Week 4 Flashcards
What is systemic lupus erythematosus?
An autoimmune disease that can affect any tissue or organ in the body, but most often affects the skin, kidneys, and joints
What is the cause of systemic lupus erythematosus?
It is unknown, but it occurs as a result of genetics and the environment
____ is an environmental risk factor for lupus
UV radiation/sunlight is an environmental risk factor for lupus
____ are present in in the body in almost all cases of lupus
Antinuclear antibodies are present in the body in almost all cases of lupus
Antigens and antibodies bind to another in the body in a case of lupus to create an antigen-antibody complex. After binding together, what do they do?
They get into the blood, drift away, and deposit/stick to the vessel wall in all organs and tissues
What are the organs and tissues that antigen-antibody complexes stick to their vessel walls?
- Kidneys
- Skin
- Joint
- Heart
Antigen-antibody complexes that deposit/stick to the vessel walls of organs and tissues lead to what?
The initiation of local inflammatory reactions
What chain of events is caused by the initiation of local inflammatory reactions, as caused by the antigen-antibody complexes that deposit/stick to the vessel walls of organs and tissues?
The initiation of local inflammatory reactions causes damage to the activation of the complement system, which after a huge cascade of enzyme activation, leave cell membrane with channels that let food and molecules pass through with no problems, causing the cell to burst and die
What is a type 3 hypersensitivity reaction?
When there is tissue damage that occurs as a result of immune complexes
What are the other potential triggers that has been associated with lupus?
- Cigarette smoking
- Viruses
- Bacteria
- Use of certain medications, like procainamide, hydralazine, and isoniazid
- Sex hormones, particularly estrogen
True or False
Lupus is more common in women
True, lupus is more common in women due to estrogen being a trigger. Hence why it is more common in women during reproductive years, than it is during non reproductive years
What is a type 2 hypersensitivity reaction?
When antibodies target red and white blood cells, and molecules like phospholipids, which can mark them for phagocytosis and destruction, which leads to additional symptoms of lupus
What is the classic presentation of lupus?
- Fever
- Joint pain
- Rash
In a woman of childbearing age
Why is the diagnosis of lupus difficult?
It can affect a wide variety of people and has a wide variety of symptoms
What are the general symptoms of lupus?
- Fever
- Weight loss
What are the specific symptoms of lupus based on?
It is based on the organ/tissue being affected
When is a diagnosis of lupus given to a person?
Only when 4 or more of the 11 diagnostic criteria is met
What are the diagnostic criteria for lupus?
- Malar rash: a rash on the cheek that spares the nasal, labial folds. Also called a butterfly rash
- Discoid rash: plaque like, chronic rash found in sun exposed areas that can form a sort of patchy redness and scar
- General skin photosensitivity: other rashes from sun exposed areas that typically last a couple of days
- Ulcers in the mucous(inner) membranes of the mouth, and nose
- Serositis which is the inflammation of the outer membrane of a cell and can lead to: pleuritis which is inflammation of the lining around the lungs or chest cavity. Or pericarditis: inflammation of the lining of the heart
- Arthritis of 2 or more joints
- Renal disorders like: abnormal amounts of urine protein, diffuse proliferative glomerulonephritis(inflammation of the glomeruli)
- Neurological disorders like seizures and psychosis
- Hematologic disorders: Anemia if RBCs are affected, thrombocytopenia if platelets are affected, leukopenia if WBCs(immune cells) are affected
- Presence of antinuclear antibodies(very sensitive, but not specific, bcos it is seen in other diseases)
- Other autoantibodies like, anti-smith which targets ribonucleoproteins, anti-dsDNA which targets double stranded DNA and is often seen during periods of active disease, and anti-phospholipid which targets protein that are bound to phospholipids
What other parts of the heart can lupus affect?
- Endocardium: which presents as libman-sacks endocarditis, where vegetations(made up of fibrin and immune cells) form on the mitral valve
- Myocardium
What are the types of other autoantibodies that are specific to lupus?
- Anti-smith which targets ribonucleoproteins
- Anti-dsDNA which targets double stranded DNA and is often seen during periods of active disease
What are the types of anti-phospholipids?
- Anticardiolipin: can cause a false positive for syphilis
- Lupus anticoagulant
- Anti beta2 glycoprotein 1
What is anti-phospholipid syndrome?
Where anti-phospholipid antibodies cause a hyper-coagulable state, meaning that they are more prone to developing clots and complications like DVTs, hepatic vein thrombosis, and a stroke
What do patients with anti-phospholipid syndrome end up needing?
