Non-Oncologic Conditions: Autoimmune Disorders

1. Non-Oncologic Conditions: Autoimmune Disorders

2. Objectives The learner will be able to: • Discuss risks for autoimmune diseases. • Discuss characteristics of autoimmune diseases in general. • Identify antineoplastic agents used for the treatment of some autoimmune diseases.

3. Autoimmune Diseases • Not completely understood • Related to the immune system’s inability to distinguish “self” from “nonself” cells • Conditions that occur when the body’s own immune cells are recognized as nonself (autoantibodies) and begin to attack other immune cells • Misguided T cells and autoantibodies contribute to many autoimmune diseases. • May range from mild/chronic to life-threatening • Symptoms can affect all body systems. • Often occur as periods of exacerbations and remissions • Treatments may consist of cytotoxic/antineoplastic agents. No cures.

4. Incidence and Prevalence • An estimated 23.5 million Americans have an autoimmune disorder. • More than 80 different diseases have been identified. • 75%85% occur in women. • One of the top 10 leading causes of death in women under age 65 • Some ethnic groups are more likely to develop specific autoimmune diseases.

5. Etiology • Known or suspected to be genetically and/or environmentally influenced • Some diseases have familial prevalence. • Believed to be secondary to another precipitating event (e.g., viral infection, drug reaction, excessive sunlight). • Estrogen may stimulate B-cell immunity, antibody production, and cytokine release, therefore making women more at risk.

6. Risks for Cancers • Due to an impaired immune system, and use of immunosuppressive agents, patients with certain autoimmune diseases are at increased risk for some cancers. Studies have demonstrated: • 2.5x risk of some cancers for women with lupus. • 2.4x risk of esophageal cancer. • 2x risk of pancreatic cancer. • Research is ongoing to determine the relationship between genetics, environmental exposures, and presence of immune disease on cancer risk.

7. Non-Oncologic Autoimmune Diseases Treated With Antineoplastic Therapies

8. Autoimmune Hepatitis (Chronic Active Hepatitis) • Can present with other autoimmune diseases • Immune system attacks liver cells, leading to hepatitis. • Symptoms/diagnosis: • Fatigue, hepatomegaly, jaundice, pruritus, rash, joint and abdominal pain, spider angiomas, nausea/vomiting, pale stools/concentrated urine • Antibody testing, liver function tests, biopsy • Treatment: • Corticosteroids, azathiopurine, mycophenylate mofetil, cyclosporine, tacrolimus, alemtuzumab, rituximab • May require liver transplant if severe

9. Guillain-Barré Syndrome • Immune system attack on the peripheral nervous system, destroying myelin • Often seen days to weeks following GI or respiratory infection, or following surgery or vaccinations (rarely) • Symptoms/diagnosis: • Progressive muscle weakness; can develop over the course of hours; can progress to paralysis, loss of reflexes, dizziness, palpitations, difficulty urinating/defecating; may require ventilator support • Nerve conduction velocity testing (signals are slowed) • Lumbar puncture (increased protein in CSF)

10. Guillain-Barré Syndrome (cont) • Treatment: • Symptomatic only; plasmapheresis; high-dose immunoglobulin therapy (IVIg); maintain function (ventilatory assistance; heart monitor; prevention of pneumonia)

11. Inflammatory Bowel Disease • Includes Crohn’s disease and ulcerative colitis • Incidence peaks at ages 1530 and 5070; family history is a risk. • Crohn’s disease: Affects end of the small bowel/beginning of colon, but can be any part of the GI tract • Ulcerative colitis: Affects colon only (large intestine) • Cause is unknown • Increases risk of colon cancer

12. Inflammatory Bowel Disease (cont) • Symptoms/diagnosis: • Diarrhea, constipation, abdominal pain, rectal bleeding, fecal urgency, weight loss, fever, dehydration, malnutrition, obstruction • Digital rectal exam; upper endoscopy; barium enema; colonoscopy, CBC • Treatment • 5-ASA agents; antibiotics, corticosteroids, antidiarrheals, immunologic and biologic agents • Surgery (20% of patients with ulcerative colitis—can be curative; surgery may be necessary for complications of Crohn’s disease but is not curative)

