FROSTED BRANCH ANGIITIS SECONDARY TO HERPES SIMPLEX VIRUS INFECTION PROGRESSING TO ACUTE RETINAL NECROSIS Andrew J. Barkmeier, MD, Stephen S. Feman, MD
Purpose: To describe a case of frosted branch angiitis secondary to herpes simplex virus type 2 infection that progressed to acute retinal necrosis. Methods: The medical records and clinical photographs were reviewed for a patient with frosted branch angiitis that progressed to acute retinal necrosis. Results: The patient rapidly developed acute retinal necrosis followed by rhegmatogenous retinal detachment. Polymerase chain reaction analysis of the vitreous was positive for herpes simplex virus type 2. Discussion: Frosted branch angiitis is a clinical sign that may represent active viral disease capable of progressing to acute retinal necrosis. RETINAL CASES & BRIEF REPORTS 3:36 –37, 2009
From St. Louis University, St. Louis, Missouri.
right eye had been phthisical and without light perception since early childhood. He believed that this was secondary to Coats disease. The left eye had developed recurrent herpetic stromal keratitis several years before our examination. The patient was being treated with prophylactic acyclovir for corneal disease but had run out of medication 72 hours before the onset of the current symptoms. He denied any other current or recent systemic illness. At our first examination, best-corrected visual acuity was 8/200 in the left eye (previously reported to be 20/80 due to stromal keratitis–related scarring). There was trace conjunctival injection but no new corneal findings; slit-lamp biomicroscopy disclosed 1⫹ anterior chamber cellular reaction and flare. Dilated fundus examination revealed frosted branch angiitis–like exudative retinal vasculitis with prominent periphlebitis and serous macular detachment in the left eye (Fig. 1). Scattered perivascular retinal hemorrhages surrounded the distal portions of numerous vessels. Fluorescein angiographic images were of poor quality due to artifact from corneal scarring. After a vitreous sample was obtained for analysis, intravenous treatment with acyclovir was started due to suspicion of herpetic disease. Herpes simplex virus type 2 was identified in the vitreous by polymerase chain reaction analysis, and the serum leukocyte count was elevated (16,200 cells/mm3). Results of blood and vitreous cultures, chest radiography, and remaining serum laboratory analyses were unremarkable, including complete metabolic panel analysis, testing for antibody to human immunodeficiency virus, antibody to cytomegalovirus, antibody to Toxoplasma, and antinuclear antibody, rapid plasma reagin testing, and serum polymerase chain reaction analysis. Despite aggressive antiviral therapy, the retinal disease progressed over the following 3 days to acute retinal necrosis (Fig. 2). The patient subsequently developed
I
n 1976, Ito et al1 described the first case of “frosted branch angiitis.” It was a case of bilateral retinal vasculitis with diffuse perivascular exudation and panuveitis in a healthy 6-year-old boy. Subsequently, frosted branch angiitis, also termed “acute frosted retinal periphlebitis,” has been reported in multiple clinical contexts and may represent a specific vascular response rather than a shared etiology.2 Although commonly treated with systemic corticosteroids,3 this clinical sign has been documented in association with several infectious agents, including cytomegalovirus4 and herpes simplex virus types 1 and 2.5,6 We report a case of frosted branch angiitis with panuveitis secondary to herpes simplex virus type 2 infection that progressed to acute retinal necrosis. Case Report A 33-year-old systemically healthy man presented with a 2-day history of decreased vision and periocular pain in the left eye. The Supported in part by a grant from Research to Prevent Blindness, Inc. (New York, NY). The authors have no proprietary interest regarding the subject matter of this report. Reprint requests: Stephen S. Feman, MD, 1755 South Grand Avenue, St. Louis, MO 63104; e-mail: [email protected]
36
37
ACUTE RETINAL NECROSIS AFTER FROSTED BRANCH ANGIITIS
Fig. 1. Inferior/inferotemporal retina in the left eye at initial presentation. Frosted branch angiitis–like exudative retinal vasculitis with prominent periphlebitis, scattered perivascular hemorrhages, and serous macular detachment were observed.
rhegmatogenous retinal detachment secondary to acute retinal necrosis and underwent retinal detachment repair.
