47.full.pdf - postgraduate medical journal

Self-assessment questions

A young man with bronchial asthma and anabnormal chest X-ray

A S Kashyap, S Kashyap

A 29-year-old man with bronchial asthma of 5 years duration was using inhaled salbutamol. Inview of recurrent exacerbations, he had been put on oral prednisolone 20 mg/day for the last year.He did not smoke tobacco or drink alcohol. He had no other complaints. Clinically he had moonfacies, buValo hump, centripetal obesity, purple striae on flanks and proximal myopathy. Hisblood pressure was 140/100 mmHg. Chest examination revealed polyphonic rhonchi in all areas.The rest of the general and physical examination was normal. Investigations revealed a normalhaemogram, urinalysis, fasting and post-prandial plasma glucose, serum sodium, potassium, cal-cium and phosphate levels. Pulmonary function test showed an obstructive pattern. His chestX-ray (postero-anterior) is shown in figure 1. Chest X-ray a year earlier had been normal. Serumcortisol levels were 130 nmol/l at 08.00 h (normal 140–690 nmol/l) and 76 nmol/l at 16.00 h(80–330 nmol/l). Urine 24-hour calcium was 3.2 mmol (< 3.8 mmol).

Questions

1 What are the abnormalities seen on the chestX-ray?

2 What is the pathophysiology of these abnor-malities ?

Figure Chest X-ray (postero-anterior)

Postgrad Med J 2000;76:41–60 © The Fellowship of Postgraduate Medicine, 2000

Department ofMedicine, ArmedForces MedicalCollege, Pune 411040,IndiaA S Kashyap

CardiothoracicCentre, GolibarMaidan, Pune 411040,IndiaS Kashyap

Submitted 29 March 1999Accepted 13 May 1999

on August 12, 2022 by guest. P

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Answers

QUESTION 1

The chest X-ray reveals diVuse osteoporosis ofthe ribs and bilateral multiple rib fractures withpartial healing and exuberant calcified callus(pseudocallus) surrounding a radiolucent zoneof nonunion in this patient with iatrogenicCushing’s syndrome. Abundant pseudocallusis a hallmark of corticosteroid-induced oste-oporosis. It is seen most frequently aroundstress fractures in the ribs, pelvis and end platesof collapsed vertebrae. Microscopically, there isa reduction in osteoblastic activity and produc-tion of a cartilaginous callus that becomeshighly mineralized in an amorphous fashion.1

Spontaneous symptomless fractures are typi-cally seen in Cushing’s syndrome (endogenousand exogenous). In addition to the ribs, thesefractures may also occur in feet, vertebrae,pubic and ischial rami, and uncommonly inlong bones. They may superficially resemblepseudofractures of osteomalacia. At timesthese fractures may be the presenting sign ofCushing’s syndrome, particularly in men.2

The estimated incidence of fractures inpatients prescribed corticosteroids is 30–50%.3

Bone loss occurs rapidly within first 6–12months after therapy is begun, rates slowingdown subsequently. Rates of bone loss aredirectly related to corticosteroid dose; signifi-cant trabecular bone loss occurs with pred-nisone doses greater than 7.5 mg/day.4 Boneloss occurs even with inhaled steroids.

Bone loss is greater at trabecular than at cor-tical sites. Fractures are predominant at sitesrich in trabecular bones such as vertebral bod-ies and ribs, but risk of hip fracture is also tri-pled due to bone loss from proximal femur,particularly Ward’s triangle, because it is com-posed of trabecular bone.4 Over a period oftime, steroids aVect cortical bones and fragilityof long bones is increased.

In corticosteroid-induced osteoporosis, ver-tical and horizontal trabeculae are equally thinand lead to a uniformly translucent appearanceof the vertebrae, whereas in postmenopausalosteoporosis, horizontal trabeculae are pre-dominantly lost, and lead to a ‘corduroy stripe’appearance.

The usual risk factors for osteoporosis do notapply to same extent to glucocorticoid-inducedbone loss. Young adult men receiving glucocor-ticoids lose bone more rapidly than do oldermen, postmenopausal and premenopausalwomen. However, postmenopausal womenreceiving equivalent doses of steroids are atgreater risk for fracture, presumably becausethey have a lower bone mass when they initiatesteroid therapy. Patients with rheumatoidarthritis, chronic pulmonary and gastro-intestinal diseases are at increased risk becausedisease associated inflammation, poor nutri-tion and immobilisation can aggravate boneloss. Patients who undergo organ transplant areat particular risk. Severe bone loss due to ster-oids may occur without other side eVects,though there is a strong association betweenglucocorticoid-induced myopathy andosteoporosis.5

QUESTION 2

The pathophysiology of osteoporosis due tocorticosteroids is a relative increase in boneresorption and decrease in bone formation.Reduced bone formation is due to directinhibitory eVects of corticosteroids at supra-physiological doses on osteoblast numbers,lifespan and function, leading to inhibition ofsynthesis of bone collagen by pre-existing osteo-blasts and diminished conversion of precursorcells to functioning osteoblasts. Glucocorti-coids also inhibit the synthesis of other boneproteins, including osteocalcin, a major bonematrix protein. Recent studies have found thatglucocorticoids accelerate the apoptosis ofosteoblast cells.6

Pharmacological doses of glucocorticoidsinhibit synthesis or the actions of growthfactors with anabolic eVects on bone. Thisincludes growth hormone, insulin-like growthfactor 1 (IGF-1) and transforming growth fac-tor â (TGF-â). Glucocorticoids may inhibitbone formation by prostaglandin synthesisinhibition.

Increased osteoclast recruitment and associ-ated parameters of bone resorption, includingeroded surfaces and calcium kinetics, may alsobe increased. Osteoclastic eVects may be medi-ated by secondary hyperparathyroidism. Acombination of corticosteroid-induced in-creased urinary calcium excretion and reducedintestinal absorption may be responsible forsecondary hyperparathyroidism. Cortico-steroids do not cause significant abnormalitiesin vitamin D metabolism.7

Corticosteroids alter gonadal function,which may indirectly influence mineral me-tabolism by increased bone resorption. A com-bination of inhibition of pituitary gonadotropinsecretion and direct eVects on the ovary or tes-tes, lead to a reduction in production of oestro-gen and testosterone. Glucocorticoids bluntthe secretion of luteinising hormone in re-sponse to luteinising hormone-releasing hor-mone in both men and women.8 They inhibitfollicle-stimulating-hormone-induced oestro-gen production, and decrease testosterone pro-duction. Circulating levels of androstenedioneand oestrone are suppressed further by re-duced adrenal production of androstenedione,caused by the suppression of adrenocorticotro-pin due to corticosteroid therapy, and by theresultant adrenal atrophy. Oestrogen deficiencyand corticosteroids may have an additive eVectin increasing the rate of bone loss.9

Skeletal manifestations of Cushing’ssyndrome

x osteoporosis, predominantly of trabecular bonesx spontaneous symptomless fractures of ribs, pubic

and ischial rami, feet bones and vertebraex healing of fractures with abundant pseudocallus

formationx osteonecrosis (avascular necrosis) of head of

femur and humerus, distal femur and vertebraex suppression of growth velocity in children

42 Self-assessment questions



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In our patient, skeletal survey revealeddiVuse osteoporosis, but no fractures in thevertebrae or elsewhere. He could not aVordbone mineral density measurement. His treat-

ment of bronchial asthma was optimised withinhaled salbutamol and beclomethasone. Oralsteroids were gradually tapered over the next 6weeks and stopped. He was put on a sodium-restricted diet (3 g/d), elemental calcium 1500mg/d, vitamin D3 800 IU and alendronate 10mg/d. He was started on a weight bearing andisometric exercise programme. Over the last 6months there has been no exacerbation ofasthma and rib fractures have shown partialhealing.

Final diagnosis

Corticosteroid-induced osteoporosis in a pa-tient with Cushing’s syndrome.

Keywords: corticosteroids; osteoporosis; Cushing’ssyndrome

1 Adachi JD. Corticosteroid induced osteoporosis. Am J MedSci 1997;313:41–9.

2 Urbanic RC, George JM. Cushing’s disease—18 years’experience. Medicine 1981;60:14–24.

3 Ruegsegger P, Medici TC, Anliker M. Corticosteroid inducedbone loss. A longitudinal study of alternate day therapy inpatients with bronchial asthma using quantitative computedtomography. Eur J Clin Pharmacol 1983;25:615–20.

