Periorbital Discoid Lupus Erythematosus

Abstract

Periorbital discoid lupus erythematosus (DLE) is an uncommon skin condition that presents a unique clinical challenge.1Walling H.W. Sontheimer R.D. Cutaneous lupus erythematosus: issues in diagnosis and treatment.Am J Clin Dermatol. 2009; 10: 365-381Crossref PubMed Scopus (62) Google Scholar We report the clinical findings and management in 4 new cases, and present an online review of the relevant literature (Appendix 1 and Table 1, available at http://aaojournal.org) and evidence-based guidelines for its diagnosis and management (Fig 1, available at http://aaojournal.org). A 49-year-old woman presented with 10 years of intermittent erythema and irritation of the left lower eyelid. This had failed to respond to lid hygiene, and topical lubricants and corticosteroids. On examination, she had a central 10×5 mm erythematous plaque reaching the lid margin. A lid biopsy was consistent with DLE and the patient commenced on topical hydrocortisone and oral hydroxychloroquine 200 mg once daily with a considerable improvement in her condition. At 3 months follow up, she is asymptomatic on hydroxychloroquine 200 mg once daily without further recurrence. A 47-year-old woman was referred with 11 years of progressive redness, irritation, and scarring of the left lower eyelid which failed to resolve with lid hygiene, erythromycin ointment, and oral minocycline. Three years later she developed an erythematous annular plaque on the left arm. Biopsies of the eyelid taken 5 years previously and the arm lesion were inconclusive. Examination revealed a 20 mm2 erythematous, scaly plaque with areas of hyperkeratosis, atrophy, and scarring associated with telangiectasia and surrounding erythema, madarosis of the central two thirds of the eyelid, and mild symblepharon (Fig 2A, available at http://aaojournal.org). The other eyelids had mild blepharitis-related changes. Discoid lupus erythematosus was subsequently diagnosed following a second eyelid biopsy. She responded well to 4 weeks of topical corticosteroids and oral chloroquine for 2 years. By 1 year posttreatment, she remains asymptomatic with no recurrence (Fig 2B, available at http://aaojournal.org). A 49-year-old woman presented with 19 months of right lower eyelid itching and a photosensitive red, scaly rash. This had failed to resolve with lid hygiene and topical chloramphenicol and hydrocortisone. Examination revealed a 14×6 mm erythematous, scaly plaque on the lateral half of the pretarsal skin with madarosis, telangiectasia, and mild tarsal conjunctival injection (Fig 2C, available at http://aaojournal.org). Histopathology of an eyelid biopsy was consistent with DLE. Direct immunofluorescence also demonstrated a positive lupus band test. She had a minimal response to 2 intralesional triamcinolone 1-2 mg injections and no response to topical tacrolimus. She was subsequently responded well to 3 months of hydroxychloroquine 200 mg once daily and remains in remission at 1 year posttreatment. A 29-year-old woman presented with a 2-month history of irritation and redness of the right lower eyelid. She had also developed an itchy, scaly, red lesion on her left cheek, and was independently referred to a dermatologist. On examination, there was a 15×5 mm erythematous plaque along the medial aspect of the right lower eyelid margin with associated telangiectasia. There was no scaling or madarosis. She had concurrent medial canthal changes related to angular blepharitis. She also had a 25 mm2 erythematous, scaly plaque at the medial aspect of her left cheek. The patient was initially treated for posterior blepharitis with lid hygiene, oral doxycycline, and betnesol ointment. Following an initial