Indian J Pediatr (2010) 77:10051010 DOI 10.

1007/s12098-010-0163-5

SYMPOSIUM ON PEDIATRIC RHEUMATOLOGY-I

Approach to Polyarthritis
Surjit Singh & Sonia Mehra

Received: 13 July 2010 / Accepted: 14 July 2010 / Published online: 24 August 2010 # Dr. K C Chaudhuri Foundation 2010

Abstract A child with polyarthritis is always a diagnostic challenge for the treating physician. By definition, polyarthritis, taken in context as a subgroup of juvenile idiopathic arthritis, is defined as inflammation of more than 4 joints on physical examination. Though the exact incidence and prevalence of polyarthritis in childhood is not known, it is not uncommon in pediatric practice. Polyarthritis can be a clinical manifestation of diverse disease processes and the differential diagnosis is understandably very broad. It can be caused directly by an infectious agent or indirectly by immune mechanisms, may be a component of a systemic disease process or may be idiopathic. The presentation can be acute or chronic. It can represent a benign self limiting illness requiring no specific treatment or may be a severely disabling condition with significant morbidity and, in some cases, even mortality. While in some situations it may be possible to arrive at a provisional clinical diagnosis right at the outset, in others the diagnosis gradually evolves over a period of time. As in most other arthritides, the most important aspects of the diagnosis are a thorough history and a detailed clinical examination. Relevant laboratory investigations can help in facilitating the diagnosis but can often also mislead the treating physician. Hereby we present a clinical approach to a child with polyarthritis. Keywords Polyarthritis . Children . Clinical approach

Introduction Although acute monoarthritis (as for instance septic arthritis) is usually considered to be a medical emergency [1], it is not often realized that patients with polyarthritis also need to be evaluated promptly to ensure timely management [2]. Delays in diagnosis and/or treatment may result in significant morbidity, as for example in rheumatic fever and Kawasaki disease [3]. It cannot be overemphasized enough that the most important clues to underlying aetiology in a patient with polyarticular disease are found not in the investigations but in the clinical history and physical examination. Some investigations (e.g. radiographs of joints) are commonly done but may have little or no role in the initial assessment of the patient [2, 4]. Polyarticular joint disease has multi-factorial etiology. It may present acutely as in self limiting viral illnesses or it can be the beginning of a chronic sinister disease. The underlying etiological process can be infectious or postinfectious, a rheumatological disease or a manifestation of systemic disease. The disease may evolve over days or sometimes weeks, thereby making the diagnosis difficult at the time of presentation [411] (Table 1). Viral infections (for e.g. Parvovirus B19) are often associated with a self-limiting symmetrical arthritis of small joints. Septic polyarthritis caused by direct invasion of the joint by microbes can occur in disseminated staphylococcal and streptococcal infections, gram negative sepsis or bacterial endocarditis. Reactive arthritis, a sterile arthritis mediated by immune mechanisms, is usually seen after genitourinary (Chlamydia) or gastrointestinal (salmonella, shigella, yersinia or campylobacter) infections. It is said that arthritis persisting for more than 6 weeks usually rules out an infective pathology [9, 10]. Polyarticular juvenile idiopathic arthritis (JIA), polyarthritis associated with systemic lupus erythematosus (SLE) and psoriatic arthritis usually present insidiously and

When an arthritis patient walked in the front door I wanted to walk out the back oneSir William Osler (18491919) Principles and Practice of Medicine, 1892
S. Singh (*) : S. Mehra Pediatric Allergy Immunology Unit, Advanced Pediatrics Centre, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India e-mail: surjitsinghpgi@rediffmail.com

1006 Table 1 Differential diagnosis of polyarthritis Etiology Viral Bacterial Other infections Parainfectious (reactive) Rheumatalogical Systemic vasculitides Spondyloarthropathies Miscellaneous Causative agent

Indian J Pediatr (2010) 77:10051010

Parvovirus B19, Enteroviruses, Adenoviruses, Mumps, Rubella, Varicella zoster virus, Hepatitis B, Coxsackie virus, Cytomegalovirus, EBV, HIV. Staphylococcal and streptococcal infections, Neisseria gonorrhae, Hemophilus influenzae; Bacterial endocarditis. Tuberculosis, Leptospirosis, Fungal infections, Brucellosis HIV, Group A streptococcal infections, Salmonella, Shigella, Yersinia, Campylobacter, Mycoplasma, Chlamydia. Juvenile idiopathic arthritis (JIA), Systemic lupus erythematosus (SLE), Juvenile dermatomyositis (JDMS), Behcet syndrome. Henoch-Schonlein purpura (HSP), Kawasaki disease (KD), Polyarteritis nodosa (PAN), Wegeners granulomatosis Juvenile ankylosing spondylitis (JAS), Psoriatic arthritis Enteropathic arthritis. Sarcoidosis, Drug/serum sickness reactions

should be considered in the differential diagnosis of such a patient.

