JOINT PAIN AND MONOARTICULAR ARTHRITIS

 

Background (AFP 2003;68:83; 2011;84:653; 2016;94:810; JAMA 2007;297:1478)

Definitions: Monoarticular (1 joint) vs. oligoarticular (2–4 joints) vs. polyarticular (>4).

History: H&P critical to clarify type of joint pain (e.g., inflammatory monoarticular, noninflammatory polyarticular); h/o trauma or prior joint pain/swelling; sexual hx (gonococcal); EtOH/diuretic use/shellfish intake (gout); IVDU, immunosuppression, prosthetic joints, DM, steroid injection, ↑ age, cellulitis (septic); renal failure (tx considerations, gout); travel, tick exposure (Lyme); anticoagulant use, bleeding d/o (↑ risk of hemarthrosis); chronicity acute (days) vs. chronic (>2 wks)

Inflammatory pain: Redness in specific joint, prolonged morning stiffness (>30 min), improvement of pain/stiffness w/ motion/exercise Articular vs. periarticular (bursitis, tendinitis): Passive ROM < painful than active ROM in periarticular process Noninflammatory, polyarticular/soft-tissue pain: Consider fibromyalgia (see “Fibromyalgia”) Extraarticular manifestations: Fevers/chills (septic arthritis), GI illness (reactive arthritis, IBD- assoc arthritis), genital pain/lesions (gonococcal), rash (psoriasis, SLE, viral exanthems, erythema migrans), mucocutaneous ulcers (SLE), inflammatory eye disease (seronegative spondyloarthropathies, RA)

Differential diagnosis: Noninflammatory: OA, mechanical (ligament injury), hemarthrosis, AVN, malignancy. Inflammatory: Crystalline dz (gout), septic arthritis, immune-mediated, spondyloarthropathy (psoriasis), SLE, sarcoid

Evaluation

 

Exam: Assess for warmth, redness, effusion, joint line tenderness, bony crepitation w/ flexion, rash or skin break, soft tissue swelling, tophi, extraarticular disease (above)

Range of motion: ↓ active ROM w/ preserved passive ROM suggests soft tissue (periarticular) cause; limited active & passive ROM more likely joint involvement; significant pain w/ minimal ROM concerning for septic arthritis

 

Arthrocentesis: If effusion present; cell count w/ diff, gram stain,

 

crystals, gram stain & Cx); also appropriate to aspirate bursa in the setting of bursitis; see discussion in “Gout”

 

Synovial Fluid Analysis
Measure	Norm	Noninflammatory	Inflammatory	Septic
Color	Clear	Yellow	Yellow	Yellow/green
Clarity	Clear	Clear	Clear-opaque	Opaque
WBC/mm3	<200	<2000	>2000	>2000 (usually >50 K)
PMNs (%)	<25	<25	>50	>75
Cx	⊖	⊖	⊖	Often ⊕
Crystals	⊕ or ⊖ May find MSU or CPPD crystals extracellularly		⊕   Intracellular if crystalline	⊕ or ⊖

(Adapted from JAMA 2007;297:1478)

Imaging: Radiographs useful to assess for fracture (h/o trauma), degenerative changes (OA) chondrocalcinosis (CPDD), erosions (RA, gout, osteomyelitis); other imaging depending on clinical setting Laboratory: BCx if septic arthritis suspected; Lyme Ab testing if suspected; ESR, CRP in inflammatory arthritis; uric acid if suspicion for gout; RF & CCP if polyarticular or monoarticular w/o other explanation Common monoarticular conditions:

Bursitis: Inflammation/injury of bursa (protect bony prominences) 2/2 to degeneration, infection, injury, crystals, RA; p/w pain on motion/rest, swelling, focal tenderness ± ↓ ROM; EtOH, DM, immunosuppression are risk factors for septic bursitis Treatment: Avoid activities that ↑ pain, joint protection, NSAIDs, ice, heat, PT; intrabursal steroid injection in refractory cases Bacterial: Risk factors: Previous joint pathology (RA, OA, gout, prosthetic joints), immunosuppressed, cutaneous infection, IVDU, prior intraarticular steroid injection (Lancet 2010;375:846) Management: Early arthrocentesis w/ cell counts & Cx; obtain BCx; early abx; if detected/high suspicion → ED/orthopedics for serial arthrocentesis

 

± surgical wash out; also involve ID for prosthetic joint infections (Infect Dis Clin N Am 2012;26:29) Nongonococcal septic arthritis: S. aureus>> other gm ⊕ or GNR; typically monoarthritis (large joint) but 20% involve >1 joint; systemic sx may be lacking; direct inoculation vs. spread from contiguous infection vs. bacteremia (e.g., endocarditis) Disseminated gonococcal infection: Usually young, sexually active (acute oligo-or poly-, typically migratory, skin lesions); see “Polyarticular Arthritis”

Hemarthrosis: Analgesics, aspiration/injection, compression sleeve to prevent reaccumulation, assessment for bleeding d/o See “Gout,” “Lyme,” “Polyarticular Arthritis,” respective joint section (e.g., “Hip”)

Patient information: JAMA 2007;297:1510

 

 

POLYARTICULAR ARTHRITIS

Background (AFP 2003;68:1151; 2015;92:35)

History: Sx acute vs. chronic (>2 mos), inflammatory vs. noninflammatory, type of joint involved (peripheral vs. axial, native vs. prosthetic, small vs. large), symmetric vs. asymmetric, episodic vs. continuous vs. migratory; # of joints involved: Mono- (1); oligo- (2–4); poly- (>4); presence of other systemic disease or sx (e.g., IBD, rash, mouth ulcers)

Workup: RF, CCP (for RA, below), ESR, CRP; acute-onset (<6 wks), consider parvovirus B₁₉, HBV, HCV, Lyme serologies

Differential diagnosis: In addition to specific disease below: OA (noninflammatory); gout/pseudogout; lupus; PMR; sarcoidosis/Lofgren’s (assoc w/ hilar adenopathy, erythema nodosum); adult-onset Still’s disease (assoc w/ high fevers, rash, ↑ ferritin); systemic vasculitides (e.g., granulomatosis with polyangiitis, eosinophilic granulomatosis with polyangiitis); hemochromatosis (esp w/ MCP &/or wrist involvement); antisynthetase syndrome; serum sickness; paraneoplastic or chemotherapy related (specifically checkpoint inhibitors)

 

 

RHEUMATOID ARTHRITIS (AFP 2011;84:1245; Ann Intern Med 2010;153:ITC1;

Lancet 2010;376:1094)

 

Definition: Symmetric, inflammatory arthritis affecting multiple peripheral joints

Epidemiology: 0.5–1% of Caucasian adults; peak incidence 50–60 y Risk factors: ↑ age, ♀>♂, FHx; HLA-DRB1 locus; smoking Extraarticular manifestations: Seen in 30–50% of pts; include Sjögren syndrome (dry eyes/mouth, most common), pulmonary (ILD), vasculitis, cardiac (pericarditis/CAD), cutaneous (rheumatoid nodules), anemia of chronic disease, Felty syndrome (RA + neutropenia + splenomegaly + recurrent infections)

Complications: ↑ risk of infection; cervical subluxation → pain, neuro deficit, instability; increased risk of CVD

 

ACR/EULAR 2010 Criteria for Diagnosis of RA (Lancet 2010;376:1094; Arthritis Rheum 2010;62:2569)
Category	Criteria (points)
Joint Involvement (any swollen or tender joint on exam, excluding DIP, 1st MTP, 1st CMC)	•  One medium to large joint (0) •  2–10 medium/large joints (shoulder, elbows, hips, knees) (1) •  1–3 small joints (i.e., MCP, PIP) (2) •  4–10 small joints (3) •  >10 joints (including ≥1 small joint) (5)
Serology	•  ⊖ RF &⊖ anti-CCP (0) •  Low- ⊕ RF or low- ⊕ anti-CCP (2) •  High- ⊕ RF or high- ⊕ anti-CCP (3)
Acute-phase reactants	•  Nl CRP & nl ESR (0) •  Abnl CRP or abnl ESR (1)
Duration of symptoms	•  <6 wks (0), ≥6 wks (1)
Scoring: ≥6 pts consistent with dx of RA; pts may meet more criteria w/ time & should be followed serially if ↑ suspicion
≥2 typical erosions or long-standing disease meeting ACR 1987 criteria also c/w dx of RA

Workup: CBC, Chem-12, UA, uric acid, ANA (r/o lupus), uric acid; plain films of hands/feet show juxta-articular erosions & symmetric joint

 

space narrowing (contrast w/ asymmetry in OA) in progressive disease (usually irreversible)

 

Labs in Rheumatoid Arthritis (Clin Chem Lab 2001;39:189; Ann Rheum Dis 2003;62:870)
Test	Se	Sp	Comments
Rheumatoid factor	66%	91%	IgM, IgA, or IgG that binds IgG Fc region; 10–30% of pts are RF ⊖ at presentation; many will turn RF ⊕ over time; False ⊕: Seen in bacterial/viral infection, healthy pts >70 y, malignancy; also can be ⊕ in Sjögren’s, cryoglobulinemia
Anti-cyclic citrullinated peptide (CCP)	68%	98%	Autoantibody to post-translational modification of arginine; ↑ correlation w/ functional status, erosions, & persistent (vs. self- limited) disease

Prognosis: ↑ Risk of early mortality (mostly 2/2 ↑ risk of CV disease); important to assess for & minimize cardiac RFs

Treatment: 1° goal is remission w/o active disease, requiring early & aggressive comanagement w/ rheumatology (BMJ 2011;343:4027; Arthritis Rheum 2005;52:3381); initial control & acute flares managed w/ NSAIDs & steroids (limit both); adverse effects of weak opioids (tramadol, codeine) may outweigh benefits (JAMA 2013;309:485); close monitoring for drug toxicity & efficacy w/ a goal of “tight control” (disease remission/low activity)

Disease-modifying antirheumatic drugs: Early Rx to prevent joint damage/disability; selection of agent(s) based on disease severity; combination tx in severe/refractory disease (see “Side Effects and Monitoring of Common DMARDs”) Nonbiologic: MTX (1° tx for most RA pts), hydroxychloroquine, sulfasalazine, leflunomide; “Triple therapy” (MTX, hydroxychloroquine, sulfasalazine) may be noninferior to etanercept + MTX (NEJM 2013;369:307); tofacitinib Biologic: TNF inhibitors (Etanercept, infliximab, adalimumab, golimumab, certolizumab pegol), IL1 receptor antagonist (anakinra), IL6 receptor antagonist (tocilizumab), T-cell costimulation blocker (abatacept), anti-CD20 B-cell (rituximab) Supportive care: PT, OT, pt education, exercise, smoking cessation

Surgery: Consider joint replacement in pts w/ uncontrolled pain or

 

severe disability despite optimal medical Rx

Patient information: JAMA 2011;305:1824

VIRAL ARTHRITIS

 

Background: Nonerosive usually managed symptomatically (Infec Dis Clin N Am 2005;19:963)

Parvovirus B₁₉: Assoc w/ exposure to children; mono → polyarticular within 48 h; sx mimic RA but very acute; ± cytopenias; usually self-limited (1 wk after presentation); dx w/ IgM anti-B₁₉± PCR

Hepatitis: HCV assoc w/ chronic arthritis in 2–4% (± cryoglobulinemia syndrome), many w/ ⊕ RF, usually – anti-CCP; acute HBV assoc w/ transient RA-like arthritis HIV: ↑ risk of septic arthritis, arthralgias common, ↑ risk of spondyloarthropathies (esp reactive/psoriatic arthritis, may be severe but ↓ frequency in HAART era) Chikungunya: Often bilateral, symmetric, small joints; suspect if other manifestations such as fever, rash with appropriate travel history; can be more chronic

SERONEGATIVE SPONDYLOARTHROPATHIES (AFP 2004;69:2853)

 

Background: Umbrella term that includes four diagnoses: ankylosing spondylitis, reactive arthritis, psoriatic arthritis, IBD associated arthritis; often with axial involvement, variably assoc w/ dactylitis (inflammation of entire finger/toe) & enthesitis (inflammation where tendon inserts to bone), as well as extraarticular manifestations such as ocular disease (e.g., uveitis) & skin disease; diagnosis & prompt rheum referral key Inflammatory back pain: SI joints (sacroiliitis), apophyseal joints of spine; characterized by IPAIN (Insidious onset, Pain at night, Age of onset <40 y, Improves w/ exercise/hot water, No improvement w/ rest), AM stiffness, responsive to NSAIDs (Rheumatology 2010;37:1978) Ankylosing spondylitis: Characterized by prominent inflammatory back pain; extraarticular manifestations include iritis, tendonitis, aortic

 

insufficiency; +HLA-B27 in 90% of pts; MRI detects SI joint inflammation earlier than radiograph; tx w/ NSAIDs (first-line treatment), TNF inhibitors, secukinumab (IL-17A antagonist) (Lancet 2011;377:2127)

Reactive arthritis: Acute onset of sterile, asymmetric, mono-or oligoarthritis (usually lower limb) 1–2 wks after GI or GU infection (e.g., Yersinia, Salmonella, Campylobacter, & Chlamydia) which can be asx;

± urethritis, conjunctivitis; 50–80% w/ +HLA-B27; tx underlying infection if GI or GU sx; tx arthritis w/ NSAIDs & steroids for severe disease; avg duration is 3–6 mos but can become chronic (Best Pract Res Clin Rheumatol

2011;25:347)

Psoriatic arthritis: Typically mono-/oligoarthritis early → polyarthritis later; dactylitis prominent; >50% have h/o psoriasis (psoriasis vulgaris most common); 20% w/ +HLA-B27; leads to joint deformity/erosive disease if untreated; DMARDs, TNF inhibitors effective, ustekinumab (IL-12/23 inhibitor) (Lancet 2013;382:780), secukinumab (NEJM 2015;73:1329; 2017;376:957) (see “Psoriasis”)

Inflammatory bowel disease: (a) axial arthritis resembling ankylosing spondylitis or isolated sacroiliitis; (b) Type I peripheral arthritis affects large joints (oligo-) of LE & acutely assoc w/ IBD flare; (c) Type II peripheral arthritis affects small joints (poly-) in a symmetrical manner & persists regardless of IBD activity (see “IBD”)

 

RHEUMATOLOGIC TESTS

Inflammatory Markers (JAMA 2015;314:827; Mod Rheumatol 2009;19:469)

C-reactive protein: Produced by liver; rapidly δs, direct measure of inflammation

Erythrocyte sedimentation rate: Slowly δs; indirect measure of inflammation; ↑ ESR suggests acute-phase proteins (e.g., fibrinogen, globulin) in plasma causing RBC aggregation; also ↑ by pregnancy, ↑ age, certain medications (e.g., OCPs), anemia

Antinuclear Ab (AFP 2002;65:1073; Arthritis Rheum 2002;47:434; Autoimmun Rev

2006;5:10; 2016;15:162)

When to perform: Not a test to r/o rheumatologic disease; use when

 

clinical suspicion for CTD exists; may be present in healthy pts (♀>♂, ↑ age), infection, malignancy, pregnancy; may be ⊕ in systemic (e.g., SLE) or single-organ autoimmune disease (e.g., autoimmune hepatitis) Titer: 1:40 (seen in 25–30% of healthy pts); 1:80 (seen in 1–15% of healthy pts); 1:160 (⊕ in 5% of healthy pts); If >1:160, less likely see in healthy pts; ⊕ titer may precede sx by several years (Arthritis Res Ther 2011;13:1; NEJM 2003;349:1526); titer significance must be considered in the clinical context

Staining pattern: 40+ patterns; somewhat specific for ENAs & related conditions (e.g., homogenous staining → anti-dsDNA → SLE; nucleolar

→ Scl-70 → systemic sclerosis), but multiple Ab & conditions for each staining pattern so not very helpful

 

Characteristics of ANA Testing by Disease
Disease	Se/Sp (%)	± Likelihood
SLE*	93/57	2.2/0.1
Systemic sclerosis	85/54	1.9/0.3
RA**	41/56	0.9/1.1
DM/PM**	61/63	1.7/0.6
Sjogren syndrome	48/52	0.99/1.01

*ANA a useful test in this disease.

