CASE REPORT
Ocular syphilis in a patient with HIV Stephanie D. Kurtz, PA-C, MMSc; Francois Rollin, MD, MPH
ABSTRACT Patients who are HIV-positive and have ocular complaints may have ocular syphilis as coinfection with HIV and syphilis is common, and genital ulcerative diseases may facilitate HIV infection. Early treatment with IV penicillin can reduce the risk of vision loss. Keywords: ocular syphilis, HIV, immunocompromised, ophthalmology, Treponema pallidum, neurosyphilis
CASE A 38-year-old woman presented to the ED with a 7-day history of eye redness and progressively worsening visual acuity and a 1-day history of sudden-onset eye pain. Eight months earlier, she was diagnosed with HIV infection; her CD4 count was unknown and she denied ever seeking or receiving treatment. She reported that her right eye had initially started draining clear fluid 1 week before admission. She thought she might have scratched it; however, the drainage gradually became more purulent and spread to the left eye. She also reported that over the past week her vision had become progressively more blurry, again starting with decreased acuity in the right eye before the left. The main reason she sought treatment was for sharp, stabbing, bilateral posterior eye pain that had started 1 day ago. At presentation, she was unable to distinguish objects and could only perceive bright light, which was associated with photophobia. She denied contact with anyone who was sick; foreign bodies, chemical exposure, or trauma to the eyes; contact lens use; or previous history of glaucoma. She reported a 2-day history of rhinorrhea and pharyngitis; she denied fever, chills, fatigue, cough, and night sweats. She also complained of a 2-month history of a nonpruritic, painless rash that began on her stomach then spread to her arms and legs. Although the rash had not improved, she said it was not overly concerning to her and she had Stephanie D. Kurtz is a PA in hematology/oncology at the Winship Cancer Institute at Emory University in Atlanta, Ga. At the time this article was written, Francois Rollin was chief resident at Grady Memorial Hospital in Atlanta, Ga. The authors have disclosed no potential conflicts of interest, financial or otherwise. DOI: 10.1097/01.JAA.0000444734.39540.fc Copyright © 2014 American Academy of Physician Assistants
32
www.JAAPA.com
FIGURE 1. Rash on the anterior trunk
not sought treatment. She denied easy bruising or bleeding but did report a prolonged menstrual cycle. The remaining review of systems was negative. The patient was not taking any medications and did not have a primary care provider. She denied alcohol and illicit/ IV drug use. She had been a heavy smoker but quit 2 months ago. Her last sexual encounter was 11 months ago, and she denied condom use. She reported a history of treatment for multiple sexually transmitted infections (STIs) in the past including gonorrhea, chlamydia, and trichomonas. She had a history of multiple incarcerations and homelessness but was currently living with a friend. Physical examination The patient was a cachectic woman in no acute distress. Vital signs were stable: temperature, 37.1° C (98.8° F); pulse, 82; respirations, 16; and BP, 142/88 mm Hg. She had extreme photophobia and was unable to open her eyes completely even in the absence of Volume 27 • Number 4 • April 2014
Copyright © 2014 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Ocular syphilis in a patient with HIV
Key points Coinfection with HIV and syphilis is common, and genital ulcerative diseases such as syphilis may actually facilitate HIV transmission. Patients with HIV and syphilis often present atypically and with a more rapid progression to neurosyphilis. Standard treatment of neurosyphilis involves IV penicillin, and penicillin desensitization is preferred over alternative treatments. Loss of visual acuity secondary to ocular syphilis can be reversed with early treatment, but patients remain at risk for irreversible vision loss. A broad differential diagnosis is key for HIV-positive or otherwise immunocompromised patients presenting with ocular complaints.
