A case of progressive pseudorheumatoid arthropathy of ‘childhood’ with the diagnosis delayed to the fifth decade

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  • A case of progressive pseudorheumatoid arthropathy ofchildhood with the diagnosis delayed to the fifth decade


    Kocaeli University,1 Medical Faculty, Department of Internal Medicine, Division of Rheumatology, Kocaeli, Istanbul

    University,2 Istanbul Medical Faculty, Department of Internal Medicine, Division of Medical Genetics, IstanbulxUniversity,3 Istanbul Medical Faculty, Department of Radiology, Istanbul, Turkey


    Progressive pseudorheumatoid arthropathy of childhood

    (PPAC) is a rare single gene disorder which is frequently

    misdiagnosed as juvenile rheumatoid arthritis. It is char-

    acterised with arthralgia, joint contractures, bony swelling

    of metacarpophalangeal and interphalangeal joints and

    platyspondyly. Clinical and laboratory signs of joint

    inflammation such as synovitis, a high erythrocyte sedi-

    mentation rate and an elevated C-reactive protein level are

    usually absent. Although the disease begins early in life

    (usually between 3 and 8 years of age), the diagnosis may

    be delayed. In the present case report, we describe a male

    patient diagnosed with PPAC at the age of 46 years,

    although he had been exhibiting the typical radiological

    and clinical features of the disease since the age of 7 years.

    Keywords: Progressive pseudorheumatoid arthropathy of


    2006 Blackwell Publishing Ltd

    I N T R O D U C T I O N

    Progressive pseudorheumatoid arthropathy of childhood

    (PPAC) is a single gene disorder which is inherited in an

    autosomal recessive manner. Alternative names of the dis-

    ease are spondyloepiphyseal dysplasia tarda (SEDT) with

    progressive arthropathy and progressive pseudorheumatoid

    dysplasia (1). Although the frequency of the disease is not

    known exactly, it is estimated to be one per million in Uni-

    ted Kingdom. The main clinical features are arthralgia, joint

    contractures, enlarged metacarpophalangeal and interphalan-

    geal joints, platyspondyly and short stature. The onset of

    the disease is usually between 3 and 8 years of age, and it is

    frequently diagnosed erroneously as juvenile rheumatoid

    arthritis (JRA). In the present case report, we describe a

    male patient diagnosed with PPAC as late as at the age of

    46 years, although he had been displaying the typical clin-

    ical and radiological features of the disease since childhood.

    C A S E

    A 46-year-old male patient was admitted due to back and hip

    pain of 4 years duration. His history was remarkable for

    swelling of the interphalangeal and metacarpophalangeal

    joints accompanied with a decrease in joint mobility which

    had begun at the age of 7 years. He also described enlarge-

    ment of knees during the following years and a gradual

    decrease of mobility involving nearly all the joints (knees,

    shoulders, hips, servical and thoracal spine). He had also

    joint pain mainly during physical activity, occasionally

    intensifying also at rest and necessitating administrations of

    non-steroidal anti-inflammatory drugs. He denied other

    signs of arthritis including erythema and soft tissue swelling.

    He had been evaluated in various hospitals without a defin-

    ite diagnosis. For the last 4 years, the hip and back pain

    worsened to the point of limiting daily activities without a

    satisfactory response to non-steroid anti-inflammatory drugs.

    The patient was born from a first-cousin marriage.

    Remarkably, his sister and mother had a joint disease with

    many similarities: swelling of interphalangeal joints and knees

    beginning in childhood, gradual limitation of mobility of

    both peripheral and axial joints and back and hip pain.

    The height of the patient was 146 cm, and the weight

    was 56 kg. On physical examination, the neck and the

    trunk were found to be shortened. Flexion contractures and

    bony enlargement of proximal and distal interphalangeal

    joints were noted (Figures 1 and 2). Also bilateral wrist,

    elbow, shoulder, knee and hip movements were limited.

    Physical examination was normal otherwise.

    The results of a urine analysis, complete blood count and

    routine blood chemistry (including serum creatinine, calcium,

    phoshorus alkaline phosphatase, aspartate aminotransferase

    and alanine aminotransferase) were normal. The thyroid-

    stimulating hormone, follicule-stimulating hormone, luteinis-

    ing hormone and testosterone levels were normal. The

    Correspondence to:Dr Kivanc Cefle, Istanbul Universitesi, Istanbul Tip Fakultesi, Ic

    Hastaliklari AD, Tibbi Genetik BD, 34093 Capa, Istanbul, Turkey

    Tel.: 90 212 414 23 22Fax: 90 212 532 42 08Email: ceflek@istanbul.edu.tr

    CASE REPORT do i : 1 0 . 1111 / j . 1 742 - 1241 . 2005 . 00662 . x

    2006 Blackwell Publishing Ltd Int J Clin Pract, October 2006, 60, 10, 13061309

  • erythrocyte sedimentation rate was 24 mm h; C-reactive pro-tein was in the normal range. The rheumatic facor was

    negative. Echocardiographic and ophtalmological examina-

    tion was unremarkable.

