This document provides information about various rheumatic diseases and conditions. It discusses osteoarthritis, rheumatoid arthritis, lupus, ankylosing spondylitis, Sjogren's syndrome, fibromyalgia and other conditions. It describes the signs and symptoms of each condition as well as how they are diagnosed. It also discusses drugs that are used to treat arthritis, including NSAIDs, their mechanisms of action, and classifications. NSAIDs are effective for pain but do not prevent tissue damage and can have side effects like ulcers if overused.

1. CLINICAL
PHARMACY IN
RHEUMATOLOGY

2. RHEUMATIC DISEASES
 Rheumatic diseases (rheumatism) are painful
conditions that affect millions. These diseases
cause inflammation, swelling, and pain in the
joints or muscles.
 Some rheumatic diseases like osteoarthritis are
the result of "wear and tear" to the joints. Other
rheumatic diseases, such as rheumatoid arthritis
, happen when the immune system goes
haywire; the immune system attacks the linings
of joints, causing joint pain, swelling, and
destruction.

3.  Rheumatism is a medical term once frequently used to
describe disorders associated with many different parts of
the body. Most often, people associate rheumatism with
arthritis, or with rheumatic fever, a complication of
strep throat that can result in damage to the heart.
However, the term rheumatism might apply to the
symptoms of numerous conditions that can cause pain
and/or weakness.
 Some conditions that were once given the general label of
rheumatism or called rheumatic diseases include,
rheumatoid arthritis, osteoarthritis, lupus, fibromyalgia, and
tendonitis. Frequently autoimmune disorders, since they
remained unnamed but caused pain as well as affecting
other organs, were classed as rheumatism. Illnesses like
lupus were particularly susceptible to being called
rheumatism. Later understanding of the actions of these
illnesses show that the problem is not dysfunction of the
joints, but rather immune systems that can attack joints,
muscles and organs.

4. Some forms of rheumatism are called non-
articular rheumatism and may affect the soft
tissues causing pain throughout the body.
Conditions like tendonitis and fibromyalgia fall
into this category. As well, non-articular
rheumatism can be localized to specific areas
in the body. Bursitis is a non-articular form of
rheumatism that affects and inflames the bursa
, which are special sacs that protect joints and
overlapping muscles. Bursitis most frequently
occurs at the site of one joint that may have
been injured through overuse.

5. Sponsored
Medical Lecture Notes – All Subjects
USMLE Exam (America) – Practice

6. Fibromyalgia

7. OsteoarthritisOA is not a normal part of aging; it usually affects the
knees, hips, lower back, neck, and fingers.
 The signs and symptoms of OA include:
 Pain in joint
 Joint swelling
 Joint may be warm to touch
 Joint stiffness
 Muscle weakness and joint instability
 Pain when walking
 Difficulty gripping objects
 Difficulty dressing or combing hair
 Difficulty sitting or bending over
To diagnose OA, doctor will ask the patient about medical
history and symptoms and do a physical exam. Blood
tests may help rule out other types of arthritis or medical
problems. A joint fluid sample from an affected joint may
also be examined to eliminate other medical problems.

8. Osteoarthritis

9. Rheumatoid Arthritis
RA is sometimes called a crippling disease. That's because it
can result in permanent joint damage and
deformity.
RA signs and symptoms include:
 Joint pain, stiffness, and swelling
 Involvement of multiple joints (symmetrical pattern)
 Other organ involvement
 Joint stiffness, especially in the morning
 Fatigue
 Fevers
 Lumps called rheumatoid
nodules
To diagnose RA, doctor will ask about medical history and do
a physical examination. Also, X-rays and blood tests will
likely be taken. One blood test may be for
rheumatoid factor; it is positive in 70% to 80% of those with
RA.

11. Rheumatoid Arthritis

12. LupusSLE or systemic lupus erythematosus is another autoimmune disease;
the cause of SLE is unknown.
Lupus signs and symptoms include:
 Joint pain
 Fatigue
 Joint stiffness
 Rashes, including the"butterfly rash" across the cheeks
 Sun sensitivity
 Hair loss
 Discoloration of the fingers or toes when exposed to cold (called
Raynaud's phenomenon)
 Internal organ involvement, such as the kidneys
 Blood disorders, such as anemia and blood clots
 Chest pain from inflammation of the lining of the heart or lungs
 Seizures or strokes
To diagnose lupus, doctor will ask about medical history, do a physical
exam, and order lab tests of blood and urine samples. One blood
test is the antinuclear antibody test (ANA). Most people with lupus
have a positive ANA blood test.

