Available from: Itzhak Rosner, Jan 29, 2014
• DeceMber
A 25 year old woman with previously diag-
nosed bromyalgia treated with amytripti-
lin at a dose of 35 mg/day was referred to a
rheumatologist for further treatment. She
complained of constant widespread pain
and fatigue, which reportedly limited her
ability to participate in most social activi-
ties. Her maximal pain was located over the
lumbar spine, pelvis and neck. It was trig-
gered by rest, worsened at night, and was
accompanied by prolonged morning sti-
ness. Her family history was relevant for a
brother with AS. Her physical examination
was signicant for a tendency to kyphotic
posture, which she mentioned was most
prominent in the early and mid-morning
hours. While all points classically related to
bromyalgia were tender on pressure, the
patient also had diminished Schober test
of 13 cm (normal 14.5), increased nger-
to-oor distance of 34 cm (normal < 5),
reduced chest expansion of 2.5 cm (normal
4.5) and occiput-to-wall distance of 3 cm
(normal 0). AxSpA was suspected, based on
the family history of AS, persistent inam-
matory-type back pain, and pronounced
limitation of spinal mobility.
Extended-release etodolac at a dose of
600 mg daily was added to amitryptilin,
and relevant blood tests and imaging stud-
ies were ordered. At follow-up, the patient
reported good but short-term (6–8 hours)
pain relief with etodolac. Her erythrocyte
sedimentation rate was 90 mm/hour, serum
level of C-reactive protein was three times
the upper limit of normal, HLA-B27 anti-
gen was negative, and X-ray lms of the
spine and sacroiliac joint were normal.
MRI of the SIJ
, performed later, was also
SIJ = sacroiliac joint
he new entity of non-radiographic axial
spondyloarthritis and classication
criteria for axial spondyloarthritis were
recently born as a result of growing dis-
sonance between the perceived need for an
earlier diagnosis of patients with ankylos-
ing spondylitis and lack of accepted tools
to make this diagnosis in the early stages of
this disease [1]. e presence of character-
istic changes on magnetic resonance imag-
ing of sacroiliac joints or positive test for
human leukocyte antigen-B27 in patients
with high or even moderate clinical sus-
picion for spondyloarthritis now enables
classication of these patients as having
in the absence of radiographic
sacroiliitis on X-ray lms. e sensitivity
of these new criteria, based on the analysis
of data of 649 patients, was established as
82.9%, still leaving approximately one of
every six patients with AxSpA out of the
disease frame. us, blind adherence to
these classication criteria for diagnostic
purposes may lead to under-diagnosis of
a signicant proportion of these patients
and delay appropriate treatment. We sug-
gest that, in the absence of validated diag-
nostic criteria, clinical diagnosis should
still be made and appropriate treatment
administered in patients with a high clini-
cal suspicion for nrAxSpA
, even if they do
not satisfy current classication criteria.
AxSpA = axial spondyloarthritis
nrAxSpA = non-radiographic axial spondylo-
considered normal. Etoricoxib and lornoxi-
cam were not more eective than etodolac.
It was therefore decided to start treatment
with a biologic agent. While iniximab
signicantly improved her ESR
and CRP
levels, it was only partially eective in
ameliorating the clinical symptoms, and
she still had to use etodolac or etorixocib
almost every morning. Golimumab, on the
other hand, led to the complete disappear-
ance of both back pain and morning sti-
ness but was eventually stopped because of
adverse eects. e temporary cessation of
anti-tumor necrosis factor treatment, which
followed, resulted in signicant increase in
pain intensity, elevation of ESR/CRP levels
and a decrease in her functional capacity.
