- Email: [email protected]
Haemophilic synovitis of the elbow: Radiosynovectomy, open synovectomy or arthroscopic synovectomy?
Thrombosis Research 132 (2013) 15–18
Contents lists available at SciVerse ScienceDirect
Thrombosis Research journal homepage: www.elsevier.com/locate/thromres
Review Article
Haemophilic synovitis of the elbow: Radiosynovectomy, open synovectomy or arthroscopic synovectomy? E. Carlos Rodriguez-Merchan ⁎ Department of Orthopaedic Surgery, La Paz University Hospital, Madrid, Spain School of Medicine, Autonomous University, Madrid, Spain
a r t i c l e
i n f o
Article history: Received 31 March 2013 Received in revised form 21 May 2013 Accepted 26 May 2013 Available online 18 June 2013 Keywords: Haemophilia Synovitis Elbow Arthroscopic synovectomy Open synovectomy Radiosynovectomy
a b s t r a c t Arthroscopic synovectomy (AS) of the elbow, while providing similar pain relief to open synovectomy (OS), may place patients at higher risk for recurrence. The primary predictor of outcome is degree of pre-existing degenerative changes within the joint. Regarding haemophilia patients, radiosynovectomy (RS) is the best choice for patients with persistent synovitis of the elbow. In the elbow we recommend a dose of 30–40 megabecquerels (mBq) in children and a dose of 56–74 mBq in adults. If three consecutive RSs with 6 months intervals are ineffective, an AS or OS must be indicated. Synovectomy (by any method) significantly reduces bleeding episodes. Although the dose of radiation of RS is minimal, 0.32 millisieverts (mSv) in children, 0.54 mSv in adults, and neither articular nor systemic neoplastic changes related to RS have been reported so far, all patients must be given opportunity to consider risk/benefit ratios. Radiation dose due to natural sources is 2 mSv per year and the recommended limit for patients (apart from natural sources is 1 mSv per year). My current recommendation is to use RS in children older than 12 years of age. Therefore, in children younger than 12 years of age an AS should be indicated. OS should be reserved for adults requiring radial head excision (due to a severe limitation of pronation-supination) and synovectomy in the same surgical session. © 2013 Elsevier Ltd. All rights reserved.
Contents Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . The Haemophilic Elbow and its Manifestations and Treatment Options Pathogenesis of Synovitis and Cartilage Damage in Haemophilia . Treatment of Haemophilic Elbow Arthropathy . . . . . . . . . . Non-surgical Treatment . . . . . . . . . . . . . . . . . . . . Radiosynovectomy . . . . . . . . . . . . . . . . . . . Chemical Synovectomy . . . . . . . . . . . . . . . . . Rehabilitation . . . . . . . . . . . . . . . . . . . . . Surgical Treatment . . . . . . . . . . . . . . . . . . . . . . Authors´ Experience . . . . . . . . . . . . . . . . . . . . . . . . Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . Conflict of Interest Statement . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . . . . . . .
. . . . . . . . . . . . .
Introduction Routine prophylaxis is an important treatment strategy for patients with severe hemophilia [1–3]. When medical management fails to
⁎ Department of Orthopaedic Surgery, La Paz University Hospital, Paseo de la Castellana 261, 28046-Madrid, Spain. Tel.: +34 606712724. E-mail address: [email protected]. 0049-3848/$ – see front matter © 2013 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.thromres.2013.05.025
. . . . . . . . . . . . .
. . . . . . . . . . . . .
. . . . . . . . . . . . .
. . . . . . . . . . . . .
. . . . . . . . . . . . .
. . . . . . . . . . . . .
. . . . . . . . . . . . .
. . . . . . . . . . . . .
. . . . . . . . . . . . .
. . . . . . . . . . . . .
. . . . . . . . . . . . .
. . . . . . . . . . . . .
. . . . . . . . . . . . .
. . . . . . . . . . . . .
. . . . . . . . . . . . .
. . . . . . . . . . . . .
. . . . . . . . . . . . .
. . . . . . . . . . . . .
. . . . . . . . . . . . .
. . . . . . . . . . . . .
. . . . . . . . . . . . .
. . . . . . . . . . . . .
. . . . . . . . . . . . .
. . . . . . . . . . . . .
. . . . . . . . . . . . .
. . . . . . . . . . . . .
. . . . . . . . . . . . .
. . . . . . . . . . . . .
. . . . . . . . . . . . .
. . . . . . . . . . . . .
. . . . . . . . . . . . .
. . . . . . . . . . . . .
. . . . . . . . . . . . .
. . . . . . . . . . . . .
. . . . . . . . . . . . .
. . . . . . . . . . . . .
15 16 16 16 16 16 17 17 17 17 18 18 18
prevent the development of elbow synovitis, techniques such as radiosynovectomy (RS), arthroscopic synovectomy (AS) and open synovectomy (OS) can be used to manage chronic synovitis. If left untreated, haemophilic synovitis (Fig. 1) followed by degenerative changes within the elbow (Fig. 2) will occur and a stiff or painful joint will result. Controversy still exists, however, about the real efficacy of such procedures in haemophilic synovitis. The purpose of this review is to analyze the efficacy of different types of synovectomy in the haemophilic elbow.
