Rheumatology - PowerPoint Presentation

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Rheumatology

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Immunologic Markers Found in Rheumatic Diseases

DiseaseImmunologic MarkersSystemic lupus erythematosus (SLE)

ANA (95% of patients)

Anti-

dsDNA antibodies (60% of patients)Anti-Sm antibodiesFalse–positive RPR (syphilis test)Drug-induced lupusAnti-histone antibodiesRheumatoid arthritis (RA)RF (75% of patients)ANA (<50% of patients)HLA-DR4 commonPolymyositis or dermatomyositisANAAnti-Jo-1 antibodiesAnkylosing spondylitisHLA-B27 (90% of patients)Psoriatic arthritisPossible HLA-B27SclerodermaAnti-scl-70 ANACREST syndromeAnti-centromere antibodiesMixed connective tissue disease (MCTD)Anti-RNP ANASjögren's syndromeAnti-Ro (anti-SSA) ANAAnti-LA (anti-SSB) ANASlide3

Rheumatoid arthritis (RA)

Chronic inflammatory disorder, with infiltration of synovial joints by inflammatory cells and progressive erosion of cartilage and boneSynovial hypertrophy, with granulation tissue formation on articular cartilage (i.e., pannus formation) caused by joint inflammationMost commonly seen in middle-aged women; increased frequency in people with HLA-DR4 serotypePIP

and

metacarpophalangeal

(MCP) joints usually first involved; symmetric polyarthropathy develops, involving ankles, knees, shoulders, hips, elbows, and spineH/P =Malaise, weight loss, insidious onset of morning stiffness with pain, decreased mobilityWarm joints, joint swelling, fevers, ulnar deviation of fingers; MCP hypertrophy, swan neck deformities (i.e., flexed DIP plus hyperextended PIP), boutonniere deformities (i.e., flexed PIP), subcutaneous nodules, pleuritis, pericarditis, scleritis, choreaSlide4

Rheumatoid arthritis

Labs =Rheumatoid factor (RF) positive in 75% of patients, but not specific for the diseasePositive antinuclear antibodies (ANA) in 40% of patients (see Table 9-5)Increased ESR, increased anticitrulline-containing protein IgM antibodiesJoint aspiration shows 5,000–50,000 leukocytes

Radiology

= x-rays may demonstrate soft tissue swellings, joint space narrowing, marginal bony erosions, or

subluxation; MRI is more sensitive than x-ray for detecting similar findingsTreatment =Initially, NSAIDs and physical therapy, as neededPatients still mildly symptomatic following NSAID use may be started on sulfasalazine or hydroxychloroquine and analgesics, as neededModerate disease can be treated with methotrexate; anti-tumor necrosis factor (TNF) drugs (e.g., infliximab) or corticosteroids may be consideredAnti-TNF drugs and corticosteroids combined with other regimens in severe diseaseSlide5

Rheumatoid arthritis

RA is a systemic disease, two-thirds of the patients present with constitutional symptoms: fatigue, anorexia, weight loss, generalized weakness before onset of the arthritis; diagnostic criteria (need four of the following):Morning stiffness (>1hr) for 6wksSwelling of wrists, MCPs, PIPs for 6wksSwelling of three joints for 6weeksSymmetric joint swelling for 6 wks

Joint

erosions on x-rays

RF positiveRheumatoid nodulesJoints never involved in RA: DIPs and joints of the lower backThe axial skeleton occurs less than peripheral, cervical spine is the most frequently affected resulting in neck pain, stiffness and hyperreflexia.RA has ↑risk of developing septic arthritis, particularly Staph. Aureu→red. swollen joint and motion limited by pain.RA @ ↑ risk of developing osteopenia and osteoporosisSlide6

