Delayed-onset progressive pseudorheumatoid dysplasia with secondary synovial chondromatosis

Abstract

A 25-year-old man presented to us with progressive multiple joint pain, enlargement, and restricted movements. X-rays showed platyspondyly, multiple epiphyseal widening, synovial chondromatosis, and decreased bone stock and cortical thickness. Genetic testing showed biallelic pathogenic variants in CCN6 which confirmed the diagnosis of progressive pseudorheumatoid dysplasia. Supportive care, physical therapy, genetic and psychological counselling were provided to the patient.

Background

Progressive pseudorheumatoid dysplasia (PPD) is a rare non-inflammatory musculoskeletal disorder involving multiple joints with a global prevalence of 1/1 000 000. It is an autosomal recessive disease caused by mutations of CCN6 gene. Age of onset is generally 3–8 years.¹ It primarily affects the articular cartilage. Patients generally present with polyarthralgia, joint stiffness, and enlarged joints with no signs of inflammation. Kyphoscoliosis, coxa vara, and genu varum/valgum can be found. Spine involvement in the growing age leads to characteristic short stature.

Synovial chondromatosis (SC) is a rare benign condition with the presence of cartilaginous loose bodies in the synovium of the large joints. It can be primary or secondary to mechanical changes due to arthropathy. It is generally seen in the fourth and fifth decades. Although its reported overall incidence is 1/100 000, the secondary type appears to be more common.² SC has been reported in only six cases of PPD until.^{3 4}

Our patient had a normal height probably due to delayed onset of the disease process. Such atypical presentation of PPD has only been reported in one family before by Marik et al.³ Also, it is important to remember that PPD can easily be mistaken for juvenile idiopathic arthritis (JIA) as both present with similar complaints at a similar age. We also highlight the consanguinity-related risk in autosomal recessive disorders.

Case presentation

A 25-year-old man presented to us with multiple joint enlargement and restricted movements associated with pain. The onset was at the age of 15 years and the symptoms had progressed since. Pain had a dull aching character, increased with activities, and got relieved with salicylates. There was no associated morning stiffness. Patient could not squat and sit cross-legged and had stiffness in all large and small joints of the body. He was a manual labourer by occupation but had left his job 2 years back due to said difficulties. Family history showed a prevalence of consanguineous marriages.

On examination, patient had a height of 178 cm, an arm span of 185 cm, weight of 54.2 kg, and a body mass index of 17.2 kg/m². All joints were enlarged. There was bilateral coxa vara (20° on both sides), bilateral genu valgum (25° on the right side and 15° on the left), bilateral cubitus valgus (20° on both sides) and bilateral manus varus. Range of motion was diminished in all joints. There was reduced spinal flexion and extension with normal spinal curvatures. Chest expansion was 4 cm (figure 1).

Figure 1.

(A) Standing attitude. (B) Complete restriction of spinal extension. (C) Normal spinal curvature. (D) Enlarged knee joints. (E) Enlarged interphalangeal joints with manus varus.

Investigations

Multiple X-rays were done which showed features characteristic of PPD, SC in bilateral shoulder, hip and knee joints, and decreased bone stock and cortical thickness (figure 2).

Figure 2.

(A) Platyspondyly (thoracic more than lumbar) with humping in the lumbar vertebrae. (B) Epiphysial widening of wrist, metacarpophalangeal and interphalangeal joints, intercarpal joint space narrowing and juxta articular osteopenia. (C) Widened and osteoarthritic knee joints with synovial chondromatosis. (D) Dysplastic hips, short and broad femoral necks with pistol-grip deformity. (E) Three-dimensional reconstructed CT images showing synovial chondromatosis and normal sacroiliac joints.

Blood investigations showed raised alkaline phosphatase (287 IU/L, reference range 20–140), low vitamin D3 (15.8 ng/mL, reference range 25–80), and normal serum calcium, serum phosphate, serum parathormone, erythrocyte sedimentation rate and C-reactive protein. Rheumatoid factor and human leukocyte antigen (HLA)B27 were negative.

Dual-energy X-ray absorptiometry (DEXA) scan showed a T-score of −2.8.

After a multidisciplinary meeting, the patient was referred for genetic testing which identified biallelic pathogenic variants in CCN6 and confirmed the diagnosis of PPD.

