Could scoliosis at the age of 7 months be a manifestation of progressive pseudorheumatoid dysplasia? A case report

Abstract

Background

Progressive pseudorheumatoid dysplasia is a rare genetic skeletal disease that usually affects children between the ages of 3 and 8 years. The pathological progression of progressive pseudorheumatoid dysplasia involves noninflammatory degeneration of the articular cartilage, resulting in progressive joint stiffness and enlargement. Previously published studies have not considered scoliosis as an early manifestation of progressive pseudorheumatoid dysplasia. However, this paper did, and showed why we should take progressive pseudorheumatoid dysplasia as a differential diagnosis if there is a scoliosis in early years of life.

Case presentation

In this paper, we report on an 11-year-old Syrian Arab girl with progressive pseudorheumatoid dysplasia who presented with progressive limitations in passive and active movement of multiple joints. The patient reported experiencing early symptoms, including lumbar scoliosis observed at the age of 7 months. However, at that time, the doctors were unable to make a definitive diagnosis. After years of follow-up with various doctors, the patient sought treatment at the Children’s Hospital in Damascus, where an accurate diagnosis was finally reached. New X-ray images were taken and compared with previous ones, and appropriate laboratory tests were also conducted. Based on all the available information, a diagnosis of progressive pseudorheumatoid dysplasia was made without performing genetic analysis owing to its unavailability in the country.

Conclusion

We have written this case report to guide future studies in determining whether there is a possible link between scoliosis in the first years of life and progressive pseudorheumatoid dysplasia. Consequently, is it worth considering progressive pseudorheumatoid dysplasia as a differential diagnosis for scoliosis in the early years?

Background

Progressive pseudorheumatoid dysplasia (PPRD), which previously called “spondyloepiphyseal dysplasia with progressive arthropathy” or “progressive pseudorheumatoid chondrodysplasia” [1], is a rare genetic skeletal disease with an incidence rate of 1 in 1,000,000 in the UK. It typically affects children between the ages of 3 and 8 years. PPRD is inherited in an autosomal recessive pattern and is associated with multiple mutations, including the WNT1-inducible signaling pathway protein 3 mutation (WISP-3) and others [1–3].

Patients with PPRD usually experience progressive degeneration of articular cartilage, leading to joint stiffness and enlargement without inflammation. The initial joints affected are typically the interphalangeal joints. As the disease progresses, it spreads to involve larger joints and the vertebral column, resulting in significant joint contractures, abnormal gait, scoliosis, and kyphosis. Additionally, patients often have a short stature that develops over time [1].

The most common differential diagnosis for PPRD is juvenile idiopathic arthritis (JIA) [1, 3, 4]. Radiography plays a major role in making a diagnosis, but the definitive diagnosis is based on genetic testing [3]. However, the clinical diagnosis of PPRD can be achieved at an early stage of the disease by gathering the patient’s family history, clinical findings, normal inflammatory markers, and characteristic radiographic findings [5]. Treatment is mainly symptomatic. Physical therapy may be relied upon, and surgery may be necessary in advanced stages [2–4]. The patient should see a specialist in skeletal dysplasia annually to monitor for orthopedic complications and secondary joint disease [1].

This paper has studied the possibility of scoliosis being an early sign of PPRD, and this association has never discussed before.

Case presentation

An 11-year-old Syrian Arab girl was admitted to the rheumatology section of The Children’s Hospital in Damascus due to progressive limitation of movement in multiple joints.

The past medical history was unremarkable. The patient has two healthy siblings without any family history of inherited or genetic diseases.

When asked for details, The parents reported several complaints, including early lumbar scoliosis observed at 7 months old, which did not improve as she grew older. They also mentioned enlarged joints with limited movement, generalized movement limitations and stiffness, darkening of the skin, and progressive dysphagia.

The parents noticed the scoliosis when the patient was 7 months old and sought help from multiple doctors who believed it was congenital scoliosis that would resolve with growth. However, the scoliosis persisted until she turned 2 years old without any improvement. At that time, symptoms of joint stiffness started to appear. X-ray images of the spine, wrists, knees, and hips were taken. Unfortunately, only the spine image (Fig. 1) was available, which showed a leftward lumbar scoliosis centered at the third lumbar vertebra (L3). The doctors were unable to make a definitive diagnosis and recommended follow-up X-ray imaging of the spine and other joints along with clinical examination to assess the progression of joint stiffness. Subsequent X-ray images revealed a relative decrease in bone density in the knees and elbows (Fig. 2). The hip X-ray showed bilateral flattening in the epiphyses of the femoral heads (Fig. 3).