13. Immune Thrombocytopenic Purpura (ITP) • Immune system develops antibodies against platelets; characterized by low platelet count and mucocutaneous bleeding. • Unknown cause; affects women > men; children > adults • Symptoms/diagnosis: • Platelets < 10,000; petechiae, epistaxis; heavy menstruation, ecchymosis • CBC, coagulation studies, (clotting tests wnl; bleeding time prolonged); thyroid studies, bone marrow biopsy (megakaryocytes or normal) • Treatment: • Children may not require treatment. • Adults: Corticosteroids, immunoglobulin, platelet transfusion; immunosuppressants, rituximab with or without alemtuzumab, vinca alkaloids

14. Myasthenia Gravis • Chronic autoimmune neuromuscular disorder of voluntary muscle groups • Antibodies are made against receptor sites of the neuromuscular junctions. • Can be contracted from rheumatoid arthritis, cystinuria, treatment with interferon alpha, or bone marrow transplant • Symptoms/diagnosis: • Muscle weakness, drooping eyelid (ptosis), blurred/double vision, slurred speech, unstable gait, shortness of breath, difficulty chewing/swallowing • Neurologic exam, antibody testing, electromyography (EMG), single fiber EMG, edrophonium (Tensilon) testing • Treatment: • Cholinesterase inhibitors, corticosteroids, immunosuppressants, IVIg, rituximab, plasmapheresis, thymectomy

15. Multiple Sclerosis • Autoimmune, inflammatory, demyelination of the central nervous system and damage to nerve fibers themselves, forming scar tissue • Four types: • Relapsing-remitting: Attacks, followed by remissions • Primary progressive: Slow worsening, no remissions • Secondary progressive: Starts as relapsing-remitting, then worsens steadily • Progressive-relapsing: Steady worsening with clear acute attacks, without remissions • More common in northern latitudes (possible vitamin D connection) • Possibly associated with viral infection • Risk increases with first-degree relative with the disease. • 23x more common in women and Caucasians • Usually diagnosed at ages 2050

16. Multiple Sclerosis (cont) • Symptoms/diagnosis: • Fatigue, ataxia, balance concerns, numbness, bladder and bowel dysfunction, vision changes, dizziness/vertigo, pain, cognitive dysfunction • Less common: Dysarthria/dysphonia, dysphagia, headache, hearing loss, tremor, seizure, respiratory distress • MRI brain/spinal cord; visual evoked potential; lumbar puncture (CNS analysis); must show two areas of damage, evidence that they occurred at least one month apart; rule out other diagnoses. • Treatment: No cure: modify course/improve function. • Immunomodulatory meds, immunosuppressants, corticosteroids; interferon, rituximab, natalizumab, or high-dose cyclophosphamide without stem cell rescue; autologous stem cell transplant for severe cases • physical/occupational/speech therapy

17. Psoriasis • Immune cells mistake skin cells as a pathogen, create antibodies; hyper- proliferation of keratinocytes result; increased T-cell activity. • Chronic, noncontagious inflammation; genetically predisposed—autosomal dominant • Triggers: Stress, cold, trauma, infections, alcohol, some drugs • Less common in the tropics/dark-skinned people • May exacerbate/remit. Is associated with cardiovascular disease, smoking, alcohol, lymphoma, suicide, depression, possibly melanoma/nonmelanoma cancers

18. Psoriasis (cont) • Symptoms: Sudden onset, or worsening of scaly area; recent streptococcal or viral infection, immunization, use of antimalarial drug, or trauma, pain, pruritus, dystrophic nails, joint pain (10% have ocular symptoms.) • Treatment: Hot weather/sun may be beneficial. • Topical agents, phototherapy; systemic agents (retinoid, cyclosporine, methotrexate, 6-thioguanine, hydroxyurea, alefacept, etanercept, infliximab,ustekinumab, adalimumab, efalizumab.); may progress to arthritis • Pregnancy can ameliorate symptoms

19. Rheumatoid Arthritis (RA) • Chronic, systemic, progressive disease. Inflammation of synovium of joints and surrounding tissues, or other organs • Cause is unknown; thought to be related to environmental, genetic, and/or hormonal factors: is an autoimmune reaction. • B and T white blood cells and certain cytokines are identified that function improperly, allowing inflammation to continue. • All races/ethnic groups; women > men; usually ages 2060

