Lupus and connection with other
autoimmune conditions
Ummara Shah, M.D.
LUPUS EDUCATION DAY
October 25, 2014
Example Case 1
 KS is a 24 year old woman with a history of hypothyroidism
due to autoimmune thyroiditis. She was diagnosed with
hypothyroid at age 17 after developing symptoms of fatigue,
weight gain, dry skin and hair.
 She was started on supplemental thyroid hormone with
improvement in her symptoms
 For the past 6 months she has developed joint pain in her
hands and wrists. She also has noticed development of a
pink rash across her cheeks, that is worse after being in the
sunlight.
 She was evaluated by a rheumatologist and diagnosed with
lupus based on her symptoms and blood-work
Example Case 2
 SG is a 48 year old hispanic woman who was relatively healthy
until 6 months ago when she developed stiffness, swelling and
pain in the joints of her hands, wrists, and knees. She also reports
developing a red raised rash when out in the sun.
 She was evaluated by her rheumatologist and found to have
significant swelling of her joints on exam, as well as bloodwork
showing antibodies seen in rheumatoid arthritis. Her x-rays of the
hands show early changes often seen in rheumatoid arthritis.
 She is started on plaquenil and prednisone but has persistent
stiffness and pain in her joints at her follow up visit a few months
later. She is then started on methotrexate with good control of her
symptoms.
Lupus and Overlap
syndromes
 What does it mean to overlap?
 When patients who have features and meet criteria for a
diagnosis of SLE also have features of other connective
tissue disease
Connective tissue
diseases that can overlap
with SLE
Auto-immune conditions
that can co-exist with SLE
Rheumatoid Arthritis
Autoimmune Thyroiditis
Sjogren’s Syndrome
Antiphospholipid Syndrome
Myositis
Celiac Disease
SLE review

Autoantibody production

Oral or nasal ulcers

Malar rash (butterfly rash)

Low blood counts

Discoid rash

Kidney disease

Joint pain

Neurologic conditions: seizures, altered
mental status

Alopecia (often non-scarring)

Fatigue

Raynauds


Pleurisy
Pericarditis
Rhupus: Rheumatoid Arthritis
overlap with SLE
Comparison of features of musculoskeletal disease in SLE and RA
SLE
Rheumatoid Arthritis
Joint Pain
Common
Common
Swelling/Inflammation
yes
yes
Symmetric
yes
yes
Joints Involved
Hands, wrists, knees
Hands, wrists, knees
Joint Damage
Rare
Common
Morning Stiffness
For a few minutes
Hours
Deforming Arthritis
Rare
Common
Rhupus Syndrome
 Clinical condition in which the same person has signs and
symptoms of both Rheumatoid Arthritis and SLE, supported
by the presence of autoantibodies seen in both SLE and
Rheumatoid Arthritis
 Arthritis has been described in 50-95% of SLE patients
 It is typically characterized as being intermittent episodes of
joint tenderness and swelling.
 Unlike Rheumatoid arthritis, the arthritis in SLE is nondeforming.
 The prevalence of both SLE and RA has been reported to
be around 2-4%
SLE and Sjogren’s Syndrome
 Sjogren’s Syndrome is a disease named after Henrik
Sjogren, a Swedish ophthalmologist from the early
1900s who was the first to recognize that dry eyes and
mouth often occurred in people with connective tissue
diseases
 Sjogren’s can exist by itself or in conjunction with other
connective tissue diseases, such as SLE and RA
 Dry eyes and dry mouth occurs because of
accumulation of white blood cells in and around tear
and saliva producing glands
Primary and Secondary
Sjogren’s Syndrome
Common Symptoms and Signs of Sjogrens
Dry eyes due to decreased tear production
Dry mouth due to decreased saliva production
Parotid gland enlargement and swelling
Vaginal dryness
fatigue
Joint pain
Lymph node enlargement and swelling
Diagnosis of Secondary Sjogrens*
Presence of dry mouth or eyes
Evidence of decreased tear production
Evidence of decreased salivary gland function
*In the presence of another connective tissue disease
SLE and Secondary Sjogrens
 Estimated prevalence of SS in SLE is about 14.8%
(based on combining data from different studies with a
total of 2, 611 SLE patients) although has been
reported to range from 8 to 30%
 Some studies have suggested that people with SLE
and Secondary Sjogrens overlap are older at time of
diagnosis and have a lower risk of developing kidney
involvement due to SLE. However they are more likely
to have rashes, joint pain and raynauds.
Iaccarino et al. Autoimmunity Rev 2013
Antiphospholipid Syndrome
 Antiphospholipid syndrome is a disorder resulting in blood clots in
either veins or arteries (or both), or multiple pregnancy losses
(excluding other causes) in the presence of certain autoantibodies.
 APS can occur by itself or in conjunction with other autoimmune
diseases, mainly lupus
 First discovered about 30 years ago in patients with lupus. Since then
we have discovered that it can occur by itself as well
 About 10-40% of patients with SLE have APS autoantibodies and
about 10% of patients with SLE have APS Alarcon-Segovia et al. 1992
 In a study with 144 SLE patients who had positive antiphospholipid
antibodies, 20% had a clotting event over the 9 year study period.
Cervera et al. A&R 2002
Autoimmune myositis
 Polymyositis and Dermatomyositis are two similar
autoimmune muscle diseases
 Characterized by muscle weakness in the upper
arms and legs
 Dermatomyositis is often associated with other
characteristic rashes
ACR Image Bank
Autoimmune Myositis
 Diagnosis is made based on findings of:




Elevated muscle enzymes
Muscle weakness
Abnormal muscle studies (EMG)
Muscle biopsy
SLE and myositis
Lupus Myositis
Polymyositis/Dermatomyositis
Less degree of muscle
elevation
Often have very high elevations
of muscle enzyme (indicates
more damage)
Mild to minimal muscle
weakness
Moderate-severe muscle
weakness
Occurs often with other SLE Associated with other systemic
symptoms
findings including lung disease,
arthritis, raynauds
 Overlap with SLE and Polymyositis or Dermatomyositis is rare, has been
reported to occur in 4-16% of patients with SLE Dayal and Isenberg Lupus 2002
 Must be differentiated from other causes of muscle weakness that can be seen
in SLE, including medication induced myopathy
Autoimmune Thyroiditis
 Chronic autoimmune thyroiditis (Hashimoto’s Thyroiditis) is
the most common cause of hypothyroidism in the developed
world and the most common autoimmune disease in the
world
 All patients with this disorder have autoantibodies against
certain thyroid gland components which results in damage
to the thyroiddecreased thyroid function
 Nearly all patients with autoimmune thyroiditis have high
concentrations of thyroid peroxidase antibodies and
thyroglobulin antibodies
 Approximately 10% of all women have these antibodies and
prevalence increases with age
Symptoms of Hypothyroidism
 Fatigue
 Dry Skin and Hair
 Constipation
 Diffuse pain
 Weight gain
SLE and Thyroid Disease
 Approximately 15-30% of patients with SLE have antithyroid antibodies
 In a recent Italian study with 213 SLE patients compared
to 430 patients without rheumatologic disease (Antonelli et al.
Metabolism 2010)
 28% of SLE patient had thyroid autoantibodies, while 6%
had actual hypothyroidism (compared to 13% of patients
without SLE having the antibodies, and 4% having
hypothyroidism)
 In an earlier Israeli study with 77 SLE patients:
 12% had hypothyroid
 No correlation between lupus disease activity and
development of thyroid disease
Celiac Disease
 An autoimmune disorder of the small intestine resulting in
inflammation upon exposure to gluten in genetically
predisposed individuals
 Occurs in 1-2% of the western population
 Presents between ages 10-40 years
 Symptoms include diarrhea, greasy stools, weight loss,
vitamin deficiences due to poor absorption of nutrients
 Diagnosis made based on presence of the autoantibodies
on bloodwork and biopsy of small intestine
Celiac and association with
SLE?
 Reports of celiac autoantibodies in other autoimmune
diseases such as SLE, RA, APS and Crohns
 Several reports of association between Celiac Disease and
SLE but most studies have reports of only a few patients
with SLE having Celiac Disease
 There are reports of patients with SLE having the antigliadin autoantibodies (the less specific antibody for celiac
disease) but no evidence of celiac disease on biopsy. Rensch et
al. Am J Gastro 2001
 A recent study in Italy with194 SLE patients found that 14%
had the anti-endomysium antibody, but that none of the
patients with this antibody had evidence of celiac disease on
biopsy. Picceli et al. Lupus 2013
“Mosaic of Autoimmunity”
 Multifactorial origin and expression of autoimmune
diseases
 Different combination of many factors is involved in
producing varying and unique expression of disease in
each individual
 Factors involved: Genetic, Immune, Hormonal, Environmental
Kamen D. Rheum dis Clin N am 40 (2014) 401-412
References

Pecceli et al. Spectrum of autoantibodies for gastrointestinal autoimmune diseases in systemic
lupus erythematosus patients. Lupus (2013) 22, 1150-1155

Dayal and Isenberg. SLE/myositis overlap: are the manifestations of SLE different in overlap
disease? Lupus 2002; 11 (5) 293-8.

Iaccarino et al. Overlap connective tissue disease syndromes. Autoimmunity Reviews 12 (2013)
363-373

Antonelli A et al. Prevalence of thyroid dysfunctions in systemic lupus erythematosus. Met Clin
and Exp 59 (2010) 896-900

Kamen D. Environmental Influences on Systemic Lupus Erythematosus Expression. Rheum dis
Clin N am 40 (2014) 401-412

Rensch MJ et al. The prevalence of celiac disease autoantibodies in systemic lupus
erythematosus. Am J Gastroenterology 2001 April 96(4)

Anaya JM et al. The kaleidoscope of autoimmunity: multiple autoimmune syndrome and familial
autoimmunity. Expert Review of Clinical Immunology. July 2007