SJOGREN'S IS SYSTEMIC
(It affects your entire body.)

Key Concepts

Sjogren’s manifestations include sicca (dryness) and systemic (non-sicca) manifestations.

Sjogren's is always systemic, never just dryness. The Sjogren's Is More Than "Just Sicca" handout shows how we know this.

This page describes systemic manifestations, using these three categories:
Classic (ESSDAI) Manifestations
Other (non-ESSDAI) Manifestations
General Systemic Manifestations

Systemic manifestations are not limited to those measured by the ESSDAI.

Manifestations are not the same thing as symptoms. Manifestations are disease states that are associated with signs (measurable/observed) and symptoms (what the patient feels).

Systemic manifestations are caused directly by Sjogren’s disease; comorbidities are not.
Clinicians sometimes confuse the two. Learn about manifestations vs comorbidities.

Short on time? Read the Sjogren's...Simplified version.

Introduction

Although studies have clearly demonstrated that Sjogren’ is a multisystem disease, many doctors still think of it as a sicca (dryness) disease. Sjogren’s is never a sicca-limited disease. Sjogren’s can impact every organ and system in the body. (38, 243).

One or more systemic manifestations can be found in nearly every Sjogren’s patient who is thoroughly evaluated (38, 92). Despite this, “the evaluation of the systemic manifestations of SS are not properly incorporated into clinical practice” (241).

Knowing how your clinician thinks about Sjogren’s will help you advocate for Sjogren’s care that goes beyond sicca. USER GUIDE FOR HANDOUT: SJOGREN'S IS MORE THAN "JUST SICCA" offers tools and strategies for discussing the serious, systemic nature of the disease with clinicians.

“Systemic” has a special meaning in Sjogren’s.

Sicca manifestations are not referred to as systemic,

even when sicca occurs in multiple areas of the body.

A systemic manifestation occurs when Sjogren's causes damage or dysfunction

to any part of the body that is not a fluid-secreting (exocrine) gland.

Manifestations vs. Symptoms

Patients usually think about diseases based on symptoms. This is because symptoms describe the patient’s experience of the disease.

Clinicians usually think about diseases based on manifestations.
Manifestations are disease states that are associated with signs (measurable/observed) and symptoms (what the patient feels).

Some manifestations have no obvious symptoms. Other manifestations have no obvious signs.
Learn more about signs, symptoms, and manifestations.

How Clinicians Think About Systemic Manifestations

Sicca manifestations often get the most attention in clinical practice and research. Systemic manifestations are often overlooked, downplayed, or misattributed to other conditions. Because there is no consistent medical education about Sjogren's, diagnosis and management varies widely.
Learn more about Sjogren’s rheumatology care.

Systemic disease terms can be confusing, even to clinicians.

Doctors use three different terms to describe the systemic manifestations of Sjogren's.

These terms do not always mean the same thing from one clinician to another.

It is important to ask your doctor what they mean when they use these terms.

Systemic Manifestations (non-sicca manifestations)

These can be divided into 3 categories:

Classic (ESSDAI) Systemic Manifestations,
Other (non-ESSDAI) Systemic Manifestations,
General Systemic Manifestations.

Some clinicians ignore or minimize the manifestations included in the “Other” and “General” categories.

Extraglandular Manifestations (EGM)

This term is used interchangeably with "systemic manifestations". Clinicians and researchers do not use this term consistently. Some of them do not count inflammatory arthritis and joint pain as EGM, even though they are part of the ESSDAI. Major salivary gland enlargement may or may not be included as an EGM.

Systemic vs. Extraglandular

I use the term "systemic manifestations" on Sjogren's Advocate
because "extraglandular manifestations" implies that glandular manifestations (sicca)
are the main feature of Sjogren's and are always present.

This misleading term reinforces the myth that Sjogren's is primarily a sicca disease.

Sicca is common, but just one of many features of the disease
and is NOT present in every Sjogren's patient.

Organ System Involvement

This term has various definitions. Rheumatologists often use it to refer to systemic manifestations that impact the solid organs, e.g., lung, kidney, etc. They may or may not include nerve and skin involvement in this category. As with EGM, clinicians vary widely in their use of this term.

Glandular Manifestations

This term usually refers to sicca (dryness) manifestations, although some rheumatologists use it more broadly to include both sicca and major salivary gland swelling.

TIP: Make sure you are on the same page as your clinician.

Any time you discuss “systemic manifestations”, “extraglandular manifestations”,
or “organ system involvement” with your clinician,
ask them to explain what they mean.

