Acute Muscle Injury Complicating By H. Ralph Schumacher, INDEX WORDS: Muscle sickle cell disease.
ischemia;
joint
Sickle Cell Crisis
Jr, William M. Murray, and Murray K. Dalinka
&fusions;
A
LTHOUGH bone and joint complications are common in sickle cell disease,re3 muscle involvement has only been recently identified by Dorwart and Gabuzda with the report of recurrent symmetric myositis and fasciitis in two men after prolonged painful crises.4 This report describes two patients (a woman and a 4-year-old boy) with dramatic localized painful muscle swelling occurring during painful crises. The first electron microscopic and magnetic resonance studies give further implications for pathogenesis. CASE REPORTS Patient 1was a 4-year-old black boy with known sickle cell disease who was admitted complaining of 3 days of pain and swelling of the left knee and thigh associated with a low grade fever. Although he had many previous bouts of joint swelling, his thighs had previously been symmetrical but somewhat atrophied because of inactivity. No trauma had been noted. Sickle cell disease had been diagnosed at age 11 months when the patient presented with bouts of bilateral painful diffuse hand and foot swelling of 2 months’ duration. His hemoglobin was 10.4 g/dL, and results of a sickle cell preparation were positive. Hemoglobin electrophoresis subsequently showed hemoglobin S and 16% fetal hemoglobin. Reticulocyte counts were 8% to 10%. He had a fever (temperature, 103OF) and improved with antibiotics and aspirin. During the next years, he had multiple admissions for febrile crises, almost always accompanied by painful joint swelling. The joints prominently involved were the ankles, elbows, and knees. Knee pain limited his activity for weeks at a time. Roentgenograms showed periosteal new bone formation along the metatarsals. Other roentgenograms were normal. Most bouts subsided with hydration and aspirin. Juvenile rheumatoid arthritis was considered on many of the admissions, and for periods he was maintained on high-dose aspirin therapy. His joints were not aspirated; results of tests for rheumatoid factor and antinuclear antibodies were negative. Westergren sedimentation rates were 40 to 60 mm/h. During his physical examination we identified tenderness at both hips. The right thigh was diffusely swollen and tender with a circumference 1 in greater than the left. The right knee was tender and warm with a 20° flexion contracture but no definite effusion. Because of the diagnostic questions raised, we performed a biopsy on the right rectus femoris muscle and right knee under general anesthesia. The knee articular cartilage ap peared normal and the synovium showed only mild hyperemia. No joint fluid was obtained. The muscle appeared edematous without other gross changes.
The results of light microscopic examination of the muscle showed occasional necrotic fibers, a variation in fiber size, no evidence of regeneration, and many interstitial erythrocytes, but few inflammatory cells. There were scattered eosinophils and occasional neutrophils in surrounding fibrous tissue (Fig 1A). Portions of muscle were also fixed in %-strength glutaraldehyde and processed for electron microscopy (EM) as previously described.s There were profuse interstitial fine granular material, cell debris, and sickled erythrocytes easily identified by their arrays of sickled hemoglobin. Some vessels were obliterated by sickled cells or platelets. Some endothelial cells were abnormally dark, and venular basement membranes were multilaminated. Muscle fibers showed increased vacuoles mostly caused by a dilated T system, some autophagic vacuoles, lipid droplets, decreased glycogen, loss of normal fibrillar organization, or frank degeneration (Fig 1B). The synovial biopsy, examined by light and electron microscopy, showed increased fixed tissue cells, mast cells with some degranulation, and