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Musculoskeletal Pain: A New Algorithm for Differential Diagnosis of a Cardinal Symptom in Pediatrics Muskuloskelettale Schmerzen: Neuer Algorithmus zur differenzialdiagnostischen Evaluation eines Leitsymptoms in der Pädiatrie Authors

G. Tallen1, S. Bielack2, G. Henze3, G. Horneff4, R. Korinthenberg5, B. Lawrenz6, T. Niehues7, J. Peitz8, R. Placzek9, P. Schmittenbecher10, E. Schönau11, L. Wessel12, T. Wirth13, H.-J. Mentzel14, U. Creutzig15

Affiliations

Affiliation addresses are listed at the end of the article

Key words ▶ children and adolescents ● ▶ musculoskeletal pain ● ▶ epidemiology ● ▶ etiology ● ▶ differential diagnosis ● ▶ primary care ●

Abstract

Zusammenfassung

Musculoskeletal pain (MSP) is a common childhood complaint associated with multiple differential diagnoses, including cancer. Considering the expanding spectrum of diagnostics, evaluating a young patient with MSP is a challenge today, particularly for non-specialists in a primary care setting. Since childhood cancer is rare and most cardinal symptoms mimic rather nonserious diseases, misdiagnosis is not uncommon, but of significant prognostic relevance. To build the appropriate bridge between primary and secondary care for a child presenting with MSP, thereby preventing treatment delay and longterm sequelae, initial evaluation should follow a comprehensive, multidisciplinary, systematic and stepwise approach, which unites the patient’s individual anamnestic, psychosocial, and clinical characteristics. After a systematic review of the literature, we generated multidisciplinarily quality-assured recommendations for efficient, rational and cost-effective primary care assessment of pediatric MSP. The algorithm promotes the identification and structured interpretation of the patient’s individual clinical clues. It should serve the primary care physician to recognize when further intervention, rather than reassurance and follow-up, is needed using the minimum amount of testing to make an appropriate, prompt diagnosis in the clinical situation “child presenting with MSP”. A German version of this algorithm has been published in the Guideline-Portal of The Association of the Scientific Medical Societies (“Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften”, AWMF) in November 2013.

Muskuloskelettale Schmerzen (MSS) sind bei Kindern und Jugendlichen häufig und mit einem breiten Spektrum an Differenzialdiagnosen, auch Krebs, assoziiert. Durch kontinuierliche Optimierung von Diagnostik und Behandlung wurden die Überlebensraten von Kindern und Jugendlichen mit Krebserkrankungen in den letzten Jahrzehnten auf über 80 % gesteigert. Für die erstversorgenden Ärzte tritt ein gezielter, kostenbewusster Umgang mit den diagnostischen Verfahren zunehmend in den Vordergrund. Aufgrund der Seltenheit von Krebs bei Kindern und Jugendlichen wird bei unspezifischen Symptomen wie MSS oft nicht gleich an ein Malignom als Ursache gedacht. So kommt es einerseits regelmäßig zu Fehldiagnosen mit prognostischer Relevanz. Andererseits belastet unnötige invasive und kostspielige Diagnostik sowohl die Patienten als auch das Gesundheitssystem. Ziel dieser Übersichtsarbeit ist die Verbreitung eines Algorithmus zur symptomorientierten Differenzialdiagnostik in der Situation „Kind/Jugendliche(r) mit MSS“ in der Primärversorgung. Damit soll zur Verbesserung der Prognose von Kindern und Jugendlichen mit MSS und entsprechender Grunderkrankung beigetragen werden. Der Algorithmus wurde von Mitgliedern der Gesellschaft Pädiatrische Onkologie und Hämatologie (GPOH) in Zusammenarbeit mit der Deutschen Gesellschaft für Kinder- und Jugendmedizin (DGKJ) und dem Bundesverband für Kinder- und Jugendmedizin (BVKJ) entwickelt. Es wird eine Vorgehensweise zur sofortigen und richtigen Diagnosestellung empfohlen, die die individuelle anamnestische, psychosoziale und klinische Befundkonstellation des Patienten systematisch erfasst und schrittweise miteinander vereinigt.

Bibliography DOI http://dx.doi.org/ 10.1055/s-0034-1366989 Klin Padiatr 2014; 226: 86–98 © Georg Thieme Verlag KG Stuttgart · New York ISSN 0300-8630 Correspondence PD Dr. med. Gesche Tallen Department of Pediatric Oncology/Hematology Charite-Universitaetsmedizin Berlin Otto-Heubner-Centrum fuer Kinder- und Jugendmedizin 13353 Berlin Germany Tel.: + 49/30/450566 032 Fax: + 49/30/450566 908 [email protected]

Tallen G et al. Musculoskeletal Pain: A New … Klin Padiatr 2014; 226: 86–98

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Schlüsselwörter ▶ Kinder und Jugendliche ● ▶ muskuloskelettale ● Schmerzen ▶ Epidemiologie ● ▶ Ätiologie ● ▶ Differenzialdiagnose ● ▶ Primärdiagnostik ●

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Background – the rocky bridge between primary and secondary care

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Musculoskeletal pain (MSP) is a common, multifaceted complaint affecting 10–20 % of children [5, 8, 12–14, 18, 23, 25, 28, 29, 33, 36, 38, 40, 41, 56, 57, 63]. According to international surveys, nearly half of all children and adolescents complain about MSP some time during their physical development [5, 8, 28, 29, 33, 40, 56, 57]. Almost a tenth of all pediatric visits in primary care clinics are due to MSP. The most frequent complaints are arthralgias of the knees, elbows and wrists, followed by soft tissue (muscle)-, heel-, hip- and back pain [5, 8, 29, 56, 57]. The incidence of an underlying serious health problem is below 1 %: only one of 10 000 children and adolescents present with MSP as the primary symptom of cancer [2, 3, 6, 11, 15–17, 22, 27, 37, 39, 46, 48–52, 61]. However, among many pediatric patients with neuroendocrine tumors (NETs), pain like chronic MSP is the cardinal symptom [44]. Also, MSP can be the presenting symptom of familial mediterranean fever, the most frequent inherited autoinflammatory disease in certain ethnic groups [26]. Therefore, the relevance of a systemic or pre-existing disease for differential diagnosis should not be underestimated when evaluating pediatric MSP at the primary care level. In addition, any type of child abuse is associated with chronic MSP and must always be considered [53]. Failure to recognize these conditions may result in treatment delay, significant morbidity, future health problems, excessive use of health care resources and of redundant, sometimes invasive diagnostic tests and overmedicalization. MSP that has been interpreted as "benign" or "idiopathic", respectively, as well as injuries that remain unexplained, can jeopardize a child’s welfare by causing chronic pain syndromes with substantial psychological and physical impairment. Hence, the primary care physician must recognize when further intervention, rather than reassurance, follow-up and subspecialty referral, is needed using the minimum amount of testing to make an appropriate, prompt diagnosis. However, considering the expanding spectrum of diagnostic options, this can be a challenge today. Various articles on the management of pediatric MSP have been published. But most of them focus either on single aspects of the complaint only or on its treatment. Information that has been narrowed down and would guide through initial evaluation is, to our knowledge, rare and controversial. Hence, a comprehensive, multidisciplinarily quality-proven, systematic and stepwise approach, that unites the patient’s individual anamnestic, psychosocial, and clinical characteristics is required.