4 Adachi JD, Bensen WG, Bell MJ, et al. Corticosteroidinduced osteoporosis: follow-up over 3 years. In: Chris-tiansen C, Overgaard K, eds. Osteoporosis 1990. ThirdInternational Symposium on Osteoporosis. Copenhagen,Denmark: Osteopress ApS, Oct 1990; pp 1745–7.

5 Askari A, Vignos PJJ, Moskowitz RW. Steroid myopathy inconnective tissue diseases. Am J Med 1976;61:485.

6 Weinstein RS, Jilka RL, Miller FL, et al. Glucocorticoidexcess causes apoptosis of osteocytes in murine corticalbone: a potential explanation for bone necrosis. J BoneMiner Res 1997;(suppl 1):S142.

7 Reid IR. Preventing glucocorticoid-induced osteoporosis. NEngl J Med 1997;337:420–1.

8 Luton JP, Thiebolt P, Valcke JC, et al. Reversible gonadotro-pin deficiency in male Cushing’s disease. J Clin EndocrinolMetab 1977;45:488–95.

9 Goulding A, Gold E. EVects of chronic prednisolone treat-ment on bone resorption and bone composition in intactand ovariectomized rats receiving B-estradiol. Endocrinology1988;122:482–7.

A rare cause of right-sided abdominal pain in ayoung woman

W K Edrees, M Hussien, M Ismail

An 18-year-old woman gravida 0, para 0, was admitted with a 3-week history of vague right-sidedabdominal pain. She denied any gastrointestinal or urinary symptoms or vaginal discharge. Herlast menstrual period was one week prior to admission and was normal. She was sexually active.Her medical history was unremarkable. On examination, she was apyrexic with tenderness alongthe right side of the abdomen extending from the costal margin to the right iliac fossa, with noguarding or rebound tenderness. Bowel sounds were normal. Pelvic examination revealed slighttenderness on the right side with no masses. White cell count was 5.5 × 109/l, erythrocyte sedi-mentation rate was not elevated. Pregnancy test and MSSU were negative. Chest and abdominalX-ray was normal. Ultrasound scan showed a small amount of fluid in the pelvis with normalovaries. She was managed conservatively, but her abdominal pain and tenderness persisted.

Questions

1 What other investigation would you consider?2 What is the probable diagnosis?

Mechanisms of glucocorticoidosteoporosis

x direct suppressive eVect on osteoblastsx decreased gut absorption of calciumx increased urinary calcium excretionx secondary hyperparathyroidism, leading to

increased osteoclastic bone resorptionx sex hormone eVects (diminished adrenal

androgens, oestrogen and testosterone) leadingto increased osteoclastic bone resorption

x catabolic eVects on proteins, including muscleand bone matrix

x diminished synthesis and/or action of growthhormone, IGF-1, TGF-â

Self-assessment questions 43

Level 5, Belfast CityHospital, LisburnRoad, Belfast BT97AB, N IrelandW K Edrees

South Tyrone Hospital,Carland Road,Dungannon BT71 4AU,Co Tyrone, N IrelandM Hussien

Downe Hospital,DownpatrickBT30 6JA, Co Downe,N IrelandM Ismail

Submitted 23 April 1999Accepted 3 June 1999



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Answers

QUESTION 1

Diagnostic laparoscopy is indicated here inview of atypical pain and non-characteristicsigns with non-diagnostic ultrasound scanfindings. It showed a normal appendix, in-flamed right fallopian tube with serosanguine-ous fluid in the pelvis. The anterior surface ofthe liver was inflamed and covered with haem-orrhagic exudate.

QUESTION 2

This is a case of perihepatitis associated withpelvic inflammatory disease, known as Fitz-Hugh-Curtis syndrome (FHC). The patientwas treated with tetracycline and metronida-zole. Her abdominal pain settled dramaticallyin 24 hours and she was discharged home inthe third postoperative day.

Discussion

The cause of right-sided abdominal pain in afertile woman is sometimes diYcult to diag-nose, especially if it is not associated with clas-sical symptoms and signs. The associationbetween pelvic inflammatory disease (PID)and perihepatitis was first described by Curtisin 1930,1 followed by Fitz-Hugh in 1934.2 Thesyndrome is more commonly observed nowa-days, a phenomenon directly associated withthe increasing incidence of PID.3

Initially, FHC syndrome was seen as a resultof gonorrhoeal infection. Recently, Chlamydiatrachomatis infection has been found to play amore significant role.4 In the acute stagepetechial haemorrhages and fibrinous exudateare observed on the liver surface and pelvicorgans. This leads to adhesions within the pel-vic organs and between liver surface andsurrounding organs (violin-string adhesions).5

DiVerent mechanisms have been postulated forthe extension of pelvic infection to the livercapsule, including transcoelmic spread via theright paracolic space, retroperitoneal lymphaticand haematogenous spread.6 It was suggestedthat chlamydial perihepatitis may be due to ahyperimmune reaction.7

The classic presenting symptom is pleuriticright upper abdominal pain with possibly bilat-eral upper abdominal pain and tenderness inthe presence of acute or subacute PID.8 Theclinical diagnosis can be diYcult and othercauses of right-sided abdominal pain have to beexcluded. Cultures of the endocervix for C tra-chomatis and Neisseria gonorrhea may bediYcult and a negative culture does notexclude the diagnosis since the sensitivity of asingle culture is limited.

Serologic evidence of acute chlamydialinfection can be obtained by demonstrating thepresence of IgM antibody, a rise in antibodytitre in serial sera, or a very high titre of IgGantibody.4 Laparoscopy plays an essential rolein the diagnosis of atypical abdominal pain.Perihepatitis cannot be diagnosed with cer-tainty unless it is directly visualised.7

The findings in cases of FHC syndromerange from haemorrhagic appearance of theliver, to dense adhesions between the liver andsurroundings associated with inflamed fallo-pian tubes.5 Antibiotic therapy specific for thepossible causative organisms (C trachomatis,gonococci and anaerobes) gives a dramaticresponse; a combination of tetracycline (ordoxycycline) and metronidazole provides ex-cellent coverage.3

Final diagnosis

Perihepatitis associated with pelvic inflamma-tory disease (Fitz-Hugh-Curtis syndrome)

Keywords: adnexitis; hepatitis; abdominal pain; pelvicinflammatory disease; Fitz-Hugh-Curtis syndrome

1 Curtis AH. A cause of adhesions in the right upperquadrant. JAMA 1930;94:1221–2.

2 Fitz-Hugh T. Acute gonococcic peritonitis of the rightupper quadrant in women. JAMA 1934;102:2094–6.

3 Shannon M. A young woman with pleuritic right upperquadrant pain. Hosp Pract 1984;June:171–3.

4 Wang S-P, Eschenbach DA, Holmes KK, Wager G,Grayston JT. Chlamydia trachomatis infection in Fitz-Hugh-Curtis syndrome. Am J Obstet Gynecol 1980;138:1034–8.

5 Toshihiko T, Hiroshi H, Wai-IP, Akira Y. Fitz-Hugh-Curtissyndrome: three cases confirmed by laparoscopy. Asia-Oceania J Obstet Gynecol 1990;16:105–10.

6 Corson SL. The Fitz-Hugh-Curtis syndrome revisited:changing perspectives after half a century. J Reprod Med1985;30:567–82.

7 Eschenbach DA, Wolner-hanssen P. Fitz-Hugh-Curtissyndrome. In: Holmes KK, Mardh PA, Sparling PF,Wiesner PJ, eds, Sexually transmitted diseases. New York:McGraw-Hill, 1990; pp 621–6.

8 Fransen L, Avonts D, Piot P. Genital chlamydial infectionassociated with perihepatitis. Acta Clin Belg 1982;37:324–7.

Learning points

x a high index of suspicion of FHC syndromeshould be considered in cases of right-sidedabdominal pain in sexually active young women

x laparoscopy is essential for the diagnosis ofatypical abdominal pain and may reveal rarecauses




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A lung cyst following blunt chest trauma

P Sundaram, K Agrawal, D Balakrishnan, R T Kamble, J M Joshi

A 48-year-old woman with no significant medical history was admitted following a road traYcaccident. She developed right-sided pleuritic chest pain, a dry cough and severe breathlessness.On physical examination, the patient had a pulse rate of 90 beats/min, blood pressure of 130/80mmHg and a respiratory rate of 30 breaths/min. There was crepitus on the right chest wall andbreath sounds were markedly diminished on that side. She also had severe tenderness in theregion of her left shoulder. Cardiovascular, abdominal and neurological examination did notreveal any abnormality.

