Wednesday, November 28, 2018

one hour ago

Scientists regrow hair on wounded skin

The findings by researchers at the New York University (NYU) School of Medicine in the US better explain why hair does not normally grow on wounded skin.

Reported by: PTI, New York [ Published on: November 28, 2018 15:32 IST ]

Researchers have regrown hair strands on damaged skin by stirring crosstalk among skin cells that form the roots of hair.

The findings by researchers at the New York University (NYU) School of Medicine in the US better explain why hair does not normally grow on wounded skin.
The study, published in the journal Nature Communications, may help in the search for better drugs to restore hair growth.
It examined the effect of distinct signalling pathways in damaged skin of laboratory mice.
Experiments focused on cells called fibroblasts that secrete collagen, the structural protein most responsible for maintaining the shape and strength of skin and hair.
Researchers activated the sonic hedgehog signalling pathway used by cells to communicate with each other.
The pathway is known to be very active during the early stages of human growth in the womb, when hair follicles are formed, but is otherwise stalled in wounded skin in healthy adults.
Researchers said this possibly explains why hair follicles fail to grow in skin replaced after injury or surgery.

"Our results show that stimulating fibroblasts through the sonic hedgehog pathway can trigger hair growth not previously seen in wound healing," said Mayumi Ito, an associate professor at NYU.
Regrowing hair on damaged skin is an unmet need in medicine, Ito said, because of the disfigurement suffered by thousands from trauma, burns, and other injuries.
However, her more immediate goal, she said, is to signal mature skin to revert back to its embryonic state so that it can grow new hair follicles, not just on wounded skin, but also on people who have gone bald from ageing.
Ito said scientists have until now assumed that, as part of the healing process, scarring and collagen buildup in damaged skin were behind its inability to regrow hair.
"Now we know that it's a signalling issue in cells that are very active as we develop in the womb, but less so in mature skin cells as we age," she said.
Key among the study's findings was that no signs of hair growth were observed in untreated skin, but were observed in treated skin, offering evidence that sonic hedgehog signalling was behind the hair growth, researchers said.
To bypass the risk of tumours reported in other experiments that turned on the sonic hedgehog pathway, the team turned on only fibroblasts located just beneath the skin's surface where hair follicle roots (dermal papillae) first appear.
Researchers also zeroed in on fibroblasts because the cells are known to help direct some of the biological processes involved in healing.
Hair regrowth was observed within four weeks after skin wounding in all treated mice, with hair root and shaft structures starting to appear after nine weeks.

Hedgehog Signaling Interactive Pathway

Pathway Description:

The evolutionarily conserved Hedgehog (Hh) pathway is essential for normal embryonic development and plays critical roles in adult tissue maintenance, renewal and regeneration. Secreted Hh proteins act in a concentration- and time-dependent manner to initiate a series of cellular responses that range from survival and proliferation to cell fate specification and differentiation.

Proper levels of Hh signaling require the regulated production, processing, secretion and trafficking of Hh ligands– in mammals this includes Sonic (Shh), Indian (Ihh) and Desert (Dhh). All Hh ligands are synthesized as precursor proteins that undergo autocatalytic cleavage and concomitant cholesterol modification at the carboxy terminus and palmitoylation at the amino terminus, resulting in a secreted, dually-lipidated protein. Hh ligands are released from the cell surface through the combined actions of Dispatched and Scube2, and subsequently trafficked over multiple cells through interactions with the cell surface proteins LRP2 and the Glypican family of heparan sulfate proteoglycans (GPC1-6).

Hh proteins initiate signaling through binding to the canonical receptor Patched (PTCH1) and to the co-receptors GAS1, CDON and BOC. Hh binding to PTCH1 results in derepression of the GPCR-like protein Smoothened (SMO) that results in SMO accumulation in cilia and phosphorylation of its cytoplasmic tail. SMO mediates downstream signal transduction that includes dissociation of GLI proteins (the transcriptional effectors of the Hh pathway) from kinesin-family protein, Kif7, and the key intracellular Hh pathway regulator SUFU.