improvement, her lesions became enlarged and more irritable. Review at 2 months demonstrated an erythematous scaly plaque along the entire length of the right lower eyelid margin extending to the medial aspect of the right upper lid (Fig 2D, available at http://aaojournal.org). A full-thickness eyelid biopsy was initially inconclusive. She also developed a new lesion on the left temporal area and a biopsy of this confirmed DLE. On further review, the initial eyelid biopsy was also consistent with DLE (Fig 3, available at http://aaojournal.org). She has responded well to hydroxychloroquine 200 mg twice daily (BD) and by 1 year follow up, remains asymptomatic with no recurrence. Periorbital discoid lupus erythematous remains a significant diagnostic challenge and can require multiple biopsies to diagnose.2Uy H.S. Pineda 2nd, R. Shore J.W. et al.Hypertrophic discoid lupus erythematosus of the conjunctiva.Am J Ophthalmol. 1999; 127: 604-605Abstract Full Text Full Text PDF PubMed Scopus (17) Google Scholar, 3Zedek D.C. Smith Jr, E.T. Hitchcock M.G. et al.Cutaneous lupus erythematosus simulating squamous neoplasia: the clinicopathologic conundrum and histopathologic pitfalls.J Am Acad Dermatol. 2007; 56: 1013-1020Abstract Full Text Full Text PDF PubMed Scopus (16) Google Scholar Oral antimalarials offer a safe and effective treatment.1Walling H.W. Sontheimer R.D. Cutaneous lupus erythematosus: issues in diagnosis and treatment.Am J Clin Dermatol. 2009; 10: 365-381Crossref PubMed Scopus (62) Google Scholar, 4Rothfield N. Sontheimer R.D. Bernstein M. Lupus erythematosus: systemic and cutaneous manifestations.Clin Dermatol. 2006; 24: 348-362Abstract Full Text Full Text PDF PubMed Scopus (53) Google Scholar Lupus erythematosus (LE) is a multisystem autoimmune condition characterized by a progressive loss of tolerance to nuclear antigens by the innate and adaptive immune systems.1Obermoser G. Pascual V. The interferon-alpha signature of systemic lupus erythematosus.Lupus. 2010; 19: 1012-1019Crossref PubMed Scopus (173) Google Scholar The pathophysiology of LE remains incompletely understood, but is believed to involve the cytokine Interferon alpha (IFN-α). IFN-α has shown to be significantly up regulated in patients with LE2Baechler E.C. Batliwalla F.M. Karypis G. et al.Interferon-inducible gene expression signature in peripheral blood cells of patients with severe lupus.Proc. Natl. Acad. Sci. U.S.A. 2003; 100: 2610-2615Crossref PubMed Scopus (1698) Google Scholar and is associated with defects in the clearance of immune complexes and apoptotic cells, altered B- and T-cell signaling and autoantibody production.1Obermoser G. Pascual V. The interferon-alpha signature of systemic lupus erythematosus.Lupus. 2010; 19: 1012-1019Crossref PubMed Scopus (173) Google Scholar Cutaneous lupus erythematosus (CLE) involves the skin which is the second most frequently affected organ system in LE after joint disease. It is present in 59-85% of patients at some point during the course of systemic lupus erythematosus (SLE).3Font J. Cervera R. Ramos-Casals M. et al.Clusters of clinical and immunologic features in systemic lupus erythematosus: analysis of 600 patients from a single center.Semin. Arthritis Rheum. 2004; 33: 217-230Abstract Full Text Full Text PDF PubMed Scopus (116) Google Scholar, 4Rothfield N. Sontheimer R.D. Bernstein M. Lupus erythematosus: systemic and cutaneous manifestations.Clin. Dermatol. 2006; 24: 348-362Abstract Full Text Full Text PDF PubMed Scopus (119) Google Scholar CLE is very rarely life-threatening5Lee H.Y. Tey H.L. Pang S.M. Thirumoorthy T. Systemic lupus erythematosus presenting as Stevens-Johnson syndrome and toxic epidermal necrolysis: a report of three cases.Lupus. 