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Managing monoarthritis in children
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Managing monoarthritis in children Valérie Devauchelle-Pensec a,b,∗ , Matthias Thepaut b,c , Romain Pecquery b,c , Laetitia Houx b,d a EA2216, ESPRI 29, IFR148, département de rhumatologie et de pédiatrie, hôpital de la Cavale-Blanche, boulevard Tanguy-Prigent, 29609 Brest cedex, France b Université de Bretagne occidentale, 29200 Brest, France c Département de chirurgie pédiatrique, CHU Morvan, 29200 Brest, France d Département de médecine physique et de réadaptation, CHRU Morvan, 29200 Brest, France
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Article history: Accepted 3 October 2014 Available online xxx Keywords: Monoarthritis Juvenile idiopathic arthritis Antinuclear antibodies Lyme disease Post-infectious arthritis
a b s t r a c t Monoarthritis, defined as inflammation of a single joint, requires a thorough physical examination in children, as pain may be lacking in 10% to 30% of cases and joint stiffness may be the only symptom. Joint aspiration is a crucial diagnostic tool that remains markedly underused. Joint aspiration may be unnecessary, however, when the family history or other investigations provide the diagnosis. Radiographs of the involved joint may supply information on the severity of the lesions. In doubtful cases and in patients with arthralgia, B-mode and Doppler ultrasound or magnetic resonance imaging (MRI) may confirm the presence of synovitis. Although suspected septic arthritis is an emergency and occurs frequently, particularly before 2 years of age, acute monoarthritis is often a post-infectious manifestation and therefore associated with a good outcome. Lyme disease should be sought, particularly when a lower limb joint is involved, as tick bites often go unnoticed. Chronic monoarthritis is very often a manifestation of juvenile idiopathic arthritis (JIA), which exists as several variants. Oligoarthritis is a specifically pediatric joint disease, whereas the other patterns of JIA have corresponding forms in adults, despite a number of specific features due to their onset during childhood. Tests for antinuclear antibodies should be performed routinely in children with monoarthritis persisting longer than 3 weeks. A decline in general health or a fever should suggest arthritis revealing a malignancy, which is a hematological disease in most cases. Finally, suggestive symptoms are often present in patients with less common causes such as auto-inflammatory diseases and connective tissue diseases. © 2015 Société franc¸aise de rhumatologie. Published by Elsevier Masson SAS. All rights reserved.
1. Introduction The prevalence of childhood arthritis is estimated at 71/100,000 [1], with 75% of cases manifesting as monoarthritis (an inflammatory effusion in a single joint). Several distinctive features of pediatric monoarthritis must be borne in mind to ensure optimal management. The initial diagnostic workup must rapidly separate the causes that mandate prompt action (bacterial infection of the joint or manifestation of a malignancy) from those requiring targeted additional investigations. Joint aspiration is crucial in the vast majority of cases but may deserve discussion depending on the
∗ Corresponding author. EA2216, ESPRI 29, IFR148, département de rhumatologie et de pédiatrie, hôpital de la Cavale-Blanche, boulevard Tanguy-Prigent, 29609 Brest cedex, France. E-mail address: [email protected] (V. Devauchelle-Pensec).
child’s age and diagnostic orientation. Evaluation in a specialized department is mandatory to establish the diagnosis. 2. Diagnosing monoarthritis in children Monoarthritis is defined as inflammation of a joint and therefore by the cytological characteristics of the joint fluid. The inflammatory nature of the condition may also be defined clinically by the combination of local erythema, increased warmth, swelling, and an inflammatory time pattern of pain; or biologically by blood test results indicating systemic inflammation. However, a number of features are specific of the pediatric population. There may be only few complaints from the child, and the problem may therefore be detected when another person notices a limp or decreased use of the affected limb. The diagnosis is particularly difficult in younger children, most notably before 2 years of age. The time pattern of the pain is often challenging to determine. Pain at night should alert to the possibility of malignant disease, which is, however, a rare cause of monoarthritis.
http://dx.doi.org/10.1016/j.jbspin.2015.06.004 1297-319X/© 2015 Société franc¸aise de rhumatologie. Published by Elsevier Masson SAS. All rights reserved.
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V. Devauchelle-Pensec et al. / Joint Bone Spine xxx (2015) xxx–xxx Table 1 History of diseases in the patient and family to be sought when evaluating a child with monoarthritis. Family
Patient
Spondyloarthritis Psoriasis Uveitis Chronic IBD
Skin Psoriasis Urticaria Erythema nodosum, migrans
Rheumatoid arthritis
Purpura Raynaud, aphthosis
Connective tissue disease Lupus Gougerot-Sjögren syndrome
Infections Recent ENT infection Cyclic recurrent fever
Auto-inflammatory diseases Recurrent fever Ethnicity
Conjunctivitis, diarrhea Immune deficiency Recent vaccination Area of endemicity for tuberculosis or rheumatic fever
Blood diseases Hemophilia Hemoglobinopathies
Bites and puncture wounds, animals Tick bite Cat scratch Sea urchin spine or plant thorn Contact with sheep or goats
IBD: inflammatory bowel disease. Fig. 1. a–d: examination of the joints in a child with suspected monoarthritis. a: limited extension and swelling of the right knee in a 5-year-old girl with antinuclear antibody-positive monoarthritis; b: monoarthritis of the right knee in a 13-year-old boy with enthesitis-related arthritis (juvenile spondyloarthritis); c: limited extension of both elbows in a 13-year-old girl with polyarticular juvenile idiopathic arthritis; d: limited extension of the fingers in a patient with chronic dry polyarthritis.
A thorough physical examination of all the joints, entheses, and spine must be performed, with the child in his/her underwear. Examination of the joints should look not only for arthritis, but also for arthralgia and motion-range limitation, with a routine comparison of the two sides (Fig. 1). Joint involvement is missed in 10% to 30% of cases [2]. Osteoarticular B-mode or Doppler ultrasonography by experienced physicians or magnetic resonance imaging (MRI) can assist in the diagnosis when the presence of arthritis is in doubt. Height and weight charts must be plotted to assess the potential systemic impact of the disease. Effects on school attendance and performance, sports participation, and sleep should be sought.
