Download Ankylosing spondylitis

Ankylosing Spondylitis
Case
 52 yo wm c 25 yr hx of AS. Recurrent iritis
and persistent bilateral knee synovitis
treated with indomethacin and local steroid
injections.
 In 2006 increasing knee pain with failure of
cortisone injections led to consideration of
TKR. Low grade fever by hx, weight loss,
anemia, malaise and an increase of creatinine
to 2.0 led to dc of indocin.
 On Clinoril or Diclofenac creatinine 1.8.
Chronic kidney stones. Sed rate 120; CRP 18.
SPEP IgM lambda monoclonal spike
0.2 gm/dl ;Ig G 2500 ; IgA and IgM normal.
Bone marrow normal. Upper and lower
endoscopies negative.
 Lab hgb 9.4 , wbc 9900, plt 792,000 sed 112;
crp 18.1; urinalysis hematuria, no protein.
Renal consult saw and found an negative ANA,
but a positive ANCA with PR3 of 97 (20).
Nephrologist thought he saw one red cell cast.
 Lung and ENT CT’s and eval neg for
Wegener’s. Kidney biopsy showed no
glomerulonephritis, very minimal interstitial
inflammation.
Attempted right TKR, but surgeon closed the
procedure thinking tissues looked infected.
Extensive evaluation of the knee tissues and
for SBE for infection were negative.
 Temporal artery biopsy was negative. PPD neg
pt was started on Enbrel and left off an NSAID.
Three weeks later ESR was 50; crp 3, pt had
gained 5 lbs had continued neck pain. Scheduled
for TKR again.
1. False positive PR3
2. Perioperative use of antiinflammatories
and immunosuppressants.
3. Effects of above meds on bone fusion
surgeries.
C-ANCA Pattern
 Demonstration of cytoplasmic antineutrophil
cytoplasmic antibodies (C-ANCA) by indirect
immunofluorescence with normal neutrophils. There is
heavy staining in the cytoplasm while the
multilobulated nuclei (clear zones) are nonreactive.
These antibodies are usually directed against
proteinase 3 and most patients have Wegener's
granulomatosis. Courtesy of Helmut Rennke, MD. , 2007 UpToDate®
P-ANCA Pattern
 Demonstration of perinuclear antineutrophil cytoplasmic
antibodies (P-ANCA) by indirect immunofluorescence with
normal neutrophils. Staining is limited to the perinuclear
region and the cytoplasm is nonreactive. Among patients
with vasculitis, the antibodies are usually directed against
myeloperoxidase. However, a P-ANCA pattern can also be
seen with autoantibodies against a number of other
antigens including lactoferrin and elastase. Non-MPO
P-ANCA can be seen in a variety of nonvasculitic
disorders. Courtesy of Helmut Rennke, MD. , 2007 UpToDate®
PR3
 Subacute bacterial endocarditis with
positive cytoplasmic antineutrophil
cytoplasmic antibodies and antiproteinase 3 antibodies.
 AU
 Choi HK; Lamprecht P; Niles JL; Gross
WL; Merkel PA
 SO
 Arthritis Rheum 2000 Jan;43(1):226-31.
 OBJECTIVE: To report a potentially
important limitation of antineutrophil
cytoplasmic antibody (ANCA) testing:
positive results in patients with
subacute bacterial endocarditis (SBE).
 METHODS: We describe 3 patients with
SBE who presented with features
mimicking ANCA-associated vasculitis
(AAV) and positive findings on tests for
cytoplasmic ANCA (cANCA) by indirect
immunofluorescence and for antiproteinase 3 (anti-PR3)antibodies by
antigen-specific enzyme-linked
immunosorbent assay (ELISA).
 RESULTS: We are now aware of a total of 7 cases
of SBE with positive cANCA and anti-PR3
antibodies. We are not aware of any cases of SBE
associated with antimyeloperoxidase/perinuclear
ANCA.
 Clinical manifestations mimicking AAV included
glomerulonephritis, purpura, epistaxis, or sinus
symptoms in 6 of the patients.
 Streptococcal species were identified in 5 patients,
and cardiac valvular abnormalities were
demonstrated in 6.
 All patients except 1, who died of a complication of
SBE, recovered with antibiotic therapy.
 CONCLUSION: Findings of tests for
anti-PR3/cANCA antibodies may be
positive in patients with SBE.
 When encountering ANCA positivity in
patients suspected of having systemic
vasculitis, physicians should take
appropriate steps to rule out infectious
diseases, including SBE, before
committing the patient to long-term,
aggressive immunosuppressive
therapy.
