Rheumatol Int (2010) 30:349–356
DOI 10.1007/s00296-009-0968-6
ORIGINAL ARTICLE
Autoimmune joint diseases in Late Medieval skeletal sample
from Croatia
Petra Rajić Šikanjić Æ Dejana Vlak
Received: 21 January 2009 / Accepted: 3 May 2009 / Published online: 20 May 2009
Ó Springer-Verlag 2009
Abstract Analysis of 25 skeletons from Late Medieval
cemetery Uzdolje-Grablje near Knin, Croatia, revealed
three cases of systematic pathological changes to joints.
Observed pathological lesions were examined macroscop-
ically and radiologically and compared to the available
paleopathological standards in order to formulate a differ-
ential diagnosis. In all three cases observed changes were
most consistent with autoimmune joint diseases including
ankylosing spondylitis, juvenile idiopathic arthritis and
psoriatic arthritis. Based on published clinical studies, we
suggest that the high prevalence of autoimmune diseases in
our skeletal sample stems from the genetic basis of the
autoimmunity, and that three individuals describe here are
possibly closely related.
Keywords Autoimmune diseases

Ankylosing spondylitis
Juvenile rheumatoid arthritis

Psoriatic arthritis
Skeletal remains
Introduction
Autoimmune diseases appear as a result of immune system
activation in the absence of any external threat to the
organism [1]. Operating through two defence mechanisms
(i.e. inherited innate and acquired adaptive immunity), the
immune system provides a defence against potential
P. Rajić Šikanjić (&)
Institute for Anthropological Research,
Gajeva 32, Zagreb 10 000, Croatia
e-mail: petra@inantro.hr
D. Vlak
Department of Anthropology, University of Toronto,
Toronto, ON, Canada
pathogens [2, 3]. Although failure of either of these
mechanisms can lead to autoimmune diseases, the majority
of these diseases are characterized by the inability of the
adaptive immune system to recognize and tolerate self
antigens. The result of this failure is activation and
expansion of self antigen-specific T and B lymphocytes,
production of antibodies, cytokines and other inflammatory
mediators that eventually lead to tissue damage [1].
Autoimmune genes and environmental triggers act
together in the initiation of the autoimmune response
[1, 4–9]. Epidemiological, family and twin studies, as well
as animal models indicate that genetic factors play a central
role to autoimmune susceptibility [1, 10]. The most
important are the human leukocyte antigens (HLA), located
in the major histocompatibility complex (MHC) region on
the short arm of the 6th chromosome. A number of non-
MHC genes are also included in the genetic aetiology of
autoimmune diseases [11, 12].
There are over 40 known and suspected autoimmune
diseases that can affect any tissue in the body. Individually
they are rare, but together they affect 5–7% of the modern
human population [2, 13]. They are even less commonly
seen in past populations because most of these diseases do
not leave visible lesions on skeletal tissue. The exception to
this rule is a small group of autoimmune joint diseases that
affects bone tissue, such as ankylosing spondylitis (AS),
reactive arthritis or Reiter’s syndrome (RS), psoriatic
arthritis (PA), rheumatoid arthritis (RA) and juvenile idi-
opathic arthritis (JIA), which have been recognized in the
archaeological skeletal populations (see [14–16]).
Several of these autoimmune diseases recognized in the
archaeological record (AS, RS and PA) belong to the
general category of spondyloarthropathy. The primary link
between them is an association with HLA-B27 antigen and
the absence of rheumatoid factor. Exposure of the immune
123
350
system to bacteria is considered to be an important initial
trigger of the diseases [17]. Skeletal involvement tends to
be asymmetric, affecting mostly the sacroiliac joint and the
spine [14, 15].
RA is a chronic inflammatory disease of connective
tissue that affects multiple synovial joints symmetrically,
especially the small joints of the hands and feet [15, 16]. In
most cases of RA, rheumatoid factor is present as well as
some of the HLA-DR antigens, usually HLA-DR4 [18].
Without treatment there is progressive damage of soft tis-
sue cartilage and bone resulting in deformity and disability
[18].
Both RA and seronegative spondyloarthropathies can
have early onset expressions of the disease that begin
before the age of 16 years [14, 15, 19]. All forms of
childhood chronic arthritis of unknown cause are gathered
under the term juvenile idiopathic arthritis (JIA) [19–21].
Even though the exact cause of JIA is still unknown, it
