What is chancroid

Chancroid is an exceedingly rare sexually transmitted disease (STD) caused by the bacterium Haemophilus ducreyi, that is spread through sexual contact ¹. Chancroid is characterized by a small bump on the genital which becomes a painful ulcer ². Men may have just one ulcer, but women often develop four or more. About half of the people who are infected with a chancroid (Haemophilus ducreyi) will develop enlarged inguinal lymph nodes, the nodes located in the fold between the leg and the lower abdomen ². In some cases, the lymph nodes will break through the skin and cause draining abscesses. The swollen lymph nodes and abscesses are often called buboes. Chancroid infections can be cured with antibiotics, including azithromycin, ceftriaxone, ciprofloxacin, and erythromycin. Large lymph node swellings need to be drained, either with a needle or local surgery. Chancroid can also get better on its own ³. Some people have months of painful ulcers and draining. Antibiotic treatment often clears up the lesions quickly with very little scarring. Lack of treatment puts the patient at risk of developing suppurative lymphadenitis. Non-response to treatment should trigger a further investigation as to the causative organism or the patient’s compliance with the treatment regimen.

Chancroid is extremely rare in the United States and other developed countries. In the United States, only seven cases in six states were reported to the Center for Disease Control and Prevention (CDC) in 2016 ¹. When infection does occur, it is usually associated with sporadic outbreaks. The reported cases involved a spectrum of individuals including minorities, heterosexuals, prostitutes, and those who engage in their services. As chancroid is a genital ulcerative disease, its lesions are more readily apparent and therefore more commonly reported among men. Uncircumcised males tend to have a greater incidence than those individuals who are uncircumcised. The likelihood of transmitting the disease to an infected individual during a single sexual encounter has been noted to be 0.35 ⁴.

Worldwide, chancroid appears to have declined as well, although infection might still occur in some regions of Africa and the Caribbean. Like genital herpes and syphilis, chancroid is a risk factor in the transmission and acquisition of HIV infection ⁵.

Chancroid also has been found to be a significant cofactor in the heterosexual acquisition and transmission of HIV disease. Genital ulcers may increase the risk of HIV infection as much as 50- to 300-fold per each unprotected encounter of vaginal intercourse ⁶. This phenomenon occurs by increasing the infectiousness of and host susceptibility for HIV infection. Interruption of the mucosa in genital ulcer disease provides a portal of entry for HIV. This, combined with an increase and activation of HIV susceptible cells, allows for enhanced viral replication and the acquisition of HIV disease.

HIV disease, in turn, may alter the appearance and clinical course of chancroid. This may include an increase in the incubation period, multiple ulcerating lesions, delays in healing, and poor response to standard courses of antibiotics, or treatment failures ⁷.

Figure 1. Chancroid sores

Chancroid prevention

Chancroid is spread by sexual contact with an infected person. Avoiding all forms of sexual activity is the only absolute way to prevent a sexually transmitted disease.

However, safer sex behaviors may reduce your risk. The proper use of condoms, either the male or female type, greatly decreases the risk of catching a sexually transmitted disease. You need to wear the condom from the beginning to the end of each sexual activity.

Chancre vs Chancroid

Syphilis is a complex sexually transmitted disease (STD) caused by the bacteria Treponema pallidum. Syphilis sexually transmitted disease is divided into 3 parts, and it is important to recognize the first part (which involves the skin) so that you can get treated before the disease progresses to the second and third parts, which affect the brain and cause early death.

The classic skin lesion of primary syphilis appears as a painless sore (ulcer) where the infection entered (usually around the genitals, anus or mouth) and may go unnoticed. The sore is known as a chancre and this phase is known as primary syphilis. The sore is typically painless and will heal on its own without treatment, but the disease will still be present, so it is very important to show the sore to your doctor. If treated early, syphilis can be completely cured. Syphilis, like other sexually transmitted diseases, is passed from person to person during oral, vaginal, or anal intercourse. It can also be passed from a mother to a baby during birth. If a baby gets syphilis, he/she often dies.

Widespread rash and ‘flu-like symptoms appear next (secondary syphilis).

If left untreated, tertiary syphilis may develop years later and cause a variety of problems affecting the brain, eyes, heart and bones.

