Syphilis Complications After Starting Treatment for HIV
Many HIV-positive individuals are engaged in sex without proper precautions or protection. Northstar is a large medical practice that serves the greater Chicago area with a special focus on the HIV-positive population. As a result, we are often one of the first to observe changes within this community.
Over the last several years, Northstar has been burdened with an epidemic of syphilis infections. This resurgence within our community is not unique to Chicago and is now common in most metropolitan cities around the U.S. Most people think that syphilis is no big deal; penicillin is always here for the rescue. This article's case presentation begs one to reconsider our evaluation of syphilis. The complications described here occurred in a young HIV-positive individual soon after beginning the cocktail.
The Plot Unfolds
Ethan is a young gay man who was diagnosed with having HIV 2½ years ago. He was not having any specific disease-related symptoms at the time. At that juncture, he elected not to start on a cocktail because his first T-cell count was at 419 cells and viral load was 11,000. He also had a negative syphilis test at the time. However, Ethan never returned to the clinic until 2½ years later, during which he had neither monitoring nor any STD testing.
Ethan finally returned for a routine doctor visit at Northstar. His T-cell count had dropped to 304 cells and his viral load was a whopping 203,000. His physician here recommended starting HIV treatment. Although Ethan is working in a business started by himself and his significant other, he did not have any medical insurance. Thus, he was enrolled in a clinical trial that offered him treatment and study-related monitoring.
At first there were no symptoms or side effects and he felt relatively well. Shortly later, however, he began experiencing some visual symptoms, specifically blurriness on one side and some redness and pain in the eye. He went to his own ophthalmologist who diagnosed him with iritis, an inflammation of the colored part of the eye (iris). He was given anti-inflammatory eye drops and an eye muscle relaxant. He was asked to return for close follow up by the ophthalmologist, but since Ethan didn't have medical insurance, he didn't go back for his follow up appointments. While he continued to cut corners, his eye redness and pain improved, but blurriness did not completely clear.
Later, Ethan began to notice blurriness occurring in the second eye and called Northstar. Dr Kaleo Staszkow, knowing that iritis does not usually occur in both eyes, referred him to a specialist. But before he went for his appointment, he awakened one morning to find near complete loss of vision. He was not able to see at all through either eye. He finally got in to see Dr. Tim Flood, an eye doctor specialist who we referred him to because Dr. Flood has worked with us for many years and has vast experience with HIV-related eye complications.
It was Friday afternoon when everyone in the clinic had already gone home for the weekend that I received a very concerning call from Dr. Flood. It seems that both of Ethan's retinae had signs of necrosis (tissue death) and one retina was also detached. Dr. Flood was concerned that Ethan had no medical insurance for any intervention. After thinking about this quickly, I advised Dr. Flood to have Ethan go to the emergency room at St. Joseph's Hospital. As an emergency, even without insurance, he would be admitted under my care so that I could begin aggressive emergency care.
While in the hospital, I started Ethan on high dose intravenous cortisone, which halted the inflammatory and immunologic process that was destroying his eyes. I also added anti-herpes medications intravenously, since shingles (of the herpes virus family) is sometimes seen to cause retinal problems (also skin outbreaks) in patients who begin antiviral therapy. With this treatment, Ethan's vision began to quickly stabilize and slightly improve over the next two days, but his vision remained poor, seeing only silhouettes of people and not their faces, and not being able to read even large signs.
At Northstar we practice as a team. During a physician meeting, we discussed Ethan and considered all the best possible interventions that could potentially help him. On rounds at the hospital, a syphilis test was ordered by Dr. Todd Hargan, and when the test came back positive, Ethan had high-dose intravenous penicillin added. This resulted in even greater improvements to Ethan's vision. But the syphilis test results were of a very high titer. Considering this and Ethan's situation, we all agreed with Dr. Staszkow to request a spinal tap for syphilis. As it turned out, this was very important, and a major breakthrough to understanding what was occurring with Ethan because his spinal fluid was teaming with syphilis organisms, so it was understood that Ethan became blind due to untreated syphilis.
The spinal fluid's infestation of syphilis required that Ethan stay in the hospital for an additional two weeks so that he could receive the required high doses of penicillin intravenously. During treatment Ethan's vision began to improve some where he could see people and things, but not able to read or perform detailed work. In this situation, blindness was the ugly complication of syphilis; had Ethan kept up with routine syphilis testing, he could have avoided a very long hospitalization, and could have avoided losing his vision in both eyes.
Immune Reconstitution Syndrome
One of the possible explanations in our patient relates to his regenerating immune system. HIV infection is often overwhelming to the immune system and can suppress its response to varying degrees. However, soon after an individual begins antiviral therapy, the immune system finally experiences a rebound in reconstituting itself. In other words, similar to unleashing a storm, the immune system suddenly has a smaller HIV barrier and it begins to quickly gain strength and re-maturate. Along with increased T-cells, interleukin cytokines are part of the storm and are also augmented (cytokines are cells producing immune response modifiers).
