The spine in idiopathic haemochromatosis · Spine in idiopathic haemochromatosis 455 Table1I Pathologicalfindings in lumbarspine ofsix autopsiedcases Caseno. I 2 M LI-SI eration LI-2andL4-5

Ann. rheum. Dis. (1971), 30, 453

The spine in idiopathic haemochromatosis

E. G. L. BYWATERS, E. B. D. HAMILTON, AND ROGER WILLIAMSM.R.C. Rheumatism Unit, Canadian Red Cross Memorial Hospital, Taplow, Maidenhead, Berks;Department ofPhysical Medicine and Rheumatology and M.R.C. Group on Metabolism and HaemodynamicsofLiver Disease, King's College Hospital, London.

The development of a specific arthropathy is now awell recognized complication of idiopathic haemo-chromatosis (Schumacher, 1964; de Seze, Hubault,Kahn, Welfling, Jaffres, Mitrovic, and Solnica, 1966;'Hamilton, Williams, Barlow, and Smith, 1968); oneof the characteristic features found in the majority ofaffected joints is the presence of calcium pyrophos-phate deposits in both hyaline and fibrocartilage.Further studies have shown a direct, but notnecessarily causal, relationship between hyalinecartilage calcification and the joint damage (Atkins,McIver, Smith, Hamilton, and Williams, 1970).Chondrocalcinosis due to calcium pyrophosphatedeposition, in the absence of other disease, was firstdescribed by McCarty, Kohn, and Faires (1962) andby Zitfian and Sit'aj (1963). Sit'aj and Zitnian (1967)also reported calcification of the cervical and lumbarintervertebral discs in a long term study of 39patients, some of whom gradually developedstiffening of the spine. Calcification of intervertebraldiscs is sometimes found in hyperparathyroidism,'where chondrocalcinosis of peripheral joints hasbeen described (Bywaters, 1959; Zvaifler, Reefe, andBl_ck, 1962; Bywaters, Dixon, and Scott, 1963), andfor many years disc calcification has also beenknown to occur in ochronosis. g.During the period of the present study, six patients

with haemochromatosis have come to autopsy, andthis paper describes the radiographic, macroscopic,and histological changes found in their lumbarspines, together with the appearances using polarizedlight microscopy. In addition, radiography of thelumbar spine has been undertaken in 47 patientswith idiopathic haemochromatosis and the results arecompared with the incidence of disc calcification in ageneral population.

ResultsIn seven (15 per cent.) of the 47 living patients with sidiopathic haemochromatosis, calcification of one or PIG. 1 Case 6 Antero-posterior radiograph of lumbarmore of the intervertebral discs was clearly visible spn, January1radiographically (Fig. 1). chondrocalcinosis in peripheral joints. Any of

All of these seven patients had arthropathy and the lumbar intervertebral discs could be involved

Accepted (or publication May 5, 1971.Addrs for reprits: Dr. B. B. D. HamIlton, King's College Hospital, Denmark Hill, London, S.E.5.

copyright. on June 21, 2020 by guest. P

rotected byhttp://ard.bm

j.com/

Ann R

heum D

is: first published as 10.1136/ard.30.5.453 on 1 Septem

ber 1971. Dow

nloaded from

http://ard.bmj.com/

454 Annals of the Rheumatic Diseases

except LS-Sl. The radiographic appearances in anantero-posterior view could closely resemble theperipheral disc ossification seen in ankylosingspondylitis, but sometimes in addition the nucleus ofthe disc was also calcified. The incidence of disccalcification in the lumbar spine in an unselectedseries of straight antero-posterior x rays taken inmale patients matched for age before an intravenouspyelogram was also recorded. One hundred filmswere examined, and in six disc calcification was seen,but in each case the changes were minimal, and wereconfined to the margin of one interspace.The clical details of the six patients who came to

