Algorithms for the diagnosis and management of musculoskeletal complaints

Algorithms for the Diagnosis and Management of Musculoskeletal Complaints

T

he following algorithms present a comprehensive guide to decision-making employed by a primary care provider when encountering a patient with musculoskeletal complaints. The initial figure provides an organizational guide to the algorithms and also delineates the overall logic of the approach. Details of each step are provided in each individual algorithm, along with supporting documentation of evidence from the literature. It should be noted that some rheumatologic conditions require prompt intervention. Triangular “flags” (A) indicate where immediate diagnosis and treatment are necessary. Failure to observe these may result in severe morbidity. Many rheumatologic conditions require joint aspiration and synovial fluid

01997 by Excerpta All riehts reserved.

Medica,

Inc.

analysis for accurate diagnosis. These are indicated by another icon (1). Points at which consultation is necessary vary; therefore, the algorithms do not include specific references to the need for consultation. This is left to the clinical judgment of the primary care provider. As in any clinical setting, however, appropriate consultation early in the course of the disease can often be helpful in establishing diagnoses, developing an appropriate therapeutic plan, and avoiding morbidity. Moreover, specific interventions including joint aspiration, surgery, or physical therapy/occupational therapy may necessitate consultation at any time during the course of the illness.

ooo2-9343/97/$17.00

PII snnn3.Q?d?la71flnnll

.A

4 9 s

This organizational guide provides a simplified overview of the algorithms for the diagnosis and management of musculoskeletal complaints. The individual algorithms are indicated by the black-boxed letter: for example, the approach to nonarticular disorders is defined more completely in Algorithm 8. A double border indicates a critical-decision point, where choosing the next step may be particularly important and/or difficult.

i Initial Assessment

Is Condition Articular?

Articular

Nonarticular

Disorders

Disorders

4

Is Complaint 2 6 wk Duration?

No ’ Yes

Acute N o -Yes

Inflammatory Mono/ nlir,...tkriti. oints Involved?

Condition

December 29. 1997 The American Journal of MedicineQ Volume 103 (6A)

51s

A Q

Algorithm A: Initial Assessment From the initial physical examination and rheumatologic history of the patient, the provider should determine whether there is a musculoskeletal condition, and if so, whether it is articular.

Consider Most Frequent Presentations of Common Rheumatologic Conditions See Table 1

1 Perform Initial History and Physical Examination

Unlikely Consider Other Diagnoses. Observe and Reevaluate Patient Periodically+

Is There a Musculoskeletal Condition? Likely or uncertain’

1Yes or uncertain*’

i / Articular D i s o r d e r \ \ See Algorithm C /

‘It is uncertain if condition is musculoskeletal in nature if history and physical findings are inconsistent and/or atypical. If the provider still feels that the patient’s report of symptoms may be explained by a musculoskeletal disorder, further evaluation as though a rheumatologic condition is present is warranted. “If provider is uncertain whether the condition is articular or nonarticular,

the patient should be evaluated for both.

+As m a n y r h e u m a t o l o g i c c o n d i t i o n s c a n n o t b e a c c u r a t e l y d i a g n o s e d a t o n s e t , p a t i e n t s s h o u l d b e r e e v a l u a t e d p e r i o d i c a l l y f o r development of a known rheumatologic disorder or resolution of the complaint.

52s

December 29, 1997 The American Journal of Medicine@ Volume 103

f6A)

ALGORITHMS FOR THE DIAGNOSIS AND MANAGEMENT OF MUSCULOSKELETAL COMPLAINTS

Algorithm B: Nonarticular Disorders I f t h e musculoskeletal c o m p l a i n t i s n o t o r p r o b a b l y i s n o t articular, t h e p r o v i d e r s h o u l d d e t e r m i n e w h e t h e r fibromyalgia or polymyalgia rheumatica is present or further investigation is necessary.

See Algorithm C No or uncertain*

I

Nonarticular Disorder I

+ Consider Local Nonarticular Disorders See Tab/e 3

Are Symptoms Localized to a Specific Structure? I

f No

Are Widespread Pain and Tender Points Typical of Fibromyalgia Present?

Consider Fibromyalgia

S e e Table 4

Treatment of

Are Features of Polymyalgia Rheumatica Present?

See Table 5 No

Is a Connective Tissue Disease Present? Consider Another Widespread Nonarticular Disorder

Order

Investigation Necessary? See Table 6

Specific Investigation S e e T a b l e s 7, 7 a

\

No Observe Patient; Utilize Symptomatic Treatment

Patient’s Condition

K

No

Are Findings Abnormal? >

1

Yes

1 Consider Specific Diagnoses and Treatments See Tab/es 7, 7a

‘If provider is uncertain whether the condition is

atticular

or nonarticular, the patient should be evaluated for both.

December 29, 1997 The American Journal of Medicine@ Volume 103 (6A)

53s

ALGORITHMS FOR THE DIAGNOSIS AND MANAGEMENT OF MUSCULOSKELETAL COMPLAINTS

Algorithm C: Atticular Disorders If the musculoskeletal complaint is or probably is articular, the provider should determine whether the complaint is c h r o n i c o r a c u t e , a n d i f acute, w h e t h e r a n i n f l a m m a t o r y o r n o n i n f l a m m a t o r y c o n d i t i o n i s p r e s e n t .

I

1Yes’

Acute Articular Condition

Acute Inflammatory Arthritis I

MonolOligoarthritis (May Be Episodic)

‘If provider is uncertain whether the condition is articular or nonarticular, the patient should be evaluated for both.

54s

December 29, 1997 The American Journal of Medicines Volume 103

(6A)

ALGORITHMS FOR THE DIAGNOSIS AND MANAGEMENT OF MUSCULOSKELETAL COMPLAINTS

Algorithm D: Acute Noninflammatory

Articular

Conditions

If the artiiular condition is acute and noninflammatory, the provider should determine whether fracture is present or further investigation is needed.

Acute Noninflammatory Artkular Condltbn

Is There Suspicion of Fracture? A

Order Approprlate Radbgraph. Is Radiograph Positive?

Yes

1

I Is

Further

Inveetlgation

Necessary? See Table 6

Otder Speclfk Investlgatbns. Are Results Abnormal? See Tables 7, 7a

4 Do Symptoms Continue? \

/

Artkular Condition

No

December 29, 1997 The American Journal of Medicinem Volume 103 (6A)

55s

ALGORITHMS FOR THE DIAGNOSIS AND MANAGEMENT OF MUSCULOSKELETAL COMPLAINTS

Ia

Algorithm E: Acute Inflammatory

MondOligoarthritis

I f t h e c o n d i t i o n i s a c u t e i n f l a m m a t o r y mono/oligoarthritis, the provider should determine whether infection is present, whether crystal-induced arthritis (gout or pseudogout) is present or whether further investigation is necessary.

Acute Inflammatory MonolOligoarthrltis

i Strongly Conslder Synovial Flub Asplratbn and Analysis B S e e Table 8 b Is Them Evidence of Infectbn? A No Is There Evfdence of Crystal-Induced Arthrltls?

Consider Gout or Pseudogout See Tables 9, 7Oa, lob, 11

lltllize Speclfk Therapy. -

obsewe and Rewa’uate Patient Periodically 4

Consider

Other

Diagnoses Resolved, Develop a Plan of

I s Further

4 lnvestlgatlon

See Table 6

Utilize Symptomatic Treahmnt. Obsewe and Reevaluate Patleot Perbdkally

Order Specific Investigatkos. Am Results Abnormal? See Tables 7, 7a

Consider Specific Diagnoses and Treatments

Do Symptoms Continue7 See Algorithm Ii

56s

December 29, 1997 The American Journal of Medicine” Volume 103 (6A)

ALGORITHMS FOR THE DIAGNOSIS AND MANAGEMENT OF MUSCULOSKELETAL COMPLAINTS

Algorithm F: Acute Inflammatory Polyarthrftis If the condition is acute inflammatory polyarthritis, the provider should determine whether infection is present or further investigation is necessary.

1 Consider Synovlal Fluid Asplmtbn and Analysb p seeTable

i

Ic Utilize Symptomatic Trembmnt 4

No

Order Speclfk Immstlgmtbn. Am Findings Abnornml? See Tables 7, 7a Yes

See Algorithm H

December 29, 1997 The American Journal of Medicine@ Volume 103 (6A)

57s

Algorithm G: Chronic Noninflammatory Articular Conditions If the condition is chronic and noninflammatory, the provider should determine whether OA is likely or further evaluation is necessary.

Chronic Articular Condition

f Is Inflammation Present? See Table 5

Yes

No

Chronic Noninflammatory Articular Condition

Yes

Chronic Noninflammatory Polyarticular Condition

Chronic Noninflammatory Mono/Oligoarticular Condition

NO

Does the Patient Have Mechanical Back and/or Neck Pain?

Yes

Consider Other Diagnoses and Evaluate Further

58s

December 29, 1997 The American Journal of Medicine* Volume 103 (6A)

Axial OA. pnnftrm Confirm Diagnosis and Begin Management anagement See Tables s 12, 12, 14 14 ) pe A l g o r i t h m /

ALGORITHMS FOR THE DIAGNOSIS AND MANAGEMENT OF MUSCULOSKELETAL COMPLAINTS

Q

Algorithm H: Chronic Inflammatory Arthritis If the condition is chronic and inflammatory, the provider should determine whether mono/oligoarthritis or polyarthritis is present. If mono/oligoatthritis, the provider should determine whether infection is present or further investigation is necessary. If polyarthritis, the provider should determine whether the condition is a spondyloarthropathy, RA, or if further evaluation is necessary.

