Rheumatol Int (2012) 32:2363–2366 DOI 10.1007/s00296-011-1970-3
O R I G I N A L A R T I CL E
Frequency of musculoskeletal complications among the patients receiving solid organ transplantation in a tertiary health-care center ShaWeh Movassaghi · Mohsen Nasiri Toosi · Alireza Bakhshandeh · Fatemeh Niksolat · Zahra Khazaeipour · Ali Tajik
Received: 2 August 2010 / Accepted: 22 May 2011 / Published online: 5 June 2011 © Springer-Verlag 2011
Abstract Solid organ transplantation is an important lifesaving procedure mainly performed in patients with endstage organ failure such as liver cirrhosis, congestive heart failure, and end-stage renal disease. While these complications are among the most preventable adverse eVects of solid organ transplantation, these are generally neglected by physicians. Accordingly, this study was performed to evaluate the frequency of musculoskeletal complications among the patients receiving solid organ transplantation in a tertiary health-care center in a developing country. This cohort study was performed from 2000 to 2009, among Wfty patients receiving organ transplantation (liver, heart, and lung) attending to a training hospital in Tehran, Iran. The main variables were musculoskeletal complaints and Wndings that were measured according to patients’ self-report and clinical examination. The mean age of the patients was 40.2 § 10.9 years ranging from 5 to 58 years. Twenty out of 50 patients (40%) had musculoskeletal complaints that the most common complaint was the arthralgia. Also, the mechanical arthritis was the most common clinical Wnding in clinical examination (24%). Low serum level of vitamin D (74.4%) and high serum alkaline phosphatase level (27.9%) were the most common biochemical abnormalities in understudy population. Finally, it may be concluded that nearly forty percent of patients receiving solid organ transplantation may develop musculoskeletal Wndings and/or complaints. These complications may be found and treated with regular examinations to reduce the burden of disease.
S. Movassaghi · M. Nasiri Toosi · A. Bakhshandeh · F. Niksolat (&) · Z. Khazaeipour · A. Tajik Imam-Khomeini Hospital, Tehran, Iran e-mail:
[email protected]
Keywords Transplantation · Complications · Musculoskeletal · Liver · Heart · Lung
Introduction Solid organ transplantation is an important lifesaving procedure mainly performed in patients with end-stage organ failure such as liver cirrhosis, congestive heart failure, and end-stage renal disease [1]. While this procedure would results in a better longtime somatic function, the short-time outcomes and early postoperative and intraoperative complications may result in numerous problems in post-transplantation phase [2–4]. Predominantly, the patients under solid organ transplantation experience infections (due to use of immunosuppressors and decrease humoral and cellular immunity), neurological complications (due to drug-induced neuropathies), pulmonary adverse eVects [5–8], and many other complications [9–11]. These complications would result in a poor prognosis and subsequently decreased quality of life and sometimes transplant rejection that may lead to increased health service costs and increased mortality and morbidity [2, 12, 13]. Hence, prevention from these side eVects is an issue of importance in patients under solid organ transplantation. One of the less considered complications of solid organ transplantation is orthopedic or musculoskeletal complications [1, 14]. These adverse eVects are probable to happen especially in patients due to elongated immobility, extensive use of immunosuppressor agents resulting in a decreased bone density, long pre-transplantation period, renal insuYciency, secondary hyperparathyroidism, and many known and unknown etiological causes [15–17]. These patients generally have decreased bone density
123
2364
especially in Wrst year of life that may results in an increased incidence of skeletal fractures [18]. While these complications are among the most preventable adverse eVects of solid organ transplantation, these are generally neglected by physicians [1, 14]. Also, the ethnic diVerences in post-transplantation complications are a motive to conduct studies in diVerent geographical regions [19, 20]. Accordingly, this study was performed to evaluate the frequency of musculoskeletal complications among the patients receiving solid organ transplantation in a tertiary health-care center in a developing country.
Materials and methods This study was performed as a retrospective, prospective cohort. From 2000 to 2009, Wfty patients receiving organ transplantation (liver, heart, and lung) attending to a training hospital in Tehran, Iran, were recruited. The study was approved by medical ethics committee of Tehran University of Medical Sciences. The patients in the transplant rejection status and those passed less than 1 month from their transplantation procedure were excluded. The patients were consecutively enrolled. Evaluated variables were age, sex, job, duration of disease before transplantation, duration passed from the transplantation, cause of transplantation, background disease, therapeutic regimen, cumulative dose of corticosteroid, musculoskeletal complaints and Wndings, biochemical parameters, and bone mineral density indices. The main variables were musculoskeletal complaints and Wndings that were measured according to patients’ self-report and clinical examination. All the bone mineral densitometries and biochemical assessments were performed by single technician and single device. Densities of L1–L4, total femoral, femoral neck, and minimum lumbar densities were measured, and values equal or less than ¡2.5 were considered as osteoporosis and values from ¡1 to ¡2.5 were considered as osteopenia. The used kits and normal range for biochemical parameters are mentioned in Table 1. Data from 50 patients were analyzed using SPSS (version 18.0) software [Statistical Procedures for Social Sciences; Chicago, Illinois, USA]. DiVerences were tested by independent-sample t, Spearman, Mann–Whitney, and chi-square tests and were considered statistically signiWcant at P values less than 0.05.
