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Acute chest syndrome in sickle-cell trait
European Journal of Internal Medicine 15 (2004) 248 – 250 www.elsevier.com/locate/ejim
Brief report
Acute chest syndrome in sickle-cell trait Two case reports in persons of Mediterranean origin and review of the literature Spyros P. Dourakis, Alexandra Alexopoulou *, Constantin Papageorgiou, Andreas Kaloterakis, Stephanos J. Hadziyannis Academic Department of Medicine, Hippokration General Hospital, Athens, Greece Received 29 August 2003; received in revised form 19 February 2004; accepted 18 March 2004
Abstract Sickle-cell trait has been characterized as a benign condition. However, life-threatening complications sometimes develop. Acute chest syndrome (ACS) is usually described in homozygous sickle cell disease, but it rarely develops in individuals with sickle-cell trait. Two cases of ACS in patients with sickle-cell trait are reported here. Factors such as advanced age at the time of presentation and absent past medical and family history can be misleading. Although ACS in sickle-cell trait has thus far only been reported in persons of Afro-American origin, persons of Mediterranean origin can, on rare occasions, also experience the syndrome. D 2004 Elsevier B.V. All rights reserved. Keywords: Acute chest syndrome; Sickle-cell trait; Mediterranean origin
1. Introduction
2. Case reports
Sickle-cell trait is generally considered to be a benign condition. Persons with sickle-cell trait have no anemia and are considered to be healthy. Yet, major vaso-occlusive complications, such as sudden death, splenic infarct [1] and acute chest syndrome (ACS) [2 – 7] in individuals with sickle-cell trait, have occasionally been reported in the literature. ACS is defined as a newly appearing pulmonary infiltrate on chest X-ray, affecting the lower lobes, or a perfusion defect demonstrable on a lung radioisotope scan in a patient with sickle-cell disease. We describe ACS in two Greek individuals with sicklecell trait and we review the literature regarding ACS in sicklecell trait.
2.1. Case 1
* Corresponding author. Present address: 20 N. Politis Street, 16346 Athens, Greece. Tel.: +30-210-9925977; fax: +30-210-9925977. E-mail address: [email protected] (A. Alexopoulou). 0953-6205/$ - see front matter D 2004 Elsevier B.V. All rights reserved. doi:10.1016/j.ejim.2004.03.010
A 25-year-old male athlete, previously in good health, had undergone exploratory laparotomy 7 days prior to admission. A mesenteric cystic lymphangioma was removed and he was discharged in good condition. On the 7th postoperative day, there was a sudden onset of left pleuritic chest pain associated with shortness of breath, fever, and non-productive cough, which led him to the emergency room. On admission he was distressed, out of breath, and febrile. Chest auscultation showed diminished breath sounds on the left base. His chest radiograph was normal and arterial blood gases were within normal limits while breathing room air. His condition deteriorated, however, in the days that followed. An arterial blood gas analysis at room air showed pH 7.43, PaO2 42 mm Hg, paCO2 47 mm Hg, HCO3 31 mEq/l, O2 Sat 79%, and BE 6.4 mEq/l. A chest radiograph at this juncture revealed bilateral pulmonary lower lobe infiltrates and a left pleural effusion, which proved to be an exudate. Perfusion scanning of the lungs
S.P. Dourakis et al. / European Journal of Internal Medicine 15 (2004) 248–250
revealed multiple filling defects suggestive of multiple pulmonary infarcts in both lungs.
249
were deemed necessary since there was a gradual improvement by the 20th hospital day.