Objective and methods: taming a clinical chamaeleon

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The goal of developing this algorithm was to contribute to efficient, rational and cost-effective primary care assessment of pediatric MSP. On behalf of the German Society of Paediatric and Adolescent Medicine (DGKJ), the development of the guideline was initiated and coordinated by representatives of the Society of Paediatric Oncology and Haematology (GT, GH, UC, SB, GPOH). Systematic review of the literature was performed based on searches in Medline, The Cochrane Library, National Guideline Clearinghouse (NGC), Google Books, archives of the "Deutsches Aerzteblatt", DGKJ (Monatsschr Kinderheilk), GPOH (Klin Padiatr), the American Academy of Family Physicians (from 03/1998-

03/2013), and information provided by the working-group consisting of 13 experts in selected pediatric subspecialties. A total of 959 records was identified and screened for duplicates and eligibility for further assessment based on their publication dates (03/1998-03/2013), as well as on the particular focus of titles (English, German) and abstracts (e. g. epidemiology, etiology, diagnostics). Based on these criteria, 826 records were excluded. The remaining 133 articles were assessed as full-texts for their potential relevance for the guideline. Based on the eligibility criteria (e. g. article type: cohort-study, case-report, questionnaire-based study; study population: pediatric; contents: information on at least one of the following: epidemiology, etiology, evaluation/assessment, history taking, physical exam, laboratory diagnostics, diagnostic imaging, differential diagnosis), a total of 90 records was included in the final version of the guideline*. 64 of these were used for this review. Because of the conceptual and clinical heterogeneity as well as the diversity of the major foci of the selected articles, statistical pooling of diagnostic data was not performed. Instead, the algorithm was developed using a multi-step, formal consensus process including the expertise of all members of the expert-group. The associated German guideline has recently been published online by the Association of the Scientific Medical Societies (“Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften”, AWMF)*.

The algorithm – identifying individual clues

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“It is far more important to know what sort of a patient has a disease than what sort of a disease a patient has.”1 For a practical initial approach to the young patient with MSP, 2 ▶ Fig. 1, 2), 5 tables ● ▶ Table 1–5) and a main text figures (● including 4 paragraphs representing major diagnostic steps were ▶ Fig. 1 shows the algorithm-graphic providing a struccreated. ● tured, stepwise assessment of the patient based on his/her individual clinical clues. It leads the user to further information by ▶ Fig. 2 for identifying age- and type of targeted referring a) to ● pain-related clues, b) to the 4 major diagnostic steps described ▶ Table 1–5, each of which represents in the main text and c) to ● an subgroup of diseases causing MSP as well as to the corresponding recommended secondary care to be initiated.

Step I “Listen to your patient. He is telling you the diagnosis.”1 – Taking the history Thorough history-taking from the patient and family helps to early on identify conditions, that do not require additional, unnecessarily invasive and expensive testing. These conditions include certain mechanical pathologies or the well-known benign nocturnal leg pain (BNLP) in children under the age of 6, often erroneously described as “growing pains” [1, 20, 34, 54, 58]. Furthermore, the primary care physician is the one responsible to rule out conditions, that do need prompt attention, such as trauma, child abuse, infection or cancer, in order not to compromise prognosis. Therefore, the following clues should be the first to assess when taking the history:

* http://www.awmf.org/leitlinien/detail/ll/025-032.html 1 Sir William Osler (1849–1919), Founder of the American Pediatric Society Tallen G et al. Musculoskeletal Pain: A New … Klin Padiatr 2014; 226: 86–98

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Fig. 1 Diagnostic algorithm for primary care assessment of pediatric musculoskeletal pain. Shapes: oval/circle – patient’s condition, rectangle – physician’s action, hexagon – to be considered ▶ Table 1; during an action. Colors: blue – see ● ▶ Table 2; red – see ● ▶ Table 3–5; green – see ● purple – see main text: step I–3 Superscripts: F2 ▶ Fig. 2; S1,2,3,4 see main text: steps I, II, see ● ▶ Table 1–5. Fx – fracture; III, IV; T1,2,3,4, 5 see ● MSP – musculoskeletal pain; n – normal findings; p – pathological findings; PE – physical exam; “ + ” – “yes”; “−” – “no”.

Child/adolescent with musculoskeletal pain (MSP) S1 age-related cluesF2

conspicuous psychosocial or lifestyle factors mechanical injury accident + competitive sports

+

History

+

additional symptoms +

+

indicative of systemic disesase

vegetative functional

pre-existing illness

+

medication

+

malnutrition malabsorption

+

pain-related cluesF2

+

localized

+

worsened by activity

– –

+

chronic recurrent

+

+

progressive

+

regional (e.g. legs/spine)

+

+

diffuse/multifocal

+

episodical / nocturnal

+

+

worsened at rest

–

chronic pain syndrome causes MSP

mechanical etiology of MSP

systemic disease causes MSP

S2

potential cause of MSP

Physical Exam (PE)

general clinical condition +

goodslightly reduced

Fx?

+

good

+

gentle PE! functional impairment

+

–

+

reduced - bad

no glucocorticoids + before malignancy is ruled out!!

–

tumor

+

signs of systemic disease

–

musculoskeletal portion +

–

‘tender points’

+

classical signs of infection

S3 laboratory testing n

p

diagnostics according to subspecialty consult

S4 diagnostic imaging

p +

abuse?

mechanical (non-infectious) T1

disease

n

n

p

+

chronic pain syndromeT2

systemic disease (malignancy/infection/ rheuma)T3–5

1. Age A child’s age frequently demarcates the likelihood of certain dif▶ Fig. 2): ferential diagnoses as causes of MSP, for example (● ▶ Trauma or mechanical pathology can generally occur at all ages and are often associated with limping or functional impairment. However, while sprains and strains are frequent in adolescents (10–16 years), the incidence of fractures (fx), rather decreases with increasing age. These include tibial fx due to child abuse, which are mostly seen in infants and todd▶ Table 1; ● ▶ Fig. 1-blue path; ● ▶ Fig. 2) lers ( < 3 years) [53] (● ▶ Limp and acute groin and/or knee pain worsened by activity in toddlers, preschool (3–5 years) and school children (6–9 years) should be considered as due to transient synovitis of the hip, particularly in patients with a history of a recent cold. Instead, teenagers presenting with this type of MSP are most likely to suffer from acute or acute on chronic slipped capital femoral ▶ Table 1; ● ▶ Fig. 1-blue epiphysis (SCFE) [8, 29, 38, 56, 57] (● ▶ Fig. 2) path; ●

Tallen G et al. Musculoskeletal Pain: A New … Klin Padiatr 2014; 226: 86–98

pre-existing conditionS1–3

▶ Aseptic osteonecroses, such as Legg-Calvé-Perthes (LCP), Osgood-Schlatter (OSD), Scheuermann and Köhler diseases, show typical age-related prevalences that should be con▶ Table 1; ● ▶ Fig. 1-blue sidered as common causes of MSP (● ▶ Fig. 2) path; ● ▶ Benign bone tumors, such as ossifying fibromas, are often asymptomatic for a while, but may in an advanced stage be the cause of jaw pain and swelling, particularly in children ▶ Table 1; ● ▶ Fig. 1-blue path) under 10 years [19] (● ▶ Nocturnal leg pain known as "growing pains" is most frequently reported for children younger than 6 years [1, 20, 34, 54, 58]. Since healthy children of this age group grow relatively less when compared to other phases of development, it is rather unlikely that these complaints are caused by growths spurts. Hence, instead of calling them "growing pains", they should be classified as BNLP into the group of chronic pain syndromes. These are defined as conditions presenting with MSP, that lacks any somatic correlate in the physical exam [5, 58, 64]. Diagnosis can usually be confirmed based on specific clues