**ANA not a useful test in this disease.

Extractable Nuclear Antigens (ENA) (Am J Clin Pathol 2002;117:316; Lupus

2011;20:250)

When to perform: ⊕ ANA indicates presence of antinuclear specific Ab or ENAs; should not be ordered before obtaining an ANA w/ ⊕ titer unless clear sx present

 

Rheumatic Conditions with Specific Antibodies (Clin Chem Lab 2001;39:189)
Disease	Antibodies	Notes
SLE	Anti-dsDNA, Anti-Sm Anti- Ro, Anti-La, Anti-RNP, Antihistone	Anti-Ro/La assoc w/ neonatal lupus incl congenital heart block Antihistone assoc w/ drug-induced LE

 

DM/PM	Anti-Jo-1, consider add’l myositis Ab testing	Myositis specific- & associated-antibodies may prognosticate
Systemic sclerosis (SSc)*	Anti-Scl-70, Anti- centromere, RNA polymerase III	Anti-Scl-70 assoc w/ dSSc >lSSc; Anti- centromere assoc w/ lSSc>dSSc; RNA pol III assoc w/ ↑ risk of renal crisis
Sjogren’s	Anti-Ro, Anti-La
MCTD	Anti-RNP
Rheumatoid Arthritis (RA)	RF & CCP	See “Polyarticular Arthritis” section

SSc includes both diffuse (dSSc) and limited (lSSc) scleroderma; limited also known as CREST =

Calcinosis, Raynaud’s, Esophageal dysmotility, Sclerodactyly, Telangiectasias syndrome

Antineutrophil Cytoplasmic Antigen (ANCA) (Clin Chem Lab 2001;39:189)

p-ANCA: Perinuclear pattern; target is usually myeloperoxidase (MPO); assoc w/ systemic vasculitis esp. microscopic polyangiitis & eosinophilic granulomatosis with polyangiitis-EGPA (formerly Churg–

Strauss); ↑titer, consider drug-or levamisole (cocaine)-induced c-ANCA: cytoplasmic pattern; targets PR-3 = major autoAg in granulomatosis w/ polyangiitis (GPA, previously Wegener

granulomatosis); 10–30% of pts w/ GPA are cANCA ⊖; ↑ titer may be

assoc w/ relapse

Cryoglobulins (Lancet 2012;379:348)

Background: Precipitate in cold, dissolve w/ rewarming, if ⊕, type & % (cryocrit) reported

Type1: Monoclonal Ig (IgG or IgM) assoc w/ myeloproliferative disease (e.g., MM); can lead to vascular occlusion & hyperviscosity Type 2: Mixed cryoglobulin (polyclonal IgG & monoclonal IgM) assoc w/ HBV & HCV & autoimmune disease; can lead to immune-complex–mediated vasculitis Type 3: Mixed cryoglobulin (polyclonal IgM & IgG) assoc w/ autoimmune disease (e.g., SLE, SS), infection (HBV, HCV, HIV), & malignancy (hematologic >> solid)

Interpretation: ⊕ or % of cryo is not necessarily diagnostic, % does not always correlate w/ active dz; if ⊖ test but ↑ clinical suspicion, test should be repeated; high false- ⊖ rate

 

OSTEOARTHRITIS

 

Background (Ann Int Med 2014;161:ITC1; Best Pract Res Clin Rheumatol 2006;20:3)

Epidemiology: Most common joint d/o (21 million pts in US); prevalence ↑↑ >40 y

Common risk factors: Age, obesity, trauma, repetitive use, ♀, genetics/FHx, neuropathy

Pathophysiology: Slow, progressive loss of articular cartilage assoc w/ bone hypertrophy (osteophytes) & sclerosis; usually 1° (idiopathic) but may also be 2/2 trauma, deformity, or inflammatory process Affected joints: Often affects multiple joints; typically hands/feet (DIP, thumb base/CMC, 1st MTP), knees, hips, spine (esp cervical/lumbar), shoulders (AC, glenohumeral joint)

Evaluation and Prognosis (AFP 2011;84:2012; 2011;85:49; JAMA 2003;289:1016;

NEJM 2007;357:1413)

History: Highly variable & depends on affected joint(s); pain worsened by activity, relieved by rest; gelling/stiffness w/ inactivity; slowly progressive; limitation in ROM; bony swelling, morning stiffness that resolves in <30 min; joint locking, popping, or instability; pt may report trauma/repetitive injury

Noninflammatory OA: Most common; pain/disability is 1° sx

Erosive OA: Subset of hand OA w/ prolonged morning pain/stiffness, effusion

Exam: Depends on joint; ↓ ROM w/ pain at end of range, typically w/o warmth; ± swelling (± tenderness) around joint line; crepitus; periarticular muscle weakness/wasting or bursitis/tendinitis

Workup: Advanced imaging (e.g., CT or MRI) is rarely necessary unless suspicion for alt dx (e.g., meniscal injury in the knee); x-ray may confirm dx (e.g., joint space narrowing w/ osteophytes & sclerosis) but late finding

Lab investigation (e.g., ANA, RF, anti-CCP, Lyme serology) should not be initiated unless suspicion for alt dx exists Consider further eval or referral to rheum: Younger pts, atypical sx or signs (e.g., atypical location, significant rest or night pain), wt

 

loss/constitutional sx, rapidly progressive pain or when dx is in question

Prognosis: Slowly progressive, may stabilize esp w/ risk factor reduction (e.g., wt loss), PT/exercise; no disease-modifying pharmacologic therapy

 

ACR Criteria for Diagnosis of Osteoarthritis
Hand	Hand aching, pain, or stiffness & 3 of 4 of the following: (1) Hard tissue enlargement of 2 or more of 10 selected joints*; (2) Hard tissue enlargement of 2 or more DIP joints; (3) <3 swollen MCP joints; (4) Deformity of at least 1 of 10 selected joints*. *10 selected joints include 2nd & 3rd DIP, 2nd & 3rd PIP, & 1st CMP joints of both hands (94% Se, 87% Sp) (Arthritis Rheum 1990;33:1601)
Hip	Hip pain & ≥2 of 3 of: (1) ESR <20 mm/h; (2) Radiographic femoral or acetabular osteophytes; (3) Radiographic joint space narrowing (89% Se, 91% Sp) (Arthritis Rheum 1991;34:505)
Knee	Clinical: Knee pain & ≥3 of 6 of: (1) Age >50 y; (2) Stiffness <30 min; (3) Crepitus; (4) Bony tenderness; (5) Bony enlargement; (6) No palpable warmth (95% Se, 69% Sp)
	Clinical and radiographic: Knee pain, osteophytes on radiographs & ≥1 of 3 of: (1) Age >50 y; (2) Stiffness <30 min; (3) Crepitus (91% Se, 86% Sp)
	Clinical and laboratory: Knee pain & ≥5 of 9 of: (1) Age >50 y; (2) Stiffness <30 min; (3) Crepitus; (4) Bony tenderness; (5) Bony enlargement; (6) No palpable warmth; (7) ESR <40 mm/h; (8) RF <1:40; (9) Synovial fluid OA (clear, viscous, or WBC <2,000/mm3) (92% Se, 75% Sp) (Arthritis Rheum 1986;29:1039)

Management (AFP 2011;83:1287; 2012;85:49; 2015;92:774; NEJM 2006;354:841;

Osteoarthritis Cartilage 2008;16:137)

Nonpharmacologic: Pt education, exercise (esp non wt-bearing), resting affected joint for brief periods (<12 h), wt loss, PT/OT, joint braces/splints, stretching, massage, heat, paraffin wax; unloading of joint wt w/ a cane/walker; soft shoes/insoles; TENS controversial (Br J Rheum 1994;33:455); acupuncture (JAMA 2007;297:1697)

Pharmacologic: Nonpharmacologic therapies should be tried 1st;

Noninflammatory OA: APAP PRN (effectiveness unclear)→ standing

→ NSAIDs (evaluate comorbidities); Erosive OA: NSAIDs PRN → standing (if persistent pain), colchicine, hydroxychloroquine

 

Osteoarthritis Medications
Drug	Dosing	Adverse Reactions	Additional Info

 

NSAIDS	Lowest effective dose; do not combine NSAIDs	–  Contraindicated in PUD & ASA sensitivity –  ↑ r/o CVD –  ↑ r/o bleeding w/ warfarin –  Avoid in CKD, CHF, cirrhosis, diuretics –  may ↑ BP –  Add PPI/H2 blocker may ↓ PUD risk –  Ibuprofen, naproxen inhibit PLT function	Nabumetone:↓ renal toxicity, ↓ antiplatelet activity Sulindac:↓ renal toxicity; contraindicated in cirrhosis/liver disease (hepatic metabolism) Diflunisal:↓ risk of PUD, ↓ antiplatelet activity COX-2 inhibitors: (celecoxib) CV risk similar to ibuprofen or naproxen (NEJM 2016:375:2519), no effect on PLT function
Duloxetine (SNRI)	Start 30 mg/d, ↑ to 60 mg/d	Nausea, dry mouth, somnolence, fatigue	Duloxetine added to oral NSAIDs improved knee OA pain (Curr Med Res Opin 2011;27:2361)
Capsaicin & Topical NSAIDs (i.e., diclofenac)	Can apply up to QID	Minimal systemic absorption	May be of only minimal benefit; capsaicin may be irritating
Tramadol	50–100 mg q4–6h PRN	Opioid use (other than tramadol) not recommended by American College of Rheumatology	Tramadol may be synergistic w/ APAP (Cochrane Database Syst Rev 2006;CD005522)
Hydroxy- Chloroquine	0.5 mg/kg/d (200– 400 mg/d)	Upset GI; retinal toxicity	Consider in pts w/ erosive OA unresponsive to NSAIDs; reduce dose of colchicine in renal failure (e.g., 0.3 mg/d)
Colchicine	0.6 QD-BID	N/V, diarrhea (↑ w/ ↑ dose); ↓ dose in CKD (however, not nephrotoxic); BM supp, myopathy, neuropathy

Glucosamine & chondroitin: Controversial but multiple negative trials, esp in advanced arthritis (NEJM 2006;354:795); glucosamine contraindicated in shellfish allergy

Intraarticular injections: Glucocorticoids (1–2 mos) may be useful in pts w/ pain refractory/contraindication to NSAIDs. Hyaluronate-related injectable agents are FDA-approved for treatment of OA of the knee, but efficacy is unclear & use is controversial (NEJM 2015;372:1040); Ineffective treatments: Intraarticular triamcinolone injections (JAMA

 

2017;317:1967); vitamin D supplementation (JAMA 2016;315:1005); lateral wedge shoe inserts (JAMA 2013;310:722); glucosamine/chondroitin supplements (AFP 2015;92:875)

Surgical: Consider joint replacement (esp knee/hip) in pts w/ severe OA who fail medical Rx; timing of surgery balanced btw limited hardware lifespan (15–20 y) & functional loss, muscle atrophy; improved outcomes for surgeons w/ ↑ volume; no benefit for arthroscopic debridement/irrigation of knee (Lancet 2012;379:1331; NEJM

2008;359:1097)

Patient information: AFP 2011;83:1294; 2012;85:57; JAMA

2010;304:114

 

 

BACK PAIN

Background (Ann Int Med 2014;160:ITC6-1; JAMA 2008;299:2067; NEJM 2001;344:363)

Epidemiology: 2nd most common complaint in primary care, 66% lifetime risk in adults; 60–70% of cases resolve in 6 wks, 80–90% by 12 wks

Evaluation (Ann Intern Med 2007;147:478; AFP 2007;75:1181; 2015;91:708)

History: Location, provocative/palliative factors, quality, radiation, severity, timing, hx trauma/back pain; Assoc sx: Fever, bowel/bladder incontinence, neuro deficits, saddle anesthesia; Risk factors: Steroid use, malignancy, infection, depression, avoidance behaviors, ergonomics

Occupational injury: Documentation of injury hx, functional limitation; risk factors for chronic disabling back pain include pre- existing psychological problems/chronic pain, job dissatisfaction, see “Chronic Pain” (NEJM 2005;352:1891)

Exam: Spine flexibility & palpation; toe/heel walk, rising from chair; neuro exam (strength, sensation, reflexes); pedal pulses; observation of walking, spontaneous activity (i.e., getting on & off exam table, getting dressed); exam of hip joint (youtube.com/watch?v=q1gX9hORtLY)

Straight-leg test: 91% sensitive, 26% specific for detecting herniated discs (Spine 2000;25:1140); w/ pt supine & leg extended, examiner lifts

 

leg at heel → considered ⊕ if sciatica reproduced between 30 & 70 degrees; Crossed straight-leg test: Elevation of opposite leg reproduces sx (↑ Sp)

Workup: Hx/PE suggestive in most cases; imaging in absence of red flags does not improve clinical outcomes (Lancet 2009;373:463)

Labs: Guided by clinical scenario: Consider ESR/CRP, CBC, BCx, AlkPhos, HLA-B27); for pts on chronic opioids, random drug testing to assess for presence of opioids to detect substance use d/o (JAMA 2013;309:919) Radiographs: Useful in diagnosing compression fractures, ankylosing spondylitis MRI: ~2/3rds of healthy adults w/o back pain have abnl findings on spine MRI & sx may not relate to imaging findings (NEJM 1994;331:69; 2013;368:999;1056) Electromyography and nerve conduction studies: Useful in pts w/ subacute radiculopathy & an unrevealing MRI

