Musculoskeletal problems and injuries - part 4 ppt

cost in 2004 of $1300–1400 per month and have common local andsystemic side effects.9Leflunomide has been shown to be superior to methotrexate andsulfasalazine for symptomatic relief of

cost in 2004 of $1300–1400 per month) and have common local andsystemic side effects.9

Leflunomide has been shown to be superior to methotrexate andsulfasalazine for symptomatic relief of rheumatoid arthritis, with seri-ous adverse effects taking place in 0% to 2% of users.15It is terato-genic, and female patients who want to become pregnant after havingtaken the drug must take cholestyramine to bind the drug Without thecholestyramine, the medication can be present in the body for up totwo years.9

Experimental Treatment and Therapy of the Future

Because of the chronicity, lack of a cure, and associated disability of

RA, patients are vulnerable to many unproved “alternative” therapies.There is definitely a need for better therapies, making RA an intenselyactive area of current research

Borrowing an idea from oncology to suppress immune responsesmaximally, combination therapy with DMARDs is being activelyinvestigated Other experimental therapies include high-dose intra-venous prednisolone, total lymphoid irradiation, interferon-␥, inter-leukin-1 (IL-1) inhibitors, cyclosporine, monoclonal antibodyantagonists against T-cell receptors, and phenytoin Tetracyclineshave been investigated for years based on the theory that infectious

agents such as Mycoplasma or Chlamydia may cause RA.17The body-absorbing column Prosorba is used with plasmapheresis, and isFood and Drug Administration (FDA) approved for moderate tosevere RA in patients refractory to methotrexate It is expensive, andlong-term efficacy is unknown

anti-Juvenile Rheumatoid Arthritis

Juvenile rheumatoid arthritis (JRA), a heterogeneous group of eases formerly known as Still’s disease, is clinically distinct from RA

dis-in adults The cause is unknown Hypotheses concerndis-ing etiologyinclude infection, hypersensitivity, an autoimmune reaction, or a com-bination of these factors Fortunately, at least 75% of children with

JRA eventually have long remissions without significant residualdeformity or loss of function About 5% of patients with adult RAhave symptoms beginning in childhood.

Clinical manifestations of JRA fall into three major categories: ciarticular (40–50%), polyarticular (25–40%), and systemic (10–20%).These classifications are helpful for determining diagnosis, treatment,and prognosis in children with chronic arthritis Consideration of otherpossibilities for arthritis, including mechanical or degenerative disor-ders, septic arthritis, reactive arthritis to extra-articular infection, con-nective tissue diseases, neoplastic disorders, endocrine disorders (type

pau-1 diabetes mellitus, hyperthyroidism, hypothyroidism), and idiopathicpediatric joint pain syndromes is recommended Diagnosis may be dif-ficult without persistent, objective joint swelling JRA is largely a diag-nosis of exclusion

In pauciarticular-onset disease, children have four or fewer jointsinvolved during the first six months of symptoms Large joints are pri-marily affected, often asymmetrically Pauciarticular type I JRAaffects girls 80% of the time, usually before age 4 Pauciarticular type

II JRA affects boys 90% of the time, usually at age 8 or older, andmany go on to develop spondyloarthropathies such as ankylosingspondylitis There is a 10% to 30% risk of chronic iridocyclitis withthis disease, and many authorities recommend frequent slit-lampexaminations to prevent scarring and loss of vision

Polyarticular-onset JRA occurs mostly in girls, involving multiplejoints including small joints RF-positive polyarticular JRA tends to

be more severe than RF-negative disease, both acutely and with term risk of severe arthritis

long-Systemic-onset JRA is characterized by high intermittent fevers(⬎102°F), rash, hepatosplenomegaly, lymphadenopathy, arthralgias,and leukocytosis Arthritis becomes chronic but the systemic symp-toms generally dissipate with time

The NSAIDs are generally used as first-line treatment for JRA asconcerns about Reye’s syndrome have discouraged use of salicylates,the drugs of choice in the past As in adults, low-dose methotrexate isbeing used more frequently as the second-line drug of choice.Sulfasalazine has also been used with success Gold compounds andantimalarials are probably less effective in JRA than in adult RA andare used less commonly Long-term systemic glucocorticoids areeffective for symptom relief but do not prevent joint damage and arebest avoided in children if possible Topical steroids are used for asso-ciated iridocyclitis Physical and occupational therapy are importantfor protecting joint mobility; this is particularly important in JRA aschildren often do not complain of pain but simply stop using affected

joints The ultimate goal is to utilize these various treatments toencourage children with JRA to live active, normal lives The familyphysician coordinates care with other members of the treatment teamand offers necessary support to the child and family.

