RHEUMATOID DISEASES Flashcards
RHEUMATOID DISEASES
INFLAMMATORY VS. NON INFLAMMATORY
- Inflammatory – acute, painful, redness, erythema, swelling with increased white blood cell count with left shift, an elevated erythrocyte sedimentation rate (ESR), and x-ray demonstration of soft-tissue swelling, periostitis, bony erosions, or uniform cartilage
ASSYMETRIC VS. SYMMETRIC
- If both sides of the body
MONOARTeICULAR VS. POLYARTICULAR
- Number of joints
ARTICULAR VS. EXTRAARTICULAR MANIFESTATIONS
INFLAMMATORY ARTHRITIS
- Inflammatory connective-tissue disease (e.g., RA, JIA, SLE, PSS, DM–PM, MCTD, psoriatic arthritis [PSA])
- Inflammatory crystal-induced disease (e.g., gout, pseudogout, basic calcium phosphate)
- Inflammation induced by infectious agents (e.g., bacterial, viral, spirochete, tuberculous, and fungal arthritis)
- Seronegative spondyloarthropathies (e.g., ankylosing spondylitis [AS], PSA, Reiter’s syndrome [RS], inflammatory bowel disease [IBD]).
NON INFLAMMATORY ARTHRITIS
- Degenerative, posttraumatic, or overuse (e.g., osteoarthritis [OA], posttraumatic aseptic necrosis [AN])
- Inherited or metabolic (e.g., lipid storage disease, hemochromatosis, ochronosis, hypogammaglobulinemia, hemoglobinopathies).
RHEUMATOID ARTHRITIS
RHEUMATOID ARTHRITIS
OSTEOARTHRITIS
- Degenerative joint disease - degeneration of cartilage that results in structural and functional failure of synovial joints.
- The lesions of OA stem from degeneration of the articular cartilage and its disordered repair.
- Early stage, chondrocytes proliferate, increase in water and decrease in proteoglycan content
- Joint mice - dislodged pieces of cartilage and subchondral bone tumble into the joint, forming loose bodies
- Bone eburnation – appear like polished ivory
Osteophytes - outgrowths - Seen in patients above 50 years old
- SYMPTOMS: joint pain that worsens with use, morning stiffness, crepitus, and limitation of range of movement include the hips, knees, lower lumbar and cervical vertebrae, proximal and distal interphalangeal joints of the fingers, first carpometacarpal joints, and first tarsometatarsal joints.
- Heberden’s nodes
JUVENILE RHEUMATOID ARTHRITIS
before age 16 and persist for at least 6 weeks
(1) oligoarthritis is more common
(2) systemic disease is more frequent
(3) large joints are affected more often than small joints
(4) rheumatoid nodules and rheumatoid factor are usually absent
(5) anti-nuclear antibody (ANA) seropositivity is common
- Genetic – HLA and PTPN22, TH1 and TH17 cells
SERONEGATIVE SPONDYLOARTHROPATHIES
- Absence of rheumatoid factor
- Pathologic changes in the ligamentous attachments rather than synovium
- Involvement of sacroiliac joints, with or without other joints
- Association with HLA-B27
- Bony proliferation leading to ankylosis (fusion of joints)
- immune mediated and are triggered by a T cell response presumably directed against an undefined antigen, possibly infectious, that may crossreact with antigens expressed on cells of the musculoskeletal system
ANKYLOSING SPONDYLITIS
- sacroiliac joints and second and third decade of lifes lower back pain and spinal immobility.
- 90% of patients are HLA-B27 positive
REACTIVE ARTHRITIS
- a triad of arthritis, nongonococcal urethritis or cervicitis, and conjunctivitis
- (Chlamydia) or the gastrointestinal tract (Shigella, Salmonella, Yersinia, Campylobacter)
- The ankles, knees, and feet are affected most often, frequently in an asymmetric pattern.
INFECTIOUS ARTHRITIS
- can become infected from hematogenous dissemination, direct inoculation through the skin, or from contiguous spread from a soft tissue abscess or osteomyelitis.
- Neonates: H. influenza, Adults: S. aureus and N. gonorrhea, Sickle cell: Salmonella
the sudden development of an acutely painful, warm, and swollen joint that has a restricted range of motion. – A SINGLE JOINT - Systemic findings of fever, leukocytosis, and elevated sedimentation rate are common
- Most commonly the knee, followed by the hip, shoulder, elbow, wrist, and sternoclavicular joints.
