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Skin/MS > Exam 5 > Flashcards

Exam 5 Flashcards

1
Q

IHC: desmin

A

Striated muscle differentiation for soft tissue tumors

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2
Q

IHC: smooth muscle actin, SMA

A

Smooth muscle differentiation, staining for soft tissue tumors

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3
Q

IHC: S – 100

A

Peripheral nerve sheath differentiation for soft tissue tumors. Example schwannoma

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4
Q

IHC: Vimentin

A

Undifferentiated, soft tissue, tumor stain, stains mesenchymal cells

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5
Q

Malignant, soft tissue neoplasms (sarcomas)

A

• 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

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6
Q

Benign lipomatous tumors: lipoma

A

• common, present at 40 to 60 years
• subcutaneous: trunk, neck, proximal extremities
• deep: thorax, pelvis
• soft, painless, freely mobile
• do not become liposarcoma’s

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7
Q

Lipoma in the retroperitoneum is usually a:

A

Liposarcoma

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8
Q

Angiolipoma

A

• common in late teens to early 20s
• most common on the forearm
• tend to be painful/tender however, excision is not needed

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9
Q

Spindle cell lipoma/pleomorphic lipoma

A

• men, 45 to 60 years old, subcutaneous, posterior neck, shoulder, and back
• lots of pleomorphism’s in the histology, but it’s still benign

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10
Q

Atypical lipomatous tumor/well differentiated liposarcoma

A

• 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)

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11
Q

Myxoid liposarcoma

A

• 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

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12
Q

Pleomorphic liposarcoma

A

• late adult life, retroperitoneum and deep extremities, 25% in subcutis
• deep tumors, have a poor prognosis
• complex cytogenetics, many abnormalities

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13
Q

Nodular fasciitis

A

• 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

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14
Q

Superficial fibromatosis

A

• 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)

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15
Q

Deep fibromatosis (desmoid tumors)

A

• 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

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16
Q

Benign rhabdomyoma/ malignant rhabdomyosarcoma

A

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)

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17
Q

Soft tissue leiomyoma

A

• 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

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18
Q

Soft tissue leiomyosarcoma

A

• sporadic, retroperitoneal and abdominal cavity, G.I. tract, vascular, and cutaneous forms are most common
• cutaneous forms have an excellent prognosis

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19
Q

Atypical intradermal smooth muscle neoplasms

A

The new name for cutaneous, soft tissue leiomyosarcomas

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20
Q

Hemangioma, adult

A

Very common, seen in skin (cherry angioma) but also internally (liver)

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21
Q

Infantile hemangioma

A

• 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

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22
Q

Primary cutaneous angiosarcoma

A

Primarily elderly, white men and women, often on the scalp or forehead

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23
Q

Lymphedema associated angiosarcoma

A

Any long-standing lymphedema

Stewart Treves syndrome: lymph edema associated angiosarcoma, following a mastectomy

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24
Q

Radiation induced angiosarcoma

A

Half of cases occur in skin of breast, following therapy for cancer, rare

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25
Q

Angiosarcoma of the liver

A

• 75% idiopathic, 25% due to toxin exposure
• vinyl chloride, thorotrast, androgenic steroids

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26
Q

Angiosarcoma definition

A

High-grade, poorly differentiated malignancy, diagnoses often based on IHC detection of vascular markers CD31, no known precursor legion, sporadic

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27
Q

Kaposi sarcoma

A

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

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28
Q

Classic Kaposi sarcoma

A

• 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

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29
Q

Endemic African Kaposi sarcoma

A

•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

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30
Q

Immunosuppression associated Kaposi sarcoma

A

• iatrogenic, transplantation associated
— renal transplants seen freq.
• AIDS related
— antiretroviral therapy both prevents lesions and causes regression of lesions

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31
Q

Peripheral nerve sheath tumors

A

• neoplastic preparation of Schwan cells
• sporadic, or associated with NF1 or NF2
• schwannoma, neurofibroma, malignant peripheral nerve sheath tumor (MPNST)

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32
Q

Neurofibromatosis type I, Von Recklinghausen disease

A

• 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

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33
Q

Neurofibroma

A

Benign tumor of Schwan cells, with other admixed cells

Three types: local cutaneous, diffuse, plexiform

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34
Q

Plexiform neurofibroma

A

Always associated with NF1, large expansion of Nerve bundles, can become malignant (MPNST)

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35
Q

Neurofibromatosis type 2

A

• 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

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36
Q

Schwannoma

A

• 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

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37
Q

Malignant, peripheral nerve sheath, tumor, MPNST

A

• 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

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38
Q

Traumatic neuroma

A

• 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.

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39
Q

Mortons neuroma (Morton metatarsalgia)

A

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.

