Approach to a child

with arthritis
By
Dr. Iman Khalifa
Assistant Professor of Pediatrics,
Helwan University
2023/2024
Agenda
• Arthralgia or arthritis?
• Acute or chronic?
• Single (mono) or several (poly) joints?
• Differential diagnosis of Monoarthritis.
• Hip monoarthritis.
• Differential diagnosis of polyarthritis.
• Juvenile Idiopathic arthritis.
• Henoch-Schönlein purpura (HSP) [IgAV]
Approach to a child with Joint Pain

§ Musculoskeletal pain in childhood is common.

§ It is important to clarify the nature and site of pain – joint, muscle or bone.
• Muscle pain in myositis (pain and tenderness are limited to muscles).
• Bone pains in trauma, fractures, osteomyelitis and malignancies.
• Growing pains which is a very common condition that occurs in children
3-6 years old and is characterized by intermittent pain in thighs and legs
bilaterally with no or minimal joint pain and it usually occurs at night
during sleep.
§ History and examination are the cornerstone of diagnosis.
1. If joint related, then is it
arthralgia or arthritis?

• Arthralgia: • Arthritis:
The presence of joint pain Presence of a swollen joint or a
alone signifies only joint having at least 2 of the
arthralgia, not arthritis. following conditions:
Limitation of range of
motion, pain on motion,
tenderness, or warmth
overlying the joint.
Swelling of the joint can arise from fluid or from synovitis or a combination of both. Synovitis with minimal or no
effusion often occurs in children with Juvenile Idiopathic Arthritis (JIA).
2. Is the arthritis acute or chronic?
i. Acute arthritis: < 6 weeks duration and tends to reflect

etiologies related to trauma or infection.

ii. Chronic arthritis: > 6 weeks duration, incudes most of

the inflammatory arthritides.

3. Is the arthritis affecting a single
(mono) or several (poly) joints?
• Monoarthritis: involving one joint.

• Oligo arthritis: involving < 5 joints.

• Poly-arthritis: involving ≥ 5 joints.

Differential Diagnosis of Monoarthritis
Infection-related • Septic arthritis
• Osteomyelitis
• Transient synovitis (toxic synovitis)
• Reactive arthritis
• Lyme disease
• Tuberculosis
Trauma • Fracture: accidental and non accidental
• Internal derangement: ligament rupture
• Foreign body synovitis
Malignancy • Leukemia
• Neuroblastoma
Inflammatory • JIA
• Inflammatory bowel disease
• Familial Mediterranean fever
Hemarthrosis • Hemophilia
• Pigmented villonodular synovitis
• Synovial hemangioma
Preliminary investigations for the evaluation of
monoarthritis
Basic screening: Further investigations:
• Cultures of throat, blood, joint fluid,
• Complete blood cell count and stool, and/or urine.
differential white blood cell count. • Partial thromboplastin time (PTT)
• Antinuclear antibody titer (ANA)
• Erythrocyte sedimentation rate • Serologic testing for Lyme disease
(ESR). • Anti-streptolysin-O-titer (ASOT)
• Urinalysis
• C-reactive protein (CRP). • Tuberculin skin test
• Renal function and liver enzymes. • Further imaging (Ultrasonography,
magnetic resonance imaging)
• Serum lactate dehydrogenase. • Bone marrow aspiration.
• Radiographs. • Slit-lamp examination of the eye.
1- Septic Arthritis
• Suppurative or Septic arthritis is a serious
bacterial infection of the joint space.
• Septic arthritis is a medical emergency
that requires prompt antibiotic therapy
and orthopedic intervention (drainage &
irrigation).
• Etiology:
1. Penetrating trauma (direct puncture
injury to a joint).
2. Hematogenous bacterial dissemination.
3. Spread from near contiguous infection
(e.g. osteomyelitis).
Septic Arthritis (Clinical
presentation and
investigations):

• Clinical Presentation: • Investigations:

1. Usually monoarticular involvement. 1. Elevated WBC count (predominance
2. Fever, localized erythema, warmth, and of neutrophils)
significant pain on passive range of 2. Elevated inflammatory markers (ESR
motion. and CRP).
3. The joint more involved knee (40%), 3. Urgent joint aspiration and a synovial
hip (20%) fluid analysis and gram stain is
essential for the diagnosis.
2- Reactive arthritis (immune-mediated synovial inflammation)
• Definition:
Arthritis occurs as a reaction to bacterial infection
elsewhere in the body.
• Causative organisms:
The classic organisms causing reactive arthritis are:
(i) Enteric (Campylobacter, Yersinia, Salmonella,
Shigella).
And (ii) Genitourinary organisms (Chlamydia
trachomatis).
The triad of conjunctivitis, urethritis, and arthritis
(formerly known as Reiter syndrome may be seen after
one of the infections.
• Clinical presentation:
1- Maybe mono-articular or poly-articular. 2- Involving
the larger joints of the lower extremities and can be
quite painful. 3- Self-limited transient.
• Treatment: Non-steroidal anti-inflammatory drugs
(NSAIDs) for the pain.
3- Lyme Disease
• Etiology
• Lyme disease is a tick-borne infection
caused by the spirochete, Borrelia
burgdorferi. Ticks usually become infected
by feeding on the white-footed mouse, which
is a natural reservoir for B. burgdorferi.
• Clinical Manifestations
üEarly: - Flu-like illness.
• - Rash (erythema migrans, is pruritic or
painful, harbors B. burgdorferià
erythematous papule that expands to form a
red, raised border, often with central clearing. Expanding annular lesion of erythema
migrans at the site of a tick bite.
Lyme Disease
-Arthritis is a late manifestation, begins weeks to months after infection and is
diagnosed in approximately 7% of children at initial presentation.
The knee is involved in greater than 90% of cases, but any joint may be affected.
Symptoms may resolve over 1–2 weeks but often recur in other joints.
Diagnosis: Indirect detection method. A positive enzyme-linked immunosorbent
assay (ELISA) or immunofluorescence assay. Western blot is the confirmatory test
Treatment:
Arthritis is treated with doxycycline (for children ≥8 years of age) or amoxicillin for 28
days.
4- Malignancy
• Must always be considered at the top of the
differential diagnosis.
• Clues to suggest malignancy:
1. Pain out of proportion with degree of arthritis.
2. Child irritable and difficult to examine.
3. Fever, lymphadenopathy or hepatosplenomegaly.
4. Leukocyte or platelet that are lower than expected.
5. Bone pain and metaphyseal lucencies seen on the
radiograph.
6. Joint involvement in malignancy tends to be oligo-
articular (≤ 4 joints) rather than polyarticular.
5- Juvenile idiopathic arthritis
• JIA is an umbrella term for several distinct arthritides lasting > 6 weeks with

unknown etiology. The term “juvenile” refers to onset of arthritis ≤ 16 years of age.
• JIA can be divided into several subtypes, depending on the number of joints
involved (<5 versus 5 or more), the presence of sacroiliac involvement, and the
presence of systemic features.

• Chronic monoarthritis can be the presenting manifestation of oligo arthritis,

enthesitis-related arthritis, and psoriatic arthritis.

6- Hemophilia
• Hemophilia may cause recurrent
monoarthritis of knees, elbows and
ankles.

• The classic presentation of hemarthrosis

is one of acute onset of increasing
fullness in a joint, with loss of range of
motion.

• Hemophilia A (factor 8 deficiency) occurs in

1 in 5,000 males. Hemophilia B (factor 9
deficiency) occurs in approximately 1 in
25,000 males.
Hip mono-arthritis
(i) Transient Etiology: uncertain; possible causes are viral illness and nonspecific inflammatory reactions.
synovitis, also Approximately 70% of children diagnosed with transient synovitis have an upper respiratory
known as (toxic tract viral infection in the preceding 7–14 days. It is a common condition.
Clinical presentation: 1- An acute onset of pain in the groin/hip, anterior thigh, or knee occurs.
synovitis) of the hip
2- The mean age at onset is 6 years, with a range of 3–8 years. It is twice as common in
male children.
3- Characterized by absence of systemic manifestations.
4- The child is generally well appearing, afebrile, walks with a painful limp.
• Normal inflammatory markers & Joint ultrasound may show widened joint space secondary
to joint effusion.
Treatment: Conservative. NSAIDs and bed rest.
(ii) Slipped capital • Classically occurs in overweight boys aged 10-14 years.
femoral epiphysis • Diagnosed radiographically.
(SCFE) • Both hips should be imaged as SCFE is bilateral in 30% of cases in which the presenting
symptoms are unilateral.
• Treatment: Referral to orthopedic.
Non-weight bearing and on bed rest.
Prescribed crutches.
(iii) Legg-Calve- • Idiopathic avascular necrosis of the capital femoral epiphysis, typically in boys 4-10 years.
Perth's (LCP) • Magnetic resonance imaging (MRI) is most sensitive for diagnosis as initial X-ray may be
syndrome normal.
• Treatment: Urgent Referral to orthopedic.
Non-weight bearing.
Differential diagnosis of POLYARTHRITIS
Infection-related • Neisseria Gonorrhea infection
• Viral infections (e.g. parvovirus B19, rubella virus/vaccine)
• Infective endocarditis
• Acute rheumatic fever (ARF)
• Post streptococcal reactive arthritis (PSRA)
• Reactive arthritis
Inflammatory • JIA
• SLE
• Systemic vasculitides
- Henoch-Schonlein purpura
- Kawasaki disease
• Familial Mediterranean Fever
• IBD-related
Hematology & • Leukemia.
Malignancy • Sickle cell anemia.
1. Acute Rheumatic Fever
§ It is a reactive arthritis characterized by:
üPolyarthritis that constitutes one of the Jones criteria for the diagnosis of
rheumatic fever.
üIt is migratory and characterized by extreme tenderness, redness, and
swelling of the affected joints. It may affect several joints but rarely the
fingers, toes, or spine. Leaves no deformity.
üThis arthritis classically responds very quickly to treatment with aspirin.
2. Systemic Lupus Erythematosus

