Ann Rheum Dis: first published as 10.1136/ard.46.9.709 on 1 September 1987. Downloaded from

Annals of the Rheumatic Diseases, 1987; 46, 709-712

Case report Pseudoseptic pseudogout in progressive pseudorheumatoid of childhood

JOHN D BRADLEY From the Department of Medicine, Rheumatology Division, Indiana University School of Medicine, Indianapolis, USA

SUMMARY Progressive pseudorheumatoid arthritis of childhood is an uncommon of unknown aetiology, which is related to spondyloepiphyseal dysplasia tarda. Previous reports have noted the absence of inflammation in this disease. An adult is described here with this arthropathy, who developed episodic acute inflammatory arthritis that mimicked , but proved to be pseudogout. The relation between pseudogout and progressive pseudorheuma- toid arthritis of childhood is discussed. Key words: spondyloepiphyseal dysplasia.

An adult with 'progressive pseudorheumatoid The patient's arthropathy involves the spine, copyright. arthritis of childhood',i-3 a heritable, non- shoulders, elbows, wrists, hips, knees, ankles, car- inflammatory arthropathy related to spondylo- pal, tarsal, metacarpophalangeal, metatarsopha- epiphyseal dysplasia tarda, developed three epi- langeal, and interphalangeal of the hands and sodes of acute inflammatory arthritis simulating feet. She is of short stature and has a barrel shaped septic arthritis. Crystals consistent with calcium chest. pyrophosphate dihydrate (CPPD) were present in Roentgenographs of the hands, feet, elbows, the synovial fluid and synovial membrane, and shoulders, knees, and hips showed irregularity of chondrocalcinosis was noted radiographically. the subchondral bone, marked distortion of the http://ard.bmj.com/ Pseudogout has not been reported previously in this epiphyseal region, joint space narrowing, and bony arthropathy. We examine here the relationship of proliferation, but no erosions (Fig 1). Platyspondyly chondrocalcinosis and pseudogout with our patient's was notable (Fig. 2), but, unlike the Morquio- joint disease. Brailsford syndrome, the odontoid process was normal and the ribs were not flared. The iliac wings Case report were mildly hypoplastic, but the mid-pelvis was not narrow, unlike the Kneist syndrome. on September 26, 2021 by guest. Protected A 37 year old white woman developed a general- The patient has four similarly affected siblings, ised, progressive, deforming arthropathy which was two male and two female, and four unaffected first noted when she was 2 years old. Despite a lack siblings, three male and one female. Neither the of clinical evidence of synovitis, and the absence of parents nor the children of the affected and un- rheumatoid factor or characteristic nodules, she was affected siblings have clinical evidence of this diagnosed as 'juvenile '. She arthropathy. The parents are first cousins. None of had required crutches for walking since the age of 12 the other affected siblings has a history of inflamma- because of severe coxa vara with femoris adductus tory arthritis. Their arthropathy has been uniformly and genu valgum. She underwent total joint arthro- unresponsive to non-steroidal anti-inflammatory plasties of both knees and hips between November agents, and they have a strong preference for 1981 and January 1984. propoxyphene. In September 1984 the patient presented with Accepted for publication 12 April 1987. Correspondence to Dr John D Bradley, Clinical Building 492, 541 increasing pain in her right elbow. She had an oral Clinical Drive. Indiana University School of Medicine. Indiana- temperature of 38-3°C. Local warmth, redness, and polis, IN 46223, USA. swelling were present about the elbow, with pain on 709 Ann Rheum Dis: first published as 10.1136/ard.46.9.709 on 1 September 1987. Downloaded from

710 Bradley scattered lymphocytes and no acute inflammatory changes. In June 1985 the patient developed increasing pain in the left elbow over five days. Her oral temperature was 3833C. Heat, redness, swelling, and limited motion of the elbow were noted. The peripheral WBC was 15-4x109/l and the ESR was 66 mm/h. Arthrocentesis yielded synovial fluid with a WBC of 41-5 x 109/l with 90% neutrophils. No organisms or crystals were seen on routine and polarised microscopic examination of the synovial fluid. Cephapirin was administered intravenously and arthrotomy was performed. The patient defer- vesced after two days in hospital. After five days of intravenous antibiotic therapy a four week treat- ment course was completed with oral cephalexin. Elbow mobility and pain improved over several weeks. A synovial membrane biopsy specimen obtained at the time of arthrotomy again showed densely fibrotic tissue with vascular proliferation, but no acute inflammation, and all cultures of the synovial fluid were negative. In August 1985 the patient awoke with severe

_~~~~~~~~~~~~~~~~~~~~~~~~~~~~~..: copyright.

