# 054

# Pages 1326-1350

Notes & Notes for MRCP                          
By Dr. Yousif Abdallah Hamad


This is a well-defined oval to round plaque that fails to meet the criteria for 
generalised morphea. 
generalized morphea,
linear morphea
pansclerotic morphea
Pathophysiology
•
autoimmune component is suggested by enhanced T helper 2 (Th2) dependent 
interleukin 4 (IL-4) activity, which in turn upregulates transforming growth factor beta (TGF 
-beta).
•
TGF-beta stimulates fibroblast production of collagen and other extracellular matrix 
proteins.
Features
•
Unlike systemic sclerosis, morphea lacks features such as sclerodactyly, Raynaud 
phenomenon, nailfold capillary changes, telangiectasias, and progressive internal organ 
involvement. 
•
Morphea can present with extracutaneous manifestations, including fever, 
lymphadenopathy, arthralgias, fatigue, central nervous system involvement, 
Investigations
•
Hypergammaglobulinaemia (↑↑IgM , IgG)
•
peripheral eosinophilia 
•
↑↑ESR and CRP
•
Anti-Cu/Zn superoxide dismutase antibodies have been found in up to 90%
Treatment
•
Superficial circumscribed morphea
Tacrolimus 0.1% ointment applied twice daily for 12 weeks may be a useful firstline
•
Generalized, linear, or deep morphea
combination therapy with oral prednisone and methotrexate
To minimize the risk of relapse, the recommended treatment duration of MTX is at 
least 2 years.
Systemic corticosteroids can be helpful in the inflammatory phases of morphea, but 
they are not recommended for long-term monotherapy
Mycophenolate mofetil is a second-line
Prognosis
•
generally resolves within 3–5 years, although sometimes a patch may persist for over 25 
years.
____________________________________________________
Polymyalgia rheumatica (PMR)
Pathophysiology
•
overlaps with temporal arteritis 30% of patients also have giant cell arteritis.
•
histology shows vasculitis with giant cells, characteristically 'skips' certain sections of 
affected artery whilst damaging others
•
muscle bed arteries affected most in polymyalgia rheumatica
Epidemiology
•
occurring in patients age 50 years or older.
•
More common in women

Notes & Notes for MRCP                          
By Dr. Yousif Abdallah Hamad
Chapter 8

Rheumatology
 
Features
•
typically patient > 60 years old
very rarely seen in the under 50s.
•
usually rapid onset (e.g. < 1 month)
•
typically presents with pain and stiffness of the shoulder and pelvic girdle muscles.
•
aching, morning stiffness in proximal limb muscles (not weakness)
Pain and muscle stiffness worst in the mornings
•
mild polyarthralgia, lethargy, 
•
depression, 
•
low-grade fever, anorexia, night sweats
•
Weight loss
Investigations
•
ESR > 40 mm/hr
the next best investigation
a high ESR would prompt immediate treatment with steroids.
•
Raised C reactive protein (CRP)
•
Alkaline phosphatase is an acute-phase reactant and is raised in approximately a third of 
patients with polymyalgia rheumatica.
•
note CK and EMG normal
•
reduced CD8+ T cells
•
Normochromic / normocytic anaemia
Differential diagnosis
•
Giant cell arteritis (GCA)
GCA and PMR frequently co-exist, 
cranial symptoms including headache, jaw claudication, and vision symptoms are 
typically absent in patients with PMR.
PMR typically has less prominent symptoms than GCA.
Treatment
•
prednisolone e.g. 15mg/od - dramatic response
Response to a moderate dose of steroids can be useful in confirming the diagnosis 
of PMR. 
The maximum dose of prednisolone should not exceed 20 mg once daily. 
Patients should report 70% improvement in symptoms within three to four weeks, 
and inflammatory markers should have normalised by this point.

Notes & Notes for MRCP                          
By Dr. Yousif Abdallah Hamad

Calcium and vitamin D supplementation should be initiated for all patients with PMR 
who are starting corticosteroid therapy. Bisphosphonates should be added for long 
term steroid therapy.
The usual starting dose is 15 mg prednisolone per day. 
Patients should expect relief of symptoms within 24-72 hours. 

One of the best ‘tests’ for Polymyalgia Rheumatica (PMR) is how patients 
respond to corticosteroid therapy.
Tapering 

Tapering should be guided by clinical response.

The dose should be increased if symptoms are not well controlled within one 
week. 

The effective starting dose should be maintained for two to four weeks after 
the patient becomes asymptomatic.

Generally, the daily dose can be lowered by 1.0-2.5 mg every two to four 
weeks to find the minimum dose needed to maintain symptom suppression. 
Once the patient is reduced to 10 mg per day, the daily dose can be tapered 
by 1 mg every four weeks.

Approximately 50-75% of patients can discontinue corticosteroid therapy after 
two years of treatment.
Methotrexate and azathioprine

If symptoms relapsed when the dose of prednisolone has been reduced
below the current dose, Continue the current dose of prednisolone 
and start methotrexate

used in patients with corticosteroid intolerance or as corticosteroid-sparing 
agents. 

These are generally reserved for patients in whom it has been difficult to 
reduce the prednisolone after prolonged high dosages (for example, 10 mg or 
more per day for more than a year).

These agents should be added to the prednisolone initially, but with a view to 
slowly reduce and withdraw prednisolone.

As with steroid therapy, azathioprine or methotrexate can be discontinued if 
there has been sufficient response.
Prognosis
•
Rapid improvement often occurs within 24 to 72 hours with low-dose prednisolone.
____________________________________________________
Temporal arteritis (Giant cell arteritis (GCA)
Overview
•
also known as giant cell arteritis (GCA).
•
Temporal arteritis is large vessel vasculitis 
•
overlaps with polymyalgia rheumatica (PMR).
•
Histology shows changes which characteristically 'skips' certain sections of affected artery 
whilst damaging others.
•
It is a clinical emergency.
GCA should always be considered in elderly patients with headaches, ocular 
symptoms (e.g. acute monocular visual loss), systemic symptoms and high ESR. 
Suspected GCA glucocorticoids immediately, even before diagnostic evaluation 
by temporal artery biopsy is complete.