Currently, the patient is under treat-
ment with adalimumab, etodolac and
amytriptilin and has returned to full social
and physical activity. X-ray lms of the SIJ
and spine, obtained aer 5 years of follow-
up, are still normal.
e combination of a strong family back-
ground of AS, inammatory back pain,
characteristically decreased spinal mobil-
ity, elevated levels of laboratory param-
eters of inammation, and good (even if
only short-term) response to non-steroi-
dal anti-inammatory drugs, as observed
in the patient described here, raised
suspicion for the presence of AxSpA.
e nding of obvious sacroiliitis and/or
HLA-B27, as required by the classica-
tion criteria, would make the diagnosis
straightforward. e absence of HLA-B27
antigen, however, and negative sacroiliitis
imaging including MRI, complicated the
ESR = erythrocyte sedimentation rate
CRP = C-reactive protein
axial spondyloarthritis (AxSpA),
sacroiliitis, magnetic resonance
2013; 15: 780–781
Indemonstrable Axial Spondyloarthritis: Does It Exist?
Gleb Slobodin MD
and Itzhak Rosner MD
Department of Internal Medicine A and
Rheumatology Unit, Bnai Zion Medical Center, affiliated with Rappaport Faculty of Medicine, Technion-Israel Institute of Technology,
Haifa, Israel
AS = ankylosing spondylitis
Page 1
• DeceMber
case. e lack of evidence for another
disorder to explain the spectrum of the
above features was an important factor in
the decision making. Fibromyalgia, which
does not induce ESR/CRP elevation, does
not decrease objective spinal mobility, and
is not typically dramatically improved by
anti-inammatory treatment, could only
be regarded as a contributory or second-
ary phenomenon in this patient [2].
MRI of the SIJ, showing typical bone
marrow edema subjacent to the joints, is
considered the modern imaging hallmark
of AxSpA and is accepted by many as nec-
essary for the diagnosis of nrAxSpA in
practice. Indeed, able to detect inamma-
tory changes in both so tissues and bone,
MRI allows visualization of sacroiliitis in
patients in whom conventional radiogra-
phy does not show any changes and pro-
vides objective evidence of disease activity.
e sensitivity of MRI of the SIJ for the
diagnosis of AxSpA has been calculated
as only 66%, according to accepted clas-
sication criteria. However, more recently
reported data suggest that the ability of
MRI to reveal existing sacroiliitis may be
even lower than previously thought. In
one study, for example, MRI of SIJ was
read as positive in only 40% of cases with
histologically proven inammation [3]. In
addition, the MRI features of sacroiliitis
can be volatile, turning from positive to
negative and vice versa, as shown by de
Hooge et al. [4] in 9% of patients with
nrAxSpA when repeated aer 3 months.
HLA-B27 is a major histocompat-
ibility class I gene, tightly related to AS
and present in about 90% of American
AS patients of Caucasian descent. e
contribution of HLA-B27 to the genetic
susceptibility to AS stands, however, at
only 25–40%, which suggests that other
genes play a role in disease susceptibility.
Of signicance, the prevalence of HLA-
B27 in cohorts of patients diagnosed with
nrAxSpA may be signicantly lower, as
compared to AS patients [5]. In addition,
the real prevalence of HLA-B27 in the
Israeli population with its complex ethnic
background, and in Israeli patients with
AS or nrAxSpA, has not been fully and
systematically studied, further complicat-
ing the interpretation of HLA-B27 testing
in Israelis.
us, conrmation of the diagnosis in
a patient with high suspicion for nrAxSpA
may be dicult and unrewarding even
aer a long period of follow-up, consider-
ing that the natural history of nrAxSpA is
also not known; i.e., it may not inevitably
evolve into fully edged advanced AS.
In summary, reaching a diagnosis in
the absence of validated diagnostic criteria
is frequently dicult and requires an indi-
vidual, thoroughly weighted, approach to
each patient. It may be particularly com-
plicated if the entity is not yet well under-
stood, as in the case of nrAxSpA.
Corresponding author:
Dr. G. Slobodin
Dept. of Internal Medicine A, Bnai Zion Medical
Center, P.O. Box 4940, Haifa 31048, Israel
Fax: (972-4) 835-9790
email: gslobodin@yahoo.com
1. Slobodin G, Rosner I, Rimar D, et al. Ankylosing
spondylitis: eld in progress. IMAJ 2012; 14: 763-7.
