Multi-Systems: Various Pathology Flashcards
- Fixed erythema, Flat or Raised
- Over the Malar eminences “Butterfly shaped”
- Tending to spare the Nasolabial folds
- UV light initiates or exacerbates
- Immunofluorescence (IF) reveals IC deposition along the basement membrane (Band Test)
Malar Rash
- Erythematous raised patches w/ adherent Keratotic scaling and Follicular plugging
- Atrophic scarring may occur in Older Lesions
Discord Rash
- Rash as a result of unusual reaction to sunlight
- UV light photosensitivity
- -> radiation induces Apoptosis of Keratinocytes
- -> releasing sequestered Intracellular Nuclear antigens
- -> Ab against nuclear anitgens forming Immunocomplexes (ICs) (Band Test)
- -> Vasculitis
Photosensitivity
- Oral or Nasopharyngeal ulceration
- Usually painless
- Observed by a physician
Oral Ulcers
-
NonErosive - NonDeforming arthritis involving two or more peripheral joints - Symmetric in Hands and Wrists
- Proximal Interphalangeal
- Metacarpophalangeal
- Tenderness
- Swelling
- Effusion
Arthritis
-
Pleuritis - convincing history of pleuritic pain or rub heard by a physician or w/ or w/out Pleural effusion
- Interstitial Fibrosis –> Restrictive Lung Disease
- -> Resulting in a Higher than 80% FEV1/FVC ratio
-
Pericarditis - documented by electrocardiogram or rub or w/ or w/out Pericardial effusion
- **Sterile vegitations over the Mitral valve (Apex)
- -> Valve deformityandMitral Regurgitation**
- -> Libman-Sacks Endocarditis
Serositis
- Kidney is the most common Visceral organ involved
- Chronic Renal failure is the most common cause of Death
-
Nephritic Syndrome
- Hematuria, RBC casts in Urine, HTN
- Persistant Proteinuria > 0.5 g/dL or > 3 if quantitation not performed
- Cellular casts - may be RBC, Hemoglobin, Granular, Tubular, or Mixed
Renal Disorder
- Headaches (most common)
- Vessel thrombosis a/w Anti-phospholipid Syndrome
- Seizures - In the absence of offending drugs or known metaboic derangements (Uremia, Ketoacidosis, or Electrolyte imbalance)
- Psychosis - In the absence of offending drugs or known metabolic derangements (Uremia, Ketoacidosis, or Electrolyte imbalance)
Neurologic Disorder
- Hemolytic anemia - w/ reticulocytosis
- Leukopenia - < 4 x109 total on two or more occasions
- Lymphopenia - < 1.5 x109 on two or more occasions
- Thrombocytopenia - < 100 x109 in the absence of offending drugs
Hematologic Disorder
- Anti-DNA antibody to Native DNA in Abnormal titer
- Anti-SM - presence of Ab to Sm nuclear antigen
- Positive finding of Antiphospholipid Ab
- Abnormal IgG or IgM anticardiolipin antibodies
- Positive for Lupus anticoagulant
- False-positive for Syphilis
Immunologic Disorder
-
Abnormal titer of Antinuclear antibody (Serum ANA) by Immunoflurescence or equivalent assay at any point in time and in the Absence of Drugs to be a/w drug induced Lupus
- Hydralazine
- Procainamide
- Isoniazid
- D-penicillamine
Antinuclear Antibody
(11) Criteria for Systemic Lupus Erythematosus?