See your doctor immediately if you are sexually active or suspect you have been exposed to someone with syphilis. DO NOT attempt self-care if you have any ulcer in the genital, mouth, or anal area. Avoid sexual activity and notify your sexual partner(s) of your illness. Additionally, you should seek medical advice if you have had intimate contact with someone with syphilis, have been using intravenous drugs, or if you have engaged in sex with multiple or unknown partners.

How is syphilis spread?

Sexually active people may be at risk of syphilis. It is passed from person to person through direct contact with syphilis ulcers or infected blood through microtraumas during unprotected sexual intercourse. Syphilis infection can occur in any sexually active person, men and women are equally at risk of syphilis, but it tends to affect young men (15–25 years old) who have sex with other men, sex workers, and people who have sex with sex workers. Syphilis is more common in the southern states and in urban areas in general.

Syphilis ulcers are most commonly on the genitals and anal area but may also be found on the lips or mouth. Hence, vaginal, anal or oral sex is the main way of passing the infection from one individual to another.

Syphilis can also be passed on through:

• Infected products e.g., blood transfusions, if donors are not screened
• The placenta to an unborn baby.
• If a pregnant woman has syphilis, the outcome for her baby is dependent on the stage of pregnancy and of the disease, and whether appropriate treatment was received.

Syphilis signs and symptoms

Initially, a dusky red, flat spot appears at the site of inoculation and is easily missed. Then, a painless ulcer (chancre) appears 18–21 days after initial infection. Genital sites in females affected are the cervix, vagina, vulva, and clitoris. Cervical and vaginal infections may not be recognized. In men, the chancre is easily seen on the penis. Other sites are limited only by human ingenuity and imagination. Other common sites for syphilis are around the mouth (perioral) and between the buttocks (perianal) areas.

Chancres vary in size from a few millimeters to several centimeters. A chancre is usually painless, solitary, and shallow, with a sharp border and a raised, hard edge. About 70–80% of patients have rubbery, non-tender, swollen lymph nodes, often on only one side of the groin, during the first week of infection.

If untreated, the chancre will remain present for 1–6 weeks. If treated, it heals without scarring in 1–2 weeks.

See your doctor immediately if you are sexually active or suspect you have been exposed to someone with syphilis. DO NOT attempt self-care if you have any ulcer in the genital, mouth, or anal area. Avoid sexual activity and notify your sexual partner(s) of your illness. Additionally, you should seek medical advice if you have had intimate contact with someone with syphilis, have been using intravenous drugs, or if you have engaged in sex with multiple or unknown partners.

Syphilis treatments your doctor may prescribe

Blood and fluid tests will be done to look for other infectious sexually transmitted diseases, which are often present along with syphilis.

Antibiotics (penicillin, doxycycline, or tetracycline) will be given, and blood tests will be done again; you will be followed for 2 years to be sure the infection is gone.

Do not engage in sexual activity until the chancre is healed and follow-up blood tests have shown that the infection has been cured.

Penicillin G, administered parenterally, is the preferred drug for treating persons in all stages of syphilis ⁸. The preparation used (i.e., benzathine, aqueous procaine, or aqueous crystalline), dosage, and length of treatment depend on the stage and clinical manifestations of the disease. Treatment for late latent syphilis and tertiary syphilis require a longer duration of therapy, because organisms theoretically might be dividing more slowly (the validity of this rationale has not been assessed). Longer treatment duration is required for persons with latent syphilis of unknown duration to ensure that those who did not acquire syphilis within the preceding year are adequately treated.

Selection of the appropriate penicillin preparation is important, because Treponema pallidum can reside in sequestered sites (e.g., the CNS and aqueous humor) that are poorly accessed by some forms of penicillin. Combinations of benzathine penicillin, procaine penicillin, and oral penicillin preparations are not considered appropriate for the treatment of syphilis. Reports have indicated that practitioners have inadvertently prescribed combination benzathine-procaine penicillin (Bicillin C-R) instead of the standard benzathine penicillin product (Bicillin L-A) widely used in the United States. Practitioners, pharmacists, and purchasing agents should be aware of the similar names of these two products to avoid using the inappropriate combination therapy agent for treating syphilis ⁹.