A chest X-ray on admission revealed rib fractures from the second to the sixth ribs, subcutan-eous emphysema and a pneumothorax on the right side (figure 1). She had also sustained a frac-ture of the neck of the left humerus. Baseline blood investigations showed a haemoglobin of 11.6g/dl, white blood count of 12.6 × 106/l. Arterial blood gas analysis revealed moderate hypoxaemia.An intercostal tube drainage was instituted in the right thoracic cavity. Her subsequent chestX-ray revealed a cystic lesion in the right lower lobe following complete expansion of the rightlung (figure 2).

Questions

1 What is the diVerential diagnosis?2 What is the most probable diagnosis?3 What is the treatment of this condition?

Figure 1 Chest X-ray showing rib fractures,subcutaneous emphysema and pneumothorax on theright side

Figure 2 Right lower lobe cystic lesion seen on thechest X-ray


Department ofRespiratory Medicine,Topiwala NationalMedical College, BYLNair Ch Hospital,Mumbai 400008, IndiaP SundaramK AgrawalD BalakrishnanR T KambleJ M Joshi

Submitted 21 August 1998Accepted 26 May 1999



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Answers

QUESTION 1

The various aetiologies to be consideredfollowing trauma are pulmonary haematoma,contusion, traumatic lung cyst, loculatedhaemopneumothorax.1 Also to be consideredin the diVerential diagnosis are pre-existingconditions in an adult like lung abscess, tuber-culous and mycotic cavities, hydatid cysts,cavitating bronchogenic carcinomas and, inchildren, congenital pulmonary cyst, post-pneumonic pneumatocoele and sequestration.

QUESTION 2

The most probable diagnosis is traumatic lungcyst.

QUESTION 3

“Clinical course of traumatic lung cysts is usu-ally uncomplicated”.1 Complete resolutionoccurs in 2–16 weeks requiring only closeobservation and symptomatic treatment. Pro-phylactic antibiotic treatment is not required,despite transient fever and leucocytosis. Sec-ondary infection of traumatic lung cyst withabscess formation is uncommon. Very rarely itmay fail to regress and may enlarge resulting inrespiratory distress or pneumothorax.

When the patient was seen a month later fol-lowing discharge, the cystic lesion had com-pletely disappeared (figure 3).

Discussion

Lung laceration due to trauma may result inpneumothorax, haemothorax, contusion, trau-matic pseudocyst and massive haemoptysis.2

Blunt chest trauma causes contusion whilepenetrating injury gives rise to haematoma.

Recognition of traumatic lung cysts is impor-tant to avoid confusion with other causes oflung masses or cavities as it resolves spontane-ously requiring no special treatment.

Closed chest trauma may result in the devel-opment of one or more cystic spaces within thelung that may remain airfilled or may partly fill.The trauma is usually blunt. Children andyoung adults seem to be more prone because ofgreater flexibility of their thoracic walls. In arecent review of 40 cases of traumatic lungcyst, 88% occurred in patients under 32 yearsof age. Three mechanisms have been suggestedto explain their development1 3:+ sudden compression of an area of the lung

closes oV a segment of peripheral bronchialtree and creates within it a bursting,explosive, pressure that is expended in therupture of successive alveolar walls withinthe lobules supplied by the occluded bron-chus

+ compression of the elastic chest wall whilethe glottis is closed may result in rupture ofthe small bronchi and pulmonary parenchy-mal disruption with cavitation because airfrom the compressed part of the lung cannotescape quickly enough

+ a concussion wave produced by the blow tothe chest generates shearing stress that tearsthe lung parenchyma and causes traumaticcavities.

The cyst may contain air or blood derived fromthe torn alveolar capillaries. The cyst wall isthin and is made up of fibrous tissue andsurrounding compressed alveolar tissue.Rarely, there may be colonisation of a post-traumatic lung cyst by an asymptomaticaspergilloma.4

Symptoms include haemoptysis, chest pain,cough, dyspnoea and low grade fever. Haemo-ptysis is present in 50% of cases and may lastfor several days. Low grade fever and leucocy-tosis lasting for one to two weeks reflectreparative process of the injured lung.

The findings on chest X-ray depend on tim-ing after the injury, associated pulmonaryparenchymal injuries (contusion/haematoma),and whether the cyst is filled with air and/orblood.1–3 5 The cyst may be single or multiple,unilocular or multilocular ranging from 2–14cm, located subpleurally and usually appears12–24 hours after injury. Occasionally theremay be a delayed appearance 3–6 days after theresolution of the surrounding lung contusion.In comparison, lung contusions usually appear

Figure 3 Chest X-ray a month after discharge

Traumatic lung cysts

x may occur following blunt chest traumax usually appear within 12–24 hours of injuryx may be single or multilocular, ranging from 2–14

cmx spontaneous regression occurs in 2–6 weeksx it is important to recognise such lesions to avoid

confusion with other causes of lung masses orcavities




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within one hour, resolve in 48–72 hours, anddisappear in 7–10 days.

Spontaneous regression occurs in 2–6 weeksalthough the cyst may occasionally persist forup to 4 months. Surgical resection is notnecessary provided there is definite evidence ofdecreasing size of the lesion by 6 weeks follow-ing injury in adults and by 3 months inchildren. Surgery is indicated if there is an

infective complication unresponsive to anti-biotic treatment or if other cavitatory lesions ofthe lung are to be excluded.

Final diagnosis

Traumatic lung cyst.

Keywords: chest trauma; lung cyst; trauma

1 Shamji FM, Sachs HJ, Perkins DG. Cystic disease of thelungs. Surg Clin N Am 1988;68:581–620.

2 Peter Pare JA, Fraser RG. Synopsis of the disease of thechest. In: ? eds, Diseases of the thorax caused by external physi-cal agents. Philadelphia: WB Saunders, 1983; pp 616–39.

3 Guenter CA. Chest trauma. In: Pulmonary medicine,Philadelphia: JB Lippincott Company, 1982; pp 512–54.

4 Torre W, Dominguez L. The colonisation of post traumaticlung cyst by an asymptomatic aspergilloma. Ann Intern Med1997;14:539.

5 Shingawa S, Fujimura M, Mizuhashik M, et al. Traumaticlung cyst. Respir Med 1996;90:115–6.

Neurological deterioration in a patient withmyeloma

A J Logan, J E Grey

A 58-year-old woman with previously asymptomatic multiple myeloma presented acutely to theemergency medical intake with a severe frontal and left-sided headache. On examination she wasapyrexial and normotensive and the rest of the general and, in particular, the neurological exam-ination was normal. Investigations at that time revealed a haemoglobin of 8.8 g/dl, white cell countof 5.01 × 109/l, erythrocyte sedimentation rate of 138 mm/h and plasma viscosity of 3.6 centipoise(1.5–1.72). Serum electrophoresis revealed a paraprotein level of 25 g/l (IgAê), a ê:ë ratio of 16.2(1–2.7) and a â2-microglobulin of 2.2 mg/l (1.2–2.4). Bone marrow aspirate demonstrated 18%plasma cells (normal < 5%).Twelve hours post admission she developed neurological symptomsand orbital pain. An urgent computed tomography (CT) scan of the orbits and paranasal sinuseswas performed (figure). The lesion demonstrated on the CT was removed surgically.

Questions

1 What is the probable diagnosis and diVeren-tial diagnosis?

2 Where are these tumours most commonlyfound?

3 Given the site of the lesion, what neurologi-cal signs might have accompanied herdeterioration?

4 What would be the treatment of choice for asolitary tumour such as this?

Figure CT scan of orbits (reproduced with thepermission of the patient’s next of kin)


Department ofIntegrated Medicine,University Hospital ofWales, Heath Park,CardiV CF4 4XW UKA J LoganJ E Grey

Submitted 29 March 1999Accepted 3 June 1999



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Answers

QUESTION 1

The diagnosis is a left retro-orbital plasmacy-toma. DiVerential diagnosis is shown in box 1.

A plasmacytoma is a not uncommon compli-cation of multiple myeloma. It may rarelymanifest as a primary tumour, occurring with-out evidence of other disease. In our patienthistology of the removed mass demonstratedmitotic figures in a plasmacytoid tumour cellinfiltrate. Immunostaining demonstrated posi-tivity for IgG, IgA, and ê-light chain consistentwith myeloma, suggesting spread of pre-existing disease.

