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Case Report *Corresponding author Anthony M. Reginato, Rheumatology Research and Musculoskeletal Ultrasound, University Medicine The Mystery of the Swollen Foundation/RIH, Medicine and Dermatology, The Warren Alpert Medical School at Brown University, 375 Wanpanoag Trail, Suite 202C, East Providence, RI Knee 02905, USA, Tel: 401-444-8083; Fax: 401-444-3558; Email:

1 2 Dan A. Cristescu and Anthony M. Reginato * Submitted: 20 September 2016 1 Division of Rheumatology, Roger Williams Medical Center, Boston University, USA Accepted: 31 October 2016 2Division of Rheumatology, The Warren Alpert Medical School at Brown University, Published: 03 November 2016 USA Copyright © 2016 Reginato et al. Abstract OPEN ACCESS We described a case of a 59-year-old male with fevers, right knee swelling, non- inflammatory synovial fluid with negative gram stain and without crystals. Ultrasound Keywords examination of the periarticular structures of the knee demonstrated intra-tendinous patellar tendon tophaceous deposits and associated deep-infrapatellar gout . • Effusion This case highlights the use of bedside ultrasound in the real-time diagnosis of patients • Tophus with monoarticular inflammatory arthritis, direct quantification of the extent of crystal • Patellar tendon deposition disease, accurate assessment of inflammatory involvement of joints, bursae, • Deep-infrapatellar bursitis tendons and soft tissues becoming a distinctive imaging modality for evaluation of • Gout ultrasound crystal arthropathies. • Power-Doppler

INTRODUCTION

artery disease, stroke, seizure disorder, obstructivest sleep apnea, chronic obstructive pulmonary disease (COPD), hypertension,nd Gout is an inflammatory disease induced by the precipitation and osteomyelitis with 2 prior amputations of his 1 and 2 distal of monosodium urate (MSU) - crystals in a variety of tissues, phalanxes of the right foot. He had a history of Osgood-Schlatter joints, periarticular, and soft-tissues. Imaging modalities diseaseMedications in childhood. and allergies such as musculoskeletal ultrasound play an important role in the diagnosis, evaluation and treatments of patients with crystal-induced arthritis. Furthermore, this case illustrates He was taking Augmentin 875/125mg BID, Aspirin 81mg, the importance of ultrasound in the detection, localization and Dilantin 200mg TID, Humalog Insulin, Metoprolol 25mg BID, aspiration of joint fluid for the presence of MSU- crystals under Nexium 40mg, Norvasc 7.5mg, Pravachol 40mg and Advair polarizedCASE PRESENTATION microscopy. DiskusFamily 250/50mcg and social BID. history He was allergic to Codeine.

54-year-old man was admitted to the hospital after four days The patient denied any family history of rheumatologic of severe pain and swelling of the right knee, associated with disorders, including psoriasis. He lived independently by himself subjective fevers. The patient was discharged from the hospital and denied alcohol abuse, smoking and illegal drug use prior to one-week prior, after a right big toe distal phalanxamputation admission.Review of systems for osteomyelitis. He was at home for three days after the surgery when he developed swelling and pain of his right knee. The symptoms worsened over the next three days and he was He complained of mild low back pain and shortness of breath, unable to ambulate, at which point he returned to the hospital. He subjective fevers and inability to ambulate. He denied morning reported mild discomfort in the right knee for a few months prior stiffness, history of tick bite, eyes pain or erythema, no skin to admission, especially with kneeling. He denied any locking or rashesPhysical suggestive examination of psoriasis and no bowel symptoms. giving out of the right knee and had no prior history of trauma. No other joints were painful, swollen or tender. On occasions, he felt hot but did not check his temperature. In the emergency room he was a febrile and received intravenous (IV) vancomycin and The vital signs were within normal range with a temperature Unasyn.MEDICAL HISTORY of 98.7F. The right knee had a large effusion and extremely limited range of motion (Figure 1A). It was tender to palpation and warm to touch without erythema. The rest of the joints were without effusions or and had normal range of motion. No He suffered from insulin dependent diabetes mellitus, tophaceous deposits were identified over the ear, elbow or other diabetic neuropathy, chronic kidney disease stage III, coronary joints. The remainder of the physical exam was unremarkable. Cite this article: Cristescu DA, Reginato AM (2016) The Mystery of the Swollen Knee. JSM Arthritis 1(3): 1016. Reginato et al. (2016) Email:

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hyaline or articular cartilage interphase known sonographically as the “double contour sign” while CPP-crystals appear as intra-cartilaginous specks within the hyaline cartilage [2]. Both of which were not appreciated under ultrasound. Microtophi can sometimes be seen in soft tissues or synovium as floating hyperechoic foci resulting in the classicsn onographic “snow storm appearance” [3]. Evaluation of the extensor mechanism of the knee showed the normal fibrillar pattern of the patellar tendon with hyperechoic, linear density identified at the insertion of the patellar tendon

Figure 1 at the tibial tuberosity (Figure 4). These hyperechoic linear Plain, non-weight-bearing Xray of the right knee. A. Anterior-posterior densities exhibited post-acoustic shadowing consistent with a view. Normal appearing joint spaces. B. Lateral view. A well corticated ossicle is bony fragment. The location correspond to the ossicle seen on the seen in the patellar tendon close to the tibial tuberosity insertion. A moderate knee X-ray (Figure 2B). The MSUS findings were characteristic sized supra-patellar effusion is also identified. of an Osgood-Schlatteras previously described in the literature Laboratory evaluation [4]. In additions, there was moderate effusion in the deep infrapatellar bursae containing some hyperechoic signals. An 3 intense power-Doppler signal was identified within the inferior WBC3 13 cells/mm , Hemoglobin 11 g/dl, Platelets 264,666 margin of the patellar tendon (Figure 5 (B and D)). Longitudinal /mm , Creatinine 1.4mg/dl, ESR 103 mm/h, CRP 43 mg/l, Uric and transverse views of the patellar tendon of affected and acid 5.9 mg/dl, Urine analysis had 100mg/dl proteinuria, +1 non affected knee are shown in Figure 5 (A and C). On further blood, without bacteria. Two blood cultures were drawn and had negative Gram stains. The chest radiography was normal and Doppler ultrasonography of the calves did not demonstrate the presence of thrombi. The radiography of the right knee showed a moderate effusion and a small ossicle in the patellar tendon consistent with prior history of Osgood-Schlatter disease in childhood (Figure 2). The right knee was aspirated and yielded clear, non- inflammatory3 fluid (Figure 3A) with a nucleated cell count of 110 CASEcells/mm SUMMARY. Gram stain, culture and crystal analysis was negative. Figure 2

A. Picture of the patient’s knees at presentation. Notice the significant 54 year-old man with recent history of osteomyelitis of his right knee swelling compared to his left side. B. US scan of the lateral supra- right toe, status post amputation, returns to the hospital after four patellar recess. Notice the anechoic effusion (E), the fibrilar pattern of the days of right and severe swelling. The synovial fluid quadriceps tendon (QT) and the hyperechoic linear signals from the patella (P) aspirated from the right knee was found to be non-inflammatory and the femur (F) casting an anechoic acoustic shadow underneath. withHospital negative course gram stain and without crystals.

Musculoskeletal ultrasound was used to further evaluate the right knee effusion and adjacent structures as well as the contralateral knee for comparison (Figure 1B). Standard scans of the knees were obtained based on the European Society of Musculoskeletal Radiology (ESSR) standardized scans [1].These include both longitudinal and transversal planes: quadriceps tendon, suprapatellar and parapatellar joint recesses, patellar tendon, medial, lateral and posterior knee. The femoral trochlea could not be visualized by ultrasound due to the patient’s inability Figure 3 to flex the knee. Evaluation of the suprapatellar, medial and A. Aspirated synovial fluid from the knee and adjacent structures. (A) lateral recesses of the knee showed moderate anechoic signal The syringe of the left side contains clear synovial fluid obtained from the tibio- on gray scale that was consistent with the moderate effusion femoral joint. (B) The syringe on the right holds the amber, opaque fluid drained (Figure 1B) as seen on X-ray. There was no appreciable synovitis under MSUS guidance from the deep infra-patellar bursa. B. Compensated and negative for power-Doppler signal. On MSUS, the presence polarized light microscopy. Analysis of the fluid aspirated from the deep infra- of crystalline deposits seen in crystal-induced arthritis have a patellar bursa reveals numerous needle-shaped negatively birefringent crystals, characteristic sonographic pattern with MSU crystals deposition consistent with mono-sodium urate crystals. The arrow indicates the polarizer’s axis. appearing as hyperechoic deposits on the surface of the synovial- JSM Arthritis 1(3): 1016 (2016) 2/4 Reginato et al. (2016) Email:

