Case presentation:
A 27-year-old woman presented to our Rheumatology department with the complaint of periorbital swelling for the past five months. Prior to coming to our clinic, she presented to the Neurology department of one of our allied hospitals, Benazir Bhutto Hospital with a complaint of drooping of eyelids for the last three months where she was presumed to be a case of MG on the basis of positive anti-acetylcholine receptor antibodies. She was given a therapeutic trial of pyridostigmine but she failed to respond to the treatment and was referred to our rheumatology clinic for an autoimmune workup.
The periorbital swelling was gradual, bilateral, and had progressed to the degree that the patient could not lift open her eyelids and had to open them with her fingers to be able to see. Figure 1 shows the extent of her ptosis and eyelid swelling. It was not associated with any pain, redness, discharge, loss of vision, or diplopia. Upon systemic inquiry, she complained of undocumented weight loss, productive cough for the past three months, dry gritty eyes, dry mouth, hair loss, and a photosensitive facial rash. There was no significant family history of disease other than her father who was treated for tuberculosis 10 years back.
On clinical examination, our patient had periorbital puffiness with closed palpebral fissures, there was no redness or discharge, and she had normal extraocular eye movements. There was no assessable lymphadenopathy and none of the salivary glands were palpable. On oral examination, Schirmer test was positive with less than five mm tear production in five minutes which is suggestive of dry eyes. On respiratory examination, bilateral coarse crepitations were heard. Her neurological examination was unremarkable and muscle strength and endurance in all muscle groups was normal which was in contrast to the symptoms of MG. We could not perform all the provocative maneuvers for ocular MG (sustained upgazed, Herring’s sign, peek sign) because of marked eyelid swelling that impaired lifted the eyelids. There was no fatigable diplopia. The rest of the systemic examination was normal.
Peripheral blood test results were as follows: hemoglobin 14.0 g/dl, total leucocyte count 14000/mm3, neutrophils 70.2%, lymphocytes 25.1%, mixed 5.7%, red blood cells 4.21 million/mm3, platelets 223000/mm3, hematocrit 38.9%, erythrocyte sedimentation rate 44mm/hour, C-reactive protein 4.1 mg/L, Serum biochemical testing results were as follows: serum urea 3.0 mmol/L, serum creatinine 55 umol/L, serum sodium 137 mmol/L, serum potassium 4.6 mmol/L, alanine aminotransferase 15 U/L, alkaline phosphatase 86 U/L, total bilirubin 0.4 mg/dl. The results of her autoimmune workup are displayed in Table 1 . Repetitive nerve stimulation showed no significant decremental or incremental response which helped rule out generalized myasthenia gravis but not ocular myasthenia.
We proceeded with a High-Resolution Computed Tomography (HRCT) scan of her chest which revealed bilateral cylindrical bronchiectasis involving all lung lobes, consolidation in the right lower lobe, and mild pleural effusion. PCR was negative for COVID-19, sputum for Gene Xpert, and QuantiFERON TB gold test were also negative. Sputum culture revealed heavy growth of Candida and Klebsiella Pneumoniae. Magnetic Resonance Imaging MRI of the brain and orbits revealed bilateral symmetrical homogenous enlargement of lacrimal glands with accompanied symmetrical swelling and edematous changes in bilateral pre-septal and para-septal soft tissues. Figure 2 shows these MRI images prior to commencing therapy .
We considered primary Sjogren syndrome, systemic lupus erythematosus as she gave a history of a photosensitive facial rash, ocular myasthenia with idiopathic orbital inflammation as she gave a history of ptosis and periorbital inflammation, sarcoidosis, ANCA associated vasculitis and IgG4 related orbital pseudotumor as our differential diagnoses. We had ruled out SLE, sarcoidosis, ANCA associated vasculitis on the basis of autoimmune investigations all of which were negative for corresponding antibodies. Myasthenia Gravis was ruled out on the basis of electrodiagnostic studies. As she tested positive for Anti SSA antibodies, we proceeded with a lip biopsy to confirm the diagnosis of primary Sjogren’s syndrome and to rule out IgG4-related disease. The lip biopsy indicated normal-looking mucinous acini with lymphocytic infiltrate. There were four microscopic foci of lymphoid aggregates per 4 mm2, with no evidence of plasma cells and fibrosis (hence ruling out IgG4-related disease), suggestive of primary Sjogren syndrome (pSS). Figure 3 shows the histopathological images of her lip biopsy .
Pulmonology consultation was sought and she was started on an antibiotic cover to control infective pulmonary etiology prior to beginning immunosuppressive treatment for pSS. The patient was advised Acetylcysteine, Azithromycin 250mg for three months along with Influenza and Pneumococcal vaccine. After her chest infection subsided, we started her on Hydroxychloroquine 200 mg/day, Azathioprine 2.5 mg/kg/day, and Prednisolone 0.5 mg/kg/day. Cyclophosphamide was deferred because we believed it would worsen her bronchiectasis. The patient was referred for an ophthalmology consultation for her persistent eyelid swelling and the consensus was to control her primary disease process which would ultimately resolve her swelling. As the persistent swelling was hampering her ability to see, she underwent a sling procedure to open her eyelids. Figure 4 shows an image of the patient after her sling procedure . Though the swelling had considerably subsided on therapy, her lacrimal gland were persistently inflamed, we shifted her towards a biological agent Rituximab, 1g IV infusion. She has received two doses and the next dose is scheduled for after 6 months.