In The Literature

Cytomegalovirus Pseudotumor

Smibert OC, Allison CC, Doerflinger M, et al. Pseudotumor presentation of CMV disease: diagnostic dilemma and association with immunomodulating therapy [manuscript published online ahead of print 29 November 2020]. Transpl Infect Dis 2020. doi:10.1111/tid.13531.

A 58-year-old woman receiving pembrolizumab for an extensive local recurrence of a mucosal squamous cell carcinoma of the oral cavity that had been previously treated with aggressive surgery and radiotherapy presented with a painless enlarging oral cavity mass. The mass was ¹⁸FDG-avid. Examination of biopsied tissue revealed ulcerated granulation tissue with focal viral cytopathologic changes and positive histochemical staining for cytomegalovirus (CMV). There was no evidence of malignancy.

The patient had a CD4 T-cell count of 350 cells/mm³ but was human immunodeficiency virus (HIV) negative. Therapy with ganciclovir followed by valganciclovir for 8 weeks resulted in only partial resolution of the lesion, which was then resected. Histological examination again demonstrated the presence of CMV infection. There was no evidence of recurrence after a follow-up of 30 months.

A 52-year-old woman who had undergone renal transplantation 12 months previously presented with a vulval lesion that had been growing for 6 months that was initially presumed to represent wart disease. Her immunosuppressive therapy consisted of monthly betacept (which had replaced tacrolimus 3 months after transplantation because of nephrotoxicity) as well as mycophenolate and 5 mg prednisolone. She had had persistent low-level CMV viremia for the past 3 months despite receipt of valganciclovir and the virus was found to have an M460V mutation in its UL97 gene. This was followed by a reduction in immunosuppression and administration of CMV immunoglobulin.

Histologic examination of biopsy material from the vulval lesion revealed squamous dysplasia, leading to radical resection surgery. Examination of the removed tissue identified the presence of CMV infection with associated cytopathic effects and immunohistochemistry confirmed the presence of CMV; malignant tissue was not identified. Although her CD4 T-cell count was only 58 cells/mm³, she was HIV negative. Betacept was discontinued and tacrolimus restarted. There was no evidence of recurrence after 20 months.

CMV pseudotumor was originally described in people with HIV in whom it almost exclusively involved the gastrointestinal tract; the first report was of an infant with resultant pyloric obstruction. A literature review identified 21 cases without evidence of HIV infection (57% were explicitly stated to be HIV negative), in addition to the 2 described by Nibert and colleagues. Of these, 78% had gastrointestinal involvement, with 15 involving the colon or rectum and 3 the stomach or small bowel. In addition, 2 involved the head and neck, 2 the lung, and 1 the vulva. Eleven (48%) were known to be immunocompromised, with 7 having undergone solid organ transplantation. CD4 T-cell counts ranged from 36 to 706 cells/mm³. Of the 8 patients tested, 4 had CMV viremia. Seven patients underwent surgical resection, 13 received antiviral therapy, and 2 received CMV immunoglobulin. Twenty-one patients had apparent resolution of their lesions after a median of 22 weeks of follow-up.

The pathophysiology of CMV pseudotumors is uncertain. The first case described above suggests that CMV infected a previously disrupted site (locus minoris resistentiae), but others do not fit this picture, suggesting that the lesion may arise de novo. Immunocompromise clearly often plays an important role, although this is not obviously present in all cases. The possibility that some lesions may become apparent as a consequence of an inflammatory reconstitution inflammatory syndrome, which may have played a role in the first case above, in whom the lesion appeared while she was receiving a checkpoint inhibitor, must be considered.

Ocular Syphilis: Case Series

Wagner LF, Lanzl I, Rothe K, et al. Clinical and ophthalmologic characteristics of ocular syphilis in a retrospective tertiary hospital cohort [manuscript published online ahead of print 4 November 2020]. Sex Transm Dis 2020. doi:10.1097/OLQ.0000000000001329.

Mathew D, Smit D. Clinical and laboratory characteristics of ocular syphilis and neurosyphilis among individuals with and without HIV infection. Br J Ophthalmol 2021; 105:70–4. doi:10.1136/bjophthalmol-2019–315699.

