702
LETTERS TO THE EDITOR
Carotid artery disease presenting as cough headache in a patient on haemodialysis Sir, Headache has been associated with all types of cerebrovascular events, such as transient ischaemic attacks, lacunar infarcts and parenchymal haemorrhage.' In addition, the association of headache to carotid artery disease is well recognized, although the mechanisms of pain remain unclear.2 Headache has been reported after spontaneous carotid dissection and carotid endarterectomy.4 Cough headache is a well described entity consisting of transient pain on coughing, sneezing, laughing or heavy lifting. This is usually a benign idiopathic state although it is occasionally associated with foramen magnum and posterior fossa pathology (Arnold Chiari, arteriovenous malformations and tumour).' To our knowledge, there is only one previous report concerning cough headache and carotid artery disease.5 We report a patient on haemodialysis with cough headache as the presenting symptom of carotid artery disease. A 54 year old patient had been on haemodialysis (HD) for 10 years because of chronic renal failure (CRF) secondary to membranous nephropathy. He had a history of heavy smoking, chronic obstructive lung disease and long-term hypertension. Clinical features of generalized atherosclerosis developed in 1987, consisting of angina pectoris and intermittent claudication. In July 1988 he began to suffer from right severe retrocular pain following cough attacks. In November, right blunted vision, weakness of the left arm with abnormal spontaneous movements of his left hand, minimal facial paresis and dysarthria were associated with cough headache. Those symptoms appeared not only with cough, but also with intradialysis hypotension (systolic blood pressure lower than 80 mmHg). Neurological symptoms reversed completely in 10- 15 minutes. He was admitted to hospital in December. Physical examination revealed a chronically ill patient. Bilateral carotid bruits were heard. Peripheral pulses were absent. Neurological examination was unremarkable. Computerized tomography of the head excluded intracranial pathology such as tumour, posterior fossa disease and hydrocephalia. The electroencephalogram was normal. Carotid Doppler showed significant stenosis of left common carotid artery. Carotid arteriogram was proposed but the patient refused. Treatment with oral platelet antiaggregants and codeine was instituted, plus manoeuvres to avoid intradialysis hypotension, with transient improvement. In January 1989 he died following a myocardial infarction. Our patient, like the one reported by Britton and Guiloff,5 had had cough headache for several months before other neurological symptoms developed. The relation of the cough headache to the carotid artery stenosis is uncertain. In our case, headache and neurological symptoms always followed cough and hypotension. These are situations that decrease cerebral flow and may cause cerebral ischaemic events in the presence of a severely stenosed carotid artery. In conclusion, cough headache can be the presenting symptom of carotid obstruction even before focal symptoms develop. We believe that in patients with cough headache, carotid arteriogram must be considered in order to exclude carotid pathology.
M. Rivera M.A. del Real' J.L. Teruel J.M. Gobernado' J. Ortuiio Nephrology Service and 'Neurology Service, Hospital Ram6n y Cajal, Madrid, Spain. References 1. Ekbom, K. Cough headache. In: Rose, C. (ed) Handbook of Clinical Neurology, Vol. 4 (48). Headache. 1986, pp. 367-371. 2. West, T.E.T., Davies, R.J. & Kelly, R.E. Horner's syndrome and headache due to carotid artery disease. Br Med J 1976, i: 818-820. 3. Messert, B. & Black, J.A. Cluster headache, hemicrania and other head pains: Morbidity or carotid endarterectomy. Stroke 1978, 9: 559-562. 4. Edmeads, J. The headaches of ischemic cerebrovascular disease. Headache 1979, 19: 345-349. 5. Britton, T.C. & Guiloff, R.J. Carotid artery disease presenting as cough headache. Lancet 1988, i: 1406-1407.
