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Polymyalgia Rheumatica
<Case
Report>
A 72-year-old Taiwanese woman presented with a four week
history of gradual onset of muscle pain, aching and morning
stiffness in both shoulders and thighs. There was no fever,
headache, visual disturbance or jaw claudication. Her history
included chronic hypertension and a subtotal thyroidectomy in
1975.
Examination revealed tenderness of both shoulders and
thighs; limited range of movement of both shoulders was also
noted. There was no abnormality of temporal arteries or joint
swelling. The other examinations were unremarkable.
Laboratory studies revealed a normocytic, normochromic
anemia with hemoglobin (Hb) of 9.0 g/dL, low serum iron of 10
mcg/dl (66-100 mcg/dL), increased ferritin of 472 mcg/dL
(10-151 mcg/dL), elevated erythropoietin (EPO) of 28.6 mU/mL
(8.2-21.4 mU/mL), an elevated ESR of >120 mm/hr, increased
CRP of 29.3 mg/dL (<0.8mg/dL) and elevated IL-6 level of
45.6 pg/mL (<5.4 pg/mL). Hyperglycemia with fasting plasma
glucose of 203 mg/dL with a normal HbA1C of 6.7 % and an
relatively increased fasting insulin level of 9.9 μU/mL
(5-20μU/mL) were also noted. Other immunology profiles
including rheumatoid factor and antinuclear antibody were
negative.
Gadolinium enhanced MRI of the
shoulders revealed synovial enhancement and small amount of
effusion in the subacromial and subdeltoid bursae, which were
compatible with bursitis (Figure
1).
A diagnosis of polymyalgia rheumatica (Table1)was made and
treatment with prednisolone 20 mg daily was initiated. She had
a prompt clinical response to prednisolone with resolution of
morning stiffness and other musculoskeletal symptoms after 3
days of corticosteroid use. Over the next 3 months, follow-up
inflammatory parameters (including ESR, CRP and IL-6) showed
gradual normalization, while the anemia and hyperglycemia also
resolved without transfusion or use of hypoglycemic agent
(Table 2)
<解說>
Polymyalgia rheumatica (PMR) is a clinical inflammatory
syndrome of unknown etiology. It is characterized by pain,
aching and stiffness symmetrically involving the neck,
shoulder and pelvic girdles. PMR often occurs in the aging
population and is closely related to giant-cell arteritis. It
is estimated that 40 to 60 percent of patients with giant-cell
arteritis have symptoms of PMR, and conversely, up to 16 to 21
percent of patients with PMR are shown to have evidence of
giant-cell arteritis1,2. Ultrasonography and magnetic
resonance imaging (MRI) often identify bursitis and synovitis
in patients with PMR3, while serologic tests often
reveal markedly elevated erythrocyte sedimentation rate (ESR),
interleukin-6 and C-reactive protein level
(CRP)4,5
. Anemia,
thrombocytosis and leukocytosis are not uncommon, which are
often thought to be a result of the acute phase response to
systemic inflammation. Corticosteroid treatment usually
rapidly ameliorates the musculoskeletal symptoms of PMR;
however, little has been known about its effectiveness on
anemia and other metabolic derangement in patients with PMR.
We describe a patient with PMR accompanied by marked anemia
and hyperglycemia who was found to have a blunted response to
erythropoietin (EPO) and an insulin resistance state, which
resolved soon after the use of corticosteroid. The finding
suggests that corticosteroid may reverse the suppressed EPO
response and lower the insulin resistance via its
anti-inflammatory effect.
<討論>
Polymyalgia rheumatica, though had
long been thought to be a common illness with a prevalence of
1 case for every 133 people older than 50 years1,
is still obscure in its etiology and pathogenesis. Two current
diagnostic criteria sets postulated by Chuang et al
6 and Healey 7 are shown in table 1,
which mainly focus on its clinical presentation, treatment
response to corticosteroid, parameters of inflammation and
exclusion of other diagnoses. Despite the lack of responsible
autoantibodies, it had been reported that anti-lamin B2
antibodies are specific for the C-terminus of lamin in PMR
patients 8, which suggests PMR can be a consequence
of autoimmunity. Vasculitis is also widely postulated to be
responsible for PMR because of the recognized association
between giant cell arteritis and PMR. Moreover, the synovial
membranes in PMR patients are infiltrated by CD4+ lymphocytes
and macrophages, which is the similar condition seen in giant
cell arteritis 9,10.
Normocytic, normochromic anemia is one
of the common features in patients with polymyalgia
rheumatica. It is widely believed that such anemia is related
to decreased hematopoiesis as a result of acute phase response
to systemic inflammation of PMR. We examined serial serum EPO
level in our patient (table 2), which were initially high
before corticosteroid treatment, falling to normal levels
gradually after conduction of steroid therapy. In contrast,
the Hb fell to the lowest point despite of the elevated EPO
level; the Hb returned to normal range gradually later and had
an inverse correlation with the change of EPO. The change of
EPO exhibited a similar pattern as those of IL-6, CRP, and
ESR, which are indicators of the extent of the inflammatory
response. Thus the elevation of EPO during the inflammatory
stress could be considered as an acute phase
response11 . An impaired or blunted response to EPO could also explain the
declining Hb level under the condition of increased EPO during
acute inflammatory stress.