Classic (ESSDAI) Manifestations (10, 37, 38)

ESSDAI stands for the EULAR Sjogren’s Syndrome Disease Activity Index.

The ESSDAI is a scoring system that uses 12 specific “domains” of systemic manifestations as a measure of disease activity. The ESSDAI is not the same as the ESSPRI, which measures patient-reported symptoms.

EULAR stands for the European League Against Rheumatism and is a professional rheumatology organization.

The ESSDAI measures an important subset of systemic manifestations but excludes many others.
Even though the ESSDAI is rarely used in routine practice, it has a big influence on Sjogren’s care.

Some rheumatologists think that the ESSDAI lists all of the important systemic manifestations.

This misunderstanding of the ESSDAI leads to a distorted view of the disease.

ESSDAI

The 12 ESSDAI domains

Constitutional: fever, night sweats, unexplained weight loss
Lymphadenopathy and lymphoma: enlarged lymph nodes or lymphoma
Glandular: swelling of the saliva glands or tear glands (this is not sicca!)
Articular: joint pain or inflammation, morning stiffness
Cutaneous (skin): vasculitis, purpura, erythema multiforma
Pulmonary (lung): multiple types of lung disease
Renal (kidney)
Muscular (myositis)
Peripheral nervous system (PNS): neurologic complications outside the CNS
Central nervous system (CNS): neurologic complications of the brain and spinal cord
Hematological: “cytopenias” not due to another cause, low red blood cells, low neutrophils, low lymphocytes, low platelets
Biological: low complement, high or low IgG, cryoglobulinemia

Learn more details about the ESSDAI here.

non-ESSDAI

Other (Non-ESSDAI) Manifestations (a partial list)

Autonomic disorders (Dysautonomia) is not included
Small fiber neuropathy (SFN) is actually included in the peripheral nervous system domain of the ESSDAI. I list it here because it is usually overlooked.
SFN is missed because clinicians have not been taught that SFN is one of the most common systemic manifestations of Sjogren's. SFN symptoms are often misattributed to fibromyalgia or even functional neurological disorder because of it often has a patchy, scattered distribution.
See SJOGREN'S BY ORGAN AND SYSTEM for more information about small fiber neuropathy.
Carpal tunnel syndrome
Raynaud's phenomenon
Vasculitis of organs in addition to the skin and CNS
Gastrointestinal (GI) manifestations are nearly ubiquitous
Extraglandular eye manifestations such as scleritis, iritis, and uveitis
Severe headaches, including migraines
Pregnancy complications
Serositis, including pericarditis, pleuritis, and abdominal serositis (perotinitis)
Interstitial cystitis, overactive bladder and frequent urinary tract infections (UTIs)
Sensorineural hearing loss
Restless legs syndrome and other sleep disorders

Learn more about non-ESSDAI systemic manifestations here.

GSM

General Systemic Manifestations

The most common general systemic manifestations include fatigue (pathological, not normal tiredness), cognitive dysfunction (“brain fog”), and widespread muscle pain.

There is no strict definition of general systemic manifestations. Symptoms that are characteristic of Sjogren’s but poorly understood are often assigned to this category or disregarded altogether. Some rheumatologists consider general systemic manifestations to be part of a sicca-limited version of Sjogren’s, which is illogical because these features are obviously not caused by sicca or are a part of sicca. The idea of a “glandular” or sicca-limited version of Sjogren’s needs to be put to rest.

A total of 3,622 Sjogren's patients participated in the Sjogren's Foundation 2021 Living with Sjogren's survey. 88% of respondents reported fatigue, 80% had brain fog, and 72% experienced muscle pain (240). These core characteristics of Sjogren’s disease should not be attributed to fibromyalgia, psychiatric issues, or functional disorders.

It's not "all in your head".
Increasing evidence supports a biologic basis for fatigue, brain fog, and widespread muscle pain.
These symptoms appear to be driven in part by neurological and immune system dysfunction (88, 204).

Comorbidities may contribute to these complex manifestations but should not be taken to be their primary cause.

General systemic manifestations are a top concern for most patients.
Multiple studies have shown that fatigue and pain, not dryness, are the primary reasons for reduced quality of life in Sjogren's patients (169, 193). These symptoms occur are common in related diseases such as rheumatoid arthritis and systemic lupus erythematosus, but are more debilitating, on average, in Sjogren’s (27, 99).

Research is urgently needed to better understand the underlying causes of these disabling Sjogren's features. This, in turn, could lead to more effective treatments.