Hypereosinophilia and acute lymphocytic leukaemia Sir, The association of acute lymphocytic leukaemia (ALL) and eosinophilia is a rare event. Few cases characterized phenotypically and genotypically have been reported.'"2 We observed a hypereosinophilic syndrome as the first finding in a patient who developed an ALL of pre-B lineage. A previously healthy 15 year old male was admitted to our hospital because of chest pain, fever and diarrhoea of acute onset. Physical examination was normal; no cutaneous lesions, enlargement of lymph nodes, spleen or liver were noted. The peripheral blood counts showed a haemoglobin of 12.8 g/dl, platelets of 121 x 109/1 and WBC of 95.7 x 109/1 with 87% eosinophils (83 x 109/1), many of them were abnormal with vacuoles and partially degranulated; no immature cells were observed in the blood smear, serum lactate dehydrogenase was 469 U/1. Haemostatic parameters, electrocardiogram and chest X-ray were normal. Bone marrow aspirate showed 30% lymphoid blasts and 40% eosinophils, some of them abnormal. The blastic population was myeloperoxidase, chloro-acetate-esterase, butyrate-esterase and cyanideresistant myeloperoxidase negative in the cytochemical stains. The CD0 and TdT, determined by immunoperoxidase technique,3 were positive. Other surface markers analysed by flow cytometry showed the HLA-DR positive in 86%, CD19 in 86%, and CD20 in 79% of the bone marrow mononucleated cells; CD3, CD2 and CD14 were positive only in 5%, 6% and 3% of the cells. Bone marrow chromosomal analysis (G-banding) showed a normal karyotype (46 XY) in 20 studied metaphases. A diagnosis of common/preB-ALL was made. The patient achieved complete remission in 4 weeks with vincristine, daunorubicin, L-asparaginase and prednisone; peripheral and bone marrow eosinophils disappeared. He remains in complete remission under chemotherapy 6 months after
diagnosis.
LETTERS TO THE EDITOR Rarely, hypereosinophilia can be the only early manifestation of ALL, as in the case we describe. Cytochemistry, phenotypic markers and karyotype analysis help to rule out, in these patients, acute or chronic eosinophilic leukaemia, acute myeloid leukaemia with eosinophilia and even idiopathic hypereosinophilia syndrome. ALL-associated eosinophilia usually precedes or is concomitant with the initial diagnosis, disappears in remission and usually appears at the time of leukaemia relapse.2 Eosinophilia does not seem to affect prognosis and there is no difference in chemotherapy response rate and overall survival between patients with and without eosinophilia; nevertheless, cardiorespiratory findings are found more frequently in this group of patients than in other ALLs.2 Apparently there is no specific ALL subtype more commonly associated with eosinophilia and both B and T-ALL have been reported. Cytogenetic studies have shown in some patients a t(5; 14); however, a normal karyotype was observed in our patient. Several hypotheses tried to explain the presence of hypereosinophilia in ALL and other lymphoid malignancies. Currently it is thought to be a reactive manifestation rather than being part of the abnormal leukaemic clone; possibly it is mediated through an eosinophilic stimulating factor secreted by the leukaemic cells. Recently the t(5;14)(q31;q32) from patients with ALL and eosinophilia has been cloned and apparently in this translocation there is a junction of the IgM gene and the interleukin-3 gene, resulting in excessive production of this factor by the leukaemic cells.4
703
Our patient has a pre-B-ALL, without evidence of specific cytogenetic abnormality, whose first manifestation was a hypereosinophilic syndrome. We believe the general internist should be aware of this rare association in the differential diagnosis of hypereosinophilia. E. Rios-Herranz R. Fores-Cachon J.L. Diez-Martin M.N. Fernandez Servicio de Hematologia, Clinica 'Puerta de Hierro',
Madrid, Spain. References 1. Catovsky, D., Bernasconi, C., Verdonck, P.J. et al. The association of eosinophilia with lymphoblastic leukaemia or lymphoma: a study of seven patients. Br J Haematol 1980, 45: 523-534. 2. Hogan, T.F., Koss, W., Murgo, A.J., Amato, R.S., Fontana, J.A. & VanScoy, F.L. Acute lymphoblastic leukemia with chromosomal 5;14 translocation and hypereosinophilia: case report and literature review. J Clin Oncol 1987, 5: 382-390. 3. Sun, T., Li, C.Y. & Yam, L.T. Atlas of Cytochemistry and Immunochemistry of Hematologic Neoplasms. American Society of Clinical Pathologist Press, Chicago, 1985. 4. Meeker, T.C., Hardy, D., Willman, C., Hogan, T. & Abrams, J. Activation of the interleukin-3 gene by chromosome translocation in acute lymphocytic leukemia with eosinophilia. Blood 1990, 76: 285-289.