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acute

+

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pediatric patient with MSP (back & lower extremities) rule out trauma & pre-existing illnessS1 (1,2) determine age-group & history of pain

worsened by activity

+

+ –

back pain

foot pain

+

+

+

LCH

Severs disease

Trauma is the most frequent cause of pediatric MSP. Any indication of an accident, including mechanical injuries due to child abuse, should be evaluated before considering other possibilities. Participation in competitive and recreational sports by school children and adolescents ( > 6 years) has increased remarkably over the last decade. Despite of multiple associated health benefits, sport-related injury is one of the adverse consequences. Overuse or repetitive trauma represent approximately 50 % of all pediatric sport-related injuries and should be consi▶ Table 1, dered when initially evaluating pediatric MSP [55] (● ▶ Fig. 1-blue path). ●

Koehler disease

2. Recent history of trauma or mechanical injuries

APR-Fx

identified in the patient’s history and physical exam. As a differential diagnosis, particularly in children older than 6 years, restless legs-syndrome (RLS) should be considered [43] ▶ Table 3; ● ▶ Fig. 1-green, -purple paths; ● ▶ Fig. 2) (● ▶ Overall, pediatric cancer can occur at any age. Although MSP as a primary symptom is generally rare (1/10 000 children with MSP), a prevalence of some malignancies, that often present with MSP, to certain age-groups does exist. These include leukemia and neuroblastoma, which mostly affect children under the age of 5 years, as well as malignant bone tumors such as osteosarcoma and Ewing sarcoma, which are more common in adolescents (> 10 years) [2, 3, 6, 11, 15–17, 22, 27, ▶ Table 3; ● ▶ Fig. 1-red path; ● ▶ Fig. 2) 37, 39, 46, 48–52, 61] (● ▶ Both infectious and inflammatory/rheumatic diseases such as subacute and acute or non bacterial osteomyelitis (NBO), respectively, may cause MSP and can affect any age-group [4, 24, 47]. Nevertheless, when assessing a child with MSP and signs of systemic disease (see Step I: 4.), certain age-related characteristics, particularly for rheumatic conditions, should be kept in mind. For example, the "little girl with knee pain" is highly suspicious of suffering from juvenile idiopathic arthritis (JIA), a typical diagnosis in toddlers, while systemic lupus erythematodes (SLE) – associated arthritis is rather rare in ▶ Table 4, 5; ● ▶ Fig. 1-red paths; ● ▶ Fig. 2). this age-group [8] (●

disc prolaps

NBO

JFMS

S1(2)

solid tumor

RLS

acute/subacute OM | discitis

JIA

leukemia

BNLP

benign bone tumor

OSD

OCD

leg length difference

LCP

SCFE**

SCFE*

adolescent (10–16y)

overuse

school child (6–9y)

present/ worsened at night/rest

septic coxitis

preschool child (3–5y)

tibial fx (child abuse)

transient synovitis of the hip

infant/ toddler ( 3 months) MSP, autonomic symptoms and normal physical exam are likely to suffer from a chronic pain syndrome such as the so-called juvenile fibromyalgia syndrome (JFMS) [2–6, 8, 11, 15–17, 22, 24, 27–30, 32, 33, 37, 39, 40, 45–52, ▶ Table 3–5; ● ▶ Fig. 1-red paths). 56, 57, 61] (● Tallen G et al. Musculoskeletal Pain: A New … Klin Padiatr 2014; 226: 86–98

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acute leg pain (limp)

Fig. 2 Age- and pain-related clues in a pediatric patient with musculoskeletal pain. Shapes: oval/ circle – patient’s condition, rectangle – physician’s action, hexagon – to be considered during an action. APR – apophyseal ring; BNLP – benign nocturnal leg pain; Fx – fracture; JIA – juvenile idiopathic arthritis; JFMS – juvenile fibromyalgia syndrome; LCH – Langerhans’ Cell Histiocytosis; LCP – Legg-Calvé-Perthes disease; NBO – nonbacterial osteomyelitis; OCD – osteochondrosis dissecans; OSD – Osgood-Schlatter disease; RLS – restless legs syndrome; SCFE – sucapital femoral epiphyseolysis (*acuta, **lenta); y – years; “ + ” – “yes”; “−“ – “no” Superscripts: S1 (1,2) see main ▶ Table 1; green text: step I-1,2. Colors: blue – see ● ▶ Table 2; red – see ● ▶ Table 3–5; purple – – see ● see main text: steps I–3.

– physiotherapy

– physiotherapy; if not successful: – low-dose analgetics; if not successful: – consult: pediatric surgery/orthopedics – physiotherapy; if not successful: – low-dose analgetics; if not successful: – consult: pediatric surgery/orthopedics

– consult: – pediatric (neuro)surgery/orthopedics

– immediate referral to pediatric emergency unit/surgery/orthopedics

– follow-up – if required: low-dose antiphlogistics

– physiotherapy; if not successful: – low-dose analgetics; if not successful: – consult: pediatric surgery/orthopedics

—

– diagnostic imaging4 (joint ultrasound/plain radiographs, MRI for synovial plica)

– diagnostic imaging (plain radiographs/MRI)4

Tallen G et al. Musculoskeletal Pain: A New … Klin Padiatr 2014; 226: 86–98

– diagnostic imaging (plain radiographs/MRI)4

diagnostic imaging (plain radiographs of pelvis, affected hip in Lauenstein planes and contralateral side)4

–diagnostic imaging (hip-ultrasound/MRI only for persistent or worsening symptoms)4

– diagnostic imaging (MRI for early diagnosis-only later stages of the disease (after 6–8 weeks) are detectable in plain radiographs (hip, pelvis, according to Lauenstein)4

2 3 4 5 6 7 for definition of age-groups/age- and type of pain-related clues: see ● ▶ Fig. 2; see main text: step I; see main text: step II; see main text: step IV; see ● ▶ Table 3; see ● ▶ Table 4; see ● ▶ Table 5

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CC – cave complications; CT – computed tomography; DD – differential diagnosis; JIA – juvenile rheumatoid arthritis; MSP – musculoskeletal pain; MRI – magnetic resonance imaging; NBO-non-bacterial osteomyelitis; RTI – respiratory tract infection

1

Perthes Disease (PeD; aseptic osteonecrosis of the femoral head)

Coxitis fugax (transient synovitis of the hip)

Epiphysiolysis Capitis Femoris (ECF)

overuse

Osteochondrosis Dissecans (OD)

patellofemoral dysfunction

joint hypermobility

Secondary care – immediate referral to pediatric emergency unit/orthopedic/surgery clinic – if child abuse is suspected: immediate intervention