Lifelong anticoagulant therapy
What is lupus characterized by?
Periods of flare ups and remittance
What is the treatment of lupus often aimed at?
Preventing flare ups or limiting their severity
What are some ways that may help prevent lupus flare ups?
Avoid sunlight
What are some ways that may help limit the severity of lupus flare ups?
- The use of corticosteroids to help limit immune responses
- The use of immunosuppressants when flare ups are really severe
What is HIV?
A type of virus that infects human immune cells. Over time, immune cells are lost, which weakens the immune system and allows patients to be infected by other viruses and develop several types of tumors
What is AIDS?
Acquired immuno-deficiency syndrome, which are the viruses and tumors that is acquired after the immune system weakness has been developed
What type of HIV is more commonly associated with AIDS in the US and worldwide?
HIV-1
What type of HIV is more commonly associated with AIDS in the western Africa and southern Asia?
HIV- 2
What type of HIV is the most uncommon?
HIV- 2
What type of cells does HIV target?
CD4+cells on them
What types of cells have CD4+cells on them?
- T helper cells
- Macrophages
- Dendritic cells
What is the role of CD4 on cells?
It helps immune cells communicate, and are particularly important for when they are launching attacks on pathogens
How does HIV cells attach to CD4?
Via a protein called gp120
What does HIV need to attach to before it can get inside a cell?
It has to attach to BOTH the CD4 molecule and the co-receptor
What is the most common co-receptor that HIV uses?
- CXCR4 co-receptor, which is found mainly at T-cells
- CCR5 co-receptor, which is found on T-cells, macrophages, monocytes and dendritic cells
What are the things that can make the spread of HIV difficult?
- Homozygous mutation, which makes co-receptors resistant or immune to attachment
- Heterozygous mutation, which can result in a slower disease progression
What kind of cell is HIV?
A single stranded, positive sense, enveloped RNA retrovirus
What is the mechanism of the action of HIV?
It injects its single stranded RNA into the T-helper cell, and it needs to use the enzyme, reverse transcriptase, to transcribe a complementary double stranded piece of proviral(ready to be integrated into the host’s DNA) DNA. The new strand enters the T-helper cell nucleus, and inserts itself into the cell’s DNA and is ready to be transcribed into new viruses
During replication, DNA cells are prone to making errors. What does this lead to?
It leads to different strains of the virus being created in the body, and they target different cells, which is called viral tropism
What strain of HIV binds to the CCR5 co-receptor?
R5 strain
What type of symptoms do patients typically experience during the acute phase of HIV?
Flu- like symptoms
At which point does a patient enter into the chronic or clinically latent phase of HIV?
At 12 weeks
How long does the chronic or clinically latent phase of HIV last?
2- 10 years
As the HIV virus increases in the body during the chronic phase, what happens to the amount of T-cells?
It decreases
What types of infections become more common and severe in patients with HIV?
Tuberculosis
During the chronic phase of the HIV infection, some patients develop a X4 strain of HIV. What does it do?
The X4 strain of HIV targets the CXCR4 co-receptor, which is essentially only T-cells. The X4 strain of HIV lays low in the lymphoid tissues and steadily destroy T-cells.
What happens when a patient’s T-cells have dropped to 200-500 Tcells/mm?
- Swollen lymph nodes (lymphadenopathy)
- Hairy leukoplakia(white patch on the tongue caused by epstein barr virus, that causes mono-nucleosis)
- Oral candidiasis (yeast infection in the mouth)
What happens when a patient’s T-cells is below 200 Tcells/mm?
- Immunse system is severely compromised
- Disease has progressed from HIV to AIDS
- Persistent fever
- Fatigue
- Weight loss
- Diarrhea
- Significant increase in HIV content of the blood
What are the AIDS defining conditions that occur once a patient’s T-cells is below 200 Tcells/mm?
- Recurrent bacterial pneumonia
- Pneumocystis pneumonia
- Fungal infections like candidiasis of the esophagus
- Tumors and malignancies like kaposi sarcoma(lesions of the skin and other soft tissue), and primary lymphoma of the brain
___ is the most common transmission of HIV in the US
Male to male is the most common transmission of HIV in the US
___ is the most common transmission of HIV in resource limited settings
Male to female is the most common transmission of HIV in resource limited settings
Where is HIV present in infected women?
In the vaginal and cervical fluids
What percent of contracted HIV is from sexual intercourse?
