Rheumatic Syndrome in Elderly Due to Treatment

Chingching Foocharoen ( ) 1

(polymyalgia rheumatica)
(temporal arteritis)

1. (statin associated myopathy)

2. (drug induced arthralgia)
3. (drug induced lupus)
4. (drug induced gout)
5. (drug induced vasculitis)
6. (drug induced scleroderma)
(statin induced myopathy)
statin (cholesterol)
HMG-CoA reductase cholesterol
simvastatin atorvastatin fluvastatin pravastatin lovastatin rosuvastatin cerivastatin
(cardiovascular event)
4 1
1. Statin myopathy
statin
2. Myalgia
(creatinine kinase ; CPK)
3. Myositis
CPK
4. Rhabdomyolysis CPK 10

myopathy myalgia 5
myositis rhabdomyolysis 2,3
statin
2,4-6

1.

apoptosis myoblast apoptosis

2. chloride channel (myocyte)
rhabdomyolysis
chloride channel

3. cholesterol

4. HMG-CoA reductase
statin coenzyme Q10 coenzyme Q10
oxidation adenosine triphosphate (ATP)
coenzyme Q10

(anaerobic metabolism) mitochondrial
myopathy
statin

statin
fluvastatin atorvastatin pravastatin (hydrophilic) cerivastatin
lovastatin simvastatin
( 1)
cerivastatin lovastatin simvastatin
fluvastatin atorvastatin pravastatin
cerivastatin rhabdomyolysis 7
statin statin
8
statin

450 (CYT-P450) 3A4

fluvastatin

CYT-P450 2C9 pravastatin

CYT-P450 ( 1)
CYT-P450
3A4

statin statin
cyclosporine-A fibrates
macrolide azole protease fibrates statin
CPK statin 2-3 9
statin gemfibrozil statin fenofibrate
gemfibrozil7 statin
fibrate statin fenofibrate7 cyclosporin-A

statin CYT-P450
P-Glycoprotein

statin statin
10
statin

 statin ezetimibe
LDL

LDL statin
statin 7 statin

1
statin

Fluvastatin
P450 CYP 2C9
Hydrophilic
Rosuvastatin
P450 CYP 2C9
Hydrophilic
Atorvastatin
P450 CYP 3A4
Hydrophilic
Lovastatin
P450 CYP 3A4
Lipophilic
Simvastatin
P450 CYP 3A4
Lipophilic
Cerivastatin
P450 CYP 3A4, CYP 2C8
Lipophilic
Pravastatin
Liver cytosol
Hydrophilic
( Quiceno GA. Rheum Dis Clin N Am 2007; 33: 123-34.) 11
statin
(hypothyroidism)
8
statin

ragged red fibers
(necrosis) (inflammation)
(mitochondrial respiratory chain dysfunction)12,13
statin

statin



CPK 2
statin

statin
statin2
CPK

statin CPK

 statin
CPK 5-10
niacin, bile sequesting salts, ezetimibe 2,14 rhabdomyolysis
statin
(myoglobin) 2
protease cyclosporinA statin
statin
statin
11

statin 3
1. statin
2. statin
3.
statin


4.
5.
statin

6. statin

macrolide

7. CPK
- CPK 5 1
- CPK 5 statin CPK
8.


- statin fibrate statin

-

statin ( creatinine 2 ./.)

cyclosporine-A macrolide
azole 70
(drug induced arthralgia)




11
1. (quinolones) (amphotericin) (acyclovir)
(minocycline)
2. quinidine, propanolol, acetabulol, nicardipine

3.
4.
5.
6.

statin, fibrate
raloxifene, tamoxifen, letrozole

(biological agents) interferons, interleukin-2, interleukin-6, immunotoxins,
tacrolimus, growth factor

(drug induced lupus)

1. American College of Rheumatology
(ACR) ..1982
2. (antinuclear antibody; ANA)
3.


30,000 3
(definitely) (probably)
(possibly) ( 2)
2
Definite
Probable
Possible
Procainamide
Phenytoin
Estrogens
Hydralazine
Methimazole
Penicillin
Methyldopa
Proprylthiouracil
Gold salts
Quinidine
Penicillamine
Tetracycline
Chlorpromazine
Lithium
Reserpine
Sulfasalazine
Griseofluvin
Beta-blockers
Para-aminosalicylic acid
Carbamazepine
Atorvastatin
Minocycline
Simvastatin
Isoniacid
Amiodarone
Infliximab
Ticlopidine
Etanercept
Terbinafine
Adalimumab
Interferons
( Quiceno GA, et al. Rheum Dis Clin N Am 2007; 33: 123-34.) 11
15
1.
(drug-DNA interaction)
(histone)

2.
(abnormal immune
regulation)

(hapten) (T-lymphocyte)

(T-cell tolerance)

3.