History Identifying the cause of polyarthritis may initially look difficult to the uninitiated. However, clinical clues in patient demographics, disease chronology, inflammatory nature, progression, distribution of joint involvement and extra-articular manifestations help narrow the diagnostic possibilities [2]. Age At the onset of the disease may give clues to the diagnosis. Polyarticular JIA (rheumatoid factor negative), Kawasaki disease and Henoch Schonlein purpura (HSP) usually present in early childhood. In mid-childhood, juvenile psoriatic arthritis, Juvenile Dermatomyositis (JDMS) and Polyarteritis Nodosa (PAN) have their peak frequencies. Juvenile ankylosing spondylitis (JAS) and SLE typically present in late childhood or early adolescence. Rheumatoid factor positive polyarticular JIA, mimicking the clinical profile of adult RA, usually presents only after the age of 10 years. Disorders like gout and crystal deposition disease are extremely uncommon in children [1113]. Sex While many rheumatological disorders (e.g. SLE, polyarticular JIA) have a predilection for girls, there are others (e.g. vasculitides like KD and PAN; spondyloarthropathies like inflammatory bowel disease and JAS) which are more common in boys [14, 15]. Onset of Disease and Duration While some arthritides may have an acute onset (e.g. septic arthritis and arthritis associated with KD/HSP) others may have a subacute or chronic insidious course as typically seen in polyaticular

JIA or sarcoidosis. Polyarthritis of less than 6 weeks duration is seen in self limiting viral arthritides, rheumatic fever or reactive arthritis [12, 13]. It may sometimes be prudent not to give a label in the first few weeks of the illness when the disease process is still evolving. Past History A transient episode of heel or back pain (indicating enthesitis) or an episode of painful red eye with visual loss (indicating acute uveitis) may unmask the inflammatory back pain in JAS [13, 15]. History of recent diarrhea, acute conjunctivitis, urethritis, and fever with or without rash may give a clue to reactive arthritis [10, 16]. Patients with systemic onset JIA may present with pyrexia of unknown origin and give history of having received multiple courses of antimicrobials. In our experience this is not an uncommon occurrence. Family History Although Mendelian inheritance is not usually seen in inflammatory polyarthritis, familial clustering of cases can be seen in ankylosing spondylitis, inflammatory bowel disease and psoriatic arthritis. The latter condition is especially intriguing because clinical manifestations of psoriasis can be subtle and very variable amongst the family members [15].

Physical Examination Articular Involvement Examination involves determining not only which joints are involved at any one time, but determining over time if possible, the evolution of joint involvement. Clinical approach to a child with polyarthritis essentially revolves around recognition of the pattern of joint involvement. It may not always be possible to give a specific diagnostic

Indian J Pediatr (2010) 77:10051010 Table 2 Common patterns of involvement in children Disease Viral arthritis Polyarticular JIA JAS Psoriatic arthritis SLE Reactive arthritis Clinical presentation Acute Chronic Chronic Chronic Chronic Acute Pattern Small Joints Small and large Large Small and large Small Large Symmetry Symmetrical Symmetrical or asymmetrical Asymmetrical Usually asymmetrical Symmetrical Asymmetrical

1007

Axial involvement No No Yes Yes / No No Yes / No

label at the first instance. The treating clinician has to identify the following components in evolution of the disease: 1. Evolution of the joint involvement Progression of joint involvement can follow one of the following patterns [11, 17]: Migratorysymptoms are present in one joint for a few days and then remit, only to reappear in
Table 3 Physical signs to be looked for in a child with polyarthritis [5, 11, 13, 23]
System involved Eye Skin/Mucosa Oral cavity Skin Physical findings

some other joint as classically seen in rheumatic fever and gonococcal arthritis. Joint involvement can occur over hours in rheumatic fever or over days in gonococcal arthritis. AdditiveNew joints are progressively involved while initial joints are still symptomatic with many joints being affected at the same time as seen in SLE, JIA and psoriatic arthritis.

