Rheumatological Conditions Flashcards
what is the first line of autoantibody defense.
B cells develop in the Bone Marrow and any antibody created which would attack a body protein found in the bone marrow is destroyed.
Without ____ of the B Cells, the body will not proliferate the autoantibody; this is the second line of defense against autoantibody production.
T Cell activation
causes of autoimmunity
- genetics
- stress
- infection
- medication SE
Rheumatology, probably more so than other fields of medicine, relies on recognition of _____ gleaned from a good H&P, labs, and imaging as many presentations will generate a large differential and labs and imaging are often non-specific
PATTERNS
difference between highly sensitive test vs highly specific test?
- Highly Sensitive Test- Very few false neg; can cause false positives making healthy ppl being improperly dx; ability to R/O dx
- Highly Specific Test- Very few positive cases will be something other than what the tester is looking for; there are positives which are not picked up - false negatives may occur. People with disease may be missed; ability to rule IN dx
the main lab to order if Suspect an autoimmune disease / Connective Tissue Disease?
ANA: Antinuclear Antibody
what is an ANA: Antinuclear Antibody?
- Autoantibodies - antibodies that attack self
- Will attack the nucleus of healthy cells
ANA is positive if titer is what ratio?
≥1:160
- Amount of saline dilution for antibodies to become undetectable
- ~5% of healthy ppl
- Higher titer = Greater likelihood; ≠ severity
- High Sensitivity; Low Specificity (more test needed)
- Once ANA is (+) - do not retest
possible causes that increase ANA?
3
- infection
- CA
- pregnancy
disease with (+)ANA based on sensitivity
- Drug-Induced Lupus (Hydralazine, Procainamide, Isoniazid) - 100%
- SLE - >95%
- Scleroderma - 85%
- Sjӧrgen Syndrome - 48%
- Dermatomyositis / Polymyositis - 61%
- RA - 40%
patterns seen with SLE
5
- Anti-dsDNA - Rim
- Anti-SSA (Anti-Ro) - Speckled
- Anti-SSB (Anti-La) - Speckled
- Anti-Smith - SnRNP
- Anti-U1-RNP - U1-SnRNP
pattern for Drug Induced Lupus
Anti-Histone, Homogenous
Pattern for Progressive Systemic Sclerosis
- Anti-RNA-Polymerase - Nucleolar
- Anti-Scl-70 - DNA Top I
patterns for Dermatomyositis
- Anti-Mi-2, Nucleolar
- Anti-Jo-1, Nucleolar
- Anti-SRP, Cytoplasmic
patterns for Polymyositis
- Anti-Jo-1, Nucleolar
- Anti-SRP, Cytoplasmic
pattern for crest syndrome
Anti-Centromere, Cytoplasmic
pattern for Sjӧgren
- Anti-SSA (Anti-Ro), Speckled
- Anti-SSB (Anti-La), Speckled
- Often a reflex lab with (+) ANA
- Leads the clinician to a more specific disease in the presence of possible Connective Tissue Disease
ENA: Extractable Nuclear Antigens
Mixed Connective Tissue Disease is a term describing ?
overlap of clinical features of SLE, Systemic Scleroderma, and polymyositis.
First detected in Rheumatoid Arthritis patients
Proteins in blood produced by immune system
RF presence indicates inflammatory process
which lab?
RF: Rheumatoid Factor
RF: Rheumatoid Factor is found in what conditions?
- Rheumatoid Arthritis
- Sjogren’s Syndrome
- Juvenile Arthritis
- Scleroderma
- Mononucleosis
- TB
- Leukemia
- Multiple Myeloma
2 most sensitive conditions to rheumatoid factor?
- Sjogren’s (75-95%)
- RA (70-90%)
not specific to RA
what other infectious conditions may present with high rheumatoid factor?
syphilis, HCV, TB
- A newer test more specific for Rheumatoid Arthritis than RF
- Is found in other diseases than RA, but at significantly lower levels.
