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Discoid Lupus Erythematosus Masquerading as Chronic Blepharoconjunctivitis
Discoid Lupus Erythematosus Masquerading as Chronic Blepharoconjunctivitis Nisha Acharya, MS, MD, Roberto Pineda II, MD, Harvey S. Uy, MD, C. Stephen Foster, MD Purpose: To recognize discoid lupus erythematosus (DLE) as a treatable cause of chronic blepharoconjunctivitis. Design: Retrospective observational case series. Participants: Records of 5 patients with biopsy-proven DLE were reviewed. Methods: Clinical and pathology records were examined. Main Outcome Measures: Patients’ clinical and histopathological characteristics and response to treatment were assessed. Results: Clinical features included meibomian gland dysfunction, blepharitis, chalazia, trichiasis, madarosis, conjunctivitis, chronic eyelid edema, and eyelid plaques. Histopathology showed hyperkeratotic epithelium, degeneration of the basal cell layer, and a perivascular lymphocytic infiltrate. There was delayed diagnosis in all cases, ranging from 4 months to 25 years. All of the patients responded to systemic hydroxychloroquine therapy. Conclusions: Heightened awareness of eyelid DLE may lead to earlier detection and specific therapy for this chronic disorder. Ophthalmology 2005;112:e19 – e23 © 2005 by the American Academy of Ophthalmology.
Lupus erythematosus is a chronic, inflammatory, autoimmune condition that has a plethora of clinical presentations. The worldwide prevalence of systemic lupus erythematosus (SLE) ranges from 17 to 48 cases per 100 000, with some type of skin involvement occuring in 70% to 85% of these patients.1,2 Discoid lupus erythematosus (DLE) is the most common form of chronic cutaneous lupus erythematosus, usually affecting women between the ages of 20 and 40.1–5 Generally considered to be a benign autoimmune condition with chronic cutaneous and mucosal manifestations, it frequently involves the face, ears, and scalp. Eyelid involvement is more unusual and, when reported, is thought to have a predilection for the external and inferior portions of the eyelid.4 –10 Discoid lupus erythematosus is thought to be at one end of the spectrum from SLE, with 5% of DLE patients later progressing to SLE.1,2,4,5 The relationship between these 2 disorders is still being elucidated, but both are considered to be the result of immune dysregulation. Because DLE may have limited or absent additional manifestations, its appearance as chronic blepharoconjunctivitis may be confusing to the clinician, often leaving the physician uncertain as to the most appropriate therapy after the usual medical management and lid hygiene fails to resolve the problem. We report a series of patients with eyelid involvement
from DLE whose clinical appearance mimicked that of chronic blepharoconjunctivitis. For most patients, the diagnosis remained obscure for years or even decades. Heightened physician awareness of this treatable disorder will allow more rapid institution of therapy, hopefully preventing permanent scarring, lid deformity, and trichiasis.
Cases Patient 1 A 33-year-old Caucasian man presented complaining of irritation of his left lower lid for 8 months. He had been diagnosed with discoid lupus 6 weeks before by biopsy of a facial lesion and had just started hydroxycholoroquine (200 mg orally twice a day). The biopsy showed hyperkeratosis of the epithelium, thickened basement membrane, basal cell vacuolation, and dermal inflammation that was interpreted as being most consistent with DLE. The left lower lid was thickened and erythematous, with scaling (Fig 1). In addition, there was mild conjunctival injection and meibomitis. The remainder of the examination was unremarkable. Antinuclear antibody was negative, and the patient did not have any other signs of systemic disease. Within 6 weeks of starting hydroxychloroquine, the lid inflammation and conjunctivitis improved and remained stable throughout the 6-month follow-up period.
Patient 2 Originally received: October 20, 2004. Accepted: January 3, 2005. Manuscript no. 2004-206. From Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts. Poster presented at: American Academy of Ophthalmology meeting, October, 1996; Chicago, Illinois. Reprint requests to Dr Roberto Pineda, Massachusetts Eye and Ear Infirmary, Department of Ophthalmology, Corneal and Refractive Surgery Services, 243 Charles Street, Boston, MA 02114. © 2005 by the American Academy of Ophthalmology Published by Elsevier Inc.