direct light. Her sclerae were significantly injected bilaterally with superior subconjunctival hemorrhages and purulent drainage. Extraocular movements were intact but her visual acuity was diminished to light perception only. Her eyelids were edematous and erythematous. The skin examination was remarkable for a diffuse erythematous rash noted on the anterior and posterior trunk, face, and bilateral upper and lower extremities (Figures 1 to 3). The rash spared the palms and soles. The lesions were non-dermatomal, papular, and not well circumscribed, with a slight scale but no evidence of vesiculation. Examination of the oral cavity showed no lesions and no lymphadenopathy was noted. Examination of the cardiovascular, respiratory, gastrointestinal, and neurologic systems was otherwise unremarkable. OPHTHALMOLOGY CONSULT Ophthalmology was consulted in the ED and performed bilateral anterior chamber taps as well as intravitreal gancyclovir injections. They noted diffuse keratic precipitates and iris bombé with 360-degree posterior adhesions. They were unable to perform a dilated fundoscopic examination secondary to poor pupil dilation. Ophthalmology also performed a B-scan ultrasound that showed the posterior hyaloid (vitreous) membrane adherent to both optic nerves. The overall diagnosis was acute bilateral panuveitis with a broad differential diagnosis given the patient’s immunocompromised state, including syphilis, toxoplasmosis, cytomegalovirus (CMV), herpes simplex, tuberculosis, and sarcoidosis. LABORATORY RESULTS Blood tests included a complete blood cell (CBC) count, complete metabolic panel, hepatitis panel, CD4 count, HIV viral load, thyroid-stimulating hormone, serum angiotensin-converting enzyme level, culture for acid-fast bacilli, rapid plasma regain (RPR), CMV IgG, cryptococ-
FIGURE 2. Rash on the posterior trunk
cal antigen, and toxoplasmosis IgG and IgM. The anterior chamber tap fluid was sent for herpes simplex virus, varicella zoster virus, and toxoplasmosis testing; CMV polymerase chain reaction assay; and Gram stain. Urine was sent for gonorrhea and chlamydia testing. A PPD skin test for tuberculosis was placed. The chest radiograph was unremarkable. The CBC count was remarkable for a white blood cell count of 3.6x103/mcL (normal range, 4.5 to 10x103/mcL), platelet count of 21x103/mcL (normal range, 150 to 450x103/mcL), and hemoglobin of 8.1 g/dL (normal range, 11.4 to 14.4 g/dL). The chemistry panel was unremarkable and the hepatitis panel was negative. The remaining laboratory results were pending at admission. HOSPITAL COURSE The patient was admitted for further workup and treatment. Ophthalmology recommended starting IV acyclovir (10 mg/kg three times daily) for empiric ocular herpes simplex treatment. The patient also was started on atropine sulfate and prednisolone eyedrops. The infectious disease team was consulted and recommended starting IV penicillin G (12 million units every 12 hours) for empiric secondary syphilis treatment. The patient experienced a fever up to 39.6° C (102.2° F) with shaking chills several hours
JAAPA Journal of the American Academy of Physician Assistants
Copyright © 2014 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
www.JAAPA.com
33
CASE REPORT
after initiation of the penicillin infusion, and she was symptomatically treated for suspected Jarisch-Herxheimer reaction. Several days later, her CD4 count was 87 cells/mm3 (normal range, 500 to 1,000 cells/mm3), consistent with a diagnosis of AIDS. She was started on opportunistic infection prophylaxis with trimethoprim-sulfamethoxazole. The RPR result on day 4 was a titer greater than 512, consistent with high levels of antibodies to toxins released by cells attacked by Treponema pallidum (normal titer is negative). Because the infectious disease specialists had a high suspicion for neurosyphilis, they recommended sending cerebrospinal fluid (CSF) for VDRL analysis. However, the lumbar puncture was delayed because of the patient’s persistently low platelet count. Immune thrombocytopenia purpura secondary to HIV immunosuppression was suspected and the patient was started on oral prednisone, but her platelet count peaked at only 50x103/mcL before trending back down, and the lumbar puncture was deferred during her hospitalization. Ultimately, the anterior chamber fluid was negative for herpes simplex virus, varicella zoster virus, toxoplasmosis, and CMV, and the acyclovir was discontinued. The patient’s other initial laboratory tests also were negative. The final diagnosis was secondary syphilis causing the rash and neurosyphilis with ocular syphilis causing panuveitis and subsequent blindness. Because of ongoing concern about the patient’s social support and ability to follow up