autopsy are shown in Table I. There were four menand two women whose ages ranged from 68 to 80 yrs.All but one were diabetic. Three had been depletedof iron by multiple venesections. Five patients had aperpheral polyarthritis with widespread chondro-calcinosis in four. The mean duration of their jointsymptoms was 12 6 yrs (range 2 to 18). Two wereseverely disabled but in none had pain or stiffness ofthe spine been prominent symptoms. Episodes ofacute arthritis occurred in one patient and, althoughcrystals of calcium pyrophosphate were not demon-strated in joint fluid during life, they were subse-quently shown to be present in the menisci of theknee joints using x-ray diffraction crystallography.

PATHOLOGICAL FINDINGS

Lumbar spine specimens from these six cases variedfrom three to seven vertebral bodies and includedligamentum flavum in four instances (Table II,opposite).

While discoloration and degeneration of some orall of the intervertebral discs was seen in four cases,it was almost absent in two (Cases 2 and 6). As maybe seen by reference to Table LI, there was noindividual correlation of disc degeneration withpresence of peripheral arthropathy or chondro-calcinosis, duration of joint symptoms, or thera-peutic iron removal. Although most disc degenera-tion was seen in the two eldest patients and least inthe youngest, there was only 12 years differencebetween them in age at death. No gross disc degen-eration was seen in Case 6, an iron depleted patientwith widespread clinical arthropathy and crystaldeposition; minimal change only was seen in onedisc of Case 2.

In others, degeneration affected 2/7 discs (Case3, Fig. 2, opposite), 2/6 discs (Case 1), 1/4 discs(Case 5), in varying degree. Prussian blue stainingfor iron in disc cartilage was negative. The sixthsubject (Case 4) showed discoloration and fissuringwithout collapse in 3/4 discs (Fig. 3, overleaf) andcollapse in the 4th disc. In this case and in two othersshowing the more severe disc degeneration, there wasdamage to the vertebral plates with break-up of theplate (at L5-S1 in Case 4 and at L4-5 in Case 3,Fig. 2). In the third subject (Case 1), vertebral bodycollapse had occurred on the upper segment of L2and L3, without plate disruption (Fig. 4, overleaf) butdegenerative changes were present in L1-2 and L4-5discs without plate damage. The degenerativechanges in the discs leading to fissuring and cavita-tion did not seem different (with the exception ofcrystal deposition) from that seen in control material

Table I Clinical details in six autopsied cases

Case Sex Age (yrs)no.

First Diagnosis Deathsymptom

Haemochromatosis

Diabetes Ironremoved(g.)

1 M 75 75 79* - 0

2

3

4

M

F

70 70 71*

68 71 73*

45 73 80

5 M 55 69 71*

+ 0

+ 3-7

+ 3 6

+ 0

6 M 52 55 68* + 19

Joints

Arthropathy Chondro- Duration ofcalcinosis symptoms

(to death)(yrs)

Hands Hands, wrists, 2hips, knees

Hands None 10

Nonet None

Hands, elbows,t Widespread in 18knees, ankles hyaline and

fibrocartilage

Widespread Widespread in 16polyarthritis hyaline and

fibrocartilage

Widespreadt Widespread inpolyarthritis hyaline and

fibrocartilage 17

* Neoplasm present t Iron absent in synovial membrane



j.com/

Ann R

heum D


ber 1971. Dow

nloaded from

http://ard.bmj.com/

Spine in idiopathic haemochromatosis 455

Table 1I Pathological findings in lumbar spine of six autopsied cases

Case no.