The effectiveness of penicillin for the treatment of syphilis was well established through clinical experience even before the value of randomized controlled clinical trials was recognized. Therefore, nearly all recommendations for the treatment of syphilis are based not only on clinical trials and observational studies, but many decades of clinical experience.

Chancroid vs Herpes

Genital herpes is a recurrent, lifelong skin infection caused by the herpes simplex virus (HSV). There are 2 types of herpes simplex virus: herpes simplex virus type 1 (HSV-1) and herpes simplex virus type 2 (HSV-2). Genital herpes is usually caused by herpes simplex virus type 2 (HSV-2) but can occasionally be due to herpes simplex virus type 1 (HSV-1). Herpes lesions on the face, sometimes referred to as cold sores, are primarily due to HSV-1. Herpes simplex virus infections are contagious and are spread to other people by skin-to-skin contact with the infected area.

Genital herpes can affect anyone who is sexually active. In fact, approximately 10–60% of the general population is infected with genital herpes.

Herpes is spread from person to person by direct skin-to-skin contact. The virus is most contagious when there are visible sores in the genital region. Herpes simplex virus can also be spread when there are no sores present, however, which is called asymptomatic shedding. Remember that only 20% of people who are infected with herpes simplex virus actually develop visible blisters or sores, which means that approximately 80% of people with herpes simplex virus have not been diagnosed and are unaware of their condition. Therefore, they can unknowingly transmit the infection to their sexual partners.

Both types of herpes simplex virus produce 2 kinds of infections: primary and recurrent. Because it is so contagious, herpes simplex virus causes a primary infection in most people who are exposed to the virus. However, only about 20% of people who are infected with herpes simplex virus actually develop visible blisters or sores. Appearing 5–6 days after a person’s first exposure to herpes simplex virus, the sores of a primary infection last about 2–6 weeks. These sores heal completely, rarely leaving a scar. Nevertheless, the virus remains in the body, hibernating in nerve cells.

Certain triggers can cause the hibernating virus to wake up, become active, and travel back to the skin, causing a recurrent infection. These outbreaks tend to be milder than primary infections and generally occur in the same location as the primary infection. The frequency of recurrence is unpredictable and tends to become less over time.

Herpes simplex virus signs and symptoms

A few days after exposure to HSV, a newly infected person typically develops a group of painful blisters or pus-filled bumps in the genital region. Because these fluid-filled lesions easily burst, many people never even notice them but instead see small, painful red sores or ulcers. These lesions usually last for 2–6 weeks for a primary infection and 5–10 days for recurrent infections. Eventually, a scab develops over each sore, which then falls off, leaving a red area that fades with time.

In women, the most common locations for herpes simplex virus type-2 infection are the external genitalia, vagina, cervix, and anus. In men, the most common locations for HSV-2 infection are the penis, scrotum, upper thighs, buttocks, and anus.

Primary genital herpes simplex virus infection can be severe, with many painful blisters causing pain or burning with urination and vaginal or urethral discharge. People may also develop fever, headache, muscle ache, and fatigue with a primary outbreak.

Recurrent herpes simplex virus infections are usually milder than the primary infection, though the lesions look similar. Many people with recurrent herpes simplex virus infections have burning, tingling, or pain in the area of the outbreak up to 24 hours before any visible signs. This is called the prodromal phase of the infection. Because many people never develop the symptoms of a primary herpes simplex virus infection, they may mistake a recurrent infection for a primary infection.

Most people will have a recurrence of genital herpes during the first year after a primary infection. On average, most people will get about 4 outbreaks per year, although the frequency of recurrence is extremely variable and tends to decrease over the years.

