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 Table of Contents  
ORIGINAL ARTICLE
Year : 2015  |  Volume : 40  |  Issue : 1  |  Page : 13-16

Analysis of 16 teenage patients with sickle cell anemia and musculoskeletal complications


1 Department of Rheumatology, Imam Khomeini Hospital, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran
2 Department of Hematology, Imam Khomeini Hospital, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran
3 Sari Azad University, Sari, Iran

Date of Submission18-Dec-2013
Date of Acceptance21-Nov-2014
Date of Web Publication24-Apr-2015

Correspondence Address:
A Hosseinian Amiri
Associated Prof. of Rheimatology, Department of Rheumatology, Imam Khomeini Hospital, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari
Iran
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/1110-1067.155785

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  Abstract 

Background Sickle cell anemia is a genetic hematological disorder characterized by red blood cell abnormality including rigidity and sickling. Once a sufficient number of rigid sickle cells have formed, microvascular occlusion will result, which leads to tissue ischemia and infarction and progressive end-organ damage.
Aim The aim of this study was to determine the pattern of musculoskeletal complications in 16 teenage patients with sickle cell disease over a period of 2 years.
Patients and methods This is a retrospective study of cases of musculoskeletal complications among sickle cell anemic patients over a period of 2 years, referred to the Rheumatologic Clinic of Mazandaran University of Medical Sciences from January 2010 to December 2012. Data were analyzed using SPSS, version 20. Variables analyzed included age, sex, and type of musculoskeletal complication.
Results There were 16 sickle cell patients referred to our Rheumatologic Clinic for musculoskeletal complications. All patients were teenagers aged between 12 and 17 years, with a median age of 14.6 years. There were 12 male and four female patients. The most common musculoskeletal complication was acute painful crisis in 10 (62.5%) patients, osteomyelitis in three (18.5%), dactylitis in four (25%), avascular necrosis of bones in six (37.5%), stress fractures and vertebral collapse in two (12.5%), septic arthritis in one (0.6%), and hyperuricemia/gout arthritis in three (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 common rheumatologic complications of this disorder.

Keywords: hemoglobinopathy, musculoskeletal complications, sickle cell anemia


How to cite this article:
Amiri A H, Shekarriz R, Yazdanian M. Analysis of 16 teenage patients with sickle cell anemia and musculoskeletal complications. Egypt J Haematol 2015;40:13-6

How to cite this URL:
Amiri A H, Shekarriz R, Yazdanian M. Analysis of 16 teenage patients with sickle cell anemia and musculoskeletal complications. Egypt J Haematol [serial online] 2015 [cited 2019 Dec 13];40:13-6. Available from: http://www.ehj.eg.net/text.asp?2015/40/1/13/155785


  Introduction Top


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 states including sickle-β-thalassemia, sickle-C (S-C) disease, and sickle-D (S-D) disease can cause rheumatologic manifestations. Homozygous (SS) sickle cell disease occurs mostly in the African population; it also occurs in southern Italy, Greece, Turkey, Saudi Arabia, and India [1] .

Sickle cell anemia is characterized by red blood cells that assume an abnormal, rigid, sickle shape [2] . Hypoxia results in polymerization of HbS, forming liquid crystals. This deforms the red cells from biconcave discs to elongated, rigid, crescent-shaped sickle cells, causing hemolysis and occlusion of the microcirculation, leading to further tissue hypoxia and sickling.

Once a sufficient number of rigid sickle cells have formed, microvascular occlusion will result. Hypoxia of tissues causes a secondary inflammatory reaction, resulting in increased intramedullary pressure and bone pain [1] . 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 SS sickle cell disease. The crises can be triggered by infection, dehydration, acidosis, cold exposure, traveling at high altitudes, and stress [3],[4] . Osteonecrosis of the femoral head occurs in ~33% of patients and that of the humeral head in 25% of patients. Other joints, including the spine, may be involved [5] . 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 [1],[4] . Osteopenia, stress fractures, vertebral collapse, and growth abnormalities may also occur in sickle cell disease [4] . Osteonecrosis and osteomyelitis can occur in patients with Hb SS disease and is due to a combination of ischemic and impaired immunity.  Salmonella More Details spp. is the most common causative organism of osteomyelitis [6],[7] . Gout is a rare complication of sickle cell disease.

It is noted that at least 5.2% of the world population has sickle cell trait [8] . Avoidance of stress, alcohol, overexertion, swimming, and high altitudes can prevent painful crises [1] .

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 augment the increasing knowledge and management of this challenging disease.


  Patients and methods Top


This retrospective study was performed at the TOOBA referral clinic of Mazandaran University of Medical Sciences over a period of 2 years from January 2010 to December 2012. Sixteen sickle cell anemic teenagers with homozygote forms were referred for musculoskeletal disorders during this period. 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 type of traumatic or congenital musculoskeletal abnormalities or incomplete data or unclear diagnosis were excluded. Avascular necrosis (AVN) of the bone was confirmed by painful limitation of joint movement and radiography of the affected joint [9] . Osteomyelitis, in contrast, 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 [10],[11] . Diagnosis of vertebra collapse and stress fractures was confirmed by physical examination and radiographical 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 levels and joint aspiration. The objective of this study was to determine the age, sex, and type and pattern of musculoskeletal complications of sickle cell anemia in these teenagers. Data were analyzed using SPSS, version 20.