seems to be related to both genetic and environmental
components which result in the heterogeneity of the illness
[19, 20]. Currently, there are three different classifications
that identify discrete clinical subsets that could correspond
to different diseases [20, 21].
Our gross examination of the skeletal remains from the
site Uzdolje-Grablje, Croatia, revealed three cases of dif-
ferent autoimmune joint diseases, including ankylosing
spondylitis, juvenile idiopathic arthritis and psoriatic
arthritis. In the following report we describe observed
pathological conditions, present a differential diagnosis and
discuss potential reasons for the high prevalence of auto-
immune joint diseases in our sample.
Materials and methods
Twenty-seven graves were revealed during rescue exca-
vation in 2006 at the site Uzdolje-Grablje, near the town of
Knin in Croatia. The recovered burials were the part of the
larger cemetery, most of which were destroyed by gypsum
exploitation. The archaeological finds [22] and direct
radiocarbon date (calibrated 1 SD range goes from 1420 to
1920 AD) (Gugo Rumštajn, personal communication)
indicate that the cemetery was in use from the Late Middle
Ages to modern times. The majority of the burials were
single inhumations oriented west/east with the deceased in
an extended position on their back with their hands over the
chest or the pelvis. Four graves with multiple commingled
skeletal remains were revealed, but were not included in
the present study.
The analysed sample consists of 25 individuals, 16
juveniles and 9 adults (three females and six males).
Skeletal remains were complete and well preserved, with
the exception of a few small bones and minor post mortem
123
Rheumatol Int (2010) 30:349–356
breakages. The sex of the juveniles was not evaluated,
while the sex of adults was determined using sexually
dimorphic pelvic and cranial characteristics [23]. Estimates
of the approximate age of the juveniles were based on
dental formation and eruption [24], and fusion of the pri-
mary and secondary ossification centres [25]. Age estima-
tion in adults was based on pubic symphyseal [26] and
auricular surface morphology [27], ectocranial suture clo-
sure [28], and sternal rib end changes [29, 30]. Joint lesions
were examined macroscopically and radiologically. In
order to formulate a differential diagnosis, we have com-
pared observed lesions to the available paleopathological
standards for joint diseases gathered from the literature
(Table 1).
In order to examine family grouping within our sample,
we conducted Mantel test analysing correlation between a
spatial and a phenotipic (non-metric) distance matrix.
Phenotipic distance matrix was generated using 13 cranial
non-metric traits in all adults that were available for
scoring. Positive correlation between two matrices would
suggest that cemetery is kin-structured with closely related
individuals buried near each other (for more details see
[31].
Results
Examination of juvenile skeletal material did not reveal
any lesions that could be associated with autoimmune joint
disease. In three adults, we observed pathological changes
that could be attributed to AS, JIA and PA.
Individual 1
The individual from Burial 11 is a 25 to 35 year-old male.
This skeleton was largely complete with only some of the
small bones of the hands and feet missing. The most
obvious pathological lesion in this individual is ankylosis
of both sacroiliac joints. Even though the pelvis suffered
considerable postmortem breakage, the symmetrical
smooth fusion of sacrum and iliac bones can be seen
(Figs. 1, 2). The vertebral column is complete, and at the
margins of the vertebral bodies of the eleventh and twelfth
thoracic and the first lumbar vertebra there are small ver-
tically oriented syndesmophytes. On the anterior surface of
the majority of the lumbar and thoracic vertebral bodies
there is new bone formation. The apophyseal joints of all
lumbar and several thoracic (7th–12th) vertebrae are
involved. Ossification of the interspinous ligament is visi-
ble on first lumbar and several thoracic (6th–12th) verte-
brae. Ossification of the supraspinous ligament is present in
all thoracic vertebrae. On both the left and right talus and
calcaneus, as well as on the proximal end of the both fifth
 Table 1 Differential diagnosis of joint diseases in skeletal remains based on the available paleopathological standards [14–16]
Rheumatoid Juvenile Psoriatic arthritis Reiter’s syndrome Anyklosing spondylitis Dish Gout OA
arthritis idiopathic
arthritis

