Rheuma Flashcards
Autoimmune disease where organs undergo damage from autoantibodies
SLE
SLE autoantibody
Antinuclear antibody ANA
NOT LIMITED to SLE also with CT and autoimmune disease
99% of SLE patients
Women of childbearing years 1:700
All are susceptible
Most autoimmune diseases are
With ratio
Age range
Race
Female
9:1
20-30yrs
Severe in Blacks
Pathogenesis for SLE
Genes (HLA-DR3) Environment Abnormal immune response Autoantibodies immune complex Inflammation Damage
Fundamental defect in SLE
Failure to maintain self tolerance
Body no longer recognizes self from non-self
Factors that predispose SLE formation
HLA D2,3,8 UV Light Infection (EBV) Medications (Procainamide, Isoniazid, Sulfonamide, PTU, Hydralazine, Methyldopa) Smoking
Clinica manifestations of SLE
Skin Oral ulcer Non-scarring Alopecia Synovitis (at least 2) Serositis (pleurisy, pericarditis) Renal Protein/Crea <0.5
Criteria for Dx SLE
More than or equal to 4 criteria
1 clinical, 1 immunologic
Dx criteria in SLE
>4 criteria at given time
Malar Discoid Photosensitivity Painless oral ulcer Symmetric arthritis Serositis Renal, neuro, hematologic, immunologic Antinuclear antibody
Clinical manifestation of SLE and Prevalance
Systemic 95% (fatigue, malaise, fever)
Musculoskeletal (arthralgia) 95%
Hematologic (Anemia) 85%
Cutaneous (photosensitivity) 80%
Most common cutaneous manifestion of SLE
Photosensitivity 70% Malar 50% Oral ulcer 40% Alopecia 40% Discoid 20%
Most common hematologic manifestation of SLE
*Anemia 70%
Leukopenia 65%
Lympho 50%
*Thrombocytopenia 15%
Most common neurologic disorder in SLE
Cognitive decline 50%
Mood disorder 40%
Patients with SLE are predisposed to stroke because of
Hypercoagulable state
Musculo manifestations of SLE
Intermittent polyarthritis most common
Rhupus
Ischemic necrosis of bone
Myalgia
Slightly raised erythema
Scaly on the face, cheeks and nose
Photosensitive rash
Butterfly/Malar rash
Acute SLE Rash
Photosensitive
Slightly raised erythema
Occasionally scaly
Scaly, red patches
Circular red-rimmed flat lesions
Subcutaneous Cutaneous Lupus Erythematosus
Rough, circular, slightly raised, scaly, hyperpigmented rims
Depigmented atrophic center
Violaceous, hyperpigmented, atrophic plaque with follicular plugging and scarring
Discoid Lupus Erythematosus
Most serious manifestation of SLE
Leading cause of mortality in first decade of disease
Nephritis
Half - nephrotic (hypoalbuminemia, edema, hyperlipidemia)
Most - hypertensive
Class I Lupus Nephritis
Minimal mesangial
Class IV Lupus nephritis
Diffuse Lupus Nephritis
poor prognosis
Wire loop appearance in microscope
Diffuse Lupus Nephritis
Most frequent renal stage of lupus nephritis
Class IV Diffuse Lupus Nephritis
CNS Lupus manifestation
Cognitive dysfunction most common manifestation difficulty with memory and reasoning Seizure Psychosis Lupus Cerebritis Stroke (thrombitis)
Most common pulmonary manifestation of SLE with or without pleura effusion
Pleuritis
Most frequent cardiac manifestation of SLE
Responds to anti-inflammatory therapy and infrequently leads to tamponade
Myocarditis
Most serious cardiac manifestations of SLE (2)
Myocarditis
Fibrinous endocarditis of Libmana-Sacks
Most common cause of myocarditis
Cocksackie B
beating heart
Hand foot and mouth disease
Coxsackie A
Coxsackie B also causes
Bornholm Disease
Pleurodynia
Presence of antibody to phospholipid
Acceleration to atherosclerosis
Hypercoagulability and acute thrombotic events
Vascular occlusion
TIA, stroke and MI
APA accelerates atherosclerosis hence hypercoagulability
thrombotic event
Anemia in SLE