• Systemic lupus erythematosus (SLE) is a multisystem disorder of

unknown etiology characterized by a production of large amounts of
circulating autoantibodies.

• Musculoskeletal manifestations: small joints of the hand and wrist are

usually affected, although any joint is at risk. Arthritis is generally non-
erosive and non-deforming.
3. Juvenile idiopathic arthritis (JIA)
• JIA is the most common chronic rheumatological disease of childhood.
• With a prevalence of 1 : 1,000 children.
• The etiology of this autoimmune disease is unknown.
• The disease has two peaks, one at 1-3 years and one at 8-12 years, but it
can occur at any age.
• Girls are affected more commonly than boys, particularly with the oligo
articular form of the illness.
• The common underlying manifestation is the presence of chronic synovitis,
or inflammation of the synovial lining of the joint. The synovium becomes
thickened and hyper vascular with infiltration by lymphocytes, which also can
be found in the synovial fluid along with inflammatory cytokines. The
inflammation leads to production and release of tissue proteases and
collagenases. If left untreated, the inflammation can lead to tissue
destruction, particularly of the articular cartilage and, eventually, the
underlying bony structures.
Criteria for the Classification of Juvenile Idiopathic
Arthritis (It is a clinical diagnosis, without any
diagnostic laboratory tests):
1. Age at onset < 16 years.
2. Arthritis (swelling or effusion, or the presence of ≥ 2 of the following signs:
limitation of range of motion, tenderness or pain on motion, increased heat) in
≥ 1 joint.
3. Duration of disease: ≥ 6 weeks
4. Exclusion of other forms of juvenile arthritis e.g. Malignancy.
• Types of JIA
1. Systemic-onset JIA
2. Oligo articular JIA
3. Polyarticular JIA: Rheumatoid factor +ve and rheumatoid factor –ve.
4. Enthesitis-related arthritis (ERA)
5. Other types of JIA: psoriatic arthritis, arthritis with inflammatory bowel diseases
and undifferentiated arthritis.
I. Systemic Juvenile Idiopathic Arthritis
SJIA is characterized by:
1. Arthritis: in ≥ 1 joints, typically
polyarticular in nature.
2. Fever: a typical recurring, spiking fever,
usually once or twice per day, which can
occur for several weeks to months.
3. Rash: morbilliform and salmon-
colored, occurs at times of high fever
only.
4. Prominent visceral involvement,
including HSM, lymphadenopathy, and
serositis (pleuritis and pericarditis).
Pericardial tamponade may rarely occur.
5. Children with systemic JIA appear sick;
they have significant constitutional
symptoms, including malaise and failure
to thrive.
Systemic JIA
Laboratory findings

1. Elevated acute phase reactants (↑

erythrocyte sedimentation rate, ↑ C-

reactive protein, and ↑ serum ferritin)