2011; 20: 647-652Crossref PubMed Scopus (30) Google Scholar, 6Ziemer M. Kardaun S.H. Liss Y. Mockenhaupt M. Stevens-Johnson syndrome and toxic epidermal necrolysis in patients with lupus erythematosus: A descriptive study of 17 cases from a national registry and review of the literature.Br J Dermatol. 2012; 166: 575-600Crossref PubMed Scopus (51) Google Scholar or sight-threatening7Arthurs B.P. Khalil M.K. Chagnon F. et al.Orbital infarction and melting in a patient with systemic lupus erythematosus.Ophthalmology. 1999; 106: 2387-2390Abstract Full Text Full Text PDF PubMed Scopus (16) Google Scholar and only 25% of patients presenting with CLE progress to SLE with clinically detectable internal organ damage.8Obermoser G. Sontheimer R.D. Zelger B. Overview of common, rare and atypical manifestations of cutaneous lupus erythematosus and histopathological correlates.Lupus. 2010; 19: 1050-1070Crossref PubMed Scopus (132) Google Scholar Nevertheless, skin disease contributes disproportionately to disease burden in relation to personal psychosocial morbidity and socioeconomic costs.9Aberer E. Epidemiologic, socioeconomic and psychosocial aspects in lupus erythematosus.Lupus. 2010; 19: 1118-1124Crossref PubMed Scopus (24) Google Scholar There are over 20 clinical subtypes of CLE, with a varying severity and course reflecting the complex interplay between environmental and genetic factors.10Pramatarov K.D. Chronic cutaneous lupus erythematosus--clinical spectrum.Clin. Dermatol. 2004; 22: 113-120Abstract Full Text Full Text PDF PubMed Scopus (28) Google Scholar Discoid lupus erythematosus (DLE) is a morphologically distinct form of CLE characterized by well-defined erythematous plaques often with overlying scaling. DLE is the commonest manifestation of CLE and is observed in 67.5% of patients with CLE.11Moghadam-Kia S. Chilek K. Gaines E. et al.Cross-sectional analysis of a collaborative Web-based database for lupus erythematosus-associated skin lesions: prospective enrollment of 114 patients.Arch Dermatol. 2009; 145: 255-260Crossref PubMed Scopus (47) Google Scholar Periorbital disease is uncommon and has been estimated to occur in up to 6% of cases of DLE.12Burge S.M. Frith P.A. Juniper R.P. Wojnarowska F. Mucosal involvement in systemic and chronic cutaneous lupus erythematosus.Br. J. Dermatol. 1989; 121: 727-741Crossref PubMed Scopus (123) Google Scholar However, it can present a unique diagnostic and management challenge.13Walling H.W. Sontheimer R.D. Cutaneous lupus erythematosus: issues in diagnosis and treatment.Am J Clin Dermatol. 2009; 10: 365-381Crossref PubMed Scopus (201) Google Scholar This article summarizes the clinical features of periorbital DLE (table 1, available at http://aaojournal.org) and presents evidence based guidelines for the diagnosis and management of this condition (Fig. 1, available at http://aaojournal.org) DLE was first described by Kaposi in 186914Kaposi M. Hebra F. On the Diseases of the Skin, Including the Exanthema. The New Sydenham Society, London1875Google Scholar who stated that the eyelid may be a primary site for the condition, however, eyelid involvement as a primary manifestation of DLE remains uncommon. A PubMed search was undertaken using the terms [discoid lupus erythematosus] and [eyelid] or [periorbital], followed by a citation search, restricting our search to English language publications. We identified 61 cases in total (including our 4 cases), with 43 (70.5%) cases in which DLE has been isolated to the eyelids. In some discussions, the term DLE has been applied to a wide range of CLE lesions without systemically detectable disease leading to a degree of ambiguity and confusion. We have only used the term to describe the morphologically distinct form of DLE as defined above.13Walling H.W. Sontheimer R.D. Cutaneous lupus erythematosus: issues in diagnosis and treatment.Am J Clin Dermatol. 