Exam 5 Flashcards
IHC: desmin
Striated muscle differentiation for soft tissue tumors
IHC: smooth muscle actin, SMA
Smooth muscle differentiation, staining for soft tissue tumors
IHC: S – 100
Peripheral nerve sheath differentiation for soft tissue tumors. Example schwannoma
IHC: Vimentin
Undifferentiated, soft tissue, tumor stain, stains mesenchymal cells
Malignant, soft tissue neoplasms (sarcomas)
• most are sporadic with no known predisposing cause
• precursor lesions are not known (except NF1)
• hematogenous metastasis is common, lymph is rare
• 80% of sarcomas have a complex karyotype, more common in adults, pleomorphic histology
• 20% of sarcomas, have a simple karyotype, more common in children, monomorphic histology
Benign lipomatous tumors: lipoma
• common, present at 40 to 60 years
• subcutaneous: trunk, neck, proximal extremities
• deep: thorax, pelvis
• soft, painless, freely mobile
• do not become liposarcoma’s
Lipoma in the retroperitoneum is usually a:
Liposarcoma
Angiolipoma
• common in late teens to early 20s
• most common on the forearm
• tend to be painful/tender however, excision is not needed
Spindle cell lipoma/pleomorphic lipoma
• men, 45 to 60 years old, subcutaneous, posterior neck, shoulder, and back
• lots of pleomorphism’s in the histology, but it’s still benign
Atypical lipomatous tumor/well differentiated liposarcoma
• atypical tumor, when in superficial or extremity locations
• well differentiated liposarcoma, when in deep locations like retroperitoneum
• peaks in 6th to 7th decade
• MDM2 amplification is a characteristic finding (P 53 inhibitor)
Myxoid liposarcoma
• peaks in the fifth decade, also almost all pediatric liposarcoma
• 75%, legs, or retroperitoneum
• aggressive tumor that often metastasizes, 10 years survival can be less than 50%
• t(12;16) translocation genetically
Pleomorphic liposarcoma
• late adult life, retroperitoneum and deep extremities, 25% in subcutis
• deep tumors, have a poor prognosis
• complex cytogenetics, many abnormalities
Nodular fasciitis
• benign, self-limiting myofibroblastic proliferation
• young adults (20-40)
• rapidly growing, most present within one month, spontaneous regression is common
• often misdiagnosed as a sarcoma, due to rapid growth, high cellularity, and high mitotic rate
• MYH9-USP6 fusion gene via chromosomal translocation
Superficial fibromatosis
• benign, fibroblastic proliferation that causes local deformity
• recurrence after excision is common, never metastasizes, do not expand in a deep tissue
Examples:
1.) Palmer fibromatosis (Dupuytren contracture)
2.) planter fibromatosis (Ledderhose disease)
3.) Penile fibromatosis (Petronius disease)
4.) knuckle pads (cosmetic concern)
Deep fibromatosis (desmoid tumors)
• locally aggressive/low-grade malignancy of fibrous tissue
• teens to 30s, more common in women
• association with pregnancy, often presenting within one year of childbirth
• mutations in a PC or CTNNB1(beta catenin) genes
• most are sporadic, but germline mutations in a PC are predisposed to desmoid tumors
• scarring typically looks like the tumor, especially in C-section
Benign rhabdomyoma/ malignant rhabdomyosarcoma
Benign: Very rare, most are seen in tuberous sclerosis
Malignant: most common sarcoma in childhood and adolescence, embryonal and alveolar types
— sinuses, head and neck, and genitourinary tract are most common locations
— diagnosis made from IHC evidence of muscle differentiation (desmin)
Soft tissue leiomyoma
• distinct from uterine leiomyoma, which are much more common
• usually not more than 3 cm
• reed syndrome: multiple skin, lesions, high risk for renal cell carcinoma
Soft tissue leiomyosarcoma
• sporadic, retroperitoneal and abdominal cavity, G.I. tract, vascular, and cutaneous forms are most common
• cutaneous forms have an excellent prognosis
Atypical intradermal smooth muscle neoplasms
The new name for cutaneous, soft tissue leiomyosarcomas
Hemangioma, adult
Very common, seen in skin (cherry angioma) but also internally (liver)
Infantile hemangioma
• affects 5% of children, more often females
• flat red mark within a few weeks of birth, grows, becomes elevated. mass peaks at 6 to 12 months, then regresses over a few years
• do not become malignant
Primary cutaneous angiosarcoma
Primarily elderly, white men and women, often on the scalp or forehead
Lymphedema associated angiosarcoma
