Rheum- Adults Flashcards
Gout- pathophysiology
Hyperuricemia
- serum urate >6.8
- rapid flucation in serum levels
Monosodium urate (MSU) level has to be high enough - crystals preciptiatate -> inflammatory response
Resolution of acute inflammation - mediated by immune mechanisms
Chronic inflammatory -> osteoclasts, blasts, chondrocytes - conttribut to tophi formation, erosion of bone, and joint injury - deforming bones
Gout- cause
Uric Acid Balance
Underexcreters - Majority
- Renal insufficiency
- Meds - low dose ASA, thiazides, loop diuretcis, nicotinic acid, cyclosporine, levodopa, ethambutol, pyrazinamide
- Acidosis - DM ketoacidosis, ketogenic diet, lactic acidosis
- Volume depletion/dehydration
- lead exposure
Overproducers - minor
- inherited defect of metabolism - lesch Nyhan syndrome, Kelley-Seegmiller
- Myeloproliferative and lymphoproliferative disorders, polycythemia, carcinoma - TLS
- Chronic hemolytic anemias
- transient hyperuricemia associated w/ ATP consumption
Gout- epidemiology
M>W M 40-60, W >60 Pacific islanders Alcohol - more drinks Food w/ hyperuricema - read meat, seafood fructose Obesity Chronic dis - HTN, hyperlipidemia, DM Meds aff urate balance - thiazide & loop diuretics, low dose ASA, cyclosporine, niacin Protective - estrogen
Gout- S/S & PE
S/S:
- Big toe hurts
- sudden onset - hurts at night
- painful, tender, swellen joint - red, arm
- maybe fever
- Max severity - 12-24 hrs
- hx of similar attacks
PE:
Swollen, very tender red and warm overlying skin
Desquamation - skin peeling off
Tophi - irregular, asymmetrci macroscopic deposits of urate
- PATHOGNOMIC FOR GOUT
- Sites - external ear, hands, olecranon, feet, knee, Achilles tendon, forearm
- Usually painless
- after years
- maintain state of inflammation -> promtoes joint and tissue destruction around them
MTP OF GREAT TOE - podagra
- usualy in one joint !
Renal
- Uric acid nephrolithiasis - kidney stones
- chronic urate nephropathy - MSU crystals are deposted in the renal medulla and pyramids
- Uric acid nephropathy - acute renal failure large amounts of uric acid crystals precipitate in the collecting ducrs and ureters
Gout- diagnosis
Stages:
- Acute gouty arthritis
- Intercritical gout - interval -> agttack resolved
- Chronic articular and tophaceous gout - may not totally resolve
Synovial fluid aspirate - monosodium urate crystals
- Negatively birefringent - needly-like, when viewed with polarized light microscopy
Ultrasound - hyperechoic linear density over:
- joint - double contour sign
- tophi - hypoechoic cloudy area
Xray - rat bite lesions - later in disease
- if next to tophus = GOUT
Gout- labs & imaging
Serum uric acid- inc or nl or low
Peripher WBC- inc
ESR/CRP- inc
- CRP- can inc at first
Gout- treatment
Asymptomatic hyperuricemia - don’t treat!
Life style mod - lose weight, reduce alcohol consuption, reduce purine-rich food consumption, DRINK FLUIDS >2L
Avoid hyperuricemic meds
Acute:
Goal - relieve pain ASAP
Start treatment as soon as possible - 12-24hrs
Urate- lowering meds - dont start during acute attack!! - continue if already on it - allopurinol
1st - NSAIDS
- Naproxen
- Indomethacin
- D/C - after 1-2 days after complete clinical resolution
- Contraindications - CKD w/CrCl <60
Cochicine - if NSAID intolerance
- D/C after 2-3 days
- SE - DIARRHEA and ABDOMINAL cramping
- reversible peripheral neuropathy
- Contra - severe hepatic or renal impairment w/ cochicine in 2w, mod-strong inhibitor of P-gp and/or CYP3A4 inhibitor
Corticosteroids - cant take NSAIDs or Cochicine
- intra-articular - only 1 or 2 joints
- PO, IV, IM
- Caution - CHF, glucose intolerance, poor HTN control
Gout- prognosis
Get a 24 hr urine acid test: <800mg Undersecreter - Uricosuric agent or XOI >800 mg Overproducer - XOI Xanthine Oxidase Inhibotrs (XOI) - reduce production of uric acid - disolve tophi 1. Allopurinol - 100mg/QD - titrate every 2-5 weeks - NEED A DOSE of >300 mg/day - Prophylactic - cochicine - SE - rash, cutaneous reactions 2. Febuxostat - 40mg/day - titrate up to 80mg at 2 w - Prophylactic - colchiicine - less hypersen reactions - abnormal LFTS and slightly higher rate of CV events