16
E.C. Rodriguez-Merchan / Thrombosis Research 132 (2013) 15–18
The Haemophilic Elbow and its Manifestations and Treatment Options
Fig. 1. MRI of a haemophilic elbow showing severe chronic haemophilic sinovitis (arrows).
It is well known that in haemophilia the elbows tend to bleed beginning during an early age of 2–5 years. The synovium is only able to reabsorb a small amount of intra-articular blood; if the amount of blood is excessive, the synovium will hypertrophy as a compensating mechamism, so that eventually the affected joint will show an increase in size of the synovium: so-called hypertrophic chronic haemophilic synovitis. The hypertrophic synovium is very richly vascularized, so that small injuries will easily make the joint re-bleed. The final result will be the classic vicious cycle of haemarthrosis-synovitis-haemarthrosis, which eventually will result in elbow haemophilic arthropathy. The best way that we have today to protecting against haemophilic arthropathy (cartilage damage) is primary haematological prophylaxis (from cradle to college). Starting prophylaxis gradually with onceweekly injections has the presumed advantage of avoiding use of a central venous access device, which is often necessary for frequent injections in very young boys. The decision to institute early full prophylaxis by means of a port has to be balanced against the child’s bleeding tendency, the family’s social situation and the experience of the specific haemophilia centre. The reported complication rates for infection and thrombosis have varied considerably from centre to centre. Risk of infection can be reduced by repeated education of patients and staff, effective surveillance routines and limitations on the number of individuals allowed to use the device. In discussing options for early therapy, the risks and benefits should be thoroughly discussed with the parents. Pathogenesis of Synovitis and Cartilage Damage in Haemophilia Hakobyan et al. [4] analyzed the pathogenesis of haemophilic synovitis in a murine model of human haemophilia A. The authors concluded that molecular changes induced by iron in the blood may be the basis of the increase in cell proliferation and the development of haemophilic synovitis. Valentino et al. [5] showed that controlled, blunt trauma to the joints consistently resulted in joint swelling, because of a combination of bleeding and inflammation. Haemosiderin was found in the synovial membrane after provoking a controlled blunt trauma to the joints. Similar to haemartrosis in human haemophilia, joint bleeding resulted in acute morbidity evidenced by inactivity, weight loss and immobility. Despite the fact that the two aforementioned papers are very interesting with regard to the understanding of haemophilic synovitis and the initial stages of cartilage damage in haemophilic joints, the link between both phenomena, is still very poorly understood. In fact, previous studies have shown that synovitis is not primarily responsible for the cartilage damage after intra-articular bleeding, but rather that the exposure of cartilage to blood induces direct adverse effects. Treatment of Haemophilic Elbow Arthropathy Patients with mild to moderate pain are often helped by using elbow orthoses, but symptomatic and incapacitated patients require arthroscopic elbow debridement, arthrodesis or arthroplasty [6,7]. Non-surgical Treatment Conservative treatment includes radiosynovectomy, chemical synovectomy, and rehabilitation (physiotherapy, orthoses). Conservative treatment should always be attempted prior to surgery [6,7].
Fig. 2. (a-b). Radiographs showing moderate arthropathy of an elbow (a) and severe arthropathy (b) of the same elbow 17 years later.
Radiosynovectomy From a practical point of view, radiosynovectomy (RS), together with primary prophylaxis to avoid joint bleeding, can help halt
E.C. Rodriguez-Merchan / Thrombosis Research 132 (2013) 15–18
haemophilic synovitis. Ideally, however, RS should be performed before the articular cartilage has eroded. RS is a relatively simple, virtually painless and inexpensive treatment for chronic haemophilic synovitis, even in patients with inhibitors and is the best choice for patients with persistent synovitis. RS consists of destruction of synovial tissue by intra-articular injection of a radioactive agent. Radioactive substances have been used for the treatment of chronic haemophilic synovitis for many years [8]. The indication for a RS is chronic haemophilic synovitis causing recurrent haemarthroses, unresponsive to haematological treatment. On average, the efficacy of the procedure ranges from 70-75%, and can be performed at any age. The procedure slows the cartilaginous damage which intra-articular blood tends to produce in the long-term. Probably the first treatment to be considered for recurrent elbow haemarthroses is RS. This consists of the injection of a radioactive material (yttrium-90 or phophorus-32) into the joint [8–11]. RS can be repeated up to three times with 6-month intervals. The most common radioactive materials used are Yttrium-90, Phosphorus32 and Rhenium-186. After 40 years of using radiation synovectomy worldwide, no damage has been reported in relation to the radioactive materials. Chemical Synovectomy Radossi et al. [12] have used intra-articular injections of ryfamicin. In Radossi et al.