2009; 10: 365-381Crossref PubMed Scopus (201) Google Scholar, 10Pramatarov K.D. Chronic cutaneous lupus erythematosus--clinical spectrum.Clin. Dermatol. 2004; 22: 113-120Abstract Full Text Full Text PDF PubMed Scopus (28) Google Scholar A summary of the clinical features can be found below. The results of the literature search are shown in table 1 (available at http://aaojournal.org). Tabled 1Key features of periorbital DLEDemographicsGenderMale 20% Female 80%Mean age at diagnosis40.7 years (Range: 0–89)Co-existing ocular/systemic pathology11.8%Clinical presentation & investigationsMedian duration prior to diagnosis2.0 years (Range: 0–25)Number of lids involvedOne: 41.5% Two: 34.1% Three: 2.4% Four: 19.5% Lesions on scalp/ears/face: 28.3 % Additional lesions elsewhere: 10.9%Lesion characteristicsErythematous plaque: 50.9% Madarosis: 50.9% Scaling 38.2% Telangiectasia: 14.5% Skin atrophy: 12.7% Adnexal involvement: 21.8% Conjunctival involvement: 14.5%Positive histopathological diagnosis86.7%Initial biopsy inconclusive/negative10.2%Immunofluorescence Positive86.9%ANA Positive17.9%TreatmentTreatment successOral antimalarials 80% Topical corticosteroid monotherapy 8.7% Spontaneous resolution 5% Open table in a new tab Periorbital DLE is 4 times more likely to affect females than males. 12 (20.0%) reports described male patients, and 48 (80.0%) females. The mean age at diagnosis was 40.7 years (range 0 (neonate) – 89 years). The most common age of onset was 20-40 years (24/53, 45.3%) which is consistent with DLE in general.15Tebbe B. Orfanos C. Epidemiology and socioeconomic impact of skin disease in lupus erythematosus.Lupus. 1997; 6: 96-104Crossref PubMed Scopus (142) Google Scholar The median duration of symptoms prior to diagnosis was 2.0 years (range 0–25 years). 45/51 cases (88.2%) did not have a co-existing systemic or ocular pathology at the time of diagnosis. One patient each had iron deficiency anemia, the palmopustular syndrome, mycotis dermatitis, a benign pigmented lid nevus, atopy and seborrheic dermatitis, and one patient had sarcoidosis, syphilis and lymphogranuloma venereum. There were 18/46 cases (39.1%) with bilateral involvement, 16/46 cases (34.8%) in which only the left eye was affected and in 12/46 cases (26.1%) only the right. It has previously been reported that the right lower eyelid was the most frequently affected site (44%), with 67% of cases isolated to one eyelid16Papalas J.A. Hitchcock M.G. Gandhi P. Proia A.D. Cutaneous lupus erythematosus of the eyelid as a mimic of squamous epithelial malignancies: a clinicopathologic study of 9 cases.Ophthal Plast Reconstr Surg. 2011; 27: 168-172Crossref PubMed Scopus (11) Google Scholar and that the lower lids were affected in only 6% of cases.17Ena P. Pinna A. Carta F. Discoid lupus erythematosus of the eyelids associated with staphylococcal blepharitis and Meibomian gland dysfunction.Clin. Exp. Dermatol. 2006; 31: 77-79Crossref PubMed Scopus (18) Google Scholar We have found that DLE most is isolated to only one eyelid in only 17/41 cases (41.5%) and in 8/41 (19.5%) of reports each, affects both lower eyelids, all four eyelids, the left lower eyelid in isolation and the right lower eyelid. 3/41 (7.3%) had disease isolated to the left upper eyelid and 1/41 (2.4%) the right upper eyelid alone. 3/42 (7.1%) cases involved both lids on the right, 3/42 (7.1%) both left lids and 1/42 (2.4%) had involvement of three eyelids. There were no reports of DLE affecting both upper eyelids alone. Additional lesions were observed on the scalp, ears and face in 13/46 cases (28.3%) and peripherally in 5/46 cases (10.9%). 