User login
ID Blog: The story of syphilis, part III
The tortured road to successful treatment
It is rare in this modern era for medicine to confront an infectious disease for which there is no cure. Today, there are comparatively few infectious diseases (in the developed world and in places where money is no object) for which medicine cannot offer at least a glimmer of hope to infected patients. Even at its most futile, modern medicine has achieved vast improvements in the efficacy of palliative care. But it wasn’t that long ago that HIV infection was a nearly inevitable death sentence from the complications of AIDS, with no available treatments. And however monstrous that suffering and death, which still continues in many areas of the developing world, it was decades rather than centuries before modern medicine came up with effective treatments. Recently, there is even significant hope on the Ebola virus front that curative treatments may soon become available.
Medicine has always been in the business of hope, even when true cures were not available. Today that hope is less often misplaced. But in previous centuries, the need to offer hope to – and perhaps to make money from – desperate patients was a hallmark of the doctor’s trade.
It was this need to give patients hope and for doctors to feel that they were being effective that led to some highly dubious and desperate efforts to cure syphilis throughout history. These efforts meant centuries of fruitless torture for countless patients until the rise of modern antibiotics.
For the most part, what we now look upon as horrors and insanity in treatment were the result of misguided scientific theories, half-baked folk wisdom, and the generally well-intentioned efforts of medical practitioners at a cure. There were the charlatans as well, seeking a quick buck from the truly hopeless.
However, the social stigma of syphilis as a venereal disease played a role in the courses of treatment.
By the 15th century, syphilis was recognized as being spread by sexual intercourse, and in a situation analogous with the early AIDS epidemic, “16th- and 17th-century writers and physicians were divided on the moral aspects of syphilis. Some thought it was a divine punishment for sin – and as such only harsh treatments would cure it – or that people with syphilis shouldn’t be treated at all.”
Mercury rising
In its earliest manifestations, syphilis was considered untreatable. In 1496, Sebastian Brandt, wrote a poem entitled “De pestilentiali Scorra sive mala de Franzos” detailing the disease’s early spread across Europe and how doctors had no remedy for it.
However, it wasn’t long before desperate physicians turned their quest for a cure to a reliable old standby treatment of the period – mercury, which had a history of being used for skin diseases. Mercury salves had been in use in the Arab world for leprosy and eczema, among other skin afflictions, and had been brought to Europe with the return of the medieval crusaders. Another way elemental mercury was administered was through the use of heated cinnabar (HgS), which gave off mercury vapors that could be absorbed by breathing and through the skin. In the 16th century, doctors would place a syphilis-infected individual inside an ovenlike chamber over pans of cinnabar, which were then heated at the person’s feet.
Oral mercury treatments were promoted by Paracelsus (1493?-1541), an alchemist and physician who prescribed calomel (HgCl), or mercury chloride, pills. Mercury treatment, administered at almost inevitably toxic doses, led to ulcerations of the lips, tongue, palate, and jaw; tooth loss; and fetid breath and excessive salivation. This last symptom was, in fact, considered the endpoint in mercury therapy for syphilis, which was “originally judged to be a copious secretion of saliva – ‘some few liters per diem.’ ” Even as recent as the late 19th century and early 20th century, syphilitic patients such as Oscar Wilde (whose teeth were blackened by the treatment), were prescribed calomel.
Looking to the “holy wood”
By 1519, an alternative treatment to mercury was available. In that year, Ulrich von Hutton, a German scholar who suffered from the “great pox,” described its treatment with guaiacum sanctum, or holy wood, in “De Morbo Gallico.” Four years later, despite such treatment, he was dead from the disease himself. But the lack of efficacy did not stop the faith that doctors placed in this botanical cure.
Holy wood was an herbal treatment derived from the bark of trees from the Guaiacum family. It was brought back on trading ships from the Caribbean and South America, the origin of syphilis’s foothold in Europe and the rest of the world. The use of holy wood matched a then-current theory that the cure to a disease could be found in the area from which it came. Other botanicals from around the world were also tried, but never came into routine use.
Guaiacum was the first treatment given to sufferers of syphilis in the Blatterhaus (pox hospital) in Augsburg after 1522, according to information from the archives at the Edward Worth Library in Dublin. The botanical therapy was given as a hot drink and followed by a sweating cure. Guaiacum extract acted as a sudorific, a compound which induces sweating when ingested. Even though the use of Guaiacum was initially popular, it was replaced almost exclusively by the use of mercury.
“Give me fever”
In the late 1800s, Julius Wagner von Jauregg (1857-1940), a Viennese neurologist, observed that Austrian army officers with neurosyphilis did not become partially paralyzed if they had also contracted malaria or relapsing fever. He initiated clinical trials in which he induced fever in syphilitics with tuberculin (1-10 mg) and observed in many the remissions their neuropsychiatric symptoms and signs. He also injected neurosyphilitic patients with a mild form of malaria to induce fever, which could then be suppressed with quinine treatment.
“Other physicians soon began using malariotherapy in uncontrolled studies of neurosyphilitics and reported clinical success rates of 33%-51% and only a 5% mortality. Persons with tabes dorsalis (the “wasting” paralysis of neurosyphilis) were hospitalized for 3 weeks of alternate-day fever therapy involving 5-hour long hot baths and extended periods wrapped in heavy blankets,” according to C.T. Ambrose, MD, of the University of Kentucky, Lexington.
A 1931 medical text summarizes in 35 studies involving 2,356 cases of general paresis treated with malaria and reported a 27.5% “full remission,” he added. A bacterial treatment developed in this period used a course of 18-23 injections of killed typhoid cells administered every 2-3 days in order to produce a fever of 103°–104°F. Animal studies of rabbits infected with syphilis showed that high temperatures could be curative.
Dr. Ambrose suggests that 16th-century syphilitics who had been subjected to mercury fumigation in ovenlike chambers endured severe sweating conditions and – for those who survived – the prolonged elevated body temperature (not the mercury) may have proved curative. Fever “was the common therapeutic denominator in the cinnabar-oven treatment, botanical sudorifics (guaiacum, China root), malarial infections (natural and iatrogenic), and bacterial (tuberculin) vaccine therapy.”
Prelude to modern antibiotics
German bacteriologist/immunologist Paul Ehrlich, MD, (1854-1915) investigated the use of atoxyl (sodium arsanilate) in syphilis, but the metallic drug had severe side effects, injuring the optic nerve and causing blindness. To overcome this problem, Ehrlich and his coworkers synthesized and tested related organic arsenicals. The antisyphilitic activity of arsphenamine (compound 606) was discovered by Sahachiro Hata, MD, (1879-1938) in 1909. This compound, known as Salvarsan, became “Dr. Ehrlich’s Magic Bullet,” for the treatment of syphilis in the 1910s, and it, and later, the less-toxic compound neoarsphenamine (compound 914) became mainstays of successful clinical treatment until the development and use of penicillin in the 1940s.
Selected sources
Ambrose, CT. Pre-antibiotic therapy of syphilis. NESSA J Infect Dis Immunology. 2016. 1(1);1-20.
Frith J. Syphilis: Its early history and treatment until penicillin and the debate on its origins. J Mil Veterans Health. 2012;20(4):49-58.
Tognotti B. The rise and fall of syphilis in Renaissance Italy. J Med Humanit. 2009 Jun;30(2):99-113.
Mark Lesney is the managing editor of MDedge.com/IDPractioner. He has a PhD in plant virology and a PhD in the history of science, with a focus on the history of biotechnology and medicine. He has served as an adjunct assistant professor in the department of biochemistry and molecular & cellular biology at Georgetown University, Washington.
The tortured road to successful treatment
The tortured road to successful treatment
It is rare in this modern era for medicine to confront an infectious disease for which there is no cure. Today, there are comparatively few infectious diseases (in the developed world and in places where money is no object) for which medicine cannot offer at least a glimmer of hope to infected patients. Even at its most futile, modern medicine has achieved vast improvements in the efficacy of palliative care. But it wasn’t that long ago that HIV infection was a nearly inevitable death sentence from the complications of AIDS, with no available treatments. And however monstrous that suffering and death, which still continues in many areas of the developing world, it was decades rather than centuries before modern medicine came up with effective treatments. Recently, there is even significant hope on the Ebola virus front that curative treatments may soon become available.
Medicine has always been in the business of hope, even when true cures were not available. Today that hope is less often misplaced. But in previous centuries, the need to offer hope to – and perhaps to make money from – desperate patients was a hallmark of the doctor’s trade.
It was this need to give patients hope and for doctors to feel that they were being effective that led to some highly dubious and desperate efforts to cure syphilis throughout history. These efforts meant centuries of fruitless torture for countless patients until the rise of modern antibiotics.
For the most part, what we now look upon as horrors and insanity in treatment were the result of misguided scientific theories, half-baked folk wisdom, and the generally well-intentioned efforts of medical practitioners at a cure. There were the charlatans as well, seeking a quick buck from the truly hopeless.
However, the social stigma of syphilis as a venereal disease played a role in the courses of treatment.
By the 15th century, syphilis was recognized as being spread by sexual intercourse, and in a situation analogous with the early AIDS epidemic, “16th- and 17th-century writers and physicians were divided on the moral aspects of syphilis. Some thought it was a divine punishment for sin – and as such only harsh treatments would cure it – or that people with syphilis shouldn’t be treated at all.”
Mercury rising
In its earliest manifestations, syphilis was considered untreatable. In 1496, Sebastian Brandt, wrote a poem entitled “De pestilentiali Scorra sive mala de Franzos” detailing the disease’s early spread across Europe and how doctors had no remedy for it.
However, it wasn’t long before desperate physicians turned their quest for a cure to a reliable old standby treatment of the period – mercury, which had a history of being used for skin diseases. Mercury salves had been in use in the Arab world for leprosy and eczema, among other skin afflictions, and had been brought to Europe with the return of the medieval crusaders. Another way elemental mercury was administered was through the use of heated cinnabar (HgS), which gave off mercury vapors that could be absorbed by breathing and through the skin. In the 16th century, doctors would place a syphilis-infected individual inside an ovenlike chamber over pans of cinnabar, which were then heated at the person’s feet.
Oral mercury treatments were promoted by Paracelsus (1493?-1541), an alchemist and physician who prescribed calomel (HgCl), or mercury chloride, pills. Mercury treatment, administered at almost inevitably toxic doses, led to ulcerations of the lips, tongue, palate, and jaw; tooth loss; and fetid breath and excessive salivation. This last symptom was, in fact, considered the endpoint in mercury therapy for syphilis, which was “originally judged to be a copious secretion of saliva – ‘some few liters per diem.’ ” Even as recent as the late 19th century and early 20th century, syphilitic patients such as Oscar Wilde (whose teeth were blackened by the treatment), were prescribed calomel.
Looking to the “holy wood”
By 1519, an alternative treatment to mercury was available. In that year, Ulrich von Hutton, a German scholar who suffered from the “great pox,” described its treatment with guaiacum sanctum, or holy wood, in “De Morbo Gallico.” Four years later, despite such treatment, he was dead from the disease himself. But the lack of efficacy did not stop the faith that doctors placed in this botanical cure.
Holy wood was an herbal treatment derived from the bark of trees from the Guaiacum family. It was brought back on trading ships from the Caribbean and South America, the origin of syphilis’s foothold in Europe and the rest of the world. The use of holy wood matched a then-current theory that the cure to a disease could be found in the area from which it came. Other botanicals from around the world were also tried, but never came into routine use.
Guaiacum was the first treatment given to sufferers of syphilis in the Blatterhaus (pox hospital) in Augsburg after 1522, according to information from the archives at the Edward Worth Library in Dublin. The botanical therapy was given as a hot drink and followed by a sweating cure. Guaiacum extract acted as a sudorific, a compound which induces sweating when ingested. Even though the use of Guaiacum was initially popular, it was replaced almost exclusively by the use of mercury.
“Give me fever”
In the late 1800s, Julius Wagner von Jauregg (1857-1940), a Viennese neurologist, observed that Austrian army officers with neurosyphilis did not become partially paralyzed if they had also contracted malaria or relapsing fever. He initiated clinical trials in which he induced fever in syphilitics with tuberculin (1-10 mg) and observed in many the remissions their neuropsychiatric symptoms and signs. He also injected neurosyphilitic patients with a mild form of malaria to induce fever, which could then be suppressed with quinine treatment.
“Other physicians soon began using malariotherapy in uncontrolled studies of neurosyphilitics and reported clinical success rates of 33%-51% and only a 5% mortality. Persons with tabes dorsalis (the “wasting” paralysis of neurosyphilis) were hospitalized for 3 weeks of alternate-day fever therapy involving 5-hour long hot baths and extended periods wrapped in heavy blankets,” according to C.T. Ambrose, MD, of the University of Kentucky, Lexington.
A 1931 medical text summarizes in 35 studies involving 2,356 cases of general paresis treated with malaria and reported a 27.5% “full remission,” he added. A bacterial treatment developed in this period used a course of 18-23 injections of killed typhoid cells administered every 2-3 days in order to produce a fever of 103°–104°F. Animal studies of rabbits infected with syphilis showed that high temperatures could be curative.
Dr. Ambrose suggests that 16th-century syphilitics who had been subjected to mercury fumigation in ovenlike chambers endured severe sweating conditions and – for those who survived – the prolonged elevated body temperature (not the mercury) may have proved curative. Fever “was the common therapeutic denominator in the cinnabar-oven treatment, botanical sudorifics (guaiacum, China root), malarial infections (natural and iatrogenic), and bacterial (tuberculin) vaccine therapy.”
Prelude to modern antibiotics
German bacteriologist/immunologist Paul Ehrlich, MD, (1854-1915) investigated the use of atoxyl (sodium arsanilate) in syphilis, but the metallic drug had severe side effects, injuring the optic nerve and causing blindness. To overcome this problem, Ehrlich and his coworkers synthesized and tested related organic arsenicals. The antisyphilitic activity of arsphenamine (compound 606) was discovered by Sahachiro Hata, MD, (1879-1938) in 1909. This compound, known as Salvarsan, became “Dr. Ehrlich’s Magic Bullet,” for the treatment of syphilis in the 1910s, and it, and later, the less-toxic compound neoarsphenamine (compound 914) became mainstays of successful clinical treatment until the development and use of penicillin in the 1940s.
Selected sources
Ambrose, CT. Pre-antibiotic therapy of syphilis. NESSA J Infect Dis Immunology. 2016. 1(1);1-20.
Frith J. Syphilis: Its early history and treatment until penicillin and the debate on its origins. J Mil Veterans Health. 2012;20(4):49-58.
Tognotti B. The rise and fall of syphilis in Renaissance Italy. J Med Humanit. 2009 Jun;30(2):99-113.
Mark Lesney is the managing editor of MDedge.com/IDPractioner. He has a PhD in plant virology and a PhD in the history of science, with a focus on the history of biotechnology and medicine. He has served as an adjunct assistant professor in the department of biochemistry and molecular & cellular biology at Georgetown University, Washington.
It is rare in this modern era for medicine to confront an infectious disease for which there is no cure. Today, there are comparatively few infectious diseases (in the developed world and in places where money is no object) for which medicine cannot offer at least a glimmer of hope to infected patients. Even at its most futile, modern medicine has achieved vast improvements in the efficacy of palliative care. But it wasn’t that long ago that HIV infection was a nearly inevitable death sentence from the complications of AIDS, with no available treatments. And however monstrous that suffering and death, which still continues in many areas of the developing world, it was decades rather than centuries before modern medicine came up with effective treatments. Recently, there is even significant hope on the Ebola virus front that curative treatments may soon become available.
Medicine has always been in the business of hope, even when true cures were not available. Today that hope is less often misplaced. But in previous centuries, the need to offer hope to – and perhaps to make money from – desperate patients was a hallmark of the doctor’s trade.
It was this need to give patients hope and for doctors to feel that they were being effective that led to some highly dubious and desperate efforts to cure syphilis throughout history. These efforts meant centuries of fruitless torture for countless patients until the rise of modern antibiotics.
For the most part, what we now look upon as horrors and insanity in treatment were the result of misguided scientific theories, half-baked folk wisdom, and the generally well-intentioned efforts of medical practitioners at a cure. There were the charlatans as well, seeking a quick buck from the truly hopeless.
However, the social stigma of syphilis as a venereal disease played a role in the courses of treatment.
By the 15th century, syphilis was recognized as being spread by sexual intercourse, and in a situation analogous with the early AIDS epidemic, “16th- and 17th-century writers and physicians were divided on the moral aspects of syphilis. Some thought it was a divine punishment for sin – and as such only harsh treatments would cure it – or that people with syphilis shouldn’t be treated at all.”
Mercury rising
In its earliest manifestations, syphilis was considered untreatable. In 1496, Sebastian Brandt, wrote a poem entitled “De pestilentiali Scorra sive mala de Franzos” detailing the disease’s early spread across Europe and how doctors had no remedy for it.
