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VERTEBRAL ankylosis in a patient with hereditary chondrocalcinosisa CHANCE ASSOCIATION.

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Reginato has reported cases of peripheral joint
ankylosis in hereditary chondrocalcinosis ( I ) . In view
of that association, we might suggest that there are
certain anatomic as well as clinical similarities between hereditary chondrocalcinosis and ankylosing
spondylitis. This report describes the index patient in a
family with hereditary chondrocalcinosis. He had cervical and thoracic vertebral ankylosis and pathologic
evidence of enthesopathy, but did not have lumbar or
sacroiliac joint ankylosis. Although classic ankylosing
spondylitis and chondrocalcinosis could have occurred by chance in the same individual, I am unaware
that any such case has been reported.
On September 27, 1977, an 83-year-old dentist
was admitted to St. Vincent Hospital, Portland, OR,
for fever, malaise, and arthritis of the right wrist,
elbow, shoulder, and left knee. He had suffered from
similar attacks of arthritis in the past and recalled
having a rather constant low backache when he was in
his 20s and 30s. Since age 43, he had suffered attacks
of polyarticular arthritis that involved both proximal
and distal joints. By age 60, his back was rigid but not
painful. He continued to practice dentistry, although
he was bothered by aching in the small joints of his
hands, shoulders, neck, and knees (treated successfully with hydrocortisone, colchicine, and, in the 19SOs,a
From the Oregon Health Sciences University and St.
Vincent Hospital, Portland, OR.
Jerome B. Brem, MD: Clinical Assistant Professor of
Medicine, Oregon Health Sciences University, and St. Vincent
Submitted for publication November 24, 1980; accepted in
revised form February 26, 1982.
Arthritis and Rheumatism, Val. 25, No. 10 (October 1982)
short course of gold). More recently, nonsteroidal
antiinflammatory medications were used. His family
history was significant for similar attacks of arthritis in
both sons, his mother, and certain other members of
his larger family (Figure I).
On examination in the hospital, he had a fever
of 102°F. The right wrist was warm and swollen, as
were the metacarpophalangeal joints. There was also
bony hypertrophy of the small joints of the hand with
ulnar deviation of the metacarpophalangeal joints.
Motion of the shoulders and elbows was restricted by
pain and joint contracture. Both ankles and the right
knee had effusions and were warm; his back and neck
were stiff, and he had a murmur of mitral insufficiency.
The results of the remainder of the examination were
normal. His cerumen was normally pigmented. Results of a routine blood chemistry and a full blood
count were normal. The erythrocyte sedimentation
rate (Westergren) was 88 mm/hr. Results of rheumatoid factor and antinuclear factor tests were negative.
He was negative for B27 antigen. Calcium pyrophosphate crystals were seen on compensated polarized
microscopy of a right knee aspirate; cultures of the
joint fluid and blood were sterile.
On roentgenograms of the hands, hypertrophic
and destructive changes at the metacarpophalangeal
joints were shown (Figure 2A) with marginal and
subchondral erosions, most marked in the thumb,
index, and third digits. Ligamentous calcification was
also seen in the wrist and knees with calcification of
quadriceps tendon (Figure 2B). The sacroiliac joints
were normal (Figure 3). Views of the spine, however,
showed extensive intradiscal calcification. Syndesmophytes fused the upper thoracic and upper cervical
vertebrae (Figure 4A) at the vertebral bodies; the
@’ Deceased
E2l Propositus
0 Examined
* Primary hyperparathyroidism
14 Possible chondrocalctnosts
Definite chondrocalcinosis
Figure 1. Family pedigree with hereditary chondrocalcinosis (see Case Report and Discursion for details).
cervical apophyseal joints were fused as well (Figure
4B). The upper thoracic and cervical vertebrae had a
squared-off appearance, a finding that is characteristic
of ankylosing spondylitis.