Any long-standing lymphedema
Stewart Treves syndrome: lymph edema associated angiosarcoma, following a mastectomy
Radiation induced angiosarcoma
Half of cases occur in skin of breast, following therapy for cancer, rare
Angiosarcoma of the liver
• 75% idiopathic, 25% due to toxin exposure
• vinyl chloride, thorotrast, androgenic steroids
Angiosarcoma definition
High-grade, poorly differentiated malignancy, diagnoses often based on IHC detection of vascular markers CD31, no known precursor legion, sporadic
Kaposi sarcoma
Multiple forms, all associated with Kaposi sarcoma associated herpes Virus, KSHV, also known as human herpesvirus 8 (HHV8)
— prevalence varies geographically, more than 50% in sub-Saharan Africa
Classic Kaposi sarcoma
• 90% are men, mostly 60 to 70 years old
• Poland, Russia, Italy, equatorial Africa
• starts as multifocal lesions on lower legs, then they coalesce
• indolent disease with prolonged course, fatalities take 8 to 10 years
Endemic African Kaposi sarcoma
•Young patients, even very young children
• kids, less than three years old, have lymphadenopathy and internal disease (often salivatory gland) with little to no skin involvement
Immunosuppression associated Kaposi sarcoma
• iatrogenic, transplantation associated
— renal transplants seen freq.
• AIDS related
— antiretroviral therapy both prevents lesions and causes regression of lesions
Peripheral nerve sheath tumors
• neoplastic preparation of Schwan cells
• sporadic, or associated with NF1 or NF2
• schwannoma, neurofibroma, malignant peripheral nerve sheath tumor (MPNST)
Neurofibromatosis type I, Von Recklinghausen disease
• loss of function notation in NF1 genes on chromosome 17 that codes for neurofibromin, a tumor suppressor
• neoplasms: neurofibromas, MPNST, optic nerve gliomas, other glial tumors, pheochromocytomas
• other features: café au lait spots, pigmented nodules in the iris (lisch nodules), skeletal defects, intellectual disability, seizures
Neurofibroma
Benign tumor of Schwan cells, with other admixed cells
Three types: local cutaneous, diffuse, plexiform
Plexiform neurofibroma
Always associated with NF1, large expansion of Nerve bundles, can become malignant (MPNST)
Neurofibromatosis type 2
• NF2 gene on a chromosome 22
encoding Merlin protein, which interacts with signaling molecules and cytoskeleton and medius cell to cell contact (tumor suppressor)
• bilateral vestibular schwannomas
• café au lait spots, and neurofibromas are NOT seen
Schwannoma
• inactivated NF2/Merlin protein
• Intercranial tumors usually occur at cerebellopontine angle, arising from the vestibular branch of the eighth cranial nerve and are often bilateral in NF2 patients
Malignant, peripheral nerve sheath, tumor, MPNST
• malignant mesenchymal tumor with neural crest differentiation
• S-100 positive
• half of cases occur in NF1 patients, most as a result of malignant transformation of a plexiform neurofibroma
Traumatic neuroma
• can occur following a trauma, represents an attempt at nerve repair, with unsuccessful connection with distal segments of severed nerve. Often presents as painful subcutaneous or submucosal mass.
Mortons neuroma (Morton metatarsalgia)
Not a neuroma, a degenerative and fibrosing process affecting the plantardigital nerve. Pain in the foot between heads of the third and fourth or second and third metatarsals.
Synovial sarcoma
• Not malignant synovium, patients are young adults, tumor is aggressive, and metastatic, sometimes to regional lymph nodes.
• t(X;18) translocation producing SS18:SSX fusion gene
Undifferentiated pleomorphic sarcoma
High grade pleomorphic sarcoma that have no morphologic, immunohistochemical, or cytogenetic evidence of differentiation or defined tumor type
— typically deep, soft tissue of the extremities (thigh). aggressive, malignancy with a poor prognosis
Eicosanoids: cyclooxygenases, cyclic pathway
• prostaglandins
• thromboxanes
Eicosanoids: lipoxygenases, linear pathway
• leukotrienes
• HETE
• Lipoxins
Eicosanoids: cytochrome P450 enzymes
• epoxides
• HETE
• diHETE
eicosanoids: phospholipase D
• annandamide
• 3-arachidonylglycerol
Eicosanoids: non-enzymatic free radical attack
• isoprostanes
Prostaglandins
Synthesized by all cell types, they function as autocrine and paracrine hormones, and have a very short half-life. They are induced by a broad rage of stimuli and mediate a broad range of biological responses.