However, it wasn’t long before desperate physicians turned their quest for a cure to a reliable old standby treatment of the period – mercury, which had a history of being used for skin diseases. Mercury salves had been in use in the Arab world for leprosy and eczema, among other skin afflictions, and had been brought to Europe with the return of the medieval crusaders. Another way elemental mercury was administered was through the use of heated cinnabar (HgS), which gave off mercury vapors that could be absorbed by breathing and through the skin. In the 16th century, doctors would place a syphilis-infected individual inside an ovenlike chamber over pans of cinnabar, which were then heated at the person’s feet.
Oral mercury treatments were promoted by Paracelsus (1493?-1541), an alchemist and physician who prescribed calomel (HgCl), or mercury chloride, pills. Mercury treatment, administered at almost inevitably toxic doses, led to ulcerations of the lips, tongue, palate, and jaw; tooth loss; and fetid breath and excessive salivation. This last symptom was, in fact, considered the endpoint in mercury therapy for syphilis, which was “originally judged to be a copious secretion of saliva – ‘some few liters per diem.’ ” Even as recent as the late 19th century and early 20th century, syphilitic patients such as Oscar Wilde (whose teeth were blackened by the treatment), were prescribed calomel.
Looking to the “holy wood”
By 1519, an alternative treatment to mercury was available. In that year, Ulrich von Hutton, a German scholar who suffered from the “great pox,” described its treatment with guaiacum sanctum, or holy wood, in “De Morbo Gallico.” Four years later, despite such treatment, he was dead from the disease himself. But the lack of efficacy did not stop the faith that doctors placed in this botanical cure.
Holy wood was an herbal treatment derived from the bark of trees from the Guaiacum family. It was brought back on trading ships from the Caribbean and South America, the origin of syphilis’s foothold in Europe and the rest of the world. The use of holy wood matched a then-current theory that the cure to a disease could be found in the area from which it came. Other botanicals from around the world were also tried, but never came into routine use.
Guaiacum was the first treatment given to sufferers of syphilis in the Blatterhaus (pox hospital) in Augsburg after 1522, according to information from the archives at the Edward Worth Library in Dublin. The botanical therapy was given as a hot drink and followed by a sweating cure. Guaiacum extract acted as a sudorific, a compound which induces sweating when ingested. Even though the use of Guaiacum was initially popular, it was replaced almost exclusively by the use of mercury.
“Give me fever”
In the late 1800s, Julius Wagner von Jauregg (1857-1940), a Viennese neurologist, observed that Austrian army officers with neurosyphilis did not become partially paralyzed if they had also contracted malaria or relapsing fever. He initiated clinical trials in which he induced fever in syphilitics with tuberculin (1-10 mg) and observed in many the remissions their neuropsychiatric symptoms and signs. He also injected neurosyphilitic patients with a mild form of malaria to induce fever, which could then be suppressed with quinine treatment.
“Other physicians soon began using malariotherapy in uncontrolled studies of neurosyphilitics and reported clinical success rates of 33%-51% and only a 5% mortality. Persons with tabes dorsalis (the “wasting” paralysis of neurosyphilis) were hospitalized for 3 weeks of alternate-day fever therapy involving 5-hour long hot baths and extended periods wrapped in heavy blankets,” according to C.T. Ambrose, MD, of the University of Kentucky, Lexington.
A 1931 medical text summarizes in 35 studies involving 2,356 cases of general paresis treated with malaria and reported a 27.5% “full remission,” he added. A bacterial treatment developed in this period used a course of 18-23 injections of killed typhoid cells administered every 2-3 days in order to produce a fever of 103°–104°F. Animal studies of rabbits infected with syphilis showed that high temperatures could be curative.
Dr. Ambrose suggests that 16th-century syphilitics who had been subjected to mercury fumigation in ovenlike chambers endured severe sweating conditions and – for those who survived – the prolonged elevated body temperature (not the mercury) may have proved curative. Fever “was the common therapeutic denominator in the cinnabar-oven treatment, botanical sudorifics (guaiacum, China root), malarial infections (natural and iatrogenic), and bacterial (tuberculin) vaccine therapy.”
Prelude to modern antibiotics
German bacteriologist/immunologist Paul Ehrlich, MD, (1854-1915) investigated the use of atoxyl (sodium arsanilate) in syphilis, but the metallic drug had severe side effects, injuring the optic nerve and causing blindness. To overcome this problem, Ehrlich and his coworkers synthesized and tested related organic arsenicals. The antisyphilitic activity of arsphenamine (compound 606) was discovered by Sahachiro Hata, MD, (1879-1938) in 1909. This compound, known as Salvarsan, became “Dr. Ehrlich’s Magic Bullet,” for the treatment of syphilis in the 1910s, and it, and later, the less-toxic compound neoarsphenamine (compound 914) became mainstays of successful clinical treatment until the development and use of penicillin in the 1940s.
Selected sources
Ambrose, CT. Pre-antibiotic therapy of syphilis. NESSA J Infect Dis Immunology. 2016. 1(1);1-20.
Frith J. Syphilis: Its early history and treatment until penicillin and the debate on its origins. J Mil Veterans Health. 2012;20(4):49-58.
Tognotti B. The rise and fall of syphilis in Renaissance Italy. J Med Humanit. 2009 Jun;30(2):99-113.
Mark Lesney is the managing editor of MDedge.com/IDPractioner. He has a PhD in plant virology and a PhD in the history of science, with a focus on the history of biotechnology and medicine. He has served as an adjunct assistant professor in the department of biochemistry and molecular & cellular biology at Georgetown University, Washington.
Does this patient have bacterial conjunctivitis?
A 54-year-old pharmacist with a history of gout, hypertension, and conjunctivitis presents for evaluation of pink eye in the summer. The morning before coming into the office, he noticed that his right eye was red and inflamed. He self-treated with saline washes and eye drops, but upon awakening the next day, he found his right eye to be crusted shut with surrounding yellow discharge. He has not had any changes to his vision but endorses a somewhat uncomfortable, “gritty” sensation. He reports no recent cough, nasal congestion, or allergies, and he has not been around any sick contacts. His blood pressure is 102/58 mm Hg, pulse is 76 bpm, and body mass index is 27.3 kg/m2. His eye exam reveals unilateral conjunctival injections but no hyperemia of the conjunctiva adjacent to the cornea. Mucopurulent discharge was neither found on the undersurface of the eyelid nor emerging from the eye. Which of the following is the best treatment for this patient’s condition?
A) Erythromycin 5 mg/gram ophthalmic ointment.
B) Ofloxacin 0.3% ophthalmic drops.
C) Antihistamine drops.
D) Eye lubricant drops.
E) No treatment necessary.
This patient is an adult presenting with presumed conjunctivitis. Because he is presenting in the summer without observed purulent discharge, his condition is unlikely to be bacterial. This patient does not need treatment, although eye lubricant drops could reduce his discomfort.
After ruling out serious eye disease, clinicians need to determine which cases of suspected conjunctivitis are most likely to be bacterial to allow for judicious use of antibiotic eye drops. This is an important undertaking as most patients assume that antibiotics are needed.
How do we know which history and clinical exam findings to lean on when attempting to categorize conjunctivitis as bacterial or not? If a patient reports purulent discharge, doesn’t that mean it is bacterial? Surprisingly, a systematic review published in 2016 by Narayana and McGee found that a patient’s self-report of “purulent drainage” is diagnostically unhelpful, but if a clinician finds it on exam, the likelihood of a bacterial etiology increases.3
Narayana and McGee analyzed three studies that enrolled a total of 281 patients with presumed conjunctivitis who underwent bacterial cultures. They then determined which findings increased the probability of positive bacterial culture. From strongest to weakest, the best indicators of a bacterial cause were found to be: complete redness of the conjunctival membrane obscuring tarsal vessels (the vessels visible on the inside of everted upper or lower eyelids) (likelihood ratio, 4.6), observed purulent discharge (LR, 3.9), matting of both eyes in the morning (LR, 3.6), and presence during winter/spring months (LR, 1.9). On the other hand, failure to observe a red eye at 20 feet (LR, 0.2), absence of morning gluing of either eye (LR, 0.3), and presentation during summer months (LR, 0.4) all decreased the probability of a bacterial cause. This review and different study by Stenson et al. unfortunately have conflicting evidence regarding whether the following findings are diagnostically helpful: qualities of eye discomfort (such as burning or itching), preauricular adenopathy, conjunctival follicles, and conjunctival papillae.3,4 Rietveld and colleagues found that a history of conjunctivitis decreased the likelihood of bacterial conjunctivitis.5
Ultimately, if the former indicators are kept in mind, primary care clinicians should be able to decrease the prescribing of topical antimicrobials to patients with non-bacterial conjunctivitis.
Pearl: The best indicators of a bacterial cause in patients with presumed conjunctivitis are complete redness of the conjunctival membrane obscuring tarsal vessels, observed purulent discharge, and matting of both eyes in the morning. Presentation during the summer months and having a history of conjunctivitis decreases the likelihood of bacterial conjunctivitis.
Ms. Momany is a fourth-year medical student at University of Washington, Seattle. Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington and serves as third-year medical student clerkship director at that university. Contact Dr. Paauw at [email protected].
References
1. Azari AA and Barney NP. JAMA. 2013 Oct 23; 310(16):1721-9.
2. Smith AF and Waycaster C. BMC Ophthalmol. 2009 Nov 25. doi: 10.1186/1471-2415-9-13.
3) Narayana S and McGee S. Am J Med. 2015;128(11):1220-4.e1.
4) Stenson S et al. Arch Ophthalmol. 1982;100(8):1275-7.
5) Rietveld RP et al. BMJ. 2004 Jul 24;329(7459):206-10.
A 54-year-old pharmacist with a history of gout, hypertension, and conjunctivitis presents for evaluation of pink eye in the summer. The morning before coming into the office, he noticed that his right eye was red and inflamed. He self-treated with saline washes and eye drops, but upon awakening the next day, he found his right eye to be crusted shut with surrounding yellow discharge. He has not had any changes to his vision but endorses a somewhat uncomfortable, “gritty” sensation. He reports no recent cough, nasal congestion, or allergies, and he has not been around any sick contacts. His blood pressure is 102/58 mm Hg, pulse is 76 bpm, and body mass index is 27.3 kg/m2. His eye exam reveals unilateral conjunctival injections but no hyperemia of the conjunctiva adjacent to the cornea. Mucopurulent discharge was neither found on the undersurface of the eyelid nor emerging from the eye. Which of the following is the best treatment for this patient’s condition?
A) Erythromycin 5 mg/gram ophthalmic ointment.
B) Ofloxacin 0.3% ophthalmic drops.
C) Antihistamine drops.
D) Eye lubricant drops.
E) No treatment necessary.
This patient is an adult presenting with presumed conjunctivitis. Because he is presenting in the summer without observed purulent discharge, his condition is unlikely to be bacterial. This patient does not need treatment, although eye lubricant drops could reduce his discomfort.
After ruling out serious eye disease, clinicians need to determine which cases of suspected conjunctivitis are most likely to be bacterial to allow for judicious use of antibiotic eye drops. This is an important undertaking as most patients assume that antibiotics are needed.
How do we know which history and clinical exam findings to lean on when attempting to categorize conjunctivitis as bacterial or not? If a patient reports purulent discharge, doesn’t that mean it is bacterial? Surprisingly, a systematic review published in 2016 by Narayana and McGee found that a patient’s self-report of “purulent drainage” is diagnostically unhelpful, but if a clinician finds it on exam, the likelihood of a bacterial etiology increases.3
Narayana and McGee analyzed three studies that enrolled a total of 281 patients with presumed conjunctivitis who underwent bacterial cultures. They then determined which findings increased the probability of positive bacterial culture. From strongest to weakest, the best indicators of a bacterial cause were found to be: complete redness of the conjunctival membrane obscuring tarsal vessels (the vessels visible on the inside of everted upper or lower eyelids) (likelihood ratio, 4.6), observed purulent discharge (LR, 3.9), matting of both eyes in the morning (LR, 3.6), and presence during winter/spring months (LR, 1.9). On the other hand, failure to observe a red eye at 20 feet (LR, 0.2), absence of morning gluing of either eye (LR, 0.3), and presentation during summer months (LR, 0.4) all decreased the probability of a bacterial cause. This review and different study by Stenson et al. unfortunately have conflicting evidence regarding whether the following findings are diagnostically helpful: qualities of eye discomfort (such as burning or itching), preauricular adenopathy, conjunctival follicles, and conjunctival papillae.3,4 Rietveld and colleagues found that a history of conjunctivitis decreased the likelihood of bacterial conjunctivitis.5
Ultimately, if the former indicators are kept in mind, primary care clinicians should be able to decrease the prescribing of topical antimicrobials to patients with non-bacterial conjunctivitis.
Pearl: The best indicators of a bacterial cause in patients with presumed conjunctivitis are complete redness of the conjunctival membrane obscuring tarsal vessels, observed purulent discharge, and matting of both eyes in the morning. Presentation during the summer months and having a history of conjunctivitis decreases the likelihood of bacterial conjunctivitis.
Ms. Momany is a fourth-year medical student at University of Washington, Seattle. Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington and serves as third-year medical student clerkship director at that university. Contact Dr. Paauw at [email protected].
References
1. Azari AA and Barney NP. JAMA. 2013 Oct 23; 310(16):1721-9.
2. Smith AF and Waycaster C. BMC Ophthalmol. 2009 Nov 25. doi: 10.1186/1471-2415-9-13.
3) Narayana S and McGee S. Am J Med. 2015;128(11):1220-4.e1.
4) Stenson S et al. Arch Ophthalmol. 1982;100(8):1275-7.
5) Rietveld RP et al. BMJ. 2004 Jul 24;329(7459):206-10.
A 54-year-old pharmacist with a history of gout, hypertension, and conjunctivitis presents for evaluation of pink eye in the summer. The morning before coming into the office, he noticed that his right eye was red and inflamed. He self-treated with saline washes and eye drops, but upon awakening the next day, he found his right eye to be crusted shut with surrounding yellow discharge. He has not had any changes to his vision but endorses a somewhat uncomfortable, “gritty” sensation. He reports no recent cough, nasal congestion, or allergies, and he has not been around any sick contacts. His blood pressure is 102/58 mm Hg, pulse is 76 bpm, and body mass index is 27.3 kg/m2. His eye exam reveals unilateral conjunctival injections but no hyperemia of the conjunctiva adjacent to the cornea. Mucopurulent discharge was neither found on the undersurface of the eyelid nor emerging from the eye. Which of the following is the best treatment for this patient’s condition?
A) Erythromycin 5 mg/gram ophthalmic ointment.
B) Ofloxacin 0.3% ophthalmic drops.
C) Antihistamine drops.
D) Eye lubricant drops.
E) No treatment necessary.
This patient is an adult presenting with presumed conjunctivitis. Because he is presenting in the summer without observed purulent discharge, his condition is unlikely to be bacterial. This patient does not need treatment, although eye lubricant drops could reduce his discomfort.
After ruling out serious eye disease, clinicians need to determine which cases of suspected conjunctivitis are most likely to be bacterial to allow for judicious use of antibiotic eye drops. This is an important undertaking as most patients assume that antibiotics are needed.
How do we know which history and clinical exam findings to lean on when attempting to categorize conjunctivitis as bacterial or not? If a patient reports purulent discharge, doesn’t that mean it is bacterial? Surprisingly, a systematic review published in 2016 by Narayana and McGee found that a patient’s self-report of “purulent drainage” is diagnostically unhelpful, but if a clinician finds it on exam, the likelihood of a bacterial etiology increases.3
Narayana and McGee analyzed three studies that enrolled a total of 281 patients with presumed conjunctivitis who underwent bacterial cultures. They then determined which findings increased the probability of positive bacterial culture. From strongest to weakest, the best indicators of a bacterial cause were found to be: complete redness of the conjunctival membrane obscuring tarsal vessels (the vessels visible on the inside of everted upper or lower eyelids) (likelihood ratio, 4.6), observed purulent discharge (LR, 3.9), matting of both eyes in the morning (LR, 3.6), and presence during winter/spring months (LR, 1.9). On the other hand, failure to observe a red eye at 20 feet (LR, 0.2), absence of morning gluing of either eye (LR, 0.3), and presentation during summer months (LR, 0.4) all decreased the probability of a bacterial cause. This review and different study by Stenson et al. unfortunately have conflicting evidence regarding whether the following findings are diagnostically helpful: qualities of eye discomfort (such as burning or itching), preauricular adenopathy, conjunctival follicles, and conjunctival papillae.3,4 Rietveld and colleagues found that a history of conjunctivitis decreased the likelihood of bacterial conjunctivitis.5
Ultimately, if the former indicators are kept in mind, primary care clinicians should be able to decrease the prescribing of topical antimicrobials to patients with non-bacterial conjunctivitis.
Pearl: The best indicators of a bacterial cause in patients with presumed conjunctivitis are complete redness of the conjunctival membrane obscuring tarsal vessels, observed purulent discharge, and matting of both eyes in the morning. Presentation during the summer months and having a history of conjunctivitis decreases the likelihood of bacterial conjunctivitis.
Ms. Momany is a fourth-year medical student at University of Washington, Seattle. Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington and serves as third-year medical student clerkship director at that university. Contact Dr. Paauw at [email protected].
