RETINAL HEMORRHAGES AND INTERMEDIATE UVEITIS IN A PATIENT WITH DRUG REACTION WITH EOSINOPHILIA AND SYSTEMIC SYMPTOMS SYNDROME: A CASE REPORT Betsy Colon, MD,* Juan M. Horta, MD,* Stella Casillas, MD,* Maria Bertoli, MD,† Carmen Gonzalez-Keelan, MD,† Armando L. Oliver, MD*

Purpose: To report a case of drug reaction (or rash) with eosinophilia and systemic symptoms syndrome in association with intraretinal hemorrhages and intermediate uveitis. Methods: Single case report. Results: A 22-year-old Hispanic woman developed a facial rash and blurry vision after the use of oral trimethoprim–sulfamethoxazole for a urinary tract infection. Fundus examination revealed bilateral +2 vitritis and intraretinal hemorrhages in all four quadrants. An oral mucosal biopsy revealed V-shaped coagulative necrosis, intraepithelial and superficial acute and lymphoplasmacytic inflammation, consistent with drug hypersensitivity reaction. Conclusion: Drug reaction (or rash) with eosinophilia and systemic symptoms syndrome can present as cutaneous rash, mucosal lesions, eosinophilia, intermediate uveitis, and intraretinal hemorrhages. In such cases, vitreoretinal manifestations may be considered as diagnostic criteria instead visceral involvement. RETINAL CASES & BRIEF REPORTS 8:150–152, 2014

diphenhydramine and the trimethoprim–sulfamethoxazole was discontinued. The patient was discharged home on oral ciprofloxacin for her urinary tract infection. The swelling improved, but 4 days later, she noticed crusted lesions on her eyelids and lips. Her vision had not improved. She returned to the local hospital where she was administered an additional course of intravenous diphenhydramine and discharged home with recommendations for an ophthalmology evaluation. One week after the development of symptoms, the patient presented to our institution for an ophthalmology evaluation. She had an uncorrected visual acuity of 20/25 and an intraocular pressure measured by applanation tonometry of 12 mmHg in both eyes. The external eye examination revealed brown papules on both superior eyelids. The palpebral and bulbar conjunctiva did not demonstrate lesions or ulcerations. The cornea and lenses were clear. Pupils were equally round and reactive to light without any relative afferent papillary defect. The anterior chamber had no evidence acute or chronic inflammation. The dilated fundus examination revealed +2 vitritis in both eyes and scattered intraretinal hemorrhages in all four quadrants (Figure 1). The optic nerves had well-defined borders, no paleness, and with a symmetric cup-to-disk ratio of 0.3. No evidence of intraretinal cystic edema was noted by physical examination nor detected by macular

From the Departments of *Ophthalmology, and †Pathology, University of Puerto Rico School of Medicine, San Juan, Puerto Rico.

Case Report A 22-year-old Hispanic woman presented to the emergency room with a blurry vision, a facial rash, and general malaise of 1 week of evolution. She reported the use of oral trimethoprim– sulfamethoxazole for the treatment of a urinary tract infection. On the day she began the medication, she developed swelling of her eyelids and lips followed by a blurry vision, photophobia, ocular pruritus, and redness. She denied transient visual loss, floaters, or photopsias. The day after the development of the symptoms, the patient went to a local hospital where she was treated with intravenous None of the authors have any financial/conflicting interests to disclose. Reprint requests: Armando L. Oliver, MD, Department of Ophthalmology, University of Puerto Rico, PO BOX 365067, San Juan, Puerto Rico 00936; e-mail: [email protected]

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Fig. 1. Right (A) and left (B) color fundus photographs at presentation. Scattered intraretinal hemorrhages are observed in the midperiphery on both eyes.

optical coherence tomography. An intravenous fluorescein angiogram was performed. As expected, fluorescence blockage was noted from the intraretinal hemorrhage sites. No evidence of retinal ischemia or retinal vasculitis was noted on the angiogram. In addition to her ocular findings, she had crusted hyperpigmented plaques on the lips, and an ulcerative lesion on the lateral portion of tongue and cheeks (Figure 2). Serologic examination revealed 12.4 · 109/L leukocytosis, with elevated 6.1 · 109/L neutrophils and 1.5 · 109/L eosinophils. Antinuclear antibody test was positive at 1:40 titer, nucleolar pattern. B-HCG, HIV, RPR, HSV-1 and 2, FTA-Abs, and hepatic profile were negative. Urine analysis, blood chemistry, hepatic and pancreatic enzymes were unremarkable. Immunologic tests demonstrated normal C3, C4, and rheumatoid factor levels. A right cheek biopsy was performed by a maxillofacial surgeon. The biopsy specimen is shown in Figure 3. It revealed oral mucosa with V-shaped coagulative necrosis covered by parakeratosis and debris, along with intraepithelial and superficial acute and lymphoplasmacytic inflammation, consistent with an adverse drug reaction. One week after the initial evaluation, the skin lesions were resolving while the intermediate uveitis (+1 vitritis) along with the intraretinal hemorrhages was still present. The patient’s last evaluation was 2 months after her initial ophthalmology evaluation, the vitritis and the retinal hemorrhages had completely resolved on this examination.

