Note: the following material is for  personal use only (see below for full disclaimer).



Cardio      Heme/Onc                Endo        ID             Neuro


Renal       Pulmonary                GI            Liver       


Rheum     Bone / Joint / Muscle               Male / Female


Allergy      Immunology      Derm                Surgery / Ortho


Acid-Base / Metabolic / Electrolytes                 Ophtho




Pediatrics         Emergency                       Pharm     Micro       Ddx



ICU Guide One [pic] – cardiac / pulmonary equations

ICU Guide Two [pic]– intubation / respiratory physiology / creatinine clearance / drug levels





General Immunology

Immunoglobulins, complement cascade



            T-cells              DiGeorge, CMC

            B-cells              CVID, IgA deficiency, Bruton’s, Duncan’s

B&T-cells        SCIDS, ADA, Wiskott-Aldrich, ataxia telangiectasia

Phagocytes       cyclic neutropenia, CD18, Job’s, Chediak-Higashi


Connective Tissue Disorders

RA, SLE, Sjögren’s, Polymyositis, Scleroderma, Sarcoidosis


Systemic Vascultides

Giant cell arteritis, Takayasu’s, Kawasaki’s, PAN, Wegener’s, Buerger’s, Churg-Strauss



B-cell surface markers [diagram]      

T-cell surface markers [diagram]


Immunoglobulins [diagram]

20% of plasma proteins / 2 light chains (kappa or lambda) and 4 heavy chains (gamma, alpha, mu, delta, epsilon)


IgA (15%) – secretions / 2 IgA molecules linked by J-segment (secreted by epithelial cells)

IgG (75%) – crosses placenta / major antibody

IgM (10%) – most efficient activator of compliment

IgE (trace) – hypersensitivity reactions / bound to Fc receptors on mast cells and basophils

IgD (1%) – surface of B-cells


4 major types of immune-response


·        Type I: hypersensitivity

·        Type II: cell-mediated

·        Type III: immune-complex

·        Type IV: delayed-type hypersensitivity


Type I hypersensitivity (derm)

IgE, mast cells (his, 5HT, TNF-a, TGF-B, IL-4), Th2, (y-IFN is inhibitory)

urticaria, atopic dermatitis, anaphylactic shock

Treatment of acute anaphylactic shock: 0.3 mg epinephrine SC

Long term: avoidance, drugs, allergen immunotherapy (how does that work?)

Insect stings: reaction in < 15 mins / venom immunotherapy may help / note: honeybee stings different from other stinging insects


Type II cell-mediated (derm)

IgM > IgG / complement / ADCC / organ-specific (Goodpasture’s, pemphigus) / receptor-specific (Grave’s, Myasthenia gravis) / hemolytic anemia / Derm: pemphigus, bullous pemphigus, herpes gestationis, epidermolysis bullosa

Treatment: immunosuppression, plasmapheresis


Type III immune-complex (derm)

leukoclastic vasculitis (PAN) / fibrinoid necrosis / polyarthritis, skin, serum sickness, arthus reaction

Treatment: anti-inflammatory agents, immunosuppression


Type IV delayed-type hypersensitivity

Th-1 - contact dermatitis, Tb, sarcoidosis, Wegener’s, IBD

Treatment: corticosteroids, cytotoxic agents, antimicrobials



Affects: skin, liver, GI tract, eye, kidney (reports)

Occurs following transplantation (e.g. BMT) / patients at high-risk for fungal infections for several weeks/months after engraftment (current debate over when and what to use for prophylaxis 1/07) / immunosuppressive agents used to prevent GVHD can look like EM [pic] [dermis]






Systemic Diseases Causing Defects of:


T-cells: HIV, sarcoidosis, steroids

B-cells: asplenia, SLE, CLL, steroids


Some genetic Immunodeficiencies may present in adulthood: CVID, CMC, more.


Defects of mainly T Cells



no thymus (no T-cells), no parathyroids / failure of 3rd (upper parathyroids), 4th pharyngeal (lower parathyroids) pouches / presents with tetany owing to hypocalcemia


Chronic Mucocutaneous Candidiasis (CMC)

            T-cells do not respond to Candida albicans


Defects of mainly B Cells


IgA deficiency

1 in 500 (most common immunodeficiency) / B-cells have it, but can’t secrete it / risk factor for celiac sprue

Presentation: recurrent sinusitis, GI infection (giardia), otitis media

Note:  do NOT give IVIG due to presence of anti-IgA antibodies (44%)


Common variable immunodeficiency (CVID)

            Most common primary immune deficiency requiring medical attention / 1 in 50,000

            sporadic / 10% familial / 15-35 yrs

Mechanism: hypo-IgG from various defects (CD27+ memory B-cells cannot differentiate into plasma cells) / suspected genes involved (BAFF, APRIL, TACI, ICOS)

Presentation: pyogenic infections (e.g. respiratory), chronic diarrhea (e.g. giardia), and increased incidence of autoimmune diseases (sprue-like syndrome, gastric atrophy, bronchiectasis, pernicious anemia) / associated T-cell abnormalities (10%)

Diagnosis: can test for response to Ag (e.g. tetanus, pneumovax)

Related syndromes: hyper IgM type 3 (CD40), autoimmune lymphoproliferative disorder (ALPS), TNF-receptor associated periodic fever syndrome (TRAPS)

            Treatment: IVIG q 2-3 wks / do NOT give live vaccines


Bruton’s X-linked agammaglobulinemia

XLR / no functional B-cells (cannot get EBV infection) / low Ig / recurrent bacterial infections beginning at age 6 months / low IG predisposes to chronic aseptic meningitis (with secondary dermatomyositis)


Duncan’s Syndrome (X-linked Lymphoproliferative Disease)

XLR / impaired response to EBV nuclear antigen (2/3 mortality ) / survivors develop hypogammaglobulinemia and/or B-cell lymphomas / decreased NK function and ADCC against EBV-infected cells


Defects of B and T Cells



            XLR / mutation of WASP gene / B and T-cells regress / cannot mount IgM response to capsular polysaccharides

elevated IgA, normal IgE, low IgM / recurrent pyogenic infections, eczema, thrombocytopenia / increased incidence of lymphoreticular neoplasm



B and T-cell deficiency, with associated IgA deficiency / presents with ataxia, spider angiomas / recurrent infections / can get lymphomas / secondary diabetes mellitus?


Severe Combined Immunodeficiency Syndrome (SCIDS)

            no functional B and T cells / defective IL-2 receptors, MHC II, or ADA (½ of autosomal



Adenosine deaminase deficiency (ADA)

excess ATP and dATP provides negative feedback on ribonucleotide reductase, prevents DNA synthesis, lowers lymphocyte count / can produce SCID


Defects of Phagocytes [NEJM]


Guideline: these are rare but important diseases, and can be diagnosed by examination of peripheral phagocytes and a few special stains / must catch these early and consider IFN-gamma, g-CSF, broad antibiotics


Cyclic Neutropenia

Autosomal dominant / ?mutation in neutrophil elastase (ELA2)

recurrent neutropenia ( < 200 cells/mL) lasts 3-6 days / cycle usually ~21 days, but in 30% of patients, ranges from 14-42 in 30%

During neutropenia: fever, apthous stomatitis, gingivitis, stomatitis, cellulitis, cervical LAD


Severe congenital neutropenia

Autosomal recessive in 90% (unknown mutation) / heterozygous in 10% /

Presents during first year of life / cellulitis, perirectal abscess, peritonitis, stomatitis, meningitis (Staph, Burkholderia) / increased risk for myelodysplasia, AML

Labs: < 500 neutrophils, but increased circulating monocytes, eosinophils

Treatments: nearly all improve with exogenous g-CSF


Schwachman-Diamond Syndrome

Autosomal recessive (rare) / Presents within first yr of life / average life expectancy 35 yrs

Exocrine pancreatic insufficiency, skeletal abnormalities, bone marrow dysfunction, recurrent infection / all have neutropenia (cyclic or intermittent), and 10-25% also have pancytopenia / increased risk of marrow aplasia, myelodysplasia, AML

Treatments: exogenous g-CSF (not considered a risk factor for malignant transformation)


CD18 (leukocyte adhesion deficiency type 1)

Autosomal recessive loss of B2 integrin adhesion molecules (from lack of CD18 or B-chain) / neutrophils cannot aggregate or bind endothelial cells / life expectancy is < 10 up to 40 yrs (depends on amount of CD18)

Delayed separation of umbilical cord, severe periodontitis (early tooth decay), recurrent infections of all mucosal surfaces, AND delayed wound healing (enlarging borders, dysplastic scars)


Leukocyte adhesion deficiency type 2

Growth retardation, dysmorphic features, neurological deficits / lack of sialyl-Lewisx (ligand for selectins) / Treatment with oral fructose has proven helpful


Job’s syndrome

neutrophils fail to respond to chemotactic stimuli (C3a, 5a, LT-B4) / recurrent cold staph abscesses / dental problems / elevated IgE levels / ?Rac2 (predominant GTPase in neutrophils)


Defective INF-gamma/IL-12 Axis

Autosomal recessive and autosomal dominant forms / complete loss of ligand-binding chain causes disseminated NTM in infancy or fatal BCG vaccination / partial loss is less severe (NTM develops in early childhood) / defect of IFN-gamma receptor signaling chain resembles complete loss of ligand-binding chain / defect in IL-12 receptor (B1 chain) and IL-12 increases susceptibility to NTM and Salmonella infections

Treatment: all respond to exogenous INF-gamma except (complete loss of ligand and receptor signaling)


Chronic Granulomatous Disease

XLR (gp91phox) make up 70% / presents within first 2 yrs / neutrophils lack hydrogen peroxide burst (myeloperoxidase system) /

Autosomal recessive (P47phox) make up 30% / onset may be later

Organisms: S. aureus, Burkholderia cepacia, aspergillus, nocardia, serratia, proteus, E. coli

Obstructive granulomas of GI/GU tracts, pneumonia, skin infections, osteomyelitis, liver abscesses, draining adenopathy (at BCG injection site, but mycobacterial disease still rare)

Diagnosis: can be delayed by blunted fever, inflammatory symptoms / severe resistant facial acne and painful inflammation of nares, gingivitis, apthous ulcers, NOT periodontal disease

Nitroblue tetrazolium test or flow cytometry with dihydrorhodamine dye

Treatment: bactrim (one/day) may reduce serious infections from 1/yr to 1 every 4 yrs / IFN gamma reduces bacterial and fungal infections by 70% / stem-cell transplantation and gene therapy protocols under investigation


Myeloperoxidase deficiency

50% have complete loss / no chlorine formation in azurophilic (primary) granules / usually asymptomatic except in diabetics who have increased risk of disseminated candidiasis



Autosomal recessive mutation in LYST (microtubule and lysosomal defects)

Recurrent staph and strep, partial albinism, mental retardation, platelet dysfunction, severe periodontal disease, and in those patients surviving into 20s, striking peripheral nerve defects (nystagmus, neuropathy)

Labs: mild neutropenia and normal IG levels

Course: 85% have fatal infiltration of CD8+ and macrophages with eventual pancytopenia


Neutrophil-Specific Granule Deficiency

S. aureus, S. epidermidis, enteric bacteria (skin/lungs) / abnormal migration and atypical nuclear morphology / lack of primary granule defensins, lack of eosinophil-specific granules


Felty’s Syndrome (see rheumatology)

neutropenia, splenomegaly, from long standing RA


Complement deficiencies [labs]


most are recessive, all occur at similar rates (except C2 may be more common, 1% prevalence) / C3 (severe disease) / C5-8 à GC meningitis, arthritis


Biology of Complement [activation cascade]


Functions:         lysis, opsonization, anaphylatoxins (degranulation), chemotaxis


Classical:        Ag:Ab complex, C1, C4, C2

attachment, activation, amplification, attack


Alternative:     microbe + P, D, B, C3b


Lectin (new):    MBP opsonizes foreign carbohydrates

C3a, C5a also anaphylatoxins

C5a is also a chemotactic factor


Deficiency syndromes


Clq, C1r, C1s, C4, C2              

SLE, some get infections


Repeated infections, partial lipodystrophy, SLE / C3 or C4 nephritic factor stabilizes convertase of alternate or classical pathway



Neisseria infections, arthritis


D and properdin (XLR)

Recurrent meningococcal meningitis


C1 inhibitor (AD)


Hereditary angioedema / may occur in SLE, lymphoproliferative disorders, paraproteinemias


MBP (3rd pathway)

Infections in SLE


DAF and CD59                      

Paroxysmal nocturnal hemoglobinuria

Factors H and I                       

Pyogenic infections, urticaria, glomerulonephritis, secondary C3 deficiency


Complement Studies


Normal C3 / Normal C4


Normal C3 / Decreased ↓C4

Alterations in vitro (improper specimen handling)

Coagulation-associated complement consumption

Inborn errors (other than C4 or C3)

Immune complex disease

Hypergammaglobulinemic states


Hereditary angioedema

Inborn C4 deficiency


Decreased ↓C3 / Normal C4

Decreased ↓C3 / Decreased ↓C4


Acute glomerulonephritis


Immune complex disease

Active SLE

Inborn C3 deficiency

Active SLE

Serum sickness

Chronic active hepatitis

Subacute bacterial endocarditis

Immune complex disease



C1 inhibitor (acquired or AD)

hereditary angioedema / may occur in SLE, lymphoproliferative disorders, paraproteinemias

recurrent GI attacks of colic are common / no pruritis or urticarial lesions






            Most common à B-lactams / ⅓ of cases are idiopathic

            5-60 minutes following exposure, but delayed reaction is possible

Angioedema with or without urticaria (not true anaphylaxis without life threatening hypotension or laryngeal edema)

Presentation: pruritis, flushing, urticaria, angioedema, diaphoresis, sneezing, rhinorrhea, congestion, hoarseness, stridor, laryngeal edema, dyspnea, tachypnea, wheezing, bronchorrhea, cyanosis, tachycardia, bradycardia, hypotension, cardiac arrest, arrhythmias, nausea, vomiting, diarrhea, abdominal cramping, dizziness, weakness, syncope, sense of impending doom, seizures


·        Epinephrine, IM (anterolateral thigh is fastest absorbed)

·        Recumbent position, elevate legs, oxygen

·        Volume replacement, pressors as needed

·        Benadryl 50 mg PO or IV every 4 hrs

Ddx: EM minor (urticarial or bullous lesions), SJS, TEN [these syndromes cause fever, headache, malaise, arthralgia, corneal ulcerations, arrhythmia, pericarditis, electrolyte abnormalities, seizures, coma, sepsis]


Dilantin hypersensitivity: very common, ranges from minor to life-threatening, mechanism unclear


Iodine allergy: not true allergic reaction; hyperosmolar dye causes degranulation of mast cells/basophils


Pretreatment protocol: 40 mg prednisone 24 hrs before then 12 hrs, etc… / H2 blockers (ranitidine), benadryl / avoid contrast dye with renal insufficiency and sickle cell disease / normal maximum dye load would be 2 CT scans within a 24 hour period (assuming normal renal function)


Drug Fever or Drug Rash

maculopapular rash, resolve after removal of agent

Timecourse: most occur several days after starting treatment, but can happen weeks after initiation of offending agent

Labs: elevated eosinophils, CRP, LFT’s (e.g. one study found increased LFT’s in 20% of cases of maculopapular rash)

Note: if you see it on the outside, the same thing can be happening on the inside (such as the liver, etc)