3. Joint aspiration: indispensable in monoarthritis? Joint aspiration is the cornerstone of the diagnostic strategy, as the results show whether the effusion reflects inflammation, a mechanical disorder, or hemarthrosis. Although joint aspiration is the first-line investigation and is easy to perform in children older than 5 years with involvement of a large or medium-sized joint, it is not consistently performed in everyday practice. In some patients, the physical findings and other investigations establish the etiological diagnosis (i.e. presence of antinuclear antibodies in a young girl), thereby obviating the need for joint aspiration. The joint-fluid tests include a cytological analysis to differentiate a mechanical condition from an inflammatory disease. The fluid should be tested for bacteria. Some of the more vulnerable organisms require special enriched media such as chocolate agar or blood culture flasks (Neisseria gonorrhea and Kingella kingae). A search for monosodium urate crystals may be useful in patients with risk factors (overweight, disorders of metabolism, high intake of soft drinks) [3].
4. Other signs to look for An in-depth medical history to collect information on the patient and family should be taken (Tables 1 and 2) and a thorough physical examination performed to look for clues to the diagnosis (e.g., psoriasis, lymphadenopathy, abdominal mass, or fever). The ethnic origin of the child may suggest specific diseases (such as auto-inflammatory conditions or Behc¸et’s disease). A chronic course may indicate incipient juvenile idiopathic arthritis (JIA). 5. Diagnostic strategy When definitive proof of the inflammatory nature of the effusion is not obtained, the diagnosis relies on the combination of an inflammatory time pattern, local evidence of inflammation, and laboratory tests indicating systemic inflammation. The main differential diagnoses are mechanical effusions, which occur chiefly at the hips and knees. Radiographs followed by MRI establish the diagnosis. A diagnosis of posttraumatic joint effusion should be viewed with circumspection, as overdiagnosis of this condition is common, particularly after a trivial trauma, and subsequent events may indicate that the cause was incipient JIA. In patients with inflammatory monoarthritis and suspected septic arthritis, several investigations must be obtained on an emergency basis, including joint aspiration, blood cultures, and a Table 2 Investigations to evaluate pediatric monoarthritis, according to the setting. Acute monoarthritis Joint fluid aspiration (cytology and microbiology) – urgent if fever Laboratory tests Blood cell counts, ESR, CRP Hemostasis Blood cultures if fever Depending on the setting Serological tests: Lyme, parvovirus B19, Salmonella, Shigella, Yersinia, Campylobacter, antistreptolysins Echocardiography Serum uric acid Imaging studies Radiograph of the involved joint (± comparative if abnormality) Mode B and Doppler ultrasonography if arthralgia and no arthritis ESR: erythrocyte sedimentation rate; CRP: C-reactive protein.
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Table 3 Most common causes of acute monoarthritis in children. Acute monoarthritis Septic arthritis (uncommon but severe) Transient synovitis of the hip Post-infectious arthritis Lyme arthritis
Juvenile idiopathic arthritis
Fever, pain, systemic inflammation Joint aspiration, bacteriological samples, admission Hip pain but no fever Sudden loss of hip function in a 3- to 6-year-old Resolves within 7 days Viral or bacterial (post-streptococcal) 3 to 15 days after the infection, rash Knees and hips predominantly involved Involvement of the knee Look for a tick bite and risk factors (endemic area, hike in wooded areas) Familial history Auto-immunity (including antinuclear factors Specialized follow-up
radiograph of the involved joint. A marked decline in general health and/or pain in the adjacent bone or metaphysis should prompt an evaluation for osteomyelitis [4]. Investigations required when JIA is suspected include tests for antinuclear factors, targeted immunological tests, and evaluation by an ophthalmologist to look for asymptomatic uveitis. 6. Differential diagnoses A joint effusion may indicate hemarthrosis or a mechanical effusion revealing an intraarticular fracture, ligament injuries, or traumatic patellar dislocation. Radiographs or an MRI can establish the diagnosis. Hemarthrosis may also reveal a clotting disorder, villonodular synovitis, or an angioma of the synovial membrane. Osteochondritis dissecans [5] chiefly involves the hip, femoral condyles, and talar dome. Radiographs or radionuclide bone scanning suggest the diagnosis, which can then be confirmed by MRI [6]. Dystrophy of the synovial membrane often manifests as recurrent monoarthritis with a sensation of joint locking similar to that produced by villonodular synovitis [7], synovial hemangioma, synovial osteochondromatosis, or lipoma arborescens. MRI provides the diagnosis. 7. Main causes of monoarthritis The causes of monoarthritis can be classified based on their relative frequencies reported in the literature (Table 3), despite some variability related to methodological differences [1,8–11]. Transient synovitis of the hip is fairly characteristic but rarely investigated by joint aspiration and usually treated by primarycare physicians. The next most common causes are post-infectious arthritis, which carries a good prognosis; Lyme disease; and incipient JIA. Septic arthritis is less common and occurs chiefly in very young children (< 2 years) but is sufficiently severe as to be considered the diagnostic priority.
