Myonecrosis in sickle cell anemia: case report and review of the literature.

Abstract: Vascular occlusion is responsible for most of the severe complications of sickle cell anemia (SCA). The involvement of muscle and fascia is uncommon in SCA, but myonecrosis may occur in SCA crisis. The data accumulated in the literature is limited to only a few reports describing mainly adult patients presenting with severe muscular pain. We report a rare case of sickle myonecrosis and secondary involvement of an associated joint after a severe painful crisis in the left thigh.

Key Words: sickle cell anemia, muscle infarction, musculoskeletal complications, myonecrosis

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Episodic vascular occlusion, the hallmark feature of sickle cell anemia (SCA), is responsible for most of the severe complications of this chronic disease. Chief among the clinical features of SCA are the acute episodes of pain in the chest, back, abdomen, or extremities. Vaso-occlusion of small and sometimes large vessels is associated with infarction and subsequent fibrosis of multiple areas in different organs. However, myonecrosis is a rare complication of SCA. In this study, we report an uncommon case of sickle myonecrosis and secondary involvement of an associated joint after a severe painful crisis in the left thigh.

Case Report

A 28-year-old African Brazilian man with SCA (HbS = 89.8%; HbA2 = 2.0%; HbF = 8.2%) was admitted to the hospital because of severe pain and swelling in the left thigh. He denied any history of fever, trauma, bleeding, or excessive exercise. He described numerous previous hospital admissions due to painful crises. On physical examination, he was afebrile and a mild nonpitting swelling of the left thigh was detected, with warmth and severe discomfort on ankle flexion and rotation. Otherwise, the physical examination was unremarkable.

Laboratory tests showed a hematocrit (Ht) of 23%, hemoglobin (Hb) concentration of 8.1 g/dL, white blood cell (WBC) count of 11 X [10.sup.6]/L with 66% neutrophils, and platelet count of 5.48 X [10.sup.9]/L. The serum lactic dehydrogenase (LDH) level was 1,164 U/L (normal: 240-480 U/L), and the serum creatine phosphokinase (CPK) level was 70 U/L (normal [less than or equal to] 167 U/L). Over the following eight days, the pain and swelling of the left thigh increased dramatically and was associated with limitation in the range of motion of the left knee. The complete blood count showed Hb of 6.3 g/dL, Ht of 19%, with normal WBC and platelet counts. The LDH level increased to 4,320 U/L and the CPK value increased to 185 U/L. No intramuscular injection had been administered to the affected muscle groups during hospitalization.

Doppler ultrasound of the left thigh demonstrated swelling of the anterior compartment muscles of the left thigh without abscess formation, and an increased amount of synovial fluid of the left knee. The magnetic resonance imaging (MRI) scan revealed increased signal intensity in the left thigh anterior muscle compartment (Figs. 1 and 2). There were few WBCs (500/[mm.sup.3]) in the synovial fluid, but no organisms were found. All cultures were negative.

After four weeks of intensive physical therapy, adequate hydration, and pain control, the patient was discharged home. No sequelae were detected in a clinical evaluation after one year of follow-up.

Discussion

Vascular occlusion, which is responsible for most of the severe complications of SCA, may occur wherever blood flows. This phenomenon is initiated and sustained by a complex interplay between sickle cells, endothelial cells, and plasma constituents. Pain results from tissue hypoxia and ischemia involving several organs, which are sometimes triggered by infection, stress, or extreme temperatures. (1,2)

The involvement of muscle and fascia is uncommon in SCA, but myonecrosis may occur in sickle cell crisis. (3-8) The data accumulated in the literature is limited to only a few reports, describing mainly adult patients presenting with severe muscular pain (Table). (3-8) Secondary involvement of associated joints may also occur as observed in the present patient. (4,7) In extremes cases, compartment syndrome can be associated and may require fasciotomies. (3,7)

[FIGURE 1 OMITTED]

[FIGURE 2 OMITTED]

Although most of the literature studies have not reported the CPK level, the level of this muscle enzyme was considered normal in three cases, (3,5,6) and extremely elevated in two other patients. (7,8) In our patient, we found a slight increase in the CPK value from 70 to 185 U/L during the first week after the acute event.

Sickle myonecrosis episodes can be acute or chronic. The acute cases have exuberant clinical signs such as sudden swelling, warmth, and tenderness of muscle groups or compartments. Chronic cases are usually associated with muscle induration, atrophy, and contractures after many painful crises. (5)

Myonecrosis is usually manifested by characteristic findings on MRI scan. The signal intensity of normal skeletal muscle is generally slightly higher than that of water, much lower than that of fat on T1-weighted images, and much lower than that of both fat and water on T2-weighted images. Myonecrosis may cause an alteration in muscle size and shape, and increase signal intensity on T2-weighted images. (9) Muscle infarction may be complicated by muscle liquefaction that simulates an abscess on clinical examination and MRI scan.