Normochromic, normocytic or
Hemolytic
EPO decreased from kidney failure
Leukopenia
Thrombocytopenia
GI SLE manifestation autoimmune causing abdominal pain
Intestinal vasculitis
During SLE flares GI manifestations:
n&v diarrhea vasculitis perforation ischemia bleeding
Ocular SLE manifestation
Sicca syndrome
Nonspecific conjunctivitis
rarely threaten vision
Serious ocular manifestation of SLE
retinal vasculitis optic neuritis (also in MS)
Musculoskeletal SLE
Intermittent polyarthritis
Cardiac SLE
Pericarditis
Myocarditis
Autoantibodies in SLE
Antinuclear antibody (ANA) 98%
Antihistone (Drug induced SLE) 70%
Antiphospholipid (APAS) 50%
Best autoantibody screening test in SLE
ANA 98%
High specificity autoantibody test
Associated with renal disease
Poor prognosis
Anti-dSDNA
Anti-Smith
3 widely accepted tests that measure different antibodies in SLE
anticardiolipin (beef heart) Calcutta antigen
anti2-glycoprotein
lupus anticoagulant
Non-specific Ab but presence fulfills 1 classification criteria of SLE
APAS
Neonatal lupus ab
Sicca syndrome Sjogrens
SLE
Anti-Ro/SS-A
Positive ANA fever malaise arthralgia serositis rash Drugs
Drug induced SLE
Drug inducing SLE
Procainamide Hydralazine Isoniazid Methyldopa Simvastatin Lithium
Dx and Tx of Lupus
Symptoms suggestive Other labs: ANA, CBC ANA + Definitive SLE criteria >/=4 or possible <4 Tx All tests normal
Treatment goals
Induce remission of acute flare
Maintain tx to supress symptom and prevent organ damage
Life organ threatening SLE TX
High dose glucocorticoids
Mycophenolate mofetil myfortic acid
Cyclophosphamide (do not exceed 6 mos)
Maintain with mycophenolate and azathioprine
Conservative SLE tx
Analgesic
Antimalarial (reduce dermatitis, arthritis and fatigue)
Hydroxychloroquine SE (2)
Retinal tox
Prolonged QT interval
SLE tx corticosteroid
1g Methylprednisone sodium succinate per day at least 3 days -5
Pulse therapy
Maintain on prednisone after
0.5-1g/kg/dayc
Chronic
Slowly progressive autoimmune disease affecting exocrine glands
Middle aged women 9:1
Sjogren’s
Prevalance for primary sjogren’s: 0.5-1%
Most common exocrine gland affected in Sjogren’s
Salivary gland
Sjogren’s pathogenesis
Lymphocytic infiltration
Clinical manifestation of Sjogren’s
Oral: xerostomia, diff swallowing, atrophy of filliform papillae, parotid gland enlargement
Ocular: sandy, gritty feeling under eye, dec tearing, erythema, itching, dry eyes!
Also causes xeropthalmia
Vit A deficiency
Sicca syndrome
Dry eyes
Dry mouth
Keratoconjunctivitis sicca
most common Extraglandular manifestation of Sjogren’s
Arthritis/arthralgia 60
Reynaud’s 37%
Fatigability/myalgia 25%
Lymphoma 6% MALT
Differential diagnosis for Sicca
HIV
Young male
Lacks autoantibodies Ro/SS-A and or B
Lymphocytic infiltration of CD8 lymphocytes
No age preference
Lack autoantibodies to Ro
Granuloma in salivary gland
Negative HIV
Sarcoidosis
Middle aged wimeb
Ro/SS A +
Lymphoid infiltrates of CD4+
HLADR3
Sjogren’s
Dx of Sjogren’s
Strongly supported by
Salivary gland biopsy
+ anti-Ro SS-A
+ anti-La SS-B
Cardiolipin
SLE
APAS
Carbonic anhydrase II
Sjogren’s
Systemic sclerosis
Centromere assoc proteins
Systemic sclerosis
Sjogren’s tx
Corticosteroid and immunosuppresive
Sjogren’s is also assoc with
RA SLE Scleroderma Primary biliary cirrhosis Autoimmune thyroid Chronic active hepatitis Mixed CTD
Autoantibody associated with primary biliary cholangitis
Antimitochondrial antibody
Most common lymphoma in Sjogren’s
MALT lymphoma
Hepatobiliary involvement in sjogren
Primary biliary cirrhosis
Tx of Sjogren’s
Azathioprine
Mycophenolate mofetil
