Sexually transmitted infections: Warts and ulcers: Pathology review
Definitions & Key takeaways
Sexually transmitted infections (STIs) are infections that are spread from person to person through sexual contact. Some can cause the formation of characteristic physical features, such as genital warts and ulcers. One STI that's known to cause warts, called condylomata acuminata, is caused by human papillomavirus, or HPV. On the other hand, STIs that may cause ulcers are numerous. They include genital herpes, caused by herpes simplex virus; syphilis caused by Treponema Pallidum; lymphogranuloma venereum, which is caused by Chlamydia Trachomatis; granuloma inguinale caused by Klebsiella granulomatis; and chancroid, which is caused by Haemophilus ducreyi. Treatment of ulcers focuses on threatening the underlying cause, whereas in condylomata acuminata, you treat the culprit microorganism, and remove the wart with topical medications like imiquimod, or techniques like cryotherapy or surgical excision.
Case Study0:00–1:19
A 35 year old female named Rae comes to the clinic one day with complaints of multiple verrucous skin lesions that have appeared over the anogenital region.
Upon further questioning, Rae tells you that her husband also developed the same lesions over the same region a few weeks ago, but hasn’t seeked medical attention.
On physical examination, you notice that the skin lesions are soft and flesh-colored, and have a unique cauliflower-like appearance.
You decide to perform a biopsy of the lesion, which reveals the presence of multiple vacuolated epithelial cells with enlarged, irregular nuclei.
A few days later, a 30 year old male named Mark comes to the clinic concerned about a painful ulcer that recently developed in his genital region.
Upon further questioning, he mentions that he’s sexually active, but doesn’t always use protection. On examination of the genital region, you notice that the ulcer is covered by exudate; in addition, Mark has inguinal lymphadenopathy, which is tender.
You obtain a sample of the exudate and order a gram staining, which shows gram-negative, rod-shaped bacteria arranged in parallel strands.
Pathology1:19–2:48
Now, based on the initial presentation, Rae has warts, while Mark has ulcers, and both cases seem to be caused by a sexually transmitted infection, or STI for short.
STIs are mainly transmitted from person to person during sexual contact through body fluids, such as vaginal secretions, semen, or blood.
The ones most at risk of contracting an STI are sexually active individuals, particularly those who have unprotected sex or multiple sexual partners.
But, it’s important to note that sexually transmitted infections can also be transmitted via contact with skin or mucous membranes, including eyes, mouth, throat, and anus.
And that’s a high yield fact!Now, a common STI that may cause warts, called condylomata acuminata, is caused by human papillomavirus, or HPV.
On the other hand, STIs that may cause ulcers include genital herpes, caused by herpes simplex virus, or HSV; syphilis caused by Treponema Pallidum; lymphogranuloma venereum, which is caused Chlamydia Trachomatis; granuloma inguinale caused by Klebsiella granulomatis; and chancroid, which is caused by Haemophilus ducreyi.
All right, let’s begin with condylomata acuminata, which are anogenital warts, or verrucae. Now, condylomata acuminata are caused by the human papillomavirus, or HPV.
Condylomata acuminata 2:48–4:13
In contrast, condylomata acuminata are caused by low risk HPV serotypes 6 and 11, so they are benign lesions. In a test question, look for lesions that’s soft, flesh-colored, and have a cauliflower-like look to their surface.
Though they are typically painless, they can cause itching or bleeding. For diagnosis, a high yield finding upon biopsy is koilocytosis, which refers to the presence of multiple vacuolated epithelial cells with enlarged, irregular nuclei.
Treatment of condylomata acuminata involves removal with topical medications like imiquimod, or techniques like cryotherapy or surgical excision.
Genital herpes 4:13–6:55
Next up, genital herpes infection is caused by the herpes simplex virus, primarily by serotype 2, or HSV-2, and sometimes serotype 1, or HSV-1.
HSV is most often transmitted through direct contact with active herpes lesions, but can also be transmitted through saliva or genital secretions of infected individuals.
When a person gets infected by HSV-2, at first it enters the skin cells, where it starts replicating. As a result, individuals develop painful and itchy vesicles and ulcers over the genital area.
In addition, there can be tender inguinal lymphadenopathy, as well as systemic symptoms like fever, headache, and myalgia.
