999 Camptodactyly- arthropathy-coxa vara- pericarditis (CACP) syndrome in two Caucasian siblings- a case report

Background CACP (Camptodactyly arthropathy coxa -vara pericarditis syndrome) is characterized by early onset non- inflammatory arthropathy with synovial hyperplasia, congenital or early onset camptodactyly, progressive coxa vara deformity and non- inflammatory pleural or pericardial effusion. Objectives Non- responsive JIA -think of alternate diagnoses Methods Electronic case records was used to collect data Results 7-year-old Caucasian boy and his 4-year-old sister were recently diagnosed with CACP syndrome. 7-year-old brother had history of joint swelling in early infancy, but was referred at 3 years of age. He presented with knees, ankles, wrists swelling. He was diagnosed with juvenile idiopathic arthritis (JIA). Despite significant treatment with steroid joint injections, methotrexate and biologics, there was no improvement. As was the case with his younger sibling, she had presented with flexion contracture of the index fingers of both hands at early infancy which was initially thought to be trigger finger. Following this she presented with bilateral knee and wrist swelling. Ultrasound of knees showed synovial thickening and was diagnosed with JIA at 2 years of age. Despite significant immune-suppression treatment, including intra-articular steroid injections, methotrexate and biologics there was no improvement. Mutation in the PRG4 gene was detected in both. Parents are awaiting genetic testing. Discussion CACP syndrome is a rare condition which causes non-inflammatory joint swelling (arthropathy), permanent bending of fingers (Camptodactyly) and sometimes changes in hip joints resulting in shortened legs and possible limb (coxa -vara). It can also cause fluid in the pericardium or pleura. Autosomal recessive mode of inheritance Camptodactyly in CACP is usually bi-lateral & congenital, but in some cases, it develops in early childhood. The degree of contracture need not be equal in both & the deformity may progress or not improve. Arthropathy principally involves large joint such as elbows, hips, knees and ankles. Histopathologic analysis of synovial tissue reveals pronounced hyperplasia of synovium without evidence of inflammatory cell infiltration or vasculitis, while synovial hyperplasia in rheumatoid arthritis is associated with chronic inflammation. Non-inflammatory pericarditis is reported in 30% of CACP, this may be mild and self-limited. The presence of coxa vara is noted in 50% of published CACP cases. Diagnosis is based on clinical findings and confirmed by genetics. Patients with CACP have mutations on the gene PRG4 which encodes the secreted protein called lubricin. Lubricin is a protein that lubricates joints and works as a lubricant between the two layers of the pleura and pericardium. CACP is often mis-diagnosed as JIA because both present with joint swelling. At present there is no cure or specific treatment for CACP. Much of the research to date is investigating mechanical benefits of lubricin allowing lubrication of joints. Treatment options are physiotherapy and analgesia focusing on relieving symptoms of the disease. Conclusions CACP mimics JIA due to similar presentation hence causing a delay in diagnosis & probably unnecessary treatment with anti-rheumatic drugs including biologics. Although it is very rare condition, if there is no or poor response to various immuno-suppression treatment in patients with JIA, we recommend looking into non -inflammatory arthropathy and possible CACP.