Treatment with nonsteroidal antiinflammatory
medications resulted in a defervescence and a resolution of the arthritis. Five months later, the patient was
readmitted to the hospital with a massive left cerebral
hemorrhage and died. A limited autopsy of the cervical
segments (C3, C4, and C5) and of the knees was
The cervical vertebrae (C3, C4, and CS) were
removed as a block. The right hemivertebrae were
decalcified and routinely processed and stained with
hematoxylin and eosin. Sections were also made of the
right knee, tibia, and meniscus. Cervical disc and knee
cartilage in its fresh state were normally colored. In
the histology shown in Figures 5 and 6, the changes
compatible with the enthesopathy of ankylosing spondylitis are shown, as well as the characteristic calcification of the anterior longitudinal ligament (see legends of Figures 5 and 6 for details).
Family pedigree. The family pedigree reported
here is similar in the spectrum of disease and age of
onset to the Dutch (2), Czechoslovakian (3), and
Chilean (4) kindreds previously described. The present
family was of Ashkenazi Jewish origin from Poland
and Eastern Europe. In this family, as in others, the
mode of inheritance seems to be a Mendelian dominant with male-to-male transmission. No HLA-A or B
locus antigens have been linked to the inheritance of
the disease (1 3).All affected persons in the present
family had onset of arthritis between the third and fifth
decades, except for family member 29, who had the
onset ofjoint aches in her 60s and had isolated primary
There were other interesting details about affected family members. Family members 38 and 64
(father and daughter) had insulin-dependent diabetes
as well as arthritis in the back, knees, and ankles, a
syndrome very similar to hemochromatosis. No other
affected family member had diabetes, however, and
both father and daughter as well as the propositus
(family member 18) and family member 48 had normal
iron and iron-binding capacities. The index patient’s 2
sons both had chondrocalcinosis. Family member SO
had had symptoms of arthritis since age 20 and had
ample radiologic evidence of chondrocalcinosis. His
younger brother, family member 51, had impressive
osteoarthritis of the first carpometacarpal joints, scalloping of the radius, and chondrocalcinosis at the
knees. Family members S and 10 died before the study
Figure 2. Roentgenograms of the index patient. A, Right hand. Note the destructive and hypertrophic changes at the
metacarpophalangeal joints of the first carpometacarpal joint, as well as chondrocalcinosis at the radial head. B, Right knee. Note
the calcification of the quadriceps tendon.
was begun. Family member 5 died in 1941. She had a
history of periodic arthritis in hands, knees, and
elbows; at the end of her life, she was confined to a
wheelchair. Family member 10 had intermittent soreness of wrists, ankles, and knees. All the affected
family members had the clinical form of arthritis that
McCarty referred to as the “pseudorheumatoid” type;
arthritis was of varying severity but seldom totally
absent (6). Of all the affected family members, only the
propositus (family member 18) had syndesmophytes
indicative of the enthesopathy of ankylosing spondylitis. All affected family members also had normal
sacroiliac joints.
The central issue this report raises is whether
the vertebral ankylosis represents a chance associa-
tion of ankylosing spondylitis and chondrocalcinosis
o r is the end stage of a process of cartilage and
periarticular ligamentous calcification from chondrocalcinosis alone. The pathologic material presented in
this case report is indistinguishable from that of ankylosing spondylitis. The cervical ankylosis on roentgenogram is also like that seen in juvenile rheumatoid
arthritis (7), psoriasis (8), and end-stage rheumatoid
arthritis (9). Yet, as a child, the index patient did not
have arthritis. Hypoplastic cervical vertebrae and fusion of carpal bones, both roentgenographic findings in
juvenile rheumatoid arthritis, were not seen in this
patient. He never had psoriasis nor any signs of
inflammatory bowel disease. His spondylitis superficially resembles that seen in diffuse idiopathic skeletal
hyperostosis (lo), except that, in his case, apophyseal
joint fusion was present, and the delicate anterior
Figure 3. The patient’s sacroiliac joints are open and have sharply defined joint margins. A thin rim of chondrocalcinosis is seen
along the femoral heads. A thin line of cartilage calcification along the right lower sacroiliac joint is visible.
longitudinal ligamentous calcification seen in the cervical and thoracic segments is much more like that
seen in ankylosing spondylitis than in skeletal hyperostosis. Fusion of the cervical vertebrae can exist as a
developmental anomaly in the Klippel-Feil syndrome
(1 1). The vertebrae in that condition, however, are
flattened, anomalously formed, or reduced in number,
whereas in our patient they were all normally formed.