some obliterated vessels. There was no inflammatory cell infiltration or lining cell proliferation. Patient 2 was a 26-year-old black woman with known homozygous sickle cell disease since 9 months of age when she had her first painful crisis. She had approximately five admissions per year for crises that occasionally were associated with joint effusions. Crises were often precipitated by weather change or upper respiratory or tuboovarian infections. She had received a transfusion 11 months earlier and had a cholecystectomy. One day before admission she developed chest, arm, and leg pain. Hydration, meperidine, 100 mg intramuscular (IM) every 2 hours, and hydroxyzine, 75 mg IM, did not relieve her pain in the emergency department so she was admitted. Abnormal findings initially were only a grade 3 systolic murmur and systolic ejection click. Pain failed to improve despite frequent IM meperidine and about 5 days after admission she developed a fever (temperature, 103°F) with
From the University of Pennsylvania School of Medicine, and the Department of Radiology, University of Pennsylvania, Philadelphia, and the Rheumatology-Immunology Center, Veterans Administration Medical Center, Philadelphia, PA. H. Ralph Schumacher, Jr, MD: Professor of Medicine, University of Pennsylvania School of Medicine. Director, Rheumatology-Immunology Center, Veterans Administration Medical Center, Philadelphia, Pa; William M. Murray, MD: Orthopedic Surgery, Camp Hill, PA; Murray K. Dali&a, MD: Professor of Radiology and Orthopedic Surgery, Department of Radiology, University of Pennsylvania, Philadelphia. Address reprint requests to H. Ralph Schumacher, Jr, MD, Rheumatology-Immunology Center, Veterans Administration Medical Center, University and Woodland Aves, Philadelphia, PA 19104. o 1990 by W.B. Saunders Company. 0049-0172/90/l 903-0003$5.00/0
Seminars in Arthritis and Rheumatism, Vol 19, No 4 (February), 1990: pp 243-247
243
244
SCHUMAWEI~, MURRAY, AND DALINKA
Fig 1. Patient 1. (A) Perimyrial connective tissue shows scattered inflammatory cells including polymorphonuclear neutrophils and some eoainophils, although the latter cannot be appreciated in black and while (hematoxylin-eosin stain, original magnlticetlon x400). (El Necrotic muscle fiber (NM) with cellular debrir (CD). Identifiable structures are separated by clear areas of edeme (E) (electron micrograph, orlgbtal magnification x 14,OWL
MUSCLE INJURY IN SICKLE CELL CRISIS
245
bilateral knee effusions and then thigh pain and swelling (Fig 2) with the left much worse than the right. Extensive evaluation was initiated because of concerns about possible muscle abscess or osteomyelitis. Meperidine injections that had been given into both thighs were discontinued, and the thigh muscle swelling gradually subsided without other treatment. Rechallenging with IM meperidine for 2% days and hydroxyzine for 1 day caused no fever or muscle pain. Laboratory test results were hemoglobin 7.8, g/dL; leukocyte count, 14,6OO/pL; and all other serum results, negative or normal. Intermediate strength purified protein derivative (PPD) was positive. The left knee was aspirated and yielded 1.5 mL of fluid with 1,750 leukocytes/pL, 40% neutrophils, no crystals, moderate numbers of red cells including sickled cells, maltese cross-like intracellular and extracellular suspected lipids, negative routine, anaerobic, and TB cultures. A second joint aspiration had 6,100 leukocytes/cl and 93% neutrophils. All cultures were again negative. A needle synovial biopsy yielded a small specimen with some surface fibrin, obliterated vessels and no inflammatory cells. Electron microscopy of synovium showed some dark endothelial cells, edema of vessel walls, some reduplication of vascular basement membrane, and strikingly increased endothelial Weibel-
Fig 2. persistent
Patient 2. Dramatic left thigh knee swelling after arthrocentesia.