A 58-year-old Caucasian woman presented with a 15-year history of eyelid redness and thickening, greater on the right side. The lid margins of the right eye were irregular, with madarosis of the lateral lower lid. In addition, there were meibomian gland dysfunction, blepharitis, and conjunctival injection superotemporally (Fig 2A, B). Eversion of the left lower eyelid showed conjunctival hypertrophy and inflammation (Fig 2C). She had not been responsive to treatment for rosacea (tetracycline and steroids) or allergy (antihistamines and cromolyn). Three biopsies of the right lower ISSN 1549-4713/05/$–see front matter doi:10.1016/j.ophtha.2005.01.035
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Ophthalmology Volume 112, Number 5, May 2005 Patient 3 A 29-year-old Caucasian woman presented with 1.5 years of redness and swelling of the right lower lid. On examination, she had erythema and edema of the right lower lid, loss of medial eyelashes, and meibomitis, along with crusting of the lid margins (Fig 3). She had been treated with steroids and antibiotic topical medications without any improvement. Antinuclear antibody was negative, and she did not have any signs of systemic disease. A full thickness biopsy of the right lower lid was performed and showed a lymphocytic infiltrate around the lash follicles and degenerative changes of the dermis, diagnostic of discoid lupus. A trial of hydroxychloroquine (200 mg twice a day) was initiated, but was stopped after 12 days due to a drug eruption. The right lower lid erythema improved after 4 days of hydroxychloroquine therapy, but the patient continued to have lupus dermatitis behind her right ear and on her scalp.
Patient 4 A 54-year-old Caucasian woman presented with 25 years of chronic inflammation and scarring of the eyelids and philtrum (Fig 4). Two previous right lower lid biopsies were nondiagnostic. She had been treated with doxycycline without improvement. On examination, there was microulceration of the right lower lid and conjunctivalization of the right lower lid margin. In addition, there was madarosis of bilateral lower lids. Antinuclear antibody was negative, and there were no systemic signs of disease other than the facial scarring. Biopsy of the right lower lid showed epithelial atrophy, focal dyskeratosis, and thickened basement membrane, with areas of focal destruction. In addition, there was lymphocytic perivascular inflammation consistent with discoid lupus. Immunofluorescence was notable for dense clusters of immunoglobulin G–positive cells in the superficial dermis and at the dermoepidermal junction, classic symptoms of DLE. The patient was started on hydroxychloroquine (200 mg twice a day), with marked improvement in 2 months. Figure 1. A, Mild conjunctivitis and left lower lid erythema. B, Eversion of left lower lid reveals tarsal conjunctival injection, meibomian gland dysfunction, and mild blepharitis.
lid had been performed previously, which were initially interpreted as benign chronic inflammation of the dermis. Review of these biopsy slides showed hyperkeratosis of the epithelium, thickened basement membrane, basal cell vacuolation, telangiectasias of the substantia propria, lichenoid infiltrates, and dermal inflammation (Fig 2D, E). These were interpreted as consistent with discoid lupus with hyperkeratosis. The patient did not have signs of systemic disease, and the antinuclear antibody was negative. Hydroxychloroquine (200 mg orally twice a day) was started, and over the next 6 months, the blepharoconjunctivitis markedly improved (Fig 2F). The patient was tapered off hydroxychloroquine after 2 years, with no recurrences in the 1-year follow-up period.
Patient 5 A 41-year-old Caucasian woman presented with a 2-year history of eyelid redness and conjunctival injection, greater on the right side (Fig 5). She had been treated for blepharitis with warm compresses, doxycycline, and steroid creams without improvement. She had a forehead skin lesion that had been biopsied recently and showed granular deposition of immunoglobulin M, immunoglobulin G, immunoglobulin A, and C3 along the dermoepidermal junction, consistent with DLE. Antinuclear antibody was negative. On examination, there were severe meibomian gland dysfunction, lid thickening, erythema, multiple chalazia, and conjunctival injection with lower tarsal conjunctival follicles. In addition, there were trichiasis and 2 small plaques on the right lower lid. Hydroxychloroquine (200 mg twice a day) was started, and within 2 weeks, there was markedly less eyelid inflammation. The facial lesions did not improve to the same extent as the eyelids.
™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™3 Figure 2. A, Bilateral eyelid erythema, scaling, blepharitis, and meibomian gland dysfunction. B, Pretreatment: marked erythema and scaling at the outer lid margins of the right eye and hypertrophic lesion on the right upper lid. C, Eversion of left lower eyelid shows conjunctival hypertrophy and inflammation. D, Biopsy of right lower lid showing hyperkeratosis and dermal mononuclear inflammation (stain, hematoxylin– eosin; original magnification, ⫻40). E, Biopsy of right lower lid shows basal cell vacuolation and basement membrane thickening (stain, hematoxylin– eosin; original magnification, ⫻100). F, Marked diminution of right eyelid redness and thickening 1 month after hydroxychloroquine therapy.
