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Flashcards in Session 4 Deck (76):


Autoimmune Rheumatic Diseases (ARDs)

1. ? group of diseases

2. Immune tolerance breakdown

3. Production of ?

4. Local or diffuse features ?


1. Heterogeneous


3. Pathogenic antibodies

4. Multisystemic features


Importance of autoantibodies? (4)

• Aid to diagnosis

• Associated with specific clinical features

• Disease prognosis

• To stratify therapy



Systemic lupus erythematosus (Lupus)

1. Female to male ratio: ? 

2. Prevalence: ?

3. Race: ?

4. What factors are important 


1. 9:1

2. 24/100,000

3. Afro-Caribbean > South Asians > Caucasians

4. - Genetic factors are important 

- Environmental factors



History taking for ARDs

1. Current symptoms: what symptoms should you ask about  

2. What should you ask about evolution?

3. Involvement of other systems: 


1. • Pain 

• Stiffness 

• Swelling 

• Pattern of joint involvement

2. • Acute or chronic? 

• Associated events 

• Response to treatment/Family history

3. • Skin, eye, lung 

• Malaise, weight loss, fevers, night sweats

• Impact on patient's lifestyle


History taking for ARDs (lupus)

1. Constitutional symptoms:

2. Explain the “Glove and sweater” approach



1. Fever, fatigue, weight loss, night sweats, Poor appetite






•  Be aware of the investigations that may be useful in assessments of these
patients LO 

Investigations for ARDs


What are the clinical features 

- Alopecia

- butterfly rash

-hand swelling 



low WCC 2.5, ANA 1:1600, anti-Sm antibodies


Treatment of systemic Lupus 

• Patient education RE:  lifestyle modification, use of sunscreen

• Start DMARDs : Hydroxychloroquine, Azathioprine, Mycophenolate

• Use of steroids: Prednisolone, methylprednislone

• In Severe cases: IV Cyclophosphamide


Lupus Mnemonic

A RASH POINTS Medical Diagnosis





Rheumatoid arthritis (RA)

1. Female to male ratio: ? 

2. Prevalence: ?

3. Race? 

4. Factors 


1. 3:1

2. 1%

3. No race predisposition 

4. Genetic factors/environmental factors


What does the statement ‘have you got the s factor’ mean?


•  Be aware of the investigations that may be useful in assessments of these
patients LO 

Investigations for RA?


What is the classification criteria for RA 


Treatment of RA (3)


• Start DMARDs early!! : Methotrexate Hydroxychloroquine, Sulfasalazine, Leflunomide

• Use of steroids: Prednisolone, methylprednisolone

• Combination therapy is usual.


What are DMARDS?

Disease-modifying antirheumatic drugs (DMARDs) is a category of otherwise unrelated drugs defined by their use in rheumatoid arthritis to slow down disease progression.

The term is often used in contrast to nonsteroidal anti-inflammatory drug (which refers to agents that treat the inflammation but not the underlying cause) and steroids (which blunt the immune response but are insufficient to slow down the progression of the disease).


What are the different types of arthritis 


What are the four ways you can get pneumonia? 

1.  Community acquired pneumonia

2.  Hospital-acquired pneumonia

3.  Ventilator-associated pneumonia

4.  Aspiration pneumonia



1. Define severe community-acquired pneumonia:

2. Patients  with  3  or  more  adverse  prognostic  features  are  at  a  high  risk  of  death  and should be managed as a severe pneumonia. Clinical adverse prognostic features (‘CURB-65’) are:-

1. Onset of infection prior to hospital admission and not within 10 days of hospital discharge

2. •  Confusion: new mental confusion (defined as an Abbreviated Mental Test score
of 8 or less)

•  Urea: raised > 7 mmol/L (new onset)

•  Respiratory rate: raised >= 30/min

•  Blood pressure: low blood pressure (systolic blood pressure < 90 mm Hg and/or diastolic blood pressure ≤ 60 mm Hg)

•  Age 65 or over.

Patients  who  have  >=  2  ‘core’  adverse  prognostic  features  on  admission  should  be reviewed medically at least 12 hourly until shown to be improving



1. CURB-65 Score 0-1 (mild) community-acquired pneumonia
Antibiotic treatment:

- Amoxicillin oral 500mg tds for 5 days

- If penicillin allergic: Doxycycline oral 200mg od for 5 days.