QUESTION 2

Extramedullary plasmacytomas (EMP) mayinvolve any extramedullary organ or tissue butmost are found in the head and neck region,usually in the mucosa of the oronasopharynx orparanasal sinuses.1 It is, however, rare for thissolitary tumour to involve the orbit.2 EMPsaccount for approximately 3% of all paranasalsinus and nasal cavity tumours.3 Localised painand epistaxis are the two most commonpresentations with proptosis and sixth nervepalsy being much rarer.4

QUESTION 3

The rapid progression of the neurologicalsymptoms was related to the mass eVect of thetumour, possibly secondary to haemorrhageinto the lesion. As the lesion was located at theapex of the orbit this led to:• diplopia secondary to a left sixth and partial

third nerve palsy• a left relative aVerent pupillary defect• rapid deterioration in vision in the left eye.

QUESTION 4

EMPs are highly radiosensitive and radio-therapy is potentially curative for a primaryEMP. Surgery is reserved as a second-linetreatment according to the tumour’s responseto radiotherapy.5 However, in patients withpre-existing multiple myeloma, radiotherapyand surgery are used more often as palliativeprocedures, in addition to the treatment of theunderlying condition.

Final diagnosis

Left retro-orbital plasmacytoma.

Keywords: plasmacytoma; myeloma; head and necktumours

1 Berbsagel DE, Pruzanski W. Syndromes and special presen-tations associated with multiple myeloma. In: Wiernik PH,Canellos GP, Kyle RA, SchiVer CA, eds.Neoplastic diseases ofthe blood, 3rd edn.Churchill Livingstone, 1996; pp 585–600.

2 Mewis-Levin L, Garcia C, Olson S. Plasma cell myeloma ofthe orbit. Ann Ophthalmol 1981;17:447–81.

3 Castro E, Lewis J, Strong H. Plasmacytoma of the paranasalsinuses and nasal cavity. Arch Otolaryngol 1973;97:326–9.

4 Kapadia S, Desai U, Cheng V. Extramedullary plasmacy-toma of the head and neck. A clinicopathologic study of 20cases. Medicine 1982;51:317–29.

5 Nofsinger YC, Mirza N, Rowan PT, Lanza D, Wienstein G.Head and neck manifestations of plasma cell neoplasms.Laryngoscope 1997;107:741–6.

DiVerential diagnosis

Nasal passage and sinus tumours:x benign: haemangioma, squamous papillomax malignant: squamous cell carcinoma,

adenocarcinomaCraniopharyngioma

Box 1

Learning points

x EMP may complicate multiple myelomax EMP is most often found in the head and neck

especially in the oronasopharynx and paranasalsinuses

x localised pain and epistaxis may be thepresenting features of orbital/paranasal EMP

x EMP may threaten sightx there should be a low threshold of suspicion of

an EMP in patients with myeloma who developneurological symptoms

x the treatment of choice of an EMP isradiotherapy

Box 2




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A 30-year-old man with stroke and skin lesions

K N Viswanathan, S Anandan, S Sreenivas, K S Kumar, S Raman

30-year-old man was admitted to our hospital with a depressed conscious level (Glasgow ComaScale score 4/15), following an attack of generalised tonic–clonic convulsions. He had smoked 30cigarettes a day for 5 years prior to the fit, but had not consumed alcohol. There was no history ofhypertension, diabetes mellitus, jaundice, fever, bleeding diatheses, trauma or prolonged bed rest.

General examination revealed a man who was apyrexial with normal pulse rate and blood pres-sure and livedo reticularis of the lower limbs (figure 1). Neurological examination revealed nor-mal sized pupils, equal and sluggishly reacting to light. Oculocephalic reflexes were absent. Therewas no neck stiVness or lateralising limb weakness, plantars being bilaterally extensor. Cardiovas-cular, respiratory and abdominal examinations were clinically normal and a detailed search formalignancy proved negative.

Cranial computed tomography (CT) showed thrombosis of the straight and superior sagittalsinuses, subsequently confirmed by magnetic resonance imaging and angiography (MRI/MRA)(figure 2). Patient had thrombocytopenia (90 × 109/l), normal erythrocyte sedimentation rate anda prolonged partial thromboplastin time (PTT). Liver function tests, whole and red blood cellcounts, haemoglobin, bleeding and clotting times were normal.

He was subjected to further special investigations which clinched the diagnosis. Incidentally,the brother and sister of the patient were found to have leg ulcers and the biochemicalabnormalities which the patient had on special investigations.

Questions

1 What is the most likely diagnosis?2 What further investigations would establish the aetiology of cerebral venous thrombosis?3 What is the line of management to be pursued?4 What is the significance of the skin lesions?

Figure 1 Livedo reticularis of the lower limbs Figure 2 Admission MRI


Sri RamachandraMedical College andResearch Institute,Porur,Chennai-600116, IndiaK N ViswanathanS AnandanS SreenivasK S KumarS Raman

Correspondence toDr K N Viswanathan, 6 FirstCross Street, Sylvan LodgeColony, Kilpauk,Chennai-600010, India

Submitted 9 June 1998Accepted 26 May 1999



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Answers

QUESTION 1

The cerebral venous thrombosis could be theresult of an underlying hypercoagulable state.The thrombocytopenia and prolonged PTTmay point to the diagnosis of antiphospholipidsyndrome (APLS).

QUESTION 2

APLS was confirmed in this patient by estima-tion of antiphospholipid antibodies in serum(anticardiolipin antibody and lupus anticoagu-lant). IgG and IgM anticardiolipin antibodieswere markedly elevated (>5SD) and lupusanticoagulant was positive (prolonged PTTwith dilute thromboplastin). Other methods ofestimation of lupus anticoagulant are byRussel’s viper venom time and kaolin clottingtime. These antibodies are known to be presentin systemic lupus erythematosus. However,antinuclear antibodies, and antibodies todouble-stranded DNA and lupus cells werefound to be negative, making the possibility ofsystemic lupus erythematosus highly unlikely.Relevant investigations to rule out other hyper-coagulable states (protein C, protein S andantithrombin-III levels) were also normal. Uri-nary cyanide nitroprusside test for homo-cystinuria was negative, as was a sucrose lysistest for paroxysmal nocturnal haemoglobinu-ria.

Serum electrophoresis showed normal pro-tein bands and blood for sickling, malarialparasite, leptospiral antibody titre, HIV, HbsAgand VDRL were negative. There was noevidence of DIC (normal serum fibrinogen,thrombin time and fibrin degradation prod-ucts). Total red cell count and packed cell vol-ume were normal, ruling out polycythaemia.Peripheral smear did not reveal abnormal cells.An echocardiogram showed neither clots in thecardiac chambers nor vegetations.

QUESTION 3

Anticerebral oedema measures, intravenousgamma globulin and plasmapheresis have arole in acute catastrophic APLS. Anticoagu-lants including aspirin are the mainstay oftreatment, maintaining an INR of >3, and ster-oids are also recommended.

Our patient was treated initially with anti-cerebral oedema measures, aspirin, heparinand methylprednisolone, with good supportivecare, switching over to warfarin, aspirin andprednisolone after 3 weeks. He is now on war-farin, aspirin and low-dose prednisolone. Theanticardiolipin antibodies are positive in lowtitres (<2SD), and lupus anticoagulant is stillpositive.

QUESTION 4

Livedo reticularis has been reported to beassociated with cerebrovascular accidents andantiphospholipid antibodies (Sneddon’s syn-drome).

Outcome

After hospital treatment for about 6 weeks, hehad fully recovered except for minimal bilateralsensorineural deafness (a consequence of thesagittal sinus thrombosis), detected on anaudiogram. A repeat MRI showed recanalisa-tion of the thrombosed sinuses (figure 3).

Discussion

APLS, first described in 1983, is an importantprethrombotic disorder associated with a spe-cific group of antibodies.1 It is more frequent infemales. Hughes originally studied it in patientswith systemic lupus erythematosus but foundthat the patients had “atypical lupus or nolupus at all”, hence the concept of primaryAPLS.2 B2-Glycoprotein and other such pro-teins are required for the binding of antibodiesto phospholipids.3 Treatment is with long-termanticoagulants and aspirin.4 It can be furtherclassified into primary and secondary varieties.

