SEXUALLY TRANSMITTED DISEASES

Rhett J. Drugge, MD

Syphilis
Chancroid
Human Papillomavirus (HPV)
Lymphogranuloma Venereum
Chlamydia
Gonorrhea
HIV
Hepatitis
Granuloma Inguinale
Prevention of STD's

Syphilis-the great imitator

Once the single most important disease in dermatology, mid-20th century antibiotics nearly wipe out this spirochete disease. However, the reported incidence of all stages of syphilis increased dramatically from 1985 (28.5 cases per 100,000 population) to 1990 (54.3 per 100,000). It then decreased to 45.3 cases per 100,000 in 1992. Congenital syphilis increased from 1985 (7 per 100,000 live births) to 1990 (91.8 per 100,000 live births), peaked in 1991 (107.2 per 100,000 live births), and then decreased in 1992 (94.3 per 100,000 live births). Over 30,000 new cases of primary and secondary syphilis occur annually, and the prevalence of HIV infection among syphilis-infected individuals increasing.

While the Oslo study by Bruusgaard indicated that 60-70% of untreated patients went through life with little or no inconvenience, still, 30-40% suffered serious inconvenience, so that the diagnosis and treatment are very worthwhile.

There are essentially three stages in syphilis: the primary (chancre),the secondary (florid rash and dissemination), and the late (gumma, aneurysm , tabes, paresis). There is a late stage of anywhere from two to forty years after the second state, during which flare-ups of the latent infection can lead to actual clinically infectious relapses. Insufficient or irregular treatment favors relapses.

Primary

This stage is characterized by chancre or indurated ulcer, which may be insignificant, on the penis, vulva, lip or anus following 18-21 days after exposure. It may be delayed by intercurrent antibiotic treatment of another infection. The diagnosis is by darkfield examination of the chancre fluid for treponemes under the microscope ( 1)

Secondary

The second stage is characterized by a florid symmetrical coppery erythematous macular exanthem that almost always involves the palms , soles and mucous membranes (buccal mucosa, 1 , 2 ) and is accompanied by general lymphadenopathy 3-6 weeks after the appearance of the chancre. Relapsing secondaries occur during the latent period in untreated or insufficiently treated and are characterized by indolent polymorphic, grouped skin or mucosal lesions that are often annular or corymbose (satellites around a central large lesion), very occasionally pustular (the pox) or rupial (oyster shell-like) and often near a mucous membrane orifice such as the mouth or nostril. Their appearance is preceded by a rise in the serologic titer.

Latent syphilis is characterized by an absence of symptoms. Meanwhile, the serology is positive, and invasion of the cardiovascular or central nervous system may silently occur. Early latent syphilis is less than two years, whereas duration of longer than this is considered late latent syphilis. Almost all central nervous system(CNS) invasion occurs before this second year (most within six months) so that lumbar punctures should be performed as soon as the diagnosis is made. A baseline chest X-ray to use for future comparison of the width of the aorta is useful since cardiovascular or CNS syphilis can precede in the presence of a negative Venereal Disease Research Lab test (VDRL) in 20% of patients.

Late

Late syphilis is characterized by an asymptomatic period in most patients, although 25% will develop symptoms of gumma, aortitis, tabes or paresis if untreated early. In the skin, nodular serpiginous copper-colored firm, scaly or smooth lesions may appear and progress slowly over the years. Gummata may occur singly or as disseminated kidney-shaped patches with punched-out ulcerations. Interstitial glossitis or mucosal gummatous ulceration may occur. Passive transfer of antibodies will give an infant positive serology for several months even if healthy. Diminishing titers indicate biologic false positive reaction, whereas a rising titer is very suggestive of luetic infection. Snuffles, frontal bossing, tender bones, periostitis or epiphysitis on x-ray, an enlarged spleen, or occasionally skin lesions may suggest syphilis in the young infant, who can be seronegative for up to six months.