Never interrupt your enemy when he is making a mistake.
--Napoleon Bonaparte

Table. Studies of sickle myonecrosis reported in the literature (a)

             Age                                     LDH      CPK
Reference    (yr)  Sex  Physical Findings            (U/L)    (U/L)

(4)           4    M    Pain, swollen and tender     NA       NA
(4)          26    F    Pain, swollen, tender and    NA       NA
                          warm
(3)          30    M    Pain, swollen, tender and    NA       300
                          warm
(3)          22    M    Pain, swollen, tender and    NA       NA
                          warm
(5)          26    M    Pain, swollen and muscle     NA       300
                          induration
(5)          36    M    Pain, swollen and indurated  NA       NA
                          joint contracture
(5)          44    F    Pain, swollen and indurated  NA       NA
                          joint contracture
(5)          30    M    Pain, swollen and indurated  NA       NA
                          joint contracture
(6)          42    F    Muscle induration            NA       Normal
(7)          24    M    Pain, swollen, warm and      592 (b)  2,140 (c)
                          erythema
(8)          24    F    Pain, swollen, warm and      NA       644
                          erythema
This report  28    M    Pain, swollen and warm       1,164    185

Reference    Muscles involved     Muscle biopsy           Complications

(4)          Right thigh, right   Necrosis, eosinophils,  None
               knee                 inflammatory cells
(4)          Bilateral thigh and  Weibel-Palade bodies    None
               knee
(3)          Bilateral deltoid,   Necrosis, eosinophils,  Compartment
               bilateral            inflammatory cells      syndrome
               quadriceps
(3)          Bilateral deltoids,  Necrosis, eosinophils,  Compartment
               bilateral thighs     inflammatory cells      syndrome
(5)          Bilateral            Collagen, necrosis,     Muscle atrophy
               quadriceps           inflammatory cells
(5)          Bilateral            Necrosis, inflammatory  Muscle atrophy
               quadriceps           cells                   and
                                                            contractures
(5)          Bilateral deltoids,  NA                      Muscle atrophy
               elbow                                        and
               contractures                                 contractures
(5)          Bilateral thigh      Collagen, inflammatory  Muscle atrophy
                                    cells                   and
                                                            contractures
(6)          Left elbow           Thromboemboli, chronic  Atrophy
                                    inflammatory cells
(7)          Left leg             Multifocal              Compartment
                                    myocytolysis            syndrome
(8)          Bilateral thighs     NA                      Abscess
This report  Left thigh           NA                      None

(a) CPK, creatine phosphokinase: LDH, lactate dehydrogenase; NA, not
available.
(b) Normal range: 118 to 242 U/L.
(c) Normal range: 24 to 195 U/L.

Accepted December 16, 2003.

References

1. Wood AJJ. Management of sickle cell disease. N Engl J Med 1999;340:1021-1030.

2. Rosse WFR, Narla M, Petz LD, Steinberg MH. New views of sickle cell disease pathophysiology and treatment, in American Society of Hematology Education Program Book. Washington, D.C., American Society of Hematology, 2002, pp 2-17.

3. Dowart BB, Gabuzda TG. Symetric myositis and fascitis: a complication of sickle cell anemia during vaso-occlusion. J Rheum 1985;12:590-595.

4. Schumacher HR, Murray WM, Dalinka MK. Acute muscle injury complicating sickle cell crises. Semin Arthritis Rheum 1990;19:243-247.

5. Valeriano-Marcet J, Kerr LD. Myonecrosis and myofribosis as complications of sickle cell anemia. Ann Intern Med 1991;115:99-101.

6. Dennis GJ, Keating RM. Muscle infarction in sickle cell anemia. Ann Intern Med 1991;115:831-832.

7. Mani S, Duffy TP. Sickle myonecrosis revised. Am J Med 1993;95:525-530.

8. Malekgoudarzi B, Feffer S. Myonecrosis in sickle cell anemia [letter]. N Engl J Med 1999;340:443.

9. May DA, Disler DG, Jones EA, et al. Abnormal signal intensity in skeletal muscle at MR imaging: patterns, pearls and pitfalls. RadioGraphics 2000;20:295-315.

RELATED ARTICLE: Key Points

* Myonecrosis is a rare complication of sickle cell anemia.

* Sickle myonecrosis episodes can be acute or chronic.

* Myonecrosis is usually manifested by characteristic finding on MRI.

* Early diagnosis and prompt involvement of a physical therapist are fundamental to avoid chronic sequelae.

Perla Vicari, MD, Ruth Achkar, MD, Kathia R.B. Oliveira, MD, Milton L. Miszpupten, MD, Artur R.C. Fernandes, MD, PHD, Maria S. Figueiredo, MD, PHD, and Jose O. Bordin, MD, PHD

From the Disciplinas de Hematologia e Hemoterapia, Reumatologia, e Departamento de Diagnostico por Imagem, Universidade Federal de Sao Paulo, Sao Paulo, SP, Brazil.

Reprint requests to Perla Vicari, MD, Universidade Federal de Sao Paulo, Disciplina de Hematologia e Hemoterapia, Rua Botucatu, 740-3[degrees] andar, CEP: 04223-900, Sao Paulo, SP, Brazil. E-mail: [e-mail]