The Egyptian Rheumatologist xxx (2016) xxx–xxx

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The Egyptian Rheumatologist

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Case reports

Spinal involvement in Camptodactyly Arthropathy Coxa-varaPericarditis (CACP) syndrome in two Yemeni sisters

http://dx.doi.org/10.1016/j.ejr.2016.10.0011110-1164/� 2016 Egyptian Society of Rheumatic Diseases. Publishing services provided by Elsevier B.V.This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Peer review under responsibility of Egyptian Society of Rheumatic Diseases.⇑ Corresponding author at: Rheumatology and Rehabilitation Department,

Faculty of Medicine, Cairo University, Cairo, Egypt.E-mail addresses: yasseremad68@yahoo.com, yasseremad68@gmail.com

(Y. Emad).

Please cite this article in press as: Emad Y et al. Spinal involvement in Camptodactyly Arthropathy Coxa-vara Pericarditis (CACP) syndrome in twosisters. The Egyptian Rheumatologist (2016), http://dx.doi.org/10.1016/j.ejr.2016.10.001

Yasser Emad a,b,⇑, Yasser Ragab c,d, Osama Ibrahim i, Maher Khalifa e, Ahmed Dawood f,g, Johannes J. Rasker h

aRheumatology and Rehabilitation Department, Faculty of Medicine, Cairo University, Cairo, EgyptbRheumatology and Rehabilitation Department, Dr. Erfan and Bagedo General Hospital, Jeddah, Saudi ArabiacRadiology Department, Faculty of Medicine, Cairo University, Cairo, EgyptdRadiology Department, Dr. Erfan and Bagedo General Hospital, Jeddah, Saudi Arabiae Pediatric Department, Dr. Erfan and Bagedo General Hospital, Jeddah, Saudi ArabiafCardiology Department, National Heart Institute, Cairo, EgyptgCardiology Department, Dr. Erfan and Bagedo General Hospital, Jeddah, Saudi ArabiahDepartment of Psychology Health and Technology, Faculty of Behavioral Sciences, University of Twente, Enschede, The NetherlandsiMorecambe Bay University Hospitals Lancaster, Lancashire, UK

a r t i c l e i n f o

Article history:Received 23 September 2016Accepted 6 October 2016Available online xxxx

Keywords:Camptodactyly Arthropathy Coxa-varaPericarditis (CACP) syndromeAxial joints affectionFacet joint arthropathyFacet joint ankylosis

a b s t r a c t

Aim of the work: The objective of this clinical report is to describe the detailed magnetic resonance imag-ing (MRI) findings of the spine, knee and hip joints in two young sisters with Camptodactyly ArthropathyCoxa-vara Pericarditis (CACP) syndrome.Cases report: In two young sisters, both had normal levels of inflammatory markers and typical featuresof the CACP syndrome with camptodactyly, symmetric joint swelling of both hand joints, knees, anklesand both feet. The affected joints were not tender on palpation with no overlying redness or hotness.Coxa vara on plain X-ray and all cases have evidence of pericarditis. The MRI studies showed the typicalrim pattern enhancement of the synovial membrane in the knee and hip joints in both, with no evidenceof pannus formation, yet a sizable amount of joint effusion. Both had protrusio acetabuli and one had aunilateral synovial cyst of the hip. MRI studies of the lumbar spine showed evidence of facet jointarthropathy and facet joint effusion, a synovial cyst in both cases and synovial enhancement in post-contrast images with no associated facet joint ankylosis.Conclusion: The findings of the two cases confirm the possible axial affection in the CACP syndrome in theform of facet joint disease as a new finding in this rare syndrome. Spinal involvement should be screenedin all cases, as it may have consequences for diagnosis and treatment.� 2016 Egyptian Society of Rheumatic Diseases. Publishing services provided by Elsevier B.V. This is anopen access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

1. Introduction

The Camptodactyly Arthropathy Coxa-vara Pericarditis (CACP)syndrome is an autosomal recessive condition characterized bythe association of congenital or early-onset camptodactyly andnoninflammatory poly-arthropathy. The disease gene has beenassigned to human chromosome region 1q25-q31, and truncatingmutations have been identified in the megakaryocyte stimulatingfactor gene [1]. This gene encodes for ‘‘proteoglycan-4” (PRG-4),which is a surface lubricant for joints and tendons [2]. Previous

molecular studies described the identification of 15 mutationsassociated with CACP syndrome and the majority of them werefound in Arabian families [3–5], in one Pakistani family segregatingCACP syndrome [6] and more recently a European cohort that com-prised 13 patients, and identified 5 novel mutations [7].

