|Year : 2016 | Volume
| Issue : 2 | Page : 111-114
Analysis of 16 teenage patients with sickle cell anemia and musculoskeletal complications
Aref Hosseinian Amiri1, Ramin Shekarriz2, Maryam Yazdanian3
1 Department of Rheumatology, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Mazandaran, Iran
2 Department of Hematology, Imam Khomeini Hospital, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Mazandaran, Iran
3 Department of Environment Health, Azad University, Sari, Mazandaran, Iran
|Date of Web Publication||5-Jul-2016|
Aref Hosseinian Amiri
Department of Rheumatology, Imam Khomeini Hospital, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari
Source of Support: None, Conflict of Interest: None
Background: Sickle cell anemia is a genetic hematological disorder characterized by red blood cell abnormalities including rigidity and sickling. Once a sufficient number of rigid sickle cells are formed, microvascular occlusion would result that leads to tissue ischemia and infarction and progressive end organ damage.
Aim: The aim of this study was to analyze 16 teenage patients with sickle cell disease to determine the pattern of musculoskeletal complications during 2 years.
Materials and Methods: This is a retrospective study of cases of musculoskeletal complications among sickle cell anemic patients who referred to the rheumatologic clinic of Mazandaran University of Medical Sciences from January 2010 to December 2012 (during a 2-year period). Data were analyzed using the SPSS version 20. Variables analyzed included age, sex, and kind of musculoskeletal complications.
Results: There were 16 sickle cell patients referring to our rheumatologic clinic for musculoskeletal complications during the study period. All were teenage patients, aged between 12 and 17 years, with a median age of 14.6 years. Twelve patients were male and four patients were female. The most common musculoskeletal complications were: Acute painful crisis in 10 (62.5%), osteomyelitis in 3 (18.5%), dactilitis in 4 (25%), avascular necrosis of bones in 6 (37.5%), stress fractures and vertebral collapse in 2 (12.5%), septic arthritis in 1 (0.6%) patient, and hyperuricemia/gout arthritis in 3 (18.5%) patients.
Conclusion: Serious musculoskeletal complications of sickle cell anemia are very important and must be considered in these patients. Painful crisis and avascular necrosis of bones are the common rheumatologic complications of this disorder.
Keywords: Hemoglobinopathy, musculoskeletal complications, sickle cell anemia
|How to cite this article:|
Amiri AH, Shekarriz R, Yazdanian M. Analysis of 16 teenage patients with sickle cell anemia and musculoskeletal complications. J NTR Univ Health Sci 2016;5:111-4
|How to cite this URL:|
Amiri AH, Shekarriz R, Yazdanian M. Analysis of 16 teenage patients with sickle cell anemia and musculoskeletal complications. J NTR Univ Health Sci [serial online] 2016 [cited 2022 Jan 19];5:111-4. Available from: https://www.jdrntruhs.org/text.asp?2016/5/2/111/185438
| Introduction|| |
Sickle cell anemia is an autosomal recessive hemoglobinopathy associated with chronic hemolytic anemia and rheumatic manifestations. Both homozygous sickle cell anemia (Hb SS) and the heterozygous types, including sickle-beta thalassemia, sickle-C (S-C) disease, and sickle-D (S-D) disease, can cause rheumatologic manifestations. SS disease occurs mostly in Africans, but is also prevalent in southern Italy, Greece, Turkey, Saudi Arabia, and India. 
Sickle cell anemia is characterized by red blood cells assuming an abnormal, rigid, and sickle shape.  Hypoxia results in polymerization of HbS, forming liquid crystals. This deforms the red cells from biconcave disks into elongated, rigid, crescent-shaped sickle cells, causing hemolysis and occlusion of the microcirculation that, in turn, leads to further tissue hypoxia and sickling.