2.2. Case 2 3. Discussion A 45-year-old male construction worker was admitted to the hospital because of right pleuritic chest pain, dyspnea, fever, and non-productive cough. He had a negative past medical and family history. His symptoms had begun 15 days earlier, when he was involved in a bicycle accident for which he was not hospitalized. His condition progressively deteriorated until the day of admission. Physical examination upon admission revealed a febrile man in respiratory distress. Examination of the chest revealed signs of consolidation in the right lung. Blood gases at room air were: pH 7.32, PaO2 56 mm Hg, PaCO2 38 mm Hg, HCO3 20 mEq/l, O2 Sat 87% and BE-5.3 mEq/l. A chest radiogram revealed a left lower lobe infiltrate, right middle and lower lobe infiltrate, and right pleural effusion, which proved to be an exudate. In both patients blood and pleural fluid cultures yielded no organism. Ultrasonography of the inferior vena cava and of the iliac and femoral veins repeatedly failed to disclose thrombi. Red cell morphology was unremarkable, but a sickling (metabisulphite) test was positive in both patients. In the first patient, hemoglobin electrophoresis showed a HbS concentration of 45%, HbA 53.2%, and HbA2 1.8%. Unfractionated heparin and broad-spectrum antibiotics were administered and exchange transfusion was begun with rapid clinical improvement. The patient was discharged in excellent condition and his chest X-ray returned to normal 2 months later. Hemoglobin electrophoresis in the second patient revealed a HbS concentration of 42%, HbA 56.5%, and HbA2 1.5%. Close monitoring, hydration, heparin, and antibiotics were instituted, but no exchange transfusions
Six case reports of an ACS-like picture in sickle-cell trait were described in the literature between 1957 and 1989 [2 –7]. The presentation and clinical course of ACS due to sickle-cell trait in both of our cases and in those of the six other published case reports were similar (Table 1). Misleading factors in the diagnosis of ACS in sickle-cell trait could be advanced age, a negative medical and family history, and the area of origin. With regard to age, the condition can occur late in life (Table 1). The patients were hospitalized for their first episode of ACS and none had previously experienced any type of vaso-occlusive event. All patients described thus far in the literature were of AfroAmerican origin [2– 7]. This is the first time that this rare condition is described in patients of Mediterranean origin. In Greece, sickle-cell trait accounts for less than 1% [8], compared with 8% in persons of Afro-American origin [1]. Documentation of the sickle-cell trait in both of our patients was based on a positive sickling test and the presence of HbS on cellulose acetate membrane electrophoresis. If a disorder resulting from double heterozygosity for HbS and a second hemoglobin, which enhances sickling, had occurred in our cases, anemia would have been present and abundant sickle cells would have been detected in peripheral blood smear. Sickling of red blood cells and vaso-occlusive events can be induced unexpectedly in persons with sickle-cell trait under certain circumstances [1– 3]. Both our patients were engaged in moderate muscular activity due to their occupational style. Yet, what occurred prior to their hospitalization, operation or trauma, must have been of significant magni-
Table 1 Characteristics of the two new cases and the six cases published previously Case 1
Case 2
Reference 2
Reference 3
Reference 4
Reference 5
Reference 6
Reference 7
Chest pain, cough and fever Multi-lobe involvement, pleural effusion Drop of the Hb and sickled cells Age Origin
Yes
Yes
Yes
Yes
Yes
Yes
No
Yes
Yes
Yes
Yes
Yes
Yes
No
Not mentioned Not mentioned
No
No
No
Yes
No
No
No
No
25 Mediterranean
45 Mediterranean
Precipitating factors HbS concentration Outcome
Operation
26 AfroAmerican Respiratory infection 33%
35 AfroAmerican Not mentioned 37%
25 AfroAmerican Cesarean section 26%
Survival
Survival
Survival
Survival
40 AfroAmerican Not mentioned Not mentioned Death
54 AfroAmerican Operation
45%
Bicycle accident 42%
48 AfroAmerican Respiratory infection 40%
Survival
Death
Not mentioned Death
250
S.P. Dourakis et al. / European Journal of Internal Medicine 15 (2004) 248–250
tude to account for severe tissue hypoxia, which precipitated the ACS. The repeatedly negative work-up of the iliac, femoral, and inferior vena cava in both patients while there was evidence of recurrent occlusive pulmonary events, rules out the possibility of the clot being completely embolized. Furthermore, the improvement that occurred after exchange transfusion was instituted in the first patient is a strong argument for the diagnosis being ACS. In conclusion, ACS in individuals with sickle-cell trait is uncommon but may occur under certain circumstances. Clinical deterioration and death are potential outcomes, and a delay in diagnosis may worsen the rates of morbidity and, most likely, of mortality. Persons of Mediterranean origin may develop the syndrome, and hemoglobin electrophoresis may be necessary when characteristic clinical presentation and imaging findings are suggestive of the syndrome.
