368
Journal of the Royal Society of Medicine Volume 84 June 1991
References 1 Goldman IL, Caldamene AA, Gauderer M, Hampel N, Wesselhoeft CW, Elder JS. Infected urachal cysts: a review of 10 cases. J Urol 1988;140:375-8 2 Blichert-Toft M, Nielson OV. Disease of the urachus simulating intra-abdominal disorders. Am J Surg 1971;122:123 3 Blichert-Toft M, Nielson OV. Congenital patent urachus and acquired variants. Diagnosis and treatment. Review of the literature and report of 5 cases. Acta Chir Scand 1971;137:807-14 4 Sterling JA, Goldsmith R. Lesions of the urachus appear in the adult. Ann Surg 1953;137:120 5 Newman BM, Karp MP, Jewett TC, Coonery DR. Advances in the management of infected urachal cysts. J Paediatr Surg, 1986;21:1051-2
6 Berman SM, Tolia BM, Laor E, Reid RE, Schweizer SP, Freed SZ. Urachal remnants in adults. Urology 1988;31:17-21 7 Blichert-Toft M, Kock F, Nielson OV. Anatomic variations of the urachus related to clinical appearance and surgical treatment of urachal disorders. Surg Gynecol Obstet 1973;137:51 8 Avni EF, Matos C, Regemarter G, Goolaerts JP, Diard F. Symptomatic patent urachus in children: the contribution of ultrasound. European Society of Paediatric Radiology, Toronto 1987;30:482-5 9 Morin ME, Tan A, Baker DA, Sue HK. Urachal cyst in the adultultrasound diagnosis. J Urol 1979;132:831
(Accepted 29 January 1991. Correspondence to Mr P T Doyle, Department of Urology, Addenbrookes Hospital, Cambridge CB2 2QQ)
Sarcoidosis and acute myeloid leukaemia
Case presented to Section of Rheumatology & Rehabilitation, 30 June 1990
E A Murphy MB ChB MRCP' J A Murphy MB ChB MRCP2 R Jackson MB MRCPI3 R D Sturrock MD FRCP' 'Centre for Rheumatic Diseases, Departments of 2Haematology and 3Pathology, Glasgow Royal Infirmary, Glasgow G4 OSF Keywords: sarcoid; acute myeloid leukaemia; glomerulonephritis; aspergillosis
A 52-year-old man with a long history of uveitis had a diagnosis of sarcoid made when he developed a seronegative polyarthropathy and was shown to have non-caseating granulomata in biopsies of bone-marrow and liver. He died 10 years later of acute myeloid leukaemia and widespread invasive aspergillosis, having developed porphyria cutanea tarda, alcoholic liver disease, cardiac failure and mesangioproliferative glomerulonephritis in the interim. Case report A 52-year-old man was referred to the rheumatology clinic in 1980 because of a history ofjoint pains over the preceding few months. He had a long history of uveitis and secondary glaucoma. X-rays showed no erosions and testing for rheumatoid factor was negative. He was noted to be anaemic with a haemoglobin of about 8 g/dl and he underwent bone marrow biopsy when initial investigations failed to reveal a cause for the anaemia. This showed a hypercellular marrow with increased reticulin staining, raising the possibility of an underlying myeloproliferative disorder. In view of this, a repeat bone-marrow biopsy was carried out 6 months later which was again hypercellular, and in addition showed the presence of a non-caseating epithelioid granuloma. Liver biopsy at this time showed similar granulomata and moderate fatty change compatible with a history of excessive alcohol intake. The result of a Kveim test was equivocal, chest X-ray was normal and pulmonary function tests showed a reduction in the transfer factor. Review of the initial hand X-rays showed coarse trabeculation, typical of sarcoid bone disease (Figure 1). On the basis ofthese findings, and the history of uveitis, a diagnosis of sarcoid was made. Because of persistent anaemia and recurrent uveitis, the patient was commenced on low dose prednisolone, on which he remained, in varying doses, until his death. Some months later, he developed a blistering skin rash which was confirmed as porphyria cutanea tarda. Over the next few years, he remained anaemic and had recurrent uveitis but was otherwise well.