Once a sufficient number of rigid sickle cells are formed, microvascular occlusion will result. Hypoxia of tissues causes a secondary inflammatory reaction resulting in increased intramedullary pressure and bone pain.  The painful crises, osteonecrosis, and dactylitis are the result of small blood vessel occlusion in the bone marrow by sickled red cells. These manifestations are most frequent in homozygous (SS) sickle cell disease. The crises can be triggered by infection, dehydration, acidosis, cold exposure, traveling at high altitudes, and stress. , Osteonecrosis of the femoral head occurs in approximately 33% of patients and in the humeral head in 25% of patients, and other joints, including the spine, may be involved.  The risk of osteonecrosis is highest in those with frequent painful crises. Dactylitis typically occurs in children, and is characterized by acute, painful swelling of the hands and feet. , Osteopenia, stress fractures, vertebral collapse, and growth abnormalities may also occur in sickle cell disease.  Osteonecrosis and osteomyelitis can occur in patients with Hb SS disease and is due to a combination of ischemic and impaired immunity. Salmonella is the most common organism causing osteomyelitis. , Gout is a rare complication of sickle cell disease.
It is found that at least 5.2% of the world population has sickle cell trait.  Avoidance of stress, alcohol, overexertion, swimming, and high altitudes can prevent painful crisis.  This study aims at determining the pattern of musculoskeletal complications in teenage patients with sickle cell anemia admitted at the Tooba clinic of Mazandaran University of Medical Sciences. The findings from this study will add to the increasing knowledge and management of this challenging disease.
| Materials and methods|| |
This retrospective study was performed at the Tooba referral clinic of Mazandaran University of Medical Sciences for 2 years from January 2010 to December 2012. Sixteen sickle cell anemic teenage patients with homozygote forms who referred for musculoskeletal disorders during this period were evaluated. Their medical history was retrieved from the hospital's medical records department and each patient was examined by a rheumatologist. Patients included in this study were 12-17 years old with hemoglobin genotype SS (diagnosed by cellulose acetate electrophoresis at pH 8.6). Cases with any kind of traumatic or congenital musculoskeletal abnormalities or incomplete data or unclear diagnosis were excluded. Avascular necrosis (AVN) of bone was confirmed by painful limitation of the joint movement and radiography of the affected joint.  Osteomyelitis, on the other hand, was diagnosed as a relapsing and persistent infection that evolves over months to years, characterized by low-grade inflammation, fever, presence of dead bone (sequestrum), new bone apposition, and fistulous tracts. , Diagnosis of the vertebral collapse and stress fractures was confirmed by physical examination and radiographic findings. Septic arthritis was diagnosed by aspiration of joint and culture of organism. Hyperuricemia and gouty arthritis were confirmed by determination of serum uric acid level and joint aspiration. The objective of this study was to determine the age, sex, kind, and pattern of musculoskeletal complications of sickle cell anemia in these teenage patients. Data were analyzed by using the SPSS version 20 software.
| Results|| |
A total of 16 patients with sickle cell anemia referred to our clinic for musculoskeletal disorders during the 2-year study period, from January 2010 to December 2012, for further evaluation. All the patients were teenaged, with age ranging between 12 and 17 years (median: 14.6 years). Twelve of the patients (75%) were males and four of them were females (25%). [Table 1] depicts the demographic profile of the patients.
|Table 1: Characteristics of Musculoskeletal Disorders in 16 Teenage Sickle Cell Anemic Patients|
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Symptoms included painful crisis, especially in fingers and toes, in 10 (62.5%) cases. Most of the patients with crisis were males (9 patients) and one case was a female.
Another musculoskeletal complication was osteomyelitis that occurred in 3 (18.5%) of the patients. Two patients with osteomyelitis were males and one patient was a female. In all three patients, the causative organism was Staphylococcus aureus. In one patient, osteomyelitis occurred in lumbar spine and in two other patients, it occurred in long cortical bones. AVN of bones occurred in 6 (37.5%) of the patients and all of them were males. Femoral head and humerus were the prominent sites of necrosis.