Fig. 1.

Spine image at the age of 2 years showing scoliosis at the level of the lumbar spine with apex towards the left (arrow)

Fig. 2.

X-ray images of the right and left knees (A) and elbows (B) showing a decrease in bone density

Fig. 3.

Hip X-ray images. A At the age of 4 years, B at the age of 6 years, and C at the age of 12 years. These photos show bilateral flattening in the epiphysis of femoral heads (arrows). The arrows indicate bilateral flattening in the epiphysis of femoral heads

After years of following up with many doctors, the parents decided to come to the Children’s Hospital in Damascus for further evaluation.

Clinical findings

During the clinical examination, it was discovered that the patient had left lumbar scoliosis and enlargements of the distal and proximal ends of the arm and forearm bones. There was limited movement at the joints of the shoulders, elbows, wrists, metacarpophalanial joints (MCPs), proximal interphalangeal joints (PIPs), distal interphalangeal joints (DIPs), knees, and others. The wrists showed cubitus valgus deformity, while the MCPs, DIPs, and PIPs were mildly fixed in a flexion position with limited ability to extend passively or actively (Fig. 4).

Fig. 4.

The hands of the patient with metacarpophalanial joints, proximal interphalangeal joints, and distal interphalangeal joints in a mild fixed flexion position. The wrists exhibit a cubitus valgus deformity

Diagnostic assessment

New X-ray images were taken to review the previously taken ones. The images revealed a progressive decrease in bone density in multiple bones. Additionally, there was no regression of scoliosis. Furthermore, changes in the shapes of the vertebrae were observed on the spine images (Fig. 5).

Fig. 5.

Anterior-posterior image of the abdomen and chest, highlighting changes in vertebral shapes, particularly in the lumbar and thoracic spines (indicated by arrows)

Laboratory tests, including complete blood count (CBC), urinalysis, and liver function tests (LFTs), showed no significant abnormalities. Urea, creatinine, and C-reactive protein (CRP) levels were within normal ranges for the patient’s age. However, there was a slight increase in erythrocyte sedimentation rate (ESR). Moreover, alkaline phosphatase levels were 480 IU/L. To help rule out certain differential diagnoses such as systemic lopus erthmatous (SLE), scleroderma, and juvenile idiopathic arthritis, antibody screening was performed. The results showed negative antinuclear antibodies (ANA), negative rheumatoid factor and anti-cyclic citrullinated peptide (CCP), negative anti-Scl-70 antibodies, and negative anticentromere B antibodies.

Based on all the previous information and the clinical examination findings, a diagnosis of progressive pseudorheumatoid dysplasia was reached.

Therapeutic intervention

The patient was discharged with recommendations to take nonsteroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen, if pain developed and to undergo physical therapy. The patient was advised to consult orthopedic surgeons if severe inability to move occurs.

Follow-up and outcomes

The patient was followed up for 6 months, during which they demonstrated total commitment to physiotherapy. However, only minimal improvement was observed in the hips, shoulders, and spine. X-ray images were used to assess the progression of the disease in the bones, but no significant changes were observed.