    Plain radiographs of the hands showed bony enlargement of

    metacarpophalangeal, proximal interphalangeal joints and joint

    narrowing.Theknee jointswereenlarged similarly.Radiographs

    of the spine (dorsal and lumber region) revealed osteophyitic

    degeneration, decreased vertebral height (platyspondyly) and

    narrowing of the intervertebral space (Figures 3, 4 and 5).

    Coxofemoral joints were found to be heavily sclerosed with

    narrowing of the joint space. Analysis of bone mineral density

    by dual energy X-ray absorptometry (DEXA) showed a lomber

    T-score of)3.65 and Z score of)3.28. Femoral T and Z scoreswere8.87and10.26, respectively.

    The patient was diagnosed with PPAC based on the typical

    clinical (childhood onset, bony swelling of interphalangeal

    joints, gradual decrease in joint mobility, disabling hip and

    back pain, lack of overt signs of arthritis and absence of

    synovial involvement) and laboratory findings (osseous enlarge-

    ment of joints and platyspondyly on skeletal radiograms,

    normal erythrocyte sedimentation rate and C-reactive protein


    D I S C U S S I O N

    PPAC was first described in 1983 by Spranger et al. (2) in five

    patients as a hereditary arthropathy affecting major and

    minor joints (2). It is a rare hereditary disorder with auto-

    somal recessive inheritance characterised by bony enlargement

    of interphalangeal and metacarpophalangeal joints, flexion

    Figure 1 Flexion deformity and apparent swelling of proximalinterphalangeal joints

    Figure 2 Bony enlargement of metacarpophalangeal andproximal interphalangeal joints

    Figure 3 X-ray of the hands revealing swelling of themetacarpophalangeal and proximal interpahalangeal joints. General

    narrowing of the joint spaces; irregularity of the first metacarpop-

    galangeal joint on the left

    Figure 4 X-ray showing osseous enlargement of the knees withextremely narrowed joint spaces. Sclerosing and irregularity of

    joint contours are noted


    2006 Blackwell Publishing Ltd Int J Clin Pract, October 2006, 60, 10, 13061309

  • deformities of fingers, reduced mobility of knees and coxofe-

    moral joints and platyspondyly; severe involvement of the

    joints may be disabling. Although apparently rare in western

    countries with an incidence of one per million in United

    Kingdom, it is probably more frequent in Middle East and

    Gulf States with more than two-thirds of the reported patients

    belonging to Arab and Mediterranean populations (3,4). To

    our knowledge, this is the third case report of a patient with

    PPAC from Turkey (5,6).

    Initial mapping studies assigned the gene responsible for

    the disease to the long arm of chromosome 6. However,

    examination of COL10A1, which is a candidate gene in this

    region, did not reveal any mutations (7,8). Using a positional

    candidate approach, Hurvitz et al. (4) found homozygous

    mutations in the WISP gene which also resides in 6q. WISP

    is a member of CCN gene family which encodes cysteine-rich

    secreted proteins with roles in cell growth and differentiation.

    However, the exact mechanism of the disease is not clear at

    the present.

    The clinical course of the present patient is typical for the

    disease. Joint involvement, characterised with painless swel-

    ling of interphalangeal joints, had begun when he was 7 years

    old. Although joint symptoms most commonly begin

    between 3 and 8 years of age, skeletal findings may be present

    even at birth (9). In this patient, severe pain, which occurred

    as a relatively late symptom, affected mainly hips and the

    back, and it was unresponsive to non-steroidal anti-inflamma-

    tory drugs. Osteoarthritic degeneration of the coxofemoral

    joints, which is revealed by intense sclerotic changes seen on

    plain radiographs, may become an indication for hip replace-

    ment (10). An interesting feature of the present case is the

    decreased bone mineral density of the lomber vertebrae.

    Because the patient did not display any clinical and laboratory

    signs of other disorders associated with osteoporosis, we sug-

    gest that the decreased bone density may be a direct conse-

    quence of PPAC. However, the exact mechanism of this

    relation is unclear at the present. On the other han