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Acharya et al 䡠 Discoid Lupus Erythematosus Masquerading as Blepharoconjunctivitis
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Ophthalmology Volume 112, Number 5, May 2005
Discussion Discoid lupus erythematosus is a chronic autoimmune disorder of the skin, characterized by raised erythematous lesions occurring most frequently in sun-exposed areas. Discoid lupus erythematosus is responsible for 50% to 85% of chronic cutaneous lupus erythematosus cases, and chronic cutaneous lupus erythematosus is thought to be 2 to 3 times more prevalent than SLE, which has a reported prevalence of 17 to 48 cases per 100 000.1,2 In DLE, females are twice as likely to be affected as males. Most patients are between 20 and 40 years old, with a mean age of 38. Discoid lupus erythematosus may be slightly more common in African Americans than in Caucasians or Asians.1,2,4 The localized form of DLE is characterized by involvement of only the head and/or scalp and accounts for 70% of DLE patients. The generalized form has more extensive involvement and accounts for the remaining 30% of cases. Facial involvement is present in 74% of DLE patients, with the scalp and ear being the most commonly involved sites.3 Twenty percent of patients with generalized DLE and 5% with localized DLE proceed to develop SLE.1–3 Clinically, a cutaneous discoid lesion begins as an erythematous patch that grows into a plaque with follicular plugging and scaling. Lesions typically follow a progression of erythema, hyperkeratosis, and atrophy, with pigmentary changes, especially in darker-skinned people.1–5 Involved skin may be asymptomatic or pruritic. Ocular manifestations of DLE reported in the literature include periorbital edema, blepharitis, madarosis, lid scarring, entropion and ectropion, trichiasis, panniculitis, conjunctivitis, hypertrophic/verrucous lesions, and stromal keratitis.4 – 6,8 –18 Although DLE lesions elsewhere have a distinctive appearance, eyelid findings may be more nonspecific. Conjunctivitis, meibomitis, blepharitis, and chronic eyelid erythema were the most common signs in our cases, and all of our patients had some findings bilaterally, although in some cases asymmetrically. The majority of patients in our study were women (80%) whose initial symptoms started between the ages of 25 and
Figure 3. Chronic right lower lid erythema, meibomian gland dysfunction, and madarosis.
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Figure 4. A, Bilateral eyelid thickening, erythema, and lower lid madarosis. B, Discoid lupus erythematosus upper lip scarring.
40. The majority of DLE eye findings were nonspecific and could be seen in any case of blepharoconjunctivitis. This may be why there was delayed diagnosis in all cases, ranging from 4 months to 25 years. The presence of other cutaneous lesions or an eyelid plaque may aid in an earlier diagnosis. In addition, all patients in our study failed standard treatment for blepharitis, such as lid hygiene, doxycycline, and steroid creams. This prompted consideration of other diagnoses, such as DLE. The differential diagnosis of DLE eyelid involvement includes rosacea blepharoconjunctivitis, seborrheic blepharitis, chronic staphylococcal blepharitis, contact dermatitis, eczema, psoriasis, sebaceous cell carcinoma, lid-involving sarcoidosis, lichen planus, lichenoid drug eruption, and tinea faciei.2,4,7,15,18 The exact pathogenesis of DLE is not known, but a genetic predisposition is suspected.2 There is an increased prevalence among first-degree relatives, as well as an association with HLA-B8. Complement components C1q, C3, and C5 deficiencies have also been associated with DLE. It is thought that perhaps deficiencies in these complement components may cause inability to clear immune complexes and apoptotic cells, causing increased immunologic stimulation.1 Different lymphocyte profiles are seen among the subtypes of cutaneous lupus erythematosus, suggesting that various immune mechanisms are present. Cytokine profiles of DLE lesions have shown that DLE is associated with type 1 cytokines characterized by expression of interleukin 2 and interferon ␥. The most populous inflammatory cell in DLE has been found to be CD45RA⫹.1 In addition, 64% of DLE patients have a positive photoprovocation test when exposed to ultraviolet A light and ultraviolet B light. It has been suggested that a heat shock protein is induced in the keratinocyte after ultraviolet light exposure or skin trauma, and this protein may act as a target for ␥␦ T-cell–mediated
Acharya et al 䡠 Discoid Lupus Erythematosus Masquerading as Blepharoconjunctivitis droxychloroquine therapy, and early treatment can prevent lid cicatrization, trichiasis, and permanent lash loss. Lastly, patients with DLE require a complete medical evaluation by their primary care physician or rheumatologist, as a small percentage of these patients will progress to SLE.