References
1. Azari AA and Barney NP. JAMA. 2013 Oct 23; 310(16):1721-9.
2. Smith AF and Waycaster C. BMC Ophthalmol. 2009 Nov 25. doi: 10.1186/1471-2415-9-13.
3) Narayana S and McGee S. Am J Med. 2015;128(11):1220-4.e1.
4) Stenson S et al. Arch Ophthalmol. 1982;100(8):1275-7.
5) Rietveld RP et al. BMJ. 2004 Jul 24;329(7459):206-10.
ID Blog: The story of syphilis, part II
From epidemic to endemic curse
Evolution is an amazing thing, and its more fascinating aspects are never more apparent than in the endless genetic dance between host and pathogen. And certainly, our fascination with the dance is not merely an intellectual exercise. The evolution of disease is perhaps one of the starkest examples of human misery writ large across the pages of recorded history.
In particular, the evolution of syphilis from dramatically visible, epidemic terror to silent, endemic, and long-term killer is one of the most striking examples of host-pathogen evolution. It is an example noteworthy not only for the profound transformation that occurred, but for the speed of the change, beginning so fast that it was noticed and detailed by physicians at the time as occurring over less than a human generation rather than centuries.
This very speed of the change makes it relatively certain that it was not the human species that evolved resistance, but rather that the syphilis-causing spirochetes transformed in virulence within almost the blink of an evolutionary eye – an epidemiologic mystery of profound importance to the countless lives involved.
Syphilis was a dramatic new phenomenon in the Old World of the late 15th and early 16th centuries – a hitherto unknown disease of terrible guise and rapid dissemination. It was noted and discussed throughout many of the writings of the time, so much so that one of the first detailed patient accounts in recorded history of the experience of a disease was written in response to a syphilis infection.
In 1498, Tommaso di Silvestro, an Italian notary, described his symptoms in depth: “I remember how I, Ser Tomaso, during the day 27th of April 1498, coming back from the fair in Foligno, started to feel pain in the virga [a contemporary euphemism for penis]. And then the pain grew in intensity. Then in June I started to feel the pains of the French disease. And all my body filled with pustules and crusts. I had pains in the right and left arms, in the entire arm, from the shoulder to the hand, I was filled with pain to the bones and I never found peace. And then I had pains in the right knee and all my body got full of boils, at the back at the front and behind.”
Alessandro Benedetti (1450-1512), a military surgeon and chronicler of the expedition of Charles VIII, wrote in 1497 that sufferers lost hands, feet, eyes, and noses to the disease, such that it made “the entire body so repulsive to look at and causes such great suffering.”Another common characteristic was a foul smell typical of the infected.
Careful analysis by historians has shown that, according to records from the time period, 10-15 years after the start of the epidemic in the late 15th century, there was a noticeable decline in disease virulence.
As one historian put it: “Many physicians and contemporary observers noticed the progressive decline in the severity of the disease. Many symptoms were less severe, and the rash, of a reddish color, did not cause itching.” Girolamo Fracastoro writes about some of these transformations, stating that “in the first epidemic periods the pustules were filthier,’ while they were ‘harder and drier’ afterwards.” Similarly, the historian and scholar Bernardino Cirillo dell’Aquila (1500-1575), writing in the 1530s, stated: “This horrible disease in different periods (1494) till the present had different alterations and different effects depending on the complications, and now many people just lose their hair and nothing else.”
As added documentation of the change, the chaplain of the infamous conquistador Hernàn Cortés reported that syphilis was less severe in his time than earlier. He wrote that: “at the beginning this disease was very violent, dirty and indecent; now it is no longer so severe and so indecent.”
The medical literature of the time confirmed that the fever, characteristic of the second stage of the disease, “was less violent, while even the rashes were just a ‘reddening.’ Moreover, the gummy tumors appeared only in a limited number of cases.”
According to another historian, “By the middle of the 16th century, the generation of physicians born between the end of the 15th century and the first decades of the 16th century considered the exceptional virulence manifested by syphilis when it first appeared to be ancient history.”
And Ambroise Paré (1510-1590), a renowned French surgeon, stated: “Today it is much less serious and easier to heal than it was in the past... It is obviously becoming much milder … so that it seems it should disappear in the future.”
Lacking detailed genetic analysis of the changing pathogen, if one were to speculate on why the virulence of syphilis decreased so rapidly, I suggest, in a Just-So story fashion, that one might merely speculate on the evolutionary wisdom of an STD that commonly turned its victims into foul-smelling, scabrous, agonized, and lethargic individuals who lost body parts, including their genitals, according to some reports. None of these outcomes, of course, would be conducive to the natural spread of the disease. In addition, this is a good case for sexual selection as well as early death of the host, which are two main engineers of evolutionary change.
But for whatever reason, the presentation of syphilis changed dramatically over a relatively short period of time, and as the disease was still spreading through a previously unexposed population, a change in pathogenicity rather than host immunity seems the most logical explanation.
As syphilis evolved from its initial onslaught, it showed new and hitherto unseen symptoms, including the aforementioned hair loss, and other manifestations such as tinnitus. Soon it was presenting so many systemic phenotypes similar to the effects of other diseases that Sir William Osler (1849-1919) ultimately proposed that syphilis should be described as the “Great Imitator.”
The evolution of syphilis from epidemic to endemic does not diminish the horrors of those afflicted with active tertiary syphilis, but as the disease transformed, these effects were greatly postponed and occurred less commonly, compared with their relatively rapid onset in an earlier era and in a greater proportion of the infected individuals.
Although still lethal, especially in its congenital form, by the end of the 16th century, syphilis had completed its rapid evolution from a devastating, highly visible plague to the covert disease “so sinful that it could not be discussed by name.” It would remain so until the rise of modern antibiotics finally provided a reliable cure. Active tertiary syphilis remained a severe affliction, but the effects were postponed from their relatively rapid onset in an earlier era and in a greater proportion of the infected individuals.
So, syphilis remains a unique example of host-pathogen evolution, an endemic part of the global human condition, battled by physicians in mostly futile efforts for nearly 500 years, and a disease tracking closely with the rise of modern medicine.
References
Frith J. 2012. Syphilis – Its Early History and Treatment Until Penicillin and the Debate on its Origins. J Military and Veteran’s Health. 20(4):49-58.
Tognoti B. 2009. The Rise and Fall of Syphilis in Renaissance Italy. J Med Humanit. 30(2):99-113.
Mark Lesney is the managing editor of MDedge.com/IDPractioner. He has a PhD in plant virology and a PhD in the history of science, with a focus on the history of biotechnology and medicine. He has served as an adjunct assistant professor of the department of biochemistry and molecular & celluar biology at Georgetown University, Washington, D.C.
From epidemic to endemic curse
From epidemic to endemic curse
Evolution is an amazing thing, and its more fascinating aspects are never more apparent than in the endless genetic dance between host and pathogen. And certainly, our fascination with the dance is not merely an intellectual exercise. The evolution of disease is perhaps one of the starkest examples of human misery writ large across the pages of recorded history.
In particular, the evolution of syphilis from dramatically visible, epidemic terror to silent, endemic, and long-term killer is one of the most striking examples of host-pathogen evolution. It is an example noteworthy not only for the profound transformation that occurred, but for the speed of the change, beginning so fast that it was noticed and detailed by physicians at the time as occurring over less than a human generation rather than centuries.
This very speed of the change makes it relatively certain that it was not the human species that evolved resistance, but rather that the syphilis-causing spirochetes transformed in virulence within almost the blink of an evolutionary eye – an epidemiologic mystery of profound importance to the countless lives involved.
Syphilis was a dramatic new phenomenon in the Old World of the late 15th and early 16th centuries – a hitherto unknown disease of terrible guise and rapid dissemination. It was noted and discussed throughout many of the writings of the time, so much so that one of the first detailed patient accounts in recorded history of the experience of a disease was written in response to a syphilis infection.
In 1498, Tommaso di Silvestro, an Italian notary, described his symptoms in depth: “I remember how I, Ser Tomaso, during the day 27th of April 1498, coming back from the fair in Foligno, started to feel pain in the virga [a contemporary euphemism for penis]. And then the pain grew in intensity. Then in June I started to feel the pains of the French disease. And all my body filled with pustules and crusts. I had pains in the right and left arms, in the entire arm, from the shoulder to the hand, I was filled with pain to the bones and I never found peace. And then I had pains in the right knee and all my body got full of boils, at the back at the front and behind.”
Alessandro Benedetti (1450-1512), a military surgeon and chronicler of the expedition of Charles VIII, wrote in 1497 that sufferers lost hands, feet, eyes, and noses to the disease, such that it made “the entire body so repulsive to look at and causes such great suffering.”Another common characteristic was a foul smell typical of the infected.
Careful analysis by historians has shown that, according to records from the time period, 10-15 years after the start of the epidemic in the late 15th century, there was a noticeable decline in disease virulence.
As one historian put it: “Many physicians and contemporary observers noticed the progressive decline in the severity of the disease. Many symptoms were less severe, and the rash, of a reddish color, did not cause itching.” Girolamo Fracastoro writes about some of these transformations, stating that “in the first epidemic periods the pustules were filthier,’ while they were ‘harder and drier’ afterwards.” Similarly, the historian and scholar Bernardino Cirillo dell’Aquila (1500-1575), writing in the 1530s, stated: “This horrible disease in different periods (1494) till the present had different alterations and different effects depending on the complications, and now many people just lose their hair and nothing else.”
As added documentation of the change, the chaplain of the infamous conquistador Hernàn Cortés reported that syphilis was less severe in his time than earlier. He wrote that: “at the beginning this disease was very violent, dirty and indecent; now it is no longer so severe and so indecent.”
The medical literature of the time confirmed that the fever, characteristic of the second stage of the disease, “was less violent, while even the rashes were just a ‘reddening.’ Moreover, the gummy tumors appeared only in a limited number of cases.”
According to another historian, “By the middle of the 16th century, the generation of physicians born between the end of the 15th century and the first decades of the 16th century considered the exceptional virulence manifested by syphilis when it first appeared to be ancient history.”
And Ambroise Paré (1510-1590), a renowned French surgeon, stated: “Today it is much less serious and easier to heal than it was in the past... It is obviously becoming much milder … so that it seems it should disappear in the future.”
Lacking detailed genetic analysis of the changing pathogen, if one were to speculate on why the virulence of syphilis decreased so rapidly, I suggest, in a Just-So story fashion, that one might merely speculate on the evolutionary wisdom of an STD that commonly turned its victims into foul-smelling, scabrous, agonized, and lethargic individuals who lost body parts, including their genitals, according to some reports. None of these outcomes, of course, would be conducive to the natural spread of the disease. In addition, this is a good case for sexual selection as well as early death of the host, which are two main engineers of evolutionary change.
But for whatever reason, the presentation of syphilis changed dramatically over a relatively short period of time, and as the disease was still spreading through a previously unexposed population, a change in pathogenicity rather than host immunity seems the most logical explanation.
As syphilis evolved from its initial onslaught, it showed new and hitherto unseen symptoms, including the aforementioned hair loss, and other manifestations such as tinnitus. Soon it was presenting so many systemic phenotypes similar to the effects of other diseases that Sir William Osler (1849-1919) ultimately proposed that syphilis should be described as the “Great Imitator.”
The evolution of syphilis from epidemic to endemic does not diminish the horrors of those afflicted with active tertiary syphilis, but as the disease transformed, these effects were greatly postponed and occurred less commonly, compared with their relatively rapid onset in an earlier era and in a greater proportion of the infected individuals.
Although still lethal, especially in its congenital form, by the end of the 16th century, syphilis had completed its rapid evolution from a devastating, highly visible plague to the covert disease “so sinful that it could not be discussed by name.” It would remain so until the rise of modern antibiotics finally provided a reliable cure. Active tertiary syphilis remained a severe affliction, but the effects were postponed from their relatively rapid onset in an earlier era and in a greater proportion of the infected individuals.
So, syphilis remains a unique example of host-pathogen evolution, an endemic part of the global human condition, battled by physicians in mostly futile efforts for nearly 500 years, and a disease tracking closely with the rise of modern medicine.
References
Frith J. 2012. Syphilis – Its Early History and Treatment Until Penicillin and the Debate on its Origins. J Military and Veteran’s Health. 20(4):49-58.
Tognoti B. 2009. The Rise and Fall of Syphilis in Renaissance Italy. J Med Humanit. 30(2):99-113.
Mark Lesney is the managing editor of MDedge.com/IDPractioner. He has a PhD in plant virology and a PhD in the history of science, with a focus on the history of biotechnology and medicine. He has served as an adjunct assistant professor of the department of biochemistry and molecular & celluar biology at Georgetown University, Washington, D.C.
Evolution is an amazing thing, and its more fascinating aspects are never more apparent than in the endless genetic dance between host and pathogen. And certainly, our fascination with the dance is not merely an intellectual exercise. The evolution of disease is perhaps one of the starkest examples of human misery writ large across the pages of recorded history.
In particular, the evolution of syphilis from dramatically visible, epidemic terror to silent, endemic, and long-term killer is one of the most striking examples of host-pathogen evolution. It is an example noteworthy not only for the profound transformation that occurred, but for the speed of the change, beginning so fast that it was noticed and detailed by physicians at the time as occurring over less than a human generation rather than centuries.
This very speed of the change makes it relatively certain that it was not the human species that evolved resistance, but rather that the syphilis-causing spirochetes transformed in virulence within almost the blink of an evolutionary eye – an epidemiologic mystery of profound importance to the countless lives involved.
Syphilis was a dramatic new phenomenon in the Old World of the late 15th and early 16th centuries – a hitherto unknown disease of terrible guise and rapid dissemination. It was noted and discussed throughout many of the writings of the time, so much so that one of the first detailed patient accounts in recorded history of the experience of a disease was written in response to a syphilis infection.
In 1498, Tommaso di Silvestro, an Italian notary, described his symptoms in depth: “I remember how I, Ser Tomaso, during the day 27th of April 1498, coming back from the fair in Foligno, started to feel pain in the virga [a contemporary euphemism for penis]. And then the pain grew in intensity. Then in June I started to feel the pains of the French disease. And all my body filled with pustules and crusts. I had pains in the right and left arms, in the entire arm, from the shoulder to the hand, I was filled with pain to the bones and I never found peace. And then I had pains in the right knee and all my body got full of boils, at the back at the front and behind.”
Alessandro Benedetti (1450-1512), a military surgeon and chronicler of the expedition of Charles VIII, wrote in 1497 that sufferers lost hands, feet, eyes, and noses to the disease, such that it made “the entire body so repulsive to look at and causes such great suffering.”Another common characteristic was a foul smell typical of the infected.
Careful analysis by historians has shown that, according to records from the time period, 10-15 years after the start of the epidemic in the late 15th century, there was a noticeable decline in disease virulence.
As one historian put it: “Many physicians and contemporary observers noticed the progressive decline in the severity of the disease. Many symptoms were less severe, and the rash, of a reddish color, did not cause itching.” Girolamo Fracastoro writes about some of these transformations, stating that “in the first epidemic periods the pustules were filthier,’ while they were ‘harder and drier’ afterwards.” Similarly, the historian and scholar Bernardino Cirillo dell’Aquila (1500-1575), writing in the 1530s, stated: “This horrible disease in different periods (1494) till the present had different alterations and different effects depending on the complications, and now many people just lose their hair and nothing else.”
As added documentation of the change, the chaplain of the infamous conquistador Hernàn Cortés reported that syphilis was less severe in his time than earlier. He wrote that: “at the beginning this disease was very violent, dirty and indecent; now it is no longer so severe and so indecent.”
The medical literature of the time confirmed that the fever, characteristic of the second stage of the disease, “was less violent, while even the rashes were just a ‘reddening.’ Moreover, the gummy tumors appeared only in a limited number of cases.”
According to another historian, “By the middle of the 16th century, the generation of physicians born between the end of the 15th century and the first decades of the 16th century considered the exceptional virulence manifested by syphilis when it first appeared to be ancient history.”
And Ambroise Paré (1510-1590), a renowned French surgeon, stated: “Today it is much less serious and easier to heal than it was in the past... It is obviously becoming much milder … so that it seems it should disappear in the future.”
Lacking detailed genetic analysis of the changing pathogen, if one were to speculate on why the virulence of syphilis decreased so rapidly, I suggest, in a Just-So story fashion, that one might merely speculate on the evolutionary wisdom of an STD that commonly turned its victims into foul-smelling, scabrous, agonized, and lethargic individuals who lost body parts, including their genitals, according to some reports. None of these outcomes, of course, would be conducive to the natural spread of the disease. In addition, this is a good case for sexual selection as well as early death of the host, which are two main engineers of evolutionary change.
But for whatever reason, the presentation of syphilis changed dramatically over a relatively short period of time, and as the disease was still spreading through a previously unexposed population, a change in pathogenicity rather than host immunity seems the most logical explanation.
As syphilis evolved from its initial onslaught, it showed new and hitherto unseen symptoms, including the aforementioned hair loss, and other manifestations such as tinnitus. Soon it was presenting so many systemic phenotypes similar to the effects of other diseases that Sir William Osler (1849-1919) ultimately proposed that syphilis should be described as the “Great Imitator.”