Systemic disease JIA, JAS, KD, Sarcoidosis, Reactive arthritis Sjogrens syndrome SLE, KD, Bechet syndrome SLE, Rheumatic fever JIA, JDMS, Systemic vasculitides, Sarcoidosis, HSP, Parvovirus infection, Reactive arthritis SLE, Psoriasis, IBD JDMS, JAS, JIA, Psoriatic arthritis

Anterior or posterior uveitis, non exudative conjunctivitis, Keratoconjuctivitis Oral ulcers, straw berry tongue Malar rash, discoid rash, macular rash, heliotrope rash, Gottorns papules, palpable purpura, petechaie, Erythema nodosum, Erythema marginatum, leg ulcers, Raynaud phenomenon, edema of hands and feet, perianal desquamation, slapped cheek appearance, genital ulcers Alopecia, nail pitting, onycholysis, clubbing Proximal muscle weakness, muscle tenderness, muscle contractures, enthesitis, bursitis, dactylitis ankylosis Leucocytosis, thrombocytosis, thrombocytopenia, eosinophilia Gangrene, stroke Lymphadenopathy Nephritis, nephrotic syndrome, hypertension, urinary sediment, sterile pyuria, amyloidosis, RPGN and ESRD Stroke, seizures, focal deficits, psychosis, chorea, blindness, aseptic meningitis, pseudotumor cerebri Mononeuritis complex, polyneuropathy Acute or chronic sinusitis Hilar adenopathy, pulmonary infiltrates, Pulmonary haemorrhage and pulmonary hypertension Myocardial dysfunction, endocarditis, pericardial effusion, Mitral regurgitation and stenosis, Aortic regurgitation, new murmurs

Nails and hair Musculoskeletal System Muscles and joints Hematological System CBC Vascular system Lymphatic system Renal System Kidneys Nervous system Central nervous system Peripheral nervous system Respiratory System Paranasal sinuses Lungs Cardiovascular System Heart

JIA, SLE, Sarcoidosis SLE, APLA Syndrome SLE, KD JIA, KD, SLE, PAN, HSP

RF, SLE, PAN, Bechet syndrome PAN, SLE Chrugg strauss syndrome Wegeners granulomatosis Sarcoidosis, PAN

RF, JAS, SLE, PAN, Bacterial endocarditis

RF rheumatic fever, JIA juvenile idiopathic arthritis, JAS juvenile ankyolising spondyolitis, HSP henoch schonlein purpura, KD Kawasaki disease, JDMS juvenile dermatomyositis, SLE systemic lupus erythematosus, PAN polyarteritis nodosa, APLA antiphospholipid antibodies

1008 Table 4 Laboratory investigations in a child with polyarthritis Investigation Markers of inflammation Hemogram Abnormality detected ESR, CRP, Globulins, thrombocytosis Normocytic normochromic anemia, leucocytosis, thrombocytosis, Eosinophilia, haemolytic anemia (DCT+) Urinary sediment, sterile pyuria, hematuria and proteinuria X-rays, CT scans or MRI Synovial fluid in JIA can also have a markedly polymorphonuclear response; should not be mistaken for septic arthritis RF, anti CCP antibodies, HLA B27, ANA and ANCA RFT, LFT, X-ray, ASO titres, Throat swab, HIV, Viral serologies, ECHO Comments

Indian J Pediatr (2010) 77:10051010

ESR and CRP elevation usually indicate activity but ESR may not always be elevated in rheumatic diseases SLE may have leucopenia and thrombocytopenia at presentation

Urine routine Radiology of the joint Synovial fluid analysis/Biopsy Specific investigations

Other investigations

Sterile pyuria commonly seen in JIA and KD; should not be mistaken for UTI Not usually required in acutely painful joint; may not be informative in acute stage. Indicated only if there is a diagnostic problem; in addition to Gram stain, pyogenic and mycobacterial cultures are sent. Biopsy can be aided by direct vision under arthroscopy Polyarticular disease can be RF +/, ANA is usually positive in SLE, HLA B27 for Juvenile spondyloarthropathies and reactive arthritis, ANCA for systemic vasculitides Baseline metabolic profile should be done in all patients and other investigations are disease specific