Chronic Inflammatory Arthritis

r-5 NO

Chronic MonolOligoarthritis

l

Consider Synovial Fluid Aspiration and Analysis and/or S y n o v i a l B i o p s y

\

DOeS Patient Have Spondyloarthropathy? See Table 76

Is There Evidence of Infection? A I

Yes

\

Yes

antior Radiographic Evidence of RA? See Table 7

i

X No

Initiate Symptomatic or Specific Therapy. Reevaluate Patient Periodically for Evolution of Symptoms See Tables 6. 15

December 29, 1997 The American Journal of Medicine@ Volume 103 f6A)

59s

ALGORITHMS FOR THE DIAGNOSIS AND MANAGEMENT OF MUSCULOSKELETAL COMPLAINTS

Algorithm I: Management of Rheumatoid Arthritis The provider should determine whether RA is slowly progressive or aggressive, develop a plan of clinical management, assess outcomes, and modify therapy as needed.

Inatltuta

t

m n l o p a Plan ol alniai Managemmt. l

lnitiie NSAlDs

SW Tat&s 2025;npPen&x A

rnmrqmutk

ApPmpliste

M0d~stim of Patiiflrs

Dsvelop

l Maintenanm - Functional S t a t u s -Patient Education l Pain Menagem.3nc

f s Plan 01 Ctlnlal Msnsgsmsnt l lntiiate NSAlDs -Strong C o n s i d e r : -oral & rtico~ero~s - DMARD

SW Tablss 2S25; Appmdx A

I

I

‘I Outmmr Awaammt

N O

Anrr Dowgo 01 C u r r a n t Msdlutlon

. H a aalwtmetapy Bwn Madmlad? YW

Pstlsnt

Ruvslustlon v Consldsr

bR-

PmgNsslvs Dtsoss. C0Mld.r: Another NSAID l htmattiiular CathXteroids (II limled no. of adirnt pints) . OMARD

AltsmsttvsThsnplss

slowly

Aggmslvs Dlsssss Conalder: l Irltmattiiukr cortiisteroids (it limited no. of sctivs joints) l Another Dh4ARD . surgical lntelvention - Combination DMARDs . lmmunosuppressivs Agent - Investigational Agent

l

SHTeble23

I

-

I

Contlnuemarapy: Rowslusts Psrlodlcrlly

b Rwponw

A ConakJer: l Intraarticukv Cortiideroid (if limited no. 01 &ii joints) l Altentd Dosage of DMARD l Another DMARD

‘Unacceptable = c o n t i n u e d p a i n and/or

605

December

i n f l a m m a t i o n , progrsssiva

disability, progressive joint damage, drug

29, 1997 The American Journal of Medicine’?’ Volume 103 (6A)

toxicity.

Acwptablr?

Algorithm J: Management of Osteoarthritis After the diagnosis of OA has been established, the provider should develop a plan of clinical management and assess outcOmes.

v Contlnuo

Thsnpeutlc

Canthue Yodllbd Regimen

Regimen

bmsDbgnNbcoKsct?

Correct Dhgnoala

InltbteThuapy for Intmwfmnl Pmt4mn;Malntalnlkmpy RraA

-

I

Alter Dosage of Current Madlatlon

4

lntrrcurronl

NO

Hucuumntmsmpy Ban Msrlmlzsd?

I

1-

I

=I

I

Patlent

-1

Fiwvhatlon

I

Connldw Mdltlon~l ThWSplSS: l Altered Dosage 01 Analgesic l Another Analgesi~NSAlD l hafutiarlar Gxticosteroids l Surgical Inlervmtim l Narcotic An&s&s l Adjunctive Thkpies l lnvestigatiod Therapies

No’

I

I \

‘Unacceptable

Pmblom?

I Yea

I

= continued pain, progressive disability, and/or drug toxicity.

December 29, 1997 The American Journal of Medicine@ Volume 103 (6A)

61s

ALGORITHMS FOR THE DIAGNOSIS AND MANAGEMENT OF MUSCULOSKELETAL COMPLAINTS

Table 1. Common Rheumatologic Conditions Conditions are listed in approximate order of prevalence. Men Noninflammatory

Age W 18-34

9 Injury/overuse’ Low back pain

l

l

l l

35-65

Women

Inflammatory

Low back pain Injury/overuse’ l OA Entrapment syndromes+ l

l

l

l

l

l l

Noninflammatory

Spondyloarthropathier? Gonococcal arthritis Gout

l l

Injury/overuse’ Low back pain

Inflammatory l l l

Bursitis Gout Spondyloarthropathies’ USP’

Osteoporosis (postmenopausal) Low back pain Injury/overuse’ Fibromyalgia Entrapment syndromes+ *OA Raynaud’s p h e n o m e n o n

Gonococcal arthritis RA Systemic lupus erythematosus

Bursitis . RA usp*

l

l

l

l

l

l

l

l

l OA

> 65

l

Low back pain Osteoporosis . Fracture l

l

l

l l l l l

Bursitis Gout USP’ RA Pseudogout Polymyalgia rheumatica Septic arthritis

l

Osteoporosis

l OA l l l

l l

Fibromyalgia Low back pain Fracture

l l l l l

Bursitis USP” RA Gout Pseudogout Polymyalgia rheumatica Septic arthritis

‘Injury/overuse includes fracture, soft-tissue injuries, tendinitis, and “nonarticular rheumatism”; ‘entrapment syndrome includes carpal tunnel and tarsal tunnel syndromes; %pondyloarthropathies include ankylosing spondylitis, psoriatic arthritis, and Reiter’s s y n d r o m e ; VJSP = u n d i f f e r e n t i a t e d s e r o n e g a t i v e ( s e l f - l i m i t e d o r p e r s i s t e n t ) p o l y a r t h r i t i s , u s u a l l y i n f l a m m a t o r y , t h a t i s n o t associated with increased titers of rheumatoid factor and is atypical of RA or fails to meet ACR criteria for the classification of RA.

rable 2. Musculoskeletal Conditions: Features That Distinguish Articular From Nonarticular Disorders Articular Nonarticular 4natomic

Structures

l l l l

symptoms and Signs

Pain/tenderness

l l l

Pain on Movement

l l l

Swelling

Limitation of Motion

l

l

l

Crepitation Instability Locking of joint Deformity

l

l

l

l l l

qadiographic

changes

l l

62s

Juxtaarticular bone Articular cartilage lntraarticular ligaments Menisci (knee)

l l l

Synovial fluid Synovium Joint capsule

Localized to joint Deep and poorly localized Specific referral patterns With active and passive movement With movement in many planes Localized to joint Common, related to articular structure 1. Synovial effusion 2. Synovial thickening 3. Bony enlargement Frequent on both passive and active range of movement Related to mechanical derangement or joint pain May be present May be present May be present May be present Localized to joint Secondary to joint damage Common in chronic conditions Uncommon in acute conditions except trauma

December 29, 1997 The American Journal of Medicine@ Volume 103 (6A)

l l l l

l l

Tendons Bursae Extraarticular ligaments Muscle

l l l l

Fascia Bone Nerve

Skin

Localized to extraarticular structure “Point” tenderness, superficial

With active movement With movement in specific planes Rarely localized to joint May be present . Not limited to articular structure

l

l l

l

l

l

l

l

l

l l

l l

May be present but usually limited to active range of movement Related to extraarticular mechanical abnormality, diffuse pain, or weakness Absent/unrelated Absent/unrelated Absenffunrelated Rare, except with antecedent trauma Associated with extraarticular abnormality Uncommon/unrelated Soft tissue calcification

ALGORITHMS FOR THE DIAGNOSIS AND MANAGEMENT OF MUSCULOSKELETAL COMPLAINTS

Table 3. Characteristics of Common Localized Nonarticular Disordem Shoulder

Rotator cuff tendinitis (subacromial bursitis)

l

l l l

Bicipital tendinitis

l

l l l

Capsulitis (frozen shoulder)

l l l

Elbow

Tennis elbow (lateral epicondylitis)

l l l

Golfer’s elbow (medial epicondylitis)

Aching and discomfort in subdeltoid region - associated with night pain - aggravated by abduction of arm History of repetitive and strenuous upper limb activity (may be absent in elderly) Onset may be acule or chronic in any age group Consider rotator cuff tear when weakness or wasting is present Pain over anterior aspect of shoulder exacerbated by resisted elbow flexion suppination Occurs at any age Night pain is rare Associated with overuse

or

Deep pain in shoulder with decreased active and passive movement Insidious onset in persons over 40 yr Associated with night pain Pain and tenderness over lateral epicondyle of the humerus, impairing grip Aggravated by resisted dorsiflexion of the wrist Often brought on by overuse in persons over 30 yr

. Pain and tenderness poorly localized to the medial epicondyle of the humerus Aggravated by resisted wrist flexion Associated with overuse l

l

Olecranon bursitis

l l

A Wrist and Hand

DeQuervain’s tenosynovitis

l

l l l

Trigger finger

l l l

Dupuytren’s contracture

l l

Hip

Trochanteric bursitis

l l l l

Knee

Prepatellar bursitis

Localized swelling and pain over the olecranon Pain is usually not aggravated by movement 25% of cases may be infected (usually with Streptococcus aufeus) Insidious onset of pain over radial aspect of the wrist during pinch grip Most common in women 30-50 yr old Related to repetitive strain and chronic overuse Pain over the flexor tendon of the finger with intermittent locking of the digit in flexion Related to stenosing tenosynovitis of the flexor tendons of the finger or thumb Related to overuse trauma from repetitive gripping Nodular thickening of the palmar fascia, drawing fingers into Usually minimal associated pain

flexion

of the MCP joints

Deep aching pain on lateral aspect of hip and thigh Pain is aggravated by activity, often present at night, related to position More frequent in women Movement of hip usually normal

Circumscribed, painful swelling anterior to the Related to recurrent trauma A* M a y b e i n f e c t e d l

patella

l

Ankle and Foot

Anserine bursitis

l

Achilles tendinitis

l l l

Plantar

fasciitis

Pain over the medial aspect of the upper tibia Pain, swelling, tenderness near the insertion of the Achilles tendon Aggravated by dorsiflexion of the ankle Related to repetitive trauma

Pain on the under surface of the heel on weight bearing Aggravated by dorsiflexion of the toes Radiographs may show a plantar spur Related to repetitive trauma l l

l

l

A = Requires immediate diagnosis and treatment.