swelling
and
Palade bodies. The latter have been proposed as a sign of neovascularization.6 A bone scan using 99m technetium methylene diphosphonate showed no acute focal bone lesions. There was increased uptake in the thigh and knee soft tissues. Magnetic resonance imaging using a 1.5 tesla superconducting magnet identified apparent sheets of fluid in the left thigh (Fig 3). There was decreased signal, as expected in sickle cell disease, throughout the marrow. Fluid was identifiable in the knees. Before discharge, the hemoglobin level decreased to 5.3 g/dL; a transfusion of 2 units increased this level to 8.3 g/dL. Isoniazid therapy was started because of the newly detected positive PPD but there was no other evidence of active infection. Naproxen, 500 mg twice a day, and oxycodone with aspirin were used with some relief for muscle and joint symptoms. Neither joint nor thigh swelling occurred during several later admissions for painful crises, despite use of IM meperidine and hydroxyzine. DISCU$SION
The two cases studied here add to only two previous cases of sickle cell disease reported with acute muscle disease by Dorwart and Gabuzda.4 A number of similarities and differences are listed in Table 1. Our patient 2 is the only woman of the four and our patient 1 at age 4 is the youngest of the patients. Although muscle injury was symmetrical and repeated in the previous cases, our patients have had asymmetric and single episodes so far. All episodes have occurred as a part of painful crises with some, as in our patient 2, occurring as relatively late manifestations. A reaction to IM injections was suggested as a cause in previous cases and our patient 2, but in all cases subsequent injections did not precipitate muscle necrosis. If they are involved, injections must only be a contributing factor. Both our patients had joint manifestations in adjacent joints along with the muscle necrosis; no immediate relation to joint disease was noted by Dorwart and Gabuzda. Neither of our patients had the temporal sequence of tense joint swelling, followed by improvement in the joint when the muscle swelled that would strongly support synovial fluid rupture into the thigh. The clinical picture in all these patients, plus the inflammatory joint effusion in our patient 2, raised concern about infections; however, infections were not a factor in any of the cases. Mechanisms for the several different muscle abnormalities in the four reported cases are not totally clear. Muscle ischemia due to microvascular changes, as previously suggested by Dorwart
SCHUMACHER,
246
MURRAY, AND DALINKA
Fig 3. Patient 2. Magnetic resonance T2 weighted image shows high signal intensity (orrows) in the muscle compatible with edema and necrosis. which is more markad on the left. There is also a left knee affusion (double arrows).
experimental microarterial embolization.’ Sickled red cells and vascular basement membrane ultrastructural changes in our patients were similar to findings described in splenic vessels in sickle cell disease.’ Creatine kinase levels have been reported as slightly elevated only in one of Dorwart and Gabuzda patients. This patient had recent IM injections, as had our patients. Creatine kinase levels for patients in crisis before injections should be investigated.
and Gabuzda,4 is a possible cause of some initial necrosis and edema. Edema was suggested as a major factor by our magnetic resonance imaging (MRI) in patient 2, histopathology in patient 1, and the aspiration of 30 mL of pale fluid from Dorwart and Gabuzda’s case 2. Necrotic vessels were seen by EM in our case 1 and obliterated synovial vessels were seen in both cases by light microscopy. Similar muscle necrosis and myopathy have occurred on an ischemic basis after
Table 1. Acute Muscle Injury in Sickle Cell Crisis
Patient 1’
InvolvedSites
Age/Sex 30/M
Bilateral deltoid
Adjacent Joint Disease None
No. of Episodes Repeated
Creatine Kinese 300 IU
MuscleBiopsyFindings Intravascular sickling
Treatment Fasciotomy
Edema
Bilateral quadriceps
Myonecrosis Fasciitis, myositis PMN Eosinophils 2*
22/M
Bilateral deltoids
Possibly
Intravascular sickling
Repeated
Fasciotomy
Edema
Bilateral thighs
Mvonecrosis Fasciitis. myositis PMN Eosinophils
3t
4/M
Right thigh
Knee pain
Single
Not done
Obliterated vessels
Biopsy only
Necrotic vessels Occasional eosinophils & PMN Edema RBC extravasation Necrotic muscle fibers
4t
26/F
Left thigh greater
Knee inflammation
than right Abbreviation: PMN, polymorphonuclear neutrophil leukocytes. *Dor.vart & Gabuzda.4 tCurrent report.
Single
Not done
Not done
Supportive
MUSCLE INJURY IN SICKLE CELL CRISIS
247
The mechanism(s) for the elevated synovial fluid leukocyte counts in our patient 2, in some previously reported joint effusions in sickle cell disease,*v3and the leukocytes found in the muscle and fascia in previous cases4 is not established. Our muscle biopsy in patient 1 showed very little inflammation but did not show clusters of eosinophils in the adjacent connective tissue. These had been more prominent in the earlier cases and had been associated with peripheral eosinophilia. Red cell extravasation and granular material that probably represented protein-rich fluid was prominent. The high signal intensity on the MRI study of patient 2 was characteristic of fluid or blood extravasation with or without necrosis. Sickled
erythrocytes can form crystal-like structures3 and can be phagocytized, although phagocytosis was not documented in our patients. Sickled cells and suspected lipid from red cell membranes’ were found in the joint fluid in patient 2 and could be possible sources of inflammation.’ In the past, patients have been treated with fasciotomy,4 and this must be considered when tense compression occurs. Conservative therapy was adequate for both of our patients. ACKNOWLEDGMENT The authors greatly appreciate the technical assistance of Susan Rothfuss, Marie Sieck, and Gilda Clayburne, and the typing of Sharon L. Johnson.
