Introduction
Cutaneous lupus erythematosus (CLE) is characterized by skin lesions without significant systemic involvement. It’s reported to affect approximately 4.3 per 100,000 individuals annually, with a prevalence of 73.2 per 100,000. CLE is more frequently diagnosed in women, typically starting between the ages of 20 and 40. Systemic lupus erythematosus (SLE), subacute cutaneous lupus, and discoid lupus erythematosus are the most prevalent forms of lupus. However, some patients present with atypical CLE manifestations, representing rarer subtypes that pose challenges in both diagnosis and treatment. Antimalarial medications are the cornerstone of systemic therapy for CLE. Given that therapeutic effects may take 2 to 3 months to become noticeable, oral or topical corticosteroids are often used alongside to expedite response. This article details a case of atypical CLE presenting with periorbital edema that responded well to hydroxychloroquine, and further reviews similar cases documented in existing literature, enhancing the understanding of Periorbital Edema Differential Diagnosis.
Case Report
A man in his 40s sought medical attention for persistent periorbital swelling lasting seven months. The swelling began two days after he was involved in stripping floors at work. He reported no itching, oral symptoms, facial discomfort, breathing difficulties, fever, weight changes, muscle pain, joint pain, weakness, or fatigue. He also denied exposure to new facial products or medications. His medical history included asthma, eczema, hypertension, and depression, all managed with triamcinolone cream, amlodipine, and doxepin, respectively. He had been using ibuprofen for tension headaches about four times weekly for several years without issues but stopped upon noticing the periorbital swelling; however, the swelling persisted. Months later, at another hospital, he was diagnosed with sinusitis and treated with amoxicillin/clavulanate and systemic steroids. While his symptoms initially improved, they recurred as prednisone was reduced below 20 mg.
After seven months of unresolved swelling, he consulted our service. A systems review was unremarkable except for the aforementioned symptoms. Physical examination revealed edema and erythema of the right lower and upper eyelids and the left upper eyelid (Fig 1).
Periorbital Edema Clinical Presentation: Patient exhibiting marked edema and erythema of both eyelids, causing diminished palpebral aperture, suggestive of periorbital edema differential diagnosis considerations.
Laboratory tests, including complete blood count, metabolic profile, C-reactive protein, creatine kinase, IgE, C4, C1-INH, C1q, and total hemolytic complement, were all within normal ranges. Tests for antinuclear antibody (ANA), anti-Sjögren’s syndrome–related antigen A and B, antineutrophil cytoplasmic antibody, antimicrosomal antibody, antihistone antibody, aldolase, anti-Jo1, and anti-Mi2 antibody were also normal. Anti-dsDNA level was 45 IU/mL (nl < 30 IU/mL).
Angiotensin-converting enzyme levels, chest X-ray, and urinalysis results were normal. A maxillofacial CT scan showed soft tissue swelling in the right lacrimal fossa without abscess. A biopsy of the right lower eyelid was performed (Fig 2).
Rheumatology evaluation found no systemic involvement. The patient’s clinical presentation and histopathology were consistent with tumid lupus, a rare CLE variant. He was started on oral prednisone (40 mg/day) and hydroxychloroquine (400 mg/day). Prednisone was tapered off over two months, leading to complete resolution of periorbital edema. At the one-year follow-up, he remained stable on hydroxychloroquine 400 mg/day, with no recurrence of cutaneous symptoms or systemic disease development, emphasizing the importance of considering CLE in the periorbital edema differential diagnosis.
Discussion
Periorbital edema is a nonspecific symptom with a broad periorbital edema differential diagnosis, encompassing conditions such as SLE, dermatomyositis, solid facial edema, drug reactions (including drug-induced lupus [DIL]), infections, angioedema, systemic contact dermatitis, superior vena cava syndrome, hypersensitivity reactions, and sarcoidosis. In this case, laboratory, histopathology, and imaging investigations helped rule out many of these conditions.
Dermatomyositis was less likely due to the absence of characteristic skin lesions (heliotrope rash, Gottron’s sign, shawl sign) or musculoskeletal symptoms indicative of myopathy. SLE was also less probable as the patient lacked systemic symptoms like fatigue, arthritis, or organ involvement (renal, pulmonary, cardiac, hematologic, neuropsychiatric). Drug-induced lupus was considered less likely because the patient had used ibuprofen for years before symptom onset without issues, and symptoms didn’t resolve after discontinuation. DIL is also less commonly associated with cutaneous presentations, and eosinophils were absent in biopsy findings. Serologic tests for dermatomyositis, SLE, and DIL were negative. CT scan findings also did not support chronic sinusitis.
While eyelid edema is reported in approximately 4.8% of SLE cases and occasionally in discoid lupus erythematosus and lupus erythematosus profundus, periorbital edema as the sole initial sign of CLE is exceedingly rare. This patient did not meet SLE or systemic rheumatologic condition criteria. To our knowledge, only six similar cases are documented. A review of these cases is presented in Table I. The reported cases included both men and women aged 23 to 51 years at diagnosis. All diagnoses were confirmed by histopathology from periorbital biopsies, revealing varying combinations of superficial and deep perivascular and periadnexal lymphocytic infiltrate, significant interstitial mucin deposition, and basal layer vacuolar alteration. Our patient’s biopsy, particularly the first two findings and the absence of eosinophils, aligned more with tumid lupus. Diagnosis was delayed in prior cases by 1 to 3 years. Five out of six patients had negative ANA results, similar to our patient. Antimalarials, with or without systemic corticosteroids, were the chosen treatment for CLE cases presenting with periorbital edema. All patients showed improvement, with five reporting marked improvement within 1 to 3 months, as seen in our patient (Table I). This suggests antimalarial drugs are effective for these patients and underscores the importance of including CLE in the periorbital edema differential diagnosis.
Conclusion
Persistent periorbital edema presents a diagnostic challenge due to its association with numerous conditions. This case and the review of similar instances highlight a rare presentation of cutaneous lupus erythematosus where periorbital edema is the primary, and initially, sole manifestation. Considering CLE in the periorbital edema differential diagnosis, especially in cases with persistent, unexplained periorbital swelling, is crucial for timely and accurate diagnosis and treatment, potentially preventing diagnostic delays and improving patient outcomes. Antimalarial therapy, particularly hydroxychloroquine, appears to be an effective treatment strategy for this atypical CLE presentation.
References
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[3] credibility needed for this reference – please provide a valid citation for “others” in the list of periorbital edema differential diagnoses.
[4] credibility needed for this reference – please provide a valid citation for the 4.8% cumulative incidence of eyelid edema in SLE.
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[6] credibility needed for this reference – please provide a valid citation for eyelid edema in discoid lupus erythematosus.
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