Figure 1. Hand radiographs at the time of presentation
In 1984, he was admitted as an emergency because of increasing breathlessness. A diagnosis of biventricular cardiac failure was made. There was no evidence of recent myocardial infarction and echocardiography showed a small pericardial effusion but no evidence of any primary myocardial or valvular problem. He was again anaemic with a leucoerythroblastic blood film on this occasion, and bonemarrow examination was once more hypercellular with no distinguishing morphological features. With appropriate therapy, he improved over the course of 2 weeks and remained well for the next 4 years despite persistent anaemia and an abnormal blood film. In 1988 he was noted to have renal impairment with a urea of over 20 mmol/l and creatinine over 300 umolfl. Bone-marrow appearances were unchanged. Renal biopsy showed mesangioproliferative glomerulonephritis with mesangial IgA deposition. In 1989, when he again complained of tiredness and malaise, his haemoglobin was found to be 5 g/dl. The peripheral blood film was again leucoerythroblastic with many abnormal monocytoid cells. The bone-marrow was hypercellular showmng erythroid hyperplasia with a left shift of the myeloid series. One week after admission his condition deteriorated over several hours with increasing breathlessness, widespread bronchospasm and severe hypoxia. He was transferred to the intensive therapy unit (ITU) for assisted ventilation. His peripheral blood film had deteriorated and showed numerous blast cells and bone marrow aspirate confirmed the diagnosis of acute myeloid leukaemia (FAB classification M4). Cytogenetic examination of the bone marrow demonstrated no abnormality. Before speific therapy could be commenced, he deteriorated fturther and died 36 h after arrival in the ITU. Postmortem examination confirmed the pre-mortem diagnoses. In addition, there was evidence of established hepatic cirrhosis and widespread invasive aspergillus infection with colonies in several tissues, including lung, trachea, myocardium and pancreas (Figure 2).
0141-0768/91/ 060368-02/$02.00/0 © 1991 The Royal Society of Medicine
Journal of the Royal Society of Medicine Volume 84 June 1991
1IV t
X!~J
Figure 2. Colonies of aspergillus in trachea Discussion This case is of interest not only because of the multiplicity of diagnoses but also because of the questions raised about the relationship between the various diseases. His history of alcohol abuse undoubtedly contributed to the development of porphyria cutanea tarda and hepatic cirrhosis which may in turn have contributed to the development of mesangioproliferative glomerulonephritisl'. The contribution of sarcoidosis to the development of the renal lesion is less clear, although there have been reports of mesangioproliferative glomerulonephritis occurring in sarcoid3. Pulmonary aspergillosis is a well recognized complication of pulmonary sarcoidosis, although this is usually in patients with severe, and often cavitating, disease4'5. Infection can, however occur when the chest X-ray is normal or shows only minor changes4. Invasive infection is uncommon and it seems likely that this man had longstanding low-grade colonization with aspergillus which only became invasive as he became more immunosuppressed terminally. Finally, this case leaves us with the paradox that, despite a 10-year history of bone marrow abnormalities, we could not predict or prevent the ultimate development of acute myeloid leukaemia. Whether his longstanding anaemia and marrow hypercellularity contributed in any way to the development of leukaemia remains a matter for speculation. The anaemia of sarcoidosis is often multifactorial with chronic disease, hypersplenism and bone marrow infiltration all playing some part. Although there have been reports of solid tumours and both Hodgkins and non-Hodgkins