The evolution of syphilis from epidemic to endemic does not diminish the horrors of those afflicted with active tertiary syphilis, but as the disease transformed, these effects were greatly postponed and occurred less commonly, compared with their relatively rapid onset in an earlier era and in a greater proportion of the infected individuals.
Although still lethal, especially in its congenital form, by the end of the 16th century, syphilis had completed its rapid evolution from a devastating, highly visible plague to the covert disease “so sinful that it could not be discussed by name.” It would remain so until the rise of modern antibiotics finally provided a reliable cure. Active tertiary syphilis remained a severe affliction, but the effects were postponed from their relatively rapid onset in an earlier era and in a greater proportion of the infected individuals.
So, syphilis remains a unique example of host-pathogen evolution, an endemic part of the global human condition, battled by physicians in mostly futile efforts for nearly 500 years, and a disease tracking closely with the rise of modern medicine.
References
Frith J. 2012. Syphilis – Its Early History and Treatment Until Penicillin and the Debate on its Origins. J Military and Veteran’s Health. 20(4):49-58.
Tognoti B. 2009. The Rise and Fall of Syphilis in Renaissance Italy. J Med Humanit. 30(2):99-113.
Mark Lesney is the managing editor of MDedge.com/IDPractioner. He has a PhD in plant virology and a PhD in the history of science, with a focus on the history of biotechnology and medicine. He has served as an adjunct assistant professor of the department of biochemistry and molecular & celluar biology at Georgetown University, Washington, D.C.
Chlamydia trachomatis is associated with adverse reproductive health outcomes
compared with women who have tested negative for C. trachomatis or who have not been tested for the bacterium, according to a retrospective cohort study.
The risk of PID increases with repeat chlamydial infections, and the use of antibiotics that are effective against C. trachomatis does not decrease the risk of subsequent PID, the researchers reported in Clinical Infectious Diseases.
Prior studies have yielded different estimates of the risk of reproductive complications after chlamydia infection, said Casper den Heijer, MD, PhD, a researcher at Utrecht Institute of Pharmaceutical Sciences in Heerlen, the Netherlands, and colleagues. To assess the risk of PID, ectopic pregnancy, and infertility in women with a previous C. trachomatis diagnosis, Dr. den Heijer and coauthors conducted a retrospective study of women aged 12-25 years at baseline in the Clinical Practice Research Datalink GOLD database. Their analysis included data from women living in England between 2000 and 2013. The investigators used Cox proportional hazard models to evaluate the risk of adverse outcomes.
The researchers analyzed data from 857,324 women with a mean follow-up of 7.5 years. Patients’ mean age at baseline was 15 years. In all, the participants had 8,346 occurrences of PID, 2,484 occurrences of ectopic pregnancy, and 2,066 occurrences of female infertility.
For PID, incidence rates per 1,000 person-years were 1.1 among women untested for C. trachomatis, 1.4 among women who tested negative, and 5.4 among women who tested positive. For ectopic pregnancy, the incidence rates were 0.3 for untested women, 0.4 for negatively tested women, and 1.2 for positively tested women. Infertility incidence rates were 0.3 for untested women, 0.3 for negatively tested women, and 0.9 for positively tested women.
Compared with women who tested negative for C. trachomatis, women who tested positive had an increased risk of PID (adjusted hazard ratio, 2.36), ectopic pregnancy (aHR, 1.87), and female infertility (aHR, 1.85). Untested women had a lower risk for PID, compared with women who tested negative (aHR, 0.57).
C. trachomatis–effective antibiotic use was associated with higher PID risk, and that risk increased as the women used more of the antibiotic prescriptions, Dr. den Heijer and associates said. This occurred in all three groups of women. A possible explanation for this association between the antibiotics and higher PID risk could be that PID can be caused by other infectious diseases that could be treated with C. trachomatis–effective antibiotics.
While the study relied on primary care data, genitourinary medicine clinics diagnose and treat “a sizable proportion” of sexually transmitted infections in the United Kingdom, the authors noted. This limitation means that the study underestimates the number of C. trachomatis diagnoses in the cohort, they said.
Nonetheless, “Our results confirm the reproductive health burden of [C. trachomatis] and show the need for adequate public health interventions,” Dr. den Heijer and associates concluded.
Iris Krishna, MD, said in an interview, “This is a well-designed population-based retrospective cohort study evaluating the incidence of PID, ectopic pregnancy, and female infertility amongst more than 850,000 women in a primary care setting with a previous diagnosis of C. trachomatis, compared with women who have tested negative for C. trachomatis and women who have not been tested for C. trachomatis. This study also evaluated the impact of antibiotic use on PID.”
Dr. Krishna, assistant professor of gynecology and obstetrics in the division of maternal-fetal medicine at Emory University in Atlanta, continued, “This study demonstrates an association between C. trachomatis infection and adverse reproductive health outcomes. It highlights the importance of prompt diagnosis and treatment of C. trachomatis to reduce the risk of both short- and long-term reproductive health complications, as well as highlighting the importance of preventing recurrent C. trachomatis infections. It also emphasizes the importance of targeted screening for high-risk groups and appropriate follow-up to ensure that optimal antibiotic treatment is provided, especially amongst women who have recently used C. trachomatis–effective antibiotics.
“The finding of progression to PID despite C. trachomatis-effective antibiotic use indicates a more complex relationship where perhaps host immunological factors or effects of antibiotics on the vaginal microbiome may play a role and requires further study,” concluded Dr. Krishna. She was not involved in the current study, and was asked to comment on the findings.
The study was supported by the Netherlands Organization for Health Research and Development. Dr. den Heijer had no relevant disclosures. Dr. Krishna said she had no relevant financial disclosures.
SOURCE: den Heijer CDJ et al. Clin Infect Dis. 2019 Aug 24. doi: 10.1093/cid/ciz429.
compared with women who have tested negative for C. trachomatis or who have not been tested for the bacterium, according to a retrospective cohort study.
The risk of PID increases with repeat chlamydial infections, and the use of antibiotics that are effective against C. trachomatis does not decrease the risk of subsequent PID, the researchers reported in Clinical Infectious Diseases.
Prior studies have yielded different estimates of the risk of reproductive complications after chlamydia infection, said Casper den Heijer, MD, PhD, a researcher at Utrecht Institute of Pharmaceutical Sciences in Heerlen, the Netherlands, and colleagues. To assess the risk of PID, ectopic pregnancy, and infertility in women with a previous C. trachomatis diagnosis, Dr. den Heijer and coauthors conducted a retrospective study of women aged 12-25 years at baseline in the Clinical Practice Research Datalink GOLD database. Their analysis included data from women living in England between 2000 and 2013. The investigators used Cox proportional hazard models to evaluate the risk of adverse outcomes.
The researchers analyzed data from 857,324 women with a mean follow-up of 7.5 years. Patients’ mean age at baseline was 15 years. In all, the participants had 8,346 occurrences of PID, 2,484 occurrences of ectopic pregnancy, and 2,066 occurrences of female infertility.
For PID, incidence rates per 1,000 person-years were 1.1 among women untested for C. trachomatis, 1.4 among women who tested negative, and 5.4 among women who tested positive. For ectopic pregnancy, the incidence rates were 0.3 for untested women, 0.4 for negatively tested women, and 1.2 for positively tested women. Infertility incidence rates were 0.3 for untested women, 0.3 for negatively tested women, and 0.9 for positively tested women.
Compared with women who tested negative for C. trachomatis, women who tested positive had an increased risk of PID (adjusted hazard ratio, 2.36), ectopic pregnancy (aHR, 1.87), and female infertility (aHR, 1.85). Untested women had a lower risk for PID, compared with women who tested negative (aHR, 0.57).
C. trachomatis–effective antibiotic use was associated with higher PID risk, and that risk increased as the women used more of the antibiotic prescriptions, Dr. den Heijer and associates said. This occurred in all three groups of women. A possible explanation for this association between the antibiotics and higher PID risk could be that PID can be caused by other infectious diseases that could be treated with C. trachomatis–effective antibiotics.
While the study relied on primary care data, genitourinary medicine clinics diagnose and treat “a sizable proportion” of sexually transmitted infections in the United Kingdom, the authors noted. This limitation means that the study underestimates the number of C. trachomatis diagnoses in the cohort, they said.
Nonetheless, “Our results confirm the reproductive health burden of [C. trachomatis] and show the need for adequate public health interventions,” Dr. den Heijer and associates concluded.
Iris Krishna, MD, said in an interview, “This is a well-designed population-based retrospective cohort study evaluating the incidence of PID, ectopic pregnancy, and female infertility amongst more than 850,000 women in a primary care setting with a previous diagnosis of C. trachomatis, compared with women who have tested negative for C. trachomatis and women who have not been tested for C. trachomatis. This study also evaluated the impact of antibiotic use on PID.”
Dr. Krishna, assistant professor of gynecology and obstetrics in the division of maternal-fetal medicine at Emory University in Atlanta, continued, “This study demonstrates an association between C. trachomatis infection and adverse reproductive health outcomes. It highlights the importance of prompt diagnosis and treatment of C. trachomatis to reduce the risk of both short- and long-term reproductive health complications, as well as highlighting the importance of preventing recurrent C. trachomatis infections. It also emphasizes the importance of targeted screening for high-risk groups and appropriate follow-up to ensure that optimal antibiotic treatment is provided, especially amongst women who have recently used C. trachomatis–effective antibiotics.
“The finding of progression to PID despite C. trachomatis-effective antibiotic use indicates a more complex relationship where perhaps host immunological factors or effects of antibiotics on the vaginal microbiome may play a role and requires further study,” concluded Dr. Krishna. She was not involved in the current study, and was asked to comment on the findings.
The study was supported by the Netherlands Organization for Health Research and Development. Dr. den Heijer had no relevant disclosures. Dr. Krishna said she had no relevant financial disclosures.
SOURCE: den Heijer CDJ et al. Clin Infect Dis. 2019 Aug 24. doi: 10.1093/cid/ciz429.
compared with women who have tested negative for C. trachomatis or who have not been tested for the bacterium, according to a retrospective cohort study.
The risk of PID increases with repeat chlamydial infections, and the use of antibiotics that are effective against C. trachomatis does not decrease the risk of subsequent PID, the researchers reported in Clinical Infectious Diseases.
Prior studies have yielded different estimates of the risk of reproductive complications after chlamydia infection, said Casper den Heijer, MD, PhD, a researcher at Utrecht Institute of Pharmaceutical Sciences in Heerlen, the Netherlands, and colleagues. To assess the risk of PID, ectopic pregnancy, and infertility in women with a previous C. trachomatis diagnosis, Dr. den Heijer and coauthors conducted a retrospective study of women aged 12-25 years at baseline in the Clinical Practice Research Datalink GOLD database. Their analysis included data from women living in England between 2000 and 2013. The investigators used Cox proportional hazard models to evaluate the risk of adverse outcomes.
The researchers analyzed data from 857,324 women with a mean follow-up of 7.5 years. Patients’ mean age at baseline was 15 years. In all, the participants had 8,346 occurrences of PID, 2,484 occurrences of ectopic pregnancy, and 2,066 occurrences of female infertility.
For PID, incidence rates per 1,000 person-years were 1.1 among women untested for C. trachomatis, 1.4 among women who tested negative, and 5.4 among women who tested positive. For ectopic pregnancy, the incidence rates were 0.3 for untested women, 0.4 for negatively tested women, and 1.2 for positively tested women. Infertility incidence rates were 0.3 for untested women, 0.3 for negatively tested women, and 0.9 for positively tested women.
Compared with women who tested negative for C. trachomatis, women who tested positive had an increased risk of PID (adjusted hazard ratio, 2.36), ectopic pregnancy (aHR, 1.87), and female infertility (aHR, 1.85). Untested women had a lower risk for PID, compared with women who tested negative (aHR, 0.57).
C. trachomatis–effective antibiotic use was associated with higher PID risk, and that risk increased as the women used more of the antibiotic prescriptions, Dr. den Heijer and associates said. This occurred in all three groups of women. A possible explanation for this association between the antibiotics and higher PID risk could be that PID can be caused by other infectious diseases that could be treated with C. trachomatis–effective antibiotics.
While the study relied on primary care data, genitourinary medicine clinics diagnose and treat “a sizable proportion” of sexually transmitted infections in the United Kingdom, the authors noted. This limitation means that the study underestimates the number of C. trachomatis diagnoses in the cohort, they said.
Nonetheless, “Our results confirm the reproductive health burden of [C. trachomatis] and show the need for adequate public health interventions,” Dr. den Heijer and associates concluded.
Iris Krishna, MD, said in an interview, “This is a well-designed population-based retrospective cohort study evaluating the incidence of PID, ectopic pregnancy, and female infertility amongst more than 850,000 women in a primary care setting with a previous diagnosis of C. trachomatis, compared with women who have tested negative for C. trachomatis and women who have not been tested for C. trachomatis. This study also evaluated the impact of antibiotic use on PID.”
Dr. Krishna, assistant professor of gynecology and obstetrics in the division of maternal-fetal medicine at Emory University in Atlanta, continued, “This study demonstrates an association between C. trachomatis infection and adverse reproductive health outcomes. It highlights the importance of prompt diagnosis and treatment of C. trachomatis to reduce the risk of both short- and long-term reproductive health complications, as well as highlighting the importance of preventing recurrent C. trachomatis infections. It also emphasizes the importance of targeted screening for high-risk groups and appropriate follow-up to ensure that optimal antibiotic treatment is provided, especially amongst women who have recently used C. trachomatis–effective antibiotics.
“The finding of progression to PID despite C. trachomatis-effective antibiotic use indicates a more complex relationship where perhaps host immunological factors or effects of antibiotics on the vaginal microbiome may play a role and requires further study,” concluded Dr. Krishna. She was not involved in the current study, and was asked to comment on the findings.
The study was supported by the Netherlands Organization for Health Research and Development. Dr. den Heijer had no relevant disclosures. Dr. Krishna said she had no relevant financial disclosures.
SOURCE: den Heijer CDJ et al. Clin Infect Dis. 2019 Aug 24. doi: 10.1093/cid/ciz429.
FROM CLINICAL INFECTIOUS DISEASES
ID Blog: The story of syphilis, part I
Rise of a global scourge
The Great Pox, the French Disease, Cupid’s Disease – syphilis has had many names throughout history.
Why should we care about the history of syphilis? Surely syphilis has reached the status of a nonentity disease – in-and-out of the doctor’s office with a course of antibiotics and farewell to the problem. And on the surface, that is certainly true. For now. In the developed world. For those with access to reasonable health care.
But that is all the shiny surface of modern medical triumph. Despite successes in prevention throughout the late 20th and early 21st century, syphilis is making comeback. A growing reservoir of syphilis, often untreated, lies hidden by the invisibility of poorer nations and increasingly in the lower economic strata of the developed world. And the danger is increased by the rise of antibiotic-resistant strains of the disease.
Over the last decade, the European Union and several other high-income countries observed an increasing syphilis trend, according to a recent report by the European Centre for Disease Prevention and Control. And in the United States, the Centers for Disease Control and Prevention has expressed concern over “the rising tide of syphilis” and a “devastating surge in congenital syphilis.” Many reasons have been suggested for this resurgence of syphilis, including the prevalence of unprotected sex and the overall increase in multiple sexual partners in the sexually active population. This trend has been ascribed to a reduced fear of acquiring HIV from condomless sex because of the rise of antiretroviral therapies, which make HIV infection no longer a death sentence for those who have access to and can afford the drugs.
Men who have sex with men are the most affected population cited, which may in part be related to the trend in unprotected sex that has accompanied the decreasing fear of HIV. But in some countries, syphilis rates among heterosexual populations are on the increase as well. Even more troubling were the increases in syphilis diagnosed among pregnant women that were reported in high-income settings outside of the European Union, which led to increases in congenital syphilis infections.
According to a 2018 update on the global epidemiology of syphilis, each year an estimated 6 million new cases are diagnosed in people aged 15-49 years, with more than 300,000 fetal and neonatal deaths attributed to the disease. An additional 215,000 infants are at increased risk of early death because of prenatal infection.
For syphilis is indeed a nasty disease. But a remarkable one as well. It presents an almost textbook example of disease evolution and adaptation writ large. It is also a disease with equally remarkable properties – acute, systemic, latent, eruptive, and congenital in its various manifestations. As Sir William Osler, one of the brightest lights of medical education of his time, said in 1897: “I often tell my students that it [syphilis] is the only disease which they require to know thoroughly. Know syphilis in all its manifestations and relations, and all other things clinical will be added unto you.”
Syphilis is caused by the spirochete Treponema pallidum subspecies pallidum and is generally acquired by sexual contact. Congenital syphilis infection occurs by transplacental transmission.
In its modern manifestation, the disease evolves through several stages – primary, secondary, and tertiary. Primary, noncongenital infection is characterized by a lesion. This chancre, as it is called, occurs at the original site of infection, typically between 10 days and 3 months after exposure. The chancre usually appears on the genitals, but given the variety of sexual behaviors, chancres can also occur on the rectum, tongue, pharynx, breast, and so on. The myth of only choosing “a clean partner,” one without visible lesions, is misleading because vaginal and rectal lesions may not be easy to spot yet still remain profoundly infectious.