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7.2. Transient synovitis of the hip Transient synovitis of the hip is a very common condition of unknown cause [1]. It usually develops between 3 and 6 years of age and affects boys twice as often as girls. Sudden functional impairment of the hip with motion range limitation and pain is the typical presentation. Radiographs are normal. Ultrasonography shows a joint effusion. Aspiration is rarely necessary when the presentation is typical with no fever or laboratory evidence of systemic inflammation. The symptoms resolve within 7 days, although some patients experience recurrences. A radiograph should be obtained routinely after 1 month to rule out osteochondritis dissecans. 7.3. Post-infectious arthritis Post-infectious arthritis is fairly common in pediatric patients and develops after a recent infection. In contrast, rheumatic fever has become exceedingly rare in nonendemic areas. 7.3.1. Reactive arthritis and post-infectious arthritis Reactive arthritis occurs after a recent infection of the gastrointestinal or respiratory tract. The joint fluid is sterile. The main causative bacteria are Yersinia, Shigella, Salmonella, and Campylobacter, whereas Chlamydia is a less common culprit. Reactive arthritis shares similarities with the spondyloarthritides. Many other bacterial infections can cause post-infectious arthritis, including Mycoplasma pneumoniae, Streptococcus A, Meningococcus, and Haemophilus influenzae. Viral infections can also cause arthralgia, within the following 3 to 15 days, with a skin rash and myalgia. The manifestations resolve within less than 6 weeks. Postviral arthralgia is common in children. The most frequently incriminated viruses are parvovirus B19; hepatitis B; the HIV; the rubella virus (after immunization); and less often herpes viruses, enteroviruses, coxsackie B, and the mumps virus. The joint fluid shows only mild inflammation or a mixture of lymphocytes and monocytes. 7.3.2. Post-streptococcal arthritis and rheumatic fever Reactive post-streptococcal arthritis is a well-known entity that is distinct from rheumatic fever [15] and can cause monoarthritis in 90% of cases involving mainly the hip, and the knee or ankle more rarely [16]. The joint symptoms develop within 1 to 2 weeks after the streptococcal infection [17]. The arthritis is often persistent and nonmigratory [9]. Rheumatic fever has become extraordinarily uncommon outside the endemic areas in tropical regions and the Maghreb [18]. The cause is group A -hemolytic Streptococcus pyogenes. The severity of rheumatic fever is related to the risk of damage to extraarticular organs, most notably the heart [19]. The joint manifestations start 3 to 4 weeks after an episode of pharyngitis and may consist in monoarthritis or oligoarthritis, typically with a migratory pattern of joint involvement and predominance at the lower limbs [18]. Laboratory tests consistently show systemic inflammation.
7.1. Septic arthritis 7.4. Lyme disease This diagnosis should be considered first, given its potential for devastating outcomes [12]. Warning signs include a fever, laboratory evidence of inflammation, and leukocytosis. The most common presentation is acute monoarthritis of a hip, knee, shoulder, or sternoclavicular joint. The organism is identified in the joint aspirate in 50% to 70% of cases [13]. A few cases are caused by tuberculosis or N. gonorrhoeae. In patients with high-grade fever or bone pain, an MRI must be obtained routinely to rule out adjacent osteomyelitis. The most common causative pathogens are Staphylococcus aureus, Streptococcus A, Haemophilus influenza, and Kingella kingae [4,14].
In children, arthritis is a common delayed manifestation of the Borrelia burgdorferi infection known as Lyme disease. Patients may have either recurrent knee arthritis with joint fluid showing a variable degree of inflammation [10] or oligoarthritis involving the large joints. A known history of tick bite or erythema migrans is fairly uncommon, even in endemic areas [20] and the diagnosis therefore rests on serological tests showing IgM and IgG antibodies followed by confirmation using western blot [21]. These tests must be performed in reference centers to avoid false-positive results.
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Table 4 Edmonton classification of juvenile idiopathic arthritis. Type of JIA b
Systemic-onset JIA 10% to 15% F=M 2 to 7 years Oligoarthritisc 35% to 50% F>M 2 to 4 years RF-positive polyarthritisd 10% to 20% F>M 10–12 years RF-negative polyarthritise 15% F>M Enthesitis-related arthritisf 10% to 15% M>F 10–12 years Psoriatic JIAg < 5% Undifferentiated JIAh 10% to 20%
Criteria
Exclusiona
Arthritis Systemic symptoms (fever, skin lesions, lymphoid organ enlargement. . .) 1 to 4 joints ANA and asymptomatic uveitis Extended forms
1,2,3,4
≥ 5 joints initially Resembles RA
1,2,3,4,5
1,2,3,4,5
a specifically pediatric joint disease. Monoarthritis of a lower limb joint is very often the first manifestation and mandates a routine ophthalmological evaluation. The other patterns of JIA share similarities with adult diseases but also exhibit specific features due to their early onset [25–27]. Thus, enthesitis-related arthritis resembles adult spondyloarthritis but predominantly affects the large joints and entheses [28] and less often the spine. Again, the presenting manifestation is often monoarthritis of the hip, knee, or ankle. 8. Less common causes of monoarthritis 8.1. Vasculitides and connective tissue diseases
Adulthood RA Chronic dry polyarthritis
1,2,3,5
Arthritis or enthesitis Involvement of peripheral joints HLA B27, anterior uveitis Arthritis and/or psoriasis Diagnostic orientation: family history Arthritis that does not meet the criteria for the other groups or that meet the criteria for more than one group
1,4,5
2,3,4,5
RF: rheumatoid factor; RA: rheumatoid arthritis; F: female; M: male; ANA: antinuclear antibodies. a Exclusion criteria. Psoriasis or history of psoriasis in a first-degree relative. Arthritis in HLA B27-positive males beginning after the age of 6 years. Ankylosing spondylitis, enthesitis-related arthritis, sacroiliitis with inflammatory bowel disease, acute anterior uveitis, or history of any of these disorders in a first-degree relative. Presence of IgM rheumatoid factor on at least two occasions at least 3 months apart. Systemic arthritis in the patient. b Systemic-onset arthritis. Definition: arthritis in one or more joints with, or preceded by, daily fever of at least 2 weeks’ duration and accompanied by one or more of the following: evanescent rash, generalized lymphadenopathy, hepatomegaly/splenomegaly, serositis. Exclusions: 1,2,3,4. c Oligoarthritis. Definition: arthritis affecting one to four joints during the first 6 months of the disease. There are two subgroups: persistent oligoarthritis and extended oligoarthritis affecting at least five joints after 6 months. Exclusions: 1,2,3,4,5. d Rheumatoid factor-positive polyarthritis. Definition: arthritis affecting five or more joints from disease onset. Two or more tests for rheumatoid factors are positive during the first 6 months of the disease. Exclusions: 1,2,3,4,5. e Rheumatoid factor-negative polyarthritis. Definition: arthritis affecting five or more joints from disease onset. Tests for rheumatoid factor are negative. Exclusions: 1,2,3,5. f Enthesitis-related arthritis. Definition: arthritis and/or enthesitis with at least two of the following: sacroiliac joint pain and/or inflammatory back pain; acute anterior uveitis; presence of HLA B27 antigen; and history of ankylosing spondylitis, enthesitis-related arthritis, or sacroiliitis with inflammatory bowel disease in a firstdegree relative. Exclusions: 1,4,5. g Psoriatic JIA. Definition: arthritis and psoriasis or arthritis and at least two of the following: dactylitis, nail pitting or onycholysis, and history of psoriasis in a first-degree relative. Exclusions: 2,3,4,5. h Undifferentiated arthritis. Arthritis that does not meet the criteria for any of the above groups or that meets criteria for two or more of the above groups.