Notes & Notes for MRCP                          
By Dr. Yousif Abdallah Hamad
Chapter 8

Rheumatology
 
Epidemiology
•
Sex: ♀ > ♂
•
Peak incidence: 70–79 years; rarely seen in patients < 50 years
Features
•
typically, patient > 60 years old
The greatest risk factor for (GCA) is aging.
almost never occurs before age 50
•
usually rapid onset (e.g. < 1 month)
•
headache (found in 85%)
•
jaw claudication (65%) is a very specific sign for temporal arteritis.
•
visual disturbances ( 50% )

secondary to anterior ischemic optic neuropathy
15-20% of patients develop permanent visual loss.
•
tender, palpable temporal artery
•
features of PMR: aching, morning stiffness in proximal limb muscles (not weakness)
•
also, lethargy, depression, low-grade fever, anorexia, night sweats
•
Large vessel GCA : Subclinical involvement of the aorta and large arteries is frequent, a 
clinical consequence of which can be aortic aneurysm (in 10 to 20 % of cases ).
Investigations
•
Raised inflammatory markers: ESR > 50 mm/hr (note ESR < 30 in 10% of patients). CRP 
may also be elevated
ESR can be within normal range in 5-10% of GCA cases.
•
Temporal artery biopsy: 
the definitive diagnostic test 
skip lesions may be present (certain sections of affected artery whilst damaging others)
An adequate length of temporal artery (3 to 5 cm) should be obtained because 
inflammatory lesions may be present in a segmental fashion. 
A negative temporal artery biopsy can occur in up to 50% of patients, often because 
the sampled region was not involved in the pathologic process. Therefore, it is not 
sensitive enough to rule out temporal arteritis.
Treatment should not be delayed while waiting for the biopsy to be performed.
•
Note: creatine kinase and EMG normal
Diagnosis
•
The American College of Rheumatology 1990 criteria requires 3 of the following for GCA 
diagnosis:
1. Age >50 y/o
2. New onset localised headache
3. Temporal artery tenderness or decreased pulsation
4. ESR >50mm/hr
5. Temporal artery biopsy positive
Treatment
•
High-dose prednisolone
there should be a dramatic response, if not the diagnosis should be reconsidered
Current BSR guidelines recommend:

Uncomplicated GCA (no jaw or tongue claudication, or visual symptoms)
prednisolone 40-60 mg daily

Complicated GCA: (with visual involvement and/or jaw/tongue 
claudication)

Notes & Notes for MRCP                          
By Dr. Yousif Abdallah Hamad

Evolving visual loss or history of amaurosis fugax: IV 
methylprednisolone 500 mg-1 g daily for three days, followed by 
oral corticosteroids
Established visual loss: at least 60 mg prednisolone daily
•
Urgent ophthalmology review. 
Patients with visual symptoms should be seen the same-day by an ophthalmologist. 
Visual damage is often irreversible
•
As GCA requires long-term steroid therapy bone sparing agents (a bisphosphonate and 
vitamin D) and a gastroprotective drug (e.g omeprazole) should be prescribed. 
•
Also, low dose aspirin should be considered as it has been shown to reduce the rate of 
visual loss and cerebrovascular accidents in GCA.
____________________________________________________
Polyarthritis
Differential diagnosis
•
rheumatoid arthritis
•
SLE
•
seronegative spondyloarthropathies
•
Henoch-Schonlein purpura
•
sarcoidosis
•
tuberculosis
•
pseudogout
•
viral infection: EBV, HIV, hepatitis, mumps, rubella
____________________________________________________
Polyarteritis nodosa (PAN)
Definition
•
systemic vasculitis of the medium-sized vessels, with necrotizing inflammation leading to 
aneurysm formation and tissue ischemia; 
•
most commonly involving skin, peripheral nerves, muscles, joints, gastrointestinal tract, and 
kidneys .
•
any organ with the exception of the lung can be affected, 
Epidemiology
•
Peak incidence: ∼45–65 years
•
Sex: ♂ > ♀
•
more common in middle-aged men 
Pathophysiology
•
diffuse vascular inflammation and ischaemia of the affected organs. 
•
PAN is a medium-vessel vasculitis that is a type III hypersensitivity reaction.
Association
•
hepatitis B infection
Features
•
Nonspecific symptoms: (found in 65% to 80% of patients)
fever, malaise, arthralgia, weight loss
•
Neurological involvement: (in 55% of patients)
polyneuropathy (mononeuritis multiplex), 
cerebral ischemia (stroke)
•
Skin involvement: (in 44%)
skin rash,
Skin ulcers, nodules
livedo reticularis

Notes & Notes for MRCP                          
By Dr. Yousif Abdallah Hamad
Chapter 8

Rheumatology
 
•
Renal involvement : (in 11%)
hypertension, 

Hypertension is a manifestation of renal ischaemia via activation of the reninangiotensin system.
haematuria

but red cell casts are absent because glomerular inflammation is not a 
feature.
renal impairment
•
Coronary artery involvement ; 
increased risk of myocardial infarction
•
GI involvement: 
abdominal pain, nausea, vomiting
can present with abdominal pain and melena due to involvement of the mesenteric 
arteries.
•
Testicular pain
testicular pain from ischaemic orchitis is a characteristic feature
uncommon presentation
•
Usually spares the lungs
PAN should be considered in young adults presenting with stroke or myocardial infarction
The diagnosis may be confirmed with a biopsy of involved tissue
Livedo reticularis
Diagnosis
•
The American College of Rheumatology (ACR) 1990 criteria 
Three of the following 10 criteria are required:
1. Weight loss ≥4 kg
2. Livedo reticularis
3. Testicular pain or tenderness
4. Myalgias, weakness, or leg tenderness
5. Mononeuropathy or polyneuropathy
6. Diastolic blood pressure >90 mmHg
7. Elevated urea or creatinine
8. Positivity for hepatitis B virus (HBV) infection
9. Arteriographic abnormality

