A Rare Manifestation of Discoid Lupus Erythematosus Solely in the Lower Eyelid of a Young Man

Discoid lupus erythematosus (DLE)-associated edema and erythema on the lower eyelid as the only manifestation of the disease is a rare clinical entity. Persistent discoid lupus-related lower eyelid manifestations are challenging to diagnose, can be mistaken for blepharitis or malignancies, and often require histopathological evaluation. If left untreated, the condition can progress, among others, to conjunctival scarring or symblepharon formation. Thus, early identification and management of the disease entity is of the utmost significance. We present a rare case of a young patient with enduring, unilateral lower eyelid edema and erythema that had been managed as blepharitis for several years. No other related cutaneous involvement was detected on the eyelids, face, or body. Following a lower eyelid biopsy and histopathological assessment, the patient was diagnosed with underlying DLE. This case report reviews the previous literature, discusses a differentiation strategy from other relevant pathologies, such as blepharitis and sebaceous cell carcinoma, and highlights the implemented diagnostic procedures.

Discoid lupus-associated erythematous lesions on the eyelids are rare and detected in barely 6% of DLE cases [1,5].Cases of eyelid involvement with well-characterized erythematous lesions on the periorbita or near the outer eyelid margins have been previously described [1,[6][7][8][9].In the reported DLE cases with eyelid abnormalities, patients already carry a prior diagnosis of DLE based on the presence of concomitant peripheral, predominantly facial, cutaneous lesions [3,4,6].Moreover, the incidence of the exclusive manifestation of DLE on the main palpebral area of a single lower eyelid, which can be misdiagnosed as a different pathology such as blepharitis, is exceptionally scarce and inadequately reported in the literature.
Here, we report a case with unusual persistent unilateral lower eyelid edema and erythema as the only manifestation of DLE.The patient had been misdiagnosed with chronic blepharitis for several years before presentation by multiple providers.A summary of the previous literature on DLE lower eyelid involvement is also provided and illustrates its scarcity.Finally, a differential diagnosis from other relevant pathologies is discussed and the implemented therapeutic procedures are highlighted.

Case Presentation
A 24-year-old otherwise healthy Caucasian male presented with a three-year history of persistent unilateral lower eyelid edema and erythema.The patient had been previously managed with eyelid hygiene, a combination of topical antibiotic and steroid regimens, and tacrolimus 0.03% ointment for presumed enduring blepharitis and meibomian gland dysfunction without much relief.Meibomian gland biopsy had been performed two years before presentation indicating no atypia or dysplasia of the squamous epithelium.However, persistent clinical signs and patient-reported exacerbation of ocular symptoms No associated cutaneous findings on the scalp, face, or body of the patient were detected.Slit-lamp biomicroscopy showed prominent thickening and inflammation across the left lower eyelid margin, which was associated with derangement of the mucocutaneous junction, hypertrophy of the meibomian glands, and focal conjunctival injection (Figure 2).No corneal involvement was identified.A biopsy of the lower eyelid skin was performed under monitored anesthesia care and controlled intraoperative hemostasis.Histopathologic examination revealed mild hyperkeratosis and areas of mild-tomoderate acanthosis alternating with epidermal atrophy and follicular plugging (Figures 3, 4).Vacuolar basal cell degeneration, albeit mild, was also featured in the specimen.Periodic acid-Schiff staining revealed mild thickening of the basement membrane zone.Moderate-to-severe chronic inflammatory lymphocytic infiltrates were observed in a perivascular and periadnexal pattern (Figures 5, 6).Occasional interstitial plasma cell and mast cell infiltrations were also detected.These microscopic findings were consistent with DLE.The patient was referred to Rheumatology for further workup and management.Serology testing for the presence of autoimmune dysregulation was performed and was negative for the lupus extractable nuclear antigen (ENA) panel (i.e., Ro, La, Sm, RNP, Scl-70, and Jo1).The patient was started on daily hydroxychloroquinolone with resolution of his signs and symptoms at his 18-month follow-up.