Antibiotic therapy should be given in compliance with current recommendations. 7.5. Juvenile idiopathic arthritis (JIA) JIA is by far the most common cause of chronic monoarthritis, and this diagnosis should be considered in all patients with monoarthritis for longer than 6 weeks [22,23]. The current classification distinguishes several patterns of JIA (Table 4) [24] but will probably be revisited in the near future to establish a closer correspondence with the categories recognized in adults. Oligoarthritis with antinuclear antibodies and a frequently typical presentation is
Arthritis can occur as the inaugural manifestation of vasculitides such as Henoch-Schönlein purpura or Kawasaki disease. The diagnosis rests on the presence of vasculitis-related cutaneous and systemic manifestations and on the results of investigations. In children, connective tissue diseases (e.g., juvenile lupus, Sjögren’s syndrome, or dermatopolymyositis) are possible, albeit rare, causes of monoarthritis [29]. 8.2. Malignancies The frequency of arthritis revealing malignant disease is difficult to evaluate but seems low. Reported values range from less than 1% to 20% [11,30]. Nevertheless, the possibility of a malignancy is a major concern for the clinician. Monoarthritis of a large joint accounts for 50% of cases [30]. Diagnostic orientation can be obtained from the growth chart, time pattern of the pain, presence of systemic inflammation, blood cell counts, and lactic dehydrogenase level. In this setting, a radionuclide bone scan and MRI are mandatory. Acute leukemia and lymphoma are the most common malignant causes of monoarthritis. Less frequent causes include epiphyseal bone malignancies (osteosarcoma, Ewing sarcoma, neuroblastoma, chondrosarcoma, lymphoma, and malignant fibrous histiocytoma) and tumors within the synovial membrane. 8.3. Auto-inflammatory diseases Auto-inflammatory diseases are a category of rare conditions for which major breakthroughs have been achieved over the last two decades regarding both their pathophysiology [31] and their treatment, most notably with the development of highly effective anti-interleukin-1 medications [32–34]. The best-known autoinflammatory diseases are the familial recurrent fevers, particularly familial Mediterranean fever. Cryopyrin-Associated Periodic syndromes (CAPS) consist of three entities in which an abnormality in the CIAS1 gene induces a deficiency in cryopyrin. Most of these inherited diseases are characterized by the childhood onset of recurrent fever episodes accompanied with laboratory evidence of inflammation, pain, neurological manifestations, and/or serositis. At the borderline of this clinical and genetic concept are a number of other granulomatous diseases (sarcoidosis, Blau syndrome, and PAPA syndrome) [35,36], which predominantly involve the lower limbs or induce true polyarthritis; as well as other disorders for which the underlying genetic abnormalities have not yet been identified, such as periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA). 8.4. Arthritis and immunodeficiency Arthritis may develop in patients with acquired or congenital hypogammaglobulinemia or cystic fibrosis [37,38]. Skin eruptions may occur concomitantly.
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Table 5 Investigations to evaluate pediatric monoarthritis of more than 3 weeks’ duration, according to the setting. Monoarthritis > 3 weeks Slit-lamp examination mandatory if unexplained monoarthritis for > 3 weeks Laboratory tests Antinuclear antibodies, rheumatoid factors by Elisa, anticitrullinated peptide antibodies Consider HLA B27 type determination Serum protein electrophoresis and immunoglobulin assays by weight Joint fluid aspiration (cytology and microbiology) if not performed previously Imaging studies depending on the setting Mode B and Doppler ultrasonography of the hands, feet, and entheses MRI Radionuclide bone scan Depending on the setting Tests for tuberculosis Bone marrow biopsy Genetic tests for familial fevers, IgD assay
8.5. Brucellosis Brucellosis is a reportable disease transmitted by contact with sheep or goats and due to coccobacilli of the Brucella genus, among which the most pathogenic for humans is Brucella melitensis. Brucellosis is extremely rare in both children and adults outside endemic areas. Typical symptoms include an undulating fever, lymphadenopathy, and asthenia. Involvement of the bones and joints occurs chiefly during the secondary phase. Monoarthritis of a large joint accounts for 70% of cases, whereas arthralgia is less common. The diagnosis rests on the Wright agglutination test and on identification of the organism within the joint [39]. 8.6. Arthritis due to puncture wounds or foreign bodies Arthritis due to puncture wounds is also extremely rare and usually due to a sea urchin spine, which may cause monoarthritis, bursitis, or tenosynovitis up to 3 months after the injury. Histological studies show features of foreign body synovitis. The treatment relies on surgical excision of the spine [40]. A similar cause of arthritis is puncture by plant thorns, usually from a palm tree (on the trunk), a blackthorn tree, or a rose bush. Another cause that should be considered in children is puncture by a foreign body such as the tip of a pencil. 9. Management strategy In practice, the management of pediatric monoarthritis rests on a thorough physical examination, joint aspiration, radiographs, and additional investigations, some of which are simple (Tables 3 and 5), in order to guide the diagnostic strategy. Septic arthritis is the only diagnosis that must be established on an emergent basis. Patients who fail to improve after 1 to 2 weeks of nonsteroidal antiinflammatory drug therapy require a more detailed workup that should include tests for autoantibodies and a routine ophthalmological evaluation. Once the diagnosis is established, specific, prolonged, multidisciplinary management must be provided. Disclosure of interest The authors declare that they have no conflicts of interest concerning this article. References [1] Riise OR, Handeland KS, Cvancarova M, et al. Incidence and characteristics of arthritis in Norwegian children: a population-based study. Pediatrics 2008;121:e299–306.
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[38] Notarangelo L, Casanova JL, Conley ME, et al. Primary immunodeficiency diseases: an update from the International Union of Immunological Societies Primary Immunodeficiency Diseases Classification Committee Meeting in Budapest, 2005. J Allergy Clin Immunol 2006;117: 883–96. [39] Bosilkovski M, Kirova-Urosevic V, Cekovska Z, et al. Osteoarticular involvement in childhood brucellosis: experience with 133 cases in an endemic region. Pediatr Infect Dis J 2013;32:815–9. [40] Guyot-Drouot MH, Rouneau D, Rolland JM, et al. Arthritis, tenosynovitis, fasciitis, and bursitis due to sea urchin spines. A series of 12 cases in Reunion Island. Joint Bone Spine 2000;67:94–100.
