Always Systemic 

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Handout- Page 1

Systemic features can be found in nearly every Sjogren’s patient who is thoroughly evaluated.

Comprehensive care, regardless of serostatus, includes ongoing monitoring for and timely treatment of systemic complications.

Sjogren's is serious. It causes

  • organ/ nerve involvement, including in SS-A negative patients (118,139,159).

  • increased risk of premature death from direct complications and comorbidities. SMR 1.5-4.66 (42, 61,167). An estimated 10% die from direct Sjogren’s complications (24).

  • marked reduced quality of life (QOL) and disability. This is the main concern for most patients (98). Fatigue and pain, not dryness, are the primary reasons for this (27,42,138,161). QOL, on average, tends to be worse than in RA, SSc, SLE (99,187).

Systemic features are often overlooked when they are

  • asymptomatic or mild, such as cytopenias, ↑IgG, ILD, dRTA.

  • symptomatic but not taken seriously, such as brain fog, dysautonomia, SFN.

  • incorrectly attributed to sicca, such as chronic cough from lung disease.

  • not easy to measure, such as fatigue and pain.

  • not included in the ESSDAI* (63), such as GI complications, Raynaud’s.

  • misclassified as SLE or RA due to the incorrect view that Sjogren’s is not systemic (23).

Sjogren’s is never just a sicca (dryness) disease

At least one systemic feature as measured by the ESSDAI* can be found in 70-80% of Sjogren’s patients at presentation (6192), and more than 90% after 6 years (38).

“A large number of non-sicca features appear up to 20 years before development of sicca symptoms” (42).

*The ESSDAI is a tool used by Sjogren’s researchers to measure systemic disease. Although it is rarely used in the clinic setting, some rheumatologists interpret “systemic” to mean those in the ESSDAI list. Many systemic manifestations are not included in the ESSDAI.
See for more information. 

Handout- Page 2

Most studies are small, retrospective, and limited to a few features. As a result, systemic involvement tends to be underestimated.  

VERY COMMON: More than half of patients impacted
Pulmonary- 50-75%-unselected patients, based on HRCT/ and PFT (54,102,158)
Articular- 50-75 % (42,79,123) w/ 5-16 % inflammatory arthritis (172) often misdiagnosed as RA 
GI- 95%, multiple: GERD, gastroparesis, gastritis, pancreatic insufficiency, dysbiosis/SIBO, dysmotility,  dysphagia (79,112) malabsorption. ↑liver enzymes 40%, AIH 1-4%, PBC 2-5% (79)
CNS- 4%-25% (42,85) plus headache, including migraine- 50-78% (41,176)
PNS- 50-70% includes LFN (32), cranial neuropathy 16-20% (79), SFN 16-25% (96,175,180)  
Dysautonomia (DYS) > 50% (50,53,87)  Sensory neural hearing loss (SNHL) 54 % (73)
SFN and DYS- the largest group, are underdiagnosed, and often dismissed/psychologized.  

General systemic features are core Sjogren’s manifestations, biologically based, not part of sicca. Often incorrectly attributed to fibromyalgia (186) or depression (100,101). 
    Disabling fatigue-70-86% (26,79,152) - probably immune, PNS/dysautonomia and CNS
    Brain fog/MCI- 50-80% (26, 86) - should be considered CNS, but rarely included
    Myalgias/widespread pain- 70% (79) likely d/t SFPN (149,184) NOT “fibromyalgia”

COMMON: 10-50% of patients impacted
Constitutional- low-grade fever, night sweats, weight loss-?10% (not including fatigue) (79)
Hematologic (Cytopenias) -30% (3,146)  AIHA, ITP may occur.
Biologic- 30-50%  Cryoglobulinemia- 10-30% (79) ↓C3 or C4 10-15% (3,79) ↑ IgG 20-50% (79) ↓IgG 5%  MGUS 10% (79)
Extraglandular eye manifestations (uveitis, scleritis, corneal ulcers)-10-30% in a tertiary center (156)
Skin-10-20% Cutaneous vasculitis, annular erythema 10% (3,79), others. More if xerosis is included.
Kidney- 10-50%, 5-10% progress to end-stage kidney disease (79).
TIN, usually mild, present as dRTA 10-50% (79,154,155), glomerulonephritis 4% (12) kidney stones (42) nephrogenic DI 17-28% (79)
Lymphadenopathy- 8-32% (79)
Glandular-30-50% (38,47,79) This is major salivary gland swelling, not sicca.
Raynaud’s-10-30% (3,81)
IC, irritable/overactive bladder- 27-75% (170,171)

Potentially fatal: Varying percentages. Early intervention is key. 
lymphoma 5-10 % lifetime risk (79), ILD, PAH, vasculitis, renal failure from GN, multiple myeloma, and comorbidities such as serious infection and cardiovascular disease (42,80). 

Please refer to the Glossary for unfamiliar terms and abbreviations.