I

2 M LI-SI

eration LI-2 and L4-5FIC mainly in these two discs

Ligamentum flavum

CALCMC

Normal(Minimal degeneration L5-1)

3 F T12-Sl Degeneration L4-5 with protrusion of L5-1

4 F L2-Si

5 M Li-S

6 M L3-5

0

Severe degeneration and discoloration withdegenerative thinning of L5-1CALCIFIC

Slight degeneration L12, L5-S1, andprotrusion L3-4Others intactCALCIPIC

No degenerationNormal heightCALCIFIC

CALCIFIC

Vertebral plate

Collapse uppersurface L2and L3

Normal

Collapse uppersurfaceLi body

IA-5 and 5-1damaged

Break-up L5-S1L3 lower face,

sagittalL5 upper face,

coronal

Normal

CALCFC Nonnal

FIG. 2 Case 3. Sagittal section. T 12-Si shows minimal degeneration except in L4-5, L5-S1 but no calcification.

of the same age. In Case 4 at the age of 80, there weremarked degenerative changes at L5-S1, with dis-coloration and plate break-up (Fig. 5, overleaf). Themarrow spaces were filled with regenerated cartilage.It is interesting that the x-ray appearances of thechondro-osseous junction resemble those character-istic changes in the peripheral joints of haemo-chromatosis; such juxta discal bone changes wereuncommon here, however, both in individualvertebrae and in individuals. Case 3 also showed

collapse of the upper surface of LI without vertebralplate damage not, apparently, due to metastases.

Crystal deposition was seen in the discs in 4/6cases and in ligamenta flava in the same cases.Calcification occurred in some discs and not inothers, corresponding in Cases 4 and 6 to that seenradiologically during life. The crystals of calciumpyrophosphate dihydrate, identified by their shapeand their positive birefringence (and by x-raydiffraction in Case 6) were laid down along the lines

Sex Segments Discs

M Ll-5 DegenCALCIF

..i..It

t.



j.com/

Ann R

heum D


ber 1971. Dow

nloaded from

http://ard.bmj.com/


.: ..........

A P-SKs

j .. e

/ ..;'..,', 1,

...e_,.;

..?

' '.e;.^;i 'i:S 5

.t .-'<. .':b4F;"

..... /.

FIG. 3 Case 4. Sagittal section. L1-5 shows gross dis- FIG. 4 Case 1. Sagittal and coronal sections, showingcoloration and degenerative changes, and break-up at L4-5; collapse ofupper surfaces ofL2 andL3. Moderate calcifica-minimal calcification on x ray. tion.

showing break-up of the

j;f ~ ~ ~ ~ ~ ~ 7,,eI. Cae4L5-i,51 Jsg

Li ~~~~~~~~~~subchondral cartila-

6-m on one side thanthe other, with pro-trusion of the disc.Haematoxylin andeosin. x6.

rr'r ,,J s



j.com/

Ann R

heum D


ber 1971. Dow

nloaded from

http://ard.bmj.com/


of the outer annular fibres (Fig. 6), usually in clearlydefined elongated globular masses (Fig. 7).

FIG. 6 Case 6. Sagittal section L3-4-5, showing crystaldeposition.

They were seen most clearly peripherally in discs iwithout degenerative changes: when, however, therewere degenerative changes the crystal masses weredeposited along the margins of the slit-like fissure FIo. 7 Case 6. Untdecalcified lumbar disc by polarized(Fig. 8). This occurred even in the minimal fissuring light. Haematoxylin and eosin. x 20.seen microscopically without gross deposition inCase 6 (Fig. 9, overleaf). These crystal masses did not occur in the neigh-

FIG. 8 Case 5. L5-S1, showing crystal deposition inmargins offissure. Haematoxylin and eosin. x 15.



j.com/

Ann R

heum D


ber 1971. Dow

nloaded from

http://ard.bmj.com/


.A.

-' In'Ft ;''' m "

+''b'')~~~~~V

4...i..S.

FIG. 9 Case 6. L2-3 undecalcified, showing deposition inmargins of minimal fissuring. Haematoxylin and eosin.x 20.

bourhood of chondrocytes or in the nests of hyper-trophied and proliferating chondrocytes, which were

JJX'+'/W..