Thromboxane
Synthesized from prostaglandin, most importantly, and platelets. Mediate vasoconstriction, platelet aggregation.
Major precursor of eicosanoids
The poly unsaturated fatty acid: arachidonic acid
— omega-3, omega-6
What can be consumed in the diet and converted to arachidonic acid by elongation and introducing to carbon carbon double bonds?
Linoleic acid
Where is arachidonic acid stored in the cell?
Cytosolic side of the plasma membrane. Usually attached to the second carbon of the glycerol backbone.
Pathways to create arachidonic acid from storage
1.) phosphatidylcholine — Lipase A2 + Ca—> arachidonic acid + monoglyceride phosphate
2.) phosphatidylinositol bisphosphate — phospholipase C—> 1,2- diacylglycerol —> diacylglycerol lipase—> arachidonic acid + monoacyl glycerol — monoacylglycerol lipase —> arachidonic acid
What prostaglandin looks like
Has a five atom ring, a hydroxyl at carbon 15, and a double bond between carbon 13 and 14
Synthesis of prostaglandins and thromboxane’s from arachidonic acid
Arachidonic acid— cyclooxygenase—> PGG2 — peroxidase + 2GSH—> PGH2 + 2 GSSG — PGI synthase—> prostacyclin (PGI2)
Linoleic acid versus linolenic acid
Linoleic: omega six— vasoconstriction, bronchoconstriction, inflammation
Linolenic: omega three— vasodilation, bronchodilation, resolution of inflammation
15-Hydroxyprostaglandin dehydrogenase inhibitors
• increase PGE2 levels and promote liver regeneration, hematopoiesis, and prevents colitis and mouse models
Leukotriene formation
5-HPETE—> epoxide—> hydroxyl (LTB4)
Glutathione + carbon-6 —> LTC4 —> remove glutamate —> LTD4 —> remove glycine —> LTE4
Function of leukotriene
LTC, LTD, LTE-4: bronchial inflammation
— receptor for these is a drug target for treatment of asthma
Lipoxins
Synthesized from 15-HPETE, promote chemotaxis and superoxide production in phagocytic vesicles by neutrophils
PGE2 binding EP2 / EP4
These receptors are coupled to adenylate, cyclase, and their activation increases cAMP and activates protein kinase A
PGI2, PGE2, PGD2
Increases: vasodilation
Decreases: platelet, leukocytes aggregation, IL-1, IL-2, WBC, proliferation and migration
PGF2
Increases: vasoconstriction, bronchoconstriction, smooth muscle contraction (inflammatory response)
TXA2
Increases: vasoconstriction, bronchoconstriction, platelet aggregation, lymphocyte proliferation
LTB4
Increases: vascular, permeability, T-cell proliferation, leukocyte aggregation, INF-gamma, IL-1, IL-2
LTC4, LTD4
Increases: bronchoconstriction, vascular permeability, INF-gamma
What does healthy vascular, endothelial cells release?
PGI2, which prevents platelet clotting and keeps blood vessels open
Thrombin
A protease that Cleaves soluble fibrinogen to form fibrin, which polymerizes into a wound covering matrix
When platelets contact thrombin, they release thromboxane A2 (TXA2), which acts as a paracrine and autocrine hormone to induce platelet aggregation and other wound responses
Endocannabinoids
Bind CB1 receptors involving nerve synapses, resulting in an analgesic effect. They also bind CB2, which is present in the spleen and immune cells.
TRPV1
When bound by Endocannabinoids, TRPV1 activation in sensory neurons causes calcium influx and neurotransmitter release
— Anandamide and 2-arachidonoylglycerol are the major endocannabinoid
Anandamide
An endocannabinoid derived from phosphatidylethanolamine that can activate CB1, CB2, and TRPV1.
Fatty acid amide hydrolase breaks down Anandamide into ethanolamine and arachidonic acid and stops signaling
NSAIDS
Interfere with the production of prostaglandins by inhibiting cyclooxygenases. Widely used in the treatment of pain, fever, and information.