Uricosuric Meds - Probenecid
- block tubular reabsorption of urate - inc rate uric acid is renally excreted
- CrCl >60
- urinate 2L/day - avoid uric acid in urinary tracte
- DONT GIVE - G6PD pts
Uricase - Pegloticase
- breaks urate down - in other animals
- REFACOTRY TO ALL OTHER THERAPIES
- IV every 2weeks
- premeds - infus reactions and
- Dont give - G6PD
Gout- acute attack and prevention
Acute attack - resolve w/out treatment
- time - will become more frequent and last longer
The younger - more pregoressive course
Rever to Rheum
With urate-lowering meds - much less chronic/ tophi/deformity
Prevention - done during intercritical period
- Serum urate level <6mg/dL - done slowly to prevent attack
- start low dose when starting therapy - reduce risk of acute flare
- indications: frequent gout attacks, tophi, clinicor or radiographic signs, renal insuff, ruccurent nephrolithiasis, Premen women, <25 male
- USE LOW DOSE COLCHICINE when initiating XOI etc
Pseudogout- pathophysiology
Idiopathic
Early onset- familial
Excess pyrophosphate production in cartilage —> Ca pyrophosphate supersaturation —> CPR crystals
CPP crystals I- involved w joint inflammation —> degrades cartilage
Pseudogout- cause
Arthropathy caused by precipitation of Ca pyrophosphate dehydrate crystals —> acute, recurrent or chronic arthritis
Pseudogout- epidemiology
Older adults- M & W - inc w age, rare <55 Joint trauma Familial chondorcalciosis Hemochromatosis
Pseudogout- S/S & PE
Asymptomatic/incidental - CPP deposition in joint on xray, no symtpoms
Acute arthritis/pseudogout:
- self-limited, sudden attacks of pain, redness, warmth diability, and swelling, monoarticor or oligoarticular
- Knee - most common - then wrists, shoulders, elbows, ankles
- Provoked by surgery, trauma or major illness
- Assoicated w/ fever/chills
Chronic CPP crystal inflammatory arthrisi - Pseudo-RA
- Inflammatory arthrisi - CPP crystals can found in joint
- multi joins in symmetric patterns - similar to RA
- usually affects joints unaffected by OA - MCPs, wrists, elbows, glenohumeral joints
- asynchornous waxing and waning of inflamed joints
OA w/ CPPD - psudo-OA
- progessive joint degernation
- knees - most comon - wrists, MCP, hips, shoulders, elbows, spine
- Clinical exam like OA - tenderness, boney enlarment, dec ROM
Pseudo-neuropathic joint ds
- severe joint degernation form CPP crystal deposition
- Resemble neuropathic arthropaythy - no neruoloigc imaprirment
Pseudogout- diagnosis
Joint aspirate- weakly positively birefingent rhomboid crystals- by polarized light microscopy
X-ray- linear and punctate densities w/in hyaline or articulate cartilage
- often see degenerative changes- subchonral cyss, osteophyte formation, fragmentation of bone and cartilage
Pseudogout- labs & imaging
Correct any underlying assoicated metabolic disorders
Acute pseduogout
- Aspiration -> intraarticular glucocorticoid injection - triamcinolone
- NSAIDs- indomethacin, naproxen, salicylates
- Colchine
- systemic cortiosteroids - PO, iV or IM
OA w/ CPPD - treat like OA
Pseudo-neuropathic joint disease - treat like charcot arthropathy
Prophylaxis
- >3 attacks per year - Cochinine -> doesnt work -> NSAIDS
Pseduo-RA
- NSAIDS - 1st - naproxen, indomethacinf
- Alternatives to NSAIDs - cochicine, hydoxycholorquine, low-dose glucocorticoids
Pseudogout- treatment
Attacks will resolve w/out treatment
Can cause chronic symptoms
Refer to rheum
Fibromyalgia- pathophysiology
Unknown cause Disorder of altered pain processing and regulation - central sensitization - allodynia & hyperalgesia - functional MRI and PET studies Genetic Psychosocial Neuro endocrine Autonomic nervous system Stressful events- sexual abuse, war Viruses/infections- EBV
Fibromyalgia- cause
Chronic clinical syndrome of generalized musculoskeletal pain
- real dx vs psych vs socially constructed
Fibromyalgia- epidemiology
W
20-50
Fibromyalgia- S/S & PE
