Step 1 Autoimmune Diseases Flashcards
What is Microscopic polyangiitis?
Similar condition granulomatosis with polyangiitis, but the trigger that initiates this condition is not known.
What symptoms are associated with Microscopic polyangiitis?
fever, anorexia, weight loss, fatigue, and renal failure (rapidly progressing glomerulonephritis is possible)
Clinical findings with Microscopic polyangiitis?
p-ANCA with specificity for myeloperoxidase or MPO-ANCA (a granule component of neutrophils)
Diagnosis of Microscopic polyangiitis?
renal function tests; measurement of MPO-ANCA titers
Treatment of Microscopic polyangiitis?
plasma exchange, anti-inflammatory drugs
What is Bullous pemphigoid?
an acute or chronic autoimmune skin disease, involving the formation of blisters, more appropriately known as bullae, at the space between the skin layers epidermis and dermis
Cause of Bullous pemphigoid?
autoimmune condition mediated by IgG specific for 2 proteins Dystonin (also called bullous pemphigoid Antigen 1) and/or type XVII collagen (also called bullous pemphigoid Antigen 2)
Symptoms of Bullous pemphigoid?
bullae (deep blisters) erupt, most commonly at the inner thighs and upper arms, but the trunk and extremities are frequently both involved. Any part of the skin surface can be involved. Oral lesions are present in a minority of cases
Diagnosis of Bullous pemphigoid?
based on two biopsies of the skin, one submitted for routine H&E staining and one for immunofluorescence studies
Treatment of Bullous pemphigoid?
topical steroids and other anti-inflammatory drugs
What is Hashimoto’s thyroidosis?
autoimmune condition that typically results in hypothyroidism (although some patients experience periods of hyperthyroidism. Can be mediated by CD4 and-or CD8 T cells or antibodies, and ADCC appears to play an important role in some patients (Ab-mediated, of course).
What are the symptoms of Hashimoto’s?
weight gain, depression, mania, sensitivity to heat and cold, paresthesia, chronic fatigue, panic, bradycardia, tachycardia, congestive heart failure, high cholesterol, reactive hypoglycemia, constipation, migraines, muscle weakness, joint stiffness, menorrhagia, myxedematous psychosis, cramps, memory loss, vision problems, infertility and hair loss
What is the cause of Hashimoto’s?
T cell infiltrates result in destruction of thyroid cells (mediated by CD8 and/or CD4 T cells); antibodies specific for thyroid peroxidase (TPO) and/or thyroglobulin can cause gradual destruction of follicles in the thyroid gland
Diagnosis of Hashimoto’s?
detecting elevated levels of auto antibodies specific for thyroid microsomes (antimicrosomal Ab), thyroglobulin (antithyroglobulin Ab), and thyroid peroxidase (anti-TPO Ab) in the serum; Testing for thyroid-stimulating hormone (TSH), Free T3, Free T4, and the anti-thyroglobulin antibodies (anti-Tg), anti-thyroid peroxidase antibodies (anti-TPO) and anti- microsomal antibodies can help obtain an accurate diagnosis
Treatment of Hashimoto’s?
thyroid hormone replacement therapy
What is Polymyositis?
an autoimmune disease mediated by CD4 and CD8 T cells (type 4 hypersensitivity)
What are the symptoms of Polymyositis?
pain, marked weakness and/or loss of muscle mass in the proximal musculature, particularly in the shoulder and
pelvic girdle. The hip extensors are often severely affected, leading to particular difficulty in ascending stairs and rising from a seated position. Thickening of the skin on the fingers and hands (sclerodactyly) is a frequent feature, although this is non- specific and occurs in other autoimmune connective tissue disorders
Cause of Polymyositis?
It is hypothesized that an initial injury causes release of muscle auto antigen, which is subsequently taken up by macrophages and presented to CD4+ T helper cells. Activated TH cells synthesize IFN-γ that stimulate further macrophages and further inflammatory mediator release like IL-1 and TNF-α. Another important event in the pathogenesis of polymyositis is the increased expression of MHC proteins by m/s cells. Auto-Ag is presented in association with MHC-I molecules on the surface of myocytes and is recognized by CD8 cytotoxic T cells that subsequently initiate cell destruction
Diagnosis of Polymyositis?
is fourfold, including elevation of creatine kinase, history and physical examination, electromyograph (EMG) alteration, and a positive muscle biopsy
Lab findings of Polymyositis?
antibodies: anti Jo-1 antibodies (in >65% of patients); anti-SRP (signal recognition particle) antibodies; anti-Mi- 2 antibodies (Mi-2 antigen is a component of the nuclesome remodeling-deacetylase complex involved in transcriptional regulation.
o elevated serum creatine kinase is characteristic, but not specific to polymyositis.
o treatment: line treatment for polymyositis is corticosteroids; other anti-inflammatory agents used in non-responsive
patients
• Dermatomyositis: similar to polymyositis except that both muscles and skin are involved
What is Celiac disease?