75%
What are the other common means of HIV transmission?
- Intravenous drug abuse
- Mother to child transmission either through the placenta, delivery or via breast milk
What are the other less common modes of HIV transmission?
- Accidental needle stick
- Blood products like a transfusion
What are the ways that HIV can be diagnosed?
- Antibody test for antibodies that body might have made against HIV
- Antibody/antigen test, used to detect antibodies against HIV and HIV itself
- RNA/DNA test. RNA test to look for viral RNA and DNA test to look for copies of the viral RNA in DNA
What is the 1st recommended test to do in the diagnosis of HIV?
Antibody/antigen test
What should be done after the 1st test for HIV has been found to be positive?
Perform a confirmatory 2nd test, via the antibody test or the RNA/DNA test
What are the characteristics of the treatment of HIV?
- Help patient live a longer and healthier life
- Reduce the risk of transmission
What is the primary method of HIV treatment?
Anti-retroviral therapy
What is anti-retroviral therapy?
A combination of medications, which are considered a HIV regimen, and is used to slow HIV replication and helps the immune system recover and fight other infections effectively
What is rheumatoid arthritis?
A chronic inflammatory disorder that mostly affects the joints, but can also affect other organ systems like the skin and the lungs.
An autoimmune condition where the immune system attacks the joints.
What are the human leukocyte antigen that can predispose a person to rheumatoid arthritis?
HLA-DR1 and HLA- DR4
What are the environmental factors that in conjunction to the genetic factors will predispose a person to RA?
- Cigarette smoke
- Pathogens like gut bacteria
Wha do environmental factors cause in a person?
It causes the modification of our own antigens, such as IgG antibodies, type 2 collagen and vimentin
Through what process does type 2 collagen and vimentin get modified?
Citrullination
What is citrullination?
When arginine, which is found in type 2 collagen and vimentin is converted to citrulline
Once antigen presenting cells have been carried to the lymph node, what is the chain of events that occur after?
- Antigens presenting cells activate CD4, T-helper cells
- T helper cells stimulate B-cells
- B cells proliferate and differentiate into plasma cells, which produce specific autoantibodies against self- antigens
In RA, T helper cells and antibodies enter the circulation and reach the joints. Once they enter the joints, what occurs?
T-cells secrete cytokines like interferon-y and interferon-17, to recruit more inflammatory cells, like macrophages into the joint space. Macrophages also produce cytokines like, TNF alpha, interleukin-1 and interleukin-6, which together with the T-cell cytokines, stimulate synovial cells to proliferate
What does the increase in synovial and immune cells in the joint lead to?
It creates a pannus, which is a thick swollen synovial membrane with granulation tissue made up of fibroblasts , myofibroblasts, and inflammatory cells.
What does pannus lead to overtime?
It causes damage to the cartilage, and other soft tissues. It also erodes the bone.
What does activated synovial cells also do?
It secretes proteases, which breaks down the proteins in the articular cartilage, which leads to the underlying bones being exposed and directly rub against each other
What does inflammatory cytokines do to T-cells?
It increases the protein on the surface of T-cells, known as RANKL
What is the function of RANKL?
It allows T-cells to bind RANK, which is a protein on the surface of osteoclasts, to get them to start breaking down bone.
What is a name of an antibody that enters the joint space in the case of RA?
- Rheumatoid Factor(RF), an IgM antibody, that targets the constant FC domain of altered IgC
- Anti - CCP, which targets citrullinated proteins, which after they bind to their targets, they form immune complexes, which accumulate in the synovial fluid, and activate the complement system
What is the complement system?
A family of 9 small proteins that work in an enzymatic cascade to promote joint inflammation and injury
What does the chronic inflammation seen in RA cause?
It leads to angiogenesis, the formation of new blood vessels around the joint, which allows more inflammatory cells to arrive
Inflammatory cytokines travel out of the joint spaces and into the blood stream, where it travels to different organs and cause extra- articular problems. What are some of the places that these cytokines travel to?
- Interleukin 1 or 6 travel to the brain, where they act as pyrogens and cause a fever
- In the skeletal muscle, they promote protein breakdown
- In the skin and many visceral organs they lead to the formation of rheumatoid nodules
- Blood vessels get inflammed
What are rheumatoid nodules?
Round shaped collections of macrophages and lymphocytes, which a central area of necrosis
What happens to the liver in response to inflammatory cytokines?
