Lupus, Antiphosoholipid syndrome, Mixed connective tissue disorder, Scleroderma, Crest syndrome, Sjorgrens syndrome

Question 1

Systemic Lupus Erythematosus (SLE)
Chronic inflammatory overview and pathophy

what ethnicity and gender and age

Answer 1

• autoimmune disease of unknown origin characterized by autoantibodies to NUCLEAR antigens that can affect virtually any organ in the body. (ANA)
• FEMALES > Males. 20- 40 y.o*
• Higher prevalence in AFRICAN AMERICAN, Hispanic, Asian, Native American, & Caucasian women*
• Genetic component
• Environmental component. Smoking, sunlight exposure, infections (EBV)

Pathophysiology
* The presence of antinuclear autoantibodies predates the development of signs & symptoms.
* anti-dsDNA & anti Smith antibodies are specific to SLE

Question 2

Systemic Lupus Erythematosus (SLE)
Clinical Manifestations and mneumonic

Answer 2

• Constitutional symptoms- FATIGUE (MC)., fever, chills, night sweats, malaise, weight loss.
• Triad: Fever, Joint Pain, Malar “butterfly” photosensitive rash **
• Discoid rash
• Photosensitivity (rash from sun exposure)
• Approx 80-90% of SLE patients will have mucocutaneous involvement and 4 of the 11 American college of Rheumatology classification criteria**

SOAP BRAIN MD: 4/11
* Serositis ( Pericarditis, Pleuritis, Peritonitis)
* Oral or nasal ulcers
* Arthritis in 2 or more joints
* Photosensitivity
* Blood disorders (anemia, leukopenia, thrombocytopenia, leukemia, lymphoma)
* Renal involvement (lupus nephritis)
* ANA
* Immunologic phenomena (other -antibodies)
* Neurologic & psychiatric
* Malar rash
* Discoid rash

Question 3

Systemic Lupus Erythematosus (SLE)
Diagnosis
Labs

Answer 3

The presence of antinuclear autoantibodies predates the development of signs & symptoms.
- ANTI SMITH (1 yr prior) AND ANTI-DsDNA (2.2 yrs prior)*
* Patients accrue different antibodies up until the time of diagnosis.
* Antinuclear antibodies (ANA)- initial screening choice. Most sensitive, but not specific. If ANA+ then test for specific antibodies.
* Anti-Ro/SSA antibodies, anti-La/SSB antibodies, Antiphospholipid antibodies are the first to appear and do so at a mean of 3.4 years prior to diagnosis.
* Antibodies to double-stranded DNA (anti-dsDNA appeared next at a mean of 2.2 years prior to diagnosis.
* Anti-Smith (anti-Sm) & anti-ribonucleoprotein (anti-RNP) were the last to appear at 1 year before diagnosis.

Labs
* Pancytopenia: Anemia of chronic disease m.c, hemolytic anemia, leukopenia,
* Increase ESR & CRP
* Decreased complement levels
* Proteinuria or hematuria may indicate renal disease.

Question 4

Systemic Lupus Erythematosus (SLE)
Treatment

Answer 4

• Lupus care is based on shared patient-physician decision making and should consider medical & societal costs and impact.
• Goals include long-term patient survival, prevention of organ damage, and improvement of quality of life.
• Treatment should aim at remission or low disease activity and prevention of flares, with the lowest possible dose of glucocorticosteroids that maximize effect.
• Flares can be treated according to severity by adjusting ongoing glucocorticoids or immunosuppressive agents or switching/adding new therapies.

Hydroxychloroquine (antimalarial) is recommended for all patients unless contraindicated. Do not exceed 5mg/kg of body weight.
* Decrease flares
* Prevents end organ damage
* Increases long-term survival

Question 5

Systemic Lupus Erythematosus (SLE)
Treatment: mild vs mod vs severe

Answer 5

Mild (skin, joint mucosal)
* Hydroxychloroquine
* +/- NSAIDs &/or short-term use of low dose glucocorticoids if no response with hydroxychloroquine
* Topical corticosteroids for skin lesions.

Moderate (significant, but non-organ threatening):
* Hydroxychloroquine + Short-term glucocorticoids

Severe (life or organ threatening):
* Hydroxychloroquine
* Systemic glucocorticoids (Indicated if glomerulonephritis, hemolytic anemia, myocarditis, alveolar hemorrhage, cns involvement, severe thrombocytopenia.
* High dose glucocorticoids
* Immunosuppressive agents- cyclophosphamide methotrexate, azathioprine, mycophenolate.
* Belimumab- monoclonal antibody that inhibits B-lymphocyte stimulator binding to B cells, which inhibits B-cell survival. Reserved for those unresponsive to other therapies.