Age of onset 20–50 \16 20–50 20–40 15–35 40? 50? 35?
Sex predilection Females Females Females Males Males Males Males No predilection
Antigen HLA-DR4 HLA-B27 HLA-B27 HLA-B27 Absent
Rheumatoid Present Present Never Absent Absent Absent
factor
Hallmark lesion Marginal bone Epiphyseal Erosion of distal Symmetrical sacroiliac Candle wax appearance on Overhanging edge Eburnation of the joint and
Rheumatol Int (2010) 30:349–356

erosion of overgrowth interphalangeal joints - ankylosis 4 vertebrae lesions osteophtytes at joint

the joint in knee ‘‘pencil and cup’’ margin
Main location Small joints of Large joints Distal IP joints of hands Joints of lower limb Axial skeleton Thoracic region MTP joint of the great Large weight bearing joints
hands (knee), and feet (midthoracic spine) toe (hip, knee) and facet
(IP & MCP) cervical joints of spine
spine
Number of Multiple One or few Few or multiple Few Few Few Usually only one One, few, multiple
joints
involved
Symmetry of the Symmetrical Asymmetrical Asymmetrical Asymmetrical Symmetrical (spine), Asymmetrical Asymmetrical Asymmetrical
lesion asymmetrical
(extraspine)
Spine segment Cervical Cervical Can be affected (cervical) Cervical spine Spreads up and down Thoracic Rarely involved Any
involved from T12 to L1
Syndesmophyte No Asymmetric Asymmetric Vertically oriented, Large, horizontal, on the Horizontally oriented
formation symmetrical, give rise right side (T 7–11)
to bamboo spine
Apophyseal Can be Fuse in Ankylosis Involved - fusion Not involved, normal Rarely involved Involved
joints affected untreated
cases
Vertebral Asymmetric Inter- and superspinous Anterior longitudinal
ligament
ossification
Sacroiliac joint Uncommonly Can be–sacroiliitis Asymmetric sacroiliitis Place of initiation May be fixed by several Involved secondary to
involved bony bridges, but not occupational stress
ankylosis
Other joints Knee, foot, Wrist, ankle, Knee, ankle, foot Hips, shoulders, knee, Feet, hands, wrist, Any joint
wrist, carpals, ankle, writs, hand, elbow, knee
elbow, tarsals foot
shoulder
Anyklosis Can occur In untreated Common If in spine - skip lesions Common - sacroiliac Of spine Unusual
cases joint or spine
Enthesophytes Not common Achilles tendon insertion, Achilles tendon Not common Ischial tuberosity, iliac Can develop
calcaneal spur insertion, calcaneal crest, pubic symphysis,
spur, ischial trochanters, patella,
tuberosity femoral linea aspera,
Achilles tendon,
calcaneal spur
351

123
352 Rheumatol Int (2010) 30:349–356

As osteophytes or lipping

DIP and PIP joints

First MCP joint

Usually only great toe, First MTP joint

In severe cases

Unusual
OA

but also others

Can be involved
Rarely present

IP joints
Gout

IP interphalangeal joint, DIP distal interphalangeal joint, PIP proximal interphalangeal joint, MCP metacarpophalangeal joint MTP metatarsophalangeal joint
Fig. 1 Radiograph of sacroiliac joint in individual 1 (Burial 11)
Extra spinal (ligaments,
tendons, cartilage)
Dish

are squared or become

Anyklosing spondylitis

Fused vertebral bodies

In vertebral bodies
bamboo spine

In spine
Only in chronic cases
Reiter’s syndrome

metacarpals,
metatarsals,
Hand and foot Shafts of the short bones of Occasionally