References [1] Wrenn, Wright SW, Kent LP. A midlife crisis. Lancet 1999;353: 1760. [2] Moser KM, Shea JG. The relationship between pulmonary infarction, Cor pulmonale and the sickle states. Am J Med 1957;22:561 – 79. [3] Rahimtoola S, Good CJ, Davies PDB. Pulmonary infarction in disorders associated with the sickle cell trait. Thorax 1960;15:320 – 4. [4] Malholra V, Prakash R, Choi YS, Chomet B, Pilz CG. Fatal pulmonary infarction in a patient with sickle cell trait. Chest 1973;64:524 – 6. [5] Israel R, Salipante JS. Pulmonary infarction in sickle cell trait. Am J Med 1979;66:867 – 9. [6] Van Dinh T, Boor PJ, Garza JR. Massive pulmonary embolism following delivery of a patient with sickle cell trait. Am J Obstet Gynecol 1982;143:722 – 4. [7] Hasleton PS, Orr K, Webster A, Lawson RA. Evolution of acute chest syndrome in sickle cell trait: an ultrastructural and light microscopy study. Thorax 1989;44:1057 – 8. [8] Boussiou M, Loukopoulos D, Christakis J, Fessas PH. The origin of the sickle mutation in Greece; Evidence from hs globin gene cluster polymorphisms. Hemoglobin 1991;15:459 – 67.
Brief report
Acute chest syndrome in sickle-cell trait Two case reports in persons of Mediterranean origin and review of the literature Spyros P. Dourakis, Alexandra Alexopoulou *, Constantin Papageorgiou, Andreas Kaloterakis, Stephanos J. Hadziyannis Academic Department of Medicine, Hippokration General Hospital, Athens, Greece Received 29 August 2003; received in revised form 19 February 2004; accepted 18 March 2004
Abstract Sickle-cell trait has been characterized as a benign condition. However, life-threatening complications sometimes develop. Acute chest syndrome (ACS) is usually described in homozygous sickle cell disease, but it rarely develops in individuals with sickle-cell trait. Two cases of ACS in patients with sickle-cell trait are reported here. Factors such as advanced age at the time of presentation and absent past medical and family history can be misleading. Although ACS in sickle-cell trait has thus far only been reported in persons of Afro-American origin, persons of Mediterranean origin can, on rare occasions, also experience the syndrome. D 2004 Elsevier B.V. All rights reserved. Keywords: Acute chest syndrome; Sickle-cell trait; Mediterranean origin
1. Introduction
2. Case reports
Sickle-cell trait is generally considered to be a benign condition. Persons with sickle-cell trait have no anemia and are considered to be healthy. Yet, major vaso-occlusive complications, such as sudden death, splenic infarct [1] and acute chest syndrome (ACS) [2 – 7] in individuals with sickle-cell trait, have occasionally been reported in the literature. ACS is defined as a newly appearing pulmonary infiltrate on chest X-ray, affecting the lower lobes, or a perfusion defect demonstrable on a lung radioisotope scan in a patient with sickle-cell disease. We describe ACS in two Greek individuals with sicklecell trait and we review the literature regarding ACS in sicklecell trait.