 

Etiologies of Back Pain and Common Presenting Symptoms
Suggestive History and Exam Findings	Etiology of Back Pain
Sudden onset, often w/ precipitating movement, may radiate to buttock, upper thigh; feeling of “something giving way”	Muscle or ligament injury (70%)
Chronic, subacute pain often assoc w/ osteoarthritis	Degenerative joint disease (10%)
L5–S1 most common; ⊕ straight leg test; worse w/ coughing, straining; sciatic pain (sharp/burning, radiating down buttock, thigh, or leg) in dermatomal distribution	Disk herniation (4%)
Sudden onset of pain in pt w/ risk factors for fracture (i.e., osteoporosis, steroid use, malignancy, elderly) after coughing, bending, lifting, or minor trauma; loss of height, point tenderness; may be presenting sign of osteoporosis	Compression fracture (4%)
Pain in lower back, buttocks (pseudoclaudication), wide gait, paresthesias (often bilateral), worsened by standing, walking (downhill > uphill, in contrast to claudication) & ↓ by sitting/bending/leaning forward (JAMA 2010;304:2628; NEJM 2008;358:818)	Spinal stenosis (3%)
Forward subluxation of vertebrae causes chronic ligamentous pain worse w/ activity, relieved by rest	Spondylolisthesis (2%)

 

Suggestive History and Exam Findings	Etiology of Back Pain
Gradual onset of pain w/ activity, unrelieved/worsened by supine position; may be accompanied by incontinence/urinary retention, saddle anesthesia, muscle weakness, wt loss; breast, gastrointestinal, lung, lymphoma/leukemia, myeloma, & prostate most common malignancies	Malignancy (<1%)
Fever, back pain, neuro deficit in minority of pts; risk factors include instrumentation, HIV, IVDU, TB, & hematogenous seeding from a UTI, catheter, or abscess (NEJM 2006;355:2012; 2010;362:1022)	Epidural abscess, vertebral osteomyelitis, discitis (0.01%)
Inflammatory back pain: onset of pain insidious, improves w/ motion, worse in the morning/better at night, improves w/ NSAIDs, typically in pts 20–45 y	Spondyloarthropathies (<1%)
Referred pain from hip, SI joint; AAA/TAA, endometriosis, fibroids, nephrolithiasis, pancreatitis, cholecystitis, pyelonephritis, neuropathy, claudication	Extraspinal (2%)

 

 

 

 

Red Flags to Prompt Imaging (Adapted from the American College of Radiology Appropriateness Criteria www.acr.org)
Red Flag	Possible Underlying Condition
Unexplained fevers or wt loss H/o cancer Immunosuppression Indwelling catheter, recent UTI or cellulitis IVDU Prolonged steroid use Back pain not improved w/ conservative tx	Cancer or infection
H/o significant trauma Minor fall or heavy lifting in elderly individual or osteoporosis Prolonged steroid use	Spinal fracture
Acute onset urinary retention or incontinence Loss of anal sphincter tone or fecal incontinence Saddle anesthesia Global or progressive motor weakness	Cauda equina syndrome or severe neurologic compromise

Treatment

 

Acute/Subacute (<12 wks)

Urgent surgical eval: Indicated for cauda equina, motor weakness, cord compression

Nonpharmacologic Therapy: 1st-Line Therapy Physical activity as tolerated: Pain relief/function improved in pts advised to stay active compared to bed rest (Cochrane Database Syst Rev 2010;16:CD007612); role of early PT referral unclear (JAMA 2015;314:1459) Reassurance: 90% of pts w/ acute, nonspecific back pain improve in <2 wks w/o intervention (BMJ 1994;308:577) CAM: Physical therapy, yoga (chronic low back pain), acupuncture, chiropractic, aquatherapy, massage tx; heat; cold compresses (acute back pain); spinal manipulation assoc w/ improvements in pain & function (JAMA 2017;317:1451) Self-care: Education books (e.g., The Back Book); back braces or abdominal binders Lifestyle modification: Good lifting techniques (bend knees, not back); lay flat w/ pillow under knees to straighten spine; firm/tempurpedic mattress; workplace ergonomic eval; padded mats if pt must stand for long periods; evidence low quality, but may be helpful Pharmacologic: 2nd-Line Therapy APAP no longer recommended (Ann Intern Med 2017;166:480; Lancet 2014;384:1586) NSAIDs: 1st- line, scheduled for short course (JAMA 2017;317:2327) Topicals: Lidocaine, capsaicin Muscle Relaxants: Cyclobenzaprine, baclofen, tizanidine, methocarbamol may be combined w/ NSAIDs for short course; caution re: sedation, drug interactions; avoid cyclobenzaprine in pts w/ arrhythmia, CHF, hyperthyroid; low-dose diazepam may also be used (2nd-line 2/2 abuse potential) Opioids: Not recommended (JAMA Int Med 2016;176:958) Steroids: Oral steroids for herniated disc did not improve pain compared to placebo but did improve

 

function somewhat (JAMA 2015;313:1915) Bisphosphonates: Consider in pts w/ osteoporotic compression fractures & pain unrelieved by PO meds

Chronic (>12 wks)

Epidural steroid injections: Consider for chronic radicular pain from disk herniation; insufficient evidence, but certain subgroups may respond (Spine 2009;34:49); contaminated steroids assoc w/ 2012 fungal meningitis outbreak (MMWR 2012;61:1)

Medications: SNRIs (i.e., duloxetine), TCAs (see “Chronic Pain”)

Behavioral modification: Wt loss, cognitive behavioral Rx (JAMA 2016;315:1240), smoking cessation

Herniated discs & spinal stenosis: Surgical correction for herniated discs (i.e., discectomy or microdiscectomy) or sx spinal stenosis (laminectomy or intraspinous spacer implantation) assoc w/ short-term benefits compared to conservative mgmt that diminish over time (Spine 2009;34:1094); pts treated w/ nonoperative mgmt for herniated discs improve substantially over 2 y (JAMA 2006;296:2441)

Vertebral fusion: Degenerative spondylolisthesis w/ laminectomy; consider for pts w/ >1 y disabling nonspecific back pain refractory to behavioral modification/intensive interdisciplinary rehabilitation (Spine 2009;34:1066)

Osteoporotic compression fractures: Vertebroplasty provided no benefit compared to sham procedures (NEJM 2009;361:557;569)

Other (multidisciplinary specialist consultation recommended): Best evidence for multidisciplinary rehab/chronic pain clinic & CBT; other options include ablation, intrathecal analgesic pumps; chronic pain clinic referral; pts who fail back surgery for disc herniation may benefit from spinal cord stimulation; facet joint injections

Patient information: JAMA 2000;284:21; 2013;309:1738 (general back pain); JAMA 2009;302:216 (sciatica); JAMA 2008;299:980 (spinal stenosis); JAMA 2010;304:114 (OA of spine); JAMA 2006;296:2512

(herniated discs); JAMA 2012;308:2047 (epidural steroid injections)

 

 

HIP PAIN

General principles: Hip pain is one of the most common musculoskeletal complaints. A patient’s report of “hip pain,” however, is often misleading since there are many causes of pain in the area of the hip, several of which do not arise from the true hip joint (where the femoral head articulates with the acetabulum).

Anatomy: Hip joint comprised of femoral head articulated with acetabulum; blood supply to head & neck of femur from the medial

 

femoral circumflex artery; total of 18 bursae; innervated by obturator nerve, femoral nerve, & sciatic nerve.

 

Causes of Pain in the Hip Region (AFP 2014;89:27)
Diagnosis	Symptoms	Demographics
Osteoarthritis (NEJM 2007;357:1413)	Groin pain w/ movement, better w/ rest, ↓ ROM	Common in the elderly
Trochanteric bursitis	Lateral hip pain w/ point tenderness over greater trochanteric bursa, exacerbated by gait impairment, walking & direct pressure	Middle-aged women, younger pts, runners
Meralgia paresthetica	Paresthesias (esp burning) over upper outer thigh (due to lateral femoral cutaneous nerve entrapment)	Obese or pregnant pts; DM patients; tight clothing
Referred pain & spinal stenosis	Back, hip & buttock pain 2° to lumbosacral disc & facet joint dz	Middle-aged & elderly
Occult hip fracture (AFP 2003;67:537)	Severe pain in “hip area” w/ partial wt bearing, pain w/ passive rotation	Elderly, osteoporosis, steroid use
Osteonecrosis (NEJM 2011;365:62)	Groin or nonspecific “hip area” pain often followed by thigh & buttock pain; rest & night pain common	Steroid use, EtOH, sickle cell, SLE, trauma
Gluteus medius tendinopathy	Buttock pain w/ hip abduction & rotation, pain above the greater trochanter, ⊕ Trendelenburg sign	More common in women (wider pelvis)
Piriformis syndrome	SI joint or sciatic notch pain → foot, w/o numbness/weakness; ↑on hard surface, ↓ w/ walking	Anatomic variation in sciatic nerve or piriformis muscle
Labral tear	Anterior hip/groin pain, clicking/locking of the hip	Pts w/ OA, athletes
Femoroacetabular impingement (AFP 2009;80:1429)	Chronic antero/lateral hip/groin pain worse w/ turning, ↓ ROM, ↑risk of early OA	Athletes

Less common causes of hip pain to consider: Malignancy (wt loss, nocturnal pain), septic arthritis (fevers, h/o IVDU, unable to bear wt), Leriche syndrome due to PAD (claudication sx)

Evaluation (Clin J Sport Med 2003;13:152; Orthop Relat Res 2009;467:638)

History: Location of pain (68% of pts w/ intraarticular pathology c/o groin pain), provocative/palliative factors, timing (constant pain

 

suggests infectious, inflammatory, or neoplastic etiology), medications (steroids, EtOH)

Exam: Natural gait & heel-to-toe; look for Trendelenburg/antalgic gait,

& short leg limp (youtube.com/watch?v=yluzGVcWEsg; youtube.com/watch? v=iTfDvFCPZ_w)

Squatting: Will be limited by mod-to-severe OA, bursitis, or muscle weakness FABER: Flexed, ABducted, And Externally Rotated hip may identify SI joint dysfunction Internal & external rotation:↓ rotation in pts w/ severe OA or septic arthritis Palpation of trochanteric bursa: w/ hip flexed to 90°, assess for tenderness Sensory exam: Anterolateral exam w/ ↓ or ↑ sensation in meralgia paresthetica Straight leg raise: ⊕ test elicits pain at 60° elevation

→ S1/L5 nerve root irritation Lasegue sign: Thigh is flexed & internally rotated; resisted abduction or adduction reproduces sx (stretches sciatic nerve)

Diagnostics:

Plain film: Assess for fracture if acute hip pain (typically wt-bearing AP pelvis & hip & axial cross-table film of the proximal femur) MRI: When radiographs inconclusive, for suspected fracture, osteonecrosis, infection, & tumor; radionuclide bone scan if MRI contraindicated Ultrasound: Useful to guide aspirations/injections & can also demonstrate bursitis; hip aspiration indicated if infection is suspected (should be image-guided)

Treatment

Osteoarthritis: Limit high impact activities, NSAIDs/APAP, rest, heat, stretching (see “Osteoarthritis”); Hip arthroplasty if failure of conservative Rx or significant disability. Meta-analysis shows diclofenac 150 mg QD more effective compared to other NSAIDs (Lancet 2016;387:2093); role of PT unclear (JAMA 2014;311:1987)

Bursitis: Avoid pressure over hip, bending & stairs; stretching, heat, NSAIDs/APAP, PT (for orthotic & gait eval); consider steroid injections if conservative measures fail

Femoroacetabular impingement: Rest, PT, NSAIDs/APAP, ortho referral if refractory

Labral tear: PT; ±arthroscopic surgery (Curr Rev Musculoskelet Med 2009;2:105)

Meralgia paresthetica: Self-limited; reassurance, avoid tight garments,

 

wt loss; if persistent consider gabapentin, carbamazepine, or phenytoin Osteonecrosis: Rest, wt-bearing as tolerated, pain control; referral to ortho for progressive dz or failure of conservative mgmt

Piriformis syndrome: PT, stretching, NSAIDs; consider gabapentin, TCA, steroid injection

Patient information: AFP 2009;80:1439; JAMA 2007;298:2442 (hip fx)

 

 

KNEE PAIN

Background (AFP 2003;68:917; 2015;92:875; JAMA 2001;286:1610; NEJM 2006;354:841; 2010;363:e5)

 

Differential Diagnosis of Knee Pain by Location

Anterior: Injury to quadriceps, patella, or patellar tendon; patellofemoral syndrome; OA; Inflammatory arthritis (e.g., gout)

Lateral: Lateral meniscal tear, lateral collateral ligament injury, iliotibial band syndrome

Medial: OA, anserine bursitis, medial collateral ligament injury, medial meniscal tear, tibial plateau fractures

Posterior: Effusion (e.g., popliteal/Baker cyst), DVT

Evaluation and Treatment (AFP 2003;68:917)

History: Trauma or constitutional sx, location of pain, acute/chronic, provocative/palliative factors, orthopedic hx; swelling, stiffness, instability, catching, popping, snapping sensation, sensory/motor changes; have pt point to area of pain w/ one finger

Red flags: Pain after trauma, constitutional sx, acutely disabling pain Exam: Examine both knees (asx knee as a control if unilateral), hip, & ankle; observe gait, squat, duck waddle (pt squats & moves forward);

test quadriceps, hamstring strength (youtube.com/watch?v=JWQ_a-k8qqM;

youtube.com/watch?v=wlLfNls75RY)

Inspection: Joint architecture, erythema, swelling/effusion

Palpation: Warmth (nl knee is cooler than anterior shin), vascular exam, tenderness to palpation (patella, tendons, lateral & medial joint lines, anserine bursa), pain w/ lateral displacement of patella (patellofemoral syndrome), swelling/effusion Range of motion:

 

Active & passive extension, (0–135° nl), varus & valgus instability at 0° for LCL & 30° for MCL; crepitus

Workup: Start w/ radiograph; consider U/S or MRI to evaluate meniscal, ligament tear, or other etiology if dx unclear; if effusion present, aspirate to assess for cell count, crystals, & infection

Ottawa knee rule: Plain films after acute injury to r/o fracture if any of the following: ≥55 yo, isolated patellar tenderness, tenderness at head of fibula, cannot flex to 90°, cannot bear wt for 4 steps immediately after injury & in ED; Se 98.5%, Sp 48.6% (Ann Intern Med 2003;139:575; 2004;140:121)