Diagnosis of Syphilis

Biologic false positive reactions will occur in persons with infectious mononucleosis, lymphogranuloma venereum (LGV), leprosy, recent vaccination and rheumatoid arthritis, as well as in terminal cancer patients. In cases of questionable VDRL, it is well to remember that "positive in high dilutions" suggests true positivity, and the treponema pallidum immobilization test (TPI), which is slow, may have negative results in 15-20% of definite secondary syphilis cases. The fluorescent treponemal antibody absorption test (FTA-ABS) gives positive results in almost every case of syphilis whether successfully treated or not and whether seronegative or not, and even earlier than the VDRL 50% of the time, but it is a sensitive test and can give false positive reactions in persons with lupus erythematosus and in terminal cancer patients. Many cardiovascular and CNS syphilis patients will be seronegative and give positive FTA-ABS test results.

Treatment

Penicillin has revolutionized the treatment of all forms of syphilis. In the days of arsenic treatment, fear of the Jarisch-Herxheimer reaction (presumably an intensification of symptoms because of the release of the antigenic protein when the spirochete is destroyed),causing swelling of the coronary ostia in cardiovascular syphilis and thereby leading to coronary occlusion usually led to the "softening" or "mild preparation" of the patient with bismuth for a few weeks before starting arsenic treatment. While many therapists feel this is unnecessary with penicillin, caution is in order when treating cases of optic atrophy or severe CNS lues or suspected aortitis patients. In one patient where inadvertent EKGs were performed three times in one day shortly after penicillin was introduced, there was a classic T wave inversion of the coronary occlusion type, although symptoms were mild.

Successful therapy requires a high enough level of penicillin over a long enough period of time to eradicate the spirochete. Whether every spirochete is killed is an academic question, and it is most likely that such does not occur. Probably enough spirochetes are killed so that the body's natural defenses can handle the remnants thereafter. Benzathine penicillin G gives adequate levels over long periods. In cases of optic atrophy, interstitial keratitis and more severe forms of symptomatic neurosyphilis, however, a Presbyterian Hospital schedule, which is closer to 25 million units over 10-14 weeks in 20-28 injection, is preferable.

All patients who refuse cerebrospinal fluid (CSF) lumbar puncture(LP) should be treated as having asymptomatic neurosyphilis (at least 12 million units over 6-8 weeks). Usually after this course the CSF cell count will return to normal (less than 6 in 6 months)and the serum protein level will normalize in one year. Follow-up requires a serologic test for syphilis (STS) every 6 months for 2 years and then yearly thereafter, plus a chest x-ray. Cephaloridine(Loridine-Lilly) 0.5 grams given intramuscularly daily for ten days, appears to be effective(2).

In questionable penicillin allergy, scratch or conjunctival tests using 5 units per ml of aqueous penicillin can be read in 20 minutes, and if negative, a 0.02 ml intracutaneous injection of the 10,000 units of aqueous solution can be used. If results are negative, the patient may be treated. If pseudopodia, wheals or flares occur, then the patient is allergic, and one of the other drugs must be used. "Prepen" (Kremers-Urban), benzylpenicilloyl-polylysine, is a method of testing for penicillin allergy(3).


Chancroid (soft chancre)

In the United States, H. ducreyi accounts for a small proportion of genital ulcers. Although the number of reported cases of chancroid has decreased every year since 1987, cases are still reported from some large urban areas. In 1994, a total of 773 cases of chancroid were reported to CDC Identification of chancroid is particularly important because it is the STD most strongly associated with an increased risk for HIV transmission (4,5). Without proper treatment, ulcers require longer periods to heal, thereby prolonging for patients their susceptibility to or risk for HIV transmission or acquisition.

The incubation period of Hemophilus Ducreyi, which stains with methylene blue, is 2 to 7 days. Chancroids appear as tender and usually multiple punched-out genital ulcers (1) with unilateral lymph gland enlargement (which suppurates if untreated). The diagnosis is by staining the direct smear to find the "school-of-fish" arrangement of the organism, which is gram negative. The intracutaneous skin test with ducreyi vaccine has positive results after the second week. Laboratory confirmation by culture is 53%-84% sensitive (Jessamine , Telzak ). Polymerase chain reaction increases sensitivity to nearly 100%, with a majority of patients testing positive in a recent Jackson, Mississippi study (Orle ).

