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Home , Oral candidiasis

Herpes Zoster Ophthalmicus in a Patient with Wegener’s Granulomatosis

Sunny Chun, DO,* Karan Lal, BS,** David Posnick, DO,* Adriana Ros, DO***

* Resident, Palisades Medical Center, Palisades, NJ **OMSIV, New York Institute of Technology- College of Osteopathic Medicine, Old Westbury, NY ***Program Director, Dermatology Residency Program, Palisades Medical Center, Palisades, NJ

Abstract Herpes zoster ophthalmicus (HZO) is a serious presentation of varicella-zoster virus infection in the periocular region that may manifest cutaneously but can progress to have ocular involvement, justifying ophthalmologic consultation. Co-morbid diseases may complicate the diagnosis and management of HZO, requiring thorough monitoring of the patient’s progress and potential drug interactions of patient’s medications. Early oral antiviral treatment decreases the rate of development of ocular complications. Post-herpetic neuralgia is a frequent complication of herpes zoster and is best managed with multi-modal drug regimens that work on different mechanisms of the disease.

Introduction Case Presentation Herpes zoster ophthalmicus is a reactivation of A 44-year-old Puerto Rican female presented to herpesvirus-3, also known as the varicella-zoster the emergency department for right periorbital virus, in the distribution of the ophthalmic branch and edema for two days’ duration. of the trigeminal nerve (CN V). It represents up She reported difficulty opening the right eye, to 25% of all herpes zoster presentations.1 Risk radiating throbbing pain along the right side factors for re-activation of the virus include old of her face, and fever. The blistering rash was age, immunosuppressive drugs and diseases, present in the right periorbital region, on the emotional stress, neoplastic disorders, fatigue, right anterior scalp and right dorsum of the nose. poor nutrition, and recreational drug abuse.2-5 The patient also complained of tenderness of Clinical presentation may be preceded by malaise, affected areas along the right hemi-facial region. fatigue, headache, fever, and/or photophobia.3 The patient also stated that over the past year, Lesions typically follow the phases of non- she’d experienced gradually increasing weakness ophthalmic zoster or “,” beginning with in the lower extremities, hearing loss, and joint unilateral dermatomal pruritus, pain, and/or pain. Past medical history included depression, tingling that may be present for up to five days , and Wegener’s granulomatosis, which before an erythematous vesicular rash appears. was diagnosed in 2010 in Puerto Rico based on The vesicles eventually rupture, form crusts, and a skin of the patient’s thigh, for which she then heal without scarring. was placed on chronic therapy by her primary physician. Past surgical history included multiple skin grafts for perforated nasal septum secondary to Wegener’s granulomatosis. The patient’s home medications included: prednisone, Figure 2. Atrophic hypopigmented plaques gabapentin, fluoxetine, tramadol, trazodone, iron located in a relatively symmetrical pattern on sulfate, and alprazolam. The patient had a family the lower extremities. history of mellitus and stroke. Physical examination revealed multiple vesicles patient was rapid plasma reagin (RPR) negative on an erythematous base in the right periorbital and human virus negative. region, forehead, scalp and nasal dorsum (Figure The patient was admitted and placed on 1). Additionally, white exudative plaques were intravenous acyclovir 200 mg (TID), visible on the anterior . Coalescing methylprednisolone 20 mg (BID), terbinafine for yellow exophytic verrucous plaques were her presumed tinea pedis, wash present on the soles of her feet. Examination of for oral , and pertinent antibiotics for extremities revealed multiple, bilateral, atrophic her periorbital . Blood cultures showed hypopigmented plaques on the anterior tibial and no growth after five days, and antibiotics were thigh regions (Figure 2). discontinued. A punch biopsy of the thigh lesion Urinalysis revealed hematuria and proteinuria. revealed dermal fibrosis with mild inflammation A bilateral renal sonogram was unremarkable; (Figure 3). Elastin staining showed fragmented, however, ultrasound of the bladder displayed thin elastic fibers indicative of scar. The scar most focal bladder irregularity. Computed tomography likely was a result of healing from a previous (CT) scan, with and without contrast, of the head active Wegener’s lesion. Subsequent laboratory testing revealed low absolute lymphocyte counts Figure 1. Vesicular rash with several crusted and neck indicated right periorbital cellulitis and pansinusitis. The ophthalmology service was (468), low absolute CD4 counts (147), and low areas presenting in a dermatomal distribution consulted, and they noted no ocular involvement. CD8 counts (147). Because the patient was and respecting the midline. Upper eyelid Laboratory tests revealed elevated p-ANCA immunosuppressed, she was given prophylactic involvement with edema and erythema. (2.7), but negative c-ANCA. The erythrocyte sulfamethoxazole/trimethoprim. The patient Concomitant conjunctivitis noted. sedimentation rate (ESR) was also elevated. The continued to complain of facial pain and was