FIG. 10 Case 4. Crystal deposition in fissure marginsavoiding chondrocyte nests. Haematoxylin and eosin. x 66.

often surrounded by a clear space of ground sub-stance (Fig. 10). Nor did they occur on the collagenfibres where these had become visible. Small and

FIG. 11 Case 1. Un-decakified, showingcrystal deposits nearvacuoles. Haematoxylinand eosin. x 150.

..jI.0 N

ml..W.A.

i.



j.com/

Ann R

heum D


ber 1971. Dow

nloaded from

http://ard.bmj.com/


hence apparently early deposits were seen in theneighbourhood of the basophil fluid accumulationsthat occur as fissuring develops in the fibrocartila-ginous matrix (Fig. 11). These balloon-like spacescontaining a delicate foamy structure staining bluewith haematoxylin are surrounded and defined bythe remains of the matrix. It is in the latter thatthe characteristic pyrophosphate crystals are deposi-ted (Fig. 12a, b, and c), at first sparingly with fairly

f e.

large crystals, then more densely packed and small.In calcified sections stained with haematoxylinand eosin the matrix in which pyrophosphate hadpreviously been embedded is clearly recognizable asa dark purple haematoxylin staining granular massin which it is often possible to see the outlines of thedissolved crystals. The crystal deposits occurred inthe degenerate discs along the margins of thefissure, sometimes superficially and sometimes just

SPWIN: FIG. 12 (a) Case I.Haematoxylinand eosin.

(b) The saie,polarized light.(c) overleaf

(b)



j.com/

Ann R

heum D


ber 1971. Dow

nloaded from

http://ard.bmj.com/


(c)

FIG. 12 (c) Highermagnificationofarea outlinedin (a), showingcrystals. x 400.

FIG. 13 Case 5. Sagit-tal section. L3-4.Haematoxylin andeosin. x 7 5.

beneath the surface, not only in the annular regionbut also in the region occupied previously by thenucleus pulposus where the fibrocartilage matrix wascut across at right angles to its fibres, themselvesshowing fraying and fissuring (Fig. 13). Crystal de-posits occurred here just below the frayed surface andagain avoided the area around the chondrocytes.

In the ligamentum flavum, crystal deposits wereseen as large mulberry-like masses pushing aside the

elastic fibres (Fig. 14), and as smaller ('earlier')accumulations appearing to develop in unalteredtissue, Occasionally a small area with basophilgranular change enveloping the elastic fibres wasseen in proximity to the crystal deposits, but itselfcontained no crystals. X-ray of these 3 * 5 mm. slicesshows them to string out along the line of the fibresas streaks (Fig. 15) and as a thin cloud of dust(Fig. 16, overleaf).



j.com/

Ann R

heum D


ber 1971. Dow

nloaded from

http://ard.bmj.com/


FIG. 14. Case 5. L2-3, ligamen-tum flavum showing pyrophos-phate deposits. Haematoxylin andeosin. x 40.

'.

rk

DiscussionIn idiopathic haemochromatosis, calcium pyrophos-phate deposition in the spine is confined to the discsand ligamentum flavum and, although in certainradiographic views there can be a superficialresemblance to ankylosing spondylitis, it differs from

FIG. 15 Case 6. Sagit-talsectionL3-4, showingdeposition in ligamen-tum flavum, gross(right) and on x ray(left).

ankylosing spondylitis in the nature and site of thecalcification, the absence of inflamnatory changes,and the fact that it is not accompanied by stiffnessand limitation of back movement.

Similar and more extensive spinal calcificationinvolving the cervical and lumbar discs has been

#60 -.

A.



j.com/

Ann R

heum D


ber 1971. Dow

nloaded from

http://ard.bmj.com/


FIG. 16 Case 5. Lateral sagittal section. X ray showing deposits in ligamentum flavum, T 12-L3.

