rheumatology

Question 1

what is psoriatic arthropathy?

Answer 1

Psoriatic arthropathy is an inflammatory arthritis associated with psoriasis and is classed as one of the seronegative spondyloarthropathies. It correlates poorly with cutaneous psoriasis and often precedes the development of skin lesions. Around 10-20% of patients with skin lesions develop an arthropathy with males and females being equally affected.

Question 2

How doe psoriatic arthropathy present?

Answer 2

symmetric polyarthritis - very similar to rheumatoid arthritis, 30-40% of cases, most common type

asymmetrical oligoarthritis: typically affects hands and feet (20-30%)
until recently it was thought asymmetrical oligoarthritis was the most common type, based on data from the original 1973 Moll and Wright paper. Please see the link for a comparison of more recent studies

sacroiliitis

DIP joint disease (10%)

arthritis mutilans (severe deformity fingers/hand, ‘telescoping fingers’)

Other signs
psoriatic skin lesions
periarticular disease - tenosynovitis and soft tissue inflammation resulting in:
- enthesitis: inflammation at the site of tendon and ligament insertion e.g. Achilles tendonitis, plantar fascitis
- tenosynovitis: typically of the flexor tendons of the hands
- dactylitis: diffuse swelling of a finger or toe
nail changes - pitting, onycholysis

Question 3

how do you investigate psoriatic arthritis?

Answer 3

often have the unusual combination of coexistence of erosive changes and new bone formation
periostitis
‘pencil-in-cup’ appearance

Question 4

how is psoriatic arthritis managed?

Answer 4

managed by a rheumatologist

mild peripheral arthritis/mild axial disease - NSAID

moderate severe disease - methotrexate

use of monoclonal antibodies such as ustekinumab (targets both IL-12 and IL-23) and secukinumab (targets IL-17)
apremilast: phosphodiesterase type-4 (PDE4) inhibitor → suppression of pro-inflammatory mediator synthesis and promotion of anti-inflammatory mediators
has a better prognosis than RA

Question 5

what is hydroxychloroquine used for?

Answer 5

Hydroxychloroquine is used in the management of rheumatoid arthritis and systemic/discoid lupus erythematosus.

Question 6

what are the adverse effects of hydroxychloroquine?

Answer 6

bull’s eye retinopathy - may result in severe and permanent visual loss

retinal photography and spectral domain optical coherence tomography scanning of the macula
baseline ophthalmological examination and annual screening is generally recommened

‘Ask patient about visual symptoms and monitor visual acuity annually using the standard reading chart’

**hydroxychloroquine is one of the medications used in rheumatology that can be given to pregnant woman

Question 7

what is Paget’s disease?

Answer 7

Paget’s disease is a disease of increased but uncontrolled bone turnover. It is thought to be primarily a disorder of osteoclasts, with excessive osteoclastic resorption followed by increased osteoblastic activity. Paget’s disease is common (UK prevalence 5%) but symptomatic in only 1 in 20 patients. The skull, spine/pelvis, and long bones of the lower extremities are most commonly affected.

Question 8

what are predisposing factors for pages disease?

Answer 8

increasing age
male sex
northern latitude
family history

Question 9

what are the clinical features of Paget’s disease?

Answer 9

Clinical features - only 5% of patients are symptomatic
the stereotypical presentation is an older male with bone pain and an isolated raised ALP
bone pain (e.g. pelvis, lumbar spine, femur)
classical, untreated features: bowing of tibia, bossing of skull

Question 10

what are the investigations for paget’s disease?

Answer 10

Bloods - isolated ALP rise (calcium and phosphate typically normal)

Other markers of bone turnover
procollagen type I N-terminal propeptide (PINP)
serum C-telopeptide (CTx)
urinary N-telopeptide (NTx)
urinary hydroxyproline

Xrays
osteolysis in early disease → mixed lytic/sclerotic lesions later
skull x-ray: thickened vault, osteoporosis circumscripta

Bone scintigraphy - increase uptake is seen focally at the sites of active bone lesions

Question 11

what are the complications of Paget’s disease?

