ACRT Journal

Introduction

Progressive Pseudorheumatoid dysplasia (PPRD) is a rare skeletal dysplasia characterized by predominant involvement of articular cartilage with progressive joint stiffness and enlargement in the absence of inflammation [1]. It is inherited in an autosomal recessive pattern and caused by mutations occurring in the WNT1-inducible signalling pathway protein 3 gene. Even though this illness has a significant arthropathy, pain is not one of its main presenting characteristics. The diagnosis of PPRD is established in a proband with characteristic radiographic features and/or identification of biallelic pathogenic variants in CCN6 on molecular genetic testing [1]. WISP3 is essential in maintaining cartilage integrity by regulating the expression of type II collagen and aggrecan in chondrocytes [2]. It is believed that PPRD is more prevalent in Turkey and Middle East population although the incidence is unknown. In UK, the prevalence is estimated to be 1 per million [3]. The clinical manifestations of juvenile idiopathic arthritis are similar to those of progressive pseudorheumatoid dysplasia. Most often, patients with progressing pseudorheumatoid dysplasia are misdiagnosed as having juvenile idiopathic arthritis.Herein, we present a case of a 15-year-old boy who was earlier diagnosed with poly-articular Juvenile Idiopathic arthritis and subsequently diagnosed with PPRD with characteristic signs and symptoms development.

Case Presentation

A 15-year-old Egyptian boy who was referred for admission from the rheumatology clinic with a previously diagnosis of JIA. His development and growth were normal during his first few years of life. However, at the age of four he was noticed to have an abnormal gait, he was evaluated in his home country and given vitamin D and calcium supplements in addition to occasional ibuprofen for pain relief. The assessment revealed no cause for concern. Then he started developing swelling in his fingers, elbows, and knees, he was assessed by a pediatric rheumatologist who diagnosed the child with JIA and prescribed steroids and methotrexate, but with no significant improvement.

Over time, his condition worsened, resulting in increased joint restrictions, discomfort, and stiffness in the morning. He began to have deteriorated lower back, hip, and knee pain a few months ago. This pain was accompanied by morning stiffness lasting more than thirty minutes. He eventually lost the ability to move, including the ability to stand or walk, and he developed hip flexion, which prevented him from extending his hip because of pain and limitation. Due to the advancement of his condition, he has not attended school for the past two years. He is now confined to his chair all the time and needs assistance with everyday tasks. He is underweight. He has no fever, rash, headaches, eye symptoms, mouth ulcer, chest pain, breathing issues, gastrointestinal symptoms, hair loss, or fatigue.

He was born to first-degree healthy cousins, and has 4 healthy older siblings. He has two maternal cousins with similar complaints who have been diagnosed with Rheumatoid Arthritis but are not receiving any medication other than calcium and vitamin D. No history of any other autoimmune diseases.

Physical Examination

He looked generally well with normal vitals. Growth chart showed he is underweight with a weight of 35kg and has short stature with his height being 115cm, both below the third centile. His musculoskeletal assessment revealed marked swelling of proximal and distal interphalangeal joints bilaterally (Figure 1) with mild tenderness, he has significant restrictions in both wrists, both elbows, and in both shoulders. Lower limb examination showed restriction of movement and stiffness of the hips and knees, there was no signs of inflammation in both joints (Figure 2). Upon assessing the gait of the patient, he had significant kyphoscoliosis (Figure 3). His rest of other systems examination were unremarkable.

Investigations

Erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), Rheumatoid factor (RF), anti-citrullinated peptides antibodies (Anti-CCP), anti-double stranded DNA (anti-dsDNA), antinuclear antibody (ANA) and HLA-B27 typing all negative and are not suggestive of inflammatory arthritis. Workup up for extra-articular involvement done including ophthalmic exams and ECHO were all unremarkable. Radiological findings showed significant changes. There was marked loss of joint space affecting multiple joints in the body with variable degree of involvement. There was involvement of both small and large joints. There was no signs of active arthritis is these joints, and most of the changes was representing chronic changes, and complications of chronic inflammation (Figures 4-7). Other imaging modality was done to assess the degree of joints involvement. The significant finding was the spine involvement. MRI of the spine showed changes that is unusual to be seen in common causes of arthritis in pediatrics such as JIA, there was spine deformity and changes involving the vertebra (Figures 8,9). Based on history, clinical and imaging findings, laboratory results, the diagnosis Progressive pseudorheumatoid dysplasia (PPRD) was suspected and Whole exome sequencing sent that revealed: A homozygous likely pathogenic variant was identified in the CCN6 gene, which confirmed the diagnosis. During his stay he started on Zoledronic acid for osteopenia, he was undergoing daily physiotherapy and occupational therapy.The patient’s joint pain was alleviated and joint motion improvement was obvious after treatment and he discharged home on a walking frame which have improved his range of motion and his pain.

Figure 1: Swelling of the proximal and Distal interphalangeal Joints with restriction of movement.

Figure 2: Legs remained flexed, with significant restriction on the hips and knees.

Figure 3: Spine has kyphoscoliosis.

Figure 4: AP radiograph of the left hand shows marked loss of joint space affecting the radiocarpal, inter-carpal and inter-phalangeal joints.

Figure 5: AP radiograph of both elbows showing loss of joint space, osteophyte formation.