Syphilis – Theory and times. The works by Hippocrates, discovered by German scientists Practice in Latvia Sushruta, Avicenna and other scien- Fritz Richard Schandinn and Erich tists and physicians of the ancient Hoffmann in 1905. This is a coiled

A. Rubins, MD, S. Rubins, I. world bear evidence of this when micro-organism. Its length equals 6– Jakobsone, L. Chigarevska they describe a disease similar to 14 µ and its cross-section 0.25– Department of Dermato-Venereo- syphilis and its treatment, using 0.30 µ, whereas the number of coils logy at the Medical Academy of mercury. Damage to human bones in varies from 8 to 12. The treponeme Latvia, Kr. Valdemara Street 76-75, a manner characteristic of syphilis is characteristic of four kinds of LV-1013 Riga, Latvia. Fax: 00371-736 has been detected in archaeological movement: rotation, contraction, os- 1615. [email protected] excavations in the Transbaikal re- cillation, undulation. Treponema gion, Japan, Italy, Egypt and other pallidum does not take up aniline areas. stains and has thus been given the Syphilis, a chronic somatic sexually name of pale treponeme. Under the transmitted disease causing non- electron microscope one can discern specific inflammation in the primary The place of origin of the pathogenic the surface of the pale treponeme as and secondary stages and specific agent of syphilis, as well as that of enveloped in a mucoid covering, lesions in the tertiary stage, is an man (according to a number of sci- under which lies the outer coat of ancient disease. There are three entists), is most likely to be Africa, the microbe, consisting of three lay- contradictory theories explaining its where one can still find such dis- ers. Beneath this outer coat one finds origin: the American theory, the eases as framboesia (yaws), bejel and a cytoplasmic membrane possessing Eurasian theory and the African pinta. Their causative agents, which both superficial and deep fibrils that theory. Adherents of the American are almost identical to those of ensure motility of the micro-organ- theory believe that South American syphilis, are difficult to discern by ism. Treponemes multiply by divid- Indians suffered from syphilis and diagnostic methods in the labora- ing crosswise (the cycle lasts for 30 that Columbus’ sailors were infected tory. Trade, migration of the popu- hours). In a special culture medium by them on the island of Haiti. After lation, the crusades, slave traffic of + 25°C the pale treponeme retains returning to Spain in 1493, one part from Africa and several other factors is motility for 3–6 days. In blood or of Columbus’ crew serving as mer- have contributed to the spread of the serum at a temperature of + 4°C the cenaries in the army of King Charles disease throughout the world. microbe may survive for 24 hours. VIII of France took part in the siege This should be taken into account of Naples. It was in Naples that the The word “syphilis” was first used in cases of direct blood infusion. first known syphilis epidemic in in 1530 by the Italian physician and Treponemes easily perish in a dry Europe broke out. Soldiers and poet G. Fracastoro in the poem writ- medium, in ultraviolet rays and at merchants were to blame for the ten in Latin “Syphilis or the French temperature above 42°C. Instantane- spread of syphilis to the whole of Disease”, describing how the gods ous destruction of treponemes oc- Western and Eastern Europe while it punish the herdsman Syphilis by curs at contact with arsenic, mercury was through Portuguese seafarers inflicting this disease. Another name and bismuth preparations. In a moist under Vasco de Gama that the dis- for the disease is lues (Latin lues, medium treponemes may preserve ease reached India and from there plague, pestilence). their vital capacity for 15 hours, in the Far East. frozen tissue for up to several weeks.

Aetiology and pathogenesis The treponeme gains entrance into Supporters of the Eurasian theory the organism through damaged skin hold that syphilis on this continent Syphilis is caused by the pale or mucous membrane. There is an has been known since prehistoric treponeme (Treponema pallidum) incubation period averaging from 3

