Immunosuppression therapy posttransplantation can be associated with a different clinical phenotype for diabetic charcot foot neuroarthropathy.
Article: Proinflammatory modulation of the surface and cytokine phenotype of monocytes in patients with acute Charcot foot.[show abstract] [hide abstract]
ABSTRACT: Despite increased information on the importance of an inappropriate inflammatory response in the acute Charcot process, there has been no previous attempt to define the specific pathways that mediate its pathogenesis. Here, the role played by monocytes was analyzed. The immune phenotype of peripheral monocytes was studied by fluorescence-activated cell sorter analysis comparing patients with acute Charcot (n = 10) in both the active and recovered phase, diabetic patients with neuropathy (with or without osteomyelitis), and normal control subjects. When compared with diabetic control subjects and healthy subjects, monocytes from acute Charcot patients showed a proinflammatory immune phenotype characterized by increased production of proinflammatory cytokines, reduced secretion of anti-inflammatory cytokines, increased expression of surface costimulatory molecules, and increased resistance to serum withdrawal-induced apoptosis. In addition, the pattern of circulating cytokines confirmed activation of proinflammatory cytokines. No modulation of the monocyte phenotype was documented in diabetic control subjects and healthy subjects, thus indicating that the proinflammatory alterations of monocytes are specific and causative of acute Charcot. Together, these data provide evidence for the role of proinflammatory changes in the immune phenotype of monocytes in the pathogenesis of acute Charcot. These alterations may explain the abnormally intense and prolonged inflammatory response that characterizes this disorder and may represent a potential therapeutic target for specific pharmacological interventions.Diabetes care 10/2009; 33(2):350-5. · 8.09 Impact Factor
Can Be Associated
With a Different
in diabetes have recently been described
(1), but the effects of immunosuppres-
sion have not been investigated. This
report describes a modified clinical phe-
notype for Charcot in three subjects on
immunosupression therapy for previous
transplantation—two live-related renal
and one simultaneous pancreas kidney
transplant. Charcot presented without
typical features such that the early acute
phase was difficult to define clinically. In
the two in whom immobilization was not
initially undertaken, deformity developed.
All had previous proliferative retinopathy,
neuropathy, and nephropathy resulting
in end-stage renal failure.
A 42-year-old woman with type 1
diabetes, duration 34 years, presented
with 3 months of intermittent right foot
and ankle swelling. Immunosuppression
therapy was tacrolimus, mycophenylate,
and magnetic resonance imaging (MRI)
demonstrated midfoot bone marrow
edema. On repeated clinical examination
over 6 months, there was no swelling,
roinflammatory changes in the im-
mune phenotype of circulating
blood monocytes in acute Charcot
right foot, and plain X-rays remained
normal. Immobilization was not under-
taken. A further 6 months later, she still
reported intermittent symptoms, but in-
creased temperature was detected, and
MRI demonstrated more bone marrow
edema and malalignment in the midfoot.
A 53-year-old man with known type
2 diabetes for 8 years presented with
8 months of intermittent left foot pain and
swelling after walking for an hour. Immu-
nosuppression therapy was tacrolimus.
Clinically, there was no increased temper-
ature or foot swelling, plain X-ray dem-
onstrated normal alignment, and MRI
demonstrated midfoot bone marrow
edema. Immobilization was not applied.
On repeated clinical examination over
5 months, there were no clinical signs,
and plain X-rays were unchanged. At 6
months, the left foot was slightly warmer
with mild swelling over the dorsum. An
bone marrow edema and collapse of the
intermediate and medial cuneiform bones.
A 48-year-old woman with type 1
diabetes, duration 41 years, presented
with 3 days of right foot discomfort and
swelling. Immunosuppression therapy
was tacrolimus, mycophenylate, and
prednisolone. On examination there
were no clinical signs. Plain X-ray was
unremarkable, and MRI demonstrated
mild midfoot bone marrow edema. She
was reviewed five times over the ensuing
2 months without signs to suggest active
Charcot. Immobilization was not applied
until further MRI of both feet demon-
strated more extensive bone marrow
edema in the right than the left midfoot.
In order to avoid deformity, immobi-
lization must be applied early in acute
Charcot while plain X-ray is still normal.
MRI is often used at this stage to confirm
suspected clinical diagnoses. However,
MRI demonstrated bone marrow edema
in midfoot and hindfoot areas in 30% of
subjects with diabetic neuropathic ulcer-
ation, did not predict future Charcot or
osteomyelitis, and was more common in
end-stage renal disease (2). Although all
three had midfoot bone marrow edema
on MRI, clinical signs were lacking so
that immobilization was not initially ap-
plied. Clinicians should be aware that
Charcot can present posttransplantation
without the cardinal clinical signs but
can still lead to deformity.
JONATHAN VALABHJI, MD, FRCP
St Mary’s Hospital, Imperial College Healthcare
NHS Trust, London, U.K.
© 2011 by the American Diabetes Association.
Readers may use this article as long as the work is
properly cited, the use is educational and not for
profit, and the work is not altered. See http://
interest relevant to this article were reported.
J.V. researched data, wrote the manuscript,
and reviewed and edited the manuscript.
c c c c c c c c c c c c c c c c c c c c c c c c
1. Uccioli L, Sinistro A, Almerighi C, et al.
and cytokine phenotype of monocytes in
patients with acute Charcot foot. Diabetes
2. Thorning C, Gedroyc WM, Tyler PA, Dick
bone marrow edema identified by mag-
netic resonance imaging in feet of subjects
with diabetes and neuropathic ulceration
is common but of unknown clinical signif-
icance. Diabetes Care 2010;33:1602–
care.diabetesjournals.orgDIABETES CARE, VOLUME 34, AUGUST 2011
O N L I N EL E T T E R S