1 report also described a patient with periorbital DLE who had concurrent enlargement of his recti muscles and lacrimal gland, with a biopsy of her lacrimal demonstrating histological features similar to DLE.18Gupta T. Beaconsfield M. Rose G.E. Verity D.H. Discoid lupus erythematosus of the periorbita: clinical dilemmas, diagnostic delays.Eye (Lond). 2012; 26: 609-612Crossref PubMed Scopus (24) Google Scholar A classical DLE lesion is described as a discoid (coin-shaped) plaque with erythema and hyperkeratotic scaling.8Obermoser G. Sontheimer R.D. Zelger B. Overview of common, rare and atypical manifestations of cutaneous lupus erythematosus and histopathological correlates.Lupus. 2010; 19: 1050-1070Crossref PubMed Scopus (132) Google Scholar, 13Walling H.W. Sontheimer R.D. Cutaneous lupus erythematosus: issues in diagnosis and treatment.Am J Clin Dermatol. 2009; 10: 365-381Crossref PubMed Scopus (201) Google Scholar In the eyelids, the most frequently observed lesion was also an erythematous plaque (28/55 cases, 50.9%), with scaling in 21/28 of these cases (75%). The primary lesion was as a papule in 3/55 reports (5.5%) and a macule in 1/55 reports (1.8%). In 3/55 cases (5.5%), the lesion was hyperpigmented and in 3/55 (5.5%) it was hypopigmented. Telangiectasia were observed in 8/55 cases (14.5%), 7/55 cases (12.7%) had atrophy of the skin, whereas 7/55 cases (12.7%) had hypertrophy of the lids. Conjunctival involvement was also observed in 8/55 cases (14.5%). Madarosis can occur from the inflammation associated with DLE19Khong J.J. Casson R.J. Huilgol S.C. Selva D. Madarosis.Surv Ophthalmol. 2006; 51: 550-560Abstract Full Text Full Text PDF PubMed Scopus (35) Google Scholar and was present in 28/55 cases (50.9%). Although many reports failed to describe the character of madarosis, it was located on the lateral aspect of the lid margin in 4/11 cases (36.4%), medially in 4/11 (36%), and centrally and in a patchy distribution in 1/11 case each (9.1%). 1/11 (9.1%) also described complete madarosis of the affected eyelid. 12/55 cases (21.8%) reported disruption of the other ocular appendages. These included scarring (9/55, 16.4%), ulceration (2/55, 3.6%), ectropion (2/55, 3.6%), entropion (2/55, 3.6%), disruption of lid margin (1/55, 1.8%), trichiasis (1/55, 1.8%) and symblepharon (1/55, 1.8%). These features were only observed in patients with a more prolonged disease course (range 3.17–25 years, mean 8.6 years). Such signs can also raise the suspicion of a malignancy such as squamous cell carcinoma or sebaceous cell carcinoma. Although malignant conditions often occur over a more rapid timescale,16Papalas J.A. Hitchcock M.G. Gandhi P. Proia A.D. Cutaneous lupus erythematosus of the eyelid as a mimic of squamous epithelial malignancies: a clinicopathologic study of 9 cases.Ophthal Plast Reconstr Surg. 2011; 27: 168-172Crossref PubMed Scopus (11) Google Scholar, 17Ena P. Pinna A. Carta F. Discoid lupus erythematosus of the eyelids associated with staphylococcal blepharitis and Meibomian gland dysfunction.Clin. Exp. Dermatol. 2006; 31: 77-79Crossref PubMed Scopus (18) Google Scholar they can only be excluded following a biopsy. Histological findings in the early stages of DLE include vacuolar degeneration of basal cells and a perivascular and peri-appendageal lymphocytic infiltrate in the upper and mid-dermis. As the lesions mature, the lymphocytic infiltrate becomes less prominent and signs of scarring and chronicity predominate. These include epidermal atrophy, hyperkeratosis with follicular plugging, basement membrane thickening, mucin deposition and Civatte body formation (due to apoptosed epithelial cells).8Obermoser G. Sontheimer R.D. Zelger B. Overview of common, rare and atypical manifestations of cutaneous lupus erythematosus and histopathological correlates.Lupus. 