Systemic Lupus Erythematosus

Systemic lupus erythematosus (SLE) is a complicated rheumatologicaldisorder with a broad range of presentations The incidence of SLE hasmore than tripled in the past 30 years, from 1.5/100,000 in 1950–79 to5.6/100,000 in 1980–92.18The incidence among female patients is threetimes that of male patients, resulting in a prevalence of 1 in 700 forwomen between the ages of 20 and 64 years.19,20The disease incidence

in African-American and Hispanic women in the same age group ishigher than in their Caucasian counterparts

The pathogenesis of SLE is not completely understood Currenttheories include polyclonal B-cell activation and antigen stimulationresulting in the immune response that characterizes this complex dis-order Studies have pointed to a genetic factor contributing to thedevelopment of SLE Twin studies have revealed a concordance rateamong monozygotic twins to be as high as 30% to 50% An associa-tion with human leukocyte antigen (HLA) groups DR2, DR3, DR4,and DR5 has also been found

Laboratory Findings

Detection of antinuclear antibodies is a highly sensitive screening testfor SLE, although it is not specific for SLE A marginally elevated anti-nuclear antibodies titer is found in 2% to 5% of normal individuals.20About 95% of SLE patients have positive antinuclear antibodies titersthat are more than two times higher than the normal limit identified byany given laboratory Other antibodies identified in SLE patientsinclude anti-double-stranded DNA, anti-DNA-histone complex, anti-

Sm (Smith antigen), and anti-Ro (Robert antigen) Antibodies todsDNA and Sm antigen are specific for SLE and have been associatedwith more severe cases Anti-Ro antibodies are associated with variousdermatological manifestations of SLE Anti-single-stranded DNA is notspecific for SLE and therefore plays no role in diagnosis

Up to 30% of SLE patients also have circulating antiphospholipidantibodies These antibodies, known as the “lupus anticoagulant” mayresult in prolonged partial thromboplastin (PTT) and prothrombin(PT) times yet paradoxically result in an increased risk of thromboticevents When counseling female patients who have circulating

antiphospholipid antibodies, it is important to discuss the increasedrisk of spontaneous abortions In fact, a history of recurrent sponta-neous midtrimester abortions should trigger testing for antiphospho-lipid antibodies.

Systemic lupus erythematosus is characterized by a wide variety ofpresentations The SLE classification system, revised in 1982 andupdated in 1997, identifies 11 symptoms of the disease or systemsaffected in SLE patients To confirm a diagnosis of SLE, patients musthave at least 4 of the 11 criteria present either serially or simultane-ously (Table 5.4)

Mucocutaneous Manifestations

The classic malar butterfly rash is present in only one third of patients

It usually presents abruptly after exposure to sunlight and lasts forseveral days or weeks More commonly, patients have a patchy macu-lopapular rash on sun-exposed areas Subacute cutaneous lupus erythe-matosus presents with a unique rash characterized by photosensitivityand superficial, nonindurated, nonscarring lesions

One third to two thirds of SLE patients are markedly photosensitive,and sun exposure not only results in rash but also may induce a flare ofsystemic manifestations Seventy percent of patients with photosensi-tivity have anti-Ro antibodies.21

Discoid lesions are raised plaques that may result in scarring Otherskin manifestations include alopecia, hyperpigmentation, and hives.Biopsy shows immunoglobulin deposition at the dermoepidermaljunction This finding is known as the lupus band test.22

Arthritis

Arthralgias are the most common complaint of SLE patients and areoften present at the time of initial diagnosis Up to 76% of patientsdevelop arthritis associated with disease activity It is difficult to dif-ferentiate the joint complaints of SLE patients from those of RApatients, but SLE patients usually present with pain out of proportion

to the degree of synovitis Also, in contrast to RA patients, SLEpatients have soft tissue involvement that can result in joint deformitywithout evidence of cartilage involvement (Jaccoud arthropathy).Tendon rupture can also occur

Serositis

SLE patients can have inflammation of the pleural, pericardial, andperitoneal membranes Exudative pleural effusions are common but

are usually small and therefore of little clinical importance.22Up to29% of SLE patients have symptoms of pericarditis including pain,friction rub, and electrocardiographic changes.