References Figure 5. Right-eye nasal eyelid plaque and chronic eyelid erythema.
epidermal cell cytotoxicity.2,3 Other proposed mechanisms for DLE lesions include viral infection, hormonal influences, and drug reactions.1,2,19 There are likely multiple mechanisms involved in the induction of DLE, and our understanding of this disease will continue to evolve. Diagnosis is aided by serologic and histopathologic testing. Only 20% of DLE patients have a positive antinuclear antibody when tested with human substrates, and ⬍5% have anti–Ro(ss-A), anti–native DNA or anti-Sm antibodies.2 Immunopathology is more useful to make a diagnosis. All of our cases were biopsy proven and demonstrated typical microscopic features of DLE: hyperkeratosis with lymphocytic infiltration of the dermoepidermal junction and telangiectasis of the substantia propria. The 2 cases that had immunofluorescence testing demonstrated immunoglobulin and complement deposition at the dermoepidermal interface. Ninety percent of patients with DLE have a positive direct immunofluorescence test when affected skin is biopsied. Although nonlesional biopsies are positive for immunoreactants in the basement membrane zone in patients with SLE (positive lupus band test), only lesional biopsies are positive in DLE.1–5,8,14 The goal of therapy is to prevent the progression of existing lesions, improve patient appearance, and prevent further lesions. Sunglasses and sunscreens are recommended because ultraviolet exposure may exacerbate this disorder. The use of topical and intralesional corticosteroids may sometimes be helpful. Antimalarials are the mainstay of therapy. Hydroxychloroquine (200 – 400 mg orally per day) may take up to 6 to 8 weeks for a response and require monitoring every 6 months by ophthalmoscopy and visual fields to screen for medication-related maculopathy.1–3,5 All patients in our study responded to systemic hydroxychloroquine therapy (200 – 400 mg/day), some dramatically when treated early (patients 1, 3, and 5). Lastly, if antimalarials cannot be used or if the lesion is resistant, immunosuppressives can be considered. Agents that have been reported to be successfully used for DLE include azathioprine, dapsone, methotrexate, cyclophosphamide, thalidomide, retinoids, and interferon alpha-2.1–3,5,11 Discoid lupus erythematosus can be difficult to diagnose because of its ability to masquerade as chronic blepharoconjunctivitis. When chronic blepharoconjunctivitis is unresponsive to conventional therapy, careful history and reexamination should be performed with consideration of DLE as a diagnosis. Biopsy with appropriate histopathological and immunohistochemical studies is also helpful to establish a diagnosis. Discoid lupus erythematosus lid involvement can be effectively treated with systemic hy-
1. Patel P, Werth V. Cutaneous lupus erythematosus: a review. Dermatol Clin 2002;20:373– 85, v. 2. Callen J. Lupus erythematosus, discoid. [Emedicine web site]. Available at: http://www.emedicine.com/derm/topic247.htm. Accessed August 1, 2004. 3. Fabbri P, Cardinali C, Giomi B, Caproni M. Cutaneous lupus erythematosus: diagnosis and management. Am J Clin Dermatol 2003;4:449 – 65. 4. Huey C, Jakobiec FA, Iwamoto T, et al. Discoid lupus erythematosus of the eyelids. Ophthalmology 1983;90: 1389 –98. 5. Foster CS. Systemic lupus erythematosus, discoid lupus erythematosus, and progressive systemic sclerosis. Int Ophthalmol Clin 1997;37:93–110. 6. Ziv R, Schewach-Millet M, Trau H. Discoid lupus erythematosus of the eyelids [letter]. J Am Acad Dermatol 1986;15: 112–3. 7. Donzis PB, Insler MS, Buntin DM, Gately LE. Discoid lupus erythematosus involving the eyelids. Am J Ophthalmol 1984; 98:32– 6. 8. Frith P, Burge SM, Millard PR, Wojnarowska F. External ocular findings in lupus erythematosus: a clinical and immunopathological study. Br J Ophthalmol 1990;74:163–7. 9. Gloor P, Kim M, McNiff JM, Wolfley D. Discoid lupus erythematosus presenting as asymmetric posterior blepharitis. Am J Ophthalmol 1997;124:707–9. 10. Uy HS, Pineda R II, Shore JW, et al. Hypertrophic discoid lupus erythematosus of the conjunctiva. Am J Ophthalmol 1999;127:604 –5. 11. Bettis VM, Vaughn RY, Guill MA. Erythematous plaques on the eyelids. Discoid lupus erythematosus (DLE). Arch Dermatol 1993;129:497, 500. 12. Tosti A, Tosti G, Giovannini A. Discoid lupus erythematosus solely involving the eyelids: report of three cases [letter]. J Am Acad Dermatol 1987;16:1259 – 60. 13. Kearns W, Wood W, Marchese A. Chronic cutaneous lupus involving the eye lid. Ann Ophthalmol 1982;14:1009 –10. 14. Selva D, Chen CS, James CL, Huilgol SC. Discoid lupus erythematosus presenting as madarosis. Am J Ophthalmol 2003;136:545– 6. 15. Foster RE, Lowder CY, Meisler DM, et al. An unusual ocular manifestation of discoid lupus erythematosus. Cleve Clin J Med 1994;61:232–7. 16. Thorne JE, Jabs DA, Nikolskaia O, et al. Discoid lupus erythematosus and cicatrizing conjunctivitis: clinicopathologic study of two cases. Ocul Immunol Inflamm 2002;10:287–92. 17. Panse I, Cordoliani F, Rybojad M, et al. Discoid lupus erythematosus involving the eyelids: 4 cases [in French]. Ann Dermatol Venereol 2004;131:58 – 60. 18. Meiusi R, Cameron JD, Holland EJ, Summers CG. Discoid lupus erythematosus of the eyelid complicated by wound dehiscence [letter]. Am J Ophthalmol 1991;111:108 –9. 19. Prokop J, Jagodzinski PP. Identification of retroviral DNA sequences in serum of cutaneous forms of lupus erythematosus patients. Eur J Dermatol 2003:13:354 – 8.