GLI proteins also traffic through cilia and in the absence of Hh signaling are sequestered by SUFU and Kif7, allowing for GLI phosphorylation by PKA, GSK3β and CK1, and subsequent processing into transcriptional repressors (through cleavage of the carboxy-terminus) or targeting for degradation (mediated by the E3 ubiquitin ligase β-TrCP). In response to activation of Hh signaling, GLI proteins are differentially phopshorylated and processed into transcriptional activators that induce expression of Hh target genes, many of which are components of the pathway (e.g. PTCH1 and GLI1). Feedback mechanisms include the induction of Hh pathway antagonists (PTCH1, PTCH2 and Hhip1) that interfere with Hh ligand function, and GLI protein degradation mediated by the E3 ubiquitin ligase adaptor protein, SPOP.

In addition to vital roles during normal embryonic development and adult tissue homeostasis, aberrant Hh signaling is responsible for the initiation of a growing number of cancers including, classically, basal cell carcinoma, edulloblastoma, and rhabdomyosarcoma; more recently overactive Hh signaling has been implicated in pancreatic, lung, prostate, ovarian, and breast cancer. Thus, understanding the mechanisms that control Hh pathway activity will inform the development of novel therapeutics to treat a growing number of Hh-driven pathologies.

Researchers regrow hair on wounded skin

Medical Xpress

3 hours ago

Tuesday, November 27, 2018

Herpes Test: What You Should Know

Genital herpes is a common sexually transmitted disease. It’s caused by two different viruses called herpes simplex type 1 (HSV-1) and herpes simplex type 2 (HSV-2
). Image result for Herpes Simplex

You get genital herpes by having sex -- vaginal, oral, or anal -- with someone who already has it.
Thinking you have genital herpes naturally can bring up strong emotions. Talk to your doctor about getting tested. It could help you to learn more about the disease and talk honestly with your sexual partner. You might want to join a support group, too.

Do I Need to Get Tested?

Many people with herpes don’t have any symptoms. If symptoms do show up, you might first feel tingling or burning near your genitals.
You might then get blisters around your genitals, anus, thighs, or buttocks. When the blisters break, they leave sores that can take a few weeks to heal. They usually won’t leave any scars.
To check for herpes, your doctor usually does a physical exam and then likely orders one of these tests:

Viral culture
Polymerase chain reaction (PCR) test
Blood test

If you get a “positive” result from the viral culture or PCR tests, it likely means you have herpes. .
A “negative” viral culture or PCR result could mean you don’t have genital herpes. But in some cases, a person could still have genital herpes and a negative result. That's likely due to other factors related to how much virus there is in the sores.
You don’t need to do anything to prepare for these tests. They don’t take long, but how soon you get your results depends on the type of test and the lab that does it.

Viral Culture

For this test, your doctor scrapes or swabs one of your sores to take a sample. A lab then checks the sample for the herpes virus. It can take up to 7 days to get your results.
This test is best used within 48 hours of when you first see symptoms. After that time, the level of herpes virus starts to drop. That means there’s a higher chance the test could say you don’t have herpes when you really do.

Polymerase Chain Reaction (PCR) Test

As with the viral culture, your doctor swabs or scrapes a sample from one of your sores. A lab gets the sample and looks for genes from the herpes virus. PCR test results usually come back to you within 24 hours.
You’re more likely to get this test if you have symptoms but it’s been longer than 48 hours since they showed up. In this case, you can rely on the results from this test more than the viral culture.

Blood Test

A small amount of blood is sent to a lab that then checks it for herpes “antibodies.” Those are something your body makes to fight the virus.

Continue Reading Below

You might get a blood test if you think you have been exposed but you don’t have any symptoms.
Labs may use different types of blood tests. With some you can get results the same day, but others may take up to 3 weeks.

Next Steps

There’s no cure for genital herpes, but it can be treated.
If you do have it, your doctor can help you manage it. There are drugs that can shorten or prevent outbreaks, ease symptoms, and lower the chances your sex partners will get it.

Sunday, November 25, 2018

First Gene-Edited Babies Claimed in China

AP Exclusive: First Gene-Edited Babies Claimed in China - The New ...

https://www.nytimes.com/.../2018/.../ap-us-med-genetic-frontiers-gene-edited-babies.ht...