Renal Disease

Renal involvement occurs in as many as 75% of patients, and theresulting glomerulonephritis is a major determinant of morbidity andmortality23(see Reference 37, Chapter 97) Immune complex deposi-tion along the glomerular basement membrane results in an inflam-matory response resulting in the characteristic glomerular findings.SLE patients should have an annual urinalysis to look for early evi-dence of proteinuria Because of renal compensatory mechanisms,even urinalysis and measurement of serum creatinine or creatinineclearance may underestimate actual parenchymal damage Renalbiopsy obviously can document the type of lesion present in sympto-matic patients, but biopsy results have not been useful for predictingdisease progression A persistently elevated serum creatinine level(⬎2 mg/dL) is the best predictor of future renal morbidity.19

Hematological Disorder

It is not surprising that most SLE patients have anemia of chronic ease Up to 25% of SLE patients may also have an autoimmune throm-bocytopenia; and 5% of these patients have severe thrombocytopenia

dis-with a platelet count as low as 20,000 cells/mm.3,23Furthermore, SLEpatients have higher incidences of both arterial and venous thromboem-bolic events Some studies have shown up to a fiftyfold increase in risk

of myocardial infarction among reproductive-aged women with SLE,compared to age-matched controls.18Some investigators have recom-mended prophylactic aspirin or other anticoagulation treatment for allSLE patients, regardless of antiphospholipid status,24 and aggressiveanticoagulation with warfarin [with a goal international normalized ratio(INR) of 2.5–3.5] for patients with known antiphospholipid antibodies.18

Like treatment of renal disease, the mainstay for treating topenia has long been glucocorticoids Patients with disease resistant toglucocorticoid treatment may respond to splenectomy, but prior to con-sideration of splenectomy providers must weigh the benefits against therisks posed by decreased immune function Cyclophosphamide andchemotherapeutic agents such as vincristine and procarbazine have alsobeen used in patients with severe disease.23

thrombocy-Reiter Syndrome

Reiter syndrome, a form of reactive arthritis, is defined as “an acute,sterile synovitis associated with a localized infection elsewhere in thebody”—generally a venereal infection.25The hallmark of Reiter syn-drome is the triad of arthritis, conjunctivitis, and urethritis Othersymptoms found in patients with Reiter syndrome include sacroiliitis,enthesopathic symptoms with the most common sites being theAchilles’ tendon and planter fascia, dactylitis, mucocutaneous lesionsincluding stomatitis, circinate balanitis, and nail lesions

The exact prevalence and incidence of Reiter syndrome isunknown It has a five- to ninefold higher incidence in men and theprevalence is increased in patients positive for HLA-B27.26Laboratory findings in Reiter syndrome patients are usually nonspe-cific and do not confirm the diagnosis There is no cure for Reiter syn-drome, but the underlying illness should be treated

Raynaud’s Disease

During the late nineteenth century Maurice Raynaud described digitalvasospasm that seemed to be cold-induced He believed that this phe-nomenon, now known as Raynaud’s disease, was due to changes inthe CNS control over vascular innervation Raynaud’s phenomenon isclassically described in patients who develop extremity blanching andnumbness with cold exposure, followed by cyanosis and then ery-thema on rewarming The fingers are affected most commonly, but thetoes and ears may also be involved

Raynaud’s disease has been divided into primary and secondaryforms Primary Raynaud’s is more common than the secondary form,occurring in 3% to 16% of the general population.27 SecondaryRaynaud’s disease is far less common, developing in only 3% to 9%

of patients; it is defined as Raynaud’s phenomenon associated withthe development of a connective tissue disease (most commonly scle-roderma)

Evaluation of a patient in whom Raynaud’s disease is suspectedincludes a thorough history and physical examination Changes con-sistent with the disease can be reproduced in the office by immersingthe patient’s affected extremity in ice water Antinuclear antibodiesare positive in 17% to 26% of patients but do not predict disease pro-gression.28

