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POLYARTERITIS IN CHILDHOODBY
A. V. NEALE, M.D., F.RC.P.(From the Department of Child Health,
University of Bristol)
With increased study of the mesenchymal tissuesand their special
reactions to toxic, infective, andallergic factors, the parficular
pathological grouping,in regrd to the place in which the blood
vessels aredirctly involved, has been widely considered.
Aconsiderable literature daling with the pathologyand the clinical
miftations of polyarteritis hasshown clearly that the connective
tissue eleents inthe vessel walls are, under certain conditions,
highlysusceptible to inflammatory and necrotizing agents.It must be
admitted that the morbid anatomy hasbeen clearly -defined, and that
cetain clnial andexperimental observations have lead to some
supportfor an etiological basis of allergy. Neverthekss theprecise
relationships cannot be considered to befully understood. In fact
it is quite evident that inthis field of pathology there is still
ample scope forclassiation, and particuLaly so in as much as
asimilar tissue response nism is concerneda wide variety of
clinical forms of disease. Poly-artertis may in some cases exist as
the only apparenttissue manifestation, but in others there is a
morewidespread nymal tissue reaction, and aninfinity of graduations
may occur.Teilum (1946), in discsing lupus erythematosus
disemninatus and related di , notes the peculiarfibrinoid
necrotizing proceses in free connectivetissue and in the walls of
blood vessels together withmiliary epithelioid cell granulomata in
the serosa;he proceeds to consider 'a state of allergy inducedby
specific processes of immnunity ' as a basis for theissue chang. In
contrast to lupus erythematosusdisinatues Teilum considers rmatic
fever tobe etiologically and cinially a tye of specificlesion.
However, this author is mindful of theclose pathological
relationship of lupus eythe-matosus disinatus, polyarteritis and
arteriolotisgranulomatosa (allrgica), and inlines to the viewthat
there is a group of ' para-rheumatic ' diseaseof simila pathognesis
and differt etiology, butposse g in common a state of
hypersensitivity tobacterl toxins and allThe cinical and
experimental observation of Rich
(1942) has ehluidated possible etiologal factorsinvolved in
polyatritis nodosa. There is in theexperiments ample evidenc for
Rich's confidentbelef that arterialesons of this type are
mnifesta-tions of anaphylactic snsiivity. Undoubtedly
there are widely different types of sensitizingantigens which
have the potentiality of causingpolyartertis in man. Galan (1945),
after experi-mental evidence, is of the sme opinion. There
is,however, the necessary adjuvant factor of con-stitutional and
special tissue susceptibility whichtends to defy clinical
recognition.
Linkage in pathology are revealed in the case ofrheumatic
carditis associated with characteristicpolyarteritis nodosa (Neale
and Whitfield, 1934).Friedberg and Gross (1934) also describe four
casesof periarteritis nodosa in rheumatic fever in whichAschoff
bodies were demonstrable in the myo-cardiumn Buckley (1946) points
out that in theLibman-Sacks syndrome vascular chang idenicalwith
those seen in polyarteritis nodosa are some-times present, and he
records an example in whichgeneralized vasculitis, in association
with ulcerousdennal changes, were present; he considered thewhole
pathology to be a sequel to chronic focalinfection.The experimental
work of Selye (1946) is remark-
able in so far as it reveals, in certain animal, anarterial
reaction with nodular inflammatory changesfollowing injections of
adrenal cortical steroidhormone or anterior pituitary extract; this
effectis inteniie if the animal is receiving excessiveamounts of
salt. Selye advances the view that insome susceptible persons an
overdosage of endo-genous cortical hormone, such as may occur
inreaction to a sore throat, a nervous shock, or anexposure to
cold, etc., may detemine the occurrenceof tissue reponses
istngishable from that ofrheumatic fever and periarteritis
nodosa.