Anti-CCP: Anti cyclic citrullinated peptide
- Sensitivity for RA - 66.0%
- Specificity for RA - 90.4%
Best at identifying Acute Inflammation
Produced by liver (not reliable test w/ liver failure)
CRP: C-reactive Protein
- Best at identifying Chronic Inflammation - Infection, Malignancy, Vasculitis, most Anemias, MI, Inflammatory Arthritis
- Normal test r/o temporal arteritis and polymyalgia rheumatica
- ↑ w/ age, pregnancy (2nd/3rd TM), medications (OCP)
ESR: Erythrocyte Sedimentation Rate
Two types of test of ANCA
- FA, immunofluorescence, (more sensitive)
- ELISA (more specific)
p-ANCA (Perinuclear pattern) is MC in what conditions
SLE, Sjogren’s, RA, PM, DM
c-ANCA (Cytoplasmic pattern) is MC in what conditions
(+) Wegener Granulomatosis & Churg-Strauss Syndrome
A chronic, systemic, multi organ autoimmune disease of connective tissues secondary to antibody formation and immune complex deposition.
Systemic Lupus Erythematosus (SLE)
SLE MC affects who?
- female
- 16-55 y/o
- Native American > African American > Asian (Chinese, Filipino) > Hispanic and Japanese > Caucasian
Precipitating factors of SLE include:
- Sun exposure
- Stress
- Infections
- Pregnancy
- Surgery
Low grade fever
Joint Pain
Rash - Covers the cheeks & nasal bridge; spares the nasolabial folds
SLE
Malar (butterfly) rash
criteria to dx SLE
4 out of 11 common s/s:
- Malar Rash
- Discoid Rash
- Photosensitivity
- Oral Ulcers
- Arthritis
- Kidney dz
- Neuro dz (In absence of lyte abnormalities or med SE)
- Serositis - pericarditis, pleuritis
- Hematologic dz - hemolytic anemia w/ reticulocytosis, lymphopenia, thrombocytopenia
- Immunologic Abnormalities
immunologic dx criteria for SLE
- abnml ANA
- Anti-dsDNA in abnml titer OR
- Anti-Smith OR
-
(+) Antiphospholipid Ab:
- abnml level IgG or IgM anticardiolipin ab OR
- (+) lupus anticoag using standard method OR
- false (+) for syphilis known to be positive for at least 6 mo and confirmed by Treponema pallidum immobilization or fluorescent treponemal ab absorption test
findings that indicate kidney disease
- > 500mg protein in 24 hrs.
- ≥3+ protein UA dipstick
- Casts: Red, Hgb, granular, tubular, mixed
what ANA ratio is needed to use the ACR/EULAR 2019 criteria?
points needed?
≥ 1:80
10 points needed for inclusion.
derm manifestations of SLE
6
- Malar Rash
- Discoid Rash
- Photosensitivity
- Oral / Nasopharyngeal Ulcers
- Raynaud’s
- Alopecia
MSK manifestations of SLE
- Arthritis - ≥2 joints, Migratory / Symmetric, Often peripheral, esp. hands
- Myalgias
CV and pulm manifestations of SLE
- Pericarditis or Pleuritis
- Myocarditis
- Valvular dz
- Vasculitis
- Interstitial Lung Disease
- Pulmonary HTN
renal manifestations of SLE
Lupus nephritis
- BX proven Lupus Nephritis guarantees SLE
- Hematuria
- Proteinuria
- Elv Creatinine
- May be asx - UA / BMP if considering SLE Dx
neuro manifestations of SLE
- Cognitive dysfunction
- Stroke
- Neuropathy
- Transverse myelitis
- HA
- Delirium
- Depression
GI manifestations of SLE
Not on the list of 11
- Dysphagia, abdominal pain, nausea
- Pancreatitis, gastritis, mesenteric vasculitis
systemic manifestations of SLE
Not on the list of 11
- Fatigue, fever, malaise, weight changes
- weakness
what is the most common manifestatio of SLE
MSK - 90%
what is drug-induced lupus?