HSV-2 can also infect nearby neurons, and travel up their axon to the neuron’s cell body, where it remains latent. So that’s ultimately where the virus settles in for life!
For your exams, remember that HSV-2 typically remains latent in the sacral ganglia. From time to time, the virus can reactivate and travel back down the axon to the skin cells.
Keep in mind that genital herpes during pregnancy can spread to the fetus through the placenta, or during childbirth, when the baby passes through infected vaginal secretions.
Neonatal herpes presents with the characteristic vesicular skin lesions, which mainly involve the scalp, the eyelid margins, and the oral mucosa; but can also lead to meningoencephalitis, or inflammation of the meninges and the brain.Now, diagnosis of HSV infection can be made by collecting a sample from a skin lesion, and performing a viral culture or a PCR.
In addition, a Tzanck smear can be done, which shows multinucleated giant cells with intranuclear inclusion bodies known as Cowdry A bodies.
Finally, serology can help identify anti-HSV antibodies. Although genital herpes typically resolves without treatment within a couple of weeks, treatment with antiviral medications like valacyclovir or acyclovir can help reduce pain and speed up healing.Another common STI that causes ulcers is syphilis, which is caused by the spirochete Treponema pallidum.
Syphilis6:55–15:20
Now, syphilis is a progressive disease that has three stages. The first stage is called primary syphilis or early localized stage, and it’s characterized by the presence of a solitary, painless genital ulcer called chancre, which has a hard base, raised borders, and is usually covered by an exudate that’s rich in spirochetes.
Generally, the chancre can appear anytime within 3 weeks from the initial infection, and typically heals on its own without any treatment within 3 to 6 weeks.
However, during that time, some spirochetes manage to disseminate into the bloodstream.This dissemination leads to the second stage, called secondary syphilis, or the dissemination stage, which can occur about 2 to 10 weeks after the initial infection.
Secondary syphilis may present with constitutional symptoms, such as fever, headache, and malaise, as well as generalized lymphadenopathy and patchy hair loss.
But what’s really important to note is that secondary syphilis is characterized by a non-itchy maculopapular rash, with small bumps that start on the trunk and spread out to the arms and legs, including the palms and soles, and eventually to the genitalia, and other mucous membranes.
Be sure you don’t get these mixed up with condylomata acuminata caused by HPV! Now, secondary syphilis usually resolves within a few weeks to months.
At this point, the disease enters a dormant stage called latent syphilis, which can last from 1 year up to even 20 years!
During the latent stage, individuals are typically asymptomatic, but may still be contagious. Eventually, individuals who don’t get any treatment can progress into the final stage of syphilis, which is called tertiary syphilis.
Here, the immune cells start to huddle around and form characteristic granulomatous lesions called gummas. Often, funnily enough, there aren’t any spirochetes at all in these lesions.
In addition to gummas, various organs get damaged during tertiary syphilis, but for your exams, the most important ones to remember are the heart and blood vessels leading to cardiovascular syphilis, as well as the brain and spinal cord leading to neurosyphilis.
Now, in cardiovascular syphilis, there’s damage to the vasa vasorum, which are the blood vessels that supply the aortic wall.
This leads to syphilitic aortitis, or inflammation of the aortic wall, which can result in complications like aortic aneurysms.
On the other hand, neurosyphilis presents with symptoms of meningitis, such as a fever, headache, and neck stiffness. Over time, neurosyphilis can lead to altered mood and behavior, as well as confusion and dementia.
Additionally, neurosyphilis can cause slow and progressive degeneration of the spinal column, leading to a loss of the sensations of pressure, fine touch, vibrations, and proprioception.
This is also known as “tabes dorsalis”. For your test, you need to know that without the sensations of vibration and proprioception, the individual will often lose coordination, and experience difficulty walking.
As a result, they may present with wide-based ataxia, meaning that they stand or walk with their feet spaced widely apart.
Another telltale finding is a positive Romberg sign which means that they can’t maintain balance with their eyes closed.
Neurosyphilis can also result in general paresis, weakness, or sometimes even paralysis, mostly in the legs. Finally, neurosyphilis can affect the eye, causing an Argyll Robertson pupil.