The secondary stage of an untreated infection occurs 2-3 months after the onset of chancre, and results in multisystem involvement as the spirochetes spread through the bloodstream. Symptoms include skin rash (involving the palms and the soles of the feet) and potentially a variety of other dermatologic manifestations. Fever and swollen lymph nodes may also be present before the disease moves into a latent stage, in which no clinical symptoms are evident. Following this, tertiary syphilis can occur 10-30 years after the initial infection in about 30% of the untreated population, resulting in neurosyphilis, cardiovascular syphilis, or late benign syphilis. Disease progression in tertiary syphilis can lead to dementia, disfigurement, and death.
Sounds bad, doesn’t it? But what we’ve just recounted is the relatively benign disease that modern syphilis has become. Syphilis began as a sweeping, lethal epidemic in the late 15th century spreading dread across the world from the Americas to Europe and then to Asia at a speed equal to the fastest sailing ships of the era.
Syphilis first appeared in Naples in its epidemic form in 1495. Recent anthropological and historical consensus has suggested that syphilis, as we know it today, like tobacco, potatoes, and maize is a product of the Americas that was brought to the Old World by the intrepid exploits of one Christopher Columbus in 1493. Just as the Spanish inadvertently brought smallpox to devastate the population of the New World, Christopher Columbus appears to have brought epidemic syphilis to the Old World in an ironic twist of fate.
Ruy Diaz de Isla, one of two Spanish physicians present when Christopher Columbus returned from his first voyage to America, wrote in a manuscript that Pinzon de Palos, the pilot of Columbus, and also other members of the crew already suffered from symptoms of what was likely syphilis on their return from the New World
Although there has been some controversy regarding the origin of the syphilis epidemic, a recent molecular study using a large collection of pathogenic Treponema strains indicated that venereal syphilis arose relatively recently in human history, and that the closest related syphilis-causing strains were found in South America, providing support for the Columbian theory of syphilis’s origin.
Syphilis flamed across Europe like wildfire, lit by a series of small wars that started shortly after Columbus’s return. Soldiers throughout history have indulged themselves in activities well primed for the spread of venereal disease, and the doughty warriors of the late 15th century were no exception. And throughout the next 500-plus years, syphilis and war rode across the world in tandem, like the white and red horsemen of the Apocalypse.
In its initial launch, syphilis had the help of Charles VIII, the King of France, who had invaded Italy in early 1495 with an army of more than 30,000 mercenaries recruited from across Europe. His forces conquered Naples, which was primarily defended by Spanish mercenaries.
When Charles VIII broke up his army, “mercenaries, infected with a mysterious, serious disease, returned to their native lands or moved elsewhere to wage war, spreading the disease across Europe.” The “Great Pox” initially struck Italy, France, Germany, and Switzerland in 1495; then Holland and Greece in the following year, reaching England and Scotland by 1497; and then Hungary, Poland, and the Scandinavian countries by 1500.
As this period was the Age of Exploration, French, Dutch, and English sailors soon carried syphilis across the rest of an unsuspecting world, with the disease reaching India in 1498 before moving also to Africa and then throughout the rest of Asia in the early 16th century.
And yet, one of the most remarkable parts of the story is the rapid transformation of syphilis from a deadly virulent epidemic to a (comparatively) benign endemic status. Which will be the subject of my next posting.
Mark Lesney is the managing editor of MDedge.com/IDPractioner . He has a PhD in Plant Virology and a PhD in the History of Science, with a focus on the history of biotechnology and medicine. He has served as an adjunct assistant professor at the Georgetown University School of Medicine, Department of Biochemistry and Molecular & Cellular Biology, Washington, DC.
Rise of a global scourge
Rise of a global scourge
The Great Pox, the French Disease, Cupid’s Disease – syphilis has had many names throughout history.
Why should we care about the history of syphilis? Surely syphilis has reached the status of a nonentity disease – in-and-out of the doctor’s office with a course of antibiotics and farewell to the problem. And on the surface, that is certainly true. For now. In the developed world. For those with access to reasonable health care.
But that is all the shiny surface of modern medical triumph. Despite successes in prevention throughout the late 20th and early 21st century, syphilis is making comeback. A growing reservoir of syphilis, often untreated, lies hidden by the invisibility of poorer nations and increasingly in the lower economic strata of the developed world. And the danger is increased by the rise of antibiotic-resistant strains of the disease.
Over the last decade, the European Union and several other high-income countries observed an increasing syphilis trend, according to a recent report by the European Centre for Disease Prevention and Control. And in the United States, the Centers for Disease Control and Prevention has expressed concern over “the rising tide of syphilis” and a “devastating surge in congenital syphilis.” Many reasons have been suggested for this resurgence of syphilis, including the prevalence of unprotected sex and the overall increase in multiple sexual partners in the sexually active population. This trend has been ascribed to a reduced fear of acquiring HIV from condomless sex because of the rise of antiretroviral therapies, which make HIV infection no longer a death sentence for those who have access to and can afford the drugs.
Men who have sex with men are the most affected population cited, which may in part be related to the trend in unprotected sex that has accompanied the decreasing fear of HIV. But in some countries, syphilis rates among heterosexual populations are on the increase as well. Even more troubling were the increases in syphilis diagnosed among pregnant women that were reported in high-income settings outside of the European Union, which led to increases in congenital syphilis infections.
According to a 2018 update on the global epidemiology of syphilis, each year an estimated 6 million new cases are diagnosed in people aged 15-49 years, with more than 300,000 fetal and neonatal deaths attributed to the disease. An additional 215,000 infants are at increased risk of early death because of prenatal infection.
For syphilis is indeed a nasty disease. But a remarkable one as well. It presents an almost textbook example of disease evolution and adaptation writ large. It is also a disease with equally remarkable properties – acute, systemic, latent, eruptive, and congenital in its various manifestations. As Sir William Osler, one of the brightest lights of medical education of his time, said in 1897: “I often tell my students that it [syphilis] is the only disease which they require to know thoroughly. Know syphilis in all its manifestations and relations, and all other things clinical will be added unto you.”
Syphilis is caused by the spirochete Treponema pallidum subspecies pallidum and is generally acquired by sexual contact. Congenital syphilis infection occurs by transplacental transmission.
In its modern manifestation, the disease evolves through several stages – primary, secondary, and tertiary. Primary, noncongenital infection is characterized by a lesion. This chancre, as it is called, occurs at the original site of infection, typically between 10 days and 3 months after exposure. The chancre usually appears on the genitals, but given the variety of sexual behaviors, chancres can also occur on the rectum, tongue, pharynx, breast, and so on. The myth of only choosing “a clean partner,” one without visible lesions, is misleading because vaginal and rectal lesions may not be easy to spot yet still remain profoundly infectious.
The secondary stage of an untreated infection occurs 2-3 months after the onset of chancre, and results in multisystem involvement as the spirochetes spread through the bloodstream. Symptoms include skin rash (involving the palms and the soles of the feet) and potentially a variety of other dermatologic manifestations. Fever and swollen lymph nodes may also be present before the disease moves into a latent stage, in which no clinical symptoms are evident. Following this, tertiary syphilis can occur 10-30 years after the initial infection in about 30% of the untreated population, resulting in neurosyphilis, cardiovascular syphilis, or late benign syphilis. Disease progression in tertiary syphilis can lead to dementia, disfigurement, and death.
Sounds bad, doesn’t it? But what we’ve just recounted is the relatively benign disease that modern syphilis has become. Syphilis began as a sweeping, lethal epidemic in the late 15th century spreading dread across the world from the Americas to Europe and then to Asia at a speed equal to the fastest sailing ships of the era.
Syphilis first appeared in Naples in its epidemic form in 1495. Recent anthropological and historical consensus has suggested that syphilis, as we know it today, like tobacco, potatoes, and maize is a product of the Americas that was brought to the Old World by the intrepid exploits of one Christopher Columbus in 1493. Just as the Spanish inadvertently brought smallpox to devastate the population of the New World, Christopher Columbus appears to have brought epidemic syphilis to the Old World in an ironic twist of fate.
Ruy Diaz de Isla, one of two Spanish physicians present when Christopher Columbus returned from his first voyage to America, wrote in a manuscript that Pinzon de Palos, the pilot of Columbus, and also other members of the crew already suffered from symptoms of what was likely syphilis on their return from the New World
Although there has been some controversy regarding the origin of the syphilis epidemic, a recent molecular study using a large collection of pathogenic Treponema strains indicated that venereal syphilis arose relatively recently in human history, and that the closest related syphilis-causing strains were found in South America, providing support for the Columbian theory of syphilis’s origin.
Syphilis flamed across Europe like wildfire, lit by a series of small wars that started shortly after Columbus’s return. Soldiers throughout history have indulged themselves in activities well primed for the spread of venereal disease, and the doughty warriors of the late 15th century were no exception. And throughout the next 500-plus years, syphilis and war rode across the world in tandem, like the white and red horsemen of the Apocalypse.
In its initial launch, syphilis had the help of Charles VIII, the King of France, who had invaded Italy in early 1495 with an army of more than 30,000 mercenaries recruited from across Europe. His forces conquered Naples, which was primarily defended by Spanish mercenaries.
When Charles VIII broke up his army, “mercenaries, infected with a mysterious, serious disease, returned to their native lands or moved elsewhere to wage war, spreading the disease across Europe.” The “Great Pox” initially struck Italy, France, Germany, and Switzerland in 1495; then Holland and Greece in the following year, reaching England and Scotland by 1497; and then Hungary, Poland, and the Scandinavian countries by 1500.
As this period was the Age of Exploration, French, Dutch, and English sailors soon carried syphilis across the rest of an unsuspecting world, with the disease reaching India in 1498 before moving also to Africa and then throughout the rest of Asia in the early 16th century.
And yet, one of the most remarkable parts of the story is the rapid transformation of syphilis from a deadly virulent epidemic to a (comparatively) benign endemic status. Which will be the subject of my next posting.
Mark Lesney is the managing editor of MDedge.com/IDPractioner . He has a PhD in Plant Virology and a PhD in the History of Science, with a focus on the history of biotechnology and medicine. He has served as an adjunct assistant professor at the Georgetown University School of Medicine, Department of Biochemistry and Molecular & Cellular Biology, Washington, DC.
The Great Pox, the French Disease, Cupid’s Disease – syphilis has had many names throughout history.
Why should we care about the history of syphilis? Surely syphilis has reached the status of a nonentity disease – in-and-out of the doctor’s office with a course of antibiotics and farewell to the problem. And on the surface, that is certainly true. For now. In the developed world. For those with access to reasonable health care.
But that is all the shiny surface of modern medical triumph. Despite successes in prevention throughout the late 20th and early 21st century, syphilis is making comeback. A growing reservoir of syphilis, often untreated, lies hidden by the invisibility of poorer nations and increasingly in the lower economic strata of the developed world. And the danger is increased by the rise of antibiotic-resistant strains of the disease.
Over the last decade, the European Union and several other high-income countries observed an increasing syphilis trend, according to a recent report by the European Centre for Disease Prevention and Control. And in the United States, the Centers for Disease Control and Prevention has expressed concern over “the rising tide of syphilis” and a “devastating surge in congenital syphilis.” Many reasons have been suggested for this resurgence of syphilis, including the prevalence of unprotected sex and the overall increase in multiple sexual partners in the sexually active population. This trend has been ascribed to a reduced fear of acquiring HIV from condomless sex because of the rise of antiretroviral therapies, which make HIV infection no longer a death sentence for those who have access to and can afford the drugs.
Men who have sex with men are the most affected population cited, which may in part be related to the trend in unprotected sex that has accompanied the decreasing fear of HIV. But in some countries, syphilis rates among heterosexual populations are on the increase as well. Even more troubling were the increases in syphilis diagnosed among pregnant women that were reported in high-income settings outside of the European Union, which led to increases in congenital syphilis infections.
According to a 2018 update on the global epidemiology of syphilis, each year an estimated 6 million new cases are diagnosed in people aged 15-49 years, with more than 300,000 fetal and neonatal deaths attributed to the disease. An additional 215,000 infants are at increased risk of early death because of prenatal infection.
For syphilis is indeed a nasty disease. But a remarkable one as well. It presents an almost textbook example of disease evolution and adaptation writ large. It is also a disease with equally remarkable properties – acute, systemic, latent, eruptive, and congenital in its various manifestations. As Sir William Osler, one of the brightest lights of medical education of his time, said in 1897: “I often tell my students that it [syphilis] is the only disease which they require to know thoroughly. Know syphilis in all its manifestations and relations, and all other things clinical will be added unto you.”
Syphilis is caused by the spirochete Treponema pallidum subspecies pallidum and is generally acquired by sexual contact. Congenital syphilis infection occurs by transplacental transmission.
In its modern manifestation, the disease evolves through several stages – primary, secondary, and tertiary. Primary, noncongenital infection is characterized by a lesion. This chancre, as it is called, occurs at the original site of infection, typically between 10 days and 3 months after exposure. The chancre usually appears on the genitals, but given the variety of sexual behaviors, chancres can also occur on the rectum, tongue, pharynx, breast, and so on. The myth of only choosing “a clean partner,” one without visible lesions, is misleading because vaginal and rectal lesions may not be easy to spot yet still remain profoundly infectious.
The secondary stage of an untreated infection occurs 2-3 months after the onset of chancre, and results in multisystem involvement as the spirochetes spread through the bloodstream. Symptoms include skin rash (involving the palms and the soles of the feet) and potentially a variety of other dermatologic manifestations. Fever and swollen lymph nodes may also be present before the disease moves into a latent stage, in which no clinical symptoms are evident. Following this, tertiary syphilis can occur 10-30 years after the initial infection in about 30% of the untreated population, resulting in neurosyphilis, cardiovascular syphilis, or late benign syphilis. Disease progression in tertiary syphilis can lead to dementia, disfigurement, and death.
Sounds bad, doesn’t it? But what we’ve just recounted is the relatively benign disease that modern syphilis has become. Syphilis began as a sweeping, lethal epidemic in the late 15th century spreading dread across the world from the Americas to Europe and then to Asia at a speed equal to the fastest sailing ships of the era.
Syphilis first appeared in Naples in its epidemic form in 1495. Recent anthropological and historical consensus has suggested that syphilis, as we know it today, like tobacco, potatoes, and maize is a product of the Americas that was brought to the Old World by the intrepid exploits of one Christopher Columbus in 1493. Just as the Spanish inadvertently brought smallpox to devastate the population of the New World, Christopher Columbus appears to have brought epidemic syphilis to the Old World in an ironic twist of fate.
Ruy Diaz de Isla, one of two Spanish physicians present when Christopher Columbus returned from his first voyage to America, wrote in a manuscript that Pinzon de Palos, the pilot of Columbus, and also other members of the crew already suffered from symptoms of what was likely syphilis on their return from the New World
Although there has been some controversy regarding the origin of the syphilis epidemic, a recent molecular study using a large collection of pathogenic Treponema strains indicated that venereal syphilis arose relatively recently in human history, and that the closest related syphilis-causing strains were found in South America, providing support for the Columbian theory of syphilis’s origin.
Syphilis flamed across Europe like wildfire, lit by a series of small wars that started shortly after Columbus’s return. Soldiers throughout history have indulged themselves in activities well primed for the spread of venereal disease, and the doughty warriors of the late 15th century were no exception. And throughout the next 500-plus years, syphilis and war rode across the world in tandem, like the white and red horsemen of the Apocalypse.
In its initial launch, syphilis had the help of Charles VIII, the King of France, who had invaded Italy in early 1495 with an army of more than 30,000 mercenaries recruited from across Europe. His forces conquered Naples, which was primarily defended by Spanish mercenaries.
When Charles VIII broke up his army, “mercenaries, infected with a mysterious, serious disease, returned to their native lands or moved elsewhere to wage war, spreading the disease across Europe.” The “Great Pox” initially struck Italy, France, Germany, and Switzerland in 1495; then Holland and Greece in the following year, reaching England and Scotland by 1497; and then Hungary, Poland, and the Scandinavian countries by 1500.
As this period was the Age of Exploration, French, Dutch, and English sailors soon carried syphilis across the rest of an unsuspecting world, with the disease reaching India in 1498 before moving also to Africa and then throughout the rest of Asia in the early 16th century.
And yet, one of the most remarkable parts of the story is the rapid transformation of syphilis from a deadly virulent epidemic to a (comparatively) benign endemic status. Which will be the subject of my next posting.
Mark Lesney is the managing editor of MDedge.com/IDPractioner . He has a PhD in Plant Virology and a PhD in the History of Science, with a focus on the history of biotechnology and medicine. He has served as an adjunct assistant professor at the Georgetown University School of Medicine, Department of Biochemistry and Molecular & Cellular Biology, Washington, DC.
In vasculitis, the skin tells the story
MILAN – , Robert Micheletti, MD, said at the World Congress of Dermatology.
