Chancroid

Sexually transmitted diseases are an important cause of morbidity and, worldwide, result in significant disorders of the reproductive system. Sexually transmitted diseases that cause genital ulcerations also significantly increase the risk of contracting human immunodeficiency virus (HIV) infection because of the break in the mucocutaneous barrier.[1-3]

The differential diagnosis of genital ulcerations includes not only the lesions of chancroid, lymphogranuloma venereum and granuloma inguinale, but also those of herpes simplex virus infection and primary syphilis (chancre). Herpes simplex is the most common cause of genital ulcerations, usually appearing as discrete, exquisitely tender vesicles, 2 to 4 mm in diameter, which rapidly become erosions (Figure 1). in immunocompromised patients, herpes simplex may present as persistent erosions or ulcers. The chancre of primary syphilis is indurated and painless. Atypical clinical presentations of chancroid and lymphogranuloma venereum may resemble herpes simplex and syphifis. Table 1 reviews typical presentations and treatments for chancroid, lymphogranuloma venereum and granuloma inguinale.

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Chancroid

Chancroid is an infrequently reported disease caused by Haemophilus ducreyi, a gram-negative streptobacillus that is difficult to culture.[1-9] This bacteria is endemic in tropical and semitropical regions. In fact, the global incidence of chancroid may actually exceed that of syphilis. It is said to be the most common cause of genital ulcerations in Kenya, Gambia and Zimbabwe.[8]

Chancroid is not common in the United States. Its incidence in North America peaked in 1947, when 9,515 cases were reported. The number of cases gradually declined until 1981, when only 93 cases were reported.[5] This reduction appears to have been due to the effectiveness of sulfonamides.[9] However, antibiotic resistance became widespread, and outbreaks of chancroid began occurring again in the early 1980s. The downward trend in the incidence was reversed, with 4,697 reported cases in 1989. In addition, chancroid may be underreported because of the difficulty of proving the clinical diagnosis by culturing the organism.[5] Contact with infected prostitutes is believed to be a primary method of spreading the disease.

CLINICAL PRESENTATION

The incubation period for chancroid is generally four to five days, ranging from one to four days.[3,8] The first lesion is a small papule or pustule, which rapidly erodes into an ulcer as a result of friction. Typically, one to several ulcers appear initially (Figure 2). The somewhat indurated ulceration is deep and exquisitely painful. Unlike the indurated ulcers of syphilis and granuloma inguinale, the ulcerated area has a soft consistency resembling putty. The ulcer is deep, with a ragged, indistinct border that may spread to undermine adjacent normal skin.

The chancroid ulcer has the configuration of an Erlenmeyer flask, with its opening at the skin surface[3] (Figure 3). The ulcer base is yellowish and may produce purulent drainage. hi men, the sites of predilection are the prepuce, coronal sulcus and frenulum of the penis. In women, labial chancres are common, but lesions may also be found on the anogenital skin, within the vagina or on the cervix. An increasing number of cases have been described that mimic herpes, syphilis or granuloma inguinale infection. Multiple ulcerations that have resulted from auto-inoculation may frequently be seen. Ulcers tend to resolve within a week or two with effective therapy; left untreated, they persist for one to three months.[8]

From 30 to 60 percent of patients have enlarged regional lymph nodes, which may also ulcerate[3] (Figure 4). The lymphadenopathy is likely to be unilateral. The lymph nodes may be firm initially but may become fluctuant, sometimes rupturing through the overlying skin. Untreated chancroid gradually progresses by direct extension, increasing the likelihood of inguinal ulceration. The primary ulcer may extend to the inguinal ulcer created by the ruptured, fluctuant lymph node. Lymphatic swelling may result, with genital edema caused by lymphatic blockage and, possibly, even lower-extremity elephantiasis.