– diagnostic imaging4 (plain radiographs/MRI/CT)2

– history of trauma/accident – major Fx-signs: dyslocation, open fx – minor Fx-signs: swelling, pain, functional impairment – most frequent: distal tibial shaft-Fx – rare: Salter-Harris-Fx – child abuse – most frequent in female adolescents – asthenic habitus – pathological laxity/hypermobility of various joints – DD: pre-existing collagenoses (Ehlers-Danlos-/Marfan-Syndrome) – often associated with chondromalacia patellae, congenital synovial plica – knee pain when walking stairs – positive patella-sign – genua valga (“knock-knees”) – athletic patient (running sports) – no or only mild joint effusion – no characteristic additional symptoms – no reproducible pain-tests – blocked/impaired joint function – DD: osteonecroses (s. below), malignancy5, osteomyelitis6, rheumatic disease7 – backpain: spondylodysis, disc prolaps – elbow-pain, tender tendon insertions of forearm muscles: epicondylitis – kneepain: injured ligament – (bilateral) heel pain: Sever’s disease – DD: malignancy5, aseptic osteonecroses (s. below), infection6 (osteomyelitis, discitis) – acute groin pain followed by painful leg position in external rotation: ECF acuta – chronic diffuse or knee/thigh pain, muscle contraction and leg in external rotation position: ECF lenta – Drehmann-sign positive – CC: acute necrosis of the femoral head (8–10 %), longterm deformation and arthrosis of femoral head – DD: coxitis fugax, Perthes Disease (s. below) – most frequent hip disease in children – short history ( < 3 weeks) of knee and/or groin pain and viral upper RTI – impaired hip-rotation – self-limiting (after 2–3 weeks) – DD: Perthes Disease (s.below), JIA7 – long ( > 3 weeks) history of knee and/or groin pain – 10 % bilateral complaints – Trendelenburg’s test positive – CC: atrophy of thigh muscles – DD: coxitis fugax (s. above), septic arthritis6, epiphyseal dysplasia (type Meyers)

fracture (Fx)

Initiate (after completion of Steps I & II) Diagnostics

Evaluate Specific Clues1–3

Common Diagnoses

Consider

Identify Major Clues 1–3: acute, localized MSP relieved by rest, worsened by activity | stable clinical Condition | somatic correlate

Table 1 Primary Care Management of mechanical (non-inflammatory, non-infectious) causes of pediatric musculoskeletal pain.

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– diagnostic imaging (plain radiographs/MRI/CT/bone scintigraphy)4

– diagnostic imaging (plain radiographs)4

– diagnostic imaging (plain radiographs/MRI)4

– diagnostic imaging (plain radiographs)4

– diagnostic imaging (plain radiographs/MRI)4

– low-dose analgetics – referrals: pediatric surgery for histological diagnosis (biopsy)/tumor removal; radiology for thermo-/lasercoagulation of osteoidosteoma

Secondary care – physiotherapy; if not successful: – low-dose analgetics; if not successful: – consult: pediatric surgery/orthopedics – physiotherapy; if not successful: – low-dose analgetics; if not successful: – consult: pediatric surgery/orthopedics – physiotherapy; if not successful: – low-dose analgetics; if not successful: – consult: pediatric surgery/orthopedics – physiotherapy; if not successful: – low-dose analgetics; if not successful: – consult: pediatric surgery/orthopedics – consult: pediatric surgery/orthopedics

– diagnostic imaging (plain radiographs/MRI)4

Initiate (after completion of Steps I & II) Diagnostics

2 3 4 5 6 7 for definition of age-groups/age- and type of pain-related clues: see ● ▶ Fig. 2; see main text: step I; see main text: step II; see main text: step IV; see ● ▶ Table 3; see ● ▶ Table 4; see ● ▶ Table 5

– clubfoot – history of trauma – osteoidosteoma most frequent in adolescents with nighttime pain attacks in legs and spine, good response of pain to non-steroidal antiphlogistics – ossifying fibroma often associated with maxillary pain and swelling – DD: malignancy5, bacterial infection6, NBO7

– swollen forefoot – contraction of toe muscles – CC: arthrosis – kyphosis – DD: overuse (s. above), malignancy5

– most frequent cause of knee pain in (physically active) adolescents – subpatellar pressure pain – DD: patellofemoral dysfunction, ECF lenta (s. above) – pressure pain at radial elbow – DD: OD (s. above)

Evaluate Specific Clues1–3

Tallen G et al. Musculoskeletal Pain: A New … Klin Padiatr 2014; 226: 86–98

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CC – cave complications; CT – computed tomography; DD – differential diagnosis; JIA – juvenile rheumatoid arthritis; MSP – musculoskeletal pain; MRI – magnetic resonance imaging; NBO-non-bacterial osteomyelitis; RTI – respiratory tract infection

1

benign solid tumor (osteoidosteoma, aneurysmatic bone cyst, osteoblastoma, chondroma, ossifying fibroma)

leg length difference

Osgood-Schlatter Disease (OSD; aseptic osteonecrosis of the tuberositas tibiae) Panner Disease (PaD; aseptic osteonecrosis of the capitulum humeri) Köhler Disease (KD; aseptic osteochondronecrosis of the os naviculare) Scheuermann Disease

Common Diagnoses

Consider

Identify Major Clues 1–3: acute, localized MSP relieved by rest, worsened by activity | stable clinical Condition | somatic correlate

Continued. Table 1 Primary Care Management of mechanical (non-inflammatory, non-infectious) causes of pediatric musculoskeletal pain.

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Table 2 Primary Care Management of chronic pain syndromes as causes of pediatric musculoskeletal pain. Identify Major Clues1–3: chronic, diffuse MSP at multiple sites | good clinical condition | no somatic correlate Consider Common Diagnoses

Evaluate Specific Clues1–3

Initiate (after completion of main text: steps I & II)2,3 Diagnostics

Secondary care

Juvenile Fibromyalgia Syndrome (JFMS)

– most frequent in female adolescents – family history of MSP – vegetative symptoms – defined “tender points” (mandatory) – no pathological findings in PE – DD: somatization disorder due to abuse, RLS1–3 – no history of additional symptoms4 – no pathological findings in PE – self-limiting – DD: RLS1–3, NBO5, benign tumor6

– laboratory testing4 (rule out infection/iron-deficiency/metabolic disease)

– consult: pediatric psychology – if required: antidepressants – interdisciplinary follow-up

—

– comprehensive, reassuring family meeting – follow-up

Benign nocturnal leg pain (BNLP)

1

2 3 4 5 6 for definition of age-groups/age- and type of pain-related clues: ● ▶ Fig. 2: see main text: step I; see main text: step II; see main text: step III; see ● ▶ Table 5, ● ▶ Table 1

5. Psychosocial and lifestyle factors Thorough evaluation of the patient’s psychosocial history and activity helps identifying conditions that do not require extended, invasive diagnostics. Hence, the primary care physician should be aware of any psychosocial problems as well as lifestyle factors, such as ▶ trouble at school, at home or with peers ▶ mood swings possibly associated with puberty ▶ signs of depression ▶ signs of anxiety disorders ▶ signs of drug abuse ▶ frequency and duration of physical activity, computer use and television viewing ▶ eating habits ▶ hobbies, interests All these factors influence pain-related fears, pain coping, painrelated parenting and social interactions when dealing with pain. They may contribute to the development of certain chronic pain syndromes, such as JFMS [1, 5, 8, 28, 29, 33, 38, 40, 43, 56– ▶ Table 2, ● ▶ Fig. 1-green path). 58, 64] (●