Rheumatoid arthritis

Once patient has erosive joint disease: a clear-cut indication for disease modifying anti-rheumatic drugs (DMARD). Indomethacin or some other NSAID may be used as an adjunct. These agents slow down the progression of bony erosions and cartilage loss and therefore these agents are now, recommended to be used earlier in the course of disease. Other indications for their use are disease refractory to conservative treatment and dependence on steroids. These agents include

methotrexate

,

hydroxychloroquine, sulfasalazine, leflunomide, etanercept, infliximab and azathioprine.Methotrexate is the initial drug of choice and if not adequate, some other DMARDs drug may be used. Its side-effects include stomatitis, nausea, anemia and hepatotoxicity.Hydroxychloroquine is inferior to methotrexate even though very safe than methotrexate.Leflunomide has a role in patients who have contraindications to methotrexate such as significant pulmonary fibrosis.Etanercept and infliximab are the new generation TNF inhibitors, and highly effective in patients who have refractory disease with methotrexate. They are very expensive and are not indicated as first line of treatment.Slide7

Rheumatoid arthritisSlide8

Still’s disease

Still’s disease (=systemic form of juvenile rheumatoid arthritis)Systemic features: high-grade fever, leukocytosis, fleeting maculopapular rashes, hepatosplenomegaly, lymphadenopathy, pleuropericarditis and myocarditis

are characteristic

Rheumatoid factor is rarely positive

Treat: NSAIDs and monitor of the liver enzymes→if not respond to NSAIDs or with myocarditis or anterior uveitis→corticosteroidsAdult still’s disease is a variant of rheumatoid arthritis. It usually presents in20-30yrhigh spiking feversevanescent salmon colored maculopapular or macular rash that involves trunk and extremities.arthritis or arthralgias and significant leukocytosis.Rash typically develops along with fever. Temperature may show variation up to 4C.To make the diagnosis of adult still’s disease, conditions like systemic lupus erythematosus (SLE), rheumatoid arthritis, malignancy, infectious mononucleosis and Parvovirus infection should not be present. Rheumatoid factor and ANA are usually negative.Slide9

Systemic lupus erythematosus (SLE)

Multisystem autoimmune disorder involving a variety of autoantibodies affecting several body systemsAntibody-mediated cellular attack occurs with deposition of antigen-antibody complexes in affected tissuesRisk factors = young women, blacks, Asians, HispanicsHydralazine, procainamide

,

isoniazid

, methyldopa, quinidine, and chlorpromazine can cause similar symptoms that resolve when the drug is discontinuedH/P =Common findings include malar and discoid rashes, serositis, oral ulcers, arthritis, photosensitivity, CNS symptoms, cardiac symptoms, and renal symptomsCan also experience fevers, malaise, weight loss, abdominal pain, vomiting, conjunctivitis, blindnessAny combination of symptoms is possible and can change during the course of the diseaseSlide10

SLE

Labs =Positive ANA in 95% of patients (see Table 9-5)Anti-double-stranded DNA (dsDNA) antibodies in 60% of patients, but not found in other rheumatologic disordersPresence of anti-Sm antibodies is very specific for diseaseAnti-histone

antibodies may be seen for drug-induced, lupus-like symptoms

Patients frequently have a

false–positive test for syphilisTreatment = avoidance of sun, NSAIDs given for pain, hydroxychloroquine improves skin and renal symptoms, corticosteroids given for immunosuppression and to decrease exacerbations, other immunosuppressant drugs given in cases resistant to corticosteroids, anticoagulation required if patient considered hypercoagulableComplications = lupus anticoagulant and anticardiolipin antibodies increase the risks of miscarriage and fetal death; disease follows variable course, with some cases remaining benign and others progressing rapidly; patient death results from progressive impairment of lung, heart, brain, and kidney functionSlide11

SLE

Systemic lupus erythematosus (SLE) is an autoimmune disorder involving multiple systems like musculoskeletal, cardiovascular, hematological, skin, lungs, kidney and serous membranes. If four or more of the diagnostic criteria set for SLE is met either serially or simultaneously diagnosis of SLE is made. Myositis can be a feature present in cases of SLE but it is not included in the diagnostic criteria of SLE

Systemic symptoms

: Fatigue, fever, and weight loss.

