American doctors focus on cases of ocular syphilis

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A ccording to the Centers for Disease Control and Prevention (CDC), in the past two years there have been more than 200 reported cases of syphilis affecting the eyes (ocular syphilis) in the U.S. The bulk of these cases have been among HIV-positive gay, bisexual and other men who have sex with men (MSM). However, some cases have also occurred among HIV-negative people, including MSM and heterosexual men and women. The trend of an apparent increase in ocular syphilis in the U.S. is occurring against a background of an overall increase in syphilis in high-income countries. It may be that there are simply more cases of ocular syphilis being reported because there are more overall cases of syphilis.

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Syphilitic eye complications are not new; they were reported in the time before the widespread availability of antibiotics. Such complications occurred in people with early and late-stage syphilis. A preliminary genetic analysis of syphilis strains present in the U.S. does not suggest that a new, more virulent strain of syphilis with a predilection for causing serious eye complications is circulating. For background information about syphilis see CATIE’s syphilis fact sheet.

A look at ocular syphilis

A team of doctors in the U.S. collaborated to compile and publish details (including symptoms, laboratory test results and response to treatment) about several cases of ocular syphilis that have recently occurred. Their reasons for doing so were to “highlight the diversity of clinical presentations and potentially devastating [complications and consequences] of this syndrome.”

In reviewing these cases the U.S. team made the following points:

  • Although most recent published cases of ocular syphilis have been in HIV-positive MSM, ocular syphilis can also occur in HIV-negative heterosexual men and women and in HIV-negative MSM.
  • “This syndrome can be challenging to diagnose because patients usually present with visual symptoms to their primary care provider or emergency/urgent care center where [sexually transmitted infections] are not often highest on the [list of possible causes of problems encountered].”
  • “Limited access to medical care, whether due to lack of knowledge or financial resources, also contributes to delays in diagnosis and treatment, which may result in poor visual outcomes….”
  • “Increased awareness of this syndrome in all clinical care settings, paired with a low threshold for syphilis screening, could lead to improved care for patients.”
  • The team urges healthcare providers who encounter patients with visual complaints and who have blood tests suggestive of syphilis to treat such cases as “an ophthalmologic emergency,” offering prompt treatment even if retinal examination results or analysis of cerebrospinal fluid (CSF) are not available or if patients refuse to undergo such assessments.

Six cases of ocular syphilis

We now summarize details from the six cases that the U.S. team released.

Case 1: Ocular syphilis in an HIV-negative man

A 41-year-old man was referred by his family doctor to a clinic that specialized in the diagnosis and treatment of sexually transmitted infections (STIs) because routine blood tests revealed that he had syphilis. At the clinic he said that he had experienced a mild rash a month earlier but that it had resolved. However, in the past several weeks he had experienced the following:

  • hazy vision
  • white halos at the edge of his vision
  • “occasional flashing lights” in his vision
  • vertigo

He disclosed having had condomless sex with two new anonymous male partners in the past three months. He did not have any genital sores or lesions.

Blood tests at the clinic were negative for HIV but positive for syphilis. Other tests for common STIs—chlamydia and gonorrhea—were negative.

Due to the man’s symptoms, staff at the STI clinic suspected ocular syphilis and referred him to an infectious disease (ID) clinic. However, because of his work schedule he could not be assessed by the ID clinic that day. So the STI clinic gave him injections of benzathine penicillin (2.4 million units) into muscle. A week later he returned to the STI clinic and received another dose of benzathine penicillin.

Subsequently he attended an appointment at the ID clinic, where he reported that his vision had somewhat improved but problems persisted. He underwent a detailed examination of his eyes and was diagnosed with ocular syphilis. He was treated with intravenous penicillin G (24 million units per day for 14 consecutive days) and made a full recovery.