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Review
Managing monoarthritis in children Valérie Devauchelle-Pensec a,b,∗ , Matthias Thepaut b,c , Romain Pecquery b,c , Laetitia Houx b,d a EA2216, ESPRI 29, IFR148, département de rhumatologie et de pédiatrie, hôpital de la Cavale-Blanche, boulevard Tanguy-Prigent, 29609 Brest cedex, France b Université de Bretagne occidentale, 29200 Brest, France c Département de chirurgie pédiatrique, CHU Morvan, 29200 Brest, France d Département de médecine physique et de réadaptation, CHRU Morvan, 29200 Brest, France
a r t i c l e
i n f o
Article history: Accepted 3 October 2014 Available online xxx Keywords: Monoarthritis Juvenile idiopathic arthritis Antinuclear antibodies Lyme disease Post-infectious arthritis
a b s t r a c t Monoarthritis, defined as inflammation of a single joint, requires a thorough physical examination in children, as pain may be lacking in 10% to 30% of cases and joint stiffness may be the only symptom. Joint aspiration is a crucial diagnostic tool that remains markedly underused. Joint aspiration may be unnecessary, however, when the family history or other investigations provide the diagnosis. Radiographs of the involved joint may supply information on the severity of the lesions. In doubtful cases and in patients with arthralgia, B-mode and Doppler ultrasound or magnetic resonance imaging (MRI) may confirm the presence of synovitis. Although suspected septic arthritis is an emergency and occurs frequently, particularly before 2 years of age, acute monoarthritis is often a post-infectious manifestation and therefore associated with a good outcome. Lyme disease should be sought, particularly when a lower limb joint is involved, as tick bites often go unnoticed. Chronic monoarthritis is very often a manifestation of juvenile idiopathic arthritis (JIA), which exists as several variants. Oligoarthritis is a specifically pediatric joint disease, whereas the other patterns of JIA have corresponding forms in adults, despite a number of specific features due to their onset during childhood. Tests for antinuclear antibodies should be performed routinely in children with monoarthritis persisting longer than 3 weeks. A decline in general health or a fever should suggest arthritis revealing a malignancy, which is a hematological disease in most cases. Finally, suggestive symptoms are often present in patients with less common causes such as auto-inflammatory diseases and connective tissue diseases. © 2015 Société franc¸aise de rhumatologie. Published by Elsevier Masson SAS. All rights reserved.
1. Introduction The prevalence of childhood arthritis is estimated at 71/100,000 [1], with 75% of cases manifesting as monoarthritis (an inflammatory effusion in a single joint). Several distinctive features of pediatric monoarthritis must be borne in mind to ensure optimal management. The initial diagnostic workup must rapidly separate the causes that mandate prompt action (bacterial infection of the joint or manifestation of a malignancy) from those requiring targeted additional investigations. Joint aspiration is crucial in the vast majority of cases but may deserve discussion depending on the
∗ Corresponding author. EA2216, ESPRI 29, IFR148, département de rhumatologie et de pédiatrie, hôpital de la Cavale-Blanche, boulevard Tanguy-Prigent, 29609 Brest cedex, France. E-mail address: [email protected] (V. Devauchelle-Pensec).
child’s age and diagnostic orientation. Evaluation in a specialized department is mandatory to establish the diagnosis. 2. Diagnosing monoarthritis in children Monoarthritis is defined as inflammation of a joint and therefore by the cytological characteristics of the joint fluid. The inflammatory nature of the condition may also be defined clinically by the combination of local erythema, increased warmth, swelling, and an inflammatory time pattern of pain; or biologically by blood test results indicating systemic inflammation. However, a number of features are specific of the pediatric population. There may be only few complaints from the child, and the problem may therefore be detected when another person notices a limp or decreased use of the affected limb. The diagnosis is particularly difficult in younger children, most notably before 2 years of age. The time pattern of the pain is often challenging to determine. Pain at night should alert to the possibility of malignant disease, which is, however, a rare cause of monoarthritis.
http://dx.doi.org/10.1016/j.jbspin.2015.06.004 1297-319X/© 2015 Société franc¸aise de rhumatologie. Published by Elsevier Masson SAS. All rights reserved.
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V. Devauchelle-Pensec et al. / Joint Bone Spine xxx (2015) xxx–xxx Table 1 History of diseases in the patient and family to be sought when evaluating a child with monoarthritis. Family
Patient
Spondyloarthritis Psoriasis Uveitis Chronic IBD
Skin Psoriasis Urticaria Erythema nodosum, migrans
Rheumatoid arthritis
Purpura Raynaud, aphthosis
Connective tissue disease Lupus Gougerot-Sjögren syndrome
Infections Recent ENT infection Cyclic recurrent fever
Auto-inflammatory diseases Recurrent fever Ethnicity
Conjunctivitis, diarrhea Immune deficiency Recent vaccination Area of endemicity for tuberculosis or rheumatic fever
Blood diseases Hemophilia Hemoglobinopathies
Bites and puncture wounds, animals Tick bite Cat scratch Sea urchin spine or plant thorn Contact with sheep or goats
IBD: inflammatory bowel disease. Fig. 1. a–d: examination of the joints in a child with suspected monoarthritis. a: limited extension and swelling of the right knee in a 5-year-old girl with antinuclear antibody-positive monoarthritis; b: monoarthritis of the right knee in a 13-year-old boy with enthesitis-related arthritis (juvenile spondyloarthritis); c: limited extension of both elbows in a 13-year-old girl with polyarticular juvenile idiopathic arthritis; d: limited extension of the fingers in a patient with chronic dry polyarthritis.
A thorough physical examination of all the joints, entheses, and spine must be performed, with the child in his/her underwear. Examination of the joints should look not only for arthritis, but also for arthralgia and motion-range limitation, with a routine comparison of the two sides (Fig. 1). Joint involvement is missed in 10% to 30% of cases [2]. Osteoarticular B-mode or Doppler ultrasonography by experienced physicians or magnetic resonance imaging (MRI) can assist in the diagnosis when the presence of arthritis is in doubt. Height and weight charts must be plotted to assess the potential systemic impact of the disease. Effects on school attendance and performance, sports participation, and sleep should be sought.
