Journal of the Royal Society of Medicine Volume 85 August 1992 restricted and levator recession has been performed. She remains clinically and biochemically euthyroid on carbimazole 5 mg a day. Discussion In adults, Graves' disease accounts for about 16% of patients presenting with unilateral exophthalmos and for the majority of those with bilateral proptosis. Extraocular muscle thickening can be unilateral or asymmetrical in 30% cases'. The inferior and medial rectus muscles are most frequently involved2. The other causes, of exophthalmos include tumours, orbital pseudotumour and arterio-venous malformations. Our patient had an atypical presentation. A pseudotumour was thought unlikely as pain is a predominant feature of this condition. There were no symptoms or signs suggestive of malignancy and it would be uncommon for a primary or secondary tumour to give rise to the rapid progression of events. CT scanning is widely used in the diagnosis of exophthalmos. The interpretation of CT scans in dysthyroid eye disease can be difficult. Minimal muscle enlargement is hard to determine and coronal views should be done to supplement
Haematological improvement with conservative management in an infant with myelodysplasia
the usual axial projections. Patient cooperation is important. It can be difficult to position patients correctly to see the inferior rectus muscle. In axial cuts through the lower orbit the enlarged muscle can have a round outline simulating retrobulbar tumours3. It is also vital that there is no movement of the eyes during scanning as this can distort the images. A discrete retro-orbital mass may be a manifestation of dysthyroid eye disease and a trial of steroids should be given before invasive investigation.
References 1 Enzmann DR, Donaldson SS, Kriss JP. Appearances of Graves' disease in orbital computerised tomography. J Comput Assist Tomogr 1979;3:815-19 2 Trokel SL, Hilal SK. Recognition and differential diagnosis of enlarged extra-ocular muscles in computed tomography. Am J Ophthal 1979;87:503-12 3 Sisler HA, Jakobiec FA, Trokel SL. Ocular examination and orbital changes of Graves' disease. Clin Ophthalmol 1982; 2:36
(Accepted 11 December 1991)
200
-
Case presented to Section of Paediatrics, 10 February 1989
070-
z 208 fi 4
A J B Emmerson DCH MRCP1 R J Grace BSc MRCP2 H Grech MRcP2 C M M Stern PhD FRCP T C Pearson MD FRCPath2 Departments of 'Paediatrics and 2Haematology, United Medical and Dental School of Guy's and St Thomas' Hospitals, St Thomas' Campus, Lambeth Palace Road, London SEl 7EH KeywordA myelodysplasia; refirctory anaemia; conservative treatment Myelodysplasia (MDS) is a rare condition in children and commonly progresses to acute myeloid leukaemia (AML). We report the long-term haematological improvement in an infant managed conservatively. Case report A 6-month-old Italian infant presented with fever, irritability, anorexia and extreme pallor. Examination revealed a tachycardia of 180 beats/min, hepatomegaly without splenomegaly, lymphadenopathy or jaundice.-Initial investigations were; haemoglobin 2.2 g/dl, mean cell volume94 fl, mean cell haemoglobin 32.8 pg, reticulocytes 2x 109/1, white blood count 4.3x1091/1, granulocytes 0.6x109/1 and platelets 142 x 1091/1. There was no acute blood loss, and the haemoglobinopathy screen and parvo. virus titres were negative. The bone marrow aspirate revealed a cellular marrow with moderately reduced erythropoiesis, dyserythropoietic vacuolated erythroblasts, increased iron stores, agranular myelocytes and promyelocytes, less than 5% blasts and increased-numbers of abnorma megakaryoqtea Peripheral and marrow-chromosomes were normal with no break seen. At 6 months post diagnsither was no growth of erythroid or myeloid precursors in pell.cultureiof mow and peripheral blood. The features were consistent with the diagnosis of myelodysplasia of the refractory anaemia type
495
t
~~~44
Cp~~~~~~~~~~~rIansuions
0
.5
0
3
6
9 12 15 18 21 24 27 30 33 Months since diagnosis
Figure 1. The granulocyte and platelet counts with their respective linear regression lines and the haemoglobin level and frequency of transfusions following diagnosis of myelodysplasia in a 6 month infant treated conservatively
according to the French-American-British (FAB) criteria. His sibling was HLA incompatible. He was managed with blood transfusions every 3 weeks but this has decreased with only one transfusion being required over the last year (Figure 1). His ferritin level increased to a maximum of 1407 g/L. He has thrived and is developmentally normaL WWhen clinically well he remains neutropsenic and thrombocytopaenic, but the mean granulocyte and platelet counts have slowly incsed since diagosis (gure 1). A recent marrow examination shows improvement with mildly megaloblastic erythropoiesis but with ring sideroblasts. Granulopoiesis,was essentially normal with only occasional agranular forms, and there were micromegakaryocytes-withreduced megakaryopoiesis, Thirty months after diansis cell culture ofhis bone marrow and peripheral blood showed detectable growth of both erythroid and myeloid piecursors. Discussion Myelodysplasia is rare in childhood, and the incidence is unknown. There are five main groups as defined by the FAB 1' These conditions have been shown to be clonal disorder- arisig from a mnltipotent stem cell2. The outlook for infants with myelodysplasia is,poor with progression to AML and a median survival of 20-36 months3'4.