- If nil by mouth or swallowing difficulties, refer to antimicrobial website



CURB-65 Score 2 (moderate) community-acquired pneumonia

Antibiotic treatment:



- Amoxicillin oral 1g tds for 5 days and Doxycycline oral 200mg od for 5 days 

- If penicillin allergic: give only Doxycycline oral 200mg od for 5 days.

- If nil by mouth or swallowing difficulties, refer to antimicrobial website


CURB-65 Score  ≥ 3 (Severe) community-acquired pneumonia

Send off legionella urine antigen test. Consider critical care referral. Antibiotic treatment:



- Co-Amoxiclav IV 1.2g tds and Doxycycline oral 200mg od for 5 days 

- If non-anaphylactic penicillin allergy: Meropenem IV 1g tds and Doxycycline oral 200mg od and for 5 days (reduce dose if renal impairment). Contact microbiology for advice if anaphylactic penicillin allergy

- If patient has difficulty swallowing, refer to antimicrobial website


1. Hospital-acquired:

2. Clinical features: 

3. Severe Hospital-acquired pneumonia is defined as having one or more of the following features: 


1. Onset of infection 48 hours or more after hospital admission or Infection present on admission but patient is within 10 days of previous in-patient stay.

2. •  Fever

•  Purulent sputum or tracheal secretions

•  Leucocytosis and new infiltrates on chest X-ray (occurring >48 hrs after hospital admission) 



Mild/moderate hospital-acquired pneumonia and not known to be MRSA carrier

Antibiotic treatment:


•  Co-amoxiclav oral 625mg tds for 5 days

•  If NBM: Co-amoxiclav IV 1.2g tds

•  If penicillin allergy: Doxycycline oral 200mg od for 5 days (Reduce dose if renal

•  If NBM and non-anaphylactic penicillin allergy: Meropenem IV 1g tds. Contact microbiology for advice if anaphylactic penicillin allergy


Severe hospital-acquired pneumonia

Antibiotic treatment:

•  Co-amoxiclav IV 1.2g tds for 5 days (reduce dose if renal impairment)

•  If non-anaphylactic penicillin allergy :

Meropenem IV 1g tds for 5 days (reduce dose if renal impairment). Contact microbiology  for advice if anaphylactic penicillin allergy


1. Ventilator-associated pneumonia: 


1. Pneumonia developing after at least 48 hours of mechanical ventilation.


Samples to be taken prior to starting antibiotics:


1. Take samples: 

2. Antibiotic treatment: 


1. •  Tracheal aspirate +/- broncheolar lavage (If BAL, contact microbiology and ask for an urgent Gram stain) 

•  Blood sample 

•  Sputum  or  throat  swab  for  viral  culture  and  immunofluorescence  if immunocompromised patient  or features  suggestive  of  influenza  infection  during
the influenza season.

2. •  Tazocin IV 4.5g tds for 5 days (reduce dose if renal impairment) 

•  If non-anaphylactic penicillin allergy:
Meropenem IV 1g tds for 5 days (reduce dose if renal impairment)
Contact microbiology  for advice if anaphylactic penicillin allergy


Ventilation pneumonia 

Antibiotic treatment:



•  Tazocin IV 4.5g tds for 5 days (reduce dose if renal impairment) 

•  If non-anaphylactic penicillin allergy:
Meropenem IV 1g tds for 5 days (reduce dose if renal impairment)
Contact microbiology  for advice if anaphylactic penicillin allergy


Aspiration pneumonia

•  Do not treat aspiration/ suspected aspiration without evidence of pneumonia

•  Routine antibiotic treatment not indicated - apart from patients with small bowel obstruction who will aspirate colonised gastric contents.

•  Treatment  - supportive. Pulmonary toilet and early ventilation. Steroids not indicated in the immediate phase.

•  If persistence of chest signs, or fever after 48 hours treat as detailed below.

1. Mild/moderate aspiration pneumonia

Antibiotic treatment:



1. •  Co-amoxiclav oral 625mg tds for 5 days

•  If NBM: Co-amoxiclav IV 1.2g tds. Convert back to above oral regimen as soon as possible to complete the 5 day course. 

