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C Laing MRCP D J Thomas FRCP R J Unwin FRCP
CASE REPORTS
Headache, hypertension and Horner's syndrome C J Mathias FRCP
J R Soc Med 2000;93:535±536
The combination of migraine-like symptoms and labile blood pressure raises questions about carotid baroreceptor function. CASE HISTORY
A woman aged 45 reported the sudden onset of pain in the left eye and face, visual obfuscation and nasal stuf®ness. On examination she had bilateral carotid artery bruits and a leftsided Horner's syndrome; her blood pressure was 130/ 85 mmHg. She had experienced episodes of headache with visual aura in adolescence. Findings on brain magnetic resonance imaging (MRI) scan were normal, but contrast MR angiography revealed a left internal carotid artery dissection and a right-sided pseudoaneurysm (Figure 1); a thready and bead-like appearance suggested ®bromuscular dysplasia as the underlying abnormality. She was anticoagulated, but the left Horner's syndrome persisted; she also reported upper body `¯ushing' and left-sided pulsatile tinnitus. Five years later she was seen again, this time with rightsided frontotemporal headache and increasing jaw pain over ®ve days. She had bilateral Horner's syndrome and carotid artery bruits, but no other neurological signs. Blood pressure was now 220/120 mmHg. A repeat MR brain scan showed no abnormality; an MR angiogram of her neck vessels revealed bilateral carotid irregularities but could not con®rm or exclude a right internal carotid artery dissection. A range of blood tests, including erythrocyte sedimentation rate, C-reactive protein, vasculitic screen and syphilis serology, as well as urinary 5-hydroxy-indoleacetic acid excretion for carcinoid, were all normal or negative. We made a clinical diagnosis of acute right internal carotid artery dissection and continued her anticoagulation. During admission her blood pressure was extremely labile; systolic blood pressures varied between 90 and 240 mmHg, especially during waking hours (Figure 2). Middlesex Hospital and National Hospital for Neurology and Neurosurgery, London, UK Correspondence to: Dr C Laing, Centre for Nephrology, Middlesex Hospital, Mortimer Street, London W1N 8AA. E-mail:
[email protected]
Figure 1 Magnetic resonance angiographic images of carotid vessels. (a) Left carotid angiogram showing acute dissection (arrow) of internal carotid artery. (b) Right carotid angiogram showing bead-like appearance with aneurysm formation (arrows)
Figure 2 Blood pressure pro®le when patient was in hospital and not on antihypertensive therapy
Systolic peaks were often associated with ¯ushing, headache and intense anxiety. Administration of oral labetalol `smoothed' the blood pressure pro®le, but she continued to have hypertensive surges. Renal artery stenosis secondary to ®bromuscular dysplasia was excluded by MR angiography. Spot plasma adrenaline, noradrenaline and dopamine concentrations were raised but 24-hour urinary excretions were not. Intravenous clonidine (0.1 mg) produced a prompt fall in heart rate and systolic blood pressure and suppressed plasma catecholamine concentrations; she was thus unlikely to have a phaechromocytoma. Autonomic nervous system testing revealed a greatly exaggerated pressor response to exercise, cold and mental arithmetic. We diagnosed carotid baroreceptor dysfunction secondary to ®bromuscular dysplasia and now bilateral carotid artery dissection. Her recovery was uncomplicated and her 24-hour blood pressure pro®le (assessed by ambulatory monitoring) steadily improved. She remains on oral anticoagulation and labetalol.
