Neurosyphilis mimicking giant cell arteritis both clinically and microscopically
- 1 Internal Medicine, Elisabeth-TweeSteden Ziekenhuis, Tilburg, The Netherlands
- 2 Internal Medicine, Canisius Wilhelmina Hospital, Nijmegen, Gelderland, The Netherlands
- Correspondence to Dr Annet Bouma-de Krijger; A.Bouma-dekrijger@cwz.nl
Abstract
Temporal arteritis is usually caused by giant cell arteritis (GCA). However, inflammation of the temporal artery can also occur secondary to autoimmune diseases or infections.
We present a remarkable case of a man in his 70s with biopsy proven temporal arteritis, who was later diagnosed with meningovascular neurosyphilis. The presentation of an acute onset monocular vision loss with inflammation of the temporal artery on biopsy appeared a GCA, misleading the physicians, as it turned out to be a manifestation of neurosyphilis.
Background
Syphilis may be accounted as the earliest described sexually transmitted disease. Its tumultuous history describes several famous historical figures suggested being infected with the disease and there is an ongoing debate about its origin.1 After an initial decrease in the incidence of syphilis in the 1990s, infection rates have risen again since the early 2000s, especially among men who have sex with men (MSM).2 Syphilis infections are often accompanied by coinfection of the HIV.3
Giant cell arteritis (GCA) is a vasculitis of the large-sized and medium-sized vessels, and is also called temporal arteritis, as the temporal artery is involved in most cases. GCA is a disease of the elderly: it almost never occurs before the age of 50 and thereafter the incidence rises and peaks between the ages of 70 and 79.4 GCA is considered a medical emergency as permanent loss of vision, mostly due to anterior ischaemic optic neuropathy (AION), is a feared complication.5
We present a case of an elderly man with various symptoms including vision loss, fitting the diagnosis of GCA reinforced by the pathological examination showing vasculitis of the temporal artery. Only after a sequence of events, the final diagnosis of neurosyphilis was made. Multiple physicians were misled, demonstrating syphilis again as the great imitator of diseases.6
Case presentation
A Caucasian man in his 70s, with a medical history of a vertebrobasilar stroke 1 year ago, initially presented to the ophthalmologist with deterioration of vision of the left eye since a week. At ophthalmic examination, the visual acuity of the left eye was 20/100 and the border of the optic disk appeared vague. Fluorescein angiography showed leakage of the optic disk without choroidal hypoperfusion. Given the absence of temporal tenderness and a normal temporal artery on Doppler ultrasound, the suspicion of GCA was low and a tentative diagnosis of non-arteritic AION was made.
However, several weeks later the erythrocyte sedimentation rate (ESR) increased to 70 mm/hour, for which he was referred to the internist. There, his history revealed 5 kg weight loss in the past 6 months, balance and hearing problems, dizziness, recent eczematous skin lesions and a sore throat with hoarseness, for which he had attended an otolaryngologist. His general examination revealed absent pulsations of the left temporal artery.
Investigations
Laboratory investigations showed a C reactive protein of 47 mg/L, haemoglobin of 121 g/L, mean corpuscular volume of 94 fL, white cell count of 6.7×109/L and creatinine of 140 μmol/L. Liver function tests, antinuclear antibody and antineutrophil cytoplasmic antibody titers were within normal ranges and no paraprotein was detected. GCA was reconsidered and biopsy of the temporal artery was performed. Pathological examination demonstrated increased cellularity of the vessel wall (figure 1). The diagnosis of GCA was made and prednisolone 1 mg/kg was given.
Temporal artery biopsy. (A) Infiltrate within the arterial wall with mild destruction of the internal elastic membrane. (B) Infiltration of the arterial adventitia.
After 3 weeks of treatment with prednisolone, vision of both eyes suddenly rapidly deteriorated and on suspicion of a recurrence of AION, the patient was referred for urgent ophthalmic examination. However, this examination revealed no AION but panuveitis of both eyes. At this moment, visual acuity of the left eye was 1/300 and visual acuity of the right eye was 3/60. In the meantime, patient also developed a right foot drop. Neurological examination revealed sensory ataxia, absent vibration sense and paresis of the right foot dorsiflexors. In the blood, tests for syphilis with chemiluminescence immunoassays and rapid plasma reagin (RPR) (titre 1:128) were positive. In the cerebrospinal fluid (CSF), Treponema pallidum haemagglutination assay (titre 1:1024) and RPR (titre 1:2) were positive. Serological tests for cytomegalovirus, herpes simplex virus, varicella zoster virus, Toxoplasma, Borrelia, Bartonella and HIV were negative, as well as interferon gamma release assay.
