Idiopathic Chondrolysis Treated With Enbrel

[Guest guest]

Idiopathic Chondrolysis Treated With Etanercept

ORTHOPEDICS 2009; 32:214

http://www.orthosupersite.com/view.asp?rID=37214

Deborah V. Appleyard, MD, MPH; R. Schiller, MD; Craig P. Eberson,

MD; G. Ehrlich,MD

Abstract

Idiopathic chondrolysis of the hip in children has been well documented in

the literature. The insidious nature of the symptoms and lack of early

radiographic findings and diagnostic testing often delay diagnosis. Children

often report a stiff, painful hip and have an associated limp in the absence

of trauma or constitutional symptoms. Despite these symptoms it remains a

poorly understood diagnosis with no identifiable cause. Some have speculated

an inflammatory cause, as this disease exhibits joint space narrowing,

presumably due to enzymatic activity similar to juvenile rheumatoid

arthritis. Despite case reports attempting traction, physical therapy,

nonsteroidal anti-inflammatories, steroids, and even operative intervention,

no current treatment regimen exists that offers proven appreciable benefit.

We hypothesized the powerful anti-inflammatory properties of etanercept

would provide symptomatic and radiographic improvement of idiopathic

chondrolysis of the hip.

This article presents a case of an adolescent boy with a stiff, painful left

hip that failed treatment with traction, physical therapy, naproxen, and

methotrexate, prior to initiating etanercept. After 1 year of daily

etanercept therapy, the patient's hip motion improved in all directions and

his pain completely resolved. This novel therapeutic approach offered

symptomatic relief and radiographic improvement, and may provide an

effective treatment strategy for this difficult disease.

Idiopathic chondrolysis of the hip in children has been a well-recognized,

though poorly understood, diagnosis. Although chondrolysis of the hip as a

consequence of treatment of slipped capital femoral epiphysis was first

described by Waldenstrom in 1930,1 it was not until 1971 that the idiopathic

form was introduced to the literature.2

In that series, 7 of 9 patients with chondrolysis of the hip had no

identifiable cause for the disorder. Interestingly, 7 of the 9 patients in

this series were adolescent African-American girls, which led to the

supposition that the disease was predominantly in adolescent

African-American girls and rarely in other groups. Although the insidious

onset of hip pain and progressive loss of hip motion in idiopathic

chondrolysis of the hip demonstrates a predilection for adolescent

African-American girls, cases have been reported in boys and in children of

Indian, Hispanic, White, and Asian descent.3-5 The frequency with which this

disease is described in African-American girls led to speculation of a

genetic basis to this disorder, although this has yet to be demonstrated.

sy and others have suggested that this perhaps represents a

seronegative type of immune reaction, since the joint space narrowing was

typical of juvenile rheumatoid arthritis. They demonstrated antibodies in

the synovium that may play a role in the development of chondrolysis.6-10

Despite many case reports available in the literature,2,3,5,11-13 few have

offered treatment options with appreciable or proven benefit. Unfortunately,

this is likely because this uncommon condition remains poorly understood

despite tremendous advances in our knowledge of the pathologic basis of many

other orthopedic disorders. As a result, novel and effective treatment

modalities for this puzzling and disabling disorder have been lacking. We

present a case using a novel therapeutic alternative for idiopathic

chondrolysis of the hip consisting of a combination of pharmacologic therapy

and traditional modalities.

Case Report

A 15-year-old African-American boy presented 18 months after the onset of

left groin pain and continued use of a wheelchair to travel substantial

distances. Prior to presentation, his treatment elsewhere consisted of

nonsteroidal anti-inflammatory drugs (NSAIDs) and physical therapy for 6

months. This offered no symptomatic or radiographic improvement and was

followed by surgical exploration. The cartilage appeared normal and a

synovial biopsy showed chronic inflammatory changes. Cultures demonstrated

no evidence of infection. Muscle releases of hip adductor and rotators were

performed to decrease the tightness of the joint. Intraoperative passive

motion of the left hip improved to 90% of the right hip. Postoperatively, he

was placed on a continuous passive motion machine for approximately 2 weeks.

Motion achieved intraoperatively was not maintained, and the patient

continued to have limited motion, most severely with abduction and internal

rotation. The lack of left hip motion, constant pain, and inability to

ambulate long distances contributed to the patient's decision to seek

further treatment.

