The child with a limp MARVIN B HARPER MD DIVISION OF EMERGENCY MEDICINE BOSTON CHILDREN’S HOSPITAL HARVARD MEDICAL SCHOOL No conflicts of interest No financial disclosures Case

— 18 month old otherwise well limping since this afternoon. Mom notes some limping but mostly child doesn’t want to stand. She isn’t sure which leg has pain — PE: afebrile, antalgic gait favoring the left leg. No swelling noted. Seems to have some pain to palpation of the left lower leg. Toddlers fracture

Herman and Martinek. Pediatr in Rev. 2015 Case

— 3 year old male woke up this morning with complaint of pain in the right leg. Still active and playing but can be seen to be limping. — PE afebrile, when sitting still is active and playful. Refuses to fully bear weight on right leg when walking. Allows some flexion/extension at the right hip but seems to have pain with full flexion/extension — Given ibuprofen with improvement of symptoms — No further studies done Focus diagnoses in the ED

— In the ED focus on diagnosis of ¡ Fracture ¡ Infection (bone, joint, post-infectious) ¡ SCFE ¡ Tumors ¡ +/- Developmental hip dysplasia — Not generally ED diagnosis ¡ Leg length discrepancy ¡ Cerebral palsy ¡ Contractures ¡ Rheumatologic causes Differential diagnosis for septic arthritis

— Trauma — Leukemia — Hemarthrosis, — Tumor — Osteomyelitis, — Henoch-Schönlein — Reactive effusion purpura — Pyomyositis — Sickle cell anemia w/VOC — Septic bursitis — Rheumatologic (e.g. JRA) — Lyme — Acute rheumatic fever — SCFE — Legg-Calvé-Perthes Etiology – differential diagnosis for joint concern

— Age 1 – 3 years ‘Toddler’ — Age 11 - 16 years ¡ Toddler’s fracture ¡ SCFE ¡ Transient synovitis ¡ Avascular necrosis of the hip ¡ Infection ¡ Chondromalacia ÷ Arthritis, osteomyelitis, ¡ Neoplasm pyomyositis ¡ GC arthritis ¡ Developmental hip dysplasia — Any age ¡ Lyme — Age 4-10 years ¡ Leukemia ¡ Transient synovitis ¡ Legg-Calve Perthes History, geography and exam

— Underlying predisposing condition — Lyme endemic area or other exposures — Physical examination ¡ Fever? ¡ Antalgic gait? ¡ Focal lower extremity pain? ÷Will child bear weight on each leg? ÷Will child bear weight on foot? ÷Will child kneel or crawl without pain? ¡ Exam of joints Imaging

— Generally the history and examination will direct the focus to bone, joint or muscle or some combination ¡ Severity of symptoms ¡ Presence or absence of fever — Driven by history and examination ¡ Worried about muscle, bone, joint, soft tissue or bursa? ¡ Most often plain films or ultrasound ¡ Occasionally MR ¡ Rare technecium 99 bone scan Transient synovitis

— Age 18 mo’s – 12 years — Males 2:1 over females — Common in children ¡ 0.2% per child/year in Sweden — Often post-infectious ¡ viruses, gut pathogens, many bacteria — Pain often waxes and wanes — Great overlap in the values for WBC, ESR, CRP — Diagnosis of exclusion Sites of septic arthritis in children

Hip, knee, ankle combined 85%

From a series of 130 culture positive pediatric cases

Pääkkönen M , Peltola H Arch Dis Child 2012 Septic arthritis

Age distribution

Anatomic site

Pathogens

Peltola H et al. Clin Infect Dis. 2009 Septic arthritis in Texas

NOI = no organism isolated Branson et al. PIDJ 2017 Septic arthritis - outcomes

— Long term morbidity is variable by pathogen and delay to treatment — Estimated that 10-25% have some residual joint dysfunction — Risk highest for infections due to S. aureus and or in young infants Septic arthritis

— Pathophysiology ¡ Hematogenous — H&P ¡ Fever, pain in the joint with movement ¡ Swelling, redness ¡ When the hip is involved ÷ mildly flexed and externally rotated ¡ Recent trauma is common (20%) but no different than controls Septic arthritis – lab findings