Discussion Drug reaction (or rash) with eosinophilia and systemic symptoms (DRESS) syndrome is a rare form of

drug hypersensitivity, with a reported 10% mortality rate. Several medications have been reported to have the potential of inducing DRESS syndrome, these include: anticonvulsants, ACE inhibitors, betablockers, allopurinol, sulfonamides, and aspirin. The skin rash may last 5 days or more, is usually morbilliform, sometimes with bullous or purpuric lesions, and is often accompanied by fever, hypereosinophilia, hepatitis, and lymphadenopathy. The interval between the starting of drug therapy and the onset of cutaneous lesions ranges from 1 week to 8 weeks.1 The pathophysiology, as with other cutaneous hypersensitivity reactions, remains unclear. The condition may be multifactorial, with possible etiologies including genetic background (family members with a history of DRESS syndrome and black individuals), altered drug metabolism (slow acetylation), oxidizing stress (sunburn and radiotherapy), and viral infection. There is increasing data that suggests that the DRESS syndrome may be related to viral reactivation especially HHV-6 virus.2,3 The diagnostic criteria for DRESS syndrome are the following: 1) Cutaneous manifestations; 2) Eosinophilia or the presence of atypical lymphocytes; and 3) The involvement of at least one additional system: enlarged lymph nodes of at least 2 cm in diameter, hepatitis, interstitial nephropathy, interstitial lung disease, or

Fig. 2. Crusted hyperpigmented plaques on the lips (A), in addition to cheek (B) and tongue (C) ulceration as noted on the day of the initial ophthalmic evaluation.

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the improvement of the ophthalmic and systemic manifestations. Conclusion

Fig. 3. Micrograph of oral mucosa biopsy specimen. Hematoxylin and eosin stain. V-shaped coagulative necrosis, intraepithelial and superficial acute and lymphoplasmacytic inflammation are present.

myocardial involvement.1,4,5 Our patient did not present any signs of cardiac, respiratory, hepatic, or renal involvement; however, skin lesions, eosinophilia, and the ophthalmic manifestations of intraretinal hemorrhages and intermediate uveitis were present. The absence of a more significant systemic involvement in our patient may be attributed to immediate discontinuation of the inciting antibiotic treatment shortly after the initial development of the cutaneous lesions. In 2006, a group from Bordeaux, France reported the case of a 63-year-old woman who developed DRESS syndrome with bilateral ophthalmic manifestations that included decreased visual acuity, visual field defects, eyelids desquamations, conjunctival hyperemia, increased intraocular pressure, granulomatous keratic precipitates, cotton-wool spots, and optic nerve swelling.6 The symptoms commenced after the patient’s ingestion of the antiepileptic medication, lamotrigine. The patient also developed cardiac, renal, and respiratory manifestations in addition to HHV-6 positive immunoglobulin G serology. The patient was treated with systemic corticosteroids that resulted in

Our patient presented with DRESS syndrome as manifested by eosinophilia, skin and mucosal lesions, and vitreoretinal involvement. In such cases, uveal and retinal manifestations should be considered as a diagnostic criterion instead the visceral involvement, which may be present in DRESS syndrome. We suggest that the criteria for DRESS syndrome, which do not specifically include ophthalmic manifestations, should be revised to include patients with vitreous or retinal involvement. Key words: DRESS syndrome, intraretinal hemorrhages, intermediate uveitis, trimetoprim– sulfamethoxazole, drug hypersensitivity. References 1. Lobo I, Ferreira M, Velho G, et al. Erupcao a farmaco com eosinofilia e sintomas sistemicos (Sindrome DRESS). Acta Med Port 2008;21:367–372. 2. Shiohara T, Inao K, Kano Y. Drug-induced hypersensitivity syndrome (DIHS): a reaction induced by a complex interplay among herpesviruses and antiviral and antidrug immune responses. Allergol Int 2006;55:1–8. 3. Tohyama M, Hashimoto K, Yasukawa M, et al. Association of human herpes 6 reactivation with flaring and severity of drug induced hypersensitivity syndrome. Br J Dermatol 2007;157: 934–940. 4. Augusto JF, Sayegh J, Simon A, et al. A case of sulphasalazineinduced DRESS syndrome with delayed acute interstitial nephritis. Nephrol Dial Transplant 2009;24:2940–2942. 5. Bocquet H, Bagot M, Roujeau JC. Drug-induced pseudolymphoma and drug hypersensitivity syndrome (Drug Rash with Eosinophilia and Systemic Symptoms: DRESS). Semin Cutan Med Surg 1996;15:250–257. 6. Schauer P, Salaun N, Bazin S, et al. DRESS syndrome with bilateral panuveitis, elevated intraocular pressure, and HHV-6 reactivation: a case report [in French]. J Fr Ophtalmol 2006;29:659–664.

Retinal hemorrhages and intermediate uveitis in a patient with drug reaction with eosinophilia and systemic symptoms syndrome: a case report.

To report a case of drug reaction (or rash) with eosinophilia and systemic symptoms syndrome in association with intraretinal hemorrhages and intermed...
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