2010; 19: 1050-1070Crossref PubMed Scopus (132) Google Scholar, 13Walling H.W. Sontheimer R.D. Cutaneous lupus erythematosus: issues in diagnosis and treatment.Am J Clin Dermatol. 2009; 10: 365-381Crossref PubMed Scopus (201) Google Scholar, 20Donnelly A.M. Halbert A.R. Rohr J.B. Discoid lupus erythematosus.Australas. J. Dermatol. 1995; 36 (quiz 11-12): 3-10Crossref PubMed Scopus (20) Google Scholar Chronic interface inflammation may also be present in epithelial malignancies16Papalas J.A. Hitchcock M.G. Gandhi P. Proia A.D. Cutaneous lupus erythematosus of the eyelid as a mimic of squamous epithelial malignancies: a clinicopathologic study of 9 cases.Ophthal Plast Reconstr Surg. 2011; 27: 168-172Crossref PubMed Scopus (11) Google Scholar with reports of squamous cell carcinoma arising in pre-existing DLE suggesting a relationship between autoimmune inflammatory skin disorders and squamous epithelial malignancy.21Alsanafi S. Werth V.P. Squamous cell carcinomas arising in discoid lupus erythematosus scars: unusual occurrence in an African-American and in a sun-protected area.J Clin Rheumatol. 2011; 17: 35-36Crossref PubMed Scopus (18) Google Scholar, 22Harper J.G. Pilcher M.F. Szlam S. Lind D.S. Squamous cell carcinoma in an African American with discoid lupus erythematosus: a case report and review of the literature.South. Med. J. 2010; 103: 256-259Crossref PubMed Scopus (20) Google Scholar, 23Parikh N. Choi J. Li M. et al.Squamous cell carcinoma arising in a recent plaque of discoid lupus erythematous, in a sun-protected area.Lupus. 2010; 19: 210-212Crossref PubMed Scopus (13) Google Scholar Positive histological features were reported in 52/60 cases (86.7%) of periorbital DLE. In 6/60 cases (10.0%), the initial lid biopsy was inconclusive and the diagnosis of DLE only confirmed following a review of the original biopsy or a subsequent biopsy at the same site or elsewhere. In view of a previous report of multiple wound dehiscence following a full-thickness incisional lid biopsy in DLE,24Meiusi R.S. Cameron J.D. Holland E.J. Summers C.G. Discoid lupus erythematosus of the eyelid complicated by wound dehiscence.Am. J. Ophthalmol. 1991; 111: 108-109Abstract Full Text PDF PubMed Scopus (11) Google Scholar some authors have advocated performing an initial partial-thickness biopsy is cases of suspected DLE16Papalas J.A. Hitchcock M.G. Gandhi P. Proia A.D. Cutaneous lupus erythematosus of the eyelid as a mimic of squamous epithelial malignancies: a clinicopathologic study of 9 cases.Ophthal Plast Reconstr Surg. 2011; 27: 168-172Crossref PubMed Scopus (11) Google Scholar, 17Ena P. Pinna A. Carta F. Discoid lupus erythematosus of the eyelids associated with staphylococcal blepharitis and Meibomian gland dysfunction.Clin. Exp. Dermatol. 2006; 31: 77-79Crossref PubMed Scopus (18) Google Scholar and only proceeding to a full-thickness biopsy if initial results are equivocal. However, we believe that superficial shave biopsies should be avoided as it can be difficult to distinguish DLE from squamous cell carcinoma and actinic keratosis.25Zedek D.C. Smith Jr, E.T. Hitchcock M.G. et al.Cutaneous lupus erythematosus simulating squamous neoplasia: the clinicopathologic conundrum and histopathologic pitfalls.J. Am. Acad. Dermatol. 2007; 56: 1013-1020Abstract Full Text Full Text PDF PubMed Scopus (22) Google Scholar We recommend a primary punch biopsy which is a quick and safe procedure that is easy to perform in the outpatient department and can provide full-thickness tissue sample of adequate size and quality.26Rice J.C. Zaragoza P. Waheed K. et al.Efficacy of incisional vs punch biopsy in the histological diagnosis of periocular skin tumours.Eye (Lond). 