Occasionally

Occasionally

Occasionally
phalanges

Fig. 2 Fusion of sacroiliac joint in individual 1 (Burial 11)

metatarsals there is a new bone formation. Several liga-

ments and tendons of the lower extremities were ossified.
Based on a review of the literature (Table 1), the
the hands and feet,

observed symmetrical fusion of the sacroiliac joints as well

around the joints
Psoriatic arthritis

as syndesmophyte formation in thoraco-lumbar area, and

In severe form

ossification of ligaments and tendons, suggest AS as the

DIP joints

most likely cause of systematic skeletal changes observed

Rarely

in this individual. This pathology would have resulted in a

severe restriction of mobility and presumably, a reduction
osteopenia

in the level of contribution that this individual could make

Periarticular
idiopathic

tubular

to his own community.

bones
Juvenile

arthritis

Individual 2
later stages

PIP involved,
Rheumatoid

evidence

involved

DIP spared
Commonly
Present in

present

Involved

The skeletal remains found in Burial 20 are of a young

arthritis

Usually

Little

adult female aged 23–27 years. Some of the bones are

Table 1 continued

poorly preserved due to the post-mortem damage and all

Joint deformity

the foot bones are missing. All the bones present appear to
Osteoporosis

formation

Metacarpals

Metatarsals

be osteopenic. Both elbows are ankylosed in a flexed

New bone

Phalanges

position at approximately 90° and involved bones are very

gracile due to the limited physical activity (Figs. 3, 4).