December 29, 1997 The American Journal of Medicine@ Volume 103

(6A)

63s

ALGORITHMS FOR THE DIAGNOSIS AND MANAGEMENT OF MUSCULOSKELETAL COMPLAINTS

Table 4. Management of Fibromyalgia Pharmacologic l l l l l

Nonpharmacologic

Simple analgesics Antidepressants, including tricyclics Muscle relaxants NSAlDs (analgesic dose) Soft tissue injection

Patient education/reassurance . Aerobic exercises - water exercise - walking - low-impact aerobics l Consider consultation with mental health professional l Acupuncture l

Table 5. Specific Features That Are Useful in Distinguishing Inflammatory From Noninflammatory Conditions Characteristics of the Condition Feature Joint pain

Inflammatory

Noninflammatory

Yes (with activity and rest)

Yes (with activity)

Joint swelling

Soft tissue

Local

Sometimes

erythema

Local warmth Morning stiffness*

Bony (if present) Absent

Sometimes

Absent

Prolonged ( > 60 min)

V a r i a b l e (< 6 0 m i n )

Systemic symptoms

Common

Rare

ESR, CRP

Increased

Normal for age

Hemoglobin

Normal or low

Normal

Serum albumin

Normal or low

Normal

S y n o v i a l f l u i d WBC/mml

L 2000

< 2000

Synovial fluid % PMN

2 75%

< 75%

*Presence, duration, and functional impact of morning stiffness have been suggested to be poor discriminators of RA and chronic noninflammatory joint pain (Hazes JMW, et al. J Rheumatol. 1993;20:1138-1142.) However, 87% of 489 practicing rheumatologists reported that prolonged (> 60 min) morning stiffness was useful in differentiating inflammatory from noninflammatory arthritis.

Table 6. Additional Clinical Features Indicating That Further Investigation Is Necessary* 1. Systemic manifestations - fever - weight loss - rash - acute ex-traarticular illness 2. Trauma - fracture - ligament tear - dislocation 3. Neurologic manifestations 4 . Lack of response during 2 to 6 weeks of treatment and observation 5. Suspicion of a specific condition requiring prompt diagnosis and treatment, based on history and physical examination - infection - connective tissue disease - endocrinopathy - malignancy - metabolic disorder ‘Investigations may involve laboratory tests, imaging procedures, biopsies, or other evaluations (see Tables 7 and 7a). Adapted from Fries JF, Mitchell DM. JAMA. 1976;253:199-204.

64s

December 29, 1997 The American Journal of Medicines Volume 103

t6A)

ALGORITHMS FOR THE DIAGNOSIS AND MANAGEMENT OF MUSCULOSKELETAL COMPLAINTS

Table 7. Specific Investigations That Might Be Useful in Diagnosing Common Muscutoskeletat If There Is... l

l

l

l

l

l

l

l

Consider..

Conditions*

To Explore a Diagnosis of..

Trauma

Radiographs

A Fracture

Localized inflammation over bursa

Bursal

A Septic bursitis

aspiration and analysis

Pain and prolonged stiffness in the neck, s h o u l d e r , o r p e l v i c g i r d l e i n a p e r s o n > 50 yr

ESR or CRP

Polymyalgia

Headache and/or person > 50 yr

rheumatica

visual changes in a ESR, temporal artery biopsy

Temporal arteritis

Weakness, muscle cramps, diffuse pain, stiffness

Thyroid function tests

Hypothyroidism

Acute back pain in a postmenopausal woman

Radiographs

Osteoporosis with fracture

Persistent hip or shoulder pain in a person with a history of steroid use, alcoholism, sickle cell anemia

Radiographs, magnetic resonance imaging

Osteonecrosis

Podagra (severe pain and swelling at the base of the great toe)

Synovial fluid aspiration

Gout

l

Urticaria/arthritis

Hepatitis Et surface antigen, complement titers

Hepatitis B, serum sickness

l

Erythema

l

l

l

l

l

l

l

l

l

l

l

Lyme titer

Lyme disease

Back pain relieved by activity and associated with morning stiffness

chronicum migrans

Radiographs of pelvis

Sacroiliitis/ankylosing

Oligoarthritis with conjunctivitis, urethritis, cervicitis, or heel pain

Urinalysis, chlamydial antibody titers, HLA-B27 test

Reiter’s syndrome/ reactive arthritis

Migratory arthritis + skin rash

AS0 titer, anti-DNAase B

Acute rheumatic fever

Symmetric inflammatory arthritis involving small joints of the hands

Rheumatoid

RA

Proximal muscle weakness

CPK

Polymyositis

Malar rash, fever, renal disease

ANA, anti-dsDNA

Systemic lupus erythematosus

Radiographic

Inflammatory bowel disease

Diarrhea/abdominal pain

factor

evaluations/colonoscopy

spondylitis

Unexplained arterial or venous thrombosis or recurrent 2nd- or 3rd~trimester abortion

Antiphospholipid

Persistent unexplained systemic symptoms

Appropriate

Polyarthropathy including OA of MCP joints with or without chondrocalcinosis

Serum iron, iron binding capacity

Hemochromatosis

Inflammatory lesions of ear, nose, or throat with lung lesions and/or glomerulonephritis

C-ANCA

Wegener’s granulomatosis

antibody

cultures

Antiphospholipid

syndrome

Infection

A = Requires immediate diagnosis and treatment. ‘Principles: Indiscriminate use of laboratory tests to screen for rheumatologic disorders is rarely helpful. Such broad-based investigations have low predictive value. It is often more useful to order specific tests, based upon the patient’s history and physical examination, to support the working diagnosis. See Table 7a for a list of specific laboratory tests and their relative usefulness in the diagnosis and prognosis of rheumatologic conditions. For many tests used to support the diagnosis of rheumatologic conditions, the value of the test is based upon the pretest probability that the diagnosis is correct. A negative or normal test, however, may not rule out the diagnosis. See Table 7a. When possible, synovial fluid aspiration and analysis should be done to evaluate all patients with acute onset of arthritis, especially those with evidence of inflammation (see Table 5) or those with a mono- or oligoarticular onset.

l

l

l

December 29, 1997 The American Journal of Medicine’” Volume 103

(6A)

65s

ALGORITHMS FOR THE DIAGNOSIS AND MANAGEMENT OF MUSCULOSKELETAL COMPLAINTS

Table 7a. Laboratory Tests: Use in the Diagnosis and Prognosis of Rheumatologic Conditions Diagnosis is Likely Based on History and Physical Examination. Need to Increase the Likelihood of Diagnosis

Altered Probability of Diagnosis, Based Upon History, Physical Examination and Lab Test Results

or

and/or

Diagnosis Established. Prognosis or Staoina of Disease Is in Question

More Accurate Staging or Prediction of Prognosis Usefulness of Test

Laboratorv Antinuclear (ANA)

Anti-DNA

Test

Antibody

Very Useful l l

Antibody

l

l

Antibodies to Extractable Nuclear Antigen (anti-Sm. RNP, Ro. La)

l l

l

c3, c4

Somewhat

Clinical suspicion of SLE Clinical suspicion of drug-induced lupus

Consideration of renal involvement in SLE patients Sequential follow-up of activity of SLE Clinical suspicion of SLE (Sm) Definition of subsets of SLE patients (Sm. RNP) Clinical suspicion of neonatal SLE (Ro)

Clinical suspicion of immune-complexmediated diseases (eg. serum sickness) or renal involvement in SLE l Sequential follow-up of activity of SLE . Clinical suspicion of hereditary angioedema l

Cl-b

l

Rheumatoid Factor (RF)

l

l

l

l

l

Clinical suspicion of RA * Prognosis or staging of RA

Z-Reactive Protein (CRP)

l l

l

Clinical suspicion of PMR Sequential follow-up of RA patients

. Sequential follow-up of RA patients

+A-B27

Anti-streptolysin

l

(ASO)

Zryoglobulins

l

l

Antineutrophil Cytoplasmic Antibody (ANCA) Serum Uric Acid

4ntiphospholipid

l

l

Antibody

l

l

66s

l

l

l

-yme A n t i b o d y

No Value . Random screening l As follow-up for patients Y with established SLE and a po sitive ANA previously