Notes & Notes for MRCP                          
By Dr. Yousif Abdallah Hamad

10.Biopsy of small- or medium-sized artery containing polymorphonuclear 
leukocytes.
Investigations
•
Hepatitis B surface antigen is positive in 30%, 
•
p-ANCA is positive only in 20%.
ANCA is classically negative in PAN. 
•
Angiography:
Conventional angiography is the imaging modality of choice, and should be 
performed if there is a clinical suspicion of PAN. 
typically demonstrates:

microaneurysms and 

focal narrowing in medium-sized blood vessels. 
•
Biopsy
should be performed if angiography is not available or does not conclusively 
show a medium-vessel vasculitis.

Shows:

focal and segmental transmural necrotising inflammation with fibrinoid 
necrosis in medium-sized vessels. 

pleomorphic cellular infiltrate of lymphocytes, neutrophils, macrophages, 
and eosinophils.

granulomas are absent.
Differential diagnosis
•
PAN are differentiated from the other small- and medium-vessel vasculitides by:

absence of anti-neutrophil cytoplasmic antibodies, 
Glomerulonephritis is not a feature of PAN, but it is common in anti-neutrophil 
cytoplasmic antibodies (ANCA) vasculitis. Making this distinction early by way of 
urinalysis for protein, blood, and casts is a simple first-line test that can guide 
further investigation and treatment.

Red cell casts are absent in PAN

If there is evidence of glomerular inflammation such as urinary casts, then an 
alternative diagnosis such as microscopic polyangiitis (MPA) or 
granulomatosis with polyangiitis (Wegener's) (GPA),must be considered.
lung involvement is not seen in PAN, and abnormal respiratory findings should 
suggest an alternative diagnosis 
and by confirmation that small vessels (i.e., arterioles, capillaries, venules) are not 
involved.
Treatment 
•
idiopathic PAN corticosteroids and cyclophosphamide
•
hepatitis B related disease plasmapheresis and antiviral agents. 
•
Azathioprine can be used as maintenance therapy, and typically has fewer side effects than 
cyclophosphamide.
Cyclophosphamide causes premature ovarian failure and infertility in both men 
and women.

Notes & Notes for MRCP                          
By Dr. Yousif Abdallah Hamad
Chapter 8

Rheumatology
____________________________________________________
Granulomatosis with polyangiitis (Wegener's 
granulomatosis)
Overview
•
Granulomatosis with polyangiitis is now the preferred term for Wegener's granulomatosis. 
•
It is an autoimmune condition associated with a necrotizing granulomatous vasculitis, 
affecting both the upper and lower respiratory tract as well as the kidneys.
•
the classical triad consists of 
1. necrotising granulomatous inflammation of the respiratory tract, 
2. glomerulonephritis 
3. small-vessel vasculitis.
Features
•
upper respiratory tract: epistaxis, sinusitis, nasal crusting
•
saddle-shape nose deformity
•
lower respiratory tract: dyspnoea, haemoptysis
migrating alveolar shadowing
•
rapidly progressive glomerulonephritis ('pauci-immune', 80% of patients)
It usually presents with rapidly progressing renal failure (within three months), 
proteinuria and microscopic haematuria.
•
also: 
vasculitis (causing carotid artery tenderness)
vasculitic rash, 
eye involvement (e.g. proptosis), 
cranial nerve lesions
Investigations
•
c-ANCA (PR3-ANCA (targeting peroxidise-3) positive in > 90%, p-ANCA (MPO-ANCA
(targeting myeloperoxidase) positive in 25%
cANCA directed against proteinase-3
cANCA  is highly specific, but is found in only 50% of patients with disease 
localised to the respiratory tract and 95% with generalised Wegener's.

Notes & Notes for MRCP                          
By Dr. Yousif Abdallah Hamad


In active Wegener’s disease with renal involvement cANCA is highly 
sensitive and specific.
After disease remission cANCA may remain elevated for years, and is not useful in 
evaluating patients for relapse.
•
chest x-ray: wide variety of presentations, including cavitating lesions
•
tissue biopsy 
renal biopsy: 

epithelial crescents in Bowman's capsule

Kidneys show vasculitis and glomerulonephritis and occasional (NOT 
always ) granulomata
Lung biopsy has a high diagnostic yield

show vasculitis and granulomas
Biopsy of the upper respiratory tract shows granulomas but not vasculitis.
Management
•
steroids
Prednisolone is given in doses of around 1 mg/kg per day initially, after which 
the dose is reduced rapidly, typically at weekly intervals.
In case of renal failure with indications for dialysis, the initial management 
Methylprednisolone

Methylprednisolone should be given immediately, followed by 
haemodialysis and then cyclophosphamide.
•
cyclophosphamide (90% response)
The combination of prednisolone and cyclophosphamide is now 
established as the standard therapy and the treatment of choice for induction 
of remission in Wegener's granulomatosis
Cyclophosphamide: Traditionally, oral dose (2 mg/kg per day), but latterly 
intravenous boluses have proved increasingly popular, given in doses of 0.5-0.75 
g/m2 body surface area at intervals of 2 weeks (at least for short periods) to 2
months.
If a patient had a vasculitic neuropathy. Current practice is to use 
cyclophosphamide for induction therapy. 
•
Both rituximab and methotrexate have also been used for induction therapy in ANCAassociated vasculitis, although they would not be first-line treatment. 
•
Azathioprine is used as maintenance treatment following cyclophosphamide 
•
ciclosporin is rarely used in the management of ANCA-associated vasculitis.
•
Evidence from controlled trials suggests that once remission is achieved azathioprine or 
methotrexate may be reasonable alternatives to cyclophosphamide.
•
In refractory Wegener's, both infliximab and rituximab have shown some degree of promise.
•
plasma exchange
•
in case of decreased conscious level with acute renal failure (with indication for 
dialysis) and respiratory function is failing. The first immediate step Endotracheal 
intubation and positive pressure ventilation, transfer the patient to a critical care
setting (especially to protect airway with a GCS 8/15).
Prognosis
•
median survival = 8-9 years