This means the pupils lose their light reflex, so they do not constrict when exposed to light, but they still have their accommodation reflex, so they do constrict when focusing on an object that is close by.
Now, keep in mind that syphilis can also be passed during pregnancy to the fetus, causing congenital syphilis. This often results in hydrops fetalis, which is when the fetus has an abnormal accumulation of fluid in soft tissues.
This poses a great risk for stillbirth, which is when the fetus dies within the womb. Babies who survive the pregnancy typically develop some characteristic features, such as frontal bossing, a saddle nose, and a short maxilla.
Now, diagnosis of syphilis starts with identifying spirochetes in the exudate from the chancre, and this can be done using dark field microscopy.
In addition, there are serological tests for syphilis, which are divided into non-treponemal tests and treponemal-tests.
Non-treponemal tests assess if the individual has antibodies that react to a beef cardiolipin antigen, and some examples you must absolutely remember include Rapid Plasma Reagin or RPR test and Venereal Disease Research Laboratory or VDRL test.
Keep in mind though that non-treponemal tests are non-specific for syphilis, and can give false-positive results in case of other infectious diseases, such as infectious mononucleosis, hepatitis, and leprosy; as well as in certain autoimmune diseases like systemic lupus erythematosus, antiphospholipid antibody syndrome, and rheumatoid arthritis; false positives may also occur during pregnancy, and in those who take certain medications like chlorpromazine and procainamide.
And that’s very high yield! On the other hand, treponemal tests are specific tests for syphilis that detect antibodies against treponemal antigens.
Important examples include fluorescent treponemal antibody absorption or FTA-ABS, Treponema pallidum particle agglutination assay or TPPA, and micro-hemagglutination test for antibodies to Treponema pallidum or MHA-TP.
What’s important to know is that generally, individuals are first tested with a non-treponemal test, and if that comes out positive, a treponemal test like FTA-ABS is performed.
If the treponemal test is also positive, diagnosis of syphilis is confirmed, but if it’s negative, then the initial non-treponemal test is considered a false-positive.
Treatment of syphilis is typically with intramuscular Penicillin G. When using penicillin, though, look out for a Jarisch-Herxheimer reaction, which is when large numbers of spirochetes die and break open, releasing a lot of antigens all at once.
As a result, the immune system goes into overdrive, causing a flu-like syndrome with sudden fever, sweating, muscle and joint pain, which may last for a few hours to a few days.
Jarisch-Herxheimer reaction is usually treated with supportive care.Another STI that may cause ulcers is lymphogranuloma venereum, or LGV LVG for short.
Lymphogranuloma venereum15:20–16:37
This is caused by serotypes L1, L2, and L3 of Chlamydia trachomatis, which is a gram-negative obligate intracellular bacterium, meaning that it needs to infect and enter a host cell to be able to replicate.
Initially, LGV LVG can present with skin lesions over the genital area, such as painless, small papules or granulomas, as well as shallow ulcers.
These lesions tend to heal very quickly and often go unnoticed by the individual. After about 2 to 4 weeks, LGV LVG moves on to infect the inguinal lymph nodes.
As a result, individuals develop painful inguinal lymphadenopathy, or enlarged lymph nodes, called buboes. If not treated, buboes can become inflamed and fixate on the overlying skin, leading to complications like abscesses, fistulas, or necrosis.
Treatment typically involves antibiotics like doxycycline or azithromycin.Moving on, the next bacterial STI is granuloma inguinale, also called donovanosis or granuloma venereum, but make sure you don’t confuse this with lymphogranuloma venereum!
Granuloma inguinale (Donovanosis)16:37–18:28
Now, granuloma inguinale is caused by Klebsiella granulomatis, which is a gram-negative obligate intracellular bacterium.
For your exams, note that granuloma inguinale is very uncommon in the United States, but can still be encountered in tropical countries, such as India, Papua New Guinea, the Caribbean, South America, and Australia.
The papule then progresses to an extensive, but still painless ulcer, which is highly vascular. This gives the ulcer a beefy red appearance, and causes it to bleed easily when touched.