Case 2: An HIV-positive man on anti-HIV therapy with worsening eye problems

A 34-year-old man sought help at the Emergency Room (ER) of a hospital because of irritation in both eyes for two weeks. He was HIV positive, taking anti-HIV therapy (ART) and blood tests revealed a CD4+ count of 752 cells/mm3 and a viral load less than 20 copies/mL. ER doctors prescribed antibiotic eye drops. However, within a week of this visit a blind spot developed in the man’s left eye. It quickly expanded over the course of several days and resulted in blindness in that eye. Two days after blindness occurred in his left eye, the man began to lose vision in his right eye. He again sought help at the ER. Examination of the interior of his eye revealed inflammation in several structures, including the light-sensitive portion of the eye—the retina.

Such a problem could, in theory, be caused by several microbes, including members of the herpes virus family, the parasite T. gondii (which causes toxoplasmosis) and the germs that cause syphilis. Fluid from the eyeball was extracted and sent for analysis. While waiting for test results, the man was given the antiviral drugs foscarnet and acyclovir intravenously. The test results found no presence of members of the herpes virus family or T. gondii; however, blood tests did find antibodies associated with syphilis. The man’s last test for syphilis was nine months earlier and was negative. He disclosed that he had recently (in the past two months) had sex with men. He was diagnosed with syphilitic uveitis (a form of ocular syphilis in which the middle layer of the eye is inflamed) and his antiviral medicines were stopped. Instead he received intravenous penicillin G for 14 consecutive days as well as anti-inflammatory drugs.

Once therapy was switched to penicillin, the man’s vision began to significantly improve but at the end of his course of penicillin his vision underwent a sudden deterioration. Analysis of his spinal fluid did not suggest that syphilis was attacking his brain. Examination of his eyes revealed that the retina at the back of each eye had peeled off from the eyeball (retinal detachment). As the retina captures light and converts light into tiny electrical signals that are sent to the brain, a detached retina is a serious problem. If surgery is not performed, the retina can permanently lose its ability to function. Doctors scheduled surgery to reattach his retinae but the patient never returned to the hospital and doctors lost contact with him.

Case 3: A married heterosexual woman without HIV

A 45-year-old woman developed redness in her left eye. Initially she did not seek care until she subsequently developed increased sensitivity to light in that eye. An ophthalmologist diagnosed inflammation of the middle layer of the eye (uveitis) and prescribed corticosteroid-containing eye drops. This initially improved her vision but one month later the problems recurred. At this time she underwent blood tests that indicated she had syphilis. Her last test for syphilis was 15 years earlier and was negative. She said that she only had sex with her husband. When doctors questioned her husband, he disclosed sexual contact with other partners.

The woman was given intramuscular injections of benzathine penicillin once weekly for three consecutive weeks. During this time her problems with light sensitivity resolved. A month later she visited an infectious disease clinic for monitoring and underwent extensive eye and neurological assessments. Doctors then found subtle defects in her eyes’ ability to focus. Analysis of her spinal fluid revealed that she had neurosyphilis. She declined to receive intravenous penicillin and was instead treated with an alternative antibiotic, ceftriaxone 2 grams daily, given intravenously for two weeks. Four months later the woman’s symptoms cleared.

Case 4: An HIV-positive man not on anti-HIV therapy

A 29-year-old HIV-positive man, not in regular care and not taking ART, sought help from an infectious disease clinic because of worsening visual problems. Four months earlier he had noticed floaters in his left eye and a blind spot in the centre of his vision as well as a sensation of burning or prickling in his skin. Nine months prior to this visit, he had peeling skin on the palms of his hands and soles of his feet and a general rash on his torso. Several weeks prior to the clinic visit he had persistent diarrhea accompanied by severe weight loss and was quite weak. He disclosed sexual activity only with his husband. He could only see what doctors described as “basic shapes and colours.” An ophthalmologist found inflamed tissue within his eye. Furthermore, the retina in each eye was beginning to peel away from the eyeball.

The man was hospitalized and analysis of his spinal fluid indicated neurosyphilis. Blood tests found an HIV viral load of 108,000 copies/mL and a CD4+ count of 64 cells/mm3. He was treated with intravenous penicillin G for two consecutive weeks. He also initiated ART and was subsequently able to leave the hospital, as his overall health had improved.