•  If penicillin allergy: Ciprofloxacin oral 500mg bd and Metronidazole oral 400mg bd for 5 days. 

•  If atypical pathogen suspected add in Doxycycline oral 200mg od or if NBM
Clarithromycin IV 500mg bd.




•  Renal  Impairment:  Dose  reductions are  required for  the following  antibiotics

in patients with renal impairment: Co-amoxiclav, Imipenem, and Meropenem.

Refer  to  the  renal  dosing  section  on  the  antimicrobial  website  on  INsite  for

dosing information.

•  Liver Impairment: No dose adjustment of antibiotics dosages recommended

in these guidelines are routinely required in patients with liver impairment.


•  Underrstand some complications that can arise in patients with SLE & RA

•  Understand important clinical signs in these patients.

•  Be aware of the investigations that may be useful in assessments of these patients

•  Understand the interpretation of the blood tests and imaging in these patients.



Underrstand some complications that can arise in patients with SLE & RA LO

1. Complications 


1. - Septic arthritis


- Hands and wrists:

+ carpal tunnel syndrome

+ ulnar drift and palmar subluxation of the MCPs

+ Fixed flexion  (buttonhole or boutonnière deformity) or  fixed hyperextension  (swan-neck deformity) of the PIP joints, which impairs hand function.


- Feet: + hammer-toe deformity


- Spleen, lymph nodes and blood 

+Felty syndrome  is splenomegaly and neutropenia in a patient with RA. Leg ulcers and sepsis are complications. HLA-DR4 is found in 95% of patients, compared with 50–75% of people with RA alone. 

+ Lymph nodes may be palpable, usually proximal to affected joints. There may be peripheral lymphoedema of the arm or leg. 

+ Anaemia  is almost universal and is usually normochromic and normocytic. It may be iron-deficient owing to gastrointestinal blood loss from NSAID ingestion, or rarely haemolytic (Coombs-positive). There may be a pancytopenia due to hypersplenism in Felty syndrome or as a complication of DMARD treatment. A high platelet count occurs with active disease. 



Be aware of the investigations that may be useful in assessments of these patients LO

Understand the interpretation of the blood tests and imaging in these patients LO 

1. Initial investigations for RA include? And what they may show?


1. • Blood count may show a normochromic, normocytic anaemia. 

• ESR and/or CRP are raised in proportion to the activity of the inflammatory process and are useful in monitoring treatment. 

• Serology reveals ACPA positivity (see p. 650 ). This is present earlier in the disease (and may predate it by many years), and in early inflammatory arthritis indicates the likelihood of progressing to RA. RF is present in approximately 70% of cases and ANA at low titre in 30%. 

• X-rays show soft tissue swelling in early disease, but ultrasound and MRI  (  Fig. 18.25  )  are useful to demonstrate synovitis and early erosions.  

• Aspiration of the joint  may be needed if an effusion is present. The aspirate looks cloudy owing to white cells. In a suddenly painful joint, septic arthritis should be suspected

• Doppler ultrasound  is a very effective way of demonstrating persistent synovitis when deciding on the need for DMARDs or assessing their efficacy.


1. What is Systemic lupus erythematosus (SLE)?

2. Epidemiology 

3. The cause is unknown but there are several predisposing factors:


1. an inflammatory, multisystem autoimmune disorder with arthralgia and rashes as the most common clinical features, and cerebral and renal disease as the most serious problems

2. - nine times as common in women as in men

- peak onset: 20 - 40 years. 

- highest in African/Caribbean women

3. • Heredity: There is a higher concordance rate in monozygotic twins (up to 25%) compared with dizygotic twins (3%). First-degree relatives have a 3% chance of developing the disease but approximately 20% have autoantibodies. 

• Genetics: Three whole-genome analyses have led to the identification of approximately 20 genes linked to the development of SLE. These include some HLA genes, as well as genes involved in T- and B-lymphocyte function. Homozygous deficiencies of the complement genes C1q, C2 or C4 are very rare but convey a high risk of developing SLE. 

• Sex hormone status: Pre-menopausal women are most frequently affected. 

• Drugs: hydralazine, isoniazid, procainamide and penicillamine can induce a form of SLE that is usually mild, in that the kidneys and central nervous system are not affected. 