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40
Q

Synovial sarcoma

A

• 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

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41
Q

Undifferentiated pleomorphic sarcoma

A

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

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42
Q

Eicosanoids: cyclooxygenases, cyclic pathway

A

• prostaglandins
• thromboxanes

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43
Q

Eicosanoids: lipoxygenases, linear pathway

A

• leukotrienes
• HETE
• Lipoxins

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44
Q

Eicosanoids: cytochrome P450 enzymes

A

• epoxides
• HETE
• diHETE

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45
Q

eicosanoids: phospholipase D

A

• annandamide
• 3-arachidonylglycerol

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46
Q

Eicosanoids: non-enzymatic free radical attack

A

• isoprostanes

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47
Q

Prostaglandins

A

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.

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48
Q

Thromboxane

A

Synthesized from prostaglandin, most importantly, and platelets. Mediate vasoconstriction, platelet aggregation.

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49
Q

Major precursor of eicosanoids

A

The poly unsaturated fatty acid: arachidonic acid
— omega-3, omega-6

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50
Q

What can be consumed in the diet and converted to arachidonic acid by elongation and introducing to carbon carbon double bonds?

A

Linoleic acid

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51
Q

Where is arachidonic acid stored in the cell?

A

Cytosolic side of the plasma membrane. Usually attached to the second carbon of the glycerol backbone.

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52
Q

Pathways to create arachidonic acid from storage

A

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

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53
Q

What prostaglandin looks like

A

Has a five atom ring, a hydroxyl at carbon 15, and a double bond between carbon 13 and 14

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54
Q

Synthesis of prostaglandins and thromboxane’s from arachidonic acid

A

Arachidonic acid— cyclooxygenase—> PGG2 — peroxidase + 2GSH—> PGH2 + 2 GSSG — PGI synthase—> prostacyclin (PGI2)

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55
Q

Linoleic acid versus linolenic acid

A

Linoleic: omega six— vasoconstriction, bronchoconstriction, inflammation

Linolenic: omega three— vasodilation, bronchodilation, resolution of inflammation

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56
Q

15-Hydroxyprostaglandin dehydrogenase inhibitors

A

• increase PGE2 levels and promote liver regeneration, hematopoiesis, and prevents colitis and mouse models

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57
Q

Leukotriene formation

A

5-HPETE—> epoxide—> hydroxyl (LTB4)

Glutathione + carbon-6 —> LTC4 —> remove glutamate —> LTD4 —> remove glycine —> LTE4

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58
Q

Function of leukotriene

A

LTC, LTD, LTE-4: bronchial inflammation

— receptor for these is a drug target for treatment of asthma

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59
Q

Lipoxins

A

Synthesized from 15-HPETE, promote chemotaxis and superoxide production in phagocytic vesicles by neutrophils

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60
Q

PGE2 binding EP2 / EP4

A

These receptors are coupled to adenylate, cyclase, and their activation increases cAMP and activates protein kinase A

61
Q

PGI2, PGE2, PGD2

A

Increases: vasodilation

Decreases: platelet, leukocytes aggregation, IL-1, IL-2, WBC, proliferation and migration

62
Q

PGF2

A

Increases: vasoconstriction, bronchoconstriction, smooth muscle contraction (inflammatory response)

63
Q

TXA2

A

Increases: vasoconstriction, bronchoconstriction, platelet aggregation, lymphocyte proliferation

64
Q

LTB4

A

Increases: vascular, permeability, T-cell proliferation, leukocyte aggregation, INF-gamma, IL-1, IL-2

65
Q

LTC4, LTD4

A

Increases: bronchoconstriction, vascular permeability, INF-gamma

66
Q

What does healthy vascular, endothelial cells release?

A

PGI2, which prevents platelet clotting and keeps blood vessels open

67
Q

Thrombin

A

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

68
Q

Endocannabinoids

A

Bind CB1 receptors involving nerve synapses, resulting in an analgesic effect. They also bind CB2, which is present in the spleen and immune cells.

69
Q

TRPV1

A

When bound by Endocannabinoids, TRPV1 activation in sensory neurons causes calcium influx and neurotransmitter release

— Anandamide and 2-arachidonoylglycerol are the major endocannabinoid

70
Q

Anandamide

A

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

71
Q

NSAIDS

A

Interfere with the production of prostaglandins by inhibiting cyclooxygenases. Widely used in the treatment of pain, fever, and information.

72
Q

Isoforms of cyclooxygenase

A

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.

73
Q

Aspirin

A

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

74
Q

Aspirin as a suicide inhibitor

A

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.