Results In this study, 50 patients who underwent organ transplantation (including 23 cases of liver, 26 cases of heart, and one case of lung transplantation) were evaluated. Among them,
123
Rheumatol Int (2012) 32:2363–2366 Table 1 Kits and normal range for biochemical parameters Complaints
Normal range
Kit (country)
Method
Uric acid
·6 (women)/ ·7 (men)
Biosystem (Spain) Calorimetric
Calcium
8.4–10.2 mg/dl Parsasmun (Iran)
Phosphorous
2.5–5 mg/dl
Parsasmun (Iran)
Calorimetric
Alkaline phosphatase
60–306 mg/dl
Parsasmun (Iran)
Calorimetric
Liasion (Italia)
CLIA
25-OH vitamin D >20 ng/ml
Calorimetric
data for 43 patients were complete (including 21 cases of liver, 21 cases of heart, and one case of lung transplantation) and remaining seven subjects had only baseline data. The mean age of the patients was 40.2 § 10.9 years ranging from 5 to 58 years (37.2 § 12.3, 43.7 § 8.7, and 38 years, in heart, liver, and lung transplantation, respectively); 76.9% in heart transplantation group, 47.8% in liver transplantation group and the only patient in lung transplantation group were men. Eight patients including 26.9% in heart transplantation group and 4.3% in liver transplantation group had no job. The mean duration of disease before transplantation was 51 § 61.15 months ranging from 4 months to 30 years (67 § 80.2 and 50 § 42.2 months in liver and heart transplantation, respectively [P = 0.3]). The mean duration passed from the transplantation was 25 § 18 months ranging from 1 to 10 years (21.6 § 21.4 and 24.8 § 21 months in liver and heart transplantation, respectively [P = 0.5]). Totally three cases of acute rejection (two in heart and one in liver transplantation) and nine cases of chronic rejection (Wve in heart [two times in one patients] and three in liver transplantation) were seen. The most common cause of heart transplant was cardiomyopathy, and lung transplantation was performed due to cystic Wbrosis. But in liver transplant group, there were two cases of PBC, seven cases of hepatitis B infection, Wve cases of autoimmune hepatitis, six cases of hepatitis C infection, and three cases of cryptogenic hepatitis. Totally 31 patients (62%) received cyclosporine (including 25, 5, and one patients under heart, liver, and lung transplant) and the remaining 38% were received tacrolimus. None of the patients had history of rheumatologic disorder, and only one patient had previous history of background disease that was seen as schizophrenia. The mean cumulative dose of corticosteroid was 1,355 § 306.3 mg. While the only patient under lung transplantation had no musculoskeletal complaint, the most common musculoskeletal complaint among the other patients was joint pain (Table 2). Also, the mechanical arthritis was the most common clinical Wnding among understudy patients (Table 3).