Answer 11

deafness (cranial nerve entrapment)
bone sarcoma (1% if affected for > 10 years)
fractures
skull thickening
high-output cardiac failure

Question 12

what is osteomalacia?

Answer 12

Osteomalacia describes softening of the bones secondary to low vitamin D levels that in turn lead to decreased bone mineral content. If this occurs in growing children it is referred to as rickets, with the term osteomalacia preferred for adults.

Question 13

what are the causes of osteomalacia?

Answer 13

vitamin D deficiency - malabsorption, lack of sunlight, diet
chronic kidney disease
drug induced e.g. anticonvulsants
inherited: hypophosphatemic rickets (previously called vitamin D-resistant rickets)
liver disease: e.g. cirrhosis
coeliac disease

Question 14

What are the features of osteomalacia?

Answer 14

bone pain
bone/muscle tenderness
fractures: especially femoral neck
proximal myopathy: may lead to a waddling gait

Question 15

what are the investigations for osteomalacia>

Answer 15

bloods
low vitamin D levels
low calcium, phosphate (in around 30%)
raised alkaline phosphatase (in 95-100% of patients)

x-ray
translucent bands (Looser’s zones or pseudofractures)

Question 16

how is osteomalacia managed?

Answer 16

vitamin D supplmentation
a loading dose is often needed initially
calcium supplementation if dietary calcium is inadequate

Question 17

what is Familial mediterranean fever?

Answer 17

Familial Mediterranean Fever (FMF, also known as recurrent polyserositis) is an autosomal recessive disorder which typically presents by the second decade. It is more common in people of Turkish, Armenian and Arabic descent.

Question 18

what are the features and management of familial mediterranean fever?

Answer 18

Features - attacks typically last 1-3 days
pyrexia
abdominal pain (due to peritonitis)
pleurisy
pericarditis
arthritis
erysipeloid rash on lower limbs

Management
colchicine may help

Question 19

what is osteopetrosis?

Answer 19

also known as marble bone disease
rare disorder of defective osteoclast function resulting in failure of normal bone resorption
results in dense, thick bones that are prone to fracture
bone pains and neuropathies are common.
calcium, phosphate and ALP are normal
stem cell transplant and interferon-gamma have been used for treatment

Question 20

How is Rheumatoid arthritis managed?

Answer 20

Initial therapy - DMARD mono therapy +/ a short course of bridging therapy

Monitoring response to treatment
NICE recommends using a combination of CRP and disease activity (using a composite score such as DAS28) to assess response to treatment

Flares - flares of RA are often managed with corticosteroid

TNF inhibits - indicated when there is inadequate response to at least 2 DMARDs including methotrexate (entanjrcept, infliximab, adalimumab)

Rituximab
anti-CD20 monoclonal antibody, results in B-cell depletion
two 1g intravenous infusions are given two weeks apart
infusion reactions are common

Abatacept
fusion protein that modulates a key signal required for activation of T lymphocytes
leads to decreased T-cell proliferation and cytokine production
given as an infusion
not currently recommend by NICE

Question 21

What are the DMARD monotherpay that can be given in RA?

Answer 21

methotrexate is the most widely used DMARD. Monitoring of FBC & LFTs is essential due to the risk of myelosuppression and liver cirrhosis. Other important side-effects include pneumonitis
sulfasalazine
leflunomide
hydroxychloroquine: should only be considered for initial therapy if mild or palindromic disease

Question 22

what is dermatomyositis?

Answer 22

an inflammatory disorder causing symmetrical, proximal muscle weakness and characteristic skin lesions
may be idiopathic or associated with connective tissue disorders or underlying malignancy (typically ovarian, breast and lung cancer, found in 20-25% - more if patient older). Screening for an underlying malignancy is usually performed following a diagnosis of dermatomyositis
polymyositis is a variant of the disease where skin manifestations are not prominent

Question 23

what are the features of dermatomyositis?