Cutaneomucous symptoms: Malar rash, discoid rash, alopecia, oral or nasopharyngeal ulcers, and photosensitivity 3.Serositis: pericarditis, pleuritis4.Nephritis: which can be-Mesangial, which is characterized by focal and segmental glomerular involvement with an increase in mesangial cells;-Focal proliferative form;-Diffuse proliferative form, which is characterized by a "wire loop" pattern resulting from immune complex deposition and subsequent thickening of the glomerular basement membranes. It can result in irreversible changes and chronic renal failure-Membranous form, which is similar to primary membranous glomerulonephritis. 5.Neurologic symptoms: Depression, psychosis, seizures, and neuropathy.6.Non-erosive arthritis (>90% patients): like RA, mostly affects MCP and PIP, migratory and asymmetrical but non- erosive. 7.Hematologic disease: Hemolytic anemia due to formation of autoantibodies against blood cells, a form of type II hypersensitivity reaction→pancytopenis (↓RBC, WBC, PLT);8. positive antinuclear antibodies; anti-dsDNA antibodies; anti-Sm antibodies;Slide12

6 subtypes of renal disorders in SLE

Type I: normal.Type II: Mesangial is the earliest and the least severe form and is present in 10-20 percent of cases. Anti-DsDNA titers are not very high.Type III: Focal proliferative is a severe form than

Mesangial

form and is present in 10-20 percent of cases. Urinalysis shows

proteinuria and hematuria and serum creatinine is elevated. Histopathology shows proliferative changes with some areas of necrosis. Less than 50 percent of glomeruli are affected.Type IV: Diffuse proliferative is the most frequent pattern of renal involvement and unfortunately is the severestform. Hematuria, proteinuria, renal insufficiency, hypertension, marked hypocomplementemia and marked elevation of anti-DsDNA are all present. Histopathology shows changes that are similar but more severe than in focal proliferative type. More than 50 percent of glomeruli are affected. It has the worst of all prognosis.Type V: Membranous glomerulonephritis is present in 10-20% cases of SLE and usually presents with nephrotic syndrome. Renal function is preserved. Basement membrane is thickened and subepithelial deposits are present. It has better prognosis than diffuse proliferative type.Type VI: Sclerosing type represents healing of previous inflammatory damage and presents with renal insufficiency and normal urinary sediment. Immunosuppressive therapy is not effective in such patients as there is no active inflammation. Slide13

Treatment of SLE renal problems

Type I (normal) and type II (mesangial proliferative) requires no treatment.Extensive type III (focal segmental proliferative), and all type IV (diffuse proliferative) require aggressive immunosuppression.Type V (membranous glomerulopathy) requires treatment when proliferative lesions are superimposed.

Drugs:

corticosteroids

→cyclophosphamide→hydroxychloroquine (safe)Corticosteroids are the mainstay of treatment; usually IV methylprednisolone is used. Immunosuppressive agents, likeCyclophosphamide, may be needed when response to steroids is inadequate to improve renal disease or the disease is aggressive.Hydroxychloroquine is the safest drug for SLE.However, rarely, it may cause serious eye disease including retinopathy like macular degeneration; corneal damage may also occur; so eye examinations at 6 months to 1 year intervals should be performed in all such patients who are taking this drug. Visual field defects, impaired color vision, bull’s eye pattern on funds and corneal whirls can all occur with its use.The most common side effects of hydroxychloroquine are allergic skin reactions and nausea but they are not serious ones. The incidence of nausea can be reduced if it is taken after meals.Contraindications to its use include G6PD deficiency, porphyria cutanea tarda, liver failure and hepatic failure. It is also need to be avoided in pregnancy.Though it may cause hepatic failure, deafness and blood dyscrasias they are very rare and can be monitored by liver function tests (LFTs), hearing examination and CBC with differential respectively. This monitoring is not recommended regularly.Slide14

MD SOAP CHAIR mnemonic for symptoms of SLESlide15

Malar rash of SLESlide16

Polymyositis and dermatomyositis

Progressive systemic diseases with skeletal muscle inflammation; one third of patients with polymyositis also have dermatomyositis (i.e., polymyositis with skin manifestations)Risk factors = more common in women, blacks, elderlyH/P

=

Symmetric progressive

proximal muscle weakness (occurs in legs first) and myalgias, muscle atrophy in later stages of diseaseCutaneous manifestations of dermatomyositis are a red heliotropic rash on the face, upper extremities, chest, or back; violet discoloration of eyelids or scaly patches over hand jointsPatients with lung involvement have dyspnea and poor oxygenation saturationSlide17