• Ultraviolet light: trigger flares of SLE, especially in the skin. 

• Exposure to Epstein–Barr virus: trigger for SLE.


1. Clinical features

The manifestations of SLE vary greatly between patients. Most patients suffer ?

1. - fatigue

- arthralgia

- skin problems. Involvement of major organs is less common but more serious


Be aware of the investigations that may be useful in assessments of these patients LO

Understand the interpretation of the blood tests and imaging in these patients. LO

1. Investigations & what they are likely to see 



• A full blood count may show a leucopenia, lymphopenia and/or thrombocytopenia. Anaemia of chronic disease or autoimmune haemolytic anaemia also occurs. The ESR is raised in proportion to the disease activity. In contrast, the CRP is usually normal but may be high when the patient has lupus pleuritis, arthritis or a coexistent infection. 

• Urea & creatinine only rise when renal disease is advanced. Low serum albumin or high urine albumin/creatinine ratio are earlier indicators of lupus nephritis. 

• Autoantibodies of many different types may be present in SLE but the most significant are ANA, anti-dsDNA, anti-Ro, anti-Sm and anti-La. Antiphospholipid antibodies are present in 25–40% of cases but not all of these patients develop antiphospholipid syndrome (see below).

• Serum complement  C3 and C4 levels are often reduced during active disease. The combination of high ESR, high anti-dsDNA and low C3 may herald a flare of disease. All these markers tend to return towards normal as the flare improves, but in some patients, anti-dsDNA levels remain high even during clinical remission.


What are your differential diagnoses for her current Emergency Department presentation?

(- Rheumatoid arthritis can affect many systems of the body

- Look up a basic definition of COPD and one or two features that would link to the history of cough and sputum)




You request a chest x-ray to evaluate her cough and shortness of breath. See image below.

a)  What are the differentials for the chest imaging in this patient? In thinking about the chest X-ray, think broadly as to what might cause the abnormal shadows. Patients with rheumatoid arthritis have an immune system that is activated (but in some areas is dysfunctional) and the treatment for rheumatoid arthritis is designed

b)  What do you do next?
Think of a common sense answer as if you were a foundation doctor.



a)  What is the likely diagnosis based on these results?
What is the D-dimer test?
What does the D-dimer test result suggest?
Look up two or three facts about the D-dimer test.  You will cover the principles of clotting separately.  However, the use of the D-dimer test is something you will come across frequently.  Do not make notes on the whole of clotting; but just a sentence on D-dimers (at this stage) Then think again about the likely explanation for her cough and green sputum
c)  What steps do you take next? If you consider that a chest infection is a possibility, you will recall from the Infection Unit that we referred you to the UHL Antimicrobial website.  You can access this via the Infection Unit on BlackBoard.  It has guidance on the assessment of pneumonia; which you will cover again in the Respiratory Unit this semester. The pneumonia guidelines are also added to the material for this session.




1. Polyarthritis is defined as? 

1. pain, with or without inflammation, that affects more than four joints. With polyarthritis, over time, there is a risk of even more joint involvement. Polyarthritis is also sometimes referred to as polyarthralgia. Arthralgia means painful joints. Arthritis means inflamed joints.


RA is an?

- autoimmune disease

- autoantibodies to the Fc portion of immunoglobulin G (rheumatoid factor) and to citrullinated cyclic peptide

- persistent synovitis, causing chronic symmetrical polyarthritis with systemic inflammation.  


Articular manifestations of Rheumatoid arthritis 

RA typically presents (approximately 70% of cases) as a progressive, symmetrical, peripheral polyarthritis, evolving over a period of a few weeks or months in patients between 30 and 50 years of age, although the disease can occur at any age RA is primarily a synovial disease, and synovitis occurs when chemoattractants produced in the joint recruit circulating inflammatory cells. Over-production of tumour necrosis factor alpha (TNF-α) leads to synovitis and joint destruction. Interaction of macrophages and T and B lymphocytes drives this over-production. TNF-α stimulates over-production of IL-6, as well as other cytokines. The increased understanding of the immunopathogenesis of this disease has informed the development of targeted biological therapies. Blockade of TNF-α and IL-6 has produced marked improvement in synovitis and systemic malaise, indicating the pivotal role of these cytokines in the chronic synovitis



Non-articular manifestations of Rheumatoid arthritis (Kumar and Clark):



Drug history:  “She has however taken ibuprofen consistently for the last 1 week.” What might be the consequence of this sentence? Ibuprofen is a common Non-steroidal Anti-inflammatory Drug (NSAID).  