Notes & Notes for MRCP                          
By Dr. Yousif Abdallah Hamad
Chapter 8

Rheumatology
____________________________________________________
Microscopic Polyangiitis
•
Microscopic polyangiitis is similar to wegener’s granulomatosis except in 3 things:
1. it only affects small blood vessels in the lungs or kidneys.

No nasopharyngeal damage like wegener's 
2. Associated with p-ANCA antibodies.

anti-MPO (pANCA, 45%) antibody is strongly positive than anti-PR3 (cANCA, 
30%)
3. No granuloma on biopsy 
____________________________________________________
Churg-Strauss syndrome
•
Churg-Strauss syndrome is an ANCA associated small-medium vessel vasculitis.
•
also known as Eosinophilic granulomatosis with polyangiitis
Features
•
asthma
•
paranasal sinusitis
•
mononeuritis multiplex
•
blood eosinophilia (e.g. > 10%)
•
Serum IgE is very commonly elevated and correlates with disease severity.
•
pANCA positive in 60%
•
Commonly associated with antimyeloperoxidase antibodies. 
•
Non-fixed pulmonary infiltrates visible on chest radiographs 
•
Rarely, it can cause ischaemic optic neuropathy, which presents with visual loss.
Leukotriene receptor antagonists may precipitate the disease
Diagnosis
•
It is diagnosed clinically, although a biopsy should be sought for pathological 
confirmation.
•
Skin biopsy reveals small-vessel arteriopathy with granuloma formation and is the 
diagnostic investigation of choice.
Blood vessels with extravascular eosinophils on biopsy.
PR3 antibody is associated with Wegener's granulomatosis, 
MPO antibody is associated with microscopic polyangiitis

Notes & Notes for MRCP                          
By Dr. Yousif Abdallah Hamad

Treatment
•
High-dose methylprednisolone, with or without cyclophosphamide is the treatment of 
choice
Prognosis
•
Without treatment, the 5-year survival rate for Churg-Strauss syndrome is around 25%; 
with appropriate therapy this rises to over 60%.
____________________________________________________
Idiopathic pulmonary haemosiderosis
Definition
•
recurrent episodes of diffuse alveolar hemorrhage of unknown aetiology
Prevalence
•
rare
•
tends to occur in younger people
Features
•
pallor, 
•
weakness, lethargy,
•
dry cough and occasional haemoptysis
•
no extrapulmonary features. 
•
After recurrent episodes of hemorrhage, pulmonary fibrosis may develop due to iron 
accumulation.
Investigations
•
no abnormal immunological features, which differentiates it from Goodpasture 
syndrome and wegener’s 
•
Gas transfer is elevated as blood is already in the alveolar space.
•
chest radiograph and high resolution computed tomography demonstrate ground glass 
alveolar opacities that are often bilateral.
•
final diagnosis requires lung biopsy documentation of large numbers of hemosiderinladen macrophages in the alveoli, without evidence of vasculitis, capillaritis, 
inflammation, granulomas, or deposition of immunoglobulins in any specific pattern.
Treatment
•
glucocorticoids +/- another immunosuppressive agent
(eg, azathioprine, or cyclophosphamide)
pulmonary hemorrhage without immunological features  Idiopathic pulmonary 
haemosiderosis
pulmonary hemorrhage + immunological features Goodpasture or wegener’s

Notes & Notes for MRCP                          
By Dr. Yousif Abdallah Hamad
Chapter 8

Rheumatology
____________________________________________________
Henoch-Schonlein purpura
Overview
•
Henoch-Schonlein purpura (HSP) is an IgA mediated small vessel vasculitis
•
involving mainly the blood vessels of the skin, GI tract, the kidneys and the joints.
•
90% of cases of HSP occur in children aged 2-10 years but can occur in any age group. 
•
In children, (HSP) is the most common cause of vasculitis affecting the kidneys.
•
typically commoner in males, 
•
may follow an infectious agent.
•
It can present one to three days following infection of an IgA secreting mucous membrane 
(commonly following pharyngitis, but can occur following infection of the gastrointestinal 
tract, bladder or breast).
•
An important risk factor in adults chronic alcohol intake. 
•
associated with: Helicobacter pylori, hepatitis B and malignancy.
Features
HSP is characterised by the tetrad of:
•
purpura
•
abdominal pain
•
arthritis, and
•
renal involvement (haematuria and proteinuria).
Patients with proteinuria have a worse prognosis than patients with haematuria 
alone.
•
palpable purpuric rash (with localized oedema) over buttocks and extensor surfaces of 
arms and legs (due to a cutaneous vasculitis)
•
abdominal pain (due to gut vasculitis, which may be severe in some cases, leading to 
bloody diarrhoea)
•
polyarthritis (common symptom)
•
features of IgA nephropathy may occur e.g. haematuria, renal failure
HSP nephritis becomes clinically manifest in only 20-30%. 
It usually presents as macroscopic haematuria and proteinuria 
Of those patients with renal involvement, as many as 10% may develop chronic 
renal failure and end-stage renal disease. However, fewer than 1% of all patients 
with HSP suffer this poor prognosis.
Diagnosis
•
Skin biopsy and immunofluorescence demonstrate leukocytoclastic vasculitis with IgA 
deposition,( meaning lots of white blood cells in the skin around small blood vessels) which is 
pathognomonic for HSP.
Immunofluorescence studies will reveal IgA deposits within blood vessel walls
Treatment
•
analgesia for arthralgia
•
treatment of nephropathy is generally supportive. 
All patients with hypertension and proteinuria (greater than 1 g/day) should be 
started on an angiotensin-converting enzyme (ACE) inhibitor, which may control 
the BP and proteinuria.
Once the BP has been controlled, patient should have a renal biopsy, and if this 
showed changes of a crescentic glomerulonephritis (GN), then an 
immunosuppression regime similar to that used in renal vasculitis should be started 
(probably with high dose steroids in the first instance +/- cyclophosphamide).
There is inconsistent evidence for the use of steroids and immunosuppressants
Management of HSP in adults often involves the use of immunomodulatory or 
immune-suppressive regiments (in contrast to children where the majority of cases 
resolve spontaneously).

