Lupus and connection with other autoimmune conditions

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

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Malar rash (butterfly rash)

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Low blood counts

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Discoid rash

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Kidney disease

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Joint pain

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Neurologic conditions: seizures, altered mental status

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Alopecia (often non-scarring)

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Fatigue

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Raynauds

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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

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Dayal and Isenberg. SLE/myositis overlap: are the manifestations of SLE different in overlap disease? Lupus 2002; 11 (5) 293-8.

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Iaccarino et al. Overlap connective tissue disease syndromes. Autoimmunity Reviews 12 (2013) 363-373

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Antonelli A et al. Prevalence of thyroid dysfunctions in systemic lupus erythematosus. Met Clin and Exp 59 (2010) 896-900

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Kamen D. Environmental Influences on Systemic Lupus Erythematosus Expression. Rheum dis Clin N am 40 (2014) 401-412

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Rensch MJ et al. The prevalence of celiac disease autoantibodies in systemic lupus erythematosus. Am J Gastroenterology 2001 April 96(4)

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Anaya JM et al. The kaleidoscope of autoimmunity: multiple autoimmune syndrome and familial autoimmunity. Expert Review of Clinical Immunology. July 2007