Three months later the man underwent a checkup at the infectious disease clinic and doctors found that his vision had improved significantly. Furthermore, his viral load was now less than 20 copies/mL and his CD4+ count was 130 cells/mm3.

Ten months after hospitalization, public health authorities asked him to revisit the infectious disease clinic because he was named as a sexual contact by someone else who had been diagnosed with syphilis. He had disclosed only sex with his husband (described as “Case 5” by the doctors). On examination, doctors found a new scaly rash on his torso, palms of his hands and soles of his feet. There was also a painful sore on his tongue. He did not have any visual problems. Doctors prescribed a single course of benzathine penicillin (2.4 million units) injected into muscle. A week later examination of his retinae and other parts of his eyes did not reveal any inflammation.

Case 5: An HIV-positive man not on anti-HIV therapy

A 35-year-old man with untreated HIV infection sought care at an infectious disease clinic because of deteriorating vision—increasing presence of floaters and loss of vision—in both eyes over the course of the past nine months. During this period he had experienced unintentional weight loss of 31 kg.

On examination he had a rash on the soles of his feet and palms of his hands. He also had painless ulcers on his penis. He had no vision in his right eye because the retina had become detached. According to the doctors, he had “minimal light perception in his left eye.”

Analysis of his spinal fluid suggested neurosyphilis. His blood tests were positive for syphilis. His viral load was 35,000 copies/mL and his CD4+ count was 111 cells/mm3. He received the same course of antibiotics as the patient described by doctors as “Case 4.” He also began ART.

Three months later the man’s rash had resolved but there was only slight visual improvement in the right eye and no change in the left eye. His viral load was now less than 20 copies/mL and his CD4+ count was 190 cells/mm3.

Seven months after he sought care at the infectious disease clinic he reported sex with three new partners. Tests done at that time did not find any STIs. However, two months later he again sought care because of a rash on his penis, forearms and thigh. As the rash had an appearance similar to a mild fungal infection, he was prescribed an antifungal skin cream. However, the rash did not resolve. What’s more, a month later when he again visited the clinic, the rash had spread to the palms of his hands where it had become scaly. There were also raised spots on his penis and an ulcer on his tongue. Evaluation of his spinal fluid did not indicate neurosyphilis but blood tests were suggestive of syphilis so doctors treated him with a single course of benzathine penicillin and the rash improved.

Case 6: An HIV-negative heterosexual man

A 33-year-old man sought care in a hospital ER because over the course of two weeks he had developed blurry vision and eye discomfort when exposed to light. Six weeks prior he recalled experiencing a sore throat and the sensation of ringing in his ears (tinnitus). A CT scan of his head revealed enlarged sinuses. He was prescribed antibiotics (trimethoprim-sulfamethoxazole), as doctors presumed that he had a sinus infection. He was also told to visit an ophthalmologist. However, doctors said that “due to financial and insurance barriers” he delayed seeking this specialty eye care. Subsequently he developed what doctors described as “near complete vision loss” and headache, and once again he visited the ER.

Upon examination at his second visit to the ER, doctors found scaly plaque on his torso, buttocks, palms of his hands and soles of his feet. There were also white patches in his mouth. He disclosed sex with two women in the past year.

Further assessments were done and he tested negative for HIV and gonorrhea and chlamydia but positive for syphilis. Analysis of fluid from his eyes was negative for the presence of members of the herpes virus family and the parasite T. gondii. His spinal fluid analysis also indicated that he had neurosyphilis. The retinae of his eyes were inflamed and dying. He was hospitalized and treated with intravenous penicillin G (24 million units daily for 10 days) together with corticosteroids. One week later his vision had not improved and doctors were pessimistic that any improvement would occur.

These cases underscore the need for regular, and in some cases frequent, screening for syphilis among sexually active people, including those with visual difficulties. The cases also highlight the importance of swift diagnosis and treatment.

Resources

Canadian guidelines on sexually transmitted infections – Management of syphilis

Québec guidelines on syphilis management - Guide ITSS - Syphilis (Updated March 2016)

CDC Clinical Advisory: Ocular syphilis in the U.S.

