118
Unusual
diagnosis of phaeochromocytoma
SiR,—Your May 19 editorial prompts us to report a patient under for the investigation of hypertension. During his admission to hospital this 54-year-old man underwent renal arteriography for a suspected renal artery stenosis. After the procedure, which our care
included femoral arterial puncture and injection of contrast medium, he became hot and perspired, and remarked to the female radiologist that it was the first time in years that a woman had made his glasses steam up. He had no further untoward side-effects over the next few hours, and his blood pressure remained stable. Review of the angiograms showed normal calibre renal arteries with no evidence of a stenosis. There was, however, a faint arterial "blush" in the left supra-renal area. Computed tomographic scanning demonstrated a 6 cm left adrenal mass with a necrotic centre. Urinary metanephrines and vanillylmandelic acid were both greatly raised at over 50 and over 200 unol/1 per 24 hours, respectively (normal 0-5 and 0-35), and an m-iodobenzylguanidine scan confirmed a solitary left phaeochromocytoma (figure). The tumour has since been safely resected and the patient remains well. I
She had a normal immunoglobulin profile with no paraprotein and a negative autoantibody screen; the direct Coombs test was negative, a whole body computed tomographic scan was normal, and she had no proteinuria. Bone-marrow examination showed diffuse infiltration by her leukaemia. She had no history of a connective tissue disorder and no family history of angioedema. She was treated with chlorambucil and prednisolone daily with little benefit to her oedema, rash, or blood picture-her white count rising to 230 x 109/1 (90% lymphocytes). At this time Cl esterase inhibitor was low (0-134 g/l; normal 026-072), as was C4 (under 0-06 g/1,0 11-0-39), and these values were subsequently confirmed twice. Chemotherapy (CHOP) was then instituted. In addition, fresh frozen plasma three units daily, stanozolol 10 mg daily, and tranexamic acid 1 g four times daily were given. The oedema and rash dramatically improved. One week after chemotherapy Cl esterase inhibitor was normal (0-392 g/1) and C4 (01 g/1) was only slightly reduced, in keeping with the clinical improvement. This patient demonstrates a previously undescribed association between acquired Clesterase inhibitor deficiency and a T-cell lymphoproliferative disorder. The angioedema was temporally related to disease progression, as indicated by a rise in the lymphocyte count and the appearance of skin infiltration. In the B-cell lymphoproliferative disorders a paraprotein was usually detected,Z and it was suggested that this was related to the associated deficiency. No such paraprotein was seen in our patient and we are tempted to implicate the leukaemic cells directly or indirectly via cytokines as the immunological trigger causing Cl activation and consequent Cl esterase inhibitor depletion. Our patient therefore demonstrates the importance of recognising this syndrome in anyone with a T-cell lymphoproliferadve disorder and unexplained oedema. R. J. GRACE Department of Haematology, St James’s University Hospital, Leeds LS9 7TF, UK
m-iodobenzylguanidine scan showing uptake in left suprarenal
region. We suspect that in this patient the occult phaeochromocytoma stimulated by the contrast injection, causing the patient to perspire heavily. This was clearly a case of serendipity which surprised the patient and the doctors, fortunately without the catastrophe so often seen with these tumours.
A. JACOB C. J. MAINWARING B. A. MCVERRY
1. Donaldson VH, Evans RR. A biochemical abnormality in hereditary angioneurotic edema: absence of serum inhibitor of C’ l esterase. Am J Med 1963; 35: 37-44. 2. Sheffer AL, Austen KF, Rosen FS, Fearon DT. Acquired deficiency of the inhibitor of the first component of complement: report of five additional cases with commentary on the syndrome. J Allergy Clin Immunol 1985; 75: 640-46.
was
K. L. DONOVAN D. J. FISHER
Cardiff Royal Infirmary, Cardiff CF2 1SZ, UK
Acquired C1
esterase inhibitor deficiency as manifestation of T-cell lymphoproliferative disorder
SiR,—Angioedema is caused by an increase in vascular permeability resulting in subcutaneous or mucosal swelling. A reduction in Cl
esterase
inhibitor has been shown
to cause
angioedema. Congenital and acquired deficiencies have been described. A review of acquired deficiency showed that 23 of 25 patients had an associated B cell abnormality-the other 2 being associated with myelofibrosis and adenocarcinoma of the rectum. We report a patient with acquired Cl esterase inhibitor deficiency associated witha T-cell lymphoprotiferative disorder. A 53-year-old woman presented at age 51 with lymphocytosis. She had no lymphadenopathy or hepatosplenomegaly. Morphologically, cytochemically, and immunologically the lymphocytosis was classified as a CD8 + /CD4 - T-cell prolymphocytic leukaemia. For 2 years she needed no treatment, during which time her white count rose from 23-3 x 109/1 (64% lymphocytes) to 35x 109/1 (90% lymphocytes). Generalised oedema then developed, especially affecting the face. This was associated with an erythematous infiltrative rash over the trunk and arms. Skin biopsy confirmed infiltration from aT-cell disorder.