Chronic pain/stiffness - wide spread - 4 quads of body - neck, shoulders, low back, hips Sleep distrubance - non restorative Fatigue Muscle weakness Paresthesias Cognitive disturbance HA Depression & anxiety IBS Dry mouth Pelvic pain Bladder symptoms Tinnitus Multiple chemical hypersensitivities TMJ Onset: acute injury, infection, childbirth, persistent stress, exposure to toxins PE - normal except for pain at tender points - apply 4kg/cm2 to points
Fibromyalgia- labs & imaging
Little benefit- no lab abnormalities
CBC, ESR, CRP, TSH
Fibromyalgia- treatment
Initial:
- education
- good sleep hygiene - dec spleep -> worse pain
- exercise - low impact aerobic activity
- CBT
Meds:
- TCAs - amitriptyline
- Cycobenzaprine
- SNRIs - Cymbalta (duloxetine)
- SSRIs - Prozac
- Anticonvulsants - Lyrica (pregablin), gabapentin
Refer: Do well w/ close FU
- Psyc
- PT
- Rheum
- Pain Managment
- Massage, acupuncture
NOT HELPFUL:
- Opiods
- Corticosteroids
- NSAIDs
Fibromyalgia- prognosis
Chronic- not progressive
Pts do well w close PCP FU
Most can work
Worse outcomes- F, low socioeconomic status, unemployed, depression, and obesity
Polymyalgia rheumatica (PMR)- pathophysiology
Unknown- associated w polymorphisms of HLA
- DR alleles
Affected joints- lymphocytes and monocytes —> inflammation
Polymyalgia rheumatica (PMR)- cause
Inflammatory condition associated w pain and stiffness of HIPS and SHOULDERS
Polymyalgia rheumatica (PMR)- epidemiology
>50 inc w age W>M Scandinavian & Northern Europeans ID? PMR > GCA
Polymyalgia rheumatica (PMR)- S/S & PE
Pain and stiffness - SHOULDERS AND PELVIC
- shoulders first
- Morning Stiffnes & Stiffness after activity - gel phenomneon
- movements inc pain
- impaired ROM
- normal muscle strength
Low-grade Fever
Malaise
weight loss
Bursal inflammation/synovitis - wrists, knees, sternoclavicular joints
- sweeling, pitting edema
Polymyalgia rheumatica (PMR)- diagnosis
Clinical
Polymyalgia rheumatica (PMR)- labs & imaging
ESR/CRP- inc Anemia WBC- nl Reactive thrombocytosis LFTs- inc ALP Albumin- low
Polymyalgia rheumatica (PMR)- treatment
Glucocorticoid therapy- prednisone- 15mg PO QD
- nl start- range 10-20 mg
- no improvement after 7 days —> in 30 mg
Rapid improvement generally seen
After stable and controlled —> taper
- flares common- inc dose and then taper slower
Polymyalgia rheumatica (PMR)- prognosis
Good w steroids
Does not cause chronic damage
Morbidity- related to long term steroid use
Refer rheum
Giant cell arteries (GCA)- pathophysiology
Unknown- associated w polymorphism of HLA- DR alleles
Infiltration of inflammatory cells into vessels—> vasculitis
- thoracic aorta, large cervical artery, branches of external carotid arteries
Active inflammation —> thrombosis
Fragmentation of elastic almina
Giant cell arteries (GCA)- epidemiology
Smoking
DM
plus, all of the above
Giant cell arteries (GCA)- S/S & PE
CLASSIC: HA, Scalp Tenderness, Jaw claudication, visual changes
- visual loss - amaruosis fugax, diplpia
- anterior ischemic optic neuropathy - occlusive arteritiis of posterior ciliary artery
HALF HAVE PMR
Fever, fagigue, weight loss, malaise
Atypical - respiratory, neurolligc, otolaryngeal
PE:
Overall look ill
Temporal artery - thickened, tender, prominent, or normal
Funduscopic - pallor, edema of optic disc, scattered cotton-wool patches, small hemorrhages - or nl
CV - asymmetry of pulses in arm, aortic regug, bruits near clavicle
Giant cell arteries (GCA)- diagnosis
Temporal artery biopsy- gold
-unilateral biopsy neg —> contralateral biopsy
Classification- does not replace biopsy for def diagnosis
Giant cell arteries (GCA)- labs & imaging
ESR/CRP- inc Anemia WBC- nl Reactive thrombocytosis LFTs- inc ALP Albumin0 low
Giant cell arteries (GCA)- treatment
DON’T WAIT FOR BIOPSY TO START TREATMENT - prevent blindness
Glucocorticoids - Prednisone - 40-60 mg PO QD
- no response - inc dose
- Once conttrolled - start tapering - no faster then 10% every 1-2 w
Will need this for months
Flares common - inc Predni by 10mg
Giant cell arteries (GCA)- prognosis
If not treated- poor prognosis and blindness Chronic course and relapses Inc CV events Long term steroid risk Refer rheum
Takayasu arthritis- pathophysiology
Chronic vasculitis- affecting aorta and main branches
- spectrum of PMR/GCA?