6. Pain characteristics Obtaining comprehensive information on the individual pain characteristics narrows the likely diseases causing MSP [5, 8, 28, 29, 33, 40, 56, 57]. Specifically, aspects like pain onset (shortly after a cold/respiratory or genitourinary infection, following athletic activity, after an accident, rapid vs gradual), localization (localized joint/muscle/bone/tendon vs diffuse pain), intensity (based on a scale of 1–10, functional impairment, morning stiffness), triggering (such as by pushing "pres▶ Table 2, ● ▶ Fig. 1-green path), worsening or sure points" – see ● alleviating (activity vs rest) factors as well as spread and course over time (self-limiting vs progressive vs persistent vs recurrent) should be solicited as follows: ▶ functional impairment and a history of sudden onset of localized pain worsened by activity are typical complaints after an acci▶ Table 1; ● ▶ Fig. 1-blue path, ● ▶ Fig. 2). dent or child abuse (● However, if the patient additionally presents with systemic symptoms (see Step I: 4.), a septic condition must be ruled out ▶ Table 4, ● ▶ Fig. 1-red path) prior to considering other causes (● ▶ recurrent localized MSP following physical exercise with the patient being otherwise in unrestrained physical condition are common and may be indicative of chronic overuse [5, 55], ▶ Table osteochondrosis dissecans or aseptic osteonecrosis (● ▶ Fig. 1-blue path; ● ▶ Fig. 2) 1, ● Tallen G et al. Musculoskeletal Pain: A New … Klin Padiatr 2014; 226: 86–98

▶ diffuse pain at multiple sites that has been developing gradually over months and is subjectively perceived as intense, but lacks ▶ Table any somatic correlate is suggestive of JFMS [13, 46] (● ▶ Fig. 1-green path; ● ▶ Fig. 2) 2, ● ▶ chronic ( > 3 months), bilateral, diffuse, mostly nocturnal pain should be diagnosed as BNLP only after RLS and a malignancy have been ruled out [1, 20, 22, 27, 34, 43, 54, 57–59, 64] (see ▶ Table 2; ● ▶ Fig.1-green, -red, -purple paths) Step I: 3, ● ▶ recurrent, localized bone, joint or back pain, particularly when accompanied by constitutional complaints (see Step I: 4.), might be caused by NBO [4, 24]. Since NBO is rare, subacute bacterial osteomyelitis, a benign bone tumor [59], and a malignancy must be considered before diagnosing NBO ▶ Table 4, 5; ● ▶ Fig. 1-blue, -red paths; ● ▶ Fig. 2) (● ▶ a long-term history ( > 6 weeks) of MSP and morning stiffness, which is relieved by activity is indicative of rheumatic disease [30]. Joint pain following an upper respiratory, gastrointestinal or urinary tract infection is frequently caused by an inflammatory arthritis, while rheumatic fever as an underly▶ Table 5; ● ▶ Fig. 1-red ing condition is rare today [32] (● ▶ path; ● Fig. 2). ▶ persistent or recurrent cervical or lower back pain (with or without segmental radiation) is often due to reduced physical activity. However, there is no correlation between these complaints and the intensity of computer or television use [10, 62]. An orthopedic (Scheuermann’s disease, disc prolaps), oncological (spinal tumor) or infectious (discitis) etiology should be ruled out initially before drawing other conclusions ▶ Table 1, 3, 4; ● ▶ Fig. 1-blue, -red paths; ● ▶ Fig. 2). (●

Step II “Failure to examine the throat is a glaring sign of omission, especially in children.”1 – Conducting the physical exam Regardless of the suspected diagnosis after having taken the history, a complete physical exam (PE) including the neurological and musculoskeletal portion is required to further differentiate various potential etiologies of pediatric MSP, thus to protect both patient and health care system from redundant, undirected, painful and costly procedures [1, 36, 60]. Whenever conducting this PE, the following basics should be followed in the recommended order:

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DD – differential diagnosis; MSP – musculoskeletal pain; NBO – non-bacterial osteomyelitis; PE – physical exam; RLS – restless legs-syndrome

– referral to pediatric oncology/ hematology clinic

– laboratory testing4 – diagnostic imaging8 (after pediatric oncology – consult) – histology (in pediatric oncology/hematology clinic)

– referral to pediatric oncology/ hematology clinic

– laboratory testing4 – diagnostic imaging8 (after pediatric oncology – consult) – histology (in pediatric oncology/hematology clinic)

– to pediatric oncology/hematology clinic

– referral to pediatric oncology/ hematology clinic

– laboratory testing4 – diagnostic imaging8 (after pediatric oncology – consult) – histology (in pediatric oncology/hematology clinic)

– laboratory testing4 – diagnostic imaging8 (after pediatric oncology – consult) – histology (in pediatric oncology/hematology clinic)

– referral to pediatric oncology/ hematology clinic

– laboratory testing4 – diagnostic imaging8 (after pediatric oncology – consult) – histology (in pediatric oncology/hematology clinic)

Secondary care – referral to pediatric oncology/ hematology clinic

– laboratory testing4 – BMB/BMP/histology (in pediatric oncology/hematology clinic)

2 3 4 5 6 7 8 for definition of age-groups/age- and type of pain-related clues: see ● ▶ Fig. 2; see main text: step I; see main text: step II; see main text: step III; see ● ▶ Table 5, see ● ▶ Table 1, see ● ▶ Table 4, see main text: step IV

– most frequent childhood malignancy (ALL)1 – diffuse, often nocturnal MSP with signs of systemic disease2,3 – CBC/differential blood cell count: cytopenia (sometimes of one cell line only)4 – early stages often without systemic symptoms or peripheral blasts4 – elevated serum LDH4 – elevated uric acid serum levels – CC: lethal if not treated appropriately – DD: NBO5, osteoidosteoma6, subacute bacterial osteomyelitis7 – most frequent malignant bone tumor in children and adolescents1 – localized, progressive MSP (metaphyses of long bones/mostly knee region)1 – CC: lethal if not treated appropriately – DD: other malignant bone tumor (see below), benign bone tumor6, NBO5, subacute bacterial osteomyelitis7 – second most frequent malignant bone tumor in children and adolescents1 – localized, progressive MSP (diaphyses of long bones/mostly pelvic region) – CC: lethal if not treated appropriately – DD: other malignant bone tumor (see above), benign bone tumor6, NBO5, subacute bacterial osteomyelitis7 – most common extracranial solid tumor in childhood (90 % of children are younger than 5 years of age) – CC: lethal if not treated appropriately – DD: other (gastroenteropancreatic) NET (especially if MSP is accompagnied by symptoms indicative of hormonal dysorder such as abdominal or chest pain, heartburn, dry cough, chronic sore throat, diarrhea, symptoms of hypoglycemia, rash) – localized, progressive MSP – visible , indolent swelling – CC: lethal if not treated appropriately – DD: benign soft tissue tumor6, soft tissue abscess – no age preference – unifocal MSP/disease: eosinophilic granuloma: 40 % – multifocal MSP/disease: bone (pathological fx, lytic lesions) and skin lesions (scalp, trunc), pathological loss of teeth, diabetes insipidus, chronic purulent otitis – BM disease: pancytopenia and associated sypmtoms of systemic disease2,3