Help rule out SLE in cases with positive ANA but atypical clinical presentation Clinical suspicion of syndrome (Ro, La)

l

Sjogren’s

Strong clinical suspicion of Lyme disease

l

To distinguish inflammatory from noninflammatory arthritis when diagnosis is uncertain Evidence of infection with intercurrent connective tissue disease or post-operatively Clinical suspicion of arthropathy

spondylo-

Follow-up of patients with established gout to assess therapy

Evaluation of patient with unexplained arterial or venous thrombosis Evaluation of patient with unexplained 2nd- or Srd-trimester abortion

l

Random screening

l

Random screening

Random screening Follow-up of SLE patients , vasculitis patients, or other ps rtients

l l

l

Random screening

l

Random screening

Random screening . Follow-up of patients with spondyloarthropathies

Follow-up of patients with established Lyme disease

cryo-

Strong clinical suspicion of pulmonary/renal vasculitis

Random screening ANA-negative patients

l

Strong clinical suspicion of rheumatic fever Strong clinical suspicion of globulinemia

l

l

Follow-up response to therapeutic intervention

Clinical suspicion of other connective tissue disease (eg, cryoglobulinemia) Sequential follow-up of activity of RA

l

Random screening

l

Random screening

l

l

l

Follow-up of patients with positive vasculitis Clinical suspicion of

gouty

ANCA-

arthritis

Evaluation of isolated t h r o m b o c y t o p e n i a , livedo reticularis. ocular ischemia

December 29, 1997 The American Journal of Medicine” Volume 103 (6A)

Random screening

* Random screening

l l

l

Random screening ANA-negative patients

l

Suspicion of immune deficiency related to absence of complement protein components

l

Erythrocyte Sedimentation Sate (ESR)

Useful

Clinical suspicion of other connective tissue diseases (eg, DM/PM, PSS)

Random screening Screening of patients with suspected gout during an a c u t e flare (may be normal in 2 30% of gout patients) 9 Random screening

rable 8. Guide to Synovial Fluid Analysis

P l l l l

l

Strongly Consider Synovial Fluid Aspiration and Analysis If There Is: Monarthritis (acute or chronic) Trauma with joint effusion Acute monarthritis in patient with chronic polyarthritis Suspicion of joint infection, crystal-induced arthritis, or hemarthrosis Uncertain diagnosis I

l

Is The Effusion Hemorrhagic?

or

l l

1 Inflammatory ( Articular

2

No

l l

Noninflammatory Condition

t Is the WBC L 2000/mm’ and/or the % PMN 2 75%?

1

Trauma or mechanical derangement Coagulopathy Neuropathic arthropathy Traumatic tap Other

1

Yes -

No

l

Consider Inflammatory or Septic Arthritis Gram stain, culture mandatory I

(4iziizT Definitive Diagnosis of CrystalInduced Arthritis’

*Presence of crystals does not rule out the possibility of concurrent infection.

December 29, 1997 The Amencan

Journal of Medicine@ Volume 103 (6A)

67s

ALGORITHMS FOR THE DIAGNOSIS AND MANAGEMENT OF MUSCULOSKELETAL COMPLAINTS Table 9. Crystal-Induced Arthritis Characteristic Prevalence

Gout l

l

l

Crystals

Chemistry Appearance

l

l

l

Articular

involvement

l

l

Most Frequently Affected Joints

l

l

Associated Findings

l

l

Predisposing Conditions/ Risk Factors

Therapeutic

Options

l

l

l

1.5 to 2.6 cases per 1000 individuals Increases with age in men and postmenopausal women 15/l 0 0 0 a t a g e 5 6 ; men: 28/1000. women: ll/lOOO Monosodium urate Negatively birefringent Needle-shaped Monarticular > oligoarticular Polyarticular < 30% 1st MTP joint - initially 50%

Pseudogout l

l

l

l

l

l

l

c 1 case per 1000 individuals Increases with age

Calcium pyrophosphate dihydrate Weakly positively birefringent Linear or rhomboidal Monarticular 5 oligoarticular Knee, wrist, other

- eventually 90% Ankles, knees, other Tophi (in chronic disorder) Hyperlipidemia Hyperuricemia,’ obesity, hypertension, hyperlipidemia, alcohol ingestion, lead ingestion, hereditary enzyme defect (rare) Acute attacks: - NSAIDs, corticosteroids, colchicine Chronic management: - urate-lowering agents, colchicine

l

l

l

l

Chondrocalcinosis (increases with age; most will not have pseudogout) Hypothyroidism, hemochromatosis, OA, chronic renal insufficiency, diabetes, hyperparathyroidism, hereditary (rare) Acute attacks: - NSAIDs, corticosteroids, colchicine Chronic management: - NSAlDs * colchicine

‘Drugs associated with hyperuricemia include diuretics, low-dose salicylates, nicotinic acid, cyclosporine, ethanol, and ethambutol. Roubenofl Ft. Rheum Dis C/in North Am. 1990;16:539-550. Doherty M, Dieppe P. Rheum Dis C/in North Am. 1988;14:305-314.

68s

D e c e m b e r 2 9 , 1 9 9 7 T h e Amencan J o u r n a l o f M e d i c i n e @ V o l u m e 1 0 3 (6A)

rable 10a. Managing Acute and Interval Gout Part A: Acute Gout The p a t i e n t h a s a n e s t a b l i s h e d d i a g n o s i s o f g o u t . A p l a n o f t r e a t m e n t s h o u l d b e e s t a b l i s h e d f o r t h e a c u t e

attack.

Patient With an Established Diagnosis of Gout

Is an Acute Attack of Synovitis Present?

1

Yes

No

Are Corticosteroids Contraindicated? I

1No

Oral Corticosteroids

F

Acute Symptoms Resolve

*Adjust dose in patients with renal insufficiency

December 29, 1997 The American Journal of Medicin@ Volume 103 (6A)

69s

ALGORITHMS FOR THE DIAGNOSIS AND MANAGEMENT OF MUSCULOSKELETAL COMPLAINTS

Table lab. Managing Acute and Interval Gout (cont’d) Part 8: Interval Gout The patient has an established diagnosis of gout. A plan of treatment should be established for the symptom-free interval between attacks.

Interval Gout

Alcohol or Weight Loss Decrease Frequency of Attacks?

I

Is There a History of Nephrolithiasis? No Are Tophi Present? \

I

I

Is Serum Urate

1 Allopurinol’ T h e r a p y (Colchicine’ Prophylaxis During Initiation or to Control Recurrent Attacks)

2 11 mg/dL? No

Yes

Yes

Cofchicine

Yes Acid > 800 m g ?

Uricosuric Such as Probenecid (Colchicine’ Prophylaxis During Initiation or to Control Recurrent Attacks)

Continue Therapy

+

No I

Alone

Gouty

Attacks?

‘Adjust dose in patients with renal insufficiency.

70s

December 29, 1997 The American Journal of Medicine-* Volume 103 (GA)

ALGORITHMS FOR THE DIAGNOSIS AND MANAGEMENT OF MIJSCULOSKELETAL

COMPLAINTS

Table 11. Treatment of Pseudogout

T

Oral Colchiolne’

Contraindicated? Yes Chronic

NSAID’

Therapy

J No lntraarticular or Oral Cortlcosteroids

Is > 1 joint involved?

‘Adjust dosage with renal insufficiency

Oral or Intramuscular Corticosteroids

tNSAlD contraindications: - renal insufficiency - CHF - peptic ulcer disease - hypersensitivity

Table 12. Discriminating Features of Common Chronic Polyarticular Disorders (see also Clinical/laboratory Finding Morning stiffness > 60 min’ Back pain Distribution of articular involvement

OA + Asymmetric

Tab/e 8)

RA

Spondyloanhropathy

+

+ +

Joints commonly involved

DIP, PIP, 1st CMC, hip, knee, spine

Symmetric PIP, MCP, MTP, wrist, knee, hip

Asymmetric Hip, knee, SI joints

Nature of joint involvement

Bony enlargement, intermittent effusion

Synovial swelling and effusion

-

WBC < 2000Imm’ PMN < 75%

+ + + WBC > 2000/mm’ PMN t 75%

Synovial swelling and effusion + + +

Joint space narrowing, osteophytes, subchondral sclerosis

Periarticular demineralization, erosions

Enthesitis Extraarticular features Increased ESR, CRP Increased rheumatoid factor Synovial fluid analysis Radiographic findings

-

WBC 2 2000lmm” PMN > 75% Sacroiliitis

+ = highly characteristic - = uncommon *Presence, duration, and functional impact of morning stiffness have been suggested to be poor discriminators of RAand chronic noninflammatory joint pain (Hazes JMW, et al. J ffheumatol. 1993;20:1138-1142.) However, 87% of 489 practicing rheumatologists reported that prolonged (> 60 min) morning stiffness was useful in differentiating inflammatory from noninflammatory arthritis.

December 29, 1997 The American Journal of Medicine@ Volume 103 (6A)

71s

ALGORITHMS FOR THE DIAGNOSIS AND MANAGEMENT OF MUSCULOSKELETAL COMPLAINTS

Table 13. Evidence-Based Approach to Acute Low Back Pain These recommendations are based on evaluation of 10,317 abstracts and 3,918 articles reviewed by a multidisciplinary panel of experts. During the first month: A 1. Look for red flags in patient history. 2. 3. 4. 5. 6. 7.

If there are no red flags, do not order tests or referrals. Educate patient on favorable natural history. Symptom control: manipulation and/or minimal use of medication ‘Only a short period of bedrest should be recommended or none at all. Encourage a gradual return to normal activity. Plain radiographs are not recommended for routine evaluation of patients with acute low back problems within the first month of symptoms, unless a red flag is noted on clinical evaluation.

