Spondyloepiphyseal dysplasia is a mimicker of arthritis

Musculoskeletal involvement in children is often challenging, with a wide range of benign conditions, such as growing pain, to severe systemic diseases. Spondylo-epiphyseal dysplasia (SED) is an autosomal recessive disease of the skeletal system that often mimics juvenile idiopathic arthritis (JIA) with no response to anti-rheumatic therapy.

Case - A young male, 22 years of age, presented with a history of pain in his upper and lower back and multiple small and large joints since five years of age. He denied any morning stiffness or increased nocturnal pain. Previously, he was treated outside as juvenile idiopathic arthritis with methotrexate, sulfasalazine and injection Adalimumab. However, his mother denied any symptomatic improvement of his pain. On examination, his growth was stunted with significant kyphoscoliosis. (Figure 1 ) He had an antalgic gait with exaggerated lumbar lordosis. He had mild tenderness in both hips, knees and ankles with flexion contracture and bony swelling at bilateral proximal & distal interphalangeal joints (PIP and DIP), referred to as camptodactyly. (Figure 2 ) His cervical and lumbar movement was severely restricted, with bilateral hip movement restricted. Laboratory investigation showed normal ESR CRP. Rheumatoid factor was low titre positive, anti-CCP antibody and HLA-B27 by PCR were negative. His skeletal radiographic images showed platyspondyly in the thoracolumbar spine, epiphyseal widening in MCP and IP joints with ovoid carpal bones (Figure 3), platyspondyly in the thoracolumbar spine (Figure 4) , hip joint sclerosis . (Figure 5 ) His diagnosis was reconsidered as spondyloepiphyseal dysplasia (SED) . He was started with extensive physiotherapy and symptomatic pain relief treatment and noticed improvement in his pain and quality of life.

Brief discussion - SED predominantly involves articular cartilage, which results in joint stiffness and epiphyseal enlargement. Typically starting at 2-8 years of age, they manifest with pain, stiffness and swelling of extremity joints. (1) On examination, the swelling is predominantly bony without any evidence of inflammation. Over time, the large joints and the spine get involved, causing significant joint contractures, gait abnormality, kyphoscoliosis, abnormal posture and poor quality of life. There are reported cases where SED have been misdiagnosed as JIA with no response to immunomodulatory treatment. (1,2) SED's radiological features differ from JIA, with platyspondyly being an early finding in the skeletal image, epiphyseal enlargement, and lack of destructive joint erosions. Though SED is considered a rare entity, one large study by Dalal et al. (3) reported 35 cases of SED from 25 unrelated families with 11 different homozygous mutations and one instance of compound heterozygosity in the WISP3 gene. It proves that this entity is not very uncommon in India.

1. Exploring Deforming J oint Pain : Understanding More Than Just Arthritis ! Title TITLE

2. Introduction A 20-year-old male came to Rheumatology OPD with a waddling gait. Chief complaints – 1. Pain in multiple small and large joints since 5 years of age 2. Pain in the back and neck for the same duration He also had significant hip pain with difficulty walking. Presently denied any morning stiffness or nocturnal pain. He could not recall the character of pain in the past.

3. Examination General survey Short stature Exaggerated lumbar lordosis and thoracic kyphosis No facial deformity Muskulo-skeletal examination – Gait – broad-based with an antalgic gait Inspection – Flexion deformity in bilateral small joints of hand (camptodactyly), genu varus, swelling in small joints including DIP. Palpation – Tenderness in all joints, including hip, lumbar and cervical spine Movement – Both hip movements restricted Restricted forward flexion, neck movement and chest expansion.

4. Past Treatment history Diagnosed with Juvenile idiopathic arthritis (JIA) with enthesitis-related arthritis in past Treated with sulfasalazine and etanercept injection for long duration However, he denied any significant improvement in pain. Currently, he is concerned about progressive deformity and walking difficulty due to hip pain.

5. Investigation Laboratory parameters Value Complete hemogram Hb – 13 mg , TLC – 8500 (N60 L25) , platelet-2.3 lakh ESR 13 mm Hg (normal, 10-20 mm HG) CRP 5 ( < 5 cut off ) Rheumatoid factor 20 (cut off 15 , by nephelometry) Anti CCP antibody normal HLA – B27 (PCR ) Not detected Detailed conventional radiography of multiple sites was done , images are in the next page .

6. Case Management He was using sulfasalazine for joint pain, which was stopped. He was counselled for hip replacement surgery. He was prescribed calcium and vitamin D supplementation with symptomatic pain relief. He was referred to physiotherapy for physical rehabilitation measures. After a two-month follow-up, he had improved his quality of life with minimal pain .

7. Audience Response Slide 1. What would you do next? A . Whole body bone scan B . MRI image of lumbar spine, SI & hip joint C . Genetic analysis D. No further test, only symptomatic therapy 2. What is the diagnosis? A . Juvenile idiopathic arthritis – Spondyloarthritis (juvenile SpA ) B . Spondylo-epiphyseal dysplasia (SED) C . Metabolic bone disease 3. Which of the following features helps distinguish the most likely cause of this patient’s symptoms ? A . Clinical examination B. Laboratory parameters C. Radiographic Image

8. Case discussion The final diagnosis was spondylo-epiphyseal dysplasia (SED ), also called pseudo-rheumatoid dysplasia. Immunomodulatory therapy has no role as it is not an inflammatory arthritis. Long-term outcomes depend on physical rehabilitation, surgical correction, and the prevention of osteoporosis.

9. Future research plan SED is not rare in India, t ypically starting at 2-8 years of age. Areas of research include - Genetic analysis. Long-term outcome. Role of physical rehabilitation.

10. Take H ome points Spondylo-epiphyseal dysplasia can mimic JIA. A thorough history and clinical examination are warranted. Pediatric history is often difficult to differentiate between inflammatory and non-inflammatory pain, so the examination should be detailed. A mild elevation of inflammatory markers and antibody levels doesn’t always indicate inflammation. Conventional radiography is the old method, but it is still gold. Unnecessary use of immunomodulatory therapy should be avoided .