13. Systemic lupus erythematosus

14. Ankylosing SpondylitisAnkylosing Spondylitis (AS) usually starts gradually as lower back
pain. The hallmark feature of AS is the involvement of the joints at
the base of the spine. This is where the spine attaches to the
pelvis, also known as the sacroiliac joints.
Ankylosing spondylitis is more common in young men, especially
from the teenage years to age 30.
AS symptoms include:
 Gradual pain in the lower back and buttocks
 Lower back pain that worsens and works its way up the spine
 Pain felt between the shoulder blades and in the neck
 Pain and stiffness in the back, especially at rest and on arising
 Pain and stiffness get better after activity
 Pain in the middle back and then upper back and neck (after 5-10
years)
With progression of AS, the spine may become stiffer. It may become
difficult to bend for common everyday activities.
To diagnose AS, doctor will ask about medical history and perform a
physical exam. X-rays of the back looking at the sacroiliac joints
may help in making an AS diagnosis. A positive blood test for
HLA-B27 protein may help confirm a diagnosis.

15. Ankylosing Spondylitis

17. Sjogren's Syndrome
Sjogren's syndrome is an inflammatory, autoimmune disease. It can
occur with other autoimmune diseases such as RA and lupus, but
also on its own. Although the cause of Sjogren's is unknown, it is
more common in
women.
Sjogren's signs and symptoms include:
 Dry eyes (the glands in eyes do not give adequate tears)
 Eye irritation and burning
 Dry mouth (the glands in mouth do not give adequate saliva)
 Dental decay, gum disease, thrush
 Swelling of the parotid glands on the sides of the face
 Joint pain and stiffness (rarely)
 Internal organ diseases (rarely)
To diagnose Sjogren's syndrome, doctor will do a physical exam and
ask about medical history. Blood tests and other tests may also be
performed. A simple biopsy of the inner lip or other area may help
confirm the diagnosis.

18. Sjogren's Syndrome
Venus Williams Diagnosed With
Sjogren’s Syndrome

20. Drugs used to treat arthritis:
 Painkillers (analgesics) - These reduce pain. They are
used for many different types of arthritis and are often
used together with other drugs.
 Non-steroidal anti-inflammatory drugs (NSAIDs)
- These reduce inflammation of the joint as well as
pain. They are used for many different types of arthritis,
often along with other drugs.
 Disease-modifying anti-rheumatic drugs (DMARDs)
- This group of drugs is used mainly in the treatment of
rheumatoid arthritis but also in some other rheumatic
diseases. They reduce pain, swelling and stiffness.
 Corticosteroids (steroids) - These drugs are very
effective in controlling inflammation.

22. NSAIDs can be very effective against inflammation, but they do not prevent
tissue damage. Even when NSAIDs are controlling the inflammation, the
joint or organ damage of arthritis can continue to get worse. NSAIDs only
lessen pain and discomfort. They do not affect underlying disease.

23. Non steroidal anti-inflammatory drugs (NSAIDs) are examples of drugs that
act on enzymes. NSAIDs inhibits the enzyme cyclo-oxygenase (COX) which
catalyses a reaction in the biochemical pathway that results in the production
of prostaglandins, important mediators in the inflammatory response.

24. NSAIDs. Mechanism(s) of Action

27. The more an NSAID blocks COX-1, the greater is its
tendency to cause ulcers and promote bleeding. One
NSAID, celecoxib (Celebrex), blocks COX-2 but has little
effect on COX-1, and is therefore further classified as a
selective COX-2 inhibitor. Selective COX-2 inhibitors
cause less bleeding and fewer ulcers than other
NSAIDs.

30. NSAIDs can be classified based on their chemical
structure or mechanism of action. Older NSAIDs were
known long before their mechanism of action was
elucidated and were for this reason classified by
chemical structure or origin. Newer substances are
more often classified by mechanism of action.
Salicylates
 Aspirin (acetylsalicylic acid)
 Diflunisal
 Salsalate

31. NSAIDs
Propionic acid derivatives
 Ibuprofen
 Naproxen
 Fenoprofen
 Ketoprofen
 Flurbiprofen
 Oxaprozin
Acetic acid derivatives
 Indomethacin
 Sulindac
 Etodolac
 Ketorolac
 Diclofenac (Safety alert by FDA)
 Nabumetone