To lubricate dry mouth
Water
To lubricate eyes
Artifical tears
Arthritis in Sjogren’s
Hydroxychloroquine
Methotrexate
Reynaud’s in Sjogren’s
Nifedipine
Renal Acidosis in Sjogren’s
Bicarbonate
Lymphoma in Sjogren’s
CHOP and anti CD20
Cyclophosphamide
Doxorubicin Adriamycin
Vincristine
Prednisone
Dilated cardiomyopathy
Cardiac toxicity
Doxorubicin
Hemorrhagic cystitis
Cyclophosphamide
Vincristine
Oncovin
R in CHOP monoclonal antibody
rituximab
Methotrexate inhibits the enzyme
Dihydrofolate reductase
RA affects
0.5-1%
F 2-3:1
RA Gene
HLA DRB1
0401 high risk
Europe and East Asian
Alleles known to confer greatest risk of RA within
Major Histocompatibility Complex MHC
Function of MHC
Bind peptide fragments from pathogens and display for cell surface recognition
Most common disease susceptibility alleles in Asians (Jap, Koreans, Chinese) in RA
0405
0901
Most risk of RA is associated with allelic variation
HLA DRB1 gene
RA environmental risk factors for RA
1 Smoking RR 1.5-3.5 related to RF and Anti CCP Ab (+) disease 2 EBV 3 Mycoplasma 4 Parvo B19 5 Silicone dust and mineral oil exposure
Infectious mononucleosis pathognomonic of
EBV Downey Type II cell
RA Pathology hallmark
1 synovial inflammation and proliferation
2 focal bone erosion
3 thinning of articular cartilage
RA has two cell types
1 Type A Synoviocyte from mac
2 Type B Synoviocyte from fibroblast
Most abundant RA cell type that produce structural components of joints such as collagen, fibronectinr and laminin
Type B Synoviocyte
Bone
Cartilage
BM
Collagen Types
I
II fibrocartilage, symphisis pubis
IV
25-55 y, F
Symmetrical, polyarthritis >5 joints
RA
Earliest joint involved in RA
Small joint of hands and feet
Early morning stiffness in RA
> 1 hr that eases with physical activity
RA symptom duration
> 6 weeks
Once disease is established, Most frequently involved joints in RA (3)
1 wrist
2 MCP
3 PIP
RA spares
1 TLS
2 DIP of fingers and IP of toes
Hallmark of RA leading to dec ROM, reduced grip strength and trigger finger
Flexor tendon synovitis
Boutinniere Deformity
PIP flexion
DIP hyperExtension
MCP hyperExtension
Swan Neck Deformity
PIP hyperExtension
DIP flexion
MCP in RA become chronically
ulnarly deviated
Heberden nodes are nodes on
DIP
Bouchard nodes are nodes on
PIP
Z line deformity is
subluxation of 1st MCP with hyperExtension of 1st IP joint
Hammer toe
Flexion of PIP of toe
MTP Extension
Piano key movement
Inflammation of ulnar styloid
Tenosynovitis of ECU
Subluxation of distal ulna at the styloid
Boutinniere Deformity
PIP flexion
DIP hyperExtension
MCP hyperExtension
Swan Neck Deformity
PIP hyperExtension
DIP flexion
MCP in RA become chronically
ulnarly deviated
Heberden nodes are nodes on
DIP
Bouchard nodes are nodes on
PIP
Z line deformity is
subluxation of 1st MCP with hyperExtension of 1st IP joint
Hammer toe
Flexion of PIP of toe
MTP Extension
Claw toes
Flexion of both PIP and DIP
Sparing the big toe
Constitutional signs and symptoms of RA
Most severe cases have cachexia TNF alpha Depression Malaise Fatigue Fever Weight loss
Cachectin
TNF a
Constitutional signs and sx in RA reflect
High degree of inflammation
Precede onset of joint symptoms
Fever in RA raises suspicion of
Systemic vasculitis
Infection
> 38.3 101F
Extraarticular manifestions in RA develop in
40% of patients
May occur prior to onset
Extraarticular manifestions of RA
Cervical myelopathy (neuro)
Keratoconjunctivitis sicca Sjogren’s, Scleritis
Anemia, Felty syndrome
Xerostomia
Pleural effusion, nodules
Pericarditis, MI, cardiomyopathy, mitral regurg
Membranous nephropathy, secondary amyloidosis
