The DMARD pyramid

How to remember the DMARDS commonly used in rheumatoid disease?

There’s a special place, where all of the people suffering from crippling rheumatoid arthritis can go for treatment. It’s a huge golden pyramid with a log flume running down from the top.

  • Gold
  • Leflunemide (pyrimidine synthesis inhibitor)
  • pyramid also describes the therapeutic pyramid of drugs in rheumatoid arthritis

At the top is a meth addict with spina bifida who tells you when you can ride the flume. He shouts go, and turns on a huge hydro-chlorine hose that fires you down the chute. The chlorine is to keep the mosquitos away.

  • Methotrexate (folate antagonist)
  • Hydroxychloroquine (antimalarial)

At the bottom you land in a huge pit full of aspirin pills that stink of sulphur, each of which is the same size as a thigh of pure chicken.

  • Sulfasalazine (5-ASA salicylate)
  • Azathioprine (purine analogue)

It’s a suitably weird story, feel free to make up your own….


The Story

Here’s a story to help remember the key features of SLE:

Mrs Lupus is an African woman who has felt tired for as long as she can remember. She has also recently noticed a rash across her cheeks. She’s also had some joint pain and has noticed her skin reacts when she is exposed to bright sunlight. She also finds she gets mouth ulcers and her hair has fallen out in some places, leaving patches of baldness that are upsetting her.

  • Ethnicity risk 
  • Female gender risk
  • fatigue
  • malar rash
  • arthritis
  • photosensitivity
  • mouth ulcers
  • alopecia

She’s recently had a nasty bout of glandular fever, which she recons is because of her low white blood cells. It’s also made her feel very low in mood, and she’s had a pounding headache ever since it started.

  • trigger – viral infection
  • lymphopaenia/leucopaenia are early clues to SLE
  • neuropsychiatric manifestations

You ask her about her chest, and whether she has had any difficulty breathing or chest pain, to which she says she feels short of breath and has chest pain a lot of the time, which is made better by sitting forward. She also doesn’t like to go out in the cold, as it makes her fingers go blue

  • Pleurisy
  • Pericarditis
  • Raynaud’s phenomenon

Mrs Lupus is planning to have a baby, but wanted to ask you about the best course of action with regard to her treatment beforehand.

  • Pre-pregnancy counselling is vital to ensure optimal disease control


You decide she most likely has SLE, so what investigations are you going to do?

To diagnose and monitor her condition:

  • Full blood count
    • White cell count
  • Urinalysis
  • Serum Creatinine
  • ANA
  • Anti-extractable nuclear antigen
  • Anti-ribonucleoprotein = mixed connective tissue disease
  • Anti-dsDNA = useful for predicting those at risk of renal disease
  • Complement
    • C3 and C4 fall with disease activity

In women who are planning pregnancy, it is important to check for:

  • anti-Ro
  • anti-La
  • antiphospholipid antibodies


So now you’re pretty convinced Mrs Lupus has Lupus. What are you going to do to help her?

There are a few categories of management that can be employed:

  • Education
  • Pharmacological intervention
  • Risk managment

Education involves ensuring your patient understands their condition and what it entails. Leaflets and websites can help with this too. You should also give lifestyle advice:

  • avoiding sun exposure
  • avoiding infection
  • using appropriate contraception

Pharmacological intervention includes:

  • Corticosteroids
  • Hydroxychloroquine
  • Azathioprine
  • Methotrexate
  • Cyclosporin
  • Leflunomide
  • Cyclophosphamide
    • often given as ‘pulse’ intravenous therapy
      • usually for systemic vasculitis and proliferative glomerulonephritis
  • Mycophenolate mofetil

The basics:

  • autoimmune, multi-system, chronic disease associated with genetic and environmental risk factors
  • more common in women and non-white ethnicities
  • Lupus nephritis occurs in around half of patients
  • patients need to be counselled before pregnancy to optimise control of the disease
  • cardiovascular disease is a growing cause of death

Clinical features:

  • Arthritis
    • non-erosive (Jaccoud’s arthropathy)
    • generalised arthralgia with morning stiffness but no swelling is very common
  • Alopecia
  • Skin rash (discoid)
  • Photosensitivity
  • Malar rash
  • Oral ulcers
  • Fever
  • Neuropsychiatric
  • Renal
  • Cardiac
    • Pericarditis
    • myocarditis
    • endocarditis
    • pericardial tamponade
    • vasculitis
  • Haematological
    • leucopaenia early clue to SLE diagnosis
    • lymphopaenia most common manifestation of SLE other than positive ANA
    • mild neutropaenia relatively common in black people, but <1.5×10(9) is usually pathological
  • Pulmonary/pleural
    • pleurisy
    • lupus pneumonitis
    • pulmonary haemorrhage
    • pulmonary embolism
    • pulmonary hypertension
  • positive ANA (antinuclear antibodies)

Genetic factors:

  • HLA-DR2 and HLA-DR3
  • Complement C1q, C4 and C2
  • FcyRIIA, FcyRIIIA and FcyRIIB
  • CTLA-4 (a negative regulator of T cells)
  • PDCD-1 (CD28 immunoreceptor)
  • Cytokine genes IFN-a and TNF-a

Environmental triggers:

  • Drugs
    • minocycline, procainamide, hydralazine
  • Ultraviolet light
  • Viral infection
    • EBV, CMV, Retroviruses, parvovirus B19
  • Hormones
    • oestrogens
    • prolactin
  • Chemicals and heavy metals
    • silica, mercury
  • Diet
    • L-canavanine in alfalfa (maybe)

Anaemia in Lupus:

  • Normochromic normocytic anaemia of chronic disease
  • Antibody-mediated haemolytic anaemia
  • Iron-deficiency due to diet
  • Iron-deficiency due to blood loss
  • Pernicious anaemia (autoimmune)

(information from ABC of Rheumatology: Adebajo)

Ankylosing Spondylitis

I find it really hard to remember the features of the individual rheumatic conditions because there is so much overlap, so I started making stories for each to try and get it straight in my head. Today’s is Ankylosing Spondylitis, one of the several seronegative spondyloarthropathies that is not massively common (1/100 000) but still important as it has a huge impact on the person’s life, and you might be able to do something about it!

The Story

You are a GP in your surgery, and you call for your next patient to come in. Three caucasian males all come limping in and very slowly sit down with a grown on the bed. One of them is 27, the next is his dad, and the third his grandad.

  • 3:1 male:female ratio
  • Caucasians more affected (higher HLA B27 prevalence)
  • Enthesitis (inflammation of tendinous insertions, particularly in the lower limbs)
  • Inflammatory back pain with reduced flexion of the lumbar spine
  • Family history
  • Usually between 20-30 years of age

You take ask them what it is that’s brought them in today.

The first man pipes up, “Well doc, I’ve just been feeling really tired, and this pain in my back has been getting worse and worse on both sides

  • Gradual onset
  • Bilateral sacroiliitis
  • Fatigue is common early sign (often before any physical symptoms)

You examine him and the first thing you notice is he has one very red eye, as does his father, and grandfather. You ask him when his eye became red, and he said it was when they were cooking sausages on the barbecue and some of the fat spat up into his eye. The father and grandfather nod bashfully.

  • Anterior uveitis
  • Iritis – typically unilateral
  • Sausage fingers – dactylitis

You then continue your exam and notice he’s got a mangled left leg, which you ask about:

Well doc, I was on my motorbike with my girlfriend Amy, and the engine started coughing and spluttering. Then a valve blew and we crashed, she died and I snapped my achilles and fractured my leg! I lost loads of blood and I’ve been having temperatures ever since – but I’ve lost some weight so that’s good I guess…”

  • Main causes of mortality in Ankylosing Spondylitis
    • Amy – Renal amyloidosis 
    • Coughing – Respiratory disease (upper lobe bilateral fibrosis)
    • Valve – Cardiovascular (particularly valve disease)
    • Fractures
  • Achilles – enthesitis particularly affecting insertion of Achilles tendon and plantar fascia (also intercostals)
  • Extra-articular features:
    • Anaemia
    • low grade fever
    • weight loss

How to examine the hands

OSCEs are interesting beasts. They’re designed to measure one’s clinical prowess, although end up being a very artificial process that requires specific attention to learn, rather than just clinical experience. As a result, examinations in particular end up becoming a rehearsed routine that can be rattled off under intense pressure, without much actual thought as to what one is looking for in the first place. What I’ve tried to do here is write the ‘script’ but also give an idea of what to be thinking along the way, to help answer examiner questions and also to help be an actual doctor (which I’m hoping is the ultimate goal). Of course everyone will have their own style, and this is simply my own, but hopefully it might provide a useful framework. In particular I find it much easier to demonstrate movements rather than trying to describe them, and it helps build rapport between you and the patient if they’re playing a game of copying you #psychologywin.

The Dance


*Student enters cubicle, washes hands and smiles*

“Good morning, my name is Will Sloper, I’m one of the fourth year medical students, I’ve been asked to do a quick examination of your hands, would that be alright?”

*Patient says yes*

“Thank you, may I ask your name? And how old are you if you don’t mind me asking”

(please could I ask you to roll up your sleeves?/remove your jumper?/put the cat down?)

“Before I begin, are you in any pain at the moment?”

*Patient says no/a little/yes my hand hurts*

“Great/Okay well I’ll be quick and do my best not to cause you any (more) pain. Is there anywhere that’s really sore to touch?”

*patient points at specific point*

“Alright, I’ll avoid that finger/bruise/bleeding open fracture as much as I can”

*Student offers cushion to patient. Patient places hands palms down on cushion on lap or table*


“Firstly I’ll have a look at your wrists…”

*Student looks intently at wrists*

“…your hands…”


“…your fingers, and nails.”