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Lupus erythematosus is a chronic, inflammatory, autoimmune condition that has a plethora of clinical presentations. The worldwide prevalence of systemic lupus erythematosus (SLE) ranges from 17 to 48 cases per 100 000, with some type of skin involvement occuring in 70% to 85% of these patients.1,2 Discoid lupus erythematosus (DLE) is the most common form of chronic cutaneous lupus erythematosus, usually affecting women between the ages of 20 and 40.1–5 Generally considered to be a benign autoimmune condition with chronic cutaneous and mucosal manifestations, it frequently involves the face, ears, and scalp. Eyelid involvement is more unusual and, when reported, is thought to have a predilection for the external and inferior portions of the eyelid.4 –10 Discoid lupus erythematosus is thought to be at one end of the spectrum from SLE, with 5% of DLE patients later progressing to SLE.1,2,4,5 The relationship between these 2 disorders is still being elucidated, but both are considered to be the result of immune dysregulation. Because DLE may have limited or absent additional manifestations, its appearance as chronic blepharoconjunctivitis may be confusing to the clinician, often leaving the physician uncertain as to the most appropriate therapy after the usual medical management and lid hygiene fails to resolve the problem. We report a series of patients with eyelid involvement
from DLE whose clinical appearance mimicked that of chronic blepharoconjunctivitis. For most patients, the diagnosis remained obscure for years or even decades. Heightened physician awareness of this treatable disorder will allow more rapid institution of therapy, hopefully preventing permanent scarring, lid deformity, and trichiasis.
Cases Patient 1 A 33-year-old Caucasian man presented complaining of irritation of his left lower lid for 8 months. He had been diagnosed with discoid lupus 6 weeks before by biopsy of a facial lesion and had just started hydroxycholoroquine (200 mg orally twice a day). The biopsy showed hyperkeratosis of the epithelium, thickened basement membrane, basal cell vacuolation, and dermal inflammation that was interpreted as being most consistent with DLE. The left lower lid was thickened and erythematous, with scaling (Fig 1). In addition, there was mild conjunctival injection and meibomitis. The remainder of the examination was unremarkable. Antinuclear antibody was negative, and the patient did not have any other signs of systemic disease. Within 6 weeks of starting hydroxychloroquine, the lid inflammation and conjunctivitis improved and remained stable throughout the 6-month follow-up period.
Patient 2 Originally received: October 20, 2004. Accepted: January 3, 2005. Manuscript no. 2004-206. From Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts. Poster presented at: American Academy of Ophthalmology meeting, October, 1996; Chicago, Illinois. Reprint requests to Dr Roberto Pineda, Massachusetts Eye and Ear Infirmary, Department of Ophthalmology, Corneal and Refractive Surgery Services, 243 Charles Street, Boston, MA 02114. © 2005 by the American Academy of Ophthalmology Published by Elsevier Inc.
A 58-year-old Caucasian woman presented with a 15-year history of eyelid redness and thickening, greater on the right side. The lid margins of the right eye were irregular, with madarosis of the lateral lower lid. In addition, there were meibomian gland dysfunction, blepharitis, and conjunctival injection superotemporally (Fig 2A, B). Eversion of the left lower eyelid showed conjunctival hypertrophy and inflammation (Fig 2C). She had not been responsive to treatment for rosacea (tetracycline and steroids) or allergy (antihistamines and cromolyn). Three biopsies of the right lower ISSN 1549-4713/05/$–see front matter doi:10.1016/j.ophtha.2005.01.035
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Ophthalmology Volume 112, Number 5, May 2005 Patient 3 A 29-year-old Caucasian woman presented with 1.5 years of redness and swelling of the right lower lid. On examination, she had erythema and edema of the right lower lid, loss of medial eyelashes, and meibomitis, along with crusting of the lid margins (Fig 3). She had been treated with steroids and antibiotic topical medications without any improvement. Antinuclear antibody was negative, and she did not have any signs of systemic disease. A full thickness biopsy of the right lower lid was performed and showed a lymphocytic infiltrate around the lash follicles and degenerative changes of the dermis, diagnostic of discoid lupus. A trial of hydroxychloroquine (200 mg twice a day) was initiated, but was stopped after 12 days due to a drug eruption. The right lower lid erythema improved after 4 days of hydroxychloroquine therapy, but the patient continued to have lupus dermatitis behind her right ear and on her scalp.