FIG. 17 Intervertebral disc from cervical spine of a man with hyperparathyroidism (Case IV of Bywaters, Dixon, andScott, 1963), bypolarized light, showingpyrophosphate crystals depositedalongfissures in the fibrocartilage. Haematoxylinand eosin. x 40.

reported in idiopathic chondrocalcinosis by 2itfian Dorling, and Sutor, 1970). Widespread disc degenera-and Sit'aj (1966). Their patients, in whom there was tion is a prominent feature in ochronosis, but ina strong familial incidence of chondrocalcinosis, haemochromatosis the degenerative changes were notfrequently developed disc calcification by the third more than to be expected in the age group involved.decade, and afterwards there was progressive spinal Crystal deposition could occur in the absence ofstiffness. Disc calcification can also occur in hyper- gross change in the disc, although its occurrenceparathyroidism (Bywaters, Dixon, and Scott, 1963) adjacent to fissures may be of significance. Crystaland here has been shown to be due to calcium deposition depends on adequate ionic concentra-pyrophosphate deposition (Bywaters, 1969; un- tions and the absence of pyrophosphatase-excludedpublished data). As in the present instances, from avascular cartilage with other large moleculescrystal deposits appeared to occur in relation to (Laurent, 1966), but its deposition in fissuresfissure spaces (Fig. 17). This contrasts with suggests that in addition to such factors there mayochronosis, in which calcium apatite is found in the be a facilitating factor, perhaps change in macro-discs, but both calcium pyrophosphate and apatite molecular concentration, in these degenerativehave been identified in a synovial joint (Bywaters, spaces.



j.com/

Ann R

heum D


ber 1971. Dow

nloaded from

http://ard.bmj.com/


It should be stressed that the changes describedhave so far not been shown to cause symptoms, andthat they were only found in patients in whom therewas peripheral arthropathy and chondrocalcinosis.There is no evidence that either the spinal changes orthe peripheral arthropathy have been influenced byreducing the iron overload by venesection therapy.

SummaryCalcium pyrophosphate deposition occurred in theligamentum flavum and in the peripheral parts andfissure surfaces of the intervertebral discs in four ofsix patients with idiopathic haemochromatosis. Inone, the X ray in vivo resembled that of ankylosing

APPENDIXCase historiesCASE 1. This man was 75 years in 1964 when a diagnosisof cirrhosis was made following haemorrhage after atooth extraction. In November, 1966, he had haemate-mesis from oesophageal varices. On examination then hewas generally pigmented with scanty body hair, smallsoft testes, and hepato- and splenomegaly. The serumiron was raised to 190 Fig./100 ml. with a total iron-binding capacity of 230 ug./100 ml. A glucose tolerancetest gave a fasting blood sugar of 64 mg./100 ml. rising to136 mg./100 ml. at 1 hour and falling to 128 mg./100 ml.at 24 hours. A liver biopsy showed cirrhosis with GradeIV iron deposition. There was no family history ofhaemochromatosis.

In view of his age it was decided not to undertakemultiple venesections; he remained reasonably well for afew months until April, 1967, when he was readmittedwith a urinary tract infection and uraemia. On thisadmission he was noted to have arthritis of several MCPjoints, and the radiographs showed chrondocalcinosis inhis hands, wrists, hips, and knees. He was dischargedafter treatment of his urinary infection but later that yearhad a further haematemesis from which he died at theage of 79.Autopsy showed a ruptured oesophageal varix. The

liver was cirrhotic and showed numerous nodules, thehistological appearances of which were those of a well-differentiated hepatoma; the liver showed Grade IV irondeposition and the characteristic appearances of haemo-chromatosis. The knee joint showed synovial irondeposition chondrocalcinosis but no arthropathy.