Serum Sickness

            7-10 days after primary exposure, 2-4 days after secondary exposure

            Findings: fever, polyarthralgia, urticaria, lymphadenopathy, glomerulonephritis

            Treatment: removal of agent, antihistamines, NSAIDs



asthma, eczema, and seasonal rhinitis and conjunctivitis

            allergic rhinitis: varies with season, treated with antihistamines/topical nasal steroids, itchy

            vasomotor rhinitis: perennial (no seasonal variation), not itchy


Food allergies

Most common à peanuts (soy beans, shellfish, eggs, milk, nuts) / incidence believe about 1 % / breastfeeding may reduce chance of developing in those predisposed / skin testing (radioallergosorbent tests or RAST ) not as good as a simple food diary / reactions usu. in GI and skin but can cause anaphylaxis/respiratory / best treatment is avoidance


Dust mite

common allergen / grow better in warm, humid environment (so humidifier actually makes worse) / can do skin testing for diagnosis of allergy


Insect allergies (e.g. hymenoptera)

range from local reactions to anaphylaxis / honeybee (Apis family) is not cross-reactive with Vespid family (e.g. wasps, hornets, yellow jackets) / venom immunotherapy is indicated with history and/or positive skin testing  


            Latex allergy

                        ranges from mild to anaphylaxis / can do scratch test





Bone             Malformations        Bone Fractures       Bone Cancer                        Osteomyelitis


Joint           Rheumatoid arthritis, SLE, Scleroderma, Sjögren’s, MCTD, JRA, Sarcoidosis

Osteoarthritis (OA), gout, pseudogout             

Infectious arthritis

Spondylarthropathies: AS, psoriatic, Reiter’s and Reactive, IBD



Muscle         Polymyositis/Dermatomyositis, PMR, RS3PE, eosinophilic fasciitis, eosinophilic myositis, other myopathy


Vascultides GCA, Takayasu’s, Kawasaki’s, PAN, Wegener’s, Churg-Strauss, Buerger’s


Ortho           Low Back Pain, Knee Pain, carpal tunnel


[Rheum H&P]  [HLA associations]


Rheum History and Physical Exam




General: CC/Chronology/demographics/functional impact/FH/ROS



                        Distal (RA), proximal (PMR, fibromyalgia)

Gentle activity often improves inflammatory but not pain of OA or fibromyalgia

Pain worse as day goes on (OA), wakens from sleep (severe OA, cancer)


Morning stiffness > 1 hr (RA, PMR)

gel phenomenon (worse on initiation/resumption of activity)


Articular (arthritis), periarticular (tenosynovitis, ganglion cyst), entire limb (lymphedema), other (lipoma, tumor)

            Dependent à worse as day goes on


            muscle vs. neurological



            Fever, inflammation (weight loss) vs. chronic pain (weight gain)


Fibromyalgia and inflammatory disease often poor sleepers (may also have sleep apnea, nocturia, narcolepsy)



Three Stages

Ischemic pallor - vasospasm (arteries/arterioles) [pic]

Cyanosis – dilation / deoxygenated blood pooling

Rubor – reactive hyperemia




                        Collagen vascular disease (SLE, SSc, others)

            Arterial occlusive disease

Pulmonary HTN

Neurologic disorders

Blood dyscrasias (e.g. Waldenstrom’s)


Other: thoracic outlet syndrome (decreased blood flow, short rib)


Arthritis Ddx by category


Acute polyarthritis

Infectious: bacterial sepsis, Neisseria, HIV, other virus, Lyme, rheumatic fever

Non-infectious: sarcoid, many CTD’s, Spondylarthropathies, juvenile chronic arthritis, gout/CPPD, HSP, HOA, sickle cell, leukemia


Intermittent Arthritis

Mechanical: loose bodies, partial tears, ligament laxities

Crystals: gout, pseudogout, hydroxyapatite

Infectious: Lyme, whipple’s

Other: palindromic RA, episodic RA, intermittent hydrarthrosis, FMF, Sarcoid


Chronic Arthritis

RA, JRA, other CTD, crystals, spondylarthropathies, HOA, hypothyroid, metabolic/infiltrative bone/joint disease


Acute Monoarthritis

Note: these can present with only one joint first, of course

Trauma, sickle cell, osteonecrosis

Crystals, bacteria, spondylarthropathies, RA, palindromic RA, JRA


Chronic Monoarthritis



OA, mechanical, osteonecrosis, neuropathic, reflex sympathetic dystrophy, adjacent bone lesion (tumor/infection)



Tb, fungal, lyme, crystals, RA, JRA, spondylarthropathies, hemophilia, synovial neoplasm, pigmented villonodular synovitis


Low Back Pain



Inflammatory: AS, Reiter’s, Psoriatic, enteropathic (reactive)

Infectious: infectious sacroiliitis, osteomyelitis

Musculoskeletal: vertebral compression, degenerative facet joint disease, herniated disc, muscular ligamentous injury


Psychogenic, worker’s comp

Visceral/vascular, referred pain

Primary or metastatic malignancy



·        musculoskeletal

o       lumbar sprain or strain (70%): acute or chronic / young adults

o       degenerative disk disease (10%)

o       spinal stenosis (3%): pain often bilateral lower legs / usu. > 60 yrs / worse w/ extension, relieved by flexion, worse with walking (uphill)

o       intervertebral (herniated disc) disease (4%): worse with sitting (lying may help)

o       spondylosis: defect in pars interarticularis, either congenital or secondary to stress fracture

o       spondylolisthesis: anterior displacement of upper vertebral body on the lower body (can mimic symptoms of spinal stenosis) / condition results from spondylosis or degenerative disk disease in elderly

o       cauda equina syndrome: difficulty in micturation, loss of anal tone, saddle anesthesia, progressive motor weakness, sensory level

o       facet joint syndrome: back pain referred to buttock, worse with extension, relieved by flexion / gradual, chronic / more in older patients / may have paravertebral muscle spasm at level

·        inflammatory: onset < 40, morning stiffness, peripheral joints, iritis, rash, urethral discharge

·        non-mechanical low back pain (1%)

·        referred or visceral pain (2%)

Diagnosis: history and physical usually enough / don’t get XR unless suspecting tumor, infection because 60% of asymptomatic patients will have positive findings on XR (which will be useless information) / MRI reserved for severe cases and/or when considering surgery

o       Straight-leg raising (not very sensitive or specific)

o       Patrick maneuver distinguishes pain from sacral-iliac joint (patient externally rotates hip, flexes knee, crosses knee of other leg like a number four while examiner presses down on flexed knee and opposite pelvis)

Duration: acute: < 3 months / early: 3 to 6 months / intermediate: 6 to 24 months / late: > 2 yrs

Red flags: young or old presentation, previous CA, steroids, drugs, HIV, constant (non-mechanical), thoracic, wt loss, ESR > 25, vertebral collapse on XR

Treatment: most cases of acute low back pain resolve in 1-6 weeks w/ analgesics (NSAIDs, other), bed rest NOT recommended, physical therapy NOT necessary (3-5% remain disabled for > 3 months)




Pain distribution


Reflex affected

Screening test


anterolateral thigh, anteromedial calf to ankle



Squat and rise (L4)


lateral thigh, anteromedial calf, medial dorsum of foot between 1st and 2nd toes

Dorsiflexion of foot


Heel walking (L5)


gluteal region, posterior thigh, posterolateral calf, lateral dorsum of sole and foot between 4th and 5th toes

Plantar flexion of foot


Walk on toes (S1)



Referred pain


facet joints, intervertebral discs

Lumbar à hip pain localizing to buttock, lateral thigh

Cervical à axilla, shoulder

hips à groin, anterior thigh

knee à

heart à shoulder, jaw, arm (pericarditis à trapezius ridge)

pancreas à back

liver à shoulder

renal (stones, etc) à flank/groin/testicle

uterine à lower back

PUD/spleen/pneumonia à right shoulder

            throat à ear (via recurrent laryngeal nerve)



Joint Diseases                                           [Synovial Fluid Table] [Polyarticular Ddx]


Inflammatory Joint Disease


Infectious arthritis

Crystal-induced: Gout, pseudogout, hydroxyapatite, calcium oxalate, LLM

Trauma: fracture, internal derangement, hemarthrosis

Osteoarthritis, RA and JRA

Spondylarthropathies: psoriatic arthritis, ankylosing spondylitis, Reiter’s, reactive arthritis

Ischemic (avascular) necrosis: Kasan’s, alcoholics, Gaucher’s

Foreign-body synovitis

Tumor: mets, osteoid osteoma, pigmented villonodular synovitis (benign, brown-yellow on MRI)

GI disease: intestinal bypass, Whipple’s, reactive arthritis (Shigella, Salmonella, Yersinia, Chlamydia, Campylobacter), IBD (Crohn’s and ulcerative colitis)

Viral infections: Parvovirus B19, rubella, HBV, HCV

Uncommon: mumps, coxsackie, echovirus, adenovirus, VZV, HSV, CMV


Other causes of arthropathy:

Relapsing polychondritis

Neuropathic joint disease

Hypertrophic osteoarthropathy and clubbing


Psychogenic rheumatism

Reflex sympathetic dystrophy syndrome

Costochondritis or Tietze’s syndrome (with swelling)

Musculoskeletal disorders associated with hyperlipidemia

Arthropathy of acromegaly, hemochromatosis, hemophilia, hemoglobinopathies,



                                    Rheum:  RA, OA, gout, CPPD, SLE, vasculitis, scleroderma, PM/DM,

Still’s, Behçet’s, relapsing polychondritis, sarcoidosis, palindromic rheumatism,

FMF, malignancy, hyperlipoproteinemia / seronegative: AS, psoriatic, IBD

Other: fibromyalgia, multiple bursitis/tendonitis, soft tissue abnormalities,

hypothyroidism, neuropathic pain, metabolic bone disease, depression, serum sickness

Infectious: lyme, endocarditis, viral (see above), gonococcal, Tb, other

Post-infectious or reactive: Reiter’s, rheumatic fever, enteric infection


HOA and clubbing


Primary HOA (pachydermoperiostosis)

AD / childhood / remits in 10-20 yrs


Secondary HOA

Causes: associated with intrathoracic malignancies, suppurative lung disease, congenital heart disease, and more / without clubbing (vascular grafting)

bronchogenic CA (usu. non-small cell) à RA-like picture (with effusions/arthralgia) can develop even before onset of clubbing

Mechanism: megakaryocyte shunting with  R to L arteriolar trapping à release of PDGF à proliferation [doesn’t seem to explain the classic pattern of progressive development of clubbing from feet to hands seen with congenital heart disease]

Treatment: after lung tumor resection (or even just radiation of mets) or lung abscess drainage, symptoms and signs of arthropathy often subside rapidly; radiographic changes remit during weeks and months / NSAID’s, ASA, bisphosphonates, even trial of low-dose steroids may relieve bone pain in some pts

Diagnosis: clinical? / bone scan will show periosteal deposition [pic], plain films may reveal changes also


Periarticular disorders:

bursitis, rotator cuff tendonitis and impingement syndrome, calcific tendonitis, bicipital tendonitis and rupture, adhesive capsulitis, lateral epicondylitis (tennis elbow), medial epicondylitis


General Points about OA, RA, gout


·        OA à affects many vertebrae, RA particularly C1/C2 (because there’s a bursa there)

·        RA causes destruction and osteoporosis; gout causes destruction but not osteoporosis


Osteoarthritis (OA)    most common joint disease

Causes: primary (80% of population > 70 yrs) or secondary 5% (previously damaged joints, weight-bearing joints, endocrinopathy, metabolic disease, neuropathy, avascular necrosis, Paget’s); 34% of patients presenting with acute knee pain

Clinical: age > 50 yrs, morning stiffness < 30 mins, crepitus, bony enlargement or tenderness;  no inflammation (no heat), slow progression / normally pain worse with weigh-bearing, motion, but can progress to point where causes pain at rest, at night

ACR: osteophytes on XR + at least one of above signs is 90% sensitive, specific for OA


            Affected Joints: DIP > PIP > CMC, knee, hip, feet

            Spared Joints: hands (except DIP/PIP/CMC), wrist, elbow, shoulder, spine

·        Heberden’s nodes (DIP) and Bouchard’s (PIP) seen more in post-menopausal women with genetic predisposition [pic] / only wrist joint involved is 1st CMC [pic]

·        Knees: medial >> lateral involvement / may develop popliteal cysts

Radiographic (weight-bearing): osteophytes (77% sensitivity/83% specificity), subchondral sclerosis, subchondral cysts, joint space narrowing (erosions), malalignment, may see soft-tissue swelling

·        Spondylosis is the formation of osteophytes in response to degenerative disc disease / thick and often project laterally (unlike in AS) / spinal stenosis can also occur from hypertrophy of posterior facet joints, spondylolisthesis, synovial cysts, Paget’s disease, epidural lipomatosis, and congenitally small spinal canal

·        Schmorl’s nodes (invasion of disc into vertebral body) are common (often associated with Scheuermann’s disease, osteopenia and degenerative disc disease) / bony margin may be visible on roentgenogram

·        Forestier’s disease (diffuse hyperostosis) can occur (usu. elderly) and may form “flowing ossification” (usu. on right side, thoracic vertebrae, but also can occur on ligamentous, tendinous attachments anywhere)

Labs: ESR < 40, RF < 1:40, non-inflammatory synovial fluid (< 2000/mm3)

Treatment: NSAIDs (some say glucosamine works in patients who cannot tolerate NSAIDs), when it’s bad enough, only treatment is joint replacement (knee/hip) (~95% 10 yr success rate) / chondroitin sulfate under investigation / multiple, short periods of rest throughout day better than one large period of rest / intraarticular steroids occasionally helpful (esp. in joint “lock up”)


            Nodal OA       DIP/PIP / runs in families


Rheumatoid Arthritis

females 4:1 / any age / mildly shortened life span

Findings: swollen, painful, warm joints (PIP, MCP, not DIP), ulnar deviation of MCP [pic], radial deviation of wrists, swan-neck fingers [pic], Boutonnière or button-hole deformities [pic][pic]

Joints: inflamed synovium (pannus) / penetrates to cause erosions, subchondral cysts / fibrin aggregates in joint space (rice bodies) / synovium eventually bridges and ossifies opposing surfaces

Skin: 25% have rheumatoid nodules (firm, oval, non-tender, fibrinoid necrosis, inflammation)

Vasculitis: rheumatoid vasculitis, ulcers, gangrene, splinter hemorrhages, raynaud’s


·        peripheral neuropathy (10%; ½ are slowly progressive, distal symmetrical sensory or sensory-motor polyneuropathy)

·        mononeuritis multiplex

·        entrapment neuropathy à carpal tunnel

Renal: early (drug-induced nephropathies), late (amyloid-like renal disease)

Lungs (almost always RF positive): [NEJM]

·        pleuritis/pleurisy, effusion

·        pulmonary nodules (CT will show them if CXR doesn’t)

·        ILD

·        alveolar hemorrhage

Heart: pericarditis > myocarditis, valves / conduction abnormalities

Eyes: (1st dry eyes or keratoconjunctivitis sicca (Sjögren’s), 2nd episcleritis – may be severe, perforate)

Heme: anemia of chronic disease

Diagnosis: r/o TB (also has RF)

Criteria: 4 of 7 required

morning stiffness > 1 hr

swelling of 3 or more joints

swelling of hand joints (PIP, MCP, wrist)

symmetrical swelling

rheumatoid nodules

positive RF

erosions of hand joints (X-ray)

Labs: 80% have RF (IgM to Fc of IgG), ANA / HLA DR4, HLA DR1 / anti-CCP (worse prognosis; ⅓ with negative RF will have positive anti-citric citrullinated peptide)

Radiography: early X-ray changes in feet (MTPs, very specific for RA), ulnar styloid changes (late becomes piano key sign), C1-2 subluxation (can be very serious and damage spinal cord, but if seen incidentally on lateral flexion c-spine at < 5 mm, can observe)

Course: usually insidious course

Treatment: aggressive therapy is the rule / immunosuppressive drugs from day one

·        Steroids

·        TNF-a inhibitors

·        Others: Immuran

·        Old school: gold, MTX, penicillamine

·        New school (example of regimens): initial tapered high-dose prednisone + MTX and sulfasalazine or infliximab + MTX

Prognosis: more nodules, DR4, anti-CCP, more systemic Sx, are worse indicators


Palindromic RA

waxing and waning course / usually resolves within 24-48 hrs / joint involvement atypical compared to classic RA


Felty’s syndrome

neutropenia, splenomegaly, leg ulcers, polyarticular arthritis (RA~) or SLE

More: nodules (75%), weight loss (70%), Sjögren’s (55%), LAD (35%), leg ulcers (25%), pleuritis (20%), skin pigmentation (15%), neuropathy (15%), episcleritis (10%)

caused by autoantibodies and cytokine/T cell suppression of granulocytopoesis / more common in elderly patients with RA (especially if untreated) / may also have vasculitis etc.