Answer 23

Skin features
photosensitive
macular rash over back and shoulder
heliotrope rash in the periorbital region
Gottron’s papules - roughened red papules over extensor surfaces of fingers
‘mechanic’s hands’: extremely dry and scaly hands with linear ‘cracks’ on the palmar and lateral aspects of the fingers
nail fold capillary dilatation

Other features
proximal muscle weakness +/- tenderness
Raynaud’s
respiratory muscle weakness
interstitial lung disease: e.g. Fibrosing alveolitis or organising pneumonia
dysphagia, dysphonia

Question 24

how do you investigate dermatomyositis?

Answer 24

vestigations
ne kinase
EMG
muscle biopsy
ANA positive in 60%
anti-Mi-2 antibodies are highly specific for dermatomyositis, but are only seen in around 25% of patients
anti-Jo-1 antibodies are not commonly seen in dermatomyositis - they are more common in polymyositis where they are seen in a pattern of disease associated with lung involvement, Raynaud’s and fever

Question 25

how is dermatomyositis managed?

Answer 25

Prednisolone

Question 26

what is pseudoxanthoma elastic?

Answer 26

Pseudoxanthoma elasticum is an inherited condition (usually autosomal recessive*) characterised by an abnormality in elastic fibres

Question 27

what are the features of pseudoxanthoma elasticum?

Answer 27

retinal angioid streaks
‘plucked chicken skin’ appearance - small yellow papules on the neck, antecubital fossa and axillae
cardiac: mitral valve prolapse, increased risk of ischaemic heart disease
gastrointestinal haemorrhage

Question 28

what is Marfan’s?

Answer 28

Marfan’s is an AD connective tissue disorder
It is caused by a defect in the FBN1 gene on chromosome 15 that codes for protein fibrillin-1. It affects around 1 in 3000 people?

Question 29

what are the features of Marfan’s syndrome?

Answer 29

tall stature with arm span to height ratio > 1.05
high-arched palate
arachnodactyly
pectus excavatum
pes planus
scoliosis of > 20 degrees
heart:
> dilation of the aortic sinuses (seen in 90%) which may lead to aortic aneurysm, aortic dissection, aortic regurgitation
> mitral valve prolapse (75%),
lungs: repeated pneumothoraces
eyes:
> upwards lens dislocation (superotemporal ectopia lentis)
> blue sclera
> myopia
dural ectasia (ballooning of the dural sac at the lumbosacral level)

Question 30

what is gout?

Answer 30

Gout is a form of microcrystal synovitis caused by the deposition of monosodium urate monohydrate in the synovium. It is caused by chronic hyperuricaemia (uric acid > 450 µmol/l)

Question 30

what is the most common cause of osteomyelitis?

Answer 30

Staph. aureus is the most common cause except in patients with sickle-cell anaemia where Salmonella species predominate

Question 31

what are the indications for urate-lowering therapy in gout?

Answer 31

ULT is particularly recommended if:
>= 2 attacks in 12 months
tophi
renal disease
uric acid renal stones
prophylaxis if on cytotoxics or diuretics

Question 32

How is gout managed?

Answer 32

NSAIDs
Colchicine
oral steroids if NSAIDs and colchicine are contraindicated

• if patient is already taking allopurinol it should continued

Urate lowering therapy - allopurinol 1st line
2nd line when allopurinol is not tolerated or ineffective is febuxostat (also a xanthine oxidase inhibitor)

In refractory cases other agent may be tired
- uricase
- pegolticase

Question 33

what lifestyle modifications should be made in gout?

Answer 33

reduce alcohol intake and avoid during an acute attack
lose weight if obese
avoid food high in purines e.g. Liver, kidneys, seafood, oily fish (mackerel, sardines) and yeast products

consideration should be given to stopping precipitating drugs (such as thiazides)
losartan has a specific uricosuric action and may be particularly suitable for the many patients who have coexistent hypertension
increased vitamin C intake (either supplements or through normal diet) may also decrease serum uric acid levels

Question 34

which medications used in IBD are safe in pregnancy ?