32. NSAIDs
Enolic acid (Oxicam) derivatives
 Piroxicam
 Meloxicam
 Tenoxicam
 Droxicam
 Lornoxicam
 Isoxicam
Fenamic acid derivatives( Fenamates )
 Mefenamic acid
 Meclofenamic acid
 Flufenamic acid
 Tolfenamic acid

33. NSAIDs
Selective COX-2 inhibitors (Coxibs)
 Celecoxib (FDA alert)
 Rofecoxib (withdrawn from market)
 Valdecoxib (withdrawn from market)
 Parecoxib FDA withdrawn
 Lumiracoxib TGA cancelled registration
 Etoricoxib FDA withdrawn
 Firocoxib used in dogs and horses
Sulphonanilides
 Nimesulide (systemic preparations are banned by several
countries for the potential risk of hepatotoxicity)
Others
 Licofelone acts by inhibiting LOX (lipooxygenase) & COX
and hence known as 5-LOX/COX inhibitor

34. NSAIDs are generally indicated for the
symptomatic relief of the following conditions:
 Rheumatoid arthritis
 Osteoarthritis
 Inflammatory arthropathies (e.g. ankylosing spondylitis,
psoriatic arthritis, Reiter's syndrome)
 Acute gout
 Dysmenorrhoea (menstrual pain)
 Metastatic bone pain
 Headache and migraine
 Postoperative pain
 Mild-to-moderate pain due to inflammation and tissue injury
 Pyrexia (fever)
 Ileus
 Renal colic
 They are also given to neonate infants whose ductus arteriosus is
not closed within 24 hours of birth
 Aspirin, the only NSAID able to irreversibly inhibit COX-1, is also
indicated for inhibition of platelet aggregation.

35. Complications of NSAIDs
NSAIDs are safe drugs. However, they have many side effects. The
side effects happen more often when they are used over long periods
of time, which is common in arthritis patients. Some of the side effects
can become very serious. GI Effects
NSAIDs irritate the gastrointestinal (GI) tract (the digestive system--your
esophagus, stomach, and intestines). They increase the production of
gastric acid, and they harm the gastric lining. NSAIDs aggravate ulcers
and GI bleeding. Up to 5 percent of people who use NSAIDs for a year
develop ulcers, bleeding, or tears in the GI tract. The risks are higher
for older patients, patients with a history of GI problems, and patients
with heart disease.
 Blood Effects
NSAIDs make it harder for the platelets in your blood to clump together at
the site of an injury. This can cause bleeding problems. Aspirin
especially has this effect. Before you have surgery, you should stop
taking aspirin for two weeks to prevent bleeding problems.
 Liver Effects
NSAIDs can be toxic to your liver. You will not feel this, but elevated
levels of certain liver enzymes can easily be seen in blood tests. Liver
function almost always returns to normal when you stop taking
NSAIDs.

36.  Kidney Effects
NSAIDs can make it hard for your kidneys to get rid of
some kinds of wastes. If you have a history of kidney
problems, or if your disease may affect your kidneys,
your doctor will use NSAIDs with caution.
 Other Effects
Some people get skin reactions and rashes from NSAIDs.
Some get a combination of runny nose, polyps in the
nose, and asthma. Different kinds of NSAIDs can have
different side effects. Salicylates can cause problems
with hearing. Other kinds of NSAIDs can cause
headaches and confusion, especially in elderly patients.
Many of the possible side effects depend on your health
and the disease for which you are being treated.
Individuals can react very differently to the same NSAIDs.
You and your doctor must work together to find the type
and dose of NSAID that controls your symptoms without
causing unwanted side effects.

37. CORTICOSTEROIDS
Corticosteroids may regulate gene expression in several ways.
Corticosteroids enter the cell to bind to GR in the cytoplasm that
translocate to the nucleus. GR homodimers bind to GRE in the
promoter region of steroid-sensitive genes, which may encode
anti-inflammatory proteins. Less commonly, GR homodimers
interact with negative GREs to suppress genes, particularly those
linked to side effects of corticosteroids. Nuclear GR also interact
with coactivator molecules, such as CBP, which is activated by
proinflammatory transcription factors, such as NF- B, thus
switching off the inflammatory genes that are activated by these
transcription factors. Other abbreviations: SLPI: secretory
leukoprotease inhibitor; MKP-1: mitogen-activated kinase
phosphatase-1; I B- : inhibitor of NF- B; GILZ: glucocorticoid-
induced leucine zipper protein; POMC: proopiomelanocortin;
CRF: corticotrophin-releasing factor.