The liver starts to produce high amounts of hepcidin, which is a protein that causes a decrease in serum iron levels, by inhibiting its absorption by the gut, and trapping it into macrophages or liver cells
What happens to the lungs in response to inflammatory cytokines?
Within the lung interstitium, fibroblast gets activated and proliferated, causing fibrotic or scar tissue, that makes it harder for the alveolar gas exchange.
The pleural cavity surrounding the lungs can get enflamed, and fill up with fluid, causing pleural effusion.
What is the usual presentation of RA?
- Usually 5 joints
- Symmetrical
What are the small joint that are commonly affected by RA?
- Metacarpo-phalangeal (MCP) joints
- Proximal inter-phalangeal (PIP) joint
- Metatarsal phalangeal (MTP) joint
As RA worsens, it can start to affect large joints. What are the joints that is affected by this?
- Shoulders
- Elbows
- Knees
- Ankles
What happens to the joints affected by RA, during flare ups?
- Swollen
- Warm
- Red
- Painful
- Become stiff over time, especially in the morning.
People with RA may develop specific deformities. What are they?
- Ulnar deviation to the fingers
- Boutonniere “buttonhole” deformity
- Swan neck deformity
When does a boutonniere “buttonhole” deformity occur?
When the extensor tendon of the finger slips, and the head of the PIP pokes through, causing flexion of the PIP an extension of the DIP
What happens in the case of a swan neck deformity?
There is PIP hyperextension and flexion of the DIP
What is a baker(popliteal) cyst?
A cyst formed by the synovial sac of the knee bulging posteriorly
What are the extra- articular symptoms of RA?
- Fever
- Low appetite
- Malaise
- Weakness
What are some organ specific manifestations of RA?
- ## Rheumatoid nodules, which are most commonly found around pressure points on the skin
Where are rheumatoid nodules found, even though it is rare?
Lungs, heart, and sclera
In patients with RA, there is an increased risk of atherosclerosis, which also increases the risk of what?
Heart attacks and stroke
A syndrome that is unique to RA, is felty syndrome. What is this?
A triad of rheumatoid arthritis, splenomegaly, and granulocytopenia, which can lead to life threatening infections
What does the diagnosis of RA usually involve?
- Blood test to look for the presence of rheumatoid factor and anti- citrullinated peptide (Anti-CCP) antibody
- Imaging like x-ray used to see decreased bone density, soft tissue swelling, narrowing of the joint space, and bony erosions
What does the long term management of RA involve?
- Disease modifying anti-rheumatic medications (DMARDs) such as methotrexate, hydroxychloroquine, and sulfasalazine which suppresses inflammation
- Biologic response modifiers like abatacept(suppress T-cells) and rituxinab(suppress Bcells)
What is the function of biologic response modifiers: adalumumab, etanercept and influximab in the treatment of RA?
Block chemokines, like tumor necrosis factor
What is the function of biologic response modifiers: anakinra in the treatment of RA?
Blocks interleukin 1
What is the function of biologic response modifiers: tocilizumab in the treatment of RA?
Blocks interleukin 6
What are the management methods of acute flares of RA?
Anti-inflammatories like NSAIDs and glucocorticoids which are used for a short term period
What is an autoimmune pathology?
Disorders of the autoimmune system, in which it attacks healthy cells by mistake
What is patient population that is affected by lupus?
- African-American, Latino, and Asian women
- Women:men- 9-10:1
- Age: 15-45
Even though there is no cure, what are the methods of self management for the avoidance of lupus?
- Avoid exposure to sunlight
- Avoid smoking
- Stress management
- Prolonged rest at night (i.e. 12 hours)
- Regular exercise
What are the common signs and symptoms of lupus?
• Joint inflammation • Kidney disease • Skin rashes with butterfly shape over the nose and cheeks • Fatigue • Muscle pain • Unexplained fever • Loss of hair • Raynaud’s phenomenon • Seizures • Sensitivity to the sun • Swelling – edema in legs or around eyes • It may affect the heart, lungs, blood, and brain in more severe cases
What are the ways lupus can be diagnosed medically?
- Blood tests
* Tissue biopsy
What are the medical management methods for lupus?
- Corticosteroid creams
- NSAIDs for joint pain and fever
- Antimalarial medications to help with joint pain and rashes
- Corticosteroid pills or intravenously.
What are the PT management methods for lupus?
• Not a medical emergency
• Medical consultation
• Manage patient’s energy
levels, so always ask how they feel
What is dermatomyositis?
An autoimmune disease that causes inflammation of the skin, resulting in typical kinds of rash
What are the typical skin presentation of dermatomyositis?