Discussion
DLE can be subdivided into generalized, childhood, and localized DLE [2].Localized DLE frequently affects areas above the neck, manifesting with skin lesions on the head and face [2].The ocular manifestations of the localized form include unilateral swelling and erythema of the upper and lower eyelids (44%) or bilateral upper eyelid involvement (33%) [1].
The incidence of lower eyelid involvement due to underlying DLE is rare with only 28 cases reported in the literature (Table 1) [1][2][3][4][5][6][7][8][9] Most patients (86%) were females with an average age of 45.3 years (range 19 to 89 years).The reported lower eyelid findings were predominantly treated as blepharitis in up to 43% of the cases, with one case being managed as both blepharitis and allergic dermatitis, one case as both rosacea and allergic dermatitis, and one case as an atypical chalazion.Among the reported cases, only four patients had a diagnosis of DLE before referral to ophthalmology.At presentation, the palpebral abnormalities comprised scaly lesions in 11 (39%) cases with concomitant blepharitis in two cases.Meibomian gland dysfunction but no scaly lesions was identified in three patients.Lower eyelid findings also encompassed marginal irregularities in five (18%) cases, madarosis in 12 (43%) cases, trichiasis in one case, and telangiectasias in three (11%) cases.Conjunctival hyperemia was present in four (14%) of the reported cases.The duration between symptom onset and diagnosis of DLE ranged between two months and 25 years.DLE-associated peripheral cutaneous manifestations were disclosed in 54% of patients with both bilateral and unilateral lower eyelid involvement.Only four (14%) patients, including, similar to our case, two young men, had solely unilateral lower eyelid involvement with no peripheral cutaneous lesions related to DLE at the time of presentation.Following DLE diagnosis, the therapeutic management included hydroxychloroquine per os in most cases (79%), in addition to topical corticosteroids, intralesional steroid injections, or topical tacrolimus.Improvement and/or resolution of the eyelid lesions was noted in 82% of the cases.One patient developed cicatricial ectropion due to poor compliance.Treatment solely with topical regimens was reported in 21% of the cases.Patients were treated with topical steroids in combination with antibiotics in three cases and with tacrolimus in one case.One patient was treated with antibiotic ointment alone.However, similar to our case, the persistence of lesions was documented in 40% of these cases, highlighting that a systemic treatment approach is crucial.Recurrence of signs and symptoms was reported in three (11%) cases, indicating that DLE with eyelid involvement can be a chronic and relapsing process.

Reports
The pathogenesis of DLE is currently unknown.The prevalence of DLE is thought to be influenced by ethnicity, female gender, and aging [1].This report represents the fifth case reported in the literature of DLE presenting as long-standing unilateral lower eyelid involvement.Such an uncommon incidence, along with the absence of any alarming DLE peripheral cutaneous anomalies or systemic involvement, has been challenging in terms of diagnosis, prognosis, and management.The differential diagnosis of lower eyelid DLE includes pathologies such as blepharitis, contact dermatitis, rosacea, sebaceous, and squamous cell carcinoma [6,7,9].Rosacea blepharokeratoconjunctivitis is an inflammatory skin condition that accounts for up to 17% of all cases of periorbital dermatitis and may simulate discoid lupus [4].However, ocular rosacea predominantly affects both eyelids, showing a more diffuse erythematous pattern.In addition, most rosacea patients present with a history of persistent extraocular erythema, papules, or pustules that precede the palpebral involvement [4].
In lower eyelid DLE, the long-standing refractory swelling and erythema of the eyelid prompts the exclusion of sebaceous gland carcinoma [5].Although rare, sebaceous gland carcinoma is an exceptionally malignant and aggressive cutaneous tumor.Early identification and appropriate management are of extreme importance to save the patient's eye and life.Ocular sebaceous carcinoma can imitate numerous benign conditions, including chalazion or posterior blepharitis, and it is strongly associated with madarosis and unilateral blepharoconjunctivitis [10].In the setting of enduring lower eyelid edema and erythema, differentiation between sebaceous carcinoma and an immune-based disease such as discoid lupus is crucial in terms of prognosis and treatment.Hence, in our case, the suspicion of malignancy dictated the need for biopsy and subsequent histopathological assessment.
Previous studies have reported the histopathological examination criteria for cutaneous lupus, as detected in dermal tissue from extraocular areas.Distinctive features include follicular plugging, vacuolar interface alteration, compact orthokeratosis, and perifollicular inflammation [2,6,9].In terms of DLE diagnosis, serology testing for ENA or antinuclear antibody (ANA) is most frequently performed.In our case, blood testing revealed a negative lupus ENA panel.This is not surprising as patients with discoid lupus have a lower ANA positivity compared to patients with other subtypes of cutaneous lupus.Positive ANA has been identified in only 22.9% of all DLE cases with ocular involvement [7].Thus, DLE diagnosis based solely on serological findings is insufficient.
Following accurate DLE diagnosis, the patient was treated with oral hydroxychloroquinolone which is considered the standard of care in the management of DLE.The most frequently prescribed dosage of hydroxychloroquine is 200 mg twice daily, while the mean reported duration of treatment ranges from two weeks to several months [2,6,9].Proper therapeutic intervention and patient compliance resulted in evident resolution of all signs and symptoms at the patient's 18-month follow-up visit.

Conclusions
Persistent unilateral lower eyelid sole manifestations due to DLE are scarce and can be challenging in terms of diagnosis and proper management.Progression of this condition can lead to conjunctival scarring or symblepharon formation.Prompt identification and differentiation from other eye and life-threatening pathologies via clinical and histopathological evaluation are of the utmost importance.

FIGURE 1 :
FIGURE 1: External photograph of the patient's left lower eyelid.Extended central erythematous lesion with peripheral hyperpigmentation, distinctive central depigmentation, madarosis, and adherent scaling and scarring.

FIGURE 2 :
FIGURE 2: External photograph of the patient's left lower eyelid.Prominent thickening and inflammation across the eyelid margin, derangement of the mucocutaneous junction, hypertrophy of the meibomian glands, and focal conjunctival injection.

FIGURE 5 :
FIGURE 5: Periodic acid-Schiff staining of the lower lid biopsy specimen.

TABLE 1 :
DLE-associated lower eyelid manifestations and management in the reviewed literature.DLE = discoid lupus erythematosus; y/o = years old