3. Joint aspiration: indispensable in monoarthritis? Joint aspiration is the cornerstone of the diagnostic strategy, as the results show whether the effusion reflects inflammation, a mechanical disorder, or hemarthrosis. Although joint aspiration is the first-line investigation and is easy to perform in children older than 5 years with involvement of a large or medium-sized joint, it is not consistently performed in everyday practice. In some patients, the physical findings and other investigations establish the etiological diagnosis (i.e. presence of antinuclear antibodies in a young girl), thereby obviating the need for joint aspiration. The joint-fluid tests include a cytological analysis to differentiate a mechanical condition from an inflammatory disease. The fluid should be tested for bacteria. Some of the more vulnerable organisms require special enriched media such as chocolate agar or blood culture flasks (Neisseria gonorrhea and Kingella kingae). A search for monosodium urate crystals may be useful in patients with risk factors (overweight, disorders of metabolism, high intake of soft drinks) [3].
4. Other signs to look for An in-depth medical history to collect information on the patient and family should be taken (Tables 1 and 2) and a thorough physical examination performed to look for clues to the diagnosis (e.g., psoriasis, lymphadenopathy, abdominal mass, or fever). The ethnic origin of the child may suggest specific diseases (such as auto-inflammatory conditions or Behc¸et’s disease). A chronic course may indicate incipient juvenile idiopathic arthritis (JIA). 5. Diagnostic strategy When definitive proof of the inflammatory nature of the effusion is not obtained, the diagnosis relies on the combination of an inflammatory time pattern, local evidence of inflammation, and laboratory tests indicating systemic inflammation. The main differential diagnoses are mechanical effusions, which occur chiefly at the hips and knees. Radiographs followed by MRI establish the diagnosis. A diagnosis of posttraumatic joint effusion should be viewed with circumspection, as overdiagnosis of this condition is common, particularly after a trivial trauma, and subsequent events may indicate that the cause was incipient JIA. In patients with inflammatory monoarthritis and suspected septic arthritis, several investigations must be obtained on an emergency basis, including joint aspiration, blood cultures, and a Table 2 Investigations to evaluate pediatric monoarthritis, according to the setting. Acute monoarthritis Joint fluid aspiration (cytology and microbiology) – urgent if fever Laboratory tests Blood cell counts, ESR, CRP Hemostasis Blood cultures if fever Depending on the setting Serological tests: Lyme, parvovirus B19, Salmonella, Shigella, Yersinia, Campylobacter, antistreptolysins Echocardiography Serum uric acid Imaging studies Radiograph of the involved joint (± comparative if abnormality) Mode B and Doppler ultrasonography if arthralgia and no arthritis ESR: erythrocyte sedimentation rate; CRP: C-reactive protein.
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Table 3 Most common causes of acute monoarthritis in children. Acute monoarthritis Septic arthritis (uncommon but severe) Transient synovitis of the hip Post-infectious arthritis Lyme arthritis
Juvenile idiopathic arthritis
Fever, pain, systemic inflammation Joint aspiration, bacteriological samples, admission Hip pain but no fever Sudden loss of hip function in a 3- to 6-year-old Resolves within 7 days Viral or bacterial (post-streptococcal) 3 to 15 days after the infection, rash Knees and hips predominantly involved Involvement of the knee Look for a tick bite and risk factors (endemic area, hike in wooded areas) Familial history Auto-immunity (including antinuclear factors Specialized follow-up
radiograph of the involved joint. A marked decline in general health and/or pain in the adjacent bone or metaphysis should prompt an evaluation for osteomyelitis [4]. Investigations required when JIA is suspected include tests for antinuclear factors, targeted immunological tests, and evaluation by an ophthalmologist to look for asymptomatic uveitis. 6. Differential diagnoses A joint effusion may indicate hemarthrosis or a mechanical effusion revealing an intraarticular fracture, ligament injuries, or traumatic patellar dislocation. Radiographs or an MRI can establish the diagnosis. Hemarthrosis may also reveal a clotting disorder, villonodular synovitis, or an angioma of the synovial membrane. Osteochondritis dissecans [5] chiefly involves the hip, femoral condyles, and talar dome. Radiographs or radionuclide bone scanning suggest the diagnosis, which can then be confirmed by MRI [6]. Dystrophy of the synovial membrane often manifests as recurrent monoarthritis with a sensation of joint locking similar to that produced by villonodular synovitis [7], synovial hemangioma, synovial osteochondromatosis, or lipoma arborescens. MRI provides the diagnosis. 7. Main causes of monoarthritis The causes of monoarthritis can be classified based on their relative frequencies reported in the literature (Table 3), despite some variability related to methodological differences [1,8–11]. Transient synovitis of the hip is fairly characteristic but rarely investigated by joint aspiration and usually treated by primarycare physicians. The next most common causes are post-infectious arthritis, which carries a good prognosis; Lyme disease; and incipient JIA. Septic arthritis is less common and occurs chiefly in very young children (< 2 years) but is sufficiently severe as to be considered the diagnostic priority.