Forum for Nord Derm Ven Vol. 7 November 2002 12 to 4 weeks after treponemes infec- barrier and via ductus thoraticus Table I. Morbidity from syphilis in tion. At this time the treponeme be- reach the blood system. Short-term Latvia (1991-2001) gin to multiply and act as an antigen. treponemal sepsis occurs, followed Intensive Cases of con- They circulate in the blood in small by generalisation of the infection in index (per genital syphilis Year 100000 (absolute amounts for a short time. At the site the organism. In this phase so-called population) proportion) of treponeme entrance the hard prodromal symptoms may be obser- 25001 254. chancre (ulcus durum, syphiloma ved in some patients: rise in temp- 21000 482. primarium, and sclerosis primaria) erature, nausea, pain in bones, 12999 663. 16998 1505. 1 develops and the first stage of syphi- muscles, joints. 14997 1221. 2 lis begins. Some 7–10 days after the 19996 1524. 2 appearance of the hard chancre an 19995 951. 1 At the site of treponeme entry, due attending bubo forms, usually as an 18994 529. to their hematogenic dissemination, 18993 301. inguinal lymph node. Antibody syn- eruptions appear in skin and mucous 13992 110. thesis is not yet intensive (negative membranes. This occurs 7–10 days 11991 81. Wassermann reaction) and this pri- following prodromal symptoms. The mary period of syphilis is called disease progresses to the secondary syphilis primaria seronegativa. or generalised stage of syphilis, sec- Treponemes gradually tend to dam- the latent period followed again by ondary fresh syphilis (syphilis age the whole lymphatic system and a relapse and this change goes on secundaria recens). The first erup- polyscleradenitis develops. It is not for several years. tions to appear in secondary syphi- until 3–4 weeks after the appearance lis are roseolae, papules, flat condy- of the chancre or 6–7 weeks after in- lomata; alopecia develops. Along Syphilis II recens differs from syphi- fection that the antibody titre in with an increase in the antigen lis II recidiva through the following blood increases and Wassermann (treponeme) count antibody titres in- symptoms: Patients suffering from reaction can be ascertained. This crease as well, reaching their highest fresh syphilis still have a primary period is called syphilis primaria limit at this period (1:160; 1:320; syphiloma. Of all polyscleradermic seropositive. (This division into 1:640; 1:2560). Antibodies bind and lymph nodes the attending bubo is seronegative and seropositive suppress treponeme increase, erup- the largest. These patients have primary syphilis was used in the tion fades and syphilis secundaria more eruptions and they are smaller days when Wassermann reaction was latens begins. At this phase of latent than is the case in secondary relapse performed. Recently more sensitive syphilis, positive serological reac- syphilis. The later the relapse the reaction tests have been developed tions constitute the only evidence of fewer eruptions to occur, grouped and introduced, e.g. treponemal syphilitic infection in the organism. only in definite areas (the skin of the enzyme immunoassay (EIA) and Antibody titres have decreased to a genitals, mucous membranes and fluorescent treponemal antibody medium level (1:80). Because of this the circum anum region are the sites absorption test (FTA-abs test), which decrease treponemes begin to most commonly affected; soles and show positive findings 1–3 weeks multiply most intensively at the sites palms may be involved). In following infection. Thus, it is not where they are still preserved. secondary fresh syphilis, eruptions currently advised to use Wasser- Eruption starts once again, being are symmetrically and regularly mann reaction and the above-men- linked with treponeme reactivation disseminated in the body skin and tioned division into periods is no as hematogenic dissemination no in flexures of extremities; during a longer of interest.) In the further longer takes place. This period of relapse phase they are more fre- course of the disease treponemes secondary syphilis is called syphilis quently observed in extensor areas. penetrate the lymphatic system secundaria recidiva. It is replaced by Alopecia and leucodermma are more