It is signiicant that eosinophilia is only exception-ally
present in childWood cases of polyarteritisnodosa, and this bears
no inhlert relationship tothe degree, extent, distribution, or the
severity ofthe lesions. In Wilmer's (1945) two very severeinfant
cases there was no increase in eosinophils.In a series of
twenty-eight cases of pobarteritis inchildren, two only also had
asthma, whereas ofthree hundred at all a with the same
arterialdiseas, fifty-four had asthma and 94 per cent. ofthese
revealed hyper-eosinophilia (Wilson, 1945). Inthe absence of
associated asthma pobarteritis issi cantly dis ted from
eosmnophilic response.Although the resech of Rich and others
have placed a definite alergic esponsibilit inpolbaitis,
clinical observations are by no meansso cear, possily owing to in
di es n
224
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POLYARTERITIS IN CHILDHOODassessing prodromal phenomena in the
disease orto the virtual impossibility of exploring sufficiently,at
a clinical level, allergic mechanisms of this order.It is of some
interest that polyarteritis in childhoodis rarely associated with
any known common formor type of allergy. This suggests that in
poly-arteritis a specially individualized arterial
receptormechanism exists for allergen action. By and large,the
incidence of this unusual vascular susceptibility,at any age group,
appears to be considerably lessthan the clinical allergies of other
tissue systems.From the clinical aspect no age group appears to
be immune in regard to arterial susceptibility andthe condition
is probably not of great rarity ininfancy. The bizarre nature of
the clinical manifes-tations may well be confusing, but Wilmer
(1945)has described two cases of polyarteritis in the firstmonth of
life. In each of these two infants sepsiswas present and the nature
of the violent and ful-minating course of the disease would
indicate aprobable peculiarly inherent arterial tissue
sensi-tivity. The intensity of this susceptibility is revealedin
the case of a baby aged nine months who diedsuddenly two months
after an attack of acutetonsillitis: the coronary arteries were
severelyaffected with nodular arteritis (Diaz-Rivera andMiller,
1946).Extended search will probably reveal that poly-
arteritis is more frequently present than is usuallyconsidered.
Moreover, there is a strong tendencyto some special sectional
distribution of the arterialinflammatory reaction in different
patients or theeffects are dominantly represented in a
particularvisceral, neural, or cutaneous zone. The
prognosisfrequently depends upon the more
particularlyindividualized locality of the disease and, in
fact,clinical studies suggest that focal arterial reactions,e.g.
cerebral, renal, coronary, may be more devastat-ing than quite
extensive cutaneous involvement.This tendency to a local dominance
is well illustratedby Malamud (1945), who describes a child
agedfive years in whom polyarteritis selectively involvedthe
meningeal vessels with resultant cerebral damageand decerebrate
rigidity. Ophthalmoscopy may bespecially helpful; inspection of the
choroidalarteries may show fusiform aneurismal
dilatations(Goldsmith, 1946) or degrees of retinal
detachment(Sampson, 1945).Although visceral involvement is rightly
regarded
as a constant menace in polyarteritis, and Bradley(1947)
considers the outstanding and special dangerto the renal vascular
mechanism, cutaneous lesionsmay exist as the only apparent
pathological distribu-tion. Downing (1947) believes that the
cutaneousarteries are associately affected in 40 per cent. of
allcases, but it has no special dominance in any agegroup.On
clinical and pathological evidence the disease
may have an exclusively subcutaneous localization.Miescher
(1946) described four examples of thiskind, and in one form the
leucocytoclastic vasculitisof the subpapillary vessels is likened
to the papulo-
haemorrhagic exanthema of the type peliosisrheumatica. In
another, the appearances weresimilar to that of a papulonecrotic
tuberculide, andyet in the others there were variable
histologicalappearances, sometimes approaching granulo-matous
changes.The cutaneous type of polyarteritis nodosa may
reveal severely acute and alarming effects, moreespecially owing
to the possibility of ischaemicnecrosis. Veran (1945) observed
massive gangreneof the foot as a result of the disease in a baby
agedfifteen months, but in whom general recoveryoccurred after
several months' illness. Particularlymutilating effects were
observed by Galan in a boywho developed gross necrosis of the
abdominalwall and gangrene of the terminal phalanges of thefingers.