as an outpatient, she remained an inpatient for the full 14-day course of IV penicillin G recommended for suspected neurosyphilis. The rash improved daily; at discharge, it was almost no longer visible on the upper extremities and much lighter on the trunk and lower extremities. Ophthalmology continued to follow the patient closely and although her photophobia and scleral injection improved, her visual acuity remained poor. At discharge she was still unable to distinguish objects directly in her field of vision. She was discharged home with home health and follow-up at a local HIV clinic for initiation of highly active antiretroviral therapy (HAART). A lumbar puncture and VDRL test were to be performed after her platelet count stabilized. DISCUSSION This case highlights the importance of a broad differential diagnosis in a patient with HIV presenting with ocular complaints. 34
www.JAAPA.com
Although CMV retinitis has decreased since the widespread initiation of HAART, the incidence of ocular syphilis has not.1 Although traditionally neurosyphilis is considered a form of late or tertiary syphilis, central nervous system invasion by T. pallidum can occur at any time after the initial infection and might actually occur more often than was previously thought.2 Genital ulcerative diseases such as syphilis can facilitate HIV transmission, and patients with HIV and syphilis often present differently than their counterparts without HIV. For example, patients with HIV may have overlapping disease stages, multiple chancres, atypical skin rashes, and a more rapid progression to neurosyphilis with symptoms such as ocular, otic, or vascular involvement.3,4 Syphilis has also been shown to negatively affect the immune status and viral load of patients with HIV.3 The case patient presented with a low CD4 count and evidence of both secondary syphilis and neurosyphilis in the form of ocular syphilis. According to the patient, she likely obtained both diseases during the same unprotected sexual encounter, although it is impossible to be certain when exactly either disease was acquired or if one facilitated the transmission of the other. This patient’s secondary syphilis rash was atypical, covering most of her body but sparing her palms and soles; the classic syphilis rash presents on the palms and soles. An ulceronodular syphilitic rash also has been reported in patients with HIV who are coinfected with syphilis and is a severe and protracted manifestation of the disease. This patient appeared to have progressed rapidly from early syphilis to neurosyphilis and presented with evidence of multiple stages of the disease. Asymptomatic neurosyphilis can occur but patients with HIV who have lower
FIGURE 3. Rash on lower extremities Volume 27 • Number 4 • April 2014
Copyright © 2014 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Ocular syphilis in a patient with HIV
CD4 cell counts are more likely than patients without HIV to have central nervous system symptoms such as ocular involvement.4 Ocular syphilis can manifest itself in multiple ways including peripheral retinitis; anterior, posterior, or panuveitis; vitritis; multifocal choroiditis; scleritis; and papillitis.5 The largest published case series in patients with HIV/AIDS, which included 101 patients with ocular syphilis and a CD4 count less than 200 cells/mm3, found that these patients have a significantly higher risk of posterior uveitis but a lower risk of panuveitis and anterior uveitis compared to patients without HIV/AIDS.1 Although ongoing data were available for a limited number of patients, the series also reported good prognosis for vision in patients with ocular syphilis, with 97% showing improved visual acuity at follow-up.1
the full regimen improves the prognosis of ocular syphilis for most patients.1 Some studies also have shown benefit in administering oral steroids at the initiation of treatment, which can potentially help decrease the Jarisch-Herxheimer inflammatory reaction systemically and in the eyes.1 However, oral steroids are not included in the standard treatment recommendations. The Jarisch-Herxheimer reaction is self-limited and is often seen hours after the initiation of penicillin therapy in patients with spirochete diseases such as syphilis. The reaction is secondary to massive spirochete destruction and inflammatory marker release. Treatment is supportive with antipyretics and IV fluids. Although early syphilis and high RPR titers are associated with an increased risk of the reaction, HIV infection itself is not associated with an increased risk of Jarisch-Herxheimer reaction.6
Penicillin desensitization under physician supervision is usually preferred to alternative therapy for patients allergic to penicillin.