Forum for Nord Derm Ven Vol. 7 November 2002 13 Table II. Distribution of syphilis according to diagnoses in Latvia (1996-2001). Epidemiology Lues Lues Lues Lues II Lues II Neuro- Ynear PIroportio Lues latens latens latens recens recidiva lues The disease is acquired from the praecox tarda ignorata 14996 3912 782 447 1013 771-5 source of infection, a person suffer- 18997 3100 642 356 1313 81116 ing from syphilis. Syphilis is classi- 17998 2659 421 258 988 917 1-- fied as acquired and congenital. The 11999 1354 198 150 451 860 131 method of infection may differ in 21001 1902 8243129 656 22- any of the cases. Infection may be 24001 539 652396397 167 transmitted through the patient’s a) eruption with an erosive and ul- cerous surface; often present in relapse syphilis pa- b) secretion (saliva, sperm, mother’s tients. rysm with rapid lethal outcome), in the liver, lungs, stomach and other milk); organs, also in bones and joints. c) blood, lymph. Tertiary syphilis starts as late as in 3–4 years after infection. At that Ways of infection time inflammation at the site of Early neurosyphilis may manifest it- treponeme localisation gets more self as a vascular lesion. Later, gum- Infection through skin and mucous specific; infection granuloma mas may develop. membranes (acquired syphilis). Ac- develops. Tertiary syphilis has cording to the prevailing opinion in- characteristic eruptions: tubercles in Late degenerative damage of grave fection is not likely to be acquired the dermis or gummas in the consequences to the nervous system through intact skin and mucous hypodermis. In tertiary syphilis are tabes dorsalis and progressive membranes. The pale treponeme there are few treponemes (no evi- paralysis, conditions to be handled gains entrance into the human dence in bacteriological tests). The by neurologists and psychiatrists. organism only if at least a reaction of the organism, however, Under unfavourable conditions (lack microscopic lesion of skin and the is dramatic. Tissue destruction of effect from antibiotics, lack of mucosa is present. Infection is by occurs and ulcers form and leave substances needed for metabolism), direct or indirect contact with the scars. Active tertiary syphilis lasts treponema pallidum may form cysts affected person. Direct infection from six months to 1–2 years. Then and L-shapes that persist in the tis- with syphilis occurs through direct the latent tertiary period sets in, dur- sues of macro-organisms. With the bodily contact, most frequently ing which remainders of the active disappearance of noxious factors re- during sexual intercourse. Infection tertiary period are observable as vival of these protective forms is can also take place without any scars and atrophy. For patients of possible. sexual contact, e.g. through kissing tertiary syphilis, serological reac- and the like. Direct bodily contact is tions may be of low titres or even the way in which infection occurs in Treponema pallidum is partly an negative. Untreated syphilis may most cases. Indirectly, in the non- anaerobic bacterium with an intri- cause damage to internal organs and sexual way, the disease may also be cate protein, polysaccharide and the nervous system. The most com- communicated through contact with lipoid antigen structure that does mon localisation of visceral syphilis articles used by a syphilitic: dishes, not grow in artificial cultures. This is in the cardiovascular system instruments etc. This is the so-called makes investigation very difficult. (particularly in the ascending aorta- “syphilis through everyday contact.” specific mesoarthritis, aneurysm of Although possible in unsanitary con- the aorta and rupture of the aneu- ditions, this kind of infection is

Forum for Nord Derm Ven Vol. 7 November 2002 14 Ulcus durum preputii Papulae erosivae ad linguam

Corona veneris Condyloma lata

Duo ulcera dura Roseolae Alopecia syphilitica rarely observed at present. Syphilis and preserving it for at least five Permanent immunity is not con- through everyday contact was days. ferred by having had syphilis and widespread in Bosnia-Herzegovina repeated infection and disease (re- after World War II and in other areas. infection) is possible. In the ill Infection of the foetus by the mother person’s organism non-sterile (congenital syphilis) immunity to the infection develops. Infection due to blood transfusion In this case infection takes place dur- It starts on the 10–14th day after (acquired syphilis). Infection by ing pregnancy as the pale treponeme appearance of the hard chancre. means of blood transfusion is chiefly from the syphilitic expectant woman While the treponeme is still in the possible in case of direct blood gets into the foetus via the placenta. patient’s organisms he or she is prac- transfusion, resulting in transfusion About 40% of infected offspring die tically immune and reinfection does syphilis. This kind of infection is rare during pregnancy (late spontaneous not occur. Immunity persists as long because: abortion, stillborn child) or in the as the pale treponeme continues to neonatal period from birth to the exist, but disappears after a com- 1) direct blood transfusion is cur- 28th day of life. plete cure from syphilis. In cases rently seldom done; where the syphilitic patient gets ad- 2) the donor’s blood is tested for Immunity ditionally infected this provokes the syphilis; appearance of syphilis. Thus on con- Natural (inborn) immunity to syphi- 3) the pale treponeme perishes tact with a syphilis case in a conta- through conservation of the blood lis has not been observed in humans.