REFERENCES 1. Schumacher HR, Andrews R, McLaughlin G: Arthropathy in sickle cell disease. Ann Intern Med 78:203-211, 1973 2. Espinoza LR, Spilberg I, Gsterland CK: Joint manifestations of sickle cell disease. Medicine 53:295-305, 1974 3. Schumacher HR: Rheumatological manifestations of sickle cell disease and other hereditary hemoglobinopathies. Clin Rheum Dis 1:37-52, 1975 4. Dorwart BB, Gabuzda TG: Symmetric myositis and fasciitis: A complication of sickle cell anemia during vasoocelusion. J Rheum 12:590-595, 1985 5. Schumacher HR: Articular cartilage in the degenerative arthropathy of hemochromatosis. Arthritis Rheum 25: 1460-1468,1982
6. Sattar A, Kumar P, Kumar S: Rheumatoid and osteoarthritis: Quantitation of ultrastructural features of capillary endothelial cells. J Path01 148:45-53, 1986 7. Choi S-J, Schumacher HR, Clayburne G: Experimental hemarthrosis produces mild inflammation associated with intracellular maltese crosses. Ann Rheum Dis 45:1025-1028, 1986 8. Hathaway PW, Engel WK, Zellweger H: Experimental myopathy after microarterial embolization. Arch Neurol 22:365-378, 1970 9. Klug PP, Kaye N, Jensen WN: Endothelial cell and vascular damage in the sickle cell disorders. Blood Cells 8:175-184, 1970
ischemia;
joint
Sickle Cell Crisis
Jr, William M. Murray, and Murray K. Dalinka
&fusions;
A
LTHOUGH bone and joint complications are common in sickle cell disease,re3 muscle involvement has only been recently identified by Dorwart and Gabuzda with the report of recurrent symmetric myositis and fasciitis in two men after prolonged painful crises.4 This report describes two patients (a woman and a 4-year-old boy) with dramatic localized painful muscle swelling occurring during painful crises. The first electron microscopic and magnetic resonance studies give further implications for pathogenesis. CASE REPORTS Patient 1was a 4-year-old black boy with known sickle cell disease who was admitted complaining of 3 days of pain and swelling of the left knee and thigh associated with a low grade fever. Although he had many previous bouts of joint swelling, his thighs had previously been symmetrical but somewhat atrophied because of inactivity. No trauma had been noted. Sickle cell disease had been diagnosed at age 11 months when the patient presented with bouts of bilateral painful diffuse hand and foot swelling of 2 months’ duration. His hemoglobin was 10.4 g/dL, and results of a sickle cell preparation were positive. Hemoglobin electrophoresis subsequently showed hemoglobin S and 16% fetal hemoglobin. Reticulocyte counts were 8% to 10%. He had a fever (temperature, 103OF) and improved with antibiotics and aspirin. During the next years, he had multiple admissions for febrile crises, almost always accompanied by painful joint swelling. The joints prominently involved were the ankles, elbows, and knees. Knee pain limited his activity for weeks at a time. Roentgenograms showed periosteal new bone formation along the metatarsals. Other roentgenograms were normal. Most bouts subsided with hydration and aspirin. Juvenile rheumatoid arthritis was considered on many of the admissions, and for periods he was maintained on high-dose aspirin therapy. His joints were not aspirated; results of tests for rheumatoid factor and antinuclear antibodies were negative. Westergren sedimentation rates were 40 to 60 mm/h. During his physical examination we identified tenderness at both hips. The right thigh was diffusely swollen and tender with a circumference 1 in greater than the left. The right knee was tender and warm with a 20° flexion contracture but no definite effusion. Because of the diagnostic questions raised, we performed a biopsy on the right rectus femoris muscle and right knee under general anesthesia. The knee articular cartilage ap peared normal and the synovium showed only mild hyperemia. No joint fluid was obtained. The muscle appeared edematous without other gross changes.
