Rheumatology

HLA B27 ,SERONEGATIVE ARTHRITIS

HLA B51- Bechets disease

HLA-B8DR3- Sjogrens syndrome

HLA DR1/DR4 RHEUMATIOD ARTHRITIS-HLA-DR4 seen in 50-80% of RA and correlates with poor
prognosis

HLA B8/DR3- GRAVES DX ( HLA B7 IS PROTECTIVE)

A) SLE(HLA B8, HLA DR2/DR3)

Monitoring disease activity in SLE:

- Anti-dsDNA levels,
- C3 and C4 levels( low levels indicate complement consumption , and there willbe high levels
of C3d and C4d),
- ESR
- CRP IS NORMAL IN SLE

Antibodies seen : ANA (95%)

Anti dsDNA( highly specific) ( anti ds DNA seen more frequently in drug induced
lupus)

RF (40%) this is testing using the IgM antibody test,

Anti Ro , Anti La, Anti SM, Anti RNp(20%)

Fetal lupus ( is due to placental transfer of anti Ro antibody)- can cause hrt block
in the baby

Anti Histone Ab( Drug induced SLE)

Signs/symptoms

- Malar rash that is photosensitive

- Arthritis- this is classically non erosive
It is present in 90% of cases
Typically radiological features will show swelling and effusion of joint.
Rarely aseptic necrosis may occur
Increased risk of osteoporosis
 Pleuritis/effusion- most common casue of breathlessness in SLE

Pericarditis: most common cause of chest pain in SLE ( there may be effusion too). They
have increased risk of cardiovascular disease

- Lymphopenia and thrombocytopenia- give an indication of disease activity.

- Haemolytic anemia
- Oral ulcers- Most common GIT presentation
- CNS- seizures, psychosis

Drug induced SLE- rarely affects the kidney. Lungs and skin are more commonly affected.

causative drugs

INH/pyrazinamide

Hydrallazine

D-penicillamine

MInocycline

Phenytoin/carbamezapine/chlopromazine

SLE treatment

a.) Lupus nephritis steroid and cyclophosphomide. If renal replacement occurs, > 50% can
have recurrence of the nephritis.
b.) Maitaininace treatment : NSAIDs and hydroxycholoquine.
c.) Steroid sparing agents : MTX, mycophentolate, azathioprine.
d.) Anti CD20 monoclonal antibody- rituximab can be used ( Not licensed yet)

B) Rheumatoid arthritis:

HLADR4 and HLA DR1 are associated with increased severity.

A chronic artrhitis

RF +ve ( 70%)- high titres indicate active and severe disease.

Anti cyclic citrullinated peptide antibody(anti-CCP) highly specific for RA

Feltys syndrome: seen more in people with HLADR4 (90-95%)- xterized by spleenomegaly, RA and
neutropenia.
RA affects MCP, PIP, MTP joints first symmetrically. Earliest joint changes seen radiologically are
effusion, osteopenia and reduction in joint space. Bony erosions are seen unlike in SLE where there
are no erosions . episcleritis, scleritis ( unlike uveitis which is seen in Seronegative arthritis)

Poor prognostic features-

female, gradual onset of disease, anaemia occurring withi 3/12 of disease, positive IgM Ab RF, Anti
CCP positive

Long term compliacations

- amyloidosis,
- Atlatoaxial joint dislocation which can cause spinal cord compression
- Frozen shoulder, carpel tunnel syndrome and de Quervian tenosynovitis
- increased rate of artherosclerosis thus increased risk of CVS and CNS disease. Cardivascular
disease is a leading cause of death in RA patients
- Rotator cuff tear- seen in elderly and there will be inability to abduct arm
- Pleural effusion- its usally an exudate and the pleural fluid will have : high levels of (LDH,
Cholesterol) Low glucose and pH < 7.2. If the glucose content is high then think of another
cause of the effusion.

Disease activity monitored by the DAS28

Treatment:

- Nsaid, PCM for pain- do not alter course of disease

- Steroids- rapidly reduce inflammation and used for flares of disease
- DMARDS ( all cause neutropenia)

A- Sulphalazine A 5 aminoslicylate given orally and metabolised by gut bacteria to form

mesalazine. Also used for the treatment of ulcerative colitis.

Major side effect

myelosupression, reversible oligospermia, Steven Johnson syndrome type of rash , oral ulcers.

Monitoring treatment: measure CBC every 2/52 for three months and then every 3/12 .

Measure LFT every month for 3/12 then three monthly thereafter.

Stop treatment if WBC < 4, neutrophil< 2, platelets < 150 or a two fold increase in ALT /AST

B. MTX( hepatotoxic, folic acid antagonist): 1st choice for DMARD. The drug is myelosupressive and
cn cause pulmonary fibrosis. Also pregnancy should be avaoided for six months after stopping the
drug

C. IM gold: Used for RA

Side effects: Rash and irreversible pigmentation on sun exposed areas.

 Protenuria, Membranous glomerulonephritis

Can cause myocardial infarction esp in people taking ACE-I

D. Leflunomide: A second line DMARD, used after MTX and Sulphalazine. The drug is teratogenic
and not to be used in pregnancy and preagnancy should be avaoided for at least two years after
stopping the drug.

