Spotlight Case: Why a High Index of Suspicion and Prompt Diagnosis are Critical

  • author profile pictureKeyvan Koushan, MD, FRCSC
  • author profile pictureShailesh K. Gupta, MD, MBA

Case history

A 23-year-old black female presented with a 2-day history of sudden-onset redness, photophobia, pain, and tearing OS. She had been placed on gentamicin drops by her primary care physician with no improvement of her symptoms. Ocular history was unremarkable and medical history was significant for mild hypertension and mild developmental delay. Social history was significant for having multiple sexual partners in the past 2 years and being repeatedly tested for HIV in the past (all being negative).

Examination revealed best corrected visual acuity of 20/20 OD and 20/30+2 OS. Pupils were equally reactive with no afferent pupillary defect. Slit lamp examination was unremarkable OD, and significant for diffuse conjunctival injection and 4+ cells and flare OS. There were no keratic precipitates. Early formation of posterior synechiae was evident OS.

Dilated fundus examination OD was unremarkable. OS demonstrated moderate swelling of the optic disc with Paton’s lines, mild macular edema, and scattered peripheral areas of retinitis in the nasal periphery with a focal area of confluent hemorrhagic retinitis in the infero-nasal peripheral retina (see Figure 1). There was mild to moderate vitritis OS. Fluorescein angiography demonstrated moderate vasculitis with leakage concentrated in inferonasal peripheral retina OS (Figure 2).

Figure 1. Scattered peripheral areas of retinitis with more confluent area of retinitis in inferonasal retina.

Figure 2. Fluorescein angiography OS showing leakage from the area of retinitis.

What’s your diagnosis?

The patient was diagnosed with uveitis with presumptive acute retinal necrosis (ARN) OS. The differential diagnosis included:

  • CMV retinitis
  • Progressive outer retinal necrosis (PORN)
  • Tuberculosis infection
  • Syphilis infection
  • Toxoplasmosis
  • Sarcoidosis

Anterior chamber aqueous sample was taken for polymerase chain reaction (PCR) analysis and the patient was admitted in consultation with the infectious diseases service. Intravenous acyclovir (10 mg/kg q8h) was started. The PCR analysis of AC sample was noted to be positive for herpes simplex virus type 2 (HSV 2).
 

Discussion

ARN is associated with members of the herpes virus family:

  • Varicella zoster virus (VZV) (most frequent virus and implicated in two-thirds of cases)
  • HSV 1, HSV 2, cytomegalovirus (few case reports)
  • Epstein-Barr virus (causation not established)

In cases attributed to VZV, ARN can present before, after, or at the same time of the skin manifestations of VZV infection. The diagnosis of ARN is clinical and identification of an etiologic agent, or knowledge of patient’s immune status is not necessarily needed.

ARN may affect healthy individuals of any sex and age with average age of 40. Patients are not immunocompromised or systemically ill, although they may demonstrate subclinical immune dysfunction. As seen in our case, HSV 2 appears to be implicated in younger patients with ARN (average age of 21). Specific HLA haplotypes may be more susceptible to ARN: HLA-DQw7, Bw62, and DR4.[1]

Prompt diagnosis with a high index of suspicion and timely treatment of ARN is paramount, as clinical findings can evolve rapidly in the affected eye. Once posterior synechiae and the concomitant uveitis limit the view to the posterior fundus, a clinical diagnosis can be more difficult. Delay in diagnosis can also lead to an adverse final outcome. Additionally, the contralateral eye will be involved in approximately one-third of untreated ARN cases, usually within 6 weeks of the onset of disease in the first eye.[2] This drops to 3% with treatment.[3] The second eye can be affected as late as 34 years after involvement of the first eye.[4] In addition to involvement of the contralateral eye, patients are also at risk of systemic sequelae such as meningitis and encephalitis (especially in cases associated with HSV 1 infection).

Our patient was admitted and treated with IV acyclovir. Her systemic workup was negative, including HIV testing and other potential infectious etiologies. A negative lumbar puncture and CT head/orbit ruled out CNS involvement. On day 2 of admission, she was noted to have nasal RD OS (Figure 3), progressing to total macula-off RD by day 5 (Figure 4). Her ocular pain, conjunctival injection, AC reaction, and the amount of peripheral retinitis OS gradually improved.

Figure 3. Inferonasal RD OS on day 3.

Figure 4. Macula-off RD OS on day 5 after the initiation of acyclovir treatment.

 
Take-home points

  • Most cases of ARN are due to VZV and other members of the herpesviridae. PCR of the anterior chamber aspirate can significantly aid the diagnosis, although identification of an etiologic agent is not necessary for the diagnosis.
  • A high index of suspicion with prompt diagnosis and treatment of ARN is critical since visual prognosis and involvement of the contralateral eye are significantly improved with treatment.
  • Treatment of ARN patients is systemic (with intravenous acyclovir) and should be in consultation with infectious diseases specialists since patients are at risk of developing CNS involvement.
  • Visual prognosis remains poor despite initiation of prompt treatment.
     

References

  1. Holland G, Cornell P, Park M, et al. An association between acute retinal necrosis syndrome and HLA-DQw7 and phenotype Bw62, DR4. Am J Ophthalmol. 1989;108(4):370-374.
  2. Blumenkranz M, Culbertson W, Clarkson J, Dix R. Treatment of the acute retinal necrosis syndrome with intravenous acyclovir. Ophthalmology. 1986;93(3);296-300.
  3. Tibbetts M, Shah C, Young L, Duker J, Maguire J, Morley M. Treatment of acute retinal necrosis [published January 15, 2010]. Ophthalmology. 2010;117(4):818-824. doi: 10.1016/j.ophtha.2009.09.001.
  4. Falcone P, Brockhurst R. Delayed onset of bilateral acute retinal necrosis syndrome: a 34-year interval. Ann Ophthalmol. 1993;25(10);373-374.
  5. Gandorfer A, Thurau S. [Acute retinal necrosis]. Ophthalmologe. 2009;106(8):751-759;quiz760. doi: 10.1007/s00347-009-1986-1. [Article in German]
  6. Lau C, Missotten T, Salzmann J, Lightman S. Acute retinal necrosis features, management, and outcomes [published online December 20, 2006]. Ophthalmol.  2007;114(4):756-762.
  7. Crapotta J, Freeman W, Feldman R, et al. Visual outcome in acute retinal necrosis. Retina. 1993;13(3):208-213.

Financial disclosures

Dr. Koushan - None.

Dr. Gupta - BEAVER VISITEC: Consultant, Honoraria.

Dr. Hau - SEQUENOM: Speaker, Honoraria; THROMBOGENICS, INC: Other, Honoraria.

Dr. Choudhry - None.

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