IntermittentJoint involvement appears and disappears with completely asymptomatic periods in between, as seen in reactive arthritis. 2. Topography and distribution Typically joint involvement can be axial (spine, centrally located joints as sacroiliac joint, sternoclavicular or manubriosternal joint), peripheral joints (in the extremities) or root joints (overlap between axial and peripheral joints e.g. shoulder and hip joint). While involvement of the axial skeleton is typical of the spondyloarthropathies, it is extremely uncommon in disorders like SLE and systemic vasculitides. Combined patterns of involvement can be seen in polyarticular or systemic JIA. A young adult who has chronic low back pain and peripheral asymmetric arthritis probably has one of the spondyloarthropathies like JAS, psoriatic

arthritis, enteropathic associated arthritis or reactive arthritis [18]. 3. Distribution Is the joint involvement symmetric or asymmetric? SymmetricInflammatory synovitis of small as well as large joints of extremities in symmetrical distribution in both upper and lower limbs is typical of JIA and SLE. AsymmetricAsymmetrical involvement of large joints of lower extremities (for e.g. ankle / knee) is typical of reactive arthritis. 4. Is any particular joint involved? The physician should assess if the joint involvement is characteristic of a particular disorder. This assessment should begin as soon as the child walks into the clinic. For example acute dactylitis or distal interpha-

Table 5 Treatment of commonly encountered polyarthritis in children Common causes of polyarthritis Specific therapy Infectious/ Parainfectious a) Viral b) Bacterial c) Reactive Rheumatological disorders Systemic Vasculitides Viral infections are often self limiting; specific antimicrobials for bacterial infections; NSAIDs for a few weeks in reactive arthritis Comments Patients with Rheumatic fever require long term penicillin prophylaxis reactive arthritis commonly seen in older children and adolescents

Miscellaneous

NSAIDs and/or steroids and immunosuppressive Physiotherapy and occupational therapy as important as therapy depending on the specific disorder drug therapy Immunoglobulin in KD, NSAIDs/steroids in HSP Immunoglobulin therapy in KD can prevent long term and other vasculitides morbidity; prompt administration of steroids in lupus can be life saving Supportive and definitive treatment depending Disease may evolve in time in any category and patients on aetiology need follow up

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langeal involvement raises the strong suspicion of psoriatic arthritis [15]. Family history of a near relation having psoriasis further corroborates the diagnosis. Enthesitis (i.e. Inflammation at the site of attachment of ligaments, tendons and fascia to the bone) is typical of the juvenile spondyloarthropathies [18]. It must, however, be noted that there can be considerable overlaps in the patterns of joint involvement and the overall clinical picture must not be ignored. 5. Is there a joint deformity? Arthritis can be deforming or non-deforming. Joint deformities usually indicate a long standing or aggressive disease. Deforming arthritis is typically seen in polyarticular JIA. Early initiation of anti-inflammatory therapy can help prevent some of these deformities. The arthritis associated with SLE and inflammatory bowel disease is usually non-deforming [19] (Table 2). Extra-articular Involvement Inflammatory arthritis may be associated with systemic features and many systemic diseases have musculoskeletal presentations. These extraarticular manifestations may provide many valuable clues to the underlying etiology (Table 3) [20, 21].

Conclusion Polyarthritis could be a benign self-limiting illness, the beginning of a serious chronic illness resulting in significant morbidity or a rheumatological emergency requiring urgent intervention. While the differential diagnosis can be very broad, a presumptive diagnosis with regard to the underlying etiology can often be made by careful attention to the clinical history and physical examination. Laboratory investigations must always be directed by the clinical presentation. Management is tailored to the requirements of a given patient.
Conflict of interest None