2003; 17: 478-481Crossref PubMed Scopus (14) Google Scholar Direct immunofluorescence of lesional skin often demonstrates a band of immunoreactants at the dermo-epidermal junction comprising of immunoglobulins (IgG, IgM, IgA), complement components (C3, C4, C1Q) and fibrinogen degradation components, and is known as the ‘lesional lupus band test.'13Walling H.W. Sontheimer R.D. Cutaneous lupus erythematosus: issues in diagnosis and treatment.Am J Clin Dermatol. 2009; 10: 365-381Crossref PubMed Scopus (201) Google Scholar, 27Burge S.M. Frith P.A. Millard P.R. Wojnarowska F. The lupus band test in oral mucosa, conjunctiva and skin.Br. J. Dermatol. 1989; 121: 743-752Crossref PubMed Scopus (18) Google Scholar This was positive in 20/23 cases (86.9%) and negative in the remaining three. However, the test cannot differentiate DLE from SLE and similar findings may be present in other connective disorders.13Walling H.W. Sontheimer R.D. Cutaneous lupus erythematosus: issues in diagnosis and treatment.Am J Clin Dermatol. 2009; 10: 365-381Crossref PubMed Scopus (201) Google Scholar Immunofluorescence can therefore provide a useful adjunct for diagnosis of DLE, particularly in cases where the histopathology may be equivocal. Anti-nuclear antibodies (ANA) were detected in 5/28 reports (17.9%) which is in concordance with a previous large series of DLE.28Callen J.P. Systemic lupus erythematosus in patients with chronic cutaneous (discoid) lupus erythematosus Clinical and laboratory findings in seventeen patients.J. Am. Acad. Dermatol. 1985; 12: 278-288Abstract Full Text PDF PubMed Scopus (55) Google Scholar Elevated Anti single-stranded-stranded DNA has also been associated with DLE,20Donnelly A.M. Halbert A.R. Rohr J.B. Discoid lupus erythematosus.Australas. J. Dermatol. 1995; 36 (quiz 11-12): 3-10Crossref PubMed Scopus (20) Google Scholar however, we were unable to find any cases of this in eyelid-specific disease. Although many reports failed to mention additional systemic investigations, ESR was elevated in three patients including one patient who also had anemia. Periorbital DLE is most often misdiagnosed as blepharitis17Ena P. Pinna A. Carta F. Discoid lupus erythematosus of the eyelids associated with staphylococcal blepharitis and Meibomian gland dysfunction.Clin. Exp. Dermatol. 2006; 31: 77-79Crossref PubMed Scopus (18) Google Scholar, 29Huey C. Jakobiec F.A. Iwamoto T. et al.Discoid lupus erythematosus of the eyelids.Ophthalmology. 1983; 90: 1389-1398Abstract Full Text PDF PubMed Scopus (52) Google Scholar and we identified 24/58 cases (41.4%) in which patients were treated for blepharitis before the correct diagnosis was confirmed. DLE may also resemble eczema, psoriasis, seborrheic dermatitis, contact dermatitis, orbital cellulitis, sarcoidosis, lymphoma, basal cell carcinoma, squamous cell carcinoma and sebaceous cell carcinoma.16Papalas J.A. Hitchcock M.G. Gandhi P. Proia A.D. Cutaneous lupus erythematosus of the eyelid as a mimic of squamous epithelial malignancies: a clinicopathologic study of 9 cases.Ophthal Plast Reconstr Surg. 2011; 27: 168-172Crossref PubMed Scopus (11) Google Scholar, 17Ena P. Pinna A. Carta F. Discoid lupus erythematosus of the eyelids associated with staphylococcal blepharitis and Meibomian gland dysfunction.Clin. Exp. Dermatol. 2006; 31: 77-79Crossref PubMed Scopus (18) Google Scholar, 29Huey C. Jakobiec F.A. Iwamoto T. et al.Discoid lupus erythematosus of the eyelids.Ophthalmology. 1983; 90: 1389-1398Abstract Full Text PDF PubMed Scopus (52) Google Scholar, 18Gupta T. Beaconsfield M. Rose G.E. Verity D.H. Discoid lupus erythematosus of the periorbita: clinical dilemmas, diagnostic delays.Eye (Lond). 