Septic arthritis was diagnosed in only one patient (0.6%) and the involved zone was right knee. The organism was S. aureus. Dactilitis occurred in 4 (25%) cases and commonly occurred in fingers. Three patients with dactilitis were males and one was a female. Stress fracture and vertebral collapse occurred in two patients; one of them was a male and the other one was female.
In three of the patients, hyperuricemia occurred; in one case, an episode of gouty arthritis was reported.
| Discussion|| |
The hemoglobinopathies include a group of genetic disorders characterized by the presence of abnormal hemoglobin in circulating erythrocytes. 
The rheumatologic manifestations of sickle cell disease are due to rigidity of RBCs and as they traverse the microvasculature, they are unable to deform in small vessels; they occlude the vascular lumina and cause obstruction and ischemia of tissues. 
Recurrent painful crisis is the hallmark of sickle disease, with marked pain in the muscles and joints; the pain may be severe enough to require narcotics. In our study, painful crisis occurred in 10 (62.5%) patients.
According to the study of Tsaras and co-workers, AVN and ischemic bone syndrome are common in sickle cell anemia. 
According to the study of Mukisi-Mukaza et al., AVN can occur in every site of the bone, but is often multifocal and characteristically affects the femoral heads and the prevalence of femoral head AVN is likely greater than 40%. Humeral heads are frequently affected. 
In our study, 6 (37.5%) patients, all of them males, had AVN and the prominent site was femoral head.
Noninfectious arthritis is a well-described musculoskeletal complication in the setting of acute vaso-occlusive crisis of sickle cell anemia in the study of Espinoza and coworkers,  Hanissian and co-workers,  and de Ceulaer and coworkers.  An ankle arthritis associated with distal leg ulcers has also been described in this study. 
In our study, only one of the patients had noninfectious arthritis that was due to gouty arthritis.
Osteomyelitis and septic arthritis were the other complications of sickle cell anemia that occurred in 3 (18.5%) of the patients. In the study of Ejindu and co-workers, the most common musculoskeletal complication was acute osteomyelitis with a prevalence of 12.8%.  In all three patients, the causative organism was S. aureus. According to the study of Hernigou and co-workers, 3% of patients had septic arthritis.  In the study of Anand and co-workers, Salmonella is an unusual cause of musculoskeletal infection associated with sickle disease.  In a retrospective study by Hernigou and co-workers, most infections were due to S. aureus and the hip was most the commonly involved joint.  It seems that the increased susceptibility of sickle cell disease patients to osteomyelitis is due to hyposplenism, impaired complement activity, and the presence of infracted or necrotic bone. , According to the study of Reynolds and co-workers, sickle cell disease is associated with hyperuricemia.  It is likely due to increased uric acid generation associated with hemolysis and erythroid proliferation. Gout has been described in young patients with sickle disease.  In our study, 3 (18.7%) cases had hyperuricemia and one of them had gouty arthritis at the right ankle. Dactilitis occurred in 4 (25%) cases and it was commonly found in fingers. In the study of Ballas and co-workers, dactylitis was found to typically occur in children, and was characterized by acute, painful swelling of the hands and feet.  The variations observed in different studies could be attributed to the differences in age of cases, geographic areas, and sample size.
| Conclusion|| |
The most common musculoskeletal complications in teenagers with sickle cell anemia are painful crisis, osteomyelitis, AVN of bones, arthritis, and hyperuricemia/gout.
Comparing with other studies, especially about sickle cell disease in children, the most common musculoskeletal complication observed was osteomyelitis. In this study, painful crisis was more common than the other findings. The small sample size and inability to explore the other risk factors also limited this work and its generalizability.
| References|| |
Ballas SK. Sickle cell disease: Clinical management. Baillieres Clin Hematol 1998;11:185-214.
Quirolo K, Vichinsky E. Haemoglobin disorders. In: Behrmen RE, Kliegman EM, Jenson HB, editors. Nelson Text Book of Paediatrics. 17 th
ed. Philadephia: Saunders Company; 2004. p. 1623-34.
Platt OS, Thorington BD, Brambilla DJ, Milner PF, Rosse WF, Vichinsky E, et al
. Pain in sickle cell disease. Rates and risk factors. N Engl J Med 1991;325:11-6.