In granulomatous vasculitis, histiocytes and giant cells can play a significant role, explained Dr. Micheletti, director of the cutaneous vasculitis clinic at the University of Pennsylvania, Philadelphia. The condition may be secondary to an autoimmune disease such as lupus erythematosus or RA; a granulomatous disease such as Crohn’s disease or sarcoidosis; infections such as tuberculosis, a fungal disease, or herpes or zoster viruses, or lymphoma, Dr. Micheletti said.
However, a primary systemic vasculitis such as granulomatosis with polyangiitis (GPA; formerly known as Wegener’s polyangiitis) or eosinophilic granulomatosis with polyangiitis (EGPA; also known as Churg-Strauss vasculitis), giant cell arteritis, or Takayasu arteritis may also be responsible, he said. Occasionally, the culprit can also be a drug-induced vasculitis.
The physical examination gives clues to the size of involved vessels, which in turn helps to classify the vasculitis, Dr. Micheletti said.
When vasculitis affects small vessels, the skin findings will be palpable purpura, urticarial papules, vesicles, and petechiae, he said, adding that “The small vessel involvement accounts for the small size of the lesions, and complement cascade and inflammation account for the palpability of the lesions and the symptomatology.” As red blood cells extravasate from the affected vessels, nonblanching purpura develop, and gravity’s effect on the deposition of immune complex material dictates how lesions are distributed.
“Manifestations more typical of medium vessel vasculitis include subcutaneous nodules, livedo reticularis, retiform purpura, larger hemorrhagic bullae, and more significant ulceration and necrosis,” he said. “If such lesions are seen, suspect medium-vessel vasculitis or vasculitis overlapping small and medium vessels.” Cutaneous or systemic polyarteritis nodosa, antineutrophilic cytoplasmic autoantibody (ANCA)–associated vasculitis, and cryoglobulinemic vasculitis are examples, he added.
The particularities of renal manifestations of vasculitis also offer clues to the vessels involved. When a vasculitis patient has glomerulonephritis, suspect small-vessel involvement, Dr. Micheletti said. However, vasculitis affecting medium-sized vessels will cause renovascular hypertension and, potentially renal arterial aneurysms.
Nerves are typically spared in small-vessel vasculitis, while wrist or foot drop can be seen in mononeuritis multiplex.
Recently, the Diagnostic and Classification Criteria in Vasculitis Study (DCVAS) looked at more than 6,800 patients at over 130 sites around the world, proposing new classification criteria for ANCA-associated vasculitis (AAV) and large-vessel vasculitis. The study found that skin findings are common in AAV, with 30%-50% of cases presenting initially with skin lesions. Petechiae and/or purpura are the most common of the skin manifestations, he said. By contrast, for EGPA, allergic and nonspecific findings were the most common findings.
Although skin biopsy can confirm the diagnosis in up to 94% of AAV cases, it’s underutilized and performed in less than half (24%-44%) of cases, Dr. Micheletti said. The study’s findings “demonstrate the importance of a good skin exam, as well as its utility for diagnosis” of vasculitis, he said.
An additional finding form the DCVAS study was that skin lesions can give clues to severity of vasculitis: “Among 1,184 patients with ANCA-associated vasculitis, those with cutaneous involvement were more likely to have systemic manifestations of disease, more likely to have such severe manifestations as glomerulonephritis, alveolar hemorrhage, and mononeuritis,” said Dr. Micheletti, with a hazard ratio of 2.0 among those individuals who had EGPA or GPA.
“Skin findings have diagnostic and, potentially, prognostic importance,” he said. “Use the physician exam and your clinical acumen to your advantage,” but always confirm vasculitis with a biopsy. “Clinicopathologic correlation is key.” A simple urinalysis will screen for renal involvement, and is of “paramount importance,” he added.
Dr. Micheletti reported that he had no relevant disclosures.
MILAN – , Robert Micheletti, MD, said at the World Congress of Dermatology.
In granulomatous vasculitis, histiocytes and giant cells can play a significant role, explained Dr. Micheletti, director of the cutaneous vasculitis clinic at the University of Pennsylvania, Philadelphia. The condition may be secondary to an autoimmune disease such as lupus erythematosus or RA; a granulomatous disease such as Crohn’s disease or sarcoidosis; infections such as tuberculosis, a fungal disease, or herpes or zoster viruses, or lymphoma, Dr. Micheletti said.
However, a primary systemic vasculitis such as granulomatosis with polyangiitis (GPA; formerly known as Wegener’s polyangiitis) or eosinophilic granulomatosis with polyangiitis (EGPA; also known as Churg-Strauss vasculitis), giant cell arteritis, or Takayasu arteritis may also be responsible, he said. Occasionally, the culprit can also be a drug-induced vasculitis.
The physical examination gives clues to the size of involved vessels, which in turn helps to classify the vasculitis, Dr. Micheletti said.
When vasculitis affects small vessels, the skin findings will be palpable purpura, urticarial papules, vesicles, and petechiae, he said, adding that “The small vessel involvement accounts for the small size of the lesions, and complement cascade and inflammation account for the palpability of the lesions and the symptomatology.” As red blood cells extravasate from the affected vessels, nonblanching purpura develop, and gravity’s effect on the deposition of immune complex material dictates how lesions are distributed.
“Manifestations more typical of medium vessel vasculitis include subcutaneous nodules, livedo reticularis, retiform purpura, larger hemorrhagic bullae, and more significant ulceration and necrosis,” he said. “If such lesions are seen, suspect medium-vessel vasculitis or vasculitis overlapping small and medium vessels.” Cutaneous or systemic polyarteritis nodosa, antineutrophilic cytoplasmic autoantibody (ANCA)–associated vasculitis, and cryoglobulinemic vasculitis are examples, he added.
The particularities of renal manifestations of vasculitis also offer clues to the vessels involved. When a vasculitis patient has glomerulonephritis, suspect small-vessel involvement, Dr. Micheletti said. However, vasculitis affecting medium-sized vessels will cause renovascular hypertension and, potentially renal arterial aneurysms.
Nerves are typically spared in small-vessel vasculitis, while wrist or foot drop can be seen in mononeuritis multiplex.
Recently, the Diagnostic and Classification Criteria in Vasculitis Study (DCVAS) looked at more than 6,800 patients at over 130 sites around the world, proposing new classification criteria for ANCA-associated vasculitis (AAV) and large-vessel vasculitis. The study found that skin findings are common in AAV, with 30%-50% of cases presenting initially with skin lesions. Petechiae and/or purpura are the most common of the skin manifestations, he said. By contrast, for EGPA, allergic and nonspecific findings were the most common findings.
Although skin biopsy can confirm the diagnosis in up to 94% of AAV cases, it’s underutilized and performed in less than half (24%-44%) of cases, Dr. Micheletti said. The study’s findings “demonstrate the importance of a good skin exam, as well as its utility for diagnosis” of vasculitis, he said.
An additional finding form the DCVAS study was that skin lesions can give clues to severity of vasculitis: “Among 1,184 patients with ANCA-associated vasculitis, those with cutaneous involvement were more likely to have systemic manifestations of disease, more likely to have such severe manifestations as glomerulonephritis, alveolar hemorrhage, and mononeuritis,” said Dr. Micheletti, with a hazard ratio of 2.0 among those individuals who had EGPA or GPA.
“Skin findings have diagnostic and, potentially, prognostic importance,” he said. “Use the physician exam and your clinical acumen to your advantage,” but always confirm vasculitis with a biopsy. “Clinicopathologic correlation is key.” A simple urinalysis will screen for renal involvement, and is of “paramount importance,” he added.
Dr. Micheletti reported that he had no relevant disclosures.
MILAN – , Robert Micheletti, MD, said at the World Congress of Dermatology.
In granulomatous vasculitis, histiocytes and giant cells can play a significant role, explained Dr. Micheletti, director of the cutaneous vasculitis clinic at the University of Pennsylvania, Philadelphia. The condition may be secondary to an autoimmune disease such as lupus erythematosus or RA; a granulomatous disease such as Crohn’s disease or sarcoidosis; infections such as tuberculosis, a fungal disease, or herpes or zoster viruses, or lymphoma, Dr. Micheletti said.
However, a primary systemic vasculitis such as granulomatosis with polyangiitis (GPA; formerly known as Wegener’s polyangiitis) or eosinophilic granulomatosis with polyangiitis (EGPA; also known as Churg-Strauss vasculitis), giant cell arteritis, or Takayasu arteritis may also be responsible, he said. Occasionally, the culprit can also be a drug-induced vasculitis.
The physical examination gives clues to the size of involved vessels, which in turn helps to classify the vasculitis, Dr. Micheletti said.
When vasculitis affects small vessels, the skin findings will be palpable purpura, urticarial papules, vesicles, and petechiae, he said, adding that “The small vessel involvement accounts for the small size of the lesions, and complement cascade and inflammation account for the palpability of the lesions and the symptomatology.” As red blood cells extravasate from the affected vessels, nonblanching purpura develop, and gravity’s effect on the deposition of immune complex material dictates how lesions are distributed.
“Manifestations more typical of medium vessel vasculitis include subcutaneous nodules, livedo reticularis, retiform purpura, larger hemorrhagic bullae, and more significant ulceration and necrosis,” he said. “If such lesions are seen, suspect medium-vessel vasculitis or vasculitis overlapping small and medium vessels.” Cutaneous or systemic polyarteritis nodosa, antineutrophilic cytoplasmic autoantibody (ANCA)–associated vasculitis, and cryoglobulinemic vasculitis are examples, he added.
The particularities of renal manifestations of vasculitis also offer clues to the vessels involved. When a vasculitis patient has glomerulonephritis, suspect small-vessel involvement, Dr. Micheletti said. However, vasculitis affecting medium-sized vessels will cause renovascular hypertension and, potentially renal arterial aneurysms.
Nerves are typically spared in small-vessel vasculitis, while wrist or foot drop can be seen in mononeuritis multiplex.
Recently, the Diagnostic and Classification Criteria in Vasculitis Study (DCVAS) looked at more than 6,800 patients at over 130 sites around the world, proposing new classification criteria for ANCA-associated vasculitis (AAV) and large-vessel vasculitis. The study found that skin findings are common in AAV, with 30%-50% of cases presenting initially with skin lesions. Petechiae and/or purpura are the most common of the skin manifestations, he said. By contrast, for EGPA, allergic and nonspecific findings were the most common findings.
Although skin biopsy can confirm the diagnosis in up to 94% of AAV cases, it’s underutilized and performed in less than half (24%-44%) of cases, Dr. Micheletti said. The study’s findings “demonstrate the importance of a good skin exam, as well as its utility for diagnosis” of vasculitis, he said.
An additional finding form the DCVAS study was that skin lesions can give clues to severity of vasculitis: “Among 1,184 patients with ANCA-associated vasculitis, those with cutaneous involvement were more likely to have systemic manifestations of disease, more likely to have such severe manifestations as glomerulonephritis, alveolar hemorrhage, and mononeuritis,” said Dr. Micheletti, with a hazard ratio of 2.0 among those individuals who had EGPA or GPA.
“Skin findings have diagnostic and, potentially, prognostic importance,” he said. “Use the physician exam and your clinical acumen to your advantage,” but always confirm vasculitis with a biopsy. “Clinicopathologic correlation is key.” A simple urinalysis will screen for renal involvement, and is of “paramount importance,” he added.
Dr. Micheletti reported that he had no relevant disclosures.
AT WCD2019
ACIP extends HPV vaccine coverage
according to a unanimous vote at a meeting of the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices.
This change affects males aged 22 through 26 years; the HPV vaccine is currently recommended for males and females aged 11 or 12 years, with catch-up vaccination through age 21 for males and age 26 for females.
The change was supported in part by increased interest in simplifying and harmonizing the vaccine schedule, said Lauri Markowitz, MD, of the CDC’s National Center for Immunization and Respiratory Diseases (NCIRD), who presented the HPV work group’s considerations.
In addition, the committee voted 10-4 in favor of catch-up HPV vaccination, based on shared clinical decision making, for all adults aged 27 through 45 years.
Although the current program of HPV vaccination for youth has demonstrated effectiveness, data from multiple models suggest that widespread HPV vaccination for adults older than 26 years is much less cost effective, and would yield relatively small additional health benefits, Dr. Markowitz said.
The HPV work group reviewed data from a range of clinical trials, epidemiology, and natural history, as well as results from five different health economic models. They concluded that an assessment of benefits and harms favors expanding the catch-up vaccination to all individuals through 26 years, said Elissa Meites, MD, of the CDC, who presented the official work group opinion. The group’s opinion on the second question was that the additional population level benefit of expanding HPV vaccination to all adults would be minimal and not a reasonable and effective allocation of resources, but that shared clinical decision making would allow flexibility.
The committee expressed strong opinions about the potential for shared clinical decision making as a policy for vaccination for adults older than 26 years. Some felt that this option was a way to include adults at risk for HPV, such as divorced women with new partners, or women getting married for the first time later in life who might not have been exposed to HPV through other relationships. In addition, supporters noted that the shared clinical decision-making option would allow for potential insurance coverage, and would involve discussion between doctors and patients to assess risk.
However, other committee members felt that any recommendation for older adult vaccination would distract clinicians from the importance and value of HPV vaccination for the target age group of 11- and 12-year-olds, and might divert resources from the younger age group in whom it has shown the most benefit.
Resource allocation was a concern voiced by many committee members. Kelly Moore, MD, MPH, of Vanderbilt University, Nashville, Tenn., said she voted no on expanding vaccination to older adults because “we didn’t have details on shared clinical decision making, in the absence of information on what that meant, and in the presence of supply questions, I didn’t feel comfortable expanding vaccination to a huge population,” she said.
Paul Hunter, MD, of the City of Milwaukee Health Department, also voted no, and expressed concern that expanding the HPV vaccination recommendations to older adults would send the message that vaccination for children and teens is not effective or important.
The text of the new recommendations for routine and catch-up vaccination states that the recommendations “also apply to MSM [men who have sex with men], transgender people, and people with immunocompromising conditions.”
The ACIP members had no financial conflicts to disclose.
according to a unanimous vote at a meeting of the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices.
This change affects males aged 22 through 26 years; the HPV vaccine is currently recommended for males and females aged 11 or 12 years, with catch-up vaccination through age 21 for males and age 26 for females.
The change was supported in part by increased interest in simplifying and harmonizing the vaccine schedule, said Lauri Markowitz, MD, of the CDC’s National Center for Immunization and Respiratory Diseases (NCIRD), who presented the HPV work group’s considerations.
In addition, the committee voted 10-4 in favor of catch-up HPV vaccination, based on shared clinical decision making, for all adults aged 27 through 45 years.
Although the current program of HPV vaccination for youth has demonstrated effectiveness, data from multiple models suggest that widespread HPV vaccination for adults older than 26 years is much less cost effective, and would yield relatively small additional health benefits, Dr. Markowitz said.
The HPV work group reviewed data from a range of clinical trials, epidemiology, and natural history, as well as results from five different health economic models. They concluded that an assessment of benefits and harms favors expanding the catch-up vaccination to all individuals through 26 years, said Elissa Meites, MD, of the CDC, who presented the official work group opinion. The group’s opinion on the second question was that the additional population level benefit of expanding HPV vaccination to all adults would be minimal and not a reasonable and effective allocation of resources, but that shared clinical decision making would allow flexibility.
The committee expressed strong opinions about the potential for shared clinical decision making as a policy for vaccination for adults older than 26 years. Some felt that this option was a way to include adults at risk for HPV, such as divorced women with new partners, or women getting married for the first time later in life who might not have been exposed to HPV through other relationships. In addition, supporters noted that the shared clinical decision-making option would allow for potential insurance coverage, and would involve discussion between doctors and patients to assess risk.
However, other committee members felt that any recommendation for older adult vaccination would distract clinicians from the importance and value of HPV vaccination for the target age group of 11- and 12-year-olds, and might divert resources from the younger age group in whom it has shown the most benefit.
Resource allocation was a concern voiced by many committee members. Kelly Moore, MD, MPH, of Vanderbilt University, Nashville, Tenn., said she voted no on expanding vaccination to older adults because “we didn’t have details on shared clinical decision making, in the absence of information on what that meant, and in the presence of supply questions, I didn’t feel comfortable expanding vaccination to a huge population,” she said.
Paul Hunter, MD, of the City of Milwaukee Health Department, also voted no, and expressed concern that expanding the HPV vaccination recommendations to older adults would send the message that vaccination for children and teens is not effective or important.
The text of the new recommendations for routine and catch-up vaccination states that the recommendations “also apply to MSM [men who have sex with men], transgender people, and people with immunocompromising conditions.”
The ACIP members had no financial conflicts to disclose.
according to a unanimous vote at a meeting of the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices.
This change affects males aged 22 through 26 years; the HPV vaccine is currently recommended for males and females aged 11 or 12 years, with catch-up vaccination through age 21 for males and age 26 for females.
The change was supported in part by increased interest in simplifying and harmonizing the vaccine schedule, said Lauri Markowitz, MD, of the CDC’s National Center for Immunization and Respiratory Diseases (NCIRD), who presented the HPV work group’s considerations.