20. Rheumatoid Arthritis (RA) (cont) • Symptoms/diagnosis: • Joint pain/tenderness/swelling, usually symmetrically; stiffness; fatigue; anemia, neuropathies, vasculitis, pleuropericarditis, subcutaneous rheumatoid nodules • Lab tests for rheumatoid factor titers, CBC, anticycliccitrullinated peptide antibody titers, erythrocyte sedimentation rate, c-reactive protein; testing of synovial fluid; x-rays of hands, feet, wrists • Treatment: • Disease-modifying antirheumatic drugs; immunosuppressives; anti-tumor necrosis factor drugs: interleukin 1 receptor antagonists, nonsteroidal anti-inflammatories, analgesics, corticosteroids

21. Sarcoidosis • Granuloma formation (clusters of immune cells) and inflammation in lymph nodes, liver, eyes, skin, other tissues; most commonly in lungs • May occur as immune response to infection; environmental or genetic factors/triggers • Occurs in African Americans > Caucasians; women > men; • Most commonly occurs between ages 2040 • Risk increases if blood relative has disease.

22. Sarcoidosis (cont) Diagnosis: • Chest x-ray; lab studies, pulmonary function test; ECG; arterial blood gases, bronchoscopy, CT, MRI, thallium/gallium scans, PET scan Treatment: • Symptoms may improve on own slowly • Maintenance of good health habits; avoid excessive amounts of calcium-rich foods; no smoking; avoid substances that irritate lungs • Corticosteroids, immunosuppressants: cyclophosphamide, methotrexate, azathioprine; Hydroxychloroquine for skin sarcoidosis

23. Scleroderma • Overproduction of collagen, leading to thickening/hardening of skin, blood vessels, and organs; dysregulation of the immune system • Women > men; ages 3050 • Morphea (localized): • Patches of thickened skin—no affect to internal organs. Can be all over, or linear; ulcerative skin, swelling, shiny-looking skin, arthritis • SSc (limited cutaneous type/diffuse type): • Skin involvement, plus Raynaud phenomenon, esophageal dysfunction, telangiectasias, pulmonary fibrosis, kidney or bowel disease, GI dysfunction(GERD, dysphagia), Sjögren syndrome (dry eyes/mouth)

24. Scleroderma (cont) • Diagnosis: • Comprehensive blood studies, ESR, C-reactive protein, antibody testing (ANA titer), physical exam • Treatment: No cure: symptomatic management • Encourage smoking cessation; treat Raynaud’s with calcium channel blockers; topical treatment for pruritus; skin thickening with d-penicillanmine, mycophenolate mofetil, cyclophosphamide, corticosteroids, photophoresis, immunosuppressives; chelating agents; peripheral vasodilators

25. Sickle Cell Disease • Inherited blood disorder leading to chronic hemolysis of red blood cells. Sickle-shaped blood cells have difficulty passing through blood vessels and are destroyed rapidly, causing anemia, lung tissue damage, pain, stroke, damage to most organs. • More common if of African, Mediterranean, South/Central American, or Middle Eastern descent • Several subtypes exists. • Symptoms/diagnosis: Usually do not occur until > 4 months of age

26. Sickle Cell Disease (cont) • Crisis: Pain in bones and chest, fatigue, paleness, shortness of breath, jaundice, tachycardia, small strokes, anemia, ulcers on lower legs, splenomegaly. Later: Bone, lung, urinary, and gallbladder infections • Treatment: Management and control of symptoms; less crises • Prophylactic antibiotics, opioids, IV fluids, oxygen, blood transfusion, hydroxyurea (pain); symptomatic management of late effects • The only curative treatment is allogeneic hematopoietic cell transplant, but is difficult to find matched donors in this population.

