The document describes the journey of a patient, Marion, in receiving a diagnosis of Sjögren's syndrome over several years. Marion experienced non-specific symptoms like fatigue, high blood pressure, and dry mucous membranes. Testing revealed anemia and slightly abnormal kidney and electrolyte levels, but nothing conclusive. Eventually, it was determined that Marion's symptoms aligned with Sjögren's syndrome, an autoimmune disease where the immune system attacks moisture-producing glands. Sjögren's syndrome can vary in severity and sometimes leads to other health issues, but most patients experience only mild effects and mortality rates are low. The document discusses the challenges of diagnosing Sjögren's syndrome due to its low frequency

1. NathanBornstein
MLAB-2238
1
Requiem for a Diagnosis
The purpose of the title serves the overall nature of what I’ve interpreted this particular
patient’s (as well as the many physicians’ involved in the) journey into coming to a final
diagnosis. Requiem in the traditional sense is a mass or celebration in the Catholic religion that
honors the dead and their souls that have since passed on. Through countless diagnoses, some
leading in the right direction and others not, all have been incorrect in identifying the main
spectrum causing the secondary symptoms until very recently. And so, I feel that this title is
appropriate in pointing out how many diagnoses haven’t been specific enough and have since
been discarded from the main problem at hand, but have been paramount in their assistance to
discovering the etiologic factor.
For the better part of the last five years or so, this patient (herein referred to as Marion)
had and has been experiencing nondescript symptoms; malaise, lethargy, hypertension (HTN)
and a general feeling of uneasiness. In fact, the most specific symptom related to Marion’s final
diagnosis was that of a lack of moisture in the majority of her mucous membranes (dry mouth,
eyes, etc.). It is understandable, however, that it took as long as it did for such a prognosis to be
made. The onset and course for this condition is rather insidious with very few discernible clues
to arrive at its’ conclusion. The location most commonly affected by this condition are the
various glands throughout the body. It is an autoimmune disease and lymphocytic infiltration is
present at the glands in the form of glandular lesions. It is also hypothesized in literature that the
condition is composed of two distinct stages in terms of the immunolytic process; first there is a
lymphocyte-independent lysis causing unnecessary apoptotic damage to the cells of the affected
gland. This lysis releases chemical signals that initially attract lymphocytes to the area of
destruction. This damage then propagates an immune response catalyzing an increased reaction
of antigen mediated destruction, termed the lymphocyte-dependent stage1. The curious aspect of
Marion was that her lab work revealed a lymphocyte level that correlated within the reference
range, albeit on the lower spectrum; these findings may suggest that the two-stage process may
be occurring with sufficient leukopoiesis or that the process is not occurring at all. I’d like to
note here the insidious nature of this disease. Without further genetic testing, it is difficult to
pinpoint the specific mechanisms at play. Routine testing revealed an anemic state with lowered
hemoglobin and hematocrit, as well as an increased red cell distribution width (RDW).
Chemistries showed an increased creatinine level and slightly elevated potassium, along with a
lowered estimated glomerular filtration rate (eGFR) and slightly decreased sodium. These
findings are very generic, as well as unremarkable and don’t point towards anything specific
related to the primary diagnosis. In large part and interestingly, the patient’s symptoms, rather
than the signs, have better identified the “typical” characteristics associated with the syndrome. It
goes without saying that this is usually not the case in most clinical diagnoses.

2. NathanBornstein
MLAB-2238
2
According to Borchers, et. al., this disease is strongly associated with a genetic
predisposition in its inheritance1. Studies on the polymorphisms of human leukocyte antigen
(HLA)-DR and HLA-DQ gene regions in this syndrome show differential susceptibility to the
syndrome due to different types of the resulting autoantibody production. A hormonal link may
also predispose an individual towards developing conditions that resemble this condition;
estrogen levels are thought to play a part in the humoral and cell-mediated impaired immune
responses. However, a combination of environmental and other factors, such as lifestyle, may
come into play as well. It has been hypothesized that the Epstein-Barr Virus (EBV), the Hepatitis
C Virus (HCV) and the Human T-Cell Leukemia Virus (HTLV) are culprits in antagonizing the
condition to arise2. However, Marion lacked any previous diagnoses of any of these possible
environmental and lifestyle factors, hinting at a genetic cause.
Currently, there are no identified cures in restoring glandular function and most treatment
regimens consists of symptomatic and supportive care. Dry mucous membranes characteristic for
this process are simply treated with artificial tears3. It has also been recommended that goggles
be worn for extended relief in helping maintain a moist environment around the periorbital
region. Punctal plugs, a small medical device, have also been recommended to block the tear
duct (puncta). This prevents any drainage from occurring and thus, to keep moisture localized.
Pharmaceuticals for maintaining orbital moisture have also been suggested via the use of
cyclosporines (Restasis). Women that have this condition may also experience vaginal dryness
and thus, a vaginal lubricant is recommended in preventing any irritation or pain that may result.
Chronic dry mouth may be treated with regular hydration, as well as lozenges and over-the-
counter dry mouth treatments. It should be noted that dental hygiene is of importance as dry
conditions within the mouth favor the bacteria responsible for dental caries. Regular visits to the
dentist and dental prophylaxis are of great importance to prevent this from occurring4
.
The disorder that Marion currently experiences is referred to as Sjögren's Syndrome. The
numerous tests conducted and procedures performed in piecemeal fashion have been supportive
in making this prognosis and the eventual diagnosis of Sjögren's Syndrome. The low frequency
of this disease makes it difficult to correctly diagnose, as many of the signs and symptoms do not
point to anything in particular and can have a wide spectrum of any one disease state. Sjögren's
Syndrome has the propensity to damage other vital organs of the body that may increase or
decrease in severity, as is typical with most autoimmune diseases. Some may experience very
mild to moderate symptoms as detailed above, while others may undergo severe secondary
complications, such as renal dysfunction (renal tubular acidosis in particular), rheumatic
disorders (rheumatoid arthritis, systemic lupus erythematosus and systemic sclerosis) or even
progress to malignant Non-Hodgkin’s Lymphoma (NHL), though the majority don’t progress to
NHL. Overall, most patient’s with Sjögren's Syndrome show only modest or clinically
insignificant deterioration in specific organ-related function. The mortality rate associated with
Sjögren's Syndrome is relatively low, with only slight increases in mortality rate relative to the
remainder of the population4.

3. NathanBornstein
MLAB-2238
3
Works Cited
1. Borchers, A. T., Naguwa, S. M., Keen, C. L. & Gershwin, M. E. Immunopathogenesis of
Sjögren's syndrome. http://www.ncbi.nlm.nih.gov/pubmed/12794264; Clin. Rev. Allergy
Immunol. 25, 89-104 (2009)
2. Voulgarelis, M. & Tzioufas, A. G. Pathogenetic mechanisms in the initiation and
perpetuation of Sjögren's syndrome.
http://www.nature.com/nrrheum/journal/v6/n9/abs/nrrheum.2010.118.html; Nature
reviews.Rheumatology 6, 529-537 (2010)
3. Delaleu, N., Jonsson, R. & Koller, M. M. Sjögren's syndrome.
http://www.ncbi.nlm.nih.gov/pubmed/15819815; Eur. J. Oral Sci. 113, 101-113 (2005)
4. Fox, R. I. Sjögren's syndrome. http://www.ncbi.nlm.nih.gov/pubmed/16039337; Lancet
366, 321-331 (2005)