A recurrence of genital herpes usually occurs spontaneously, but it can also be triggered by the following:

• Fever or illness
• Sun exposure
• Hormonal changes, such as those due to menstruation or pregnancy
• Stress
• Trauma, such as those caused by dental work or cuts from shaving
• Surgery
• Immunosuppression
• Friction to the area – for example, with sexual intercourse or tight-fitting clothes

Genital herpes diagnosis

In the United States, most young, sexually active patients who have genital, anal, or perianal ulcers have either genital herpes or syphilis ¹⁰. The frequency of each condition differs by geographic area and population; however, genital herpes is the most prevalent of these diseases. More than one etiologic agent (e.g., herpes and syphilis) can be present in a genital, anal, or perianal ulcer. Less common infectious causes of genital, anal, or perianal ulcers include chancroid and donovanosis. Genital herpes, syphilis, and chancroid have been associated with an increased risk for HIV acquisition and transmission. Genital, anal, or perianal lesions can also be associated with infectious as well as noninfectious conditions that are not sexually transmitted (e.g., yeast, trauma, carcinoma, aphthae, fixed drug eruption, and psoriasis).

A diagnosis based only on medical history and physical examination frequently is inaccurate. Therefore, all persons who have genital, anal, or perianal ulcers should be evaluated; in settings where chancroid is prevalent, a test for Haemophilus ducreyi also should be performed. Specific evaluation of genital, anal, or perianal ulcers includes 1) syphilis serology, darkfield examination, or polymerase chain reaction (PCR) testing if available; 2) culture or polymerase chain reaction (PCR) testing for genital herpes; and 3) serologic testing for type-specific herpes simplex virus antibody.

No FDA-cleared polymerase chain reaction (PCR) test to diagnose syphilis is available in the United States, but two FDA-cleared polymerase chain reaction (PCR) tests are available for the diagnosis of HSV-1 and HSV-2 in genital specimens. Some clinical laboratories have developed their own syphilis and HSV PCR tests and have conducted Clinical Laboratory Improvement Amendment (CLIA) verification studies in genital specimens. Type-specific serology for HSV-2 might be helpful in identifying persons with genital herpes. In addition, biopsy of ulcers can help identify the cause of ulcers that are unusual or that do not respond to initial therapy. HIV testing should be performed on all persons with genital, anal, or perianal ulcers not known to have HIV infection.

Because early treatment decreases the possibility of transmission, public health standards require health-care providers to presumptively treat any patient with a suspected case of infectious syphilis at the initial visit, even before test results are available. Presumptive treatment of a patient with a suspected first episode of genital herpes also is recommended, because successful treatment depends on prompt initiation of therapy. The clinician should choose the presumptive treatment on the basis of clinical presentation (i.e., HSV lesions begin as vesicles and primary syphilis as a papule) and epidemiologic circumstances (e.g., high incidence of disease among populations and communities and travel history). For example, syphilis is so common in men who have sex with men that any man who has sex with men presenting with a genital ulcer should be presumptively treated for syphilis at the initial visit after syphilis and HSV tests are performed. After a complete diagnostic evaluation, at least 25% of patients who have genital ulcers have no laboratory-confirmed diagnosis ¹¹.

Genital herpes treatment at home

Acetaminophen (Tylenol®) or ibuprofen (Advil®, Motrin®) may help reduce pain, fever, and muscle aches that accompany the herpes sores. Applying ice packs or baking soda compresses may relieve some of the swelling and discomfort. Wear loose-fitting clothes and cotton underwear, and keep the infected area clean and dry.

Because herpes simplex virus infections are very contagious, it is important to take the following steps to prevent spread of the virus during the prodrome phase (burning, tingling, or pain) and active phase (presence of blisters or sores) of genital herpes simplex virus infections:

• Avoid sharing towels and other personal care items.
• Wash your hands with soap and water if you touch an active lesion. Herpes simplex virus can be spread to other parts of your body via infected hands.
• Avoid sexual contact (including oral, vaginal, and anal sex) during both the prodrome phase and the active phase.

Unfortunately, the herpes simplex virus can still be spread even when someone does not have lesions. Therefore, condoms should be used between outbreaks, even if no sores are present.

Recurrent outbreaks of genital herpes simplex virus usually do not require a visit to the doctor. However, because some people have milder forms of herpes, you should also see a doctor for any recurring rash in the genital area, even if you think it is from bug bites, jock itch, or any other condition.

If you have an underlying medical condition such as cancer or HIV, if you have undergone organ transplantation, or if you are pregnant, you are at higher risk for more serious complications from genital herpes. Seek medical advice as soon as possible if you develop any lesions.