In all previous reports, non-inflammatory pattern of arthropa-thy involving the peripheral joints with typical coxa vara deformitywas described [8–10].

CACP syndrome has distinctive radiological and histological fea-tures, which are important to recognize since it may clinicallymimic juvenile idiopathic arthritis (JIA) at first presentation [2].We recently described the first case in the literature with CACPsyndrome and spinal involvement [11]. The magnetic resonanceimaging (MRI) and computed tomography (CT) showed evidenceof bilateral facet joint arthropathy at L5/S1 level and bony ankylo-sis together with bony ankylosis and enhancement pattern of the

Yemeni

2 Y. Emad et al. / The Egyptian Rheumatologist xxx (2016) xxx–xxx

facet synovial lining in post gadolinium enhanced MRI. The aims ofthe current report is to present the pattern of axial spinal affectionas well as enhanced MRI features of hips and knees in two newcases with this rare syndrome and to review the literature regard-ing MRI findings in CACP syndrome.

2. Case reports

Two female cases in one Yemeni family with CACP syndromewere included. They were 3 and 5 years of age and shared the sametypical features of the syndrome with non inflammatory poly-arthropathy that involved wrist, elbow, knee and ankle joints inbilateral and symmetrical patterns with associated sizable synovialeffusion to variable degrees. Both have coxa vara of both hips caus-ing a waddling gait pattern, congenital camptodactyly and peri-carditis. Routine laboratory investigations were carried outincluding the erythrocyte sedimentation rate (ESR) 1st hour, C-reactive protein (CRP) levels and autoimmune profile in the formof rheumatoid factor (RF), anti-cyclic citrullinated peptide (anti-CCP) antibodies and anti-nuclear antibody (ANA). Echocardiogra-phy was performed to investigate the pattern and the degree ofassociated pericarditis. In both contrast enhanced MRI studieswere performed for lumbar spine, hip- and knee joints. All MRIstudies were analyzed by two experienced musculoskeletal radiol-ogist (YR) and (OI). The study was approved by the local ethicscommittee of Dr. Erfan and Bagedo General Hospital and thepatients’ guardians gave their consent to be included in the casereport.

Laboratory findings showed typically normal ESR 1st hour, neg-ative CRP levels, negative RF, negative anti-CCP antibodies andANA. Echocardiography showed evidence of pericarditis in both,with minimal pericardial effusion in one case and moderate peri-cardial effusion in the other with associated thickened pericardium(Fig. 1).

MRI of the lumbar spine showed facet joint (axial) involvement.The MRI of the lumbar spine featured evidence of facet joint effu-sion and synovial enhancement of facet joints in post contrastimages in both cases and synovial cysts (Figs. 2c, d & 3e, respec-tively) with no associated facet joint bony ankylosis.

Figure 1. Echocardiography showing pericar

Please cite this article in press as: Emad Y et al. Spinal involvement in Camptodsisters. The Egyptian Rheumatologist (2016), http://dx.doi.org/10.1016/j.ejr.20

Contrast enhanced MRI in knee and hip joints showed evidenceof synovial enhancement in both with no evidence of hypertrophyof the synovial membrane lining or pannus formation, yet sizableknee and hip effusion was observed in both cases (Figs. 2a, b, f–hand 3a–d respectively). In both cases no evidence of cartilaginousor bone erosions were seen and joint space was maintained. Inone case a synovial cyst in the hip joint was observed (Fig. 2g)and both cases have bilateral protrusio acetabuli.

3. Discussion

In our first report [11] we assumed that the facet joint involve-ment in the CACP syndrome is disease related for many reasons:the most important being that it can be expected that facet jointsare synovial lined joints and will also be involved in CACP syn-drome as it primarily affects synovial lined joints. In post-contrast MR images we found enhancement of the synovial liningof the involved facet joints reflecting chronic synovial pathologythat eventually may lead to bony ankylosis in the facet joints[11]. The facet joints were bilaterally affected suggesting a diseaserelated process, together with intact disco-vertebral junction, therewas no other argument to suggest other pathology that can lead tofacet joint arthropathy (e.g. spondyloepiphyseal dysphasia, septicarthritis of the facet joints and spondylodiscitis) and there wereno paravertebral masses or other destructive and/or lytic lesions[11].