Large Granular Lymphocytes (LGL)

Usually polyclonal, 20% have RA (the rest are considered neoplastic) / usually associated with Felty’s / course is variable


Juvenile Rheumatoid Arthritis (JRA) (Still’s disease)       

children under 16

Presentation: fever, rash (transient, macular), hepatosplenomegaly, serositis

Findings: RF and nodules usually absent (only in older, more severe cases)

Complications: pericarditis, myocarditis, pulmonary fibrosis, glomerulonephritis, growth retardation, iridocyclitis (anterior uveitis – main systemic symptom in up to 25% of girls with mono/pauciarticular RA, insidious yet may lead to blindness), 40% incidence of myopia / 70% recover, 10% with severe deformities


Adult Onset Still’s Disease (AOSD)

Presents with fever, transient rash, joint inflammation / notable for persistent plaques and linear pigmentation

Labs: over 2/3 will have elevated AST/ALT (2-5x) and AST/GGT / (-) RF, ANA / often extremely elevated ferritin


Cogan’s syndrome

Still’s + hearing loss / Treatment: high-dose steroids and pulse Cytoxan


Infectious Arthritis


Infectious Monoarthritis


Neonates: group B strep, H. influenza

Children: S.aureus (45%), Strep A (25%), GNR (20%), Gonococcus (5%), Tb (1%)

Adults: Neisseria (50%), S. aureus (35%), Strep A (10%), GNR (5%), Tb (1%)

Other causes: Pseudomonas (IV drugs, wounds), Klebsiella/E. Coli (IV users, GU infections), lyme disease, Salmonella in sickle cell patients, syphilis (2nd stage and Charcot’s joints) / HACEK organisms

Pathology: usually hematogenous spread / polymicrobial from surgical implantation or elderly with peripheral vascular disease / usually monostotic (except newborns and sickle cell pts)

Neonates: metaphyses, epiphyses

Children: usually metaphyseal only as growth plate prevents spread into joint

Adults: growth plate closed, vessels reunite, bacteria can go everywhere


Clinical symptoms:

early: fever, skin, arthralgias / knee is hot, tender (pain on active AND passive movement; joint movement that is NOT limited by passive motion suggests soft-tissue problem, e.g. bursitis))


Gonococcal:                 hand and feet lesions (erythematous, +/- pustular)

Non-gonococcal:          another focus / debilitating illness / other? / pre-existing joint abnormality


Synovial fluid from joint aspiration or arthrocentesis of knee [video]


·        WBC is a helpful value:

 < 200 is normal ( < 25% WBC)

200-2000 is non-inflammatory ( < 25% WBC; PMNs)

2000-100,000 is inflammatory ( > 50% WBC)

> 80,000 is purulent/septic ( > 75% WBC)


Fungal: 10-40 WBC, 70% neutrophils       Syphilis: 10-40 WBC in 2nd


·        glucose: 25% less than fasting blood glucose indicates infection

·        culture and gram stain (60-80% sensitive)

·        wet prep (not always used, many false negatives by non-expert labs)

·        synovial biopsy (may be needed to diagnose Tb or hemochromatosis)


XR shows pale bone necrosis (sequestrum) / surrounding deposition of new bone (involucrum)

Treatment: empiric antibiotics / joint drainage


Tuberculous arthritis (see TB)

Usually knees / most common is chronic granulomatous monoarthritis / 1% of Tb / 10% of extrapulmonary Tb / onset is months/years / systemic symptoms only in ½ / Synovial fluid: 20 WBC 50% neutrophils, culture positive in 80%, gram stain positive in 1/3 / Pott’s (spine) / scrofula (TB of neck)


Poncet’s disease

reactive arthritis from Tb / bilateral, no organisms found in joints


Lyme arthritis (see Lyme Disease)

            large joints, weeks to months duration, periods of remission, permanent deformities in 10%


Viral Arthritis (from systemic infection)

Parvovirus B19, rubella, HBV, HCV



usually not before 30 yrs / many are asymptomatic / asymptomatic intervals get shorter over time (severe cases can mimic RA)

Pathology: tophi may occur in joints, ligaments, tendons, soft tissue, earlobes, palms, soles, kidney (uric acid > 8 à causes gout, > 20 à causes renal damage (due to very rapid cell turnover)

·        Hyperuricemia (10%) ( > 750 mg/dl)

?HGPRT deficiency

Increased turnover: myeloproliferative disorders, hemolytic anemias, lymphoproliferative malignancy, psoriasis, glycogen storage diseases

·        Impaired renal excretion of uric acid (90%) ( < 700 mg/dl)

polygenic inheritance

hypovolemia (adrenal insufficiency, diabetes insipidus)

Toxins: heavy alcohol use / lead toxicity / ASA interferes with tubular secretion / organic acids compete for secretion (ketones, LA)

Other drugs: thiazide, radiocontrast agents, allopurinol/probenecid (if given during attack)


Some classify in stages:

I – asymptomatic hyperuricemia

II – acute gouty arthritis

more at night, last hours to weeks, 1st attack usually only in one joint / Podagra (90%) – 1st MTP (great toe)

III – intercritical gout

            most patients have next attack within 1-2 years

IV – chronic tophaceous gout

erosion of underlying bone from chronic inflammation

Precipitation: dietary excess, alcohol, acute medical illness, surgical procedures,  joint trauma

Renal complications:  urate crystals in medullary interstitium (pyelonephritis, obstruction) / 20% of chronic gout die of renal failure (typical to have mild albuminuria, not glomerulonephritis)

Diagnosis: needle-shaped urate crystals in synovial fluid - yellow, parallel to polarizing light

Note: don’t rule out infection just because you see crystals as infection frequently coexists with hyperuricemia


Acute attack:

colchicine (0.6 mg bid or until diarrhea, unless renal impairment)

NSAIDs (indocin and tolectin thought to work best)

steroids (prednisone 40 mg qd x 2-3d with rapid taper)

Prevention: low purine diet / weight loss  / avoid alcohol / colchicine (low dose daily)

Probenecid: frequent attacks / stones / tophi / do not use with renal insufficiency

Allopurinol: diminishes uric acid production (do not start during acute attack)


Pseudogout (CPPD) far less  common than gout

elderly man/woman (over 85) / calcium pyrophosphate dihydrate in synovial membranes et al / usually asymptomatic   rhomboid crystals / familial form chr 8q and chr 5p

Labs: mildly elevated ESR / chondrocalcinosis (+ / -) / CPPD crystals - coffin-shaped, weakly  (+) positive birefringence (blue when parallel)

Presentation: warmth, erythema, tenderness, swelling, may have fever, leukocytosis / self-limited to several days / usually knee (50% of acute attacks) / pseudopodagra is almost impossible

Radiography: calcific deposits (chondrocalcinosis present in 26% of asymptomatic adults > 60 yrs) / hook-like osteophytes/subchondral cysts (similar to OA)

Associated metabolic conditions:

Hyperparathyroidism (primary or secondary)

Hemochromatosis (perform basic Fe studies), maybe Wilson’s, A1AT



Hypomagnesemia (mild hypomagnesemia potentiates PTH action)



Neuropathic joints, aging, trauma/surgery

            Note: urate gout and rheumatoid arthritis have a strong negative association (10x)

Work-up for newly diagnosed CPPD: Ca, Mg, PO4, Alk Phosphate, ferritin, Fe, TIBC, TSH (less Mg and PO4 in over 60 yrs?)

Treatment: symptomatic relief from NSAIDs (indomethacin), steroids (injection or PO), joint aspiration, joint immobilization, IV or PO colchicines (only if you can use high doses) /

correction of underlying metabolic problem does not always stop progression


Pseudogout (Type A) (25% of CPPD)

Almost never causes podagra / males / asymptomatic between attacks / usually have radiographic evidence (such as chondrocalcinosis seen in AP pelvis, PA wrists)

20% with hyperuricemia, 5% with urate gout

HC associated shows 2nd/3rd MCP enlargement and/or attacks of pseudogout


Pseudorheumatoid arthritis (Type B)

10% with low titre RF / joints inflamed “out of phase” (like gout, not like RA), osteophytes, CPPD, lack of typical erosion patterns on X-ray

can mimic sepsis in elderly patients (fever, WBCs, mental status, polyarthritis)


Hydroxyapatite (HA)

secondary to many systemic disease states (apparently, mostly with elevated Ca2+) / crystals so small, a special stain is required to detect / anti-inflammatory treatment may shorten duration of attacks, long-term changes cannot be undone?


Calcium oxalate (CaOx)

strong positive (+) birefringence

Primary: rare genetic disorder, death < 20 yrs

Secondary:  renal failure or vitamin C abuse



usu. middle-aged women / hypersensitivity to physical stimulation causing pain, fatigue, poor sleep(mechanism poorly understood)

Diagnosis: diagnosis by exclusion of other disorders and demonstrating ≥ 11 of 18 trigger points

Labs: no specific lab abnormalities

Treatment: no good treatment, but TCA’s might provide some relief


Relapsing polychondritis

Inflammation of cartilage (breakdown of chondroitin sulfate)

Findings: saddle-nose deformity, scleral thinning (scleromalacia), floppy ear, aneurysms, valvular insufficiency (AR, MR, TR), tracheal narrowing (steeple sign)


Liquid lipid microspherules?


Other Bone Disorders



adolescent females > males / 20% with positive family history


slipped capital femoral epiphyses

20% with referred knee pain (can be misleading) / occurs in pubescent males, happens gradually, can be bilateral / Treatment: surgical with pinning


Villonodular synovitis (benign neoplasms)

            aggregates of polyhedral cells, hemosiderin, foam cells, giant cells, zones of sclerosis

            Treatment: surgery if possible, usually difficult to excise


            pigmented villonodular synovitis (PVNS)

                        single or multiple, diffuse involvement, red-brown projections


            giant cell tumor of tendon sheath (localized tenosynovitis)

                        small, discrete nodule


Bone Cancer


mets most common form: BLT2KP       lung > breast (lytic) > prostate (blastic) > testes, kidney

primary malignant: OS, malignant fibrous histiocytoma, adamantinoma, chordoma



most common primary bone lesion / young males / sessile or stalked / cartilage cap / usually stops growing as bones mature



single or multiple (Olier’s Disease, Maffucci’s syndrome) / short bones of hands, feet / radiolucent [XR] / lobulated, hypercellular, disorganized / focal calcification w/in lesion / self-limited disease


Chondrosarcoma - good prognosis

proliferation of malignant cartilage / older males / axial skeleton / surgery only useful option


Osteoid osteoma

very common / young males / < 2 cm growth / appendicular skeleton / produces pain at night (relieved by aspirin) / radiolucent lesion surround by reactive bone formation / surgical removal / 25% relapse due to poor nidus locating by surgeon


Osteosarcoma (OS) - poor prognosis

pre-op and post-op chemotherapy / arm, leg bones / produces bone, cartilage, spindle cells usually have mets / cortical destruction w/ extension in soft tissues (Codman’s triangle)


Parosteal osteosarcoma (POS) - excellent prognosis

young, early middle age, women / long bones / radiolucent ‘string sign’ along cortex / spindle cells produce well-formed bone                    


Ewing’s sarcoma (variable prognosis)

small cell neoplasia / unknown histiogenesis / very young, males, lower extremities / XR: moth-eaten intramedullary pattern, ‘onion skin’ periosteal reactive bone / diaphysis to metaphysis / PAS+ cytoplasm / therapy evolving           


Fibrous cortical defect

very common / young, males, long bones / XR: metaphysis, sub-cortical, soap bubbles, sclerosis at interface spindle cells, foamy macrophages, hemosiderin, chronic infiltrate / self-limiting at skeletal maturity


Fibrous dysplasia

very common / single, multiple / young, localization random / XR: radiopaque, ‘shepherd’s crook’ of proximal femur / spindle, cells, woven bone, lack of osteoblastic rimming, Chinese character appearance / no treatment unless symptomatic / excellent prognosis


Malignant fibrous histiocytoma (poor prognosis)

similar demographics to OS / XR: metaphysis, destructive, radiolucent / anaplastic spindle cells, storiform pattern / treatment same and prognosis slightly worse than OS


Giant cell tumor of bone

benign but aggressive local tumor / young, wide distribution / hemorrhage / surgery when possible / extended curettage (experimental) or resection / prosthesis / 98% monostotic / radiation contraindicated (secondary sarcomas)


Adamantinoma (good prognosis)

primary malignant bone tumor / young males, tibia/fibula / XR: may be multifocal (observe carefully) / epithelial or endothelial proliferation / complete surgical extirpation



malignant bone tumor arising from notochord / 40s to 60s / males / physaliferous cells in acid mucoid background / surgery and post-op radiation

            survival: sacral 60% (fair) 5 yr, cervical (horrible) 50% 5 yr 0% 8 yr


Myositis ossificans   

athletic adolescents, history of trauma (50%) / central fibroblast proliferation, intermediate zone of osteoid formation, peripheral shell of organized bone / Treatment: usually cured by excision


Connective Tissue Diseases


Rheumatoid arthritis (see bone)                                


Systemic Lupus Erythematosis (SLE)

1 in 300 black women / HLA-DR3 / HLA-DR2

Differential: psoriasis (i.e. avoid UV light therapy), lyme disease, drug reactions, tinea

Diagnosis: must meet 4 of 11 criteria (malar rash, discoid rash, photosensitivity, mucosal

ulcers, arthritis, serositis, renal, neurologic, hematologic, positive ANA, positive LE or anti-ds or anti-Sm)


General: fatigue, weight loss, fever

Skin: malar rash (fixed erythema, flat or raised over malar area, tends to spare nasolabial folds), discoid rash (erythematous raised patches with adherent keratotic scaling and follicular plugging), photosensitivity, periungual telangiectasia, alopecia

Renal: many forms possible / note: 80-90% of SLE becomes dormant when ESRD occurs

·        mesangial (earliest: may remit or transition to other forms)