´s series there were five patients with inhibitors to factor VIII (three high responders and two low responders). Their average age was 34 years (range 15–60 years). Ryfamicin (250 mg) was diluted in 10 mL of saline solution and 1-5 mL was then injected into the joint. There are two main limitations for the use of antibiotics in ryfamicin synovectomy: the procedure is painful, and it should be repeated weekly for many weeks to be effective. Rehabilitation The importance of preoperative and postoperative rehabilitation of the elbow joint in haemophilia must be emphasized. Children must utilize the resources available and seek early consultation with their centre rehabilitation physician and/or physiotherapist. Using the techniques avalible, rehabilitation has been shown to speed recovery, reduce pain and prevent contractures. Physiotherapy is important in elbow rehabilitation of patients following surgical procedures and the physiotherapist must work closely with the orthopaedic surgeon [13,14]. Surgical Treatment The most common surgical approaches performed at the elbow joint are arthroscopic synovectomy, arthroscopic joint debridement, arthroplasty and arthrodesis [6,7,15,16]. When RS fails to control synovitis, an arthroscopic synovectomy must be indicated [8–11,17]. Sometimes a large radial head can cause severe loss of pronation-supination. Surgical removal of the hypertrophic radial head is sometimes indicated [15]. In advanced haemophilic arthropathy, an elbow arthrodesis or total elbow arthroplasty should be considered [7,8,15,16]. The main indications for these are intractable pain not relieved by alternative treatments and severe deformity. Regular prophylactic transfusions of clotting factor may prevent recurrent bleeds and further development of haemarthrosis. Elbow arthrodesis and elbow arthroplasty are rarely performed in haemophilia today. There are only four reports in the literature on the efficacy of elbow AS in haemophilic synovitis, all of them with a low grade of evidence [18–21]. Five elbows with moderate or severe haemophilia reported by Journeycake et al. [18] underwent AS when synovitis did not improve with prophylactic factor replacement. Each patient received aggressive physical rehabilitation and regular factor replacement for 6 weeks
17
following surgery. AS significantly reduced haemorrhage into the index joint and allowed for stabilization of joint range of motion. Therefore, they stated that this procedure should be considered in young haemophilia patients with chronic synovitis. Twenty-one elbows reported by Dunn et al. underwent AS [19]. The median age at surgery was 10 years. Joints with sufficient follow-up data showed a median bleeding frequency decline of 84%. Median arc of motion was stable or improved in the year after surgery. According to Verma et al. [20] AS must be indicated after failure of appropriate medical management with recurrent bleeding. The benefits of AS include the ability to perform adequate synovial debridement, but also concomitant lysis of adhesion and capsular release to regain range of motion. Results of AS demonstrated a significant decrease in episodes of haemarthrosis, and significant improvement in pain, range of motion and function. The primary predictor of outcome is degree of pre-existing degenerative changes within the joint. In more severe cases, the results of AS are unpredictable and serious consideration should be given to primary elbow arthroplasty. In a cost-benefit analysis, Tamuarian et al. [21] determined the financial efficacy of AS in haemophilia patients with recurrent haemarthroses. The average age of the patients was 8 years. In this series of patients with intermediate follow-up, AS was found to be cost effective in the treatment of patients with recurrent haemarthroses. Authors´ Experience In a 38-year period (1974–2012) one hundred and eight patients with synovitis affecting 179 elbow joints despite a 3-month trial of prophylactic substitution therapy, were treated by synovectomy. RSs were done on 164 elbows (93 patients), and 15 (15 patients) had a resection of the radial head and partial OS. Synovectomy (by any method) significantly reduced bleeding episodes, but did not halt the radiographic deterioration of the joints. It was thought that RS (Fig. 3) is the best choice for patients with persistent synovitis of the elbow unresponsive to a 3-month trial of prophylactic factor replacement. If three consecutive RSs with 6 months intervals had been ineffective, an OS should be indicated. For elbow haemophilic synovitis, we currently use Rhenium-186 at a dose of 30–40 megabecquerels (mBq) in children older than 12 years of age and 56–74 mBq in adults. The dose of radiation is 0.32 millisieverts (mSv) and 0.54 mSv, respectively. The recommended limit for patients (apart from natural sources) is 1 mSv per year. Although the dose of radiation of RS is minimal and neither articular nor systemic neoplastic changes related to RS have been reported so far, all patients must be counseled about malignancy concerns and given opportunity to consider risk/benefit ratios.
Fig. 3. The technique of elbow radiosynovectomy. The entry point is shown in the centre of the triangle formed by the lateral epicondyle, the radial head and the tip of the olecranon.
18
E.C. Rodriguez-Merchan / Thrombosis Research 132 (2013) 15–18
a
fails to control synovitis, an arthroscopic synovectomy must be indicated. Only in late stages of haemophilic arthropathy elbow fusion or total elbow arthroplasty should be carried out in cases of severe and incapacitating pain. Arthroscopic elbow debridement is an attractive alternative to the more commonly used surgical options of elbow fusion or total elbow arthroplasty. Conflict of Interest Statement No conflict of interest. References
b
Fig. 4. (a-b). Radiographs of an elbow (a) before performing an open surgical synovectomy and removal of a hypertrophic radial head (arrows) due to the severe lack of pronationsupination of the joint before surgery. (b) View of the joint after removal of the radial head (arrow).
