Festschrift for Sir John McMichael

The Cheshire Cat syndrome

E. G. L. BYWATERSM.R.C. Rheumatisnm Research Unit, Canadian Red Cross Memorial Hospital,

Taplow, Maidenhead, Berks.

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FIG. 1

'Well, I've often seen a cat without a grin,' thoughtAlice, 'but a grin without a cat! It's the most curiousthing I ever saw in all my life.'

ONE of the pleasures and privileges of workingwith Sir John McMichael at the Royal Post-graduate Medical School was the encouragementgiven to speculation, public or private-as withhis predecessor, Sir Francis Fraser, with hisfavourite phrase 'I'm just thinking aloud....'While unbridled imagination unsupported byfacts met with instant retribution, fair licencewas always given to the possible. The 'formefruste' may often be a measure of our imagin-ation rather than of our perspicacity, but the'forme sine', or the 'Cheshire Cat syndrome' asI prefer to call it, is simply innate commonsenseuntrammelled by the rigorous laws of proof.As a tribute to Sir John, I record here threecases of polyarteritis nodosa sine polyarteritisnodosa (I would add that he probably would

have shot them down without mercy, but ineach of these three cases, there is a small mea-sure of ultimate justification, fulfilling perhapsCarroll's criteria* rather than Koch's).

Case 1B.W.P. (39175), a boy of 6, in December 1965

developed prolonged intermittent fever and 2months later was admitted to another hospitalwith abdominal pain, lymphadenopathy and amorbilliform rash, later scaling. Skin oedema andhair fall followed. He was started on prednisonebut by May 1956 generalized oedema was pre-sent: he had lost weight and had difficulty inwalking.He was admitted to the M.R.C. Rheumatism

Unit at Taplow on 6 July 1956 on ACTH gelinjections with a tentative diagnosis of dermato-myositis. He was severely ill with fever to 105°F,wasted and dehydrated with vomiting and poly-uria. The limbs showed no contractures but therewas a pigmented reticular rash on the legs (Fig.2). This was thought to be more in favour of avascular disease such as polyarteritis than ofdermatomyosities. There was a polymorph leu-cocytosis. There was proteinuria, 20 mg/100 ml.

I.V. fluids and hydrocortisone corrected hisdehydration and electrolyte depletion but he re-mained desperately ill and febrile, occasionallyreaching a temperature recorded as 106-4°F.Towards the end of August' a urinary infection

developed and a blood culture grew coagulasepositive Staph. aureus for which he was givenchloramphenicol followed by other antibioticsand an increase in steroid dosage. Abscesses de-veloped in the right buttock and left forearm.

.... after watching it a minute or two, she made it outto be a grin, and she said to herself "It's the Cheshire Cat:now I shall have somebody to talk to."'"How are you getting on?" said the Cat, as soon as

there was mouth enough for it to speak with.'Alice waited till the eyes appeared, and then nodded.

"It's no use speaking to it," she thought, "till its ears havecome, or at least one of them." In another minute the wholehead appeared, and then Alice put down her flamingo, andbegan an account of the game . . .'

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FIG. 2. Case 1. Left forearm showing livedo reticularis.

By mid-August he was beginning to improveslightly but towards the end of the month de-veloped twitching of right hand, right side offace and right leg, drowsiness and amaurosis,later convulsions, incontinence and neck stiffness,loss of abdominal reflexes and right extensorplantar response suggesting cerebral abscess per-haps secondary to vasculitis: this progressed toakinetic mutism.

In September he was seen by Dr DenisWilliams who diagnosed a large lesion at the topof the mid-brain affecting particularly the leftside and extending into the cerebrum. He diedin the same decerebrate and unconscious stateon 28 September 1956.At necropsy (Dr L. E. Glynn) there were wide-

spread areas of necrosis and abscess formationin the white matter of both cerebral hemispheresand in the neighbourhood of the red nucleus(Fig. 3). There was no evidence of polyarteritisnodosa (Dr Blackwood, National Hospital,Queen's Square). The only other lesion of notewas in the pancreas which showed a small areaof fibrosis and, on re-examination, one vesselwith acute fibrinoid arteritis (Fig. 4). No arteritiswas found in other organs.