Initiate (after completion of main text: steps I & II)

osteomyelitis

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BM – bone marrow; BMB – bone marrow biopsy; BMP – bone marrow punction; CBC – complete blood cell count; CC – cave complications; DD – differential diagnosis; LDH – lactate-dehydrogenase; MSP – musculoskeletal pain; NBO – non-bacterial

1

Langerhans Cell Histiocytosis (LCH)

soft tissue sarcoma

neuroendocrine tumors (NETs, e. g. neuroblastoma)

ewing sarcoma

osteosarcoma

leukemias (acute lymphoblastic leukemia, ALL; acute myeloid leukemia, AML)

Diagnostics

Evaluate Specific Clues1–3

Consider

Common Diagnoses

Identify Major Clues1–3: Acute/chronic, diffuse/localized, progressive MSP | reduced/bad general clinical condition | additional symptoms | somatic correlate

Identify Major Clues1–3:

Table 3 Primary Care Management of malignancies as causes of pediatric musculoskeletal pain.

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In patients with MSP shortly after trauma, particularly when suspicious of fx, the PE should be subtle, thus limited to ▶ inspection of local perfusion ▶ gross motor skills ▶ testing of sensitivity ▶ screening of a potentially fx-associated dislocation PE must not include palpation of painful sites, functional tests or active checking on typical fx-signs such as crepitation.

A child or adolescent with MSP, but in stable general condition (i. g. normal vitals and growth pattern, lack of functional impairment and/or constitutional deficiencies) is less likely to suffer from a serious underlying disease than an MSP-patient presenting with ▶ characteristic signs of trauma/fx/mechanical injury (e. g. swelling, joint/bone dislocation, limp) ▶ general signs of acute local infection (rubor, dolor, calor, tumour, functio laesa) ▶ general signs of chronic or systemic disease (e. g. pallor, fever, malaise, signs of poor growth, spleno-, hepatomegaly, lymphadenopathy, muscle weakness) ▶ characteristic rashes representing certain inflammatory or autoimmune diseases (e. g. Gottron papules: dermatomyositis; Café au lait-spots: McCune-Albright syndrome; macular or maculopapular exanthema: JIA; palmoplantar pustulosis: NBO; butterfly rash: SLE) [10, 15, 16, 56, 57].

3. Identifying clues in the musculoskeletal portion

Tallen G et al. Musculoskeletal Pain: A New … Klin Padiatr 2014; 226: 86–98

The musculoskeletal portion of the PE of a child with MSP should always include the ▶ evaluation of muscle girths, -strength, gait, spinal posture and function ▶ assessment of (differences of) extremity lengths ▶ a functional check of both affected and adjacent joints (except in trauma-patients, see Step II: 1.) ▶ identification of “tender points” (except in trauma-patients, see Step II: 1.). The findings particularly help distinguishing between MSP caused by leg-length differences (e. g. idiopathic, after trauma or following gonarthrosis), myositis or arthritis: leg-length differences often cause hip and knee pain. Typical signs of arthritis include local signs of inflammation and functional impairment accompanied by a protective flexion-posture [6, 27]. Septic arthritis frequently results in pseudoparalysis, while chronic arthritis often leads to local muscle atrophy and joint contractures. Instead, painful muscle or tendon insertions lacking a somatic correlate are indicative of JFMS [64]. To achieve optimal reproducibility of the initial findings, initial and follow-up assessment of musculoskeletal function/joint range of motion is recommended to be performed according to the standard of the neutral-null method.

Step III Who really needs which poke? – Laboratory testing Except when dealing with JFMS, management of pediatric patients with MSP and benign characteristics in history, including trauma, and in the PE does usually not require laboratory

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2. Identifying alarming signs that require prompt additional testing

MSP – musculoskeletal pain; TBC – tuberculosis; TC – tissue culture; WBC – white blood cell count

ASL – anti streptolysine; BC – blood cultures; BSR – blood sedimentation rate; CRP – C-reactive protein; CC – cave complications; DD – differential diagnosis; LCH – Langerhans’ Cell Histiocytosis; MRI - magnetic resonance imaging;

2 3 4 5 6 7 for definition of age-groups/age- and type of pain-related clues: see ● ▶ Fig. 2; see main text: step I; see main text: step II; see ● ▶ Table 3; see ● ▶ Table 1, see main text: step III; see main text: step IV

↑: elevated

subacute bacterial osteomyelitis

1. Dealing extra gently with patients with mechanical injuries

1

Secondary care

– no antibiotic treatment prior to BC/TC – no glucocorticoids before having ruled out malignancy4 – consult: pediatric infectious diseases clinic or general pediatrics – in case of sepsis: referral to childrens’ hospital emergency unit – antibiotic treatment – if needed: referral to pediatric surgery clinic for removal of infected tissue/biopsy – laboratory testing6(WBC↑, CRP↑, BSR↑, ASL↑, identification of pathogen in BC/TC, TBC-screening) – diagnostic imaging7 (ultrasound/MRI) – histology/microbiology (after joint puncture/ bone biopsy) – laboratory testing6(TBC-screening, other lab parameters rather unspecific) – diagnostic imaging7 (MRI) – histology/microbiology (after joint puncture/ bone biopsy) – recent history of (bacterial) infection/foreign body inoculation – acute, intense, localized MSP (bone, joints) with signs of systemic disease2,3 – painful functional impairment/pseudoparalysis – CC: sepsis, endocarditis – DD: malignancy4 – recent history of (viral) upper airway infection/common cold (mandatory) – localized (diaphyses), intermittent MSP, sometimes with joint swelling and mild functional impairment – rarely additional symptoms2,3 – benign course if treated with antibiotics – CC: slowly progressive without treatment – DD: malignant bone tumor4, LCH4, osteoidosteoma5, TBC, fungal infection acute bacterial arthritis/ (multifocal) osteomyelitis/ discitis

Initiate (after completion of main text: steps I & II)

Diagnostics Common Diagnoses

Evaluate Specific Clues1–3 Consider

Acute, mostly localized MSP | reduced/bad general clinical condition | additional symptoms (fever) | somatic correlate (classical signs of infection) Identify Major Clues1–3:

Table 4 Primary Care Management of bacterial infections as causes of pediatric musculoskeletal pain

94 Report

– interdisciplinary care (pediatric rheumatology, orthopedics, physiotherapy, ophthalmology) – antiphlogistics (NSAR)

– referral to pediatric rheumatology clinic – interdisciplinary longterm care (pediatric rheumatology, orthopedics, neurology, physiotherapy, ophthalmology) – interdisciplinary care (pediatric rheumatology, orthopedics, physiotherapy, ophthalmology) – NBO does not respond to antibiotics – antiphlogistics (NSAR) – if needed: glucocorticoids (only when malignancy is ruled out), biophosphonates, sulfasalacine – systemic antibiotic treatment – antiphlogistics (NSAR)

– laboratory testing7 (infection and inflammation parameters ↑, but unspecific; often HLA-B27 + , ANA/RF often −) – diagnostic imaging8 (ultrasound, MRI) – microbiology (e. g. identification of pathogen in urethral swab)