Rheumatol Int (2012) 32:2363–2366
2365
Table 2 Musculoskeletal complaint among transplantation recipients Complaints
Table 5 Frequency of biochemical disturbance, osteopenia, and osteoporosis among transplantation recipients
Heart transplant
Liver transplant
Total
Joint pain
8 (30%)
6 (26%)
14 (28%)
Joint swelling
1 (3.8%)
0
1 (2%)
Hypercalcemia
Muscular weakness
1 (3.8%)
1 (4.3%)
2 (4%)
Hypocalcemia
Fracture
1 (3.8%)
1 (4.3%)
2 (4%)
Hyperphosphatemia
1 (2%)
High alkaline phosphatase
Skeletal pain
0
1 (4.3%)
Complaint
Heart transplant
Liver transplant
1 (4.8%)
1 (4.8%)
2 (4.6%)
1 (4.8%)
0
1 (2.2%)
5 (23.8%)
1 (4.8%)
6 (13.9%)
4 (19%)
8 (38.1%)
12 (27.9%)
Low vitamin D
14 (66.6%)
17 (80.9%)
32 (74.4%)
Hyperuricemia
4 (19%)
3 (14.2%)
8 (18.6%)
12 (57.1%)
6 (28.5%)
21 (48.8%)
2 (9.5%)
9 (42.8%)
11 (25.5%)
Table 3 Musculoskeletal Wndings among transplantation recipients
Osteopenia
Complaints
Osteoporosis
Heart transplant
Liver transplant
Total
Periarthritis
2 (7.7%)
1 (4.3%)
3 (6%)
Myopathy
1 (3.8%)
1 (4.3%)
2 (4%)
Mechanical arthritis
6 (23%)
6 (26%)
12 (24%)
Table 4 Biochemical parameters among transplantation recipients Biochemical parameter Uric acid
Calcium
Phosphorous
Alkaline phosphatase
25-OH vitamin D
Mean
Standard deviation
Heart
5.7
1.1
Liver
5.1
1.3
Total
5.5
1.3
Heart
9.5
0.5
Liver
9.3
0.4
Total
9.3
0.5
Heart
4.6
0.6
Liver
4
0.9
Total
4.3
0.8
Heart
228.4
90.4
Liver
328.1
306.1
Total
281
223
Heart
17.8
10.5
Liver
14.3
9.6
Total
15.9
P value
0.11
0.19
0.011
0.19
0.26
10
However, the lung transplant recipient had no clinical musculoskeletal Wnding. The only biochemical measurement diVered between heart and liver transplantation was phosphorous (Table 4). The frequency of biochemical disturbances, osteopenia, and osteoporosis is shown in Table 5.
Discussion The prevalence of musculoskeletal symptoms is relatively high in patients receiving solid organ transplantation leading to a decreased quality of life and increased mortality
Total
and morbidity, but these complications are generally neglected. So, in current study, we evaluated the frequency of musculoskeletal Wndings and complaints among patients receiving solid organ transplantation. We found that 20 out of 50 patients (40%) had musculoskeletal complaints that the most common complaint was the arthralgia. Also, the mechanical arthritis was the most common clinical Wnding in clinical examination (24%). Low serum level of vitamin D (74.4%) and high serum alkaline phosphatase level (27.9%) were the most common biochemical abnormalities in understudy population. We had no death report in this study. But previous studies have reported nearly 7% mortality rate [1]. Also, we had no case of non-traumatic fracture in our study. Diep et al. [14] reported that arthralgia and myalgia were the most common diagnoses as well as our study. Also, they found that hyperuricemia was common that this biochemical Wnding was in third order in our study. They believed that arthralgia is presumably secondary to tacrolimus/sirolimus; osteoarthritis, and peripheral neuropathy [14]. Unterman et al. [1] showed that gastrointestinal symptoms were the most common complications after liver transplantation and the musculoskeletal adverse eVects reported to be very uncommon. But we found that four out of each ten patients receiving solid organ transplantation would develop musculoskeletal symptoms. In a study by Egan et al. [21] in Republic of Ireland, it was demonstrated that twenty percent of patients receiving cardiac transplantation developed orthopedic complications including avascular necrosis of the hip, soft tissue infections, osteoporosis, stress fractures, osteomyelitis and osteomalacia. They reported that the mainly the patients who develop bony complications have had increased doses of steroids for episodes of rejection as well as our study. However, among the reported complications by them, we found only the osteoporosis. Also, the prevalence of complications in our study was relatively twofold higher than that reported by them.
123
2366
Another study by Johnson et al. [22] in United Kingdom showed that relatively ten percent of patients under cardiothoracic transplantation had orthopedic complaints that this incidence rate is one-fourth of frequency obtained in our study. They also supposed that musculoskeletal problems after cardiothoracic transplantation do not place an excessive burden to patients that may be congruent with Wndings in current study [22]. However, the patients under liver transplantation may develop numerous adverse eVects, but there are few reports about the musculoskeletal symptoms among them [23, 24]. While only one patient receiving lung transplantation was evaluated in this study, he experienced no musculoskeletal complication. Lifetime prognosis of patients receiving solid organ transplantation is generally good, but in the other hand, it may be very poor especially in patients remaining treatment-dependent for a lifetime [25]. In the absence of proper interventional strategies before transplantation, musculoskeletal complications can intensify after the transplantation, as a result of continued poor nutrition intake, bed rest, and pharmacotherapies [26] that this matter shows the importance of interventional strategies for reduction in musculoskeletal complications after solid organ transplantation to improve the postoperative management outcomes [27] and decrease the health-care costs [28]. In current study, we found that up to 75 percent of patients may develop biochemical abnormalities that this frequency was reported to be very less than ours and even less than ten percent [1]. This matter may be due some technical insuYciencies and/or due to inclusion of patients in our study without respecting their biochemical history. Finally, according to the obtained results in this study, it may be concluded that nearly forty percent of patients receiving solid organ transplantation may develop musculoskeletal Wndings and/or complaints especially joint pain, respectively. These complications may be found and treated with regular examinations to reduce the burden of disease. However, further studies should be carried out to determine the contributing factors for musculoskeletal complications in patients receiving solid organ transplantation.