2 hours ago - A Chinese researcher claims that he helped make the world's first genetically edited babies — twin girls whose DNA he said he altered with a ...

Nov. 25, 2018

HONG KONG — A Chinese researcher claims that he helped make the world's first genetically edited babies — twin girls born this month whose DNA he said he altered with a powerful new tool capable of rewriting the very blueprint of life.

If true, it would be a profound leap of science and ethics.

A U.S. scientist said he took part in the work in China, but this kind of gene editing is banned in the United States because the DNA changes can pass to future generations and it risks harming other genes.

Many mainstream scientists think it's too unsafe to try, and some denounced the Chinese report as human experimentation.

The researcher, He Jiankui of Shenzhen, said he altered embryos for seven couples during fertility treatments, with one pregnancy resulting thus far. He said his goal was not to cure or prevent an inherited disease, but to try to bestow a trait that few people naturally have — an ability to resist possible future infection with HIV, the AIDS virus.

He said the parents involved declined to be identified or interviewed, and he would not say where they live or where the work was done.

There is no independent confirmation of He's claim, and it has not been published in a journal, where it would be vetted by other experts. He revealed it Monday in Hong Kong to one of the organizers of an international conference on gene editing that is set to begin Tuesday, and earlier in exclusive interviews with The Associated Press.

"I feel a strong responsibility that it's not just to make a first, but also make it an example," He told the AP. "Society will decide what to do next" in terms of allowing or forbidding such science.

Some scientists were astounded to hear of the claim and strongly condemned it.

It's "unconscionable ... an experiment on human beings that is not morally or ethically defensible," said Dr. Kiran Musunuru, a University of Pennsylvania gene editing expert and editor of a genetics journal.

"This is far too premature," said Dr. Eric Topol, who heads the Scripps Research Translational Institute in California. "We're dealing with the operating instructions of a human being. It's a big deal."

However, one famed geneticist, Harvard University's George Church, defended attempting gene editing for HIV, which he called "a major and growing public health threat."

"I think this is justifiable," Church said of that goal.

In recent years scientists have discovered a relatively easy way to edit genes, the strands of DNA that govern the body. The tool, called CRISPR-cas9, makes it possible to operate on DNA to supply a needed gene or disable one that's causing problems.

It's only recently been tried in adults to treat deadly diseases, and the changes are confined to that person. Editing sperm, eggs or embryos is different — the changes can be inherited. In the U.S., it's not allowed except for lab research. China outlaws human cloning but not specifically gene editing.

He Jiankui (HEH JEE'-an-qway), who goes by "JK," studied at Rice and Stanford universities in the U.S. before returning to his homeland to open a lab at Southern University of Science and Technology of China in Shenzhen, where he also has two genetics companies.

The U.S. scientist who worked with him on this project after He returned to China was physics and bioengineering professor Michael Deem, who was his adviser at Rice in Houston. Deem also holds what he called "a small stake" in — and is on the scientific advisory boards of — He's two companies.

The Chinese researcher said he practiced editing mice, monkey and human embryos in the lab for several years and has applied for patents on his methods.

He said he chose embryo gene editing for HIV because these infections are a big problem in China. He sought to disable a gene called CCR5 that forms a protein doorway that allows HIV, the virus that causes AIDS, to enter a cell.

All of the men in the project had HIV and all of the women did not, but the gene editing was not aimed at preventing the small risk of transmission, He said. The fathers had their infections deeply suppressed by standard HIV medicines and there are simple ways to keep them from infecting offspring that do not involve altering genes.

Instead, the appeal was to offer couples affected by HIV a chance to have a child that might be protected from a similar fate.

He recruited couples through a Beijing-based AIDS advocacy group called Baihualin. Its leader, known by the pseudonym "Bai Hua," told the AP that it's not uncommon for people with HIV to lose jobs or have trouble getting medical care if their infections are revealed.

Here is how He described the work:

The gene editing occurred during IVF, or lab dish fertilization. First, sperm was "washed" to separate it from semen, the fluid where HIV can lurk. A single sperm was placed into a single egg to create an embryo. Then the gene editing tool was added.