 

Useful Exam Maneuvers (Described for R Knee)
Name	Description
Lachman test (ACL injury) 87% sensitive, 93% specific	L hand on femur grasped just above the knee, R hand on the tibia, apply slight flexion; pull sharply toward your abdomen w/ R hand while stabilizing w/ the L hand; muscles must be relaxed; ⊕ for ACL injury if tibia feels unrestrained during sharp pull
Posterior drawer test (PCL injury) 51–86% Se	Pt supine w/ knee flex to 90°, stabilize foot by sitting on it, place hands around tibia w/ thumbs meeting along front; apply pressure backward in plane parallel to the femur; ⊕ for PCL injury w/ unrestrained backward motion
McMurray test (Meniscal injury) 53– 97% Sp	Place left hand on medial joint line w/ knee fully flexed; w/ right hand evert foot, apply valgus stress & gently flex & extend knee; ⊕ test w/ clicking around medial joint line

(JAMA 2001;286:1610; Ann Intern Med 2003;139:575)

Patellofemoral syndrome (“Runner’s knee”): Most common cause of knee pain in primary care, pts typically ♀, <45 y, p/w pain, popping/clicking/snapping going up/down stairs, rising from seated position, while running, or after prolonged sitting

Exam: Tenderness over patellofemoral joint or behind patella, reproduced on compression of patella against femur; dx of exclusion Treatment: Rest, ice, NSAIDs, PT, stretching, wt loss; quadriceps strengthening (i.e., stationary cycling); consider foot orthoses; orthopedic referral if refractory

Osteoarthritis (see “Osteoarthritis”): Pain w/ activity & relieved by rest,

 

↓ ROM, gelling/stiffness w/ inactivity, slowly progressive; crepitus; medial pain prominent; Tai chi as effective as PT (Ann Int Med 2016;165:77)

Treatment: Wt loss (if overweight), PT, APAP, NSAIDs; in surgery candidates, unilateral total knee replacement followed by nonsurgical treatment superior to nonsurgical treatment in improving pain & QOL at 1 y in pts w/ mod–sev OA (NEJM 2015;373:1597). Hyaluronate-related injectable agents are FDA- approved for treatment of OA of the knee, but efficacy is unclear & use is controversial (NEJM 2015;372:1040) Ineffective treatments: Intraarticular triamcinolone injections (JAMA 2017;317:1967); vitamin D supplementation (JAMA 2016;315:1005); lateral wedge shoe inserts

(JAMA 2013;310:722); ? glucosamine/chondroitin supplements (AFP 2015;92:875)

Anterior cruciate ligament injury: Trauma → “pop,” immediate pain; swelling (may be delayed), mechanical sx; ⊕ Lachman test, tear visible on MRI; pt cannot squat/duck waddle; ♀ at ↑ risk; ACL injury ↑ risk of OA (NEJM 2008;359:2135)

Treatment: Rest, ice, elevation, APAP, compression, PT; ortho referral if pt young, has significant instability, wishes to return to vigorous activity, or s/sx of other joint damage; rehabilitation + early ACL reconstruction = rehabilitation ± delayed ACL reconstruction (NEJM 2010;363:331)

Bursitis: Local pain on rest & motion; anserine bursa is medial & 6 cm below joint line; pain typically at night; prepatellar bursa is anterior & between patella & skin; inflammation caused by trauma/repetitive kneeling

Treatment: Compression dressing/knee pads (protection), NSAIDs, ice, PT; chronic bursitis may respond to steroid injections, aspiration

Iliotibial band syndrome: Lateral aching/burning/stinging where the iliotibial band traverses the knee, esp over lateral femoral condyle, often seen in runners, cyclists; pain may radiate to hip

Treatment: Rest, ice, NSAIDs, stretching, temporary avoidance of activities that ↑ pain; steroid injections or surgery for cases refractory to conservative Rx

Gout/pseudogout: Other joints affected, joint swollen/tender; often w/

 

effusion; crystals in joint aspirate; (see “Gout and Pseudogout”) Medial collateral ligament injury: Typically injured after twisting or hyperextension of leg; medial knee pain, pain w/ walking, twisting, pivoting

Treatment: Rest, ice, compression; NSAIDs, early mobilization as tolerated; ortho referral if knee unstable or pain/disability persists

Meniscal injury: Often asx, but can p/w mechanical sx (buckling, locking), tenderness over joint line, pain w/ twisting, ⊕ McMurray test; commonly occurs when knee twists w/ foot locked on ground; pt cannot duck waddle, tear visible on MRI (JAMA 2001;286:1610; NEJM 2008;359:1108)

Treatment: Rest, avoid activities that cause pain, ice, crutches, patellar brace, PT; exercise therapy as effective as arthroscopic partial meniscectomy for degenerative tears (BMJ 2016;354:1); arthroscopic partial meniscectomy showed no benefit compared to sham surgery for mechanical sx in pts w/ degenerative meniscus tears (Ann Int Med 2016;165:449).

Plica syndrome: Irritation/injury of the plica, a component of synovial tissue → medial knee pain & popping sensation w/ flexion in runners/athletes or after trauma; pain ↑ w/ flexion of knee or sitting; (Curr Rev Musculoskeletal Med 2008;1:53)

Treatment: Rest, ice, stretching, NSAIDs, PT; arthroscopic surgery may be curative

Popliteal cyst: Cyst in popliteal fossa due to ↑ pressure in joint 2° to joint disease (OA, RA, meniscal injury); mass in popliteal fossa ↓ w/ flexion at 45°. May consider arthrocentesis/steroid injection

Stress fracture: Pain after an ↑ in activity; activity worsens pain, relieved by rest; may not be visible on plain film in 1st 2 wks, but may be seen on MRI (AFP 2011;83:39)

Treatment: Avoid activities causing pain, NSAID, bracing, shoe inserts for cushioning, calcium/vitamin D supplementation, PT; high-risk fractures (i.e., patella, anterior tibia) should be referred to ortho

Tendinitis: Pain going up/down the stairs, commonly seen in runners

Patient information: AFP 2007;75:204; JAMA 2007;297:1740

 

SHOULDER PAIN

 

Background (AFP 2016;94:119; Ann Int Med 2015;162:ITC1-15; BMJ 2005;331:1124)

Epidemiology: In young pts, often related to injuries (e.g., GH joint instability or overuse); in older pts, more commonly rotator cuff tendinitis, tears, adhesive capsulitis, & OA

Evaluation (AFP 2000;61:3079; 3291; 2008;77:453; JAMA 2000;284:1559; 2004;292:1989;

2013;310:837)

 

Differential Diagnosis of Shoulder Pain
Disorder	Presenting Features
Cervical disease	Pain radiating below elbow, ↓ C-spine ROM
Labral tear	Fall on outstretched arm or repetitive overhead loading activities; p/w deep shoulder pain catching sensation, instability
RC impingement & tendinopathies	Anterolateral pain worse w/ abduction &/or reaching, typically in context of repetitive activity at or above level of shoulder
RC tear (NEJM 2008;358:2138)	Pain & weakness w/ lifting shoulder (i.e., combing hair); suspect full thickness tear if pain w/ abduction 60–120° (painful arc sign), weakness w/ external rotation & ⊕ drop-arm test (below)
Biceps tendinitis	Gradual onset anterior shoulder pain typically w/ heavy lifting
Adhesive capsulitis (AFP 2011;83:417)	Progressive, ↓ active & passive ROM, w/ pain, often at night in pts w/ DM, thyroid disease, trauma & restricted ROM (i.e., stroke); plain films & MRI typically nl
AC or GH Joint Osteoarthritis (AFP 2008;78:605)	>50 y, pain w/ activity, stiffness, ↓ ROM, crepitus w/ arm elevation; may affect AC (pain w/ elevation of arm >90°) or GH joint (pain w/ external/internal rotation when arm is in neutral position)
GH joint instability	Shoulder pain in throwing athletes
Other (AFP 2004;70:1947)	Sternoclavicular pain; fracture; MI; inflammatory/septic arthritis; UE DVT; lung malignancy; avascular necrosis; PMR
RC, rotator cuff; GH, glenohumeral; AC, acromioclavicular

Exam: Examine C-spine; palpate AC, SC, & GH joints, biceps tendon, subacromial bursa, trapezius muscles (youtube.com/watch?v=g8xtOqZFTwo; youtube.com/watch?v=GxswYxiUdzI)

 

Distinguish pain w/ active motion (muscular or tendon) from passive motion (concerning for joint involvement) Distinguish rotator cuff tear from impingement or bursitis by assessing weakness w/ external rotation & abduction Assess sensation, reflexes, & motor strength for nerve impingement

 

Shoulder Exam Maneuvers
Test	Maneuver (AFP 2000;61:3079)	Positive in
Apley scratch test	Touch superior & inferior aspects of opposite scapula	Rotator cuff injury or OA
Drop-arm test	Cannot smoothly adduct arm from shoulder to waist	Rotator cuff tear
Neer test	Fully pronate arm then place arm in full flexion	Subacromial impingement
Hawkin test	Elevate arm forward to 90° while forcibly internally rotating the shoulder
External rotation	Flex both elbows to 90° while the examiner provides resistance against external rotation	Teres minor & infraspinatus tear or impingement
Empty can/full can test	90° elevation in the scapula plane & full internal rotation (empty can) or 45° external rotation (full can); examiner applies downward pressure at wrist	Supraspinatus tear or impingement
Yergason sign	Elbow flexion to 70°; pt forces supination against resistance	Biceps tendinitis

Workup: Imaging (beginning with radiograph) may be useful if hx, sx, or exam inconsistent with RC tendinopathy (w/o tear). In pts w/ persistent shoulder pain attributed to RC tendinopathy despite w/ 2–3 mos of conservative Rx, obtain radiograph (AFP 2000;61:3291; J Am Coll Radiol 2011;8:602)

Radiograph: True AP (glenohumeral joint) & axillary lateral & Y view (AC joint) MRI w/o contrast: 95% Se & Sp in RC tears; may identify abnormality in asx pts; indicated w/ persistent pain, unrevealing plain films, nonspecific H&P

Arthrography: Invasive; good at identifying complete RC tears, labral tears, or capsulitis Ultrasound: Good for complete RC tears, bursitis, but operator-dependent CT: May be useful for

 

subtle dislocation, prosthetic joints

Treatment (AFP 2003;67:1271; 2008;77:493)

General approach: For most shoulder pain in older adults without e/o joint instability, marked muscle weakness/atrophy, or infection, initial trial of NSAIDS/APAP±PT (if↓ ROM or strength) for 2–4 wks; consider steroid injection; if no improvement, consider ortho referral

Shoulder impingement: Ice, rest, PT, glucocorticoid injection in refractory cases

Adhesive capsulitis: PT; glucocorticoid injection; surgery referral for manipulation under anesthesia or release in refractory/severe cases Osteoarthritis: NSAIDs/APAP, PT, glucocorticoid injections

Rotator cuff tears: Surgical repair of acute, complete tears; rest, ice, NSAIDs, PT, glucocorticoid injection for partial thickness & chronic full thickness tears w/ surgical referral in refractory cases

Dislocation or fracture: Relocation & immobilization but w/ early ROM to prevent adhesive capsulitis, PT

When to refer: Urgent eval needed in fracture, dislocation, separation, rotator cuff tear, joint instability/infection; ortho referral if gross deformity or joint instability as joint separation may require surgery; injury in high- functioning athlete; suspect full labral tear or full thickness RC tear; if sx not improving w/ 3 mos of conservative mgmt & PT

Patient information: AFP 2008;78:612; 2011;83:423

 

 

ELBOW PAIN

Background (AFP 2014;89:649)

 

Etiologies of Elbow Pain

Lateral elbow: Lateral epicondylitis (“tennis elbow”) is caused by damage to extensor carpi radialis brevis & longus tendons; worsened by repetitious use of forearm/wrist, hand shaking; referred pain worsened by movement of shoulder/neck

Medial elbow: Medial epicondylitis (“golf elbow”) is caused by damage to flexor carpi radialis tendon; worsened by contraction of wrist flexors (i.e., lifting); injury to ulnar collateral ligament (often due to throwing injury); ulnar neuropathy or entrapment

Elbow joint pain: Pain w/ supination/pronation as well as extension

 

Olecranon bursitis: Swelling/fullness over the olecranon as opposed to in the humeroulnar or humeroradial joint

Throwing injury: Ulnar collateral ligament injury

Evaluation

History: “Popping” sound or immediate swelling suggests a soft tissue injury or bleeding into the joint; locking, catching, or joint instability; numbness or tingling; prior injury; hobbies involving joint (i.e., pitching, golf); nocturnal awakening

Exam: Flexion, extension, supination, pronation of joint (youtube.com/watch?v=rNXZlbamJuY); percussion of ulnar nerve at ulnar groove, cubital tunnel, & Guyon canal to test for ulnar neuropathy Workup: Elbow radiographs (AP, lateral, oblique); MRI if soft tissue injury or ulnar neuropathy suspected; musculoskeletal U/S; EMG if ulnar neuropathy suspected

Treatment

Epicondylitis: NSAIDs (systemic or topical), counterforce bracing, physical therapy; splinting generally not effective & may worsen sx; steroid injections may temporarily improve sx but do not lead to improved long-term outcomes (JAMA 2013;309:461; Lancet 2002;359:657; 2010;376:1751); benefit of autologous blood injection unclear (PM R 2016;8:780); orthopedic referral for refractory sx

Olecranon bursitis: Joint protection; fluid aspiration along w/ an elbow orthosis; surgical excision of bursa if chronic

Ulnar neuropathy at elbow: Splinting to limit flexion beyond 45, foam elbow pads, activity modification, avoidance of provocative factors (leaning on elbows, prolonged elbow flexion), ulnar nerve decompression

 

HAND DISORDERS

Evaluation

History: Characteristic of given condition (below); hx injuries; systemic dz

Exam: Examine skin, muscle mass, joints, nails, & overall posture of the digits & wrist, then compare to the contralateral side; grip strength;

 

joint palpation; Range of motion: Test finger & thumb ROM by asking pt to actively extend all digits & then forming a composite fist; general alignment of fingernails & overlap of fingertips in fist

Imaging: Radiographs after trauma; imaging rarely useful for common dx above

 