Red Flags: Potentially Serious Conditions A Fracture:

l

A

l

Tumor/Infection:

l l l l

A Cauda Equina:

l l l

History of trauma > 50 yr or < 20 yr of age History of cancer Fever, weight loss Recent infection, drug abuse, immune suppression Night pain Bladder, bowel dysfunction Saddle anesthesia Progressive lower extremity neurological deficit

Quebec Task Force, 1987.

Table 14. Guidelines for the Treatment of Chronic Axial Osteoarthritis 1. Perform complete physical examination, including musculoskeletal, spinal, and neurologic examinations, to exclude other serious causes of axial pain, such as cauda equina syndrome, spinal fracture, infection, or neoplasia. 2. Initiate conservative management of condition: - provide patient education - discuss modification of activity - recommend low impact/stress exercise (eg, walking, swimming, biking) - recommend normal activity and/or return to work - use nonprescription analgesics (acetaminophen, NSAIDs, salicylates) - use prescription NSAlDs 3. Interventions with uncertain or unproven benefit: - additional radiographs or more extensive evaluations (eg, EMG, MRI) - muscle relaxants - antidepressants - bed rest - opiate analgesics - physical modalities (eg, massage, ultrasound, diathermy, heat or cold applications) - lumbosacral corsets or braces - persistent use of cervical collars - local injections (eg, facet, trigger point, epidural) 4. Consider specific diagnostic tests for possible other causes of persistent axial pain: Suspected Cause Diagnostic Test Spondylolisthesis Radiographs Vertebral compression fracture Radiographs Spinal stenosis CT or MRI scans Radicular impingement EMG or MRI Infection or neoplasia CBC, ESR, SPEP, or bone scan

72s

December 29, 1997 The American Journal of Medicine@ Volume 103

(6A)

Table 15. Chronic Inflammatory Polyarthritis: Diagnosis Diagnosis

Joint

RA Spondyloarthropathy See Table 16

l

l

Manifestations

Extraarticular

Symmetric polyarthritis involving typical joints

l

Asymmetric oligoarthritis Inflammatory back pain l Sacroiliitis

l

l

l l l

Psoriatic Arthritis

l l

l

Gout See Table 9

Pseudogout See Table 9 Systemic Lupus Erythematosus

Asymmetric oligoarthritis Erosive peripheral arthritis involving DIP and/or PIP joints Spondylitis

Rheumatoid nodules, vasculitis, ocular, pulmonary lesions Typical skin rash Ocular involvement Genitourinary tract inflammation Bowel inflammation

Psoriatic skin lesions * Nail changes l

l

E p i s o d i c mono/oligoarthritis Rarely symmetric chronic arthritis

l

E p i s o d i c monololigoarthritis

l

l

Nondeforming inflammatory arthritis

l

l

Manifestations

l

Tophi

Associated endocrinopathy Criteria for systemic lupus er-ythematosus

Laboratory l

l

Intermittent nondeforming inflammatory arthritis

l

Classic features of individual disease

Elevated rheumatoid factor level in 2 80% of patients

Radiographic findings of sacroiliitis . MA-627 l

l

Normal rheumatoid factor level in 80% of patients

Intracellular monosodium urate crystats in synovial fluid * Serum urate level elevated at some time in > 90% of patients with chronic disease l

l

l

l

Other Connective Tissue Diseases

Findings

l

Calcium pyrophosphate crystals in synovial fluid Antinuclear antibodies, other autoantibodies Rheumatoid factor usually not elevated Relevant autoantibodies or laboratory abnormalities

December 29, 1997 The American Journal of Medicine@ Volume 103 (6A)

73s

‘able 16. Diagnosis of the Spondyloarthropathies

Is There: Inflammatory arthritis that is asymmetric or predominantly lower extremity? and/or Back pain of insidious onset of > 3 mo duration associated with morning stiffness and improvement with activity?

l

l

Yes

No

+I (A> Is There Evrdence

of Psonasrs

or

No pYes

l l l l l l l l

Is There One or More of the Following? Radiographic evidence of sacroiliitis Enthesopathy Dactylitis Buttock pain (unilateral or alternating) Urethritis or cervicitis Family history lritis Acute diarrhea or nongonococcal urethritis within 1 mo of onset

NO AYes +,

74s

*,

December 29, 1997 The American Journal of Medicine@ Volume 103 (6A)

ALGORITHMS FOR THE DIAGNOSIS AND MANAGEMENT OF MUSCULOSKELETAL COMPLAINTS

Table 17. Therapy ot the Spondyloarthropathies

Diagnosis of Spondyloarthropathy

Patient

Evaluation:

Continue Therapeutic Program

Yes Been Optimized?

‘Not approved by the FDA for treatment of spondyloarthropathies.

December 29, 1997 The American Journal of Medicinea

Volume 103 (6Al

75s

ALGORITHMS FOR THE DIAGNOSIS AND MANAGEMENT OF MUSCULOSKELETAL COMPLAINTS Table 18. Confirming a Diagnosis of Rheumatoid Arthritis 1. RA often begins insidiously with vague constitutional and musculoskeletal symptoms that may last for weeks or months before synovitis becomes apparent. 2. During the first 6 mo of RA, < 50% of patients will be RF-positive and the sensitivity of the 1987 ACR criteria is reduced. 3. A variety of less common chronic inflammatory seronegative articular conditions may clinically resemble early RA. It may be necessary to observe and evaluate the patient repeatedly for evolution of the disorder and manifestation of features that will distinguish them from RA. The following disorders can mimic RA:

Diagnosis

Sex

Laboratory Tests

Age

Comments

Undifferentiated seronegative polyarthritis

F>M

35-65

1 O-1 5% RF+

Psoriatic arthritis

ti=F

30-55

< 20% RF+

Tophaceous gout

M>F

Male 25-70 Female > 45

95% RF>95% t serum urate

Erosive inflammatory OA

F>M

> 60

Pseudogout

F=M

> 60

Reiter’s syndrome

M>F

16-50

Enteropathic arthritis

M=F

All age groups

95% RF-

20% of patients with Crohn’s disease or ulcerative colitis will develop peripheral arlhritis. Diagnosis may be difficult until GI involvement becomes apparent. Associated with oral ulcerations, GI symptoms or other features of spondyloarthropathy (see Table 16).

SLE

F>M

15-40

IO-15% RF+ Usually ANA+

Chronic nondeforming inflammatory polyarthritis associated with ANA positivity and other features of SLE.

Polymyositisl dermatomyositis

F>M

30-60

95% RF50% ANA+ 70% t CPK

Chronic inflammatory arthritis uncommonly occurs early in course of PM/DM. Features of proximal muscle weakness, bulbar dysphagia, muscle enzyme elevation or skin involvement (ie, Gottron’s papules) should be sought.

Scleroderma

F>M

30-50

95% RF>90% ANA+

Chronic inflammatory polyarthritis may predominate over skin changes early in the disease. Associated with Raynaud’s phenomenon, sclerodactyly, dysphagia, hypertension, or renal abnormalities.

Sarcoid arthritis

F>M

20-40

25% RF+

Parvovirus B18associated arthritis

F>M

Any age

Polymyalgia rheumatica

F>M

s 50

76s

Chronic seronegative inflammatory polyarthritis, atypical of RA or fails to meet classification criteria for RA. Up to 20% of cases may evolve into RA and nearly 50% will go into remission. 10% of those with psoriatic arthritis will have an RA-like distribution (MCPs, PIPS, wrists) Cutaneous psoriasis will be evident in the vast majority of cases. Intermittent inflammatory arthritis during the onset, with evolution of tophi and chronic inflammatory polyarthritis. Elevated serum urate and tophi help distinguish from RA.

Chronic polyarthritis with intermittent or sustained RFinflammation affecting PIP and DIP joints. Radiographs (or normal for age) demonstrate distinctive erosions and evidence of OA. 6-l 0% RF+

5% of patients will have “rheumatoid-like” inflammatory arthritis with stiffness, fatigue, synovitis, and elevated ESR, often lasting 4 wk to several mo.

95% RFSee criteria for spondyloarthropathies (see Table 16). 50-80% HLA-B27+ Often associated with low back pain, ocular, genitourinary, or GI symptomatology and enthesitis (heel pain).

15% of patients with sarcoidosis will develop arthritis. Early in the disease a chronic inflammatory oligo- or polyarthritis lasting weeks to months may develop and typically involve the ankles and knees. Other features of sarcoidosis (ie, etythema nodosum, hilar adenopathy) are usually apparent.

< 10% RF+ Adults manifest a flu-like picture, seldom develop the “slapped> 80% anti-B19 IgM cheek” rash and arthralgias are more common than arthritis. antibodies (acutely) Arthritis is an acute inflammatory polyarthtttis with an F&like distribution lasting 2 wk. < 10% develop a chronic inflammatory arthritis. 90% RF> 95% tt ESR

Proximal girdle pain and stiffness without synovitis.