40. CORTICOSTEROIDS

41. Uses of Corticosteroids
 Corticosteroids are chemical copies of hormones that
occur naturally in your body. The most commonly used
corticosteroids are prednisone, prednisolone, and
methylprednisolone. Corticosteroids can be given orally or
put directly into the bloodstream through an intravenous
needle. They can also be injected directly into an inflamed
spot. Corticosteroid cream can be rubbed on the skin.
 Corticosteroids are powerful drugs. They drastically
decrease inflammation. But they are also highly toxic.
Doctors have different opinions about how corticosteroids
should be used.
 Corticosteroids can't cure your disease. But they do seem
to affect the development of some diseases, including
rheumatoid arthritis (RA).

42. CORTICOSTEROIDS

43. Complications of Corticosteroids
Corticosteroids can have many unwanted effects on your body. Whether or not
you develop these complications depends on many factors: what type of
corticosteroid you take, your dose, the length of time you are on it, and how
sensitive your body is to these hormones. The most common side effects
are.
 Osteoporosis
 All corticosteroids slow bone growth and create conditions that lead to
osteoporosis, a disease process that results in reduction of bone mass.
Compression fractures of the vertebrae can happen with long-term
corticosteroid use. Men and women past menopause are most likely to
develop osteoporosis. Your doctor may recommend that you take calcium
and vitamin D pills while you take corticosteroids.
 Infections
 High levels of corticosteroids hinder your body's ability to fight bacterial
infections. High-dose corticosteroids can even mask the symptoms of some
types of infections, such as abscesses and bowel tears. Most viral infections
are not a problem, except for herpes.
 Adrenal Insufficiency
 This means that your pituitary and adrenal glands can't produce enough of
certain kinds of hormones. This can happen after taking corticosteroids in
moderate doses for only a few days. Adrenal insufficiency is most likely to
happen as you are reducing the dosage. It can be a problem if you need
surgery or if you get an infection or serious injury.

45. Withdrawal
 When stop taking corticosteroids, the doses will be slowly reduced
over a period of days or weeks. Even if patient has only been taking
steroids for a few weeks, he will still need to taper off. Corticosteroid
withdrawal can be very difficult for body. In many patients, the
disease symptoms become worse. Some people experience a
sickness that includes fevers, nausea, vomiting, low blood pressure,
and low blood sugar. Others have withdrawal symptoms that include
muscle and joint pain, weight loss, fever, and headaches. If patient
have problems coming off corticosteroids, doctor will have taper off
the drug more slowly.
 Different people, and different diseases, react very differently to
corticosteroids.

46. Contraindications to Use
Corticosteroids are contraindicated in
systemic fungal infections and in people who are
hypersensitive to drug formulations. They should be
used with caution in clients at risk for infections (they
may decrease resistance), clients with infections (they
may mask signs and symptoms so that infections
become more severe before they are recognized and
treated), diabetes mellitus (they cause or increase
hyperglycemia), peptic ulcer disease, inflammatory
bowel disorders, hypertension, congestive heart failure,
and renal insufficiency.

47. Disease-modifying Anti-rheumatic
Drugs (DMARDs)
 The early use of disease-modifying anti-rheumatic drugs
(DMARDs) has been recommended in recent years to
reduce disease progression and long-term disability.The
need for early use of DMARDs is incorporated in new
National Institute for Health and Clinical Excellence
(NICE) guidance. Early use requires early referral in part
because DMARD initiation is the province of specialists in
secondary care. The optimum use of these drugs requires
specialist experience and is complicated not only
because of their potential toxicity, but also by the range
and combination of drugs used. There are a number of
new DMARDs.

48. DMARDs
 The prevailing guidelines for the management of rheumatoid
arthritis (RA) recommend that, once the disease has been
diagnosed and its impact on the patient's life documented,
DMARDs should be commenced. DMARDs should be part of a
range of treatments from different professional disciplines. For
further details see separate article Management of Rheumatoid
Arthritis.
 DMARDs either affect the immune response or suppress the
disease process. As well as improving the symptoms and signs
of the arthritis, they may also improve the extra-articular
manifestations such as vasculitis in addition to exerting systemic
effects.
Any DMARD that has been prescribed should be recorded in a
patient's notes, both written and electronic, so that all doctors
prescribing for that patient will be aware of any potential
interactions with other drugs.