At presentation, physical exam of the left hip revealed a flexion

contracture of 45°; 5° of active flexion (right hip 110°); and no extension

(right hip 20°), abduction (right hip 60°) or rotation (right hip 30°

internally, 40° externally). The patient was admitted to the hospital and

spent 3 weeks in 10 lb of skin traction while receiving daily physical

therapy consisting of range-of-motion exercises. Radiographs and magnetic

resonance imaging (MRI) confirmed a prior diagnosis of idiopathic

chondrolysis of the left hip. Work-up included an erythrocyte sedimentation

rate of 2 (mm/hr); normal creatine phosphokinase; and negative anti-nuclear

antibody, rheumatoid factor, HLA-B27, and purified protein derivative skin

tests.

In view of some published case reports suggesting a rheumatologic etiology,

rheumatology consultation was obtained to consider the start of

disease-modifying agents. The patient was started on naproxen (250 mg twice

daily) and methotrexate (200 mg once a week). After 2 weeks, active motion

in his left hip improved: 50° of flexion from 5°, 5° of extension, 20° of

abduction, and 5° to 10° of internal and external rotation from 0°. The

patient was discharged on naproxen (250 mg twice daily) and methotrexate

(200 mg once a week), as well as 10 lb of skin traction for 18 hours per day

and daily physical therapy for range-of-motion exercises.

After 6 months of treatment, despite modest improvement in mechanical pain,

the patient reported stiffness and no further improvement of range of

motion. Due to the presumed inflammatory component of this disease and the

failure of the current medication regimen to improve the patient's symptoms,

the naproxen and methotrexate were discontinued and the patient was started

on etanercept (25 mg twice weekly).

After 3 months of etanercept treatment combined with the prior physical

therapy regimen and reduction of traction to only 3 times per week, his hip

motion improved significantly. Hip flexion increased to 100° (initially 5°),

extension to 35°, and abduction/adduction to 40° and 20°, respectively.

Internal and external rotation continued to be limited (5° to 10°), and was

worse with the hip flexed. Radiographs suggested an increase in available

joint space.

After 8 months of etanercept treatment, the patient maintained his range of

motion and experienced increased internal and external rotation to 10° and

30°, respectively, despite discontinuing the nightly skin traction 3 times

per week. The patient maintained his range of motion for 2 years while

continuing etanercept (25 mg twice weekly) and daily range of motion

exercises. Prior to leaving our care due to a family move, the patient was

pain free and able to play basketball. He was given rheumatology follow-up

and 1 additional year of etanercept therapy.

Discussion

Idiopathic chondrolysis of the hip presents an interesting, though

difficult, diagnostic and therapeutic dilemma for the clinician and patient.

The diagnosis is often delayed secondary to the insidious onset of symptoms,

progressive radiographic findings, and absence of diagnostic laboratory

tests. Typically reporting no history of trauma or constitutional symptoms,

patients present with pain in the hip, knee, or leg; an associated limp;

progressive loss of range of motion in the affected hip; and in some

instances fixed flexion, abduction, or adduction deformities.3,13,14 Usual

laboratory work-up includes complete blood count, white blood cell count

with differential, erythrocyte sedimentation rate, rheumatoid factor, and

anti-nuclear antibody test. Some have included HLA-B27 screening, Coombs

testing, serum immunoelectrophoresis, and serum immunoglobulin level, but no

significant pattern has been identified, and therefore laboratory testing is

potentially more useful in ruling out other pathology.3,11,12,15

Histological features include capsular thickening and edema, lymphocyte and

plasma cell infiltration of the synovium, fibrillation and fragmentation of

the articular surface with progressive loss of articular cartilage, and even

chondrocyte degeneration and empty lacunae.2-5,11 Open synovial biopsy and

joint aspiration aid in identifying infectious or neoplastic causes of pain

such as septic arthritis, tuberculosis, pigmented villonodular synovitis,

and juvenile rheumatoid arthritis.3

Radiographic changes seen in idiopathic chondrolysis of the hip have been

well documented and facilitate differentiating between idiopathic

chondrolysis of the hip and the typical radiographic findings in slipped

capital femoral epiphysis and Perthes disease.11,13,14,16,17 Early features

consist of localized osteoporosis, subchondral erosions, femoral head

change,15,18 and reduction of the joint space. Later changes include

complete loss of the joint space, subchondral cysts, trochanteric and

epiphyseal physeal closure, osteophytes, and in severe cases, protrusion

acetabuli, ankylosis, and osteoarthritis.