Investigations into the pathophysiology of Raynaud’s disease haveled to identification of a number of abnormalities, but the complete

mechanism has not been fully established Studies have shown thatpatients with this disorder have an abnormal adrenergic response.Neuropeptide release (possibly due to sensory nerve system damage)and endothelial factors have also been identified.27–29

It is important to discuss with patients the role of behavior tion Conservative approaches to treatment include warm socks or mit-tens and cold avoidance Patients are encouraged to stop smoking and

modifica-to avoid vasoconstrictive drugs, such as amphetamines, cocaine, andover-the-counter decongestants Caffeine may also exacerbate symp-toms by causing a rebound vasoconstriction after an initial vasodilata-tion In patients with vasospasm associated with emotional stress,relaxation and stress management strategies have also been helpful.When conservative strategies fail, patients may respond to calciumchannel blockers Nifedipine has been the most widely studied atdoses of 10 mg sublingually for immediate treatment of acutevasospasm or 30 to 60 mg of nifedipine taken on a chronic basis,although care must be taken to avoid symptomatic hypotension

Scleroderma

Scleroderma, or systemic sclerosis, is a connective tissue disorderwhose hallmark is tissue fibrosis Systemic scleroderma is character-ized by progressive fibrosis of the skin, lungs, heart, gastrointestinaltract, and kidneys An association of limited skin involvement and late

visceral involvement is known as CREST syndrome (calcinosis, Raynaud’s phenomenon, esophageal dysmotility, sclerodactyly, and telangiectasias) A localized form of scleroderma, known as linear

scleroderma or morphea, exists when fibrotic changes are localized tothe skin; it does not involve the GI tract.30

As with many other connective tissue diseases, scleroderma affectswomen three times as often as men, and the incidence in the UnitedStates is estimated to be 1/100,000 persons per year The incidencepeaks in women between the fifth and sixth decades of life.31Clinically, patients with systemic involvement present earlier in thedisease course with mostly skin complaints

The histopathologic features found in patients with sclerodermainclude diffuse small artery and arteriolar vasculitis with fibrinoidnecrosis, intimal thickening, and mucopoly–saccharide deposition.The exact mechanism responsible for excess deposition is unknown.Because there is no cure for scleroderma, treatment goals are tooptimize function of involved organ systems The skin is involved inmost patients, so it is important that patients use moisturizers to help

maintain skin integrity For patients with Raynaud’s phenomenon,refer to the treatment guidelines discussed above Patients mayrequire antihypertensive drugs and treatment for gastroesophagealreflux Immunosuppressive agents may slow disease progression.

Sjögren Syndrome

Sjögren syndrome is a rare, chronic inflammatory autoimmune der characterized by the combination of keratoconjunctivitis sicca(dry eyes), xerostomia (dry mouth), and rheumatoid arthritis or con-nective tissue disease Vaginal dryness is also common, and restrictivelung disease is also associated.32Sjögren syndrome affects women tentimes more often than men Other causes of xerostomia (i.e., drug-related) must be excluded prior to diagnosis Unfortunately, treatmentoptions are limited The mainstay of treatment has long been the use

disor-of lubricants for the affected areas, as well as combined care provided

by a rheumatologist, ophthalmologist, and family physician

Ankylosing Spondylitis

Ankylosing spondylitis is an inflammatory disease of the spine thatcan also involve other joints and extra-articular organs Ankylosingspondylitis is considered a seronegative spondyloarthropathy becausepatients with this disorder do not usually have a positive rheumatoidfactor The disease most commonly affects men (male/female ratio5:1) and usually presents during adulthood (in the thirties) Onsetafter age 40 is unusual More than 90% of Caucasian patients withankylosing spondylitis have HLA-B27; however, it is important toremember that most patients with back pain who are positive forHLA-B27 do not have ankylosing spondylitis

The key to diagnosis of ankylosing spondylitis is having a highclinical suspicion More than half of the patients with ankylosingspondylitis initially present complaining of low back pain Featuresthat distinguish the low back pain associated with ankylosingspondylitis are morning stiffness, pain unrelieved with rest (rather,patients may try to “work the pain out”), and awakening from sleepwith pain Patients may also complain of pain in the buttocks or hipsbut usually do not complain of pain radiating below the knees Manypatients also have peripheral joint involvement Large joints are morecommonly involved than the small joints of the hands and feet.Enthesopathy is also common and can be demonstrated radiographi-cally Uveitis is a common extra-articular manifestation and often pre-cedes joint disease