Case 2A.I., female, 19 when first admitted to M.R.C.

Rheumatism Unit at Taplow, gave a 2-monthhistory of pain, weakness and paresthesiae inboth legs and later both arms, with loss of weightand dyspnoea, which had necessitated admissionto another hospital as suspected poliomyelitis.Eosinophilia was found and a diagnosis of poly-arteritis made, although muscle biopsy was nega-tive. She was started on steroid therapy. She hadhad asthma for 3 years.

Examination showed a raised JVP, a loud

pansystolic murmur confirmed on phonocardio-graphy, ankle oedema and respiratory dyspnoea:liver and spleen enlarged 3 fingers' breadth, ab-sent triceps and Achilles reflexes with loss ofsensation in both hands and both feet. Therewere bilateral pleural effusions and proteinuria.Blood urea 64 mg/100 ml. Eosinophilia 20%.She improved on steroid, digitalis and diuretics.

The flexion contractures were straightened: sen-sation and power returned although reflexesstayed absent. Symptomless urinary infection(with normal pyelogram) was treated and shewas discharged much improved after 7 monthswith a diagnosis of polyarteritis nodosa despitenegative biopsy. Followed in outpatients, she wasadmitted four times in the next 2 years, firstbecause of increased peripheral neuritis, thenbecause of left loin pain and colic and markedleft hydronephrosis due to periureteric fibrosis(relieved by operation), again with heart failureand enlargement and finally with a recurrenceof left loin pain. During this period she hadcontinued with asthma, cardiac failure, eosino-philia, peripheral neuropathy and urinary infec-tion despite which, with treatment, she led anear normal life and got married. Furtherbiopsy specimens of muscle and periureteric tisueshowed no arteritis. She died suddenly in status

FIG. 3. Case 1. Cerebrum in cross-section showingsoftening and abscess formation.

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Festschrift for Sir John McMichael 21

asthmaticus, 2 months after a further uretero-plasty. Necropsy (Dr Gerald Loewi) showed thelungs to be distended with marked alveolar dila-tation and rupture. Bronchioles were pluggedwith mucus and surrounded by eosinophils. Thepericardial space was obliterated by old fine ad-hesions. Valves and myocardium were normal.The left kidney (109 g) showed hydronephrosis

due to periureteric fibrous tissue with pyelone-phritis. The right kidney was normal (146 g).Sections showed one healed lesion of polyarteritisin the heart and several in the kidneys, right andleft (Fig. 5). None was seen in other organs orin multiple sections from many muscles.

Case 3H.F., a man of 52 years, was admitted to the

M.R.C. Rheumatism Unit at Taplow in Septem-ber 1965 with a 4-week history starting withacute pain in the left shoulder and right anklefor 3 days, later in the right knee, and con-tinuing with a migratory polyarthralgia lasting3-4 hr in each joint, not responding to salicy-lates. Four days before admission the right eyebecame inflamed.

Examination showed episcleritis, polyarthritisaffecting wrists, metacarpal and proximal inter-

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FIG. 4. Case 1. Artery from pancreas showing fibrinoidnecrosis. Masson's trichrome, x 100.