Fig. I Roentgenograph of patient's knee showing bicompartmental joint space loss and irregularity of the -- articulating surfaces. motion and further restriction of range of motion. The peripheral white blood cell count (WBC) was http://ard.bmj.com/ 20x 109/l and the Westergren erythrocyte sedi- mentation rate (ESR) was 95 mm/h. Arthrocentesis yielded 4 ml of cloudy yellow fluid with poor viscosity and mucin clot. The crystal analysis by polarised microscopy and the Gram stain were negative. The synovial fluid WBC was 95 x 109/l, of

which 92% were neutrophils. on September 26, 2021 by guest. Protected Treatment with intravenous nafcillin was initi- ated. The following day repeat arthrocentesis showed a synovial fluid WBC of 20x 109/l. The peripheral WBC fell to 9*5x 109/l, and the patient .ii' i became afebrile. Arthrotomy drainage with synovial biopsy was performed. Routine bacterial cultures of _ synovial fluid, blood, and urine, and cultures of the cervix and rectum for Neisseria gonorrhoea were all negative. The patient received two weeks' treatment i with intravenous nafcillin followed by two weeks with oral dicloxacillin. Her wound healed well, and the range of motion of the elbow gradually returned l __ to baseline. Histological examination of the syn- Fig. 2 Roentgenograph of the patient's lumbar spine ovium showed fibrosis and vascular proliferation. showing marked irregularity of the subchondral plate Only minimal inflammation was noted, with and mild platyspondyly. Ann Rheum Dis: first published as 10.1136/ard.46.9.709 on 1 September 1987. Downloaded from

Pseudoseptic pseudogout 711 pain in her right elbow. On presentation she had an from the previous admissions showed amorphous oral temperature of 38-3°C and heat, redness, and calcific deposits in the subsynovium, which stained swelling of the elbow. The initial peripheral WBC with von Kossa stain, and scattered rod-shaped was 18*2x109/l, the ESR was 51 mm/h. Serum crystals showing weakly positive birefringence, calcium, phosphate, uric acid, alkaline phosphatase, varying from 2 to 12 [tm in length. and serum creatinine were normal. Arthrocentesis showed a synovial fluid WBC of 68-5x109/l with Discussion 96% neutrophils; the Gram stain and crystal analysis were negative. Therapy was initiated with intra- Calcium pyrophosphate dihydrate disease may venous nafcillin. Repeat arthrocentesis one day later mimic many diseases, including , showed a WBC of 47.5 x 109/l with 90% neutrophils. rheumatoid arthritis, and .4 Pseudogout may Numerous small (2-4 urm) chisel-shaped crystals mask or mimic septic arthritis.5 6 Our patient had a showing weakly positive birefringence were noted longstanding degenerative arthritis vaguely simulat- both intracellularly and extracellularly. Indo- ing rheumatoid arthritis and developed three epi- methacin, 150 mg/day, was added, and the patient sodes of acute arthritis with fever, high synovial improved rapidly. Her serum creatinine, however, fluid and peripheral blood WBC, and intense local rose abruptly despite a decrease in the indomethacin signs of inflammation. These episodes were each dose to 75 mg/day. Both indomethacin and nafcillin initially thought to represent sepsis and were treated were discontinued after fouj days of therapy, and as such. Cultures were negative, however, in all the patient recovered over one week. three episodes. Furthermore, synovial biopsy speci- Review of the patient's roentgenographs showed mens obtained within days of the onset of arthritis chondrocalcinosis in the triangular cartilage of the and shortly after initiation of antibiotic therapy wrist (Fig. 3). Review of the synovial histopathology showed a paucity of inflammatory cells and absence of significant neutrophil infiltration. This strongly contradicts the diagnosis of septic arthritis.7 On the other hand, amorphous calcium deposits and posi- copyright. tively birefringent crystals, consistent with CPPD, were found in the synovium, and chondrocalcinosis was noted in the wrist. The patient, therefore, meets criteria for 'definite' CPPD disease.8 Chondrocalcinosis may go undetected on routine radiographs of patients with CPPD disease owing to low density of deposits, extensive loss of cartilage

and joint space, and bony deformities obscuring http://ard.bmj.com/ clear view of the cartilage.4 9 The last two considera- tions are particularly relevant in our patient. Review of all available radiographs of our patient and her affected siblings showed calcification of interverteb- ral discs in several and the symphysis pubis in one. Views of the shoulders, hips, and knees uniformly showed joint space loss and deformity, which could prevent detection of chondrocalcinosis. on September 26, 2021 by guest. Protected Our patient's underlying arthropathy conforms to the description of 'progressive pseudorheumatoid arthritis of childhood',' which has also been called 'spondyloepiphyseal dysplasia tarda with progres. sive arthropathy'.2 3 The accelerated, generalised degenerative arthritis suffered by these patients is reminiscent of the osteoarthritis variant of CPPD disease.9 The extremely early age of onset, the marked bone dysplasia, the severe involvement of the axial and the appendicular skeleton, and the lack of prior reports of chondrocalcinosis and pseudo- gout in patients with this arthropathy all suggest that Fig. 3 Roentgenograph of the patient's wrist showing progressive pseudorheumatoid arthritis of childhood calcification of the triangular cartilage. is a distinct entity and not a subset of CPPD disease. Ann Rheum Dis: first published as 10.1136/ard.46.9.709 on 1 September 1987. Downloaded from