December 29, 1997 The American Journal of Medicine@ Volume 103 (6A)

Tabb 19. Rheumatoid Arthritb: Patbnnt Evaluatbn Classification Slowty Progressive

of Disease

Actiiity Aggressive

Swollen joints Few Many ESR or CRP N o & a l o r m o d e s t l y e l e v a t e d .May’be.present” M a r k e d l y elevated Radiographic erosions ” Absent Rheumatoid nodules Absent May b e p r e s e n t Extraarticular manifestations May be present Absent S e r u m rheu&ioid”fa&& Normai o r m o d e s t l y elevaied Markedly elevited Functional status Preserved Impaired

”

Tabb 20. Rhaumatold Arthrltb: Goab ofThampy l l l l l l

Educate patient, family Relieve pain Reduce inflammation Protect artiiular structures Control systemic involvement Maintain function

Tabb 21. Rheumatoid Arthrltb: Treatment of Pain

l l l l l

Pharmacologic Non-narcotic analgesics NSAI Ds Toplcal a g e n t s (eg, c a p s a i c l n ) Antidepressants, including tricyclics Narcotic analgesics

l l l l l l

Table 22. Madkal Management of lnflammatoly Slowly Prograrrlve Frequently used in analgesic or antiinflammatory doses Infrequently used Occasionally used Consider in patients with s y m p t o m a t i c d i s e a s e d e s p i t e NSAID t h e r a p y

Nonpharmacologic Ambulatory assistii devices OrthotWsplints Physical therapy/occupational therapy Exercise Rest Self-help programs

Dbaaw (MO Appendix A) Agent*f NSAlDsS

Aggrearlve Frequently used in antiinflammatory doses

Oral Cortkoatarolds (bw dusa)S

Frequently used

Intnturtkular Cotilcostemlds

Often used

DMARDa (see Tabk 23)

Consider early in course of disease

‘May be used sequentially or contemporaneously depending upon disease activii and functional disability. Each category of therapeutic agent should bs consldered In each patient. The decision to use a specific agent depends upon the patient’s functional disabilii, the duration of disease, disease activity, comorbid conditions. response to previous therapy, and the presence of extraarticular disease. tRequire specific monitoring (see T&k 25, Appendix A). *Persons at increased risk for NSAID-induced gastrointestinal (GI) ulceration. including the elderly, those wfih a previous history of peptic u l c e r d i s e a s e o r G I b l e e d , t h o s e w i t h a s e r i o u s c o m o r b i d disease, a n d t h o s e r e c e i v i n g c o n c o m i t a n t t h e r a p y w i t h c o t t i i o s t e r o i d s should be considered for prophylaxis with misopmstol. §S5% o f 4 4 7 practicing r h e u m a t o l o g i s t s u s e d l o w - d o s e o r a l c o r t i c o s t e m i d s t o t r e a t R A , e i t h e r r o u t i n e l y ( 3 3 % ) o r a s b r i d g e t h e r a p y when beginning a DMARD (52%). However, only 23% believed that the treatment retarded the progression of erosion. Half of those surveyed defined “low-dose” as < 7.5 mg/day of prednisone, and half defined it as < 10 mglday. Half initiated pmdnisone therapy with < 7.5 mglday and 07% with < 10 mglday.

December 29, 1997 The American Journal of Medicine@ Volume 103

(6A)

77s

rabk 23. Rheumatoid Arthrltlr: Me&xl Managament of inflammatory Diseaoe With DMARDs Slowtv Prooressive Disease AooressNe Disease C o n s i d e r i n NSAIDConsider early in course nonresponsive patients: of disease: Hydroxychloroquine Methotrexate Auranofin intramuscular gold Sulfasalazine Hydroxychloroquine Minocycline’ Suffasalazine Fish oil’ Azathioprine openicillamine l

l

l

l

l

l

l

l

l

l l

For patients refractory to the above, c o n s i d e r : Cyclophosphamide’ Combinations of DMARDs’ Cyclosporine Dapsone’ l l l l

4 survey of 460 practicing rheumatologists revealed that 67% prescribed hydroxychloroquine as the initial DMARD in patients thought to rave slowly progressive RA, whereas 62% initiated methotrexate as the first DMARD in patients identified with aggressive FtA. 01 this group, 26% believed that DMARDs should be used in the first 3 months of disease; 32% whhin the first 6 months; 9% within the first e a r ; 2 5 % a c c o r d i n g t o t h e r e s p o n s e t o NSAIDs; 5 % f o r d e t e c t a b l e e r o s i o n s ; 3 % a c c o r d i n g t o t h e r e s p o n s e t o l o w - d o s e c o t t i c o s t e r o i d s ; rnd 0% for severe pain. 16% o f 4 5 9 r h e u m a t o l o g i s t s s u r v e y e d r e p o r t e d u s i n g c o m b i n a t i o n D M A R D s i n t h e f o l l o w i n g p e r c e n t a g e s : “ a f e w p a t i e n t s ” - 3 2 % ; “ m o r e han a few patients but less than half of patlents’41%; and “in more than half of patients”-25%.The most frequent combination of )MARDs u s e d w a s h y d r o x y c h l o r o q u i n e p l u s m e t h o t r e x a t e ( 6 4 % o f a l l c o m b i n a t i o n s ) . Not approved by the FDA for use in RA.

Table 24. Crltlcal Da&ions In the Management of Patlents Wlth Rheumutold Arthrltir l l l l l l l l l

78s

Aggressive versus slowly progressive disease Determination of dfsabilii Indications for inltiation of oral corticosteroids Indications for use of intraarticular corticosteroids Initiation of DMARD therapy Change in DMARD therapy R e c o g n i t i o n a n d t r e a t m e n t of serious adverse effects Recognition and treatment of extraarticular manifestations Indications for surgery

December 29, 1997 The American Journal of Medicine@ Volume 103 (6A)

ALGORITHMS FOR THE DIAGNOSIS AND MANAGEMENT OF MUSCULOSKELETAL COMPLAINTS

Table 25. Therapy of Rheumatoid Arthritis: Monitoring for Toxicity

Agent NSAlDs

Frequency of follow-up’ (‘4 4

CBC

Creatinine

J

J

Oral corticosteroids

4-12

DMARDs Hydroxychloroquine

4-12

5

Sulfasalazine

4-8

J5

Auranofin

4-8

J

Parenteral gold

l-4

J

Methotrexate

4-8

J

o-penicillamine

44

/

Azathioprine

24

J

Cyclosporine

2-4

Cyclophosphamide

2-4

Glucose

LFTs

Urinalysis*

/ /

Occult GI Blood Loss3

Ophthalmologic Exam

Liver Biopsy

J J (glucose) 6 mo

/ / (protein) / (protein) J6

J

J J (protein)

J J

J

J6

J (RBC)

‘Determined by consensus. *Urinalysis to determine glycosuria, proteinuria, or hematuria. 3Examination of stool for occult blood loss is an insensitive measure of gastrointestinal (GI) bleeding. If GI symptoms persist or anemia develops, further investigation should be considered. Persons at increased risk for NSAID-induced GI ulceration, including the elderly, those with a previous history of peptic ulcer disease or GI bleed, those with a serious comorbid disease, and those receiving concomitant therapy with corticosteroids should be considered for prophylaxis with misoprostol. 4During the first 6 mo, the patient should be evaluated every 4 to 8 wk. After 6 mo, the patient may be seen less frequently (eg, every 6 mo) depending upon age and comorbid conditions. 5Consider analysis for glucose 6 phosphate dehydrogenase deficiency. 6To adjust dosage.

Table 26. Osteoarthritis: Patient Evaluation Functional Status l

l

l

l

l

l

Joint function-limitation of movement/muscular atrophy Comorbid disease Psychological factors Socioeconomic factors/vocational factors Functional assessments (activities of daily living evaluations, functional questionnaires) Obesity

‘eripheral J o i n t P a i n Pain with activity or weight-bearing . Pain at rest/night pain/sleep disturbance Small joint involvement Large joint involvement, damage, or instability Periarticular pain l

l

l

l

Axial Pain See Table 14 l

Table 27. Osteoarthritis: Goals of Therapy l

l

l

l

Relieve pain Maintain function Protect articular

structures

Educate patient, family

December 29, 1997 The American Journal of Medicine@ Volume 103

(6A)

79s

Table 28. Critical Decisions in the Management of Osteoarthritis 1. Is OA the cause of the symptoms? 2. Is OA the cause of disability? 3. Recognition of inflammatory OA 4. Use of intraarticular corticosteroids 5. Necessity for weight reduction 6. Determination of need for physical therapy 7. Use of NSAlDs versus analgesics 8. Use of joint lavage 9. Indications for surgery

Table 29. Maintenance of Functional Status in Osteoarthritis l l

l

l

l

Weight loss Joint protection Splinting Ambulatory assistive devices Physical therapy

l

Occupational therapy

l

Vocational counseling

l

Patient education

Table 30. Osteoarthritis: Pain Management l

l

l

OA of the hand usually responds adequately to analgesics and occupational therapy OA of the hip may require additional therapy, including NSAlDs at analgesic or antiinflammatory doses, physical therapy, or surgical intervention OA of the knee may require additional therapy, including NSAlDs at analgesic or antiinflammatory doses, intermittent intraarticular corticosteroids, physical therapy, or surgical intervention Pharmacologic

l

-

Primary therapy non-narcotic analgesics topical agents (eg, capsaicin) nonacetylated salicylates NSAlDs (consider analgesic dose initially) intraarticular corticosteroids

l l l l l l l

Nonpharmacologic Modification of activities Exercise (bike, walk, swim) Physical therapy Heat/cold application Psychosocial support Pain management Self-help programs

A survey of 440 practicing rheumatologists revealed the following preferences for initial treatment of OA of the knee: non-narcotic analgesic, 37%; low-dose NSAIDs, 35%; high-dose NSAlDs, 13%; physical therapy, 10%; and intraarticular corticosteroids, 6%. If the initial treatment failed to curtail symptoms, the preferred second treatment was intraarticular corticosteroids, 33%; high-dose NSAIDs, 30%; low-dose NSAIDs, 23%; physical therapy, 8%; and non-narcotic analgesics, 5%.