- Pink cheeks
- Purple hue over the eyelids
- Red skin rashes along the elbows, knuckles and knees
What are the typical muscle presentation of dermatomyositis?
- Inflammation
- Weakness
- Achy
- Tiredness, fever and chills
What is the main feature of the symptoms of dermatomyositis?
They get worse over time, and the patient gets weaker, which may interfere with ADLs
What is the prognosis of dermatomyositis?
- Prognosis is good
- Early detection and treatment improves outcomes
- It can rarely be recurrent
- Medical management using medications
- Treatment may take up to 2 years
- If it reoccurs, medication must be resumes
True or False
In the case of dermatomyositis, there can be skin manifestations in the absence of muscle
weakness and subtle skin
manifestations make it hard to diagnose
True, In the case of dermatomyositis, there can be skin manifestations in the absence of muscle weakness and subtle skin manifestations make it hard to diagnose
What is the main difference in the rash presentation between dermatomyositis and lupus?
In dermatomyositis, the nose and mouth are covered in rashes, while in lupus, they are not(butterfly rashes)
What is scleroderma?
A chronic connective tissue disease, generally classified as one of the rheumatic autoimmune diseases
What is the cause of scleroderma?
Unknown, but it is known that it involves an overproduction of collagen
What is the prognosis of scleroderma?
No cure
What is the incidence of scleroderma?
- Localized form is more common in children
- Systemic form is more common in adults (1/3 of cases)
- Women more predominant (4:1)
- Possibly genetic
- Age: 25-55
What are the medical management methods for scleroderma?
Medications. Greatly variable, due to the variability seen from patient to patient
What are the clinical manifestations of scleroderma?
- Hardening of the Skin (most visible manifestation)
- Affects different body parts
- Prompt and proper referral may minimize symptoms, and reduce the chance irreversible damage
What are the major classifications of scleroderma?
- Localized scleroderma
- Systemic scleroderma
What is limited scleroderma?
A subset of systemic scleroderma, which is slower and more benign, and is found in about 50% of cases. It is also called CREST syndrome
What does the letters of CREST syndrome stand for?
Calcinosis Raynaud Phenomenon Esophageal dysfunction Sclerodactyly Telangiectasia
What are the medical diagnosis methods of scleroderma?
- Blood tests
* Other specialized tests
Patient with limited scleroderma, and occasional those with diffuse scleroderma can develop ___
Patient with limited scleroderma, and occasional those with diffuse scleroderma can develop pulmonary HTN, a condition in which the lung’s blood vessels are narrow and lead to impaired blood flow to the lungs, and resulting in SOB
What should be done if suspected that a patient might have scleroderma?
Refer out, but it is not a medical emergency
What is psoriatic disorder?
An autoimmune disease that is commonly associated with crohn’s disease, and speeds up the life cycle of skin cells, by causing them to build up rapidly on the surface of the skin
What is the cause of psoriatic disorder?
Idiopathic, and is thought to be related to an immune system problem with T cells and other white cells/ neutrophils
What are the comorbidities that psoriatic disorder can be associated with?
- Autoimmune thyroid disease
- Diabetes
- Metabolic Syndrome
- Psoriatic Arthritis: present in 1/3 of the patient population and may manifest 10 years after diagnosis of the skin disease
What are the common signs and symptoms of psoriatic disorder?
- Red patches of skin covered with thick, silvery scales
- Small scaling spots (commonly seen in children)
- Dry, cracked skin that may bleed
- Itching, burning or soreness
- Thickened, pitted or ridged nails
- Swollen and stiff joints
What are the other clinical manifestations of psoriatic disorder?
Discomfort and pain
• Routine tasks difficult
• Concern about the appearance of patient’s skin
• Joint problems like pain, swelling, and the inability to perform daily tasks
What are the predisposing factors to psoriatic disorder?
• Infections, such as strep throat or skin infections
• Injury to the skin, such as a cut or scrape, a bug bite, or a
severe sunburn
• Stress
• Smoking
• Heavy alcohol consumption
• Vitamin D deficiency
• Certain medications — including lithium, which is prescribed for bipolar disorder, high blood pressure medications such as beta blockers, antimalarial drugs, and iodides
What are the medical management methods for psoriatic disorder?
- Diet
- Exercise
- Weight control
- Avoid smoking
- Medications such as TNF alpha inhibitors
- Monitor and treat signs of depression such as difficulty sleeping, anxiety and fatigue