Discussion

PPRD is an autosomal recessive disorder and is the result of a mutation in the WISP-3 gene. This mutation affects the formation of collagen II, which is an essential component of many connective tissues, including cartilage [3]. Patients are born healthy, and the disease manifests between the ages of 3 and 8 with progressive limitation of movement in many joints. The situation deteriorates over the years [2]. The first affected joints are usually the interphalangeal joints [1]. However, a cohort study with 44 included patients concluded that genu varum deformity can be recognized earlier than swelling of the interphalangeal joints, which can help suspect an earlier diagnosis [6]. The disease progresses throughout life and affects many other joints such as hips, knees, and elbows. Moreover, about half of the patients show short stature [1]. Classic findings on clinical examination include limited movement in small and large joints with inflammatory markers within normal ranges. This helps distinguish PPRD from its mimic disorder juvenile idiopathic arthritis (JIA) [2, 4]. Radiographic studies are essential for confirming the diagnosis. X-ray imaging of the joints may reveal broadening of epiphyses and metaphyses, narrowing joint space, and irregular articular surfaces—all similar to findings in JIA. Spine X-rays may show platyspondyly and short pedicles with Scheuermann-like irregular endplates [7]. However, studies have reported that spine involvement occurs after other joint involvement during adolescence and manifests with scoliosis and/or kyphosis [1, 8]. The cervical spine is usually spared from involvement [1]. Diagnosis of PPRD can be established by typical radiologic findings. The joint-forming bones appear large and prominent with metaphyseal enlargement mimicking joint swelling [9]. However, the definitive diagnosis is based on genetic analysis [1, 6]. In this case, we relied on excluding other differential diagnosis to diagnose PPRD, as genetical analysis was not available. PPRD is an incurable disease and treatment remains supportive [1, 4, 10].

In this paper, we introduce a 12-year-old girl who complains of limited ability to move at many joints. The patient has been to many doctors since she was 2 years old, and all of them recommended follow-up without considering PPRD as a differential diagnosis. Honestly, they were not able to suspect a specific diagnosis. When the patient was admitted this time, careful review of previous images of the hips, spine, and hands revealed multiple changes including flattened femoral heads with short femoral necks, as well as enlargement of the epiphysis at the elbow and wrist bilaterally. Along with laboratory studies, clinical examination excluded JIA, scleroderma, and other possible connective tissue disorders. PPRD was diagnosed on the basis of clinical findings and the elimination of other potential diagnoses. Although genetic analysis was unavailable owing to limited resources in the country, the clinical presentation and constellation of symptoms in this patient led to the diagnosis. A review of literature revealed cases of the disease that were diagnosed clinically on the basis of symptoms similar to those reported in our case [10, 11]. What is worth mentioning about this case is the presence of scoliosis at the age of 7 months, which was considered congenital scoliosis. Follow-up with spine imaging did not show any regression for this scoliosis over the years. Moreover, the patient started to develop other clinical and radiological features of PPRD, which include progressive decrease in bone density at many bones, bilateral flattening in the epiphyses of the femoral heads, broadening of epiphyses and metaphysis, narrowing joint space, and irregular articular surfaces. Additionally, changes in vertebral shapes support the diagnosis. However, due to the rarity of the disease and poor knowledge about it, the diagnosis was delayed, and the patient lost the opportunity to receive appropriate physical rehabilitation at an earlier stage, which might have helped slow down symptom deterioration.

In the previously published studies, scoliosis was considered a late manifestation of PPRD. However, a study by Montané et al. suggested that scoliosis could be an early manifestation, appearing at the age of 13 years [8]. Previous studies have reported that many cases of PPRD are underdiagnosed owing to the rarity of the disease, lack of knowledge, and its overlap with JIA [2, 4, 10].

Conclusion

This case report aims to guide future studies in determining if there is a possible link between scoliosis in the first years of life and PPRD. Therefore, can we conclude that there is a correlation? Should PPRD be considered as a differential diagnosis for scoliosis in the early years? Previous studies were unable to answer this question; however, future studies will hopefully provide more insight.

Abbreviations

PPRD

Progressive pseudorheumatoid dysplasia

JIA

Juvenile idiopathic arthritis

MCPs

Metacarpophalanial joints

PIPs

Proximal interphalangeal joints

DIPs

Distal interphalangeal joints

CBC

Complete blood count

LFTs

Liver function tests

CRP

C-reactive protein

ESR

Erythrocyte sedimentation rate

SLE

Systemic lopus erthmatous

ANA

Antinuclear antibodies

CCP

Cyclic citrullinated peptide

NSAIDs

Nonsteroidal anti-inflammatory drugs

Author contributions

All authors participated in writing and reviewing the whole paper.

Funding

We received no funding in any form.

Availability of data and materials

The datasets used during the current study are available from the corresponding author on reasonable request.

Declarations

Ethics approval and consent to participate

Ethical approval was taken from Faculty of Medicine at Damascus University.

Consent for publication

Written informed consent was obtained from the patient’s legal guardian for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.

Competing interests

The authors declare that they have no competing interests.