LETTERS TO THE EDITOR
Carotid artery disease presenting as cough headache in a patient on haemodialysis Sir, Headache has been associated with all types of cerebrovascular events, such as transient ischaemic attacks, lacunar infarcts and parenchymal haemorrhage.' In addition, the association of headache to carotid artery disease is well recognized, although the mechanisms of pain remain unclear.2 Headache has been reported after spontaneous carotid dissection and carotid endarterectomy.4 Cough headache is a well described entity consisting of transient pain on coughing, sneezing, laughing or heavy lifting. This is usually a benign idiopathic state although it is occasionally associated with foramen magnum and posterior fossa pathology (Arnold Chiari, arteriovenous malformations and tumour).' To our knowledge, there is only one previous report concerning cough headache and carotid artery disease.5 We report a patient on haemodialysis with cough headache as the presenting symptom of carotid artery disease. A 54 year old patient had been on haemodialysis (HD) for 10 years because of chronic renal failure (CRF) secondary to membranous nephropathy. He had a history of heavy smoking, chronic obstructive lung disease and long-term hypertension. Clinical features of generalized atherosclerosis developed in 1987, consisting of angina pectoris and intermittent claudication. In July 1988 he began to suffer from right severe retrocular pain following cough attacks. In November, right blunted vision, weakness of the left arm with abnormal spontaneous movements of his left hand, minimal facial paresis and dysarthria were associated with cough headache. Those symptoms appeared not only with cough, but also with intradialysis hypotension (systolic blood pressure lower than 80 mmHg). Neurological symptoms reversed completely in 10- 15 minutes. He was admitted to hospital in December. Physical examination revealed a chronically ill patient. Bilateral carotid bruits were heard. Peripheral pulses were absent. Neurological examination was unremarkable. Computerized tomography of the head excluded intracranial pathology such as tumour, posterior fossa disease and hydrocephalia. The electroencephalogram was normal. Carotid Doppler showed significant stenosis of left common carotid artery. Carotid arteriogram was proposed but the patient refused. Treatment with oral platelet antiaggregants and codeine was instituted, plus manoeuvres to avoid intradialysis hypotension, with transient improvement. In January 1989 he died following a myocardial infarction. Our patient, like the one reported by Britton and Guiloff,5 had had cough headache for several months before other neurological symptoms developed. The relation of the cough headache to the carotid artery stenosis is uncertain. In our case, headache and neurological symptoms always followed cough and hypotension. These are situations that decrease cerebral flow and may cause cerebral ischaemic events in the presence of a severely stenosed carotid artery. In conclusion, cough headache can be the presenting symptom of carotid obstruction even before focal symptoms develop. We believe that in patients with cough headache, carotid arteriogram must be considered in order to exclude carotid pathology.
M. Rivera M.A. del Real' J.L. Teruel J.M. Gobernado' J. Ortuiio Nephrology Service and 'Neurology Service, Hospital Ram6n y Cajal, Madrid, Spain. References 1. Ekbom, K. Cough headache. In: Rose, C. (ed) Handbook of Clinical Neurology, Vol. 4 (48). Headache. 1986, pp. 367-371. 2. West, T.E.T., Davies, R.J. & Kelly, R.E. Horner's syndrome and headache due to carotid artery disease. Br Med J 1976, i: 818-820. 3. Messert, B. & Black, J.A. Cluster headache, hemicrania and other head pains: Morbidity or carotid endarterectomy. Stroke 1978, 9: 559-562. 4. Edmeads, J. The headaches of ischemic cerebrovascular disease. Headache 1979, 19: 345-349. 5. Britton, T.C. & Guiloff, R.J. Carotid artery disease presenting as cough headache. Lancet 1988, i: 1406-1407.