The results of light microscopic examination of the muscle showed occasional necrotic fibers, a variation in fiber size, no evidence of regeneration, and many interstitial erythrocytes, but few inflammatory cells. There were scattered eosinophils and occasional neutrophils in surrounding fibrous tissue (Fig 1A). Portions of muscle were also fixed in %-strength glutaraldehyde and processed for electron microscopy (EM) as previously described.s There were profuse interstitial fine granular material, cell debris, and sickled erythrocytes easily identified by their arrays of sickled hemoglobin. Some vessels were obliterated by sickled cells or platelets. Some endothelial cells were abnormally dark, and venular basement membranes were multilaminated. Muscle fibers showed increased vacuoles mostly caused by a dilated T system, some autophagic vacuoles, lipid droplets, decreased glycogen, loss of normal fibrillar organization, or frank degeneration (Fig 1B). The synovial biopsy, examined by light and electron microscopy, showed increased fixed tissue cells, mast cells with some degranulation, and some obliterated vessels. There was no inflammatory cell infiltration or lining cell proliferation. Patient 2 was a 26-year-old black woman with known homozygous sickle cell disease since 9 months of age when she had her first painful crisis. She had approximately five admissions per year for crises that occasionally were associated with joint effusions. Crises were often precipitated by weather change or upper respiratory or tuboovarian infections. She had received a transfusion 11 months earlier and had a cholecystectomy. One day before admission she developed chest, arm, and leg pain. Hydration, meperidine, 100 mg intramuscular (IM) every 2 hours, and hydroxyzine, 75 mg IM, did not relieve her pain in the emergency department so she was admitted. Abnormal findings initially were only a grade 3 systolic murmur and systolic ejection click. Pain failed to improve despite frequent IM meperidine and about 5 days after admission she developed a fever (temperature, 103°F) with
From the University of Pennsylvania School of Medicine, and the Department of Radiology, University of Pennsylvania, Philadelphia, and the Rheumatology-Immunology Center, Veterans Administration Medical Center, Philadelphia, PA. H. Ralph Schumacher, Jr, MD: Professor of Medicine, University of Pennsylvania School of Medicine. Director, Rheumatology-Immunology Center, Veterans Administration Medical Center, Philadelphia, Pa; William M. Murray, MD: Orthopedic Surgery, Camp Hill, PA; Murray K. Dali&a, MD: Professor of Radiology and Orthopedic Surgery, Department of Radiology, University of Pennsylvania, Philadelphia. Address reprint requests to H. Ralph Schumacher, Jr, MD, Rheumatology-Immunology Center, Veterans Administration Medical Center, University and Woodland Aves, Philadelphia, PA 19104. o 1990 by W.B. Saunders Company. 0049-0172/90/l 903-0003$5.00/0
Seminars in Arthritis and Rheumatism, Vol 19, No 4 (February), 1990: pp 243-247
243
244
SCHUMAWEI~, MURRAY, AND DALINKA
Fig 1. Patient 1. (A) Perimyrial connective tissue shows scattered inflammatory cells including polymorphonuclear neutrophils and some eoainophils, although the latter cannot be appreciated in black and while (hematoxylin-eosin stain, original magnlticetlon x400). (El Necrotic muscle fiber (NM) with cellular debrir (CD). Identifiable structures are separated by clear areas of edeme (E) (electron micrograph, orlgbtal magnification x 14,OWL
MUSCLE INJURY IN SICKLE CELL CRISIS
245
bilateral knee effusions and then thigh pain and swelling (Fig 2) with the left much worse than the right. Extensive evaluation was initiated because of concerns about possible muscle abscess or osteomyelitis. Meperidine injections that had been given into both thighs were discontinued, and the thigh muscle swelling gradually subsided without other treatment. Rechallenging with IM meperidine for 2% days and hydroxyzine for 1 day caused no fever or muscle pain. Laboratory test results were hemoglobin 7.8, g/dL; leukocyte count, 14,6OO/pL; and all other serum results, negative or normal. Intermediate strength purified protein derivative (PPD) was positive. The left knee was aspirated and yielded 1.5 mL of fluid with 1,750 leukocytes/pL, 40% neutrophils, no crystals, moderate numbers of red cells including sickled cells, maltese cross-like intracellular and extracellular suspected lipids, negative routine, anaerobic, and TB cultures. A second joint aspiration had 6,100 leukocytes/cl and 93% neutrophils. All cultures were again negative. A needle synovial biopsy yielded a small specimen with some surface fibrin, obliterated vessels and no inflammatory cells. Electron microscopy of synovium showed some dark endothelial cells, edema of vessel walls, some reduplication of vascular basement membrane, and strikingly increased endothelial Weibel-
Fig 2. persistent
Patient 2. Dramatic left thigh knee swelling after arthrocentesia.
