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Eyelid Swelling and Proptosis with Systemic Implications

Published:February 08, 2016DOI:https://doi.org/10.1016/j.amjmed.2016.01.027

      Presentation

      A 20-year-old woman presented with a 4-day history of left upper eyelid swelling with erythema and tenderness (Figure 1). Two months prior to presentation, she had a similar episode on the left side, which was diagnosed at an outside facility as a chalazion with associated preseptal cellulitis. Her symptoms resolved with 4 days of oral cephalexin. One month later, she developed similar symptoms on the right side. She was again diagnosed with preseptal cellulitis in the setting of a chalazion, and her symptoms resolved with 7 days of oral cephalexin.
      Figure thumbnail gr1
      Figure 1Swelling and erythema of the left upper eyelid. There was also moderate conjunctival injection and mild chemosis. The lacrimal gland was enlarged and palpable.
      Her review of systems was positive for 3-4 years of intermittent joint swelling and pain. Initially, small joints, but recently also medium joints, were involved. The pain and swelling would occur in 1-2 joints for 1-2 weeks and then shift to another 1-2 joints. In addition, she noticed several enlarged cervical and axillary lymph nodes for the past 2 years. She also had dry mouth in the morning, but no significant dry eye symptoms. She noted no fever, chills, night sweats, or weight loss, but had chronic fatigue for 2 months. She also had mild chronic facial erythema that did not worsen with sun exposure. Her family history was notable for her mother having been affected by an unspecified connective tissue disease.
      On ophthalmologic examination, her visual acuity was 20/20 in both eyes, with normal color vision. Her pupils were normal, with no relative afferent pupillary defect. Her intraocular pressure was normal. She was orthophoric and had no subjective double vision. Right extraocular movements were full, but her left eye showed mildly limited abduction and supraduction. Her confrontation visual fields were full. She had 3.5 mm of left proptosis, with slightly increased resistance to retropulsion on the left.
      External examination revealed moderate left upper eyelid edema, erythema, and warmth with slight tenderness to palpation. The lacrimal gland was palpable. With the left upper eyelid elevated, the lacrimal gland could be visualized from the conjunctival side and was noted to be enlarged and injected. The rest of her slit lamp and dilated fundoscopic examination was within normal limits. There was no evidence of chalazia or underlying meibomian gland dysfunction. Schirmer testing revealed decreased tear production (4 mm right, and 2 mm left, with anesthetic).
      She then underwent a complete assessment by Rheumatology. On examination, she was noted to have no palpable cervical lymphadenopathy, but had a palpable 2-cm-diameter left axillary lymph node that was nontender. Her chest was clear to auscultation bilaterally. She had regular heart rate and rhythm with no murmurs, rubs, or gallops. Her abdomen was soft and nontender, with no organomegaly. Her extremities were warm and well perfused with no edema. The joints of her upper and lower extremities were with full range of motion without swelling, redness, or tenderness to palpation. Her sensation and strength were intact bilaterally in upper and lower extremities. Her skin was notable for patchy malar erythema of her face, which did not spare the nasolabial fold, and mild livedo reticularis over the hands with dilated and disorganized nail fold capillaries of the left fourth and fifth digits. She had no psoriasis, digital ulcers, or sclerodactyly.

      Assessment

      This patient was a 20-year-old woman with 3 episodes of bilateral sequential upper eyelid swelling, erythema, and pain. The differential diagnoses included infection (preseptal cellulitis, orbital cellulitis, and bacterial or viral dacryoadenitis), inflammatory conditions (such as idiopathic orbital inflammation, sarcoidosis, granuloma annulare, Sjögren syndrome, and other systemic autoimmune disorders), lymphoid hyperplasia, and lymphoma. She had been given the diagnosis of chalazion for 2 previous episodes of eyelid swelling, sequentially affecting the left and right upper eyelids, 1 month apart. While a chalazion with associated preseptal cellulitis can lead to eyelid swelling, redness, and pain, she had no chalazia on examination, and this diagnosis could not account for her lacrimal gland enlargement, proptosis, and eye movement abnormalities.
      Orbital ultrasound revealed increased reflectivity and diffuse widening of the left lacrimal gland, consistent with inflammation. Orbital computed tomography with contrast revealed left orbital soft tissue swelling most pronounced in the superior and lateral aspect of the lacrimal gland (Figure 2). Computed tomography of the neck and chest showed mildly enhancing lymph nodes throughout the neck and within the parotid gland (Figure 2). Serologies were positive for antinuclear antibody, double-stranded DNA, rheumatoid factor, centromere B, SSa/SSb, and low C3 and C4.
      Figure thumbnail gr2
      Figure 2Orbital computed tomography (CT) scan with contrast (left top and left bottom) reveals left orbital soft tissue swelling most pronounced in the superior and lateral aspect of the lacrimal gland with increased contrast enhancement. Neck CT (right) demonstrates numerous mildly enhancing lymph nodes in neck and parotid gland.
      Left lacrimal gland biopsy revealed patchy, severe chronic dacryoadenitis with ductal epithelial infiltration by small lymphocytes, epithelial apoptosis, and lymphoepithelial lesions, classically seen in Sjögren syndrome (Figure 3). Cultures for bacteria and mycobacteria of the biopsy specimen were negative. To confirm the diagnosis of Sjögren syndrome, a salivary gland biopsy was performed. This revealed predominantly chronic periductal inflammation with patchy lobular lymphoplasmacytic inflammation, with a focus score of 2 (>100 lymphocytes adjacent to glandular tissue and surrounding a duct in a 4-mm2 area of glandular tissue) (Figure 4).
      Figure thumbnail gr3
      Figure 3Histopathology of left lacrimal gland biopsy. Photomicrograph of lacrimal gland biopsy shows chronic dacryoadenitis, a lymphoepithelial lesion, and infiltration of ductal epithelium by lymphocytes. H&E stain, 200× magnification.
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      Figure 4Histopathology of salivary gland biopsy. The salivary gland biopsy shows lymphocytic infiltrates surrounding ductal epithelium and acini with focus score of 2. H&E stain, 200× magnification.