Hypereosinophilia and acute lymphocytic leukaemia Sir, The association of acute lymphocytic leukaemia (ALL) and eosinophilia is a rare event. Few cases characterized phenotypically and genotypically have been reported.'"2 We observed a hypereosinophilic syndrome as the first finding in a patient who developed an ALL of pre-B lineage. A previously healthy 15 year old male was admitted to our hospital because of chest pain, fever and diarrhoea of acute onset. Physical examination was normal; no cutaneous lesions, enlargement of lymph nodes, spleen or liver were noted. The peripheral blood counts showed a haemoglobin of 12.8 g/dl, platelets of 121 x 109/1 and WBC of 95.7 x 109/1 with 87% eosinophils (83 x 109/1), many of them were abnormal with vacuoles and partially degranulated; no immature cells were observed in the blood smear, serum lactate dehydrogenase was 469 U/1. Haemostatic parameters, electrocardiogram and chest X-ray were normal. Bone marrow aspirate showed 30% lymphoid blasts and 40% eosinophils, some of them abnormal. The blastic population was myeloperoxidase, chloro-acetate-esterase, butyrate-esterase and cyanideresistant myeloperoxidase negative in the cytochemical stains. The CD0 and TdT, determined by immunoperoxidase technique,3 were positive. Other surface markers analysed by flow cytometry showed the HLA-DR positive in 86%, CD19 in 86%, and CD20 in 79% of the bone marrow mononucleated cells; CD3, CD2 and CD14 were positive only in 5%, 6% and 3% of the cells. Bone marrow chromosomal analysis (G-banding) showed a normal karyotype (46 XY) in 20 studied metaphases. A diagnosis of common/preB-ALL was made. The patient achieved complete remission in 4 weeks with vincristine, daunorubicin, L-asparaginase and prednisone; peripheral and bone marrow eosinophils disappeared. He remains in complete remission under chemotherapy 6 months after
diagnosis.
LETTERS TO THE EDITOR Rarely, hypereosinophilia can be the only early manifestation of ALL, as in the case we describe. Cytochemistry, phenotypic markers and karyotype analysis help to rule out, in these patients, acute or chronic eosinophilic leukaemia, acute myeloid leukaemia with eosinophilia and even idiopathic hypereosinophilia syndrome. ALL-associated eosinophilia usually precedes or is concomitant with the initial diagnosis, disappears in remission and usually appears at the time of leukaemia relapse.2 Eosinophilia does not seem to affect prognosis and there is no difference in chemotherapy response rate and overall survival between patients with and without eosinophilia; nevertheless, cardiorespiratory findings are found more frequently in this group of patients than in other ALLs.2 Apparently there is no specific ALL subtype more commonly associated with eosinophilia and both B and T-ALL have been reported. Cytogenetic studies have shown in some patients a t(5; 14); however, a normal karyotype was observed in our patient. Several hypotheses tried to explain the presence of hypereosinophilia in ALL and other lymphoid malignancies. Currently it is thought to be a reactive manifestation rather than being part of the abnormal leukaemic clone; possibly it is mediated through an eosinophilic stimulating factor secreted by the leukaemic cells. Recently the t(5;14)(q31;q32) from patients with ALL and eosinophilia has been cloned and apparently in this translocation there is a junction of the IgM gene and the interleukin-3 gene, resulting in excessive production of this factor by the leukaemic cells.4
703
Our patient has a pre-B-ALL, without evidence of specific cytogenetic abnormality, whose first manifestation was a hypereosinophilic syndrome. We believe the general internist should be aware of this rare association in the differential diagnosis of hypereosinophilia. E. Rios-Herranz R. Fores-Cachon J.L. Diez-Martin M.N. Fernandez Servicio de Hematologia, Clinica 'Puerta de Hierro',
Madrid, Spain. References 1. Catovsky, D., Bernasconi, C., Verdonck, P.J. et al. The association of eosinophilia with lymphoblastic leukaemia or lymphoma: a study of seven patients. Br J Haematol 1980, 45: 523-534. 2. Hogan, T.F., Koss, W., Murgo, A.J., Amato, R.S., Fontana, J.A. & VanScoy, F.L. Acute lymphoblastic leukemia with chromosomal 5;14 translocation and hypereosinophilia: case report and literature review. J Clin Oncol 1987, 5: 382-390. 3. Sun, T., Li, C.Y. & Yam, L.T. Atlas of Cytochemistry and Immunochemistry of Hematologic Neoplasms. American Society of Clinical Pathologist Press, Chicago, 1985. 4. Meeker, T.C., Hardy, D., Willman, C., Hogan, T. & Abrams, J. Activation of the interleukin-3 gene by chromosome translocation in acute lymphocytic leukemia with eosinophilia. Blood 1990, 76: 285-289.
