CASE REPORT

Niger J Paed 2013; 40 (4): 431 – 433

Onubogu UC

Okoh BAN

Eke G

Acute Lymphoblastic Leukaemia

presenting as Juvenile Idiopathic

Arthritis in a Nigerian boy

Joboy-okei EA

DOI:http://dx.doi.org/10.4314/njp.v40i4,18

Accepted: 28th April 2013

Abstract Background: Acute

Lymphoblastic Leukaemia in chil-

dren commonly presents with

osteo articular manifestations that

may mimic Juvenile Idiopathic

Arthritis. This may create consid-

erable diagnostic difficulty and

lead to delay in commencing ap-

propriate treatment.

Case: An eight year old boy who

presented with multiple joint

pains and swellings of two

months duration, had an elevated

Rheumatoid factor and X-ray

findings suggestive of Juvenile

Idiopathic Arthritis. A blood film

and bone marrow aspirate how-

ever, confirmed the diagnosis of

Acute Lymphoblastic Leukaemia

for which he was managed.

Conclusion: This report empha-

sizes the need for a high index of

suspicion in children presenting

with osteo articular manifestations

of Acute Lymphoblastic Leukae-

mia in order to make a prompt

diagnosis and institute treatment.

(

)

Onubogu UC

Department Paediatrics,

Shawsand Medical Center,

Port Harcourt, Rivers State,

Nigeria.

Email: utchayonubogu@yahoo.co.uk

Tel: +234 803 327 9486

Okoh BAN, Eke G

Joboy-okei EA

Department of Paediatrics,

University of Port Harcourt Teaching

Hospital, Port Harcourt,

Rivers State,

Key words: Acute Lymphoblastic

Leukaemia, Juvenile Idiopathic

Arthritis.

Nigeria.

Introduction

inappropriate intervention. We present the case of an 8

year old male who presented with features suggestive of

Juvenile Rheumatoid Arthritis (JRA), also known as

Juvenile Idiopathic Arthritis (JIA) but was finally diag-

nosed with ALL.

Leukaemia is one of the common malignant neoplasms

in childhood, accounting for about 41% of all

malignancies that occur in children <15year of age and

Acute lymphoblastic leukaemia (ALL) accounts for

1

about 77% of cases of childhood leukemias. Bone pain,

Case Report

particularly of the lower extremities is a common

manifestation of childhood ALL. Although the initial

presentation of childhood ALL is usually nonspecific

and relatively brief, symptoms may be of several months

duration, may be localized predominantly to the bones

or joints, and may include joint swelling. Joint lesions

are less frequent but have been reported in at least 10 to

An 8year old male presented with a three month history

of recurrent fever, two month history of paleness of the

body and joint pains. The fever was high grade and in-

termittent, with occasional chills. He had two episodes

of pallor in the two months preceding presentation and

was transfused with blood donated by the father in a

private hospital. The Joint pains involved his left shoul-

der, left elbow, left knees, left ankle and all fingers. Pain

was severe enough to make him cry and keep him awake

at night. There was associated swelling of the joints. He

was initially hospitalized in a private hospital where he

received intramuscular injections and blood transfu-

sions. Genotype done there was AS. With no remarkable

improvement, he presented to the University of Port

Harcourt Teaching Hospital (UPTH). He had a rash on

the trunk that lasted for about a week at onset of symp-

toms. The review of systems showed he had haemopty-

sis and epistaxis. On physical examination he was

1

mia.

5%₂_,₃of children and 3% of adults with acute leukae-

Joint manifestations in leukaemia have been attributed

to a variety of causes. These include leukaemic synovial

infiltrations, haemorrhage into the joint or periarticular

structures, synovial reaction to adjacent bony, pe₄riosteal

or capsular lesions, and crystal induced synovitis.

Radiographic bone abnormalities have been said to oc-

cur at presentation in more than half₅_,₆of children with

ALL with bone and joint symptoms. Radiographs of

involved joints may sh₂_,o₃w lesions in the adjacent bone,

or show joint effusion.

moderately pale, febrile with submandibular lymphade-

nopathy. His left ankle was swollen and he had Swan

neck deformity of his left ring and middle fingers. There

was diffuse swelling on the middle phalanges on the

The orthopaedic manifestations of ALL in children may

create considerable diagnostic difficulty. This may lead

to both a delay in commencing appropriate treatment or

4

32

right hand with differential warmth and tenderness. He

had no organomegaly and ophthalmology examination

was normal.

frequency and severity of bone symptoms in children

have been attributed to a more active bone metabolism,

more red marrow with little res₁e₁rve marrow space, and a

less firmly attached perioteum.