DIAGNOSIS

Laboratory diagnosis of chancroid is aided by a recently developed, more reliable culturing system for H. ducreyi.[3,5,9] Specimens should be inoculated directly into selective media, which may produce the pure culture necessary for confirmatory biochemical tests. However, culture still remains difficult without considerable laboratory support. The organisms are difficult to grow unless provided with an optimal environment.[9,10]

DNA probes and use of the polymerase chain reaction test may make the diagnosis of chancroid much easier at some time in the future.[5,7] Cytologic examination of exudate from the ulcer base, using a Giemsa or Gram stain, may show the classic "school of fish" parallel chains of pleomorphic gram-negative rods. However, this method is suboptimal, because it lacks both sensitivity and specificity. Histologically, three zones overlie each other and show characteristic vascular alterations that strongly suggest the diagnosis.[6]

The ulcer base consists of neutrophils, red blood cells, fibrin and necrosis. Below it is a relatively large area of blood-vessel formation, with endothelial cell proliferation and vascular thromboses. The deepest zone has a dense infiltrate of plasma cells and lymphocytes.

TREATMENT

H. ducreyi has developed resistance to many of the previously effective antibiotics. For example, sulfonamide is a superb therapy, but many strains are now resistant to monotherapy with this agent.[8] In vitro sensitivity is predictive of a good therapeutic outcome.[9]

Current recommendations for therapy must take into account geographically variable antibiotic sensitivity. The current treatments of choice for chancroid are erythromycin base, 500 mg orally four times daily for seven days, or ceftriaxone (Rocephin), 250 mg intramuscularly in a single dose.[3] Alternative therpies include a three- to seven-day course of amoxicillin-clavulanic acid (Augmentin); 500/250 mg three times daily, or trimethoprim-sulfamethoxazole (Bactrim, Septra), 160/800 mg twice daily for seven days. It is recommended that all sexual contacts of an infected patient be treated, regardless of symptoms.[8]

Lymphogranuloma Venereum

The causative agent in lymphogranuloma venereum is an infection with Chlamydia trachomatis, serotypes L1, L2 or L3.[2,3,11-13] This sexually transmitted disease is endemic in tropical regions, but the number of reported cases in the United States remains fewer than 1,000 per year. It seems likely, however, that the disease is underreported. It tends to occur in travelers to areas where the disease is endemic or in sexual contacts of these persons. The course of lymphogranuloma venereum has been divided into primary, secondary and tertiary stages.

STAGE I

The initial lesion appears after about a seven-day incubation period (the range is five to seven days).[3] In heterosexual men, the initial lesion is located on the glans penis; in women, the lesion is found on the labia or the cervix. However, nongenital lesions may also occur.

Four types of lesions are seen: a papule, an eroded or ulcerated nodule, herpetiform coalescent lesions and urethritis. The primary lesion is usually a pustule, but it may be a papule. It rapidly ulcerates, as a result of friction between opposing cutaneous surfaces (Figures 5 and 6). One or several ulcers are seen. About 50 percent of initial lesions are asymptomatic and heal without scarring within a few days. Because the lesions are often so small and transient, they may go unnoticed and patients may present with no history of genital lesions. In a study of 27 patients, only five recalled having a genital sore within weeks of the onset of the inguinal lymphadenopathy or proctitis.[13]

STAGE II

Stage 11 of lymphogranuloma venereum is characterized by acute and chronic features. As an anogenital syndrome, it is associated with unilateral or, occasionally, bilateral bubo formation. A bubo is a tender, firm lymph node collection. It evolves from discrete mobile nodes into a coalescent, firm, mobile mass several centimeters in diameter. It may occur above and below Poupart's ligament, producing a groove sign. The bubo may become fluctuant. Although it usually heals without complications, it may rupture with chronic sinus formation (Figure 7). Almost 20 percent of patients also present with enlarged femoral lymph nodes. An uncomfortable proctitis may occur as a result of anal intercourse, anal spread from vaginal secretions or translymphatic spread from cervical or posterior vaginal lesions. At this stage of the disease, hematogenous dissemination may occur, with fever and nausea, headache and meningismus. A recent study of 27 patients found that systemic symptoms occur infrequently.

STAGE III

The inguinal adenopathy typically resolves after two to three months if left untreated. Rarely, men develop elephantiasis of the penis or scrotum. In both women and men with rectal involvement, rectal stricture and perineal fistulas are more likely. Abscess of the supralevator muscle caused by chronic rectal lymphogranuloma venereum has been reported.[14]

DIAGNOSIS

Culture for C. trachomatis is the most specific laboratory test for the diagnosis of lymphogranuloma venereum and is obtained by aspirate from an involved lymph node. This technique is expensive and not always available. Serologic tests include a complement fixation test and a microimmunofluorescence test, the latter being more specific but less available than the complement fixation test. Few practioners use the Frei skin test these days, since it is positive for all chlamydial infections. Histologic examination of the initial papule of lymphogranuloma vanereum is nonspecific. In lymph nodes, stellate abscesses are suggestive of the disease.