When the embryos were 3 to 5 days old, a few cells were removed and checked for editing. Couples could choose whether to use edited or unedited embryos for pregnancy attempts. In all, 16 of 22 embryos were edited, and 11 embryos were used in six implant attempts before the twin pregnancy was achieved, He said.

Tests suggest that one twin had both copies of the intended gene altered and the other twin had just one altered, with no evidence of harm to other genes, He said. People with one copy of the gene can still get HIV, although some very limited research suggests their health might decline more slowly once they do.

Several scientists reviewed materials that He provided to the AP and said tests so far are insufficient to say the editing worked or to rule out harm.

They also noted evidence that the editing was incomplete and that at least one twin appears to be a patchwork of cells with various changes.

"It's almost like not editing at all" if only some of certain cells were altered, because HIV infection can still occur, Church said.

Church and Musunuru questioned the decision to allow one of the embryos to be used in a pregnancy attempt, because the Chinese researchers said they knew in advance that both copies of the intended gene had not been altered.

"In that child, there really was almost nothing to be gained in terms of protection against HIV and yet you're exposing that child to all the unknown safety risks," Musunuru said.

The use of that embryo suggests that the researchers' "main emphasis was on testing editing rather than avoiding this disease," Church said.

Even if editing worked perfectly, people without normal CCR5 genes face higher risks of getting certain other viruses, such as West Nile, and of dying from the flu. Since there are many ways to prevent HIV infection and it's very treatable if it occurs, those other medical risks are a concern, Musunuru said.

There also are questions about the way He said he proceeded. He gave official notice of his work long after he said he started it — on Nov. 8, on a Chinese registry of clinical trials.

It's unclear whether participants fully understood the purpose and potential risks and benefits. For example, consent forms called the project an "AIDS vaccine development" program.

The Rice scientist, Deem, said he was present in China when potential participants gave their consent and that he "absolutely" thinks they were able to understand the risks.

Deem said he worked with He on vaccine research at Rice and considers the gene editing similar to a vaccine.

"That might be a layman's way of describing it," he said.

Both men are physics experts with no experience running human clinical trials.

The Chinese scientist, He, said he personally made the goals clear and told participants that embryo gene editing has never been tried before and carries risks. He said he also would provide insurance coverage for any children conceived through the project and plans medical follow-up until the children are 18 and longer if they agree once they're adults.

Further pregnancy attempts are on hold until the safety of this one is analyzed and experts in the field weigh in, but participants were not told in advance that they might not have a chance to try what they signed up for once a "first" was achieved, He acknowledged. Free fertility treatment was part of the deal they were offered.

He sought and received approval for his project from Shenzhen Harmonicare Women's and Children's Hospital, which is not one of the four hospitals that He said provided embryos for his research or the pregnancy attempts.

Some staff at some of the other hospitals were kept in the dark about the nature of the research, which He and Deem said was done to keep some participants' HIV infection from being disclosed.

"We think this is ethical," said Lin Zhitong, a Harmonicare administrator who heads the ethics panel.

Any medical staff who handled samples that might contain HIV were aware, He said. An embryologist in He's lab, Qin Jinzhou, confirmed to the AP that he did sperm washing and injected the gene editing tool in some of the pregnancy attempts.

The study participants are not ethicists, He said, but "are as much authorities on what is correct and what is wrong because it's their life on the line."

"I believe this is going to help the families and their children," He said. If it causes unwanted side effects or harm, "I would feel the same pain as they do and it's going to be my own responsibility."

___

AP Science Writer Christina Larson, AP videographer Emily Wang and AP translator Fu Ting contributed to this report from Beijing and Shenzhen, China.

Friday, November 23, 2018

Now, a way to diagnose ovarian cancer early Australian scientists develop a blood test that can

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Thursday, November 22, 2018

Herpes

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Home Diseases and Conditions Herpes

Condition

Herpes

What is herpes?

Herpes is the name of a group of viruses that cause painful blisters and sores. The most common viruses are:

Herpes zoster – causes chickenpox and shingles
Herpes simplex virus (HSV) type 1 and type 2 – causes cold sores or fever blisters around the mouth and sores on the genitals (sexual organs).

Genital herpes is a sexually transmitted infection (STI). Once you are infected, you have the virus for the rest of your life.