Social and sexual anamnesis revealed that the patient had a monogamous, heterosexual relationship for 55 years. However, further questioning brought to light some other sexual contacts multiple decades ago, of which the patient did not want to go into detail.
Differential diagnosis
Considering the combination of signs and symptoms of multiple organ systems with anaemia and high ESR at presentation, the differential diagnosis besides GCA consisted of (autoimmune) vasculitis, systemic lupus erythematosus and malignancy. As investigations showed no clues for any of these other diagnoses, GCA was reconsidered and confirmed at pathological examination.
The panuveitis that surprisingly developed during prednisolone treatment later on resulted in a new differential diagnosis. The differential diagnosis of panuveitis includes tuberculosis, candidiasis, herpes simplex, herpes zoster, cytomegalovirus, toxoplasmosis, bartonellosis, toxocariasis, Lyme disease, leprosy and syphilis. Serological testing for the most probable diagnoses led to the final diagnosis of meningovascular neurosyphilis with panuveitis. The high RPR titre of 1:128 indicates secondary syphilis, as this titre is much lower or absent in tertiary syphilis. Retrospectively, the stroke which occurred 1 year earlier might have been a first manifestation of the meningovascular neurosyphilis, although CT angiography did not reveal any signs of vasculitis.
Treatment
The patient was started on benzylpenicillin 18 million international units per day. Prednisolone was withdrawn over 2 weeks.
Outcome and follow-up
The vision and the infiltrates of both eyes impressively improved within several days. His mobility improved and he was discharged from the hospital to home, where he continued benzylpenicillin via outpatient parenteral antimicrobial therapy.
The patient denied any other sexual contact than with his regular partner in the last 10 years.
The regular partner was advised to test syphilis serology. However, she did not want to test syphilis serology despite repeatedly counselling.
Unfortunately, 2 weeks after discharge, which was 3 weeks after start of treatment with benzylpenicilline, the patient developed a severe bilateral pneumonia. Two different nasopharyngeal swabs for SARS-CoV-2 PCR were negative. Pneumocystis jirovecii pneumonia was considered and treatment with cefuroxime and high-dose cotrimoxazol was given. However, the patient deceased due to respiratory failure.
Discussion
In this report, we demonstrate the case of an elderly man with acute vision loss and multiple systemic symptoms, eventually all fitting in the diagnosis of meningovascular neurosyphilis with panuveitis. Interestingly, an initial misdiagnosis of GCA was made after finding arteritis at temporal artery biopsy. To our knowledge, this is the second case describing biopsy-proven temporal arteritis mistaken for GCA in a patient with neurosyphilis.7
After inoculation with T. pallidum, the bacterium causes primary syphilis within several weeks, presenting with a localised painless ulcer termed a chancre. After weeks to a few months, approximately 25% of untreated individuals develops secondary syphilis with a wide variety of systemic signs and symptoms. Meningovascular syphilis mostly presents after 4–10 years and can be a manifestation of both secondary and tertiary syphilis. Very late manifestations of syphilis may occur decades after infection, including cardiovascular syphilis, gummatous syphilis and neurosyphilis, presenting as general paresis or tabes dorsalis (table 1 summarises the different stages of syphilis). Ocular syphilis is a form of neurosyphilis with many possible manifestations, of which panuveitis is most common.8
Clinical manifestations and incubation periods of syphilis stages
| Stage of syphilis | Clinical manifestations | Incubation period |
| Primary | Chancre and regional lymphadenopathy | 3 weeks (3–90 days) |
| Secondary | Rash, fever, malaise, lymphadenopathy, mucus lesions, condyloma lata, alopecia and meningitis (headache, photophobia, nausea, vomiting, cranial nerve palsy and seizure) | 2–12 weeks (2 weeks–6 months) |
| Secondary and tertiary | Meningovascular syphilis: acute stroke, headache, personality change, emotional liability, vertigo and insomnia | 4–10 years |
| Ocular syphilis: panuveitis, posterior uveitis, intermediate uveitis, anterior uveitis, interstitial keratitis, chorioretinitis, retinal vasculitis, retinitis, perineuritis, papillitis, retrobulbar neuritis and optic atrophy | 4 weeks–20 years | |
| Tertiary | Cardiovascular: aortic aneurysm, aortic regurgitation and coronary artery ostial stenosis | 10–30 years |
Neurosyphilis:
|
5–20 years | |
| Gumma: monocytic infiltrates with tissue destruction of any organ | 1–46 years (most cases 15 years) | |
| Latent | Asymptomatic | Early, <1 year; late, >1 year |
Meningovascular syphilis seems to be the predominant manifestation of neurosyphilis (10%–35%) in HIV-uninfected patients,9–11 contrary to HIV-infected individuals in whom syphilic meningitis is more common.12 In meningovascular syphilis, two categories of syphilic vasculitis have been described: Heubner arteritis describes endarteritis obliterans of medium and large arteries,13 while Nissl-Alzheimer arteritis affects small vessels with intimal and adventitial thickening.14 Both variants mostly emerge as acute stroke. The anterior circulation is most frequently affected14 but stroke can also occur in the posterior circulation.13 15 16