Notes & Notes for MRCP                          
By Dr. Yousif Abdallah Hamad

Prognosis
•
usually excellent, HSP is a self-limiting condition, especially in children without renal 
involvement
•
There is often a more complicated course in adults, and 50% of patients who present with 
renal involvement develop renal insufficiency.
•
around 1/3rd of patients have a relapse
MRCPUK-part-1-September 2019 exam: What is the most likely renal outcome in HenochSchonlein purpura? Full renal recovery

Notes & Notes for MRCP                          
By Dr. Yousif Abdallah Hamad
Chapter 8

Rheumatology
____________________________________________________
Kawasaki disease
Overview
•
Kawasaki disease is a type of vasculitis which is predominately seen in children. 
•
Whilst Kawasaki disease is uncommon it is important to recognise as it may cause 
potentially serious complications, including coronary artery aneurysms
Features
•
high-grade fever which lasts for > 5 days. Fever is characteristically resistant to antipyretics
•
conjunctival injection
•
bright red, cracked lips
•
strawberry tongue
•
cervical lymphadenopathy
•
red palms of the hands and the soles of the feet which later peel
Diagnosis
•
Kawasaki disease is a clinical diagnosis as there is no specific diagnostic test
Management
•
high-dose aspirin
Kawasaki disease is one of the few indications for the use of aspirin in children. Due 
to the risk of Reye's syndrome aspirin is normally contraindicated in children.
•
intravenous immunoglobulin
Combination therapy with intravenous immunoglobulin (IVIG) and aspirin 
during the acute phase of Kawasaki disease produces a more marked antiinflammatory effect and reduction in coronary artery abnormalities than does 
aspirin alone.
•
echocardiogram (rather than angiography) is used as the initial screening test for coronary 
artery aneurysms
Complications
•
coronary artery aneurysm (25% of cases)
•
lakayasu1s arter1 t1s

Notes & Notes for MRCP                          
By Dr. Yousif Abdallah Hamad

____________________________________________________
Takayasu’s arteritis
Definition
•
Chronic inflammatory granulomatous pan-arteritis of the major arteries
It typically causes occlusion of the aorta (the ascending arch of the aorta)
The subclavian artery is commonly affected, and subclavian steal syndrome may 
occur 
The brachial, radial and ulnar arteries can also be involved. 
Pathology
•
continuous or patchy granulomatous inflammatory process involving macrophages, 
lymphocytes, and multinucleated giant cells which causes progressive occlusive disease of 
the aorta and its branches.
Epidemiology
•
most commonly affects women (the ratio of women to men is 8:1). 
•
typical age onset of 25-30 years. 
•
most common in Asia.
Features
•
questions commonly refer to an absent limb pulse.
•
systemic features of a vasculitis e.g. malaise, headache
•
unequal blood pressure in the upper limbs
•
carotid bruit
•
vascular symptoms such as claudication. (intermittent claudication)
•
systemic symptoms of fever, arthralgia and weight loss.
•
neurological symptoms such as transient ischaemic attacks.
•
Cardiac features include angina, heart failure, and aortic regurgitation. 
•
Renal manifestations may include mesangial proliferative glomerulonephritis. 
•
aortic regurgitation (around 20%)
•
ESR and CRP are usually elevated, 
•
levels of pentraxin 3 may be a useful marker of disease activity. 
Associations
•
renal artery stenosis
Treatment
•
Corticosteroids with the addition of steroid sparing second agents such as methotrexate or 
azathioprine are the mainstay of therapy. 
Prognosis
•
With good care, 15-year survival rates approach 90%.

Notes & Notes for MRCP                          
By Dr. Yousif Abdallah Hamad
Chapter 8

Rheumatology
 
Subclavian steal syndrome (SSS)
The proximal part of left subclavian is blocked on left side so 
no flow in vertebral and to left arm. Blood from right vertebral 
enters left vertebral and flows back to supply left arm
Etiology
•
Atherosclerosis
•
Cervical rib
•
Takayasu's arteritis
Features
•
Presyncope (sensation that one is about to faint)
•
Syncope (fainting)
•
Neurologic deficits
•
Blood pressure differential between the arms
•
severe memory problems
•
hands showing circulation problems (hands can have 
blotchy patches of red and white) (associated with other 
stigma to vascular disease (e.g. vascular 
insufficiency ulcers of the foot).
____________________________________________________
Buerger’s disease 
Overview 
•
Thromboangiitis obliterans (Buerger’s disease) is a disease of small and medium-sized 
arteries and veins resulting in inflammation and ulceration, in which the distal vessels
become blocked in the hands and feet.
•
There is no excessive atheroma and it does not involve the coronary arteries like 
atherosclerosis.
•
The disease occurs mainly in cigarette smokers; it has not been documented in nonsmokers.
•
Although there is florid histological inflammation within vessels, the disease is not a 
systemic vasculitis, is not accompanied by any elevation in acute phase markers and does 
not respond to immune suppression.
Epidemiology
•
Prevalence is higher in men and people of Far Eastern origin.
•
seen in young (usually < 40 years) male smokers.
Feature
•
symptoms of arterial ischaemia resulting in gangrene of the digits.
claudication with diminished or absent pulses. 
The feet or legs may be cyanosed or dusky; the skin is thin and without hair. 
Ulcerations occur, and necrosis follows
•
Migratory phlebitis in the superficial vein is present in 40% of cases. 
Diagnosis
•
usually clinical. 
•
Arteriogram will show occlusion of distal arteries of the hands and feet. 
•
Histopathology 
examination of affected arteries reveals fresh inflammatory thrombus within both 
small and medium-sized arteries and veins, with giant cells surrounding the 
thrombus.
Treatment
•
Supportive
•
stop smoking.