In the new two cases that belong to one family, enhanced MRIshowed facet joint effusion and enhancement of the synovial liningwhich again document and support our early findings regarding apossible spinal affection in this syndrome. These new findingsshould be taken into consideration while evaluating newly diag-nosed cases with CACP syndrome.

Regarding the knee joint our MRI findings are consistent withthose previously reported by El-Garf et al. [10] who investigated10 Egyptian patients with CACP syndrome, the authors observeda rim pattern of synovial enhancement. Likewise in our two stud-ied cases we did not observe any evidence of bone or cartilaginouserosions and joint spaces were perfectly preserved. Additionallysizable knee effusion was a prominent MRI sign with no tendencyfor synovial hypertrophy or any tendency for synovial proliferation

dial effusion and thickened pericardium.

actyly Arthropathy Coxa-vara Pericarditis (CACP) syndrome in two Yemeni16.10.001

Figure 2. (a) Sagittal T2WI showing sizable knee effusion (white arrow); (b) Sagittal T1WI Fat Sat showing synovial enhancement (rim pattern) without synovial membranethickening or proliferation (white arrow); (c, d, e) Sagittal T1 post contrast Fat Sat of the lumbar spine showing synovial cysts (white arrows) and enhancement related to L4/L5 and L5/S1 facet joints; (f,g,h) Coronal T1WI Fat Sat post contrast of both hips showing bilateral sizable joint effusion without synovial proliferation and intraosseoussynovial cyst (white arrow), also bilateral coxa-vara and protrusio acetabuli.

Figure 3. (a, b) Coronal T2WI for hip and knee joints showing bilateral large joint effusion without evidence of synovial proliferations (white arrow); (c, d) T1WI post contrastFat Sat for hip and knee joints showing synovial enhancement without thickening (white arrows) with no evidence of cartilaginous or bone erosions and maintained jointspace; (e, f) Sagittal T2WI Fat Sat of lumbar spine showing synovial cysts related to L4/L5 and L5/S1 facet joints (white arrows).

Y. Emad et al. / The Egyptian Rheumatologist xxx (2016) xxx–xxx 3

Please cite this article in press as: Emad Y et al. Spinal involvement in Camptodactyly Arthropathy Coxa-vara Pericarditis (CACP) syndrome in two Yemenisisters. The Egyptian Rheumatologist (2016), http://dx.doi.org/10.1016/j.ejr.2016.10.001

4 Y. Emad et al. / The Egyptian Rheumatologist xxx (2016) xxx–xxx

on post contrast MR images. Especially protrusio acetabuli was aprominent MRI feature and synovial cysts were also observed inboth cases. These MRI features match well with the symmetricnon inflammatory pattern of joint arthropathy observed in CACPsyndrome bases on clinical findings of affected joints which arenot tender on palpation and with no overlying redness or hotness.The normal ESR and CRP levels again document the non inflamma-tory nature of the disease.

A synovial biopsy was not performed for these two sisters. Inthe study of El-Garf et al. [10] synovial histopathology revealednoninflammatory synovial hyperplasia in the six obtained out of10 cases and described the presence of multinucleated giant cellsin four of them. In another study [12], synovial biopsy in 3 casesreported the presence of macrophage.

Lubricin, a glycoprotein specifically synthesized by chondro-cytes located at the surface of articular cartilage, has been shownto provide boundary lubrication of congruent articular surfacesunder conditions of high contact pressure and near zero slidingspeed. Given the fact that mutations in the gene proteoglycan 4(PRG4), affecting lubricin production, which is an essential proteinfor joint function and lubrication of these surfaces is critical to nor-mal joint function. Moreover, mutations or lacking of lubricin genehave been shown to link to the joint disease such as CACP syn-drome, synovial hyperplasia and failure of joint function, suggest-ing an important role of lubricin in the pathogenesis of these jointdisease [13].

In conclusion, in this report we documented our early findingsand explained possible facet joint disease in CACP syndrome. Axialaffection in CACP syndrome in the form of facet joint disease is anew finding in this rare syndrome and should be taken into consid-eration in further studies to delineate the exact prevalence and itsassociation with this rare syndrome.

Conflicts of interest

None.

Please cite this article in press as: Emad Y et al. Spinal involvement in Camptodsisters. The Egyptian Rheumatologist (2016), http://dx.doi.org/10.1016/j.ejr.20

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