Superior oblique palsy following ethmoidal surgery
G M B Dawidek FRCS FCOphth E Kelly DBO(T) C Lane FRCS FCOphth Department of Ophthalmology, University Hospital of Wales, Heath Park, Cardiff CF4 4XW Keywords: superior oblique palsy; ethmoidal surgery
The ethmoid sinus and its adjacent structures are involved in many ophthalmic and nasal operations. Procedures such as ethmoidectomy, orbital decompression, transsphenoidal hypophysectomy, dacrocystorhinostomy and ligation of the anterior ethmoidal artery for epistaxis are examples. Superior oblique palsy following such operations is rare. It has rarely
369
lymphoma occurring in association with sarcoidosis"9 there have been no previous reports of acute leukaemia complicating sarcoid. The association with solid tumours and lymphomas is controversial since granulomata may occur as a reaction to the tumour7'9. One can speculate on the effects of bone marrow granulomata on local cell growth and differentiation since it is well recognized that local influences are of critical importance in haemopoietic differentiation and development10. Granulomata may produce many lymphokines and other biologically active molecules11, all or some of which may affect haemopoietic events. Furthermore, the associated impairment of cellular immunity may lead to defective immune surveillance and therefore facilitate the expansion of malignant clones. This is the first reported case of acute myeloid leukaemia complicating sarcoidosis and it highlights both the multisystem nature of the disease and many of the difficulties encountered in diagnosis and management. References 1 Nochy D, Callard P, Bellon B, Bariety J, Druet P. Association of overt glomerulonephritis and liver disease: a study of 34 patients. Clin Nephrol 1976;6:422-7 2 Cameron JS. In Marsh FP, ed. Postgraduate nephrology. London: William Heinemann Medical, 1985:257 3 McCoy RC, Tisher TC. Glomerulonephritis associated with sarcoidosis. Am J Pathol 1972;68:339-58 4 Winterbauer RH, Kraemer KG. The infectious complications of sarcoidosis. Arch Intern Med 1976;136:1356-62 5 Tomlinson JR, Sahn SA. Aspergilloma in sarcoid and tuberculosis. Chest 1987;92:505-8 6 Daly PA, O'Briain DS, Robinson I, Guckian M, Prichard JS. Hodgkins disease with a granulomatous pulmonary presentation mimicking sarcoidosis. Thorax 1988;43:407-9 7 Brinckner H. Solid tumours preceding or following sarcoidosis. Med Pediatr Oncol 1987;15:82-8 8 Volckaert A, van der Niepen P, de Hou MF, van Hercke H, van Belle S. Association of sarcoid like lesions in the bone marrow with an adenocarcinoma of the ovary: report of a case. Acta Clin Beig 1986;41:426-30 9 Srincker H. Sarcoid reactions in malignant tumours. Cancer Treat Rev 1986;13:147-56 10 Yoshida T, Siltzbach LE, Masih N, Cohen S. Lymphokine activity in sarcoidosis and in experimental granulomas. In: Jones Williams W, Davies BH, eds. Sarcoidosis and other granulomatous diseases. Cardiff: Alpha Omega Publishing Ltd., UK 1980:472 11 Goldman JM. In: Hoffbrand AV, Lewis SM, eds. Postgraduate haematology, 3rd edn. Oxford: Heinemann, 1989:294
(Accepted 14 January 1991)
been reported in the literature'. We have recently seen three patients with such a palsy following ethmoidal surgery. All had previously normal binocular function.
