Rachmat Gunadi Wachjudi was born in Garut, Indonesia in 1955. He received his medical education in Indonesia, obtaining degrees in general medicine, internal medicine, and rheumatology. He has worked as a rheumatology staff member at Dr. Hasan Sadikin Hospital. He is a member of several Indonesian medical organizations. The document provides biographical information about Rachmat Gunadi Wachjudi's education, career, and professional affiliations.

1. Rachmat Gunadi Wachjudi
Lahir di Garut, 16-1-1955
Pendidikan
 SD-SMA : Garut
 Dokter umum: FK UNSRI Palembang
 Internist: FK UNPAD Bandung
 Konsultan Reumatologi : FK UI Jakarta
 Clinical Rheumatology & Osteoporosis training
Arthritis foundation of WA
Pekerjaan:
 Staf Reumatologi RS Dr Hasan Sadikin
Organisasi Profesi
 IDI, IRA, PAPDI, PEROSI, PERALMUNI,
IPS, ISS

2. The Role of Corticosteroid in
Rheumatic Diseases
Rationale
&
Therapeutic principles

3. INTRODUCTION
 Corticosteroid use is one of the most important and
controversial subjects in rheumatology.
 The dramatic anti-inflammatory effects of
corticosteroids were first described in the setting of treating
rheumatoid arthritis (RA). This unexpected discovery by
Philip Hench resulted in Nobel price in 1950.
 Long-term supraphysiologic therapy produced
devastating side effects led to polarized views of the
role of corticosteroids in the pathogenesis & therapy of
rheumatic diseases.
Hench PS etal. Proc Staff Meet Mayo Clin 24:181, 1949
Hench PS etal. Arch Intern Med 85:545,1950

4. Steroids the Sleaziest of Drugs
Steroids are fast catching up with
antibiotics as the most abused class of
drugs in doctor's black bag.
High doses of corticosteroids and
other immunosuppressive agents cause AIDS
Mohammed Ali Al-Bayati Ph.D

5. Corticosteroid Physiology
 Essential for normal development &
maintenances of homeostasis during both basal
and stress conditions.
 Represent one of the most important products
of the hypothalamic – pituitary – adrenal (HPA)
axis & the central response system.
 Regulate a broad array of metabolic and central
nervous system (CNS) functions
 Potent anti-inflammatory actions.

7. Cortisol Secretion

11. Anti-inflammatory actions of corticosteroids
Corticosteroid inhibitory effect

17. Role in Rheumatic diseases
Most of the desired clinical effects of GC
treatment in rheumatic patients are
mediated by transrepression.
These include:
1. Reduction of clinical signs & symptoms of
inflammation by reducing synthesis of
enzymes involved in the biosynthesis of
prostaglandin E2 and pro inflammatory
cytokines, such as IL1 & TNF – alpha.
2. Retardation of the radiological progression
in rheumatoid arthritis

18. Major Rheumatic Diseases
 Osteoarthritis  Poly-
 Rheumatoid Arthritis Dermatomyositis
 Systemic Lupus
 Crystal - Induced
erythematosus Arthritis
 Septic Arthritis
 Systemic Sclerosis
 Vasculitis
 Spondyloarthropathies

19. Joint Swelling
inflammation

20. What happens in inflammation?
 Associated with the production of cytokines (TNF & IL1,
IL6)  stimulate HPA axis and corticosteroid production
 feedback suppression of cytokine production & the
inflammatory response.
 Inadequate corticosteroid production amplify
inflammatory mechanisms & concomitant tissue injury.
 Defects in this bidirectional feedback loop between CNS
& peripheral inflammatory pathways and/or tissue
resistance to the actions of corticosteroids are
suspected to contribute to several rheumatic disorders
including RA.
Wilder RL. Annu Rev Immunol, 13:307,1995
Chrousos GP. N Engl J Med 332:1351,1995

21. Glucocorticoid Use in Daily Practice
. GC dosages in different clinical conditions is
essentially empirical
. High activity & severity need higher doses
. The rationale is:
a/ Higher doses increase cGCR saturation in a
dose dependant manner which intensifies the
therapeutically relevant, genomic actions.
b/ Non genomic action of GCs increasingly come
into play with increasing dosage

22. Standardized nomenclature for glucocorticoid doses
and glucocorticoid treatment regimens.
Terminology Dosage Clinical Genomic actions Nongenomic actions
application (receptor
saturation
Low dose <=7.5 Maintenance +(<50%) ?
therapy for
many rheumatic
diseases
Medium dose >7.5 to <=30 Initially given in ++ (>50% to (+)
primary chronic <100%)
rheumatic
diseases
High dose >30 to <= 100 Initially given in ++(+)(almost +
subacute 100%)
rheumatic
diseases
Very high dose >100 Initially given in +++([almost] ++
acute and/or 100%) ++
potentially life-
threatening
exacerbations of
rheumatic
diseases
Pulse therapy >=250 for one +++(100%) +++
or a few days

23. Short Acting Preparations (t1/2 < 12 h)
Drug Anti-inflam. Salt retaining Preapartions & dose
Cortisol 1 1.0 5 mg tablet
100 mg/vial (i.m., i.v)
Topical; enema
Cortisone 0.8 0.8 5 mg tablet
25 mg/vial (i.m)
Intermediate Acting Preparations (t1/2 = 12 -36 h)
Prednisone 4 0.8 -
Prednisolone 5 0.3 5, 10 mg tablet
20 mg/vial (i.m, intrarti)
Methyl 5 0 0.5, 1.0 gm inj. for i.m.
prednisolone or slow i.v.
Triamcinolone 5 0 4 mg Tab.,
10, 40 mg/ml for i.m. &
intrarticular inj.