PR3
 Antineutrophil cytoplasmic antibodies
reacting with human neutrophil elastase
as a diagnostic marker for cocaineinduced midline destructive lesions but
not autoimmune vasculitis.
 AU
 Wiesner O; Russell KA; Lee AS; Jenne
DE; Trimarchi M; Gregorini G; Specks U
 Arthritis Rheum 2004 Sep;50(9):295465.
 OBJECTIVE: Human neutrophil
elastase (HNE) and proteinase 3
(PR3) are structurally and
functionally related. PR3 is the
prominent target antigen for
antineutrophil cytoplasmic
antibodies (ANCAs) in Wegener's
granulomatosis (WG). Reported
frequencies of HNE ANCAs in WG
and other autoimmune diseases
range from 0% to 20%.
 HNE ANCA reactivity in 25
patients with CIMDL was
characterized and compared
with that in a control cohort of
604 consecutive patients (64
with WG, 14 with microscopic
polyangiitis [MPA], and 526
others) and 45 healthy
volunteers
 Among patients with CIMDL, HNE
ANCAs were detectable by 1 assay
in 84%, by 2 assays in 68%, and
by all 3 assays in 36%. Fifty-seven
percent of HNE ANCA-positive
CIMDL sera were also PR3 ANCApositive by at least 1 assay.
 In contrast, only 8 (1.3%) of 604
control sera reacted with HNE in at
least 1 assay, 3 (0.5%) reacted in 2
assays, and only 1 serum sample
(0.16%) reacted in all 3 assays.
 Sera obtained from patients with WG
or MPA were universally HNE ANCAnegative, as were sera obtained from
healthy controls. CONCLUSION:
Optimal sensitivity for HNE ANCA
requires multimodality testing.
PR3
 Clinical interpretation of antineutrophil
cytoplasmic antibodies: parvovirus B19
infection as a pitfall.
 AU
 Hermann J; Demel U; Stunzner D;
Daghofer E; Tilz G; Graninger W
 SO
 Ann Rheum Dis 2005 Apr;64(4):641-3.
Epub 2004 Oct 14.
 OBJECTIVE: To investigate whether
positive ANCA test results may be a
common feature of acute parvovirus
B19 infection.
 METHODS: Sera were analysed from
1242 patients from a rheumatology
outpatient clinic for reactivity with
parvovirus B19 and EBV antibodies.
They were tested for the presence of
PR3-ANCA and MPO-ANCA
 ANCA were found in 10% (5/50) of
the sera positive for IgM antibodies
to parvovirus and in 3/51 sera
containing IgM antibodies to EBV.
 Three of six patients with arthritis
and concomitant parvovirus infection
were found positive for PR3-ANCA
and two were found positive for
MPO-ANCA. All six patients tested
negative for ANCA after six months
of follow up.
 CONCLUSIONS: PR3-ANCA and MPO-ANCA
may occur transiently in patients with
acute B19 infection or infectious
mononucleosis, highlighting the
importance of repeated antibody tests in
oligosymptomatic clinical conditions in
which systemic autoimmune disease is
suspected.
 Department of Medicine, Johns Hopkins
University Vasculitis Center, 1830 E.
Monument Street, Suite 7500, Baltimore,
MD 21205, USA.
PR3
 Prevalence of antineutrophil cytoplasmic
antibodies in patients with various
pulmonary diseases or multiorgan
dysfunction.
 The Henry Dunant Hospital, Athens, Greece.
 OBJECTIVE: To determine the prevalence of
antineutrophil cytoplasmic antibodies (ANCA)
in patients with diseases that may mimic
systemic vasculitides, such as severe
multiorgan dysfunction (MOD) and
parenchymal pulmonary disorders.
 METHODS: We conducted a prospective study of
patients with MOD admitted to the medical intensive
care unit and patients with various lung diseases
seen at the outpatient pulmonary clinic of a tertiary
care hospital. Patients with a documented diagnosis
of Wegener's granulomatosis (WG) served as positive
controls.
 RESULTS: Ninety-nine patients with MOD, 29
outpatients with various lung disorders, and 18
patients with WG were included in the study. ANCA
were detected by IIF alone in 16% (15/96) of
patients with nonvasculitic MOD and 17% (5/29) of
outpatients with various pulmonary disorders. The
majority of the positive IIF specimens from each
group displayed an atypical IIF pattern (73% and
80%, respectively). Only 1 specimen from patients
with nonvasculitic disorders was positive for anti-MPO
 CONCLUSION: Detection of ANCA by the
combination of IIF and antigen-specific assays
for proteinase 3 and myeloperoxidase in
diseases that mimic systemic vasculitides is
highly specific for WG, microscopic
polyangiitis, and Churg-Strauss syndrome.