*Student dwells on nails slightly to ensure examiner knows they have been thoroughly inspected*

“Lovely, please could you turn your hands over?”


*Patient turns hands over, while student watches patient’s face*

“Was there any pain while turning your hands over?”


“I’ll have a quick look at your palms…”

*Student looks intently at palms*

“…and wrists…”



Now if it’s alright I’ll feel your wrists and palms”

*Student feels pulses, then the thenar and hypothenar eminences and then the palm*

“Lovely, thank you, can you please close your eyes for a moment and say ‘yes’ if you can feel me touch your hand?”

*Student lightly touches both eminences and index and little finger tips*

*yes, yes, yes, yes…*

“Does this make your fingers tingle?”

*Student lightly taps skin over carpal tunnel*


“Great, put your palms down again please and I’ll do the same on the back”

*Patient turns hands over, student watches face again*

“Close your eyes again and say yes if you can feel this”

*Student lightly touches first dorsal interosseous*


“Thank you”

*Student places backs of hands on forearm for 2 seconds, wrist, then over the mcp joints*

“Let me know if this is at all tender” (if patient has identified tender area, address the fact that you do have to touch it, but will be as careful as possible)

*Student lightly squeezes the mcp joints while watching the patient’s face*

“I’ll now have a quick feel of each joint in turn”

*Student bimanually palpates each joint in turn, comparing each group with the other hand, and watching the patient’s face the whole time*

“Thank you, I’ll just do the same on your wrists”

*Student bimanually palpates wrists, guess what, while watching the patient’s face*

“Lovely, now I will just feel your forearms”

*Student runs hand up ulnar aspect of forearm while holding wrist with other hand*


“Right, we’re almost there!” *smiles*

“Lastly I need you to do some movements for me if that’s alright, could I ask you to straighten your fingers as much as you can”

*Student then passively extends patient’s fingers gently, while watching the patient’s face*

“Thank you, next can you make a fist for me?”

*Student passively flexes patient’s fingers gently, again… FACE*

“Now could you do this?” *Student extends own wrists and places them together in prayer position in friendly and personable style*

*Patient copies student, #facialsurveillance*

“And now this?” *Student flexes own wrists and places together in equally nonthreatening manner*

*Patient copies student, #facialsurveillance*

Squeeze my fingers as hard as you can?”

“Finally could you spread your fingers as far as you can, and then do this?…”

*Student opposes thumb to each finger in turn, and patient does the same*

“…and could you pick this up for me with your index finger and thumb?”

*Student produces coin/magic bean/small rodent*


“Well thank you very much, I’ve finished my examination, do you have any questions for me?”

*Patient says no*

“Thanks again”

*Student smiles, washes hands and turns to examiner*


“I performed an examination of the hands and wrists on Mrs Phalange who reported tenderness in her left wrist and upon inspection, noted the presence of a longitudinal scar/slight bruise on the dorsum of the right hand. The rest of the examination was normal, with sensation of the median, ulnar and radial nerves intact and good movement and function of all joints”

(Obviously this bit is going to vary hugely – practice making up a bunch of different presentations and you might find that in the exam, you can adapt one you’ve already made to fit your current patient)

“To complete my examination, I would like to:

  • take a full history
  • do a regional musculoskeletal exam of the elbow
  • do a neurological and peripheral vascular exam of the upper limbs

Why do the exam?

The main purpose of the hand exam is to elicit whether the patient has any:

  • pain
  • stiffness
  • reduction of function
  • evidence of previous disease/surgery

And as with all musculoskeletal examinations, it’s a good idea to follow a structure of:

  • look
  • listen
  • feel
  • move

And always, always, always…

  • ask about pain
  • compare the two sides

The things to look out for in the hand exam are as follows:

  • Looking
    • swelling
    • muscle wasting
    • deformity
    • skin changes
      • bruising
      • thinning
      • rashes
    • scars
    • nail changes
      • onycholysis
      • pitting
      • vasculitis of nail folds
  • Feeling
    • pulses
      • vascular impairment?
    • muscle wasting
      • may suggest nervous injury or carpal tunnel syndrome
    • tendon thickening
    • sensation
      • carpal tunnel, peripheral neuropathy
    • temperature
      • inflammation is hot
      • Raynaud’s is cold
    • nodules
      • Heberden’s nodes in osteoarthritis
      • gouty tophi
      • rheumatoid nodules
    • squeezing
      • tenderness is early sign of inflammation
    • joint palpation
      • warm, rubbery swollen joints are suggestive of active synovitis
    • Tinel’s test
      • special test for carpal tunnel syndrome
    • Phalen’s test
      • same idea
  • Moving
    • failure of movement could be:
      • muscular
      • neurological
      • tendinous
      • articular
    • Passive extension may help determine which
    • Picking up a coin/small rodent gives an idea of function