Patient 4 A 54-year-old Caucasian woman presented with 25 years of chronic inflammation and scarring of the eyelids and philtrum (Fig 4). Two previous right lower lid biopsies were nondiagnostic. She had been treated with doxycycline without improvement. On examination, there was microulceration of the right lower lid and conjunctivalization of the right lower lid margin. In addition, there was madarosis of bilateral lower lids. Antinuclear antibody was negative, and there were no systemic signs of disease other than the facial scarring. Biopsy of the right lower lid showed epithelial atrophy, focal dyskeratosis, and thickened basement membrane, with areas of focal destruction. In addition, there was lymphocytic perivascular inflammation consistent with discoid lupus. Immunofluorescence was notable for dense clusters of immunoglobulin G–positive cells in the superficial dermis and at the dermoepidermal junction, classic symptoms of DLE. The patient was started on hydroxychloroquine (200 mg twice a day), with marked improvement in 2 months. Figure 1. A, Mild conjunctivitis and left lower lid erythema. B, Eversion of left lower lid reveals tarsal conjunctival injection, meibomian gland dysfunction, and mild blepharitis.
lid had been performed previously, which were initially interpreted as benign chronic inflammation of the dermis. Review of these biopsy slides showed hyperkeratosis of the epithelium, thickened basement membrane, basal cell vacuolation, telangiectasias of the substantia propria, lichenoid infiltrates, and dermal inflammation (Fig 2D, E). These were interpreted as consistent with discoid lupus with hyperkeratosis. The patient did not have signs of systemic disease, and the antinuclear antibody was negative. Hydroxychloroquine (200 mg orally twice a day) was started, and over the next 6 months, the blepharoconjunctivitis markedly improved (Fig 2F). The patient was tapered off hydroxychloroquine after 2 years, with no recurrences in the 1-year follow-up period.
Patient 5 A 41-year-old Caucasian woman presented with a 2-year history of eyelid redness and conjunctival injection, greater on the right side (Fig 5). She had been treated for blepharitis with warm compresses, doxycycline, and steroid creams without improvement. She had a forehead skin lesion that had been biopsied recently and showed granular deposition of immunoglobulin M, immunoglobulin G, immunoglobulin A, and C3 along the dermoepidermal junction, consistent with DLE. Antinuclear antibody was negative. On examination, there were severe meibomian gland dysfunction, lid thickening, erythema, multiple chalazia, and conjunctival injection with lower tarsal conjunctival follicles. In addition, there were trichiasis and 2 small plaques on the right lower lid. Hydroxychloroquine (200 mg twice a day) was started, and within 2 weeks, there was markedly less eyelid inflammation. The facial lesions did not improve to the same extent as the eyelids.
™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™3 Figure 2. A, Bilateral eyelid erythema, scaling, blepharitis, and meibomian gland dysfunction. B, Pretreatment: marked erythema and scaling at the outer lid margins of the right eye and hypertrophic lesion on the right upper lid. C, Eversion of left lower eyelid shows conjunctival hypertrophy and inflammation. D, Biopsy of right lower lid showing hyperkeratosis and dermal mononuclear inflammation (stain, hematoxylin– eosin; original magnification, ⫻40). E, Biopsy of right lower lid shows basal cell vacuolation and basement membrane thickening (stain, hematoxylin– eosin; original magnification, ⫻100). F, Marked diminution of right eyelid redness and thickening 1 month after hydroxychloroquine therapy.