Common Nontraumatic Hand Disorders
Disorder	Description	Presentation	Treatment Options
Osteoarthritis (Arthritis Rheum 1990;33:1601) (see “Osteoarthritis”)	Hand pain, characteristically involving PIP, DIP & CMC joints Heberden nodes (bumps created by bone spurs); PIP 2nd & more variable (Bouchard nodes)	Pain worsened w/ activity (opening jar, writing), relieved by rest; gelling/stiffness w/ inactivity; morning stiffness <30 min	Heat; splinting for CMC OA Topical NSAIDs, topical capsaicin, oral NSAIDs (if no contraindication); consider Tramadol (Arthitis Care Res 2012; 64:465)
Dupuytren Contracture	Genetic fibroproliferative disease (autosomal dominant, incomplete penetrance); collagen within palmar fascia proliferates, thickens, & contracts	Painless palmar skin nodules or cords, which sometimes cause flexion contracture (inability to straighten finger)	Nonoperative: Observation of isolated nodules; percutaneous needle fasciotomy, or injectable collagenase for substantial contractures Surgery: Excision of diseased palmar fascia (fasciectomy)
Trigger finger (Stenosing tenosynovitis)	Thickening of the flexor tendon & A1 pulley of the flexor sheath	Sometimes painful snapping (triggering) at PIP joint w/ active motion; reluctance to form fist; tender A1 pulley nodule & triggering open from tight fist	Nonoperative: NSAIDs, splinting; corticosteroid injection into the tendon sheath (works ~50% of the time, can take 2 mos to show efficacy) Surgery: Release of digital A1 pulley
De Quervain tendinopathy	Thickening & swelling of the tendons of the 1st extensor	Tenderness, pain, & swelling at radial aspect of wrist; ⊕ Finkelstein test (pain	Nonoperative: NSAIDS, thumb spica wrist splint, corticosteroid injection in the 1st dorsal

 

	compartment	w/ radial deviation w/ thumb in fist)	compartment Surgery: Release of 1st extensor compartment
Ganglion cyst	Mucin-filled synovial cyst	Painless mass, Δ in size, characteristic locations: dorsal & volar-radial wrist; dorsal DIP (assoc w/ OA); over A1 pulley (retinacular ganglion cyst)	Nonoperative: Observation, as many spontaneously resolve; avoid aspiration (clear, gelatinous fluid) on volar surface as often abuts radial artery Surgery: Excision (5– 10% recurrence rate)
Carpal tunnel syndrome (idiopathic median neuropathy in carpal tunnel)	–  Compression of median nerve → sensory & motor neuropathy –  Indications for Electrodiagnostic testing debated: Used to (1) R/o CTS in reports of paresthesias where it is a possible but less likely dx, (2) Provide objective data to manage postoperative expectations in pts w/ severe dz	– Transient numbness in median nerve distribution w/ wrist flexion (sleeping, driving) → eventual constant numbness, thenar atrophy, & weakness – Provocative factors: Wrists flexion/extension; nocturnal worsening since wrist often flexed during sleep – Provocative maneuvers: see below	Nonoperative: Splinting: holds wrist in neutral position; steroid injection into carpal tunnel; NSAID trial. Surgery: Indicated if failure of nonoperative Rx or median nerve denervation demonstrated on clinical or electrodiagnostic testing (JAAOS 2009;17:389). Severe dz w/ constant numbness & atrophy is permanent; the sx from moderate disease usually disappear
Cubital tunnel syndrome (idiopathic ulnar neuropathy in cubital tunnel)	Compression of ulnar nerve at elbow → neuropathy	Initially transient then constant numbness of 4th & 5th digits; weakness & atrophy of 1st dorsal interosseous muscle; medial elbow pain	Nonoperative: Brace or pillow to limit elbow flexion at night; avoid leaning on elbow Surgery: Mod to sev neuropathy; progressive symptoms & signs less than 6 months duration despite conservative measures. Benefit may be less for patients with chronic involvement

 

CARPAL TUNNEL SYNDROME (AFP 2011;83:952; 2016;94:993; Ann Int Med

2015;163:ITC1; BMJ 2007;335:343; JAMA 2000;283:3110)

 

 

 

Definition: Peripheral mononeuropathy of median nerve at level of wrist

Anatomy: The carpal tunnel, made up of the carpal bones & the transverse carpal ligamment, keeps the flexor tendons & the median nerve in position when the wrist is flexed. Median nerve divides within carpal tunnel into (1) recurrent motor branch to thenar eminence (→ thumb weakness) & (2) digital sensory cutaneous branches to thumb, index, middle, & radial half of ring finger (→ hand tingling/numbness) Epidemiology: Estimated 1–5% of entire population (JAMA 1999;282:153); very common dz, ↑ risk w/ age; many pts don’t seek medical attention Risk factors: Evidence that it is related to environmental factors is low quality & inconsistent.

DDx: Cubital tunnel syndrome, neuropathy, cervical radiculopathy History: Intermittent numbness & tingling of the thumb, index, middle, ring finger (patient may describe as the “entire hand”); Classic: Awakens patient from sleep or present on waking; not a painful condition except that the numbness can be very intense & experienced as pain; patients may report aching in the forearm & arm

Provocative factors: Wrist flexion/extension; nocturnal worsening since wrist often flexed during sleep Palliative factors: Shaking or wringing hands, placing hand dependent at side of bed Hand sx

 

diagram: Pts mark specific location of sx on self-administered diagram depicting dorsal & palmar aspect of hands/arm; results reflect likelihood of syndrome

Exam: (J Am Acad Orthop Surg 2009;17:389)

Sensory: Affects threshold sensibility initially (light touch measured w/ Semmes–Weinstein) then discriminatory sensibility later (measure with two-point discrimination) Motor: In severe dz only: weakness of thumb palmar abduction against resistance; atrophy (or concavity) of thenar muscles Provocative maneuvers: Test is

⊕ if paresthesias (not pain) occur in median nerve distribution; combining results from >1 test can increase Se/Sp

 

Provocative Tests for Carpal Tunnel Syndrome (J Hand Ther 2004;17:309)
Test	Maneuver	Se	Sp
Phalen	Wrists flexed for 30 s	68%	73%
Tinel	Tap on median n. proximal to carpal tunnel to elicit paresthesias	50%	77%
Durkan	Press both thumbs over transverse carpal ligament for 30 s	64%	83%

Diagnosis: Clinical dx is suspected w/ report of classic sx

Workup: Indications for electrodiagnostic testing debated: used to (1) r/o CTS in reports of paresthesias where it is a possible but less likely dx, (2) provide objective data to manage postoperative expectations in pts w/ severe dz; imaging generally not useful in dx

Nerve conduction studies (NCS): Document location & severity of median neuropathy; standard tests include median sensory NCS across the wrist w/ distal latency compared to ulnar & radial nerve, & median motor NCS from abductor pollicis brevis (Neurology 1993;43:2404); 85% sensitive, >95% specific Electromyography (EMG): Excludes other peripheral neuropathies

Treatment:

 

Preferred Nonsurgical Treatment Modalities
Modality	Description
Splinting	Brace at night holds wrist neutral to prevent waking w/ numbness; improvement

 

	usually occurs within 2 wks
Steroid inj	Single injection into carpal tunnel; methylprednisolone injections ↓ pain at 10 wks & risk of surgery at 1 y compared to placebo (Ann Int Med 2013;159:309)

Modalities w/ insufficient evidence: Carpal bone mobilization; nerve gliding; yoga; ergonomic keyboard; oral steroids, ultrasound Modalities w/ no significant benefit: Diuretics, vitamin B6, magnet therapy, laser acupuncture, exercise (Neurology 1998;51:390)

Surgery: Indicated if failure of nonoperative Rx or median nerve denervation demonstrated on clinical or electrodiagnostic testing (JAAOS 2009;17:389)

Carpal tunnel release: Decompression of the carpal tunnel through open or endoscopic complete division of the transverse carpal ligament Postoperative care: No indications for wrist immobilization or rehabilitation Complications: Nerve injury rare but problematic; incomplete release of transverse carpal ligament very uncommon & difficult to distinguish persistent from recurrent sx Prognosis: Severe dz w/ constant numbness & atrophy is permanent; the sx from mod disease usually disappear, but the NCV/EMG don’t return to nl

Patient information: AFP 2011;83:965; JAMA 2011;306:2283

CUBITAL TUNNEL SYNDROME (AFP 2013;87:568)

 

Anatomy: Ulnar nerve formed by C7/8/T1, passes near medial epicondyle of humerus (at elbow) & between pisiform/hamate bone in wrist

History: Ulnar neuropathy at elbow → paresthesias in 4th & 5th fingers, worsened by elbow flexion

Exam: Tinel test at elbow (percuss elbow → sx); neck motion to r/o C8/T1 radiculopathy

Workup: NCS or EMG to confirm dx & localize lesion

Nonoperative treatment: Brace or pillow to limit elbow flexion at night Surgery: Nonoperative mgmt insufficient; constant numbness, weakness, atrophy

 

FOOT & ANKLE DISORDERS               

 

Evaluation (BMJ 2003;326:1)

History: Inciting injuries, specific location of pain, functional impairment, chronicity of sx, exacerbating conditions; medical hx incl DM, arthropathies, vascular dz, neuropathy

Exam: Assess gait, ability to toe rise; look at ankle alignment from behind; assess hindfoot alignment & arch (cavus vs. neutral vs. planus); assess for swelling & bruising; visually inspect pedal skin & nails for soft tissue breakdown or asymmetry in color, temp, texture; palpate foot for areas of tenderness, masses or swelling; assess active ROM, incl tibialis anterior (ankle dorsiflexion), gastrocsoleus (plantarflexion), inversion w/ the foot plantarflexed (posterior tibialis), eversion w/ the foot dorsiflexed (peroneals); check tenderness & passive ROM of tibiotalar (ankle) joint (dorsi & plantarflexion), subtalar joint (hindfoot inversion & eversion), transverse tarsal joint, Lisfranc joint (plantarflexion of 1st metatarsal & adduction), & MTP joints; palpate pulses (dorsalis pedis & posterior tibial) & capillary refill; test reflexes & sensation to light touch & pinprick (Semmes–Weinstein 5.07 monofilament)

Imaging: Radiograph of ankle should include AP, lateral, mortise; radiograph of feet should include AP, lateral, oblique; all x-rays should be wt-bearing unless assessing for fracture or pt unable to bear wt; stress fracture may take 2–6 wks to be apparent on radiographs; MRI more sensitive

Ottawa rules: Ankle radiograph for ankle injury if: Pain near malleoli + either (1) inability to bear wt (4 steps) immediately after injury & at eval or (2) bone tenderness at posterior edge/tip of either malleolus; Foot radiograph for injury if: Pain at midfoot + either (1) inability to bear wt (4 steps) immediately after injury & at eval or (2) bone tenderness at navicular bone or base of 5th metatarsal (Se nearly 100%, Sp 30–50%)

ATRAUMATIC FOOT PAIN (AFP 2007;76:975; 2011;84:676; NEJM

2004;350:2159)

 

Calcaneal bursitis: Infra-or retrocalcaneal pain in SC or subtendinous bursa; Dx: Tenderness & swelling, pain w/ supracalcaneal squeeze; DDx: Achilles tendinopathy; Tx: Time, boot, NSAIDs, ice

Hallux rigidus: OA of the 1st MTP joint; Dx: Sx include ↓ motion, crepitation, tenderness, ✓ radiographs; Tx: Orthotic w/ a Morton’s extension to shield the 1st MTP joint, stiff sole or rocker sole shoe; 1st MTP injection, surgery

Morton (interdigital) neuroma: Irritation of digital nerve usually in 3rd or 4th web space; burning pain in webspace ± numbness of involved digits; Dx: Reproduction of sx w/ pressure in the web space; Mulder click—palpable click between metatarsal heads elicited by compressing forefoot; DDx: Stress fracture, MTP synovitis; Tx: Metatarsal pad to shield forefoot; steroid injection or surgical excision in refractory cases Plantar fasciitis: Medial/plantar heel/arch pain ↑ in AM & w/ standing after prolonged sitting (Ann Intern Med 2012;156:ITC-1) appears to be a self- limiting enthesopathy

Risk factors: Middle-aged; ♀ gender, obesity, tight gastrocnemius

Dx: Tenderness at plantar fascia origin from calcaneus; DDx: Tibial nerve compression aka tarsal tunnel syndrome (Tinel sign behind medial malleolus & plantar numbness), Baxter’s neuropathy (pain more medial & less plantar), insertional Achilles tendinitis, calcaneal stress fracture (squeeze test), heel pad pain (pain more posteriorly at center of heel pad), posterior tibial tendinitis (palpate tendon behind medial malleolus), plantar fibromatosis Tx: NSAIDs, ice, dorsiflexion night splint, Achilles & plantar fascia stretches, silicone gel heel cups, PT; steroid injection usually avoided; wt loss; surgery in refractory cases

Cysts/ganglions: Pain w/ wt bearing, friction; Dx: Clinical, transillumination, U/S, MRI; Tx: If painful – aspiration (~50% recurrence), surgical excision (~10% recurrence)

Bunions: 1st MTP joint w/ medial prominence; pain onset gradual, progressive, ↑ w/ ROM, weight-bearing, shoe pressure; assoc w/ RA, female, ↑ age, FHx, shoewear w/ narrow toe box; Tx: APAP/NSAID’s, shoewear modification (wide toe box), shoe stretching (ball & ring shoe stretcher), bunion brace, toe spacers, surgical correction only for refractory pain or deformity severe enough to prevent reasonable shoewear (i.e., not for cosmesis)

 

Pes planus (flat foot) Dx: Clinical, plain films, hindfoot valgus & low arch, unable to single leg rise. Often have medial ankle pain →suspect adult-acquired flat foot 2/2 posterior tibialis pathology; Tx: Boot for acute PTT tendinitis then orthotic w/ medial arch support (off the shelf vs. custom), PT for PTT conditioning; surgical correction vs. fusions if assoc w/ arthritis

Pes cavus (high arch): Dx: Clinical – high arch ± varus hindfoot, plain films; often assoc w/ neuromuscular disease (CMT); can lead to recurrent ankle sprains, peroneal tendon tears, 5th MT fx’s; Tx: Lateral posting orthotics; surgery in refractory cases

Plantar fibromatosis: Foot manifestation of Dupuytren disease; genetic (autosomal dominant; British Isles & Scandinavia); firm, palpable SC plantar nodules, continuous w/ plantar fascia; can be painful; most pts do not bring this problem to the attention of a doctor; Tx: Accommodative orthotics; surgery doesn’t work well

SKIN AND NAIL DISORDERS (AFP 2001;63:677; 2002;65:2095; 2009;79:303;

2012;85:779)

 

Hyperkeratotic: Pressure induced (corns) vs. shear-induced (calluses); assoc w/ neuropathy, deformity, activity, middle to advanced age; DDx: Verruca plantaris, dermatofibroma, hypertrophic scar, porokeratosis; Tx: Topical keratolytics (lactic acid 12% lotion, urea 20– 40% cream, footwear modification)