When medical treatment fails my current recommendation is to use RS in children older than 12 years of age. Therefore, in children younger than 12 years of age an AS should be indicated. OS (Fig. 4) should be reserved for adults requiring a combined procedure, that is to say, radial head excision (due to a severe limitation of pronationsupination) and synovectomy in the same surgical session. Conclusions Prophylactic replacement therapy and physiotherapy are paramount to slow the development of elbow synovitis and arthropathy. Prophylactic treatment from ages 2 to 18 years could avoid the development of haemophilic arthropathy if the concentration of the patient´s deficient factor is prevented from falling below 1% of normal. Early treatment is of paramount importance because the immature skeleton is very sensitive to the complications of haemophilia; severe structural deficiencies may develop quickly. When synovitis develops, RS should be performed very early instead of an arthroscopic synovectomy. RS can be repeated up to three times with 6-month intervals. When RS
[1] Key NS, Negrier C. Coagulation factor concentrates: past, present, and future. Lancet 2007;370:439–48. [2] Manco-Johnson MJ, Abshire TC, Shapiro AD, Riske B, Hacker MR, Kilcoyne R, et al. Prophylaxis versus episodic treatment to prevent joint disease in boys with severe hemophilia. N Engl J Med 2007;357:535–44. [3] Dodson CC, Nho SJ, Williams III RJ, Altchek DW. Elbow arthroscopy. J Am Acad Orthop Surg 2008;16:574–85. [4] Hakobyan N, Kazarian T, Jabbar AA, Jabbar KJ, Valentino LA. Pathobiology of hemophilic synovitis I: overexpression of mdm2 oncogene. Blood 2004;104:2060–4. [5] Valentino LA, Hakobyan N, Kazarian T, Jabbar KJ, Jabbar AA. Experimental haemophilic synovitis: rationale and development of a murine model of human factor VIII deficiency. Haemophilia 2004;10:280–7. [6] Luck Jr JV, Silva M, Rodriguez-Merchan EC, Ghalambor N, Zahiri CA, Finn RS. Hemophilic arthropathy. J Am Acad Orthop Surg 2004;12:234–45. [7] Rodriguez-Merchan EC. Aspects of current management: orthopaedic surgery in haemophilia. Haemophilia 2012;18:8–16. [8] Rodriguez-Merchan EC. Radionuclide synovectomy (radiosynoviorthesis) in hemophilia: a very efficient and single procedure. Semin Thromb Hemost 2003;29: 97–100. [9] De la Corte-Rodriguez H, Rodriguez-Merchan EC, Jimenez-Yuste V. Radiosynovectomy in patients with chronic haemophilic synovitis: when is more than one injection necessary? Eur J Haematol 2011;86:430–5. [10] De la Corte-Rodriguez H, Rodriguez-Merchan EC, Jimenez-Yuste V. Radiosynovectomy in hemophilia: quantification of its effectiveness through the assessment of 10 articular parameters. J Thromb Haemost 2011;9:928–35. [11] De la Corte-Rodriguez H, Rodriguez-Merchan EC, Jimenez-Yuste V. What patient, joint and isotope characteristics influence the response to radiosynovectomy in patients with haemophilia? Haemophilia 2011;17:e990–8. [12] Radossi P, Baggio R, Petris U, De Biasi F, Risato R, Davoli PG, Tagariello G. Intra-articular ryfamicin in haemophilic arthropathy. Haemophilia 2003;9:60–3. [13] Forsyth AL, Quon DV, Konkle BA. Role of exercise and physical activity on haemophilic arthropathy, fall prevention and osteoporosis. Haemophilia 2011;17: e870–6. [14] De la Corte-Rodriguez H, Rodriguez-Merchan EC. The role of physical medicine and rehabilitation in haemophiliac patients. Blood Coagul Fibrinolysis 2013;24: 1–9. [15] Silva M, Luck Jr JV. Radial head excision and synovectomy in patients with hemophilia. J Bone Joint Surg Am 2007;89:2156–62. [16] Kamineni S, Adams RA, O'Driscoll SW, Morrey BF. Hemophilic arthropathy of the elbow treated by total elbow replacement. A case series. J Bone Joint Surg Am 2004;86-A:584–9. [17] Rampersad AG, Shapiro AD, Rodriguez-Merchan EC, Maahs JA, Akins S, Jimenez-Yuste V. Radiosynovectomy: review of the literature and report from two haemophilia treatment centers. Blood Coagul Fibrinolysis Mar 13 2013 [Epub ahead of print]. [18] Journeycake JM, Miller KL, Anderson AM, Buchanan GR, Finnegan M. Arthroscopic synovectomy in children and adolescents with haemophilia. J Pediatr Hematol Oncol 2003;25:726–31. [19] Dunn AL, Busch MT, Wyly JB, Sullivan KM, Abshire TC. Arthroscopic synovectomy for hemophilic joint disease in a pediatric population. J Pediatr Orthop 2004;24: 414–26. [20] Verma N, Valentino LA, Chawla A. Arthroscopic synovectomy in haemophilia: indications, technique and results. Haemophilia 2007;13(Suppl. 3):38–44. [21] Tamurian RM, Spencer EE, Wojtys EM. The role of arthroscopic synovectomy in the management of hemarthrosis in hemophilia patients: financial perspectives. Arthroscopy 2002;18:789–94.