CONCLUSION When evaluating a patient presenting with ocular symptoms and rash, consider syphilis in the differential. Early consultation with the appropriate specialists is key when approaching a patient with a history of HIV and sudden onset of visual complaints, as the differential diagnosis is broad and the risk of permanent visual compromise is high. Although this patient presented atypically with panuveitis and her vision failed to recover at least initially with proper treatment, her visual acuity still may improve, especially with proper ophthalmology follow-up. This patient’s outcome is not known because she has not followed up as arranged. In patients with evidence of neurosyphilis, lumbar puncture, treatment with IV penicillin G, and close outpatient follow-up are all keys to preventing complications and improving outcomes. JAAPA
The CDC recommends that all patients with HIV and syphilis presenting with neurologic symptoms undergo a lumbar puncture for VDRL testing of CSF. This test is very specific for neurosyphilis, although false negatives are possible. In a patient with a negative test result but in whom neurosyphilis is highly suspected, a confirmatory test, the CSF fluorescent treponemal antibody absorption test, should be performed. Any patient with evidence of neurosyphilis should undergo a full course of IV penicillin regardless of the CSF analysis results. The lumbar puncture can be used for tracking treatment response, and should be repeated 3 to 6 months after the completion of treatment and then every 6 months until the VDRL is nonreactive. Unfortunately, this patient’s low platelet count precluded performing the lumbar puncture safely during her hospitalization, but arrangements were made for the procedure to be performed as an outpatient pending stabilization of her platelet count at greater than 50x103/mcL. Variations on the standard IV penicillin G for neurosyphilis include IM procaine penicillin G plus probenecid or IV ceftriaxone; however, these alternative treatments lack supporting data. Penicillin desensitization under physician supervision is usually preferred to alternative therapy for patients allergic to penicillin. Completion of
REFERENCES 1. Tucker JD, Li JZ, Robbins GK, et al. Ocular syphilis among HIV-infected patients: a systematic analysis of the literature. Sex Transm Infect. 2011;87(1):4-8. 2. Lukehart SA, Hook EW 3rd, Baker-Zander SA, et al. Invasion of the central nervous system by Treponema pallidum: implications for diagnosis and treatment. Ann Intern Med. 1988;109(11): 855-862. 3. Jarzebowski W, Caumes E, Dupin N, et al. Effect of early syphilis infection on plasma viral load and CD4 cell count in human immunodeficiency virus-infected men: results from the FHDH-ANRS CO4 cohort. Arch Intern Med. 2012;172(16): 1237-1243. 4. Musher DM, Hamill RJ, Baughn RE. Effect of human immunodeficiency virus (HIV) infection on the course of syphilis and on the response to treatment. Ann Intern Med. 1990;113(11):872-881. 5. Hughes EH, Guzowski M, Simunovic MP, et al. Syphilitic retinitis and uveitis in HIV-positive adults. Clin Experiment Ophthalmol. 2010;38(9):851-856. 6. Yang CJ, Lee NY, Lin YH, et al. Jarisch-Herxheimer reaction after penicillin therapy among patients with syphilis in the era of the HIV infection epidemic: incidence and risk factors. Clin Infect Dis. 2010;51(8):976-979.
JAAPA Journal of the American Academy of Physician Assistants
Copyright © 2014 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
www.JAAPA.com
35
Ocular syphilis in a patient with HIV Stephanie D. Kurtz, PA-C, MMSc; Francois Rollin, MD, MPH
ABSTRACT Patients who are HIV-positive and have ocular complaints may have ocular syphilis as coinfection with HIV and syphilis is common, and genital ulcerative diseases may facilitate HIV infection. Early treatment with IV penicillin can reduce the risk of vision loss. Keywords: ocular syphilis, HIV, immunocompromised, ophthalmology, Treponema pallidum, neurosyphilis
CASE A 38-year-old woman presented to the ED with a 7-day history of eye redness and progressively worsening visual acuity and a 1-day history of sudden-onset eye pain. Eight months earlier, she was diagnosed with HIV infection; her CD4 count was unknown and she denied ever seeking or receiving treatment. She reported that her right eye had initially started draining clear fluid 1 week before admission. She thought she might have scratched it; however, the drainage gradually became more purulent and spread to the left eye. She also reported that over the past week her vision had become progressively more blurry, again starting with decreased acuity in the right eye before the left. The main reason she sought treatment was for sharp, stabbing, bilateral posterior eye pain that had started 1 day ago. At presentation, she was unable to distinguish objects and could only perceive bright light, which was associated with photophobia. She denied contact with anyone who was sick; foreign bodies, chemical exposure, or trauma to the eyes; contact lens use; or previous history of glaucoma. She reported a 2-day history of rhinorrhea and pharyngitis; she denied fever, chills, fatigue, cough, and night sweats. She also complained of a 2-month history of a nonpruritic, painless rash that began on her stomach then spread to her arms and legs. Although the rash had not improved, she said it was not overly concerning to her and she had Stephanie D. Kurtz is a PA in hematology/oncology at the Winship Cancer Institute at Emory University in Atlanta, Ga. At the time this article was written, Francois Rollin was chief resident at Grady Memorial Hospital in Atlanta, Ga. The authors have disclosed no potential conflicts of interest, financial or otherwise. DOI: 10.1097/01.JAA.0000444734.39540.fc Copyright © 2014 American Academy of Physician Assistants