75
Q

Common, OTC NSAIDs, that are nonspecific inhibitors of COX1 and COX2

A

Ibuprofen (Advil), acetaminophen (Tylenol), naproxen (Aleve)

76
Q

Specific inhibitor of COX2

A

Celecoxib (celebrex): however it increases the risk of stroke and heart attack

77
Q

Prednisone and dexamethasone

A

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

78
Q

Long-term management of asthma drugs

A

Montelukast (Singulair) and Zafirlukast (Accolate): they work by blocking the CysLT1 receptor to reduce leukotriene activity (bronchoconstriction)

79
Q

Inflammation

A

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.

80
Q

Mediators of the inflammatory response

A

Endogenous substances (autacoids or local hormones). They’re stored or rapidly synthesized, intended to act only at the side of injury.

81
Q

Redundancy of the inflammatory response

A

Many different substances or mediators can cause the symptoms of inflammation

82
Q

Acute inflammation

A

• changes in blood vessel caliber and flow, arteriolar, dilation
• increased vascular permeability
• leukocyte infiltration
• redness, swelling, heat, and pain

83
Q

Causes of redness, swelling, heat, and pain

A

Histamine, prostaglandins, leukotrienes, Kinins, products of complement system, activation, cytokines, interleukins, adhesion molecules

84
Q

What mediates many inflammatory effects of rheumatoid arthritis?

A

Prostaglandins

85
Q

Inflammatory effects of prostaglandins

A

•PGE: most potent at inducing fever
• PGE and PGI2: vasodilation, redness, and heat, increased vascular permeability (swelling), pain

86
Q

Sources of cyclooxygenase products

A

Platelets—> thromboxane (vasoconstrictor)

Endothelium —> prostacyclin (vasodilator)

Mast cells —> PGD2 (broncoconstrictor)

87
Q

Five major types of receptors for prostaglandins

A

1.) DP (PGD)
2.) FP (PGF)
3.) IP (PGI2)
4.) TP (TXA2)
5.) EP (PGE)— for subtypes, EP1 through EP4

88
Q

Shared therapeutic activities of COX1 and COX2 inhibitors:

A

• 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)

89
Q

Drugs that inhibit COX

A

• aspirin (acetylsalicylate), irreversible
• tNSAIDs (traditional NSAIDs, nonselective)
• Celecoxib: selectively COX2 inhibitor
• acetaminophen (very wimpy)

90
Q

Aspirin toxicity: Reye syndrome

A

Encephalopathy and fatty liver, following viral infection in children with the use of aspirin

91
Q

Acetaminophen

A

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

92
Q

Adverse effects of NSAIDs

A

• 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)

93
Q

Aspirin hypersensitivity

A

• 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

94
Q

Corticosteroids

A

• glucocorticoids are transcriptional regulators, they reduce WBC and increase RBC
• it’s a broad anti-inflammatory
• reduces host resistance to microbial and fungal infections

95
Q

Examples of corticosteroids

A

Dexamethasone, hydrocortisone, methylprednisolone, prednisone

96
Q

Toxicity limits prolong to use of steroids because of:

A

Osteoporosis, immunosuppression, peptic ulcers, myopathy, Cataracts, fluid accumulation, and hyperglycemia

97
Q

DMARDS: disease modifying antirheumatic drugs

A

• do not have immediate analgesic affect (no stopping pain)
• slow, or delay the progression of RA
• methotrexate, hydroxychloroquine, sulfasalazine are the first line

98
Q

Methotrexate

A

• 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

99
Q

Methotrexate as an anti-rheumatic arthritis drug

A

• 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

100
Q

Hydroxychloroquine

A

• 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

101
Q

Sulfasalazine

A

• 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

102
Q

Leflunomide

A

• 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

103
Q

Gold and minocycline

A

• minocycline is a tetracycline antibiotic with some anti-inflammatory properties (minor drug)
• gold salts: intramuscular gold therapy (standard of treatment previously)

104
Q

bDMARDS: biological DMARDs

A

• 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

105
Q

Rheumatoid arthritis drugs to never mix

A

bDMARDS and a JAK inhibitor— not recommended because of increased risk of infection

106
Q

TNF inhibitors

A

• 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

107
Q

PEG: polyethylene glycol

A

• 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

108
Q

Abatacept

A

• 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

109
Q

Rituximab

A

• binds to CD20 on B cells, and they are depleted
• serious infections can occur, rashes, common, potential reactivation of hep B
• given by infusion

110
Q

Interleukin receptor inhibitors

A

• 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.