In this case there was also a ilivedoreticularis ' and a phasic
variation of 0-10 per cent.in the eosinophil polynuclear
leucocytes. Despitethe severe cutaneous effects, slow but
satisfactoryrecovery occurred. Peripheral panarteritis
followingscarlet fever is recorded by Hoyne and Smoller(1941).An
appraisal of the clinical signs of the disease
in childhood (44 cases) revealed purpuric rash in34 per cent.,
other rashes, including urticarial type,in 27 per cent., and
palpable nodules in 4- 5 per cent.(Keith and Baggenstoss, 1941).The
cutaneous form of polyarteritis offers special
advantages in the clinical study of the disease.
Case ReportsCase 1. D.J.W. was a girl aged nine years, the
first child of two. There was no family history ofdisease. The
child's past history was one ofpertussis and measles only. In May,
1943, thepresent illness began. The child developed a fairlysevere
acute streptococcal tonsillitis with moderatesubmaxillary adenitis.
A few days later' rheumatic'pains commenced in the shoulders, back
and legs,and shortly afterwards an ' unusual ' skin rash madeits
appearance. The child felt generally ill andremained in bed until
admitted to hospital. Underhospital observation it was clear that a
somewhatunusual syndrome was present. She was irritableand in
continued discomfort and had variable limbpains. The two
outstanding visible signs were thepersistent flexural position of
the limbs in bed anda very marked mottled rash all over the
body,especially marked on the limbs. The rash wassimilar to that of
'cadaveric staining ', and wasstriking in so far as the face was
also affected andthe intensity varied from day to day,
sometimesbeing peculiarly prominent and unlike any otherknown rash.
There was a fluctuating appearanceand disappearance of subcutaneous
tender noduleswhich left no doubt that the subcutaneous
arterieswere affected by acute focal, nodular, and inflam-matory
changes. There was never, in this girl, anyevidence of tissue or
skin necrosis, which presumablyindicated that the arterial lumen
was in no area
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POLYARTERITIS IN CHILDHOOD 227by copyright.
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ARCHIVES OF DISEASE IN CHILDHOODobliterated. There was no
evidence at any time ofany arterial disease in the deeper
structures or in theviscera. Repeated examination revealed no
evidenceof renal involvement and the heart remainedclinically and
electrocardiographically normal. Theoutstanding clinical feature
was the persistent rash,traces of which can still be seen (three
years later).Considerable general wasting accompanied theillness,
and over an observed course of eight months(May, 1943, to February,
1944) there was anundulating pyrexia with maximal levels around
1030.The pulse rarely reached above 120 and therespiratory rate was
30. There was no abnormalsweating. There was a persistnt
lucocytosis of15,000 per c.mm., but eosinophils were never morethan
4 per cent. Blood cultures were sterile.A biopsy of the skin
(forearm) was done on
March 14, 1944. The majority of the arteries in thesubcutaneous
tissue, and in a lesser degree thoseof the cutis vera, showed
severe pathologicalchanges. There was proliferation of the
sub-endothelial connective tissues of the intima,necrobiotic
changes of the media, and proliferationof the vascular granulation
tissues of the media withmuch disarrangement of the muscle fibres.