0141-0768/92 080495-02/$02.00/0 © 1992 The Royal Society of Medicine
496
Journal of the Royal Society of Medicine Volume 85 August 1992
The therapeutic options are limited, and there is little experience of bone marrow transplantations in infants with myelodysplasia, but one study has reported cure in around 50%8. Another option is the use of intensive chemotherapy similar to that given for AML6. However, this produces prolonged periods of marrow hypoplasia, and although there was complete remission in 70% of patients in adult studies, most long-term remissions were obtained after subsequent bone marrow transplantation7. Maturational agents such as low dose cytarabine, retinoids and vitamin D3 have been studied, but found to be ineffective5. There has been some temporary improvement with the use of the cytokines granulocyte and granulocytemacrophage colony stimulating factors. However, there is concern that these might accelerate the progression to AML5. The remaining option is conservative treatment until there is evidence of progression to AML. In the absence of an HLA matched sibling donor and with a diagnosis of one of the milder forms of myelodysplasia we adopted this approach, and have seen slow but definite improvement in the number and maturity of all cells lines. There do not appear to be reports of apparent improvement in the haematological parameters as seen in this case, and though reversion to a completely normal state has not yet been achieved there has been improvement in all haematopoietic cell lines. This case illustrates a rare and serious condition which generally progresses to AML in which there is an apparent haematological improvement over a 3-year period with conservative treatment.
Acknowledgment We thank Mr N B Westwood for performing the cell cultures.
Tendon contractures in hypercholesterolaemia
of ischaemic heart disease, a Z-lengthening procedure was performed to the tendon. Following this, the patient again became mobile in callipers.
J F Nolan FRCS Department of Orthopaedics, St Bartholomew's Hospital; London Keywords: tendo achilles; hypercholesterolaemia
Achilles tendinitis is a well recognized complication of type IIa hypercholesterolaemia. Tendon contractures, however, are previously unreported. Case report In 1968, a 29-year-old Caucasian woman first presented with tendo-achilles pain, swelling and tenderness. She was treated by immobilization in plaster. In 1974, a diagnosis of tenosynovitis of the tendo-achilles led to treatment with anti-inflammatory medication, steroid injections, and stretching under anaesthesia. In 1982, stripping of the tendo-achilles was performed, when xanthoma-like nodules were found in the tendon. Histology, however, demonstrated non-specific degeneration only, with cleft-like spaces. Further surgery and stretches were performed for a fixed equino-varus deformity, confirmed under anaesthesia, despite which the patient became wheelchair-bound. In 1989, following the diagnosis of type Ha hypercholesterolaemia and exposure of a strong family history Correspondence to: Mr J F Nolan, Orthopaedic Department, Princess Alexandra Hospital, Hamatel Road, Harlow, Essex CM20 1QX