In 1965, Ian Bruce Sneddon, a Britishdermatologist, had described patients withlivedo reticularis and cerebrovascular accidentswhich he attributed to some form of vasculitis.5

Later, this entity was found to be associatedwith the presence of antiphospholipid antibod-ies (Sneddon’s syndrome).6 Its mode of inher-itance is autosomal dominant and only 126cases have been reported in the literature up to

Clinical features of antiphospholipidsyndrome

x arterial and venous thrombosesx thrombocytopeniax choreax haemolytic anaemiax livedo reticularisx leg ulcersx heart valve diseasex recurrent spontaneous abortions

Figure 3 MRA after treatment




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1992. We would strongly advise investigation ofa young individual with stroke and skin lesionsfor antiphospholipid antibodies.

Final diagnosis

Sneddon’s syndrome.

Keywords: stroke; livedo reticularis; antiphospholipid syndrome; anticoagulants; Sneddon’s syndrome

1 Hughes GRV. Thrombosis, abortion, cerebral disease andthe lupus anticoagulant. BMJ 1983;287:1088–9.

2 Hughes GRV. The anticardiolipin syndrome. Clin ExpRheumatol 1985;3:285–6.

3 Roubey RAS. Autoantibodies to phospholipid bindingplasma proteins:a new view of lupus anticoagulants andother antiphospholipid antibodies. Blood 1994;84:2854–67.

4 Khamashta MS, Cuadro MJ, Mujic F, et al. Themanagement of thrombosis in antiphospholipid syndrome.N Engl J Med 1995;332:993.

5 Sneddon IB. Cerebrovascular lesions and livedo reticularis.Br J Dermatol 1965;77:180.

6 Rebollo M, Val JF, Garijo F, et al. Livedo reticularis and cer-ebrovascular lesions (Sneddon’s syndrome). Brain 1983;106:965–79.

A young man with a characteristic syndrome

J Ray, D O’Gradaigh, R Tighe

A 21-year-old man presented with a 12-day history of feverish symptoms with a sore throat,polyarthralgia, and left-sided pleuritic pain. On direct questioning, a recent history of nasalcrusting and weight loss was elicited. His right shoulder was painful and the pain in his left hipmade walking increasingly diYcult. On examination, he was mildly icteric, thin, and lookedunwell with a low-grade pyrexia and very tender cervical lymphadenopathy. There were petechiaeand ulcerations on the palate. The left groin was also tender and a fluctuant swelling was palpa-ble on the lateral border of the thigh 10 cm below the anterior superior iliac spine. Active andpassive movement of the left hip in all directions was limited by pain, whilst a full range of move-ment was seen in the right shoulder.

Investigations revealed haemoglobin 10.2 g/dl, mean corpuscular volume 90.1 fl, platelets 310× 109/l, white blood cell count 14.9 × 109/l (neutrophils 12.56, lymphocytes 1.13, eosinophils0.01), C-reactive protein 157 mg/l, erythrocyte sedimentation rate 67 mm, bilirubin 58 m/hµmol/l, ã-glutamyl transpeptidase 211 IU/l, alanine transaminase 114 IU/l, prothrombin time17.3 s, XDP <10 mg/dl, cANCA weakly positive. Urine microscopy was normal, Paul Bunnel testfor Epstein Barr virus was negative, and a ventilation/perfusion scan showed a low probability ofpulmonary embolus. A transthoracic echo and X-ray of the left hip were normal. His chest X-rayis shown in the figure.

Questions

1 How would you report this chest X-ray?2 What further investigations are required?3 What is the most probable diagnosis?

Figure Chest X-ray


Norfolk and NorwichHospital, BrunswickRoad, Norwich,Norfolk NR1 3FR, UKJ RayD O’GradaighR Tighe

Submitted 22 January 1999Accepted 3 June 1999



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Answers

QUESTION 1

The chest X-ray demonstrates multiple lesions.On the left side is a cavitating lesion in theregion of the heart shadow near the costoverte-bral angle.

QUESTION 2

Blood cultures and aspiration of the left hipusing ultrasound guidance should be per-formed.

QUESTION 3

The most probable diagnosis is Lemierre’ssyndrome.1 2

Discussion

The diVerential of multiple cavitating lunglesions is broad and includes infections,inflammatory conditions, and metastic disease.An infection with embolisation would be inkeeping with the history and examination find-ings. A range of infective conditions wouldneed consideration, for example, infectiveendocarditis, tuberculosis, or opportunisticinfection in an immunocompromised indi-vidual.

Ultrasound of the left hip joint demonstratedan eVusion which extended laterally and thiswas aspirated. Subsequent culture isolatedFusobacterium necrophorum. This Gram-negative anaerobe can cause a rare septicaemiawhich is also known as Lemierre’s syndrome.The infection was successfully treated with a2-week course of intravenous antibiotics (1.2 gbenzylpenicillin qid and 500 mg metronidazoletid, in accordance with proven microbiologysensitivities), followed by 2 weeks of oralantibiotics.

A diVerential diagnosis of Wegener’sgranulomatosis3 was considered in view of thearthralgia, upper respiratory tract involvement

and systemic upset. On immunofluorescencestaining for ANCA, our patient had a weaklypositive reaction with a cytoplasmic pattern.However, further clarification is important, andin this case, ELISA identified reactivity to bac-terial permeability inhibitor, suggesting theantibodies were secondary to infection. AdiVerential antigen, PR3, is strongly associatedwith Wegener’s granulomatosis. Furthermore,the liver enzyme abnormalities and very shortprodrome militate against this diagnosis, andwhile arthralgia can be marked, joint eVusionsare uncommon. Histological confirmation isessential before considering immunosuppres-sion, and in this case, the microbiology fromthe hip eVusion suggested the correct diagno-sis, and obviating the need for further investiga-tion. The consequences of undertaking immu-nosuppression in this patient, assuming adiagnosis of Wegener’s granulomatosis, couldhave been very serious.

Lemierre’s syndrome is caused by an acuteoropharyngeal infection with secondary septicthrombophlebitis of the internal jugular vein,which is frequently complicated by metastaticinfection. Painful cervical lymphadenopathy isusual. Systemic infection, characteristicallyinvolves the lung and joints, as occurred withour patient. Other sites of infection includeliver, spleen, kidney and meninges. The earlyempirical use of antibiotics in the treatment ofpharyngitis makes this a rarely seen condition.Lemierre’s description of the clinical findingsconstituted, “a syndrome so characteristic thatmistake is almost impossible.”4

Final diagnosis

Lemierre’s syndrome (metastatic Fusobacte-rium necrophorum infection).

Keywords: Lemierre’s syndrome; necrobacillosis

1 Golpe R, Marin B, Alonso M. Lemierre’s syndrome (necro-bacillosis). Postgrad Med J 1999;75:141–4.

2 Lemierre A. On certain septicaemias due to anaerobicorganisms. Lancet 1936;1:701–3.

3 Leavitt RY, Fauci AS, Bloch DA, et al. The American Col-lege of Rheumatology criteria for the classification of Wege-ner’s granulomatosis. Arthritis Rheum 1990;33:1101–7.

4 Vohra A, Saiz E, Ratzan KR. A young woman with a sorethroat, septicaemia, and respiratory failure. Lancet 1997;350:928.




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The collar sign

K B Agrawal, R T Kamble, P Sundaram, J M Joshi

A previously healthy 26-year-old man presented with the chief complaint of acute onset left-sidedpleuritic type of chest pain. On enquiry he gave a history of blunt trauma to the lower chest andthe abdomen due to a fall 6 years earlier which had been managed conservatively. On examina-tion, the patient was obviously distressed and had tachycardia and tachypnoea. Breath soundswere absent in the left infrascapular and infra-axillary regions. His haematological and biochemi-cal parameters were within normal limits. Arterial blood gases revealed hypoxaemia with PaO2 66mmHg, PaCO2 36 mmHg, pH 7.41. Chest X-ray and computed tomography (CT) scans areshown in figures 1–3.

Questions

1 What is the diVerential diagnosis of the chestX-ray ?

2 What do the CT scans show?

Figure 1 Chest X-ray

Figure 2 Thoracic CT scan (scout scan)

Figure 3 Thoracic CT scan


Department ofRespiratory Medicine,BYL Nair Ch Hospital,Mumbai Central,Maharashtra, 400 008IndiaK B AgrawalR T KambleP SundaramJ M Joshi

Correspondence toDr JM Joshi

Accepted 26 May 1999



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Answers

QUESTION 1

The chest X-ray shows an apparent elevation ofthe left hemidiaphragm with a large gas collec-tion below it. The diagnostic considerationsinclude eventration or paralysis of the dia-phragm and diaphragmatic hernia.

