Herpes Zoster Ophthalmicus in a Patient with Wegener’s Granulomatosis Sunny Chun, DO,* Karan Lal, BS,** David Posnick, DO,* Adriana Ros, DO*** *Dermatology 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 erythema 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 “shingles,” 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 asthma, 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 biopsy of the patient’s thigh, for which she then heal without scarring. was placed on chronic prednisone 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 diabetes 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 immunodeficiency 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 tongue. Coalescing methylprednisolone 20 mg (BID), terbinafine for yellow exophytic verrucous plaques were her presumed tinea pedis, nystatin mouth wash present on the soles of her feet. Examination of for oral candidiasis, and pertinent antibiotics for extremities revealed multiple, bilateral, atrophic her periorbital cellulitis. 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 immunosuppression 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 herpes simplex, 8. Bullen CL, Liesegang TJ, McDonald TJ, DeRemee instructed to continue her home medications. vasculitis, trigeminal neuralgia, erysipelas, RA. Ocular complications of Wegener’s granulomatosis. cellulitis, sarcoidosis, trigeminal trophic Ophthalmology. 1983;90:279–90. syndrome, cutaneous lupus erythematosus, 9. Marinaki S, Neumann I, Kalsch AI, Grimminger Discussion syphilis, cutaneous anthrax, leshmaniasis, leprosy, P, Breedijk A, Birck R, et al. Abnormalities of CD4+ Wegener’s granulomatosis, also known as zygomycosis, and sporotrichosis. 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