His peripheral blood film showed hypochromic normo-

cytic anaemia with few normoblast, There was leukocy-

tosis with a White Blood Cell count (WBC) of greater

Typically, children with ALL have asymmetric

oligoarthritis, particularly in the large joints of the lower

limbs in the following descending order of frequency:

ankle 63%, knee 59%, and hip 20%. In the upper limbs

the descending order is elbow 32%, carpal 16%, and

shoulder 8%. In the metacarpophalangeal and interpha-

langeal small joints of hands 14% and 2% in the

9

than 30 x 10 /L and greater than 50% were blasts. The

Platelets were scanty on the blood film but normal in

size, shape and granularity. His serum uric acid was

elevated. The X-ray of the hands showed juxtaarticular

osteoporosis with soft tissue swelling suggestive of

rheumatoid arthritis (Figure 1). The Rheumatoid factor

was raised and antinuclear antibodies were negative.

The bone marrow aspirate confirmed ALL type L2.

He was treated using the protocol for high risk ALL. He

had three cycles of chemotherapy but was yet to achieve

remission before he defaulted from treatment. Contact

made with the family revealed that he died 2 months

after default.

tarsometatarsal, small interphalangeal joints of the feet

3

and vertebrae. Our patient however, had polyarticular

involvement of the left shoulder, left elbow, left knees,

left ankle and all fingers. About 7% of children with

ALL with initial musculoskeletal manifestations meet

diagnostic criteria for JIA. Our patient met the criteria

1

2

for polyarticular rheumatoid positive JIA, considering

the duration of symptoms (>6weeks), number of joints

involved (>6), swan neck deformity of the interphalag-

eal joint, preceeding history of a transient rash and high

rheumatoid factor. In such cases, diagnosis of ALL is

generally considered in subsequent stages when atypical

clinical characteristics of JIA manifest. The atypical

presentations of JIA in our patient were severe anaemia,

Fig 1: Plain radiograph

of both hands of patient

showing soft tissue

swelling

1

3,14

bleeding disorder and lymphadenopathy. Studies

have shown that important features that predicted a

diagnosis of ALL and differentiated it from JIA include

a history of night pain, non-articular bony pain and the

presence of joint pain out of proportion to physical signs

(

all of which was seen in our patient). Other distinguish-

ing findings were anemia, leucopenia), lymphocytic

predominance and thrombocytopenia. Non-osseous

involvement such as hepatosplenomegaly or enlarged

lymph nodes occurs in 60% of ALL cases at presenta-

tion. Night pain has been observed frequently in

children with leukaemia. Children with JRA usually

describe achiness, stiffness, and a dull discomfort over

the joint(s) that is worse in the mornings. Pain that is

excruciating and wakes the child from sleep is not typi-

cal for JIA.

Discussion

1

5

Acute lymphoblastic leukaemia (ALL) is the_,₈ second

7

most prevalent childhood cancer in Nigeria. It is a

malignant disease of the bone marrow in which early

lymphoid precursors proliferate and replace the normal

hematopoietic cells of the marrow. ALL may initially

present with osteoarticular manifestation that mimic

Juvenile idiopathic arthritis (JIA). Such presentation can

occur in 15% to 30% of ALL cases at disease onset,

when peripheral blood changes are subtle or even ab-

A bone marrow aspiration is the confirmatory test in

making a diagnosis for ALL, while the diagnosis of JIA

is clinical. Rheumatoid factor has 90% sensitivity in

diagnosing rheumatoid arthritis in clinically established

diseases. It has a limited diagnostic value as it can be

5

9

sent. Barbosa et al showed that 8% of patients with

leukaemia had been diagnosed with rheumatic fever or

JIA before referral, and some of these patients had al-

ready received steroids, delaying the commencement of

1

6

positive in 20% of patients w₇ ith leukaemia and in

1

.3% of a healthy population. Secondary hyperuricae-

4

1

0

mia may rarely be as_,₄sociated with arthritis in patients

definitive treatment for ALL. In another study on chil-

dren presenting with musculokeletal symptoms in which

occult cancer was found, ALL was the most prevalent

3

with acute leukemia. The radiographic bone lesions of

acute leukaemia are radiolucent metaphyseal bands,

generalized osteoporosis, osteolytic bone destruction,

periosteal infiltration with new bon_,e₃ formation and os-

(

60%), followed by lymphoma (20%).

2

teosclerotic new bone formation. The radiographic

The cause of the osteoarticular manifestation of acute

leukaemia has been attributed to direct extension of

leukemic cells from the marrow or to hematogenous

signs of JIA are periarticular soft-tissue swelling with a

fusiform appearance and juxta-articular osteopenia (both

of which were seen in our patient). Osteopenia

subsequently becomes more generalized as the disease

progresses, widening of joint spaces initially then

narrowing, joint subluxation and malalignment at a later

3

dissemination of leukemic cells. The proliferating

leukemic cells cause bone destruction, increase intrame-

dullary pressure which interferes with nutrition, or

induce osteoclastic or blastic responses. The increased

4

33

1

8

stage. In a study carried out among children with mus-

culoskeletal symptoms and a diagnosis of ALL or JIA, it

was noted that on plain X-ray, soft tissue swelling and

osteopaenia were significantly more common in patients

with JIA. On the other hand, radiolucent metaphyseal

bands and coarse trabeculations were significantly more

common in patients with ALL.

suspicion is required in order do a bone marrow biopsy

to confirm presence of blasts in the marrow. Our patient

though had blasts on his peripheral blood film, he had

been symptomatic for two months and was transfused on

two occasions. We could not establish if he had a blood

film done prior to the transfusion and if he had periph-

eral blasts at onset of his symptoms. We recommend

therefore, that any child with severe anaemia necessitat-

ing blood transfusion should have blood samples taken

out for peripheral blood film prior to transfusion.

