Discussion
This case highlights a rare presentation of pSS. The patient developed bilateral ptosis along with prominent eyelid swelling which evolved to the extent that she could not lift her eyelids to see. Eyelid swelling has been reported in primary Sjogren’s syndrome but to our knowledge, this is the first case in which the swelling has evolved to the extent that impairs the patient’s ability to lift open her eyes.4 Sjogren syndrome has a multitude of ophthalmological manifestations ranging from chronic conjunctivitis, sterile keratolysis, and non-healing corneal ulcers, but lacrimal gland involvement is reported to be rare.1,5
Due to her initial presentation with ptosis and eyelid swelling along with a positive anti-acetylcholine receptor antibody test, we presumed her to be a case of MG and she was given a therapeutic trial of pyridostigmine to which she failed to respond. This made us reconsider her initial diagnosis of MG and we started her autoimmune workup. Our case is unique in this aspect as well because MG and Sjogren’s syndrome very rarely co-exist in the same patient and very few cases have been reported in the current literature. 6,7,8 There are many diagnostic modalities for MG including Ice pack test, Tensilon test, Anti-acetylcholine receptor antibodies, Repetitive nerve stimulation, and Electromyography, all with varying sensitivity and specificity.9 Of these, the positive titer of anti-acetylcholine receptor antibodies has the highest specificity (97-99%) for the diagnosis of MG. 10 Our patient had no typical signs or symptoms of MG aside from ptosis but she had a positive titer of anti-acetylcholine receptor antibodies. We proceeded with repetitive nerve stimulation tests which showed no incremental or decremental response hence ruling out generalized MG but not ocular MG. A positive titer for this assay in the absence of typical signs and symptoms, a negative therapeutic trial of pyridostigmine and electrodiagnostic studies ruling out generalized MG could mean that the test result was spuriously positive in our patient. The pathogenesis of false positive antibody test results in the context of autoimmune diseases is very interesting and has been reported in a number of other autoimmune diseases as well 11,12. These false positive antibody results can be attributed to the phenomenon of heterophil antibody interference in which some of the patient’s antibodies react with the immunometric sandwich assays and cross-link the assay antibodies yielding a false positive test result.13 Heterophil antibody interference has been well documented in the literature and there are examples of catastrophic patient outcomes due to this phenomenon such as the HCG scandal in which false positive HCG levels, later attributed to heterophil antibodies, caused unnecessary treatment in a number of women.14Heterophile antibodies are common in autoimmune diseases and should be suspected in cases of positive antibody titers in absence of a solid clinical picture of the disease and clinicians need to be made aware of this phenomenon. If such a spurious test result is encountered either on a single occasion or repeatedly, it should be followed by confirmatory testing and taking the clinical context into account. Our case thus highlights the importance of interpreting antibody test results in the context of clinical findings as our patient did not have MG despite a positive anti-acetylcholine receptor antibody test result indicated by a negative therapeutic trial of pyridostigmine and electrodiagnostic studies.
The recent 2016 ACR-EULAR Classification Criteria for primary Sjögren’s Syndrome is most commonly used to establish a diagnosis of pSS.15 On the basis of focal lymphocytic sialadenitis upon labial salivary gland biopsy, positive Anti-SSA(RO) antibodies, and positive Schirmer test, our patient scored seven out of nine where a score of 4 or more is required for a definite diagnosis of pSS.
Based on the HRCT findings, our patient was also had co-existent bronchiectasis, because of which she could not be started on immunosuppressive therapy for pSS immediately until the pulmonary infection had been resolved. Pulmonary involvement is an extraglandular manifestation of pSS and it can be in the form of both interstitial parenchymal disease and airway disease. Bronchiolitis and bronchiectasis are the common airway lung diseases seen in pSS. The prevalence of bronchiectasis is up to 10% with involvement of the inferior lobes being more common.16 Cylindrical bronchiectasis is the most common type seen and patients of bronchiectasis have a higher frequency of respiratory infections and pneumonia.17Our patient similarly had bilateral cylindrical bronchiectasis involving all of the lung lobes along with a positive sputum culture for Klebsiella pneumoniae thus indicating an infective etiology coexisting with her autoimmune pulmonary manifestation. The pathogenesis of pulmonary involvement in pSS seems to involve epithelial damage due to any environmental factor such as infection or an extension of the primary immune response in salivary glands, followed by epitope spreading, antigen presentation and lymphocyte activation, formation of antibodies and release of cytokines leading to an inflammatory state damaging airways and lung parenchyma.16 Pulmonary involvement also proved to be a challenge in management as we had to control the infective etiology with antibiotics prior to commencing immunosuppressive therapy to avoid a flare-up of the lung disease.