Page 24 HERPES ZOSTER OPHTHALMICUS IN A PATIENT WITH WEGENER’S GRANULOMATOSIS are usually focally present on the forehead multiple mechanisms of disease with combination and periocular region of the affected side, with therapies is logical, and often gabapentin, tricyclic some involvement of the nose.6 Nasociliary antidepressants and/or topical lidocaine patches nerve involvement, identified by lesions on the are used as first-line agents, followed by opioids tip of the nose, also known as Hutchinson’s and capsaicin as second-line agents.27 sign, prognosticates ocular involvement due to the nerve’s location.6 Zoster ophthalmicus may References also present as a blepharitis causing difficulty 1. Ragozzino MW, Melton LJ 3d, Kurland LT, Chu CP, opening the eye with non-neural ptosis.6 About Perry HO. Population-based study of herpes zoster and 66% of patients with HZO have been found its sequelae. Medicine. 1982;61:310–6. to have corneal denervation associated with 2. Cohen JI, Brunell PA, Straus SE, Krause PR. Recent keratitis and mesencephalic nuclear brainstem advances in varicella-zoster virus infection. Ann Intern injury.16 Corneal nerve involvement and injury Med. 1999;130:922-932. results in neurotrophic keratopathy, which may 3. Gnann JW, Whitley RJ. Herpes Zoster. N Engl J cause several complications, including blindness; Med. 2002;347(5):340-46. Figure 3. H&E staining (10x): Examination of therefore, it is imperative to seek ophthalmologic an atrophic hypopigmented lower-extremity 4. Shaik S, Ta CN. Evaluation and Management of evaluation to determine the extent of the disease Herpes Zoster Ophthalmicus. Am Fam Physician. plaque revealing fibroblastic proliferation 17 and whether ocular involvement is present. 2002 Nov;66(9):1723-1730. within the dermis with blood vessels in an Other ocular presentations of HZO include arrangement perpendicular to the epidermis 5. Zwick OM, Fischer DH, Flanagan JC. “Ecstasy” conjunctivitis, uveitis, episcleritis, acute retinal induced and herpes zoster with a focal perivascular inflammatory infiltrate necrosis, progressive retinal necrosis, optic ophthalmicus. Br J Ophthalmol. 2005;89:923–924. indicative of a scar. neuritis, and cranial nerve palsies.6 6. Shafiei K, Luther E, Archie M, Gulick J, Fowler The diagnosis of HZO is clinical; however, some MR. Wegener Granulomatosis: Case Report and treated with nortriptyline. Serial complete blood cases of HZO may be difficult to delineate in Brief Literature Review. J Am Board Fam Med. counts revealed decreasing red blood cell counts, the presence of other co-morbid diseases such as 2003;16(6):555-59. hemoglobin levels, and hematocrit levels. granulomatosis with polyangiitis or periorbital 7. Anderson G, Coles ET, Crane M, et al. Wegener’s The patient was eventually discharged with cellulitis, as was the situation in our patient. Viral granuloma. A series of 265 British cases seen between residual erythema and pain for which she was cultures may be performed from lesions, but 1975 and 1985. A report by a sub-committee of the prescribed famciclovir PO 500 mg TID for five they are less sensitive and more time-consuming British Thoracic Society Research Committee. Q J 3,18 Med. 1992;83:427-38. days, sulfamethoxazole/trimethoprim for three than direct immunoflourescence assay. days, gabapentin and amitriptyline. She was Differential diagnoses include , 8. Bullen CL, Liesegang TJ, McDonald TJ, DeRemee instructed to continue her home medications. , trigeminal neuralgia, erysipelas, RA. Ocular complications of Wegener’s granulomatosis. cellulitis, sarcoidosis, trigeminal trophic Ophthalmology. 