T. pallidum has a very high affinity to the central nervous system (CNS). Animal models showed that the microorganism reaches the CNS within 1 day after the primary syphilitic infection.17 T. pallidum replicates slowly, preventing its clearance by immune response, and can spend months to years in the immune privileged CNS environment.18 Finally, down-regulation of the systemic immune response may promote disease progression towards neurological involvement. Conversely, CNS damage can occur due to an uncontrolled local host immune response, resulting in clinical neurosyphilis.19 20
Syphilis is notorious for its uncommon and non-specific presentations and is called the great imitator. However, only a high degree of suspicion for disease will lead clinicians to perform a lumbar puncture.21 Even when CSF has been obtained, establishing the diagnosis may be difficult due to limited sensitivity of CSF tests.22 In contrast to the challenge to diagnose the disease, the treatment with penicillin is easy and effective and its introduction changed syphilis from a common into a rare disease in the postantibiotic era. Therefore, it is important to consider syphilis early on and to treat it appropriately to prevent life-threatening complications.
The mimicking of GCA by neurosyphilis with acute vision loss has previously been reported once more in 1967.7 In this case, binocular blindness was caused by AION, unlike our patient who had monocular AION at the primary deterioration of vision, but manifested binocular panuveitis at the moment of blindness. This same case also is the only one reporting temporal arteritis at pathological examination in a patient with neurosyphilis. Furthermore, two other case reports have described secondary syphilis resembling GCA with headache, scalp tenderness and elevated ESR.23 24
Temporal arteritis is caused by GCA in most cases. However, the temporal artery can also be involved in patients with systemic vasculitis due to other autoimmune diseases25 or due to infection with varicella zoster virus.26 Our case shows that syphilis can cause inflammation of the temporal artery as well, which has a clear rationale since widespread vascular inflammation can occur in meningovascular syphilis. In addition, Smith et al reported about 10 patients with temporal arteritis of whom 4 had positive syphilis blood tests.7 A relation between syphilis and temporal arteritis could therefore be hypothesised, but no further studies into this topic have been published to date.
Our case illustrates that syphilis should also be considered in patients who are not in any classic risk group. However, in a patient in his 70s with a stable monogamous, heterosexual relationship and a history of stroke, syphilis should be part of the differential diagnosis. In addition, syphilis can manifest multiple years after infection27 and sexual history is not always reliable as people often do not want to tell about sexually risk behaviour due to taboos on MSM and adultery.
In conclusion, this is the second report of biopsy-proven temporal arteritis in a patient with neurosyphilis. Meningovascular syphilis is an uncommon cause of vasculitis of the temporal artery. As both ocular involvement of neurosyphilis and GCA can cause acute loss of vision, physicians may be misled to an incorrect diagnosis of GCA, even after temporal artery biopsy. Therefore, physicians should be aware of this phenomenon and should consider syphilis when patients present with systemic signs and symptoms of various organ systems, regardless of finding temporal arteritis at pathological examination.
Learning points
-
Inflammation of the temporal artery is an unusual manifestation of meningovascular syphilis.
-
When patients present with signs and symptoms of various organ systems, consider syphilis as a rare but treatable diagnosis.
-
Do not exclude sexually transmitted diseases on the basis of sexual history or elderliness.
-
Neurosyphilis can become manifest multiple years to decades after inoculation with Treponema pallidum.
Ethics statements
Patient consent for publication
Acknowledgments
The authors would like to thank pathologist Dr AJW Kooij for providing the microscopic images of the temporal artery biopsy.
Footnotes
-
Contributors NvR: design and conceptualisation of the case report, involved in clinical care and drafting of manuscript. MvK: design and conceptualisation of the case report, involved in clinical care and revision of manuscript for intellectual content. AB-dK: design and conceptualisation of the case report, involved in clinical care and revision of manuscript for intellectual content.
-
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
-
Case reports provide a valuable learning resource for the scientific community and can indicate areas of interest for future research. They should not be used in isolation to guide treatment choices or public health policy.
-
Competing interests None declared.
-
Provenance and peer review Not commissioned; externally peer reviewed.
- © BMJ Publishing Group Limited 2022. No commercial re-use. See rights and permissions. Published by BMJ.
References
Use of this content is subject to our disclaimer