The mode of action of the NSAIDs is via inhibition of Cyclo-oxygenase (COX) enzyme. This affects a number of inflammatory molecules.  NSAIDs can cause damage to the stomach directly on ingestion and systemically. Renal adverse drug reactions can also occur in susceptible individuals although therapeutic dosage in otherwise healthy patients do not cause problems. However, in this patient there may well be some renal compromise as part of the SLE.

1. It's one of a group of painkillers called non-steroidal anti-inflammatory drugs (NSAIDs) and can be used to:




ease mild to moderate pain – such as toothache, migraine and period pain

control a high temperature (fever) – for example, when someone has the flu (influenza)

ease pain and inflammation (redness and swelling) caused by conditions that affect the joints, bones and muscles – such as rheumatoid arthritis and osteoarthritis

ease pain and swelling caused by sprains and strains – such as sports injuries


You should use ibuprofen with caution if you're aged 65 or over, breastfeeding, or have:


kidney or liver problems 


Crohn's disease or ulcerative colitis

previously had any bleeding in your stomach 

high blood pressure (hypertension)

narrowing of the arteries (peripheral arterial disease) 

any problems with your heart, such as angina, heart attacks, or mild or moderate heart failure

had a stroke


Common side effects of ibuprofen include:

nausea or vomiting 

constipation or diarrhoea 

indigestion (dyspepsia) or abdominal pain


Bilateral feet swelling: Bilateral swelling of feet is an important clinical presentation.  You covered some aspects of this in Year 1 when you looked at the composition of blood and the movement of fluids.  You also had a session on heart failure, where swelling of feet can occur.  You are presently doing the Urinary Unit where you will learn how the kidney helps to maintain the level of protein in the blood.  Albumin is the main protein.  If the kidney loses protein in the urine (rather than keeping it in the blood) then the level of albumin in the blood will fall and the oncotic pressure in blood vessels will fall and fluid will leak out of the blood vessels into the surrounding tissue. 


1.  What are the differential diagnoses you consider for this current presentation?

i) Poorly controlled lupus with new lupus nephritis

ii) Acute kidney injury from NSAID use

iii) Flare of lupus

2.  She had blood tests and a urine dipstick done. The blood tests are still awaited but the urine dipstick is available.  See image below.



NOTES: In a later session in the Urinary Unit you will have a practical using dipstick to test various urine samples.  By then you will have a better understanding of the abnormalities found in urine. However:
•  In the Infection Unit last year you had a case of a patient with a urine
infection.  We discussed the interpretation of Nitrites and Leucocytes in the Urine.  Look this up.
•  In the Urinary Unit, you will learn that the finding of blood and/or protein
in the urine is almost always abnormal.  Blood can come from anywhere in the urinary tract.  The combination of blood and protein in the urine usually implies an abnormality of the glomerulus.
a)  What abnormalities are indicated in the urine dipstick?
b)  What possible causes do you consider?
c)  What investigations would you do based on this result?
d)  What do you do next?
Urine dipstick suggests
•  Urinary tract infection suggested by nitrites and leukocytes
•  Some problem of the kidney with both blood and protein. Investigations i)   Send of urine for urine protein-creatinine ratio to quantify proteinuria ii)   Send-off Urine MCS in view of positive nitrites Next step:  Inform her rheumatologist



NOTES You will cover both of the points below in the Urinary Unit. Serum creatinine is an important indicator of renal health because it is an easily measured byproduct of muscle metabolism that is excreted unchanged by the kidneys. If the filtration in the kidney is deficient, creatinine blood levels rise.  A rise in blood creatinine level is a late marker, observed only with marked damage to functioning nephrons. Glomerular filtration rate (GFR) describes the flow rate of filtered fluid through the kidney The eGFR is the estimated glomerular filtration rate and is calculated from a blood test. If the GFR falls and is below normal it implies the kidney and glomerulus is not working properly What is the likely diagnosis (or diagnoses) and why is the CRP elevated?
i)  Raised anti-DSDNA antibodies and low complement is in keeping with
ii)  Also Antibiotics for UTI is required as CRP rise in the context of SLE is
active lupus with lupus nephritis. suggestive of infection.