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Acharya et al 䡠 Discoid Lupus Erythematosus Masquerading as Blepharoconjunctivitis
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Ophthalmology Volume 112, Number 5, May 2005
Discussion Discoid lupus erythematosus is a chronic autoimmune disorder of the skin, characterized by raised erythematous lesions occurring most frequently in sun-exposed areas. Discoid lupus erythematosus is responsible for 50% to 85% of chronic cutaneous lupus erythematosus cases, and chronic cutaneous lupus erythematosus is thought to be 2 to 3 times more prevalent than SLE, which has a reported prevalence of 17 to 48 cases per 100 000.1,2 In DLE, females are twice as likely to be affected as males. Most patients are between 20 and 40 years old, with a mean age of 38. Discoid lupus erythematosus may be slightly more common in African Americans than in Caucasians or Asians.1,2,4 The localized form of DLE is characterized by involvement of only the head and/or scalp and accounts for 70% of DLE patients. The generalized form has more extensive involvement and accounts for the remaining 30% of cases. Facial involvement is present in 74% of DLE patients, with the scalp and ear being the most commonly involved sites.3 Twenty percent of patients with generalized DLE and 5% with localized DLE proceed to develop SLE.1–3 Clinically, a cutaneous discoid lesion begins as an erythematous patch that grows into a plaque with follicular plugging and scaling. Lesions typically follow a progression of erythema, hyperkeratosis, and atrophy, with pigmentary changes, especially in darker-skinned people.1–5 Involved skin may be asymptomatic or pruritic. Ocular manifestations of DLE reported in the literature include periorbital edema, blepharitis, madarosis, lid scarring, entropion and ectropion, trichiasis, panniculitis, conjunctivitis, hypertrophic/verrucous lesions, and stromal keratitis.4 – 6,8 –18 Although DLE lesions elsewhere have a distinctive appearance, eyelid findings may be more nonspecific. Conjunctivitis, meibomitis, blepharitis, and chronic eyelid erythema were the most common signs in our cases, and all of our patients had some findings bilaterally, although in some cases asymmetrically. The majority of patients in our study were women (80%) whose initial symptoms started between the ages of 25 and
Figure 3. Chronic right lower lid erythema, meibomian gland dysfunction, and madarosis.
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Figure 4. A, Bilateral eyelid thickening, erythema, and lower lid madarosis. B, Discoid lupus erythematosus upper lip scarring.
40. The majority of DLE eye findings were nonspecific and could be seen in any case of blepharoconjunctivitis. This may be why there was delayed diagnosis in all cases, ranging from 4 months to 25 years. The presence of other cutaneous lesions or an eyelid plaque may aid in an earlier diagnosis. In addition, all patients in our study failed standard treatment for blepharitis, such as lid hygiene, doxycycline, and steroid creams. This prompted consideration of other diagnoses, such as DLE. The differential diagnosis of DLE eyelid involvement includes rosacea blepharoconjunctivitis, seborrheic blepharitis, chronic staphylococcal blepharitis, contact dermatitis, eczema, psoriasis, sebaceous cell carcinoma, lid-involving sarcoidosis, lichen planus, lichenoid drug eruption, and tinea faciei.2,4,7,15,18 The exact pathogenesis of DLE is not known, but a genetic predisposition is suspected.2 There is an increased prevalence among first-degree relatives, as well as an association with HLA-B8. Complement components C1q, C3, and C5 deficiencies have also been associated with DLE. It is thought that perhaps deficiencies in these complement components may cause inability to clear immune complexes and apoptotic cells, causing increased immunologic stimulation.1 Different lymphocyte profiles are seen among the subtypes of cutaneous lupus erythematosus, suggesting that various immune mechanisms are present. Cytokine profiles of DLE lesions have shown that DLE is associated with type 1 cytokines characterized by expression of interleukin 2 and interferon ␥. The most populous inflammatory cell in DLE has been found to be CD45RA⫹.1 In addition, 64% of DLE patients have a positive photoprovocation test when exposed to ultraviolet A light and ultraviolet B light. It has been suggested that a heat shock protein is induced in the keratinocyte after ultraviolet light exposure or skin trauma, and this protein may act as a target for ␥␦ T-cell–mediated
Acharya et al 䡠 Discoid Lupus Erythematosus Masquerading as Blepharoconjunctivitis droxychloroquine therapy, and early treatment can prevent lid cicatrization, trichiasis, and permanent lash loss. Lastly, patients with DLE require a complete medical evaluation by their primary care physician or rheumatologist, as a small percentage of these patients will progress to SLE.
References Figure 5. Right-eye nasal eyelid plaque and chronic eyelid erythema.