123
Rheumatol Int (2010) 30:349–356
Fig. 3 Radiograph of right elbow in individual 2 (Burial 20)
Fig. 4 Detail of ankylosed right elbow in individual 2 (Burial 20)
Also, the right tibia and fibula are fused at their proximal
ends. Unfortunately due to the post mortem damage of
proximal ends of both left tibia and fibula, bilateralism of
this condition could not be established. Hand phalanges
and metacarpals are not affected. All segments of the spine
and the sacroiliac joints are well preserved but no lesions
are observed.
According to the literature summarized in Table 1 most
of the systematic joint diseases, with the exception of RA,
are characterised with asymmetrical joint involvement.
However, elbow erosion with no hand involvement would
be unusual for RA as per present day disease expressions
[32]. Also, majority of the paleopathological sources
[14–16] state that joints of the hands are often first
involved, and are most characteristic feature of RA in
archaeological skeletal material. The severity of the
353
Fig. 5 Distal interphalangeal joints of hands and feet in individual 3
(Burial 4)
observed skeletal changes suggest a long history of the
condition and in combination with the young age of the
individual, allow us to consider juvenile idiopathic arthritis
as the most likely cause.
Individual 3
The skeletal remains from Burial 4 belong to 45- to
50-year-old male. All the bones are well preserved with
only the left femur and tibia missing. Distal interphalangeal
joints of the hands and feet show pathological changes in
the form of articular lipping (Fig. 5), while the heads of the
distal foot and hand phalanges have a ‘‘mouse ear’’
appearance. Intermediate and distal phalanges of one toe
are fused. On both calcanei there are bony exostoses at the
insertion of Achilles tendons and plantar fascia. All ver-
tebrae are present and there are asymmetrically distributed
syndesmophytes on all lumbar, lower thoracic (T 7–12) and
some cervical vertebrae (C4, C7), which are in case of C5
and C6 fused. Apophyseal joints of all lumbar and some
thoracic vertebrae (T 1–5, 11, 12), as well as costovertebral
joints on lower thoracic vertebrae are also involved. There
is new bone formation on the margins of the coronoid, and
on the olecranon fossa of the left humerus. Also, marginal
bony formations are recorded on the trochlea and capitu-
lum of both humeri, and on the olecranon and coronoid
process of both ulnae. The manubrium and the body of the
sternum are fused and the xiphoid process and the costal
cartilage of the first rib are ossified. On both scapulae
glenoid cavities show marginal lipping. On the left side of
the promontory there is vertically oriented exostose, also
123
354
midline projections of the medial crest of the sacrum are
pronounced, as well as marginal osteophytes on both
superior articular facets.
Other observed pathological conditions include a healed
oblique fracture of right tibia’s and fibula’s distal third, and
a fracture of the right tibia distal articular surface.
Observed osteoarthritic changes on right lower extremity
are probably results of these fractures. The skeletal lesions
described above are consistent with descriptions of PA and
RA in the literature (Table 1). Although erosive destruction
of the joints could be found in AS and RA as well, erosion
of distal interphalangeal joints of hands and feet, which
lead to the ankylosis of one toe, is the hallmark lesion of
PA, making the PA the most likely origin of systematic
skeletal lesions recorded in this individual.
Discussion and conclusions
Even though pathological changes of the joints are fre-
quently seen in skeletal material from archaeological
context, it is often difficult to make a precise diagnosis.
Ideally, the whole skeleton is required to establish the
distribution of the lesions and propose potential diagnosis.
In the majority of the published cases observed patholog-
ical changes are categorized as joints diseases or arthrop-
athies. Amongst these are autoimmune joint diseases which
are rarely interpreted through autoimmunity, but rather
presented as isolated case studies [33–37] or analysis of