Prenatal diagnosis of cytochrome-deficient chronic granulomatous disease SIR,-We have established a method for the prenatal diagnosis of cytochrome bss8-deficient chronic granulomatous disease (CGD) and its carrier state. This type of CGD is the most common (about 70%) and most severe of all CGD. The method is based on the immunostaining of Hofbauer cells (villous macrophages) in villi of placentas with a monoclonal antibody raised against cytochrome bss8’ The samples are obtained by chorionic villi sampling (CVS) at the 7th to 8th week of gestation. Villi obtained by CVS (or at abortion) were fixed with 4% paraformaldehyde at 4°C for 2 h, and frozen sections were immunohistochemically stained with a monoclonal antibody 7D5 against cytochrome1 After immunoperoxidase/diaminobenzidine staining, the samples were counterstained with haematoxylin. In the villi obtained in the 7th or later weeks of gestation large cells lying between capillaries and trophoblastic shells were deeply stained with antibody (figure). These cells were identified as Hofbauer cells, on the basis of morphology and location and specific staining with OKM14, which binds to CD14 in monocytes and
macrophages. We examined the chorionic villi for female offspring from a carrier mother who had once delivered a boy with X-linked, cytochrome-b-deficient CGD. Phagocytic cells from a carrier ought to consist of cytochrome b positive and negative populations, resulting in decrease in 7D5 + cells. However, the density of 7D5 antigen-positive (cytochrome bss8-positive) cells in the villi was normal, which suggested that the baby was not a carrier. This was confirmed later by other means. Cells in her villi obtained at
Unusual
diagnosis of phaeochromocytoma
SiR,—Your May 19 editorial prompts us to report a patient under for the investigation of hypertension. During his admission to hospital this 54-year-old man underwent renal arteriography for a suspected renal artery stenosis. After the procedure, which our care
included femoral arterial puncture and injection of contrast medium, he became hot and perspired, and remarked to the female radiologist that it was the first time in years that a woman had made his glasses steam up. He had no further untoward side-effects over the next few hours, and his blood pressure remained stable. Review of the angiograms showed normal calibre renal arteries with no evidence of a stenosis. There was, however, a faint arterial "blush" in the left supra-renal area. Computed tomographic scanning demonstrated a 6 cm left adrenal mass with a necrotic centre. Urinary metanephrines and vanillylmandelic acid were both greatly raised at over 50 and over 200 unol/1 per 24 hours, respectively (normal 0-5 and 0-35), and an m-iodobenzylguanidine scan confirmed a solitary left phaeochromocytoma (figure). The tumour has since been safely resected and the patient remains well. I
She had a normal immunoglobulin profile with no paraprotein and a negative autoantibody screen; the direct Coombs test was negative, a whole body computed tomographic scan was normal, and she had no proteinuria. Bone-marrow examination showed diffuse infiltration by her leukaemia. She had no history of a connective tissue disorder and no family history of angioedema. She was treated with chlorambucil and prednisolone daily with little benefit to her oedema, rash, or blood picture-her white count rising to 230 x 109/1 (90% lymphocytes). At this time Cl esterase inhibitor was low (0-134 g/l; normal 026-072), as was C4 (under 0-06 g/1,0 11-0-39), and these values were subsequently confirmed twice. Chemotherapy (CHOP) was then instituted. In addition, fresh frozen plasma three units daily, stanozolol 10 mg daily, and tranexamic acid 1 g four times daily were given. The oedema and rash dramatically improved. One week after chemotherapy Cl esterase inhibitor was normal (0-392 g/1) and C4 (01 g/1) was only slightly reduced, in keeping with the clinical improvement. This patient demonstrates a previously undescribed association between acquired Clesterase inhibitor deficiency and a T-cell lymphoproliferative disorder. The angioedema was temporally related to disease progression, as indicated by a rise in the lymphocyte count and the appearance of skin infiltration. In the B-cell lymphoproliferative disorders a paraprotein was usually detected,Z and it was suggested that this was related to the associated deficiency. No such paraprotein was seen in our patient and we are tempted to implicate the leukaemic cells directly or indirectly via cytokines as the immunological trigger causing Cl activation and consequent Cl esterase inhibitor depletion. Our patient therefore demonstrates the importance of recognising this syndrome in anyone with a T-cell lymphoproliferadve disorder and unexplained oedema. R. J. GRACE Department of Haematology, St James’s University Hospital, Leeds LS9 7TF, UK
m-iodobenzylguanidine scan showing uptake in left suprarenal
region. We suspect that in this patient the occult phaeochromocytoma stimulated by the contrast injection, causing the patient to perspire heavily. This was clearly a case of serendipity which surprised the patient and the doctors, fortunately without the catastrophe so often seen with these tumours.