      Diagnosis

      Sjögren syndrome is an autoimmune disorder characterized by lymphocytic infiltration of exocrine glands, classically causing dry eyes and dry mouth.
      • Sjogren H.
      Zur Kenntnis der Keratoconjunctivitis Sicca (Keratitis filiformis bei Hypofunktion der Tranendrusen).
      Sjögren syndrome may be a primary disease or can be secondary to autoimmune diseases such as systemic lupus erythematosus or rheumatoid arthritis. Sjögren syndrome frequently causes extraglandular ocular and systemic complications such as arthritis, peripheral neuropathy, and interstitial lung disease.
      • Oxholm P.
      • Asmussen K.
      • Axéll T.
      • et al.
      Sjögren's syndrome: terminology.
      • Akpek E.K.
      • Mathews P.
      • Hahn S.
      • et al.
      Ocular and systemic morbidity in a longitudinal cohort of Sjögren's syndrome.
      The American-European Consensus for the diagnosis of Sjögren syndrome includes six criteria. Two of these are subjective: I. ocular symptoms of dry eyes; and II. oral symptoms of dry mouth or swollen salivary glands. Four of these are objective: III. ocular signs of dry eyes and decreased tear production; IV. histopathology of salivary gland biopsy showing focal lymphocytic sialoadenitis; V. oral signs of decreased salivary flow; and VI. positive autoantibodies of SS-A or SS-B. For a diagnosis of primary Sjögren syndrome, one must satisfy any 4 of the 6 criteria and must include IV or VI, or any 3 of the 4 objective criteria (III, IV, V, or VI). For a diagnosis of secondary Sjögren syndrome, the patient needs to have a well-defined major connective tissue disease, and satisfy 1 of the 2 subjective, and 2 of the 4 objective criteria.
      • Fox R.I.
      Sjögren's syndrome.
      • Vitali C.
      • Bombardieri S.
      • Jonsson R.
      • et al.
      Classification criteria for Sjögren's syndrome: a revised version of the European criteria proposed by the American-European Consensus Group.
      Our patient satisfied one of the subjective, and 3 of 4 objective criteria for Sjögren syndrome. In addition, she satisfied the diagnostic criteria of systemic lupus erythematosus given her malar rash, arthritis, and antinuclear antibody as well as anti-dsDNA positivity. Therefore, she was diagnosed with acute dacryoadenitis in the setting of systemic lupus erythematosus and secondary Sjögren syndrome.

      Management

      This patient was started on a daily regimen of prednisone (20 mg per day) and Plaquenil (300 mg per day). She had rapid improvement, and her orbital signs and symptoms resolved in 1 week.
      It is important to note that patients with Sjögren syndrome often present with eye symptoms. Interestingly, clinically acute onset dacryoadenitis as seen in this patient is not a common initial presentation of Sjögren syndrome, and rarely reported.
      • Akpek E.K.
      • Mathews P.
      • Hahn S.
      • et al.
      Ocular and systemic morbidity in a longitudinal cohort of Sjögren's syndrome.
      • Satue M.
      • Garcia-Martin E.
      • Bambo M.
      • Prieto E.
      • de la Mata G.
      • Fernandez-Peri S.
      Acute dacryoadenitis as atypical presentation in Sjögren Syndrome.
      More common ocular manifestations of Sjögren syndrome at initial presentation include dry eyes, conjunctivitis, corneal haze and scarring, and corneal perforation.
      • Akpek E.K.
      • Mathews P.
      • Hahn S.
      • et al.
      Ocular and systemic morbidity in a longitudinal cohort of Sjögren's syndrome.
      Indeed, symptoms of dry eye can precede other systemic findings up to 10 years.
      • Akpek E.K.
      • Mathews P.
      • Hahn S.
      • et al.
      Ocular and systemic morbidity in a longitudinal cohort of Sjögren's syndrome.
      Therefore, chronic dry eye patients with positive review of systems should be thoroughly evaluated for Sjögren syndrome. Sjögren syndrome is an independent risk factor for non-Hodgkin's lymphoma. These patients have a 44-times-higher relative risk than the general population to develop lymphoma.
      • Kassan S.S.
      • Thomas T.L.
      • Moutsopoulos H.M.
      • et al.
      Increased risk of lymphoma in sicca syndrome.
      Therefore, they require long-term follow-up for this complication.

      References

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        Ocular and systemic morbidity in a longitudinal cohort of Sjögren's syndrome.
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        Sjögren's syndrome.
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        Classification criteria for Sjögren's syndrome: a revised version of the European criteria proposed by the American-European Consensus Group.
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        • Garcia-Martin E.
        • Bambo M.
        • Prieto E.
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        Acute dacryoadenitis as atypical presentation in Sjögren Syndrome.
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