TREATMENT

Lymphogranuloma venereum can be treated with doxycycline, 100 mg orally twice daily for 21 days. Alternative options are erythromycin, 500 mg orally four times daily for 21 days, or sulfisoxazole (Gantrisin), 500 mg four times daily for 21 days.[3]

Adequate therapeutic response is suggested by gradual diminution of lymph node size and closure of any fistula, or by resolution of proctitis.[13] Although a new macrolide antibiotic, azithromycin (Zithromax), is effective against uncomplicated genital Chlamydia infection, there is, to our knowledge, no reference to its use for lymphogranuloma venereum. Repeated aspiration of tense or fluctuant lymph nodes may ease inguinal discomfort.[13]

Because the clinical presentation of lymphogranuloma venereum may resemble herpes simplex, syphilis, chancroid and granuloma inguinale, careful follow-up is necessary.

Granuloma Inguinale

Granuloma inguinale (Donovanosis) is manifested as a chronic, painless, ulcerative, granulomatous process.[2,3,15-20] The causative organism is Calymmatobacterium granulomatis, a gram-negative rod. For the most part, sexual transmission is presumed for this bacterium, which is endemic in tropical and semitropical regions. Its incidence has fallen dramatically in developed countries.

The incubation period varies from eight to 80 days. The lesion is usually a painless, irregular, clean-based but granulomatous ulcer The initial lesion may be nodular or take other forms. The ulcer feels hard when palpated. The hypertrophic form usually occurs in the perianal region. When the hypertrophic form becomes superinfected, it may revert to a necrotic form.

As the lesion enlarges, the ulcerode-structive process can be quite mutilating, causing urethral stenosis; rarely, the infection can become life-threatening as a result of systemic involvement of the bones, liver and spleen. In men, the sites of predilection are the prepuce, the coronal sulcus and the frenulum. In women, labial lesions are most common, but vaginal and cervical lesions also occur.

Granuloma inguinale does not produce enlarged lymph nodes (except when they become superinfected). An occasional deep granuloma may appear to be a fluctuant node. This "pseudo bubo" may erode through the overlying skin and slowly extend by local enlargement.

As with chancroid and lymphogranuloma venereum, granuloma inguinale that is left untreated may result in lymphatic obstruction, producing genital edema that may progress to lower-extremity elephantiasis.

DIAGNOSIS

Diagnosis of granuloma inguinale requires identification of the infectious agent, which appears as short, pleomorphic rods with bipolar staining. The rods are usually detected histologically at the ulcer border, using Giemsa or Wright's staining of multiple routine histologic sections.[3]

Reliable culture techniques are not yet available. The histologic diagnosis of granuloma inguinale is often difficult. It depends on finding intracytoplasmic inclusion bodies (Donovan bodies) within histiocytes.[15] These bodies are seen with Giemsa stain as oval structures, with bipolar staining, surrounded by a fighter staining capsule. Granuloma inguinale must be distinguished histologically from leishmaniasis, rhinoscleroma and histoplasmosis. Donovan bodies are smaller than the histiocyte inclusions that are seen in these other disorders.

TREATMENT

The treatment of choice for granuloma inguinale is doxycycline, 100 mg orally twice daily until the lesions have healed. Trimethoprim-sulfamethoxazole, 160/800 mg orally twice daily, is an alternative therapy.[3] Other effective options are available, including norfloxacin (Noroxin), 400 mg twice daily for seven to 10 days,[21] and erythr-omycin, 500 mg four times daily for two to three weeks.[22]