QUESTION 2

On a chest X-ray it may be diYcult todetermine whether an abdominal organ lyingunusually high is located beneath an elevatedhemidiaphragm (in conditions like eventrationor paralysis of hemidiaphragm) or is herniatingthrough a deficit in the diaphragm.1 In this casea diagnosis of herniation can be easily made onthe basis of the CT scans, which show focalconstriction of the stomach at the site ofherniation (collar sign).2

Clinical course

On the basis of the clinical and radiologicalfindings, a diagnosis of traumatic diaphrag-matic hernia was made. Surgery confirmed thepresence of an 8-cm tear in the posterolateralaspect of the left hemidiaphragm along withherniation of the stomach, transverse colon andspleen in the thorax. The patient made anuneventful recovery postoperatively.

Discussion

Diaphragmatic rupture occurs in approxi-mately 5% of patients who have experiencedmajor blunt trauma,3 and 90% of the diaphrag-matic ruptures are on the left side. Left-sidedhemidiaphragmatic injury predominates prob-ably because of the protective eVect of the liveron the right hemidiaphragm and/or underdiag-nosis of right-sided injuries. The clinicaldiagnosis of laceration of the hemidiaphragmwith herniated viscera is diYcult, but may besuggested by bowel sounds auscultated in thelower thorax, unilateral absence of breathsounds, respiratory distress, and/or a scaphoidabdomen. Often, bedside physical findings aremasked by concurrent abnormalities or thesesigns may be overlooked because of moreapparent and life-threatening injuries in theacute post-trauma period. An early correctdiagnosis is made in less than 50% of cases.Because the intrathoracic pressure is lowerthan the intra-abdominal pressure, there isprogressive herniation of abdominal contentsinto the thorax. Carter et al4 have proposedthree time phases following traumatic dia-phragmatic rupture. The acute phase extendsfrom the time of injury to 14 days later. If thepatient survives the initial trauma and the her-nia is not manifest within the first 14 days, thesecond or interval phase is entered. This inter-val phase extends until the third stage which isthe phase of obstruction or strangulation.Delayed presentation of diaphragmatic rupturewith visceral herniation and strangulation isassociated with higher morbidity and mortalityrates than when the correct diagnosis is madeand the condition managed acutely.

Chest X-ray is the principal screeningmethod for thoracic injury after blunt trauma.Diagnostic or strongly suggestive findings onchest X-ray include the definite presence ofair-filled viscera or the tip of the nasogastrictube above the diaphragm, as well as adiaphragm that is ‘very elevated’. Obscurationof a non-elevated hemidiaphragm also suggestsdiaphragmatic hernia. The value of chestX-rays in diagnosing right-sided traumatic dia-phragmatic rupture is limited.

CT of the diaphragm has been reported to beuseful in assessing for traumatic diaphragmaticrupture.5 One can usually see more of the lefthemidiaphragm than the right. The postero-lateral portions of both hemidiaphragms areusually best demonstrated, and thus the tears atthose sites are more readily detected. The domeof the diaphragm is a diYcult area to demon-strate with CT, the plane of the scan being tan-gential to the diaphragm at that point. The mostcommon finding in diaphragmatic tear is a sharpdiscontinuity of the diaphragm. A large gapbetween the torn ends of the diaphragm resultsin the absent diaphragm sign. On the transverseCT scan, the abdominal contents lie central tothe diaphragm and the thoracic contents lieperipherally. Intrathoracic herniation of perito-neal fat or organs can thus be identified bymeans of the abnormal position of thesestructures relative to the diaphragm. The struc-tures that most commonly herniate through thedefect are peritoneal fat, stomach, and colon. Ontransverse CT scans, to determine whether anabdominal organ lying in an unusually cephaladposition, is located beneath an elevated hemidi-aphragm or is herniating through a defect in thediaphragm, the presence of a focal constrictionof the bowel or stomach at the site of herniation(collar sign) is very useful. The use of contrastmaterial is essential in the demonstration of thecollar sign in herniated stomach or colon whenthe diagnosis is made on the basis of findings inupper gastrointestinal or barium enema series.4

Other imaging methods that have beenreported to be of value in evaluating thediaphragm include X-rays taken after nasogas-tric tube placement, fluoroscopy, upper andlower gastrointestinal contrast examination,sonography, magnetic resonance imaging, con-trast or air peritoneography and liver/spleenscintigraphy. The appearance of herniated liveron the nuclear liver/spleen scan is rather

Learning points

x a high index of suspicion should be maintainedfor the possibility of traumatic diaphragmatichernia in all cases of blunt trauma

x CT enables detection of the majority of suchdiaphragmatic tears

x the most common findings include a localiseddefect of the diaphragm, the absent diaphragmsign and herniation of solid or hollow organs andomentum into the hemithorax

x the identification of the ‘collar sign’ on CT scanhelps to diVerentiate diaphragmatic hernia fromparalysis or eventration of the diaphragm




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characteristic and its use is recommended.Newer techniques such as spiral CT scanningallow better visualisation of the dome of the dia-phragm owing to multiplanar capabilities.

Final diagnosis

Left-sided traumatic diaphragmatic hernia.

Keywords: diaphragmatic hernia; chest trauma; collar sign

1 Probert NR, Havard C. Traumatic diaphragmatic hernia.Thorax 1961;16:99–113.

2 Naidich DP, Zerhouni EA, Siegelmann SS. Computed tomog-raphy and magnetic resonance of the thorax. New York, NY:Raven, 1991.

3 Meyers BF, McCabe CJ. Traumatic diaphragmatic hernia:occult marker of serious injury. Ann Surg 1991;218:783–90.

4 Carter BN, Giusefti J, Felson B. Traumatic diaphragmatichernia. AJR 1951;65:56–71.

5 Worthy SA, Kang EY, Hartman JE, Kwong JS, Mayo JR,Muller NL. Diaphragmatic rupture: CT findings in 11patients. Radiology 1995;194:885–8.

An adolescence girl with an anterior mediastinalmass

W S Chow, A W C Kung

A 14-year-old Chinese girl was referred to us for assessment of her thyrotoxicosis before correc-tive surgery of genu varus. On questioning, she mentioned significant weight loss with occasionalpalpitations. She had also experienced episodic lower limb proximal muscle weakness, but therewas no history of paralysis.

Physical examination showed sinus tachycardia of 110 beats/min. There was no lid retractionor lid lag. Her goitre was enlarged three-fold with audible bruit, but there was no retrosternalextension. Eye examination revealed no evidence of Graves’ ophthalmopathy. Abdominal exam-ination was normal. There was no lymphadenopathy, splenomegaly nor pretibial myxoedema.Her proximal muscle power was grade 4/5 and the jerks were all brisk.

Investigations showed a raised free thyroxine of >170 pmol/l (normal range 10–19 pmol/l) anda suppressed thyrotropin of <0.03 mIU/l (0.35–5.5 mIU/l). Chest X-ray, however, revealed amediastinal shadow with clear lung field. Complete blood count and routine biochemistry werenormal. Acetylcholamine receptor antibody was normal. A computed tomography (CT) scan wasarranged for further visualization of the mediastinal mass (figure 1). Carbimazole and propanololwere started for her thyrotoxicosis. Subsequently she became euthyroid and her muscle weaknessdisappeared. A follow-up CT scan, taken 8 months later, is shown in figure 2.

Questions

1 What is the abnormality seen in the initial CT scan?2 What are the diVerential diagnoses?3 What is the underlying cause of the abnormality?

Figure 1 Initial CT scan Figure 2 Follow-up CT scan 8 months later


Division ofEndocrinology,UniversityDepartment ofMedicine, Queen MaryHospital, 102 PokfulamRoad, Hong KongW S ChowA W C Kung

Submitted 21 April 1999Accepted 3 June 1999



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Answers

QUESTION 1

The initial CT scan showed an anterior media-stinal mass, which is a diVusely enlargedthymus. Since the normal configuration of thegland was preserved, the findings were compat-ible with thymic hyperplasia. There was noabnormal mediastinal lymphadenopathy.