Forum for Nord Derm Ven Vol. 7 November 2002 15 Table III. Scheme of the course of acquired syphilis

Ddiagnosis Dsuration of the perio Symptom Diagnostic methods

Isncubation period 3-– 4 week IFR/IF A

A. bacterioscopic 1. Primary syphiloma (erosion, ulcer, fissure) B. SED (VDRL)/RPR Psrimary syphilis 6– 7 week 2. Regional lymphadenitis C. TPHA 3. Polyscleradenitis D. IFR/IFA

1,2,3 A, B, C, D secondary syphilids: E. TPI (Treponema pallidum 4. Roseola immobilisation) Ssecondary fresh syphilis 1.5– 2 month 5. Papules F. Examination of cerebrospinal 6. flat condylomata liquor 7. diffuse hair loss 8. pustule ±

Early latent ssyphilis 1-.5– 2 month A, B, C, D, E, F, G

Secondary relapse 4, 5, 6, 7, 8 1.5– 2 months A, B, C, D, E, F, G syphilis 9. leukoderma

Lsate latent syphilis 6-months– 2 year B, C, D, E, F, G

Secondary syphilids (tendency to group): Secondary relapse 4, 5, 6, 7, 8, 9 syphilis (repeated x 1.5– 2 months A, B, C, D, E, F, G times)

Lsate latent syphilis X-year D, E, G, G

1. Tubercles B, C, D, E, F Tsertiary syphilis X year 2. Gumma G. Histologic examination

gious form a person suffering from similar to treponeme antibodies that simultaneously. At various stages of secondary latent syphilis gets still results in positive findings in syphilis some of the globulin frac- more treponemes and the eruption complement (KSR, Wassermann re- tions prevail in the patient’s plasma. of secondary syphilis appears. Pen- action) and flocculation tests in At the onset of syphilis large etrating into human organisms which lipid suspensions obtained molecular IgA and IgM antibodies treponemes give rise to response re- from normal tissues of mammals, (immunofluorescines) are the first to action from the organism’s immune e.g. cor bovinum muscle (cardiolipin appear, while antibodies to protein system: formation of various anti- antigen) are used as an antigen. antigens develop later (reagins, bodies to treponeme antigens. The precipitins). The last to form are following antibodies exist: immuno- immobilisins, chiefly IgG class anti- In the affected person’s organism fluorescines, immobilisins, reagins. bodies. specific antibodies to Treponema A number of laboratory diagnostic pallidum antigens start developing tests are based on their presence in as immunoglobulins according to Incubation period the patient’s serum. In the organism their structure. IgG, IgM and to some the pale treponeme provokes the for- In young healthy individuals the in- extent IgA are of diagnostic value in mation of a substance (reagin) cubation period usually falls be- syphilis. The antibodies do not form tween 21–24 days. In cases of

Forum for Nord Derm Ven Vol. 7 November 2002 16 Table IV. Advised therapy for acquired syphilis this phase Wassermann reaction is negative and this is called the seron- IIIIIVI I egative period. The following 3–4 1. Benzathini benzylpenicillinum weeks comprise the seropositive pe- For (Retarpen). 2.4 mill. 2 3 continuation of riod. Clinically this period differs units i/m at 2 5 injections - injections injections therapy 3 injection sites once injections from the previous one only by a posi- weekly tive Wassermann reaction. In Latvia, this reaction is no longer applied, 2. Procainpenicillinum (Benzylpenicillinum-- due to its non-specific character, and novocainum). 600 000 1s2 days 1s8 day 2-1 day units i/m once daily the division into two periods is not of current interest. Advisable for neurosy-philis 10– 14 days, 10– 14 days, patients, 12– 24 3. Benzylpenicillinum therapy is therapy is 10– 14 10– 14 million units i/v Secondary fresh syphilis (syphilis 1 millon units i/m continued with continued with days days daily, as 2– 4 once a day preparation No preparation No secundaria recens) sets in following million units 1– 3 injections 1– 3 injections every 4 hours for treponeme dissemination. Second- 14– 21 days ary syphilids appear and the primary 4. Benzylpenicillinum For Advisable for syphiloma gradually regresses. At 400 000 units i/m 1s4 days 2s8 day 28 day continuation pregnant women every 3 hours therapy 28 days this period the number of treponem-