SOS

December 29, 1997 The American Journal of Medicine@ Volume 103 (6A)

ALGORITHMS FOR THE DIAGNOSIS AND MANAGEMENT OF MUSCULOSKELETAL COMPLAINTS

‘.a-

.

-

’

.

.

.

.

-*

.

.

.I

-

-

Protocol for Nonsteroidaf Antiinflammatory Drugs

.

-

-

.

,,,.I

1

(NSAfDs)

Toxicity: Gf:

Peptic ulcer, dyspepsia (persons at increased risk of NSAID-induced Gf ulceration include those with a history of peptic ulcer disease, history of GI bleed, advancing age, history of serious comorbid disease, and concomitant corticosteroid therapy. In such patients, prophylactic therapy with misoprostol should be considered)

Renal:

Azotemia, interference with antihypertensives

Allergic: Triad of rhinitislnasal pofyposis/asthma Interference with platelet Iunction. bleeding Heme: Monitoring: Initial Evaluation:

CBC, creatinine, liver function tests

Follow-up:

CBC, BUN/creatinine Cl 6 months. During the first 6 mo. the patient should be evaluated every 4 to 8 wk. After 6 mo, the patient may be seen less frequently (eg, Q 6 mo) depending upon age and comorbid conditions.

Usual Dosing Regimens: Doses vary depending upon the specific agent, however, lower doses often provide analgesia while higher doses are required for antiinflammatory effects Hold NSAlDs and/or Evaluate if the Following Occur: 1) Evidence of GI bleed 2) Azotemia (increasing creatinine) 3) Worsening hypertension 4) Evidence of bleeding from other organ systems

Protocol for Low-Dose Oral Cortfcosteroids Toxicity: (most toxicities are dose-dependent) Osteoporosis (dose-, time-related); risk of osteonecrosis Bone: Endocrine:

Rapid withdrawal of corticosteroids after chronic use, or insufficient supplement of corticosteroids during periods of stress for patients using corticosteroids chronically precipitate adrenal insufficiency

Immune:

Increased risk of infection; may “mask” signs and symptoms of infection by dampening inflammatory response

Metabolic: GI: Muscle:

May precipitate/exacerbate hyperglycemia and/or diabetes meliitus; dose-related hyperchoiesterolemia May potentiate risk of peptic ulceration in patients concurrently receiving NSAlDs May be associated with myopathy

Monitoring: Initial Evaluation: Glucose, urinalysis, consider DXA scan Follow-up: Glucose, urinalysis, Q 3 months Usual Dosing Regimens: “Low dose” corticosteroids are typically considered by rheumatologists to be 5 7.5 mg/day prednisone. Ensure adequate calcium and vitamin D intake. Consider Holding or Decreasing Doses of Corticosteroids and/or Evaluate if the Following Occur: 1) Active infectious problem 2) Hyperglycemia 3) Gf bleed

December 29, 1997 The American Journal of Medicine@ Volume 103 (6A)

81s

ALGORITHMS FOR THE DIAGNOSIS AND MANAGEMENT OF MUSCULOSKELETAL COMPLAINTS

Protocol for Gold Therapy Preparations Injectable: Aurothioglucose, gold sodium thiomalate Auranofin Oral: Toxic@ T r a n s i e n t n i t r i t o i d r e a c t i o n ( f l u s h i n g , h e a d a c h e , e t c . ) m a y o c c u r i m m e d i a t e l y p o s t - d o s e Skin: Pruritic rash, oral ulcerations (- 20%) Renal: Proteinuria (- 20%) Heme: T h r o m b o c y t o p e n i a > l e u k o p e n i a (< 5%) Oral Gold: Above reactions less common, diarrhea very common Usual Dosing Regimens: IM G o l d : Typically, therapy is initiated weekly (50 mg/wk, after test doses of 10 mg and/or 25 mg) until a total dose of 1 0 0 0 m g h a s b e e n r e c e i v e d . T h e d o s i n g i n t e r v a l i s t h e n i n c r e a s e d t o Q 3 or 4 wk. O r a l G o l d : 3 m g p o , b i d ; m a x i m u m d o s e 9 mg/day Monitoring: Initial Evaluation: CBC, urinalysis Follow-up: CBC, urinalysis before each injection H o l d G o l d and/or E v a l u a t e i f t h e F o l l o w i n g O c c u r : 1 ) W B C < 3500/mma, o r a b s o l u t e P M N c o u n t < 2000/mm’ 2 ) P l a t e l e t c o u n t < 150,00O/mm’; falling Hb or Hct 3) Pruritic rash 4) Mouth ulcers 5) > t r a c e p r o t e i n u r i a o n d i p s t i c k ( i f c o n s i s t e n t , c h e c k 2 4 ” u r i n e ) 6) Oral gold: hold for persistent diarrhea Protocol for o-Peniclllamlne

Therapy

Factors Affecting Drug Levels: Renal function Common Toxicities: Pruritic rash, oral ulcerations Skin: Heme: Leukopenia, thrombocytopenia Renal: Proteinuria Uncommon Toxicities Autoimmune: Pemphigus, myasthenia gravis, Goodpasture’s syndrome, SLE-like syndrome Other: Severe bone marrow depression, bronchiolitis U s u a l D o s i n g R e g i m e n s : T h e r a p y i s t y p i c a l l y i n i t i a t e d a t 1 2 5 m g o r 2 5 0 mg/day, a n d t h e n i n c r e a s e d b y 2 5 0 mg/day a t m o n t h l y / b i m o n t h l y i n t e r v a l s ; u s u a l m a x i m u m d o s e < 1 , 0 0 0 mg/day. Monitoring: Initial Evaluation: CBC, urinalysis. F o l l o w - u p : C B C , u r i n a l y s i s Q 2 w k X 2 , t h e n C B C , u r i n a l y s i s Q 4 w k i n d e f i n i t e l y ( m a y i n c r e a s e i n s o m e p a t i e n t s t o Q 6-S w k f o l l o w - u p ) H o l d o - P e n i c i l l a m i n e and/or E v a l u a t e i f t h e F o l l o w i n g Occur: 1 ) W B C .Z 3500/mm’, o r a b s o l u t e P M N c o u n t < 2000/mm’ 2 ) P l a t e l e t c o u n t < 150,000/mma; falling Hb or Hct 3) Pruritic rash 4) Mouth ulcers 5) > t r a c e p r o t e i n u r i a o n d i p s t i c k ( i f c o n s i s t e n t , c h e c k 2 4 ” u r i n e )

82s

December 29, 1997 The American Journal of Medicine@ Volume 103

(6A)