Contents lists available at SciVerse ScienceDirect
Thrombosis Research journal homepage: www.elsevier.com/locate/thromres
Review Article
Haemophilic synovitis of the elbow: Radiosynovectomy, open synovectomy or arthroscopic synovectomy? E. Carlos Rodriguez-Merchan ⁎ Department of Orthopaedic Surgery, La Paz University Hospital, Madrid, Spain School of Medicine, Autonomous University, Madrid, Spain
a r t i c l e
i n f o
Article history: Received 31 March 2013 Received in revised form 21 May 2013 Accepted 26 May 2013 Available online 18 June 2013 Keywords: Haemophilia Synovitis Elbow Arthroscopic synovectomy Open synovectomy Radiosynovectomy
a b s t r a c t Arthroscopic synovectomy (AS) of the elbow, while providing similar pain relief to open synovectomy (OS), may place patients at higher risk for recurrence. The primary predictor of outcome is degree of pre-existing degenerative changes within the joint. Regarding haemophilia patients, radiosynovectomy (RS) is the best choice for patients with persistent synovitis of the elbow. In the elbow we recommend a dose of 30–40 megabecquerels (mBq) in children and a dose of 56–74 mBq in adults. If three consecutive RSs with 6 months intervals are ineffective, an AS or OS must be indicated. Synovectomy (by any method) significantly reduces bleeding episodes. Although the dose of radiation of RS is minimal, 0.32 millisieverts (mSv) in children, 0.54 mSv in adults, and neither articular nor systemic neoplastic changes related to RS have been reported so far, all patients must be given opportunity to consider risk/benefit ratios. Radiation dose due to natural sources is 2 mSv per year and the recommended limit for patients (apart from natural sources is 1 mSv per year). My current recommendation is to use RS in children older than 12 years of age. Therefore, in children younger than 12 years of age an AS should be indicated. OS should be reserved for adults requiring radial head excision (due to a severe limitation of pronation-supination) and synovectomy in the same surgical session. © 2013 Elsevier Ltd. All rights reserved.
Contents Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . The Haemophilic Elbow and its Manifestations and Treatment Options Pathogenesis of Synovitis and Cartilage Damage in Haemophilia . Treatment of Haemophilic Elbow Arthropathy . . . . . . . . . . Non-surgical Treatment . . . . . . . . . . . . . . . . . . . . Radiosynovectomy . . . . . . . . . . . . . . . . . . . Chemical Synovectomy . . . . . . . . . . . . . . . . . Rehabilitation . . . . . . . . . . . . . . . . . . . . . Surgical Treatment . . . . . . . . . . . . . . . . . . . . . . Authors´ Experience . . . . . . . . . . . . . . . . . . . . . . . . Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . Conflict of Interest Statement . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . . . . . . .
. . . . . . . . . . . . .
Introduction Routine prophylaxis is an important treatment strategy for patients with severe hemophilia [1–3]. When medical management fails to
⁎ Department of Orthopaedic Surgery, La Paz University Hospital, Paseo de la Castellana 261, 28046-Madrid, Spain. Tel.: +34 606712724. E-mail address: [email protected]. 0049-3848/$ – see front matter © 2013 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.thromres.2013.05.025
. . . . . . . . . . . . .
. . . . . . . . . . . . .
. . . . . . . . . . . . .
. . . . . . . . . . . . .
. . . . . . . . . . . . .
. . . . . . . . . . . . .
. . . . . . . . . . . . .
. . . . . . . . . . . . .
. . . . . . . . . . . . .
. . . . . . . . . . . . .
. . . . . . . . . . . . .
. . . . . . . . . . . . .
. . . . . . . . . . . . .
. . . . . . . . . . . . .
. . . . . . . . . . . . .
. . . . . . . . . . . . .
. . . . . . . . . . . . .
. . . . . . . . . . . . .
. . . . . . . . . . . . .
. . . . . . . . . . . . .
. . . . . . . . . . . . .
. . . . . . . . . . . . .
. . . . . . . . . . . . .
. . . . . . . . . . . . .
. . . . . . . . . . . . .
. . . . . . . . . . . . .
. . . . . . . . . . . . .
. . . . . . . . . . . . .
. . . . . . . . . . . . .
. . . . . . . . . . . . .
. . . . . . . . . . . . .
. . . . . . . . . . . . .
. . . . . . . . . . . . .
. . . . . . . . . . . . .
. . . . . . . . . . . . .
. . . . . . . . . . . . .
15 16 16 16 16 16 17 17 17 17 18 18 18
prevent the development of elbow synovitis, techniques such as radiosynovectomy (RS), arthroscopic synovectomy (AS) and open synovectomy (OS) can be used to manage chronic synovitis. If left untreated, haemophilic synovitis (Fig. 1) followed by degenerative changes within the elbow (Fig. 2) will occur and a stiff or painful joint will result. Controversy still exists, however, about the real efficacy of such procedures in haemophilic synovitis. The purpose of this review is to analyze the efficacy of different types of synovectomy in the haemophilic elbow.