Discussion Frosted branch angiitis is a poorly understood vascular response that has been reported in association with numerous stimuli. Although it has been postulated to occur secondary to an immune complex reaction, this etiology has yet to be proven. Several cases of “primary” frosted branch angiitis, whether postviral
or idiopathic, have been reported anecdotally to respond to systemic corticosteroid treatment.3 However, as demonstrated in our case, potential infectious etiologies must be ruled out before initiating corticosteroid therapy because this clinical sign may be associated with active viral disease capable of progressing to widespread retinitis. Although disease progression was documented in this case despite intravenous treatment with acyclovir, it may still be advisable to initiate antiviral therapy while awaiting the results of a directed infectious and immunologic workup. Furthermore, polymerase chain reaction analysis of the vitreous or aqueous humor should be considered when clinical suspicion of an infectious etiology is high because it is sensitive and specific for herpes simplex virus and many other potential infectious agents.7 To our knowledge, the presence of pain at presentation has not been documented in previous cases of frosted branch angiitis–like exudation. This symptom should probably increase the suspicion of herpetic or other infectious disease. Although acute retinal necrosis often presents with periocular discomfort and episcleritis or scleritis, this specific exudative retinal vascular response has not, to our knowledge, been previously reported in association with acute retinal necrosis. Key words: acute frosted retinal periphlebitis, acute retinal necrosis, frosted branch angiitis, herpes simplex virus, herpes simplex virus type 2. References 1. 2. 3. 4.
5.
6.
Fig. 2. Inferior/inferotemporal retina in the left eye on day 4. Acute retinal necrosis with diffuse retinitis and hemorrhage despite intravenous acyclovir treatment were found.
7.
Ito Y, Nakano M, Kyu N, Takeuchi M. Frosted branch angiitis in a child. Jpn J Clin Ophthalmol 1976;30:797–803. Kleiner RC, Kaplan HJ, Shakin JL, et al. Acute frosted retinal periphlebitis. Am J Ophthalmol 1988;106:27–34. Walker S, Iguchi A, Jones NP. Frosted branch angiitis: a review. Eye 2004;18:527–533. Spaide RF, Vitale AT, Toth IR, Oliver JM. Frosted branch angiitis associated with cytomegalovirus retinitis. Am J Ophthalmol 1992;113:522–528. Chatzoulis DM, Theodosiadis PG, Apostolopoulos MN, et al. Retinal perivasculitis in an immunocompetent patient with systemic herpes simplex infection. Am J Ophthalmol 1997; 123:699–702. Markomichelakis NN, Barampouti F, Zafirakis P, et al. Retinal vasculitis with a frosted branch angiitis-like response due to herpes simplex virus type 2. Retina 1999;19:455–457. Van Gelder RN. Applications of the polymerase chain reaction to diagnosis of ophthalmic disease. Surv Ophthalmol 2001;26: 248–258.
Purpose: To describe a case of frosted branch angiitis secondary to herpes simplex virus type 2 infection that progressed to acute retinal necrosis. Methods: The medical records and clinical photographs were reviewed for a patient with frosted branch angiitis that progressed to acute retinal necrosis. Results: The patient rapidly developed acute retinal necrosis followed by rhegmatogenous retinal detachment. Polymerase chain reaction analysis of the vitreous was positive for herpes simplex virus type 2. Discussion: Frosted branch angiitis is a clinical sign that may represent active viral disease capable of progressing to acute retinal necrosis. RETINAL CASES & BRIEF REPORTS 3:36 –37, 2009
From St. Louis University, St. Louis, Missouri.
right eye had been phthisical and without light perception since early childhood. He believed that this was secondary to Coats disease. The left eye had developed recurrent herpetic stromal keratitis several years before our examination. The patient was being treated with prophylactic acyclovir for corneal disease but had run out of medication 72 hours before the onset of the current symptoms. He denied any other current or recent systemic illness. At our first examination, best-corrected visual acuity was 8/200 in the left eye (previously reported to be 20/80 due to stromal keratitis–related scarring). There was trace conjunctival injection but no new corneal findings; slit-lamp biomicroscopy disclosed 1⫹ anterior chamber cellular reaction and flare. Dilated fundus examination revealed frosted branch angiitis–like exudative retinal vasculitis with prominent periphlebitis and serous macular detachment in the left eye (Fig. 1). Scattered perivascular retinal hemorrhages surrounded the distal portions of numerous vessels. Fluorescein angiographic images were of poor quality due to artifact from corneal scarring. After a vitreous sample was obtained for analysis, intravenous treatment with acyclovir was started due to suspicion of herpetic disease. Herpes simplex virus type 2 was identified in the vitreous by polymerase chain reaction analysis, and the serum leukocyte count was elevated (16,200 cells/mm3). Results of blood and vitreous cultures, chest radiography, and remaining serum laboratory analyses were unremarkable, including complete metabolic panel analysis, testing for antibody to human immunodeficiency virus, antibody to cytomegalovirus, antibody to Toxoplasma, and antinuclear antibody, rapid plasma reagin testing, and serum polymerase chain reaction analysis. Despite aggressive antiviral therapy, the retinal disease progressed over the following 3 days to acute retinal necrosis (Fig. 2). The patient subsequently developed