Conclusion

In conclusion, since up to 75% of children presenting

with osteo arthritic manifestation of ALL do not have

blast in the peripheral blood film, a high index of

Conflict of Interest: None

Funding: None

References

1

.

Tubergen DG, Bleyer A. The leu-

kaemias. In: Behrman RE, Klieg-

man RM, Jenson HB, Stanton BF

editors. Nelson textbook of Paedi-

9. Barbosa CM, Nakamura C, Ter-

14. Gupta D, Singh S, Suri D, Ahlu-

walia J, Das R, Varma N. Arthritic

presentation of acute leukemia in

children: experience from a tertiary

care centre in North India. Rheu-

matol Int. 2010; 30(6):767-770.

15. Tuten HR, Gabos PG, Kumar SJ,

Harter GD. The limping child: a

manifestation of acute leukaemia. J

Pediatr Orthop. 1998; 18; 625 –

629.

16. Chell J, Fernandes JA, Bell MJ.

The orthopaedic presentation of

acute leukaemia in childhood. Ann

R Coll Surg Engl. 2001; 83: 186-

189.

reri MT, Lee ML, Petrilli AS,

Hilario MO. Musculoskeletal

manifestations at the onset of

acute leukemias in childhood. J

Pediatr. 2002; 78(6):481–484.

10. Trapani S, Grisolia F, Simonini

G, Calabri GB, Falcini F. Inci-

dence of occult cancer in chil-

dren presenting with muscu-

loskeletal symptoms: A 10-year

survey in a pediatric rheumatol-

ogy unit. Semin Arthritis Rheu.

2000; 29(6):348–359.

11. Parker BR, Marglin S, Castellino

RA. Skeletal manifestations of

acute leukemia, Hodgkin’s dis-

ease and non-Hodgkin’s lym-

phoma. Semin Roentgenol. 1980;

15:302-315.

th

atrics. 18 Ed. Pennsylvania:

Saunders; 2007. p. 2116 – 2120.

Resnick D, Niwayama G. Diagno_s_t-

sis of bone and joint disorders. 1

Ed. Philadelphia: W. B. Saunders,

2

3

4

.

1

981. p. 1992-2001.

Thomas LB, Forkner CE, Frei E,

Besse BE, Stabenau JR. The skele-

tal lesions of acute leukemia. Can-

cer. 1961; 14:608-62I.

Weinberger A, Schumacher HR,

Schimmer BM. Arthritis in acute

leukaemia: Clinical and histopa-

thological observations. Arch In-

tern Med. 1981; 141:1183 – 1187.

Rogalsky RJ, Black GB, Reed

MH. Orthopedic manifestations of

leukemia in children. J Bone Joint

Surg Am. 1986; 68:494-501.

Clausen N, Gotze H, Pedersen A,

Riis-Petersen J, Tjalve E. Skeletal

scintigraphy and radiography at

onset of acute lymphocytic leuke-

mia in children. Med Pediatr On-

col. 1983; 11: 291-296.

Edache SO, Ibrahim IA, Isaac EO,

Seline NO. Pattern of Childhood

Malignancies in Jos, North Central

Nigeria. Journal of Medicine in the

Tropics. 2011; 13(2):109-114.

Parkin DM, Ferlay J, Hamdi-

17. Nielsen SF, Bojeson SE, Schnohr

P, Nordestaarg BG. Elevated rheu-

matoid factor and long term risk of

rheumatoid arthritis: a prospective

cohort study. BMJ.

5

6

.

12. Miller ML, Cassidy JT. Juvenile

Rheumatoid Arthritis. In: Behr-

man RE, Kliegman RM, Jenson

HB, Stanton BF editors. Nelson

2012;345:e5244.

18. Tafaghodi F, Aghighi Y, Yazdi

HR, Shakiba M, Adibi A. Predic-

tive plain X-ray findings in distin-

guishing early stage acute lym-

phoblastic leukemia from juvenile

idiopathic arthritis. Clin Rheuma-

tol. 2009; 28(11):1253 – 1258.

th

textbook of Paediatrics. 18 Ed.

Pennsylvania: Saunders; 2007. p.

1001 – 1010.

13. Jones OY, Spencer CH, Bowyer

SL, Dent PB, Gottlieb BS, Rabi-

novich CE. A Multicenter Case-

Control Study on Predictive

Factors Distinguishing Child-

hood Leukemia From Juvenile

Rheumatoid Arthritis. Pediat-

rics. 2006;117; 840-884.

7

8

.

Cherif M et al., editors. Cancer in

Africa: Epidemiology and Preven-

tion. Lyon, France: IARC Press,

2

003.