Isoforms of cyclooxygenase
COX1: constitutive cyclooxygenase. It is not induced by abnormal physiological conditions, rather it is constitutively active. Produces prostaglandins which maintain normal processes. An ideal drug would not inhibit COX1
COX2: induced cyclooxygenase. It is induced by cell damage and infection, and is responsible for producing prostaglandins, which mediate inflammation, fever, and pain. It is the preferred drug target.
Aspirin
Acetylsalicylic acid, inhibits, both COX1 and COX2.
Activity against COX2: produces anti-inflammatory, pain, relief, fever reduction
Activity against COX1: produces undesirable side effects, stomach ulcers
Aspirin as a suicide inhibitor
Aspirins acetyl group is transferred to the side chain of a serine amino acid near the active site permanently disabling the enzyme.
— platelets have no nucleus, killing the cyclooxygenase will eliminate prostaglandin synthesis for the life of a cell.
Common, OTC NSAIDs, that are nonspecific inhibitors of COX1 and COX2
Ibuprofen (Advil), acetaminophen (Tylenol), naproxen (Aleve)
Specific inhibitor of COX2
Celecoxib (celebrex): however it increases the risk of stroke and heart attack
Prednisone and dexamethasone
Interfere with phospholipase A2 and cyclooxygenase at the transcriptional level. This prevents inflammation blocking the production of both leukotrienes and prostaglandins.
— pts on high doses of corticosteroids may develop hyperglycemia
Long-term management of asthma drugs
Montelukast (Singulair) and Zafirlukast (Accolate): they work by blocking the CysLT1 receptor to reduce leukotriene activity (bronchoconstriction)
Inflammation
A process which begins following sublethal injury to tissue and ends with permanent destruction of tissue or complete healing. Injury can be mechanical, heat, chemicals, bacteria, biases, antigen-antibody reactions.
Mediators of the inflammatory response
Endogenous substances (autacoids or local hormones). They’re stored or rapidly synthesized, intended to act only at the side of injury.
Redundancy of the inflammatory response
Many different substances or mediators can cause the symptoms of inflammation
Acute inflammation
• changes in blood vessel caliber and flow, arteriolar, dilation
• increased vascular permeability
• leukocyte infiltration
• redness, swelling, heat, and pain
Causes of redness, swelling, heat, and pain
Histamine, prostaglandins, leukotrienes, Kinins, products of complement system, activation, cytokines, interleukins, adhesion molecules
What mediates many inflammatory effects of rheumatoid arthritis?
Prostaglandins
Inflammatory effects of prostaglandins
•PGE: most potent at inducing fever
• PGE and PGI2: vasodilation, redness, and heat, increased vascular permeability (swelling), pain
Sources of cyclooxygenase products
Platelets—> thromboxane (vasoconstrictor)
Endothelium —> prostacyclin (vasodilator)
Mast cells —> PGD2 (broncoconstrictor)
Five major types of receptors for prostaglandins
1.) DP (PGD)
2.) FP (PGF)
3.) IP (PGI2)
4.) TP (TXA2)
5.) EP (PGE)— for subtypes, EP1 through EP4
Shared therapeutic activities of COX1 and COX2 inhibitors:
• analgesia (prostaglandin slower the pain threshold)
• anti-inflammatory
• antipyretic
— preventing PGE2 synthesis with NSAIDs you can control fever in many situations (inflammation—> cytokines (IL-1)—> PGE2 —> hypothalamus—> fever)
Drugs that inhibit COX
• aspirin (acetylsalicylate), irreversible
• tNSAIDs (traditional NSAIDs, nonselective)
• Celecoxib: selectively COX2 inhibitor
• acetaminophen (very wimpy)
Aspirin toxicity: Reye syndrome
Encephalopathy and fatty liver, following viral infection in children with the use of aspirin
Acetaminophen
Weak inhibitor of COX, with minimal anti-inflammatory activity. Inhibits cyclooxygenase in the brain, but not at sites of inflammation.