For In case of es is the highest, the highest 5. Doxycyclinum 0.1 1s5 days 3s0 day 30 day continuation of intolerance to twice daily antibody titre is present, as well as therapy 30 days penicillin the largest amount of eruption. This 30 days for In case 6. Eryhtromycinum 1s5 days 1s5 day 30 day continuation of intolerance to is a most contagious period lasting 0.5 4 times daily therapy penicillin for 1,5–2 months. The duration of therapy and methods used in various stages of syphilis are different. For treatment we advise the following division into groups: Early latent syphilis [syphilis Group I. Syphilis primaria seronegativa, syphilis primaria seropositiva; (secundaria) latens praecox] Group II. Syphilis secundaria recens, syphilis secundaria recidiva, syphilis latens praecox (duration of the disease up to 2 years); With the disappearance of secondary Group III. Syphilis secundaria recidiva, syphilis latens tarda (duration of the syphilids the latent period of syphi- disease more than 2 years); lis sets in and syphilis can be diag- Group IV. Neurosyphilis, syphilis cardiovascularia, syphilis tertiaria. nosed only serologically. Following secondary fresh syphilis the stage of early latent syphilis lasts for 1,5–2 months. However, after each follow- massive infection the incubation Periods of acquired syphilis and their ing relapse, the latent periods last period may be as short as 14 days. characterisation increasingly longer and may persist For patients with immunodepression Primary syphilis (syphilis primaria), for years. The period is considered (alcoholics, drug addicts, persons which starts after the incubation pe- to be early latent syphilis if it sets in having a chronic infection etc.) and riod with the formation of a primary two years after infection. for those who have used syphiloma, persists for 6–7 weeks. antibacterial preparations for other During the first week regional lym- Secondary relapse syphilis (syphilis diseases at this time the incubation phadenitis develops, with polyscela- secundaria recidiva) period may persist for several denitis occurring at the end of the months. Secondary syphilids occur at the period. In the first three weeks of sites of treponeme reactivation, a

Forum for Nord Derm Ven Vol. 7 November 2002 17 stage lasting for 1.5–2.5 months. In- appears as a fissure with even mar- giving evidence of treponemal terchanging with latent syphilis gins and a smooth, flat, dish-like sur- dissemination. The roseola is usually periods of varying extension, face (diameter 0.5–1 cm). At its base localised on lateral surfaces of the secondary relapse syphilis may recur a densely elastic plate-like infiltrate body as a pale pink patch the size several times. It is often said that the forms. As a rule the genitals are af- of a nail without sharply demarcated “older” the syphilis, the “poorer” it fected although it may occur borders. It does not desquamate. is, meaning there are less eruptions. extragenically as well. The most com- In cases of late relapse syphilis there mon form of non-typical primary Differential diagnosis may be very few secondary syphilids syphiloma is indurative edema • Toxicodermia. that are difficult to discern for both (oedema indurativum) that may com- • Pityriasis rosea Gibert. patient and physician. bine with a typical primary syphi- • Cutis marmorata. loma. Amigdalitic chancre occurs by • Roseola typhosa. way of orogenital infection and Late latent syphilis [syphilis • Maculae caeruleae. simulates common tonsillitis in (secundaria) latens tarda] being only unilateral and with This is of at least a two-year dura- erosion or ulcer on the tonsil. Depigmented patches (leucoderma) tion. Contrary to early latent syphi- Chancre panaritium is rare and may of various size and localised on the lis serological reactions are of low be chiefly due to professional posterior and lateral surfaces of the titres. Sexual partners of recent infection acquired by the physician. neck are a characteristic symptom years are not likely to contract the This primary syphiloma bears of relapse syphilis rarely seen as disease and a non-specific pathology resemblance to common panaritium. early as the sixth month after of internal organs and the nervous infection. In most cases leucoderma system is possible. gives proof of early neurosyphilis Regional lymphadenitis (scleradenit- (most commonly of asymptomatic is regionaris) develops in a week’s meningitis). Tertiary syphilis (syphilis tertiaria) time following primary syphiloma.

In tertiary syphilis (syphilis tertiaria) Lymph nodes are densely elastic and Differential diagnosis there are few treponemes in the or- non-confluent. In the overlying skin Pityriasis versicolour. ganism whereas the humoral im- changes are not evident. • Leucoderma secundarium. mune system has become exhausted • • Vitiligo. and cellular immunity predominates Differential diagnosis in the organism’s defence reactions. • Traumatic erosion. The onset of this stage is highly in- • Herpes progenitalis. Papulous syphilids (papulae dividual – from 3–20 and more years • Ulcus molle. lenticulares). The preferred localisa- depending on the state of the • Pyodermia chancriformis. tion sites are the genitals, the region immune system. • Scabies on genitals. of the anal orifice, oral mucosa, • Carcinoma. palms, soles, and areas where the skin gets irritated (body creases). Primary syphilomas (Syphilis • Balanopostites. Papules are of a copper red primaria) coloration, flat, and do not become Secondary syphilids (syphilis Clinical picture. The classical forms confluent. There may be secundaria) are hard chancre (ulcus durum) or desquamation on their surface erosion at the site of treponeme en- Clinical picture. Maculous syphilids. (papulae psoriasiformes) whereas on try. In its classical appearance the Roseola (roseola corporis) is the first scratching the scales separate and in primary syphiloma is round, oval or symptom of secondary syphilis the periphery of the papule a de-

