; 2. adhesion (attraction); 3. immersing of treponema into protoplasm; 4. digesting.

Immunity
Realisation of immunity involves macrophages, T- and Blymphocytes. As the reaction to the presence of treponema antibodies (immunoglobulins) are formed: JgM (reagines), JgG (immobilizines), JgA (fluorescins). In the beginning of the disease larger antibodies are found (JgM and JgA); at the later forms of congenital and acquired syphilis one can find practically only JgG.

Superinfection
SUPERINFECTION is the condition of an organism of a syphilitic patient, when it receives additional infection (a dose of new t. Pallidum strain), additional infection of an uncured patient. The manifestations of superinfection differ with different periods of the disease. Thus, in the incubation period and in the first 10-14 days of the primary period of syphilis, when there is still no pronounced infectious immunity, repeated infection leads to the successive development of a new chancre. It is smaller and usually develops after a shorter (up to 10-15 days) incubation period. Such changes are called successive.

Superinfection
It is believed that in superinfection the body reacts to the entry of new treponemas by eruptions of that stage, that period, which the patient is undergoing at the time (e.g. If superinfection occurs in the period of secondary latent syphilis, papules, rose-coloured spots appear). In the tertiary period of syphilis, general paresis and tabes dorsalis, when the patients organism is weakened and immunological activity is not high, superinfectioion may look as a new infection when the hard chancre is formed and symptoms of secondary syphilis appear.

Reinfection
Reinfection-recurrent infection after a patient has been cured from syphilis (not less than a year should pass after treatment for the first infection has been completed). It is necessary to disclose the new source of infection with active form of syphilis.

Differential Diagnosis of erosion

Signs Number of lesions Size of the erosion Form of erosion Infiltrate of the base Character of base Subjective feeling Presence of T. pallidum in tissue fluid Serologic reaction Primary syphilis single (often) Various Rounded Dense and elastic Clean Absent + Genital herpes multiple From crushed seeds to the size of lentils Rounded Dough Clean Less irritation Erosive Scabious balanoposthitis ecthyma multiple multiple Various Uneven Absent With pus Irritation, pain From size of lentils to peas. Rounded Dough With pus Itch

Differential Diagnosis of ulcer

Primary syphilis Age of the patient Mostly young Form of the ulcer Rounded Borders of the Even, gently ulcer sloping Base of ulcer Clean, red Signs Chancriform pyoderma Various Rounded Even, gently sloping With a little secretion Moderate elastic Soft-elastic, not attached, painless Skin cancer Mostly old Uneven Big Soft chancre Mostly young Uneven Toothed

Infiltrate in the base Character of regional lymph nodes

Dense elastic Dense elastic, not attached, painless

With necrotic With secretion intensive purulent secretion Dense spilled Soft Dense, sometime attached to the skin and each other, painless Soft, attached to the skin, may open, painless Streptobacillus Dukreya Unna

Bacterioscopy Serologic reaction

T. pallidum

Staphylococci, streptococci