CASE 2. The first clinical manifestation of haemo-chromatosis in this man was diabetes which was diag-nosed at the age of 70 in 1967 and treated successfullywith chlorpropamide (250 mg. daily). In 1968 he devel-oped temporal arteritis which responded to prednisonebut later that year he was referred to King's CollegeHospital because of hepatomegaly and ascites. He gavea history of low back pain for 3 months and morerecently abdominal swelling with severe epigastric pain.For about 10 years he had had occasional rheumaticpains in several joints.On admission in September, 1968, he was thin and

spondylitis, with pseudosyndesmophytes, and histo-logical studies revealed deposition of calciumpyrophosphate crystals in the outer and peripherallayers of the annulus fibrosus. In other cases in whichdisc degeneration had occurred, deposits were local-ized to the immediate neighbourhood of the fissures.Even in the earliest phases, pyrophosphate depositionseems to be associated with microfissure formationand the accumulation of mucopolysaccharide in be-tween collagen bundles. It did not seem to be relatedexcept geographically to disc degeneration, and theappearances were the same in the untreated case andin those who had had multiple venesections. Noiron staining was seen in disc cartilage.

pigmented, with ascites and an enlarged liver palpable10 cm. below the costal margin. The serum iron was125 pg./100 ml. and total iron-binding capacity 155 jg./100 ml. Liver function was abnormal.Minor osteophytic lesions were seen in the lumbar

spine and knees. In the hands there was loss of cartilagein the second left MCP joint with a few small cysticchanges in the interphalangeal joints. Synovial biopsyshowed slight reduplication of synovial lining cells whichcontained considerable haemosiderin. The connectivetissue showed no increase of chronic inflammatory cells,but there were a number of haemosiderin-laden macro-phages. Crystals from the joint fluid had the characteris-tics of calcium pyrophosphate.A liver scan revealed a filling defect in the left lobe

corresponding to the palpable epigastric nodule, and abiopsy from this area showed an anaplastic carcinoma.This condition deteriorated rapidly and he died in Octo-ber, 1968, the final cause of death being bleeding fromoesophageal varices. At autopsy the liver showed amicronodular cirrhosis, with Grade IV iron depositionand the characteristic histological appearances ofhaemochromatosis. Approximately three-fifths of theleft lobe were replaced by a well-differentiated hepatoma.The knee joint was normal apart from synovial irondeposition. No calcification was visible in the spinalsegment removed.

CASE 3. This woman had developed diabetes at the ageof 68 in 1963, which was controlled on chlorpropamide.In 1966, after a history of indigestion for 18 months, hergall bladder was removed and showed a small tumourat the fundus, histologically a poorly-differentiated adeno-carcinoma. At the time of surgery the liver was noted tobe nodular, and a liver biopsy showed a micronodularcirrhosis with Grade IV siderosis.

Subsequent investigations in 1967, at the age of 72,showed a raised serum iron of 215 ,ug./100 ml. and a totaliron-binding capacity of 240 ,ug./100 ml. She was pig-mented with sparse body hair and the liver was enlarged6 cm. below the costal margin. She had no joint symptomsand her joints were clinically and radiologically normal.There was no family history of haemochromatosis or of



j.com/

Ann R

heum D


ber 1971. Dow

nloaded from

http://ard.bmj.com/


diabetes.She was then treated by multiple venesections and

3-7 g. iron were removed. In March, 1968, she wasreadmitted complaining of upper abdominal pain of 2months' duration and the loss of 14 lb. in weight. Theliver was larger than previously with a hard nodule in thelower edge. Her condition slowly deteriorated and shedied in November, 1968.At autopsy white hard tumour tissue extended from the

bed of the gall bladder into the liver. The histologicalappearances were those of a poorly-differentiatedadenocarcinoma similar to the primary tumour. Other-wise, the liver showed a micronodular cirrhosis with someiron still present in the parenchymal cells (Grade I).Examination of the right knee joint showed slightirregularity of the medial surfaces of the patella and ofboth condyles, but no calcification of the articular ormeniscal cartilages could be detected. Iron stains of thesynovial tissue were negative. The MCP joint of the leftindex finger was also normal.