CATIE fact sheet on syphilis

—Sean R. Hosein

REFERENCES:

  1. Marx GE, Dhanireddy S, Marrazzo JM, et al. Variations in clinical presentation of ocular syphilis: Case series reported from a growing epidemic in the United States. Sexually Transmitted Diseases. 2016 Aug;43(8):519-23.
  2. Woolston S, Cohen SE, Fanfair RN, et al. A cluster of ocular syphilis cases—Seattle, Washington and San Francisco, California, 2014-2015. Morbidity and Mortality Weekly Report. 2015 Oct 16;64(40):1150-1.
  3. Hook E. Ocular syphilis in context. Sexually Transmitted Diseases. 2016 Aug;43(8):528-9.
  4. Oliver S, Sahi SK, Tantalo LC, et al. Molecular typing of Treponema pallidum in ocular syphilis. Sexually Transmitted Diseases. 2016 Aug;43(8):524-7.
  5. Totten S, MacLean R, Payne E. Infectious syphilis in Canada: 2003-2012. Canada Communicable Disease Report. 5 February 2015;41(2). Available at: http://www.phac-aspc.gc.ca/publicat/ccdr-rmtc/15vol41/dr-rm41-02/surv-3-eng.php
  6. Sullivan PS, Hamouda O, Delpech V, et al. Reemergence of the HIV epidemic among men who have sex with men in North America, Western Europe and Australia, 1996-2005. Annals of Epidemiology. 2009 Jun;19(6):423-31.
  7. Abara WE, Hess KL, Neblett Fanfair R, et al. Syphilis trends among men who have sex with men in the United States and Western Europe: A systematic review of trend studies published between 2004 and 2015. PLoS One. 2016 Jul 22;11(7):e0159309.
  8. Lukehart SA, Hook EW 3rd, Baker-Zander SA, et al. Invasion of the central nervous system by Treponema pallidum: implications for diagnosis and treatment. Annals of Internal Medicine. 1988 Dec 1;109(11):855-62.
  9. Leber A, MacPherson P, Lee BC. Epidemiology of infectious syphilis in Ottawa. Recurring themes revisited. Canadian Journal of Public Health. 2008 Sep-Oct;99(5):401-5.
  10. McKee SH, Courtenay HD. Some cases of syphilis of the eye following treatment by Salvarsan. Canadian Medical Association Journal. 1916; Nov;6(11):996-7.
  11. Branger J, van der Meer JT, van Ketel RJ, et al. High incidence of asymptomatic syphilis in HIV-infected MSM justifies routine screening. Sexually Transmitted Diseases. 2009 Feb;36(2):84-5.
  12. Fenton KA, Breban R, Vardavas R, et al. Infectious syphilis in high-income settings in the 21st century. Lancet Infectious Diseases. 2008 Apr;8(4):244-53.
  13. CDC. Transmission of primary and secondary syphilis by oral sex—Chicago, Illinois, 1998-2002. Morbidity and Mortality Weekly Report. 2004 Oct 22;53(41):966-8.
  14. Mishra S, Walmsley SL, Loutfy MR, et al. Otosyphilis in HIV-coinfected individuals: a case series from Toronto, Canada. AIDS Patient Care and STDs. 2008 Mar;22(3):213-9.
  15. Kunkel J, Schürmann D, Pleyer U, et al. Ocular syphilis—indicator of previously unknown HIV infection. Journal of Infection. 2009 Jan;58(1):32-6.
  16. Tran THC, Cassoux N, Bodaghi B, et al. Syphilitic uveitis in patients infected with human immunodeficiency virus. Graefe’s Archives in Clinical and Experimental Ophthalmology. 2005;243:863-869.
  17. Kofoed K, Gerstoft J, Mathiesen LR, et al. Syphilis and human immunodeficiency virus (HIV)-1 coinfection: influence on CD4 T-cell count, HIV-1 viral load and treatment response. Sexually Transmitted Diseases 2006;33(3):143-8.