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7.2. Transient synovitis of the hip Transient synovitis of the hip is a very common condition of unknown cause [1]. It usually develops between 3 and 6 years of age and affects boys twice as often as girls. Sudden functional impairment of the hip with motion range limitation and pain is the typical presentation. Radiographs are normal. Ultrasonography shows a joint effusion. Aspiration is rarely necessary when the presentation is typical with no fever or laboratory evidence of systemic inflammation. The symptoms resolve within 7 days, although some patients experience recurrences. A radiograph should be obtained routinely after 1 month to rule out osteochondritis dissecans. 7.3. Post-infectious arthritis Post-infectious arthritis is fairly common in pediatric patients and develops after a recent infection. In contrast, rheumatic fever has become exceedingly rare in nonendemic areas. 7.3.1. Reactive arthritis and post-infectious arthritis Reactive arthritis occurs after a recent infection of the gastrointestinal or respiratory tract. The joint fluid is sterile. The main causative bacteria are Yersinia, Shigella, Salmonella, and Campylobacter, whereas Chlamydia is a less common culprit. Reactive arthritis shares similarities with the spondyloarthritides. Many other bacterial infections can cause post-infectious arthritis, including Mycoplasma pneumoniae, Streptococcus A, Meningococcus, and Haemophilus influenzae. Viral infections can also cause arthralgia, within the following 3 to 15 days, with a skin rash and myalgia. The manifestations resolve within less than 6 weeks. Postviral arthralgia is common in children. The most frequently incriminated viruses are parvovirus B19; hepatitis B; the HIV; the rubella virus (after immunization); and less often herpes viruses, enteroviruses, coxsackie B, and the mumps virus. The joint fluid shows only mild inflammation or a mixture of lymphocytes and monocytes. 7.3.2. Post-streptococcal arthritis and rheumatic fever Reactive post-streptococcal arthritis is a well-known entity that is distinct from rheumatic fever [15] and can cause monoarthritis in 90% of cases involving mainly the hip, and the knee or ankle more rarely [16]. The joint symptoms develop within 1 to 2 weeks after the streptococcal infection [17]. The arthritis is often persistent and nonmigratory [9]. Rheumatic fever has become extraordinarily uncommon outside the endemic areas in tropical regions and the Maghreb [18]. The cause is group A -hemolytic Streptococcus pyogenes. The severity of rheumatic fever is related to the risk of damage to extraarticular organs, most notably the heart [19]. The joint manifestations start 3 to 4 weeks after an episode of pharyngitis and may consist in monoarthritis or oligoarthritis, typically with a migratory pattern of joint involvement and predominance at the lower limbs [18]. Laboratory tests consistently show systemic inflammation.
7.1. Septic arthritis 7.4. Lyme disease This diagnosis should be considered first, given its potential for devastating outcomes [12]. Warning signs include a fever, laboratory evidence of inflammation, and leukocytosis. The most common presentation is acute monoarthritis of a hip, knee, shoulder, or sternoclavicular joint. The organism is identified in the joint aspirate in 50% to 70% of cases [13]. A few cases are caused by tuberculosis or N. gonorrhoeae. In patients with high-grade fever or bone pain, an MRI must be obtained routinely to rule out adjacent osteomyelitis. The most common causative pathogens are Staphylococcus aureus, Streptococcus A, Haemophilus influenza, and Kingella kingae [4,14].
In children, arthritis is a common delayed manifestation of the Borrelia burgdorferi infection known as Lyme disease. Patients may have either recurrent knee arthritis with joint fluid showing a variable degree of inflammation [10] or oligoarthritis involving the large joints. A known history of tick bite or erythema migrans is fairly uncommon, even in endemic areas [20] and the diagnosis therefore rests on serological tests showing IgM and IgG antibodies followed by confirmation using western blot [21]. These tests must be performed in reference centers to avoid false-positive results.
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Table 4 Edmonton classification of juvenile idiopathic arthritis. Type of JIA b
Systemic-onset JIA 10% to 15% F=M 2 to 7 years Oligoarthritisc 35% to 50% F>M 2 to 4 years RF-positive polyarthritisd 10% to 20% F>M 10–12 years RF-negative polyarthritise 15% F>M Enthesitis-related arthritisf 10% to 15% M>F 10–12 years Psoriatic JIAg < 5% Undifferentiated JIAh 10% to 20%
Criteria
Exclusiona
Arthritis Systemic symptoms (fever, skin lesions, lymphoid organ enlargement. . .) 1 to 4 joints ANA and asymptomatic uveitis Extended forms
1,2,3,4
≥ 5 joints initially Resembles RA
1,2,3,4,5
1,2,3,4,5
a specifically pediatric joint disease. Monoarthritis of a lower limb joint is very often the first manifestation and mandates a routine ophthalmological evaluation. The other patterns of JIA share similarities with adult diseases but also exhibit specific features due to their early onset [25–27]. Thus, enthesitis-related arthritis resembles adult spondyloarthritis but predominantly affects the large joints and entheses [28] and less often the spine. Again, the presenting manifestation is often monoarthritis of the hip, knee, or ankle. 8. Less common causes of monoarthritis 8.1. Vasculitides and connective tissue diseases
Adulthood RA Chronic dry polyarthritis
1,2,3,5
Arthritis or enthesitis Involvement of peripheral joints HLA B27, anterior uveitis Arthritis and/or psoriasis Diagnostic orientation: family history Arthritis that does not meet the criteria for the other groups or that meet the criteria for more than one group
1,4,5
2,3,4,5
RF: rheumatoid factor; RA: rheumatoid arthritis; F: female; M: male; ANA: antinuclear antibodies. a Exclusion criteria. Psoriasis or history of psoriasis in a first-degree relative. Arthritis in HLA B27-positive males beginning after the age of 6 years. Ankylosing spondylitis, enthesitis-related arthritis, sacroiliitis with inflammatory bowel disease, acute anterior uveitis, or history of any of these disorders in a first-degree relative. Presence of IgM rheumatoid factor on at least two occasions at least 3 months apart. Systemic arthritis in the patient. b Systemic-onset arthritis. Definition: arthritis in one or more joints with, or preceded by, daily fever of at least 2 weeks’ duration and accompanied by one or more of the following: evanescent rash, generalized lymphadenopathy, hepatomegaly/splenomegaly, serositis. Exclusions: 1,2,3,4. c Oligoarthritis. Definition: arthritis affecting one to four joints during the first 6 months of the disease. There are two subgroups: persistent oligoarthritis and extended oligoarthritis affecting at least five joints after 6 months. Exclusions: 1,2,3,4,5. d Rheumatoid factor-positive polyarthritis. Definition: arthritis affecting five or more joints from disease onset. Two or more tests for rheumatoid factors are positive during the first 6 months of the disease. Exclusions: 1,2,3,4,5. e Rheumatoid factor-negative polyarthritis. Definition: arthritis affecting five or more joints from disease onset. Tests for rheumatoid factor are negative. Exclusions: 1,2,3,5. f Enthesitis-related arthritis. Definition: arthritis and/or enthesitis with at least two of the following: sacroiliac joint pain and/or inflammatory back pain; acute anterior uveitis; presence of HLA B27 antigen; and history of ankylosing spondylitis, enthesitis-related arthritis, or sacroiliitis with inflammatory bowel disease in a firstdegree relative. Exclusions: 1,4,5. g Psoriatic JIA. Definition: arthritis and psoriasis or arthritis and at least two of the following: dactylitis, nail pitting or onycholysis, and history of psoriasis in a first-degree relative. Exclusions: 2,3,4,5. h Undifferentiated arthritis. Arthritis that does not meet the criteria for any of the above groups or that meets criteria for two or more of the above groups.