111
Q

JAK inhibitors

A

• targeted synthetic tsDMARD
• Janus kinase inhibitors: Tofacitinib, baracitinib
• given orally, side effects are significant

112
Q

Osteoarthritis

A

• non-inflammatory arthritis, most common form
• found in the knees, hips, spine, hands and feet
• progressive loss of articular cartilage
• age-related disorder

113
Q

Clinical presentation of osteoarthritis

A

• gradual onset
• intermittent and self limited “ overdo it”
• use related pain relieved by rest
• morning stiffness LESS than 30 minutes

114
Q

Risk factors of osteoarthritis

A

• increased age
• major joint trauma
• obesity, knees
• repetitive activities
• general predispositions/congenital developmental defects
• females

115
Q

Osteoarthritis physical exam

A

• 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

116
Q

X-ray findings of osteoarthritis

A

1.) sclerosis: white, new bone formation in a subchondral trabeculae
2.) osteophytes: spurs, formation of new bone at joint margins
3.) loss of cartilage

117
Q

Management of osteoarthritis

A

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

118
Q

Osteoarthritis general features

A

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

119
Q

Rheumatoid arthritis population

A

• 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

120
Q

Rheumatoid arthritis

A

• 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

121
Q

ACPAs

A

Antibodies to citrullinated proteins/peptide antigens found in rheumatoid arthritis

122
Q

Extra-articular manifestations of rheumatoid arthritis

A

• 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

123
Q

Rheumatoid arthritis classification: acute versus chronic

A

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

124
Q

Causes of rheumatoid arthritis

A

Combination of genetics and environment, HLADRB1 alleles are overrepresented among RA patients

125
Q

Articular manifestations of rheumatoid arthritis

A

• 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

126
Q

Management of rheumatoid arthritis

A

• recognition and early treatment
• PT/OT/exercise
• medication:
1.) NSAIDs
2.) glucocorticoids/steroids: short term
3.) DMARDs and bDMARDs to slow down destruction

127
Q

csDMARDs options for rheumatoid arthritis

A

hydroxychloroquine/plaque I’m
Sulfasalazine
Methotrexate
Leflunomide /Arava
Azathioprine/ imuran

128
Q

bDMARDs for rheumatoid arthritis

A

Anti-TNF
T-cell cosimulator
B cell (rituximab)
IL-6 inhibitor
IL-1 inhibitor
-JAK inhibitor

129
Q

Juvenile idiopathic arthritis, JIA

A

• 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)

130
Q

JIA systemic onset

A

• between two and five years old
• daily spiking, fevers, accompanied by an evanescent, salmon colored rash
• many systemic features
• RA and ANA generally negative

131
Q

JIA: polyarticular onset

A

• 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

132
Q

JIA: oligoarticular onset

A

• 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)

133
Q

JIA TREATMENT

A

• 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

134
Q

Drug induced lupus caused by:

A

Procainamide, hydralazine, methyldopa, chlorpromazine, isoniazid, quinidine, minocycline

135
Q

Gout: Crystal induced arthritis

A

• 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

136
Q

Causes of hyperuricemia

A

1.) uric acid overproduction. (10%)
2.) uric acid underexcretion. (90%)

137
Q

Acute gouty arthritis

A

• 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

138
Q

Diagnosing Gout

A

• 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

139
Q

Triggering factors of gout

A

1.) alcohol ingestion
2.) trauma/severe illness
3.) medication: thiazide, diuretics, low-dose aspirin, cyclosporine
4.) high purine foods
5.) contrast dye

140
Q

Advanced gout

A

• uncontrolled hyperuricemia, chronic arthritis, constant pain, polyarticular
• TOPHI: solid uric acid deposits, white chalky material— generally painless, but may cause stiffness and become infected

141
Q

Chronic tophaceous gout

A

Location of tophi:
1.) helix of the ear
2.) periarticular regions— fingers (Heberden’s nodes) wrists, olecranon bursa

142
Q

Genetic factors and gout

A

• familial occurrence: 40% have family history of gout
• excellent inheritance of HPRT deficiency and PRPP synthase super activity
• autosomal inheritance, G6PD deficiency

143
Q

Gout treatment

A

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

144
Q

Pseudogout: calcium pyrophosphate (CPP arthritis)

A

• 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

145
Q

Spondyloarthropathy

A

• multisystem, inflammatory disease affecting the spine (most common), sacroiliitis, peripheral joints, periarticular structures (Achilles common)
• seronegative (RH factor (-))
• positive HLAB27

146
Q

Spondyloarthropathies: ankylosing spondylitis

A

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

147
Q

Psoriatic arthritis: spondyloarthropathy

A

• 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

148
Q

Reactive arthritis (a.k.a. Reiter’s syndrome) spondyloarthropathy

A

• 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

149
Q

Treatment of spondyloarthropathies

A

1.) physical therapy/ROM/posture
2.) medication: NSAIDs for all
Peripheral arthritis: sulfasalazine, methotrexate
Axial arthritis: biologics
Antibiotic RX for chlamydia

Skin/MS (5 decks)

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