Notes & Notes for MRCP                          
By Dr. Yousif Abdallah Hamad

Prognosis
•
can be excellent (i.e. complete resolution of symptoms) with smoking cessation
•
in some cases, however, amputation is unavoidable
______________________________________________________________________________
IBD-associated arthropathy 
•
The history of weight loss, diarrhoea and a mono/oligo-arthropathy suggests a diagnosis of 
inflammatory bowel disease (IBD).
•
IBD-associated arthropathy is considered a subtype of seronegative spondyloarthropathy. 
•
A variety of joint involvement has been described, from large joint pauciarticular arthropathy 
to a rheumatoid pattern polyarthropathy.
•
Peripheral arthritis is generally non-erosive and the oligoarticular variant particularly may 
correlate with intestinal disease activity.
•
Axial arthritis may include inflammatory back pain, sacroilitis, or ankylosing spondylitis and 
is less likely to correlate with gastrointestinal symptoms. 
•
mechanisms remain unclear. 
•
Treatment of the gastrointestinal disease is not always sufficient for control of arthritis, and 
biologic agents may be indicated.
The description of weight loss, diarrhoea and a mono/oligo-arthropathy suggests a 
diagnosis of inflammatory bowel disease. (IBD).
____________________________________________________
Differential diagnoses of arthropathies associated with iron 
deposition in the joints →brown-stained synovial fluid.
•
Haemophilia
•
Haemosiderosis from recurrent haemarthrosis
•
Haemochromatosis, and
•
Pigmented villonodular synovitis (PVNS).
____________________________________________________
SAPHO syndrome
SAPHO is an acronym for synovitis, acne, pustulosis, hyperostosis, and osteitis. It is 
characterised by osteosclerotic bone lesions, sterile osteomyelitis, and a variety of skin lesions.
•
Synovitis - may be present rarely, and associates with erosions.
•
Acne - may be severe (conglobate or fulminans) and recur with new bony involvement.
•
Pustulosis - palmo-plantar pustulosis occurs in approximately 50% of patients, other skin 
lesions may include psoriasis, hidradenitis suppurativa, acne, and rarely Sweet's syndrome.
•
Hyperostosis (increase in bone substance) and osteitis (inflammation of the bones) - the 
bony lesions typically involve the acromioclavicular, and sternoclavicular joints. Other sites 
include anterior chest wall, sternum, clavicle, pubic symphysis, spine, and mandible. These 
lesions are visualised on 99m technetium bone scan or MRI.
The cause of the SAPHO syndrome is unknown. 
Investigation
•
skin lesions are characterised by neutrophilic pseudoabscesses.
•
Bone biopsy can reveal sterile osteomyelitis.
Diagnosis should be suspected when there is an association of rheumatic pain with a 
pustular skin disease.
treatment 
•
no specific treatment,
•
some cases remit spontaneously

Notes & Notes for MRCP                          
By Dr. Yousif Abdallah Hamad
Chapter 8

Rheumatology
 
•
Typical treatment can be used for the arthritic symptoms (i.e. non-steroidal antiinflammatories and disease modifying anti-rheumatic agents). 
•
Isotretinoin and aciretin can be used to treat the skin disease. 
•
In the more severe cases corticosteroids, calcitonin, bisphosphonates and TNF-inhibitors 
can be used.
____________________________________________________
Elbow pain
The table below details some of the characteristic features of conditions causing elbow 
pain:
Lateral 
epicondylitis 
(tennis elbow)
Features
•
pain and tenderness localised to the lateral epicondyle
•
pain worse on resisted wrist extension with the elbow extended 
or supination of the forearm with the elbow extended
•
episodes typically last between 6 months and 2 years. Patients 
tend to have acute pain for 6-12 weeks
•
most appropriate to gain short term relief for the patient? 
Local steroid/anaesthetic injection
Medial 
epicondylitis 
(golfer's elbow)
Features
•
pain and tenderness localised to the medial epicondyle
•
pain is aggravated by wrist flexion and pronation
•
symptoms may be accompanied by numbness / tingling in the 4th and 
5th finger due to ulnar nerve involvement
Radial tunnel 
syndrome
•
Most commonly due to compression of the posterior interosseous 
branch of the radial nerve. 
•
It is thought to be a result of overuse.
Features
•
symptoms are similar to lateral epicondylitis making it difficult to 
diagnose
•
however, the pain tends to be around 4-5 cm distal to the lateral 
epicondyle
•
symptoms may be worsened by extending the elbow and pronating
the forearm
Cubital tunnel 
syndrome
Due to the compression of the ulnar nerve.
Features
•
initially intermittent tingling in the 4th and 5th finger
•
may be worse when the elbow is resting on a firm surface or flexed for 
extended periods
•
later numbness in the 4th and 5th finger with associated weakness
Olecranon 
bursitis
Swelling over the posterior aspect of the elbow. There may be associated 
pain, warmth and erythema. It typically affects middle-aged male patients.

