Seronegative Arthropathies

Tom Grant

Professional spoon cleaner Dan Waite enters your clinic, and says that he has been casually reading about arthritis on Bing. You tell him that Bing is a terrible search engine. He wants to know what on earth is a “seronegative spondyloarthropathy”. You decide to break it down for him. What is it?

Sero Negative Spondylo arthr opathy

Serum (plasma) absence of RF vertebra joint of disease

Nick Gould, a loveable rogue, enters your clinic with symmetrical knee joint pain. Knowing only this, which of the conditions below is it likely to be?a) Psoriatic arthritis

b) Rheumatoid arthritis

c) Reactive arthritis

d) Gout

e) Pseudogout

* Note that symmetrical joint involvement tends to occur in systemic syndromes such as RA and SLE.

What antigen would most likely be present in a seronegative arthropathy?

a) HLA DR2

b) HLA DR3

c) HLA DR4

d) HLA B27

e) PSA

What is the difference between septic arthritis and reactive arthritis? (2)Septic arthritis is an infection of a joint

Reactive arthritis is a systemic autoimmune inflammatory reaction to infection. The joint(s) is sterile.

Septic arthritis (a clinical emergency – look for the triad of fever, pain and impaired range of motion)

Alison Gourley, 64, angry Canadian, rides into your clinic on her pet moose. She complains that over a few hours yesterday evening her right knee had become red, swollen and extremely sore. She is unable to move it for pain. She has also been feeling quite feverish. What condition is important to rule out early on?

What will not be present in blood tests of most people with seronegative arthropathies?

a) HLA B27

b) CRP

c) Rheumatoid factor

d) T lymphocytes

e) Neutrophils

What joint is usually inflamed first in ankylosing spondylitis?

a) PIPs

b) DIPs

c) Axial-Atlas Pivot joint

d) Sacroiliac joints

e) Hip joints

Which of the following in particular might we expect to find in a patient with gout?

a) Hypercalcaemia

b) Hyperkalaemia

c) Hypernatraemia

d) Hyperuricaemia

e) Hypovolaemia

Your lecture refers to “primary” and “secondary” hyperuricaemia. What is the difference between primary and secondary hyperuricaemia?

Primary = Increased production of uric acid from purine, kidneys cannot get rid

Secondary = high uric acid levels due to another disease or condition (e.g. cancer, CKD, chemotherapy)

NOTE: Generally be aware that a primary condition is not preceded by a different condition. Consider:

-Primary hyperthyroidism vs secondary hyperthyroidism

-Primary hyperparathyroidism vs secondary hyperparathyroidism

-Primary/essential hypertension vs Secondary hypertension

(see slide notes)

Gout involves the deposit of sodium urate crystals. What forms the crystals in pseudogout?

a) Methamphetamine

b) Hydroxyapatite

c) Potassium

d) Calcium oxalate

e) Calcium pyrophosphate

A disreputable shmuck named Sherif Kirollas comes into your clinic. He smells a bit like cucumber. He has a history of ankylosing spondylitis, and you ask him to bend forwards after making a mark 5cm below his fifth lumbar process and 10cm above. The distance barely increases, to 16cm on flexion. What test have you performed?a) Weber’s test

b) Rinne’s test

c) Thompson test

d) Schober test

e) Thomas test

Autoimmune inflammation -> formation of bony ankyloses -> vertebral fusion

Why is the distance increase here less than we might expect? (1)

You give Mr Kirollas some drugs for his pain. He comes in 2 weeks later, complaining that he is suffering from heartburn. Which of the drugs prescribed for his ankylosing spondylitis is likely to have caused this new symptom?

a) Ibuprofen

b) Methotrexate

c) Sulfasalazine

d) Amitriptyline with gabapentin

e) Paracetamol

Fine diner James Goadsby comes into clinic complaining of joint pain towards the end of his fingers. You notice the following on physical examination:

Pitting of nails Psoriatic plaques Dactylitis

Psoriatic arthritis

What is the likely diagnosis? (1)

What is evident in each of the above images? (3)

Mr Ranika Bennett, 34, comes into your clinic, and he complains that his knees and hips have felt quite stiff for about a week, and that they are painful on movement. A couple of days before this started he had painful urination, and this was shortly followed by a painful eye, with a white stringy discharge. About 3 weeks before he had come in with a bout of food poisoning. What is the likely diagnosis?

The classical triad of symptoms is conjunctivitis, urethritis, arthritis

MNEMONIC -> *Can’t see, can’t wee, can’t climb a tree*

The condition commonly occurs a few weeks after a GI or urogenital infection

Reactive arthritis (Reiter’s syndrome)

Will rheumatoid factor be raised in Ranika Bennett?No – it is a seronegative condition

Yes (meaning blood cells will sediment faster, due to increased fibrinogen)

Yes – and this is raised more rapidly than ESR (and will also return to normal more rapidly than ESR – since it takes time for fibrinogen to be removed from serum)

Will CRP be raised in Ranika Bennett?

Will ESR be raised in Ranika Bennett?

And now for a little bit of microbiology…

Rheumatoid Arthritis Ankylosing Spondylitis/Reactive arthritis/Psoriatic arthritis

Associated antigen HLA DR4 HLA B27

What MHC corresponds to the antigen?

MHC class 2 MHC class 1

What immune cells respond to the MHC molecules?

T4 cells (helper cells) -> these activate B cells, which produce immunoglobulins such as rheumatoid factor (an isotope of IgM)

Mainly T8 (cytotoxic) cells (but also NK cells)

Therefore, will condition be seropositive, or seronegative?

Seropositive -> presence of rheumatoid factor immunoglobulin

Seronegative -> absence of rheumatoid factor

We’re told all about MHC1 and 2, HLA DR4, HLA B27, and immune cells. How does it all fit together?

Memory tip: HLA A-, B- and C- have one letter after HLA, so are MHC class 1.HLA DR-, DQ-, DS- have two letters, so are MHC class 2

Any questions?t.s.grant@warwick.ac.uk

Any stinging criticism?

d.waite@warwick.ac.uk