References 1. Unterman S, Zimmerman M, Tyo C et al (2009) A descriptive analysis of 1251 solid organ transplant visits to the emergency department. West J Emerg Med 10:48–54 2. Rosenblum DS, Rosen ML, Pine ZM, Rosen SH, Borg-Stein J (1993) Health status and quality of life following cardiac transplantation. Arch Phys Med Rehabil 74:490–493 3. Evans RW, Kitzmann DJ (1997) Contracting for services: liver transplantation in the era of mismanaged care. Clin Liver Dis 1:287–303 4. Evans RW (1995) Liver transplantation in a managed care environment. Liver Transpl Surg 1:61–75
123
Rheumatol Int (2012) 32:2363–2366 5. Patel R, Paya CV (1997) Infections in solid-organ transplant recipients. Clin Microbiol Rev 10:86–124 6. Montoya JG, Giraldo LF, Efron B et al (2001) Infectious complications among 620 consecutive heart transplant patients at Stanford University Medical Center. Clin Infect Dis 33:629–640 7. Hotson JR, Pedley TA (1976) The neurological complications of cardiac transplantation. Brain 99:673–694 8. O’Brien JD, Ettinger NA (1996) Pulmonary complications of liver transplantation. Clin Chest Med 17:99–114 9. Zhao J, Yan L, Li B et al (2009) Diabetes mellitus after living donor liver transplantation: data from mainland China. Transplant Proc 41:1756–1760 10. Teixido M, Kron TK, Plainse M (1990) Head and neck sequelae of cardiac transplantation. Laryngoscope 100:231–236 11. Ng P, McCluskey P, McCaughan G, Glanville A, MacDonald P, Keogh A (1998) Ocular complications of heart, lung, and liver transplantation. Br J Ophthalmol 82:423–428 12. Ammori JB, Pelletier SJ, Mathur A et al (2008) Financial implications of surgical complications in pediatric liver transplantation. Pediatr Transplant 12:174–179 13. Ammori JB, Pelletier SJ, Lynch R et al (2008) Incremental costs of post-liver transplantation complications. J Am Coll Surg 206:89–95 14. Diep JT, Kerr LD, Barton C, Emre S (2008) Musculoskeletal manifestations in liver transplantation recipients. J Clin Rheumatol 14:257–260 15. Fahrleitner A, Prenner G, Kniepesis O et al (2002) Serum osteoprotegrin levels in Patients after live transplantation. Wein klin wochenschr 114:717–724 16. Shane E, Rivas M, Donald J et al (1997) Bone loss and turnover after cardiac transplantation. J Clin End 82:1497–1501 17. Lindsy R (2004) Bone loss after cardiac transplantation. NEJM 350:751–754 18. Radino M, Shane E (1998) Osteoporosis after organ transplantation. Am J Med 104:459–469 19. Higgins RSD, Fishman JA (2006) Disparities in solid organ transplantation for ethnic minorities: facts and solutions. Am J Transplant 6:2556–2562 20. Showstack J, Katz PP, Lake JR et al (1999) Resource utilization in liver transplantation: eVects of patient characteristics and clinical practice. NIDDK Liver Transplantation Database Group. JAMA 281:1381–1386 21. Egan B, O’Byrne JM, O’Farrell D et al (1996) Orthopaedic complications following cardiac transplantation. Ir Med J 89:26–27 22. Johnson DS, Meadows TH (1997) Orthopaedic referrals from a cardiothoracic transplant population. Ann R Coll Surg Engl 79:134–137 23. Tager AM, Ginns LC (1996) Complications of lung transplantation. Crit Care Nurs Clin North Am 8:273–292 24. Schoch OD, Speich R, Schmid C et al (2000) Osteonecrosis after lung transplantation: cystic Wbrosis as a potential risk factor. Transplantation 69:1629–1632 25. Hetzer R, Albert W, Hummel M et al (1997) Status of patients presently living 9 to 13 years after orthotopic heart transplantation. Ann Thorac Surg 64:1661–1668 26. Vintro AQ, KrasnoV JB, Painter P (2002) Roles of nutrition and physical activity in musculoskeletal complications before and after liver transplantation. AACN Clin Issues 13:333–347 27. Wood DE, Raghu G (1997) Lung transplantation. Part II. Postoperative management and results. West J Med 166:45–55 28. Foxton MR, Al-Freah MA, Portal AJ et al (2010) Increased model for end-stage liver disease score at the time of liver transplant results in prolonged hospitalization and overall intensive care unit costs. Liver Transpl 16:668–677