Question 6

Lupus Nephritis: overview - classes and tx

Answer 6

• Nephritis is a major complication of Lupus.
• A Renal biopsy should be done when SLE is suspected.
• 6 classes of Lupus Nephritis
• Class I & II- usually do not require immunosuppressive therapy.
• Class III & IV (proliferative)
• Induction phase- control inflammation and limit damage 3-6 months - Glucocorticoids
• Maintenance phase- aims to maintain or improve the remission achieved with induction therapy and decrease another renal flare - IV Cyclophosphamide
• Class V (membranous)- treated similar to Class III & IV
• Class VI- culminates in end stage renal disease, hemodialysis and kidney transplant.

Question 7

cutaneous lupus: manifestations and tx

Answer 7

• Cutaneous manifestations
• Subacute cutaneous lupus erythematosus (SCLE), discoid lupus, and malar rash are the most photosensitive.

tx:
* Photoprotection!!!!!!!!
* Avoid prolonged exposure to sunlight & other sources of UV light (halogen & fluorescent lights).
* Smoking cessation
* Topical glucocorticoids

Photoprotection is the central tenet to the management of all forms of cutaneous lupus.

Question 8

Drug Induced Lupus: overview and sx

Answer 8

• Similar to SLE caused by certain drugs - PROCAINAMIDE (antiarrhythmic) MC***
• Hydralazine, Isoniazid, Quinidine (PHIQ)
• MINOCYCLINE in young women treated for acne**
• Males = Females

Signs & Symptoms:
* Rash, fevers, arthralgia, myalgia, serositis (pleuritis, pericarditis). Pleuritis common with Procainamide.
* Not associated with alopecia, hematologic, renal injury, cns involvement or or major organ complications **

Question 9

Drug Induced Lupus
dx and tx

Answer 9

Diagnosis:
* Anti-histone bodies are hallmark (>95%) **
* Positive ANA
* Anti-Ro/SSA antibodies (>80%)
* Hypocomplementemia & anti-double stranded DNA usually not seen.

Treatment:
* Stop the offending agent. Symptoms decrease from several weeks to several months.
* NSAIDs for inflammation
* Topical corticosteroids for cutaneous symptoms.

Question 10

Antiphospholipid Syndrome: def and etiology

Answer 10

Def:
* Defined as thrombosis (venous, arterial, or microvascular) or pregnancy morbidity occurring in individuals with antibodies against phospholipid-binding plasma proteins (antiphospholipid antibodies [apl]).
* The autoantibodies react against platelet membranes or prothrombin-platelet membrane complex activating endothelial cells, platelets, and complement-mediated thrombosis.
* Individuals produce antiphospholipid antibodies which attack the phospholipids in the cell membrane of their own cells, or attack proteins that are bound to those phospholipids.
* Women > men
* May occur as primary disease or secondary to other autoimmune diseases (e.g. SLE)

Etiology:
* Exact cause is unknown. There are known genetic and environmental factors.
* The HLA-DR7 gene encodes a specific type of a protein called major histocompatibility complex or MHC class II, which sits on the surface of the B cell.
* These surface proteins help activate B cells so that they can start producing antibodies.
* Having a mutated HLA-DR7 gene predisposes individuals to activate B cell production of antiphospholipid antibodies
* But the presence of the mutated HLA-DR7 gene alone isn’t enough to develop antiphospholipid syndrome- an environmental trigger must also be present.

Question 11

What can trigger APS to occur?

Answer 11

• Smoking
• Infections (syphilis, Hep C, HIV, malaria)
• Drugs (cardiovascular - quinidine, propranolol, hydralazine) Antipsychotic drugs
• Immobilization
• Estrogen (oral contraceptives, pregnancy, postpartum, HRT.
• Malignancy
• Hyperlipidemia
• Hypertension
  *

Question 12

antiphospholipid syndrome manifestations and bad outcomes

Answer 12

• Antiphospholipid antibodies → Hypercoagulable state (causes thrombosis {blood clot in arteries or veins})
• Arterial thrombosis - m.c. in males. Heart attack, Stroke, Limb Ischemia.
• Venous thrombosis - m.c. in females. DVT→ May break off (embolus) and travel to lungs (Pulmonary Embolism). Life Threatening!!
• Antiphospholipid Syndrome
• DVT & PE are most common manifestations.
• Livedo reticularis - swelling of the venules due to clots. Reticular = lacy or mottled violaceous rash.
• Antiphospholipid Syndrome
• Pregnancy related complications: miscarriage, thrombosis → placental infarction.
• Neurologic symptoms - Unknown. Headaches & seizures.
• Catastrophic Antiphospholipid Syndrome - generalized thrombosis that can lead to rapid organ failure & death.

Question 13

Antiphospholipid Syndrome
Diagnosis and tx

Answer 13

Diagnosis
* 1 clinical and 1 laboratory
* 2 clinical criteria
* History of thrombosis
* Pregnancy complications
* 3 laboratory criteria
* Presence of anticardiolipin
* Anti-Beta2 glycoprotein antibodies
* Lupus anticoagulant

Treatment
* Prevent thrombosis
* Aspirin - activates platelets (lifelong)
* Avoid triggers/risk factors
* History of clot
* Warfarin (toxic to fetus)
* Low-molecular weight heparin if pregnant
* Direct oral anticoagulants
* Asymptomatic
* Corticosteroids to limit immune response.