·        focal proliferative (50%)

·        membranous (50%)

·        diffuse proliferative (20%, worst)


·        endocarditis (Libman-Sacks/caused by APA syndrome)

·        pericarditis

·        hypercoagulability

·        Raynaud’s (20-30%)

·        purpuric lesions (see hematologic)


·        hypercoagulable state (in addition, there is arterial-specific hypercoagulability in SLE patients due to variant mannose-binding lectin genes)

·        leukopenia (<4000/mm3), lymphopenia (<1500/mm3), thrombocytopenia (<100,000/mm3), hemolytic anemia


More common à pleuritis (LE cells are very specific, WBC’s with pushed aside nucleus, very characteristic appearance, but make sure pathologist looks for them), pleural effusion (mildly exudative, unilateral or bilateral)

Less common à ILD (including pneumonitis)

PE (from APA)

pulmonary HTN

diffuse alveolar hemorrhage (rare): 90% will have concurrent nephritis, abrupt onset, young women, association with pneumonia)

            malignancy: ↑ risk of lung cancer > lymphoma

            other: BOOP, shrinking-lung syndrome, lymphadenopathy, infections

GI: painless oral or vaginal ulcers, non-specific abdominal complaints / GI vasculitis (less common, serious)

Musculoskeletal: arthralgias (symmetric/peripheral, two or more joints, swelling, effusion,

tenderness but NOT erosive; only small percentage actually get joint deforming arthritis as in RA)

CNS:  diffuse psychosis, depression or focal neurological deficits (including seizures) [Ddx] / 50% experience some degree of neuropsychiatric problems / may see cystoid bodies in fundus

Other: hepatosplenomegaly (functional hyposplenism), LAD


decreased C3/C4 (can be marker of active disease, either can be depressed first depending on if classical or alternate pathway is activated, can also be decreased from poor synthesis such as in liver disease)

thrombocytopenia, anemia

schistocytes generally not seen without active vasculitis or major HTN

anticardiolipin Ab (30-50% have it, fewer actually have APA syndrome)

false positive VDRL

anti-nuclear antibodies (ANA) (labs)

98% sensitivity, often high titre (1:80 happens in many people is non-specific) / 10% of SLE in whites may be ANA only (no other positive Abs), this is rare in non-whites


Specific Patterns


Peripheral à active disease, renal involvement

Diffuse à SLE, RA, discoid lupus, normal elderly (rare) / can mask speckled or peripheral pattern

Speckled à RA, SLE, MCTD, chronic discoid lupus, chronic lung disease, scleroderma, normal elderly (rare)

Nucleolar pattern à scleroderma (occasionally SLE, RA, Sjogren’s)


anti-ds DNA                specific for SLE, can fluctuate with treatment

RPGN, rash, pneumonitis

anti-Sm                        very specific

anti-Ro (SSA)              Sjogren’s, SLE, myositis, etc.

anti-La (SSB)               cannot have La without Ro


SLE, PSS, myositis / cytoplasmic Ab, thus can be negative ANA / very strong correlation with blacks + Raynaud’s and/or myositis and primary pulmonary HTN (uncommon)

anti-ribosomal P

            specific for SLE, can be sole antibody with ANA negative SLE

ANA to histone (diffuse pattern)

suggests drug-induced (90% sensitive, but not so specific in that 20-30% of idiopathic SLE will have anti-histone Abs)


Note: each patient has there own idiosyncratic pattern of lab markers to follow (compliment, platelets, WBC?, Anti-DS)


Drug-induced SLE

SLE-like syndrome / (+) ANA to histone /  (+) genetic predisposition, ANA may remain positive for years

Course: usually much less severe, resolves within 6 months of stopping drug

Drugs: procainamide, INH, hydralazine, chlorpromazine, methyldopa


            Cutaneous lupus erythematosus

Pathology: interface dermatitis and granular deposition of IgG along the dermal-epidermal junction


            Chronic Discoid Lupus


            Chilblain’s Lupus – rare

violaceous digital plaques, nodules develop after cold exposure / anti-Ro (SSA), Raynaud’s, changes in nail-fold capillaries / lesions contain papillary and deep dermal T-cells


Pregnancy and SLE

antibodies DO cross placenta and affect infant up to 6 months after birth / can cause irreversible congenital heart block (anti-Ro/SSA) (often before mother is diagnosed)

Treatment: education! If disease is controlled (and < 10 mg prednisone), then it is okay to proceed with pregnancy


Sjögren’s syndrome (Keratoconjunctivitis Sicca) [NEJM]

females (usu. peri-menopause) / HLA-DR3 / can have primary or secondary (with SLE/RA)

Mechanism: lymphocytic infiltration and destruction of lacrimal and salivary glands

Presentation: dry eyes, dry mouth, dry skin, enlarged parotid, enlarged lacrimal gland / patient avoids sour foods

Findings: dry skin, GI, GU, arthritis (more synovitis), bronchitis


·        Peripheral neuropathies (50-60%) / usu. pure sensory, asymmetric chronic neuropathy (may precede other symptoms by many years)

·        GERD

·        increased risk of B-cell lymphoma (1-5%)

·        association with decreased PFTs (lung disease)

Diagnosis: eye exam (Schirmer test), lip biopsy (salivary gland) in uncertain cases, SSA (anti-Ro), SSB (anti-La) occur in only 3% of cases [note, one does not have anti-SSB without anti-SSA], often have elevated RF, ESR

Treatment: symptomatic (fake tears, benzodiazepines for anxiety, etc.), pro-cholinergic agents, steroids for severe systemic complications





Many with (-) Ab’s, but if (+) à very specific for autoimmune myositis


·        anti-Jo1 (his-tRNA synthetase) – moderate prognosis

30% of PM, 20% of DM

                        arthritis, interstitial lung disease, fever, Raynaud’s, mechanics hands

                        all patients with Jo-1 are DR52, whites may also have DR3 or DR6


·        anti-SRP (signal recognition particle) – poor prognosis

                        cardiac (with palpitations), myalgias, mostly blacks / DR5


·        Anti-Mi-2 – good prognosis

8% PM/DM, 20% of DM

classic DM picture / 7, DRW53



Onset usually > 50 yrs

Genetics: HLA-DR3, DQA1*0501 (whites and blacks), 0401 (blacks)

Mechanism: CD8 T-cell mediated destruction

Muscle: inflammatory myopathy

Lungs: pulmonary inflammation / mostly CD8, some CD4

            Heart: can get cardiomyopathy (even heart block)

Diagnosis: clinical, EMG, biopsy

Presentation: proximal muscle weakness, up to 30% with esophageal dysphagia, Raynaud’s (30%); eyes are spared; unlike myasthenia gravis; up to 50% will have additional connective tissue disease at same time

Diagnosis: electromyography, biopsy (not always conclusive) / often confused with other forms of myopathy


·        elevated plasma CK

·        ESR may be elevated (but a super-high ESR may hint that something else instead or along with myositis is happening)


·        Anti-Jo-1 associated ILD responds more to steroids than other ILD (scleroderma, RA)

·        Anti-Ku à SCL/PM overlap (mostly in Japanese) / association with Graves, pulmonary HTN, and RNAP-II

Course: less prolonged than muscular dystrophies / mortality usually from aspiration (pharyngeal weakness)

Malignancy: risk ~2.0 x (no particular types, usually occur after PM diagnosis)

Treatment: high-dose steroids (up to ~100 mg/day IV then PO) / improvement should occur with first few weeks with continued improvement over 3 to 6 months / continue initial dose until strength and CK normalizes for 4-8 weeks / CK can remain elevated due to leaky membranes and strength can remain low with normal CK due to steroid myopathy (i.e. steroid myopathy does not cause elevated CK) / reduce steroids by 10 mg/month, then qod dosing / 90% will improve at least partially / 50-75% will enter remission / can try MTX, azathioprine or even both together after 6 weeks of non-response to steroids / Plaquenil can help with skin manifestations of DM / others like cyclosporin and Cytoxan have been used / IVIG is useful for DM, and is being tried for IBM



bimodal age peaks [15-20] and [45-55]

Mechanism: CD4 T-cell and B-cell mediated destruction / humoral response more important

Skin changes without muscle involvement occurs in ~10% of cases

Skin/Joints: heliotrope rash on face (Shawl sign) [pic], V-sign, mechanic’s hands, cuticle

Changes (capillary engorgement, capillary dropout), periungual telangiectasia [pic], calcinosis [pic] [dermis], Gotron’s papules over finger joints, knuckles, elbows, patella

Lungs: can have bad lung disease (usu. w/ anti-Jo1)

Vasculitis of the gastrointestinal tract, kidneys, lungs, and eyes can complicate dermatomyositis (but not polymyositis), particularly in children

Malignancy: relative risk 6.2 (about 20%, no particular type) / DM often diagnosed after or at same time as cancer, then risk decreases to 1.6 after 5 yrs

Biopsy: classically different pattern than PM / ?can it look like SLE

Treatment: similar to PM (with exception that IVIG can be particularly useful) / newly diagnosed cancer patients should have basic workup for malignancy


Juvenile Dermatomyositis (JDM)

            ANA negative / disease usually lasts about 2 years / diagnosis often suggested by

calcinosis on plain films [pic]



more in females

Presentation: CREST (60-98%), raynaud’s (20%) [pic], diffuse systemic sclerosis (10%) / cardiovascular, skin, kidney, GI, lungs / fibrosis, infarction may develop rapidly progressing renal disease / malignant hypertension in 1-2 weeks


·        Diffuse type: rapid, early visceral involvement, diffuse skin involvement [dermis] (morphea)

~50% mortality rate at 5 years

Lungs: pulmonary fibrosis or primary pulmonary HTN

Diagnostic criteria: major - proximal skin thickening / minor – sclerodactyly, digital pitting (ischemia), pulmonary fibrosis (CXR)

Early signs: look for drop out capillaries in nail folds

Genetics: anti-Scl 70 or anti-topoisomerase I


·        CrEST type: calcinosis, Raynaud’s, esophageal dismotility (loss of smooth muscle may occur anywhere in GI tract), sclerodactyly, telangiectasia (mat and periungual)


Labs: schistocytes on peripheral blood smear, ANA (20-30%), RF (20%)

·        SCl-70 (DNA topoisomerase I) à 70-80% of diffuse scleroderma

·        Anti-centromere à 70-80% CrEST, 25% Raynaud’s

·        Nucleolar antigens à 4-8% of scleroderma

·        PM-Scl à polymyositis, scleroderma overlap

·        Anti U1-RNP/nRNP

·        Anti-Ku (see PM)

Ddx: eosinophilic fasciitis, porphyria cutanea tarda, papular mucinosis (i.e., scleromyxedema), lichen sclerosis et atrophicus, melorheostosis, chronic GVHD, eosinophilia-myalgia syndrome

Treatment: ACE inhibitors, Ca blockers (Raynaud’s), metoclopramide, sucralfate, omeprazole (GI problems), cisapride (from Mexico)

Prognosis: may survive up to 20 years before succumbing to pulmonary hypertension



            more common in women, African-Americans

Presentation: various protean manifestations / adults: CNS, lungs > heart >> renal

·        Lungs: restrictive lung disease, pleurisy (with effusion) / actually does not produce rales (too much fibrosis)

·        Liver: hepatomegaly (20-30%)

·        Skin: both acute and chronic changes / lupus pernio (violaceous indurated lesions with a predilection for the nose, ears, lips, and face), skin plaques [dermis], maculopapular/papules (red-brown, waxy), subcutaneous nodules, and erythema nodosum, vitiligo (hypo or hyperpigmented), alopecia, old cars

Ddx (for skin changes): Tb, berylliosis, leprosy, leischmaniasis, syphilis, deep fungal infection / other panniculitis (Behçet’s, superficial thrombophlebitis, cutaneous vasculitides)

·        CNS: can present with only CNS problems (peripheral neuropathy, aseptic meningitis) or focal (cranial nerves, hypothalamus, pituitary)

Ddx (for CNS): cancer with mets, fungal or Tb, lymphoma, Langerhans histiocytosis, other

·        Joints: knees, ankles, elbows, wrists, small joints of the hands / swollen, warm, tender, painful


·        Lungs: hilar lymphadenopathy, pleural effusion

·        Eye: variety of conditions / uveitis / others (20% incidence)

·        ENT: parotitis / nasal involvement

·        CNS: Bell’s palsy, diabetes insipidus (posterior pituitary > anterior), cranial nerves, basal meninges, hypothalamus, seizures, etc. / [MRI] / elevated ACE in CSF (66%)

·        Heart: restrictive cardiomyopathy

·        Liver: very common, but usually no symptoms, can be good biopsy site

·        Renal: very uncommon

Diagnosis: can be diagnosis of exclusion when biopsies inconclusive, often first recognized from CXR in asymptomatic patients (60-70% will have some abnormality on chest CT)

·        Biopsy (of involved lesions): widespread non-caseating granulomas with Schaumann and asteroid bodies / may look like Tb / any one of following has 50-80% sensitivity (all three combined have 99% sensitivity) / note: granulomas in scalene, liver nodes are not (by themselves) sufficient for diagnosis (because granulomas are so frequent in these nodes)

·        Transbronchial biopsy (TBLB)

·        Transbronchial needle aspiration (TBNA)

·        BAL showing lymphocyte predominance ( > 12%), high CD4:CD8 ratio (should not have high neutrophils or eosinophils at same time; ratio > 3.5 has 90% specificity, 50% sensitivity)


·        Hypercalcemia (10%) (elevated 1-hydroxylase produces 1,25-OH D3) (hypercalciuria in 33%)

·        serum ACE elevated in 66% (many false positives including Mycobacteria and malignancy)

·        lysozyme

·        elevated d-dimer (correlates with disease activity)

Course: often asymptomatic and self-limiting

Children under 5: skin rash, eyes (uveitis), arthritis (worse prognosis)

Older children: lungs (usu. bilateral, hilar lymphadenopathy), lymph nodes, eyes

Treatment: for stage I (asymptomatic), observation only, may regress / for stage II-III or with any serious organ involvement, corticosteroids (40 mg/day), other DMARDs

            Prognosis: earlier onset tends to mean better prognosis


            Lofgren’s syndrome

acute sarcoidosis / usually with symmetric, periarticular ankle inflammation / may have erythema nodosum



Systemic vasculitides


Complement levels


all have normal complement levels except variable in PAN, leukocytoclastic, connective tissue disease, endocarditis / decreased in urticarial vasculitis


Vasculitis Associations

PAN and hairy cell leukemia

Wegener’s and Hodgkin’s disease

Granulomatous angiitis of CNS and lymphoma

GCA and lymphoma

HSP and lymphoma


grouped by vessel-size



giant-cell arteritis

Takayasu’s arteritis

primary CNS vasculitis


Medium (with or w/out involvement of small)








            leukocytoclastic (HSP, cryoglobulinemia, infectious)

connective tissue diseases


microscopic PAN

urticarial vasculitis


Any size (pseudovasculitis)


endocarditis (bacterial/marantic)

other embolic

cholesterol embolism

drugs (amphetamines and rarely cocaine)


Infectious Vasculitis Ddx


                Bacterial agents

Acute septic meningitis agents



Treponema, Borrelia sp., Leptospira

            Other agents

Brucella species

Bartonella henselae



Viral agents


More: hantavirus, California encephalitis virus, EEE encephalitis virus, influenza, rubella


            Aspergillus, Coccidoides, Candida





CNS vasculitis


Ddx:    reversible cerebral vasoconstriction syndromes (RCVS)