24. Therapeutic principles
 Dose selection empiric; Needs frequent
evaluation
 Single dose: No harm
 Few days therapy unlikely to be harmful
 Incidence of side effects related to duration of
therapy
 Use is only palliative (except replacement
therapy)
 Inter-current illness: Dose is doubled
 Abrupt cessation of prolonged high dose leads to
adrenal insufficiency (contraindicated)

25. Steroids in RA
. Attractive options for many patients with new-onset inflammatory
arthritis since they are rapid acting and may be used intra articularly
or systemically & since the dose may be titrated to achieve meaningful
control while evaluation continues.
. Dramatically effective when used acutely but may be hazardous when
used chronically. For these reasons, steroids should be avoided,
weaned or used at the lowest possible dose after their introduction.
. Adverse events are numerous. The long term use of these drugs, even
at low doses, may be associated with significant reversible &
irreversible toxicities.
. The frequency of toxicity is proportional to the dose & duration of
therapy.

27. Corticosteroids therapy is most effective
and appropriate in three scenarios of early
inflammatory arthritis.
1/ New onset early (<12 weeks) undifferentiated
inflammatory arthritis in which oral, IM or IA steroids can
be given in very early patients with the hope of inducing
remission.
2/ New – onset RA for which prednisolone can be used as
symptomatic therapy (usually in doses of 5-20 mg/day) in
the first few weeks while the workup & symptoms evolve.
3/ Early – aggressive RA for which prednisone can be used
as adjuvant therapy (usually part of DMARD combination
regimen) where in high – dose prednisone (60 mg/day)
acutely is followed chronically by 5-10mg daily

28. Acute Gout

29. Intraarticular Corticosteroids
Indicated in:
1/ Patients with new onset inflammatory
monoarthritis
2/ Acute focal flares of one or few joints
3/ Patients disabled by synovitis in one joint despite
effective systemic therapy
Should be avoided in:
1/ Neuropathic joints
2/ Infected joint or overlying cellulitis
Most effective initially and less effective with
repeated injections.

30. Preparation
 Methyl Prednisolone
 Triamcinolone: 40 mg/ml
or 10 mg / ml

31. Knee joint
Patella
Lateral
Suprapatellar
Bursa
Anteriolateral
Inferiopatellar
Approach
Patellar
Tibial Tendon
Plateau

32. Joint Swelling - Synovial Effusion
Arthrocentesis and Injection therapy

33. Subacromial bursa

34. De Quervain’s
tenosynovitis

35. Trigger finger

36. Plantar fasciitis

37. Pulse Corticosteroid Therapy
. Indicated in severe Lupus
. 3 daily IV infusions of 1000 mg methyl
prednisolone
. Reserved for life threatening complications
as nephritis, vasculitis, severe cytopenias,
pericardial tamponade.
. Concomitant Cyclophosphamide

38. Lupus nephritis (WHO III)

39. Vasculitis

40. Adverse reactions (1/2)
 Metabolic toxicity:
 Iatrogenic Cushing’s syndrome
 Hyperglycaemia, glycosuria, diabetes
 Myopathy (negative nitrogen balance)
 Osteoporosis (vertebral compression fracture)
 Retardation of growth (children)
 Hypertension, oedema,CCF
 Avascular necrosis of femur
The frequency of steroid toxicity is proportional to the dose
and duration of therapy

41. Avascular bone-necrosis

43. Adverse reactions (2/2)
• HPA axis suppression
• Behavioral toxicity: Euphoria, psychomotor
reactions, suicidal tendency
• Ocular toxicity: steroid induced glaucoma,
posterior subcapsular cataract.
• Others:
– Superinfections
– Delayed wound healing
– Steroid arthropathy
– Peptic ulcer
– Live vaccines are dangerous

44. Contraindications
 Infections
 Hypertension with CCF
 Psychosis
 Peptic ulcer
 Diabetes mellitus
 Osteoporosis
 Glaucoma
 Pregnancy : (prednisolone preferred)

45. Precautions during therapy
Following examinations of the patient to be
done before, during and after steroid
therapy
 Body weight
 X-ray of spine
 Blood glucose
 Examination of the eye
 B.P.

46. Information >>> Judgement

47. New Glucocorticoid Receptor Ligands
1/ Time-release tablets:
Already availabe in USA. Taken by night to optimize suppression of
proinflammatory cytokines.
2/ Liposomes:
small molecules 100nm in size, used as carrier system for GC.
Reported in mice to accumulate selectively at site of inflammation.
Metselaar JM etal. A&R 2003,48:2059
3/ Glycyr-rhetinic acid:
Inhibits 11 beta hydroxysteroid dehydrogenase thus increases level & action of
endogenous GC.
4/ Nitrosteroids:
Aromatic molecules which links a conventional GC drug with nitric oxide (NO).
enhance anti-inflammatory effect & induces less osteoporosis than CG in
animal models.
Paul – Clark MJ. Prox Natl Acad Sci USA 2002, 99:1677
5/ Selective glucocorticoid receptor agonists (SERGAs):
Transrepression >> Transactivation
Schackett etal. Proc Natt Acad Sci USA, 2004, 101:227

48. Thanks for your patience

49. Have a nice weekend