2012; 26: 609-612Crossref PubMed Scopus (24) Google Scholar All patients with a diagnosis of DLE should receive smoking cessation counseling, as this can directly exacerbate the disease and interfere with antimalarial drugs.30Ostrowski R.A. Robinson J.A. Antiphospholipid antibody syndrome and autoimmune diseases.Hematol. Oncol. Clin. North Am. 2008; 22: 53-65Abstract Full Text Full Text PDF PubMed Scopus (27) Google Scholar Photoprotection advice should also be given as DLE can be highly photosensitive and disease flare-up can be triggered by UV radiation.31Herzinger T. Plewig G. Röcken M. Use of sunscreens to protect against ultraviolet-induced lupus erythematosus.Arthritis Rheum. 2004; 50: 3045-3046Crossref PubMed Scopus (52) Google Scholar Oral antimalarials have demonstrated good efficacy and a favorable safety profile in treating DLE.32Jessop S. Whitelaw D.A. Delamere F.M. Drugs for discoid lupus erythematosus The Cochrane Collaboration [serial online] 2009.http://summaries.cochrane.org/CD002954/drugs-for-discoid-lupus-erythematosusGoogle Scholar Hydroxychloroquine is the preferred first-line agent because of its favorable efficacy and safety profile. This should be initiated at 6.5mg/kg/day in divided doses (typically 200mg twice a day). A clinical response should be seen in 2-3 months and the dose can subsequently be reduced to 200mg once a day. Treatment should be maintained for 1-2 years to minimise the risk of reactivation.4Rothfield N. Sontheimer R.D. Bernstein M. Lupus erythematosus: systemic and cutaneous manifestations.Clin. Dermatol. 2006; 24: 348-362Abstract Full Text Full Text PDF PubMed Scopus (119) Google Scholar If monotherapy with hydroxychloroquine is insufficient, dual-therapy with mepacrine 100mg/day can be commenced. If the combination therapy fails, hydroxychloroquine can be substituted by chloroquine 4mg/kg/day (typically 250mg/day).4Rothfield N. Sontheimer R.D. Bernstein M. Lupus erythematosus: systemic and cutaneous manifestations.Clin. Dermatol. 2006; 24: 348-362Abstract Full Text Full Text PDF PubMed Scopus (119) Google Scholar, 13Walling H.W. Sontheimer R.D. Cutaneous lupus erythematosus: issues in diagnosis and treatment.Am J Clin Dermatol. 2009; 10: 365-381Crossref PubMed Scopus (201) Google Scholar, 33Knott H.M. Martínez J.D. Innovative management of lupus erythematosus.Dermatol Clin. 2010; 28: 489-499Abstract Full Text Full Text PDF PubMed Scopus (10) Google Scholar We identified 31 reports of treatment with oral antimalarials as a monotherapy (22/31, 71.0%), and in combination with topical corticosteroid (2/31, 6.5%), intralesional triamcinolone (2/31, 6.5%), systemic corticosteroid (2/31, 6.5%), topical isotretinoin (1/31, 3.2%), topical tacrolimus (1/31, 3.1%) and systemic mycophenolate (1/31, 3.1%). 24/31 cases (77.4%) showed an excellent response to treatment with oral antimalarials (hydroxychloroquine: 19/24 (79.2%), chloroquine: 5/24 (20.1%)). Hydroxychloroquine monotherapy was ineffective in 3/31cases (9.7%) and 2/31 cases (6.5%) failed to respond to chloroquine, however, this included a case on a sub-therapeutic dose. Three isolated cases described patients not responding well to dual therapy with antimalarials and systemic corticosteroids, topical isotretinoin and topical tacrolimus respectively. There were also 2/31 (6.5%) reports of a drug-related eruption necessitating discontinuation of hydroxychloroquine. One occurred after 12 days of commencing treatment and another at four weeks. Topical corticosteroids can be used in the treatment of DLE with a recent Cochrane review recommending topical 0.05% fluocinonide as being more effective than 1% hydrocortisone.32J