16
E.C. Rodriguez-Merchan / Thrombosis Research 132 (2013) 15–18
The Haemophilic Elbow and its Manifestations and Treatment Options
Fig. 1. MRI of a haemophilic elbow showing severe chronic haemophilic sinovitis (arrows).
It is well known that in haemophilia the elbows tend to bleed beginning during an early age of 2–5 years. The synovium is only able to reabsorb a small amount of intra-articular blood; if the amount of blood is excessive, the synovium will hypertrophy as a compensating mechamism, so that eventually the affected joint will show an increase in size of the synovium: so-called hypertrophic chronic haemophilic synovitis. The hypertrophic synovium is very richly vascularized, so that small injuries will easily make the joint re-bleed. The final result will be the classic vicious cycle of haemarthrosis-synovitis-haemarthrosis, which eventually will result in elbow haemophilic arthropathy. The best way that we have today to protecting against haemophilic arthropathy (cartilage damage) is primary haematological prophylaxis (from cradle to college). Starting prophylaxis gradually with onceweekly injections has the presumed advantage of avoiding use of a central venous access device, which is often necessary for frequent injections in very young boys. The decision to institute early full prophylaxis by means of a port has to be balanced against the child’s bleeding tendency, the family’s social situation and the experience of the specific haemophilia centre. The reported complication rates for infection and thrombosis have varied considerably from centre to centre. Risk of infection can be reduced by repeated education of patients and staff, effective surveillance routines and limitations on the number of individuals allowed to use the device. In discussing options for early therapy, the risks and benefits should be thoroughly discussed with the parents. Pathogenesis of Synovitis and Cartilage Damage in Haemophilia Hakobyan et al. [4] analyzed the pathogenesis of haemophilic synovitis in a murine model of human haemophilia A. The authors concluded that molecular changes induced by iron in the blood may be the basis of the increase in cell proliferation and the development of haemophilic synovitis. Valentino et al. [5] showed that controlled, blunt trauma to the joints consistently resulted in joint swelling, because of a combination of bleeding and inflammation. Haemosiderin was found in the synovial membrane after provoking a controlled blunt trauma to the joints. Similar to haemartrosis in human haemophilia, joint bleeding resulted in acute morbidity evidenced by inactivity, weight loss and immobility. Despite the fact that the two aforementioned papers are very interesting with regard to the understanding of haemophilic synovitis and the initial stages of cartilage damage in haemophilic joints, the link between both phenomena, is still very poorly understood. In fact, previous studies have shown that synovitis is not primarily responsible for the cartilage damage after intra-articular bleeding, but rather that the exposure of cartilage to blood induces direct adverse effects. Treatment of Haemophilic Elbow Arthropathy Patients with mild to moderate pain are often helped by using elbow orthoses, but symptomatic and incapacitated patients require arthroscopic elbow debridement, arthrodesis or arthroplasty [6,7]. Non-surgical Treatment Conservative treatment includes radiosynovectomy, chemical synovectomy, and rehabilitation (physiotherapy, orthoses). Conservative treatment should always be attempted prior to surgery [6,7].
Fig. 2. (a-b). Radiographs showing moderate arthropathy of an elbow (a) and severe arthropathy (b) of the same elbow 17 years later.
Radiosynovectomy From a practical point of view, radiosynovectomy (RS), together with primary prophylaxis to avoid joint bleeding, can help halt
E.C. Rodriguez-Merchan / Thrombosis Research 132 (2013) 15–18
haemophilic synovitis. Ideally, however, RS should be performed before the articular cartilage has eroded. RS is a relatively simple, virtually painless and inexpensive treatment for chronic haemophilic synovitis, even in patients with inhibitors and is the best choice for patients with persistent synovitis. RS consists of destruction of synovial tissue by intra-articular injection of a radioactive agent. Radioactive substances have been used for the treatment of chronic haemophilic synovitis for many years [8]. The indication for a RS is chronic haemophilic synovitis causing recurrent haemarthroses, unresponsive to haematological treatment. On average, the efficacy of the procedure ranges from 70-75%, and can be performed at any age. The procedure slows the cartilaginous damage which intra-articular blood tends to produce in the long-term. Probably the first treatment to be considered for recurrent elbow haemarthroses is RS. This consists of the injection of a radioactive material (yttrium-90 or phophorus-32) into the joint [8–11]. RS can be repeated up to three times with 6-month intervals. The most common radioactive materials used are Yttrium-90, Phosphorus32 and Rhenium-186. After 40 years of using radiation synovectomy worldwide, no damage has been reported in relation to the radioactive materials. Chemical Synovectomy Radossi et al. [12] have used intra-articular injections of ryfamicin. In Radossi et al.