swelling
and
Palade bodies. The latter have been proposed as a sign of neovascularization.6 A bone scan using 99m technetium methylene diphosphonate showed no acute focal bone lesions. There was increased uptake in the thigh and knee soft tissues. Magnetic resonance imaging using a 1.5 tesla superconducting magnet identified apparent sheets of fluid in the left thigh (Fig 3). There was decreased signal, as expected in sickle cell disease, throughout the marrow. Fluid was identifiable in the knees. Before discharge, the hemoglobin level decreased to 5.3 g/dL; a transfusion of 2 units increased this level to 8.3 g/dL. Isoniazid therapy was started because of the newly detected positive PPD but there was no other evidence of active infection. Naproxen, 500 mg twice a day, and oxycodone with aspirin were used with some relief for muscle and joint symptoms. Neither joint nor thigh swelling occurred during several later admissions for painful crises, despite use of IM meperidine and hydroxyzine. DISCU$SION
The two cases studied here add to only two previous cases of sickle cell disease reported with acute muscle disease by Dorwart and Gabuzda.4 A number of similarities and differences are listed in Table 1. Our patient 2 is the only woman of the four and our patient 1 at age 4 is the youngest of the patients. Although muscle injury was symmetrical and repeated in the previous cases, our patients have had asymmetric and single episodes so far. All episodes have occurred as a part of painful crises with some, as in our patient 2, occurring as relatively late manifestations. A reaction to IM injections was suggested as a cause in previous cases and our patient 2, but in all cases subsequent injections did not precipitate muscle necrosis. If they are involved, injections must only be a contributing factor. Both our patients had joint manifestations in adjacent joints along with the muscle necrosis; no immediate relation to joint disease was noted by Dorwart and Gabuzda. Neither of our patients had the temporal sequence of tense joint swelling, followed by improvement in the joint when the muscle swelled that would strongly support synovial fluid rupture into the thigh. The clinical picture in all these patients, plus the inflammatory joint effusion in our patient 2, raised concern about infections; however, infections were not a factor in any of the cases. Mechanisms for the several different muscle abnormalities in the four reported cases are not totally clear. Muscle ischemia due to microvascular changes, as previously suggested by Dorwart
SCHUMACHER,
246
MURRAY, AND DALINKA
Fig 3. Patient 2. Magnetic resonance T2 weighted image shows high signal intensity (orrows) in the muscle compatible with edema and necrosis. which is more markad on the left. There is also a left knee affusion (double arrows).
experimental microarterial embolization.’ Sickled red cells and vascular basement membrane ultrastructural changes in our patients were similar to findings described in splenic vessels in sickle cell disease.’ Creatine kinase levels have been reported as slightly elevated only in one of Dorwart and Gabuzda patients. This patient had recent IM injections, as had our patients. Creatine kinase levels for patients in crisis before injections should be investigated.