I
n 1976, Ito et al1 described the first case of “frosted branch angiitis.” It was a case of bilateral retinal vasculitis with diffuse perivascular exudation and panuveitis in a healthy 6-year-old boy. Subsequently, frosted branch angiitis, also termed “acute frosted retinal periphlebitis,” has been reported in multiple clinical contexts and may represent a specific vascular response rather than a shared etiology.2 Although commonly treated with systemic corticosteroids,3 this clinical sign has been documented in association with several infectious agents, including cytomegalovirus4 and herpes simplex virus types 1 and 2.5,6 We report a case of frosted branch angiitis with panuveitis secondary to herpes simplex virus type 2 infection that progressed to acute retinal necrosis. Case Report A 33-year-old systemically healthy man presented with a 2-day history of decreased vision and periocular pain in the left eye. The Supported in part by a grant from Research to Prevent Blindness, Inc. (New York, NY). The authors have no proprietary interest regarding the subject matter of this report. Reprint requests: Stephen S. Feman, MD, 1755 South Grand Avenue, St. Louis, MO 63104; e-mail: [email protected]
36
37
ACUTE RETINAL NECROSIS AFTER FROSTED BRANCH ANGIITIS
Fig. 1. Inferior/inferotemporal retina in the left eye at initial presentation. Frosted branch angiitis–like exudative retinal vasculitis with prominent periphlebitis, scattered perivascular hemorrhages, and serous macular detachment were observed.
rhegmatogenous retinal detachment secondary to acute retinal necrosis and underwent retinal detachment repair.
Discussion Frosted branch angiitis is a poorly understood vascular response that has been reported in association with numerous stimuli. Although it has been postulated to occur secondary to an immune complex reaction, this etiology has yet to be proven. Several cases of “primary” frosted branch angiitis, whether postviral
or idiopathic, have been reported anecdotally to respond to systemic corticosteroid treatment.3 However, as demonstrated in our case, potential infectious etiologies must be ruled out before initiating corticosteroid therapy because this clinical sign may be associated with active viral disease capable of progressing to widespread retinitis. Although disease progression was documented in this case despite intravenous treatment with acyclovir, it may still be advisable to initiate antiviral therapy while awaiting the results of a directed infectious and immunologic workup. Furthermore, polymerase chain reaction analysis of the vitreous or aqueous humor should be considered when clinical suspicion of an infectious etiology is high because it is sensitive and specific for herpes simplex virus and many other potential infectious agents.7 To our knowledge, the presence of pain at presentation has not been documented in previous cases of frosted branch angiitis–like exudation. This symptom should probably increase the suspicion of herpetic or other infectious disease. Although acute retinal necrosis often presents with periocular discomfort and episcleritis or scleritis, this specific exudative retinal vascular response has not, to our knowledge, been previously reported in association with acute retinal necrosis. Key words: acute frosted retinal periphlebitis, acute retinal necrosis, frosted branch angiitis, herpes simplex virus, herpes simplex virus type 2. References 1. 2. 3. 4.
5.
6.
Fig. 2. Inferior/inferotemporal retina in the left eye on day 4. Acute retinal necrosis with diffuse retinitis and hemorrhage despite intravenous acyclovir treatment were found.
7.
Ito Y, Nakano M, Kyu N, Takeuchi M. Frosted branch angiitis in a child. Jpn J Clin Ophthalmol 1976;30:797–803. Kleiner RC, Kaplan HJ, Shakin JL, et al. Acute frosted retinal periphlebitis. Am J Ophthalmol 1988;106:27–34. Walker S, Iguchi A, Jones NP. Frosted branch angiitis: a review. Eye 2004;18:527–533. Spaide RF, Vitale AT, Toth IR, Oliver JM. Frosted branch angiitis associated with cytomegalovirus retinitis. Am J Ophthalmol 1992;113:522–528. Chatzoulis DM, Theodosiadis PG, Apostolopoulos MN, et al. Retinal perivasculitis in an immunocompetent patient with systemic herpes simplex infection. Am J Ophthalmol 1997; 123:699–702. Markomichelakis NN, Barampouti F, Zafirakis P, et al. Retinal vasculitis with a frosted branch angiitis-like response due to herpes simplex virus type 2. Retina 1999;19:455–457. Van Gelder RN. Applications of the polymerase chain reaction to diagnosis of ophthalmic disease. Surv Ophthalmol 2001;26: 248–258.