CASE 4. This woman had had diabetes since 1932 andhad been taking insulin since 1943. In 1959, at the ageof 71, she noticed brown pigmentation of the skin of herfeet and arms. On examination in 1960 the liver wasfound to be enlarged. The serum iron was 246 pg./100 ml.and total iron-binding capacity 303 ug./100 ml. A liverbiopsy showed septal fibrosis with early nodule forma-tion. The portal tracts contained a mixed inflammatorycell infiltrate and there was Grade IV siderosis. Hermother and one aunt had diabetes and two of her sonson subsequent investigation proved to have hepaticsiderosis with a raised serum iron level. She was treatedby multiple venesections and between February andAugust, 1961, 3*6 g. iron were removed.

She attended sporadically and remained reasonablywell until April 28, 1967, when she developed an acutearthritis of the right elbow. 5 ml. of fluid were aspirated;this contained no crystals. On direct questioning sheadmitted to episodes of acute arthritis in her knees andleft hand, and that she had had an acute arthritis of theright elbow some 18 years earlier. A skeletal x-ray surveyshowed chondrocalcinosis in the hips, knees, and ankles,in the left shoulder, and in the fibro-cartilage of thesymphysis pubis and the triangular ligament of the wrist.The following year, in August, 1968, she was readmittedwith diabetic precoma after a urinary tract infection.She recovered only to collapse suddenly and died on the8th day after admission with a massive pulmonaryembolus.At autopsy the liver showed portal fibrosis with some

bridging in the portal tracts and mild chronic inflamma-tory infiltration in the portal areas. The knee and hipjoints showed gross chondrocalcinosis and there was asevere arthritis of the right elbow joint. The liver andjoints showed no iron deposition.CASE 5. This man had developed diabetes in 1952 andsoon afterwards arthritis in his hands and feet. Hisknees and hips were subsequently involved and hebecame progressively disabled despite intensive physio-therapy and courses of gold, indomethacin, and phenyl-butazone. In 1965 a cup was inserted Into the right hipjoint which had to be removed 5 weeks later because ofinfection. Since then he has been able to walk only

slowly. Hepatomegaly and pigmentation were firstnoted in 1966. There was no family history of diabetesor cirrhosis, but one brother was subsequently found tohave a raised serum iron and hepatic siderosis.On admission to King's College Hospital in December,

1967, at the age of 70, he was pigmented and the liverwas enlarged 10 cm. Body hair and testes were normal.Biopsy showed cirrhosis with Grade IV iron deposition.He was severely crippled. There was bony swelling of theMCP and PIP joints but no ulnar deviation. Both hipjoints were severely restricted, the elbows lacked 100 offull extension, and there was crepitus and bony swellingof the knees without effusion.

Synovial biopsy of the knee showed moderate villoushyperplasia and iron deposition in synovial lining cellsand subjacent macrophages. Radiographs showed severearthritis of the second and third MCP joints of bothhands as well as both hip joints, and there was widespreadchondrocalcinosis which involved both the hyaline andthe fibro-cartilage.Ring arthroplasty of the right hip performed in

February, 1968, gave some relief, but on May 16, 1968,he was readmitted with increasingly severe pain in thejoints, abdominal pain, fever, and loss of weight. A liverscan showed a filling defect suggestive of a hepatoma.He died on August 8, 1968. Autopsy showed a well-differentiated hepatoma and the typical appearances ofuntreated idiopathic haemochromatosis. Joints showedarthropathy, chondrocalcinosis, and synovial irondeposition.CASE 6. A bank cashier, aged 55 came to King's CollegeHospital in 1954, giving a 3-year history of generalill-health with more recent polyuria and polydipsia. Onexamination he was markedly pigmented with hepatome-galy and testicular atrophy, the diagnosis of haemochro-matosis being later confirmed by livei biopsy. FromAugust, 1957, to May, 1961, 19 g. iron were removed bymultiple venesections. With this he improved and the pig-mentation and hepatomegaly became less marked thoughthere was no change in the hypogonadism or insulin re-quirements In 1966 his health deteriorated and in Novem-ber, after several haematemeses, he was admitted to St.Bartholomew's Hospital and died on February 26, 1967.Autopsy showed a large hepatoma; the joints showedarthropathy and chondrocalcinosis but were iron-free.The arthritis had first appeared in both knees in 1950