The diagnosis can be confirmed radiographically if there is dence of sacroiliitis If the disease has progressed, patients have the

evi-“bamboo spine” seen on radiographs The ESR is elevated It is easy

to measure the flexibility of the spine, which is decreased in mostpatients The two most commonly used tests to assess spinal flexionare Schober’s flexion test and Moll’s lateral flexion test Schober’stest is performed by identifying, with the patient standing, the top ofthe sacrum and marking on the spine points 10 cm above this pointand 5 cm below In normal individuals, with forward flexion this dis-tance increases by at least 5 cm The Moll’s lateral flexion test is per-formed by marking the point in the midaxillary line of the iliac crestand the point 20 cm above this site When the normal patient bends tothe opposite side, this distance increases by at least 3 cm.33

The goals of treatment of ankylosing spondylitis are to decreasepain and maintain functional status NSAIDs are the drugs of choice

to control inflammation and decrease pain Oral prednisone has notbeen shown to be helpful It is also important in the preservation offunctional status to encourage the patient to strengthen back extensormuscles At the present time, spinal ossification cannot be prevented,but function is better preserved if the patient’s spine is ossified in anerect position in contrast to stooped over

Psoriatic Arthritis

Psoriatic arthritis is a form of inflammatory arthritis seen in mately 20% of psoriasis patients (see Reference 37, Chapter 115).Like ankylosing spondylitis, patients with psoriatic arthritis haveserum negative for rheumatoid factor Psoriatic arthritis is usually amild form of arthritis that is sometimes difficult to distinguish fromrheumatoid arthritis Points for differentiating psoriatic arthritis fromrheumatoid arthritis are as follows Psoriatic arthritis is found inpatients with psoriasis, distal joint involvement, tenosynovitis, andenthesopathy Psoriatic arthritis is generally treated with NSAIDs orantimalarials In up to one third of patients a flare in the skin diseasemay precede a flare of joint symptoms.34

approxi-Polymyalgia Rheumatica

Patients with polymyalgia rheumatica are usually over age 50 andpresent with complaints of myalgias and arthralgias referable to thehips and shoulders The pain usually has been present for several

months, and patients may suffer from constitutional symptomsincluding fatigue, weight loss, and low-grade fever Patients complainthat these muscles or joints are achy, and that they have morning stiff-ness.

Polymyalgia rheumatica has a prevalence of approximately 1 in

150 persons over age 50.35On clinical examination, patients are der to palpation, but their strength is intact and creatine phosphoki-nase levels are normal, ruling out muscle destruction The mostcharacteristic finding in polymyalgia rheumatica is an elevated ESR

ten-In fact, many patients have ESRs in excess of 100 mm/hr It is mated that one fourth to one half of patients with polymyalgiarheumatica also have temporal arteritis

esti-Some patients with polymyalgia rheumatica respond to NSAIDs,but the key to treatment has traditionally been a prolonged course of

a corticosteroid Patients generally respond quickly to prednisone at adose of 10 to 20 mg/day If a patient does not respond quickly to cor-ticosteroids, consider other diagnoses Patients often require dailysteroids for a minimum of two years When attempts are made towean a patient off prednisone, the dose is decreased by only 1 mg/month

Temporal Arteritis

Temporal, or giant cell, arteritis, like polymyalgia rheumatica, ents in persons over 50 years of age with an annual incidence18/100,000 people over age 50 It is more common among theCaucasian population but has been reported in nonwhite patients; itoccurs more commonly in women with a female/male ratio of 3:1.Most patients present with headache and may have tenderness to pal-pation over the temporal artery (see Reference 37, Chapter 63).Patients may also have visual symptoms including diplopia, hemi-anopia, or amaurosis fugax (visual changes usually described as awindow shade being pulled down over one eye)

pres-As with polymyalgia rheumatica, patients with temporal arteritisusually have an elevated ESR to levels higher than 100 mm/hr; con-firmation of this diagnosis requires biopsy of the temporal artery.Biopsy results are more likely to be positive if specimens are obtainedless than 24 hours after beginning treatment It is recommended not towithhold treatment pending biopsy results in patients with a high clin-ical suspicion because of the risk of blindness Patients are started onprednisone 1 mg/kg/day, and the dosage is decreased based on symp-toms and the ESR.36

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