Verruca: Virally-induced (HPV) hyperkeratotic lesions w/ punctate bleeding, disrupted skin lines, pain w/ compression; ↑ in youth, immunosuppressed, skin trauma, gym/pool use; Tx: Topical acids/vesicants (see “Benign Skin Lesions”)

Blisters: Serous/blood filled vesicles/bullae; ↑ w/ friction, shear, deformity, activity, tight shoes, hyperhidrosis, neuropathy; Tx: Neoprene insoles, acrylic socks, off-loading, aspiration (do not de-roof); if de-roofed, hydrocolloid dressing (Sports Med 1995;20:3)

Tinea pedis (Athlete’s foot): Rubor, scaling, desiccated vesicles, moccasin distribution, maceration fissuring, pustules, malodor; Dx:

+KOH; DDx: Eczema, xerosis, dermatitis; Tx: Topical antifungal (see

“Tinea”)

 

Xerosis cutis: Skin dry, rough, pruritic, fissuring; ↑ w/ age, DM, autonomic dysregulation; Tx: Topical emollients, barrier creams; discourage prolonged, frequent, or hot foot soaks

Ingrown nail (Onychocryptosis): Nail plate encroaching upon nail fold w/ pain, swelling, bleeding/drainage, hypertrophy of nail fold ± paronychia (see below); assoc w/ HAV, tight footwear, improper trimming; Tx: Foot soaks, wide shoe, Podiatry referral Onychodystrophy: Δ in nail plate morphology ± pain; ↑ w/ age, DM, runners; Hutchinson sign: Brown/black pigmentation of nail assoc w/ melanoma

Onychomycosis: Fungal nail infection; onychodystrophy + nail erosion; ↑ w/ DM, immunocompromised, ↑ age, nail salon use, trauma, tinea pedis; Dx: +KOH, +PAS; Tx: Podiatry referral, antifungal tincture (ciclopirox), PO terbinafine (✓ LFTs); see “Tinea”

Paronychia: Nail fold infection assoc w/ onychocryptosis; erythema,

warmth, edema, purulent d/c, pain; Tx: Saline soaks BID, topical antiseptic, consider oral abx, prompt podiatry referral

Nail contusion: Subungual hematoma/seroma s/p stubbing or crush injury; if pain in toe, obtain plain film; DDx: Glomus tumor (benign subungual vascular lesion); Tx: If no fracture, Podiatry referral; if fracture + nail bed laceration, podiatry/ortho referral

FOOT & ANKLE TRAUMA (AFP 1999; 59:2156;2003;68:2413;2007;76:817;2016;93:183)

 

Achilles tendon rupture: “Popping” & sudden onset of posterior ankle pain

Dx: Ecchymosis & palpable deficit at Achilles tendon, Thompson test

⊕ (no plantarflexion of foot w/ calf squeeze – compare to other side), check resting dorsiflexion of both feet when prone w/ legs in the air; MRI or U/S rarely needed Tx: Referral to ortho, in the interim splint in 20° of plantar flexion (not neutral): Non-op vs. surgery

Fractures: High index of suspicion if pain onset acute, ↑ age, osteopenia, neuropathy, hx Fx, smoking, ± trauma; Dx: Tenderness, difficulty w/ weight-bearing, edema, ecchymosis, plain films (if ⊖, could

 

still be stress Fx).

Ankle fracture: Key is the stability of the ankle joint. If stable, can be managed nonoperatively w/ splint/boot, elevation, APAP; if joint unstable usually requires surgery; weight-bearing radiographs help determine joint stability Indications for orthopedic referral for metatarsal fractures: Open fractures, fracture + dislocation, multiple metatarsal fractures, 2nd–5th metatarsal fracture w/ ≥3 mm displacement, ≥10° angulation in dorsoplantar plane; first metatarsal fracture w/ any displacement or angulation 5th Metatarsal: Often reported as an ankle sprain because it occurs w/ ankle inversion; 3 zones of proximal 5th MT fx’s: Zone 1 – tuberosity avulsion Fx from peroneus brevis; Tx: WBAT in boot; Zone 2 aka “Jones Fx” involves the articulation at the base of the 4th & 5th MT’s; notoriously slow to heal; Tx: NWB in boot or cast; Zone 3 – Often proximal shaft stress fractures; Tx: NWB in boot; distal 5th MT fx aka “Dancer’s Fx,” acute Tx: WBAT in boot; check all patients for Vit D deficiency; check radiograph to document healing Metatarsals other than 5th: If acute injury, suspect a Lisfranc fracture/dislocation injury (see below); o/w often stress fractures; Tx: WBAT in boot; check for Vit D deficiency; healing time 4–6 wks; check radiograph to document healing Sesamoid: Pain under 1st MTP joint; Tx: WBAT in boot then orthotic w/ 1st metatarsal head recession Calcaneus: Heel pain ± deformity s/p fall/jump; pain w/ lateral squeeze, Mondor sign (ecchymosis extending to sole); assoc w/ lumbar spine fx’s; Tx: bulky jones splint & ortho referral for possible surgery; stress Fx may present like plantar fasciitis, however unlike plantar fasciitis, tenderness on sides of calcaneus present (+ squeeze test) Toes: Toe alignment & joint involvement are key

Tx: Boot or post-op shoe; buddy toe taping × 4–6 wks for lesser toe fractures; if big toe, intraarticular or toe malaligned then Podiatry/Ortho eval

Lisfranc fracture/dislocation: Often high energy injury → damage to Lisfranc ligament (between medial cuneiform & base of 2nd MT) → midfoot pain/swelling, plantar ecchymoses; must have a high index of suspicion & cannot r/o unless have wt-bearing radiographs (may only displace w/ wt bearing); if pt unable to wt bear, repeat radiographs in 1–

 

2 wks when pt able to wt bear; if missed can lead to midfoot collapse & arthritis; Dx: Widening of space between medial cuneiform & base of 2nd MT (compare to other side), 2nd metatarsal step off, fleck sign (bony fragment at base of 2nd metatarsal), ± metatarsal fracture on plain films, CT, MRI; Tx: NWB, splint, Orthopedic eval

Plantar plate injury (Turf toe): Dorsiflexion injury causing attenuation of 1st MTP joint plantar plate w/ pain, swelling, ecchymosis; DDx: Gout, sesamoid injury, 1st MTP arthritis; Dx: Clinical, MRI; Tx: Cast or boot, Podiatry/Orthopedic referral (Am J Sports Med 2011;29:1)

ANKLE PAIN (AFP 2009;80:1107; 2012;85:1170)

 

Achilles tendinitis: Can be insertional or noninsertional, assoc w/ fluoroquinolone use, may have a bump on Achilles tendon; pain w/ exercise, relieved by rest, radiograph may show insertional calcification (spur); Tx: Rest, ice, APAP/NSAID’s, dorsiflexion night splint, heel lift, Achilles stretching, PT for eccentric stretching protocol; surgery for refractory cases

Ankle sprain: Low ankle sprain—inversion injury; high ankle sprain – eversion injury; limited wt bearing, swelling, ecchymoses; Tx: Rest, Ice, Compression, Elevation; NSAID’s; period of rest & immobilization in boot or brace (1–2 wks) then start PT for peroneal strengthening & proprioception. If no improvement after PT consider MRI

Patient information: AFP 2011;84:686; JAMA 2003;290:1542 (plantar fasciitis); JAMA 2010;303:188 (Achilles tendinopathy); www.AOFAS.org/footcareMD

 

FIBROMYALGIA

Background (Arthritis Care Res 2010;62:600; JAMA 2014;311:1547; J Rheumatol

2007;34:1415)

Definition: Generalized pain amplification w/ widespread musculoskeletal pain & fatigue, thought due in part to aberrant central pain processing; sleep disturbance, anxiety, & depression

 

contribute/exacerbate sx

Epidemiology: Affects 2–5% US adults, ♂:♀, 7:1; common comorbidity of rheumatic dz (e.g., RA, SLE)

Differential diagnosis: Rheum dz (SLE, RA, Sjögren, spondyloarthritis, PMR), malignancy, drug toxicity (i.e., statins), OSA, hypothyroidism, small fiber neuropathy

Evaluation (Arthritis Rheum 2010;62:3101; Mayo Clin Proc 2011;86:457)

History: Diffuse (bilateral, upper/lower body) migratory pain, often affecting joints & soft tissue between joints that may be worsened w/ touch/tight clothes; fatigue, sleep disturbance, anxiety, depression, cognitive difficulties, stiffness, HA, pelvic, abdominal wall & chest wall pain; sx of neuropathy; hyperresponsiveness to light, odor, noise; screen for depression, anxiety, sleep apnea, other sleep disturbance Exam: Often w/ diffuse tenderness, especially in certain trigger points Findings inconsistent w/ fibromyalgia: Synovitis, rash, abnl labs (e.g.,↑ESR/CRP), focal neuro findings (numbness, weakness) Workup: Labs not necessary to confirm dx, but useful to r/o other dz; consider ESR, CRP, Chem-12, TFTs, CBC, vit D; consider iron studies, B₁₂ (based on hx & PE)

Not recommended: ANA, RF, CCP unless H&P suggestive or if ↑ ESR/CRP

Prognosis: Important to acknowledge the pain may not completely resolve

 

 

 

Treatment (AFP 2015;91:472; Ann Rheum Dis 2017;76:318)

First Line:

1. Education: About dx, tx, prognosis, reassure about benign nature, validate pain/sx; education may need to occur over several visits
2. Address comorbidities: Sleep disturbance/insomnia (see “Insomnia”), anxiety (see “Anxiety”), depression (see “Depression”); consider cognitive behavioral therapy for comorbidities Physical activity: Tai Chi more effective than wellness education + stretching (NEJM 2010;363:743); consider acupuncture, massage, yoga; cognitive behavioral therapy • When to refer to rheumatology: Uncertain dx, unusual sx, abnl labs

Pharmacologic: If persistent/sev sx despite first-line tx; no clear guidance for one agent over another; Fibromyalgia should never be treated w/ opioids, which can amplify pain; consider starting w/ amitriptyline or cyclobenzaprine; consider combination therapy; among antiepileptics, only pregabalin assoc w/ meaningful reduction in pain

(JAMA 2014;312:182)

Prominent fatigue: Consider duloxetine or milnacipran in AM

Sleep disturbance: TCA or pregabalin at night helpful

Patient information: cfidsselfhelp.org; treatcfsfm.org, JAMA

 

2014;311:1577

 

Fibromyalgia Treatments
Drug	Dosing	Particular Benefit	Adverse Reactions
Amitriptyline (TCA)	Start 5–10 mg QHS, ↑ to 25–50 mg QHS	Sleep disturbance	Constipation, dry mouth, ↑ wt ↓ concentration. QHS dosing may improve tolerability
Cyclobenzaprine	Start 10 mg QHS, ↑ to 10 mg QAM & 20–30 mg QHS	Sleep disturbance, myalgia
Pregabalin	Start 75 mg BID, ↑ to 150–225 mg BID	↓ Pain vs. placebo	Dizziness, dry mouth, ↑ wt, somnolence
Duloxetine (SNRI)	Start 30 mg/d, ↑ to 60 mg/d		Nausea, dry mouth, somnolence, fatigue
Milnacipran (SNRI)	Start 12.5 mg/d, ↑ to 50 mg BID		Nausea, HA, dizziness, palpitations
Gabapentin	Start 100 mg QHS, ↑ to 600 mg TID	May be easier to get coverage for than pregabalin	Sedation, dizziness, lightheadedness, ↑ wt

 

 

GOUT AND PSEUDOGOUT

 

GOUT

 

Background (AFP 2007;76:801; Arthritis Care Res 2012;64:1431; Lancet 2016;22:2039)

Pathophysiology: Acute gout attacks are due to deposition of monosodium urate (MSU) crystals in joints, bones, & soft tissue which can precipitate intermittent inflammation. Asx hyperuricemia → Acute intermittent gout → Increased frequency of attacks → Chronic tophaceous gout; tophi (collections of MSU deposits) are a pathognomonic feature of gout; common areas include the pinna, olecranon bursa, Achilles, & joints

Anatomy: Typical joints include 1st MTP (“podagra”), other MTP joints, ankles, knees, & sometimes fingers, but may be anywhere

DDx includes septic arthritis, OA, RA, cellulitis, psoriatic arthritis,

 

sarcoidosis; low threshold to aspirate (see “Joint Pain”)

Risk factors:↑ age, M > F (7–9:1); consumption of red meat, shellfish, EtOH; meds (ASA, thiazide & loop diuretics), trauma/surgery, hospitalization

Asymptomatic hyperuricemia: Pts should be assessed for gouty arthritis, urolithiasis (see “Kidney Stones”), & kidney damage (see “Chronic Kidney Disease”); pts w/ asx hyperuricemia do not require tx

Evaluation (AFP 2014;90:831; JAMA 2003;289:2857; 2012;308:2133; NEJM 2003;349:1647)

History: Intermittent, acute onset of painful, erythematous, warm, swollen joint; w/ time, episodes often evolve from monoarticular → polyarticular flares; w/o active Rx, almost always resolves in days to weeks

Exam: Synovitis (erythema, swelling, tende, reduced ROM), inspect for tophi (NEJM 2012;366:e6)

 

 

 

Workup: Joint fluid w/ 3 C’s: Cell count (WBCs often 2K–60K/µL, but can be >100K), Cx (⊖), & crystal analysis w/ strongly negatively birefringent needle-shaped crystals (monosodium urate crystals, see below); ideally, Dx will be made based on joint aspirate, however clinical criteria exist (Ann Int Med 2017;166:52; JAMA 2012;308:2133)

Imaging: Radiographs to evaluate for erosions; Ultrasound findings (e.g., double-contour sign) may be observed by skilled ultrasonographer & can assist w/ dx; Dual-Energy CT (DECT) reveals MSU crystal deposition (Ann Rheum Dis 2015;74:1868) Serum uric acid:↑ UA is supportive but not diagnostic; during acute

 

flares, UA can be falsely low; only 22% of pts w/ UA >9 have sx so not specific (Am J Med 1987;82:4210); all pts w/ gout at some point have

↑ UA, however not all pts w/ ↑ UA develop gout

Treatment (Ann Intern Med 2016;165:ITC-1; 2017;166:37; 58; Arthritis Rheum 2012;64:1447)

Acute flare: Treat ASAP to ↓ duration of sx; urate-lowering Rx & low- dose ASA (81 mg) should be continued in pts already on these meds; no tx is clearly superior, consider comorbidities when choosing tx