The following treatment is usually curative: tetracycline 2 g daily for 14 days. Occasional cases need treatment of up to 4 weeks, with local soaks and antibiotic locally assisting.


Granuloma Inguinale

The incubation period is 1-12 weeks and is caused by the Donovania granulomatis. "Closed safety pin" inside the cytoplasm of cells stains with the Wright stain. Scrapings (not smears)show the organism. The disease consists of progressive granulomatous ulceration with fleshy edges, almost invariably in blacks. The lesion is not very uncomfortable, and there is usually no regional lymph node involvement.

Treatment should be with tetracycline 2 g daily for 21 days or one g four times a day for 7 days.


Lymphogranuloma Venereum

This disease, with incubation 5-20 days, is characterized by a "bubo" leading to a sinus that usually drains a longtime, finally producing convoluted scarring.

In the male, there is unilateral inguinal adenopathy following an insignificant lesion on the genitals. A good treatment is sulfadiazine, 4 g daily for 21 days. In the female, adenopathy is more apt to occur in the pararectal nodes, producing rectal stricture. The best treatment is tetracycline, 2 g daily for 3 weeks.

Treatment is as for granuloma inguinale, although tetracycline, sulfa and Chloromycetin can be used (in decreasing order of choice).

The LGV complement fixation test is highly specific and shows positive results early in the infection. The Frei test (antigen is hard to get; try Hollister-Stier) intracutaneously, 0.1 ml, is read in 72 hours. Infiltration of more than 7 mm is a positive reaction.


Herpes Progenitalis

(overview from the NIH) herpes simplex (clinical description ), Neonatal consequences (clinical description), (Patient Support Groups ) (Current clinical study for couples where one partner is affected.)

The herpes virus family are encapsulated double stranded DNA (EM ), related to cytomegalovirus,

Symptoms are grouped vesicles (1, 2,) on the genitals, which often ulcerated early and heal rapidly. They recur, and if you can elucidate the trigger and eliminate it (e.g., wine, cheese, chocolate), this is the best management.

Acidophilus milk, active culture yogurt or Lactinex tablets may, by altering the local environment, have some effect. Condoms should be worn during intercourse. Neosporin powder or Vioform hydrocortisone lotion usually heals the attack, and occasionally Castellani's paint is helpful. The differential diagnosis includes psoriasis 1 , 2, candidasis, 1.


Balanitis Erosiva

A long foreskin leads to moisture, which with retained smegma produces irritation and a bright red glans. Occasionally the foreskin becomes edematous, leading to phimosis. Yeasts or Vincent's spirillum, along with other bacteria, thrive in this milieu, and mild cleansing and soothing wet dressings with 0.25% silver nitrate, or Burrow's or boric acid solution, help. Antibiotic dusting powder or hydrocortisone Mycostatin lotion, with or without Vioform, and occasionally aqueous gentian violet are of assistance here. I generally suggest Phisoderm for normal skin as a washing agent. Balneol (Westwood) is useful also as a gentle cleanser. Ointments are often aggravating here unless cleaned off occasionally. One-half strength Carbol-fuchsin is occasionally curative.

Recent reports from Helsinki have mentioned a type of treatment that is successful where there is a lot of moisture, e.g., a long foreskin, using beads of a dextran polymer called Debrisan (Pharmacia)which is dusted on like salt twice a day. It cleans things up in short order. One case of balanitis xerotica obliterans was successfully treated with 2.5% testosterone propionate in an ointment.


Human Papillomavirus (HPV)

(overview from the NIH) Condyloma Acuminatum , (EM ), Testing for HPV in the clinic can be done by whitening with 5% acetic acid solution. (Patient Support Groups ) Sexually transmitted HPV infections are common, frequently affecting the anogenital region as well as the oropharynx (penis, vulva). HPV types 16, 18 and 31 have carcinogenic potential for squamous cell carcinomas, especially of the cervix and the anus. Treatment consists of a variety of destructive methods, including cryosurgery, electrosurgery, laser surgery and podophyllin (a DNA gyrase inhibitor).