Case reports Case 1 A 35-year-old man presented with thyrotoxicosis due to a small TSH-secreting pituitary tumour. Partial transsphenoidal hypophysectomy was performed through the right ethmoidal sinus with a skin incision medial to the canthus. The wound and eye were padded for 10 days. When the pad was removed he complained of diplopia. On examination a right hyperphoria was present. Right superior oblique underaction with marked overaction of the contralateral synergist was demonstrated on Hess chart (Figure 1). The palsy resolved within 3 months of surgery. Case 2 A 61-year-old man presented with uncontrollable epistaxis which failed to respond to nasal packing. Ligation ofthe right
Cases presented to Section of Ophthalmology, 14 June 1990
0141-0768/91/ 060369-02/$02.00/0 © 1991 The Royal Society of Medicine
Journal of the Royal Society of Medicine Volume 84 June 1991
References 1 Goldman IL, Caldamene AA, Gauderer M, Hampel N, Wesselhoeft CW, Elder JS. Infected urachal cysts: a review of 10 cases. J Urol 1988;140:375-8 2 Blichert-Toft M, Nielson OV. Disease of the urachus simulating intra-abdominal disorders. Am J Surg 1971;122:123 3 Blichert-Toft M, Nielson OV. Congenital patent urachus and acquired variants. Diagnosis and treatment. Review of the literature and report of 5 cases. Acta Chir Scand 1971;137:807-14 4 Sterling JA, Goldsmith R. Lesions of the urachus appear in the adult. Ann Surg 1953;137:120 5 Newman BM, Karp MP, Jewett TC, Coonery DR. Advances in the management of infected urachal cysts. J Paediatr Surg, 1986;21:1051-2
6 Berman SM, Tolia BM, Laor E, Reid RE, Schweizer SP, Freed SZ. Urachal remnants in adults. Urology 1988;31:17-21 7 Blichert-Toft M, Kock F, Nielson OV. Anatomic variations of the urachus related to clinical appearance and surgical treatment of urachal disorders. Surg Gynecol Obstet 1973;137:51 8 Avni EF, Matos C, Regemarter G, Goolaerts JP, Diard F. Symptomatic patent urachus in children: the contribution of ultrasound. European Society of Paediatric Radiology, Toronto 1987;30:482-5 9 Morin ME, Tan A, Baker DA, Sue HK. Urachal cyst in the adultultrasound diagnosis. J Urol 1979;132:831
(Accepted 29 January 1991. Correspondence to Mr P T Doyle, Department of Urology, Addenbrookes Hospital, Cambridge CB2 2QQ)
Sarcoidosis and acute myeloid leukaemia
Case presented to Section of Rheumatology & Rehabilitation, 30 June 1990
E A Murphy MB ChB MRCP' J A Murphy MB ChB MRCP2 R Jackson MB MRCPI3 R D Sturrock MD FRCP' 'Centre for Rheumatic Diseases, Departments of 2Haematology and 3Pathology, Glasgow Royal Infirmary, Glasgow G4 OSF Keywords: sarcoid; acute myeloid leukaemia; glomerulonephritis; aspergillosis
A 52-year-old man with a long history of uveitis had a diagnosis of sarcoid made when he developed a seronegative polyarthropathy and was shown to have non-caseating granulomata in biopsies of bone-marrow and liver. He died 10 years later of acute myeloid leukaemia and widespread invasive aspergillosis, having developed porphyria cutanea tarda, alcoholic liver disease, cardiac failure and mesangioproliferative glomerulonephritis in the interim. Case report A 52-year-old man was referred to the rheumatology clinic in 1980 because of a history ofjoint pains over the preceding few months. He had a long history of uveitis and secondary glaucoma. X-rays showed no erosions and testing for rheumatoid factor was negative. He was noted to be anaemic with a haemoglobin of about 8 g/dl and he underwent bone marrow biopsy when initial investigations failed to reveal a cause for the anaemia. This showed a hypercellular marrow with increased reticulin staining, raising the possibility of an underlying myeloproliferative disorder. In view of this, a repeat bone-marrow biopsy was carried out 6 months later which was again hypercellular, and in addition showed the presence of a non-caseating epithelioid granuloma. Liver biopsy at this time showed similar granulomata and moderate fatty change compatible with a history of excessive alcohol intake. The result of a Kveim test was equivocal, chest X-ray was normal and pulmonary function tests showed a reduction in the transfer factor. Review of the initial hand X-rays showed coarse trabeculation, typical of sarcoid bone disease (Figure 1). On the basis ofthese findings, and the history of uveitis, a diagnosis of sarcoid was made. Because of persistent anaemia and recurrent uveitis, the patient was commenced on low dose prednisolone, on which he remained, in varying doses, until his death. Some months later, he developed a blistering skin rash which was confirmed as porphyria cutanea tarda. Over the next few years, he remained anaemic and had recurrent uveitis but was otherwise well.