Thecellular infiltrations consisted of neutrophil poly-morphs,
lymphocytes, monocytes, and a feweosinophils. The infiltration
extended sometimesthroughout the whole vessel wall and often
diffruselyinto the perivascular connective tissue. Foci ofextensive
necrosis were seen in the perivasular tissue,and a form of giant
cell granulation tisse could beseen in some areas. There was
occasional dis-ruption of the muscle fibres. The pictue was thatof
panarteritis nodosa.From time to time the child had severe limb
pains
and very strongly resented being handled or moved.Skin nodules
appeared and disappeared, and thewho illness presented considerable
phasic vari-ability. Many symptomatic remedie were pre-scrbed, but
it seemed clear that the diseas wasrefractory. In view of the
possibility of retainedtonsil sepsis, tonsillectomy was performed,
but noappreciable improvement occurred. Three monthslater a very
severe exacerbation of all the symptomsand signs appeared with some
oedema of the feet.The mesh-like general rash and
erythematousnodular foci again became prominent. The
clinialprogress indicated a waxing and waning of arteritisnodosa of
cutaneous form.
After a prolonged stay in hospital, gradualimprovement occurred,
although limb pains occurredwhen she was unduly warm in bed. The
rashgradually diminished.
In the following two years occasional crops ofperiarterial
nodules made their appearance and wereusually accompanied by limb
pains and some daysof immobility. Finally, in 1945, she semed to
befree from all effects of the prolonged illess. Oneyear later she
developed diphtheria and was givenadequate doses of anti-serum
without any adverseeffects. In 1948, at the age of thirteen years,
she
was cliicaly well. Puberty occurred normally andmenstruation
appeared.
Case 2. H.J. was a boy aged eight years and thefifth child of
seven. There was no family historyof disease, and the child had a
past history ofmeasles only.
This boy was admitted to hospital in June, 1943,seventeen days
after a sore throat, and actuallyduring the same time as the
previous case. Theclinical picture at that time was identical.
Thirteendays before admission he had received sulphonamideand three
days later a Macular rash appeared allover the body and also
numerous red-purple focalswellings. Pains in the joints, varying in
the mannerof rheumatic fever, also occurred. There was noevidence
of any visceral disturbance.
Histology of a subcutaneous nodule confirmedthe diagnosis of
periarteritis nodosa. The bloodshowed a fluctuating neutrophil
leucocytosis,reaching a maximum of 21,400, but at no time didthe
eosinophils exceed I 5 per cent.
This boy was particularly troubled with limbpains, and on
several occasions temporary jointswellings with small effusions
appeared. Clinicallythe intensity of the disease was more severe in
thiscase. The ' mesh-work ' erythema was very markedand quite
prominent on the face. The feet wereswollen and very painful and
there were manysubcutaneous nodules along the course of
thearteries. The heart was clinically normal andelectrocardiograms
were normal. A variablepyrexia with maxima of 103° continued over
manyweeks. Intensive doses of penicilln had no favour-able effect,
and sulphathiazole was given without anyresponse. Over a period of
one year the diseasevaried in intensity, but eventually he
becameambulatory and comfortable, and his motherthought he was very
well. However, a few cutaneousarterial nodules continued to appear
at intervals andthe ' cadaveric ' staining on the limbs was
persistent.Eighteen months after the onset the boy was
gainingweight and had no symptoms, but he had clearlynot reached a
phase of real health. Three weekslater he had a 'cold ' and a
recurrence of theprevious limb pains and a marked accentuation
ofthe cutaneous erythema. His condition quicklydeteriorated and
necrosis appeared in the fingersand in some other skin areas.
Necropsy revealedno evidence of any visceral involvement in
thearterial disease. There was no tonsil sepsis or anyother
evidence of active focal infection. There wasno renal
pathology.