Symptoms of herpes

Many people who get herpes never have symptoms. Sometimes the symptoms are mild and are mistaken for another skin condition. If you experience symptoms, they may include:

painful sores in the genital area, anus, buttocks, or thighs
itching
painful urination
vaginal discharge
tender lumps in the groin.

During the first outbreak (called primary herpes), you may experience flu-like symptoms. These include body aches, fever, and headache. Many people who have a herpes infection will have outbreaks of sores and symptoms from time to time. Symptoms are usually less severe than the primary outbreak. The frequency of outbreaks also tends to decrease over time.

Stages of infection

Once you have been infected with the virus, you’ll go through different stages of infection.

Primary stage

This stage usually starts 2 to 8 days after you’re infected. Usually, the infection causes groups of small, painful blisters. The fluid in the blisters may be clear or cloudy. The area under the blisters will be red. The blisters break open and become open sores. You may not ever notice the blisters, or they may be painful. It may hurt to urinate during this stage. You may run a fever, feel achy, and have other flu-like symptoms.

While most people have a painful primary stage of infection, some don’t have any symptoms at all. They may not even know they’re infected.

Latent stage

During this stage, there are no blisters, sores, or other symptoms. The virus is traveling from your skin into the nerves near your spine.

Shedding stage

In the shedding stage, the virus starts multiplying in the nerve endings. If these nerve endings are in areas of the body that make or are in contact with body fluids, the virus can get into those body fluids. This could include saliva, semen, or vaginal fluids. There are no symptoms during this stage, but the virus can be spread during this time.

Recurrences

Many people have blisters and sores that come back after the first herpes attack goes away. This is called a recurrence. Usually, the symptoms aren’t as bad as they were during the first attack.

Stress, being sick, or being tired may start a recurrence. Being in the sun or having your menstrual period may also cause a recurrence. You may know when a recurrence is about to happen because you may feel itching, tingling, or pain in the places where you were first infected.

What causes herpes?

The virus that causes genital herpes is usually spread from one person to another during vaginal, oral, or anal sex. The virus can enter your body through a break in your skin. It can also enter through the skin of your mouth, penis, vagina, urinary tract opening, or anus. Herpes is most easily spread when blisters or sores can be seen on the infected person. But it can be spread at any time, even when the person who has herpes isn’t experiencing any symptoms.

Herpes can also be spread from one place on your body to another. If you touch sores on your genitals, you can carry the virus on your fingers. Then you can pass it onto other parts of your body, including your mouth or eyes.

A pregnant woman should tell her doctor if she has genital herpes, or if she has ever had sex with someone who had it. If you have an active genital herpes infection at or near the time of delivery, you can pass it to your baby. When the baby passes through the birth canal, it may come in contact with sores and become infected with the virus. This can cause brain damage, blindness, or even death in newborns.

If you have an active herpes outbreak when you go into labor, your doctor may do a cesarean section (C-section). Then the baby won’t have to go through the birth canal and be exposed to the virus.

How is herpes diagnosed?

Your doctor will do a physical exam and look at the sores. He or she can do a culture of the fluid from a sore and test it for herpes. Blood tests or other tests on the fluid from a blister can also be done.

Can herpes be prevented or avoided?

The best way to prevent getting herpes is to not have sex with anyone who has the virus. It can be spread even when the person who has it isn’t showing any symptoms. If your partner has herpes, there is no way of knowing for sure that you won’t get it.

There is no time that is completely safe to have sex and not spread herpes. If you have herpes, you must tell your sex partner. You should avoid having sex if you have any sores. Herpes can spread from one person to another very easily when sores are present.

You should use condoms every time you have sex. They can help reduce the risk of spreading herpes. It is still possible to spread or get herpes if you are using a condom.

Herpes treatment

If you think you have herpes, see your doctor as soon as possible. It is easier to diagnose when there are sores. You can start treatment sooner and perhaps have less pain with the infection.

There is no cure for herpes. But medicines can help. Medicines such as acyclovir and valacyclovir fight the herpes virus. They can speed up healing and lessen the pain of herpes for many people. They can be used to treat a primary outbreak or a recurrent one.