— analgesic and antipyretic, not anti-inflammatory
Adverse effects of NSAIDs
• gastric or intestinal ulceration
• prolongation of gestation
• renal function/hepatic function
• increase bleeding time
• aspirin sensitivity
— effects are minimized with COX2 specific inhibitors (less constitutively expressed than COX1)
Aspirin hypersensitivity
• occurs in 3 to 10% of asthmatics
• atopic individuals
• symptoms include rhinitis, urticaria, asthma, and laryngeal edema
— this happens due to a shift from arachidonate utilization to Lipoxygenase pathway (more leukotriene production) when blockading COX
Corticosteroids
• glucocorticoids are transcriptional regulators, they reduce WBC and increase RBC
• it’s a broad anti-inflammatory
• reduces host resistance to microbial and fungal infections
Examples of corticosteroids
Dexamethasone, hydrocortisone, methylprednisolone, prednisone
Toxicity limits prolong to use of steroids because of:
Osteoporosis, immunosuppression, peptic ulcers, myopathy, Cataracts, fluid accumulation, and hyperglycemia
DMARDS: disease modifying antirheumatic drugs
• do not have immediate analgesic affect (no stopping pain)
• slow, or delay the progression of RA
• methotrexate, hydroxychloroquine, sulfasalazine are the first line
Methotrexate
• anticancer drug at high doses
• cytotoxic for rapidly proliferating cells
• works as an anti-folate in cancer (blocks dihydrofolate reductase—> inhibiting, pyrimidines, and purines synthesis)
• inhibits, amino-imidazole carboxamide ribonucleotide transformylase (AICART) and thymidylate synthase and AMP deaminase
Methotrexate as an anti-rheumatic arthritis drug
• May take 3 to 6 weeks to become apparent, administered orally once per week
• contraindicated with liver disease, severe renal impairment, or heavy alcohol ingestion
Hydroxychloroquine
• antimalarial drug with ocular toxicity at high doses
• generally well-tolerated, although not well understood
• accumulates in lysosomes and increases the pH, inhibits MHC class II autoantigen presentation (TLR signaling), reduces the production of pro-inflammatory cytokines
Sulfasalazine
• metabolized into active substances
1.) sulfapuridine: a free radical scavenger
2.) 5-amino salicylic acid: a cyclooxygenase antagonist
• primarily an alternative, because it tends to be more toxic with more SE
Leflunomide
• inhibits pyrimidine synthesis, arresting cells in the G1 phase
• primarily affects T cells, and potentially B cells, decreases lymphocyte activation
• diarrhea is a frequent SE
Gold and minocycline
• minocycline is a tetracycline antibiotic with some anti-inflammatory properties (minor drug)
• gold salts: intramuscular gold therapy (standard of treatment previously)
bDMARDS: biological DMARDs
• no immediate, analgesic affect, can slow or delay the progression of RA
• not usually a first line drug for RA
• combining csDMARD with a bDMARD is often recommended for patients with moderate to high disease activity
Rheumatoid arthritis drugs to never mix
bDMARDS and a JAK inhibitor— not recommended because of increased risk of infection
TNF inhibitors
• faster, onset of action than csDMARDS
• given by infusion or SC injection at multi week intervals (not a home drug)
• increased risk of serious infection, including TB, hepatitis B, fungal, infections, legionella, and listeria
• increased risk of skin cancer
PEG: polyethylene glycol
• widely used to improve drug pharmacokinetics and bioavailability
• PEGylation significantly increases the circulating half-life of FAB molecules, permitting a minimum dosing interval of two weeks
Abatacept
• binds to CD80 or CD86 And inhibits binding to CD28, that’s preventing the activation of T cells
• increased risk of serious infection, including TB, hepatitis B, URI
Rituximab
• binds to CD20 on B cells, and they are depleted
• serious infections can occur, rashes, common, potential reactivation of hep B
• given by infusion
Interleukin receptor inhibitors
• require an increase the level of care
1.) Anakinra: blocks IL-1 receptor. Infrequently used. Injected sc daily.
2) Toclizumab: blocks IL-6 receptor. Given by IV infusion at four week intervals. Serious infections are possible.