LYME ARTHRITIS
- caused by infection with the spirochete Borrelia burgdorferi, which is transmitted by deer ticks of the Ixodes ricinus complex
- Early localized stage – skin lesion
- Early disseminated stage - involving skin, cranial nerves, heart, and meninges
- Arthritis – if untreated, MIGRATORY
- Treatment by antibiotics, diagnosis by Serology
GOUT
- Marked by transient attacks of acute arthritis initiated by urate crystals deposited within and around joints.
- Hyperuricemia (plasma urate level above 6.8 mg/dL) is necessary, but not sufficient, for the development of gout.
- In primary gout, elevated uric acid most commonly results from reduced excretion, the basis of which is unknown in most patients.
- The inflammation in gout is triggered by precipitation of urate crystals in the joints, stimulating the production of cytokines that recruit leukocytes
- Risk factors: Age of the individual and duration of the hyperuricemia, Genetic predisposition, Alcohol consumption, Obesity. • Drugs (e.g., thiazides) that reduce excretion of urate
- Acute arthritis is characterized by a dense inflammatory infiltrate that permeates the synovium and synovial fluid.
- Chronic tophaceous arthritis evolves from the repetitive precipitation of urate crystals during acute attacks
- Tophi in the articular cartilage, ligaments, tendons, and bursae are pathognomonic of gout
- Gouty nephropathy refers to the renal complications caused by urate crystals or tophi in the renal medullary interstitium or tubules.
- TREATMENT: Diet, NSAIDS and drugs than inhibit production
PSEUDOGOUT
- Calcium pyrophosphate crystal deposition disease (CPPD)
than 50 years old and becomes more common with increasing age. The genders and races are equally affected. - CPPD is divided into sporadic (idiopathic), hereditary, and secondary types.
- the articular cartilage, menisci, and intervertebral discs, and as the deposits enlarge they may rupture and seed the joint
the knees, followed by the wrists, elbows, shoulders, and ankles
SYSTEMIC LUPUS ERYTHEMATOSUS
- multisystemic disease thata is associated with abnormalities of immune regulation and immune complex– mediated tissue injury.
- classic autoimmune disease, as a result of an abundance of autoantibodies generated against cytoplasmic and nuclear cellular components.
- The hallmark of these is generation of IgG antibodies to double stranded DNA.
acute or insidious onset and will become chronic, remitting, relapsing, febrile illness - Characterized by injury to skin, joints, kidney, serosal membranes (polyserositis)
- Predominantly females F:M = 9:1
-Age incidence: 20-30s
-Unknown etiology - Failure of mechanisms that maintains self-tolerance
- ANA (anti-nuclear antibodies) - HALLMARK OF THE DISEASE but NON - specific
1. Abs to DNA
2. Abs to histones
3. Abs to non-histones bound to RNA
4. Abs to nucleolar Ags - Detected due to fluorescence
- Anti double stranded DNA and anti- Smith – DIAGNOSTIC
- Genetic predisposition
- 1St degree 20% , Monozygotic twins >20%, HLA DQ (ds Ab, anti SM, antiPL), Inherited deficiency - C2, C4, or C1q
- Immunological factors: Defective elimination of self reactive B cells in BM, CD4 helper T cells escape tolerance, Nuclear DNA & RNA activate B lymphocytes (TLR)
Environmental factors: - UV light, Sex hormone, Female in reproductive year, - Pregnancy
Drugs:
Hydralazine, Procainamide - Most visceral lesions - are type 3 hypersensitivity
- In tissues nuclei of damaged cells react with ANA
- In vitro: Phagocytic cell engulfs denatured nucleus of injured cell “LE cell”
BLOOD VESSELS: Acute necrotizing vasculitis
JOINTS: Non erosive synovitis
CNS: Non inflammatory occlusion of small vessels and impaired neuronal function
CVS: Libman-Sacks endocarditis –non bacterial
SPLEEN: Capsular thickening, Follicular hyperplasia
LUNGS: Pleuritis, effusions, Interstitial pneumonitis
SKIN: Malar erythema, including bridge of nose (butterfly rash), Sunlight exacerbates the lesions, VACUOLAR degeneration of epidermal basal laye Edema, perivascular inflammation dermis
CRITERIA FOR DIAGNOSIS 1. Malar rash 2. Discoid rash 3. Photosensitivity 4. Oral ulcers 5. Arthritis 6. Serositis 7. Renal 8. Neurologic 9. ANA, Ab titers 10. Hematologic: A.) Anemia B.) . Thrombocytopenia
