Pseudo-rheumatic manifestations of limping: Camptodactyly–arthropathy–coxa vara–pericarditis syndrome: Single case report and review of the literature

Abstract

Camptodactyly–arthropathy–coxa vara–pericarditis (CACP) syndrome is a rare genetic disease characterized by tetrad camptodactyly, noninflammatory arthropathy, coxa vara deformity, and pericardial effusion. Arthropathy typically affects large joints and presents with joint swelling in the absence of other signs of inflammation. We described the case of a girl affected by CACP syndrome caused by a novel compound heterozygous variant in proteoglycan 4 gene (c.2831_2832insT; c.3892C > T) and associated with temporomandibular involvement. The patient received treatment with intra-articular hyaluronic acid injections, which presented rapid but transient improvements of pain and range of motion. A literature review of previously reported CACP patients has been performed. Of the patients. 69.2% (101 out of 146) were Middle Eastern, and 65.7% (96) were consanguineous. The median age of onset was 24 months (interquartile range of 12–36 months), and median age of diagnosis was 96 months (interquartile range of 48–156 months). Arthropathy was always present, mainly involving hips (95.2%), knees (92.4%), wrists (87.7%), elbows (79.5%), and ankles (57.5%). Camptodactyly and pericardial effusion were described, respectively, in 97.3% (142) and 15.1% (22) of patients. The main radiological findings were coxa vara (95.2%), femoral changes (64.4%), intraosseus cysts (14.4%), and bone erosion (5%). Of the patients, 32.9% (48) had received a previous juvenile idiopathic arthritis diagnosis. CACP syndrome can be easily misdiagnosed with juvenile idiopathic arthritis. A prolonged lack of response to immunosuppressive therapy associated with typical clinical and radiological features should prompt consideration of this rare syndrome.

PRG4 deficiency in mice alters skeletal structure, mechanics, and calvarial osteoclastogenesis, and rhPRG4 inhibits in vitro osteoclastogenesis

“…In combination with the greater GT calvarial osteoclast numbers, these findings indicate that the bone loss in PRG4 deficient mice is likely not driven by inflammation, but rather through some other mechanism. This is consistent with human patients with CACP, in which the absence of overt clinical and biochemical signs of inflammation facilitate its diagnostic differentiation from juvenile rheumatoid arthritis, and yet 36% of CACP patients have osteoporosis 16 . Moreover, this demonstrates the Prg4 GT mouse studied here replicates the phenotype of the human disease CACP.…”

“…This is consistent with human patients with CACP, in which the absence of overt clinical and biochemical signs of inflammation facilitate its diagnostic differentiation from juvenile rheumatoid arthritis, and yet 36% of CACP patients have osteoporosis. 16 Moreover, this demonstrates the Prg4 GT mouse studied here replicates the phenotype of the human disease CACP.…”

“…CACP is a rare disease, estimated to affect about 7000 people worldwide 14 . However, in many cases, CACP can mimic more common diseases such as juvenile idiopathic arthritis (JIA), 15,16 an autoimmune disease characterized by systemic inflammation that leads to issues such as pain, swelling, joint stiffness, and bone loss 17 . Even though CACP and JIA can have similar symptoms, including bone loss, they have different underlying causes 18 .…”