PAN – classic, microscopic/HBV, HIV



hypersensitivity angiitis – drug-induced, HSP

neoplasia (many)

infection (see below)


primary angiitis of CNS (PACNS) – CNS angiography, brain biopsy


Diagnosis: start with MRI, then CNS angiography à vessel wall irregularities, focal dilations, supraclinoid internal carotid artery narrowing, and distal branch occlusions [MRI][MRI][MRI][MRI]


Infectious  Causes of Vasculitis


Bacterial agents

Acute septic meningitis agents

Mycobacteria (5%)


Treponema, Borrelia sp., Leptospira (Weil syndrome)

Brucella species

Bartonella henselae



Viral agents



            Aspergillus, Coccidoides, Candida







Neonate (<1 month)

Streptococcus agalactiae (44%)

Escherichia coli (26%)

Gram-negative bacilli (10%-22%)

Listeria species (5%-10%)


Children (1 mo to 15 yrs)

Neisseria meningitidis (25%-40%)

Streptococcus pneumoniae (10%-20%)

Haemophilus influenzae (8%-12%)


Adults (>15 years)

Streptococcus pneumoniae (30%-50%)

Neisseria meningitidis (10-25%)

Staphylococci (1%-15%)

Gram-negative bacilli (1%-10%)

Listeria species (5%)

Streptococci (5%)


Head trauma, surgery


Gram-negative bacilli




Listeria monocytogenes



Respirator support

Proteus species





Ruptured brain abscess

Gram-negative bacilli





Neonates get arteritis/thrombophlebitis (larger, +/- hemorrhagic infarcts, +/- secondary abscess formation) / venous thrombosis and hemorrhagic necrosis (associated with Pseudomonas, Proteus, Enterobacter, and Serratia)

Septic venous sinus thrombosis/thrombophlebitis (up to 5%, usu. < 1 or 2 weeks)


Note: sinus, middle ear, skull infection can beget cerebral vasculitis without detectable meningitis / also, basilar infection can causes vasculitis of ascending arteries


Peripheral Nervous System

Lyme disease à multifocal axonal radiculoneuropathy

HIV-1 à multiple mononeuropathies


HCV à cryoglobulinemia

HSV, VZV à sensory ganglia, radicular syndrome



Giant Cell Arteritis (GCA) (temporal arteritis)

Not uncommon (1 in 5000) / usually > 50 yrs / women > men (2:1) / whites, Scandinavians / HLA-DRB1*04 and DRB1*01

Presentation: gradual > abrupt / 15% fever / headache (66%, unilateral >> bilateral, dull and boring, superimposed sharp pain), jaw claudication (50%), temporary blindness, fever, weight loss, myalgias/arthralgia, malaise, cough/hoarseness (10%), neuropathies (10%), TIA, polymyalgia rheumatica (50%)

Complications: blindness (can occur early on, retinal changes like edema of optic disk, cotton-wool patches, small hemorrhages, usu. occur after blindness, usu. from nerve ischemia), eye exam can be helpful / thoracic aortic aneurysm (17x) normal incidence

Associations: lymphoma (vasculitis may precede lymphoma) /

Pathology: mainly external carotids and vertebral / can hit central retinal artery (but intracranial arteries are NOT involved)

Diagnosis: biopsy temporal artery, try to get affected site (if cannot localize on exam, then get larger piece, 3-5 cm), can do bilateral biopsy to increase yield, yield of biopsy decreases with each day of steroids but can still be positive even at 1-2 wks post-steroid (lymphocytes, plasma cells, giant cells) / high ESR (over 50, often > 100, can be expected to decrease within days of

treatment, ~20% have normal ESR) / CRP is more sensitive / NOTE: careful exam may reveal findings prior to onset of symptoms


·        prednisone (1 mg/kg qd 1-2 months then taper by 5-10% q 1-2 wks) / usually see improvement within days (if not, question diagnosis) / can use 100 mg qd for optic nerve involvement / can begin cyclophosphamide (maybe other DMARDS) if necessary / can begin to think about tapering after 1-2 months (10-20% every 2 weeks), but must continue to treat for a long time (1-4 yrs to reduce recurrence) / qod therapy thought to be less effective but open question of whether some patients can start at lower doses (20-30 mg qd) / ½ of patients have serious complication of extended steroid use

·        ASA also thought to decrease risk of occlusions

Recurrence: 30-50% have spontaneous exacerbations independent of steroid regimen / most often, recurrence involves PMR Sx and can be treated by increasing steroids by 2 to 5 mg/qd


Takayasu’s Arteritis

Granulomatous inflammation of large arteries / young women (>Asian) / complications may develop over months to years / affects aorta and branches (subclavian), pulmonary arteries (up to 50%), renal artery

Presentation: weak pulse in upper extremities (arm claudication), ocular disturbances, HTN (renal artery) / Raynaud’s / systemic: fever, weight loss

Diagnosis: CT may reveal circumferential thickening / MRI may show enhancement on T1

Labs: increased ESR



            Mostly children (4-5/years) / medium-sized arteries

5 diagnostic criteria: more than 5 days of fever, bilateral conjunctival injections, oral mucosa and pharynx (infected and dry fissured lips, strawberry tongue), peripheral extremities (edema, erythema, desquamation – rash, primarily truncal), cervical adenopathy

Complications: hydrops of gallbladder, more -


restrict activity 3-4 wks


Immunoglobulin 2 gm/kg  single / 400 mg/kg/day x 4 days

MMR should be delayed 6 months

Aspirin – 80-100 mg/kg/day QID until afebrile

Anti-platelet agents

Treat for 3 months, but indefinitely and add more agents? if coronary involvement


ANCA Associated Vasculitides (AAV)


Polyarteritis Nodosum (PAN)

rare / occlusion (infarct) of medium to small arteries (NOT capillaries) / type III hypersensitivity

Presentation: usually present with constitutional symptoms

Associations: HBV, hairy cell leukemia

Findings: cotton-wool patches, pericarditis, myocarditis, palpable purpura aneurysm (hemorrhage)

Diagnosis: 3 or more of 10 criteria (sensitivity 80%, specificity 85%)


Weight loss > 4 kg


livedo reticularis


testicular pain

testicular biopsy useful if involved


CK usually normal


50-80% (only 15% in MPA)

good chance of recovery within 1 yr

diastolic ( > 90)

elevated BUN/Cr

Renal vasculitis (not RPGN)

Renal failure may occur later

HBV positive

Not in MPA

GI aneurysms by MRA

GI pain in 30% (risk of perforation)

positive biopsy



Labs: elevated ESR (~85), CRP, WBC, eosinophils, normochromic anemia, HBsAg found in 10-30%,  HCV rarely associated, 20% have positive p-ANCA to myeloperoxidase (MPO), RF  (+) in 20%

Treatment: steroids, cyclophosphamide, plasma exchange (2nd line)



            More HTN than classic PAN

Remember to treat both HBV and PAN

Treatment: plasmapheresis and lamivudine


Microscopic Polyangiitis (MPA)

May have capillary involvement in addition to small/medium arteries (unlike classic PAN)

Glomerulonephritis (usu. RPGN) common (not in PAN), alveolar hemorrhage (not in PAN)

Presentation: can have arthralgias, hemoptysis et al for months/yrs!!! before explosive onset

(longer prodrome than with PAN) / most with constitutional symptoms before diagnosis

Labs: almost always have p-ANCA (+) and MPO (+) / rarely c-ANCA will be (+)  / other P-ANCA (but not MPO): Felty’s, UC (directed against different proteins)

Course: relapse in MPA (35%) > HBV-PAN and c-PAN (10%)

Treatment: ?similar to classic PAN


Wegener’s Granulomatosis

medium to small arteries / type IV DTH

Presentation: chronic sinusitis, epistaxis, mucosal ulcers, cough (45%), hemoptysis (30%), fever, night sweats, arthritis, myalgia, skin nodules, renal failure / mean interval from symptoms

to diagnosis 15 months

Affected: nose, throat, bronchi, kidneys

Complications: renal failure (hematuria, RBC casts, RPGN) / saddle-nose deformities, sepsis, hemorrhage, DIC / usu. does not lead to respiratory failure

Associations: Hodgkin’s lymphoma

Diagnosis: cANCA (confirm with anti-proteinase 3) (90% sensitivity, few false positives) / ~10%

with p-ANCA / ~10% with anti-GBM / biopsy of ENT likely to show only necrosis, biopsy of kidney likely to show only non-specific RPGN, you can’t stain for IF (that’s why it’s called pauci-immune!!!), biopsy of lung most likely to confirm diagnosis

Chest CT [CT] [CT] [CT] pulmonary infiltrates or nodules (up to 85%) / not pleural


Labs: elevated ESR


Prognosis: higher ESR, older age gives worse prognosis / ENT involvement gives better prognosis

Treatment: cyclophosphamide (1st), steroids (2nd or 1st for pulmonary hemorrhage) / bactrim is

sometimes helpful (prevention of infection may avoid a potential trigger) / not MTX


            Hypertrophic pachymeningitis (HP)

pANCA positive CNS disease, which some think of as Wegener’s limited to CNS/cranial nerves /

treat as Wegener’s


Buerger’s (Thromboangiitis Obliterans) [NEJM]

male, smokers / medium to small arteries AND veins

Presentation: hypercoagulability, claudication, pain, Raynaud’s, gangrene

Exam: Allen’s test

Treatment: perhaps ca-blockers, stopping smoking will hopefully stop progression of disease


Churg-Straus Angiitis [NEJM]

            3 stages (order can vary) / asthma, eosinophilia, vasculitis

Asthma           may occur up to 30 yrs (mean 3) before vasculitis, onset with vasculitis in 10%, after in 2%) / sinusitis, allergic rhinitis, nasal polyps

Eosinophilia    can mimic chronic eosinophilic pneumonia

Vasculitis        mononeuritis multiplex (72%), weight loss (>50%), fever, myalgia, skin lesions (60%) > GI (50%) > spleen > heart (myocarditis, infarction) > kidneys (FSGN)

Diagnosis: angiitis and extravascular necrotizing granulomas with eosinophils

Labs: P-ANCA (50%, usu. anti-MPO), RF, elevated ESR (80% of cases), eosinophilia (over 10% in 90% of cases)

Often seen in asthma patients being tapered from PO or inhaled steroids (may be associated with leukotriene antagonists)



Hypersensitivity Angiitis

            adverse drug reaction


HSP (Henoch Schönlein Purpura) (see renal)

            small vessel vasculitis


Behçet’s Disease (Behcets) [NEJM]

mostly in people of Middle East, Japanese descent / onset in 20 to 30s

Course: chronic, relapsing acute attacks / manifestations (except uveitis) usually self-limited


Mouth: aphthous oral [pic] / genital ulcers [pic]

Eye: uveitis, retinitis (can cause blindness), hypopyon

Skin: superficial migratory thrombophlebitis, erythema nodosum (including pseudofolliculitis and acneiform nodules / pathergy

Joints: mono/polyarthritis (50%, knees > wrist, elbows, ankles) (non-deforming)

Coagulopathy: vasculitis/ hypercoagulability (major concern is retino-occlusive disease), venous 7 times more than arterial (however, can get aneurysms, stenoses), 25% will have at least superficial venous thromboembolism

Less common: GI, CNS (early onset males 10-20%), large vessels / may have

Diagnosis: oral ulcers + 2 other criteria / can look for HLA-B51 (not in S. American, N. American), elevated IgD levels

CSF: elevated IgG (not oligoclonal), pleocytosis

MRI: multiple high-intensity focal lesions in brain stem, basal ganglia, and cerebral white matter are typical on T2-weighted MRI

Ddx: chronic oral aphthosis, Sweet’s, HSV, AS / GI (IBD), CNS (MS), pathergy (Sweet’s, pyoderma gangrenosum), retinitis (sarcoid, viral retinitis)


Skin: topical steroids, thalidomide, colchicines, oral steroids

Ocular, GI, CNS: oral steroids / other immunosuppressives (Cytoxan, Immuran, others) / note: cyclosporin may worsen CNS symptoms (it’s not a first line agent) / IFN-a, IVIG under investigation

Arthritis: steroids, NSAIDS, colchicines, sulfasalazine, IFN-a (highly effective)

Vasculitis: steroids / be careful with anticoagulation for venous thrombosis (can get big time hemoptysis with arteritis) / treatment of vascular complications is very tricky in this disease since mechanisms are multiple and unclear / CV surgery for complications


HLA Associations [HLA genetics diagram]



HLA allele

Relative risk factor



Hashimoto’s thyroiditis



Rheumatoid arthritis



Dermatitis herpetiformis

SLE (esp. subacute cutaneous, neonatal)






Multiple sclerosis




Ankylosing spondylitis


Postgonococcal arthritis





Psoriasis vulgaris



Myasthenia gravis







Reversible cerebral vasoconstriction syndromes (RCVS) (or Call-Fleming Syndrome or Migraine Angiitis [AIM]

must be distinguished from classical cerebral angiitis (using CNS imaging)

Associated conditions (many) [table] / unlike migraine, no aura, presentation is hyperacute

Causes: vasoactive drugs, diet pills, stimulants, some antidepressants, decongestants, illicit drugs (amphetamines, cocaine, ecstasy)

Treatment: calcium channel blockers, steroids (mechanisms and treatments being worked out 1/07)


Spondylarthropathies AS, psoriasis, Reiter’s and Reactive, IBD


(1)   spondylitis

(2)   sacroiliitis

(3)   enthesopathy

(4)   asymmetric oligoarthritis


Other: inflammatory eye disease, urethritis, and mucocutaneous lesions

Labs: all have negative RF


Ankylosing spondylitis (AS) (Marie-Stumpell Disease)

inflammation and ossification of the joints and ligaments of the spine and of the sacroiliac joints

Epidemiology: young people (~24 yrs) / males=females / HLA B27 (90%) / may occur in association with IBD

Pathology: chronic, progressive (insidious) inflammatory disease of axial joints (hips, shoulders, sacroiliac) / asymmetrical, oligoarticular (1-4 joints) / inflammation at site of insertion / autoantibodies to joint elements following infection

Complications: kyphosis and eventually complete fusion or “bamboo spine” / aortic insufficiency / peripheral joint involvement / pulmonary fibrosis / uveitis (25%) (can lead to glaucoma and blindness)

Diagnosis: do sacral XR 1st reveals squaring, syndesmophytes,

Presentation: morning stiffness (“gel”) / pace floor at night / improves with exercise / pain may move from one joint to another

Treatment: therapeutic goal is to maximize the likelihood that fusion will occur in a straight line physical therapy / avoid smoking (pulmonary compromise)

·        NSAIDS (for symptomatic relief)

·        Anti-TNF-alpha (showing some real benefits on slowing disease progression)

·        methotrexate and sulfasalazine (were tried before TNF-alpha available)

·        surgical procedures to correct some spine and hip deformities may be used in select cases

Course: only 6% die from actual disease; most commonly (cervical fracture, heart block, amyloidosis), and more rarely from the restrictive lung disease


Psoriatic arthritis (see skin psoriasis)

hereditary, 20 to 40 yrs / 7-40% of psoriasis patients get arthritis (may precede skin findings) / also has sporadic form presenting later on in life