32
www.JAAPA.com
FIGURE 1. Rash on the anterior trunk
not sought treatment. She denied easy bruising or bleeding but did report a prolonged menstrual cycle. The remaining review of systems was negative. The patient was not taking any medications and did not have a primary care provider. She denied alcohol and illicit/ IV drug use. She had been a heavy smoker but quit 2 months ago. Her last sexual encounter was 11 months ago, and she denied condom use. She reported a history of treatment for multiple sexually transmitted infections (STIs) in the past including gonorrhea, chlamydia, and trichomonas. She had a history of multiple incarcerations and homelessness but was currently living with a friend. Physical examination The patient was a cachectic woman in no acute distress. Vital signs were stable: temperature, 37.1° C (98.8° F); pulse, 82; respirations, 16; and BP, 142/88 mm Hg. She had extreme photophobia and was unable to open her eyes completely even in the absence of Volume 27 • Number 4 • April 2014
Copyright © 2014 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Ocular syphilis in a patient with HIV
Key points Coinfection with HIV and syphilis is common, and genital ulcerative diseases such as syphilis may actually facilitate HIV transmission. Patients with HIV and syphilis often present atypically and with a more rapid progression to neurosyphilis. Standard treatment of neurosyphilis involves IV penicillin, and penicillin desensitization is preferred over alternative treatments. Loss of visual acuity secondary to ocular syphilis can be reversed with early treatment, but patients remain at risk for irreversible vision loss. A broad differential diagnosis is key for HIV-positive or otherwise immunocompromised patients presenting with ocular complaints.
direct light. Her sclerae were significantly injected bilaterally with superior subconjunctival hemorrhages and purulent drainage. Extraocular movements were intact but her visual acuity was diminished to light perception only. Her eyelids were edematous and erythematous. The skin examination was remarkable for a diffuse erythematous rash noted on the anterior and posterior trunk, face, and bilateral upper and lower extremities (Figures 1 to 3). The rash spared the palms and soles. The lesions were non-dermatomal, papular, and not well circumscribed, with a slight scale but no evidence of vesiculation. Examination of the oral cavity showed no lesions and no lymphadenopathy was noted. Examination of the cardiovascular, respiratory, gastrointestinal, and neurologic systems was otherwise unremarkable. OPHTHALMOLOGY CONSULT Ophthalmology was consulted in the ED and performed bilateral anterior chamber taps as well as intravitreal gancyclovir injections. They noted diffuse keratic precipitates and iris bombé with 360-degree posterior adhesions. They were unable to perform a dilated fundoscopic examination secondary to poor pupil dilation. Ophthalmology also performed a B-scan ultrasound that showed the posterior hyaloid (vitreous) membrane adherent to both optic nerves. The overall diagnosis was acute bilateral panuveitis with a broad differential diagnosis given the patient’s immunocompromised state, including syphilis, toxoplasmosis, cytomegalovirus (CMV), herpes simplex, tuberculosis, and sarcoidosis. LABORATORY RESULTS Blood tests included a complete blood cell (CBC) count, complete metabolic panel, hepatitis panel, CD4 count, HIV viral load, thyroid-stimulating hormone, serum angiotensin-converting enzyme level, culture for acid-fast bacilli, rapid plasma regain (RPR), CMV IgG, cryptococ-
FIGURE 2. Rash on the posterior trunk
cal antigen, and toxoplasmosis IgG and IgM. The anterior chamber tap fluid was sent for herpes simplex virus, varicella zoster virus, and toxoplasmosis testing; CMV polymerase chain reaction assay; and Gram stain. Urine was sent for gonorrhea and chlamydia testing. A PPD skin test for tuberculosis was placed. The chest radiograph was unremarkable. The CBC count was remarkable for a white blood cell count of 3.6x103/mcL (normal range, 4.5 to 10x103/mcL), platelet count of 21x103/mcL (normal range, 150 to 450x103/mcL), and hemoglobin of 8.1 g/dL (normal range, 11.4 to 14.4 g/dL). The chemistry panel was unremarkable and the hepatitis panel was negative. The remaining laboratory results were pending at admission. HOSPITAL COURSE The patient was admitted for further workup and treatment. Ophthalmology recommended starting IV acyclovir (10 mg/kg three times daily) for empiric ocular herpes simplex treatment. The patient also was started on atropine sulfate and prednisolone eyedrops. The infectious disease team was consulted and recommended starting IV penicillin G (12 million units every 12 hours) for empiric secondary syphilis treatment. The patient experienced a fever up to 39.6° C (102.2° F) with shaking chills several hours
JAAPA Journal of the American Academy of Physician Assistants
Copyright © 2014 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
www.JAAPA.com
33
CASE REPORT