49. Types of disease-modifying anti-
rheumatic drugs
DRUGS WHICH SUPPRESS THE DISEASE
PROCESS
Gold:
 May be given either orally as auranofin or by intramuscular
injection as sodium aurothiomalate.
 Sodium aurothiomalate is licensed for the treatment of
rheumatoid arthritis (RA) and juvenile idiopathic arthritis.
 Can be an effective treatment but use is restricted by severe
adverse reactions (up to 5% of recipients).
 Sodium aurothiomalate has a greater toxicity than auranofin,
but tends to be more effective and has a faster onset of
action.
 Either drug should be withdrawn if no benefit is seen after six
months.

50. Types of disease-modifying anti-rheumatic drugs
DRUGS WHICH SUPPRESS THE DISEASE PROCESS
Penicillamine
 It is a chelating agent licensed for the treatment of severe
active rheumatoid arthritis, including juvenile forms (and a
range of other conditions, including Wilson's disease).
 It has a similar method of action to gold and more patients
are able to tolerate it, but side-effects occur frequently.
 The rate of onset of action is slow, improvement may not be
seen for three months but, in patients who have shown no
benefit after a year of treatment, the drug should be
discontinued.
Sulfasalazine
 It is licensed for the treatment of RA which has failed to
respond to non-steroidal anti-inflammatory drugs (NSAIDs).
 It has a similar action to gold.
 It has slightly more side-effects than methotrexate.

51. Types of disease-modifying anti-
rheumatic drugs
Drugs which affect the immune process
Chloroquine and hydroxychloroquine
 Hydroxychloroquine is an antimalarial agent licensed for the
treatment of RA, juvenile idiopathic arthritis, discoid and
systemic lupus erythematosus, and dermatological conditions
caused, or aggravated, by sunlight.
 They are usually better tolerated than gold or penicillamine.
Methotrexate
 May be used in the treatment of RA and psoriatic arthritis.
 It is a disease-modifying agent with both anti-inflammatory and
immunosuppressant activity.
 It is also classified as an antimetabolite cytotoxic agent, and is
the most common first-line agent for the early treatment of RA in
the UK.

52. Types of disease-modifying anti-
rheumatic drugs
Drugs which affect the immune process
Azathioprine
 It is a cytotoxic drug and a prodrug of mercaptopurine.
 It is used as an immunosuppressant for many autoimmune conditions and to
suppress transplant rejection.
 It acts in a similar manner to methotrexate but is usually reserved as second-
line due to its toxicity.
Ciclosporin
 It is a powerful immunosuppressant that appears to act specifically on
lymphocytes (mainly helper T cells) resulting in depression of the cell-
mediated immune response.
 Unlike cytotoxic immunosuppressants (such as cyclophosphamide) it has
little effect on bone marrow.
 It is licensed for the treatment of severe active rheumatoid arthritis when the
usual second-line therapy is inappropriate or ineffective.
Leflunomide
 Leflunomide has antiproliferative properties.
 It is licensed for the treatment of adults with active RA and also for active
psoriatic arthritis.
 It is used in the treatment of moderate-to-severe, active RA, often in
combination with methotrexate.

53. Antitumour necrosis factor or
biological agents
The term biological agents
encompasses tumour necrosis factor
(TNF)-alpha blockers (infliximab,
etanercept, and adalimumab) and other
agents, including abatacept, anakinra,
and rituximab.

54. Choosing the right DMARD
Current evidence suggests that combinations of
DMARDs are more effective, and probably less toxic,
than monotherapy.Methotrexate is often used as an
anchor drug, combined with hydroxychloroquine,
sulfasalazine or leflunomide. An anti-TNF-alpha drug
such as etanercept or infliximab may also be used in
combination. There is a stronger evidence base for the
disease-modifying effects of methotrexate,
sulfasalazine, leflunomide and intramuscular gold than
for hydroxychloroquine, penicillamine, oral gold,
ciclosporin or azathioprine, although these agents do
improve symptoms and some objective measures of
inflammation. The choice of first agent or combination
of agents should be based on a risk/benefit analysis for
individual patients.

55. Monitoring
The use of disease-modifying anti-rheumatic
drugs (DMARDs) is limited by potentially serious
side-effects, and therefore patients who are
taking these drugs should be monitored on a
regular basis as in the table below. Note
throughout that, whilst absolute values are
useful indicators, trends are also important.
Hence any rapid fall or consistent downward
trend in any parameter warrants extra vigilance.