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COMMENT
Barore¯ex failure syndrome is a rare complication of iatrogenic or traumatic damage to the (mainly carotid) arterial baroreceptors in the neck. It is characterized by sympathetic overactivity in response to environmental stress. Failure of the barore¯ex to buffer changes in blood pressure (by altering central sympathetic out¯ow) results in large ¯uctuations in blood pressure, often with associated ¯ushing, sweating, headache and anxiety1. Hypertension may be severe and cases of encephalopathy and intracerebral haemorrhage have been reported2,3. Orthostatic hypotension is unusual, and is more typical of syndromes with pure autonomic failure. As in this case, spot plasma catecholamine concentrations may be raised, but 24-hour urine values are normal. This, together with the prompt, or exaggerated, suppressive effect of clonidine, is characteristic and differentiates barore¯ex dysfunction from phaeochromocytoma4. Clonidine and phenoxybenzamine have been used successfully to treat this syndrome1, but we would also advocate the use of labetolol, which shares their combined a and b adrenergic blocking properties. Improvement in the patient's blood pressure pro®le without an increase in maintenance therapy suggests a degree of baroreceptor recovery. Morbidity from cervicocephalic dissections is usually due to thromboembolic stroke or, rarely, complete arterial occlusion. The `migrainous' presentation described here is typical of internal carotid artery dissection. Horner's syndrome (due to disruption of branches of the superior cervical ganglion), pulsatile tinnitus and lower cranial nerve phenomena are features that often precede retinal or cerebral embolic events. Fibromuscular dysplasia accounts for around 15% of non-traumatic internal carotid artery dissections5,6, especially if bilateral5,7. It is an incidental
Surgical management of Mycobacterium avium intracellulare infection in children M L Cowan MB BS S K Clark MD FRCS H C Grundy FRCPath 1 E M Chisholm ChM FRCS J R Soc Med 2000;93:536±537
Children with persistent lymphadenopathy or abscesses are usually referred to surgeons for diagnostic lymph node Department of Surgery and 1Microbiology, St Peter's Hospital, Chertsey, Surrey, UK
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Correspondence to: Miss SK Clark, Academic Department of Surgery, Royal London Hospital, London E1 1BB, UK
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®nding in 51% of the population8 and tends to be diagnosed in mid-life, being more common in women than in men and in patients with connective tissue disorders such as Marfan's syndrome5,8. The long-term outlook after arterial dissection is generally good, with over 75% of patients making a complete recovery without sequelae6. MR angiography is the investigation of choice and prophylactic anticoagulation, though unproven in trials, remains standard practice9. We thank Professor Martin Brown and Dr Dawn Saunders for their help and advice.
Acknowledgments
REFERENCES
1 Robertson D, Hollister AS, Biaggioni I, Netterville JL, Masqueda-Garcia R, Robertson RM. The diagnosis and treatment of barore¯ex failure. N Engl J Med 1993;329:1449±55 2 Ille O, Woimant F, Pruna A, Corabianu O, Idatte JM, Haguenau M. Hypertensive encephalopathy after bilateral carotid endarterectomy. Stroke 1995;26:488±91 3 Ejaz AA, Meschia JF. Thalamic haemorrhage following carotid endarterectomy-induced labile blood pressure: controlling the lability with clonidineÐa case report. Angiology 1999;50:327±30 4 Mathias CJ, Bannister R. Autonomic Failure, 6th edn. Oxford: Oxford University Press, 1999 5 Schievink WI, Bjornsson J, Piepgras DG. Coexistence of ®bromuscular dysplasia and cystic medial necrosis in a patient with Marfan's syndrome and bilateral carotid artery dissections. Stroke 1994;25:2492±6 6 Mokri B, Sundt TM Jr, Houser OW, Piepgras DG. Spontaneous dissection of the cervical internal carotid artery. Ann Neurol 1986;19:126±38 7 Milandre L, Perot S, Salamon G, Khalil R. Spontaneous dissection of both extracranial internal carotid arteries. Neuroradiology 1989;31:435±39 8 Furie DM, Tien RD. Fibromuscular dysplasia of arteries of the head and neck: imaging ®ndings. Am J Roentgenol 1994;162:1205±9 9 Leys D, Lucas C, Gobert M, Deklunder G, Pruvo JP. Cervical artery dissections. Eur Neurol 1997;37:3±12
biopsy or incision and drainage; the most frequent ®ndings are of reactive lymphadenopathy, bacterial infection, neoplasia or Mycobacterium tuberculosis infection. Infection with atypical mycobacteria can present in a similar way1. CASE HISTORIES
Case 1
A two-year-old girl had a tender, ¯uctuant mass in her left preauricular region. An abscess was incised and drained and the remnants of a preauricular lymph node were found and excised. Culture of the specimen yielded Mycobacterium avium intracellulare (MAI). She was then treated with rifabutin, azithromycin and cipro¯oxacin for twelve months. The wound healed without complications.
