Dr. Debashish Danda discusses the lesser-known and often misunderstood Sjogren’s syndrome. He also reveals its data-based reality and prevalence among Indians.

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'Sjogren' is a German word, pronounced as ‘show-grin'. The syndrome was earlier identified as a dry-eyes or a dry-mouth disease. Due to the lack of complete information about the syndrome, physicians and rheumatologists often overlook the possibility of Sjogren’s in a patient. They misunderstand the symptoms and do not know for sure, what symptoms to look for.

In this article, we will debunk several myths surrounding the symptoms of the disease and offer more insights on the syndrome.

Myths vs Facts

Myths	Facts
Sjogren’s is a dry-eye or dry-mouth disease.	It is a multisystem disease so patients will not approach physicians only for eye-related complaints. To elaborate further, Sjogren’s syndrome is a chronic autoimmune exocrinopathy with multisystem involvement.
Sicca symptoms are common to patients of Sjogren’s.	Majority of the patients are not even bothered by it and you may not come to know unless you ask them about a broad description of the history of their symptoms.
Sjogren’s is rare among the Indian population.	Again, untrue! The reality is that the disease is grossly underdiagnosed.

 

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What is the common perception of Sjogren’s in India?

Up until the last 2 to 3 years, most physicians and rheumatologists had a knowledge bias that a Sjogren’s patient can either have completely destroyed glands. Doctors, depending upon their knowledge of the syndrome and their specialty and/or hospital, look for different symptoms. Some common symptoms that doctors look for include salivary gland enlargement and lacrimal gland endotrophy.

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How to identify Sjogren’s syndrome; what symptoms should you look out for?

Sjogren’s is a complex heterogenous disease. A rheumatologist could check for any chronic inflammatory non-deforming or Jaccoud-type arthiritis. There could also be chronic pain with fibromyalgia features, premature loss of teeth, and/or poor oral dental-gingival hygiene.

A doctor may ask the patient his history for oral or ocular Sicca symptoms, dry skin, dyspareunia and hypokalemic periodic paralysis. One can identify Chronic inflammatory demyelinating polyneuropathy (CIDP) patients and look for Sicca symptoms or other features of Sjogren’s, such as small vasculitis or medium vessel vasculitis. Occult Sjogren’s syndrome can also be there and extra-glandular features can precede many years before Sjogren’s syndrome.

Lacrimal gland endotrophy is less common but if suspected, the patient should be prescribed Schirmer’s test and lip biopsy; the pathologist should be familiar with scoring to enable diagnosis of Sjogren’s syndrome.

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Is Sjogren’s syndrome really rare in India?

The understanding of the syndrome among Indian physicians and rheumatologists has now improved on diagnostic armamentarium. It is a low-grade disease, which presents with varied protean manifestations. There are thirteen criteria till date and there is varied prevalence reported in literature but, it is mostly underdiagnosed.

Looking at the worldwide data on Sjogren’s, the prevalence range was 0.00045 to up to 5%, with consideration for inconsistencies, changing criteria, and ethnic and geographic variations. The modest estimate now is 0.5% of the population, almost the same as rheumatoid arthritis.

A Chinese study from 2010 reported their patients to be younger with less Raynaud’s and more of seropositivity. A study was also done for Indian patients, titled “Clinical Characteristics and Outcome of Primary Sjogren’s Syndrome: A Large Asian Indian Cohort”. It presented a retrospective analysis for clinical and immunological outcomes. The American-European Consensus Group (AECG) criteria available those days were also looked at. Any secondary Sjogren’s and overlaps were ruled out. Exclusions as described in AECG were also ruled out. Some people fulfilled the AECG criteria and yet, were suspected for Sjogren’s. However, the Sicca criteria helped with objectivity in the outcomes, which showed that the disease is not as rare as it was thought.

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How is the Sicca criteria used for diagnosing Sjogren’s syndrome?

The Sicca criteria has been modified. It has been adjusted after exclusion of other antibodies and inclusion of IgG4 diseases. In an Indian study of 423 patients who were screened, 294 fulfilled the AECG criteria and 129 did not fulfil it. Of these, 91 fulfilled the Sicca criteria, which we can call American College of Rheumatology (ACR) criteria. So, there were 332 patients with definite Sjogren’s. [1]

The findings pertaining to Sjogren’s made basis the Sicca criteria were:

• High female predominance, much more than any ocular disease
• Mean age was around perimenopausal age but younger than the western population of Sjogren’s
• Mean duration of delay in diagnosis was 5 years
• Presenting features, with a rheumatology clinic bias, was 2/3rd patients had arthralgia and arthritis
• Sicca was present in only 8.1% of patients, which meant that only 8.1% patients had a clear complaint of Sicca symptoms; the remaining also could have had it
• 6.3% from 20% of patients had chronic pain syndrome
• Other clinical features such as dry eye, dry mouth were present in 90% of patients
• Schirmer’s test was positive in 90%, lip biopsy was positive for those who were tested, and antibodies were present in about 2/3^rd of the patients
• SS, SSA positivity, anti-nuclear antibody (ANA) test and rheumatoid factor test positivity were found in about 60% of patients
• 121 out of 332 patients had systemic features, including vasculitic features and other neurological major organ involvement
• As per the slide, the skin showed a whole lot of manifestations, including palpable purpura, ILD as well as other obstrective error disease; there was mononeuritis multiplex, CIDP-like features, GI – irritable bowel syndrome and autoimmune hepatitis and so on
• There was haematological citopenias, interstitial nephritis and few had glomerulonephritis
• Bad obstetric instances were found in 14 patients but out of them only 2 had APS and almost all of them had SS, SSB positivity
• Two different clusters emerged on analysis- One is mild manifestations with chronic pain, arthritis, arthralgia, dental, Sicca and another, where patients had serious problems such as vasculitis, major renal tubular acidosis (RTA), and seropositivity
• Predictors of systemic involvement were present when SSA-SSB antibodies were found in high titers with odds ratio of 3.4 and 2.26 respectively
• The chronic pain syndrome at the bottom had a negative predictive value.
• The patient had fibromyalgia features, in Sjogren’s they do not have major systemic features and they do not have seropositivity.
• The likelihood ratio was worked out and it was found that the high titres anti-SSA and anti-SSB had 2 to 3 times more likely systemic vasculitic manifestations involving renal and neurological systems
• Only 5 patients were found to have malignancies out of this large series

When compared with different populations across the world, it was discovered that Indian patients have a younger age of onset, had delayed diagnosis, less of Raynaud’s, and high titre seropositivity. They were also found to have very less hyperglobulinaemia.

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Objectivity in diagnosis of Sjogren’s

The ACR/EULAR criteria is much more objective and this is an effective scoring system that helps diagnose Sjogren’s with much more definitiveness. [2]

	2002 AECG criteria	2016 ACR / EULAR criteria	Weight
Items	1. Ocular dryness symptoms 2. Oral dryness symptoms 3. Ocular signs: Schirmer’s test ≤5 mm/5 min or van Bijsterveld score ≥4 4. Focus score ≥1 foci/4 mm2 on minor salivary gland biopsy 5. Salivary gland involvement: unstimulated whole salivary flow ≤0.1 mL/min 6. Positive anti-SSA or SSB antibodies	1. Labial salivary gland with focal lymphocytic sialadenitis and focus score of ≥1 foci/4 mm2	3
		2. Anti-SSA/Ro-positive	3
		3. Ocular Staining Score ≥5 (or van Bijsterveld score ≥4) in at least one eye	1
		4. Schirmer’s test ≤5 mm/5 min in at least one eye	1
		5. Unstimulated whole saliva flow rate ≤0.1 mL/min	1
Rules for classification	− Absence of exclusion criteriaa − Presence of any 4 of the 6 items with at least item 4 or 6, or − Presence of any 3 of the 4 objective items (3, 4, 5, and 6)	Applies to any individual: − who meets the inclusion criteriab with at least one symptom of ocular or oral dryness or ESSDAI ≥1 − does not have any of the conditions listed as exclusion criteriac − and has a score of ≥4 when the weights from the 5 criteria items are summed

AECG American-European Consensus Group, ACR American College of Rheumatology, Sjogren’s syndrome, ESSDAI EULAR SS Disease Activity Index, anti-SSA anti-Sjogren’s-syndrome-related antigen A

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Insights on Sjogren’s based on big data

Another study titled “Systemic manifestations of primary Sjogren’s syndrome out of the ESSDAI classification: prevalence and clinical relevance in a large international, multi-ethnic cohort of patients” was based on European Sjogren’s Syndrome Disease Activity Index (ESSDAI) scoring system. [3]

What the study shows:

1. More than 1/4^th of patients in the Sjogren’s Big Data group had systemic manifestations
2. Sjogren’s is a like a mild lupus and can affect almost everything
3. The auto-antibodies correlate to major manifestations
4. Some of the organ-specific clinical manifestations are:
   1. Neurology with mononeuritis multiplex
   2. CIDP or unexplained thrombocytopenia or lymphoma
   3. Pulmonary- Interstitial lung disease, or lymphocytic interstitial pneumonia
   4. Nephrology- Interstitial nephritis
   5. Obstetrics- Foetal loss
   6. ENT- Recurrent parotid enlargement
   7. Paediatrics- Recurrent parotid enlargement
   8. Dermatology- Vascular manifestations
   9. Urological urolithiasis and interstitial cystitis
   10. Cardiovascular Raynaud’s and pulmonary arterial hypertension

Just like how a bamboo spine is too late in ankylosing spondylitis, similarly, in Sjogren’s syndrome, if you wait for parotid involvement or very significant dry eye and dry mouth, it is too late. Times have changed. Only when questions enable the patient to give in-depth answers, revealing their history, can we ensure the correct diagnosis of Sjogren’s.

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This document is a transcription of a portion of a webinar conducted by Dr. Debashish Danda. While it is believed to be accurate, it is not warranted to be so.

The views and opinions expressed in this article are those of the speaker's and do not necessarily reflect the official policy or position of M3 India.