— CBC with diff, CRP, ESR, blood cultures, (lyme) ¡ Leukocytosis ¡ Elevated CRP (if normal will be elevated within 12-24 hours of onset of symptoms) ¡ ESR >20 mm/hr in the majority Septic arthritis

— Imaging ¡ Plain radiographs ÷ Fracture, mass, demineralization but likely normal ¡ Ultrasound ÷ Most useful for the hip (and shoulder) as other joints effusions are commonly clinically evident ÷ MRI if concern for associated osteomyelitis or pyomyositis — Arthrocentesis ¡ Cell counts, culture , +/- PCR Kingella Infectious arthritis

— In Boston we send lyme serology on any patient with arthritis regardless of cell count unless bacteria isolated ¡ Send lyme regardless of month of the year — Remember that malignancies, Rheumatic Fever, and osteomyelitis can all give arthritis ¡ Consider the possibility of reactive arthritis Septic arthritis - diagnosis

Culture source Rate positive Blood 40% Joint fluid 50% Either blood or joint 60 - 70% fluid

Gram stain of joint fluid positive in ~50%. Intrepreting the joint fluid

Etiology WBC /mm3 WBC/mm3 (variable) Viral 15,000 300 – 50,000

Bacterial >50,000 200 – 300,000

Lyme >20,000 100 – 150,000

TB 10,000 – 20,000 400 – 140,000 Transient synovitis or septic arthritis Kocher rules

— Fever — Non-weight bearing — ESR >40 mm/hr — Serum WBC > 12,000

— If all four criteria met >99% septic arthritis

— Successfully validated in subsequent BCH group — Results not reproducible at other institutions ¡ Performance of this rule is also not as good for Kingella infections (Yagupsky et al J Pediatr 2014)

Kocher et al. J Bone Joint Surg Am 1999 and 2004 Transient synovitis or septic arthritis

Singhal et al. J of Bone Joint Surg Br 2011 Differentiating causes of arthritis

CRP ESR

Thompson A et al. Pediatrics 2009;123:959-965 Differentiating causes of arthritis

Joint WBC

Thompson A et al. Pediatrics 2009;123:959-965 Joint fluid Septic Lyme Other • WBC arthritis arthritis arthritis • ANC — 56% of lyme patients with >50K WBC — Variable WBC for septic arthritis

Dart et. al. Pediatrics 2018 Limp - Joint pain

— Septic arthritis identified – am I done? Risk of adjacent infections in septic arthritis

Welling et al; Clin Orthop Relat Res 2018 Risk of adjacent infections in septic arthritis

Age 4 Symptoms 3 CRP 2 Platelets ANC 1

Sensitivity 86% (32/37)for adjacent infection Only 5% (3) unnecessary scans per algorithm AUC 0.93

Welling et al; Clin Orthop Relat Res 2018 Risk of adjacent infections in septic arthritis

— Five variables ¡ age above 3.6 y (Welling 4) ¡ CRP > 13.8 mg/L (Welling 8.9) ¡ duration of symptoms >3 d (Welling same) ¡ platelets ≤314K cells/µL (Welling <310K) ¡ Patients with >= 3 risk factors are high risk for septic arthritis with adjacent infection ¡ (Does not include Welling ANC >7.2K cells/µL) ÷(sensitivity: 90%, specificity: 67%, positive predictive value: 80%, negative predictive value: 83%)

Rosenfeld et al, J Pediatr Orthop 2016 Osteomyelitis Osteomyelitis

!Children ¡ hematogenous by far most common — Most commonly acute — Peak in late summer and early autumn — 1/3 of pediatric cases occur in the first 2 yrs of life — >90% have only a single bone involved Organisms causing hematogenous osteomyelitis

— Children > 6 months of age ¡ S. aureus 80% ¡ GABHS 5-10% ¡ S. pneumoniae 1-5% ¡ H. influenzae b <2% ¡ others: Salmonella, E. coli, P. aeruginosa, Klebsiella, fungi/yeast, anaerobes Osteomyelitis - clinical presentation