Figure 1. Hand radiographs at the time of presentation
In 1984, he was admitted as an emergency because of increasing breathlessness. A diagnosis of biventricular cardiac failure was made. There was no evidence of recent myocardial infarction and echocardiography showed a small pericardial effusion but no evidence of any primary myocardial or valvular problem. He was again anaemic with a leucoerythroblastic blood film on this occasion, and bonemarrow examination was once more hypercellular with no distinguishing morphological features. With appropriate therapy, he improved over the course of 2 weeks and remained well for the next 4 years despite persistent anaemia and an abnormal blood film. In 1988 he was noted to have renal impairment with a urea of over 20 mmol/l and creatinine over 300 umolfl. Bone-marrow appearances were unchanged. Renal biopsy showed mesangioproliferative glomerulonephritis with mesangial IgA deposition. In 1989, when he again complained of tiredness and malaise, his haemoglobin was found to be 5 g/dl. The peripheral blood film was again leucoerythroblastic with many abnormal monocytoid cells. The bone-marrow was hypercellular showmng erythroid hyperplasia with a left shift of the myeloid series. One week after admission his condition deteriorated over several hours with increasing breathlessness, widespread bronchospasm and severe hypoxia. He was transferred to the intensive therapy unit (ITU) for assisted ventilation. His peripheral blood film had deteriorated and showed numerous blast cells and bone marrow aspirate confirmed the diagnosis of acute myeloid leukaemia (FAB classification M4). Cytogenetic examination of the bone marrow demonstrated no abnormality. Before speific therapy could be commenced, he deteriorated fturther and died 36 h after arrival in the ITU. Postmortem examination confirmed the pre-mortem diagnoses. In addition, there was evidence of established hepatic cirrhosis and widespread invasive aspergillus infection with colonies in several tissues, including lung, trachea, myocardium and pancreas (Figure 2).
0141-0768/91/ 060368-02/$02.00/0 © 1991 The Royal Society of Medicine
Journal of the Royal Society of Medicine Volume 84 June 1991
1IV t
X!~J
Figure 2. Colonies of aspergillus in trachea Discussion This case is of interest not only because of the multiplicity of diagnoses but also because of the questions raised about the relationship between the various diseases. His history of alcohol abuse undoubtedly contributed to the development of porphyria cutanea tarda and hepatic cirrhosis which may in turn have contributed to the development of mesangioproliferative glomerulonephritisl'. The contribution of sarcoidosis to the development of the renal lesion is less clear, although there have been reports of mesangioproliferative glomerulonephritis occurring in sarcoid3. Pulmonary aspergillosis is a well recognized complication of pulmonary sarcoidosis, although this is usually in patients with severe, and often cavitating, disease4'5. Infection can, however occur when the chest X-ray is normal or shows only minor changes4. Invasive infection is uncommon and it seems likely that this man had longstanding low-grade colonization with aspergillus which only became invasive as he became more immunosuppressed terminally. Finally, this case leaves us with the paradox that, despite a 10-year history of bone marrow abnormalities, we could not predict or prevent the ultimate development of acute myeloid leukaemia. Whether his longstanding anaemia and marrow hypercellularity contributed in any way to the development of leukaemia remains a matter for speculation. The anaemia of sarcoidosis is often multifactorial with chronic disease, hypersplenism and bone marrow infiltration all playing some part. Although there have been reports of solid tumours and both Hodgkins and non-Hodgkins
Superior oblique palsy following ethmoidal surgery