Notes & Notes for MRCP                          
By Dr. Yousif Abdallah Hamad

___________________________________________________________________
Shoulder problems
The table below summarises the key features of common shoulder problems:
Condition
Notes
Adhesive 
capsulitis
(frozen shoulder)
Common in middle-age and diabetics
Characterised by painful, stiff movement
Limited movement in all directions, with loss of external rotation and 
abduction in about 50% of patients
Supraspinatus 
tendonitis
(Subacromial 
impingement,
painful arc)
Rotator cuff injury
Painful arc of abduction between 60 and 120 degrees
Tenderness over anterior acromion
____________________________________________________
Prepatellar bursitis 

The most useful in initial diagnosis of prepatellar bursitis 
Crepitation of the knee
____________________________________________________
Polymyositis
Polymyositis is the commonest cause of inflammatory muscle disease in people under 50years-old (inclusion body myositis is the commonest in those over 50-years-old).
Definition 
•
Inflammatory disorder causing symmetrical, proximal, painless muscle weakness
Pathophysiology 
•
thought to be a T-cell mediated cytotoxic process directed against muscle fibres
Epidemiology 
•
Typically affects middle-aged
•
Female: male 3:1
Associated conditions 
•
Connective tissue disorders
•
Interstitial lung disease → evaluate with chest x-ray and pulmonary function tests.
•
Malignancy , commonly Adenocarcinomas , stronger for dermatomyositis, than for 
polymyositis. The most appropriate next investigation CT chest, abdomen and 
pelvis

Notes & Notes for MRCP                          
By Dr. Yousif Abdallah Hamad
Chapter 8

Rheumatology
 
Features
•
Proximal muscle weakness +/- tenderness
•
Raynaud's
•
Mechanics hands found in a subtype of polymyositis called anti-synthetase syndrome or 
Jo-1 syndrome →fissuring and cracking on the distal digital pads of several fingers.
•
Respiratory muscle weakness
•
Interstitial lung disease: e.g. fibrosing alveolitis or organising pneumonia
•
Dysphagia, dysphonia
Investigations
•
Elevated creatine kinase
(the initial investigation)
•
Electromyography (EMG): abnormal in almost all patients (90%).
Triad of:
1. Short, small polyphasia motor units
2. Fibrillation and sharp waves 
3. Bizarre, repetitive discharges  
•
Muscle biopsy
the definitive investigation to establish the diagnosis
Histopathology endomysial mononuclear inflammatory infiltrate with CD8 T
cells (MHC class I) and muscle fiber necrosis.
•
Anti-Jo-1 antibodies
seen in pattern of disease associated with lung involvement, Raynaud's and fever
•
Antinuclear antibody - Positive in one third 
Treatment
•
Prednisolone is the mainstay of treatment, at an initial dose of 1 mg/kg/d. 
•
In patients who fail to show improvement, disease-modifying steroid-sparing agents may be 
added. 
•
A high-protein diet and supervised exercise may further improve symptoms. 
Prognosis
•
Most patients have a favourable response to corticosteroid therapy, and 5-year survival 
rates approach 80%.
____________________________________________________
Dermatomyositis
Proximal weakness with normal reflexes and sensation and absence of fasciculations:
without skin lesion →polymyositis
with skin lesion → dermatomyositis
Definition
•
Dermatomyositis is a variant of an inflammatory myositis causing symmetrical, proximal 
muscle weakness and characteristic skin lesions, for example a purple Heliotrope rash on
the cheeks and eyelids or Gottron's papules: roughened red papules over extensor 
surfaces of fingers

Notes & Notes for MRCP                          
By Dr. Yousif Abdallah Hamad

Pathophysiology
•
Autoantibodies binding to the vasculature, muscle atrophy, and lymphocytic 
inflammation
•
caused by CD4 T cells that cause perimysial inflammation and atrophy.
Features 
•
Features of polymyositis (proximal muscle weakness, Raynaud's, respiratory muscle 
weakness, interstitial lung disease, dysphagia, dysphonia)
•
Pathognomonic skin features
Heliotrope rash in the periorbital region

a violaceous or erythematous rash in a symmetrical distribution involving 
periorbital skin. 

its presence is highly suggestive of dermatomyositis .
Gottron's papules: roughened red papules over extensor surfaces of fingers
•
Other skin lesions 
Photodistributed erythema, poikiloderma, nailfold changes
Mechanic's hands: (rough, cracked skin)
Fingers telangiectasia: Nail fold capillary dilatation.
Shawl sign: macular rash over back and shoulder 
V-neck sig : Violaceous erythema or poikiloderma involving the anterior chest 
•
↑↑↑risk of malignancy
Associated features 
•
Malignancies (dermatomycotic increases the risk of malignancy more than 
polymyositis ). typically lung cancer, found in 20-25%
•
Interstitial lung disease (ILD) occurs in at least 10%
Image shows: Gottron’s papules
Image shows: Heliotrope rash
Investigations
•
Elevated creatine kinase → the most helpful initial test
•
EMG
•
Muscle biopsy
high levels of the complement component C5b-9 around the capillary vessels.
Perimysial inflammation with lymphocytic infiltrate
•
ANA positive in 60%

Notes & Notes for MRCP                          
By Dr. Yousif Abdallah Hamad
Chapter 8

Rheumatology
 
•
Anti-Mi-2 antibodies are highly specific for dermatomyositis, but are only seen in around 
25% of patients
•
Screen for malignancy
Management
•
Prednisolone
•
Glucocorticoid-sparing agents: azathioprine or methotrexate.
Prognosis
•
Relatively good, with most patients reaching remission after 2–3 years, except of course 
where there is an associated underlying malignancy.
____________________________________________________
Inclusion body myositis (IBM)
Definition 
•
a syndrome of diffuse, progressive, asymmetric, proximal, and distal weakness that is 
generally refractory to immunosuppressive treatment.
•
The aetiology of IBM is largely unknown.
Epidemiology
•
IBM occurs more frequently in men than women.
•
More common in older Caucasian males.
•
the most common acquired myopathy in patients older than 50 years
Features
•
Muscle weakness can affect both proximal and distal muscles
unlike polymyositis and dermatomyositis, asymmetry is common.
characteristically early affects quadriceps and finger/wrist flexors are usually more 
severely 
The onset of muscle weakness in IBM is generally gradual (over months or years).
•
Dysphagia is common, occurring in 40-66% of patients
•
Difficulties with breathing →the most common cause of death is respiratory system 
disorders.
Diagnosis
•
creatine kinase (CK) levels: no striking elevation (less than 10 times normal)
•
anti-cN1A autoantibodies
•
Muscle biopsy 
shows intranuclear or cytoplasmic tubofilaments on electron microscopy.