— Focal pain - constant (may fluctuate with load) ¡ occurs in >90% ¡ onset is gradual — inflammatory signs (redness, warmth, swelling) usually do not appear until there is pus in the tissues OUTSIDE the bone ¡ historically 2/3 of of patients have evidence of local soft tissue inflammation at the time of diagnosis — The spine, pelvis and hips are often more difficult and localized inflammation more easily concealed Osteomyelitis - clinical presentation

— Fever is not a constant feature ¡ approx 2/3 of children have fever ÷2/3 of those with fever have low grade fever (<39 degrees C) — Fever is less common in neonates and adults Osteomyelitis - clinical presentation

100% 80% 60% 40% 20% 0%

Pain Fever DROM Trauma Limping Swelling WarmthAnemia Erythema Sex (male) Tenderness Medical history Underlying disease Abx before admissionFever, pain, limping and local inflammation

Saavedra-Lozano et al, J Ped Ortho 2008 Differential diagnosis

— Fairly limited by history and examination ¡ Malignancy – primary or secondary ÷ Osteosarcoma, Ewing’s, neuroblastoma, leukemia etc ¡ Fracture ÷ Acute or chronic ¡ Chronic recurrent multifocal osteomyelitis ¡ Histiocytosis X Skeletal Distribution of Acute Osteomyelitis in Children

Peltola H, Pääkkönen M. NEJM 2014 Skeletal Distribution of Acute Osteomyelitis in Children

Peltola H, Pääkkönen M. NEJM 2014 Osteomyelitis

— CRP ¡ 98% have elevated CRP (>2 mg/dL) — ESR ¡ 90% have elevated ESR (>20mm/hr) — WBC ¡ only 34% with WBC > 12,000 /mm3 Osteomyelitis

— Blood culture ¡ positive in 35-40% — Bone aspirate ¡ positive in 35-40% — Blood culture AND bone aspirate ¡ Positive in at least one specimen for 50- 70% ¡ Blood the only positive culture in 10-15% ¡ Aspirate the only positive culture in 25- 30% CRP and ESR in uncomplicated hematogenous osteomyelitis

90 80 •• • CRP (mg/L) 70 • 60 • ESR (mm/h) • 50 • • • 40 • 30 • • 20 • • 10 • •• • • 0 • • • • 0 5 10 15 20 25 30 Days from diagnosis Unkila-Kalllio et al. Pediatrics 1994 Staphylococcus aureus osteomyelitis distal right humerus of a 12-month-old infant.

Conrad D A Pediatrics in Review 2010 Findings on plain radiographs with osteomyelitis vary with time

— First week ¡ Mild blurring of deep muscles/tissue planes — 10-14 days ¡ Erosion or bony destruction - area of lucency ÷requires 30-40% bone loss over ~1cm ¡ Periostial reaction - new bone parallel to cortex in the metaphysis separated by a thin lucent line 2 - 10 mm wide — >= 3 weeks ¡ Sequestra - encapsulation of dead bone by new bone Imaging: plain radiographs

— Generally no need for further forms of imaging if plain films are positive — Plain films are useful for distinguishing osteomyelitis from fractures & tumors — If the child is afebrile and otherwise well it may be sufficient to simply obtain follow-up radiographs in 10-14 days if the pain fails to resolve ¡ further evaluation sooner if worse Case

— 6 month old infant with chicken pox 5d and 3 days of left leg pain. Now with higher fever.

— PE: T41.2, P 160. Mild RLQ tenderness. Left hip was flexed and externally rotated with very limited ROM, skin with scattered vesicles and scabs, none with evident secondary infection. — WBC 8.8 (53P, 35Bd). — US normal without effusion

Case: 6 year old female

— 4d PTA when she caught her R foot between two metal pipes while riding a bike. The next day she developed high fever, vomiting and R foot and leg pain. She presents to the ED with continued fever, increasing right foot and ankle pain and fatigue. — PE: 38.5C; unable to bear weight on her right foot; point tenderness of posterior aspect of right medial malleolus, no erythema, no edema. — WBC 9.18 (52P,33L, 8M) an ESR 60. — Radiograph reveals mild soft tissue swelling inferior to the medial malleolus without underlying bone or joint abnormality. — A bone scan was obtained the next morning. 6 yo F with fever and ankle pain 6 yo F with fever and ankle pain