  Results Top


A total of 16 patients with sickle cell anemia were referred to our clinic for musculoskeletal disorders from January 2010 to December 2012 for further evaluation. All patients were teenagers with ages between 12 and 17 years (median: 14.6 years). There were 12 (75%) male and four (25%) female patients. [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 patients with crisis were male (nine patients) and one was female.

Other musculoskeletal complications included osteomyelitis, AVN of bones, septic arthritis, dactylitis, and hyperuricemia/gout. Osteomyelitis occurred in three (18.5%) patients; of them, there were two male patients and one female patient. In all three patients the causative organism was Staphylococcus aureus. In one patient osteomyelitis occurred in the lumbar spine and in the other two it occurred in long cortical bones.

AVN of bones occurred in six (37.5%) patients all of them were male. The 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 the right knee. The causative organism was S. aureus.

Dactylitis occurred in four (25%) patients and commonly in fingers. Of them, three were male and one was female. Stress fracture and vertebral collapse occurred in two patients (one male and one female).

In three patients hyperuricemia occurred, and in one case an episode of gouty arthritis was reported.


  Discussion Top


The hemoglobinopathies include a group of genetic disorders characterized by the presence of abnormal hemoglobin in circulating erythrocytes [12] .

The rheumatologic manifestations of sickle cell disease is due to the rigidity of red blood cells; as they traverse the microvasculature they are unable to deform into small vessels and occlude the vascular lumina and cause obstruction and ischemia of tissues [13] .

The 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 a study by Tsaras et al. [14] , AVN and ischemic bone syndromes are common in sickle cell anemia.

According to a study by Mukisi-Mukaza et al. [15] , AVN can occur in any site of the bone but is often multifocal and characteristically affects the femoral heads; the prevalence of femoral head AVN is likely greater than 40%. Humeral heads are also frequently affected.

In our study, six (37.5%) patients (all of them male) had AVN: 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 a study by Espinoza et al. [16] , Hanissian and Silverman [17] , and De Ceulaer et al. [18] . An ankle arthritis associated with distal leg ulcers also has been described in this study [18] .

In our study, only one patient had noninfectious arthritis that was due to gouty arthritis.

Osteomyelitis and septic arthritis were other complications of sickle cell anemia that occurred in three (18.5%) patients. In a study by Ejindu et al. [19] , the most common musculoskeletal complication was acute osteomyelitis, with a prevalence of 12.8%.

In all three patients the causative organism was S. aureus.

In a study by Hernigou et al. [20] , 3% of patients had septic arthritis.

In a study by Anand et al. [21] , Salmonella spp. was found to be an unusual cause of musculoskeletal infection associated with sickle disease.

In a retrospective study by Hernigou et al. [20] , most infections were due to S. aureus, and the hip was the most 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 [19],[22] .

In a study by Reynolds [23] , sickle cell disease was found to be 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 [24] .

In our study, three (18.7%) cases had hyperuricemia; of them, one had gouty arthritis at the right ankle.

Dactylitis occurred in four (25%) cases and commonly occurred in fingers.

According to a study by Ballas [1] , dactylitis typically occurs in children and is characterized by acute, painful swelling of the hands and feet. The reason for variations in different studies could be due to differences in patients' ages, in geographical locations, and in sample size.


  Conclusion Top


The most common musculoskeletal complications in teenagers with sickle cell anemia are painful crisis, osteomyelitis, AVN of bones, arthritis, and hyperuricemia/gout.

In comparison with other studies, especially those on sickle cell disease in children, that reported osteomyelitis to be the most common musculoskeletal complication, this study reports painful crisis to be a more common complication. The small sample size and inability to explore other risk factors limited this work and its generalizability.


  Acknowledgements Top


Conflicts of interest

There are no conflicts of interest.

 
  References Top

1.
Ballas SK. Sickle cell disease: clinical management. Baillieres Clin Hematol 1998; 11 :185-214.  Back to cited text no. 1
    
2.
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Mukisi-Mukaza M, Elbaz A, Samuel-Leborgne Y, Kéclard L, le Turdu-Chicot C, Christophe-Duchange E, Mérault G Prevalence, clinical features, and risk factors of osteonecrosis of the femoral head among adults with sickle cell disease, Orthopedics 2000; 23 :357-363.  Back to cited text no. 15
    
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Hanissian AS, Silverman A. Arthritis of sickle cell anemia, South Med J 1974; 67 :28-32.  Back to cited text no. 17
    
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Ejindu VC, Hine AL, Mashayekhi M, Shorvon PJ, Misra RR. Musculoskeletal manifestations of sickle cell disease. Radiographics 2007; 27 :1005-1021.  Back to cited text no. 19
    
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Hernigou P, Daltro G, Flouzat-Lachaniette CH, Roussignol X, Poignard A Septic arthritis in adults with sickle cell disease often is associated with osteomyelitis or osteonecrosis. Clin Orthop Relat Res 2010; 468 :1676-1681.  Back to cited text no. 20
    
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Anand AJ, Glatt AE. Salmonella osteomyelitis and arthritis in sickle cell disease, Semin Arthritis Rheum 1994; 24 :211-221.  Back to cited text no. 21
    
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Pszolla N, Sarkar MR, Strecker W, Kern P, Kinzl L, Meyers WM, PortaelsF. Buruli ulcer: a systemic disease. Clin Infect Dis 2003; 37 :e78-e82.  Back to cited text no. 22
    
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