Annals ofthe Rheumatic Diseases 1991; 50: 717-721 717 Ann Rheum Dis: first published as 10.1136/ard.50.10.717 on 1 October 1991. Downloaded from Pseudoseptic arthritis: an unusual presentation of neuropathic arthropathy

Worawit Louthrenoo, Barbara E Ostrov, Young S Park, Susan Rothfuss, H Ralph Schumacher Jr

Abstract left shoulder was moderately swollen, warm, A 49 year old black man with scoliosis with a large effusion and was painful with presented with bilateral shoulder swelling motion. Intrinsic muscles of his right hand were eventually shown to be due to neuropathic atrophied. Muscle strength of both arms arthropathy related to underlying syringo- seemed decreased but was difficult to assess myelia. The synovial fluid was highly inflam- owing to the mechanical limitation of the matory, but cultures from synovial fluid and shoulders. Biceps and triceps reflexes were synovial tissue were all sterile. Profuse fat absent bilaterally. Pinprick, temperature, and droplets were noted and considered as a proprioceptive sensations were decreased in possible cause of the inflammation. This is an both arms, but loss' was more severe on the unusual presentation of neuropathic arthro- right. Movement of his left hip was limited pathy in a patient who was also harbouring an without pain. Results of the remainder of the adenocarcinoma that was undetected until eamination were unremarkable. later. Initial laboratory tests showed a haemoglobin of 66 g/l, packed cell volume 0-2, white blood cell count 8 9x I09/l with a normal differential Neuropathic arthropathy is a destructive count, platelets 1127xlO9/l, and reticulocyte process which is thought to be caused by count 2-4%. Erythrocyte sedimentation rate was impaired articular proprioceptive and pain 150 mm/h. Peripheral blood smear showed sensation leading to overuse and repetitive hypochromic and microcytic red cells without injury and by altered blood flow to the joints.' other significant abnormalities. Urine analysis Synovial fluid is usually 'non-inflammatory' or results were normal. Stool occult blood was haemorrhagic.1 We present a patient with negative. syringomyelia who had neuropathic arthropathy Chest radiograph showed marked right of the shoulder and had an unusual highly thoracic scoliosis. The heart and lungs were

inflammatory synovial fluid which mimicked normal. Cervical spine radiographs showed http://ard.bmj.com/ septic arthritis. cervical spondylosis of C3-4 with narrowing of the intervertebral disc spaces. Neuroforamina were normal. Radiographs of his right shoulder Case report showed a large soft tissue density around the A 49 year old black man presented with bilateral shoulder. The joint space was widened. There shoulder swelling. Seven months before admis- were destructive changes with resorption of the humeral head and the sion he developed intermittent tingling and portions of glenoid on September 27, 2021 by guest. Protected copyright. numbness in his right hand. Six months later he (fig 1). Soft tissue calcification, chondro- Department ofMedicine, noted painless swelling of his right shoulder, University of with weakness and increased numbness in his Pennsylvania School of Medicine right arm. Soon after this his left shoulder W Louthrenoo began to swell, with pain on motion. He B E Ostrov denied any history of fever, weight loss, joint H R Schumacher stiffness,. back pain, diarrhoea, homosexual Department of activity, intravenous drug abuse, exposure to Pathology, Medical College of Pennsylvania tuberculosis or syphilis, or trauma to his neck or Y S Park shoulders. Medical history included hyper- Ardritis-Immunolog tension, and scoliosis diagnosed when he was in Center and the Pathology the army. He had a left total hip arthroplasty in Section, Veterans 1982. The cause of his left hip disease was not Administration Medical Center, Phidelphia, ascertained. He had gonococcal urethritis on Pennsylvania, USA several occasions but had been last treated six W Louthrenoo months before admission. He admitted past Y S Park S Rothfuss heavy tobacco and alcohol consumption. He H R Schumacher also had a history of exposure to asbestos. Correspondence to: Examination showed a pale, alert man with Dr H R Schumacher Jr, normal vital signs. His back showed marked Arthritis-Immunology Center, Veterans right thoracic scoliosis with the apex at the T9 Administration Medical vertebral body and a secondary left lumbar Center, Philadelphia, Figure I Radiograph ofthe right shouldr showing a large PA 19104, USA. scoliosis. His right shoulder was markedly soft tissue density around the shouderjoint. Thejoint space is Accepted for publication swollen with a massive warm effusion. Range of widened and there is lysis ofthe humeral head and the glenoid 14 August 1990 motion was decreased but was without pain. His surface. No soft tissue calcif,catwns or osteophytes are seen. 718 Louthrenoo, Ostrov, Park, Rothfuss, Schumacherjr