epidermal cell cytotoxicity.2,3 Other proposed mechanisms for DLE lesions include viral infection, hormonal influences, and drug reactions.1,2,19 There are likely multiple mechanisms involved in the induction of DLE, and our understanding of this disease will continue to evolve. Diagnosis is aided by serologic and histopathologic testing. Only 20% of DLE patients have a positive antinuclear antibody when tested with human substrates, and ⬍5% have anti–Ro(ss-A), anti–native DNA or anti-Sm antibodies.2 Immunopathology is more useful to make a diagnosis. All of our cases were biopsy proven and demonstrated typical microscopic features of DLE: hyperkeratosis with lymphocytic infiltration of the dermoepidermal junction and telangiectasis of the substantia propria. The 2 cases that had immunofluorescence testing demonstrated immunoglobulin and complement deposition at the dermoepidermal interface. Ninety percent of patients with DLE have a positive direct immunofluorescence test when affected skin is biopsied. Although nonlesional biopsies are positive for immunoreactants in the basement membrane zone in patients with SLE (positive lupus band test), only lesional biopsies are positive in DLE.1–5,8,14 The goal of therapy is to prevent the progression of existing lesions, improve patient appearance, and prevent further lesions. Sunglasses and sunscreens are recommended because ultraviolet exposure may exacerbate this disorder. The use of topical and intralesional corticosteroids may sometimes be helpful. Antimalarials are the mainstay of therapy. Hydroxychloroquine (200 – 400 mg orally per day) may take up to 6 to 8 weeks for a response and require monitoring every 6 months by ophthalmoscopy and visual fields to screen for medication-related maculopathy.1–3,5 All patients in our study responded to systemic hydroxychloroquine therapy (200 – 400 mg/day), some dramatically when treated early (patients 1, 3, and 5). Lastly, if antimalarials cannot be used or if the lesion is resistant, immunosuppressives can be considered. Agents that have been reported to be successfully used for DLE include azathioprine, dapsone, methotrexate, cyclophosphamide, thalidomide, retinoids, and interferon alpha-2.1–3,5,11 Discoid lupus erythematosus can be difficult to diagnose because of its ability to masquerade as chronic blepharoconjunctivitis. When chronic blepharoconjunctivitis is unresponsive to conventional therapy, careful history and reexamination should be performed with consideration of DLE as a diagnosis. Biopsy with appropriate histopathological and immunohistochemical studies is also helpful to establish a diagnosis. Discoid lupus erythematosus lid involvement can be effectively treated with systemic hy-
1. Patel P, Werth V. Cutaneous lupus erythematosus: a review. Dermatol Clin 2002;20:373– 85, v. 2. Callen J. Lupus erythematosus, discoid. [Emedicine web site]. Available at: http://www.emedicine.com/derm/topic247.htm. Accessed August 1, 2004. 3. Fabbri P, Cardinali C, Giomi B, Caproni M. Cutaneous lupus erythematosus: diagnosis and management. Am J Clin Dermatol 2003;4:449 – 65. 4. Huey C, Jakobiec FA, Iwamoto T, et al. Discoid lupus erythematosus of the eyelids. Ophthalmology 1983;90: 1389 –98. 5. Foster CS. Systemic lupus erythematosus, discoid lupus erythematosus, and progressive systemic sclerosis. Int Ophthalmol Clin 1997;37:93–110. 6. Ziv R, Schewach-Millet M, Trau H. Discoid lupus erythematosus of the eyelids [letter]. J Am Acad Dermatol 1986;15: 112–3. 7. Donzis PB, Insler MS, Buntin DM, Gately LE. Discoid lupus erythematosus involving the eyelids. Am J Ophthalmol 1984; 98:32– 6. 8. Frith P, Burge SM, Millard PR, Wojnarowska F. External ocular findings in lupus erythematosus: a clinical and immunopathological study. Br J Ophthalmol 1990;74:163–7. 9. Gloor P, Kim M, McNiff JM, Wolfley D. Discoid lupus erythematosus presenting as asymmetric posterior blepharitis. Am J Ophthalmol 1997;124:707–9. 10. Uy HS, Pineda R II, Shore JW, et al. Hypertrophic discoid lupus erythematosus of the conjunctiva. Am J Ophthalmol 1999;127:604 –5. 11. Bettis VM, Vaughn RY, Guill MA. Erythematous plaques on the eyelids. Discoid lupus erythematosus (DLE). Arch Dermatol 1993;129:497, 500. 12. Tosti A, Tosti G, Giovannini A. Discoid lupus erythematosus solely involving the eyelids: report of three cases [letter]. J Am Acad Dermatol 1987;16:1259 – 60. 13. Kearns W, Wood W, Marchese A. Chronic cutaneous lupus involving the eye lid. Ann Ophthalmol 1982;14:1009 –10. 14. Selva D, Chen CS, James CL, Huilgol SC. Discoid lupus erythematosus presenting as madarosis. Am J Ophthalmol 2003;136:545– 6. 15. Foster RE, Lowder CY, Meisler DM, et al. An unusual ocular manifestation of discoid lupus erythematosus. Cleve Clin J Med 1994;61:232–7. 16. Thorne JE, Jabs DA, Nikolskaia O, et al. Discoid lupus erythematosus and cicatrizing conjunctivitis: clinicopathologic study of two cases. Ocul Immunol Inflamm 2002;10:287–92. 17. Panse I, Cordoliani F, Rybojad M, et al. Discoid lupus erythematosus involving the eyelids: 4 cases [in French]. Ann Dermatol Venereol 2004;131:58 – 60. 18. Meiusi R, Cameron JD, Holland EJ, Summers CG. Discoid lupus erythematosus of the eyelid complicated by wound dehiscence [letter]. Am J Ophthalmol 1991;111:108 –9. 19. Prokop J, Jagodzinski PP. Identification of retroviral DNA sequences in serum of cutaneous forms of lupus erythematosus patients. Eur J Dermatol 2003:13:354 – 8.
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