References 1 Tefferi A, Thibodeau SN, Solberg LA Jr. Clonal studies in the myelodysplastic syndrome using X-linked restriction fragment length polymorphisms. Blood 1990;75:1770-3 2 Bennett JM, Catovsky D, Daniel MT, et al Proposals for the classification of the myelodysplastic syndromes. Br J Haematol 1982;51:189-99 3 Weber RFA, Geraedts JPM, et al The preleukaemia syndrome. I. Clinical and haematological findings. Acta Med Scand 1980;207:391-5 4 Joseph AS, Cinkotai KL. Natural history of smouldering leukaemia. Br J Cancer 1982;46:160-6 5 Chessels JM. Myelodysplasia. In: Hann IM, Gibson BES, eds. Bailliere's Clinical Haematology. London: Bailliere Tindall, 1991: 459-82 6 Cheson BD. The myelodysplastic syndromes: current approaches to therapy. Ann Intern Med 1990;112:932-41 7 De Witte T, Zwaan F, Hermans J, et aL Allogeneic bone marrow transplantation for secondary leukaemia and myelodysplastic syndrome: a survey by the Leukaemia Working Party of the European Bone Marrow Transplantation Group. Br J Haematol 1990;74:151-55 8 Guinan EC, Tantravahi R, Weinstein HJ. Bone marrow transplantation for children with myelodysplasia. Blood 1989;73: 619-22
(Accepted 5 February 1992)
Discussion Classical xanthomata of the tendo-achilles are of cosmetic concern only, although type Ha hypercholesterolaemia may present with tendinitis or arthritis1'3. Pain is then exacerbated by tension in the tendon, which exhibits a tender swelling, sometimes nodular, and warmth'. The tendon collagen is infiltrated by xanthoma, which may involve adjacent soft tissues and skin, increasing the tendon thickness by two or three times. This is significantly greater than occurs in secondary hypercholesterolaemia and differentiates these disorders4. Bilateral involvement occurs in 90% of patients, 66% also suffering from deposits in the extensor tendons ofthe hands, and 26% with patellar tendon disease5. The number and size of the lesions show some correlation with the cholesterol level and the increasing age of the individual6. Microscopically, xanthoma may be seen, with degenerative connective tissue. Inflammation is caused by cholesterol crystal deposition, which is responsible for clefts seen ifthe lipid is dissolved out during specimen preparation7. Tendo-achilles xanthomata usually present in young adulthood; occurrence under the age of 10 years being indicative of a homozygous patient8. These patients have exceptionally high cholesterol levels, and coronary artery atherosclerosis is severe. Survival beyond 30 years is rare6. Type Ha familial hypercholesterolaemia is acquired as an autosomal dominant trait, and affects approximately 0.2% of the population. It is characterized by a discrete rise in the beta-lipoproteins, with a marked elevation of cholesterol, and little or no rise in triglycerides. Recognition of the disorder at the earliest possible age is highly desirable in order that dietary and drug therapy may begin. This may reduce serum cholesterol levels by 15-25%, and with bezafibrate reducing the size of tendon xanthomas,
Case presented to Clinical Section, 8 November 1991
0141-0768/92
080496-02/$02.00/0 © 1992 The Royal Society of Medicine
Haematological improvement with conservative management in an infant with myelodysplasia
the usual axial projections. Patient cooperation is important. It can be difficult to position patients correctly to see the inferior rectus muscle. In axial cuts through the lower orbit the enlarged muscle can have a round outline simulating retrobulbar tumours3. It is also vital that there is no movement of the eyes during scanning as this can distort the images. A discrete retro-orbital mass may be a manifestation of dysthyroid eye disease and a trial of steroids should be given before invasive investigation.