Labs =

Increased creatinine, aldolase, CK, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lactate dehydrogenase (LDH)

ANA frequently positive

Anti-Jo-1 antibodies in patients with interstitial lung disease (see Table 9-5)

Muscle biopsy shows inflammatory cells and muscle degeneration, inflammatory cells within muscle fascicles in polymyositis and surrounding muscle fascicles in dermatomyositisEMG = spontaneous fibrillationsTreatment = high-dose corticosteroids, methotrexate, or azathioprine for 4–6 wk followed by tapered dosing; IV immune globulin or other immunosuppressants can be added to regimen in resistant casesComplications = possible interstitial lung disease, increased risk of several malignanciesPolymyositis and dermatomyositisSlide18

Gottron’s sign = Scaly patches over the dorsum of proximal

interphalangeal and metacarpophalangeal joints Slide19

Polymyalgia rheumatica (PMR)

Rheumatic disease with multiple sites of muscle pain and frequently associated with temporal arteritis; most common in elderly womenH/P = pain and stiffness in shoulder and pelvic girdle, difficulty raising arms and getting out of bed because of pain, malaise, unexplained weight loss; fever, minimal joint swelling, muscle strength maintained, although movement limited by painLabs

= decreased

Hct

, markedly increased ESR, negative RFRadiology = MRI demonstrates increased signal at tendon sheaths and synovial tissue outside of joints; positron emission tomographic (PET) scan shows increased uptake in large vesselsTreatment = low-dose corticosteroids, followed by tapered dosingWeakness is a symptom of polymyositis, but not of polymyalgia rheumatica.Slide20

Fibromyalgia

Disease causing chronic pain in muscles and tendons in absence of apparent inflammationUnknown etiology, but frequently associated with depression, anxiety, and irritable bowel diseasePossible predisposition with hypothyroidism, RA, sleep apnea; more common in women, 20–50 yr of ageH/P = myalgias

and weakness without inflammation; “trigger points” on examination (i.e., specific locations that when stimulated reproduce pain symptoms), fatigue; possible depression, sleep disturbances, dizziness, headaches, and mood disturbances

Treatment

= stretching, antidepressants (e.g., tricyclic antidepressants [TCAs], selective serotonin reuptake inhibitors [SSRIs]), patient education, physical therapy modalitiesSlide21

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tionDiffuse, multiple tenderpointsPectoral and pelvic girdles,neckProximal musclescomplainmusculoskeletal pain,Stiffness (>1hr) and painMuscle weaknessMuscle weaknessESR-↑↑↑↑↑↑↑↑EMG/biopsy-NormalT cell damagemyofibers→inflammClassicfindingsAnxiety, stress,insomnia, point tenderness over affected muscleTemporal arteritis, greatresponse to steroids, very high , elderly↑, abnormal EMG/biopsy, high risk for cancerheliotrope rash;Gottron’s sign; high risk for cancer (ovarian cancer)TreatmentAntidepressants(amitriptyline), NSAIDS, restLow-dose steroids; if withgiant cell arteritis→high- dose prednisolonesteroidsprednisone→ methotrexateSlide22

Ankylosing spondylitis

Chronic inflammatory disease of the spine and pelvis that results in eventual bone fusionRisk factors = 20–40 yr of age, male > female, white > blackH/P =Hip and low back pain that is worse in the morning and

following inactivity

;

pain improves over course of dayPossible limited range of motion in spine, hip, or chestPainful kyphosis that is relieved by bending forwardPossible self-limited anterior uveitisLabs = positive HLA-B27 in 90% of patients, increased or normal ESR, negative RF, negative ANARadiology = x-ray shows bamboo spine (multiple vertebral fusions); MRI shows increased signal in sacroiliac joints (sacroilitis) and vertebraeTreatment = physical therapy, NSAIDs; exercise helps to prevent or delay permanent deformities; sulfasalazine, methotrexate, or anti-TNF drugs may be beneficial in more significant disease; joint replacement may be needed in extremitiesSlide23