SIDE EFFECT. hypertension, oral ulcers, teratogenic. Measure Blood pressure every month

E. Hydroxycholoquine (irreversible retinopathy)

Synovium in RA produces TNF-A, IL-6 and IL-1, TGF-ALPHA, and PDGF

F. Biological agents: (TNF-A inhibitors)- given there is failure to respond to > 2 DMARD

Etharnecept, infliximab. Admnistered subcutaneously.

Contraindicated in those with : history of Hep B/C, Multiple sclerosis, pregnancy, stage 3 or 4
cardiac failure, Latent TB , Haematological malignancy, and not to be used with sulphasalazine
because it can cause profound neutropenia.

Side effect : hrt failure, lymphomas, reactication of TB

Avaoid pregnancy for 6/12 after stopping treatment

Monoclonal Anti CD20 ( rituximab) used with MTX where Anti TNF a have failed

Seronegative arthrtitis

- HLA B27
- RF ngative
- Classically affect axial spine( sacroiliac joint)
- Enthesitis ( Achilles tendon rupture, costochondritis)
- Dactilytis( sausage shaped digits)
- Assymmetrical olioarthropathy
- Uveitis, scleritis, aortic valve incompetence, oral ulcers, inflammatory bowel disease,
osteoporosis( 60%) ,
- Psoriaform rash

Ankylosing spondilitis

Earliest radiological finding in AS- blurring of sacroiliac margin, sacroilitis and subchondral scelrosis
at sacroiliac joint, Late features seen are formation of syndesmophytes due to entisitis of tendons
attacing to spine, and very late features seen is fusion of the spine (bamboo spine)
Complications of AS- apical pulmonary fibrosis, aortic valve incompetence, osteoporosis( >60%) ,
anterior uveitis,

- treated with NSAIDS, TNF-A inhibitors in severe disease

Long term complication ( amyloidosis, heart disease)

Psoriatic arthritis

Affects DIP joints

Asymmetrical oligoarthritis

Causes joint erosion ( pencil in cup deformity)

There will be nail changes in >80% cases

Treatments- if there is psoriasis with arthritis the treatment of choice is TNF-A inhibitors

Pseudo gout

( positively bifringent rhomboid shaped crystals)

Risk factor for pseudogout

Old age, Diabetes, Wilsons disease, hemechromatosis, osteoarthritis, hypomagnesaemia,

hypophospataemia, hypothyroidism, hyperparathyroidism.

Gout

( negatively bifringent needle shaped crystals)

Indications for allupurinol in gout

: recurrent attacks, tophi, uric acid stones, patient on chemotherapy.

 Osteoporosis

Normal calcium , normal phosphate, normal alkaline phosphatise

Dexa scan is used to screen for bone demineralization .The hip is scanned and a T score is used to
determine the level of decreased bone mas

T score 0 to -1 : normal

T score -1 to -2.5 : osteopenia

Tscore < -2.5 : osteoporosis

Bisphosphonates: ( reduce the risk of further fractures once one has occurred.) Bisphosphonates,
are incorporated in to bone and are resistant to enzymatic destruction. Thus they prevent
dissolution of bone minerals and inhibit osteoclast action

NICE guidelines for use as 1st line treatment in

- All aged > 75yrs

- All aged > 65yrs with T score less than -2.5
- All aged < 65yrs with DEXA less than -3 and confirmed osteoporosis

If Bisphosphonates cant be tolerated then

Raloxifene may be used.

Uses of Bisphosphontes:

- Osteoporosis ( post menopausal and steroid induced)

- Hypercalcaemia due to malignancy
- Pagets disease
- Bone pain due to lytic bone metastasis

Bisphosphontes should be taken standing with alot of water on an empty stomach 30mins before
food. They can cause oesophageal erosions. Avoid in achalasia.

S.E of bisphosphonates

Osteonecrosis of jaw

Hypocalcaemia ( esp if given I.V)- Calcium supplements and Vit D analogues should always be given

Gastric/oesophageal erosions
Tumors more likely to cause hypercalcaemia: breast, Squamous cell lung cancer, myeloma,
genitourinary tumors.

Treatment is :

Rehydrate with 6-8L of saline over 48hrs

Give potassium supplementation

Give Palindronate: the bisphosphonate takes 3-5 days to act and reduce calcium and the effect lasts
upto a month.

Raloxifene

A selective oestrogen receptor modulator (SERM)

SERM are beneficial to : endometrium, CVS, Lipids, Ovulation, Feminization

SERM are harmful to Breast and cause Thromboembolism

SERM drugs bid to oestrogen receptors and can have both agonist and antagonist effect.

Raloxifene reduces rates of vertebral fractures

Raloxifene does not cause emdometrial call proliferation , but other SERM ( Tamoxifen, Toremifen)
can cause increased risk of endometrial cancer.

Raloxifene reduces total cholesterol and LDL

Toremifen causes long QT interval

SERM potentiate the effect of warfarin

Recombinant parathyroid hormone

Teriparatide- can be used to treat osteoporosis if patients still suffer fractures despite treatment
with other agents. There use increases the risk of Renal cell Carcinoma.