- Strong Genetic predisposition
- resolves with DC of offending agent
- Not associated w/ CNS/Kidney/Alopecia
- ANA+ - 100% sensitivity
- (+) Anti-Histone Ab - 95%
common medications that causes SLE
- (High Risk >5%) Procainamide, hydralazine, Penicillamine
- (Moderate Risk 1-5%) Quinidine
- Many other Low risk medications…
monitoring for SLE
- q 6 mo if completely stable; 3-4 mo
- Complete H/PE
- CBC: thrombocytopenia (acute flare); Anemia
- CMP
- UA w/ micro
- +/- ESR, CRP, Complement levels, Anti-dsDNA - fluctuate with flares
nonpharm mgmt for SLE
- refer
- psychological
- sun protection & SPF >55; avoid meds w/ photosensitivity
- diet: balanced, vit D supp, daily vitamins if GI concerns
- exercise
- smoking cessation
- immunization: flu, pneuomococcal, HPV, HBV
- avoid pregnancy during flares - “dormant” x 6 mo before trying
what medications to avoid in SLE
- Sulfa Antibiotics (Bactrim) - rash in >30%,
- Minocycline
mgmt for mild SLE
Skin joint and mucosal
- Hydroxychloroquine, (+/-) NSAID
- < 7.5 mg prednisone daily if needed
mgmt for moderate SLE
Significant but non-organ threatening disease
- Hydroxychloroquine + NSAID
- 5-15 mg prednisone daily, tapered
- Immunosuppressive (MTX or Azathioprine)
mgmt for severe SLE
Renal/CNS involvement
- Hydroxychloroquine + NSAID
- High dose IV prednisone
- Immunosuppressive agent (Belimumab, Rituximab, Cyclosporine)
possible tx options for joint sx in SLE
- Hydroxychloroquine (Plaquenil)
- Naproxen
- Prednisone
which joint symptom meication is known to cause the “Bull’s Eye Retinopathy”
what is this called?
- Hydroxychloroquine
- Chloroquine Retinopathy
epidemiology of scleroderma
- 1-2/100,000 in USA
- Females
- MC 30-50 years of age
skin manifestations of scleroderma
- puffiness
- sclerodactyly
- rest of body tightens
- pigmentation changes and itching
vascular manifestations of scleroderma
- raynauds - 95%
- fingertip ulcerations
- cutaneous telangiectasia
- CAD
GI manifestations of scleroderma
- GERD, hoarsenss, dysphagia
- dyspepsia, early satiety, bloating
- constipation, fecal incontinence
- malnutrition and chronic iron def anemia
rsp manifestations of scleroderma
- dyspnea - progressive
- chest pain - pulm HTN
- cough, dry - restrictive lung disease
MSK manifestations of scleroderma
- arthralgia, myalgia
- Loss of ROM, muscle weakness
- carpal tunnel
cardiac manifestations of scleroderma
- CHF
- arrhythmias, palpitations
- systemic sclerosis - independent risk for MI
renal manifestations of scleroderma
- HTN
- AKI
- CKD
GU manifestation sof scleroderma
- ED
- dyspareunia
- vaginal narrowing, dryness
ENT manifestations of scleroderma
- sicca syndrome w/ poor dentition
- tongue CA
- blindess - retinal artery occlusion
sicca: lymphocytic infiltration of salivary and lacrimal glands
neuro manifestations of scleroderma
- TN
- peripheral neuro
- HA and CVA
There are at minimum 4 subsets of Scleroderma:
- Limited Cutaneous Systemic Sclerosis - s/s distal to the elbows and the face and neck. Many manifest CREST.
- Diffuse Cutaneous Systemic Sclerosis - proximal and even truncal manifestations.
- Systemic Sclerosis Sine Scleroderma - other s/s present w/o skin manifestations - RARE
- Systemic Sclerosis w/ Overlap Syndrome - Any of the above w/ overlap features of another systemic rheum dz (ex: SLE, Sjogren’s, RA, etc…)
what is CREST syndrome?
- calcinosis
- raynauds
- esopahgeal dysfunction
- sclerodactyly
- telangiectasias
difference between CREST vs systemic
CREST - mainly head and hands
systemic - includes trunk and proximal extremities
MC GI manifestation of scleroderma
esophageal (90%)
Other GI sx:
- GERD
- Choking
- Cough after swallowing
- Bloating
- Early Satiety
- Dysphagia
w/u for scleroderma
- CBC - anemia, dec MCV (iron def and/or blood loss)
- BMP - dec kidney function
- ANA (+)
- Anti-DNA top I (Scl-70) - diffuse cutaneous SSc - risk of lung dz
- Anti-Centromere - assoc w/ CREST
- Anti-RNA polymerase III - Diffuse dz - risk of renal failure and CA
All patients should have baseline imaging/testing to determine if ____ ____ _____ is present
what are these testings?