Almeida A, Roberts I. Bone involvement in sickle cell disease. Br J Haematol 2005;129:482-90.
Vichinsky EP, Neumayr LD, Haberkern C, Earles AN, Eckman J, Koshy M, et al
. The perioperative complication rate of orthopedic surgery in sickle cell disease: Report of the national sickle cell surgery study group. Am J Hematol 1999;62:129-38.
Snakaran M, Sandat AM, Kannen K. Septic arthritis in sickle cell disease. Int Orthop 1988;12:255-57.
Ware HE, Brooks AP, Toye R, Berney SI. Sickle cell disease and silent avascular necrosis of the hip. J Bone Joint Surg Br 1991;73:947-9.
Modell B, Darlison M. Global epidemiology of haemoglobin disorders and derived service indicators. Bull World Health Organ 2008;86:480-7.
Mont MA, Jones LC, Hungerford DS. Nontraumatic osteonecrosis of the femoral head: Ten years later. J Bone Joint Surg Am 2006;88:1117-32.
Zuluaga AF, Galvis W, Saldarriaga JG, Agudelo M, Salazar BE, Vesga O. Etiologic diagnosis of chronic osteomyelitis: A prospective study. Arch Intern Med 2006;166:95-100.
Ballas SK, Lieff S, Benjamin LJ, Dampier CD, Heeney MM, Hoppe C, et al
. Definitions of the phenotypic manifestations of sickle cell disease. Am J Hematol 2010;85:6-13.
Angastiniotis M, Eleftheriou A. Thalassaemic bone disease. Pediatr Endocrinol Rev 2008:6(Suppl 1):73-80.
Babhulkar SS, Pande K, Babhulkar S. The hand-foot syndrome in sickle-cell haemoglobinopathy, J Bone Joint Surg Br 1955;77:310-2.
Tsaras G, Owusu-Ansah A, Boateng FO, Amoateng-Adjepong Y: Complications associated with sickle cell trait: A brief narrative review. Am J Med 2009;122:507-12.
Mukisi-Mukaza M, Elbaz A, S
amuel-Leborgne Y, Kéclard L, Le Turdu-Chicot C, Christophe-Duchange E, et al
. Prevalence, clinical features, and risk factors of osteonecrosis of the femoral head among adults with sickle cell disease. Orthopedics 2000;23:357-63.
Espinoza LR, Spilberg I, Osterland CK. Joint manifestations of sickle cell disease. Medicine (Baltimore) 1971;53:295-305.
Hanissian AS, Silverman A. Arthritis of sickle cell anemia. South Med J 1974;67:28-32.
de Ceulaer K, Forbes M, Roper D, Serjeant GR. Non-gouty arthritis in sickle cell disease: Report of 37 consecutive cases. Ann Rheum Dis 1984;43:599-603.
Ejindu VC, Hine AL, Mashayekhi M, Shorvon PJ, Misra RR. Musculoskeletal manifestations of sickle cell disease. Radiographics 2007;27:1005-21.
Hernigou P, Daltro G, Flouzat-Lachaniette CH, Roussignol X, Poignard A. Septic arthritis in adults with sickle cell. disease is associated with osteomyelitis or osteonecrosis. Clin Orthop Relat Res 2010;468:1676-81.
Anand AJ, Glatt AE. Salmonella
osteomyelitis and arthritis in sickle cell disease. Semin Arthritis Rheum 1994;24:211-21.
Pszolla N, Sarkar MR, Strecker W, Kern P, Kinzl L, Meyers WM, et al
. Buruli ulcer: A systemic disease. Clin Infect Dis 2003;37:e78-82.
Reynolds MD. Gout and hyperuricemia associated with sickle cell anemia. Semin Arthritis Rheum 1983;12:404-13.
Schumacher HR, Andrews R, McLaughin G. Arthropathy in sickle cell disease. Ann Intern Med 1973;78:203-11.