calcinosis, or osteophytes were not identified. cells. There were no monosodium urate or Radiographs of his left shoulder showed calcium pyrophosphate dihydrate crystals. Ann Rheum Dis: first published as 10.1136/ard.50.10.717 on 1 October 1991. Downloaded from minimal soft tissue swelling and widening of the Alizarin red S staining for calcium crystals was glenohumeral joint space. Magnetic resonance also negative. Numerous intracellular and extra- imaging of his cervical spine (fig 2) showed a cellular fat droplets were identified by Sudan long thin slit in the middle of the upper cervical stains. Electron microscopy of the synovial fluid spinal cord, which is characteristic of collapsed showed degranulated neutrophils containing syrngomyelia. homogeneous grey globular bodies and other Repeated arthrocenteses of his right shoulder unusual angulated osmiophilic, presumably obtained 100-500 ml of cloudy serosanguinous lipid related, electron dense structures. Closed synovial fluids. The white blood cell counts needle synovial tissue biopsy was performed in ranged between 37-3 and 61-1x109/1 with his right shoulder (fig 3A). The synovium was 93-98% neutrophils. Arthrocentesis of his left oedematous, had areas with congested vessels, shoulder produced 250 ml of serosanguinous and was infiltrated with neutrophils, lympho- fluid. The white blood cell count was 41 -6x 109/1 cytes, plasma cells, and some necrotic cells, with 97% neutrophils. All fluids contained red which were scattered throughout the tissue. Extravasation of red blood cells was also noted. Tissues stained for micro-organisms were nega- tive. Cultures for bacteria, fungi, and myco- bacteria from synovial fluid and synovial tissue were sterile. As there was still concern about the possibility of infection an open arthrotomy and synovial biopsy of his right shoulder was performed two weeks later. At surgery the humeral head was found to be grossly deformed with a thick fibrin exudate covering the bone. The cartilage was completely destroyed. There was no synovial fluid obtainable at this time. Microscopically, the synovial surface was covered with fibrin. There was proliferation of the synovial lining cells. The subsynovial cell layer showed pro- liferation of small blood vessels, prominent fibrous tissue, and some chronic inflammatory cell infiltration. There was no evidence of Figure 2 Magnetic resonance imaging ofthe cervical spine shows a thtn transverse slit (arrow) in the middle ofthe granulomas or tumour. Fragments of bone and atrophic cervical cord. This is characteristic ofa collapsed cartilage were seen embedded in the synovium

syrzngomyelia. (fig 3B). Smears stained for micro-organisms http://ard.bmj.com/ on September 27, 2021 by guest. Protected copyright.

Figure 3 Synovial tissue ofthe right shoulder. (A) The ynovium obtained by needle biopsy after one month ofswelling in this area is heavily infiltrated with acute inflammatory cells (haematoxylin and eosin). (B) Two weeks later most areas ofthe synoviun show vessels with thickened walls. Fragments ofbone (arrows) are seen in the synovium (haematoxylin and eosin, usinggreenfilter). Pseudoseptic arthritis 719

were negative as were stains for amyloid. received physical treatment. He was never given