Arguments can be made that the patient coincidentally had ankylosing spondylitis and chondrocalcinosis, but the clinical and radiologic patterns of his
disease are atypical of ankylosing spondylitis. While
his upper neck and thoracic spine were fused in a
manner identical to that of ankylosing spondylitis, the
lower cervical and lumbar segments had the severe
degenerative spondylosis characteristic of chondrocalcinosis. The sacroiliac joints were patent. The fact that
his tissue type was B27 negative was of no help in
explaining the radiologic pattern (complete tissue typ-
ing was not done). Although psoriatic spondylitis
without sacroiliitis has been described @)-and rarely,
ankylosing spondylitis without sacroiliitis (12)-ankylosis of only upper cervical and thoracic segments and
patent sacroiliac joints would be quite uncommon for
chronic ankylosing spondylitis. Neither the patient nor
his kindred had diseases associated with ankylosing
spondylitis, such as iritis, psoriasis, or inflammatory
bowel disease.
There have been no reports of vertebral ankylosis and chondrocalcinosis, but calcification of the
peripheral fibers of annulus fibrosis and “occasional
localized bony ankylosis” of the cervical apophyseal
joints were described by Resnick et a1 (13), who also
pointed out that apophyseal joint changes were less
frequent and less severe in the thoracic and lumbar
regions than in the neck. The identical findings are
noted in our patient. Zitnan and Sitaj also described
calcification of the anterior margins of the cervical
Figure 4. Roentgenograms of the index patient’s thoracic and cervical vertebrae. A , Thoracic spine. Note the intradiscal
calcification in the bottom 2 discs. The discs seen above these appear to have syndesmophytes bridging the disc space anteriorly
(arrows). The apophyseal joints are patent (A). B, Apophyseal fusion is seen at the C2-3 and C3-4, to a lesser extent at C5-6, and
is not seen at C4-5. Disc space is preserved at the higher cervical levels, where there has been calcification of the anterior margins
of the disc. Extensive degenerative disc disease with hypertrophic osteophytes typical of spondylosis deformans is seen at C5-6
and C6-7. The interspinous ligaments are calcified posteriorly.
discs but found no areas of apophyseal fusion ( 3 ) .
An argument against the patient having ankylosing chondrocalcinosis is the presence of vertebral
rather than peripheral ankylosis. None of the Chileans
described by Reginato et al had axial ankylosis (1). Yet
the pattern of ankylosing chondrocalcinosis in hips
and knees is that associated with ankylosing spondylitis. N o ankylosis of hands, wrists, or feet was described in the Chiloe Islanders, although chondrocalcinosis had certainly affected those joints. Since
occasional cervical apophyseal ankylosis has been
observed in chondrocalcinosis (13), the pattern of axial
ankylosis described in this report may be within the
spectrum of the disease described by Reginato.
If the index patient in this report had ankylosing
chondrocalcinosis, one would have expected another
similarly affected family member. This was not the
case in the other 6 of the kindred who had chondrocalcinosis and whose radiographs were available for
study. Reginato found, however, that only 2 of 10
Chiloe Islanders with ankylosing chondrocalcinosis
were in the same family (personal communication);
thus, it seems that the gene(s) responsible for chondrocalcinosis and ankylosis may segregate independently.
He also noted that ankylosis occurred in the family
members most severely affected with chondrocalcinosis. In view of that finding, it is interesting that our
index patient was the most severely affected of all
living family members with chondrocalcinosis.