2. Slobodin G, Reyhan I, Avshovich N, et al. Recently
diagnosed axial spondyloarthritis: gender dier-
ences and factors related to delay in diagnosis. Clin
Rheumatol 2011; 30 (8): 1075-80.
3. Maksymowych W. Challenges in imaging – clinical
correlations. Materials of 8th International Congress
on Spondyloarthritis. Clin Exp Rheumatol 2012;
30: 600.
4. De Hooge M, van den Berg R, Reijnierse M, et al.
Localization of bone marrow edema in sacroiliac
joints in spondyloarthritis patients: does the site of
lesions change over a 3-month period. Materials of
8th International Congress on Spondyloarthritis.
Clin Exp Rheumatol 2012; 30: 627.
5. Rudwaleit M. Early cohorts in spondyloarthritis.
Materials of 8th International Congress on
Spondyloarthritis. Clin Exp Rheumatol 2012;
30: 601-2.
Chronic infections are difficult to treat with antibiotics but
are caused primarily by drug-sensitive pathogens. Dormant
persister cells that are tolerant to killing by antibiotics
are responsible for this apparent paradox. Persisters are
phenotypic variants of normal cells and pathways leading to
dormancy are redundant, making it challenging to develop
anti-persister compounds. Biofilms shield persisters from
the immune system, suggesting that an antibiotic for
treating a chronic infection should be able to eradicate the
infection on its own. A compound capable of corrupting
a target in dormant cells will probably kill persisters. The
acyldepsipeptide antibiotic (ADEP4) has been shown to
activate the ClpP protease, resulting in death of growing cells.
Conlon et al. show that ADEP4-activated ClpP becomes a
fairly non-specific protease and kills persisters by degrading
over 400 proteins, forcing cells to self-digest. Null mutants of
arise with high probability, but combining ADEP4 with
rifampicin produced complete eradication of
biofilms in vitro and in a mouse model of a chronic
infection. These findings indicate a general principle for
killing dormant cells – activation and corruption of a target,
rather than conventional inhibition. Eradication of a biofilm in
an animal model by activating a protease suggests a realistic
path towards developing therapies to treat chronic infections.
2013; 503: 365
Eitan Israeli
Activated ClpP kills persisters and eradicates a chronic biofilm infection
“You can out-distance that which is running after you, but not what is running inside you”
Rwandan proverb
Page 2
  • [Show abstract] [Hide abstract] ABSTRACT: To evaluate the diagnostic value of spectral computed tomography (CT) of sacroiliac joints for axial spondyloarthritis (SpA). We retrospectively analyzed the records of 125 patients with low back pain (LBP) suspected of having SpA. Each patient underwent sacroiliac joint spectral CT examination. Water- and calcium-based material decomposition images were reconstructed. After 3-6 months of follow-up, 76 were diagnosed with SpA, and the remaining 49 patients were diagnosed with nonspecific LBP (nLBP). The slope of sacroiliac bone marrow HU (Hounsfield unit) curve (λHU), CT value, and bone marrow to normal muscle ratios of water and calcium concentrations in the ilium and sacrum were calculated and compared between nLBP and SpA patients. The iliac λHU was 8.26 ± 3.91 for nLBP and 9.81 ± 4.92 for SpA. The mean iliac ratios of water and calcium concentrations were 1.04 ± 0.03 and 21.67 ± 4.40, respectively, for nLBP, and 1.07 ± 0.04 and 111.5 ± 358.98, respectively, for SpA. The mean iliac CT values were 311.12 ± 86.52 HU for nLBP and 423.97 ± 127.51 HU for SpA. There were statistically significant differences in iliac ratios of water and calcium concentrations, CT value, and λHU between nLBP and SpA patients (p < 0.05). The sensitivity of iliac λHU was the highest. The diagnostic odds ratio of ratio of iliac calcium concentration was the highest, and its negative likelihood ratio was the lowest. Spectral CT not only shows bone erosion and sclerosis, but also shows and quantitatively measures bone marrow edema in the sacroiliac joints of SpA patients. Copyright © 2015. Published by Elsevier B.V.
    No preview · Article · Sep 2015 · Journal of the Formosan Medical Association