- Malar rash
- Discoid rash
- Photosensitivity
- Oral ulcers
- Arthritis
- Serositis
- Renal disorder
- Neurologic disorder
- Hematologic disorder
- Immunologic disorder
- Antinuclear antibody
Double-stranded DNA Ab
SLE
U1-RNP Ab
SLE
Sm antigen (Smith) Ab
(core protein in small RNP particles)
SLE
Ro / La Nucleoprotein Ab
(SS-A / SS-B)
Congenital Heart Block
Neonate
SLE
anti-Pl Ab
(Phospholipid-protein complexes)
SLE
anti-Scl 70
DNA topoisomerase 1 Ab
Diffuse skin disease, Lung disease
Systemic Sclerosis
Centromeric Proteins A, B, C
(CENPs)
Limited Skin Disease
Ischemic Digital Loss
Pulmonary HTN
Systemic Sclerosis
RNA Polymerase III Ab
Acute Onset
Sclerodermal Renal Crisis
Cancer
Systemic Sclerosis
Ro / La
(SS-A / SS-B)
w/ No Association
Sjogren Syndrome
Jo1 Ab
Histidyl aminoacyl-tRNA synthetase
Interstitial Lung Disease
Raynaud Phenomenon
Autoimmune Myositis
Mi-2 Nuclear antigen Ab
Dermatomyositis
Skin Rash
Autoimmune Myositis
MDA5 Ab
(Cytoplasmic receptor for Viral RNA)
Vascular Skin Lesions
Interstitial Lung Disease
Autoimmune Myositis
TIFIγ Nuclear Protein Ab
Dermatomyositis
Cancer
Autoimmune Myositis
CCP Ab
(Cyclic Citrullinated Peptides
Various citrullinated proteins
Rheumatoid Arthritis
Rheumatoid Factor Ab
Rheumatoid Arthritis
Anti-acetylcholine receptor Ab
(1x)
Myasthenia Gravis
Anti-basement Membrane Ab
(1x)
Goodpasture Syndrome
Anti-centromere Ab
(1x)
CREST Syndrome Diffuse Systemic Sclerosis
Anti-endomysial IgA Ab
(1x)
Celiac Disease
Anti-gliadin IgA Ab
(1x)
Celiac Disease
Anti-histone Ab
(1x)
Drug-Induced Lupus
Anti-insulin Ab
(2x)
Systemic Lupus Erythematosus
Type 1 Diabetes
Anti-intrinsic Factor Ab
(1x)
Pernicious Anemia
Anti-microsomal Ab
(1x)
Hashimoto Thyroiditis
Anti-Smith (Sm) Ab
(1x)
Systemic Lupus Erythematosus
Anti-SS-A Ab
(Ro)
(2x)
Sjogren Syndrome
Systemic Lupus Erythematosus
Anti-SS-B Ab
(La)
(1x)
Sjogren Syndrome
Anti-Thyroglobulin Ab
(2x)
Systemic Lupus Erythematosus
Hashimoto Thyroiditis
Anti-tissue Transglutaminase IgA Ab
(1x)
Celiac Disease
Anti-DNA Topoisomerase Ab
(1x)
Diffuse Systemic Sclerosis
Anti-mitochondrial Ab
(2x)
CREST Syndrome
Primary Biliary Cirrhosis
Anti-myeloperoxidase Ab
(1x)
Microscopic Polyangiitis
Anti-nuclear Ab
(3x)
Systemic Lupus Erythematosus
Systemic Sclerosis
Dermatomyositis
Anti-proteinase 3
(4x)
Polymyositis
MCTD
Primary Biliary Cirrhosis
Wegener Granulomatosis
Anti-ribonucleoprotein Ab
(2x)
MCTD
Systemic Lupus Erythematosis
Anti-TSH receptor Ab
(1x)
Graves Disease
(4x) Environmental Triggers for SLE
- Infectious agents (EBV)
- Ultraviolet light
- Induces Apoptosis of Keratinocytes
- -> Releasing sequestered Intracellular nuclear antigens –> Immunocomplexes –> Vasculitis
- -> Malar rash
- Induces Apoptosis of Keratinocytes
- Estrogen
- Triggers B cells against DNA
- Medications (4x)
(2x) Coxsackievirus a/w autoimmune disorder?
Myocarditis (B3)
Type I Diabetes Mellitus (B4)
(1x) Measles virus a/w autoimmune disorder?
Allergic Encephalitis
(1x) CMV a/w autoimmune disorder?
Systemic Sclerosis
(3x) EBV a/w autoimmune disorders?
Hepatitis B
Systemic Lupus Erythematosus (SLE)
Rheumatoid Arthritis (RA)
(1x) Human Herpes Virus (HHV-6)
Influenza A Virus
Both a/w autoimmune disorder?