- inflammation of blood vessels
Takayasu arthritis- epidemiology
W
Asian
10-40 y
Takayasu arthritis- S/S & PE
Constitutional symptoms - early
Vascular insufficiency - later
- claudication, cool extremities, subclavian steal syndrome, syncope, BP differential, arthralgia, skin lesions, pul, abdominal pain, diarrhea, GI hemorrhae, angina pectoris
PE: BP differential - 10mmHg Pulses am/legs - diminished, asymmetrical Burits Synovitis - large joints Renovascular HTN
Takayasu arthritis- diagnosis
Clinical
Imaging- arterial luminal narrowing or occlusion w wall thickening
Takayasu arthritis- labs & imaging
Anemia
ESR/CRP- inc
Albumin- low
Takayasu arthritis- treatment
Glucocorticoids- prednisone 45-60mg PO QAM
- taper w controlled labs good
- may need chronic use
- 2nd line- immunosuppressed
Surgery- PCTA, bypass grafting, aortic repair
Takayasu arthritis- prognosis
Chronic
Relapse- remitting
Self limited
Vascular- progressive
Polyarteritis nodosa (PAN)- pathophysiology
Inflamed wall of vessel thickens and lumen narrows —> less blood flow (thrombosis) —> ischemia or infarction of tissue
Systemic necrotizing vasculitis
- medium sized or small arteries
- VEINS not involved
Can affect any organ
- skin, muscle, peripheral nerves, kidneys, GI tract, heart- most common
LUNGS SPARED
Polyarteritis nodosa (PAN)- cause
Idiopathic
Associated- Hep B, Hep C, hairy cell leukemia
Polyarteritis nodosa (PAN)- epidemiology
M 40-60 No racial group 1/100,000 Hep B
Polyarteritis nodosa (PAN)- S/S & PE
Systemic - fatiuge, arthralgia, fever, weight loss, weakness, pain in extremities
Skin:
- LOWER EXTREMITIY ULCERATION - classic
- subcut nodules, Livedo reticularis, Bullous or vesicular eruption, palpable purpura, Infarction or dgital gangrene
Renal:
- MOST COMMON AFFECTED ORGAN
- HTN and RENAL INSUFF
- severe - infarct
- perirenal hematoma - rupture of renal arterial aneurysms
GI
- ABDOMINAL PAIN - after meals
- N/V/D, Infarc - lead to acalculous cholecysts
Cardiac - MI, CHF w/ uncontrolled HTN or ICM
Lungs - NOT INVOLVED
MSK - pain in extremities, arthralgia, myalgia, muscles weakness
Eye - retinal hemorrhage, visual impairment, optic ischemia
Nervous System:
- MONONEURITIS multiplex - foot drop
- sensory -> then motor
- CNS involvment - encephalopathy, seizure, stroke
Other - ischemic orchitis
Polyarteritis nodosa (PAN)- diagnosis
Biopsy of involved organ- necrotizing inflammation of medium sized arteries
Angiogram
- small aneurysm- rosary sign
- irregular constrictions of large vessels and occlusion to smaller vessels
CT and MR angio- show extent of organ involvement
Clinical- need 3/10
Polyarteritis nodosa (PAN)- labs & imaging
ESR/CRP- inc LFTs/Hep panel- abnormal Cr- inc Anemia- GI involvement/chronic disease CK- inc
Polyarteritis nodosa (PAN)- treatment
Viral hep? —> antiviral- limit steroids
Mild disease:
- corticosteroids alone- prednisone- 1 mg/kg QD
- taper after 4 weeks- if improved
- resistance?—> methotrexate, azathioprine
Mod/severe- renal, HTN, ischemia, infarct
- high dose corticosteroid + immunosuppressant
- prednisone and cyclophosphamide- IV or PO
- live/organ threatening- IV Methylprednisone
- Max 12 m on cyclophsom
Polyarteritis nodosa (PAN)- prognosis
No treatment- V bad
W treatment- 80%
Worse- CKD w CR >1.6, proteinuria >1g/dl, GI ischemia, CNS dis, CV invol
Reactive arthritis (ReA)- pathophysiology
Asymmetric polyarthritis that develops after GI or GU infection- large lower extremity joint
Reactive arthritis (ReA)- cause
GI infections- shigella, salmonella, Yersinia, campylobacter, E. coli, C diff
- inflammation in gut dec wall integrity and activates pro inflammatory cytokines —> microlesions —> cytokines migrate to joint
STI- CT, ureaplama urealyticum
HLA-B27- predisposed
Reactive arthritis (ReA)- epidemiology
Rare
M>F
YA
HLA-B27 gene
Reactive arthritis (ReA)- S/S & PE
Diarrhea or urethritis - 1-4 weeks earlier
Asymmetric Arthritis
- large weight bearing joints - knee, ankle
- Spine, SI joint
Enthesitis - swelling at heel
Dactylitis - sausage joints
General - fever, fatigue, weight loss Eye - conjunctivits, anterior uveitis Mucocutaneous - balanitis, stomatitis, keratoderma, blennorrhagicum Nails - minic psoriasis - CANT SEE, CANT PEE, CANT climb a tree
Reactive arthritis (ReA)- diagnosis
Clinical- no single test
MSK findings
Preceding infect
No other thing
Reactive arthritis (ReA)- labs & imaging
CRP/ESR- inc
Stool culture or urethral swab- pos
Synovial fluid analysis- WBC inc- neutrophils
Reactive arthritis (ReA)- treatment
Treat underlying infection Arthritis: NSAIDS- mainstay/initial - Naproxen, diclofenac, indomenthacin- 2w No response - intraarticular glucocorticoids - PO glucocorticoids - DMARD- sulfasalazine or methotrexate
Reactive arthritis (ReA)- prognosis
Self limiting
Lasts 3-5m- remit 6-12
Require PT
Refer to rheum
Sjogren syndrome- pathophysiology
Systemic autoimmune disease- affects LACRIMAL and SALIVARY glands —> mouth and eye dryness aka xerostomia and keratoconjunctivitis sicca
Sjogren syndrome- cause
Primary or sec to another autoimmune dx