Rasoldier V, Gueudry J, Chapuzet C, Bodaghi B, Muraine M, Tubiana R, et al. Early symptomatic neurosyphilis and ocular syphilis: a comparative study between HIV-positive and HIV-negative patients [manuscript published online ahead of print 22 October 2020]. Med Mal Infect 2020. doi:10.1016/j.medmal.2020.10.016.

The incidence of syphilis, including ocular syphilis, is reported to be increasing in many countries. Many cases occur in people living with human immunodeficiency virus (HIV). Several groups have recently reported their experience.

Wagner and colleagues retrospectively analyzed the cases of 23 adults with ocular syphilis seen at a single hospital in Munich between 2008 and 2018. All but 2 were male. Five of 22 (23%) tested were HIV infected. Six (26%) had mucocutaneous lesions consistent with secondary syphilis. Fifteen (65%) had uveitis: posterior uveitis in 11 (48%), panuveitis in 5 (22%), and anterior uveitis in 1 (4%). “Irregularities” of the retinal pigment epithelium were seen in approximately two-thirds. Other findings included papillitis, vasculitis, and vitreous “conspicuities.” The cerebrospinal fluid (CSF) protein and/or white blood cell count was elevated in 17 of the 20 (85%) patients who underwent lumbar puncture; the median leukocyte count and protein concentration were 14 cells/μL (interquartile range [IQR], 4–33 cells/μL) and 581 mg/dL (IQR, 402–756 mg/dL), respectively. All 15 patients with follow-up had improved visual acuity after treatment.

Mathew and Smit reviewed the case records of 146 patients with ocular syphilis involving a total of 215 eyes that were examined over 5 years ending in December 2018 at a single hospital in South Africa. Of the 146 patients, 76 (52.1%) were HIV infected (the prevalence of HIV infection in South Africa is 12.6%). The diagnosis of HIV infection was newly made at the time of presentation with ocular syphilis in 18 (23.7%). The median CD4 T-cell count, which was available in 63.8% of the patients with HIV, was 411 cells/μL (range, 45–726 cells/μL). The uveitis, which was nongranulomatous in 89.4% of involved eyes, was anterior or intermediate (the latter mostly vitreous) in 20.7%, posterior in 40.9%, and panuveitis in 38.1%. The uveitis was bilateral in approximately 50% of the entire cohort but was bilateral in 68% of those with HIV. Eyes from HIV-infected patients were more likely to have reduced visual acuity of ≤20/200 than those from HIV-uninfected patients. Of the 146 patients, (77.4%) underwent lumbar puncture. “Confirmed” and probable neurosyphilis was present in 16 and 27, respectively, and approximately half of each group was HIV infected.

Rasoldier and colleagues in Paris reviewed the records of 67 patients with ocular syphilis, 14 patients with both ocular syphilis and neurosyphilis, and 15 with neurosyphilis alone. Of the total, 96% were male and 49% were HIV infected. The patients were seen at 2 centers in Rouen, France, from 2000 to 2016. Bilateral involvement was present in 24 (62%) and 15 (38%) (P = .045) of those with and without HIV infection, respectively. Half of the patients had secondary syphilis. In the 81 patients with ocular disease, 43 (57%) had posterior uveitis and 18 (22%) had panuveitis. Fifty patients with ocular syphilis underwent lumbar puncture and the CSF treponemal test was positive in 50 (78%), while the VDRL was positive in only 10 (20%). Visual acuity gradually improved after treatment in the 26 patients with follow-up results.

Ocular syphilis may involve any part of the eye but often affects the uveal tract, with posterior uveitis and panuveitis the most common locations [1]. Retinitis, including retinal vasculitis, may occur and this is often accompanied by inflammation of the vitreous. The optic nerve may be involved with a potential late consequence of optic atrophy. Interstitial keratitis is also seen.

Ocular syphilis may be accompanied by meningovasculitis and, as a consequence, patients with eye involvement should undergo CSF examination. The treatment regimen used for patients with ocular syphilis is the same as that recommended for neurosyphilis, whether or not the latter diagnosis is confirmed. Corticosteroids are often administered as adjunctive therapy to control the inflammation associated with ocular syphilis.

The reference below has an excellent array of photographs illustrating the variety of manifestations of ocular syphilis [1].

Reference