Periop Management-UpToDate®
 Only limited data have been published to guide
perioperative management. A randomized trial in
orthopedic patients found no increased rate of
infection in patients who continued weekly
methotrexate compared with those who discontinued
methotrexate two weeks before surgery [89]. There
are no available human data regarding other
DMARDs in the perioperative period. Many DMARDs
are renally excreted, and thus impaired kidney
function can lead to buildup of DMARDs or their
metabolites; this may lead to bone marrow
suppression.
 We recommend that in patients with normal
renal function, methotrexate can be continued
in the perioperative period. In patients with
renal insufficiency, methotrexate should be
held for two weeks. Sulfasalazine and
azathioprine should be held for a week prior to
surgery and resumed after surgery.
Leflunamide should be held for two weeks
before surgery and resumed after surgery.
Hydroxychloroquine has few potential side
effects and can be continued without
interruption, if the patient can take oral
medications. The biologic response modifiers
should be stopped one to two weeks prior to
surgery and resumed one to two weeks after
surgery.
 UpToDate®
 High dose nonsteroidal anti-inflammatory
drugs compromise spinal fusion.
 Acute Pain Service, Baystate Medical Center
and Tufts University School of Medicine, 759
Chestnut Street, Springfield, Massachusetts
01199, USA. [email protected]
 The goal of this retrospective study was to
assess the incidence of non-union following
the perioperative administration of ketorolac,
celecoxib, or rofecoxib. METHODS: We
retrospectively analyzed the data of 434
patients receiving perioperative ketorolac
[20-240 mg day(-1)], celecoxib [200-600 mg
day(-1)], rofecoxib [50 mg day(-1)], or no
NSAIDs in the five days following spinal fusion
surgery.
 RESULTS: There were no significant
differences in the incidence of non-union
among the groups that received no NSAIDs
(11/130; 8.5%), celecoxib 5/60; 8.3%), or
rofecoxib (9/124; 7.3%).
 In contrast, 23/120 of patients (19.2%) that
received ketorolac had a higher incidence
(P < 0.001) of non-union compared to nonNSAID users. However, only 3/50 patients
(6%) receiving low-dose ketorolac [< or =
110 mg day(-1)] resulted in non-union which
was not significantly different from non-NSAID
users.
 Patients administered higher doses of
ketorolac [120-240 mg day(-1)] resulted in a
higher incidence (P < 0.0001) of non-union
(20/70; 29%) compared to non-NSAID users.
 CONCLUSIONS: This study revealed that the
short-term perioperative administration of
celecoxib, rofecoxib, or low-dose ketorolac
[< or = 110 mg day(-1)] had no significant
deleterious effect on non-union.
 In contrast, higher doses of ketorolac
[120-240 mg day (-1)], history of smoking,
and two level vertebral fusions resulted in a
significant increase in the incidence of nonunion following spinal fusion surgery.
 The effect of cyclooxygenase-2 inhibition
on analgesia and spinal fusion.
 Baystate Medical Center and Tufts University
School of Medicine, 759 Chestnut Street,
Springfield, MA 01199, USA.
[email protected]
 METHODS: Eighty patients who were
scheduled to undergo spinal fusion received
either celecoxib or placebo one hour before
the induction of anesthesia and every twelve
hours after surgery for the first five
postoperative days.
 RESULTS: There were no differences in
demographic data or blood loss between the two
groups. Pain scores were lower in the celecoxib
group at one, four, eight, sixteen, and twenty
hours postoperatively. There were no differences
between the two groups with regard to the pain
scores at twelve and twenty-four hours
postoperatively.
 CONCLUSIONS: The perioperative administration
of celecoxib resulted in a significant reduction in
postoperative pain and opioid use following spinal
fusion surgery. In addition, the short-term
administration of this COX-2-specific non-steroidal
anti-inflammatory drug had no apparent effect on
the rate of nonunion at the time of the one-year
follow-up.
 Time-dependent inhibitory effects of
indomethacin on spinal fusion.
 Department of Orthopaedic Surgery, BarnesJewish Hospital at Washington University,
St. Louis, Missouri 63110, USA.