The specific finding is the presence of sarcoplasmic “rimmed” vacuoles
Treatment
•
Optimal treatment for IBM is not known 
•
In contrast to dermatomyositis and polymyositis, IBM is relatively resistant to standard 
immunomodulatory therapies.

Polymyositis
Dermatomyositis
IBM
Onset 
Subacute 
Subacute 
Slow
Commonest < 50 years
commonest > 50 years
age
Commonest < 50 
years
Affected muscles 
Proximal 
Proximal
Proximal and distal
symmetry
symmetrical
symmetrical
Asymmetrical 
Common 
incidence 
Female 
Female 
Male
Skin lesion
NO
Characteristic rash 
NO
CK
Highly elevated (up 
to 50 fold)
Highly elevated (up to 50 
fold)
antibodies
anti-Jo-1 are more 
common
anti-Mi-2 are highly 
specific
anti-cN1A 
autoantibodies
Muscle biopsy
endomysial 
mononuclear 
inflammatory 
infiltrate and muscle 
fiber necrosis.
perivascular and 
interfascicular 
inflammatory infiltrates 
with adjoining groups of 
muscle fiber 
degeneration/regeneration
T cell 
CD8 T cell
CD4 T cell
good
Good 
Poor 
Response to 
steroids
Painless weakness and wasting with selective involvement of long finger flexors and 
quadriceps is characteristic of inclusion body myositis.
Inclusion body myositis occurs in older people, has an insidious onset, and does not 
associate with striking elevations in CK.
Notes & Notes for MRCP                          
By Dr. Yousif Abdallah Hamad

Mild elevated (up to 10 
fold) or normal
intranuclear or 
cytoplasmic 
tubofilaments

Notes & Notes for MRCP                          
By Dr. Yousif Abdallah Hamad
Chapter 8

Rheumatology
 
____________________________________________________
Fibromyalgia (FM)
Definition
•
Fibromyalgia is a syndrome characterised by widespread pain throughout the body with
tender points at specific anatomical sites.
Epidemiology
•
Prevalence: occur in 1 - 2% of the general population
•
Gender: women are 10 times more likely to be affected
•
Age: typically presents between 30-50 years old
Features
•
general symptoms: lethargy
•
musculoskeletal symptoms: 
chronic pain: at multiple site, sometimes 'pain all over'
allodynia: (pain in response to non-painful stimuli)
Morning fatigue 
morning stiffness 
tissue swelling, 
•
neurological and psychiatric symptoms: 
sleep disturbance, headaches, dizziness are common
patients often look unwell and may appear depressed and anxious.
•
GIT symptoms:
50% of patients with fibromyalgia complain of diarrhoea and constipation, often 
associated with abdominal bloating.
Diagnosis
•
The diagnosis of FM should be considered in any patient with ˃three months of widespread,
multisite pain without apparent causative found.
•
is clinical pain in all four quadrants of the body, as well as tenderness in 11 of 18 
anatomically defined trigger areas. 
•
The normal ESR in patients with FM contrasts with the high ESR in elderly patients with 
polymyalgia rheumatica.
•
Other causes of fatigue should be excluded e.g. hypothyroidism, anaemia and other 
rheumatological diseases 
Management
•
explanation
•
aerobic exercise: has the strongest evidence base
•
cognitive behavioural therapy
•
medication: pregabalin, duloxetine, amitriptyline
Key facts:
•
How to diagnose?
A female, presented with a feature of pain and tenderness over multiple area + 
normal ESR and CRP.
•
What is the best management?
aerobic exercise

Notes & Notes for MRCP                          
By Dr. Yousif Abdallah Hamad

____________________________________________________
Dupuytren’s contracture
Definition
•
progressive painless contracture of the palmar facial bands, causing flexion deformities of 
the fingers.
•
autosomal-dominant condition with variable penetrance.
Prevalence
•
has a male: female predominance of 10:1. 
•
prevalence rates approaching 25% in elderly Scandinavians. 
•
most commonly observed in persons of Northern European descent and affects 4-6% of 
Caucasians worldwide.
Pathophysiology
•
fibroblast proliferation, and collagen deposition leading to contractures of the palmar 
fascia.
•
Interleukin 1 (IL-1) is the most abundant cytokine 
•
Normal palmar fascia is primarily composed of type I collagen; Dupuytren disease is 
associated with an increase in type III collagen.
Risk factor
•
Alcoholism (10%),
•
diabetes mellitus (8%).
•
previous myocardial infarction, 
•
hand trauma, 
•
HIV infection, 
•
cigarette smoking. 
Features
•
bilateral in 45%;
•
in unilateral cases, the right side is more often affected.
•
The ring finger is most commonly involved, followed by the fifth digit and then the middle 
finger. The index finger and the thumb are typically spared.
•
Penile fibromatosis (Peyronie's disease) is seen in about 7-10% of patients.
Rheumatoid arthritis seems to protect against the development of Dupuytren disease.
Management
•
Surgery followed by physiotherapy to improve finger function is the recommended course of 
action. 
•
Collagenase therapy may be an alternative to surgery in some cases.