Chlamydia (overview from the NIH)

Chlamydial infections are the most commonly reported STD in the United States. They are caused by Chlamydia trachomatis. In men, symptoms usually appear between 7 and 28 days after infection, usually with mild burning when urinating, a more frequent need to urinate, and a white discharge from the penis. Occasionally, blood may appear in the urine. The symptoms occur most frequently in the morning. The majority of women show no symptoms, although vaginal discharge, mild burning when urinating, a more frequent need to urinate, abdominal pain, and pain during intercourse may occur. Other sites of infection may include the throat, rectum and ocular conjuctiva of both sexes. Late term complications in men include sterility, urethritis, arthritis, eye infections, or skin lesions. Women may develop pelvic inflammatory disease (PID) and sterility from tubal scarring. Infants born to infected women frequently develop eye infections and pneumonia.
The antibiotics Doxycycline, 100 mg po BID times one week. Erythromycin and sulfisoxazole are also used to treat chamydial infections.


Gonorrhea (overview from the NIH)

Urethral Discharge (1) Neisseria gonorrhoeae (gonococcus) is the bacterium that causes gonorrhea. Gonorrhea is spread by sexual contact, and from mother to baby during delivery The bacterium is found in infected body fluids from the penis, vagina, mouth or rectum, and spread by direct sexual contact (touching, rubbing). Babies eyes can get infected if their mother has a cervical infection at the time of birth. Symptoms to look for: Discharge from the penis, vagina, or rectum Sore throat, possibly with difficulty swallowing Bad cramping or severe pain in the pelvic area in women (pelvic inflammatory disease, or PID) Pain in the testicles in men Pain when urinating The gonococcus may disseminate, especially in women, and form sterile purupuric macules usually fewer than twenty in number on the upper trunk and extremities. It can also seed joints causing a septic arthritis. Symptoms can start from 2 to 7 days after infection. Ceftriaxone, 250 mg IM is the treatment of choice due emerging resistance to quinolones and penicillines. Anyone treated for gonorrhea should also be treated for chlamydia infection, another STD.


HIV (overview from the NIH)


Hepatitis (overview from the NIH)

References

Clark EG, Danbolt N. The Oslo study of the natural course of untreated syphilis: an epidemiologic investigation based on a restudy of the Boeck-Bruusgaard material . Med ClinN Am 1964; 48:613-23.

Stamm WE, Handsfield HH, Rompalo AM, et al. The association between genital ulcer disease and acquisition of HIV infection in homosexual men. JAMA, 1988; 260: 1429-33.

Holmberg SD, Stewart JA, Gerber AR, et al., Prior herpes simplex virus type 2 infection as a risk factor for HIV infection. JAMA 1988; 259:1048-50.

Centers for Disease Control. Relationship of syphilis to drug use and prostitution -- Connecticut and Philadelphia, Pennsylvania. MMWR 1988; 37:755-8,64.

Guidelines for the prevention and control of congenital syphilis. MMWR [Suppl 1] 1988; 37.

Congenital syphilis, United States, 1983-1985. MMWR 1986; 35:625-8.

Hart G. Syphilis tests in diagnostic and therapeutic decision making. Ann Intern Med 1986; 104:368-76.

Screening to control infectious diseases. Rev Infect Dis 1980; 2:701-12.

Feder HM, Manthous C. The asymptomatic patient with a positive VDRL test. Am Fam Physician 1988; 37:185-90.

Wentworth BB, Thompson MA, Peter CR, et al. Comparison of a hemagglutination treponemal test for syphilis (HATTS) with other serologic methods for the diagnosis of syphilis. Sex Transm Dis 1978; 5:103-11.

Hashisaki P, Wertzberger GG, Conrad GL, et al. Erythromycin failure in the treatment of syphilis in a pregnant woman. Sex Transm Dis 1983; 10:36-8.

Fenton LJ, Light IJ. Congenital syphilis after maternal treatment with erythromycin. Obstet Gynecol 1976; 47:492-4.

Stray-Pedersen B. Economic evaluation of maternal screening to prevent congenital syphilis. Sex Transm Dis CommunityMed 1985; 7:37-42.