– laboratory testing7 (e. g. CBC: cytopenia (70 %), ab-titers: ab: ANA↑, anti-DNA-ab↑ (73 %); anti-cardiolipin-ab↑ (65 %); anti-Smith-ab↑ (30 %); complement factors for early diagnosis of nephritis, urine-analysis for proteinuria)

– laboratory testing7 (borrelia-ab + in serum and/or synovial fluid by Western immunoblotting or enzyme-linked immunosorbent assay (ELISA)) – laboratory testing7 (e. g.: CRP↑, throat-swab + for Streptococcus) – diagnostic imaging8 (ultrasound, MRI, ECHO)

– antiphlogistics (NSAR) – physiotherapy – in case of complications (see CC): – consult/collaboration/follow-up with pediatric rheumatology clinic

– consult/collaboration with pediatric rheumatology clinic

– rule our DD: laboratory testing7, diagnostic imaging8

– microbiology/histology (after biopsy, laboratory testing provides mostly unspecific results) – diagnostic imaging8 (MRI)

Secondary care

Diagnostics

Initiate (after completion of main text: steps I & II)

2 3 4 5 6 7 8 for definition of age-groups/age- and type of pain-related clues: see ● ▶ Fig. 2; see main text: step I; see main text: step II; see ● ▶ Table 1; see ● ▶ Table 3, see ● ▶ Table 4, see main text: step III, see main text: step IV

– history of borrelia-infection/erythema chronicum migrans ( > months/years ago) – episodic/chronic mono-/oligoarthritis: knee, ankle, elbow – DD: orthopedic conditions4, malignancy5, infection6 – rare – history of streptococcal throat infection (2–3 weeks ago) – migrating polyarthritis – subcutaneous nodules – CC: endocarditis, chorea, transition into Streptococcus-associated arthritis (if persistent after 5 days of NSAR-treatment)

– chronic ( > 6 weeks) arthritis in one or more joints, other etiologies ruled out (see DD below) – characteristic rash (patients with systemic JIA)3 – asymptomatic uveitis (10–30 %) – signs of systemic disease2,3 – DD: orthopedic conditions4, malignancy5, infection6, Lyme disease (see below), ITP – often positive family history – clinical trials: arthritis (mono-/polyarticular), enthesitis, HLA-B27 + – juvenile ankylosing spondylitis (M. Bechterew): male adolescent with back pain and uveitis – reactive arthritis (Reiter syndrome): male adolescent with acute MSP (asymmetric oligoarthritis of lower extremities) and recent history of GI-infection/non-gonococcal urethritis – psoriasis-arthritis: typical rash, MSP with affection of any joint(s) – arthritis with inflammatory bowel diseases (Crohn’s disease, Colitis ulcerosa): chronic, recurrent MSP (any joint(s)), chronic abdominal pain, pathological growth pattern/weight loss, uveitis – DD: orthopedic conditions4, malignancy5, infection6 – symmetric arthritis – typical butterfly-rash – signs of systemic disease: e. g. mucositis, lymphadenopathy, neurological symptom – CC: nephritis: complement factor-serum levels ↓ – DD: orthopedic conditions4, malignancy5, infection6 – overall rare metaphyseal inflammation – recurrent, uni-/multifocal, often nocturnal MSP: bone pain in lower extremities, shoulders, pelvis, spine – signs of systemic disease: joint swellings, uveitis, palmolantar pustulosis, psoriatic rash, acne conglobata, inflammatory bowel disease) – DD: benign bone tumor (osteoidosteoma)4, malignancy5, subacute bacterial osteomyelitis6, enthesitis/psoriasis-arthritis (see above)

Evaluate Specific Clues1–3

rheumatic treatment; RF – rheumatoid-factor

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ELISA - enzyme-linked immunosorbent assay; GI – gastrointestinal; HLA-B27 – human leukocyte antigen-B27; ITP – idiopathic thrombocytopenic purpura; MRI - magnetic resonance imaging; MSP – musculoskeletal pain; NSAR – non-steroidal anti-

ab – antibody; ANA – antinucleic antibodies; ASL – anti-streptolysine; CBC – complete blood cell count; CC – cave complications; CRP: C-reactive protein; DD – differential diagnosis; DNS – desoxyribonucleid acid; ECHO – echocardiogram;

↑: elevated; ↓ decreased; + : positive; − : negative

1

Lyme disease (Borreliosis stage III) acute rheumatic fever

chronic autoimmune diseases (Systemic lupus erythematodes, SLE) Non-bacterial Osteomyelitis (NBO)

spondylarthropathies

Juvenile idiopathic arthritis (JIA)

Diagnoses

Common

Consider

signs of inflammation and chronification)

Identify Major Clues1–3: Chronic, multifocal MSP ( > one joint), relieved by activity, worsened by rest| good – reduced general clinical condition | additional symptoms | somatic correlate (rash, characteristic

Table 5 Primary Care Management of inflammatory/rheumatic diseases as causes of pediatric musculoskeletal pain.

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96 Report 3. Magnet resonance imaging (MRI) ▶ should be initiated for patients with conspicuous symptoms and/or ambiguous x-ray findings at certain skeletal sites (e. g. chest, pelvis), and ideally after consultation of a pediatric trauma-surgeon, since plain radiographs are not sensitive enough to rule out pathologies in these regions ▶ is highly sensitive for infections such as primay subacute ▶ Table 5; epiphyseal and metaepiphyseal osteomyelitis (● ▶ ● Fig. 1-red path) [21]

4. Plain radiographs or MRI ▶ both plain radiographs and MRI provide characteristic results confirmative of fx (including pathological fx associated with osteomalacia or osteogenesis imperfecta), osteoidosteoma or a malignancy such as osteosarcoma, Ewing’s sarcoma or ▶ Table 3; ● ▶ Fig. 1-blue, Langerhans’ Cell Histiocytosis (LCH) (● -red paths) [5, 8, 29, 56, 57, 59]

5. Ultrasound (US) ▶ is the recommended first-line imaging procedure to assess soft tissue and joint problems. US also plays a guiding role in diagnostic and therapeutic management of patients with MSP that may be caused by sepsis, inflammation or a tumor by revealing joint effusions characteristic of coxitis fugax or JIA by distinguishing subperiostal fluids (abscess vs. hematoma) [31, 35]

6. Computed Tomography (CT)/other imaging procedures ▶ are indicated in individual situations only, such as diagnostic or therapeutic interventions or to assess complex fx that may involve the adjacent joint

7. Echocardiography (ECHO) ▶ is used to identify and monitor cardial symptoms associated with rheumatic disease

8. Nuclear medicine diagnostic studies ▶

99m

Tc-disphosphonate bone scintigraphy and 123I-MIBG (metaiodobenzylguanidine) scintigraphy have become the preferred diagnostic tests for neuroblastoma and bone metastases.