- by itself or with another autoimmune
Sjogren syndrome- epidemiology
F >M Middle aged All races- Caucasian HLA-DQ HLA- DB
Sjogren syndrome- S/S or PE
Ocular: Keratoconjuntivitis Sicca
- diminished aqueous tear production
- dry, gritty, sandy, foreign body sensation, burning, itching, intolerance to contacts, photphbia, eye fatigue
- Conjunctival or cornal damge - Rose bengal, lissamine green or fluorescein stainging
- Schirmer test - dec tear production
- Mucus filaments, dilation of bulbar conjunctival vessels, lacrimal gland enlargement
Mouth - Xerostomia
- cotton mouth, dysphagia, trouble w/ prolonged speaking, loss of taste
- Dental caries, gingival recession, oral candidiasis common, laryngotracheal reflus, chronic esophagitis
- salivary gland enlarmentt - partoid
- Saxon test - chew on dry sponge and weigh to see how much produced
- Sialometry - spit out saliva
Constiutional - Fatigue, low-grade fever
Skin - xerosis, purpura, raynaud phenomenon, cutaneous vasculitis, angular chelitis, annular erythema
MSK - arthraliga, symmetric nondeforming, intermittent - mild myopathy w/ weakness
Lungs - dry cough, excessive throat clearning, rhinitis, sinusistis, hoarseness, pneumonitis, pneumonia
CV - rare - pericarditis, heart block
GI - atrophic chronic gastritis, celiac dis, biliary cirrhosis, autoimmune hep
Renal - chronic interstitial nerphritis, glomerular disease
UG - vaginal dryness, dyspareunia, pruritis, dysuria, urinary frequency/urgency, nocturia in absence of UTI
Neurologic/Psych - peripheral neuropathy, ataxia, trigeminal neuropathy, mono, neuropathics, CNS , affective disorders - depression
Sjogren syndrome- diagnosis
Salivary gland biopsy- gold
- real life- only do this if diag unclear
- > 4 lobules removed from inner lip
- positive= focus score >1 per 4mm2
- focus= >50 lymphocytes
- Objective test of dry eye or xerostomia or imaginst consistent w glandular abnormalities
- Anti-Ro/SSa and/or anti-La/SSb antibodies, positive lip biop, or established rheum dis
Sjogren syndrome- labs & imaging
ANA- pos Anti-Ro/SSA and anti-La/SS-B- pos antibodies RF- pos Centromere antibodies, anti-CCp, antimitrochondrial Anemia- mild Cytopenia- mild Hypergammaglobulnemia- mild ESR- inc CRP- nl/inc LFTs- abnormal Renal impairment- inc cr and dec bicarb
Sjogren syndrome- treatment
Oral:
- Symptomatic
- Artificial Saliva
- Mouth lubrication - sugar free hard candies
- Oral care
Ocular:
- Environment management
- artificial tears - every 2-4 hrs, at night ointments
- still no relief -> ocular cyclosporine
- topical steroids - if all else fails
- punctal occlusion plugs
Immunosuppressive therapy
- Hydroxychoroquine
- Methotrexate
Refer to rheum
Sjogren syndrome- prognosis
Depends on extent
Severe exocrine involvemnt - higher lymphoma risk - DLBCL
Risk - autoimmune
Extraglandular dx - inc M&M
Refer if - systemic signs/symptoms, oculur dryness doesn’t respond to artifical tears
Rheumatoid arthritis (RA)- pathophysiology
HLA- DR MHC genes
-shared epitope
Synovial tissues main target —>
Tcells, Bcells, and macrophages, synovial cells go to synovial tissues —>
synovial tissue proliferates —>
excess synovial fluid and pannus forms —>
pannus invades nearby bone and cartilage, destroying them and stretching the joint capsule —>
destruction and deformity
Rheumatoid arthritis (RA)- epidemiology
F>M F- 4th-5th decade M- 6th-8th decade Genetic Smoking
Rheumatoid arthritis (RA)- S/S & PE
Indisious onset
Morning stiffness >30 min
Symmetric swelling of joints
Tender, pianful joints
Joints affected: PIP, MCp, wrists, ankles, knees, MTPs
Synovial cysts, tendon rupture, entrapment syndrome
Hands
- Ulnar deviation of MCP joints
- Swan neck - hyperextension of PIP, flexion of DIP
- Boutonniere - Flexion of PIP, extension of DIP
- Z deformity - hyperextended interphalangeal joint
General - fatigue, weight loss, low-grade fever
Skin
- Rheumatoid nodlues - subcutaneous nodules, extensor surfaces over joints, firm/nontender
- vasculitis
Ocular - keratoconjunctivitis sicca, scleritis/episcleritis, scleromalacia
Pulm - pleural effusions, rheumatoid nodues, interstitial lung disease
CV - pericardial effusions, pericarditis
Felty Syndrome Triad - splenomegaly, neutropenia, RA
Rheumatoid arthritis (RA)- diagnosis
Inflammatory arthritis involving >3 joints Pos RF and/or anti-CCP- can be neg Elevated ESR and/or CRP Duration >6w Excluded everything else
Rheumatoid arthritis (RA)- lab & imaging
Anti-CCP antibodies - most specific, more aggressive
RF - more severe disease
- 15% are seronegative - neg anti-CCP and RF
ESR/CRP - inc Anemia - mild Thormbocytosis - mild WBC - normla/mild leukocytosis Synovial fluid - inflammatory effusion, leukocytes 1500-2500, PMNs predominate
Xray - most specific
- early - nl
- Initial - soft tissue swelling, osteopenia - wrists or feet
- later - joint space narrowing and erosions
MRI - more sensitive then xray
- see erosions earlier
U/S - more senstivie then xray
Rheumatoid arthritis (RA)- treatment
Control pain and inflammation
preserve function, prevent deformity
Early diagnosis and intiation of DMARDs!!!