after initiation of the penicillin infusion, and she was symptomatically treated for suspected Jarisch-Herxheimer reaction. Several days later, her CD4 count was 87 cells/mm3 (normal range, 500 to 1,000 cells/mm3), consistent with a diagnosis of AIDS. She was started on opportunistic infection prophylaxis with trimethoprim-sulfamethoxazole. The RPR result on day 4 was a titer greater than 512, consistent with high levels of antibodies to toxins released by cells attacked by Treponema pallidum (normal titer is negative). Because the infectious disease specialists had a high suspicion for neurosyphilis, they recommended sending cerebrospinal fluid (CSF) for VDRL analysis. However, the lumbar puncture was delayed because of the patient’s persistently low platelet count. Immune thrombocytopenia purpura secondary to HIV immunosuppression was suspected and the patient was started on oral prednisone, but her platelet count peaked at only 50x103/mcL before trending back down, and the lumbar puncture was deferred during her hospitalization. Ultimately, the anterior chamber fluid was negative for herpes simplex virus, varicella zoster virus, toxoplasmosis, and CMV, and the acyclovir was discontinued. The patient’s other initial laboratory tests also were negative. The final diagnosis was secondary syphilis causing the rash and neurosyphilis with ocular syphilis causing panuveitis and subsequent blindness. Because of ongoing concern about the patient’s social support and ability to follow up as an outpatient, she remained an inpatient for the full 14-day course of IV penicillin G recommended for suspected neurosyphilis. The rash improved daily; at discharge, it was almost no longer visible on the upper extremities and much lighter on the trunk and lower extremities. Ophthalmology continued to follow the patient closely and although her photophobia and scleral injection improved, her visual acuity remained poor. At discharge she was still unable to distinguish objects directly in her field of vision. She was discharged home with home health and follow-up at a local HIV clinic for initiation of highly active antiretroviral therapy (HAART). A lumbar puncture and VDRL test were to be performed after her platelet count stabilized. DISCUSSION This case highlights the importance of a broad differential diagnosis in a patient with HIV presenting with ocular complaints. 34
www.JAAPA.com
Although CMV retinitis has decreased since the widespread initiation of HAART, the incidence of ocular syphilis has not.1 Although traditionally neurosyphilis is considered a form of late or tertiary syphilis, central nervous system invasion by T. pallidum can occur at any time after the initial infection and might actually occur more often than was previously thought.2 Genital ulcerative diseases such as syphilis can facilitate HIV transmission, and patients with HIV and syphilis often present differently than their counterparts without HIV. For example, patients with HIV may have overlapping disease stages, multiple chancres, atypical skin rashes, and a more rapid progression to neurosyphilis with symptoms such as ocular, otic, or vascular involvement.3,4 Syphilis has also been shown to negatively affect the immune status and viral load of patients with HIV.3 The case patient presented with a low CD4 count and evidence of both secondary syphilis and neurosyphilis in the form of ocular syphilis. According to the patient, she likely obtained both diseases during the same unprotected sexual encounter, although it is impossible to be certain when exactly either disease was acquired or if one facilitated the transmission of the other. This patient’s secondary syphilis rash was atypical, covering most of her body but sparing her palms and soles; the classic syphilis rash presents on the palms and soles. An ulceronodular syphilitic rash also has been reported in patients with HIV who are coinfected with syphilis and is a severe and protracted manifestation of the disease. This patient appeared to have progressed rapidly from early syphilis to neurosyphilis and presented with evidence of multiple stages of the disease. Asymptomatic neurosyphilis can occur but patients with HIV who have lower
FIGURE 3. Rash on lower extremities Volume 27 • Number 4 • April 2014
Copyright © 2014 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Ocular syphilis in a patient with HIV
CD4 cell counts are more likely than patients without HIV to have central nervous system symptoms such as ocular involvement.4 Ocular syphilis can manifest itself in multiple ways including peripheral retinitis; anterior, posterior, or panuveitis; vitritis; multifocal choroiditis; scleritis; and papillitis.5 The largest published case series in patients with HIV/AIDS, which included 101 patients with ocular syphilis and a CD4 count less than 200 cells/mm3, found that these patients have a significantly higher risk of posterior uveitis but a lower risk of panuveitis and anterior uveitis compared to patients without HIV/AIDS.1 Although ongoing data were available for a limited number of patients, the series also reported good prognosis for vision in patients with ocular syphilis, with 97% showing improved visual acuity at follow-up.1
the full regimen improves the prognosis of ocular syphilis for most patients.1 Some studies also have shown benefit in administering oral steroids at the initiation of treatment, which can potentially help decrease the Jarisch-Herxheimer inflammatory reaction systemically and in the eyes.1 However, oral steroids are not included in the standard treatment recommendations. The Jarisch-Herxheimer reaction is self-limited and is often seen hours after the initiation of penicillin therapy in patients with spirochete diseases such as syphilis. The reaction is secondary to massive spirochete destruction and inflammatory marker release. Treatment is supportive with antipyretics and IV fluids. Although early syphilis and high RPR titers are associated with an increased risk of the reaction, HIV infection itself is not associated with an increased risk of Jarisch-Herxheimer reaction.6
Penicillin desensitization under physician supervision is usually preferred to alternative therapy for patients allergic to penicillin.