Colchicine: 1.2 mg at onset, → 0.6 mg an h later → 0.6 mg BID (various regimens exist); continue for 2–3 d after attack ends Prednisone: Consider if multiple joints involved; many options for dosing, but often treat for total 1–2 wks, tapering quickly; pts can re-flare if prednisone tapered too quickly Steroid injection (if monoarticular): Aspirate to verify crystals & r/o infection NSAIDS: Naproxen, indomethacin (JAMA 2015;313:2276); continue 1–2 d after attack; use cautiously in pts w/ CKD, hx GIB, CVD, CHF, anticoagulant Rx IL-1 Inhibition (e.g., Anakinra): Not FDA- approved; may be useful in the setting of contraindications to other options (Curr Rheumatol Rep 2014;16:398)

Uric acid lowering therapy (Long-term therapy): May begin during or after acute flare; Indications: ≥2 attacks/y, erosive dz on radiograph, nephrolithiasis, gout & CKD ≥ stage 2, tophi, or urinary UA >1.1 g/d

Goals: Serum UA <6; <5 mg/dL if tophaceous dz; no recurrent flares (though may occur while uric acid is being lowered by uric acid- lowering therapy) Diet/Lifestyle:↓ meat, seafood, high-purine vegetables, EtOH, high-fructose corn syrup; avoid HCTZ & loop diuretics; cherry juice may prevent or ↓ attacks Allopurinol: 1st- line agent; xanthine oxidase inhibitor; start 100 mg QD (50 mg/d in CKD stage IV or higher) × 2 wks, then ↑ by 100 mg QD q 2–4 wks; titrate to UA goal every 2–4 weeks (monitor UA, CBC, creatinine q 2–4 wks); typical dose 300–800 mg/d; monitor for toxicities (i.e., acute gouty attack, rash, diarrhea, cytopenia, fever); avoid discontinuation during acute hospitalizations (↑ risk of gout flare)

Risk of Allopurinol Hypersensitivity Syndrome: Life- threatening drug reaction similar to DRESS; pts of Han Chinese, Thai, & Korean pts w/ stage 3 CKD ancestry are at

 

↑↑↑ risk (screen for HLA-B*5801 & avoid if +) (Pharmacogenomics 2011;12:1741) Febuxostat: Xanthine oxidase inhibitor; 40 mg/d starting dose, up to 80 mg/d after 2 wks if UA not at goal; s/e include abnl LFTs, nausea, rash, arthralgias Probenecid: Promotes UA secretion (uricosuric); appropriate for pts w/ ↓ renal UA secretion (verified by 24 h urine UA); contraindications include CKD, nephrolithiasis, tophi; losartan has a mild uricosuric effect Refractory gout: Pegloticase (converts UA to allantoin, which is more soluble) indicated in pts who have contraindications to or who are refractory to above agents; should be used w/ advice from rheumatologist, high risk of infusion reaction/neutralizing Ab

Prophylactic medications: Administer during initiation of urate- lowering Rx to ↓ risk of triggering a flare as uric acid is lowered; Options: Colchicine (0.6 mg QD-BID, ↓ frequency in CKD); low-dose NSAIDs or prednisone (≤7.5 mg/d); Duration: Continue for at least 6 mos or 3 mos after achieving target serum UA (no tophi) or 6 mos after achieving target serum UA & tophi resolution (tophi present)

 

Patient information: AFP 2007;76:811; JAMA 2012;308:2161

PSEUDOGOUT (CALCIUM PYROPHOSPHATE DEPOSITION DISEASE)

 

Background (NEJM 2016;374:2575)

Pathophysiology: Mono-or oligoarthritis typically of knee (>50%), wrist, ankle but can occur nearly anywhere; compared to gout, less predilection for 1st MTP

Risk factors: ↑ age, hemochromatosis (see “Hemochromatosis”), hyperparathyroidism, hypo-Mg, hypophosphatasia (congenital syndrome)

Evaluation

History: Presentation similar to gout—acute pain, inflammation of one to several joints; may be provoked by illness, trauma, surgery, or rapid

↓ Ca

Workup: Arthrocentesis to r/o gout, infection, other inflammatory

 

arthritis; fluid shows crystals are rectangular/rod/rhomboid shaped w/

weak, ⊕ birefringence

Imaging: Radiograph can show chondrocalcinosis (calcifications within the joint space/cartilage) though this is not specific to pseudogout; U/S may show characteristic changes in tendons/joints Metabolic Disease Workup: Recommended in those <60 y; iron studies, PTH, Mg, Phos

 

Treatment

Acute flare: Similar to gout; joint aspiration & injection (for dx & tx); NSAIDs or colchicine; oral & intraarticular steroids may be helpful; ice & immobilize joint

Prophylaxis: Low-dose colchicine (0.6 mg PO BID-QOD), NSAID, or MTX

Patient information: mayoclinic.com/health/pseudogout/DS00717; arthritis.org

 

MYALGIAS

Background (AFP 2001;64:1565; Am J Med 2004;117:420; JAMA 2011;305:183; Lancet

2003;362:971;NEJM 2005;352:1448)

Definitions: Myalgia or muscle ache/pain is nonspecific & may be a feature of many conditions; myositis refers to inflamed/damaged

 

muscle (see “Myositis”) in which pain is not typically a prominent feature (as opposed to weakness) when due to immune-mediated causes (e.g., dermatomyositis, polymyositis); polymyalgia rheumatica (see “PMR”) is assoc w/ aches in the muscle & soft tissue around the shoulders, hips, & neck, often assoc w/ prominent stiffness & ↓ ROM

 

Differential Diagnosis of Generalized Myalgias
Category	Examples
Infectious	Viral (enterovirus, hepatitis B/C, influenza, dengue, HIV), spirochetal (see “Tick-Borne Illness”)
Pain syndromes	Fibromyalgia (see “Fibromyalgia”)
Rheumatologic	PMR, polymyositis/dermatomyositis, RA, SLE, spondyloarthropathy, vasculitis
Metabolic	Scurvy, metabolic myopathy, vit D deficiency
Endocrine	Adrenal insufficiency, hypothyroidism
Medications	Statins, antipsychotics, fibrates, colchicine, AZT, bisphosphonates, aromatase inhibitors, withdrawal from antidepressants
Leg cramps (AFP 2012;86:350)	Flat feet, dialysis, pregnancy, spinal stenosis, radiculopathy, claudication, ↓ Mg, ↓ Ca, neuropathy
Differential of localized myalgia: Exercise/overuse (strain/sprain), pyomyositis, infarction (e.g., diabetic muscle infarction), compartment syndrome, bursitis

 

Distinguishing Features of Myalgias (AFP 2002;65:907; NEJM 2010;363:e17)
Presenting Features	Potential Diagnosis
Pain out of proportion to exam	Necrotizing fasciitis/cellulitis/myositis, compartment synd
Sudden onset ± fever	Acute bacterial (systemic or focal) or viral
Gradual onset	Med, chronic infx, endocrinopathy, fibromyalgia, PM/DM
Shoulder/hip girdle	PMR, RA
Weakness (see “Weakness”)	PM/DM, hypothyroidism, statin-induced
Dysphagia, dyspnea	PM/DM
Red/brown urine + weakness	Rhabdomyolysis
Redness, swelling, asymmetry	Pyomyositis, compartment syndrome
Delayed reflexes	Hypothyroidism

 

Statin exposure	May cause myalgia or inflammatory myositis
Hyperpigmentation	Adrenal insuff
Malar rash	SLE
Erythema migrans	Lyme dz
Gottron papules (occur on dorsal MCP & IP joints), heliotrope eruption on upper eyelids, shawl or V-sign→ Dermatomyositis

General myalgia workup: CBC, U/A, CMP (±Mg, Phos), TSH, Vit D, HIV, HBV, HCV; consider CK, aldolase, LDH if weak; depending on level of suspicion for certain explanations, consider add’l testing (e.g., ESR/CRP, auto-antibodytesing, imaging)

Myopathy: EMG/NCS, bx, neuro c/s

Dermatomyositis/polymyositis: ↑CK, aldolase, LDH; ⊕ ANA, ⊕ anti-Jo-1, or other myositis Ab (see “Myositis”); EMG &/or MRI; muscle or skin biopsy Pyomyositis: CT or MRI, BCx, biopsy/fluid aspiration

Management

Medication-induced: D/c medication, may take wks to mos for sx to resolve

See specific sections “Fibromyalgia,” “Myositis,” “PMR,” “Thyroid Disease”

Chronic fatigue syndrome: Cognitive behavioral therapy & graded exercise therapy (no evidence for medications or dietary changes) Dermatomyositis/polymyositis: See below

Pyomyositis: Abx &/or drainage, ID c/s

 

 

MYOSITIS

Background (JAMA 2011;305:183; Lancet 2003;362:971; NEJM 2015;372:1734)

Four primary immune-mediated myositis syndromes: Dermatomyositis (DM), polymyositis (PM), inclusion body myositis (IBM), necrotizing autoimmune myositis (NAM, often assoc w/ statin exposure); may be feature of another systemic connective tissue dz (overlap)

Epidemiology: Incidence 1.2–19/1,000,000/y; peaks in presentation

 

during childhood (DM) & adulthood (DM & PM); IBM generally consider a dz of older men

Differential Diagnosis: See “Muscle Pain”

 

Disease Specific Features of Myositis

Dermatomyositis & polymyositis: Insidious onset of symmetric proximal weakness ± dysphagia; extramuscular manifestations such as ILD, polyarthritis; skin changes seen in DM but not PM; DM maybe amyopathic; DM ↑ risk of cancer 3–5 years after onset (ovarian, breast, colon, melanoma, NHL, nasopharyngeal [Asian patients]); overlap: DM/PM features above + features of a connective tissue dz (systemic sclerosis, SLE, MCTD)

Inclusion body myositis: Most common myopathy after age 50; slow-onset of distal & proximal weakness (maybe asymmetric); mild facial muscle weakness; 50% dysphagia, autophagic vacuoles on bx; poor response to steroids & other immunosuppression

Necrotizing autoimmune myositis: Acute or subacute proximal weakness w/ very high CK, ++ dysphagia; necrosis on bx (Curr Rheumatol Rep 2015;17:72). Associations: Postviral infection, CTD, cancer, statins; most will have anti-HMG-CoA Ab (in statin exposure) or anti-SRP Ab

Evaluation

History: Painless, symmetric proximal weakness (DM/PM); ⊕ rash (DM); asymmetric, proximal & distal (IBM); symmetric proximal weakness ± pain (NAM); all w/ ↑ muscle enzymes (e.g., CPK); syndromes often assoc w/ other organ involvement (e.g., antisynthetase syndrome)

Laboratory: CBC, Cr, LFTs, TSH, ANA. Muscle enzymes: CPK, aldolase, LDH; ESR & CRP (may be normal despite intense inflammatory myositis)

Autoantibody testing: Myositis specific & associated antibody testing may support dx, suggest etiology (e.g., statin, malignancy), & prognosticate (other organ involvement, outcomes); consult w/ local neurologist/rheumatologist/lab regarding advanced myositis antibody testing availability

Imaging and neuro testing: MRI shows muscle edema, vs. atrophy, fibrosis; helpful for dz activity, localizing muscle bx; EMG demonstrates myopathic potentials; useful for active vs. chronic & r/o neurogenic cause

Biopsy: Dx can be made w/o bx; if necessary, consider EMG or MRI to increase yield of bx; findings not always specific; NAM typically w/o 1° inflammation (>>>necrosis)

 

Malignancy evaluation: In DM & NAM; age-appropriate cancer screen

+ CT C/A/P + mammogram/TVUS (↑ incidence of ovarian Ca); or PET- CT; consider cancer-specific biomarker screening; repeat screening for

>2 years since may present after diagnosis

Swallow evaluation: If sx of dysphagia are present

Respiratory Involvement: PFTs (lung volumes, DLCO, 6 minute walk test), high-resolution chest CT

Management

DM/PM/NAM: Steroids (e.g., prednisone 1 mg/kg [max dose = 100 mg/QD] → taper after 4–6 wks; ±DMARD [MTX, AZA, MMF, RTX]); NAM often requires aggressive therapy; comanagement w/ rheum &/or neuro ± derm if DM

Cutaneous manifestations of DM: Consider topical therapy

IBM: Resistant to immunosuppressive therapies

Intravenous immunoglobulin (IVIG): May be helpful if oropharyngeal involvement

Physical therapy/occupational therapy: Once inflammation somewhat controlled

 

POLYMYALGIA RHEUMATICA

Background (AFP 2013;88:676; Lancet 2013;381:63; NEJM 2014;371:50)

Diagnostic features: Age >50 y,↑ ESR/CRP, bilateral aching or pain, tenderness, & AM stiffness (>30–45 min) of proximal muscles groups (shoulder/upper arm >> neck &/or pelvic girdle), rapid response to mod dose (~20 mg/d) steroids, & exclusion of other conditions (Arthritis Rheum 2012;64:943)

Other symptoms: Fatigue, low-grade fever, mild synovitis (MCPs/knees/wrists), anorexia, wt loss, distal extremity swelling Muscle weakness: Not characteristic of the dz (exam may be limited by pain)

Epidemiology: Typically occurs in M:F 1:2–3; incidence in pts >50 y

~50/100,000; average age of dx >70 y

Differential diagnosis: RA, spondyloarthropathy, pseudogout, inflammatory myositis, infection (e.g., viral syndrome, SBE),

 

endocrinopathy (e.g., hypo-or hyperthyroidism), OA, rotator cuff d/o, fibromyalgia, malignancy (MM)

Association w/ giant cell arteritis (GCA):Large-to medium-sized arteritis (e.g., branches of the aorta). Key Features: New or different headache, jaw claudication, scalp tenderness, blurred vision; PMR & GCA hypothesized to be different manifestations of one dz process; 16–30% of pts w/ PMR have GCA; 40–60% of pts w/ GCA have PMR. Diagnosis: Temporal artery (TA) biopsy (may be false ⊖), consider bilateral; cross-sectional imaging suggestive of aortitis (large vessel vasculitis)

Evaluation (JAMA 2016;315:2442)

Exam: ↓ active & passive ROM in shoulders, neck, &/or hips; ± swelling of hands/feet; nonerosive peripheral arthritis; assess tenderness in scalp & TA

Workup: ✓ESR & CRP; ✓TFTs, Chem-12, CBC w/ diff; RF & anti-CCP typically ⊖; assoc w/ anemia of chronic dz; muscle enzymes (e.g., CK) should be nl; nl ESR does not exclude PMR (ESR <50 mm/h seen in

10%) (BMJ 2012;344:e1408)

Radiographs: Rarely helpful; may aid dx if nl ESR; MRI or U/S can demonstrate periarticular inflammation; joint erosions are not assoc w/ PMR

Giant cell arteritis: Screen for in PMR pts; temporal artery bx if GCA sx present

Management (Ann Int Med 2017;166:ITC65; JAMA 2016;315:2442)