Forum for Nord Derm Ven Vol. 7 November 2002 18 tached wall of the epidermis Biett During the period of secondary the secondary stage (see Table II) [1, collarette becomes evident. At sites syphilis, focal, rarely diffuse hair 2]. of irritation to the papules (mucosa, loss (alopecia areolaris et diffusa) is skin creases) erosions (papulae observed in the hairy part of the In the management of syphilis in erosivae) develop on their surface. head. At the sites of hair loss hair Latvia doctors follow the guidelines These erosive papules may become sacs are preserved, signs of developed in this country [1] that are hypertrophic and form flat condylo- inflammation are not evident and in very similar to the European guide- mas (condylomata lata). Typical sites 1–1.5 months hair starts growing lines for the management of syphilis affected are the genitals, the region again. [3, 4], with some insignificant differ- of the anal orifice, and skin creases. ences. In Latvia, we follow the divi- In the relapse phase syphilis papules Differential diagnosis sion of syphilis in stages of primary, group and progress to the skin of • Alopecia areata. secondary, and tertiary as opposed the forehead at the hairline (corona • Trichophytia adultorum chronica. to such phases as early or late. Thus, veneris). • Alopecia seborrhoica. the doses for a course are larger in some cases, aimed at preventing Differential diagnosis relapses. For about 70% of adult Papulous syphilids develop in pa- Psoriasis vulgaris. patients in Latvia prolonged • tients with immune depression. Parapsoriasis guttata. procainpenicillinum or benzyl- • Syphilitic impetigo (impetigo Lichen ruber planus. penicillinum is used. In cases of • syphilitica) may develop as well as Mycosis pedum. intolerance to penicillin, doxycycline • syphilitic ecthyma (ecthyma Haemorrhoides. or erythromycin is used [1, 3, 5] (see • syphiliticum) syphilitic acne (acne Table IV). syphilitica) and some other In the phase of secondary syphilis conditions simulating various forms the oral mucosa presents an ery- of pyodermia. Syphilitic pustules are References thematous appearance. Erythema of sterile and a papulous infiltrate is the mucosa of the fauces (angina found at their base. 1. Rubins A., Gutmane R., Rubins S., Chigarevska L., Treija I., Syphilis in: erythematosa) is a characteristic sign Sexually Transmitted Diseases, LDF with sharply demarcated borders 2001, Riga, p. 8–37. Differential diagnosis and a cyanotic coloration. There are 2. Rubins A., Rubins S., Jakobsone I., • Impetigo streptogenes. Syphilis and gonorrhoea in the Baltic no subjective complaints. Oral • Ecthyma vulgare. countries, J. Sexually Trans. Infec- syphilitic papules are most • Acne vulgare. tion., June 2000, Vol 76, Nr.3 p. 214. frequently present in the mucosa of 3. Goh B.T., Van Voorst Vader P.C., the fauces, on the lips, tongue and European guideline for the manage- ment of syphilis, International Jour- palate (diameter 0.5–1 cm). Erosions In the past decade morbidity from nal of STD & AIDS, 2001; 12 (suppl.): syphilis in Latvia has increased dra- easily form on their surfaces with a 14–26. characteristic pale fibrosal tunic in matically, reaching the highest level 4. Van Voorst Vader P.C., Syphilis the centre. Erosive papules are often in 1996 when 124.9 cases per management and treatment, Dermatol Clin., 1998; 16: 699–711. observed in oral mucosa. 100,000 inhabitants were registered, 5. Akovbyan V.A., Kubanova A.A., or 3,124 cases (the population of Akovbyan G.V. et al., Benzylpenicillin Latvia is 2.6 million), including 25 benzathine (Extencillin) in the treat- Differential diagnosis cases of congenital syphilis (see ment of syphilis: five years’ experi- Angina catarrhalis. ence [in Russia], Vestnik Dermatologii • Table I.) More than æ of the patients Lichen ruber planus. I Venerologii, 1998, no. 4: 61–64. • were diagnosed as having syphilis in • Stomatitis.

Forum for Nord Derm Ven Vol. 7 November 2002 19