Synoyial tissue cultures for bacteria, myco- antibiotics. Both shoulders showed some func- Ann Rheum Dis: first published as 10.1136/ard.50.10.717 on 1 October 1991. Downloaded from bacteria, and fungi were all sterile. Electron tional improvement and were less swollen. After microscopy of the synovial lining cells showed discharge from hospital he was lost to follow up many lipid droplets and osmiophilic mem- until he was admitted again one year later with branous arrays suggestive of phospholipids (fig chronic cough and progressive shortness of 4). No crystals or any suggestions of viral or breath. Examination showed diminished breath bacteria-like particles were seen under electron sounds in his right lung and palpable right microscopy. supraclavicular and axillary lymph nodes. His Blood electrolyte and liver enzyme levels right shoulder showed minimal swelling with- were normal. Serum albumin was 24 g/l (normal out effusion. There were no changes in neuro- 35-55) and globulin 66 g/l (normal 25-29). logical findings. A chest radiograph showed Serum protein and immune electrophoresis diffuse alveolar infiltrates in the lower two showed IgG and IgA polyclonal hypergamma- thirds ofthe right lung, thickening ofthe pleura, globulinaemia. Results of iron studies were and a minimal right pleural effusion. He was consistent with anaemia of chronic illness. hypoxaemic. His haemoglobin had risen to Immunological test results, including anti- 134 g/l and the thrombocytosis had disappeared. nuclear antibodies, rheumatoid factors, anti- He still had an erythrocyte sedimentation rate of SSA, anti-SSB, anti-Sm, anti-RNP, serum and 160 mm/h. His liver panel and acid phosphatase cerebrospinal fluid test for syphilis, purified were normal. Radiographs of his right shoulder protein derivative skin tests, Lyme antibody, showed progressive destruction of the humeral serum complements, circulating immune com- head and the glenoid. Pleural fluid study was plexes, HIV antibody, HLA-B27.and B7, were negative for malignancy. Supraclavicular lymph all normal or negative. Cerebrospinal fluid was node biopsy was done for further evaluation of normal. Bone marrow biopsy showed a hyper- his lung problem and showed metastatic adeno- cellular marrow with mature erythroid, myeloid, carcinoma thought most likely to have been and megakaryocytic series. Plasma cells were from the lung. He declined further investigation. normal. Bone marrow iron storage was in- creased. He was given non-steroidal anti-inflammatory Discussion drugs for the mild left shoulder pain and The diagnosis of neuropathic arthropathy is often delayed. Our patient had disease for seven months but had not had any previous evaluation of his painless right shoulder swelling. Various diseases have been associated with neuropathic arthropathy. In addition to syringomyelia found in this case, these include tabes dorsalis, diabetes mellitus, spinal cord and peripheral nerve injury, leprosy, myelomeningocele, amyloidosis, http://ard.bmj.com/ congenital insensitivity to pain, and familial dysautonomia.' 2 Two forms of neuropathic arthropathy have been described-the 'atrophic or resorptive' and the 'hypertrophic or pro- ductive' forms.' 2 The former usually affects the non-weightbearing joints-for example, shoulder, elbow, and wrist. These joints on September 27, 2021 by guest. Protected copyright. develop severe destruction rapidly, sometimes in less than six weeks.3 The mechanism is believed to include neurovascular changes in that a loss of neural supply causes alteration in blood-bone flow, leading to active hyperaemia and active bone resorption.2 In contrast, the hypertrophic form usually affects the weight- bearing joints-for example, hip and knee. In these areas the disease often takes months to years to develop and hypertrophic osteophytes are present.' Impaired sensation may cause overuse and the unprotected joints are subjected to repeated minor injury. The full reasons underlying the development of the two distinct forms or extremes of neuropathic arthropathy are not clear. Norman believed that both types were the same disease but differed in time sequence of manifestation.3 Our patient had the atrophic form of neuropathic arthropathy; he developed rapid destruction ofhis right shoulder over a month and the radiographs showed destruction of the humeral head and the Figure 4 Electron microscopic study ofthe synovium shows synovial lining cells with glenoid homogeneous lipid droplets (L) and membranous arrays ofpresumed lipids (arrows). without hypertrophic osteophytes. The intensely SLC=nucleus of ynovial lining cells. F=fibrin on the surface. inflammatory synovial fluid noted in our patient 720 Louthrenoo, Ostrov, Park, Rothfuss, SchumacherJr