JAK inhibitors
• targeted synthetic tsDMARD
• Janus kinase inhibitors: Tofacitinib, baracitinib
• given orally, side effects are significant
Osteoarthritis
• non-inflammatory arthritis, most common form
• found in the knees, hips, spine, hands and feet
• progressive loss of articular cartilage
• age-related disorder
Clinical presentation of osteoarthritis
• gradual onset
• intermittent and self limited “ overdo it”
• use related pain relieved by rest
• morning stiffness LESS than 30 minutes
Risk factors of osteoarthritis
• increased age
• major joint trauma
• obesity, knees
• repetitive activities
• general predispositions/congenital developmental defects
• females
Osteoarthritis physical exam
• localized pain, does not hurt everywhere, at joint lines that gets worse with use
• decreased ROM
• bony enlargement (osteophytes), soft tissue swelling, crepitus
• instability/deformity
• HARD BONY PIP and DIP
X-ray findings of osteoarthritis
1.) sclerosis: white, new bone formation in a subchondral trabeculae
2.) osteophytes: spurs, formation of new bone at joint margins
3.) loss of cartilage
Management of osteoarthritis
1.) therapies: exercise, PT, assistive devices, joint replacement
2.) pharmacologic therapy: acetaminophen, nsaid, OTC topical agents, steroid injections
** no disease modifying drugs, only symptom modification
Osteoarthritis general features
1.) clinical: > 50, morning stiffness < 30 minutes, crepitus, no inflammation, bony enlargement or tenderness
2.) laboratory: ESR < 40 mm/hr, RF titer <1:40, non-inflammatory synovial fluid
3.) radiographic: osteophytes, joint space narrowing, subchondral, cysts, and sclerosis, malalignment
Rheumatoid arthritis population
• prevalence is around one percent of adult population, increases to 5% in women by age 70
• 40-60 year old onset, W-M 3:1
• risk factors include smoking, and periodontal disease
Rheumatoid arthritis
• symmetric inflammatory arthritis
• insidious onset—> subacute—> acute
• erosive, chronic, progressive, disabling disease
• 80% have positive rheumatoid factor
• positive anti-CCP antibody
• systemic, disease: fatigue, fever, weightloss, extra articular manifestations
ACPAs
Antibodies to citrullinated proteins/peptide antigens found in rheumatoid arthritis
Extra-articular manifestations of rheumatoid arthritis
• subcutaneous nodules on elbows/pressure areas
• pericarditis
• pulmonary: nodules, effusions, interstitial lung disease
• inflammatory eye, disease: episcleritis, scleritis
• vasculitis
— symptoms must be present for at least six weeks to be chronic
Rheumatoid arthritis classification: acute versus chronic
1.) swollen joints: small joints= wrists, MCP, PIP, MTP. Large joints= ankles, knees, elbows, shoulders
2.) serology: (-) RF, (-) anti-CCP, low or high titer (<3xULN or >3xULN) RF and anti-CCP, and then (+) RF, (+) CCP-Ab,
3.) inflammatory markers: normal CRP/ESR —> elevated CRP/ESR
Causes of rheumatoid arthritis
Combination of genetics and environment, HLADRB1 alleles are overrepresented among RA patients
Articular manifestations of rheumatoid arthritis
• shiny: stretching of the skin/edema and swelling
• tender, warm, redness, wrinkles, less prominent
• DIPs not affected
• bouncy, step down: subluxation of knuckles
• ulnar drift of MCP joints
• RA nodules
• bone erosion
Management of rheumatoid arthritis
• recognition and early treatment
• PT/OT/exercise
• medication:
1.) NSAIDs
2.) glucocorticoids/steroids: short term
3.) DMARDs and bDMARDs to slow down destruction
csDMARDs options for rheumatoid arthritis
hydroxychloroquine/plaque I’m
Sulfasalazine
Methotrexate
Leflunomide /Arava
Azathioprine/ imuran
bDMARDs for rheumatoid arthritis
Anti-TNF
T-cell cosimulator
B cell (rituximab)
IL-6 inhibitor
IL-1 inhibitor
-JAK inhibitor
Juvenile idiopathic arthritis, JIA
• chronic synovial, inflammation lasting longer than six weeks in children under 16
• subgroups: systemic onset (sJIA), polyarticular onset (5 or more joints), oligoarthritis onset (1-4 joints)
JIA systemic onset
• between two and five years old
• daily spiking, fevers, accompanied by an evanescent, salmon colored rash
• many systemic features
• RA and ANA generally negative
JIA: polyarticular onset
• arthritis in five or more joints, 20% of children with JIA