Treatment

Following discussion between orthopaedics, rheumatology, and endocrinology teams, it was decided that the patient should be offered supportive care. He was started on analgesics, calcium supplements, and bisphosphonates. Physical therapy was started and the need for lifestyle modifications was explained to the patient. Patient was counselled about the nature and progression of the disease. Genetic counselling was done to explain to the patient that the chances of an offspring having the disease would be much higher in case he has a consanguineous marriage and hence was advised against it.

Outcome and follow-up

Patient was followed-up once every 3 months for 1 year. We reassessed the range of motion of his joints, which had remained the same as 1 year back when he first presented to us, and ran routine blood investigations. His vitamin D3 level had normalised. Having been on drugs, physical therapy, and lifestyle modifications, he had become less symptomatic than before. He had changed his job to a less physically demanding one. Understanding the affordability of the patient, we plan to get a subsequent DEXA scan after 1 year.

Discussion

PPD, also known as spondyloepiphysial dysplasia tarda with progressive arthropathy, is a rare genetic disease with a global prevalence of 1/1 000 000. Boys are more commonly affected.^{5 6} Although spinal involvement generally causes stunted growth of the trunk leading to disproportionate short stature, our patient had a normal height probably because the onset of the disease process was late and closer to the closure of his growth plates.

PPD has the characteristic radiological findings of dysplastic epiphyseal widening, platyspondyly with anterior peaking of vertebral bodies, short femoral necks, osteoarthritis, and osteoporosis.⁷ Our patient, in addition to these, also had SC of multiple large joints, a condition with multiple loose chondroid bodies in the joint. We believe that it occurred secondary to osteoarthritis and hence, large joints with large articular surfaces were involved. An association between progressive cartilaginous destruction in PPD and secondary SC can be hypothesised, but it cannot be established as only six cases have been reported until where the two conditions coexisted.

PPD can be mistaken for JIA considering both present with polyarthralgia at a similar age. Lack of inflammatory signs, normal laboratory studies, characteristic radiological features and worsening of symptoms despite being on antirheumatic therapy favour the diagnosis of PPD and thus prevent over-diagnosis and unnecessary treatment of JIA.⁸

Although radiological findings have a high accuracy in diagnosing PPD, a definitive diagnosis can only be established on the basis of CCN6 mutations on molecular genetic testing.

Treatment is mainly supportive. Pain generally responds to non-steroidal anti-inflammatory drugs (NSAIDs). Physical therapy and rehabilitation are encouraged to preserve joint mobility and lifestyle modifications are advised. Psychological counselling is done to make the patient understand the disease process and avoid overzealous treatment. Genetic counselling is done to explain to the patient the chances of an offspring having the same disease. Surgical management in form of arthroplasty and osteotomy, if needed, should be done.^{9 10}

Prognosis depends on the age of onset, progression rate, and severity of the disease, as well as on patient education and rehabilitation.⁸ In our case, the disease had a late onset and although it had progressed leading to restricted movements at all joints, it had not become crippling to the patient. He could do all his daily activities, barring some difficulties. Considering the late onset and relatively slow progression of the disease, we believe that, with lifestyle changes and continued physical therapy, our patient might have a better quality of life.

Patient’s perspective.

I was alright till the age of 15 years when I started having pain in multiple joints. Initially, I saw it as a trivial thing and would take analgesics as per need. But gradually, the symptoms progressed and became debilitating to the extent that I had to leave my job.

The doctors have explained to me the nature of my disease and I understand that this is going to stay with me for life. I have started regular exercise and am starting to make small lifestyle changes, the first of which was getting a western-style commode installed in my house. I go to a Yoga instructor daily. I understand the importance an active lifestyle would hold for me and am trying to do the same. I already feel better than how I felt a year ago.

Learning points.

• Progressive pseudorheumatoid dysplasia (PPD) affects the articular cartilage leading to polyarthralgia and epiphyseal widening.

• A patient with PPD can have normal height in case of delayed onset of the disease process.

• It can be differentiated from juvenile idiopathic arthritis based on an absence of inflammatory signs and normal laboratory reports.

• Being an autosomal recessive disorder, its risk increases with consanguinity.

• Treatment is mainly supportive by physical therapy, psychological and genetic counselling.