Genital herpes can also be passed to a newborn baby during delivery through contact with a lesion in the mother’s genital tract. Be sure to speak with your obstetrician about the possible risk to your baby if you have genital herpes.

Genital herpes treatments your doctor may prescribe

Most herpes simplex virus infections are easy for physicians to diagnose. On occasion, however, a swab from the infected skin may be sent to the laboratory to confirm the diagnosis. A blood test may also be performed to determine if you have been exposed to the virus. Your doctor may also recommend a blood test for your partner to determine if he/she has been exposed to herpes in the past, or is at risk for contracting the virus.

Untreated herpes simplex virus infections will go away on their own, but antiviral medications can reduce symptoms, shorten the duration of outbreaks, and decrease the chance of spreading the virus. These medicines are most effective if taken during the first 24 hours of symptoms. If you experience burning and tingling before the appearance of blisters, you can start the medicine as soon as you feel these symptoms. Unfortunately, these medicines do not cure herpes simplex virus infections.

Treatment for primary and recurrent herpes simplex virus infections are oral antiviral medications, such as acyclovir (Zovirax®), valacyclovir (Valtrex®), and famciclovir (Famvir®). Each of these medications is equally effective and usually taken for 7–10 days for primary infections and 1–5 days (depending on dose) for recurrent infections. Talk to your doctor about getting a prescription for these medicines for possible future outbreaks, as they are most effective if taken early on.

More severe herpes simplex virus infections may require additional medications such as:

• Oral antibiotics if the area is also infected with bacteria
• Oral antifungals if the area is also infected with yeast
• Topical anesthetic cream, such as lidocaine ointment, to reduce pain

If you have frequent or severe herpes outbreaks, your doctor may recommend taking an antiviral medication every day to decrease the frequency and severity of attacks. This type of therapy may also be effective in decreasing the chance that an uninfected partner will acquire the virus. If you are taking a daily antiviral medicine to suppress your outbreaks, talk to your doctor about stopping these medicines yearly to see if you still need daily treatment.

Chancroid symptoms

Within 1 day to 2 weeks after becoming infected, a person will get a small bump on the genitals. The bump becomes an ulcer within a day after it first appears.

The chancroid ulcer:

• Ranges in size from 1/8 inch to 2 inches (3 millimeters to 5 centimeters) in diameter
• Is painful
• Is soft
• Has sharply defined borders
• Has a base that is covered with a gray or yellowish-gray material
• Has a base that bleeds easily if it is banged or scraped

About one half of infected men have only a single ulcer. Women often have 4 or more ulcers. The ulcers appear in specific locations.

Common locations in men are:

• Foreskin
• Groove behind the head of the penis
• Shaft of the penis
• Head of the penis
• Opening of the penis
• Scrotum

In women, the most common location for ulcers is the outer lips of the vagina (labia majora). “Kissing ulcers” may develop. Kissing ulcers are those that occur on opposite surfaces of the labia.

Other areas, such as the inner vagina lips (labia minora), the area between the genitals and the anus (perineal area), and the inner thighs may also be involved. The most common symptoms in women are pain with urination and intercourse.

The ulcer may look like the sore of primary syphilis (chancre).

About one half of the people who are infected with a chancroid develop enlarged lymph nodes in the groin.

In one half of people who have swelling of the groin lymph nodes, the nodes break through the skin and cause draining abscesses. The swollen lymph nodes and abscesses are also called buboes.

Chancroid possible complications

Complications include urethral fistulas and scars on the foreskin of the penis in uncircumcised males. People with chancroid should also be checked for other sexually transmitted infections, including syphilis, HIV, and genital herpes.

In people with HIV, chancroid may take much longer to heal.

Chancroid diagnosis

A definitive diagnosis of chancroid requires the identification of Haemophilus ducreyi (Gram-negative rod bacteria) on special culture media that is not widely available from commercial sources; even when these media are used, sensitivity is <80% ¹². No FDA-cleared polymerase chain reaction (PCR) test for Haemophilus ducreyi is available in the United States, but such testing can be performed by clinical laboratories that have developed their own PCR test and have conducted Clinical Laboratory Improvement Amendments (CLIA) verification studies in genital specimens.