References
1. Baker DG, Schumacher HR. Acute monoarthritis. N Engl J Med. 1993;329:101320. 2. Mies Richie A, Francis ML. Diagnostic approach to polyarticular pain. Am Fam Physician. 2003;68:115160. 3. Special Writing Group of the Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease of the Council on Cardiovascular Disease in the Young of the American Heart Association. Guidelines for the diagnosis of rheumatic fever. JonesCriteria, 1992 update [published correction appears in JAMA.1993; 269(4): 476]. JAMA 1992;268(15):206973. 4. Allen R. Differential diagnosis of arthritis in childhood. Baillieres Clin Pediatr. 1993;1:66594. 5. Khubchandani RP, DSouza S. Initial evaluation of a child with arthritisan alogrithmic approach. Indian J Pediatr. 2002;69 (10):87580. 6. Klinkhoff A. Rheumatology: 5. Diagnosis and management of inflammatory polyarthritis. CMAJ 2000;162:18338. 7. Meador R, Schmacher HR. Evaluating and treating patients with polyarthritis of recent onset. Hosp Physician. 2003;39:3745. 8. Pinals RS. Polyartrits and fever. New Engl J Med. 1994;330:76974. 9. Rose CD, Eppes SC. Infection related arthritis. Rheum Dis Clin North Am. 1997;23:67795. 10. Leirisalo-Repo M. Early infection and arthritis. Curr Opin Rheumatol. 2005;17(4):4339. 11. Malaviya A. Approach to the patient with polyarthritis. In: Rao URK, eds. Manual of rheumatology. 3rd ed. Indian Rheumatology Association; 2009. 1120. 12. Miller ML. Evaluation of a suspected rheumatic disease. In: Kliegman RM, Behrman RE, Jenson HB, Stanton BF, eds. Nelson textbook of pediatrics. 18th ed. Philadelphia: Elsevier Saunders; 2007. 9957. 13. Cassidy JT, Petty RE. Polyarthritis. In: Cassidy JT, Petty RE, Laxer RM, Lindsley CB, editors. Textbook of pediatric rheumatology. 5th ed. Philadelphia: Elsevier Saunders; 2005. p. 26173. 14. Sathanathan R, David J. The adolescent with rheumatic disease. Arch Dis Child. 1997;77:3558. 15. Burgos-Vargas R. Spondyloarthropathies and psoriatic arthritis in children. Curr Opin Rheumatol. 1993;5:63443. 16. Townes JM. Reactive arthritis after enteric infection in the United States: the problem of definition. Clin Infect Dis. 2010;50(2):24754. 17. Hubscher O. Pattern recognition in arthritis In: Kippel JH, Dieppe PA, editors. Rheumatology. 2nd ed. Mosby International; 1998; 2: p. 3.13.6. 18. McGonagle D, Gibbon W, Emery P. Classification of inflammatory arthritis by enthesitis. Lancet 1998;352:113740.

Laboratory Investigations It is said that 80% of the rheumatological diagnosis comes from clinical history, 15% from examination and only 5% from investigation. This aphorism is applicable to the clinical approach to polyarthritis as well. Laboratory investigations, by themselves, have very little role in arriving at a diagnosis and one should never fall in the trap of treating the investigation rather than the patient. As most of the rheumatological tests lack the desired specificity, results should always be interpreted in the context of a given patient [22] (Table 4). Further, the tendency to send for routine panels of tests (e.g. arthritis panel, lupus panel) without keeping the patients clinical picture in perspective can never be justified. Management Management necessarily has to be multidisciplinary with involvement of the physiotherapist and the occupational therapist (Table 5). One has to address parental concerns for the disease and the issues regarding its prognosis, medications, and school absenteeism [23]. Symptomatic relief should be provided while the child is being evaluated. Specific therapy, however, depends on the underlying etiology of the arthritis.

1010 19. Martel W, Holt JF, Cassidy JT. Roentgenologic manifestations of juvenile rheumatoid arthritis. Am J Roentgenol Radium Ther Nucl Med. 1962;88:40042. 20. Baldassano VF. Ocular manifestations of rheumatic diseases. Curr Opin Ophthalmol. 1998;9:858. 21. Griffiths ID. Extra- articular features of rheumatic diseases. In: Maddison PJ, Isenberg DA, Woo P, Glass DN, eds. Oxford

Indian J Pediatr (2010) 77:10051010 textbook of rheumatology. 2nd ed. London: Oxford University Press; 1998. 16979. 22. Kunnamo I, Kallio P, Pelkonen P, Hovi T. Clinical signs and laboratory tests in the differential diagnosis of arthritis in children. Am J Dis Child. 1987;141:3440. 23. Singh S. Chronic arthritis: current perspectives [editorial]. Indian Pediatr. 2003;40:3937.