CONCLUSION When evaluating a patient presenting with ocular symptoms and rash, consider syphilis in the differential. Early consultation with the appropriate specialists is key when approaching a patient with a history of HIV and sudden onset of visual complaints, as the differential diagnosis is broad and the risk of permanent visual compromise is high. Although this patient presented atypically with panuveitis and her vision failed to recover at least initially with proper treatment, her visual acuity still may improve, especially with proper ophthalmology follow-up. This patient’s outcome is not known because she has not followed up as arranged. In patients with evidence of neurosyphilis, lumbar puncture, treatment with IV penicillin G, and close outpatient follow-up are all keys to preventing complications and improving outcomes. JAAPA
The CDC recommends that all patients with HIV and syphilis presenting with neurologic symptoms undergo a lumbar puncture for VDRL testing of CSF. This test is very specific for neurosyphilis, although false negatives are possible. In a patient with a negative test result but in whom neurosyphilis is highly suspected, a confirmatory test, the CSF fluorescent treponemal antibody absorption test, should be performed. Any patient with evidence of neurosyphilis should undergo a full course of IV penicillin regardless of the CSF analysis results. The lumbar puncture can be used for tracking treatment response, and should be repeated 3 to 6 months after the completion of treatment and then every 6 months until the VDRL is nonreactive. Unfortunately, this patient’s low platelet count precluded performing the lumbar puncture safely during her hospitalization, but arrangements were made for the procedure to be performed as an outpatient pending stabilization of her platelet count at greater than 50x103/mcL. Variations on the standard IV penicillin G for neurosyphilis include IM procaine penicillin G plus probenecid or IV ceftriaxone; however, these alternative treatments lack supporting data. Penicillin desensitization under physician supervision is usually preferred to alternative therapy for patients allergic to penicillin. Completion of
REFERENCES 1. Tucker JD, Li JZ, Robbins GK, et al. Ocular syphilis among HIV-infected patients: a systematic analysis of the literature. Sex Transm Infect. 2011;87(1):4-8. 2. Lukehart SA, Hook EW 3rd, Baker-Zander SA, et al. Invasion of the central nervous system by Treponema pallidum: implications for diagnosis and treatment. Ann Intern Med. 1988;109(11): 855-862. 3. Jarzebowski W, Caumes E, Dupin N, et al. Effect of early syphilis infection on plasma viral load and CD4 cell count in human immunodeficiency virus-infected men: results from the FHDH-ANRS CO4 cohort. Arch Intern Med. 2012;172(16): 1237-1243. 4. Musher DM, Hamill RJ, Baughn RE. Effect of human immunodeficiency virus (HIV) infection on the course of syphilis and on the response to treatment. Ann Intern Med. 1990;113(11):872-881. 5. Hughes EH, Guzowski M, Simunovic MP, et al. Syphilitic retinitis and uveitis in HIV-positive adults. Clin Experiment Ophthalmol. 2010;38(9):851-856. 6. Yang CJ, Lee NY, Lin YH, et al. Jarisch-Herxheimer reaction after penicillin therapy among patients with syphilis in the era of the HIV infection epidemic: incidence and risk factors. Clin Infect Dis. 2010;51(8):976-979.
JAAPA Journal of the American Academy of Physician Assistants
Copyright © 2014 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
www.JAAPA.com
35