If the medicines are being used to treat a repeat outbreak, they should be started as soon as you feel any tingling, burning, or itching. They can also be taken every day to prevent recurrences. Acyclovir also comes in a cream to put on sores during the primary stage or during recurrences.

What if I have herpes and become pregnant?

If you have genital herpes and are pregnant, be sure to tell your doctor. He or she will give you an antiviral medicine. This will make it less likely that you will have an outbreak at or near the time you deliver your baby. If you do have an outbreak of genital herpes at the time of delivery, your doctor will most likely deliver your baby by C-section. With a C-section, the risk of giving herpes to your baby is small.

What if I get herpes during pregnancy?

If you have your first genital herpes outbreak during pregnancy, tell your doctor. He or she may want to treat you with an antiviral medicine. The risk of your baby getting herpes is much higher if you have your first genital herpes outbreak near the time of delivery.

It is important to avoid getting herpes during pregnancy. If your partner has herpes and you do not have it, be sure to use condoms during sexual intercourse at all times. Your partner could pass the infection to you even if he is not currently experiencing an outbreak. If there are visible sores, avoid having sex completely until the sores have healed.

Living with herpes

It’s common to feel guilty or ashamed when you are diagnosed with herpes. You may feel that your sex life is ruined or that someone you thought you could trust has hurt you. You may feel sad or upset. Talk to your family doctor about how you’re feeling.

Keep in mind that herpes is very common. About 1 in 6 adults have it. Herpes may get less severe as time goes by. You can help protect your sex partner by not having sex during outbreaks and by using condoms at other times.

Tips on dealing with herpes

Talk to your doctor if you think you may have herpes.
Remember that you’re not alone. Millions of people have herpes.
Keep yourself healthy and limit your stress.
Don’t touch your sores.
Tell your sex partner and use condoms.

Tips to soothe the pain

Take aspirin, acetaminophen (Tylenol) or ibuprofen (Advil, Motrin).
Place lukewarm or cool cloths on the sore place.
Take lukewarm baths. (A woman may urinate in the tub at the end of the bath if she is having pain urinating. This may help dilute the urine so it doesn’t burn the sores so badly.)
Keep the area dry and clean.
Wear cotton underwear.
Wear loose-fitting clothes.

Questions to ask your doctor

What is the best treatment for me?
Is it safe to have unprotected sex if I don’t have any sores?
Can I give myself genital herpes if I also have oral herpes?
What is the best way to prevent herpes outbreaks?
If I give my baby herpes, is there any treatment?
Are there any side effects to my treatment?
Can I live a normal life with herpes?
Am I at risk of developing any other diseases?
Are there any support groups in my area?
Can I give someone else herpes even if I’m not having an outbreak?

Resources

U.S. National Library of Medicine, Genital Herpes

Centers for Disease Control and Prevention, Genital Herpes

U.S. Department of Health and Human Services, Office on Women’s Health, Genital herpes

This information provides a general overview and may not apply to everyone. Talk to your family doctor to find out if this information applies to you and to get more information on this subject.

Is it herpes, syphilis, or something else?

By Sharon Adler, MD, MPH

May 18, 2007

Clinical Feature

Is it herpes, syphilis, or something else?

Share this content:

Genital ulcers could be one of many sexually transmitted diseases or an infection that is not transmitted by sex. An expert walks you through a case.
This is the first of a three-part series on sexually transmitted diseases. Part 2 will appear in the June issue.
A 30-year-old man presents with mildly painful sores that have been present on his penis for three days. He had no symptoms before the lesions appeared, and he has never had similar genital lesions before. The patient has no other symptoms and otherwise feels well. He has no significant medical history and no drug allergies.
Examination of the penile shaft reveals multiple shallow ulcerations with some exudate. Minimal bilateral inguinal lymphadenopathy is nontender. The remainder of his genital exam is unremarkable.
Q: What patient information should be obtained to assist in making a diagnosis?
A complete sexual history is particularly important in patients presenting with genital complaints. This patient reveals that his partners are male and that in the past three months he has had sex with three men, two of whom are new partners. He gives and receives oral sex and engages in insertive anal sex. He uses condoms for anal sex, but not with his primary boyfriend. Results of his latest HIV test four months ago were negative. His only prior sexually transmitted disease (STD) was gonorrhea (urethral) five years ago. His boyfriend is HIV negative and doesn’t have any STD symptoms. The patient denies any drug use and occasionally uses alcohol.
Q: Given your patient’s sexual history and genital findings, should you perform further examination?
Yes. All patients being evaluated for STDs should have an exam that includes: skin, oral cavity, lymph nodes, and genitals. An anal exam should be done if there is a history of any type of anal sex. Any patient with lesions suspicious for syphilis should have a neurologic exam focusing on cranial nerves and motor and sensory deficits. This patient’s history of receptive oral sex and multiple partners accompanied by genital lesions, possibly from an STD, necessitate further physical exam.
Examination of the patient’s skin is unremarkable and without rash. Oropharyngeal exam is within normal limits; no mucous patches or ulcerative lesions are found. There is no lymphadenopathy.
Q: What is your differential diagnosis?
The differential for genital ulcers is broad and includes genital herpes, syphilis, and chancroid, along with other less common STD causes of genital ulcer (lymphogranuloma venereum, granuloma inguinale, and acute HIV infection) and non-STD causes of genital ulcer (including candidiasis, psoriasis, trauma, Reiter’s syndrome, Behçet’s syndrome, fixed-drug eruption, and scabies). Co-infections can occur. In approximately 25% of patients, no etiology is found. Based on this patient’s sexual history, he is at high risk for a sexually transmitted infection.
Q: What laboratory tests should be done?
Tests for herpes and syphilis are warranted. Herpes viral culture of the lesion(s) is recommended. Polymerase chain reaction (PCR), which is more sensitive, can also be used, but it is more expensive and is not FDA-approved for diagnosing genital lesions. If neither culture nor PCR testing is available, a direct fluorescent antibody test can be used. (Other antigen detection methods do not distinguish between herpes simplex virus [HSV]-1 and HSV-2 and are not recommended.) Type-specific glycoprotein G serologic testing for HSV-2 can be considered if genital lesions are crusted or if direct testing of the lesion is negative. Keep in mind that it may take up to four months for any of these serologic tests to be positive after initial infection.
With regard to syphilis, direct assessment of the genital ulcer(s) with darkfield microscopy exam or direct fluorescent antibody toTreponema pallidum is reliable, though access to these tests is frequently limited. Serologic testing with a nontreponemal syphilis test, a rapid plasma reagin test (RPR), or a Venereal Disease Research Laboratory (VDRL) test, are also acceptable alternatives. Both tests are nonspecific and measure an antibody to a cardiolipin that is present in other inflammatory conditions.
A specific treponemal test, such as the T. pallidum agglutination assay (TP-PA) or the fluorescent treponemal antibody absorption test (FTA-ABS), is necessary to confirm a syphilis diagnosis when using RPR or VDRL as the first screening test. Most laboratories will automatically perform the treponemal tests on all positive RPR or VDRL samples. The sensitivity of RPR or VDRL tests in early primary syphilis is 74%-87%, so a negative test does not rule out syphilis, particularly if the lesion has been present for only a few days.
Additional testing to assess for chancroid is not necessary in this case. This would be considered if the patient had traveled to an endemic area or exchanged sex for drugs or money.