G M B Dawidek FRCS FCOphth E Kelly DBO(T) C Lane FRCS FCOphth Department of Ophthalmology, University Hospital of Wales, Heath Park, Cardiff CF4 4XW Keywords: superior oblique palsy; ethmoidal surgery
The ethmoid sinus and its adjacent structures are involved in many ophthalmic and nasal operations. Procedures such as ethmoidectomy, orbital decompression, transsphenoidal hypophysectomy, dacrocystorhinostomy and ligation of the anterior ethmoidal artery for epistaxis are examples. Superior oblique palsy following such operations is rare. It has rarely
369
lymphoma occurring in association with sarcoidosis"9 there have been no previous reports of acute leukaemia complicating sarcoid. The association with solid tumours and lymphomas is controversial since granulomata may occur as a reaction to the tumour7'9. One can speculate on the effects of bone marrow granulomata on local cell growth and differentiation since it is well recognized that local influences are of critical importance in haemopoietic differentiation and development10. Granulomata may produce many lymphokines and other biologically active molecules11, all or some of which may affect haemopoietic events. Furthermore, the associated impairment of cellular immunity may lead to defective immune surveillance and therefore facilitate the expansion of malignant clones. This is the first reported case of acute myeloid leukaemia complicating sarcoidosis and it highlights both the multisystem nature of the disease and many of the difficulties encountered in diagnosis and management. References 1 Nochy D, Callard P, Bellon B, Bariety J, Druet P. Association of overt glomerulonephritis and liver disease: a study of 34 patients. Clin Nephrol 1976;6:422-7 2 Cameron JS. In Marsh FP, ed. Postgraduate nephrology. London: William Heinemann Medical, 1985:257 3 McCoy RC, Tisher TC. Glomerulonephritis associated with sarcoidosis. Am J Pathol 1972;68:339-58 4 Winterbauer RH, Kraemer KG. The infectious complications of sarcoidosis. Arch Intern Med 1976;136:1356-62 5 Tomlinson JR, Sahn SA. Aspergilloma in sarcoid and tuberculosis. Chest 1987;92:505-8 6 Daly PA, O'Briain DS, Robinson I, Guckian M, Prichard JS. Hodgkins disease with a granulomatous pulmonary presentation mimicking sarcoidosis. Thorax 1988;43:407-9 7 Brinckner H. Solid tumours preceding or following sarcoidosis. Med Pediatr Oncol 1987;15:82-8 8 Volckaert A, van der Niepen P, de Hou MF, van Hercke H, van Belle S. Association of sarcoid like lesions in the bone marrow with an adenocarcinoma of the ovary: report of a case. Acta Clin Beig 1986;41:426-30 9 Srincker H. Sarcoid reactions in malignant tumours. Cancer Treat Rev 1986;13:147-56 10 Yoshida T, Siltzbach LE, Masih N, Cohen S. Lymphokine activity in sarcoidosis and in experimental granulomas. In: Jones Williams W, Davies BH, eds. Sarcoidosis and other granulomatous diseases. Cardiff: Alpha Omega Publishing Ltd., UK 1980:472 11 Goldman JM. In: Hoffbrand AV, Lewis SM, eds. Postgraduate haematology, 3rd edn. Oxford: Heinemann, 1989:294
(Accepted 14 January 1991)
been reported in the literature'. We have recently seen three patients with such a palsy following ethmoidal surgery. All had previously normal binocular function.
Case reports Case 1 A 35-year-old man presented with thyrotoxicosis due to a small TSH-secreting pituitary tumour. Partial transsphenoidal hypophysectomy was performed through the right ethmoidal sinus with a skin incision medial to the canthus. The wound and eye were padded for 10 days. When the pad was removed he complained of diplopia. On examination a right hyperphoria was present. Right superior oblique underaction with marked overaction of the contralateral synergist was demonstrated on Hess chart (Figure 1). The palsy resolved within 3 months of surgery. Case 2 A 61-year-old man presented with uncontrollable epistaxis which failed to respond to nasal packing. Ligation ofthe right
Cases presented to Section of Ophthalmology, 14 June 1990
0141-0768/91/ 060369-02/$02.00/0 © 1991 The Royal Society of Medicine