4 major forms of arthritis

1.      most have peripheral, asymmetric oligoarticular arthritis

2.      DIP with nail disease

3.      25% have symmetric polyarthritis similar to RA

4.      spondylitis/sacroiliitis less common

Findings: DIP swelling, sausage digits [pic] / nail problems (onychodystrophy, onycholysis, nail pitting, and subungual keratosis, onychauxis) [pic] / psoriatic lesions on extensor surfaces

Diagnosis: must have skin or nail changes for definitive diagnosis

Labs: mildly elevated ESR / hyperuricemia in severe cases

Synovial fluid: 2 to 15 WBCs / Radiography: distal interphalangeal erosions or telescoping joints, asymmetric sacroiliitis, isolated axial syndesmophytes


·        TNF-alpha blockers now shown to slow progression of arthritis and skin complications

·        NSAIDs (indomethacin) and intra-articular steroids (avoid injections through psoriatic plaques) for symptomatic relief / 2nd line: MTX, penicillamine, gold, hydroxychloroquine


Reiter’s syndrome (see reactive arthritis)

HLA B27 / males, 20-30s / HIV patients

Presentation: asymmetric oligoarthritis, (non G-C) urethritis, conjunctivitis, uveitis, characteristic skin and mucous membrane lesions low back pain

Onset: 2-4 weeks after inciting GI or GU infection( Chlamydia)

Common complications:

·        lower extremities: ankles, knees, feet, heels (enthesitis of Achilles tendon)

·        oligoarticular

·        sausage digits (dactylitis)

Other complications:

·        transient conjunctivitis (40%) / may need urgent opthalmological referral (topical or systemic steroids) for (3-5%) disabling iritis, uveitis (can be difficult to treat), corneal ulceration

·        oral ulcers and glans penis (circinate balanitis; 25-40%; painless, red rash)

·        keratoderma blennorrhagicum (mollusk shell skin lesions on palms and soles, may have severe desquamation; similar appearing to papular psoriasis

·        nail changes

·        myocarditis: heart block (<5%), aortic insufficiency

Note: many people have single reactive arthritis symptoms without multiple findings

Causative organisms: chlamydia trachomatis (decreasing), Neisseria (culture-negative), GI: Shigella, Salmonella, Campylobacter jejuni, Yersinia enterocolitica

Labs: elevated ESR and leukocytosis / 0.5 to 75 WBC’s in synovial fluid / bacterial antigens present in joints (chlamydia is dormant) / ANA and RF usu. negative

Radiography: asymmetric syndesmophytes along spine (ankylosing spondylitis has symmetric and contiguous)

Course: most recover (one to several months), 50% recurrence (varying degrees of disability)

Prevention: must take antibiotics (doxycycline) prior to travel / even with HLA B27 – 20% risk of reactive arthritis with proper infection

Treatment: symptomatic relief with NSAIDs (2nd line sulfasalazine) and intra-articular steroids / topical steroids for skin complications / prolonged doxycycline may be useful in cases with chlamydia infection


Reactive arthritis

may follow GI infection (Shigella flexneri, Salmonella species, or Yersinia enterocolitica infections / same joint problems as Reiter’s / extra-articular symptoms tend to be mild / treatment will be similar to Reiter’s (doxy?)



Ankylosing Spondylitis (90%)

Reiter’s Syndrome (75%)

Psoriatic arthritis (20%) / with sacroiliitis/spondylitis (50%)

Enteropathic arthritis (IBD) (8%) / with sacroiliitis/spondylitis (50%)


Arthritis of inflammatory bowel disease

Crohn’s or UC (10-20%) / similar to that of AS

spondylitis, sacroiliitis, and peripheral arthritis ( > knee / ankle)

peripheral arthritis may correlate with colitis activity (spinal disease does not)

antibiotics not effective, but still must rule out septic joints

Treatment: NSAIDS (not salicylates) / GI intolerance more likely in these patients, misoprostol may cause unacceptable diarrhea / sulfasalazine may also be effective / local steroid injection / PT





Drugs causing myositis (by mechanism)



L-dopa, procainamide, cimetidine, D-penicillamine, L-tryptophan,


Non-inflammatory necrotizing or vacuolar

cholesterol-lowering agents, chloroquine, colchicine, emetine, aminocaproic acid, labetalol, cyclosporine and tacrolimus, isoretinoic acid (vitamin A analog), vincristine, alcohol


Rhabdomyolysis and myoglobinuria

cholesterol-lowering drugs, alcohol, heroin, amphetamine, toluene, cocaine, aminocaproic acid, pentazocine, phencyclidine


Malignant hyperthermia

halothane, ethylene, diethyl ether, methoxyflurane, ethyl chloride, trichloroethylene, gallamine, succinylcholine



Zidovudine (AZT)



2,4- d-chlorophenoxyacetic acid, anthracene-9-carboxycyclic acid, cholesterol-lowering drugs, chloroquine, cyclosporine


Myosin loss

non-depolarizing neuromuscular blocking agents, IV steroids


Drugs causing myopathy (painful vs. painless)



Alcohol (chronic), steroids


            CNS depressants, CNS stimulants, CO, cyanide, arsenic, snake venom


Diuretics, laxatives, licorice, carbenoxolone, ampho B, toluene, alcohol




Procainamide, phenytoin, levodopa, interferon alpha, cimetidine, leuprolide, PTU, penicillamine


            AZT, germanium

Drugs of abuse

            Alcohol, cocaine, heroin, PCP, volatile chemicals


Focal myopathy

IM injections, IVDA, cephalothin, lidocaine, diazepam, pethidine, pentazocine, meperidine, antibiotics in children



Alcohol (acute), NMJ blockers (vecuronium, pancuronium), lovastatin < simvastatin, clofibrate, gemfibrozil, aminocaproic acid, excess vitamin E, etritinate, ipecac, emetine (overuse), organophosphates (acute poisoning), toxic oil syndrome, eosinophilia myalgias syndrome, snake venom (peak at 24-48 hrs)


Chronic Alcohol Myopathy

Painless, progressive proximal muscle weakness / ½ of alcoholics / damage is cumulative, but strength often restored after cessation

Histology: type 2b fiber atrophy, no necrosis


Acute Alcohol Myopathy

Weak, painful, swollen muscles and cramps / may be limited to only one limb or muscle

in most cases, cramps resolve in 1-2 days, pain and swelling takes 1-2 weeks, strength normal in 10-14 days / can develop rhabdomyolysis / lag time between alcohol consumption and elevated CK (several indirect mechanisms proposed)

Labs: CK, LDH, myoglobin elevated

Histology: necrosis and myofibrillar disorganization (inflammation is debatable)



Severe, painless proximal muscle weakness (no cramps, no swelling) / develops over hours/days / serum K between 1.4 – 2.5 / can cause rhabdomyolysis / complete reversal with K replacement

Labs: CK, AST, aldolase elevated

Histology: vacuolar changes, macrophages, +/- necrosis, regeneration


Steroids (esp. dexamethasone, triamcinolone)

Symmetrical, proximal muscle weakness / lower > upper / occasionally myalgias / may have generalized weakness, atrophy (severe cases) / very unlikely with < 10 mg/day or alternate day dosing


                        Chronic Steroids

Usually > 3 weeks / usually with other stigmata of steroids use

Labs: CK usually normal / EMG shows normal rest activity, short-duration, low-amplitude motor units / Histology: type II atrophy, increased glycogen in type II fibers, lipid droplets in Type I fibers / EM shows sarcolemmal projections, vesicular bodies


High-dose steroids

Can occur 1-2 days after treatment / often seen when treating severe asthma / may be generalized / may involve respiratory muscles / additional risk factors such as NMJ blockers, sepsis / near total recovery in weeks

Histology: changes in both fiber types, vacuolar changes, regenerating fibers / normal EMG


Licorice, carbenoxolone

Pseudo-hyperaldosteronism / Na retention, edema, hypokalemia



Usually starts in legs / takes 6 months to occur / may also have neuropathy

EMG shows fibrillations, positive waves, occasionally myotonic discharges

Histology: degeneration and acid phosphatase positive vacuoles in up to 50% of fibers / type I fibers predominantly affected / EM shows myeloid bodies and curvilinear bodies similar to neuronal ceroid lipofuscinosis

Hydroxychloroquine (Plaquenil) is supposed to be safer, but I suspect the findings are similar



May occur as early as 1 month / also get peripheral neuropathy, tremor, ataxia



Anti-anginal agent / myopathy usually with long-term use only (reported as soon as 2 weeks, associated with rash, resolved with discontinuation

Other side effects include weight loss, hypoglycemia, hepatic dysfunction, peripheral neuropathy




Note: sometimes misdiagnosed for polymyositis

Sensory or motor nerve conduction is low-amplitude or absent

EMG shows fibrillations, positive waves, myopathic motor units

Histology: vacuolar myopathy



Histology: segmental necrosis, phagocytosis, spheromembranous degeneration / probably can have myopathy without neuropathy


Zidovudine (AZT)

Mechanism: ?false substrate for mitochondrial DNA polymerase

Dose-related proximal muscle weakness and myalgias with pronounced wasting / elevated CK / usually improves with discontinuation

Histology: ragged RED fibers / rod-body formation, necrosis, microvacuolization / EM has various changes

Cannot always distinguish from HIV myositis



Rapidly progressive, necrotizing myopathy / weakness, myalgias, CK 8000-30,000 / can lead to rhabdomyolysis / incidence of 0.5% (compare to incidence of elevated LFT of 2%) / risk increased with combination of lovastatin, gemfibrozil, niacin, immunosuppressive agents

            Histology: necrosis

Much less common with Simvastatin


Aminocaproic acid

usu. > 4 wks, can occur as early as several days


Etritinate (dermatology drug)

mild-transient myalgias occur in 15%, do not require discontinuation / occasionally, can be more severe


Synovial fluid analysis



























Mucin clot







3-50 K



> 50 K


% poly

> 70






10-25% less than serum






> 3.0 g/dl












RA cells















WBC (% Poly)



early RA




chronic/subsiding crystal




















sickle cell












Osteochondritis dessicans




Group II
























Acute crystal
























Group III
















Acute crystal




Group M












Bleeding Disorders (hemophilia, vWF, anticoagulation, scurvy, TCP, thrombocytosis)








Tumor, VNS, hemangioma




Prosthesis, post-op aneurysm




Sickle cell









[a bunch of images]


General Circulatory               HTN, Edema, Thrombosis, PE, DIC, Shock, CHF, Cor Pulmonale

General Metabolic                  hyperlipidemia, atherosclerosis (PVD)        

Ischemic                                  ANGINA, MI (myocardial infarction)

Cardiomyopathies                              dilated, restrictive, HOCM

Arrhythmias                            bradycardia, heart block, atrial fibrillation, atrial flutter, SVT

MAT, VT,  prolonged QT, torsades de pointes

Valvular                                  AS, MS, AR, MR, TR, Rheumatic Fever

antibiotic prophylaxis


Aortic Aneurysm           Aortic Dissection          Endocarditis        Myocarditis


Pericardial Disease       pericardial effusions, acute pericarditis, infectious pericarditis, Dressler’s, uremic,

restrictive pericarditis, cardiac tamponade


Cardiac Tumors, Cardiac Malformations


[cardiac pre-op][cardiac physiology][cardiac physical exam][EKG reading] [cardiac labs]



Cardiac Physiology


Single Cardiac Cycle [see diagram]

Jugular Venous Pulses [see diagram]

Swan-Ganz catheter [interpretation of values]


·        Radiology of the Heart in Cecil’s at MDconsult (great pictures)


Fick equation                CO = (O2 consumption) / (AO2% - VO2%)(Hg)(1.36)(10)


Cardiac Physical Exam


Systolic murmurs [see diagram]

Diastolic murmurs [see diagram]


Low-Pitched Sounds à Bell à S3, S4, MS, AR (Austin-Flint)

High-Pitched Sounds à Diaphragm à everything else




Best Heard



2nd/3rd LICS           


3rd/4th LPS and apex / increased with inspiration


3rd/4th  LPS and apex


1st/2nd LICS mid-clavicular












can radiate to various places






“pulmonic area” of the chest / may radiate to back as with pulmonary stenosis




S1 increased (↑)

LVH (muscle), MS

S1 decreased (↓)

LVH (collagen), LV dilatation/dysfunction, some MR, AR, prolonged PR, LBBB


Note: mechanisms can be way too complex and you’ll make yourself crazy; just refer to this


S2 (normally S2 splitting increases with inspiration due to increase venous return and RVEF; it follows that inspiration will increase most right-sided murmurs/gallops)


·        abnormally increased split S2

Delayed RV (electrical): incomplete RBB, pacemaker, PVC

Delayed RV (mechanical): VSD (if LàR flow), pulmonic stenosis, severe pulmonary edema (↑ impedance)

Shortened LV ejection time:, MR


·        fixed split S2


(explanation; why not variable? RV already ~max overloaded; and L/R atrial pressures equalized so no net Δ in LV/RV output with inspiration—unlike VSD)

mild pulmonary HTN



·        paradoxically split S2 (decreases with expiration)

usually from delayed A2 due to electrical (complete LBB (1st), RV PVC) or mechanical (AS, HOCM, acute ischemia, myocarditis, CHF)


S3        AR, TR, MR / don’t confuse with “tumor plop”

S4        stiff ventricle (various causes) / it can’t happen during Afib


            Jugular Venous Pulsations (JVP) [diagram]

                        “dip and plateau” or “square root” sign à constrictive pericarditis

                        Kussmaul’s sign à constrictive pericarditis

                        Prominent y descent à constrictive pericarditis

                        Large V wave à TR

                        Canon a wave à AV dissociation


Pericardial effusion

r/o tamponade (pulsus paradoxus, undulating pulses)

elevated venous pressure

Borderline – expiration/inspiration 105/94


Electrical alternans or alternating voltage

big pericardial effusions from TB and tumor [< 5 mm leads 1-aVF] / can also be from AV fistula in lungs/coronary vessels

Treatment: pericardial window / can also obliterate pericardial space with nitrogen mustards, talc, tetracycline to prevent recurrence


Pulsus paradoxus

> 10 mmHg fall in SBP during inspiration / occurs in 95% of cardiac tamponade (as well as disorders involving intrathoracic pressure changes, such as COPD) / 4 mechanisms

1)      septal shift/pressure, RV enlargement (prevents filling of LV)

2)      tensing of pericardium (impairs cardiac output)

3)      increased capacitance of pulmonary capillary bed (decreases LV filling)

4)      decreased afterload (negative intrathoracic pressure, this is normal)


Tilt Table Testing

Decreased preload stimulates Bezal Jarisch reflex / catecholamines can be used to

enhance this reflex / hold vasoactive drugs for 5 half-lives before / endpoint is

pre-syncope w/ hypotension or bradycardia



Reading EKG’s   [Vectorial diagram of Limb Leads]


·        EKGs of the Major Arrhythmias [tutorial with pictures]


Method for EKG reading: heart rate / heart rhythm / intervals / axis deviation / hypertrophy


EKG reading in myocardial ischemia


For ECG changes associated with electrolyte disturbances (see lytes) [potassium ECG]



If the QRS complex begins with a negative deflection, it is called a Q wave

1st positive deflection is R wave

a negative deflection following an R wave is an S wave

T waves are positive because the ventricles repolarize from epicardium to endocardium (opposite of contraction)


Heart Rate


Each small box is 0.1 mV and 0.04 seconds / one large square is 0.2 seconds (5 small boxes of 0.04)


HR is 300/# of large boxes in RR interval [ex., 4 large boxes between R waves à 300/4 or 75 bpm or just count # of large squares from 1,2,3,4,5,6 corresponds to 300, 150, 100, 75, 60, 50


Heart Rhythm


Regular? Are P waves present?