Multiple Sclerosis
CREST Syndrome is a Acronym for what?
- Limited Systemic Sclerosis
- C - Calcification
- R - Raynaud phenomenon
- E - Esophageal dysmotility
- S - Sclerodactyly (tapered, claw-like)
- T - Telangiectasias (multiple punctate blood vessel dilations)
- Females 30 - 40 y.o.
- Black females greatest population
- CD4 TH2 cells
- Anti-Scl-70 (Anti-Topoisomerase I Ab)
- PDGF and TGF-β
- Raynaud phenomenon
- Gastrointestinal Hypomotility and Dysphagia
- Malabsorption due to Loss of Villi and Diverticula
- Constipation
- Pulm. HTN –> Right Heart Failure –> cor Pulmonale
- Renal problems w/ Vasculitis and Malignant HTN
Systemic Sclerosis
- Female dominant, esp. w/ Black Population
- 40 - 60 y.o.
- Increased Risk of Lung and Bladder cancer
- Fever, Morning stiffness, Fatigue, Weight loss
- Symmetrical and Proximal Muscle weaknes w/ or w/out Pain in both Upper and Lower extremities, Trunk Shoulders and Hips
- Dysphagia in Upper Esophagus
- Interstitial Lung disease
- Serum ANA, Anti-transfer RNA synthetase (Jo-1) Ab
Polymyositis
- Reddish-purple papules - “Gottron patches” - Knuckles / Proximal Interphalangeal (PIP) joints Both Hands
- Purple-red eyelids - Heliotrope eyelids “Racoon eyes”
- CD4 T cells –> Capillaries in Skeletal Muscle
- -> Ab and Complement –> capillary damage
- -> Ischemia and Atrophy of Muscle fibers
Dermatomyositis
- Female dominant
- 15 - 25 y.o.
- T cells and B cells –> Anti-Ribonucleoprotein (U1-RNP)
- Raynaud phenomenon and Sclerodactyly
- Arthralgia and Arthritis involving the Hands
- Esophageal dysmotility
- Pulmonary HTN, Pleuritis –> a/w anti-Phospholibid Ab
- Pericarditis
- Trigeminal neuralgia –> Face pain
- Serum ANA, Rheumatoid factor, anti-dsDNA,
anti-DNA Topoisomerase
Mixed Connective Tissue Disease (MCTD)
- Fatigue, Dyspnea, Pitting Edema, Parasthesias, Weight Loss, Diarrhea of Malabsorption, Macroglossia
- Restrictive Cardiopathy, Dementia (Alzheimer disease), Hepatomegaly w/ Pressure Atrophy, Muscle weakness
- Fibrillar protein deposited in Interstitial, β-pleated sheets
- Congo red and Apple Green Birefringence
- Immunoglobulin light chains; λ chains > κ chains
- Bence jones proteins = Light chains in Urine
- Serum Amyloid A (SAA)
- Amyloid Precursor Protein (APP)
- Transthyretin; carrier for Thyroxine / Retinoic Acid (Vit. A)
- β2-Microglobulin = Light chain component of MHC
Amyloidosis
AL
λ Chains
Amyloid derived from Immunoglobulin Light Chains
Immunocyte Dyscrasias - Systemic Amyloidosis
(Primary Amyloidosis)
AA
Amyloid derived from Serum Amyloid A Protein
Reactive Systemic Amyloidosis - Systemic Amyloidosis
(Secondary Amyloidosis)
Aβ2m
Amyloid derived from β2-microglobulin
Hemodialysis-associated Amyloidosis - Systemic Amyloidosis
(Chronic Renal Failure)
AA
Derived from Serum Amyloid Protein, Autosomal Recessive
IL-1
Familial Mediterranean Fever - Hereditary Amyloidosis
ATTR
Amyloid derived from Transthyretin, Autosomal Dominant
Familial Amyloidotic Neuropathies - Hereditary
Peripheral and Autonomic Nerve Disorders
Amyloidosis of Elderly Patients
(70+ years old)
Systemic Senile Amyloidosis - Hereditary
Predominantly Involves the Heart
(Restrictive cardiomyopathy, Conduction defects)
Aβ
Amyloid derived from Amyloid Precursor Protein, Chrom 21)
Senile Cerebral Amyloidosis - Localized
Alzheimer disease
A Cal
Amyloid derived from Calcitonin
Medullary Carcinoma of Thyroid - Endocrine Amyloid
Sporadic and Familial MEN IIa and MEN IIb
AIAPP
Amyloid derived from Islet Amyloid Polypeptide
Islets of Langerhans - Endocrine Amyloid
Type II Diabets Mellitus
- “Sand in my eyes” - Keratoconjunctivitis sica
- “Can’t swallow crackers” - Xerostomia or Dry Mouth
- Rheumatoid arthritis
- Female dominant
- Dental caries
- Autoimmune destruction of Minor Salivary Glands and Lacrimal Glands
- Anti-SS-A (Anti-Ro)
- Anti-SS-B (Anti-La)
- Serum ANA, Serum RF
- Confirm w/ Lip Biopsy
Sjogren Syndrome
- Chronic Joint Inflammation
- Females, 30 - 50 y.o.