712 Bradley

Previous series have emphasised the non- disorder simulating rheumatoid arthritis. Eur J Pediatr 1983; inflammatory nature of this arthropathy, with ab- 140: 34-40. 2 Wynne-Davies R, Hall C, Ansell B M. Spondylo-epiphyseal sence of soft tissue swelling, synovitis, synovial fluid dysplasia with progressive arthropathy: a 'new' disorder of leucocytosis, and radiographic erosions and perios- autosomal recessive inheritance. J Bone Joint Surg [Br] 1982; titis. Pathological changes in the cartilage include 64B: 442-5. disorganisation and hypoplasia with abnormalities 3 Al-Awadi S A, Farag T I, Naguib K, et al. Spondyloepiphyseal dysplasia tarda with progressive arthropathy. J Med Genet 1984; of both the cellular and extracellular components.' 21: 193-6. Changes suggestive of CPPD disease have not been 4 McCarty D J. Diagnostic mimicry in arthritis-patterns of joint described. involvement associated with calcium pyrophosphate dihydrate Most patients with chondrocalcinosis do not crystal deposits. Bull Rheum Dis 1975; 25: 804-9. 5 Zyskowski L P, Silverfield J C, O'Duffy J D. Pseudogout develop pseudogout. Crystal shedding from the masking other arthritides. J Rheumatol 1983; 10: 449-53. cartilage into the synovial fluid, with subsequent 6 Bong D, Bennett R. Pseudogout mimicing systemic disease. phagocytosis by neutrophils and synovial mac- JAMA 1981; 246: 1438-40. rophages, is required. Septic arthritis or gout may 7 Goldenberg D L, Cohen A S. Synovial membrane histopathol- ogy in the diffential diagnosis of rheumatoid arthritis, gout, cause 'enzymatic strip mining' of the cartilage, pseudogout, systemic lupus erythematosus, infectious arthritis resulting in crystal release.'0 Ion fluxes have been and denerative joint disease. Medicine (Baltimore) 1978; 57: proposed as a mechanism of crystal shedding," but 239-52. the most obvious cause is trauma. Chondrocalcino- 8 McCarty D J. Pseudogout; articular chondrocalcinosis. Calcium pyrophosphate crystal deposition disease. In: Hollander J L, sis and pseudogout have been reported in patients McCarty D J, eds. Arthritis and allied conditions. Philadelphia: with tabes dorsalis,'2 articular instability, 13 and Lea and Febiger, 1972: 1140. trauma.14 Our patient uses forearm crutches and 9 Martel W, Champion C K, Thompson G R, Carter T L. A bears weight with her severely degenerated elbows roentgenographically distinctive arthropathy in some patients with pseudogout syndrome. AJR 1970; 109: 587-605. and shoulders. Trauma is the most tenable explana- 10 Smith J R, Phelps P. Septic arthritis, gout, pseudogout and tion for our patient's pseudogout. osteoarthritis in the knee of a patient with multiple myeloma.

Arthritis Rheum 1972; 15: 89-96. copyright. I would like to thank Dr Kenneth Brandt for his critical review of 11 Caswell A M, Guilland-Cumming D F, Hearn P R, McGuire the report, and Roberta Fehrman and Donna Faulkner for the K B, Russell R G G. Pathogenesis of chondrocalcinosis and preparation of the manuscript. This work was supported in part by pseudogout. Metabolism of inorganic phosphate and produc- grants from the National Institute of Arthritis, Diabetes and tion of calcium pyrophosphate dihydrate crystals. Ann Rheum Digestive and Kidney Diseases (AM 20582 and AM 7448), and Dis 1983; 42 (suppl 1): 27-37. awards from the Arthritis Foundation and the Grace M Showalter 12 Bennett R M, Mall J C, McCarty D J. Pseudogout in acute Trust. : a clue in pathogenesis? Ann Rheum Dis 1974; 33: 563-7. References 13 Settas C, Doherty M, Dieppe P. Localised chondrocalcinosis in unstable joints. Br Med J 1982; 285: 175-6.

1 Spranger J, Albert C, Bartsocas C, Stoss H. Progressive 14 deLange E E, Keats T E. Localized chondrocalcinosis in http://ard.bmj.com/ pseudorheumatoid arthritis of childhood (PPAC). A hereditary traumatized joints. Skeletal Radiol 1985; 14: 249-59. on September 26, 2021 by guest. Protected