ALGORITHMS FOR THE DIAGNOSIS AND MANAGEMENT OF MUSCULOSKELETAL COMPLAINTS

Protocol for Methotrexate Therapy Contraindications: Ethanol abuse; active infection; pregnancy; history of hepatitis; severe hepatic, renal, hematologic, or interstitial pulmonary disease. Increased Risk: Ethanol use, obesity, diabetes meffitus, elderly, impaired renal function. F a c t o r s A f f e c t i n g D r u g L e v e l s : R e n a l f u n c t i o n ; u s e o f s u l f a a n t i b i o t i c s , d i l a n t i n , NSAIDs, p r o b e n e c i d , d i u r e t i c s ; r o u t e o f a d m i n i s t r a t i o n (po vs IM or SQ). Toxicity: Folic a c i d m a y b e p r e s c r i b e d c o n c u r r e n t l y t o t r y t o d e c r e a s e s i d e e f f e c t s . GI: Nausea, vomiting, anorexia, diarrhea (10%); increased liver function tests Skin: M u c o s i t i s . r a s h (lo%), a l o p e c i a ( 1 % ) Heme: L e u k o p e n i a > a n e m i a , t h r o m b o c y t o p e n i a (< 5%) P u l m o n a r y : P n e u m o n i t i s ( i d i o s y n c r a t i c ) , f i b r o s i s (c 5%) Other: N o d u f o s i s , o p p o r t u n i s t i c i n f e c t i o n s ( P C P , a s p e r g i f f u s , histo. crypto, Zoster, etc) U s u a l D o s i n g R e g i m e n s : T h e r a p y t y p i c a l l y i n i t i a t e d a t 7 . 5 mg/wk i n a s i n g l e d o s e ; d o s e m a y b e i n c r e a s e d b y 2 . 5 mg/wk a t b i w e e k l y o r m o n t h l y i n t e r v a l s . T y p i c a l d o s e r a n g e 7 . 5 - 1 5 mg/wk ( m a x i m u m d o s e u s u a l l y 5 2 5 mg/wk). Monitoring: Initial Evaluation: CBC, liver function tests (ALT, AST, GGT, alk phos, albumin, bilirubin), urinalysis. Also, serum and RBC folate, s e r u m 812, a n d s e r u m f e r r i t i n i f t h e r e i s a c l i n i c a l s u s p i c i o n o f d e f i c i e n c y . C h e s t r a d i o g r a p h * pulmonary function testing if there is clinical suspicion of pulmonary disease. Consider screening for hepatitis B and C. F o l l o w - u p : CBC, liver function tests, creatinine Cl 2 wk X 2, then Cl 4 wk (when patient is stable, this may eventually be increased to Q 6-6 wk follow-up) Hold Methotrexate and/or Evaluate if the Following Occur: 1) WBC < 3500/mm’, or absolute PMN count < 2000/mm’ 2 ) P l a t e l e t c o u n t < 150,000/mm’ 3) Liver function tests > 3X upper limit of normal or > 2X on two visits’ 4) Mucosal ulcers 5 ) S e v e r e G I u p s e t o r a c t i v e GI b l e e d 6) Pulmonary symptoms (SOB, cough, chest pain, fever; abnormal chest radiograph) Protocol for Azathfoprine Contraindications: Severe hepatic or hematologic disease, pregnancy, concomitant administration of allopurinol. Toxicity: Heme: D o s e - d e p e n d e n t l e u k o p e n i a ( a p p r o x i m a t e l y 2-6% w i t h W B C < 2500/mm’) and thrombocytopenia (O-l%). G.I.: N a u s e a , v o m i t i n g , a n o r e x i a ( a p p r o x i m a t e l y lO-15% of patients); lessened with divided dosages, and administration with or after meals. Increased liver function tests (approximately 1%) Skin: Rash (approximately 2%) I n c r e a s e d r i s k o f i n f e c t i o n ( e g , Z o s t e r ) ; risk o f t r e a t m e n t - r e l a t e d m a l i g n a n c y ( e g , l y m p h o p r o l i f e r a t i v e ) w i t h l a r g e c u m u l a t i v e Other: doses. Usual Dosing Regimens: Therapy typically initiated at < 1 .O mg/kg/day (eg, - 50 mg/day). Dose may be increased at monthly intervals by - 0 . 5 mg/kg/day. Maintenance dose depends on efficacy and toxicity (particularly WBC count); usually c 2.5 wWcW. Monitoring: Initial Evaluation: CBC, liver function tests Follow-up: C B C , l i v e r f u n c t i o n t e s t s , Q 2-4 wk Hold Azathioprine and/or Evaluate if the Following Occur: 1) WBC < 3500/mm’, or absolute PMN count < 2000/mm’ 2 ) P l a t e l e t c o u n t < 150,000/mma 3 ) S e v e r e GI u p s e t ( n a u s e a , v o m i t i n g , a n o r e x i a ) 4) LFTs z 3 X u p p e r l i m i t o f n o r m a l o r > 2 X o n t w o v i s i t s 5) Skin rash

December 29, 1997 The American Journal of Medicine@ Volume 103 (6A)

83s

Protocol for Sulfasalazine Therapy Contraindictions: Documented allergic reaction to sulfa drugs or aspirin; history of severe hepatic or hematologic disease. Factors Affecting Drug Levels: Acetylator status (may not affect efficacy or outcome, however) Toxicity: Adverse reaction usually minor and reversible; 75% occur within first 3 mo of treatment. GI: Nausea, vomiting, anorexia (lO-20% d/c Rx), lessened with slow increase in dose, enteric-coated tablets, and dosing with meals; T increased liver function tests (OS-1.5%) CNS:

Irritability, headache, dizziness (5-l 0% d/c Rx)

Skin:

Rash, urticaria (4-5% d/c Rx); rarely Stevens-Johnson, TEN

Heme:

Anemia (megaloblastic > hemolytic; < 1%). neutropenia (l-l .5%),

thrombocytopenia (O-l%)

Usual Dosing Regimens: Maintenance therapy typically 1000 mg bid. In order to minimize GI adverse effects, therapy may be begun at 500 mg/day, and increased at weekly intervals. Maximal dose usually 34 g/day. Monitoring: Initial Evaluation:

CBC, liver function tests, consider analysis for GGPD deficiency

Follow-up:

CBC, liver function tests Cl 4-6 wk

Hold Sulfasalazine and/or Evaluate if the Following Occur: 1) WBC -Z 3500/mms, or absolute PMN count < 2000/mm’ 2) Platelet count < 150,000/mma Hb < 9 g. 3) Severe GI upset 4) Severe rash 5) Liver function tests > 3X upper limit of normal or > 2X on two visits

Protocol for Hydroxychforoquine Therapy Contraindications: Preexisting retinopathy or other serious ophthalmologic condition Toxicity: Adverse reactions are infrequent, and (except for ocular toxicity) usually minor and reversible GI: Nausea, vomiting, anorexia Irritability, nervousness CNS: Heme: Anemia (hemolytic; rare) Eye: Reversible: blurring of vision, halos around lights (ciliary body and comeal effect); irreversible: retinopathy, macular atrophy (very rare if dosed < 6.5 mg/kg/day) Usual Dosing Regimens: Typical therapeutic dose is 400 mg/day. mg/day) may be utilized.

Occasionally higher doses (600 mg/day)

or lower doses (200

Monitoring: Initial

Evaluation:

Follow-up:

CBC, consider baseline ophthalmologic examination, consider analysis for GGPD deficiency Ophthalmologic evaluation Cl 6 mo

Hold Hydroxychloroquine and/or Evaluate if the Following Occur: 1) Altered visual acuity or other ocular complaint 2) New onset or worsening of anemia 3) Severe GI upset

84s

December 29, 1997 The American Journal of Medicinea

Volume 103 (6A)

Protocol for Cycloeportne

Therapy

Contraindications: Renal failure, uncontrolled hypertension, active infection, malignancy. Increased Risk: Impaired renal function, hypertension Factors Affecting Drug Levels: Threefold individual differences in bioavailability (affected by GI motility, etc). # absorption with food. CsA i s m e t a b o l i z e d b y t h e h e p a t i c P - 4 5 0 s y s t e m . M e d i c a t i o n s t h a t T CsA l e v e l s : Ca” c h a n n e l b l o c k e r s ( d i l t i a z e m > verapamil, nicardipine; amlodipine, nifedipine have no effect), antibiotics (erythromycin, ketoconazole, fluconazole), metoclopramide, bromocriptine, androgens, oral contraceptives, methylprednisolone. Medications that L CsA l e v e l s : r i f a m p i n , dilantin, p h e n o b a r b i t a l , c a r b a m a z e p i n e . Toxicity: Renal: Acutely decreases glomerular filtration rate (reversible). Chronic high dose use may lead to irreversible decrease in renal function GI: Anorexia, nausea/vomiting. cramping/bloating Skin: Hypertrichosis (increased hair on face, arms, trunk), gingival hypertrophy Articular: G o u t (CsA i n c r e a s e s s e r u m u r i c a c i d ) I m m u n e : P o t e n t i a l f o r o p p o r t u n i s t i c i n f e c t i o n s ( P C P , a s p e r g i l l u s . histo, crypto, Zoster, etc) Neuro: Tremors, paresthesia, headache Other: Hypertension (probably not involving renin-angiotensin system; therefore may want to use Ca” c h a n n e l b l o c k e r s , c e n t r a l sympathetic blockers, vasodilators, low-dose diuretics); hyperglycemia; ?’ a l k a l i n e p h o s p h a t a s e U s u a l D o s i n g R e g i m e n s : U s u a l l y b e g u n a t 2 - 3 mgRg/day, either as a single or split dose. May be increased; for autoimmune d i s e a s e s , m a x i m u m d o s e i s u s u a l l y 5 5 mgkglday) Monitoring: Initial Evaluation: Creatinine, blood pressure (BP) Follow-up: Creatinine, BP: 0 2 wk X 2, then Q 4 wk Hold Cyclosporine and/or Evaluate if the Following Occur: 1) Creatinine > 3.0, or an increase in creatinine of b 30% over baseline (eg, if serum creatinine ? from 1 .O to 1.3 between visits) 2 ) H y p e r t e n s i o n ( B P > 160/90 m m H g ) o r B P s u b s t a n t i a l l y i n c r e a s e d f r o m b a s e l i n e 3) Infectious symptoms 4) Severe symptoms in other organ systems Protocol

for

Cyclophosphamide

Therapy

Contraindications: Pregnancy, history of malignancy, active inlection. GI Nausea, vomiting, anorexia (highly emetogenic; prophylaxis useful) Heme: L e u k o p e n i a ( n e u t r o p e n i a , l y m p h o c y t o p e n i a ) > > .L Pit, a n e m i a Hemorrhagic cystitis, risk of bladder cancer GU: Cancer: Increased risk, especially lymphoproliferative and bladder. Other: Alopecia (reversible), increased risk of infection (especially herpes zoster), infertility (premature ovarian failure) U s u a l D o s i n g R e g i m e n s : T h e r a p y t y p i c a l l y i n i t i a t e d a t _< 1 . 0 m9n(g/day ( e g , - 5 0 mg/day). D o s e m a y b e i n c r e a s e d a t m o n t h l y i n t e r v a l s by - 0 . 5 mg/kg/day. Maintenance dose depends on efficacy and toxicity (particularly WBC count); usually c 2.0 mglkglday. Monitoring: Initial Evaluation: CBC, creatinine, urinalysis. Follow-up: CBC, creatinine, urinalysis Cl 4 wk H o l d C y c l o p h o s p h a m i d e and/or E v a l u a t e i f t h e F o l l o w i n g O c c u r : 1) WBC < 3000/mm’, or absolute PMN count -Z 1500/mm’ 2) Severe GI upset 3) Active infection 4) Pregnancy 5) Hematuria

December 29, 1997 The American Journal of Medicine@ Volume 103

(6A)

85s