scleroderma
Interstitial Lung Disease
- PFTs
- Echo
- CT of Chest
tx for scleroderma
- No Definitive Cure
- Usually Organ System based
- Raynaud’s - CCB, GERD - PPI
- Arthritis: Similar to lupus
- NSAID (If kidneys stable)
- Inflammatory (RA), add in stepwise approach - Low dose steroids, Hydroxychloroquine, MTX, Biologics - PT and wt loss
- Diffuse skin sclerosis or organ involvement - MTX: 15-25 mg weekly
- REFER to Rheumatology!!!
chronic autoimmune inflammatory disorder characterized by diminished lacrimal and salivary gland function with resultant dryness of the eyes and mouth
Sjӧgren’s Syndrome
epidemiology of Sjӧgren’s Syndrome
- one of the more common autoimmune disorders
- Female
- 50-60 y/o
pathophys of Sjӧgren’s Syndrome
Ab attack:
- exocrine glands - xerostoma, dry eyes, parotid gland enlargement
- endocrine glands - thyroid dysfunction
- extraglandular - arthritis, GI, ILD, neuropathies
if secondary Sjӧgren’s Syndrome, it is often associated with what other conditions? (2)
- RA
- SLE
- Dry eyes - burning, itching, difficulty with contacts, ropy secretions, FB sensation, photophobia
- Dry Tongue - Halitosis, insatiable thirst, cavities - often at the gum line, dysphagia without liquid,
- Dry skin, vagina, nose, throat, larynx
dx?
w/u?
Sjӧgren’s Syndrome
- Basic labs - pancytopenia, hypokalemia, low bicarb, inc AST/ALT possible
- Elevated ESR (CRP is not)
- ANA (-)
- Anti-SSA (Anti-Ro) / Anti-SSB (Anti-La) (+) in primary disease
- (+) HLA-DR52 gene
- Labial salivary gland bx may confirm
- eye sx - Schirmer Test & surface staining
what other conditions may mimic sjogren’s syndrome?
HIV, HCV, and Vit A def
tx for Sjӧgren’s Syndrome
- Eye drops
- Avoid smoking
- Omega-3 Fatty Acids
- Counsel women that SS is associated with congenital heart block if high titers of Ro/La
- Lotion for skin
- Dental exams q 6 mo w/ fluoride tx
-
Pilocarpine: Cholinergic
- Xerostomia: 5 mg PO QID
- SE of pilocarpine?
- what other med can help with SE?
diaphoresis, flushing, sweating, bradycardia, diarrhea, N/V, incontinence, blurred vision. (Cyclosporine may help with blurred vision)
Epidemiology of Polymyositis / Dermatomyositis
- DM MC > PM
- females
- DM in childhood or adulthood vs PM in adulthood
s/s of DM and PM
- Insidious onset
- symmetric, progressive, painless proximal weakness, eye and facial muscles spared, +/- dysphagia; extramuscular manifestations (ILD, polyarthritis, skin changes in DM, not PM)
- Pain possible
- Muscle Atrophy: difficulty rising from a chair, climbing steps, ADLs, etc
- Overlap with other autoimmune disease possible
DM and PM have an Increased risk of ? 3-5 years after onset
- cancer
- DM > PM
Ovarian, breast, colon, melanoma, Non-hodgkin’s
Skin manifestations common with DM
- Gottron’s Papules - raised, violaceous scaly eruptions on knuckles
- Heliotrope Eruption (Blu-purple)
- Mechanic Hands - hyperkeratotic with dirty appearance
- Shawl Sign
w/u for Polymyositis / Dermatomyositis
- Basic labs
- elevated ESR (CRP is not)
- Muscle Enzymes - Aldolase, CK (>10x ULN in active disease, inc CK-MB w/o Troponins)
- ANA (+) MC
- Anti-Mi-2: DM
- Anti-Jo-1: DM/PM - Interstitial Lung Fibrosis, Mechanic Hands
- Anti-SRP: DM/PM - More exclusive to PM, MSK weakness and cardiac s/s
- Imaging
- MRI: Muscle edema or atrophy, fibrosis
- EMG: Myopathic Potentials - Muscle Bx - not necessary
tx for Polymyositis / Dermatomyositis
- CA screening + CT chest, abd, pelvis, TVUS, Mammogram - q 2 years
- Swallow evaluation if dysphagia
-
Prednisone 1 mg / kg [max = 100 mg/QD]
- Taper after 4-6 weeks
- +/- DMARD (MTX / Sulfasalazine)
- topicals for skin
- PT for muscle weakness