A. JACOB C. J. MAINWARING B. A. MCVERRY
1. Donaldson VH, Evans RR. A biochemical abnormality in hereditary angioneurotic edema: absence of serum inhibitor of C’ l esterase. Am J Med 1963; 35: 37-44. 2. Sheffer AL, Austen KF, Rosen FS, Fearon DT. Acquired deficiency of the inhibitor of the first component of complement: report of five additional cases with commentary on the syndrome. J Allergy Clin Immunol 1985; 75: 640-46.
was
K. L. DONOVAN D. J. FISHER
Cardiff Royal Infirmary, Cardiff CF2 1SZ, UK
Acquired C1
esterase inhibitor deficiency as manifestation of T-cell lymphoproliferative disorder
SiR,—Angioedema is caused by an increase in vascular permeability resulting in subcutaneous or mucosal swelling. A reduction in Cl
esterase
inhibitor has been shown
to cause
angioedema. Congenital and acquired deficiencies have been described. A review of acquired deficiency showed that 23 of 25 patients had an associated B cell abnormality-the other 2 being associated with myelofibrosis and adenocarcinoma of the rectum. We report a patient with acquired Cl esterase inhibitor deficiency associated witha T-cell lymphoprotiferative disorder. A 53-year-old woman presented at age 51 with lymphocytosis. She had no lymphadenopathy or hepatosplenomegaly. Morphologically, cytochemically, and immunologically the lymphocytosis was classified as a CD8 + /CD4 - T-cell prolymphocytic leukaemia. For 2 years she needed no treatment, during which time her white count rose from 23-3 x 109/1 (64% lymphocytes) to 35x 109/1 (90% lymphocytes). Generalised oedema then developed, especially affecting the face. This was associated with an erythematous infiltrative rash over the trunk and arms. Skin biopsy confirmed infiltration from aT-cell disorder.
Prenatal diagnosis of cytochrome-deficient chronic granulomatous disease SIR,-We have established a method for the prenatal diagnosis of cytochrome bss8-deficient chronic granulomatous disease (CGD) and its carrier state. This type of CGD is the most common (about 70%) and most severe of all CGD. The method is based on the immunostaining of Hofbauer cells (villous macrophages) in villi of placentas with a monoclonal antibody raised against cytochrome bss8’ The samples are obtained by chorionic villi sampling (CVS) at the 7th to 8th week of gestation. Villi obtained by CVS (or at abortion) were fixed with 4% paraformaldehyde at 4°C for 2 h, and frozen sections were immunohistochemically stained with a monoclonal antibody 7D5 against cytochrome1 After immunoperoxidase/diaminobenzidine staining, the samples were counterstained with haematoxylin. In the villi obtained in the 7th or later weeks of gestation large cells lying between capillaries and trophoblastic shells were deeply stained with antibody (figure). These cells were identified as Hofbauer cells, on the basis of morphology and location and specific staining with OKM14, which binds to CD14 in monocytes and
macrophages. We examined the chorionic villi for female offspring from a carrier mother who had once delivered a boy with X-linked, cytochrome-b-deficient CGD. Phagocytic cells from a carrier ought to consist of cytochrome b positive and negative populations, resulting in decrease in 7D5 + cells. However, the density of 7D5 antigen-positive (cytochrome bss8-positive) cells in the villi was normal, which suggested that the baby was not a carrier. This was confirmed later by other means. Cells in her villi obtained at