When cells die by apoptosis, the cellular remnants appear on the cell surface as
small blebs that carry self antigens. These antigens include nuclear constituents
(e.g. DNA and histones), which are normally hidden from the immune system. In people with SLE, removal of these blebs by phagocytes is inefficient, so that they are transferred to lymphoid tissues, where they can be taken up by antigen-
presenting cells. The self antigens from these blebs can then be presented to T
cells, which in turn stimulate B cells to produce autoantibodies directed against
these antigens.
 It has been shown that, in some patients, the autoantibodies are present in stored blood samples that were taken years before the patient developed clinical features of SLE. The combination of availability of self antigens and failure of the immune system to inactivate B cells and T cells that recognize these self antigens (i.e. a breakdown of tolerance) leads to the following immunological consequences.

•  Development of autoantibodies that either form circulating complexes or deposit by binding directly to tissues.

•  Activation of complement and influx of neutrophils, causing inflammation in those tissues.

•  Abnormal cytokine production



Clinical features of Systemic Lupus Erythematosus



•  Definition of autoimmunity vs autoimmune diseases

•  Recognize the clinical evidence that supports a role of autoimmunity in the pathogenesis of autoimmune disease

•  Understand the difference between organ specific and non-organ specific autoimmune disease

•  Describe the causes and mechanisms of autoimmunity

•  Describe the current and future therapeutic strategies of autoimmune disease



Definition of autoimmunity vs autoimmune diseases LO

1. Autoimmunity: 

2. Autoimmune disease: 


1. Autoimmunity: Immune response against the host due to the loss of immunological tolerance of self-antigen(s)

2. Autoimmune disease: Disease caused by tissue damage or disturbed physiological responses due to an auto-immune response



Understand the difference between organ specific and non organ specific autoimmune disease LO


State some common autoimmune organ specific diseases and non - organ specific diseases



Give the breifest description (one word) of these autoimmune diseases 


Immune mechanisms of tissue damages 


Set of criteria for the diagnosis of a disease as autoimmune: (3)


1. Presence of autoantibodies/autoreactive T cells

2. Levels of autoantibodies correlate with disease severity

3. Autoantibodies/autoreactive T cells found at the site of tissue damage

4. Transfer of autoantibody or autoreactive T cells to a healthy host induces the autoimmune disease

5. Clinical benefit provided by immunomodulatory therapy

6. Family history




Detection of autoantibodies and autoimmune disease

Which autoimmune diseases are specific and non-organ specific 


Always think about the specificity of the tests



What tissues must you use to detect the autoantibodies and the technique you use to detect it?


1. Which immunoglobulin is transferred during preganancy

2. Complete the table 



Briefly describe the causes and mechanisms of autoimmunity & the current and future therapeutic strategies LO 



What triggers autoimmunity?



Genetic factors

• Increased risk with an affected sibling (8X)

• Increased risk with an affected identical twin (30X)

• AIRE mutations (APECED syndrome) that affect central tolerance 

• Autoimmune disease associated with MHC variants (HLADR3/DR4)

Environmental factors

• Hormones

• Infections

• Drugs


Give examples of infection-induced autoimmune disorders



Give examples of drug-induced autoimmune syndromes



Briefly describe the causes and mechanisms of autoimmunity & the current and future therapeutic strategies




1. Autoimmunity is responsible for large spectrum of major chronic disabling conditions

2. Autoimmunity can affect any organ in the body leading to either tissue damage or altered physiological function

3. Different criteria must be fulfilled to confirm that a particular autoimmune cause a corresponding autoimmune disease

4. Interactions between different factors such as ? could play an important role in the causation of autoimmune disease

5. Therapy is guided by the ?

6. ? appear to be the next promising therapeutic alternative for autoimmune disease


4. infection, drugs, gene susceptibility

5. targeted organ, the type of immunological mechanisms involved and the harmful effects

6. Monoclonal antibodies