- HLA-DR4
- EBV, Parvovirus, HH-6, Mycoplasma
- Inflamed synovial cells –> Triggers B cells
- RF is a IgM Ab w/ specificity for Fc portion of IgG
- -> RF + IgG = ICs –> Activate Compliment –> C5a
- -> Chemotactic for Neutrophils and Leukocytes
- Chronic Synovitis and Pannus (ILs, TNF) –> Desroy Articular Cartilage –> Fusion of Joint (Ankylosis)
- Swan Neck deformity and Boutonniere deformity
Rheumatoid Arthritis
- Fever of unknown origin
- Middle aged Men
- HBsAg, HCV, HBV a/w Polyarteritis Type III
- Acute and Chronic inflammation
- Focal vasculitis produces Aneurysms (angiography)
- Medium sized vessels, spares Pulmonary
- Kidnesy (Renal failure, Hematuria)
- Heart (Acute MI)
- Bloody diarrhea
- Ischemic Ulcers on Skin
- Testicular Pain
Polyarteritis Nodosa
- Metabolic syndrome, Obesity, DM2, Insulin resistance, Dyslipidemia, HTN
- Excessive synthesis of TGs in the Liver
- DHAP + NADH –> G3-P + 3x FAs –> TG
- Apoprotein B (apoB)-100 protein component of VLDL serves to enhance the secretion into the Blood
- Kwashiorkor –> Increased intake of Carbs and no Protein
- -> CHO (carbs) –> DHAP and more TGs
- -> No protiens –> reduced apoB-100 –> less secretion
- Yellow-liver discoloration
- Pushing nucleus to side
Nonalcoholic Fatty Liver Disease (NAFLD)
(Kwashiorkor)
- Micronodular cirrhosis (ALL pts.)
- Diabetes Mellitus Type I (75 - 80%) “Bronze Diabetes”
- Abnormal skin pigmentation (75 - 80%)
- 40 - 50 y.o. in Men, Later in women, Menses counters
- Hereditary - regulation of Intestinal absorption of dietary Iron is abnormal –> Net Iron accumulation (sig. @ 20gm)
- HFE gene C282Y (whites) and H63D (world),
HLA-A3, Transferrin receptor 2 (TFR2), Hepcidin
- HFE gene C282Y (whites) and H63D (world),
- Secondary - consequence of Parenteral administraion
Hemochromatosis
- Kayser-Fleisher Rings (70%)
- Deposits in Descemet membrane in the Cornea
- CNS disease
- Deposits in Putamen –> Parkinsonism
- Deposits in Subthalamic nucleus –> Hemiballismus
- Deposits in Cerebral Cortex –> Dementia
- Hepatosplenomegaly (50%)
- Hemolytic anemia
- Renal disease and Proximal tubule dmg –> Fanconi synd.