Question 14

Scleroderma: overview

Answer 14

• Chronic connective tissue disorder
• Rare autoimmune disorder in which normal tissue is replaced with thick dense tissue.
• Affects skin, blood vessels and internal organs.
• Sclero = Hard. Derma = skin
• Two types
• Limited - Crest syndrome
• Diffuse cutaneous diffuse scleroderma
• Most common in women 30-50 y.o.
• Pathology not understood
• Genetic predisposition
• Viral exposure -cytomegalovirus, parvovirus
• Environmental- silica dust
• Drugs- cocaine
• Scleroderma
• Injury to endothelial cells lining the small arteries →inflammation outside in the soft tissue which damages the lining and leads to cytokines which produce fibroblasts. Fibroblasts produce collagen. Increase connective tissue is called fibrosis.
• Fibrosis & blood vessel damage decrease blood flow →ischemic tissue damage.
• Scleroderma
• Fibrosis of skin, muscles, soft tissues, & internal organs (lung, heart, kidney, GI)
• Vascular dysfunction (e.g, Raynauds, pulmonary arterial hypertension.
• Characterized by tight, shiny, thickened skin of hand, fingers, face, neck** Sclerodactyly = claw hand.
• Raynaud Phenomenon: red - white -blue vasospastic changes of the digits***

Question 15

Scleroderma sx: limited vs diffuse

Answer 15

Limited (80%) -Progresses slower
* CREST syndrome.
* Calcinosis,
* Raynaud’s, 1st symptom
* Esophageal dysmotility,
* Sclerodactyly,
* Telangiectasias.
* Damage to organs comes later.

Diffuse (20%)- Progresses quicker
* Restrictive lung disease due to pulmonary fibrosis (m.c. lung condition), myocardial fibrosis, renal involvement.
* Damage to organs comes earlier

Question 16

Scleroderma: dx and tx

Answer 16

Diagnosis
* Based on symptoms
* Blood pressure
* CBC
* Pulmonary function
* Specific antibodies
* Anti- centromere antibodies
* Anti-SCL70 antibodies
* ANA

Treatment
* Immunosuppressants - inhibit or decrease the intensity of the immune response in the body
* Manage symptoms
* Vasodilators (Ca channel blockers for raynaud’s)
* PPI for GERD
* NSAID’s
* ACEI for HTN

Question 17

Mixed Connective Tissue Disorder: overview and sx

Answer 17

• An overlap of patients with signs & symptoms of a connective tissue disease. Constellation of SLE, systemic sclerosis and polymyositis.
• May evolve into classic SLE

Signs & Symptoms
Arthralgias
Myalgias
Swollen hands & puffy fingers
Raynaud phenomenon
Fatigue
Low grade fevers

Question 18

Mixed Connective Tissue Disorder
dx and tx

Answer 18

Diagnosis: Clinical
* High anti-U1 ribonucleoprotein antibodies
* High ANA, RF, anti-dsDNA, anti-SM, anti-Ro.

Treatment:
* Depends on predominant autoimmune disease.
* Corticosteroids to suppress the immune system.

Question 19

Sjorgrens syndrome: overview, primary vs secondary

Answer 19

• Autoimmune disorder in which immune cells attack exocrine glands. (e.g. salivary and lacrimal glands)
• Characterized by dryness of mouth & eyes.
• Females 40-60 y.o.
• Unknown cause:
• Genetic - HLA DRW52 gene
• Environmental- Infections
• Focal lymphocytic infiltration of lymphocytes, CD4+ T cells, and memory cells promote inflammation of the exocrine tissue →fibroblasts replace damaged tissue resulting in loss of secretory cells in glands.

Primary
* Occurs alone
* Known as Sicca Syndrome

Secondary
* Occurs with other autoimmune diseases.
* RA, Hashimoto, SLE

Question 20

Sjorgrens syndrome
Symptoms

Answer 20

• Middle aged women
• Dryness of body surfaces
• Lacrimal glands
• Blurred vision, itching, redness dryness.
• Salivary glands
• Dryness, of mouth, cracks and fissuring
• Nose & Respiratory
• Ulceration & perforation of nasal septum
• Larynx
• Difficulty speaking

Question 21

Sjorgrens syndrome
Diagnosis and tx

Answer 21

dx:
* Based on decreased exocrine glands
* Measure saliva flow
* Presence of anti-ssa and anti-ssb antibodies
* Lip Bx confirms dx. - increase CD4+ T cells, plasma cells and macrophages. Thickening of inner duct wall.

Treatment
* Suppress the immune response - Corticosteroids
* Increase exocrine secretions - Pilocarpine