Target of treatment - remission or low disease activity
Refer to Rheum
Pretreatment Screening:
- Hep B&C
- Baseline CBC, Cr, LFTs, ESR, CRP
- Ophthalmic screening
- Check for latent TB
- Baseline radiographs
NSAIDs - help w/ symptoms
- Not monotherapy
- All about equal
Corticosteroids - Prednisone 5-20mg QD
- very helpful for symptom relief and slowing rate of joint damage
- Not recommended for monotherapy or long-term use
- Bridge - as start DMARD
DMARD
- Methotrexate - INITIAL
- starting - 7.5mg PO weekly
- improve at 2-6w
- Contraindicated - prego, liver disease, heavy alcohol, severe renal impairment
- SE: GI, stomatitis
- Close monitor - CBC, LFTs
- ALL TAKE FOLIC ACID or leucovorin calcium - TNF inhibitors - Etanercept
- SQ or IV
- Expensive!!
- well tolerated
- higher risk of serious bacterial infections - must screen for latent TB
- worsen CHF
- work well w/ severe disease
F/U
- assess symptoms and functional status
- monitor lab work - disease activty and toxicities
- radiographs every 2 yr
Rheumatoid arthritis (RA)- prognosis
- Pre MTX - very poor
- good treatment - better
- disease flares
- higher mortality w/ CV disease
- Poor - RF or anti-CCP pos, extrarticular dis, functional limitation, eroisions on xray
Systemic sclerosis (Scleroderma)- pathophysiology
Chronic systemic autoimmune with fibrosis of skin and other organs
2 froms: Limited, Diffuse
Unknown exact
Widespread proliferative/obliterative vasculopathy of small & medium arteries and capillary rarefaction - Hallmark!!
- Vascular injury + activation
- Hypertorphy of intima
- Excessive deposition of fibrin can occlude lume -> loss vascular supply -> tissue hypoxia
Fibroblasts overporduce extracellular matrix -> inc collagen deposition in the skin
Collagen cross-linking -> skin tightening
Systemic sclerosis (Scleroderma)- cause
1. Limited- CREST Calcinosis Cutis Raynaud Esophageal dysmotility Sclerodactyly- local thickening /tightness Telangiectasia
- Diffuse
Systemic sclerosis (Scleroderma)- epidemiology
F>M 30-50yo AA- early onset, diffuse NA in OK 1st degree relatives
Systemic sclerosis (Scleroderma)- S/S & PE
Raynaud - first sign
Constitutional symtpoms - diffuse disease
Skin:
- initial - edema + pruritis
- later - thick hide-like skin
- hyperpigmentation, digital ulcers, pitting of fingertips, loss of appendicular hair, telangiectasias calcinosis
GI:
- Dysphagia, reflux symptoms, hypomotility
- Vascular ectasia - stomach antrum - watermelon stomach
Lung:
- pulmonary fibrosis
- pulmonary vascular dis -> pHTN
CV:
- pericarditis
- heart block
- myocardial fibrosis
- heart failure
- arrhythmia
Sicca syndrome - sjoren syndrome
Reanal:
- SCLERODERMA RENAL CRISIS - sudden onset of mealignant HTN can lead to renal failure and death
Thromboembolic disease - inc risk
Musculoskeletal - joint pain, contractures, immobility, tendon friction rubs
Neuro - neuropathies, myopathy/myosisits
GU - eractile dysfunction, femal sexual dysfunction
Systemic sclerosis (Scleroderma)- diagnosis
> 9 = sclera derma
Systemic sclerosis (Scleroderma)- labs & imaging
ANA - pos
Anti-SCL-70 - pos
Anti-centromere antibodies - limited skin involvement, pHTN, & digital ischemia
Anti-RNA polymerase III antibody - diffuse disease - inc SRC
Anemia - mild
Peripheral smear - microangiopathic hemolytic anemia - SRC
Proteinuria w/ renal involvment
CT - lung changes
PFTs - baseline, repeat Q4-12m
Echo - pHTN
EGD - Barrett’s
Systemic sclerosis (Scleroderma)- treatment
No proven disease-modifying drug - TREAT TARGETED ORGANS
Refer to Rheum and any other specialist!