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Case 2
Another two-year-old girl was referred with a left submandibular abscess. Incision and drainage was performed; staining of the `pus' showed acid-fast bacilli and subsequent culture grew MAI. She was started on rifampicin, isoniazid and pyrazinamide in the postoperative week, but this was stopped once the organism had been identi®ed. A chronic discharging sinus formed, and seven months later she was examined under anaesthesia. No lymph-node remnants were found; the sinus was thoroughly excised and the wound then healed. Case 3
A boy aged two had an enlarged lymph node in his left axilla, which was excised. Histological examination revealed giant cell granulomata and central caseation and he was started on rifampicin, isoniazid and pyrazinamide. These drugs were stopped when MAI was identi®ed. The wound initially healed well, but an abscess formed within three months; all the involved lymph nodes were then excised, with primary closure. The wound healed well and there were no further complications. Case 4
A 19-month-old girl was referred for surgical drainage of an abscess in her right axilla. No acid-fast bacilli were seen on initial staining of the contents, but the wound failed to heal. Four weeks later, culture revealed MAI. The persistent sinus and surrounding regional lymph nodes were excised with primary closure. The wound then healed without complications. COMMENT
There has been a resurgence of mycobacterial disease associated with the spread of AIDS, but the rate of atypical mycobacterial infections in immunocompetent individuals seems to be increasing independently2. The commonest of these organisms is MAI, which predominantly infects children under ®ve years of age, girls more often than boys. It causes localized abscesses and lymphadenitis, pulmonary infections resembling tuberculosis or disseminated disease. The four children reported here, with extrapulmonary atypical infection, were seen in the past ®ve years. None had any evidence of immunosuppression. As well as infecting wild and domestic animals and birds, MAI is a ubiquitous environmental saprophyte. Lymphadenitis, commonest in the head and neck, is thought to be caused by primary infection of the oropharynx or traumatic inoculation, particularly of the extremities. Atypical mycobacteria are not thought to be transmissible
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between human beings. Considerable resistance to the standard antituberculous drugs3 complicates treatment and chemotherapy relies on protracted courses of multiple second-line agents. For this reason, some suggest that surgical excision is the treatment of choice for localized MAI infection, including pulmonary lesions4. In our series the failure of incision and drainage, whether combined with antibiotics or not, is notable. In three children further surgery was needed to treat chronic infection, and excision of the lymph-node mass or clearance of infected tissue without a full course of antibiotics was then successful. In case 1 the infected lymph node was probably removed completely at the initial procedure, though this child did also receive a full course of antibiotics. The possibility of atypical mycobacterial infection should be considered in children with lymphadenopathy or abscesses, and specimens should be sent to the laboratory both in formalin for histological examination and fresh for microbiological investigation. Culture, sometimes taking weeks, is needed to distinguish other mycobacterial infections from tuberculosis, though new genetically based assays or liquid based automated culture systems may speed up diagnosis in future. Surgical excision of the affected nodes is diagnostic and therapeutic; incomplete removal often results in chronic sinus formation, ®brosis and unsightly scarring. We recommend early surgical excision of residual affected lymph nodes to prevent these complications, once the diagnosis has been established, together with careful follow-up in all cases. The place of antituberculous treatment is controversial in view of the frequent resistance of MAI to these agents. The high cure rates with surgery alone5 mean that lengthy multidrug treatment is probably super¯uous in localized disease, unless proximity to structures such as the facial nerve prevents full excision without unacceptable morbidity. In such cases antimicrobial therapy is the treatment of choice.
REFERENCES
1 Grange JM, Yates MD, Pozniak A. Bacteriologically con®rmed nontuberculous mycobacterial lymphadenitis in south east England: a recent increase in the number of cases. Arch Dis Child 1995;72:516±17 2 Lamden K, Watson JM, Knerer G, Ryan MJ, Jenkins PA. Opportunist mycobacteria in England and Wales: 1982 to 1994. Commun Dis Rep CDR Rev 1996;6:R147±51 3 Watt B. In-vitro sensitivities and treatment of less common mycobacteria. J Antimicrob Chemother 1997;39:567±74 4 Moran JF, Alexander LG, Staub EW, Young WG Jr, Sealy WC. Longterm results of pulmonary resection for atypical mycobacterial disease. Ann Thoracic Surg 1983;35:597±604 5 Salyer KE, Votteler TP, Dorman GW. Surgical management of cervical adenitis due to atypical mycobacteria in children. JAMA 1968;204:1037±40