1983;90:279–90. syndrome, cutaneous erythematosus, 9. Marinaki S, Neumann I, Kalsch AI, Grimminger Discussion , cutaneous anthrax, leshmaniasis, , P, Breedijk A, Birck R, et al. Abnormalities of CD4+ Wegener’s granulomatosis, also known as , and . T cell subpopulations in ANCA-associated vasculitis. granulomatosis with polyangiitis, represents Clin Exp Immunol. 2005;140:181–91. a systemic, anti-neutrophil, cytoplasmic- Treatment of HZO is important because 10. Christensson M, Pettersson E, Sundqvist KG, autoantibody vasculitis that affects small and approximately half of untreated patients suffer Christensson B. T cell activation in patients with medium vessels, particularly within the kidneys from ophthalmologic complications.19 Acyclovir, 6 ANCA-associated vasculitis: inefficient immune and within the respiratory system. Although valacyclovir, and famciclovir are FDA-approved suppression by therapy. Clin Nephrol. 2000;54:435-42. upper airway involvement, including pansinusitis for the treatment of herpes zoster.3 Patients with an active rash can be treated with acyclovir 800 11. Schlesier M, Kaspar T, Gutfleisch J, Wolff-Vorbeck and/or , is the most common initial G, Peter HH. Activated CD4+ and CD8+ T-cell presentation of disease, ocular involvement may mg five times daily for up to 10 days’ duration. subsets in Wegener’s granulomatosis. Rheumatol Int. represent up to 16% of initial presentations of Based on numerous studies, this regimen has 1995;14:213-9. the disease.6-8 Our patient’s chronic prednisone been shown to prevent the formation of new 12. Gutfleisch J, Baumert E, Wolff-Vorbeck G, lesions, decrease pain, reduce viral shedding, therapy, similar to regimens of many other Schlesier M, Strutz HJ, Peter HH. Increased expression patients with vasculitides, may have played a and decrease the incidence of certain late of CD25 and adhesion molecules on peripheral blood role in her immunosuppression and concurrent ocular complications including anterior uveitis lymphocytes of patients with Wegener’s granulomatosis 20-22 pansinusitis, which ultimately led to the and early-to-late keratitis. Patients with (WG) and ANCA positive vasculitides. Adv Exp Med recurrence of varicella-zoster virus manifesting immunosuppressive states should be treated with Biol. 1993;336:397-404. 23,24 as HZO. It has been identified that regardless intravenous acyclovir. Due to our patient’s 13. Ikeda M, Watanabe Y, Kitahara S, Inouye T. of disease status, patients with Wegener’s concurrent vasculitis and low CD4 counts, she Distinctive increases in HLA-DR+ and CD8+57+ granulomatosis have been reported to have was placed on , but was lymphocyte subsets in Wegener’s granulomatosis. Int decreased numbers of total, absolute, and relative discharged on oral valacyclovir, 1000 mg twice Arch Allergy Immunol. 