DisassThese two cases of polyarteritis indicate (1) that
the disease reaction may be apparently confined toa particular
section of the arterial system; (2) thatsuch pathological response
may have a prolongedand clinically fluctuant course and be
compatiblewith a satisfactory recovery without sequelae; or,
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POLYARTERITIS IN CHILDHOOD 229(3) by an acute exacerbation, lead
to quicklyspreading ischaemic necrotic changes.The clinical
features of the dermal form of
arteritis are distinguishable more particularly by theoccurrence
of painful nodular swellings visible andpalpable in the skin. The
arterial nodules may beextremely numerous and yet apparently the
incidenceof intra-arterial thrombosis is minimal. This
isparticularly indicated in the case of D.J.W., in whomit was not
possible at any time during her relapsingillness of many months to
detect any effects arisingout of lumenal occlusion. The type of
generalizedrash is peculiarly characteristic in its meshwork
ofbluish discoloration and resemblance to that seenin cadaveric
staining; this is most marked on thelower limbs and is very
persistent throughout, andfor some time after the active phase of
the diseasehas subsided. In the two cases here recorded theface
showed a variable general swelling in relation-ship to the periodic
intensification of the rash.The mucous membranes were unaffected
butconjunctival suffusion was present.No definite etiological
factors were discovered,
but in each case the arteritis was preceded by rathersevere sore
throat, so that bacterial toxaemia wasprobably causally related. In
neither case could anydefinable allergic susceptibility be
established in anindividual or familial basis. The bouts of
fevermay be merely related to pyrogenic products in thenecrotizing
arteritis.
TreatmentThe life history of the disease and its refractory
nature to any known specific therapeutic measurereduces the
treatment to symptomatic remedies forpain, insomnia, etc. The
tendency for lower limbcontractures, owing to prolonged decubitus
immobi-lization, must be overcome by suitable temporarysplinting.
The peripheral vascular ischaemic effectsmight be in part remedied
by nicotinic acid.Benadryl and other anti-histamine drugs have
alsoreceived clinical trial, without, however, anydetectable
effect.
aummrySome considerations of the possible etiological
relationships in polyarteritis in childhood arepresented and two
cases of the 'dermal ' form arerecorded. A prolonged illnes, with
an ever-presentmenace of possible visceral involvement,
wassuccessfully negotiated and clinical recovery withoutsequelae
occurred in one child. In another child theprolonged and variable
clinical course seemed tohave reached a favourable outcome, but
unexpect-edly a sudden and intense relapse quickly progressedto
acute obliterative cutaneous arteritis and spread-ing ischaemic
necrosis.
REFERENCESBogeart, L. van et al., (1932). Ann. Med., 31,
530.Bradley, E. J. (1947). J. Pediat., 31, 78.Buckley, S. (1946).
Helvet. Paediat. Acta., 1, 524.Downing, J. G. (1947). New Eng. J.
Med., 237, 906.Diaz-Rivera, N. S., and Miller, A. J. (1946).
Annals
Int. Med., 24, 420.Friedberg, C. K., and Gross, L. (1934). Arch.
Int. Med.,
54, 170.Galan, E. (1945). Bol. Soc. Cubana Pediat., 17,
293.Goldsmith, J. (1946). Amer. J. Ophthal., 29, 435.Hoyne, A. L.,
and Smollar, L. (1941). J. Pediat., 18,
242.Keith, H. M., and Baggenstoss, A. H. (1941). J. Pediat.,
18,494.Malamud, N. (1945). J. Neuropath. exp. Neurol., 4,
88.Middleton, W. S., and McCarter, J. C. (1935). J. Amer.
Med. Sc., 190, 291.Miescher, G. (1946). Dermatologica Basel, 92,
225.Neale, A. V., and Whitfield, G. W. (1934). Brit. med. J.,
2,104.Rich, A. R. (1942). Bull. Johns Hopk. Hosp., 71, 123.
and Gregor, J. E. (1943). Ibid., 72, 65.(1945). Ibid., 77,
43.
Sampson, R. (1945). Brit. J. Ophthal., 29, 282.Selye, H. (1946).
J. clin. Endocrinal, 6, 117.Teilum, G. (1946). Acta. med. scand.,
123, 126.Wilmer, H. A. (1945). Bull. Johns Hopk. Hosp., 77,
275.Wilson, K. S., and Alexander, H. L. (1945). J. Lab.
clin. Med., 30, 195.Veran, P. (1945). Arch. Mal. Coeur., 38,
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