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FIG. 5. Case 2. Artery from kidney showing healedarteritis. Orcein, x 90.

phalangeal joints, ankles, one knee and tarsaljoints, a small intracutaneous nodule on oneelbow and a macular rash on the right ankle.ESR 50 mm/hr; WBC 13,300/mm3; eosino-

phils 23 %; ANF +; LE cells neg.; DAT andLatex neg.; ASO 200; Addis count abnormalwith 90 mg/100 ml proteinuria.Biopsy of the nodule showed an ischaemic

lesion but no vasculitis was seen. Blood urea,normal on entry, started to rise and he developedpurpura. Treatment with prednisone 60 mg/dayreduced to 30 mg effected enough improvementfor him to take his own discharge. Seen monthlyas an outpatient, he remained clinically well buton 20 January 1966 blood urea was 100 mg/100ml; ESR 32 mm/hr; BP 145/95; proteinuria3 g/day.He was admitted to St Peter's Hospital, Chert-

sey, under the care of Dr Goadby in August1966 with haemoptysis and right knee effusion;X-ray showed streaky opacities extending outfrom the lung hila and ? pulmonary oedema;BP 150/80 with multiple ventricular extrasystoles.He died 3 weeks later with a 'shock-like' illness.

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FIG. 6. Kidney showing periglomerular lesions.a, H & E, x12*5; b, H & E, x150.

Necropsy (Dr Ross) showed oedema of legsand purpura. The cerebrum showed oedema, thelungs were oedematous and the heart enlarged(560 g). Kidneys were contracted (85 g each).Histologically no arteritis or healed arteritis wasfound either by the pathologist or on review atTaplow, but the kidneys showed gross ischaemicchanges with the development of granulomatouslesions surrounding the sites of glomeruli, char-acteristic of the Davson type of polyarteritis(Fig. 6) (Wainwright & Davson, 1950).

DiscussionDubious but at least ultimate justification is

poor present consolation, but I have always feltsorry for those unhappy patients-or rather cases-left in the limbo of the lost, ignored in text-books, unrecorded in the journals, moulderingin the basement record store, just because theydid not have five criteria, just four or perhapseven just three; there are many of these-every-one has them, although we contrive to forgetthem easily because they have no pigeonhole,but they suffer, they are diseased and sometimesthey die. This is a vicious circle; since theseunfortunates never achieve the full purple of arecognized nosological entity, medical students,brought up on the classical cases of the teachinghospitals, the textbooks and the Membershipexamination, never see them and so the circle isperpetuated. To use a different metaphor, thestudent of geography knows the mountain rangesthe river valleys and even the plains, but mostpeople live in places which are really neithermountain, valley or plain but somewhere in be-tween. Diagnostic entities are all very well butevery conscientious physician knows that he can-not fit all his patients into these categories with-

out Procrustean measures. The most frequentlyencountered trouble is lack of data: the patientemigrated to Canada and no follow-up was pos-sible, or was observed before some crucial testwas invented, but even in patients with themaximum of follow-up including post-mortemexamination, there is occasionally a regrettablelack of evidence conclusive enough for pigeon-holing. These are the patients whose historiesfail to get recorded, who dog our memories fora brief period; their only fault was that theyfailed to achieve the level of textbook diagnosisor of epidemiologic criteria. They thereforefailed to influence textbook description. It seemsprobable that there are more of them than eventhe most obsessive of us are aware. Is it notpossible that there are more formes frustes of adisease than formes pleines? Medical literature isthe description of those patients who conformto the mean-give or take a few standard devi-ations-and leaves out in the cold neglected andundocumented those numerous characters whohave not had the fortune to develop all five ofthe recommended criteria. I sing therefore ofthe patient with a demi-semi syndrome. Of rheu-matism and the man, I sing. These are theunderprivileged, the cats known only by theirgrin. Lewis Carroll was perhaps less than logicalnot to deploy other Cheshire Cats known onlyby their grin and never substantiated. This isour everyday dilemma.

AcknowledgmentsI am indebted to my colleagues Dr L. E. Glynn and Dr

Loewi, to Dr Blackwood and to Dr C. F. Ross for patho-logical data and material, and to Dr Goadby for clinical data.

ReferencesLEWIS CARROLL (1865) Alice's Adventures in Wonderland.London.

WAINWRIGHT, J. & DAVSON, J. (1950) J. Path. Bact. 62, 189.

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