may be an important factor as is described with phagocytosis of the fat droplets, possibly below. leading to the inflammatory fluid. Ann Rheum Dis: first published as 10.1136/ard.50.10.717 on 1 October 1991. Downloaded from Neuropathic arthropathy is present in up to Synovial tissues in neuropathic joints have one third of patients with syringomyelia. The been reported to show hyperplastic synovium fingers are affected in up to 800/o of these with bone or cartilage debris, or both, and large patients.' Shoulder swelling can be the present- amounts of haemosiderin in deep macrophages. ing sign and the shoulder, as in our patient, is Chronic inflammatory cell infiltrates with the most common joint affected.4 5 Scoliosis, clustered or scattered lymphocytes have been most often in the thoracic spine, is common in described in some.'7 18 Subintimal fibrosis has syringomyelia and is seen in up to 63% of been seen.3 Infiltration by neutrophils has not patients.6 ' Scoliosis can present for many years been reported. The first synovial biopsy speci- before the clinical neurological deficits become men in our case showed an acute and chronic apparent.7 It is not clear whether a shared inflammatory reaction with dramatic poly- developmental defect predisposes to both morphonuclear leucocyte infiltration; two scoliosis and syringomyelia or whether an weeks later this was replaced with fibrous and imbalance of muscle tension results from the chronic inflammatory cells in the second neuropathic process in the same case.6 synovial biopsy specimen. We could not identify The presence of such an inflammatory bone or cartilage fragments in the first small synovial fluid in our case is of interest. The synovial biopsy specimen but could identify negative synovial fluid and synovial tissue some in the second open synovial biopsy speci- cultures ruled out septic arthritis as a cause of men. The presence of severe anaemia and this patient's joint disease. Synovial fluids in polyclonal hypergammaglobulinaemia in our neuropathic joints have been examined in several patient could not be explained by the syrinx and studies and have generally had leucocyte counts neuropathic arthropathy. The absence of less than 065 x109/l but with widely varying abnormal plasma cells in the bone marrow and percentages ofneutrophils (O_95%).8 Occasional the absence of a monoclonal gammaglobulin higher leucocyte counts up to 19 Ox 109/l have spike made an underlying plasma cell dyscrasia been seen. in patients who had associated unlikely. The iron studies were more consistent calcium pyrophosphate dihydrate deposition.9 with the anaemia of chronic disease rather than Hydroxyapatite crystals also have been reported iron deficiency. The negative amyloid stains in as a cause ofa rapid destructive arthropathy. 0 I I synovial tissue ruled out systemic amyloidosis as Neither type of crystal was found in our a cause of the arthropathy. The subsequently patient's joint fluid despite the occasional bone identified adenocarcinoma might have been the fragments in the synovium and bone lysis that cause of these abnormalities and is probably might have released bone apatites. Patients coincidental to the syringomyelia in our case. specifically identified as having the most rapid In summary, we present the case of a patient resorptive atrophic form of neutropathic joints with shoulder neuropathic arthropathy and with 12 13 have not of by radiologists3 had details severe inflammatory synovial fluid. The http://ard.bmj.com/ their synovial fluid analysis or histology mechanism for the inflammatory reaction in the reported. It might be important to study more synovial fluid is not known, but fat droplets ofthese patients to see if they might have highly must be considered as a possible cause. Further inflammatory effusions early in the disease like studies of joint fluids and tissues in patients our patient. with the atrophic, resorptive type of neuro- At this time we cannot totally exclude the pathic arthropathy may help us better to under- possibility that the inflammation in the neuro- stand the mechanisms involved. pathic joint of our patient was due to a separate on September 27, 2021 by guest. Protected copyright. process superimposed on the neuropathic arthropathy, such as a seronegative spondylo- 1 ElIman M H. Neuropathic joint disease (Charcot joints). In: arthropathy, because he had a history of McCarty D J, ed. Artris and allied conitio. I1th ed. urethritis. He had no other clues to this, Philadelphia: Lea and Febiger, 1989: 1255-72. 2 Brower A C, Allman R M. Pathogenesis of the neuropathic however, was negative for both HLA-B7 and joint: neurotraumatic vs neurovascular. RadiolV 1981; B27, and involvement limited to the joints with 139: 349-54. 3 Norman A, Robbins H, Migram J E. The acute neuropathic neuropathic arthropathy would be most unusual arthropathy-a rapid, serverely, disoizing form of unlesssomehow thevascularcongestionfavoured arthritis. Radioo 1968; 90: 1159-6. 4 Skall-Jensen J. Oste athy in syringyclia. Analysis this. A paraneoplastic syndrome was also con- of seven cases. Acta Radial 1952; 38: 3824. sidered, but all signs of inflammation had 5 SackeJlsresJ C, Swift T R. Shoulder enlment as the presenting signs in s yeia. Report ofto cases and subsided even as the tumour progressed. review of the literatue. JAMA 1976; 236: 2878-9. The presence of fat droplets has not been 6 Huebert H T, MacKinnon W B. Syringomyelia and scoliosis. I BoneJo6int Surg [Br) 1%9; 51: 338-43. reported in the synovial fluid or synovial tissue 7 Raininko R. Syringomyelia in scoliotic patients. Amals of of patients with neuropathic arthropathy. Lipid Clinical Research 1986; 18: 93-8. 8 Ropes M W, Bauer W. Syovial changes in joint disease. droplets can come from membranes of de- Cambridge: Harvard University Press, 1953: 83-5. generated erythrocytes or other cells, or from 9 Jacobelli S, McCarty D J, Silcox D C, Mail j C. Calcium pyrophosphate dihydrate deposition in neuropathic joints. bone marrow as a result of fracture or other Four cases of polyarticular involvement. Ann Intern Med destruction giving the marrow access to the 1973; 79: 340-7. 10 Dieppe P A, Doherty M, MacFarlane D G, Hutton C W, joint space. '4 Fat droplets or lipid liquid crystals Brandfield J W, Watt I. Apatite asociated destructive have been shown to be causes of an inflam- arthritis. BrJ Rhemnatol 1984; 23: 84-91. 11 Klimaitis A, Carroil G, Owen E. Rapidly progressive matory arthritis. 5 16 We suggest that the neuro- destructive arthropathy of the shoulder-a viewpoint on pathic arthropathy of the shoulder in our pathogenesis. J Rheunatol 1988; 15: 1859-62. 12 Katz I, Rabinowitz J G, Dziadiw R. Early changes in patient might have caused chronic bleeding into Charcot's ioints. American Joumnal of Roentgenology 1961; the destroyed joint space or marrow fat release 86: 965-74. Pseudoseptic arthritis 721

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