and later spread to involve his hands, wrists, hips, ankles,and feet. Rheumatoid arthritis was diagnosed and in1959 he was given a short course of prednisone with noappreciable benefit. In 1960 there was swelling of the smalljoints of the hands and limited abduction of both hipjoints, and the knees and ankles were swollen. X raysdemonstrated the presence of articular chondrocalcinosis.Since then he had become progressively disabled by thearthritis in his hips and knees, and could walk only withgreat difficulty.Examination in 1967 showed obvious bony swelling of

the interphalangeal and MCP joints. There was no ulnardeviation of the fingers or tendon involvement. Move-ments of the wrists were limited, abduction and rotationwere severely restricted in both hip joints, and there wasbony swelling of the knees with restriction of full flexion.The ankle joints were markedly limited and the subtaloidjoints fixed.



j.com/

Ann R

heum D


ber 1971. Dow

nloaded from

http://ard.bmj.com/


RfeATKiNS, C. J., McIvoR, J., SmrrH, P. M., HAMILTON, E., AND WILIAM, R. (1970) Quart. J. Med., 39, 71

(Chondrocalcinosis and arthropathy: studies in haemochromatosis and idiopathic chondrocalcinosis).BYWATEs, E. G. L. (1959) Ann. rheum. Dis., 18, 64 (discuion).

-, DIXON, A. ST. J., ANm Scrr, J. T. (1963) Ibid., 22, 171 (Joint lesions of hyperparathyroidism).DoP.uNo, J., Am SuroR, J. (1970) Ibid., 29, 563 (Heberden Society report-Ochronotic densification).

HAMLTON, E., Wniums, R., BARLwW, K. A., Aim Simr, P. M. (1968) Quart. J. Med., 37, 171 (The arthropathyof idiopathic haemochromatosis).

LAURENT, T. C (1966) 'The Chemical Physiology of the Mucopolysaccharides'. Boston.McCARTY, D. J., KoHN, ~4. N., Aim FAss, J. S. (1962) Ann. intern. Med., 56, 711 (The significance of calcium

phosphate crystals in the synovial fluid of arthritic patients: the 'pseudogout' syndrome).SCHUMACHER, H. R. (1964) Arthr. and Rheum., 7, 41 (Hemochromatosis and arthritis).SkZ3, S. DE, HUBAULT, A., KAHN, M. F., WBLNG, J., JAFFRS, R., Mrrovic, D., AND SOLNICA, J. (1966)

Sem. HMp. Paris, 42, 2472 (Les arthropathies des h6mochromatoses).Srr'AU, S. Am 2rr&AN, D. (1967) 'Proc. VI Congresso Europeu de Reumatologia,' Lisbon, p. 547 (Spinal changes

in chondrocalcinosis).Zrr1AN, D., AN SrrtU, S. (1963) Ann. rheum. Dis., 22, 142 (Chondrocalcinosis articularis).ZVAILR, N. J., REEF, W. E., A BLACG, R. L (1962) Arthr. and Rheum., 5, 237 (Articular manifestations in

primary hyperparathyroidism).



j.com/

Ann R

heum D


ber 1971. Dow

nloaded from

http://ard.bmj.com/

Documents

The spine in idiopathic haemochromatosis · Spine in idiopathic haemochromatosis 455 Table1I Pathologicalfindings in lumbarspine ofsix autopsiedcases Caseno. I 2 M LI-SI eration LI-2andL4-5