Hypoandrogenism
Pyoderma gangrenosum
Osteoporosis
Piano key movement
Inflammation of ulnar styloid
Tenosynovitis of ECU
Subluxation of distal ulna at the styloid
IBS assoc with pyoderma gangrenosum
Ulcerative colitis
30-40%
Firm nontender adherent to periosteum tendon, bursa
Develop in areas subject to repeated trauma (forearm, sacral, achilles)
Lungs, pleura, pericardium and peritoneum
Rhematoid nodule
Clinicial features of RA Pulmonary
Pleuritis most common
ILD
Pulmonary nodule
Pleuritis present with
Pleuritic chest pain and dyspnea
Pleural friction rub and exudative effusion
Rare subset of pulmonary nodulosis characterized by development of nodules and pneumoconiosis following silica exposure
Caplan’s syndrome
Caplan’s syndrome
Pulmonary nodule
pneumoconiosis
silica
Caplan’s is associated with
RA
Most frequently involved site of extraarticular affectation of RA
Pericardium
Cardiomyopathy in RA
Necrotizing and granulomatous myocarditis
CAD
Diastolic dysfunction
Most common valvular abnormality in RA
Mitral regurgitation
Caplan’s syndrome
Pulmonary nodule
pneumoconiosis
silica
Rare 1%
Most common in long standing disease
Rheumatoid factor
Hypocomplementenemia
Vasculitis
Cutaneous signs of RA
Gangrene digital infarct Petechiae Purpura Livedo reticularis Ulcer
Amantadine and minocycline may cause
Livedo reticularis
Also used in influenza
pd
Most common hematologic feature of RA
Anemia
Normo, normo
Degree parallels inflamm
Thrombocytosis
Parasite assoc with B12 deficiency
D latum
Felty Syndrome
1% Neutropenia Splenomegaly Nodular RA Thrombocytopenia
Most common lymphoma in RA
2-4% inc risk
Diffuse large B cell Lymphoma
Most common form of non hodgkin lymphoma in adults
Assoc with RA
Also in HIV
Diffuse Large B Cell Lymphoma
Most common cause of death in RA
Cardiovascular disease
Inc incidence of CAD and carotid atherosclerosis
CHF 2 fold higher
Bone problem in RA
Osteoporosis in 20-30% of px
From chronic glucocorticoid use
Disability related immobilitg
Associated condition in RA
hypoandrogenism
Criteria for RA
Joint involvement
Serology
Acute phase reactant (CRP)
Duration of symptoms (6wk)
More than 6 fulfills requirement
Changes in 2010 ACR/EULAR classification for RA
Inclusion of Anti cyclic citrullinated protein antibody
No longer takes into account presence of rheumatoid nodule or radiographic joint damage
RA Lab results
75-80% with RF
also seen in Sjogrens, SLE
Anti CCP
Specificity
Prognosis
95%
poor prognosis
Synovial fluid in RA predominantly has
neutrophil
5000-50000
Earliest radio finding in RA
Juxtaarticular osteopenia
Soft tissue swelling, symmetric joint space loss, subchondral erosion
Joint sublux and collapse
Imaging with greatest sensitivity for RA
MRI
detects synovitis, joint effusion and early bone marrow changes
RA tx
NSAIDs
Glucocorticoid
Glucocorticoid in RA
Low to moderate dose
5-10mg/day
Risk for osteoporosis in glucocorticoids
> 5mg/day for more than 3 months
DMARD of choice for RA
Methotrexate 10-25mg/week
Hydroxychloroquine
Dose
SE
DMARD
200-400mg/day
Retinal toxicity, cardiotoxicity
Other DMARD tx
Leflunomide 10-20mg/day
Sulfasalazine 500mg also in IBS
se: Hemolytic anemia and SJS
Biologic agents in RA
AE
Anti TNF a
Infliximab
Adalimumab
AE: opportunistic funga infection and TB activation
RA Prognosis
10% spont remission within 6 mos
MC cause of death
IHD
RA Prognosis
10% spont remission within 6 mos
MC cause of death
IHD
Most common cause of MONOarticular arthritis
TB
Lupus flare
Fatigue
Arthritis
Mucocutaneous lesion
Autoantibody specific tor lupus like sx in INH use
Anti histone