REFERENCES

[1.] Aral SO, Holmes KK. Sexually transmitted diseases in the AIDS era. Sci Am 1991;264:62-9. [2.] Buntin DM, Rosen T, Lesher JL Jr, Plotnick H, Brademas ME, Berger TG. Sexually transmitted diseases: bacterial infections. J Am Acad Dermatol 1991;25(2 Pt 1):287-99. [3.] Kraus SJ. Diagnosis and management of acute genital ulcers in sexually active patients. Semin Dermatol 1990;9:160-6. [4.] Kirby PK, Munyao T, Kreiss J, Holmes KK. The challenge of limiting the spread of human immunodeficiency virus by controlling other sexually transmitted diseases. Arch Dermatol 1991;127:237-42. [5.] Jones CC, Rosen T. Cultural diagnosis of chancroid. Arch Dermatol 1991;127:1823-7 [6.] Margolis RJ, Hood AF. Chancroid: diagnosis and treatment. J Am Acad Dermatol 1982;6(4 Pt 1):493-9. [7.] Fiumara NJ, Rothman K, Tang S. The diagnosis and treatment of chancroid. J Am Acad Dermatol 1986;15(5 Pt 1):939-43. [8.] Boyd AS. Clinical efficacy of antimicrobial therapy in Haemophilus ducreyi infections. Arch Dermatol 1989;125:1399-405. [9.] Ronald AR, Plummer F. Chancroid. A newly important sexually transmitted disease [Editorial]. Arch Dermatol 1989;125:1413-4. [10.] Parsons LM, Shayegani M, Waring AL, Bopp LH. DNA probes for the identification of Haemophilus ducreyi. J Clin Microbiol 1989;27:1441-5. [11.] Bolan RK, Sands M, Schachter J, Miner RC, Drew WL. Lymphogranuloma venereum and acute ulcerative proctitis. Am J Med 1982;72:703-6. [12.] Schachter J, Osoba AO. Lymphogranuloma venereum. Br Med Bull 1983;39:151-4. [13.] Scieux C, Barnes R, Bianchi A, Casin I, Morel P, Perol Y Lymphogranuloma venereum: 27 cases in Paris. J Infect Dis 1989;160:662-8. [14.] Mostafavi H, O'Donnell KF, Chong FK. Supralevator abscess due to chronic rectal lymphogranuloma venereum. Am J Gastroenterol 1990; 85: 602-6. [15.] Hacker P, Fisher BK, Dekoven J, Shier RM. Granuloma inguinale: three cases diagnosed in Toronto, Canada. Int J Dermatol 1992;31:696-9. [16.] Rosen T, Tschen JA, Ramsdell W, Moore J, Markham B. Granuloma inguinale. J Am Acad Dermatol 1984;11:433-7 [17.] Sehgal VN, Prasad AL. Donovanosis. Current concepts. hit J Dermatol 1986;25:8-16. [18.] Sehgal VN, Jain MK. Pattern of epidemics of donovanosis in the "nonendemic" region. Int J Dermatol 1988;27:396-9. [19.] Sehgal VN, Jain MK. Tissue section Donovan bodies--identification through slow-Giemsa (overnight) technique. Dermatologica 1987;174:228-31. [20.] Niemel PL, Engelkens HJ, van der Meijden WI, Stolz E. Donovanosis (granuloma inguinale) still exists. hit J Dermatol 1992;31:244-6. [21.] Ramanan C, Sarma PS, Ghorpade A, Das M. Treatment of donovanosis with norfloxacin. Int J Dermatol 1990,29:298-9. [22.] Pernoll ML, ed. Current obstetric and gynecologic diagnosis and treatment. 7th ed. Lange, 1991:779-80.

The Authors

JEAN L. GOENS, M.D. is assistant professor of dermatology at the Free University of Brussels in Brussels, Belgium, and a staff dermatologist at the Hopitaux Universitaires Saint-Pierre et Brugmann in Brussels. A graduate of the Free University of Brussels School of Medicine, Dr. Goens is board-certified in dermatology.

ROBERT A. SCHWARTZ, M.D., M.P.H. is professor and head of dermatology, professor of medicine and professor of pediatrics at UMDNJ-New Jersey Medical School, Newark. He received his medical degree from New York Medical College, Valhalla, and completed a residency in dermatology at the University of Cincinnati College of Medicine. Dr. Schwartz is a member of the AFP editorial advisory board.

KATHLEEN DE WOLF, M.D. is assistant professor of dermatology at the Free University of Brussels and a staff dermatologist at the Hopitaux Universitaires Saint-Pierre et Brugmann in Brussels. An alumna of the Free University of Brussels School of Medicine, Dr. Wolf is board-certified in dermatology

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