Sometimes certain infections that have been indolent or hidden become reactivated during this storm of a liberated immune response. Since cytokines can also intensify inflammation, it can worsen the symptoms of an infection during the reconstitution.
One example of an infection that can get reactivated soon after beginning HAART (HIV cocktail) is shingles. Shingles is the chicken pox virus reactivated and is in the same virus family as herpes. Patients developing shingles often have a reactivation of herpes or chicken pox due to stress or immune system changes. But HIV-positive individuals can experience a shingles outbreak when their HIV is not yet treated because of a failing immune system. Ironically, shingles can also easily occur during immune reconstitution, soon after starting HIV treatment. Knowing that shingles can occur in this situation led to my decision of starting Ethan on high-dose intravenous herpes medications when he entered the hospital, which helped initially.
Did immune reconstitution play a role here during Ethan's complications? Did a latent syphilis infection get activated? Or, was this simply syphilis spreading to the brain or neuro-syphilis complications? We can't say for certain. But certainly, one thing is for sure: had Ethan been tested and treated twice yearly for routine screening, you would not be reading this article.
Syphilis on the Move
Various factors are responsible for the upsurge in syphilis, including the advent of the Internet as a means of readily finding sex, visiting certain sex establishments such as bathhouses and adult book stores, and participating in private sex parties. All can nearly guarantee one to eventual exposure or infection by syphilis. However, anyone who is sexually active at all is at risk for contracting syphilis.
When an individual contracts syphilis, it often presents with a skin rash or some other elusive symptom, but it may also occur without any symptoms. Thus a blood test is often the only way of diagnosing infection. Once uncomplicated syphilis is diagnosed, the treatment is three weekly doses of penicillin, 2.4 million units each dose, given as six separate gigantic horse-size needles in your buttocks by your friendly doc; that's why it's called the Big S. However, complications may mandate more extensive therapy, such as a two week hospitalization.
The Three Stages of Syphilis
Historically, being exposed to syphilis usually caused symptoms of primary infection (a painless chancre or ulcer on the penis or genitals) within 2-4 weeks of contact. However, this can also begin as late as 90 days from exposure. Secondary stage would have occurred 6-8 weeks later with possible signs of skin rash, ulcers in the mouth or genitals, warts on the area around the anus or mouth, patchy hair loss, and possibly fever, fatigue, weight loss, and other generalized symptoms. Finally, untreated tertiary syphilis can occur (historically it used to wait 10-20 years later). It ensues with heart and heart valve complications, as well as brain involvement, often with paralysis, visions of grandeur, and dementia. Adolf Hitler and dictator Idi Amin of Uganda ("The Last King of Scotland" fame) were said to have suffered from syphilis. Ophthalmic (eye) involvement of syphilis has also been seen to occur on occasion.
These days all bets are off; the orderly staging has gone out the window and individuals often skip over the first or second stage, and have even presented with brain or eye complications, for example. The current climate of high prevalence of HIV, meth use, and unsafe sex seems to have catapulted syphilis into being more serious and more often seen. During the past few years, at Northstar and other gay and HIV-focused clinics, syphilis often gets diagnosed initially with different presentations that are not typical of primary stages. Beware, syphilis if untreated, can be dangerous.
The Moral of the Story
Being sexually active, Ethan should have had routine syphilis testing done. Once infection is detected by a simple blood test it should be followed by prompt treatment, available at any city clinic. It is likely that Ethan would still be the normal young gay male having HIV-positive status, without the permanent vision loss. Although his vision has improved with the aggressive treatment, his vision will never be the same. Reading and seeing nature's beautiful details may be lost forever.
HIV-positive individuals who believe their "undetectable" status protects them when having sex with other HIV-positives should be aware: transmitting HIV is not out of the picture, nor is syphilis, hepatitis C nor other STD's. There is no coincidence with the high incidence of crystal meth use in HIV-positive men and the developing epidemic of new sexually transmitted infections. Finally, anyone starting on antiviral therapy should also consider screening for all STD's, especially syphilis.
Editor's Note: Free syphilis testing is available at TPAN through the Access clinic. Call TPAN at (773) 989-9400 and ask for the clinic to make an appointment.
Daniel S. Berger, M.D., is Medical Director of Chicago's largest private HIV treatment and research center, Northstar Healthcare. Through a generous donation from Nan Goldin, Northstar has expanded its addiction recovery services. Northstar offers free services within its Matrix support groups and free one-on-one peer counseling. Dr. Berger can be reached at DSBergerMD@aol.com or (773) 296-2400.