Williams K. Screening for syphilis in pregnancy: an assessment of the costs and benefits. Community Med 1985; 7:37-42

Canadian Task Force on the Periodic Health Examination. The periodic health examination. Can Med Assoc J 1979; 121:1-45.

American College of Obstetricians and Gynecologists. Standards for obstetric-gynecologic services. Washington, D.C.: American College of Obstetricians and Gynecologists, 1985:16.

American Academy of Pediatrics. Role of the pediatrician in management of sexually transmitted diseases in children and adolescents. Pediatrics 1987; 79:454-6.

Centers for Disease Control. Syphilis and congenital syphilis, United States, 1985-1988. MMWR 1988; 37:486-9.

Schulte JM, Martich FA, Schmid GP. Chancroid in the United States, 1981-1990: evidence for underreporting of cases. MMWR 1992;41(no. SS-3):57-61.

Morse SA. Chancroid and Haemophilus ducreyi. Clin Microbiol Rev 1989;2:137-57.

Orle KA, Martin DH, Gates CA, Johnson SR, Morse SA, Weiss JB. Multiplex PCR detection of Haemophilus ducreyi, Treponema pallidum, and herpes simplex viruses types -1 and -2, from genital ulcers [Abstract no. C-437]. In: Abstracts of the 94th general meeting of the American Society for Microbiology. Washington, DC: American Society for Microbiology, 1994.

Jessamine PG, Plummer FA, Achola JON,et al. Human immunodeficiency virus, genital ulcers, and the male foreskin: synergism in HIV-1 transmission. Scand J Infect Dis 1990;69(suppl):181-6.

Telzak EE, Chiasson MA, Bevier PJ, Stoneburner RL, Castro KG, Jaffe HW. HIV-1 seroconversion in patients with and without genital ulcer disease. Ann Intern Med 1993;119:1181-6.

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Wasserheit JN. Epidemiological synergy: interrelationships between human immunodeficiency virus infection and other sexually transmitted diseases. Sex Transm Dis 1992;19:61-77.

Prevention of Sexually Transmitted Diseases-(Table from U.S. Preventive Services Task Force )

Table A-4.
Prevention of Sexually Transmitted Diseases
 
_______________________________________________________________________
                         Preventive           Quality of    Strength of
    Disease             Intervention           Evidence     Recommendations
_______________________________________________________________________
                         General Recommendations
 
                  Epidemiologic treatment^        I               A
                  Contact tracing                II-2             B
                  Disease reporting              III              B
                  Barrier methods                II-3             B
                  Patient education              III              C
 
                                Gonorrhea
 
Gonorrhea         Culture of high-risk           II-1             A
                  group members
Gonococcal        Erythromycin ophthalmic         I               A
ophthalmia        ointment postpartum
neonatorum
Gonococcal        Culture of pregnant women      III              C
ophthalmia
neonatorum
 
                                 Syphilis
 
Syphilis          Epidemiologic treatment         I               A
                  of sexual contacts of
                  established infection
Syphilis          VDRL testing of high-risk      II-3             B
                  group members
Congenital        VDRL testing of pregnant       II-3  Risk group: B
syphilis          women                                No-risk group: C
 
                    Human Immunodeficiency Virus (HIV)
HIV infection     HIV antibody testing           III   Risk group: B
                                                       Pregnant women: B
                                                       No-risk group: C
HIV infection     Use of heat-treated blood       II              A
                  product^
HIV infection     Blood and needle precau-        II              A
                  tions for persons exposed
                  to infected secretions^
 
       Sexually Transmitted Infections Caused by Enteric Pathogens
 
Hepatitis A       Immune serum globulin           I               A
 
           Sexually Transmitted Human Papillomavirus Infection
 
Genital warts     Physical examination of        III              C
                  risk group members^
 
           Sexually Transmitted Herpes Simplex Virus Infection
 
Neonatal herpes   Cesarean section in women      III              B
                  with active genital
                  herpes during labor^
 
           Sexually Transmitted Chlamydia trachomatis Infection
 
Ophthalmia        Erythromycin eye ointment       I               A
neonatorum
Neonatal          Culture screening of           III      Risk group: B
chlamydia         pregnant women
infection
 
_______________________________________________________________________
 



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