(also called Coeliac disease or celiac sprue): autoimmune condition of the small intestine that is caused by hypersensitivity to gluten; autoimmune response causes damage to intestinal villi, diminishing intestinal absorption
Symptoms of Celiac disease?
pain and discomfort in the digestive tract, chronic constipation and diarrhea, failure to thrive (in children), anemia and fatigue
Genetic pre-disposition to Celiac disease?
Almost all people with coeliac disease have either the variant HLA-DQ2 allele or (less commonly) the HLA-DQ8 allele
Causes of Celiac disease?
It is unclear whether this disease is mediated by auto-antibodies alone, CD4 or CD8 T cells alone, or some combination of those three immune responses. It is likely a combination of all three.
Clinical findings of Celiac disease?
anti-tissue transglutamase antibodies (anti-tTG) are highly diagnostic; another good diagnostic is the presence of antiendomysial antibodies in the patient’s serum. The antiendomysial antibody test is a histological assay for patient serum binding to esophageal tissue from on-human primates.
What is Polyarteritis nodosa?
a systemic autoimmune vasculitis characterized by necrotizing inflammatory lesions that affect medium-sized and small muscular arteries, preferentially at vessel bifurcations, resulting in microaneurysm formation, aneurysmal rupture with hemorrhage, thrombosis, and, consequently, organ ischemia or infarction.
Causes of Polyarteritis nodosa
it is believed to be autoimmune, but the effectors of tissue damage remain unidentified. The fact that rituximab (anti-CD20 MAb) treatment can be effective, it seems likely that B cell responses are the effectors
Symptoms of Polyarteritis nodosa
fever, fatigue, weakness, loss of appetite, and weight loss. Muscle and joint aches are common. The skin show rashes, swelling, ulcers, and lumps. Neurological symptoms can occur (numbness, pain, burning, and weakness); kidney damage occurs in some cases
Clinical Findings of Polyarteritis nodosa
small aneurisms strung like the beads of a rosary; elevated CRP, arteritis noted upon biopsy; elevated CBC and ESR
Treatment of Polyarteritis nodosa?
immunosuppressants (prednisone and cyclophosphamide); rituximab treatment sometimes induces remission
What is 1st biliary cirrhosis?
an autoimmune disease of the liver with unknown etilology. Marked by the slow progressive destruction of the small bile ducts of the liver, resulting in buildup of bile (cholestasis) that damages the tissue over time.
Cause of 1st biliary cirrhosis
unknown
Symptoms of 1st biliary cirrhosis
fatigue, pruritus (itchy skin), jaundice, xanthoma (local collections of cholesterol in the skin, especially around
the eyes [xanthelasma]), and complications of cirrhosis and portal hypertension (Fluid retention in the abdomen [ascites],
hypersplenism, esophageal varices, and hepatic encephalopathy (including coma in extreme cases)
Clinical findings of 1st biliary cirrhosis
anti-mitochondrial antibodies (AMA, specific for pyruvate dehydrogenase complex [PDC-E2]) in 90% of patients; anti-nuclear antibody (ANA); deranged liver function tests
What is Autoimmune hepatitis?
similar in many ways to 1 ̊biliary cirrhosis. It is an autoimmune condition of unknown etiology.
Cause of Autoimmune hepatitis?
unknown
Symptoms of Autoimmune hepatitis?
similar to 1 ̊ biliary cirrhosis except for the bile-duct specific damage that occurs in 1 ̊ biliary cirrhosis
Clinical findings of Autoimmune hepatitis?
presence of ANA and anti-smooth muscle antibodies (SMAs); deranged liver function tests
Treatment of Autoimmune hepatitis?
the corticosteroid prednisone in combination with azathioprine
What is Churg-Strauss syndrome?
an autoimmune medium and small vessel vasculitis in persons with a history of airway allergic hypersensitivity (atopy). It usually (but not always) manifests in three stages. The early (prodromal) stage is marked by airway inflammation: almost all patients experience asthma and/or allergic rhinitis; the second stage is characterized by abnormally high numbers of eosinophils (hypereosinophilia), which causes tissue damage, most commonly to the lungs and the digestive tract. The third and final stage consists of vasculitis, which can eventually lead to necrosis and is potentially life threatening.
Cause of Churg-Strauss syndrome?
the cause of the eosinophilia is unknown. Some of the inflammation is certainly caused by neutrophils that are stimulated by anti-neutrophil cytoplasmic antibodies (ANCA). Priming of ANCA likely occurs because of the frequent and/or chronic inflammation that accompanies asthma and other upper airways hypersensitivities.
Symptoms of Churg-Strauss syndrome?
highly variable presentation that ranges from mild (skin lesions and nasal polyps) to severe and life threatening (gastrointestinal involvement and heart disease). Almost all patients experience asthma or allergic rhinitis. Most experience hypereosinophilia (weight loss, night sweats, asthma, cough, abdominal pain, and gastrointestinal bleeding). Most patients experience vasculitis that can cause symptoms all over the body. Some patients develop non- vascular granulomas
Diagnosis of Churg-Strauss syndrome?
presence of myeloperoxidase-specific p-ANCA (or MPO-ANCA) is highly diagnostic.
Treatment of Churg-Strauss syndrome?
lucocorticoids (such as prednisolone) and other immunosuppressive drugs