2.1. Case 1
* Corresponding author. Present address: 20 N. Politis Street, 16346 Athens, Greece. Tel.: +30-210-9925977; fax: +30-210-9925977. E-mail address: [email protected] (A. Alexopoulou). 0953-6205/$ - see front matter D 2004 Elsevier B.V. All rights reserved. doi:10.1016/j.ejim.2004.03.010
A 25-year-old male athlete, previously in good health, had undergone exploratory laparotomy 7 days prior to admission. A mesenteric cystic lymphangioma was removed and he was discharged in good condition. On the 7th postoperative day, there was a sudden onset of left pleuritic chest pain associated with shortness of breath, fever, and non-productive cough, which led him to the emergency room. On admission he was distressed, out of breath, and febrile. Chest auscultation showed diminished breath sounds on the left base. His chest radiograph was normal and arterial blood gases were within normal limits while breathing room air. His condition deteriorated, however, in the days that followed. An arterial blood gas analysis at room air showed pH 7.43, PaO2 42 mm Hg, paCO2 47 mm Hg, HCO3 31 mEq/l, O2 Sat 79%, and BE 6.4 mEq/l. A chest radiograph at this juncture revealed bilateral pulmonary lower lobe infiltrates and a left pleural effusion, which proved to be an exudate. Perfusion scanning of the lungs
S.P. Dourakis et al. / European Journal of Internal Medicine 15 (2004) 248–250
revealed multiple filling defects suggestive of multiple pulmonary infarcts in both lungs.
249
were deemed necessary since there was a gradual improvement by the 20th hospital day.
2.2. Case 2 3. Discussion A 45-year-old male construction worker was admitted to the hospital because of right pleuritic chest pain, dyspnea, fever, and non-productive cough. He had a negative past medical and family history. His symptoms had begun 15 days earlier, when he was involved in a bicycle accident for which he was not hospitalized. His condition progressively deteriorated until the day of admission. Physical examination upon admission revealed a febrile man in respiratory distress. Examination of the chest revealed signs of consolidation in the right lung. Blood gases at room air were: pH 7.32, PaO2 56 mm Hg, PaCO2 38 mm Hg, HCO3 20 mEq/l, O2 Sat 87% and BE-5.3 mEq/l. A chest radiogram revealed a left lower lobe infiltrate, right middle and lower lobe infiltrate, and right pleural effusion, which proved to be an exudate. In both patients blood and pleural fluid cultures yielded no organism. Ultrasonography of the inferior vena cava and of the iliac and femoral veins repeatedly failed to disclose thrombi. Red cell morphology was unremarkable, but a sickling (metabisulphite) test was positive in both patients. In the first patient, hemoglobin electrophoresis showed a HbS concentration of 45%, HbA 53.2%, and HbA2 1.8%. Unfractionated heparin and broad-spectrum antibiotics were administered and exchange transfusion was begun with rapid clinical improvement. The patient was discharged in excellent condition and his chest X-ray returned to normal 2 months later. Hemoglobin electrophoresis in the second patient revealed a HbS concentration of 42%, HbA 56.5%, and HbA2 1.5%. Close monitoring, hydration, heparin, and antibiotics were instituted, but no exchange transfusions
Six case reports of an ACS-like picture in sickle-cell trait were described in the literature between 1957 and 1989 [2 –7]. The presentation and clinical course of ACS due to sickle-cell trait in both of our cases and in those of the six other published case reports were similar (Table 1). Misleading factors in the diagnosis of ACS in sickle-cell trait could be advanced age, a negative medical and family history, and the area of origin. With regard to age, the condition can occur late in life (Table 1). The patients were hospitalized for their first episode of ACS and none had previously experienced any type of vaso-occlusive event. All patients described thus far in