and Gabuzda,4 is a possible cause of some initial necrosis and edema. Edema was suggested as a major factor by our magnetic resonance imaging (MRI) in patient 2, histopathology in patient 1, and the aspiration of 30 mL of pale fluid from Dorwart and Gabuzda’s case 2. Necrotic vessels were seen by EM in our case 1 and obliterated synovial vessels were seen in both cases by light microscopy. Similar muscle necrosis and myopathy have occurred on an ischemic basis after
Table 1. Acute Muscle Injury in Sickle Cell Crisis
Patient 1’
InvolvedSites
Age/Sex 30/M
Bilateral deltoid
Adjacent Joint Disease None
No. of Episodes Repeated
Creatine Kinese 300 IU
MuscleBiopsyFindings Intravascular sickling
Treatment Fasciotomy
Edema
Bilateral quadriceps
Myonecrosis Fasciitis, myositis PMN Eosinophils 2*
22/M
Bilateral deltoids
Possibly
Intravascular sickling
Repeated
Fasciotomy
Edema
Bilateral thighs
Mvonecrosis Fasciitis. myositis PMN Eosinophils
3t
4/M
Right thigh
Knee pain
Single
Not done
Obliterated vessels
Biopsy only
Necrotic vessels Occasional eosinophils & PMN Edema RBC extravasation Necrotic muscle fibers
4t
26/F
Left thigh greater
Knee inflammation
than right Abbreviation: PMN, polymorphonuclear neutrophil leukocytes. *Dor.vart & Gabuzda.4 tCurrent report.
Single
Not done
Not done
Supportive
MUSCLE INJURY IN SICKLE CELL CRISIS
247
The mechanism(s) for the elevated synovial fluid leukocyte counts in our patient 2, in some previously reported joint effusions in sickle cell disease,*v3and the leukocytes found in the muscle and fascia in previous cases4 is not established. Our muscle biopsy in patient 1 showed very little inflammation but did not show clusters of eosinophils in the adjacent connective tissue. These had been more prominent in the earlier cases and had been associated with peripheral eosinophilia. Red cell extravasation and granular material that probably represented protein-rich fluid was prominent. The high signal intensity on the MRI study of patient 2 was characteristic of fluid or blood extravasation with or without necrosis. Sickled
erythrocytes can form crystal-like structures3 and can be phagocytized, although phagocytosis was not documented in our patients. Sickled cells and suspected lipid from red cell membranes’ were found in the joint fluid in patient 2 and could be possible sources of inflammation.’ In the past, patients have been treated with fasciotomy,4 and this must be considered when tense compression occurs. Conservative therapy was adequate for both of our patients. ACKNOWLEDGMENT The authors greatly appreciate the technical assistance of Susan Rothfuss, Marie Sieck, and Gilda Clayburne, and the typing of Sharon L. Johnson.
REFERENCES 1. Schumacher HR, Andrews R, McLaughlin G: Arthropathy in sickle cell disease. Ann Intern Med 78:203-211, 1973 2. Espinoza LR, Spilberg I, Gsterland CK: Joint manifestations of sickle cell disease. Medicine 53:295-305, 1974 3. Schumacher HR: Rheumatological manifestations of sickle cell disease and other hereditary hemoglobinopathies. Clin Rheum Dis 1:37-52, 1975 4. Dorwart BB, Gabuzda TG: Symmetric myositis and fasciitis: A complication of sickle cell anemia during vasoocelusion. J Rheum 12:590-595, 1985 5. Schumacher HR: Articular cartilage in the degenerative arthropathy of hemochromatosis. Arthritis Rheum 25: 1460-1468,1982
6. Sattar A, Kumar P, Kumar S: Rheumatoid and osteoarthritis: Quantitation of ultrastructural features of capillary endothelial cells. J Path01 148:45-53, 1986 7. Choi S-J, Schumacher HR, Clayburne G: Experimental hemarthrosis produces mild inflammation associated with intracellular maltese crosses. Ann Rheum Dis 45:1025-1028, 1986 8. Hathaway PW, Engel WK, Zellweger H: Experimental myopathy after microarterial embolization. Arch Neurol 22:365-378, 1970 9. Klug PP, Kaye N, Jensen WN: Endothelial cell and vascular damage in the sickle cell disorders. Blood Cells 8:175-184, 1970
