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.