the literature were of AfroAmerican origin [2– 7]. This is the first time that this rare condition is described in patients of Mediterranean origin. In Greece, sickle-cell trait accounts for less than 1% [8], compared with 8% in persons of Afro-American origin [1]. Documentation of the sickle-cell trait in both of our patients was based on a positive sickling test and the presence of HbS on cellulose acetate membrane electrophoresis. If a disorder resulting from double heterozygosity for HbS and a second hemoglobin, which enhances sickling, had occurred in our cases, anemia would have been present and abundant sickle cells would have been detected in peripheral blood smear. Sickling of red blood cells and vaso-occlusive events can be induced unexpectedly in persons with sickle-cell trait under certain circumstances [1– 3]. Both our patients were engaged in moderate muscular activity due to their occupational style. Yet, what occurred prior to their hospitalization, operation or trauma, must have been of significant magni-
Table 1 Characteristics of the two new cases and the six cases published previously Case 1
Case 2
Reference 2
Reference 3
Reference 4
Reference 5
Reference 6
Reference 7
Chest pain, cough and fever Multi-lobe involvement, pleural effusion Drop of the Hb and sickled cells Age Origin
Yes
Yes
Yes
Yes
Yes
Yes
No
Yes
Yes
Yes
Yes
Yes
Yes
No
Not mentioned Not mentioned
No
No
No
Yes
No
No
No
No
25 Mediterranean
45 Mediterranean
Precipitating factors HbS concentration Outcome
Operation
26 AfroAmerican Respiratory infection 33%
35 AfroAmerican Not mentioned 37%
25 AfroAmerican Cesarean section 26%
Survival
Survival
Survival
Survival
40 AfroAmerican Not mentioned Not mentioned Death
54 AfroAmerican Operation
45%
Bicycle accident 42%
48 AfroAmerican Respiratory infection 40%
Survival
Death
Not mentioned Death
250
S.P. Dourakis et al. / European Journal of Internal Medicine 15 (2004) 248–250
tude to account for severe tissue hypoxia, which precipitated the ACS. The repeatedly negative work-up of the iliac, femoral, and inferior vena cava in both patients while there was evidence of recurrent occlusive pulmonary events, rules out the possibility of the clot being completely embolized. Furthermore, the improvement that occurred after exchange transfusion was instituted in the first patient is a strong argument for the diagnosis being ACS. In conclusion, ACS in individuals with sickle-cell trait is uncommon but may occur under certain circumstances. Clinical deterioration and death are potential outcomes, and a delay in diagnosis may worsen the rates of morbidity and, most likely, of mortality. Persons of Mediterranean origin may develop the syndrome, and hemoglobin electrophoresis may be necessary when characteristic clinical presentation and imaging findings are suggestive of the syndrome.
References [1] Wrenn, Wright SW, Kent LP. A midlife crisis. Lancet 1999;353: 1760. [2] Moser KM, Shea JG. The relationship between pulmonary infarction, Cor pulmonale and the sickle states. Am J Med 1957;22:561 – 79. [3] Rahimtoola S, Good CJ, Davies PDB. Pulmonary infarction in disorders associated with the sickle cell trait. Thorax 1960;15:320 – 4. [4] Malholra V, Prakash R, Choi YS, Chomet B, Pilz CG. Fatal pulmonary infarction in a patient with sickle cell trait. Chest 1973;64:524 – 6. [5] Israel R, Salipante JS. Pulmonary infarction in sickle cell trait. Am J Med 1979;66:867 – 9. [6] Van Dinh T, Boor PJ, Garza JR. Massive pulmonary embolism following delivery of a patient with sickle cell trait. Am J Obstet Gynecol 1982;143:722 – 4. [7] Hasleton PS, Orr K, Webster A, Lawson RA. Evolution of acute chest syndrome in sickle cell trait: an ultrastructural and light microscopy study. Thorax 1989;44:1057 – 8. [8] Boussiou M, Loukopoulos D, Christakis J, Fessas PH. The origin of the sickle mutation in Greece; Evidence from hs globin gene cluster polymorphisms. Hemoglobin 1991;15:459 – 67.