In addition, the committee voted 10-4 in favor of catch-up HPV vaccination, based on shared clinical decision making, for all adults aged 27 through 45 years.
Although the current program of HPV vaccination for youth has demonstrated effectiveness, data from multiple models suggest that widespread HPV vaccination for adults older than 26 years is much less cost effective, and would yield relatively small additional health benefits, Dr. Markowitz said.
The HPV work group reviewed data from a range of clinical trials, epidemiology, and natural history, as well as results from five different health economic models. They concluded that an assessment of benefits and harms favors expanding the catch-up vaccination to all individuals through 26 years, said Elissa Meites, MD, of the CDC, who presented the official work group opinion. The group’s opinion on the second question was that the additional population level benefit of expanding HPV vaccination to all adults would be minimal and not a reasonable and effective allocation of resources, but that shared clinical decision making would allow flexibility.
The committee expressed strong opinions about the potential for shared clinical decision making as a policy for vaccination for adults older than 26 years. Some felt that this option was a way to include adults at risk for HPV, such as divorced women with new partners, or women getting married for the first time later in life who might not have been exposed to HPV through other relationships. In addition, supporters noted that the shared clinical decision-making option would allow for potential insurance coverage, and would involve discussion between doctors and patients to assess risk.
However, other committee members felt that any recommendation for older adult vaccination would distract clinicians from the importance and value of HPV vaccination for the target age group of 11- and 12-year-olds, and might divert resources from the younger age group in whom it has shown the most benefit.
Resource allocation was a concern voiced by many committee members. Kelly Moore, MD, MPH, of Vanderbilt University, Nashville, Tenn., said she voted no on expanding vaccination to older adults because “we didn’t have details on shared clinical decision making, in the absence of information on what that meant, and in the presence of supply questions, I didn’t feel comfortable expanding vaccination to a huge population,” she said.
Paul Hunter, MD, of the City of Milwaukee Health Department, also voted no, and expressed concern that expanding the HPV vaccination recommendations to older adults would send the message that vaccination for children and teens is not effective or important.
The text of the new recommendations for routine and catch-up vaccination states that the recommendations “also apply to MSM [men who have sex with men], transgender people, and people with immunocompromising conditions.”
The ACIP members had no financial conflicts to disclose.
REPORTING FROM AN ACIP MEETING
Syphilis rates high in HIV-positive women
SEATTLE – The frequency of syphilis in HIV-infected women is unusually high, prompting concerns about congenital syphilis among newborns. The finding comes from a Centers for Disease Control analysis of the U.S. Center for Aids Research Clinical Network of Integrated Clinical Systems (CNICS) cohort.
“We found significant associations [between syphilis infection] and drug use and hepatitis C infection, which adds to some information from the CDC that what’s driving the epidemic in women is drug use – it’s a very different epidemic potentially in women with HIV than in men with HIV,” said Jodie Dionne-Odom, MD, chief of women’s health services at the University of Alabama, Birmingham’s 1917 Clinic. She described the results of her study at a press conference at the Conference on Retroviruses and Infectious Diseases.
“These predictors are important to understand so that we can come up with interventions to try to reduce the problem. Syphilis screening is relatively easy to do. USPSTF [U.S. Preventive Services Task Force] doesn’t even have a recommendation for that periodicity of screening frequency, so we have a ways to go to define how often we need to be looking, particularly in high-risk groups,” she said.
The likely force driving the increased incidence of syphilis is transactional sex. To explore that possibility, the researchers examined the number of sexual partners and found that more partners were linked to greater likelihood of having syphilis. “So I don’t think it’s the drug use itself – it’s the behavior that comes with the drug use,” Dr. Dionne-Odom said.
The findings shed more light on the interplay between drug use epidemics and disease epidemics. “As we have an increasing opioid epidemic and methamphetamine abuse that we’re all seeing in our clinics, it’s interesting to see this intersection between the drug use problem and the syphilis problem in this country. I think they’re not unrelated,” she said.
She believes the results should have broad implications for screening programs. Women admitted to drug treatment programs should be tested for syphilis. And women who abuse drugs and are pregnant should be screened repeatedly – at entry to care, at their 20-week scan, and at delivery. “We know we have about 6,000 women with HIV who deliver each year, so this is potentially very impactful,” Dr. Dionne-Odom said.
The researchers extracted data from the CNICS cohort, including 4,795 women with records between 2005 and 2016. They defined incident syphilis as a newly positive nontreponemal serologic test or a 300% titer increase, followed by a confirmatory test.
After adjustment, factors associated with syphilis included prior intravenous drug abuse (adjusted odds ratio, 2.3; 95% confidence interval, 1.3-3.9), hepatitis C antibody positivity (aOR, 2.1; 95% CI, 1.3-3.7), as well as black race (aOR, 2.3; 95% CI, 1.4-3.9). There was no association between age and HIV viral load with respect to risk of syphilis.
The frequency appears to be rising, with later entry into the CNICS cohort assorted with a more than doubled risk of syphilis (aOR, 2.3; 95% CI, 1.4-3.9 for 2011-2016, compared with 1994-2004).
The study was funded by the National Institute of Child Health and Human Development. Dr. Dionne-Odom reported no relevant conflicts of interest.
SOURCE: J Dionne-Odom et al. CROI 2019, Abstract 47
SEATTLE – The frequency of syphilis in HIV-infected women is unusually high, prompting concerns about congenital syphilis among newborns. The finding comes from a Centers for Disease Control analysis of the U.S. Center for Aids Research Clinical Network of Integrated Clinical Systems (CNICS) cohort.
“We found significant associations [between syphilis infection] and drug use and hepatitis C infection, which adds to some information from the CDC that what’s driving the epidemic in women is drug use – it’s a very different epidemic potentially in women with HIV than in men with HIV,” said Jodie Dionne-Odom, MD, chief of women’s health services at the University of Alabama, Birmingham’s 1917 Clinic. She described the results of her study at a press conference at the Conference on Retroviruses and Infectious Diseases.
“These predictors are important to understand so that we can come up with interventions to try to reduce the problem. Syphilis screening is relatively easy to do. USPSTF [U.S. Preventive Services Task Force] doesn’t even have a recommendation for that periodicity of screening frequency, so we have a ways to go to define how often we need to be looking, particularly in high-risk groups,” she said.
The likely force driving the increased incidence of syphilis is transactional sex. To explore that possibility, the researchers examined the number of sexual partners and found that more partners were linked to greater likelihood of having syphilis. “So I don’t think it’s the drug use itself – it’s the behavior that comes with the drug use,” Dr. Dionne-Odom said.
The findings shed more light on the interplay between drug use epidemics and disease epidemics. “As we have an increasing opioid epidemic and methamphetamine abuse that we’re all seeing in our clinics, it’s interesting to see this intersection between the drug use problem and the syphilis problem in this country. I think they’re not unrelated,” she said.
She believes the results should have broad implications for screening programs. Women admitted to drug treatment programs should be tested for syphilis. And women who abuse drugs and are pregnant should be screened repeatedly – at entry to care, at their 20-week scan, and at delivery. “We know we have about 6,000 women with HIV who deliver each year, so this is potentially very impactful,” Dr. Dionne-Odom said.
The researchers extracted data from the CNICS cohort, including 4,795 women with records between 2005 and 2016. They defined incident syphilis as a newly positive nontreponemal serologic test or a 300% titer increase, followed by a confirmatory test.
After adjustment, factors associated with syphilis included prior intravenous drug abuse (adjusted odds ratio, 2.3; 95% confidence interval, 1.3-3.9), hepatitis C antibody positivity (aOR, 2.1; 95% CI, 1.3-3.7), as well as black race (aOR, 2.3; 95% CI, 1.4-3.9). There was no association between age and HIV viral load with respect to risk of syphilis.
The frequency appears to be rising, with later entry into the CNICS cohort assorted with a more than doubled risk of syphilis (aOR, 2.3; 95% CI, 1.4-3.9 for 2011-2016, compared with 1994-2004).
The study was funded by the National Institute of Child Health and Human Development. Dr. Dionne-Odom reported no relevant conflicts of interest.
SOURCE: J Dionne-Odom et al. CROI 2019, Abstract 47
SEATTLE – The frequency of syphilis in HIV-infected women is unusually high, prompting concerns about congenital syphilis among newborns. The finding comes from a Centers for Disease Control analysis of the U.S. Center for Aids Research Clinical Network of Integrated Clinical Systems (CNICS) cohort.
“We found significant associations [between syphilis infection] and drug use and hepatitis C infection, which adds to some information from the CDC that what’s driving the epidemic in women is drug use – it’s a very different epidemic potentially in women with HIV than in men with HIV,” said Jodie Dionne-Odom, MD, chief of women’s health services at the University of Alabama, Birmingham’s 1917 Clinic. She described the results of her study at a press conference at the Conference on Retroviruses and Infectious Diseases.
“These predictors are important to understand so that we can come up with interventions to try to reduce the problem. Syphilis screening is relatively easy to do. USPSTF [U.S. Preventive Services Task Force] doesn’t even have a recommendation for that periodicity of screening frequency, so we have a ways to go to define how often we need to be looking, particularly in high-risk groups,” she said.
The likely force driving the increased incidence of syphilis is transactional sex. To explore that possibility, the researchers examined the number of sexual partners and found that more partners were linked to greater likelihood of having syphilis. “So I don’t think it’s the drug use itself – it’s the behavior that comes with the drug use,” Dr. Dionne-Odom said.
The findings shed more light on the interplay between drug use epidemics and disease epidemics. “As we have an increasing opioid epidemic and methamphetamine abuse that we’re all seeing in our clinics, it’s interesting to see this intersection between the drug use problem and the syphilis problem in this country. I think they’re not unrelated,” she said.
She believes the results should have broad implications for screening programs. Women admitted to drug treatment programs should be tested for syphilis. And women who abuse drugs and are pregnant should be screened repeatedly – at entry to care, at their 20-week scan, and at delivery. “We know we have about 6,000 women with HIV who deliver each year, so this is potentially very impactful,” Dr. Dionne-Odom said.
The researchers extracted data from the CNICS cohort, including 4,795 women with records between 2005 and 2016. They defined incident syphilis as a newly positive nontreponemal serologic test or a 300% titer increase, followed by a confirmatory test.
After adjustment, factors associated with syphilis included prior intravenous drug abuse (adjusted odds ratio, 2.3; 95% confidence interval, 1.3-3.9), hepatitis C antibody positivity (aOR, 2.1; 95% CI, 1.3-3.7), as well as black race (aOR, 2.3; 95% CI, 1.4-3.9). There was no association between age and HIV viral load with respect to risk of syphilis.
The frequency appears to be rising, with later entry into the CNICS cohort assorted with a more than doubled risk of syphilis (aOR, 2.3; 95% CI, 1.4-3.9 for 2011-2016, compared with 1994-2004).
The study was funded by the National Institute of Child Health and Human Development. Dr. Dionne-Odom reported no relevant conflicts of interest.
SOURCE: J Dionne-Odom et al. CROI 2019, Abstract 47
REPORTING FROM CROI 2019
2019 ID update for dermatologists: Ticks are the “ride of choice” for arthropods
ORLANDO – New tricks from ticks, near-zero Zika, and the perils of personal grooming: Dermatologists have a lot to think about along the infectious disease spectrum in 2019, according to Justin Finch, MD, speaking at the Orlando Dermatology Aesthetic and Clinical Conference.
Anaphylaxis from alpha-gal syndrome is on the rise, caused in part by the geographic spread of the Lone Star tick. Beginning in 2006, isolated cases of an anaphylactic reaction to cetuximab, the epidermal growth factor receptor antagonist used to treat certain cancers, began to be seen in a curious geographic distribution. “The anaphylaxis cases were restricted to the southeastern United States, the home of the Lone Star tick,” said Dr. Finch, of the department of dermatology at the University of Connecticut, Farmington.
With some detective work, physicians and epidemiologists eventually determined that patients were reacting to an oligosaccharide called galactose-alpha–1,3-galactose (alpha-gal) found in cetuximab. This protein is also found in the meat of nonprimate mammals; individuals in the southeastern United States, where the Lone Star tick is endemic, had been sensitized via exposure to alpha-gal from Lone Star tick bites.
“Alpha-gal syndrome is on the rise,” said Dr. Finch, driven by the increased spread of this tick. Individuals who are sensitized develop delayed anaphylaxis 2-7 hours after ingesting red meat such as beef, pork, or lamb. “Ask about it,” said Dr. Finch, in patients who develop urticaria, dyspnea, angioedema, or hypotension without a clear offender. Because of the delay between allergen ingestion and anaphylaxis, it can be hard to connect the dots.
A number of drugs other than cetuximab contain alpha-gal, so patients must also be told to avoid these agents, said Dr. Finch, who noted that alpha-gal syndrome isn’t the only emerging culprit for tick-borne diseases. “The tick is the ride of choice for arthropod-borne diseases in the U.S.,” he added. “Year after year, tick-borne diseases top mosquito-borne diseases in the U.S.” Zika’s explosion in 2016 made that year the exception to the rule.
Now, Zika virus may be on the wane – the number of case reports have plummeted both in the United States and in Central and South America this past year – but it hasn’t completely gone away. “It looks like it fell off all the maps,” but the virus is still present at low levels, he said.
When Zika virus is symptomatic, there’s often a nonspecific maculopapular rash. Critically, Dr. Finch said, “women with a rash are four times as likely to have adverse congenital outcomes. This is the important point for us to take home as dermatologists. ... It’s really important to have a high index of suspicion and to screen these women as they are coming into our clinic.”
Turning back to ticks, Lyme disease continues to be a problem in endemic areas in the Northeast, the mid-Atlantic region, and the Midwest, said Dr. Finch, so it’s a perennial on the differential diagnosis for dermatologists.
An Asian tick new to North America was seen for the first time in New Jersey in the summer of 2017. The Asian longhorned tick carries a phlebovirus that causes severe fever with thrombocytopenia syndrome, a disease with a 15% fatality rate. The reservoir host of this virus in Asia isn’t known, said Dr. Finch, adding that no cases of the virus have yet been seen in the United States. As of November 2018, according to the Centers for Disease Control and Prevention, the tick had been found in nine states (Arkansas, Connecticut, Maryland, North Carolina, New Jersey, New York, Pennsylvania, Virginia, and West Virginia).
“What’s not on the rise? Pubic lice. We are destroying their natural habitat!” said Dr. Finch, citing surveys about personal grooming that show that more than 90% of women remove at least some of their pubic hair. Most college campuses are currently reporting essentially no cases of pubic lice, he noted.
However, the same personal grooming practices may be contributing to increases in molluscum contagiosum, herpes simplex virus, some strains of human papillomavirus, and cutaneous Streptococcus pyogenes infections, he said.
Another STI has had a resurgence in geographic pockets around the nation and among specific populations, said Dr. Finch. Syphilis is on the rise among gay and bisexual men and African Americans. Known as the “great imitator,” syphilis should be on the differential for dermatologists when the clinical picture isn’t quite adding up. “Think of this, and screen with an RPR [rapid plasma reagin],” he said.
Finally, an old enemy is back: A total of 11 measles outbreaks were reported in 2018. “We need to know about measles because of the complications,” said Dr. Finch. Even years later, such dire sequelae as subacute sclerosing panencephalitis can crop up, he added.
After a 2-week incubation period, measles begins with a fever and cough, congestion, and conjunctivitis. The rash begins on the head and spreads inferiorly by day 3. As the rash blooms, the classic morbilliform eruption becomes apparent. A biopsy of affected skin will be nonspecific; measles is diagnosed with a nasopharyngeal culture and serologic assay. Dr. Finch pointed out that dermatologists are unlikely to see measles in its earliest stages because their expertise will be called on only after it becomes clear that the patient is not experiencing just a mild illness with a viral exanthem.
When there’s suspicion for measles, a full-body skin exam is needed. “Koplik’s spots – the gray white papules on the buccal mucosa – are not pathognomonic in themselves, but in the clinical scenario of a person with measles” they can help the dermatologist make a definitive call, he said.
Vitamin A can be given to a patient with active measles, but prevention via immunization at age 12 months and 5 years is the only way to stop the disease, Dr. Finch noted.
Dr. Finch reported that he has no relevant conflicts of interest.
ORLANDO – New tricks from ticks, near-zero Zika, and the perils of personal grooming: Dermatologists have a lot to think about along the infectious disease spectrum in 2019, according to Justin Finch, MD, speaking at the Orlando Dermatology Aesthetic and Clinical Conference.
Anaphylaxis from alpha-gal syndrome is on the rise, caused in part by the geographic spread of the Lone Star tick. Beginning in 2006, isolated cases of an anaphylactic reaction to cetuximab, the epidermal growth factor receptor antagonist used to treat certain cancers, began to be seen in a curious geographic distribution. “The anaphylaxis cases were restricted to the southeastern United States, the home of the Lone Star tick,” said Dr. Finch, of the department of dermatology at the University of Connecticut, Farmington.
With some detective work, physicians and epidemiologists eventually determined that patients were reacting to an oligosaccharide called galactose-alpha–1,3-galactose (alpha-gal) found in cetuximab. This protein is also found in the meat of nonprimate mammals; individuals in the southeastern United States, where the Lone Star tick is endemic, had been sensitized via exposure to alpha-gal from Lone Star tick bites.