Q: Are there other laboratory tests that should be done?
Sexually active men who have sex with men (MSM) should be screened for urethral gonorrhea and chlamydia, rectal gonorrhea and chlamydia (if engaging in receptive anal sex), and pharyngeal gonorrhea (if engaging in oral receptive sex). An HIV test should be performed even though his latest test was just four months ago. Presentation with a new STD indicates possible concurrent HIV exposure.
Q: What is your presumptive diagnosis?
This case of an MSM with multiple mildly painful, shallow genital ulcers and nontender inguinal lymphadenopathy demonstrates the challenges of diagnosing the cause of genital ulcers. The presentation is consistent with herpes, which classically appears as multiple shallow lesions with exudate. However, if these were primary lesions, one would expect them to be more painful and accompanied by tender regional lymphadenopathy and systemic symptoms. Recurrent herpes is another possibility, though it typically has fewer lesions.
This patient’s lesions are not classic for syphilis, which typically presents as a solitary, painless indurated ulcer with nontender, bilateral lymphadenopathy. Atypical presentations of syphilis (and herpes) do occur, particularly in HIV-infected persons. The lesions are not consistent with chancroid, which classically presents as painful deep ulcer(s) with ragged edges and tender, inguinal lymphadenopathy that may suppurate. A non-STD etiology can be considered, although given this man’s sexual history, STDs should first be excluded.
Q: Does the current epidemiology of herpes, syphilis, and chancroid influence your presumptive diagnosis?
Yes. In the United States, genital herpes is the most common cause of STD-related genital ulcers among sexually active adults, followed by syphilis. Chancroid is rare in this country. Even though syphilis is not as common as herpes, rates of primary and secondary syphilis among MSM have been increasing since 2001. Factors associated with high rates of syphilis among MSM are HIV coinfection, high-risk sexual behavior, methamphetamine use, and meeting sexual partners via the Internet. The fact that this patient is an MSM engaging in high-risk sex should raise your suspicion of syphilis.
Q: What is your management strategy?
Presumptive treatment for syphilis, herpes, or both is often necessary for patients with genital ulcers. In general, patients with classic syphilis lesions or those at high risk for syphilis should be offered presumptive syphilis treatment. Those with a classic presentation of vesicles or prodrome consistent with herpes should be offered herpes treatment. Also, patients at risk for being lost to follow-up should be treated for syphilis, given the serious sequelae of untreated syphilis and risk of transmission to partners. In this patient, empiric treatment for syphilis is recommended despite the atypical presentation. He is at sufficient risk for syphilis given his sexual orientation and high-risk behavior. Penicillin G benzathine (Bicillin L-A) is the only recommended regimen for early syphilis. Errors in use of other preparations of penicillin G benzathine (particularly Bicillin C-R) have been documented, so caution to avoid such errors should be exercised. The patient is told that malaise, fever, arthralgias, and other flulike reactions can occur within 24 hours. He is also warned that syphilis can be transmitted orally as well as ano-genitally, and he is encouraged to consistently use condoms.
Q: Should you contact your local health department to report this possible syphilis case?
Yes. Nationally, syphilis is a reportable condition, and presumptive cases generally should be reported. For specifics, check with your locality. Your local health department will generally provide assistance in partner management for confirmed cases.
Q: Is there any further follow-up necessary for this patient?
Yes. The patient returns one week later and his lesions are resolving. His lab results reveal a reactive RPR with titer of 1:256 and a reactive confirmatory TP-PA. All other tests (i.e., herpes culture, gonorrhea, chlamydia, and HIV) are negative. The health department has already contacted him to obtain information on his partners so they can be evaluated and treated.
This patient should have repeat RPR tests at six and 12 months to ensure adequate response to treatment, which is reflected by a fourfold drop in his RPR titer.
Annual screening with a nontreponemal serology test (RPR or VDRL) is recommended after adequate treatment response. MSM with ongoing risk for syphilis should have more frequent screening, with some experts recommending intervals of three to six months. The patient in this case was counseled about his risk for STDs and the importance of STD screening.

This case demonstrates both an atypical presentation of syphilis that could be easily misdiagnosed as herpes and the importance of syphilis testing for all patients with genital ulcers. The case also shows that knowledge of current STD epidemiology is important when assessing patients with genital ulcers and why clinicians should have a low threshold for presumptive treatment of syphilis in MSM with such lesions.
For more about genital ulcer disease and syphilis, visit the National Network of Prevention Training Centers’ (NNPTC) online case series (www.stdhivtraining.org/nnptc). To find out about STD training, go to the NNPTC Web site (www.depts.washington.edu/nnptc).
For a list of references used in this article, contact the editor via e-mail (editor@clinicaladvisor.com) or telephone (646.638.6077).

Dr. Adler, a family physician by training, is a clinical instructor at the California STD/HIV Prevention Training Center in Oakland. She would like to thank colleagues Heidi Bauer, MD, MS, MPH, Helene Calvet, MD, and Linda Creegan, MS, FNP, for their assistance.

From the May 2007 Issue of Clinical Advisor »

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