Answer 34

Azathioprine, mesalazine and sulfasalazine (with folic acid) are safe to use in pregnancy and breastfeeding.

Question 35

what is azathioprine?

Answer 35

Azathioprine is metabolised to the active compound mercaptopurine, a purine analogue that inhibits purine synthesis. A thiopurine methyltransferase (TPMT) test may be needed to look for individuals prone to azathioprine toxicity.

Question 36

what are the adverse effects of azathioprine?

Answer 36

bone marrow depression - consider a full blood count if infection/bleeding occurs
nausea/vomiting
pancreatitis
increased risk of non-melanoma skin cancer

Question 37

what is systemic sclerosis?

Answer 37

Systemic sclerosis is a condition of unknown aetiology characterised by hardened, sclerotic skin and other connective tissues. It is four times more common in females.

Question 38

what are the different patterns of systemic sclerosis?

Answer 38

Limited cutaneous systemic sclerosis
Raynaud’s may be the first sign
scleroderma affects face and distal limbs predominately
associated with anti-centromere antibodies
a subtype of limited systemic sclerosis is CREST syndrome: Calcinosis, Raynaud’s phenomenon, oEsophageal dysmotility, Sclerodactyly, Telangiectasia

Diffuse cutaneous systemic sclerosis
scleroderma affects trunk and proximal limbs predominately
associated with anti scl-70 antibodies
the most common cause of death is now respiratory involvement, which is seen in around 80%: interstitial lung disease (ILD) and pulmonary arterial hypertension (PAH)
other complications include renal disease and hypertension
patients with renal disease should be started on an ACE inhibitor
poor prognosis

Scleroderma (without internal organ involvement)
tightening and fibrosis of skin
may be manifest as plaques (morphoea) or linear

Question 39

what antibiodies are seen in systemic sclerosis?

Answer 39

ANA positive in 90%
RF positive in 30%
anti-scl-70 antibodies associated with diffuse cutaneous systemic sclerosis
associated with a higher risk of severe interstitial lung disease
anti-centromere antibodies associated with limited cutaneous systemic sclerosis

Question 40

what is the most common cause of death in systemic sclerosis?

Answer 40

respiratory involvement: interstitial lung disease and pulmonary arterial hypertension

Question 41

what is Langerhans cell histiocytosis?

Answer 41

a rare disorder characterised by the proliferation of Langerhans cells, which are specialised dendritic cells that normally function to present antigen to T lymphocytes. The disease can affect multiple organs, including the bones, skin, lungs, and endocrine system. It is notable for its variable clinical presentation, ranging from isolated bone lesions to multisystem disease.

Question 42

what are the features of Langerhans cell histiocytosis?

Answer 42

bone pain, typically in the skull or proximal femur
cutaneous nodules
pituitary involvement: leads to diabetes insipidus due to pituitary stalk involvement
pulmonary involvement: More common in adults, presenting with dyspnoea, cough, and chest pain
recurrent otitis media/mastoiditis
tennis racket-shaped Birbeck granules on electromicroscopy

Question 43

How is Langerhans cell histiocytosis diagnosed?

Answer 43

biopsy: confirmation is through biopsy showing Langerhans cells with characteristic grooved nuclei and positive staining for CD1a and S100 protein
imaging: radiographs and MRI for bone lesions; CT may be used for chest and abdominal involvement

Question 44

How is Langerhans celll histiocytosis managed?

Answer 44

localized disease: surgical resection or limited radiotherapy for isolated lesions.
multisystem disease: systemic therapy including steroids, chemotherapy (e.g., vinblastine, cytarabine), and targeted therapies for refractory cases.
supportive care: management of diabetes insipidus, pain control, and treatment of secondary infections.