Magnetic resonance imaging of the hip demonstrates cartilage loss, joint

effusion, marrow edema, femoral and acetabular remodeling, significant

regional muscle atrophy, and synovial enhancement, though this is not a

consistent feature of the disease.16 Cartilage loss was found to be most

severe in the central part of the joint. When left untreated, the natural

history of this disease often leads to complete or near-complete ankylosis

of the joint.13,14,16 Only after eliminating traumatic, infectious,

neoplastic, or autoimmune etiologies, combined with diagnostic loss of the

joint space to <3 mm,11,19-21 can a diagnosis of idiopathic chondrolysis be

made.

According to the literature, many idiopathic chondrolysis therapies have

been tried, although none with great success. The mainstays of most

treatment algorithms have been nonsteroidal anti-inflammatory medication,

physical therapy,22 and traction.17 After failure of conservative treatment,

operative intervention has been attempted to achieve satisfactory results.

Surgical procedures include subtotal hip capsulectomies with or without

psoas and/or adductor tenotomies,11,17 hanging hip operation,23 hip

arthrodesis,14,24-26 hinged distraction,27 and excision arthroplasty.17 The

results of operative intervention other than arthrodesis or excision

arthroplasty are inconsistent and the goals of these procedures are

accordingly modest: pain relief, deformity correction, and restoration of

functional hip range of motion.11,18

However, Korula et al's17 case series of 20 patients (21 hips) found

near-normal hip range of motion could be achieved when the affected hip was

examined under anesthesia, suggesting muscle spasm is a prominent and

consistent feature of this condition. In 2005, Thacker et al28 reported a

series of 11 adolescents with severe hip joint arthritis, 3 of whom carried

a primary diagnosis of idiopathic chondrolysis, treated with articulated

hinged distraction arthroplasty. The authors concluded that hinged hip

distraction was an effective treatment in eliminating pain, restoring joint

space, and improving function. However, the complication rate of 36.4%

stressed the importance of correct application of the hinged device, patient

compliance, and supervised rehabilitation postoperatively.

The limited success of surgical intervention has emphasized the need for

alternate yet effective medical treatment of this condition. While NSAIDs

have been the mainstay of medical therapy, their effectiveness is limited

and the associated gastrointestinal toxicity precludes their use in certain

patients. Etanercept was chosen as a possible treatment for this disorder

due to its powerful anti-inflammatory effect. The drug is a soluble, dimeric

fusion protein consisting of 2 copies of the extracellular ligand-binding

portion of the human tumor necrosis factor p75 receptor linked to the

constant portion of human immunoglobulin G1.29 This protein complex binds to

the tumor necrosis factor and thereby blocks its interaction with cell

surface receptors and attenuates its pro-inflammatory effects.

Importantly, the drug, which is administered as a twice-weekly subcutaneous

injection (adult dose 25 mg; pediatric dose 0.4 mg/kg, maximum 25 mg), has

been shown to be widely distributed throughout the body and even reaches the

synovium.30 The medication has been used primarily to treat rheumatoid

arthritis and has been shown to be significantly better than placebo at

reducing disease activity in patients who had an inadequate response to

previous treatment with disease-modifying antirheumatic drugs.31 Etanercept

has also been used successfully to treat psoriatic arthritis and

polyarticular juvenile rheumatoid arthritis.31 However, its action as a

biological response modifier results in a significantly decreased immune

response; thus, patients must be followed for potential infection. The

reduced immune response may be what was successful in this case.

Idiopathic chondrolysis of the hip is a rare and devastating disease with

limited therapeutic options. Although no etiology for this disease has been

identified, synovial biopsies suggest an inflammatory component to the

disorder, possibly secondary to an abnormal immunologic response, suggesting

a potential target for intervening in the disease process. We have presented

a case of an adolescent boy who achieved substantial symptomatic improvement

with the use of etanercept in combination with physical therapy and

traction, suggesting this innovative approach may be an effective treatment

strategy for future patients.

Authors

Drs Appleyard, Schiller, Eberson, and Ehrlich are from the Department of

Orthopedics, Brown Alpert Medical School/Rhode Island Hospital, Providence,

Rhode Island. Drs Appleyard, Schiller, Eberson, and Ehrlich have no relevant

financial relationships to disclose. Correspondence should be addressed to:

R. Schiller, MD, Department of Orthopedics, Brown Alpert Medical

School/Rhode Island Hospital, 593 Eddy St, Providence, RI 02903.