Diffuse skin/ systemic involvement - immune process target
- glucocorticoids, methotrexate, mycophenolate mofetil, cycophophamide, IVIG
Raynaud phenomenon - CCB, Sildenafil, exposure precautions
GI
- prokinetic agents - metoclopramide, erythromycin
- Malabsorption - treat small bowel bacterial overgrowth with abx
- Reflux - lifestyle mod, PPIs,H2blockers
Lung
- pHTN - dont smoke, diuretic, digoxin, sildenafil or prostaglandins
- ILD - immunosuppreants - cyclophosphamide, MMF
Renal
- SRC - ACEI to return to baseline, dialysis, transplant
C V - treat per usual
Erectile dysfunction - on-demand pills dont work, Viagra, Cialis
Systemic sclerosis (Scleroderma)- prognosis
Depends on organ involvment
Lung dx - may cause of mortality
Worse prog - diffuse, M, pulmonary invovlement, SRC, CV
limited - 90%
Diffuse - 70-80%
May be linked w/ breast and lung cancer
Systemic lupus erythematosus- pathophysiology
Chronic inflammatory disease w antibodies and vary presentations that can affect every organ —> fatigue, joint pain, rash
Exact etiology unclear
Lupus antibodies target intracellular particles that have nucleic acid and nucleic acid binding proteins
Antibodies bind to targets —> activate inflammatory pathway —> immune complexes and complement deposited in organs- esp skin, kidneys, heart valves
Systemic lupus erythematosus- epidemiology
Childbearing females- use of estrogen
OCP, early monarch, estrogen, post menopausal
Black, Hispanic, Asian > Caucasian
Urban
MHC and genes code for complement pathway
Smoking
Systemic lupus erythematosus- S/S & PE
Constitutional symptoms - fever, fatigue, malaise, weight loss
Skin
1. Acute cutaneous lupus erythematosus -
- Localized: malar ““butterfly”” rash, spares nasolabial folds, triggered by sun exposure, scaly, indurated
- Generalized: maculopapular lesions in a photosensitive distribution - any part of body
2. Subacute cutaneous lupus erythematosus
- MOST photosensitive of all rashes
- scaly, erythematous papules
3. Chronic cutaneous lupus erythematosus
- discoid lupus - raised erythematous plaques w/ scale, raised erythmeatous ring around lesion
- lead to scaring -> skin atrophy
- lupus panniculitis
- Alopecia, plaques or psoriasiform lesions, nail fold infarcts, periungual erythema, livedo reticularis, mucosal ulcerations - not painful, on hard palate
MSK - arthralgia and nonerosive arthritis - early - PIP, MCP, writs, knees
Renal - commonly involved - poor prognostic indicator - lupus glomerulonephritis
Vascular
- raynaud phenomenonz
- Vasculitis - all sizes, esp small
- Thromboembolis - antiphospholipid antibodies
CV - pericarditis, inc risk CAD, arrhthmias, MR from atypical verrucous endocarditis
Lung - pleuritis, pleural effusion, ILD, pneumonitis, pHTN, alveolar hemorrhage
GI - dysphagia, PUD, intestinal pseudo-obstruction, protein-losing enteropathy, mesenteric vasculitis, acute pancreatitis,peritonitis, perfoation
Eye - Keratoconjunctivitis sicca, retinal vasculopathy
Neuro - cognitive dysfucntion, psychosis, mood disorder, seizures, cerebrovascular disease, neuropathy, HA
Lymphadenopathy - cervical, axillary, inguinal nodes
Hematologic - anemia of chronic disease, leukopenia and midl thrombocytopenia
Systemic lupus erythematosus- diagnosis
Even if it doesn’t meet criteria- still dx w 2-3 features plus 1 other feature e
Systemic lupus erythematosus- labs & imaging
ANA - pos
Anti-dsDNA - specific, but not sensitive - levels correspond to disease
Anti-SM - specific, but not sensitive
Antiphospholipid antibodies - false pos for syphilis
Anti-Ro and anti-LA - maybe!
Anemia Leukopenia Thrombocytopenia Elevated Cr False-positive suphilis Proteinuria - abnormal urine sediment Hematuria Hypocomplementemia Direct coombs - pos
Systemic lupus erythematosus- treatment
Regular exercise
Smoking cessation
Sun protection - DAILY
Healthy diet
Prevent glucocortioid induced osteoposis
Stay up to date on vacc
Treated w/ antimalarials
Cutaneous:
- initial - topical glucocorticoids - start low
- can do - intralesional injections of triamcinolone - refractory
- may need systemic - hydroxycholorquin
Musculoskeletal - NSAIDs or Tylenol - may add hydroxychloroquine
Serositis - NSAIDs or/and low-mod glucocorticoids
- hydroxychlorquine or PO colchicine - persistent/recurrent
- mod/high steroids - taper -> switch to MTX, azathioprine, or MMF - severe or refractory
Renal - renal biopsy -> get exact path
- ACEI or ARB - HTN/proteinuria
- immunosuppressent?