[email protected]
 METHODS: Seventy New Zealand White
rabbits underwent posterior intertransverse
process arthrodesis at L5-L6 with use of iliac
autograft. Rabbits randomly received
indomethacin (10 mg/kg orally) starting at
two weeks after surgery (twenty-four
animals), indomethacin starting at four
weeks postoperatively (twenty-three), or
saline starting at two weeks postoperatively
(twenty-three) (the control group).
 RESULTS: Sixty-five percent (fifteen) of the twentythree spines in the control group and 48% (eleven) of
the twenty-three in the four-week group fused.
However, only 21% (five) of the twenty-four spines in
the two-week group fused. The difference between the
two-week and control groups was significant
(p <
0.002), as was the difference between the two and
four-week groups (p = 0.05).
 CONCLUSIONS: The earlier that indomethacin was
resumed postoperatively, the greater was its negative
effect on fusion. Indomethacin appears to play a
significant inhibitory role in the early phase of healing.
Initiating indomethacin treatment in the latter phase of
healing does not appear to significantly affect fusion
rates, although there was a nonsignificant trend
toward inhibition.
 Infectious and healing complications after elective
orthopaedic foot and ankle surgery during tumor
necrosis factor-alpha inhibition therapy.
 Department of Orthopaedic Surgery, Marshfield Clinic, WI
54449, USA. [email protected]
 METHODS: Patients with rheumatoid arthritis undergoing
elective foot and ankle surgery over a 12-month period
were prospectively followed for the development of
complications in the postoperative period. All patients
continued their antirheumatic medication schedule
unaltered in the perioperative period
 Patients were then stratified into two groups based on
the use of immunomodulation via TNF-alpha inhibition
(group 1) versus patients who did not receive TNF-alpha
inhibition therapy (group 2). Groups 1 and 2 were
followed and compared for the development of
infectious/healing complications.
 RESULTS: Thirty-one patients were enrolled in the
study. Group 1 (n = 16) and group 2 (n = 15)
patients were comparable for sex distribution,
number of orthopaedic procedures performed, and
use of steroids, methotrexate, leflunamide, and
nonsteroidal anti-inflammatory drugs. Group 1
contained six times the number of smokers in
group 2. At mean follow-up of 10.6 months
(group 1) and 9.7 months (group 2), healing or
infectious complications were similar in both
groups. However, when total complications (healing
+ infection) were analyzed, group 1 (TNF-alpha
inhibition, "higher risk") patients demonstrated a
lower complication rate (p = .033).
 CONCLUSIONS: The data suggest that in patients
with rheumatoid arthritis undergoing elective foot
and ankle surgery, the use of TNF-alpha inhibition
agents may be safely undertaken in the
perioperative period without increasing the risk of
healing or infectious complications.

Methotrexate and early postoperative complications
in patients with rheumatoid arthritis undergoing
elective orthopaedic surgery.

Wrightington Hospital NHS Trust, Hall Lane, Appley Bridge,
Wigan WN6 9EP, UK.

OBJECTIVES: To determine whether continued methotrexate
treatment increases the risk of postoperative infections or of
surgical complications in patients with rheumatoid arthritis
(RA) within one year of elective orthopaedic surgery.
DESIGN: A prospective randomized study of postoperative
infection or surgical complications occurring within one year
of surgery in patients with RA who underwent elective
orthopaedic surgery.

SUBJECTS: 388 patients with RA who were to undergo
elective orthopaedic surgery. Patients who were receiving
methotrexate were randomly allocated to groups who either
continued methotrexate (group A) or who discontinued
methotrexate from two weeks before surgery until two
weeks after surgery (group B). Their complication rates were
compared with complications occurring in 228 patients with
RA (group C) who were not receiving methotrexate and who
also underwent elective orthopaedic surgery.
 RESULTS: Signs of infection or surgical complications
occurred in two of 88 procedures in group A (2%), 11 of
72 procedures in group B (15%), and 24 of 228
(10.5%) procedures in group C. The surgical
complication or infection frequency in group A was less
than that in either group B (p<0.003) or group C
(p=0.026).
 At six weeks after surgery there were no flares in group
A, six flares in group B (8%), and six flares in group C
(2.6%). Logistic regression analysis of the overall
surgical complication rate in all the patients with RA
studied showed that methotrexate, whether continued or
discontinued before surgery, did not increase the early
complication rate in the patients with RA who underwent
elective orthopaedic surgery.
 CONCLUSION: Continuation of methotrexate treatment
does not increase the risk of either infections or of
surgical complications occurring in patients with RA
within one year of elective orthopaedic surgery. Thus
methotrexate treatment should not be stopped in
patients whose disease is controlled by the drug before
elective orthopaedic surgery.