´s series there were five patients with inhibitors to factor VIII (three high responders and two low responders). Their average age was 34 years (range 15–60 years). Ryfamicin (250 mg) was diluted in 10 mL of saline solution and 1-5 mL was then injected into the joint. There are two main limitations for the use of antibiotics in ryfamicin synovectomy: the procedure is painful, and it should be repeated weekly for many weeks to be effective. Rehabilitation The importance of preoperative and postoperative rehabilitation of the elbow joint in haemophilia must be emphasized. Children must utilize the resources available and seek early consultation with their centre rehabilitation physician and/or physiotherapist. Using the techniques avalible, rehabilitation has been shown to speed recovery, reduce pain and prevent contractures. Physiotherapy is important in elbow rehabilitation of patients following surgical procedures and the physiotherapist must work closely with the orthopaedic surgeon [13,14]. Surgical Treatment The most common surgical approaches performed at the elbow joint are arthroscopic synovectomy, arthroscopic joint debridement, arthroplasty and arthrodesis [6,7,15,16]. When RS fails to control synovitis, an arthroscopic synovectomy must be indicated [8–11,17]. Sometimes a large radial head can cause severe loss of pronation-supination. Surgical removal of the hypertrophic radial head is sometimes indicated [15]. In advanced haemophilic arthropathy, an elbow arthrodesis or total elbow arthroplasty should be considered [7,8,15,16]. The main indications for these are intractable pain not relieved by alternative treatments and severe deformity. Regular prophylactic transfusions of clotting factor may prevent recurrent bleeds and further development of haemarthrosis. Elbow arthrodesis and elbow arthroplasty are rarely performed in haemophilia today. There are only four reports in the literature on the efficacy of elbow AS in haemophilic synovitis, all of them with a low grade of evidence [18–21]. Five elbows with moderate or severe haemophilia reported by Journeycake et al. [18] underwent AS when synovitis did not improve with prophylactic factor replacement. Each patient received aggressive physical rehabilitation and regular factor replacement for 6 weeks
17
following surgery. AS significantly reduced haemorrhage into the index joint and allowed for stabilization of joint range of motion. Therefore, they stated that this procedure should be considered in young haemophilia patients with chronic synovitis. Twenty-one elbows reported by Dunn et al. underwent AS [19]. The median age at surgery was 10 years. Joints with sufficient follow-up data showed a median bleeding frequency decline of 84%. Median arc of motion was stable or improved in the year after surgery. According to Verma et al. [20] AS must be indicated after failure of appropriate medical management with recurrent bleeding. The benefits of AS include the ability to perform adequate synovial debridement, but also concomitant lysis of adhesion and capsular release to regain range of motion. Results of AS demonstrated a significant decrease in episodes of haemarthrosis, and significant improvement in pain, range of motion and function. The primary predictor of outcome is degree of pre-existing degenerative changes within the joint. In more severe cases, the results of AS are unpredictable and serious consideration should be given to primary elbow arthroplasty. In a cost-benefit analysis, Tamuarian et al. [21] determined the financial efficacy of AS in haemophilia patients with recurrent haemarthroses. The average age of the patients was 8 years. In this series of patients with intermediate follow-up, AS was found to be cost effective in the treatment of patients with recurrent haemarthroses. Authors´ Experience In a 38-year period (1974–2012) one hundred and eight patients with synovitis affecting 179 elbow joints despite a 3-month trial of prophylactic substitution therapy, were treated by synovectomy. RSs were done on 164 elbows (93 patients), and 15 (15 patients) had a resection of the radial head and partial OS. Synovectomy (by any method) significantly reduced bleeding episodes, but did not halt the radiographic deterioration of the joints. It was thought that RS (Fig. 3) is the best choice for patients with persistent synovitis of the elbow unresponsive to a 3-month trial of prophylactic factor replacement. If three consecutive RSs with 6 months intervals had been ineffective, an OS should be indicated. For elbow haemophilic synovitis, we currently use Rhenium-186 at a dose of 30–40 megabecquerels (mBq) in children older than 12 years of age and 56–74 mBq in adults. The dose of radiation is 0.32 millisieverts (mSv) and 0.54 mSv, respectively. The recommended limit for patients (apart from natural sources) is 1 mSv per year. Although the dose of radiation of RS is minimal and neither articular nor systemic neoplastic changes related to RS have been reported so far, all patients must be counseled about malignancy concerns and given opportunity to consider risk/benefit ratios.
Fig. 3. The technique of elbow radiosynovectomy. The entry point is shown in the centre of the triangle formed by the lateral epicondyle, the radial head and the tip of the olecranon.
18
E.C. Rodriguez-Merchan / Thrombosis Research 132 (2013) 15–18
a
fails to control synovitis, an arthroscopic synovectomy must be indicated. Only in late stages of haemophilic arthropathy elbow fusion or total elbow arthroplasty should be carried out in cases of severe and incapacitating pain. Arthroscopic elbow debridement is an attractive alternative to the more commonly used surgical options of elbow fusion or total elbow arthroplasty. Conflict of Interest Statement No conflict of interest. References
b
Fig. 4. (a-b). Radiographs of an elbow (a) before performing an open surgical synovectomy and removal of a hypertrophic radial head (arrows) due to the severe lack of pronationsupination of the joint before surgery. (b) View of the joint after removal of the radial head (arrow).