Differential diagnosis of genital ulcers:

• Infectious (most common)* (Listed in order of frequency)
  • Genital herpes simplex virus
  • Syphilis
  • Chancroid
  • Lymphogranuloma venereum
  • Granuloma inguinale (donovanosis)
  • Fungal infection (e.g., Candida)
  • Secondary bacterial infection
• Noninfectious (less common)
  • Behçet syndrome
  • Fixed drug eruption
  • Psoriasis
  • Sexual trauma
  • Wegener granulomatosis

The combination of a painful genital ulcer and tender suppurative inguinal lymphadenopathy suggests the diagnosis of chancroid ¹³.

For both clinical and surveillance purposes, a probable diagnosis of chancroid can be made if all of the following criteria are met ¹⁴:

1. Patient has one or more painful genital ulcers;
2. The clinical presentation, appearance of genital ulcers and, if present, regional lymphadenopathy are typical for chancroid;
3. Patient has no evidence of Treponema pallidum (syphilis) infection by darkfield examination of ulcer exudate or by a serologic test for syphilis performed at least 7 days after onset of ulcers; and
4. A herpes simplex virus PCR test or herpes simplex virus culture performed on the ulcer exudate is negative.

Chancroid treatment

Successful treatment for chancroid cures the infection, resolves the clinical symptoms, and prevents transmission to others. In advanced cases, scarring can result despite successful therapy.

Recommended treatment regimens ¹⁴:

• Azithromycin 1 g orally in a single dose
  OR
• Ceftriaxone 250 mg IM in a single dose
  OR
• Ciprofloxacin 500 mg orally twice a day for 3 days
  OR
• Erythromycin base 500 mg orally three times a day for 7 days

Azithromycin and ceftriaxone offer the advantage of single-dose therapy. Worldwide, several isolates with intermediate resistance to either ciprofloxacin or erythromycin have been reported. However, because cultures are not routinely performed, data are limited regarding the current prevalence of antimicrobial resistance.

Other Management Considerations

Men who are uncircumcised and patients with HIV infection do not respond as well to treatment as persons who are circumcised or HIV-negative. Patients should be tested for HIV infection at the time chancroid is diagnosed. If the initial test results were negative, a serologic test for syphilis and HIV infection should be performed 3 months after the diagnosis of chancroid.

Follow-Up

Patients should be re-examined 3–7 days after initiation of therapy. If treatment is successful, ulcers usually improve symptomatically within 3 days and objectively within 7 days after therapy. If no clinical improvement is evident, the clinician must consider whether 1) the diagnosis is correct, 2) the patient is coinfected with another STD, 3) the patient is infected with HIV, 4) the treatment was not used as instructed, or 5) the H. ducreyi strain causing the infection is resistant to the prescribed antimicrobial. The time required for complete healing depends on the size of the ulcer; large ulcers might require >2 weeks. In addition, healing is slower for some uncircumcised men who have ulcers under the foreskin. Clinical resolution of fluctuant lymphadenopathy is slower than that of ulcers and might require needle aspiration or incision and drainage, despite otherwise successful therapy. Although needle aspiration of buboes is a simpler procedure, incision and drainage might be preferred because of reduced need for subsequent drainage procedures.

Management of Sex Partners

Regardless of whether symptoms of the disease are present, sex partners of patients who have chancroid should be examined and treated if they had sexual contact with the patient during the 10 days preceding the patient’s onset of symptoms.

Special Considerations

Pregnancy

Data suggest ciprofloxacin presents a low risk to the fetus during pregnancy, with a potential for toxicity during breastfeeding ¹⁵. Alternate drugs should be used during pregnancy and lactation. No adverse effects of chancroid on pregnancy outcome have been reported.

HIV Infection

Persons with HIV infection who have chancroid should be monitored closely because they are more likely to experience treatment failure and to have ulcers that heal slowly. Persons with HIV infection might require repeated or longer courses of therapy, and treatment failures can occur with any regimen. Data are limited concerning the therapeutic efficacy of the recommended single-dose azithromycin and ceftriaxone regimens in persons with HIV infection.

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