From Cole Eye Institute, Cleveland Clinic, Cleveland, Ohio.
Supported in part by Research to Prevent Blindness, Inc., New York, New York.
The authors have no financial or proprietary interest in the materials presented herein.
Address correspondence to Julian D. Perry, MD, Cole Eye Institute, Cleveland Clinic, 9500 Euclid Avenue, i-32, Cleveland, OH 44195.
Darier’s disease (also known as Darier–White disease and keratosis follicularis) represents an uncommon autosomal dominant disorder of epithelial desmosomes characterized by dyskeratosis, acantholysis, and hyperkeratosis. On a macroscopic level, patients present with pruritic hyperkeratotic papules that coalesce to form verrucous plaques in seborrheic areas of the skin. Keratotic lesions often manifest secondary bacterial overgrowth that may cause skin infections1 and potentially render inadequate the efficacy of standard “sterile” surgical preparations.
A 58-year-old man presented 3 days following left-sided cataract extraction complaining of progressively worsening pain, redness, and decreased vision in the left eye for 2 days. At the time of surgery, the patient was prepared with 10% povidone iodine swabs and 5% povidone iodine flush and draped in the usual sterile fashion. The patient suffered no intraoperative complications and received an Alcon SA60AT intraocular lens (Alcon Laboratories, Fort Worth, TX) within the capsular bag. Blepharitis related to the patient’s history of Darier’s disease was noted preoperatively, but no specific preoperative or intraoperative treatment was instituted. The right eye underwent uncomplicated cataract extraction 17 days previously using the same lens. The patient reported compliance with the postoperative regimen, which included topical neomycin/polymyxin/dexamethasone eye drops four times daily.
Medical history included Darier’s disease, type 2 diabetes mellitus, hemodialysis-dependent renal disease, hypertension, herpes zoster dermatitis, and major depression. The patient also suffered from recurrent cellulitis secondary to the Darier’s disease, with cutaneous cultures on different occasions growing Pseudomonas aeruginosa, methicillin-resistant Staphylococcus aureus, Proteus mirabilis, and Escherichia coli.
Visual acuity was light perception in the left eye. The left eye showed conjunctival chemosis and injection, corneal stromal edema, 4+ cell and fibrin in the anterior chamber, and a 10% hypopyon. Anterior chamber reaction obscured the view of the left posterior segment. Exophthalmometry revealed no proptosis and extraocular motility was normal. B-scan ultrasonography of the left eye showed vitreous opacities and an attached retina. Cutaneous examination revealed thick hyperkeratotic plaques on a background of diffuse erythema over the back, elbows, anterior lower legs, buttocks, pinnae, eyelids, and eyebrows (Figure).
Figure. External Photograph After Uncomplicated Right-Sided Cataract Extraction Demonstrating Diffuse Hyperkeratotic Plaques Involving the Patient’s Eyelids and Eyebrows.
In concordance with the Endophthalmitis Vitrectomy Study, the patient underwent emergent vitrectomy, vitreous biopsy, and intravitreal vancomycin and ceftazidime.2 Vitreous cultures grew P. aeruginosa susceptible to ceftazidime and ciprofloxacin. The patient received 500 mg of ciprofloxacin orally two times daily and hourly topical fortified vancomycin and ceftazidime. On daily follow-up, visual acuity decreased to no light perception with worsening pain and no improvement in intraocular findings. The patient underwent evisceration of the left eye with placement of a 20-mm polymethylmethacrylate implant 19 days following cataract extraction surgery. The patient healed well after evisceration, with no sign of orbital infection or implant extrusion after 3 months of follow-up.