(DNA hypomethylation)
(DNA methylation) (gene expression)
(cellular differentiation) hypomethylation CD4+ T-lymphocyte

4.
hydralazine D-penicillamine
isoniacid classical pathway C4 C2
(immune complex)
5.
(immunogenetic factor)
(slow acetylator)

(idiopathic systemic

lupus erythematosus) ACR ..1982
4 11
2-3

16
lupus diathesis15
80
hydralazine

procainamide (pleuritis)
(pericarditis) (pneumonitis)16
(cutaneous vasculitis)
(pulmonary thromboembolism) (pericardial
tamponade) (constrictive pericarditis) (scleritis)
(granulocytopenia) 17-20
(idiopathic systemic lupus erythematosus)

( 3)
3


()
()

>75
>75

50-75
>75

25-50
>75

<25 (quinidine 25-50)

>75

(hydralazine<25)
25-50

<25 (procainamide 50-75)

50-75

5-15
15

(hydralazine <25)
50-75

25-50

<25 (procainamide <25)

25-50

<25
25-50

<25
25-50
( Yung RI, et al. Rheum Dis Clin North Am 1994; 20: 61-86. . :
, . SLE. : Text and journal publication Co., Ltd, 2544: 311-22.)15,27

ANA

ANA speckle homogenous11
(anti-histone) ( 2)
(anti-DNA)
Coombs test
(antiphospholipid) 21
( 4)
4

Antinuclear antibody (ANA)
>95
>95
Antihistone
>75
Procainamide
H2A-H2B
Hydralazine
H3, H4
Anti double strand DNA (anti dsDNA)
<25
25-50
Anti smith antibody (anti sm)

25
Anemia
<25
50-75
Leucopenia
<25
25-50
Thrombocytopenia
<25
25-50
(quinidine 25-50)
Low complement level

50-75
(quinidine 50-75)

( Yung RI, et al. Rheum Dis Clin North Am 1994; 20: 61-86. . :
, . SLE. : Text and journal publication Co., Ltd, 2544: 31122.)15,27
ANA
50 hydralazine
ANA 10 11
ANA

ANA 1
(nonsteroidal anti-inflammatory agents)

(drug induced gout)

atherosclerosis

( 5)
5

Ethanol
Ethanol
Cytotoxic drugs
Diuretics (loop diuretic, thiazide)
Warfarin
Low dose aspirin
Cyclosporine
Ethambutol
Pyrazinamide
Levodopa
Nicotinic acid
( Quiceno GA, et al. Rheum Dis Clin N Am 2007; 33: 123-34.) 11
( 5)

(drug induced vasculitis)
( 6)

(immune-mediated disorder)22-23

 6

Allopurinol
Amphetamine
Cocaine
Hydrochlorothiazide
Pencillamine
Propylthiouracil
Trimethoprim-sulfamethoxazole
Montelukast
Cytarabine
Minocycline
Hepatitis B vaccine
TNF inhibitor (infliximab, etanercept,
adalimumab)
( Quiceno GA, et al. Rheum Dis Clin N Am 2007; 33: 123-34.) 11

propylthiouracil 8 24
antineutrophilic cytoplasmic antibody
(perinuclear)
propylthiouracil
(cyclophosphamide)
(drug induced scleroderma)

( 7)
7

Bleomycin
Docetaxel
Pentazocine
Carbidopa
L-tryptophan
Organic solvent exposure
Rapseed oil
Vinyl chloride
( Quiceno GA, et al. Rheum Dis Clin N Am 2007; 33: 123-34.) 11



25 ANA anti-topoisomerase anti-SCL 70
26