Sacroilitis seen in ankylosing

spondylitisSlide24

Reiter’s syndrome or Reactive arthritis

Classic triad of urethritis, arthritis or arthralgias and eye disease of conjunctivitis and the presence of circinate balanitis

(painless shallow ulcers present on the

glans

penis or urethra).Onset of arthritis after infection with Chlamydia, Salmonella, Shigella, Yersinia and Campylobacter. E. Coli and Neisseria have not been implicated as possible causes of reactive arthritis.Patients have negative rheumatoid factor. HLA-B27 positiveNSAIDs are the mainstay of treatment of Reiter’s syndrome/reactive arthritis.Slide25

Typical skin lesion of Reiter’s syndrome is

Keratoderma blennorrhagicum - It is found on palms and soles. These lesions present as clear vesicles on red bases and later on develop into macules or papules. They resemble very closely to pustular psoriasis.

Reiter’s syndrome or Reactive arthritisSlide26

Psoriatic arthritis

Arthritis that develops in approximately 1% of patients with psoriasis; DIP joints and spine most commonly affectedH/P = asymmetric joint pain and stiffness, symptoms worse in morning and improve with activity, symptoms usually less severe than RA, possible anterior uveitis; joint line pain, pain with stress on joints, pitting of nailsLabs = negative RF and ANA, possible positive HLA-B27 Radiology

= x-rays show findings similar to RA and highly destructive lesions of DIP and PIP joints (i.e., “pencil in cup” deformities); MRI is more sensitive in finding marrow edema

Treatment

= NSAIDs, methotrexate, sulfasalazine, or anti-TNF drugs, depending on severitySlide27

Psoriatic arthritis

Psoriatic arthritis: DIP joints; psoriatic nail disease (pitting)→sausage-shaped digit; typically: skin→joint; 15% joint→skinIt can present in 5 different forms.

Distal

interphalangeal

(DIP) joint involvement.Asymmetric oligoarthritis.Symmetric polyarthritis, similar to rheumatoid arthritis.Arthritis mutilans, characterized by deforming and destructive arthritis.Spondyloarthropathy, including both sacroiliitis and spondylitis.These patients often have nail changes (pitting nails and onychodystrophy). Majority patients with psoriatic arthritis typically have skin lesions for years before the joint involvement. However, 15% of patients may develop joint disease prior to skin disease. DIP involvement and the presence of nail changes may be the only clue in these patients. X-ray of the joints shows both combination of erosion and bone growth. Other changes include pencil cup deformity of fingers, fluffy periostitis, and bilateral asymmetrical fusiform soft tissue swelling.Slide28

Psoriatic arthritisSlide29

Scleroderma

Chronic multisystem sclerosis with accumulation of connective tissue, skin thickening, and visceral involvementH/P = arthralgias, myalgias, hand swelling, Raynaud's phenomenon (i.e., blue distal extremities caused by arteriolar spasm), skin thickening

,

esophageal

dysmotility, intestinal hypomotility, dyspnea, possible arrhythmias or heart failureLabs = positive anti-scl-70 ANA (see Table 9-5)CREST syndrome is a variant, with Calcinosis, Raynaud's phenomenon, Esophageal dysmotility, Sclerodactyly, and TelangiectasiasSkin thickening limited to distal extremities and faceLabs show anticentromere antibodiesBetter prognosis than sclerodermaTreatment = supportive care; angiotensin-converting inhibitors (ACE-I) for malignant renal hypertension; calcium channel blockers and avoidance of caffeine, nicotine, and decongestants to relieve Raynaud symptoms; methotrexate or corticosteroids may improve skin thickening and pulmonary symptomsComplications = pulmonary fibrosis, heart failure, acute renal failure caused by malignant renal hypertensionSlide30

SclerodermaSlide31

Scleroderma

Diffuse scleroderma: diffuse fibrosis of skin and internal organs.It usually occurs in women in their third to fifth decades.These patients have thickening of the skin begins in acral sites (hands and feet) with loss of folds and wrinkles giving a mask like appearance. Some areas may show both depigmentation and hyper pigmentation.Raynaud