Darier’s disease, an autosomal dominant disorder that manifests primarily as abnormal keratinization and acantholysis, affects an estimated 1 in 30,000 to 1 in 100,000 individuals.3 A mutation in the ATP2A2 gene produces a defective gene product (SERCA2, sarco/endoplasmic reticulum calcium adenosine triphosphatase type 2 isoform pump), leading impaired desmosome assembly and poor cellular adhesion to cause disease.4 Patients typically present in the second or third decade of life with yellow-brown, mildly greasy papules concentrated in seborrheic areas of the body (scalp, forehead, nasolabial folds, retroauricular folds, front and back of the central trunk, and groin). The lesions exhibit hyperkeratosis and often grow in a vegetative, malodorous fashion. The course exacerbates and remits, and treatment aims primarily to control pruritus using topical emollients, retinoids and steroids, and oral retinoids for severe disease.3 Cutaneous infection with S. aureus and herpes simplex and zoster viruses occurs with increased incidence over the general population, although cell-mediated immunity usually functions normally in these patients.5
Postoperative endophthalmitis following cataract extraction with intraocular lens implantation occurs in 0.2% to 0.367% of cases.6 Most pathogens causing endophthalmitis originate from the patients’ own periocular flora and enter the eye during surgery.7 Preoperative sterile preparation techniques focus on minimizing operative site contamination from native bacterial flora. In the Endophthalmitis Vitrectomy Study, 70% of culture-confirmed endophthalmitis cases resulted from gram-positive coagulase-negative staphylococcus and micrococci; other isolates included S. aureus (9.9%), Streptococcus species (9%), Enterococcus species (2.2%), and miscellaneous gram-positive organisms (3.1%). Gram-negative species occurred least frequently, in only 5.9% of cases.2
Patients with Darier’s disease manifest secondary overgrowth of bacteria and fungi that colonize the keratotic debris.1 Standard preoperative sterile preparation techniques may inadequately penetrate these cavernous vegetative plaques, increasing the risk for postoperative endophthalmitis. To our knowledge, two cases of endophthalmitis in patients with Darier’s disease have been reported.8,9 Both cases involved Staphylococcus species and both improved with intravitreal and topical antibiotics. Our case of endophthalmitis in the setting of Darier’s disease involved an atypical and more virulent species, ultimately resulting in loss of the eye.
Several considerations may help to decrease the risk of postoperative endophthalmitis in patients with Darier’s disease undergoing cataract extraction or other intraocular surgery. Prior to surgery, the surgeon should consider discussing with the patient the theoretically increased risk of postoperative infection. Preoperative eyelid scrubs in addition to topical and systemic antibiotics may minimize periocular flora. The surgeon may consider preoperative periocular skin cultures to guide appropriate perioperative prophylactic antibiotic therapy. Vegetative plaques that may increase bacterial load can be addressed preoperatively through dermabrasion, photodynamic therapy, or laser vaporization. Skin preparation at surgery can address hyperkeratotic plaques with maximal penetration of antiseptic solution. After skin preparation, sterile adhesive drapes can isolate keratotic plaques from the sterile field. Finally, a high level of suspicion for postoperative endophthalmitis in the setting of Darier’s disease may expedite early endophthalmitis treatment to improve outcome.
This case of postoperative endophthalmitis with an atypical and virulent organism in the setting of Darier’s disease highlights the increased risk of infection in these patients and offers insights into prevention of this complication.
- Burge SM, Wilkinson JD. Darier-White disease: a review of the clinical features in 163 patients. J Am Acad Dermatol. 1992;27:40–50. doi:10.1016/0190-9622(92)70154-8 [CrossRef]
- Han DP, Wisniewski SR, Wilson LA, et al. Spectrum and susceptibilities of microbiologic isolates in the Endophthalmitis Vitrectomy Study. Am J Ophthalmol. 1996;122:1–17.
- Cooper SM, Burge SM. Darier’s disease: epidemiology, pathophysiology, and management. Am J Clin Dermatol. 2003;4:97–105. doi:10.2165/00128071-200304020-00003 [CrossRef]
- Ikeda S, Mayuzumi N, Shigihara T, Epstein EH Jr, Goldsmith LA, Ogawa H. Mutations in ATP2A2 in patients with Darier’s disease. J Invest Dermatol. 2003;121:475–477. doi:10.1046/j.1523-1747.2003.12400.x [CrossRef]
- Sehgal VN, Srivastava G. Darier’s (Darier-White) disease/keratosis follicularis. Int J Dermatol. 2005;44:184–192. doi:10.1111/j.1365-4632.2004.02408.x [CrossRef]
- Lemley CA, Han DP. Endophthalmitis: a review of current evaluation and management. Retina. 2007;27:662–680. doi:10.1097/IAE.0b013e3180323f96 [CrossRef]
- Speaker MG, Milch FA, Shah MK, Eisner W, Kreiswirth BN. Role of external bacterial flora in the pathogenesis of acute postoperative endophthalmitis. Ophthalmology. 1991;98:639–649.
- Carlsson AM, Barrett GD. Postoperative endophthalmitis in a patient with Darier-White disease. Can J Ophthalmol. 2007;42:134–135.
- Macsai MS, Agarwal S. Staphylococcal endophthalmitis following cataract extraction in a patient with Darier’s disease. Cornea. 1998;17:335–337. doi:10.1097/00003226-199805000-00012 [CrossRef]