In sinus rhythm, P waves should be upright in lead II (unless reversal of leads or dextracardia)

Are P waves related to QRS?

[sinus arrhythmia v. multifocal atrial tachycardia v. atrial fibrillation v. ventricular arrhythmias etc.]




PR interval [0.12 to 0.21]       becomes shorter as HR increases


QRS Axis

Extreme left axis (-90 to -180°)

Right-axis deviation in presence of LBBB (+90 to +180°)


QRS interval [0.04 to 0.1]


LBBB: >160 msec

RBBB: >140 msec


QRS Morphology


QT interval                             normal is less than ½ RR interval with HR < 100


Prolonged QT interval

QTc – corrected for heart rate / women > men / can be a sign of ischemia (lack of ATP and reduced inward K current) / can cause torsades de pointes

Prolonged QT: class Ia and III agents, sotalol, amiodarone, TCA’s, phenothiazines, ketoconazole, quinolones, erythromycin, clarithromycin, antiemetics, antipsychotics, pentamidine, hypomagnesemia, hypokalemia, hypocalcemia, hyperthyroid, hypothyroid, intracranial bleeds, congenital long QT

Shortened QT: hypercalcemia, digitalis (scooping)


Tip: regarding intracellular electrolytes (K, Ca, Mg)

·        ↑ Elevations  à shorten ↓ QT interval

·        ↓ Depressions à prolong ↑ QT interval



low voltage is any 3 limb leads < 15 mm or any one precordial lead < 10 mm

            Causes: pericardial effusion/tamponade, emphysema, obesity


Axis [vectorial diagram of limb leads]


Calculate Axis

If lead I and II /aVF are both positive à 0 to 90 and normal axis (down and to the left)

                        If lead I is positive and II/aVF is negative à LAD

If lead I is negative and II/aVF is positive à RAD

Note: axis can also be determined by finding the isoelectric deflection (i.e., shortest QRS) (axis is perpendicular to that vector)

Frontal planes: axis deviation (I, II/AVF)

                        Horizontal planes: axis rotation (V1-6)


·        LAD à LVH, LBBB, LAFB


·        RAD à RVH, RBBB, LPFB, RV strain (pulmonary HTN, PE), emphysema / may be normal in children, young adults


Note: mean QRS tends to point away from infarct,  toward hypertrophy




·        LVH

1.      sum of deepest S in V1 or V2 and tallest R in V5 or V6 is > 35 mm (in patients > 35 yrs)

2.      R in aVL > 12 mm (strain pattern)

3.      R in V6 > 25-35 mm

Note: may see asymmetrical or inverted T in V5 or V6 (strain pattern ~ ST ↓ with upward hump in middle)


Criteria for LVH (sensitivity/specificity)

RaVL + SV3 > 28 mm (men)  (40/95)

  or RaVL + SV3 > 20 mm (women)

SV1 + RV5 or RV6 > 35 mm (30/95)

RV5 or RV6 >/= 25 mm (20/95)

RaVL > 11 mm (20/95)


·        RVH

right atrial enlargement, right axis deviation, incomplete RBBB, low voltage, tall R wave in V1, persistent precordial S waves, right ventricular strain


Criteria for RVH (sensitivity/specificity)

Limb lead criteria R in I  </= 0.2 mV (40/100)

S2 S2 S3 (45/75)

Precordial lead criteria R/S ratio in V1 > 1 (30/100)

R wave height in V1 > 0.7 mV (30/100)

S wave depth in V1 < 0.2 mV (20/100)

R/S ratio in V5 or V6 < 1.0 (10/100)

QR in V1 (-/100)

QRS axis > + 90 degrees (15/100)

P wave amplitude > 0.25 mV in II, III, aVF, V1 , or V2 (20/100)


·        LAE (P-mitrale)

broad, notched (M-shaped) P waves in mitral leads (I, II, aVL) or deep terminal negative component to P in lead V1 (biphasic V1 is the most specific criterion)  / causes include MS, HTN


·        RAE (P-pulmonale)

P waves are prominent V1 or > 2.5 mm in any limb lead (tall, peaked in II)


EKG segments [anterior heart] [posterior heart]


·        Q waves

Septal depolarization normally moves from R to L causing small downward deflection in V6


Significant Q waves

> 1 mm wide or > ⅓ QRS amplitude (measured from top to bottom) / can start early in MI or in ensuing weeks

Small, insignificant Q waves

o       normal is < 0.04 seconds in I, aVL and V1-6 / < 0.025 in II and < 0.030 in aVF

o       small “septal Q’s” commonly seen in lateral leads (I, aVL, V4, V5, or V6)

o       mid-septal depolarization (from LBB) moving L to R

o       medium to large Q waves may be normal in aVR if not lead placement

o       Q in V2 could be lead placement, LVH, LBB, pulmonary disease

o       downgoing delta waves in II, III, aVF can mimic Q waves

o       large (deep, broad) Q’s in I and III may occur in HOCM


·        R waves

o       R in V1, V2 with posterior MI (see below)

o       Intrinsicoid deflection > 50 mm with some LVH

o       Delta wave with WPW, large R in I with LBBB and LAFB, large R in inferior leads with LPFB


R wave progression

transition should occur between V2 and V4; LVH may change vector of conduction such that R wave progression seems poor (yet not ischemic); poor R wave progression is c/w prior anteroseptal infarct; early R wave progression can be sign of prior inferior infarct


·        S waves

o       V6 with RBBB

o       Large S in inferior leads with LAFB

o       Large S in lateral leads with LPFB


·        T wave changes [diagram]cannot definitively  localize MI’s

o       subepicardial ischemia (inverted, symmetric), subendocardial ischemia (peaked)

o       hyperacute MI (tall, peaked, may have associated ST ↑ and/or Q’s)

o       RBBB, LVH, RVH (septal leads), LBBB (lateral leads)

o       hyperkalemia (peaked, also with widened QRS, prolonged PR, sine wave) [ECG]

o       hypokalemia (may have flat, inverted T)

o       pericarditis (inverted), intracranial hemorrhage (ICH)

Note: can be normal in limb leads, but usually pathological in V2 to V6

      • Wellen’s T waves – deep, symmetric TWI (usu. early precordial leads) may occur in significant left main or proximal LAD


·        ST segment changes [diagram]

shape more important than size of changes / J point is the beginning of the ST segment / ST segment changes tell you where the injury is because the injured tissue remains depolarized when surrounding tissue is repolarized / diffuse ST elevations with chest pain [table]

·        ventricular aneurysm: can produce baseline ST elevations

·        pericarditis: ST elevations are flat or concave (often entire QT segment)


ST elevation

Diffuse: pericarditis, myocarditis, cerebral hemorrhage, others

Localized: transmural ischemia, MI, wall motion disorder (e.g. aneurysm), others


ST depressions – cannot definitively localize MI’s

o       subendocardial ischemia (e.g. angina)

o       ST ↓ V1, V2 with posterior MI (flip and invert EKG to see posterior ST ∆’s)

o       reciprocal changes with ST elevation MI’s (note:)

o       LVH, LV strain with repolarization (inverted T’s)

o       hypokalemia

o       digoxin toxicity


·        U waves

o       (+) > 1 mm / caused by class Ia drugs, hypokalemia [pic], hypomagnesemia, CNS disease (TU fusion waves) [pic], LQTS (+/-) [pic] / predisposes to torsades de pointes

o       (-) HTN, AV valvular disease, RVH, major ischemia, 60% of anterior MI, 30% of inferior MI, 30% of angina


ECG changes suggestive of MI


ST changes: convex suggests infarction (concave could be pericarditis, other)


ST ↑ > 2 mm in 2 contiguous (by grouping) precordial leads

ST ↑ > 1 mm in 2 contiguous (by grouping) limb leads


> 1 mm ↓ in at least 2 contiguous leads suggests ongoing ischemia (subendothelial

infarct, positive stress test) or digoxin effect


In presence of LBBB: cannot exclude MI but MI very likely if:

1.      ST ↑ > 1 mm concordant with QRS (in same direction as QRS)

2.      ST ↑ > 5 mm discordant (not in same direction as QRS)

3.      ST ↓ > 1 mm in V1, V2 or V3


Indication for thrombolysis: > 2 mm ST elevation in 2 limb leads, new onset LBBB

Contraindications include SBP > 180 (at any time, despite what happens after BP meds)


    • Reciprocal changes suggest ischemia (where to look)
      • Inferior ST depression, T inversion à anterior leads
      • Anterior ST depression, T inversion à inferior lateral
      • Lateral ST depression, T inversion à inferior, anterior


Localization of infarct


·        Which artery is/was occluded

I, aVL (high lateral) – L circumflex

V1- V4 (anteroseptal) – LAD (see below)

V5- V6 (lateral) – L circumflex

II, III, aVF (inferior) – RCA (85%), L circumflex (15%)


Note: minimal ST changes and inverted T waves in II, III, aVF à common with circumflex a. occlusion


·        ⅓ of inferior MI involve right ventricle / get right sided ECG if inferior leads involved, because right ventricular MI requires much different treatment! (see treatment of MI and avoid nitrates)


·        Anterior Vs. Posterior MI

·        V2 is most reliable for determining anterior vs. posterior (it lies in the A-P vectorial plane through LV)

·        Don’t confuse anterior sub-endocardial MI with posterior MI

·        acute posterior MI (would be mirror of anterior MI) à V1-V2 w/ large R wave, ST depression


·        LAD occlusion


Scenario A (wrap-around LAD)

V3 V4 ST ­



Scenario B

                        V1V2 ST ­

                        II, III, AVF may be normal 2o to cancellation of vectorial forces

                        I, AVL, ST ­ if affecting high diagonal


Scenario C

                        ST ­ I, AVL, V1-6



Swan-Ganz Catheter – Interpretation of Values


Complications: dysrhythmias (75%), thrombosis (3%), sepsis (2%), pulmonary infarction (2%), pulmonary valve perforation (1%)


RAP [0 to 8 mm Hg]


PAP [systolic: 15-30, diastolic 5-12, mean 10-20 mm Hg]


PCWP [5 to 12 mm Hg]           normally LVEDP = PCWP

o       PCWP > LVEDP in MS, LA myxoma, pulmonary venous obstruction, patient on PEEP

o       PCWP < LVEDP with “stiff” left ventricle ( > 25 mm Hg)


Cardiac output [3.5 to 7 L/min]

Cardiac index [2.4 to 4 L/m2]

SVR [900-1300 dynes/sec/cm-5]

PVR [155-255 dynes/sec/cm-5]




            Normal EF roughly 55%

            McConnell’s sign: reduced RV function with apical sparing (suggestive of PE)

            Detect intracardiac shunt with agitated saline bubbles


General Circulatory Disturbances


Edema             Hypothermia




Hypertension              Cor Pulmonale                        ACLS





Ddx: CHF, renal disease, inflammation, various drugs, hypothyroid, exogenous estrogen, thiamine (B1) deficiency

Effects: hypovolemia, hydrocephalus, pulmonary edema

anasarca (severe edema) / chronic passive congestion of lungs (hemosiderin, brown induration) / chronic passive congestion  of liver (nutmeg liver) and spleen (splenomegaly)




            Free Water Deficit:


    0.6* • weight (kg) •| current Na 

             -----------      - 1


*0.5 if female




stage I              compensated

stage II tissue hypoperfusion / dilated arterioles, fall in urinary output, DIC ?

stage III            cell and organ injury / decreased CO from hypoxia or pancreatic myocardial depressant

factor / ATN (kidney) / ischemic encephalopathy / hemorrhage, necrosis in heart (zonal lesions, bands) / Phases 1) brain and CVS changes 2) renal dysfunction (2-6 days) 3) diuretic phase (renal tubules recover fxn)


hypovolemic     replace with saline/ringer’s


cardiogenic       this is due to left ventricular failure (MI, cardiomyopathy, etc)

consider Swann-Ganz catheter to maintain wedge of ? 17

Consider ongoing occlusion: coronary reperfusion with PTCA

Pressors: dopamine, dobutamine, levafed

With LV failure: consider intraaortic balloon pump placement to increase coronary flow (increased diastolic pressure) and decrease afterload / can also use left-ventricular assist device (LVAD) (risk of infection, thrombosis, mechanical pump failure)


Septic shock     decreased SVR / goal is to maintain preload of ?>higher than normal

consider Swann-Ganz catheter

IVF: saline or lactated ringer’s to maintain wedge

Pressors: dopamine, dobutamine, levafed

Course: Capillary leak combined with a catabolic state will decrease albumin and cause 3rd spacing of fluid / pre-renal state will occur as renal arteries constrict as the body diverts blood to brain and other organs / after recovery, there will be a diuresis as fluid re-enters circulation and renal tubules are somewhat leaky

may be associated with DIC


Congestive Heart Failure (CHF) [NEJM]


·        Systolic dysfunction (pump failure) à all systolic also has some diastolic failure


·        Diastolic dysfunction (impaired filling) à can have isolated diastolic failure


Note: RHF usually from LHF or cor pulmonale (RHF alone can actually cause pulmonary edema from pleural venous drainage)

Causes: myocardial injury (see cardiomyopathies), chronic overload (AS, HTN), chronic volume overload (MR, other), infiltrative (amyloid, HC, other)


Systolic dysfunction


Framingham Criteria

Clinical diagnosis of CHF can be made with at least one major and two minor

Major: PND, neck vein distension, JVP, rales, cardiomegaly, acute pulmonary edema, S3 gallop, positive hepatojugular reflex, weight loss > 4.5 kg with 5 days treatment

Minor: peripheral edema, night cough, DOE, hepatomegaly, pleural effusion, reduced VC (↓ ⅓)


NYHA Functional Classification


I – no limitation during ordinary physical activity

II – slight limitation of physical activity. Develops fatigue or dyspnea with moderate exertion.

III – marked limitation of physical activity. Even light activity produces symptoms.

IV – symptoms at rest. Any activity causes worsening.


Exam Findings

·        Elevated JVP

·        Pulmonary edema (see other)

·        Orthopnea

                              LV failure or inflow obstruction causes raised PCWP and dyspnea

·        Paroxysmal nocturnal dyspnea (PND)

      similar phenomenon that occurs after several hours of recumbency (similar findings with pulmonary disease)

·        Leg Swelling

·        Pulsus alternans

·        S3


Treatment of CHF (stages I-IV):

I – ACE inhibitors

II – ACE inhibitors + salt restriction + diuretics +/- B-blockers (metoprolol, carvedilol)

III – add inotropic agents and vasodilators

IV – add aortic balloon pump or cardiac transplantation


Note: if cannot tolerate ACEI, isosorbide dinitrate + hydralazine has proven mortality benefit over placebo (Imdur alone has not been proven as of 3/07)



·        Anticoagulants with atrial fibrillation or other risk factors for thrombus formation (such as very low EF with severe hypokinesis)welling

·        Anti-arrhythmia agents vs. AICD

§         Some patients may need anti-arrhythmia agents for chronic atrial fibrillation (B-blockers are safest and might be useful)

§         Some studies favor AICD’s (+/- sotalol) over anti-arrhythmia agents alone for severe CHF with high-risk of ventricular tachycardia

·        Cardiac resynchronization therapy (CRT) or biventricular pacing may decrease mortality by decreasing sympathetic activation; consider for moderate to severe HF


The intra-aortic balloon pump (IABP) is positioned in the aorta with its tip distal to the left subclavian artery. Balloon inflation is synchronous with the cardiac cycle and occurs during diastole. The hemodynamic consequences of balloon counterpulsation are decreased myocardial oxygen demand and improved coronary blood flow. Additionally, significant preload and afterload reduction occurs, resulting in improved cardiac output. Severe aorto-iliac atherosclerosis and aortic valve insufficiency are relative contraindications to intra-aortic balloon pump placement.