Another high yield fact is that, unlike other bacterial STIs like lymphogranuloma venereum or syphilis, granuloma inguinale does not usually cause lymphadenopathy.Now, diagnosis of granuloma inguinale can be confirmed by collecting a smear or biopsy of the ulcer, which reveal the characteristic Donovan bodies, which are gram-negative cytoplasmic bacteria within the host cells that resemble “safety pins” on microscopic examination.
Treatment of granuloma inguinale usually involves at least 3 weeks of antibiotics, most often with oral azithromycin.Last but not least is chancroid, which is caused by the gram-negative bacterium Haemophilus ducreyi.
Chancroid18:28–19:53
Now, the hallmark symptom of the chancroid is a painful ulcer with soft irregular margins that develops over the genital region.
So what sets chancroid apart is that the ulcer is painful, so painful you do cry… get it? In addition, many cases of chancroid can present with painful inguinal lymphadenopathy.
And that’s an important difference with granuloma inguinale. Chancroid can be diagnosed by PCR, culture, and gram staining of the ulcer exudate.
What’s unique about chancroid is that the gram stain shows gram-negative rods arranged in a parallel formation, also called school of fish appearance.
Treatment of chancroid typically involves a single dose of antibiotics, most often with oral azithromycin or an intramuscular injection of ceftriaxone.All right, as a quick recap… Condylomata acuminata are caused by low risk HPV serotypes 6 and 11, and manifest as benign anogenital warts that are typically soft, flesh-colored, and have a cauliflower-like look.
Recap19:53–22:51
For diagnosis, a characteristic finding upon biopsy is koilocytosis, and treatment involves removal. Genital herpes is most commonly caused by HSV-2, and presents with painful and itchy vesicles and ulcers, as well as tender inguinal lymphadenopathy, and systemic symptoms like fever, headache, and myalgia.
Diagnosis can be done with viral culture, PCR, and a Tzanck smear to show multinucleated giant cells with Cowdry A bodies; and treatment can involve acyclovir.
Syphilis is caused by Treponema pallidum. Primary syphilis presents with a painless chancre.
Secondary syphilis presents with constitutional symptoms; and generalized lymphadenopathy; as well as a maculopapular rash that starts on the trunk and spreads out to the rest of the body, including the palms and soles; and condylomata lata over the genital area.
Finally, tertiary syphilis is characterized by gummas, and may lead to cardiovascular syphilis or neurosyphilis. Diagnosis can involve dark field microscopy of the chancre exudate; non-treponemal tests like RPR and VDRL; and treponemal-tests like FT-ABS, TPPA, and MHA-TP.
Treatment of syphilis involves penicillin G, but to look out for a Jarisch-Herxheimer reaction. Lymphogranuloma venereum is caused by chlamydia trachomatis serotypes L1, L2, and L3, and presents with painless genital ulcers, as well as painful and enlarged inguinal lymph nodes called buboes.
Granuloma inguinale, or donovanosis, is caused by Klebsiella granulomatis, and presents with a painless, beefy red ulcer that bleeds easily when touched.
Diagnosis involves the detection of Donovan bodies on microscopic examination. Chancroid is caused by Haemophilus ducreyi, and presents with painful genital ulcers covered with purulent exudate, as well as painful inguinal lymphadenopathy.
For diagnosis, gram stain shows a characteristic school of fish arrangement. Okay, back to our cases.
Rae is a 35 year old female who presents with multiple anogenital warts. A relevant clue is the fact that also her husband developed the same lesions over the same region, which indicates that it’s probably a sexually transmitted infection.
Summary22:51–24:11
The most important clue though is physical examination, which reveals a soft, flesh-colored, lesion with a unique cauliflower-like appearance.
This should already point you to the right answer, that Rae presents with condylomata acuminata, but as a bonus finding, there’s koilocytosis upon biopsy, which confirms the diagnosis.On the other hand, Mark is a 30 year old male with a history of unprotected sexual contact, and presents with a genital ulcer with exudate associated with tender inguinal lymphadenopathy.
This presentation is very common among many STIs, so a big clue here is that the ulcer is painful, which points to either genital herpes or chancroid.
The real key is the exudate gram-staining, which reveals gram-negative rods arranged in a school of fish pattern, confirming the diagnosis of chancroid.
which revealed gram-negative rods arranged in a school of fish pattern, confirming the diagnosis of chancroid.
No notes for this video yet
Try adding a note below