population occurrence of specific disease [38–41]. To our
knowledge, this is the first study that interprets the presence
of autoimmune joint diseases in one archaeological popu-
lation through autoimmune origin of the diseases.
What is intriguing in our study is the appearance of three
different autoimmune diseases in three out of nine adults in
a single sample. High prevalence of autoimmune diseases
within families and/or at the population level has been
recognized in clinical studies [10, 42, 43] as well as in
archaeological samples [37, 38, 40]. The results from
segregation analyses and twin studies imply that certain
genetic variants (HLA and some non-MHC susceptibility
loci) predispose to autoimmunity in general [44], while
development of specific autoimmune disease depends on
the additional genes that govern specific organ vulnera-
bility and modulate disease severity [1, 45–48]. Based on
the published data, we speculate that the reason for
appearance of different autoimmune diseases in this sample
stems from to the genetic basis of the autoimmunity, and
that three individuals describe here were possibly members
of the same family or lineage.
Grave organization, orientation and body position of the
deceased, as well as repeated use of the cemetery over a
long period of time [22], suggest that cemetery at Uzdolje
123
Rheumatol Int (2010) 30:349–356
was probably used by the local group. Two out of three
burials described here (4 and 20) were found in close
vicinity to each other, at the same depth, and oriented west/
east. In both cases, graves were surrounded by irregular
stones. The deceased were in an extended position on their
back, with their hands on their pelvis (hands of the indi-
vidual from the Burial 20 were above the pelvis due to
ankylosis). The calibrated 1SD range of a direct radiocar-
bon date for Burial 4 is 1490–1660 AD (Z-3784:
300 ± 50 years BP) (Gugo Rumštajn, personal communi-
cation). Burial 11 was situated approximately 20 m NE
from Burial 4 and 20. The position and orientation of this
individual was the same as in two previously described.
The only difference was the grave construction in which
burial pit was lined by stone slabs.
Results of the Mentel test (r = 0.0649, p = 0.6456)
suggest that cemetery is not kin-structured. Due to the
small sample size and the fact that a large section of the site
was destroyed, familial relationship between individuals
affected with autoimmune joint diseases cannot be estab-
lished. However, use of the cemetery over a long period of
time by the inhabitants of the Uzdolje can indicate that we
should look for the cause of autoimmunity on population,
rather than familial level. Appearance of other rare traits
such as sixth lumbar vertebra (graves number 7 and 17) and
elongated styloid process (graves number 4, 5 and 7) [49]
within the sample support the assumption that individuals
buried in the cemetery are closely related.
At the moment population susceptibility and accumu-
lation of the alleles responsible for autoimmunity in gen-
eral seem to be more appropriate cause of the appearance
of the high prevalence of the autoimmune joint disease
among the individuals buried at the Uzdolje-Grablje site.
Acknowledgments We would like to thank Michael Schillaci for
his valuable comments and Katarina Gugo Rumštajn, Kninski muzej
for providing access to the skeletal material examined in this study.
Research was supported by the Ministry of Science, Education and
Sport of the Republic of Croatia (project no. 196-1962766-2740).
References
1. Davidson A, Diamond B (2006) General features of autoimmune
disease. In: Rose NR, Mackay IR (eds) The autoimmune diseases.
Elsevier, St. Louis, pp 25–36
2. Fox SI (2006) Human physiology. Mc-Graw Hill, Boston
3. Taneja V, David CS (2006) Genetics and autoimmunity: HLA
and MHC genes. In: Rose NR, Mackay IR (eds) The autoimmune
diseases. Elsevier, St. Louis, pp 261–271
4. Reveille JD (1993) The interplay of nature versus nurture in
predisposition to the rheumatic diseases. Rheum Dis Clin North
Am 19:15–27
5. Luppi P, Rossiello MR, Faas S, Trucco M (1995) Genetic
background and environmental contribute synergistically to the