27. Systemic Lupus Erythematosus (SLE) • Chronic autoimmune disorder of connective tissue, affecting skin, joints, kidneys, brain, other organs; four types • Affects women > men; more often in ages 1050. Affects African Americans and Asians more than other populations • Exact cause unknown; may be genetic, environmental, hormonal factors

28. Systemic Lupus Erythematosus (SLE) (cont) • Symptoms/diagnosis: • Varies: Joint pain and swelling; also may have arthralgias, arthritis, vasculitis, facial cheek rash, fever, malaise, fatigue, hair loss, mucositis, photosensitivity, lymphadenopathy, headache, serositis, renal or cardio disease, anemia, nausea/vomiting, pleural effusions. Will have exacerbations and remissions. • Extensive antibody testing, complete blood count ESR, urinalysis (protein), skin biopsy, kidney biopsy, chest x-ray • Treatment: No cure: symptom management and control • NSAIDs, corticosteroids, antimalarials (arthritis), immunosuppressants, thalidomide, IVIg, rituximab; hematopoietic stem cell transplant; kidney failure in some patients may result in need for dialysis or transplant.

29. Less Common Autoimmune Diseases Treated With Antineoplastic Therapies Blood/Blood Vessel Disorders: Antiphospholipid syndrome Autoimmune aplastic anemia Behcet disease Cryoglobulinemia Hemolytic anemia Vasculitides (15 types) Skin Disorder: Chronic autoimmune urticaria Endocrine Disorder: Grave disease MuscloskeletalDisorders: Polychondritis Sjögrensyndrome

30. References American Autoimmune Related Diseases Association. (2010). What’s the cancer risk for lupus patients? Retrieved from http://www.aarda.org/research_display.php?ID=90 American Autoimmune Related Diseases Association. (2012). Autoimmune disease in women. Retrieved from http://www.aarda.org/women_and_autoimmunity.php Foundation for Clinical Research in Inflammatory Bowel Disease. (2011). Disease basics. Retrieved from http://www.myibd.org/PatientEducation/DiseaseBasics/index.html Jimenez, S.A.(2012). Scleroderma. Medscape Reference. Retrieved from http://emedicine.medscape.com/article/331864-overview Mancardi, G., & Saccardi, R. (2008). Autologous haematopoietic stem-cell transplantation in multiple sclerosis [Abstract]. Lancet Neurological, 7, 626636. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/18565456 Meffert, J.M., & O’Connor, R.E. (2012). Psoriasis. Medscape Reference.Retrieved from http://emedicine.medscape.com/article/1943419-overview

31. References (cont) Moore, S. (2003). Bronchiolitis obliterans organizing pneumonia: A late complication of stem cell transplantation. Clinical Journal of Oncology Nursing, 7, 659662. Myasthenia Gravis Foundation of America. (2010). What is myasthenia gravis (MG)? Retrieved from http://www.myasthenia.org/WhatisMG.aspx National Institute of Allergy and Infectious Diseases. (2005). National Institutes of Health Autoimmune Diseases Coordinating Committee: Autoimmune diseases research plan. Retrieved from http://www.niaid.nih.gov/topics/autoimmune/Documents/adccfinal.pdf National Institute of Neurological Disorders and Stroke. (2011). Guillain-Barré syndrome information page. Retrieved from http://www.ninds.nih.gov/disorders/gbs/gbs.htm National Institutes of Health. (2012). Idiopathic thrombocytopenic purpura (ITP). MedlinePlus.Retrieved from http://www.nlm.nih.gov/medlineplus/ency/article/000535.htm National Multiple Sclerosis Society. (2012). What we know about MS. Retrieved from http://www.nationalmssociety.org/about-multiple-sclerosis/what-we-know-about-ms/index.aspx

32. References (cont) Rheumatoidarthritis.com. (2011). Understanding RA. Retrieved from http://www.rheumatoidarthritis.com/ra/understanding-ra/default.htm Sickle Cell Disease Association of America. (2012). About sickle cell disease. Retrieved from http://www.sicklecelldisease.org/index.cfm?page=about-scd U.S. National Library of Medicine. (2011). Sarcoidosis. PubMed Health. Retrieved from http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0001140 U.S. National Library of Medicine. (2012a). Sickle cell anemia. PubMed Health. Retrieved from http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0001554 U.S. National Library of Medicine. (2012b). Systemic lupus erythematosus. PubMed Health. Retrieved from http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0001471 Volker, N. (1999). Do autoimmune diseases raise the risk of cancer? Journal of the National Cancer Institute, 91, 19921993. Retrieved from http://jnci.oxfordjournals.org/content/91/23/1992.full Zack, E. (2012). Chemotherapy and biotherapy agents for autoimmune diseases. Clinical Journal of Oncology Nursing, 16, E125E 132.