QUESTION 2

The diVerential diagnosis of an anterior medi-astinal mass includes a variety of clinicalentities (box).

It is useful to recognise the clinical associ-ation of thymic hyperplasia with hyperthy-roidism, although massive enlargement of thethymus detected radiologically has only rarelybeen reported. Some studies have shown thatapproximately 38% of patients with thyrotoxi-cosis have an abnormal thymus gland, andbiopsy shows the formation of medullary lym-phoid follicles.1 Michie et al showed that theenlarged thymus regresses upon treatment ofhyperthyroidism with antithyroid agents.2 Thedecrease in thymic size on treatment withantithyroid drugs could be related to a directimmunosuppressant eVect of the antithyroiddrugs or an indirect eVect by lowering of circu-lating thyroid hormones. It has been reportedthat exogenous thyroxine treatment in animalscould result in thymic enlargement.3

QUESTION 3

Recent studies have demonstrated mRNA andprotein expression of the thyroid-stimulatinghormone (TSH) receptor in thymic tissues ofpatients with Graves’ disease.4 As Graves’disease results from the development ofantibodies against the TSH receptor, the

thymic TSH receptor may act as an auto-antigen responsible for the initiation or per-petuation of the autoimmune response. How-ever, the underlying pathophysiology of thymichyperplasia is still not well delineated.

Outcome

Bergman et al recommended deferring invasivediagnostic manoeuvres until the eVects of spe-cific antithyroid treatment could be evaluated.5

We adopted this approach with close imagingmonitoring. The thymus soon returned to nor-mal size after euthyroidism had been achievedwith antithyroid drugs. Although there was nohistological confirmation, thymic hyperplasia isthe most probable diagnosis based on thesequence of events.

Final diagnosis

Thymic hyperplasia.

Keywords: thymic hyperplasia

1 Michie W, Gunn A. The thyroid, the thymus andautoimmunity. Br J Clin Pract 1966;20:9–13.

2 Michie W, Beck JS, MahaVy RG, Honein EF, Fowler GB.Quantitative radiological and histological studies of the thy-mus in thyroid disease. Lancet 1967;1:691–5.

3 ScheiV JM, Cordier AC, Haumont S. Epithelial cellproliferation in thymic hyperplasia induced by triiodothyro-nine. Clin Exp Immunol 1977;27:516−21.

4 Murakami M, Hosoi Y, Negishi T, et al. Thymic hyperplasiain patients with Graves’ disease. J Clin Invest 1996;98:2228–34.

5 Bergman TA, Mariash CN, Oppenheimer JH. Anteriormediastinal mass in a patient with Graves’ disease. J ClinEndocrinol Metab 1982;55:587–8.

DiVerential diagnoses

x thymic hyperplasiax thymomax mediastinal lymphomax retrosternal goitrex germ cell neoplasmx thymic hyperplasia associated with Graves’

disease




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A pain in the neck

G V McDonnell, K E Bell, S A Hawkins

A previously healthy and independent 84-year-old woman was referred to the neurology depart-ment with leg weakness. Nine days earlier she had experienced an acute onset of severe neck painwhilst sitting at rest, which radiated down both arms. Although initially feeling unable to move,she attended a casualty department where analgesics and diazepam were prescribed and she wassent home. However, on leaving the hospital her legs felt heavy and she required the assistance oftwo people.

At home the next day she was unsteady on her feet and fell. Over the ensuing 4 days she devel-oped leg cramps, urinary retention and constipation, necessitating her admission to hospital. Onneurological examination, cranial nerves were intact but there was a quadriparesis mainly aVect-ing the distal arm muscles and leg flexors with grade 3–4/5 power in the wrist extensors and fin-ger abductors, 4/5 power in quadriceps and 3/5 strength in the hamstrings. Plantar responses werebilaterally extensor. Neck movements were markedly restricted by pain. Because of the nature ofthe history and the distribution of clinical signs, magnetic resonance imaging (MRI) of the spinewas undertaken (figure).

Questions

1 What is the diVerential diagnosis of the spastic quadriparesis in this patient?2 What do the MRI scans show?3 What is the diagnosis?4 What further elements of the history are relevant and what other investigations are indicated?5 How should the patient be managed?

Figure MRI images of the spine. (A) Sagittal T1-weighted image of the cervical spine (TR 440 ms, TE 15 ms),(B) sagittal T2-weighted image of the cervical spine (TR 4000 ms, TE 102 ms); (C) sagittal T1-weighted imageof the dorsal spine (TR 440 ms, TE 15 ms)


Northern IrelandRegional NeurologyService, Royal VictoriaHospital, Belfast,Northern IrelandG V McDonnellK E BellS A Hawkins

Correspondence toDr GV McDonnell,Department of Neurology,Ward 21, Quin House, RoyalVictoria Hospital, GrosvenorRoad, Belfast BT12 6BA,Northern Ireland

Submitted 24 February 1999Accepted 3 June 1999



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Answers

QUESTION 1

The diVerential diagnosis of spastic quadri-paresis is obviously wide, as indicated by thenon-exhaustive list in box 1. However, theacute nature of the onset in this patient narrowsthe list considerably, with a vascular aetiologyand an acute central cervical disc herniationbeing most likely, given the lack of any obviousspinal cord trauma. The absence of a prodro-mal illness or systemic upset weighs heavilyagainst an inflammatory aetiology whilst demy-elinating disease and hereditary spastic para-plegia would be unlikely to present for the firsttime in this late age group.

Although they would in any case have a morechronic course, syringomyelia would mostcommonly manifest with lower motor neuronesigns in the arms and a dissociated sensory losswhereas motor neurone disease does not ingeneral present with a ‘pure’ spastic quadri-paresis. HTLV-1 mediated tropical spasticparaparesis usually spares the upper limbs andis rare in Caucasian populations.

QUESTION 2

Figure (A) demonstrates high signal presentanterior to the cord on T1-weighted images ofthe cervical spine from the level of C7. TheT2-weighted image in figure (B) shows a simi-lar area of high signal intensity arising from thesame area. Figure (C) indicates that this area ofhigh signal intensity also extends down theanterior surface of the dorsal cord and indeedreaches as far as the conus (not visible).

QUESTION 3

The MRI appearances are typical of a subacutehaematoma in the epidural space. Within 24hours of onset a haematoma is usuallyisointense with the cord on T1-weightedimages but with the development of methae-moglobin in the haematoma it becomes of high

signal intensity on both T1- and T2-weightedimages. The thin rim of low signal intensity justvisible in the figures separating the haematomafrom the cord is dura mater.

QUESTION 4

Although spinal epidural haematoma is ‘spon-taneous’ with no obvious precipitating factorsin over 50% of cases, certain conditions andtriggers are believed to be associated. Theseinclude: bleeding diatheses associated withhaematological disorders and with the use ofanticoagulants and thrombolytics; spinaltrauma including surgery and spinal puncture;tumours; hypertension, and arteriovenous mal-formations. Rarer associations have been re-ported with rheumatological conditions, alco-hol, pertussis and pregnancy. Furtherquestioning and investigations should thereforebe directed appropriately. In this instance therehad been no history of anticoagulant therapy,trauma or hypertension and there was noevidence of a tumour or vascular malformationon MRI. Clotting profile and platelet aggrega-tion studies were normal.

QUESTION 5

The options in the management of this condi-tion include surgical intervention, involvinglaminectomy and removal of the clot, or a con-servative approach. In view of the extensivenature of the lesion and the advanced age of thepatient, the latter approach was adopted. Therewas no further clinical deterioration and within72 hours a slow clinical improvement wasbecoming apparent. Within 8 weeks there hadbeen a full neurological recovery with return ofsphincter function and the patient was livingindependently once more.

Discussion

Spinal epidural haematoma is an uncommonand rarely reported clinical entity which does,however, represent a neurological emergency.Although a painless onset has been described,this is exceptional and, as in this case, the dis-ease is typically characterised by sudden onsetof neck or back pain followed by sensory andmotor dysfunction. The full symptom complexmay evolve rapidly within one hour or may takeweeks or even months to develop fully (box 2).