onset of autoimmune diseases. J Mol Med 73:381–393. doi:
10.1007/BF00240137
Rheumatol Int (2010) 30:349–356
6. Dahlquist G (1988) The aetiology of type 1 diabetes: an epide-
miological perspective. Acta Paediatr Suppl 425:5–10
7. Ginn LR, Lin JP, Plotz PH, Bale SJ, Wilder RL, Mbauya A,
Miller FW (1998) Familial autoimmunity in pedigrees of idio-
pathic inflammatory myopathy patients suggests common genetic
risk factors for many autoimmune diseases. Arthritis Rheum
41:400–405. doi:10.1002/1529-0131(199803)41:3\400::AID-
ART4[3.0.CO;2-5
8. Noseworthy JH, Lucchinetti C, Rodriguez M, Weinshenker BG
(2000) Multiple sclerosis. N Engl J Med 343:938–952. doi:
10.1056/NEJM200009283431307
9. Salvetti M, Ristori G, Bomprezzi R, Pozzilli P, Leslie RD (2000)
Twins: mirrors of the immune system. Immunol Today 21:342–
347. doi:10.1016/S0167-5699(00)01658-3
10. Tomer Y (2006) Genetics and autoimmunity: non-MHC genes.
In: Rose NR, Mackay IR (eds) The autoimmune diseases. Else-
vier, St. Louis, pp 273–287
11. Djilali-Saiah I, Benini V, Daniel S, Assan R, Bach JF, Caillat-
Zucman S (1996) Linkage disequilibrium between HLA class II
(DR, DQ, DP) and antigen processing (LMP, TAP, DM) genes of
the major histocompatibility complex. Tissue Antigens 48:87–92.
doi:10.1111/j.1399-0039.1996.tb02612.x
12. Gebe JA, Swanson E, Kwok WW (2002) HLA class II peptide
binding and autoimmunity. Tissue Antigens 59:78–87. doi:
10.1034/j.1399-0039.2002.590202.x
13. Jacobson DL, Gange SJ, Rose NR, Graham NM (1997) Epide-
miology and estimated population burden of selected autoim-
mune diseases in the United States. Clin Immunol Immunopathol
84:223–243. doi:10.1006/clin.1997.4412
14. Aufderheide AC, Rodrı́gue-Martı́n C (2003) Cambridge ency-
clopedia of human paleopathology. Cambridge University Press,
Cambridge
15. Ortner D (2003) Identification of pathological conditions in human
skeletal remains. Smithsonian University Press, Washington
16. Roberts C, Manchester K (2005) The archaeology of disease.
Cornell University Press, Ithaca
17. Burmester GR, Dörner T, Sieper J (2006) Spondyloarthritis and
chronic idiopathic arthropathies. In: Rose NR, Mackay IR (eds)
The autoimmune diseases. Elsevier, St. Louis, pp 437–452
18. Mackie S, Quinn M, Emery P (2006) Rheumatoid arthritis. In:
Rose NR, Mackay IR (eds) The autoimmune diseases. Elsevier,
St. Louis, pp 417–436
19. Lovell DJ (2008) Juvenile idiopathic arthritis. In: Klippel JH,
Stone JH, Crofford LJ, White PH (eds) Primer on the rheumatic
diseases. Springer, New York, pp 142–153
20. Borchers AT, Selmi C, Cheema G, Keen CL, Shoenfeld Y,
Gershwin ME (2006) Juvenile idiopathic arthritis. Autoimmun
Rev 5:279–298. doi:10.1016/j.autrev.2005.09.011
21. Ravelli A, Martini A (2007) Juvenile idiopathic arthritis. Lancet
369:767–778. doi:10.1016/S0140-6736(07)60363-8
22. Gugo Rumštajn K (2007) Zaštitno istraživanje provedeno godine
2006. na arheološkom položaju Uzdolje-Grablje kod Knina.
Obavijesti Hrvatskog arheološkog društva 39:98–103
23. Buikstra J, Ubelaker D (1994) Standards for data collection
from human skeletal remains. Arkansas Archaeological Survey,
Fayetteville
24. Ubelaker DH (1978) Human skeletal remains. excavation, anal-
ysis, interpretation. Aldine Publishing Company, Chicago
25. Scheuer L, Black S (2000) Developmental juvenile osteology.
Academic Press, San Francisco
26. Brooks S, Suchey JM (1990) Skeletal age determination based
on the os pubis: a comparison of the Acsádi-Nemeskéri and
Suchey-Brooks methods. Hum Evol 5:227–238. doi:10.1007/
BF02437238
27. Lovejoy CO, Meindl RS, Pryzbeck TR, Mensforth RP (1985)
Chronological metamorphosis of the auricular surface of the
355
ilium: a new method for the determination of age at death. Am J
Phys Anthropol 68:15–28. doi:10.1002/ajpa.1330680103
28. Meindl RS, Lovejoy CO (1985) Ectocranial suture closure: a
revised method for the determination of skeletal age at death
based on the lateral–anterior sutures. Am J Phys Anthropol
68:57–66. doi:10.1002/ajpa.1330680106
29. Işcan MY, Loth SR, Wright RK (1984) Age estimation from the
rib by phase analysis: white males. J Forensic Sci 29:1094–1104
30. Işcan MY, Loth SR, Wright RK (1985) Age estimation from the