R L R L

Bone scan blood flow phase Bone scan 4 hr scan

— Increased uptake means increased osteoblast activity ÷ increased uptake with tumors, trauma, vascular or metabolic injury — “Cold” areas can also represent infection ÷ vascular occlusion and ischemic necrosis 13 yo M with back pain bone scan

T12 lesion

Afebrile ESR 25 mm/hr

R L R L

Right distal tibia Case: 9 year old female

— 2 days prior to admission fell down a couple of steps and landed on her knee. Since then with complaint of worsening knee pain and fever. — T 39.4C, walking with a mild left sided limp, and the medial aspect of the knee was slightly tender and warm. No effusion was noted. — WBC 7.1 (63P), ESR 29, blood culture sent and knee films obtained as shown. Hip films also done and were normal. Aspiration of the knee was negative — Blood culture grew S. aureus — MR done 9 yo girl with knee pain and fever 9 yo girl with knee pain, fever - MRI

T1 without gadolinium T1 with gadolinium Initial treatment options for osteomyelitis – consider the patient and local epidemiology

! First generation cephalosporin or anti- staphylococcal penicillin if >90% MSSA in community ! Clindamycin if MRSA ≥10 and prevalence of clindamycin resistance S. aureus is <10% ! Vancomycin if prevalence of MRSA and clindamycin resistant S. aureus ≥ 10% ! If disease mild and can await results of empiric treatment with above then start with one of the above. If clinical concern then

Peltola H, Pääkkönen M. N Engl J Med 2014;370:352-360 Case: 6 yo male

— 2 days ago mild R hip pain exiting car but able to swim and play normally at camp. That evening he developed fever and vomiting. — 1 d PTA he spent most of the day on the couch and complained that his leg hurt — PE: Temp 40F. Unable to bear weight and complained of pain to even light touch over the right lateral thigh — WBC 11,000 — Ultrasound Doppler done because of the thigh swelling demonstrated Occlusive deep venous thrombosis within right external iliac and common femoral veins. — Blood cultures grew MSSA Right proximal femoral osteomyelitis Pyomyositis

6 yo male with 2 day history of hip pain and new onset of fever Grew MSSA from blood cultures DVT of right external iliac and common femoral veins — Filling defect at the junction between right upper and right interlobar pulmonary arteries extending into the right upper lobe pulmonary artery. — Multifocal parenchymal disease likely secondary to emboli – septic or sterile Venous thrombosis as a complication of osteomyelitis

— Gonzalez et al. reported on children with osteomyelitis ¡ 9 children with DVT; most femoral and popliteal ¡ 4/9 had pulmonary emboli — Hollmig et al. reported on children with osteomyelitis ¡ 5% had DVT identified (11 children of 212) — Crary et al. reported on children with osteomyelitis of the proximal humerus, proximal tibia/fibula, femur, pelvis, or vertebrae ¡ 29% had DVT (10 of 35) ¡ 8 thrombi adjacent to infection ¡ 2 related to central venous catheters ¡ 6 of 10 children with DVT - evidence of infection disseminated to lung, brain, or heart (vs 1 of 25 patients without DVT)

Gonzalez et al. Pediatrics 2006; Hollmig ST, et al. J of Bone and Joint Surg 2007; Crary et al. J Pediatrics 2006 CRP peak & AUC predict risk of VTE in pediatric musculoskeletal infections

AUC for CRP Peak CRP

Amaro et. al. J Ped Orth. 2019 DOI: 10.1097/BPO.0000000000001256 CRP peak & AUC predict risk of VTE in pediatric musculoskeletal infections

— Each 20 mg/L increase in peak CRP conferred a 28% increased risk of VTE

Amaro et. al. J Ped Orth. 2019 DOI: 10.1097/BPO.0000000000001256 — Limping child ¡ It is all about the history and exam to direct testing ¡ Plain films of the impacted area ¡ How severe are the symptoms – able to walk? Able to move the joint? — Know toddlers fracture, SCFE — When to perform labs and/or arthrocentesis — When to ultrasound or obtain MR The end

— Thank you so much

— Any questions?