Step IV Who really needs which pic? – Diagnostic imaging Children or adolescents with MSP and a history of trauma or systemic illness and/or pathological findings in the PE or laboratory tests, need diagnostic imaging for further evaluation (see Steps I–III, ▶ Table 1–5; ● ▶ Fig. 1). The following aspects should be consid● ered when initiating radiology exams [5, 8, 29, 31, 35, 56, 57]:

1. Plain radiographs in 2 planes ▶ of the affected site are the gold standard of first-line diagnostic imaging ▶ should include radiographs of the adjacent joints for initial assessment of a mechanical injury such as after trauma

2. Single-plane radiographs ▶ are sufficient for certain follow-up studies such as determination of the Cobb’s angle in scoliosis-patients, monitoring hip development in children with dysplasia and planning surgery for patients with a leg-length difference

Tallen G et al. Musculoskeletal Pain: A New … Klin Padiatr 2014; 226: 86–98

3. Take-home-messages

▼

▶ MSP is a common complaint and its broad spectrum of associated differential diagnoses forms a challenge for physicians in a pediatric primary care setting. A child with MSP needs an initial evaluation according to a comprehensive, systematic and stepwise approach, that unites the patient’s individual anamnestic, psychosocial, and clinical conditions. This ensures prompt and accurate diagnosis, builds an appropriate bridge between primary and secondary care, and prevents treatment delay, longterm sequelae and redundant diagnostic procedures. ▶ We therefore recommend an algorithm for primary assessment of a child or adolescent with MSP, which was initiated by the GPOH and the DGKJ and developed as well as qualityassured by various experts in selected pediatric subspecialties, cardinal symptoms of which include MSP, and based on a systematic review of the international scientific literature on pediatric MSP.

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▶ Table 1, 2; ● ▶ Fig. 1-blue, -green paths) [1, 60]. Charactesting (● teristics of benign conditions include ▶ no constitutional symptoms/no signs of systemic, chronic or pre-existing disease (see Step I: 3., 4.; Step 2: 2.) ▶ nighttime pain relieved by mild analgetics and local massage ▶ hypermobile joints (after Ehlers-Danlos syndrome has been ruled out) ▶ no bony or tendon-tenderness ▶ no joint swelling In contrast, patients with a worrisome history, systemic symp▶ Fig. 1-red paths), do need toms or abnormal physical findings (● prompt laboratory diagnostics, mostly of blood and urine samples with the following aspects to be kept in mind: ▶ Costly screening for rheumatic disease, including the determination of antinuclear antibodies (ANA), rheumatoid factor (RF) or human leukocyte antigen B27 (HLA-B27) is considered obsolete [1, 8, 38, 60]. These tests should only be undertaken after an either infectious or oncological etiology of MSP has been ruled out. Informative parameters in this context are the complete blood cell count (CBC), blood sedimentation rate (BSR), serum-levels of C-reactive protein (CRP), blood cultures, lactate dehydrogenase (LDH), creatinine and uric acid [5, 8, 29, 56, 57] ▶ Elevated LDH serum-levels can be associated with a rheumatic, but also a malignant disease, even if the CBC is normal [52]. Hence, a malignancy should be ruled out (e. g. by biopsy) before a rheumatic condition is diagnosed [6, 11, 27, 49, 50] ▶ The combination of elevated CRP, high white blood cell counts (WBC) and clinical signs of infection are indicative of a septic etiology of MSP [15] ▶ Subtle alterations of the differential blood cell count, such as cytopenia of one cell line only – particularly in a child with diffuse, mainly nighttime MSP and/or constitutional symptoms – maybe representing an early stage of leukemia, even if no blasts are detectable yet [8, 15, 16, 22, 49, 50, 56, 57] ▶ Elevated levels of catecholamines or their metabolites or of other hormones, respectively, are found in the urine or blood of patients with NETs, such as neuroblastoma ▶ Low Ferritin serum-levels may be indicative of iron-deficiency, which has been associated with the etiology of RLS (see Step I: 3.) [43].

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Acknowledgements

▼

The development of this guideline was supported by the German Jose Carreras Leukemia Foundation (DJCLS, project-no. SP 11/02). The authors would like to thank Frank Kirchhoff, MD, Rostock, Germany (Task Force Pediatrics of the German Society of Sleep Research and Medicine) who gave additional advice to the expert group as well as Marc Steinborn, MD (Society of Pediatric Radiology) and Joachim Stegemann, MD (Society of Pediatric Radiology) for providing additional expertise to the diagnostic-imaging-chapter. This guideline was coordinated with the following societies, work groups and collaborating institutions: German Society of Pediatric and Adolescent Medicine (Deutsche Gesellschaft für Kinder- und Jugendmedizin, DGKJ), German Society of Pediatric Surgery (Deutsche Gesellschaft für Kinderchirurgie, DGKCH), German Society of Pediatric Neurology (Deutsche Gesellschaft für Neuropädiatrie, DGNeuropäd), National Society of Pediatric Oncology and Hematology (Gesellschaft für Pädiatrische Onkologie und Hämatologie, GPOH), Society of Pediatric and Adolescent Rheumatology (Gesellschaft für Kinder- und Jugendrheumatologie, GKJR), Work Group Pediatric Immunology (Arbeitsgemeinschaft Pädiatrische Immunologie, API), Task Force Pediatrics of the German Society of Sleep Research and Medicine (Arbeitsgemeinschaft Pädiatrie der Deutschen Gesellschaft für Schlafforschung und Schlafmedizin, DGSM), Professional Association of Pediatricians (Berufsverband der Kinder- und Jugendärzte, BVKJ), Union of Pediatric Orthopedics (Vereinigung für Kinderorthopädie, VKO), Work Group of Pediatric Endocrinology (Arbeitsgruppe Pädiatrische Endokrinologie, APE) and the Society of Pediatric Radiology (Gesellschaft für pädiatrische Radiologie, GPR).

Conflict of interest: The authors have no conflict of interest to disclose. Affiliations 1 Department of Pediatric Oncology/Hematology, Charite-Medical School, Berlin, Germany 2 Children’s Hospital Stuttgart, “Pediatrics 5”, – Olgahospital, Stuttgart, Germany 3 Department of Pediatric Oncology/Hematology, Charite-Medical School, Berlin, Germany 4 Department of Pediatrics, Asklepios Hospital, Sankt Augustin, Germany 5 Department of Pediatric Neurology and Muscle Diseases, Children’s Hospital Freiburg, Freiburg-Medical School, Freiburg, Germany 6 Pediatrician, Arnsberg, Germany 7 Department of Pediatrics, HELIOS Clinics Krefeld, Krefeld, Germany 8 Department of Pediatics, University Hospital Cologne, Cologne, Germany 9 Department of Pediatric Orthopedics and Neuroorthopedics, University Hospital Bonn, Bonn, Germany 10 Department of Pediatric Surgery, Hospital Karlsruhe, Karlsruhe, Germany 11 Department of General Pediatrics, University Hospital Cologne, Cologne, Germany 12 Department of Pediatrics, Heidelberg Medical School/ Hospital Mannheim, Mannheim, Germany 13 Department of Pediatrics/Division of Pediatric Orthopedics, Hospital Stuttgart, Stuttgart, Germany 14 Department of Pediatric Radiology, Jena University Hospital, Jena, Germany 15 Department of Pediatric Hematology and Oncology, Medical High School Hanover, Hanover

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▶ A German version of this guideline can be found online at http://www.awmf.org/leitlinien/detail/ll/025-032.html. A digital app is currently in development and, once completed, will be provided upon request.

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