Ventricular assist devices (VADs) require surgical implantation and are indicated for patients with severe HF after cardiac surgery, in patients who have intractable cardiogenic shock after acute MI, and in patients who deteriorate while awaiting cardiac transplantation. Currently available devices vary with regard to degree of mechanical hemolysis, intensity of anticoagulation required, and the difficulty of implantation. Therefore, the decision to institute VAD circulatory support must be made in consultation with a cardiac surgeon experienced in this procedure.


·        75% five-year survival with transplant

·        peak oxygen uptake of 20 mL/min/kg is associated with a good 1-year prognosis


Physiology of CHF


Vasoconstriction / Salt-retention

·         Left ventricle, carotid sinus, aortic arch, renal afferent à increased ADH, renin

·         Brain-derived natriuretic peptide (BNP) promotes diuresis


Sympathetic System

·         B1 and B2 are uncoupled (B1 ↑ HR, B2 ↑ TPR)

·         NE causes myocyte hypertrophy, direct myocyte toxicity / NE (over 4.7 nmol/L) carries poor prognosis


Treatment: B-blockers may survival by counteracting NE affects (may also have anti-oxidant properties), diastolic filling time (via slowing HR) / biventricular pacing


Renin-angiotensin system

·         No escape from renal sodium retention / combination of NE and ATII stimulation increases Na transport in proximal tubule and decreases delivery to distal tubule (which helps explain lack of escape phenomenon in CHF, unlike Conn’s syndrome) / resistance to atrial natriuretic peptide may result from decreased distal delivery of Na

·         ACE inhibitors and ATII blockers also reduce mitogenic effect on cardiac muscle (which would crowd capillaries and decrease blood delivery) / they may actually reverse LVH

·         ATII receptors may stimulate thirst despite hyponatremia


Treatment: ACE inhibitors and spironolactone both reduce mortality


ADH (AVP) System

·         ADH V2 receptors in collecting duct principal cells à AC à aquaporin-2 translocation and production

·         ADH V1 receptors constrict vascular smooth muscle

·         Baroreceptors override atrial receptors (Henry-Gauer atrial reflex)


Endothelial hormones

·         Endothelin Prostacyclin and PGE2 counteracts (afferent?) renal vasoconstriction à NSAIDS can precipitate acute renal failure in severe CHF

·         Endothelin receptor antagonist BQ-123 (in development) may also counteract vasoconstriction


Diastolic Dysfunction


Inadequate filling during diastole / can be due to variety of causes

Treatment depends on cause

·        control heart rate and increase relaxation with B-blockers (1st), Ca channel blockers (2nd)

·        normalize any arrhythmias (i.e. atrial fibrillation, atrial flutter)


Cor Pulmonale


Pulmonary HTN and RV dysfunction

·        vasoconstriction (ex. CF)

·        primary idiopathic

·        part of autoimmune disease (scleroderma)

·        chronic pulmonary embolism

·        parenchymal (sarcoidosis, ILD)

·        obesity hypoventilation syndrome   

ECG: peaked P waves in II, III, aVF (RA enlargement), deep S in V6 with ST changes (RVH), R-axis deviation, RBBB occurs in 15% of patients

CXR: edema (if pleural effusion, think more of LV failure instead)

Treatment: treat pulmonary HTN (see other)



Hypertension [see pulmonary hypertension]




> 140/90 (stage I)        >160/100 (stage II)


            essential HT                  90% of HTN / genetics, environment / older age, except blacks


malignant HT (5%)       50% essential, 50% secondary (10% renal, 40% endocrine, vascular, neurogenic (rare))


Secondary causes

Renal parenchymal (chronic pyelonephritis, glomerulonephritis, APKD)

Tubular interstitial (reflux and analgesic)

Endocrine: hyperthyroidism, primary aldosteronism, Cushing’s syndrome, pheochromocytoma, acromegaly, oral contraceptives

Other: pain!, hypervolemia (posttransfusion, renal failure), hypercalcemia, drugs (steroids, TCAs, sympathomimetics, NSAIDs, cocaine), coarctation of aorta, vasculitis, renovascular hypertension (RAS), fibromuscular dysplasia


Clues to renovascular HTN: epigastric or flank bruits, accelerated or malignant HTN, < 35 or > 55, sudden development or worsening, concomitant poor renal function, refractory to anti-HTN meds, extensive occlusive disease in peripheral circulation (including CAD/CVA)




cardiac hypertrophy à heart failure, MI


vascular            à aortic dissection

à hyaline arteriolosclerosis: retinal, renal disease

à arteriolosclerosis: MI, CVA, renal failure

à fibroelastic hyperplasia

à retinal changes

grade III retinal changes (hemorrhages, cotton wool spots, hard exudates)

                                    grade IV retinal changes (papilledema)


Other               à 2x risk of renal cell carcinoma


Initial work-up: CBC, chemistries (K, Ca, PO4, BUN/Cr), UA (protein, blood, glucose, micro), consider TSH / lipid profile / fasting glucose / EKG / consider CXR, head CT, echo

            Secondary: captopril-enhanced radionuclide renal scan, MRA, spiral CT / pheo labs /



Goal is to reduce BP by 10-15% or diastolic 110

Organ dysfunction usually at > 130 diastolic


Outpatient Treatment:


Clinical Trials


HOT showed 51% reduction in cardiovascular events with diastolic < 80 (not 90)

UKPD suggested systolic should be < 120

HOPE à ramipril ↓ MI (22%), ↓ CVA (33%), ↓ mortality (24%)

LIFER à losartan decreased mortality more than atenolol for DM with LVH


ACE inhibitors


Ca blocker

Diuretics (HCTZ)


Avoid B-blockers with asthma, CHF (depends), peripheral vascular disease, theoretical risk of increasing sugars with DM or hyperlipidemia (nobody really worries about that)

Avoid diuretics with gout (impairs urate excretion)

With pregnancy, ACE contraindicated (fetal kidney agenesis) and diuretics risky; use aldomet or hydralazine


HTN emergency – must lower BP in < 1 hr

Causes: malignant HTN, associated with MI, flash pulmonary edema, ARF, intracranial events, post-operative bleeding, eclampsia, pheochromocytoma) à SZ, coma, death

MRI: posterior leukoencephalopathy (parietooccipital regions) can be missed on CT


Cerebral blood flow autoregulation à maintains MAP 60-120 (curve shifts to right in chronic HTN; which is why BP must not be lowered > 25% over ~1 hr, especially in presence of neurological effects)


HTN urgency – must lower BP in < 24 hrs

Causes:  accelerated HTN, associated with CHF, stable angina, TIA, peri-operative


Pre-eclampsia and Eclampsia (Toxemia of Pregnancy)

Presentation: headache, epigastric pain, visual disturbances, swelling

Criteria: hypertension (systolic > 140 or +30, diastolic > 90 or +15), proteinuria, edema

Complications: placental ischemia, hypertension, DIC, seizures (true eclampsia)

6% of pregnancies / often last trimester (20 wks to 6 wks post-partum) /

Risk factors: hydatidiform moles, age extremes

Mechanism: angiotensin hypersensitivity may result from decreased PGE synthesis

Treatment: IV MgSO4 or BZ for seizures

Screening: neurokinin B test under development / maternal serum inhibin A concentration is elevated in established preeclampsia (early indicator of risk?)


Treatment for HTN emergency/urgency


Hypertensive encephalopathy


Labetalol, nicardipine, fenoldopam, nicardipine

Avoid: b-blockers, clonidine, methyldopa

Subarachnoid Hemorrhage

Nimodipine, nitroprusside, fenoldopam, labetalol

Avoid: beta-Blockers, clonidine, methyldopa, diazoxide

Intracerebral Hemorrhage

No treatment, nitroprusside, fenoldopam, labetalol

Avoid: beta-Blockers, clonidine, methyldopa, diazoxide

Ischemic Stroke

Nitroprusside, labetalol, fenoldopam

Avoid: beta-Blockers, clonidine, methyldopa, diazoxide

Acute MI/unstable angina                       

b-blocker + nitroglycerin

Avoid: diltiazem, hydralazine, diazoxide

Acute LV failure

Nitroprusside, IV nitroglycerin

Avoid: diltiazem, b-lockers, labetalol

Acute pulmonary edema                        

1st line Nitroprusside or fenoldopam + Lasix

2nd line nitroglycerin (up to 200 mug/min)

Acute aortic dissection

(B-blocker then nitroprusside) or labetalol or trimethaphan

Avoid: Hydralazine, diazoxide

Acute renal failure        

Fenoldopam, nitroprusside, nicardipine, labetalol

Avoid: beta-blockers, trimethaphan

Sympathetic Crisis (pheochromocytoma)

Phentolamine, labetalol, nitroprusside, clonidine (for clonidine withdrawal only)

Note: block a then b to avoid problems

Microangiopathic hemolytic anemia




Magnesium sulfate, hydralazine, labetalol, calcium antagonists

Avoid: ACE inhibitors, diuretics, trimethaphan

Postoperative crisis

Labetalol, fenoldopam, nitroglycerin, nicardipine, nitroprusside

Avoid: trimethaphan




            Pathological Types


            Senile sclerosis insidious / aging

            Monckeberg’s            medial calcification / wear and tear lesion?

            Atherosclerosis see below


                        hyaline              benign HT, DM / slow, stenosis / plasma proteins, thick BM

                        hyperplastic      malignant HT / flea-bitten kidney

                        transplant          accelerated 2 to 5-10 yrs




            abdominal aorta > coronary > popliteal > carotid

Pathology: diffuse intimal thickening (normal aging) / gelatinous lesions (focal edema) / microthrombi / fatty streaks (normal aging)

Causes: by hyperlipidemia (diet, DM, gout), chronic HTN, smoking, Fabry’s, elevated homocysteine

Markers: CRP is associated with increased risk / other markers are associated but not useful for screening: homocysteine, lipoprotein A, plasminogen activator factor 1 / C. pneumoniae and CMV also implicated


Coronary Artery Disease (see other)


            Peripheral Vascular Disease [NEJM]

Presentation: < 20% report typical symptoms of intermittent claudication / leg fatigue, difficulty walking, other atypical leg pain

Exam findings: cyanosis (with dependent rubor), decreased temperature, atrophic changes (shiny skin, thick nails, absence of hair), decreased pulses / ulceration usu. toes, heels, anterior shin and extended over malleoli

Risk factors: smoking, diabetes, HTN, hyperhomocysteinemia, hyperlipidemia

Diagnosis: [table]

·        ankle-brachial index (ABI) > 1.0 normal / 0.41 to 0.9 intermediate / < 0.40 critical

·        ultrasound – limited compression of calcified vessels, operator dependent

·        MRA/CTA – usual considerations

·        angiography – good because could also do stenting at same time

Ddx [table]: Buerger’s disease, fibromuscular dysplasia, Takayasu’s, acute arterial occlusion, compartment syndrome, venous congestion, spinal stenosis

Treatment: reduce contributing factors (smoking, DM, etc) à smoking cessation reduces related/CAD mortality 50% / exercise (as tolerated re: possible CAD) actually helps

Medical therapy

·        cilostazol – phosphodiesterase type 3 inhibitor à vasodilation + mild anti-platelet activity / shown to increase walking distance 50%

·        pentoxifylline (Trental) à immunomodulator à people doubt efficacy

·        ASA or plavix à more to prevent MI and CVA

Note: other vasodilators (CA blockers, a-blockers, hydralazine) may worsen symptoms by decreasing perfusion to affected area

Surgery: critical leg ischemia, persistent foot pain at rest, non-healing ulcers, disabling claudication

·        PTA (PCI) versus bypass / must take several factors into decision [table]


Leriche syndrome

claudication in buttock, buttock atrophy and impotence in men due to aortoiliac occlusive disease / treat with bypass


Acute arterial occlusion

embolic or in situ / consider source / consider HIT Ab

Treatment: heparin (to prevent propagation), limb placed below horizontal plane without pressure, urgent vascular consult




diagnose based on FH, blood tests (cholesterol not changed by fasting, TG are decreased) Friedwald formula: LDL chol = total - (HDL chol + TG/5) / 100 - 139 (mild) / >139 (severe)

Note: very severe hyperlipidemia can affect platelets causing elevated ESR


            CARE trial à no benefit shown for lowering LDL < 125 mg/dL in post-MI patients

HPS trials à simvastatin reduced coronary or vascular events by 33% (regardless of lipid levels)

            SSSS trial à simvastatin reduced MI (55%), mortality (43%)

VA-HDLIT à 24% reduction in stroke/MI with gemfibrozil and LDL > 140 and HDL < 40


Combination of statin and fibrate is promising; fibrate alone probably not as good as statin alone


            Current trend is treat CHD or CHD equivalents (DM, stroke, PVD) with goal of LDL < 100


Primary hyperlipidemias


            FH                   AD / chol

            Familial HTG    AD / TG

            combined         AD / chol, TG

            broad beta        (rare disorder)

(85%)  polygenic        chol

            sporadic           TG


Secondary hyperlipidemia


            elevated cholesterol

            elevated TG (DM, other)



                        AR disorders


Diabetes Mellitus (see endocrine)


            Drug-Induced: certain b-blockers, protease inhibitors



Coronary Artery Disease [chest pain Ddx] [angina] [MI]


1st COD in US / 90% of cardiac deaths

PDA to AV node – 90% L circumflex / 10% RCA


Risk Factors:

DM à extremely important risk factor [annals]

Family history (MI < 40 yrs)



Male, post-menopausal


Hypercholesterolemia (LDL > 100 / HDL < 50 / TG > 170)

Cocaine (vasospasm, promotes blood clotting)

Obesity (BMI > 27)







            Initial testing guidelines:

Pt’s over 50 yrs old: LDL, smoking, fasting glucose

ankle-brachial index can be checked in patients over 55-60 yrs old


Second line tests (not part of any initial work-up)

·        low serum folate (required for homocysteine à methionine)

·        elevated CRP, homocysteine, ApoA, ApoB


            Physical Exam

                        Retinal changes – AV nicking and/or copper-wire changes (HTN)

                        S4 (HTN)

                        Peripheral bruits

Absent/decreased peripheral pulses

                        Xanthomas (hyperlipidemia)


Common causes of chest pain (see Ddx)

Cardiac: aortic dissection, myocarditis, pericarditis, valvular heart disease (MVP, AS, HOCM, MS)

Lungs: pulmonary embolism, pleurisy, pneumonia, pneumothorax, pulmonary HTN

GI: cholelithiasis, cholecystitis, GERD, esophageal spasm, PUD, pancreatitis

Musculoskeletal: costochondritis, chest wall trauma, cervical arthritis with radiculopathy, muscle strain, myositis

Other: Herpes zoster


Diagnosis of CAD (sensitivity/specificity of various criteria)


Exercise electrocardiography

>1 mm ST depression (70/75)

>2 mm ST depression (33/97)

>3 mm ST depression (20/99)

Perfusion scintigraphy

                                    Planar (83/88)