“Alpha-gal syndrome is on the rise,” said Dr. Finch, driven by the increased spread of this tick. Individuals who are sensitized develop delayed anaphylaxis 2-7 hours after ingesting red meat such as beef, pork, or lamb. “Ask about it,” said Dr. Finch, in patients who develop urticaria, dyspnea, angioedema, or hypotension without a clear offender. Because of the delay between allergen ingestion and anaphylaxis, it can be hard to connect the dots.
A number of drugs other than cetuximab contain alpha-gal, so patients must also be told to avoid these agents, said Dr. Finch, who noted that alpha-gal syndrome isn’t the only emerging culprit for tick-borne diseases. “The tick is the ride of choice for arthropod-borne diseases in the U.S.,” he added. “Year after year, tick-borne diseases top mosquito-borne diseases in the U.S.” Zika’s explosion in 2016 made that year the exception to the rule.
Now, Zika virus may be on the wane – the number of case reports have plummeted both in the United States and in Central and South America this past year – but it hasn’t completely gone away. “It looks like it fell off all the maps,” but the virus is still present at low levels, he said.
When Zika virus is symptomatic, there’s often a nonspecific maculopapular rash. Critically, Dr. Finch said, “women with a rash are four times as likely to have adverse congenital outcomes. This is the important point for us to take home as dermatologists. ... It’s really important to have a high index of suspicion and to screen these women as they are coming into our clinic.”
Turning back to ticks, Lyme disease continues to be a problem in endemic areas in the Northeast, the mid-Atlantic region, and the Midwest, said Dr. Finch, so it’s a perennial on the differential diagnosis for dermatologists.
An Asian tick new to North America was seen for the first time in New Jersey in the summer of 2017. The Asian longhorned tick carries a phlebovirus that causes severe fever with thrombocytopenia syndrome, a disease with a 15% fatality rate. The reservoir host of this virus in Asia isn’t known, said Dr. Finch, adding that no cases of the virus have yet been seen in the United States. As of November 2018, according to the Centers for Disease Control and Prevention, the tick had been found in nine states (Arkansas, Connecticut, Maryland, North Carolina, New Jersey, New York, Pennsylvania, Virginia, and West Virginia).
“What’s not on the rise? Pubic lice. We are destroying their natural habitat!” said Dr. Finch, citing surveys about personal grooming that show that more than 90% of women remove at least some of their pubic hair. Most college campuses are currently reporting essentially no cases of pubic lice, he noted.
However, the same personal grooming practices may be contributing to increases in molluscum contagiosum, herpes simplex virus, some strains of human papillomavirus, and cutaneous Streptococcus pyogenes infections, he said.
Another STI has had a resurgence in geographic pockets around the nation and among specific populations, said Dr. Finch. Syphilis is on the rise among gay and bisexual men and African Americans. Known as the “great imitator,” syphilis should be on the differential for dermatologists when the clinical picture isn’t quite adding up. “Think of this, and screen with an RPR [rapid plasma reagin],” he said.
Finally, an old enemy is back: A total of 11 measles outbreaks were reported in 2018. “We need to know about measles because of the complications,” said Dr. Finch. Even years later, such dire sequelae as subacute sclerosing panencephalitis can crop up, he added.
After a 2-week incubation period, measles begins with a fever and cough, congestion, and conjunctivitis. The rash begins on the head and spreads inferiorly by day 3. As the rash blooms, the classic morbilliform eruption becomes apparent. A biopsy of affected skin will be nonspecific; measles is diagnosed with a nasopharyngeal culture and serologic assay. Dr. Finch pointed out that dermatologists are unlikely to see measles in its earliest stages because their expertise will be called on only after it becomes clear that the patient is not experiencing just a mild illness with a viral exanthem.
When there’s suspicion for measles, a full-body skin exam is needed. “Koplik’s spots – the gray white papules on the buccal mucosa – are not pathognomonic in themselves, but in the clinical scenario of a person with measles” they can help the dermatologist make a definitive call, he said.
Vitamin A can be given to a patient with active measles, but prevention via immunization at age 12 months and 5 years is the only way to stop the disease, Dr. Finch noted.
Dr. Finch reported that he has no relevant conflicts of interest.
ORLANDO – New tricks from ticks, near-zero Zika, and the perils of personal grooming: Dermatologists have a lot to think about along the infectious disease spectrum in 2019, according to Justin Finch, MD, speaking at the Orlando Dermatology Aesthetic and Clinical Conference.
Anaphylaxis from alpha-gal syndrome is on the rise, caused in part by the geographic spread of the Lone Star tick. Beginning in 2006, isolated cases of an anaphylactic reaction to cetuximab, the epidermal growth factor receptor antagonist used to treat certain cancers, began to be seen in a curious geographic distribution. “The anaphylaxis cases were restricted to the southeastern United States, the home of the Lone Star tick,” said Dr. Finch, of the department of dermatology at the University of Connecticut, Farmington.
With some detective work, physicians and epidemiologists eventually determined that patients were reacting to an oligosaccharide called galactose-alpha–1,3-galactose (alpha-gal) found in cetuximab. This protein is also found in the meat of nonprimate mammals; individuals in the southeastern United States, where the Lone Star tick is endemic, had been sensitized via exposure to alpha-gal from Lone Star tick bites.
“Alpha-gal syndrome is on the rise,” said Dr. Finch, driven by the increased spread of this tick. Individuals who are sensitized develop delayed anaphylaxis 2-7 hours after ingesting red meat such as beef, pork, or lamb. “Ask about it,” said Dr. Finch, in patients who develop urticaria, dyspnea, angioedema, or hypotension without a clear offender. Because of the delay between allergen ingestion and anaphylaxis, it can be hard to connect the dots.
A number of drugs other than cetuximab contain alpha-gal, so patients must also be told to avoid these agents, said Dr. Finch, who noted that alpha-gal syndrome isn’t the only emerging culprit for tick-borne diseases. “The tick is the ride of choice for arthropod-borne diseases in the U.S.,” he added. “Year after year, tick-borne diseases top mosquito-borne diseases in the U.S.” Zika’s explosion in 2016 made that year the exception to the rule.
Now, Zika virus may be on the wane – the number of case reports have plummeted both in the United States and in Central and South America this past year – but it hasn’t completely gone away. “It looks like it fell off all the maps,” but the virus is still present at low levels, he said.
When Zika virus is symptomatic, there’s often a nonspecific maculopapular rash. Critically, Dr. Finch said, “women with a rash are four times as likely to have adverse congenital outcomes. This is the important point for us to take home as dermatologists. ... It’s really important to have a high index of suspicion and to screen these women as they are coming into our clinic.”
Turning back to ticks, Lyme disease continues to be a problem in endemic areas in the Northeast, the mid-Atlantic region, and the Midwest, said Dr. Finch, so it’s a perennial on the differential diagnosis for dermatologists.
An Asian tick new to North America was seen for the first time in New Jersey in the summer of 2017. The Asian longhorned tick carries a phlebovirus that causes severe fever with thrombocytopenia syndrome, a disease with a 15% fatality rate. The reservoir host of this virus in Asia isn’t known, said Dr. Finch, adding that no cases of the virus have yet been seen in the United States. As of November 2018, according to the Centers for Disease Control and Prevention, the tick had been found in nine states (Arkansas, Connecticut, Maryland, North Carolina, New Jersey, New York, Pennsylvania, Virginia, and West Virginia).
“What’s not on the rise? Pubic lice. We are destroying their natural habitat!” said Dr. Finch, citing surveys about personal grooming that show that more than 90% of women remove at least some of their pubic hair. Most college campuses are currently reporting essentially no cases of pubic lice, he noted.
However, the same personal grooming practices may be contributing to increases in molluscum contagiosum, herpes simplex virus, some strains of human papillomavirus, and cutaneous Streptococcus pyogenes infections, he said.
Another STI has had a resurgence in geographic pockets around the nation and among specific populations, said Dr. Finch. Syphilis is on the rise among gay and bisexual men and African Americans. Known as the “great imitator,” syphilis should be on the differential for dermatologists when the clinical picture isn’t quite adding up. “Think of this, and screen with an RPR [rapid plasma reagin],” he said.
Finally, an old enemy is back: A total of 11 measles outbreaks were reported in 2018. “We need to know about measles because of the complications,” said Dr. Finch. Even years later, such dire sequelae as subacute sclerosing panencephalitis can crop up, he added.
After a 2-week incubation period, measles begins with a fever and cough, congestion, and conjunctivitis. The rash begins on the head and spreads inferiorly by day 3. As the rash blooms, the classic morbilliform eruption becomes apparent. A biopsy of affected skin will be nonspecific; measles is diagnosed with a nasopharyngeal culture and serologic assay. Dr. Finch pointed out that dermatologists are unlikely to see measles in its earliest stages because their expertise will be called on only after it becomes clear that the patient is not experiencing just a mild illness with a viral exanthem.
When there’s suspicion for measles, a full-body skin exam is needed. “Koplik’s spots – the gray white papules on the buccal mucosa – are not pathognomonic in themselves, but in the clinical scenario of a person with measles” they can help the dermatologist make a definitive call, he said.
Vitamin A can be given to a patient with active measles, but prevention via immunization at age 12 months and 5 years is the only way to stop the disease, Dr. Finch noted.
Dr. Finch reported that he has no relevant conflicts of interest.
EXPERT ANALYSIS FROM ODAC 2019
Digoxin-furosemide reduces viral load, diameter of cutaneous warts
Topical ionic contraviral therapy decreased the size of cutaneous warts caused by human papillomavirus virus (HPV) by a mean of 3 mm, a significant improvement compared with placebo, in a proof-of-concept study, Dr. Melanie Rijsbergen and her associates reported in the British Journal of Dermatology.
The Dr. Rijsbergen of the Center for Human Drug Research, Leiden, the Netherlands, and her coauthors wrote.
“It has been shown that DNA viruses, such as HPV, rely on potassium influx ... for replication. The cardiac glycoside digoxin and loop diuretic furosemide both inhibit potassium influx by interacting with the cell membrane ion cotransporters,” they said, noting that in 2006, an in vitro study found that “the inhibitory effect on DNA replication was most potent when digoxin and furosemide were combined.”
The placebo-controlled phase 2a trial randomized 80 patients with at least two plantar or common warts to one of four arms: digoxin 0.125% plus furosemide 0.125%; digoxin 0.125%; furosemide 0.125%; or placebo applied once a day for 42 consecutive days. A subset of 20 warts underwent histopathology and immunohistochemistry. In all, 139 warts were treated.
Patients were a mean of 26 years old and had developed warts a mean of 6 years before study onset. They had a mean of three warts each; about half were common and half were plantar.
In an analysis of all treated warts, each active treatment conferred a significant benefit, compared with placebo. The combination treatment was the most effective, with a mean diameter reduction of 3 mm. Warts exposed to digoxin alone or furosemide alone showed a mean reduction of about 2 mm.
At the study’s end, primary wart clearance rates were similar in all treatment groups – around 15%. None of the primary warts in the placebo group cleared. Common warts were more responsive to treatment than were plantar warts (24%-27% vs. 8%-15%). “The increased treatment resistance of plantar warts was previously described and seems to be mainly due to callus formation resulting in a decrease in cutaneous permeability of a drug,” the authors wrote.
The HPV viral load decreased by 94% in warts exposed to the combination therapy – a significant benefit, compared with placebo.
There were no discontinuations because of adverse events, and no serious adverse events related to treatment. There was no topical irritation associated with the treatment.
One author is an employee of Cutanea Life Sciences, which funded the study. Dr. Rijsbergen and the remaining authors declared no financial conflicts.
SOURCE: Rijsbergen M et al. Br J Dermatol. 2018 Dec 22. doi: 10.1111/bjd.17583.
Topical ionic contraviral therapy decreased the size of cutaneous warts caused by human papillomavirus virus (HPV) by a mean of 3 mm, a significant improvement compared with placebo, in a proof-of-concept study, Dr. Melanie Rijsbergen and her associates reported in the British Journal of Dermatology.
The Dr. Rijsbergen of the Center for Human Drug Research, Leiden, the Netherlands, and her coauthors wrote.
“It has been shown that DNA viruses, such as HPV, rely on potassium influx ... for replication. The cardiac glycoside digoxin and loop diuretic furosemide both inhibit potassium influx by interacting with the cell membrane ion cotransporters,” they said, noting that in 2006, an in vitro study found that “the inhibitory effect on DNA replication was most potent when digoxin and furosemide were combined.”
The placebo-controlled phase 2a trial randomized 80 patients with at least two plantar or common warts to one of four arms: digoxin 0.125% plus furosemide 0.125%; digoxin 0.125%; furosemide 0.125%; or placebo applied once a day for 42 consecutive days. A subset of 20 warts underwent histopathology and immunohistochemistry. In all, 139 warts were treated.
Patients were a mean of 26 years old and had developed warts a mean of 6 years before study onset. They had a mean of three warts each; about half were common and half were plantar.
In an analysis of all treated warts, each active treatment conferred a significant benefit, compared with placebo. The combination treatment was the most effective, with a mean diameter reduction of 3 mm. Warts exposed to digoxin alone or furosemide alone showed a mean reduction of about 2 mm.
At the study’s end, primary wart clearance rates were similar in all treatment groups – around 15%. None of the primary warts in the placebo group cleared. Common warts were more responsive to treatment than were plantar warts (24%-27% vs. 8%-15%). “The increased treatment resistance of plantar warts was previously described and seems to be mainly due to callus formation resulting in a decrease in cutaneous permeability of a drug,” the authors wrote.
The HPV viral load decreased by 94% in warts exposed to the combination therapy – a significant benefit, compared with placebo.
There were no discontinuations because of adverse events, and no serious adverse events related to treatment. There was no topical irritation associated with the treatment.
One author is an employee of Cutanea Life Sciences, which funded the study. Dr. Rijsbergen and the remaining authors declared no financial conflicts.
SOURCE: Rijsbergen M et al. Br J Dermatol. 2018 Dec 22. doi: 10.1111/bjd.17583.
Topical ionic contraviral therapy decreased the size of cutaneous warts caused by human papillomavirus virus (HPV) by a mean of 3 mm, a significant improvement compared with placebo, in a proof-of-concept study, Dr. Melanie Rijsbergen and her associates reported in the British Journal of Dermatology.
The Dr. Rijsbergen of the Center for Human Drug Research, Leiden, the Netherlands, and her coauthors wrote.
“It has been shown that DNA viruses, such as HPV, rely on potassium influx ... for replication. The cardiac glycoside digoxin and loop diuretic furosemide both inhibit potassium influx by interacting with the cell membrane ion cotransporters,” they said, noting that in 2006, an in vitro study found that “the inhibitory effect on DNA replication was most potent when digoxin and furosemide were combined.”
The placebo-controlled phase 2a trial randomized 80 patients with at least two plantar or common warts to one of four arms: digoxin 0.125% plus furosemide 0.125%; digoxin 0.125%; furosemide 0.125%; or placebo applied once a day for 42 consecutive days. A subset of 20 warts underwent histopathology and immunohistochemistry. In all, 139 warts were treated.
Patients were a mean of 26 years old and had developed warts a mean of 6 years before study onset. They had a mean of three warts each; about half were common and half were plantar.
In an analysis of all treated warts, each active treatment conferred a significant benefit, compared with placebo. The combination treatment was the most effective, with a mean diameter reduction of 3 mm. Warts exposed to digoxin alone or furosemide alone showed a mean reduction of about 2 mm.
At the study’s end, primary wart clearance rates were similar in all treatment groups – around 15%. None of the primary warts in the placebo group cleared. Common warts were more responsive to treatment than were plantar warts (24%-27% vs. 8%-15%). “The increased treatment resistance of plantar warts was previously described and seems to be mainly due to callus formation resulting in a decrease in cutaneous permeability of a drug,” the authors wrote.
The HPV viral load decreased by 94% in warts exposed to the combination therapy – a significant benefit, compared with placebo.
There were no discontinuations because of adverse events, and no serious adverse events related to treatment. There was no topical irritation associated with the treatment.
One author is an employee of Cutanea Life Sciences, which funded the study. Dr. Rijsbergen and the remaining authors declared no financial conflicts.
SOURCE: Rijsbergen M et al. Br J Dermatol. 2018 Dec 22. doi: 10.1111/bjd.17583.
FROM THE BRITISH JOURNAL OF DERMATOLOGY
Key clinical point: The combination of digoxin and furosemide in a topical gel reduced the diameter of cutaneous warts caused by HPV.
Major finding: Wart diameter was reduced by a mean of 3 mm among those treated with the combination.
Study details: The randomized, placebo-controlled phase 2a study compared the furosemide-digoxin combination with the two components separately, and placebo separately, in 80 adults.
Disclosures: One author is an employee of Cutanea Life Sciences, which funded the study. Dr. Rijsbergen and the remaining authors declared no financial conflicts.
Source: Rijsbergen M et al. J Dermatol. 2018 Dec 22. doi: 10.1111/bjd.17583.