Marked hyperglycemia was observed in
the patient without history of diabetes. Serial fasting blood
glucose and insulin level were followed, which showed a
parallel change between the two during and after the acute
illness. The abnormally elevated blood sugar and insulin level
returned to normal range gradually after the inflammatory
stress subsided with the use of corticosteroid. Fasting
insulin level is an indirect assessment of insulin
sensitivity, and its elevation in this patient implicated an
increased insulin resistance during the acute stress. The
increased insulin resistance came from increased production of
insulin antagonists, such as catecholamines, cortisol and
glucagons, in responding to the inflammatory
stress12
In conclusion, the case demonstrated that polymyalgia
rheumatica, as a systemic inflammatory condition, can be
complicated with stress-related impaired EPO response and
increased insulin resistance, which in turn causes anemia and
hyperglycemia, respectively. With the treatment of
corticosteroid, we can not only relieve the musculoskeletal
symptoms but also correct the anemia and hyperglycemia via
anti-inflammatory mechanisms.
<References>
- Salvarani C, Gabriel SE, O'Fallon
WM, et al. Epidemiology of polymyalgia rheumatica in Olmsted
County, Minnesota, 1970-1991. Arthritis Rheum
1995;38:369-73.
- Cimmino MA. Genetic and
environmental factors in polymyalgia rheumatica. Ann Rheum
Dis 1997;56:576-7.
- Cantini F, Salvarani C, Olivieri I,
et al. Shoulder ultrasonography in the diagnosis of
polymyalgia rheumatica: a case-control study. J Rheumatol
2001;28:1049-55.
- Cantini F, Salvarani C, Olivieri I,
et al. Erythrocyte sedimentation rate and C-reactive protein
in the evaluation of disease activity and severity in
polymyalgia rheumatica: a prospective follow-up study. Semin
Arthritis Rheum 2000;30:17-24.
- Roche NE, Fulbright JW, Wagner AD,
et al. Correlation of interleukin-6 production and disease
activity in polymyalgia rheumatica and giant cell arteritis.
Arthritis Rheum 1993;36:1286-94.
- Chuang TY, Hunder GG, Ilstrup DM,
et al. Polymyalgia rheumatica: a 10-year epidemiologic and
clinical study. Ann Intern Med 1982;97:672-80.
- Healey LA. Long-term follow-up of
polymyalgia rheumatica: evidence for synovitis. Semin
Arthritis Rheum 1984;13:322-8.
- Brito J, Biamonti G, Caporali R, et
al. Autoantibodies to human nuclear lamin B2 protein.
Epitope specificity in different autoimmune diseases. J
Immunol 1994;153:2268-77.
- Meliconi R, Pulsatelli L, Uguccioni
M, et al. Leukocyte infiltration in synovial tissue from the
shoulder of patients with polymyalgia rheumatica.
Quantitative analysis and influence of corticosteroid
treatment. Arthritis Rheum 1996;39:1199-207.
- Weyand CM, Hicok KC, Hunder GG, et
al. Tissue cytokine patterns in patients with polymyalgia
rheumatica and giant cell arteritis. Ann Intern Med
1994;121:484-91.
- Elliot JM, Virankabutra T, Jones S,
et al. Erythropoietin mimics the acute phase response in
critical illness. Crit Care 2003;7:R35-40.
- Reaven GM. Pathophysiology of insulin resistance in
human disease. Physiol Rev 1995;75:473-86.
Table 1 Diagnositc Criteria for
Polymalgia Rheumatica
Criteria of Chunag et al., 6
- Age of 50 years or older
- Bilateral aching and stiffness for one month or
more and involving two of thefollowing areas: neck or
torso, shoulders or proximal regions of the arms, and
hips or proximal aspects of the thighs
- Erythrocyte sedimentation rate greater than
40mm/hour
- Exclusion of all other diagoses except giant-cell
arteritis
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Criteria of Healey, 7
- Pain persisting for at least one month and
involving two of the following areas: neck, shoulders,
and pelvic girdle
- Morning stiffness lasting more than one hour
- Rapid response to prednisone (≦20 mg/day)
- Absence of other disease capable of causing the
musculoskeletal symptoms
- Age of more than 50 years
- Erythrocyte sedimentation rate greater than
40mm/hour
| *All the
findings must be present for the diagnosis of polymyalgia
rheumatica for each set of the criteria.
Table 2
Clinical parameters of the patient with
polymyalgia rheumatica
| |
Day 1 |
Day 10 |
Day 35 |
Day 90 |
| ESR (mm/hr) |
>120 |
100 |
84 |
61 |
| IL-6 (pg/mL) |
45.6 |
12.2 |
1.7 |
- |
| CRP (mg/dL) |
29.3 |
8.28 |
3.49 |
1.25 |
| Hb (g/dL) |
9.0 |
9.8 |
10.5 |
12.4 |
| EPO (mU/mL) |
24.6 |
28.6 |
24.4 |
20.3 |
| AC Sugar (mg/dL) |
162 |
191 |
96 |
103 |
| Fasting Insulin (μU/mL) |
9.9 |
10.2 |
8.8 |
7.9 |
*ESR: erythrocyte sediment rate, IL-6: interleukin-6, CRP:
C-reactive protein, Hb: hemoblobin, EPO: erythropoietin, AC
sugar: fasting plasma glucose
*Corticosteroid with prednisolone 20mg per day was given
since day 7 after admission. The patient discharged on day15
and the dosage of steroid was gradually tapered and maintained
on 7.5mg per day at day 90
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Case Discussion
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