References 1 Enzmann DR, Donaldson SS, Kriss JP. Appearances of Graves' disease in orbital computerised tomography. J Comput Assist Tomogr 1979;3:815-19 2 Trokel SL, Hilal SK. Recognition and differential diagnosis of enlarged extra-ocular muscles in computed tomography. Am J Ophthal 1979;87:503-12 3 Sisler HA, Jakobiec FA, Trokel SL. Ocular examination and orbital changes of Graves' disease. Clin Ophthalmol 1982; 2:36
(Accepted 11 December 1991)
200
-
Case presented to Section of Paediatrics, 10 February 1989
070-
z 208 fi 4
A J B Emmerson DCH MRCP1 R J Grace BSc MRCP2 H Grech MRcP2 C M M Stern PhD FRCP T C Pearson MD FRCPath2 Departments of 'Paediatrics and 2Haematology, United Medical and Dental School of Guy's and St Thomas' Hospitals, St Thomas' Campus, Lambeth Palace Road, London SEl 7EH KeywordA myelodysplasia; refirctory anaemia; conservative treatment Myelodysplasia (MDS) is a rare condition in children and commonly progresses to acute myeloid leukaemia (AML). We report the long-term haematological improvement in an infant managed conservatively. Case report A 6-month-old Italian infant presented with fever, irritability, anorexia and extreme pallor. Examination revealed a tachycardia of 180 beats/min, hepatomegaly without splenomegaly, lymphadenopathy or jaundice.-Initial investigations were; haemoglobin 2.2 g/dl, mean cell volume94 fl, mean cell haemoglobin 32.8 pg, reticulocytes 2x 109/1, white blood count 4.3x1091/1, granulocytes 0.6x109/1 and platelets 142 x 1091/1. There was no acute blood loss, and the haemoglobinopathy screen and parvo. virus titres were negative. The bone marrow aspirate revealed a cellular marrow with moderately reduced erythropoiesis, dyserythropoietic vacuolated erythroblasts, increased iron stores, agranular myelocytes and promyelocytes, less than 5% blasts and increased-numbers of abnorma megakaryoqtea Peripheral and marrow-chromosomes were normal with no break seen. At 6 months post diagnsither was no growth of erythroid or myeloid precursors in pell.cultureiof mow and peripheral blood. The features were consistent with the diagnosis of myelodysplasia of the refractory anaemia type
495
t
~~~44
Cp~~~~~~~~~~~rIansuions
0
.5
0
3
6
9 12 15 18 21 24 27 30 33 Months since diagnosis
Figure 1. The granulocyte and platelet counts with their respective linear regression lines and the haemoglobin level and frequency of transfusions following diagnosis of myelodysplasia in a 6 month infant treated conservatively
according to the French-American-British (FAB) criteria. His sibling was HLA incompatible. He was managed with blood transfusions every 3 weeks but this has decreased with only one transfusion being required over the last year (Figure 1). His ferritin level increased to a maximum of 1407 g/L. He has thrived and is developmentally normaL WWhen clinically well he remains neutropsenic and thrombocytopaenic, but the mean granulocyte and platelet counts have slowly incsed since diagosis (gure 1). A recent marrow examination shows improvement with mildly megaloblastic erythropoiesis but with ring sideroblasts. Granulopoiesis,was essentially normal with only occasional agranular forms, and there were micromegakaryocytes-withreduced megakaryopoiesis, Thirty months after diansis cell culture ofhis bone marrow and peripheral blood showed detectable growth of both erythroid and myeloid piecursors. Discussion Myelodysplasia is rare in childhood, and the incidence is unknown. There are five main groups as defined by the FAB 1' These conditions have been shown to be clonal disorder- arisig from a mnltipotent stem cell2. The outlook for infants with myelodysplasia is,poor with progression to AML and a median survival of 20-36 months3'4.
0141-0768/92 080495-02/$02.00/0 © 1992 The Royal Society of Medicine
496
Journal of the Royal Society of Medicine Volume 85 August 1992
The therapeutic options are limited, and there is little experience of bone marrow transplantations in infants with myelodysplasia, but one study has reported cure in around 50%8. Another option is the use of intensive chemotherapy similar to that given for AML6. However, this produces prolonged periods of marrow hypoplasia, and although there was complete remission in 70% of patients in adult studies, most long-term remissions were obtained after subsequent bone marrow transplantation7. Maturational agents such as low dose cytarabine, retinoids and vitamin D3 have been studied, but found to be ineffective5. There has been some temporary improvement with the use of the cytokines granulocyte and granulocytemacrophage colony stimulating factors. However, there is concern that these might accelerate the progression to AML5. The remaining option is conservative treatment until there is evidence of progression to AML. In the absence of an HLA matched sibling donor and with a diagnosis of one of the milder forms of myelodysplasia we adopted this approach, and have seen slow but definite improvement in the number and maturity of all cells lines. There do not appear to be reports of apparent improvement in the haematological parameters as seen in this case, and though reversion to a completely normal state has not yet been achieved there has been improvement in all haematopoietic cell lines. This case illustrates a rare and serious condition which generally progresses to AML in which there is an apparent haematological improvement over a 3-year period with conservative treatment.
Acknowledgment We thank Mr N B Westwood for performing the cell cultures.
Tendon contractures in hypercholesterolaemia
of ischaemic heart disease, a Z-lengthening procedure was performed to the tendon. Following this, the patient again became mobile in callipers.