1993;102:205-8. CD4+ T cell counts compared to controls. This daily dosing for one week, which has been shown 14. Iking-Konert C, Vogl T, Prior B, Wagner C, Sander can be attributed not only to immunosuppressive to prevent ocular complications such as keratitis O, Bleck E, et al. T lymphocytes in patients with 25 systemic medications but also to the relocation of and conjunctivitis. It has also been found to primary vasculitis: expansion of CD8+ T cells with the blood T cells to diseased organs.9-13 In contrast, decrease average time of zoster-related pain in propensity to activate polymorphonuclear neutrophils. CD8+ T cell counts tend to be comparatively comparison to acyclovir.26 Rheumatology. 2008;47:609-16. increased, with reduced CD4:CD8 ratios in all 15. Ikeda M, Tsuru S, Watanabe Y, Kitahara S, Inouye 10,11,14,15 Post-herpetic neuralgia is a significant spectrums of disease. complication of herpes zoster, particularly in T. Reduced CD4-CD8 T cell ratios in patients with Wegener’s granulomatosis. J Clin Lab Immunol. Herpes zoster ophthalmicus typically presents the elderly population. It occurs in up to 20% 1992;38:103–9. with a vesicular rash along the distribution of patients with herpes zoster within the same of the ophthalmic division of the trigeminal region of the infection and can last anywhere 16. Pavan-Langston D. Herpes zoster ophthalmicus. Neurology. 1995;45:S50–1. nerve and its branches, including the lacrimal, from a few months to a few years, at times nasociliary, and supraorbital nerves. Lesions being intractable to many medications.27 In the 17. Hamrah P, Cruzat A, Dastjerdi MH, Prüss H, management of post-herpetic neuralgia, targeting Zheng L, Shahatit BM, Bayhan HA, Dana R, Pavan- CHUN, LAL, POSNICK, ROS Page 25 Langston D. Unilateral Herpes Zoster Ophthalmicus Results in Bilateral Corneal Nerve Alteration. Ophthalmology. 2013;120(1):40-47. 18. Dahl H, Marcoccia J, Linde A. Antigen detection: the method of choice in comparison with virus isolation and serology for laboratory diagnosis of herpes zoster in human immunodeficiency virus-infected patient. J Clin Microbiol. 1997;35:345-349. 19. Cobo M, Foulks GN, Liesegang T, et al. Observations on the natural history of herpes zoster ophthalmicus. Curr Eye Res. 1987;6:195-199. 20. Huff JC, Bean B, Balfour HH, et al. Therapy of herpes zoster with oral acyclovir. Am J Med. 1988;85(2A):84- 88. 21. Morton P, Thomson AN. Oral acyclovir in the treatment of herpes zoster in general practice. N Z Med J. 1989;102:93-95. 22. McKendrick MW, McGill JI, White JE, Wood MJ. Oral acyclovir in acute herpes zoster. Br Med J. 1986;293:1529-1532. 23. Balfour HH Jr, Bean B, Laskin OL, Ambinder RF, Meyers JD, Wade JC, et al. Acyclovir halts progression of herpes zoster in immunocompromised patients. N Engl J Med. 1983;308:1448–53. 24. Balfour HH Jr. Varicella zoster virus infections in immunocompromised hosts. A review of the natural history and management. Am J Med. 1988;85:68-73. 25. Colin J, Prisant O, Cochener B, Lescale O, Rolland B, Hoang-Xuan T. Comparison of the efficacy and safety of valaciclovir and acyclovir for the treatment of herpes zoster ophthalmicus. Ophthalmology. 2000;107:1507- 11. 26. Beutner KR, Friedman DJ, Forszpaniak C, Andersen PL, Wood MJ. Valaciclovir compared with acyclovir for improved therapy for herpes zoster in immunocompetent adults. Antimicrob Agents Chemother. 1995;39:1546- 1553. 27. Massengill JS, Kittredge JL. Practical considerations in the pharmacological treatment of post-herpetic neuralgia for the primary care provider. 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Correspondence: Karan Lal, BS; [email protected]

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