2. Anemia, leucocytosis (↑ white blood

cell count), and platelet counts and

anemia.
Systemic JIA
Complications
• Macrophage activation syndrome (MAS), is a very serious complication of
systemic JIA.
• There is overwhelming inflammation.
• The patient develops high fevers, hepatosplenomegaly, lymphadenopathy, and a
bleeding diathesis.
• Laboratory studies reveal pancytopenia, elevated ferritin, transaminases, and
triglycerides, as well as elevated soluble CD25. There is evidence of
disseminated intravascular coagulation with low fibrinogen, increased D-dimer,
and abnormal blood smear.
• Bone marrow sampling may identify mature macrophages displaying
hemophagocytic activity.
• MAS can lead to multisystem organ failure. Even with early detection and
aggressive treatment, mortality rates for MAS approximate 8%.
II. Oligo-articular JIA
• Arthritis in fewer than five joints within 6 months of diagnosis.
• Incidence: This is the most common form of JIA, accounting for
approximately 50% of cases.
• Peak age at 1–3 years. Girls are more affected than boys.
• Pattern of arthritis: asymmetrical involvement in medium-sized to
large joints; the knee is the most common joint involved, followed
by the ankle and the wrist.
• Children often develop pain and stiffness in the joint that limit use, but
refusing to walk or severe pain is rare. Morning stiffness and gelling also
can occur in the joint and, if present, can be followed in response to
therapy.
Oligo-articular JIA
• Children often develop pain and stiffness in
the joint that limit use, but refusing to walk
or severe pain is rare. Morning stiffness and
gelling also can occur in the joint and, if
present, can be followed in response to
therapy.
• Children with oligoarticular JIA may be
otherwise well without any evidence of
systemic inflammation (fever, weight
loss, or failure to thrive) or any laboratory
evidence of systemic inflammation
(elevated white blood cell count or
erythrocyte sedimentation rate).
Oligo-articular JIA

• All children with chronic arthritis are at risk for chronic iridocyclitis or
uveitis.
• The presence of a positive antinuclear antibody identifies children with
arthritis who are at higher risk for chronic uveitis.
• Young girls, with oligoarticular JIA and a positive antinuclear antibody are
at highest risk, with an incidence of uveitis of 80%.
• The uveitis associated with JIA can be asymptomatic until the point of
visual loss.
• It is crucial for children with JIA to undergo regular ophthalmologic
screening with a slit-lamp examination to identify anterior chamber
inflammation and to initiate prompt treatment of any active disease.
III. Polyarticular JIA
• Arthritis in five or more joints within the first 6 months of diagnosis
• Incidence: Accounts for about 20–30% of cases.
• Peak age: in early childhood. There is a second peak in adolescence, but
these children differ by the presence of a positive rheumatoid factor or
anticyclic citrullinated protein (anti-CCP) antibody and most likely
represent a subgroup with true adult rheumatoid arthritis; the clinical
course and prognosis are similar to the adult entity
• Pattern of arthritis Children with polyarticular JIA tend to have symmetric
arthritis, which can affect any joint but typically involves the small joints of
the hands, feet, ankles, wrists, and knees. The cervical spine can be
involved, leading to fusion of the spine over time.
• Children can present with evidence of systemic inflammation, including
malaise, low-grade fever, growth retardation, anemia of chronic disease,
and elevated markers of inflammation.
IV. Enthesitis-Related Arthritis (ERA)
• Arthritis and enthesitis (inflammation of tendinous insertions).
• A group of arthritides that include inflammation of the axial skeleton,
sacroiliac joints, peripheral large joints, and were previously referred to as
spondyloarthropathies.
• These include: juvenile ankylosing spondylitis, psoriatic arthritis, reactive
arthritis, arthritis of inflammatory bowel disease, and undifferentiated
juvenile arthritis.
• Frequent presence of HLA-B27.
• Need for earlier treatment with tumor necrosis factor (TNF) blockers
as axial disease can have a poor response to conventional disease-
modifying antirheumatic drugs (DMARDs) like methotrexate.
Summary of COMPLICATIONS
1. Loss of function of an involved joint secondary to
contractures, bony fusion, or loss of joint space.

2. More serious complications stem from associated uveitis; if

left untreated, it can lead to serious visual loss or blindness.