• girls > boys, 3:1
• weight, loss, low-grade fever, lymphadenopathy, anemia
• can either be RF positive (severe disease, aggressive treatment), or RF negative
JIA: oligoarticular onset
• occurs in 50 to 80% of all children with JIA
• early onset, 2 to 4 years old, girls > boys 3-4:1
• joints: knees most common, angles, rest, elbows
• ANA (+) : important to evaluate for inflammatory eye disease, which may lead to blindness (uveitis)
JIA TREATMENT
• patient parent education
• PT/OT
• NSAIDs
• steroids: intra-articular/oral
• DMARDS:
1.) methotrexate
2.) sulfasalazine
3.) leflunomide
4.) anti-TNF, anti-IL1, anti-IL6, JAK inhibitors
Drug induced lupus caused by:
Procainamide, hydralazine, methyldopa, chlorpromazine, isoniazid, quinidine, minocycline
Gout: Crystal induced arthritis
• deposition of monosodium urate
• joints: acute inflammatory arthritis
• skin: accumulation of crystals, tophi
• kidney: uric acid urolithiasis, nephropathy
Stages of gout :
1.) asymptomatic hyperuricemia
2.) acute intermittent gout
3.) chronic tophaceous gout
Causes of hyperuricemia
1.) uric acid overproduction. (10%)
2.) uric acid underexcretion. (90%)
Acute gouty arthritis
• abrupt onset of inflammatory arthritis, local release of inflammatory mediators, often occurring at night
• pain escalates over 8 to 10 hours and may subside within 3 to 10 days
• fever, chills, in severe cases
Involvement of: joints (MTP common), periarticular, structures, bursa, tendons
Diagnosing Gout
• serum uric acid levels (not sensitive, nor specific)— helpful in long-term Management
• H&P clinical manifestations
• GOLD STANDARD: synovial fluid analysis (tap the joint)- and look for crystals
Triggering factors of gout
1.) alcohol ingestion
2.) trauma/severe illness
3.) medication: thiazide, diuretics, low-dose aspirin, cyclosporine
4.) high purine foods
5.) contrast dye
Advanced gout
• uncontrolled hyperuricemia, chronic arthritis, constant pain, polyarticular
• TOPHI: solid uric acid deposits, white chalky material— generally painless, but may cause stiffness and become infected
Chronic tophaceous gout
Location of tophi:
1.) helix of the ear
2.) periarticular regions— fingers (Heberden’s nodes) wrists, olecranon bursa
Genetic factors and gout
• familial occurrence: 40% have family history of gout
• excellent inheritance of HPRT deficiency and PRPP synthase super activity
• autosomal inheritance, G6PD deficiency
Gout treatment
1.) allopurinol, unless HLAB5801(+)
2.) aspiration of joint/analysis of fluid
3.) NSAIDs
4.) Colchicine right away during attack
5.) glucocorticoids, analgesics
6.) Pegloticase IV
Pseudogout: calcium pyrophosphate (CPP arthritis)
• associated with aging, familial, metabolic disease, prior trauma
• mono articular or oligoarticular arthritis, most common in the knees
• 75% of x-rays will show chondrocalcinosis
Spondyloarthropathy
• multisystem, inflammatory disease affecting the spine (most common), sacroiliitis, peripheral joints, periarticular structures (Achilles common)
• seronegative (RH factor (-))
• positive HLAB27
Spondyloarthropathies: ankylosing spondylitis
Inflammatory back/spinal pain:
• Onset before 40
• persisting longer than 3 months
• morning stiffness > 30 minutes
• pain improves with exercise, no improvement with rest (pain at night)
• M > F
• inflammatory eye disease: uveitis
• aortitis, cardiac arrhythmias
Psoriatic arthritis: spondyloarthropathy
• skin and nail lesions (pits/plaques)
• inflammatory eye disease
• peripheral arthritis, DIP joints
• dactylitis/sausage toe
• Achilles tendinitis/plantar fasciitis/sacroiliitis
• arthritis mutilans: disappearing joints
• high familial genetic component
Reactive arthritis (a.k.a. Reiter’s syndrome) spondyloarthropathy
• history, important, develops after an infection: bowel or a genital common
• genetic predisposition: HLAB27
• typically in males between 20-50
• arthritis of large joints, extra-articular manifestations, such as conjunctivitis, urethritis, or cervicitis, genital, ulcers, rash in palms or soles
— rash is keratoderma blenorrhagica
Treatment of spondyloarthropathies
1.) physical therapy/ROM/posture
2.) medication: NSAIDs for all
Peripheral arthritis: sulfasalazine, methotrexate
Axial arthritis: biologics
Antibiotic RX for chlamydia