rib by phase analysis: white females. J Forensic Sci 30:853–863
31. Stojanowski CM, Schillaci MA (2006) Phenotypic approaches for
understanding patterns of intracemetery biological variation. Ybk
Phys Anthropol 131(S43):49–88. doi:10.1002/ajpa.20517
32. Tehlirina CV, Bathon JM (2008) Rheumatoid arthritis. Clinical
an laboratory manifestations. In: Klippel JH, Stone JH, Crofford
LJ, White PH (eds) Primer on the rheumatic diseases. Springer,
New York, pp 114–121
33. Waldron T, Rogers J, Watt I (1994) Rheumatoid arthritis in an
English Post-medieval skeleton. Int J Osteoarchaeol 4:165–167.
doi:10.1002/oa.1390040208
34. Rogers J, Watt I, Dieppe P (1984) Paleopatholgy of spinal oste-
ophytosis, vertebral ankylosis, ankylosing spondylitis, and ver-
tebral hyperostosis. Ann Rheum Dis 44:113–120. doi:10.1136/
ard.44.2.113
35. Blondiaux J, Cotten A, Fontaine C, Hänni C, Bera A, Flipo RM
(1997) Two Roman and Medieval cases of symmetrical erosive
polyarthropathy from Normandy: anatomico-pathological and
radiological evidence of rheumatoid arthritis. Int J Osteoarchaeol
7:451–466. doi:10.1002/(SICI)1099-1212(199709/10)7:5\451::
AID-OA334[3.0.CO;2-4
36. Rothschild BM, Hershkovitz I, Bedford L, Latimer B, Dutour O,
Rotschild C, Jellema LM (1997) Identification of childhood
arthritis in archaeological material: juvenile rheumatoid arthritis
versus juvenile spondyloarthropathy. Am J Phys Anthropol
102:249–264. doi:10.1002/(SICI)1096-8644(199702)102:2
\249::AID-AJPA7[3.0.CO;2-T
37. Inoue K, Takigawa W, Sato M, Kumgai M, Dodo Y, Katayama K
(2005) A possible case of spondyloarthropathy in a prehistoric
Japanese skeleton. Int J Osteoarchaeol 15:186–195. doi:10.1002/
oa.768
38. Arriaza BT (1993) Seronegative spondyloarthropathies and dif-
fuse idiopathic skeletal hyperostosis in ancient Northern Chile.
Am J Phys Anthropol 91:263–278. doi:10.1002/ajpa.1330910302
39. Zias J, Mitchell P (1996) Psoriatic arthritis in a fifth-century
Judean Desert monastery. Am J Phys Anthropol 101:491–502.
doi:10.1002/(SICI)1096-8644(199612)101:4\491::AID-AJPA4[
3.0.CO;2-Z
40. Rothschild BM, Arriaza B, Woods RJ, Dutour O (1999) Spond-
yloarthropathy identified as the etiology of Nubian erosive
arthritis. Am J Phys Anthropol 109:259–267. doi:10.1002/(SICI)
1096-8644(199906)109:2\259::AID-AJPA10[3.0.CO;2-3
41. Inoue K, Hukuda S, Nakai M, Katayama K, Huang J (1999)
Erosive peripheral polyarthritis in ancient Japanese skeletons: a
possible case of rheumatoid arthritis. Int J Osteoarchaeol 9:1–7.
doi:10.1002/(SICI)1099-1212(199901/02)9:1\1::AID-OA464[
3.0.CO;2-1
42. Mumford CJ, Wood NW, Kellar-Wood H, Thorpe JW, Miller
DH, Compston DA (1994) The British Isles survey of multiple
sclerosis in twins. Neurology 44:11–15
43. Tait KF, Marshall T, Berman J, Carr-Smith J, Rowe B, Todd JA,
Bain SC, Barnett AH, Gough SC (2004) Clustering of autoim-
mune disease in parents of siblings from the Type 1 diabetes
Warren repository. Diabet Med 21:358–362. doi:10.1111/j.1464-
5491.2004.01162.x
44. Becker KG, Simon RM, Bailey-Wilson JE, Freidlin B, Biddison
WE, McFarland HF, Trent JM (1998) Clustering of non-major
123
356
histocompatibility complex susceptibility candidate loci in
human autoimmune diseases. Proc Natl Acad Sci USA 95:9979–
9984. doi:10.1073/pnas.95.17.9979
45. Henderson RD, Bain CJ, Pender MP (2000) The occurrence
of autoimmune diseases in patients with multiple sclerosis
and their families. J Clin Neurosci 7:434–437. doi:10.1054/jocn.
2000.0693
46. Shamim EA, Miller FW (2000) Familial autoimmunity and the
idiopathic inflammatory myopathies. Curr Rheumatol Rep 2:201–
211. doi:10.1007/s11926-000-0080-0
123
Rheumatol Int (2010) 30:349–356
47. Prahalad S, Shear ES, Thompson SD, Giannini EH, Glass DN
(2002) Increased prevalence of familial autoimmunity in simplex
and multiplex families with juvenile rheumatoid arthritis.
Arthritis Rheum 46:1851–1856. doi:10.1002/art.10370
48. Russell RK, Nimmo ER, Satsangi J (2004) Molecular genetics of
Crohn’s disease. Curr Opin Genet Dev Curr Opin Genet Dev
14:264–270
49. Rajić Šikanjić P, Vlak D (2008) Elongated stlyoid process in late
medieval skeletons from Uzdolje-Grablje, Croatia. Int J Osteo-
archaeol. doi:10.1002/oa.1022