The findings of Reginato suggest that hereditary
Figure 5. Micrographs of patient’s cervical spine. A, Disc space at C3-4, cut vertically. (Original magnification X20.) The cartilage end plate
has been eroded away superiorly. Characteristic of hereditary chondrocalcinosis is calcification of the vascular connective tissue that replaces
the disc (cct). What remains of the normal disc can be seen in the upper left corner (d). Note the darker staining remnant, anteriorly and
superiorly, of the annulus fibrosis which is calcified (caf). Where Sharpey’s fibers of the annulus insert into the superior vertebral bony rim,
there has been bony remodeling, as evidenced by the formation of new or woven bone and a thin layer of uncalcified osteoid that can be seen on
higher magnification. This remodeling and calcification of the annulus could be viewed as an antecedent to the syndesmophyte found in Figure
6. Periosteal calcification can be seen at the anterior surface of the vertebra (square), deep to the anterior longitudinal ligament, as can be seen
in ankylosing spondylitis. B, Inset, detailing this process of periosteal calcification. (Original magnification x 130.)
ankylosing chondrocalcinosis, while uncommon, does
exist. Of the 200 Chiloe Islanders afflicted with chondrocalcinosis, only 10 (5%) had this ankylosing type.
In a review of published kindreds of hereditary chondrocalcinosis (2,3), we did not find any affected subjects with joint ankylosis. Vertebral or peripheral joint
ankylosis has not been noted in ochronosis (14) or
Wilson’s disease (15). Bywaters et al were impressed,
however, with the similarity between hemochromatosis and ankylosing spondylitis, both radiologically and
pathologically (16).
In the last analysis, it is not possible to conclude whether the index patient in the present family
kindred had two diseases or one. Much has been
written about the clinical similarity between chondro-
calcinosis and ankylosing spondylitis. In this case,
roentgenographic evidence of vertebral ankylosis and
pathologic evidence of syndesmophyte formation blur
the usual distinctions further. More study is needed to
explain the ankylosis of certain joints afflicted with
I acknowledge with gratitude the help given me by
Sheldon Jacobson, MD, Emeritus Professor of Pathology,
Oregon Health Sciences University, in reviewing the pathologic material presented in this report. I am also grateful to
both Dr. Jacobson and Robert Bennett, MD, Professor of
Medicine, Oregon Health Sciences University, for reviewing
the manuscript. I also thank Brigit Morrison for typing it.
2. Van der Korst JK, Geerards J, Driessens FCM: A
hereditary type of idiopathic articular chondtocalcinosis-survey of a pedigree. Am J Med 56:307-314, 1974
3. Zitnan D, Sitaj S: Natural course of articular chondrocalcinosis. Arthritis Rheum 19:363-389, 1976
4. Reginato AJ: Articular chondrocalcinosis in the Chiloe
Islanders. Arthritis Rheum 19:395-403, 1976
5 . Nyulassy S, Stefanovic J, Sitaj S, Zitnan D: HLA
Figure 6. Micrograph of the patient’s cervical spine. This is a
deeper section of the disc space shown in Figure 5A. (Original
magnification ~ 2 0 . )Vascular connective tissue moving in from the
anterior longitudinal ligament replaces what had been a disc. Note
that syndesmophyte (s) has formed where the annulus fibrosis would
lie. The darkened areas at the base of the syndesmophyte represent
newly formed bone. No ledge is formed anteriorly for the osteophyte, as is seen in spondylosis deformans. No round cell infiltrate
is at the head of the syndesmophyte, but a vascular connective
tissue participates in the remodeling. New woven bone is formed at
the vertebral rim superiorly, but there is no erosion.
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macher HR, Fuentes C, Galdamez M: HLA antigens in
chondrocalcinosis and ankylosing chondrocalcinosis.
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19:391-393, 1976
McCarty DJ: Calcium pyrophosphate dehydrate crystal
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Lambert J k , Wright V: Psoriatic spondylitis: a clinical
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patients, associations, chance, vertebrate, ankylosis, hereditary, chondrocalcinosis
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