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examination of the patellar tendon proximally by ultrasound, we were able to confirm anheterogeneous hyperechoic formationon gray-scale (Figure 5 (B and D)). The round formation extended through the entire tendon thickness, disrupted the normal fibrilar pattern of the tendon and contained multiple hyperechoic specs w/o post-acousticshadowing. A large deep infrapatellar bursitis was also identified under the intratendinous lesion. The differential diagnosis of this lesion included an infectious abscess, gouty tophus, heterotropic calcification, chronic partial tear of the tendon with calcifications, benign or malignant tumors. Using ultrasound guidance, the deep infrapatellar bursa was aspirated. The aspirated fluid was pink and3 cloudy (Figure 4A (B)) and had 43,000 nucleated cells/mm . Under polarized light microscopy, the synovial fluid revealed many intra and extra cellular monosodium urate (MSU) crystals (Figure 4B). Both the knee and the deep infrapatellar bursa were injected Figure 5 with triamcinoloneacetonide and he was able to bear weight and Longitudinal and transverse gray-scale image of the patellar tendon ambulate 3 days later. The final diagnosis in our case was an acute from the affected and non-affected knee. (A) Longitudinal axis of unaffected side. gout flare with patellar tendon tophus, infrapatellar bursitis and (B) Longitudinal axis of unaffected side, (C) transverse axis of unaffected side, sympatheticDISCUSSION effusion of the knee joint. (D) transverse axis of affected side. The unaffected side scans, A and C, display normal sonographic fibrillar pattern of the patellar tendon (PT), Hoffa’s fat pad (HFP), small deep infra-patellar bursa (DIB), tibia (T) and tibial tuberosity (TT). MSU of the affected side reveals a round, heterogeneous formation (F)within The evaluation of a hot knee with a large effusion is usually the patellar tendon with hyperechoic debris (D) are seen floating in an enlarged straightforward and does not require additional imaging. The deep infra-patellar bursa (DIB) seen in both transverse and longitudinal views. history, physical examination, routine labs and a complete synovial fluid analysis will indicate the diagnosis in the majority of cases. In our patient however, the non-inflammatory effusion of tendons [6]. A study evaluating asymptomatic hyperurecemic and the absence of crystals in the synovial fluid made the usual patients found tophi by MSUS inside the tendons in one third of etiologies unlikely and failed to explain the subjective fevers, patients, which suggests that tendons are a preferred location for elevated WBC and ESR. early MSU crystal deposition [7]. US allowed us to identify the intra-tendinous tophus and There are only a fewcase reports in which the initial gout infra-patellar bursitis which revealed the presence of MSU- manifestation is a tophuscausing patellar tendonitis [8,9]. The crystals under polarized light microscopy and settled the reported cases occurred in athletes and a man with history of diagnosis. Tophi have a fairly characteristic appearance under Osgood-Schlatter disease [8]. The latter case shared many of ultrasound evaluation [5]. They are usually heterogeneous and the uncommon findings of our case: the intra-patellar tendon hyperechoic, with poorly defined contours and hypoechogenic tophus as the initial gout manifestation, normal uric acid value halos. Using the power Doppler signal, active inflammation and a history of Osgood-Schlatter disease with a residual ossicle can be detected to confirm active inflammatory disease. MSUS in the patellar tendon. Tophi tend to form at friction points such appears as sensitive if not better than the MRI for the evaluation as the extensor surface of the elbows. It is possible that chronic recurrent micro-traumas to the patellar tendon favored MSU- crystal depositions and tophi formation. The treatment of intra-tendinous tophaceous gout follows the general treatment guidelines with a few caveats. Acute attacks are best treated with intra-articular or peri-tendinous glucocorticoid injections. They take longer to resolve and occasionally the symptoms do not respond to injections. Surgical excision (tophectomy) might be useful in the latter situation. Serum uric acid lowering therapy is employed after the attack subsides, with concomitant flare prophylaxis for 6 months. The Figure 4 target for the serum uric acid level should lower, at <5 mg/dl in

Longitudinal scan of the right patellar tendon at insertion site. (A) an attempt to dissolve the tophi in a timely fashion. The time to Grayscale mode. (B) power-Doppler mode. The ossicle (O) is seen on gray scale tophi resolution is directly dependent upon the median serum as a hyperechoic linear density inside the patellar tendon (PT) close to the uric acid [10]. The lower the uric acid concentration, the quicker tendon’s insertion into the tibia (T) with post-acoustic shadowing. An enlarged the tophus dissolves. In a case series, pegloticase was used in two deep infra-patellar bursa is identified containing large anechoic fluid (E) with patients with tophaceous gout of the hands [11]. The uric acid hyperechoic debris. Power Doppler (PD) signal was noticed within the inferior concentration dropped close to zero and it took 12 weeks for aspect of the patellar tendon. the tophi to dissolve. The choice of the uric acid lowering agent JSM Arthritis 1(3): 1016 (2016) 3/4 Reginato et al. (2016) Email:

Central Bringing Excellence in Open Access REFERENCES will vary depending on the response to injections, recurrences and desired level of activity. Oral agents such as allopurinol and 1. Martinoli C. Musculoskeletal ultrasound: technical guidelines. Insights febuxostat, will likely take longer to decrease the uric acid and Imaging. 2010; 1: 99-141. dissolve the tophus, but they should be considered first line 2. Grassi W, Meenagh G, Pascual E, Filippucci E. “Crystal clear”- agents if the clinical situation permits. sonographic assessment of gout and calcium pyrophosphate This brief case highlights three important things to consider deposition disease. Semin Arthritis Rheum. 2006; 36: 197-202. in our daily rheumatology practice when dealing with a 3. Farina A, Filippucci E, Grassi W. Sonographic findings for synovial monoarthritis. In the presence of a hot, swollen knee with normal fluid. Reumatismo. 2002; 54: 261-265. synovial fluid analysis that fails to explain the overall clinical and 4. Zbigniew Czyrny. Ossgood-Schlatter disease in ultrasound diagnostics laboratory scenario, attention should be given to the adjacent – a pictorial essay. Med Ultrason. 2010; 4: 323-335. structures such as the patellar tendon and infra-patellar bursa that may provide diagnostic clues. This is the first reported 5. de Ávila Fernandes E, Kubota ES, Sandim GB, Mitraud SA, Ferrari AJ, Fernandes AR. Ultrasound features of tophi in chronic tophaceous case in which a tophus in the patellar tendon causes a non- gout. Skeletal Radiol. 2011; 40: 309-315. inflammatory knee effusion as initial manifestation of gout. If this possibility is not considered, unnecessary workup and treatment 6. Kamel M, Eid H, Mansour R. Ultrasound detection of knee patellar : acomparison with magnetic resonance imaging. Ann could ensue. The high likelihood of infection in this case would Rheum Dis. 2004; 63: 213–214. have required surgical washout and long-term antibiotics, which would not have improved the symptoms, leading to expensive 7. Puig JG, de Miguel E, Castillo MC, Rocha AL, Martínez MA, Torres readmissions. Furthermore, it highlights the utility of ultrasound RJ. Asymptomatic hyperuricemia: impact of ultrasonography. Nucleosides Nucleotides Nucleic Acids. 2008; 27: 592-595. with power-Doppler signal in the diagnosis, detection, localization and aspiration of joint fluid for evaluation under polarized light 8. Rodas G, Pedret C, Català J et al. Intratendinous gouty tophus mimics microscopy [12]. US proves to be an extremely useful, inexpensive patellar tendonitis in an athlete. J Clin Ultrasound. 2013; 41: 178-182. and accurate tool to aid the clinical examination of challenging 9. Gililland JM, Webber NP, Jones KB, Randall RL, Aoki SK. Intratendinous cases involving the knee or any other affected joint and facilitates tophaceous gout imitating patellar tendonitis in an athletic man. corticosteroid injections under ultrasound guidance [13], when Orthopedics. 2011; 34: 223. nonsteroidal anti-inflammatory drugs and oral therapy are not 10. Perez-Ruiz F, Calabozo M, Pijoan JI, Herrero-Beites AM, Ruibal A. tolerated or contraindicated. Lastly, our case raises the question Effect of urate-lowering therapy on the velocity of size reduction of whether patients with a history of Osgood-Schlatter disease have tophi in chronic gout. Arthritis Rheum. 2002; 47: 356-360. an increased risk of developing tophi in the patellar tendon. This 11. Baraf HS, Matsumoto AK, Maroli AN, Waltrip RW. Resolution of gouty hypothesis will certainly need further evaluation with a formal tophi after twelve weeks of pegloticase treatment. Arthritis Rheum. study.ACKNOWLEDGEMENTS 2008; 58: 3632-3634. 12. Slot O, Terslev L. Ultrasound-guided dry-needle synovial tissue aspiration for diagnostic microscopy in gout patients presenting AuthorThis workcontributions was supported by grants P20GM104937 (A.M.R.). without synovial effusion or clinically detectable tophi. J Clin Rheumatol. 2015; 21: 167-168. 13. Kang MH, Moon KW, Jeon YH, Cho SW. Sonography of the first All authors were involved in the patient’s care, in obtaining metatarsophalangeal joint and sonographically guided intraarticular the MSUS images and in the drafting of the article. All authors injection of corticosteroid in acute gout attack. J Clin Ultrasound. approved the final version of the manuscript to be published. 2015; 43: 179-186.

Cite this article Cristescu DA, Reginato AM (2016) The Mystery of the Swollen Knee. JSM Arthritis 1(3): 1016.

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