Antibiotic therapy should be given in compliance with current recommendations. 7.5. Juvenile idiopathic arthritis (JIA) JIA is by far the most common cause of chronic monoarthritis, and this diagnosis should be considered in all patients with monoarthritis for longer than 6 weeks [22,23]. The current classification distinguishes several patterns of JIA (Table 4) [24] but will probably be revisited in the near future to establish a closer correspondence with the categories recognized in adults. Oligoarthritis with antinuclear antibodies and a frequently typical presentation is
Arthritis can occur as the inaugural manifestation of vasculitides such as Henoch-Schönlein purpura or Kawasaki disease. The diagnosis rests on the presence of vasculitis-related cutaneous and systemic manifestations and on the results of investigations. In children, connective tissue diseases (e.g., juvenile lupus, Sjögren’s syndrome, or dermatopolymyositis) are possible, albeit rare, causes of monoarthritis [29]. 8.2. Malignancies The frequency of arthritis revealing malignant disease is difficult to evaluate but seems low. Reported values range from less than 1% to 20% [11,30]. Nevertheless, the possibility of a malignancy is a major concern for the clinician. Monoarthritis of a large joint accounts for 50% of cases [30]. Diagnostic orientation can be obtained from the growth chart, time pattern of the pain, presence of systemic inflammation, blood cell counts, and lactic dehydrogenase level. In this setting, a radionuclide bone scan and MRI are mandatory. Acute leukemia and lymphoma are the most common malignant causes of monoarthritis. Less frequent causes include epiphyseal bone malignancies (osteosarcoma, Ewing sarcoma, neuroblastoma, chondrosarcoma, lymphoma, and malignant fibrous histiocytoma) and tumors within the synovial membrane. 8.3. Auto-inflammatory diseases Auto-inflammatory diseases are a category of rare conditions for which major breakthroughs have been achieved over the last two decades regarding both their pathophysiology [31] and their treatment, most notably with the development of highly effective anti-interleukin-1 medications [32–34]. The best-known autoinflammatory diseases are the familial recurrent fevers, particularly familial Mediterranean fever. Cryopyrin-Associated Periodic syndromes (CAPS) consist of three entities in which an abnormality in the CIAS1 gene induces a deficiency in cryopyrin. Most of these inherited diseases are characterized by the childhood onset of recurrent fever episodes accompanied with laboratory evidence of inflammation, pain, neurological manifestations, and/or serositis. At the borderline of this clinical and genetic concept are a number of other granulomatous diseases (sarcoidosis, Blau syndrome, and PAPA syndrome) [35,36], which predominantly involve the lower limbs or induce true polyarthritis; as well as other disorders for which the underlying genetic abnormalities have not yet been identified, such as periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA). 8.4. Arthritis and immunodeficiency Arthritis may develop in patients with acquired or congenital hypogammaglobulinemia or cystic fibrosis [37,38]. Skin eruptions may occur concomitantly.
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Table 5 Investigations to evaluate pediatric monoarthritis of more than 3 weeks’ duration, according to the setting. Monoarthritis > 3 weeks Slit-lamp examination mandatory if unexplained monoarthritis for > 3 weeks Laboratory tests Antinuclear antibodies, rheumatoid factors by Elisa, anticitrullinated peptide antibodies Consider HLA B27 type determination Serum protein electrophoresis and immunoglobulin assays by weight Joint fluid aspiration (cytology and microbiology) if not performed previously Imaging studies depending on the setting Mode B and Doppler ultrasonography of the hands, feet, and entheses MRI Radionuclide bone scan Depending on the setting Tests for tuberculosis Bone marrow biopsy Genetic tests for familial fevers, IgD assay
8.5. Brucellosis Brucellosis is a reportable disease transmitted by contact with sheep or goats and due to coccobacilli of the Brucella genus, among which the most pathogenic for humans is Brucella melitensis. Brucellosis is extremely rare in both children and adults outside endemic areas. Typical symptoms include an undulating fever, lymphadenopathy, and asthenia. Involvement of the bones and joints occurs chiefly during the secondary phase. Monoarthritis of a large joint accounts for 70% of cases, whereas arthralgia is less common. The diagnosis rests on the Wright agglutination test and on identification of the organism within the joint [39]. 8.6. Arthritis due to puncture wounds or foreign bodies Arthritis due to puncture wounds is also extremely rare and usually due to a sea urchin spine, which may cause monoarthritis, bursitis, or tenosynovitis up to 3 months after the injury. Histological studies show features of foreign body synovitis. The treatment relies on surgical excision of the spine [40]. A similar cause of arthritis is puncture by plant thorns, usually from a palm tree (on the trunk), a blackthorn tree, or a rose bush. Another cause that should be considered in children is puncture by a foreign body such as the tip of a pencil. 9. Management strategy In practice, the management of pediatric monoarthritis rests on a thorough physical examination, joint aspiration, radiographs, and additional investigations, some of which are simple (Tables 3 and 5), in order to guide the diagnostic strategy. Septic arthritis is the only diagnosis that must be established on an emergent basis. Patients who fail to improve after 1 to 2 weeks of nonsteroidal antiinflammatory drug therapy require a more detailed workup that should include tests for autoantibodies and a routine ophthalmological evaluation. Once the diagnosis is established, specific, prolonged, multidisciplinary management must be provided. Disclosure of interest The authors declare that they have no conflicts of interest concerning this article. References [1] Riise OR, Handeland KS, Cvancarova M, et al. Incidence and characteristics of arthritis in Norwegian children: a population-based study. Pediatrics 2008;121:e299–306.
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Please cite this article in press as: Devauchelle-Pensec V, et al. Managing monoarthritis in children. Joint Bone Spine (2015), http://dx.doi.org/10.1016/j.jbspin.2015.06.004