Neuropsychiatric -depends
- Seizures - anticonvulsants
- CVA - b/c of antiphopholipid? - long term anticoag
- Glucorticoids - controversial
Hematologic
- leukopenic w/ recurrent infection - prednisone (inc WBC)
- Thrombocytopenia <20k or < 50k + bleeding and severe autoimmue anemai
- high dose glucocorticoids - taper
- IVIG, immunosuppressants, Splenectomy - last
Systemic lupus erythematosus- prognosis
Biomodal mortality
Early- infections, renal, CNS
Later- atherosclerosis form chronic inflammation- MI
Higher malignancy risk
A vascular necrosis of bone- long term effects of steroids
Drug induced lupus
Procainamide, hydralazine, isoniazid, chloropromazine, methydopa, minocycline, quindine
F=M
No nephritis and CNS involvement
No anti-dsDNA antibodies or hypocomplementemia
Labs and S/S normalize once drug is discontinued
Polymyositis- pathophysiology
Autoimmune myopathy characterized by proximal muscle weakness
Myosistis-specific antibodies and myosistits associated antibodies
Inflammatory cell infiltrates muscle tissue
Non immune also plays a role?
Path poorly understood
Polymyositis- epidemiology
Rare F>M Black > Caucasian 45-60 yo HLA polymorphism
Polymyositis- S/S & PE
Proximal muscle weakness/muscle fatigue
- gradual and progressive
- symmetric
- leg weakness- first
- arm and neck weakness
- trouble rising out of chair, climbing stairs, washing hair
- dysphagia, difficulty breathing, fetal incontinence
Muscle pain/tenderness
Intestinal lung disease, myocarditis, overlap syndrome- connective tissue disease
Polymyositis- diagnosis
No validated way Can do w/out biopsy if: - characteristic clinical symptoms - abnormal muscle enzyme - no better explanation Get an EMG or MRI
Polymyositis- labs & imaging
CK - inc Troponin - see if CV involved LDH, aldolase, AST, ALT - inc ESR/CRP - not helpful ANA - pos Anti-Jo-1 antibody Anti-SRP - progressive, severe Anti-Mi-2 & anti-155/140- dermatomyositis
Muscle Biopsy - Gold
- muscle that is weak, but not atrophied
- Quds or delts
- Inflammatory infiltrate - invade fascicle
EMG & MRI - identify which muslce to biopsy
- bx oposite side - wont get needle artifact
- differentiate myosisit rom a neruopathic cause
- EMG - early recrutiment
- MRI - muscle inflammation, edema, fibrosis, calcification
Polymyositis- treatment
Steroid- Prednisone
- 4-6 w for disease control
- Taper
Osteoporosis prophylaxis
Immunosuppressant - combined
- initial or when steroid fail
- Azathioprine
- Methotrexate
Exercise!!
PT
Polymyositis- prognosis
Good w/ meds Delayed treatment - worse prognosis Don’t regain completely Anti-Jo-1 - don’t completely respond to treatment Inc risk of malignancy Steroid - SE from long term use
Psoriatic arthritis- pathophysiology
Chronic inflammatory arthritis associated w psoriasis
Unknown
HLA alleles
Develops after or same time as onset of psoriasis
Psoriatic arthritis- S/S & PE
Pain and stiffness - affected joints
- morning stiffness >30min - worse w/ no movement
Symmetric polyarthritis - common
Asymmetirc oligoarthritis - less common
Distal arthritis - DIP
Arthritis mutilans - deforming destructive
Spondyloarthritis - sarcoiliitis & spondylitis - C spine involvement
Enthesitis - inflammation at site of insertion of tendons
- soft tissue swelling, TTP
Tenosynovitis - flexor tendons of hands, extensor carpi ulnaris
Dactylitis - sausage digit - diffuse swelling of entire finger or toe
Skin lessions - onset
- erythematous plaques with scaling
Nails - pitting, ridging, onycholysis, nail bed hyperkeratosis, splinter hemorrahage
Pitting edema in hands/feet
Eyes - ocular inflammation - uveitis, conjunctivitis
Psoriatic arthritis- diagnosis
Nonspecific Both psoriasis and inflammatory arthritis Diagnose in a sense of psoriasis - distal joint involvement - asymmetric distribution - nail lesion - dactylitis - FH of psoriasis - presence of HLA-C
Psoriatic arthritis- labs & imaging
ESR/CRP- inc
Synovial fluid- inflammatory
RF- neg
Imaging
- joint space narrowing
- erosions involving DIP, PIP
- pencil-in-cup deformity
Psoriatic arthritis- treatment
Refer to Derm and Rheum
Early treatment
PT/OT/exercise
Weight reduction
Mild peripheral or axial - NSAIDs - naproxen, celebrex
Severe or unresponsive to NSAIDs
- DMARDs - Methotrexate, sulfasalazine, azathioprine, cyclospoirne, hydroxychloroquine
- Biologic TNF inhibitors - etanercept, infliximab, adalimumab, golimumab, cerolizumab pegol
- Immunosupprssion - reactivation of latent TB
DONT USE PO STEROIDS!!- cause flare
Psoriatic arthritis- prognosis
Comorbidities
- inc risk of CV
- DM, atherosclerosis, metabolic syndrome
- inc rates of depression and anxiety