3. A very serious complication of sJIA, macrophage activation

syndrome (MAS).
JIA TREATMENT
• The treatment of JIA focuses on:

1. Suppressing inflammation.

2. Preserving and maximizing function.

3. Preventing deformity.

4. Preventing blindness.
JIA TREATMENT
1. Nonsteroidal anti-inflammatory drugs (NSAIDs) e.g. Ibuprofen, diclofenac (in
oligo-articular).
2. Disease-modifying anti-rheumatic drugs (DMARDs): Methotrexate, preferably
given subcutaneously, has become the drug of choice for poly-articular and systemic
JIA, which may not respond to baseline agents alone, and for oligo-articular patients
who do not respond to standard therapy and have high disease activity and risk
factors for poor prognosis. Methotrexate can cause bone marrow suppression and
hepatotoxicity; regular monitoring can minimize these risks. Leflunomide, has also
been used.
3. Systemic corticosteroid, for severe systemic JIA with internal organ involvement or
for significant active arthritis leading to the inability to ambulate. For patients with a
few isolated inflamed joints, intraarticular corticosteroids (oligo-articular type).
4. Second-line medications, such as hydroxychloroquine and sulfasalazine, have
been used in patients whose arthritis is not completely controlled with NSAIDs alone.
5. Biologic agents that inhibit TNFα and block the inflammatory cascade, including
etanercept, infliximab, and adalimumab, are effective in the treatment of JIA and
may be superior to methotrexate in the spondyloarthropathy group. The risks of
these agents are greater, however, and include serious infection and, possibly,
increased risk of malignancy. Anakinra, an interleukin-1 receptor antagonist, is very
beneficial in the treatment of the systemic features of systemic JIA.
4. Henoch-Schönlein purpura (HSP) (immunoglobulin A
vasculitis [IgAV])
Henoch-Schönlein purpura (HSP) [IgAV]
§ ETIOLOGY

• Is a vasculitis of unknown etiology characterized by inflammation of small

blood vessels with leukocytic infiltration of tissue, hemorrhage, and ischemia.
The immune complexes associated with IgAV are predominantly composed of
IgA, suggesting a hypersensitivity process.

§ EPIDEMIOLOGY

• IgAV is the most common systemic vasculitis of childhood and cause of

nonthrombocytopenic purpura.

• Incidence: It occurs primarily in children 3–15 years of age.

• More common in males than females.

IgAV CLINICAL MANIFESTATIONS
1. Rash: palpable purpura. Classically found in dependent areas:
below the waist, on the buttocks, and on lower extremities.
2. Arthritis: most common in the lower extremities, particularly the
ankles and knees. The arthritis is acute and very painful, with
refusal to bear weight.
3. Gastrointestinal involvement: mild to moderate crampy
abdominal pain, due to ischemia caused by small vessel
involvement of the gastrointestinal tract. Abdominal distention,
bloody diarrhea, intussusception, or abdominal perforation occurs
and requires emergent intervention.
4. Renal involvement: acute glomerulonephritis manifested by
hematuria, hypertension, or proteinuria.
5. IgAV occasionally is associated with encephalopathy, pancreatitis,
and orchitis.
The hallmark of HSP is non-thrombocytopenic palpable
purpura, which predominantly occurs on the buttocks and
lower extremities.
IgAV: LAB AND IMAGING
1. CBC: white blood cell count are elevated, the platelet count is the most
important test, because IgAV is characterized by nonthrombocytopenic
purpura with a normal, or even high, platelet count.
2. Erythrocyte sedimentation rate, C-reactive protein are elevated.
3. Urinalysis screens for evidence of hematuria.
4. Serum blood urea nitrogen and creatinine should be obtained to evaluate
renal function.
5. Occult blood in stools: may identify evidence of gut ischemia. Any question of
gut perforation requires radiologic investigation.
6. If performed, the skin biopsy will show leukocytoclastic vasculitis (LCV) with
predominant IgA deposition differentiating it from other forms of LCV.
IgAV: TREATMENT
• Supportive.
1. A short-term course of non- steroidal anti-inflammatory drugs can be
administered for the acute arthritis or skin manifestations.
2. Systemic corticosteroids usually are reserved for children with
significant pain from gastrointestinal disease. A typical dosing regimen is
prednisone (1–2mg/kg/day, maximum 60mg/day) with a gradual taper
plan over 4–6 weeks. Recurrence of abdominal pain and other
symptoms as corticosteroids are weaned necessitate the longer course
of treatment.
3. Acute nephritis typically is treated with corticosteroids but may
require more aggressive immunosuppressive therapy.
IgAV: COMPLICATIONS
1. Most cases of IgAV are monophasic, lasting 3–4 weeks and
resolving completely.
2. The rash can wax and wane,à Parents should be warned
regarding possible recurrences.
3. The arthritis of IgAV does not leave any permanent joint damage; it
does not typically recur.
4. Gastrointestinal involvement can lead to temporary abnormal
peristalsis that poses a risk of intussusception, which may be
followed by complete obstruction or infarction with bowel
perforation.
5. Renal involvement rarely may lead to renal failure.