OTHER SYNDROMES
1.) Chronic discoid LE
Skin manifestation mimics SLE,rare sytemic involvement with in the face and scalp, skin plaques; ANA test 35%
2.) Subacute cutaneous LE
Skin rash widespread,superficial, non-scarring, Anti SS-A, HLA-DR3 genotype
3.) Drug induced LE
Hydralazine, procainamide, INH, d-penicillamine
ANA+, UNCOMMON renal and CNS involvememt
SYSTEMIC SCLEROSIS/SCLERODERMA
- Unknown but there is autoimmune response, vascular damage,& collage deposition contribute to tissue injury, excessive systemic fibrosis especially in the skin
- CD4+ T cells associated
- Female: 3:1
- ABNORMAL IMMUNE RESPONSE
- CD4+ T cells responds to an antigen
- Accumulate in skin & release cytokines that activates inflammatory cells & fibroblasts
- (+) inappropriate activation of humoral immunity produces autoantibodies
ANTIBODIES
ANTIBODIES
- Anti DNA topoisomerase 1 (anti Scl 70)- 10-20% of patients
- Patients have pulmonary fibrosis& peripheral vascular resistance
- Highly specific for diffuse scleroderma
- Anti centromere antibody - 20-30% of patients
- Patients with CREST or limited cutaneous systemic sclerosis
MECHANISM OF INJURY
o Vascular damage:
- Microvascular disease present in EARLY course and may be the initial lesion
- Cause in not known widespread narrowing of microvasculature leads to ischemic injury & scarring
o Fibrosis
- Primary abnormality in collagen production and culmination of multiple abnormalities
- Example: Fibrogenic cytokines, Hyper responsiveness of fibroblasts, Scarring
CHRONIC DISEASE
- Chronic inflammation, Widespread damage to small blood vessels, progressive interstitial & perivascular fibrosis in skin & other organ
TWO MAJOR CATEGORIES:
DIFFUSE:
a. Widespread skin involvement
b. rapid progression & early visceral involvement
c. DNA tropoisomerase I2.
LIMITED: Skin involvement is confined:. Fingers, Forearm,. Face,. Some with CREST syndrome
- Calcinosis in skin
- Raynaud phenomenon (sensitive to cold)
- Esophageal dismotility
- Sclerodactyly
- Telengiectasia
TREATMENT
- “treatment pyramid”
- based on use of initial rest, patient education, joint protection, and nonsteroidal anti-inflammatory drugs (NSAIDs) with progression to steroids and sequential monotherapy, and use of DMARDs .
- At the onset of disease symptoms and diagnosis, the patient would begin early rehabilitation interventions: education, orthotics, physical modalities, joint protection, energy conservation, and strengthening, along with NSAIDs and low-dose steroid therapy in some cases.
PHARMACOLOGIC
- Aspirin (Acetylsalicylate)
- Aspirin blocks PG synthesis
affects leukocyte migration and vascular permeability
- Non-steroidal anti-inflammatory drugs
cyclooxygenase-2 (COX-2) inhibitors, continue to be used in part as first-line agents in the management
drugs also suppress inflammation through the inhibition of synthesis of PG.
GLUCOCORTICOIDS
- influence leukocyte movement, leukocyte function, and humoral factors; inhibit recruitment of neutrophils and monocytes into inflammatory sites;
- Cushing’s syndrome
- DISEASE-MODIFYING ANTIRHEUMATIC DRUGS
- Methotrexate by inhibition of dihydrofolate reductase, an enzyme required for DNA synthesis
- Inhibit inflammation by by binding surface receptors on lymphocytes, monocytes, and neutrophils and inhibit interleukin production.
DISEASE-MODIFYING ANTIRHEUMATIC DRUGS
- Hydroxychloroquine – anti-malarial drugs
shown to impair enzymatic reactions, including phospholipase, cholinesterase-hyaluronidase, and proliferation of lymphocytes.
- seem to block depolymerization by DNAase and interfere with DNA replication
IMMUNOREGULATORY AGENTS
- Cyclophosphamide and Cyclosporine
- Cyclosporine
PHARMACOLOGIC
GOLD
- inhibiting lysosomal enzymes or by inhibiting phagocytic activity in macrophages and polymorphonuclear leukocytes.
OTHER AGENTS
- Rituximab is a monoclonal antibody directed against the extracellular domain of the CD20 antigen on B-Cell and initiates compliment-mediated B-cell lysis
REHAB and other options
- Passive exercises
- Active exercises
- Strengthening exercises
- Splinting and orthosis
- Alternative medicine
- Surgery – last resort