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Tuberous sclerosisÐ could it be? N Melikian BSc MRCP
P Giordano MD FRCS 1
J R Soc Med 2000;93:538±539
Tuberous sclerosis is an autosomal dominant inherited multisystemic disorder with a prevalence of about 1 per 5800±15 000. Classically it presents with the triad of mental retardation, seizures and angio®bromas1, but its expression is highly variable. CASE HISTORY
A Turkish woman aged 30 came to the casualty department with low back pain. She gave no past or family history of note. On examination there was nothing remarkable apart from an erythematous facial rash, which had been present since her teens (treated unsuccessfully as acne). A sacral/ pelvic X-ray revealed sclerotic lesions suggestive of bony metastases (Figure 1). Investigations that gave normal results included blood picture, renal and bone biochemical pro®les, tumour markers (aFP, CEA, CA-125, 5HIAA), ultrasound and technetium radioisotope scans of the thyroid, and mammography. A bone radioisotope scan showed extensive uptake in the long bones and intertrochanteric regions but no evidence of discrete metastases. The ®ndings were interpreted as neoplastic involvement of the bone marrow; however, aspirate and a trephine biopsy revealed a normocellular marrow with no evidence of malignancy. Multiple myeloma was also ruled out by the absence of Bence Jones proteinuria and the lack of serum paraprotein. Computed tomographic (CT) scans of the abdomen revealed multiple hepatic and renal lowattenuation lesions which were suggestive of angiolipomas. By this stage her symptoms had improved with simple analgesia and bed rest. Renal angiolipomas are a major diagnostic feature of tuberous sclerosis2, so the patient was investigated further. A CT scan of the head revealed multiple calci®ed subependymal nodules and parenchymal lesions which were consistent with calci®ed hamartomas, and biopsy of the rash disclosed angio®broma. Our patient was assigned a diagnosis of tuberous sclerosis since she expressed three of the major diagnostic criteria (facial angio®bromas, subependymal nodules and renal angiolipomas) when only Department of Medicine, Guy's and St Thomas' Hospital Trust, London SE17, UK; 1Department of Surgery, Cleveland Clinic, Fort Lauderdale, Florida, USA
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Correspondence to: Dr N Melikian, Renal Department, Guy's Hospital, London SE1 9RT, UK
Figure 1 Pelvic X-ray showing multiple sclerotic lesions mimicking metastases
two are required for a de®nitive diagnosis2. Sclerotic bony appearances are not included in the diagnostic criteria but such lesions mimicking metastases have been noted previously3. COMMENT
Clinical diagnosis of tuberous sclerosis can be dif®cult. No single clinical or radiographic sign is absolutely speci®c2. Accurate diagnosis is essential since the condition can affect multiple organ systems with debilitating consequences. Furthermore, there is a 50% probability of transmission to offspring. Skeletal involvement in tuberous sclerosis usually consists of localized areas of sclerosis3. The differential diagnosis can include Paget's disease, bone metastases, osteopoikilosis and sclerotic bone islands3. In tuberous sclerosis the radiographic abnormalities are not accompanied by symptoms and raised alkaline phosphatase as they are in Paget's disease and bone metastasis. Two tuberous sclerosis genes have been isolated and mapped to chromosome 9 (TSC 1) and chromosome 16 (TSC 2). Molecular testing is currently being developed and when commercially available it should enter widespread diagnostic use4. It would be a particularly valuable tool in diagnosis of clinically normal members of an affected family and individuals who do not ful®l the clinical diagnostic criteria. However, cases arising from germline mosaicism will still present diagnostic dif®culties2,4. REFERENCES
1 Schur RE. Tuberous sclerosisÐthe persistent challenge of clinical diagnosis. Arch Dermatol 1995;131:1460±2 2 Roach ES, Gomez ER, Northurp H. Tuberous sclerosis consensus conference: revised clinical diagnostic criteria. J Child Neurol 1998;13:624±8
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3 Hoffman AD. Imaging the skeleton and the great vessels. In: Gomez MR, Sampson JR, Whittemore VH, eds. Tuberous Sclerosis Complex, 3rd edn. Oxford: Oxford University Press, 1999:240±9
4 Roach ES, diMario FJ, Kandt RS, Northurp H. Tuberous sclerosis consensus conference: recommendations for diagnostic evaluation. J Child Neurol 1999;14:401±7
Minimal change nephropathy with adenocarcinoma of breast
increased and, after 4 weeks, proteinuria was absent, serum albumin had risen to 37 g/L, and serum cholesterol and triglycerides were normal. Steroids were discontinued after three months and she remained free from proteinuria. A second abdominal ultrasound, undertaken a month later, showed multiple small nodules in the liver suggestive of metastatic disease and a liver biopsy specimen contained metastatic poorly differentiated adenocarcinoma. On mammography there was a mass in the medial part of the right breast 13 mm in diameter which proved to be a primary breast adenocarcinoma. The patient was treated with tamoxifen, with little response, and died six months later.