Early diagnosis may be diYcult since a com-bination of interscapular and radicular paincan mimic an aortic dissection and radicularpain may be diYcult to diVerentiate from paindue to a cardiac or pulmonary event. Acute

DiVerential diagnosis of spasticquadriparesis

x vascular: anterior spinal artery occlusion, aorticdissection, arteriovenous malformation, epiduralor subdural haematoma

x degenerative: central spondylosis, central cervicaldisc herniation, syringomyelia, Paget’s disease

x neoplastic: intramedullary (glioma,ependymoma, lymphoma); extramedullary(neurofibroma, meningioma, ependymoma,bronchial and breast metastases, myeloma)

x inflammatory: viral, bacterial, fungal, parasitic,granulomatous, post-infectious, post-vaccine

x demyelinating: multiple sclerosisx metabolic: subacute combined degeneration of

the cordx hereditary: hereditary spastic paraplegiax other: motor neurone disease, HTLV-1 mediated

tropical spastic paraparesis, parasagittalmeningioma

Box 1

Typical presentation of spinal epiduralhaematoma

x neck/back painx radicular painx sensory disturbancex motor weaknessx sphincter disturbance

Box 2




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onset of pain in the upper neck may also raisesuspicion of subarachnoid haemorrhage. How-ever, bilateral symptoms of myelopathy in con-nection with neck or interscapular pain radiat-ing into the upper extremities should lead tosuspicion of cervical pathology including discprolapse, spinal tumour or metastasis and epi-dural haematoma.

Spinal epidural haematomas occur in all agegroups but are more common in middle orlater life and are more frequent in males thanfemales. Usually the haematoma lies in thedorsal epidural space but the anterior locationdemonstrated in this patient has been previ-ously described.1 The most frequent levels ofinvolvement are the cervical and thoracicsegments with thoracolumbar and lumbarregions being less commonly aVected.2 Theextent of the lesion in this patient is unusualsince most epidural lesions involve just 2–4segments although a haematoma extendingover 11 segments has been reported.3

Although no underlying cause for spinal epi-dural haematoma can be determined in at least50% of cases,4 it is well recognised that predis-posing factors include trauma, bleeding diathe-ses and anticoagulant therapy (box 3). Caseshave also been reported as occurring inconnection with apparently routine proceduressuch as epidural anaesthesia and diagnosticlumbar puncture.5 The significance of factorssuch as hypertension and underlying vascularmalformations remains more controversialsince it has been noted that hypertension is nomore prevalent in patients with spinal epiduralhaematoma than in age-matched controls,4 andvascular malformations have been associated inless than 5% of cases at most.6

The MRI characteristics of spinal epiduralhaematoma are quite specific.7 On sagittalsections it is clearly outlined with tapering supe-rior and inferior margins. Dura mater is seen asa curvilinear low signal separating the hae-matoma from the cord. Within 24 hours of onsetthe haematoma is isointense with the cord onT1-weighted images and heterogenous on T2-weighted images. However, methaemoglobinaccumulates after 24 hours causing T1 shorten-ing and an increase in the signal on T1-weightedimages. The diVerential diagnosis of suchappearances should include spinal subduralhaematoma, epidural neoplasm and abscess.

The spinal subdural haematoma is far lessfrequent than the epidural haematoma and israrely spontaneous, usually occurring in rela-tion to anticoagulant therapy, blood dyscrasiasor spinal trauma. MRI does not show a lowsignal dural rim. Epidural metastases give lowsignal or are isointense with the cord, withirregular margins and without tapering ends.These are generally associated with vertebralinfiltration, which appears as diVuse or focalareas of homogenous low signal on T1-weighted images. Epidural abscesses are fusi-form and contiguous with an infected disc andvertebral bodies. They are centred on the discand in most cases give lower signal than thespinal cord on MRI. Both metastases andabscesses usually also show enhancement onT1-weighted images post gadolinium.

In general, surgical intervention in cases ofspinal epidural haematoma has been consid-ered mandatory. Indeed it has been found thatdelay of more than 36 hours before decompres-sive laminectomy and evacuation of clot isassociated with a poor prognosis.8 However inrecent years there have been several reportedinstances of spontaneous recovery followingconservative management in patients with mildor non-progressive neurological deficits.9 Theoutcome in this case lends further support tothese observations.

In conclusion, although the diVerential diag-nosis of spastic quadriparesis is wide, this caseemphasises the importance of suspecting adiagnosis of spinal epidural haematoma in anypatient presenting with acute onset of severeneck or back pain when this is associated withradicular symptoms or neurological signs con-sistent with cord compression. Predisposingfactors should be sought and urgent surgicalintervention should be considered although thepotential for spontaneous recovery does exist incertain cases.

Final diagnosis

Spontaneous spinal epidural haematoma.

Keywords: epidural haematoma; MRI; spine

Conditions associated with spinalepidural haematoma

x bleeding diathesesx drugs: aspirin; anticoagulants; thrombolyticsx spinal surgery, trauma, puncturex spinal tumoursx arteriovenous malformationsx rheumatological disordersx pregnancyx alcohol

Box 3

Summary points

x spinal epidural haematoma is a neurologicalemergency which occurs most commonly inmiddle life or later and is more common in males

x MRI is the diagnostic tool of choicex cervical and upper thoracic spinal segments are

most commonly involvedx about 50% of cases occur spontaneouslyx bleeding/clotting disorders should be excludedx urgent decompressive laminectomy and

evacuation of clot is indicated in patients withsignificant or progressive deficits

x conservative management may be appropriate inmild and non-progressive cases and culminate inspontaneous recovery

Box 4




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1 Chen CJ, Fang W, Chen CM, Wan YL. Spontaneous spinalepidural haematomas with repeated remission and relapse.Neuroradiology 1997;39:737–40.

2 Rothfus WE, Chedid MK, Deeb ZL, Abla AA, Maroon JC,Sherman RL. MR imaging in the diagnosis of spontaneousepidural haematomas. J Comput Asst Tomogr 1987;11:851–4.

3 Larsson EM, Holtås S, Cronqvist S. Emergency magneticresonance examination of patients with spinal cord symp-toms. Acta Radiol 1988;26:69–75.

4 Groen RJM, Ponssen H. The spontaneous spinal epiduralhaematoma: a study of the aetiology. J Neurol Sci1990;98:121–38.

5 Peltola J, Sumelhati M-L, Kumpulainen T, Dastidar P,Helén P. Spinal epidural haematoma complicating diagnos-tic lumbar puncture. Lancet 1996;347:131.

6 Foo D, Rosier AB. Preoperative neurological status inpredicting surgical outcome of spinal epidural haematomas.Surg Neurol 1981;15:389–401.

7 Boukobza M, Guichard JP, Boissonet M, et al. Spinalepidural haematoma: report of 11 cases and review of theliterature. Neuroradiology 1994;36:456–9.

8 McQuarrie IG. Recovery from paraplegia caused by sponta-neous spinal epidural haematoma. Neurology 1978;28:224–8.

9 Anderson TJ, Donaldson IMacG. Spontaneous resolutionof cervical spinal epidural haematoma. Postgrad Med J 1989;65:488–90.

Images in medicine

Epidural lipomatosis

A 51-year-old man presented with radicular-like pain in the left lower limb and intermittentclaudication lasting for 1 year. Pain in the legswas evoked by standing or walking more than300 meters and rapidly relieved by sitting.Clinical examination only disclosed significantoverweight (weight 100 kg; height 163 cm;BMI: 37.6 kg/m2). Electromyography showedchronic neurogenic abnormalities in the mus-cles supplied by the left L5 nerve root.Magnetic resonance imaging (MRI) of thelumbar spine disclosed cauda equina compres-sion by epidural lipomatosis (see figure onopposite page, A and B).

After 3 months on a hypocaloric diet leadingto 20 kg weight loss, pain and claudication hadcompletely resolved. MRI showed a dramatic

regression of the epidural lipomatosis (figure,C and D). In the diVerential diagnosis of lum-bar stenosis, the clinician must keep in mindthe possibility of epidural lipomatosis, even inpatients without systemic glucocorticoidtherapy or Cushing’s disease.

YVES BOUTSENDepartment of Rheumatology

JULIAN DONCKIERDepartment of Internal Medicine and Endocrinology

UCL (Université Catholique de Louvain), UniversityHospital of Mont-Godinne,

5530 Yvoir, Belgium

Keywords: epidural lipomatosis

Submitted 3 February 1999Accepted 12 July 1999




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Figure Sagittal (A, C) and axial (B, D) T1-weighted MRI showing epidural fat-induced compression of thethecal sac before hypocaloric diet (A, B) and normal apprearance after weight loss (C,D)

Epidural lipomatosis 61



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