Steroids: Mainstay of Rx w/ initial dose of 20 mg/d (maximum 30 mg/d) of prednisone or equivalent; anticipate initial improvement within 24– 48h & continued improvement over subsequent wks; failure to respond to steroids should raise suspicion for alt dx

Duration: Steroid Rx often continues for ~12 mos w/ slow taper guided by sx and labs; 50% of pts relapse & require steroids; flares may be managed by raising steroids by 10–20% & retapering; pts should be evaluated for osteoporosis

Steroid-sparing agents: Methotrexate (Arthritis Rheum 2007;56:2789) may be useful in pts who cannot take steroids; tocilizumab (IL-6 blockade) recently demonstrated effective (NEJM 2017;377:317)

 

Patient information: AFP 2006;74:1557

 

 

SYSTEMIC LUPUS ERYTHEMATOSUS

Background (AFP 2016;94:284; Ann Int Med 2013;159:ITC4-1; Arthritis Rheum

2007;56:2092; NEJM 2011;365:2110)

Definition: Chronic inflammatory dz 2/2 Ab formation & immune complex deposition, w/ notoriously varied presentation that can affect nearly every organ

Epidemiology: 10–150/100,000; 8:1 ♀: ♂ ratio; 65% of pts w/ onset 16–55 y

Pathophysiology: Combination of genetic (complement deficiency), hormonal (estrogen), immunologic (autoantibodies), & environmental factors

Clinical course: Variable; periods of acute flares, remission, & chronic; common manifestations affect skin/mucosa, joints, kidneys, pleura/pericardium, central nervous system, & blood elements; for cutaneous lupus, see “Rheumatologic Skin Disease”

Precipitating factors: Sun exposure, infections, stress, surgery, pregnancy

 

Clinical Manifestations (Arthritis Rheum 1982;25:1271; 2012;64:2677)
	1982 ACR Classification Criteria*	Clinical Features
Systemic	If ≥4 of 11 criteria below are met (either serially or simultaneously), Se & Sp for SLE is 96%	Systemic sx include fatigue, fever, malaise, wt loss/gain, weakness
Derm > 80%	1.  Malar rash (acute cutaneous lupus) 2.  Discoid rash (chronic cutaneous lupus, erythematous plaques w/ keratosis & plugging) 3. Photosensitivity 4. Oral/nasopharyngeal ulcers	Raynaud’s, alopecia Malar “butterfly” rash: facial erythema sparing nasolabial folds & exacerbated by UV light (photosensitivity) Many other types of rashes assoc w/ SLE (e.g., subacute cutaneous lupus) Ulcers usually painless & on hard palate
Msk > 90%	5. Arthritis (nonerosive, ≥2	Myalgias, arthritis (migratory & symmetric

 

	peripheral joints)	involving hands, typically nonerosive)
CV & Pulm	6. Pleuritis or pericarditis	Also myocarditis, valvular dz, vasculitis, pleurisy, pleural effusions, pneumonitis, ILD, pHTN, hemorrhage
Renal 16–38%	7. Proteinuria (>500 mg/d or ≥3+ dipstick) or casts (RBC, Hgb, granular, tubular, mixed)	Lupus nephritis (hematuria, proteinuria, or ↑ Cr) (May be asx – need screening UA)
Neuro 10–80%	8. Seizures or psychosis	Cognitive dysfunction, stroke, neuropathy, transverse myelitis, HA, delirium, depression, psychosis
Heme 36%	9. Hemolytic anemia (⊕ Coombs) or leukopenia or lymphopenia or ↓ PLT	Anemia of chronic dz; LAD; Antiphospholipid syndrome (APLS): Thrombocytopenia, venous & arterial thrombosis, recurrent miscarriages
Serologies	10. + Anti-DNA or + Anti-Sm or antiphospholipid Ab 11. + ANA
GI 25– 40%		Dysphagia, abdominal pain, nausea, mesenteric vasculitis, pancreatitis, gastritis
Misc		Sicca (dry eyes or mouth) symptoms

*Updated criteria (SLICC, Arthritis Rheum 2012;64:2677) similar but we present original criteria given ease of presentation; Note that classification criteria are meant for clinical trial enrollment, not diagnosis

Evaluation and Prognosis (AFP 2003;68:2179)

Diagnosis: Based on sx, exam findings, & lab testing; ACR & SLICC criteria are useful but meant for use in clinical trials (some SLE patients will not meet criteria)

History: Presence of sx described above; precipitating events for lupus flare

Exam: Full exam, incl CV (pericardial rub, murmurs), skin, joints, liver/spleen, LN

Workup & monitoring disease activity: CBC (cytopenias), Chem-12, ESR, CRP, UA (proteinuria, RBC); complement testing (C3, C4 frequently low in active dz); (see “Rheumatologic tests”); dsDNA (other ENA testing not typically repeated serially)

 

Autoantibody Testings in SLE (Arthritis Rheum 2002;47:546; 2004;51:1030)

 

Test	Notes
ANA	1st-line test; ⊕ at high titer (1:160 or higher) in virtually all pts w/ active SLE; if ⊕, proceed w/ additional autoantibody testing
Anti-dsDNA	Especially correlated with renal activity in some pts; Se 57%, Sp 97.4% for SLE
Anti-Smith (Sm)	Low Se (24%) but high Sp (98%) for SLE
Antiphospholipid	Includes lupus anticoagulant, anti-cardiolipin, & anti-b2-glycoprotein (not b2 microglobulin)

Imaging: Not required, but may confirm clinical sx & guided by sx/signs Other: Bx may be warranted for confirmation of specific organ involvement (i.e., skin, kidney); crucial to review meds for drug-induced lupus (see below)

Prognosis: Course varies btw pts, ranging from relatively quiescent dz to rapidly progressive organ damage; 5 y survival >90%; active dz the most common cause of death, along w/ premature CVD & immunosuppression complications (infection)

Poor prognostic factors: Renal dz, HTN, ♂, extremes of age at presentation, African ancestry, APLS, ↓ socioeconomic status

Treatment (Arthritis Rheum 1999;42:1785)

General approach: Avoid sun, smoking, & estrogen (OCPs, caution with pregnancy during active dz); Rheum referral if dz suspected & for continuing co-mgmt; hydroxychloroquine for most pts & immunosuppressive Rx based on organ involvement; med tx requires monitoring for toxicities; pt education on signs of flare

Medications:

NSAIDs: Useful for musculoskeletal sx, fevers, HAs, & mild serositis Hydroxychloroquine: Useful for skin & musculoskeletal sx, & mild overall dz; requires optho monitoring for eye toxicity (baseline & q5 years).

Glucocorticoids: Used for flares; low/mod dose for joints, serositis sx & high dose for nephritis, CNS sx; topical steroids for skin lesions (see “Rheumatologic Skin Disease”) Steroid-sparing agents: Targeted for specific organ involvement; MTX, azathioprine, mycophenolate (often used as remission induction & maintenance for lupus nephritis rather than CYC), & belimumab

 

(esp cutaneous/MSK manifestations) Cyclophosphamide (CYC) for sev (e.g., renal, neuro) sx (NEJM 2013;368:1528)

Monitoring: Follow clinical manifestations; serologic studies useful in some pts (anti-dsDNA titers, C3, C4, ESR, CRP); periodic CBC, CMP, & UA for protein/blood

Patient information: rheumatology.org; lupus.org

DRUG-INDUCED LUPUS

 

Background: Mechanism unclear; related to drug-induced autoantibodies (particularly antihistone, & ANA, but not dsDNA except in anti-TNF mediated DLE); 1:1 ♂:♀ ratio

Associated medications: Procainamide, hydralazine, minocycline, penicillamine, INH, anti-TNF drugs, IFN, methyldopa, chlorpromazine, diltiazem; others implicated: anticonvulsants, antimicrobials, & βB History: Fever, rash, myalgias, arthritis, serositis; many anti-TNF treated patients developed +dsDNA of no clinical significance Treatment: Withdrawal of offending medication; sx should resolve within several mos; symptomatic tx w/ NSAIDs & steroids may be considered

 

GLUCOCORTICOIDS AND DISEASE- MODIFYING ANTIRHEUMATIC DRUGS

Evaluation and Management (NEJM 2013;369:307; Semin Neurol 2014;34:467)

General principles: With few exceptions (e.g., hydroxychloroquine), DMARDs are immunosuppressants that ↑ the risk of infection (Curr Opin Rheumatol 2014;26:404); screening, appropriate vaccination, and PPx mitigate these risks (Rheum Dis Clin North Am 2017;43:1)

Women of child-bearing age: Discussion of potential teratogenicity, contraception and pregnancy planning critical; consult rheumatologist, pharmacist; consider high-risk OB if pregnant; male fertility may be affected by certain agents (Arthritis Care Res 2015;67:313)

 

 

Pre-Treatment Infection Screening, Vaccination, & Prophylaxis (MMWR 1993;42:RR-4)
Infection	Screening	Prevention/Treatment
Tuberculosis (TB)	PPD, T-Spot, or QuantiFERON Gold	If ⊕, delay DMARD initiation & evaluate latent vs. active TB
Hepatitis B (HBV)	HBV core Ab, HBV surface Ab, HBV surface Ag	If c/w prior exposure or active dz ✓ VL, c/s with ID/hepatology re tx or PPX; consider DMARD delay
Hepatitis C (HCV)	HCV Ab, ±HCV VL
Varicella Zoster Virus (VZV)	VZV IgG and IgM	Do not administer live vaccine* while on biologic DMARD or prednisone ≥20 mg/d; delay treatment by 4 wks
Measles, Mumps, Rubella (MMR)	MMR IgG and IgM
Influenza	Killed vaccines are safe to administer while on tx; efficacy may be reduced
S. pneumonia

Ab, antibody; Ag, antigen; VL, viral load; *If inadvertent vaccination with VZV, c/s with ID and consider empiric several week course of appropriate antiviral therapy

Glucocorticoid side-effects (GC): GC are critical for swiftly controlling immune-mediated conditions, but goal is to minimize GC exposure by early introduction of DMARD (aka steroid-sparing agents) (Curr Rheumatol Rep 2015;17:513)

Glucocorticoid-induced osteoporosis (GIOP): Baseline DXA, consider bisphosphonate (esp if ≥3 mo of tx ≥7.5 mg/d prednisone equivalent), Calcium/Vitamin D

PCP pneumonia: Consider PPX for prolonged GC ≥ equivalent 20 mg/day of prednisone Endocrine: Wt gain; DM (✓baseline A1c, consider insulin and/or dose Δ) Neuro-psych: Sleep-wake cycle Δ; depression, psychosis, mania, anxiety Gastritis: Consider PPI for GI protection with ↑dose, h/o gastritis, prolonged tx Adrenal insufficiency: May require stress-dose steroids for shock or perioperatively Others: Ophthalmic (e.g., glaucoma, cataract), Derm (thin skin, bruising), Myopathy

Conventional DMARDs: First-line treatment in RA, other types of

 

inflammatory arthritis, and connective tissue dz (e.g., SLE)

 

Common Conventional DMARDs, Side Effects, Monitoring (Ann Rheum Dis 2014;73:529)
DMARD	Unique Side Effects	Monitoring
Hydroxychloroquine (HCQ, PO)	GI upset, retinal toxicity, rarely myo-or neurotoxicity	Baseline eye exam (then q5 y)
Methotrexate (MTX, SC or PO)*	Fatigue, GI upset, oral ulcers, hair loss, ↑LFT, BM suppression	q1 mo CBC, creatinine, LFT until stable dose than q3 mo
Sulfasalazine (SSZ, PO)	GI upset, drug rash, sun Se
Leflunomide (PO)**	Diarrhea, ↑ LFT, ↓wt
Azathioprine (AZA, PO)	GI upset, BM suppress (esp if ↓TPMT activity), pancreatitis, ↑LFT	✓ TPMT activity prior to tx; CBC, Cr, LFT q1m initially then q3 m
Mycophenolate mofetil (MMF, PO)	BM suppression, GI upset (often dose- limiting)	CBC, Cr, LFT q1 m initially then q3 mo
Cyclophosphamide (CYC, PO or IV)	BM suppression, permanent infertility, hemorrhagic cystitis (HC), malignancy	Depending on IV vs PO route, frequent CBC; monthly UA (HC), Cr, LFT; routine UA/cytology after tx to monitor for bladder cancer

*EtOH should be avoided while on MTX due to risk of hepatotoxicity **hepato-enteric recirculation which may require special tx to completely remove from body in presence of toxicity or pregnancy

Biologic DMARDs: Often used as the second-line tx in inflammatory arthritis & other rheumatologic conditions; all are assoc w/ ↑ risk of infection though, risk may vary (Lancet 2015;386:258)

 

Common Biologic DMARDs (Cochrane Database Syst Rev 2011;2:CD008794)
Representative DMARD (Target)	Unique Side Effects	Monitoring
Adalimumab (TNF)	Rare neutropenia, infusion reaction (IV route), drug-	Periodic CBC, LFT

 

	induced lupus
Tocilizumab (IL-6)	Cytopenias, ↑ LFT, bowel perforation (avoid if h/o diverticulitis)	CBC, Creatinine, LFT q1 m initially then q3 m; lipid q6 m*
Anakinra (IL-1)	Injection-site reaction	Periodic CBC, LFT
Abatacept (CTLA- 4)	IV may cause false ↑ glucose on test-strips day of tx
Rituximab (CD20)	Infusion reaction, flu-like illness, hypo-IgG, late-onset neutropenia	CBC, IgG; may monitor peripheral blood CD20 levels to guide retreatment
Tofacitinib (JAK)**	Cytopenias, possible increased VZV infection	CBC, Creatinine, LFT q1 m initially then q3 m
Belimumab (BLyS)	Cytopenias, infusion reaction	Periodic CBC, LFT
Other agents: Secukinumab (IL-17), Ustekinumab (IL-12/23), Apremilast (PDE4)

*Lipid change on IL-6 blockade of unclear significance **PO (all others IV or SQ); biologics should not be combined with one another, in general

Perioperative DMARDs: Continuing tx ↑ risk of infection; holding or discontinuing tx ↑ risk of flare pre-/post-op which can also require GC therapy (Arthritis Rheum 2008;59:762)

Methotrexate and other conventional DMARDs: Generally considered safe to continue through the perioperative period (esp arthroplasty) though evidence is controversial (Seminars Arthritis Rheum

2015;44:627)

Hydroxychloroquine: Safe to continue through the perioperative period (does not increase the risk of infection)

Biologics: Hold perioperatively, often 1.5 × half-life; most evidence based on TNF-inhibitors; review risks/benefits with patient and providers

Patient Resources: www.rheumatology.org; www.arthritis.org