J F Nolan FRCS Department of Orthopaedics, St Bartholomew's Hospital; London Keywords: tendo achilles; hypercholesterolaemia
Achilles tendinitis is a well recognized complication of type IIa hypercholesterolaemia. Tendon contractures, however, are previously unreported. Case report In 1968, a 29-year-old Caucasian woman first presented with tendo-achilles pain, swelling and tenderness. She was treated by immobilization in plaster. In 1974, a diagnosis of tenosynovitis of the tendo-achilles led to treatment with anti-inflammatory medication, steroid injections, and stretching under anaesthesia. In 1982, stripping of the tendo-achilles was performed, when xanthoma-like nodules were found in the tendon. Histology, however, demonstrated non-specific degeneration only, with cleft-like spaces. Further surgery and stretches were performed for a fixed equino-varus deformity, confirmed under anaesthesia, despite which the patient became wheelchair-bound. In 1989, following the diagnosis of type Ha hypercholesterolaemia and exposure of a strong family history Correspondence to: Mr J F Nolan, Orthopaedic Department, Princess Alexandra Hospital, Hamatel Road, Harlow, Essex CM20 1QX
References 1 Tefferi A, Thibodeau SN, Solberg LA Jr. Clonal studies in the myelodysplastic syndrome using X-linked restriction fragment length polymorphisms. Blood 1990;75:1770-3 2 Bennett JM, Catovsky D, Daniel MT, et al Proposals for the classification of the myelodysplastic syndromes. Br J Haematol 1982;51:189-99 3 Weber RFA, Geraedts JPM, et al The preleukaemia syndrome. I. Clinical and haematological findings. Acta Med Scand 1980;207:391-5 4 Joseph AS, Cinkotai KL. Natural history of smouldering leukaemia. Br J Cancer 1982;46:160-6 5 Chessels JM. Myelodysplasia. In: Hann IM, Gibson BES, eds. Bailliere's Clinical Haematology. London: Bailliere Tindall, 1991: 459-82 6 Cheson BD. The myelodysplastic syndromes: current approaches to therapy. Ann Intern Med 1990;112:932-41 7 De Witte T, Zwaan F, Hermans J, et aL Allogeneic bone marrow transplantation for secondary leukaemia and myelodysplastic syndrome: a survey by the Leukaemia Working Party of the European Bone Marrow Transplantation Group. Br J Haematol 1990;74:151-55 8 Guinan EC, Tantravahi R, Weinstein HJ. Bone marrow transplantation for children with myelodysplasia. Blood 1989;73: 619-22
(Accepted 5 February 1992)
Discussion Classical xanthomata of the tendo-achilles are of cosmetic concern only, although type Ha hypercholesterolaemia may present with tendinitis or arthritis1'3. Pain is then exacerbated by tension in the tendon, which exhibits a tender swelling, sometimes nodular, and warmth'. The tendon collagen is infiltrated by xanthoma, which may involve adjacent soft tissues and skin, increasing the tendon thickness by two or three times. This is significantly greater than occurs in secondary hypercholesterolaemia and differentiates these disorders4. Bilateral involvement occurs in 90% of patients, 66% also suffering from deposits in the extensor tendons ofthe hands, and 26% with patellar tendon disease5. The number and size of the lesions show some correlation with the cholesterol level and the increasing age of the individual6. Microscopically, xanthoma may be seen, with degenerative connective tissue. Inflammation is caused by cholesterol crystal deposition, which is responsible for clefts seen ifthe lipid is dissolved out during specimen preparation7. Tendo-achilles xanthomata usually present in young adulthood; occurrence under the age of 10 years being indicative of a homozygous patient8. These patients have exceptionally high cholesterol levels, and coronary artery atherosclerosis is severe. Survival beyond 30 years is rare6. Type Ha familial hypercholesterolaemia is acquired as an autosomal dominant trait, and affects approximately 0.2% of the population. It is characterized by a discrete rise in the beta-lipoproteins, with a marked elevation of cholesterol, and little or no rise in triglycerides. Recognition of the disorder at the earliest possible age is highly desirable in order that dietary and drug therapy may begin. This may reduce serum cholesterol levels by 15-25%, and with bezafibrate reducing the size of tendon xanthomas,
Case presented to Clinical Section, 8 November 1991
0141-0768/92
080496-02/$02.00/0 © 1992 The Royal Society of Medicine