’ s phenomena

and

calcinosis cutis are commonly seen.Polyarthralgia is an early symptom.Kidney: involvement→HT→scleroderma renal crisisPulmonary arterial HT→RH failureEsophageal and gastric dysmotility→GERDPatients with scleroderma have positive ANA and anti Scl 70, anti-topoisomerase-I Ab.Slide32

Mixed connective tissue disease (MCTD)

Overlapping features of SLE, scleroderma, and polymyositisCan progress to a single diagnosisH/P = Raynaud's phenomenon, polyarthralgias, arthritis, swollen hands, proximal muscle weakness, esophageal hypomotility, pulmonary symptoms; absence of renal and neurologic symptoms

Labs

= positive anti-

ribonucleoprotein (RNP) ANATreatment = NSAIDs, corticosteroids, ACE-I, supportive measuresSlide33

Sjögren's syndrome

Autoimmune disorder, with lymphocytic infiltration of exocrine glandsCan be seen in association with RA, SLE, or primary biliary cirrhosisH/P = dry eyes, dry mouth, enlarged parotid glands, purpura on legs, peripheral neuropathy, possible symmetric arthritis associated with other autoimmune conditions

Labs

= positive anti-Ro (anti-SSA) and anti-La (anti-SSB) antibodies

Treatment = supportive care, corticosteroids for significant symptomsSicca syndrome is Sjögren's syndrome without a secondary autoimmune associationSlide34

Gout

Peripheral monoarthritis caused by deposition of sodium urate crystals in jointsRisk factors = renal disease, male gender, urate underexcretion

, diuretic use, cyclosporine use, cancer,

hemoglobinopathies

, excessive alcohol consumptionH/P =Sudden severe pain and swelling in one joint that frequently starts at nightFirst metatarsophalangeal joint most commonly affected (i.e., podagra); ankle, knee, and foot joints also common sitesPossible concurrent fever, chills, or malaiseLabs = serum uric acid can be normal or increased; joint aspiration shows needle-shaped, negatively birefringent crystals and several white blood cells (WBCs)Radiology = x-ray may show punched-out bone lesions in chronic casesTreatment =NSAIDs (especially indomethacin), colchicine, corticosteroidsDecreasing alcohol and diuretic use and avoiding foods high in purines (e.g., red meats, fish) help prevent exacerbationsProbenecid (inhibits kidney uric acid resorption) or allopurinol (inhibits uric acid formation) used in cases of chronic gout to prevent flare-upsComplications = long-standing disease leads to chronic tophaceous gout with formation of nodular tophi (large deposits of crystals in soft tissues), leading to permanent deformityAllopurinol should not be administered in acute attacks of gout.Slide35

Synovial aspirate from patient with gout; under polarized lightSlide36

Pseudogout (calcium pyrophosphate dihydrate deposition disease, or CPPD)

Calcium pyrophosphate dehydrate crystal deposition in jointsFamilial condition associated with other endocrine diseases (e.g., DM, hyperparathyroidism)H/P = similar presentation to gout, but less severe symptoms; knee and

wrist

most commonly initially affected joints

Labs = joint aspiration shows positively birefringent, rhomboid crystalsRadiology = x-ray may show chondrocalcinosis (i.e., calcification of articular cartilage in joints)Treatment = NSAIDs, colchicinePodagra rules out CPPD and suggests a diagnosis of gout.Slide37

Synovial aspirate from patient with pseudogout; under polarized lightSlide38

Pseudogout

Hemochromatosis is clearly associated (50%) with pseudogout. Pseudogout also occurs more frequently in patients with transfusion hemosiderosis, hyperparathyroidism, hypomagnesemia,

hypophosphatemia

and hypothyroidism.Pseudogout: acute inflammatory changes of the large joints, most commonly the knee joint. It is associated with fever, chills, and leukocytosis. Synovial fluid analysis may show a leukocyte count as high as 100,000/cmm. Do not confuse with septic arthritis. Gram stain is usually negative in pseudogout. Episodes may be precipitated by surgery or trauma and can last up to 10 days if not treated. The diagnosis is confirmed by the finding of positively birefringent calcium pyrophosphate crystals released from sites of chondrocalcinosis (calcification of articular cartilage) into joint space.