Wilson Disease
- Autosomal dominant (codominant)
- Most common cause of Cirrhosis in Children
- A/w Panacinar Emphysema
- Accumulation of AAT in Hepatocytes
Hepatitis –> Cirrhosis –> Liver damage
–> Increased risk of Hepatocellular carcinoma
α1-Antitrypsin Deficiency (AAT)
- Multisystem noninfectious Granulomatous disease that produces chronic interstitial Fibrosis
- Blacks and Non-smokers
- F > M
- CD4 TH cells (Mold, Mildew, Pesticides, Mycobacterial KatG protein) –> Cytokines –> Noncaseating Granulomas
- Granulomas located in Lung and Dyspnea
- Violaceous rash (nose and cheeks –> Lupus pernio)
- Erythema nodosum
- Blurry vision, Glaucoma, Corneal Opacities
- Granulomatous Hepatitis
- Enlarge Salivary and Lacrimal Glands
- Central Diabetes Insipidus
- Calcium Renal Stones, Nephrocalcinosis
Sarcoidosis
- Monosodium Urate (MSU)
- Men > 30 y.o.
- Primary - Deficiency of Hypoxanthine-guanine phosphoryltransferase (HGPRT) in Lesch-Hyhan Syn.
- Secondary - Underexcretion of Uric Acid
- Lead poisoning, Alcoholism, Red meat, Seafood, Thiazides, Beer
- Overproduction of Uric acid - Leukemia, Psoriasis
- UA crystals create Tophus –> Destroy adjacent bone
- -> Erosive Arthritis
Gout
- Characteristics
- Rheumatoid factor (RF) negative
- Axial skeleton (spondylitis)
- HLA-B27 Positive
- M > F
- Sacroiliitis w/ or w/out Peripheral arthritis
- Types
- Ankylosing
- Reactive arthritis
- Reiter syndrome, A/w Gastroenteritis
- Psoriatic arthritis
- Enteropathic arthritis
Spondyloarthritis
(Seronegative Spondyloarthropathies)
- Morning Stiffness w/in the Sacroiliac Joint
- -> eventually involves the Vertebral column
- -> Fusion of vertebrae (bamboo spine)
- -> Kyphosis (forward curvature)
- Leads to reduced Chest wall movement
- Nonpulmonary Restrictive Lund Disease
- Aortitis w/ Aortic Regurgitation
- Anterior Uveitis
- Blurry vision, may lead to Blindness
Ankylosing Spondylitis (AS)
- Urethritis due to Chlamydia trachomatis
- Arthritis and Achilles Tendon periostitis
- Bone formation at junction of Achilles tendon w/ Plantar Fascia
- Conjunctivitis - non-infectious
- Circinate Balanitis
- Rash on distal Shaft and Glans Penis
- Appears as Vesicles
- Shallow ulcerations
Reiter Syndrome
- Sausage-shaped DIP joints
- Finger or Toe
- Radiographs show Erosive Joint Disease
- “Pencil-in-cup” deformity
- Extensive nail pitting
Psoriatic Arthritis
- Most common non-gonococcal cause of Septic Arthritis
- Tx: Nafcillin + Cephalosporin (3rd generation)
Staphylococcus aureus - Septic Arthritis
- Most common Septic arthritis in Urban areas
- Disseminated Gonococcemia
- Deficiency of C6 - C9 complement
- Septic arthritis - Knee
- Tenosynovitis - Wrist and Ankles
- Dermatitis - Pustules on Wrists and Ankles
- Tx: Ceftriaxone
Neisseria gonorrhoeae - Septic Arthritis
- Borrelia burgdorferi (spirochete) transmitted by Ixodes
- Vesicular red center “Bull’s eye” Lesion
- Empirical therapy is recommended
- Fever, Flu-like symptoms, chills, Headache, Arthralgia and Neck Stiffness
- Skin Lesions and Lymphadenopathy
- Migratory Polyarticular Arthritis (Bursa, Tendons, Joints)
- Neuroborreliosis w/ Cranial Neuropathy (Bell’s Palsy) Bilaterally, Nucal rigidity
Lyme Disease (LD) arthritis