When medical treatment fails my current recommendation is to use RS in children older than 12 years of age. Therefore, in children younger than 12 years of age an AS should be indicated. OS (Fig. 4) should be reserved for adults requiring a combined procedure, that is to say, radial head excision (due to a severe limitation of pronationsupination) and synovectomy in the same surgical session. Conclusions Prophylactic replacement therapy and physiotherapy are paramount to slow the development of elbow synovitis and arthropathy. Prophylactic treatment from ages 2 to 18 years could avoid the development of haemophilic arthropathy if the concentration of the patient´s deficient factor is prevented from falling below 1% of normal. Early treatment is of paramount importance because the immature skeleton is very sensitive to the complications of haemophilia; severe structural deficiencies may develop quickly. When synovitis develops, RS should be performed very early instead of an arthroscopic synovectomy. RS can be repeated up to three times with 6-month intervals. When RS
[1] Key NS, Negrier C. Coagulation factor concentrates: past, present, and future. Lancet 2007;370:439–48. [2] Manco-Johnson MJ, Abshire TC, Shapiro AD, Riske B, Hacker MR, Kilcoyne R, et al. Prophylaxis versus episodic treatment to prevent joint disease in boys with severe hemophilia. N Engl J Med 2007;357:535–44. [3] Dodson CC, Nho SJ, Williams III RJ, Altchek DW. Elbow arthroscopy. J Am Acad Orthop Surg 2008;16:574–85. [4] Hakobyan N, Kazarian T, Jabbar AA, Jabbar KJ, Valentino LA. Pathobiology of hemophilic synovitis I: overexpression of mdm2 oncogene. Blood 2004;104:2060–4. [5] Valentino LA, Hakobyan N, Kazarian T, Jabbar KJ, Jabbar AA. Experimental haemophilic synovitis: rationale and development of a murine model of human factor VIII deficiency. Haemophilia 2004;10:280–7. [6] Luck Jr JV, Silva M, Rodriguez-Merchan EC, Ghalambor N, Zahiri CA, Finn RS. Hemophilic arthropathy. J Am Acad Orthop Surg 2004;12:234–45. [7] Rodriguez-Merchan EC. Aspects of current management: orthopaedic surgery in haemophilia. Haemophilia 2012;18:8–16. [8] Rodriguez-Merchan EC. Radionuclide synovectomy (radiosynoviorthesis) in hemophilia: a very efficient and single procedure. Semin Thromb Hemost 2003;29: 97–100. [9] De la Corte-Rodriguez H, Rodriguez-Merchan EC, Jimenez-Yuste V. Radiosynovectomy in patients with chronic haemophilic synovitis: when is more than one injection necessary? Eur J Haematol 2011;86:430–5. [10] De la Corte-Rodriguez H, Rodriguez-Merchan EC, Jimenez-Yuste V. Radiosynovectomy in hemophilia: quantification of its effectiveness through the assessment of 10 articular parameters. J Thromb Haemost 2011;9:928–35. [11] De la Corte-Rodriguez H, Rodriguez-Merchan EC, Jimenez-Yuste V. What patient, joint and isotope characteristics influence the response to radiosynovectomy in patients with haemophilia? Haemophilia 2011;17:e990–8. [12] Radossi P, Baggio R, Petris U, De Biasi F, Risato R, Davoli PG, Tagariello G. Intra-articular ryfamicin in haemophilic arthropathy. Haemophilia 2003;9:60–3. [13] Forsyth AL, Quon DV, Konkle BA. Role of exercise and physical activity on haemophilic arthropathy, fall prevention and osteoporosis. Haemophilia 2011;17: e870–6. [14] De la Corte-Rodriguez H, Rodriguez-Merchan EC. The role of physical medicine and rehabilitation in haemophiliac patients. Blood Coagul Fibrinolysis 2013;24: 1–9. [15] Silva M, Luck Jr JV. Radial head excision and synovectomy in patients with hemophilia. J Bone Joint Surg Am 2007;89:2156–62. [16] Kamineni S, Adams RA, O'Driscoll SW, Morrey BF. Hemophilic arthropathy of the elbow treated by total elbow replacement. A case series. J Bone Joint Surg Am 2004;86-A:584–9. [17] Rampersad AG, Shapiro AD, Rodriguez-Merchan EC, Maahs JA, Akins S, Jimenez-Yuste V. Radiosynovectomy: review of the literature and report from two haemophilia treatment centers. Blood Coagul Fibrinolysis Mar 13 2013 [Epub ahead of print]. [18] Journeycake JM, Miller KL, Anderson AM, Buchanan GR, Finnegan M. Arthroscopic synovectomy in children and adolescents with haemophilia. J Pediatr Hematol Oncol 2003;25:726–31. [19] Dunn AL, Busch MT, Wyly JB, Sullivan KM, Abshire TC. Arthroscopic synovectomy for hemophilic joint disease in a pediatric population. J Pediatr Orthop 2004;24: 414–26. [20] Verma N, Valentino LA, Chawla A. Arthroscopic synovectomy in haemophilia: indications, technique and results. Haemophilia 2007;13(Suppl. 3):38–44. [21] Tamurian RM, Spencer EE, Wojtys EM. The role of arthroscopic synovectomy in the management of hemarthrosis in hemophilia patients: financial perspectives. Arthroscopy 2002;18:789–94.