M Macanovic PhD FRCP
Danielle Peat PhD MRCPath 1
J R Soc Med 2000;93:539
The association between malignant disease and nephrotic syndrome has been appreciated for a long time. Membranous nephropathy has been linked with carcinoma and minimal-change disease with lymphoma (in particular Hodgkin's lymphoma). The association of minimal-change nephropathy and carcinoma is uncommon. CASE HISTORY
A previously healthy woman aged 74 noticed swollen ankles and was admitted to hospital 24 hours later. She was found to have nephrotic syndrome with proteinuria 18.4 g/24 h and renal impairment (serum urea 15.4 mmol/L, creatinine 231 mmol/L). Other laboratory results included total protein 43 g/L, albumin 18 g/L, creatinine clearance 20 mL/min, total cholesterol 11.94 mmol/L, triglycerides 4.44 mmol/L, potassium 2.8 mmol/L, thyroid stimulating hormone 19.4 mU/L, free thyroxin 6.9 pmol/L, antinuclear factor negative, complements C3 and C4 within normal range. Bence Jones protein was not found in urine, nor were paraproteins detected on serum protein electrophoresis. On abdominal sonography the kidneys were of normal size, and an incidental ®nding was a 4 cm mass in the right lobe of the liver. Rather than undergo liver biopsy at that stage, the patient opted to have a repeat scan later. A renal biopsy specimen showed normal glomeruli with no segmental sclerosis and no immune complex deposition, consistent with minimal change disease. Steroids were given at the dose of 1 mg/kg per day, initially intravenously (methylprednisolone) and subsequently orally (prednisolone). Her additional therapy included ranitidine, atorvastatin, thyroxin, amphotericin B, amiloride, bendro¯uazide and ramipril. After a week the oedema began to subside and she lost 10 kg in body weight. Gradually the serum albumin Renal Unit, Dorset County Hospital, Dorchester DT1 JY, UK; 1Histopathology Department, Southmead Hospital, Bristol BS10 5NB Correspondence to: M Macanovic, Renal Unit, Dorset County Hospital, Dorchester DT1 2JY, UK
COMMENT
The close association between solid organ tumour and minimal change nephropathy implies, but does not prove, causality. In most reports the tumour is renal cell carcinoma1±5. Others that have been linked with minimalchange nephropathy are adenocarcinoma of the colon6,7, small-cell lung carcinoma8 and pancreatic adenocarcinoma metastatic to the liver9. An association with breast cancer (with lymph node and bone metastases) has been reported once8. In some cases the nephrotic syndrome remitted completely after surgery for carcinoma2,6,9. Although the association of carcinoma with minimal change disease is rare, it should be borne in mind particularly in older patients. REFERENCES
1 Tashiro M, Yokoyama K, Nakayama M, et al. A case of nephrotic syndrome developing during postoperative gamma interferon therapy for renal cell carcinoma. Nephron 1996;73:685±8 2 Auguet T, Lorenzo A, Colomer E, et al. Recovery of minimal change nephrotic syndrome and acute renal failure in a patient with renal cell carcinoma. Am J Nephrol 1998;18:433±5 3 Woodrow G, Innes A, Ansell ID, Burden RP. Renal cell carcinoma presenting as nephrotic syndrome. Nephron 1995;69:166±9 4 Abouchacra S, Duguid WP, Somerville PJ. Renal cell carcinoma presenting as nephrotic syndrome complicated by acute renal failure. Clin Nephrol 1993;39:340±2 5 Martinez-Vea A, Panisello JM, Garcia C, et al. Minimal change glomerulopathy and carcinoma. Report of two cases and reviews of literature. Am J Nephrol 1993;13:69±72 6 Gandini E, Allaria P, Castiglioni A, d'Amato I, Schiaf®no E, Giangrande A. Minimal change nephrotic syndrome with caecum adenocarcinoma. Clin Nephrol 1996;45:268±70 7 Caruana RJ, Grif®n JW Jr. Nephrotic syndrome in a patient with ulcerative colitis and colonic carcinoma. Am J Gastroenterol 1980;74:525±8 8 Meyrier A, Delahousse M, Callard P, Rainfray M. Minimal change nephrotic syndrome revealing solid tumors. Nephron 1992;61:220±3 9 Whelan TV, Hirszel P. Minimal change nephropathy associated with pancreatic carcinoma. Arch Intern Med 1988;148:975±6
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