Disease
Description
Signs and Symptoms
Tests
Treatment
Sjögren's
syndrome
- Associated with the HLA-DR3
gene.
- This is essentially an
autoimmune reaction against
the bodies exocrine glands,
specifically the salivary and
lacrimal glands. This leads to
dry mouth (xerostomia), eye
problems (xeropthalmia) and
lymphocytic infiltration of
the glands. It eventually
destroys the glands.
- There are two types, primary
and secondary. Primary
presents as only sjogren’s,
without any other disorders.
Associated with the HLA-DR4
gene. 860/100,000 people
affected. RhF is an
autoantibody against igG.
Dry eyes, dry mouth, vaginal
dryness, lack of mucous production.
- Blood tests for anti-nuclear antibody (ANA)
and rheumatoid factor (because SS
frequently occurs secondary to rheumatoid
arthritis).
- Typical Sjögren's syndrome ANA patterns
are SSA/Ro and SSB/La, (SSB/La is far more
specific; SSA/Ro is associated with
numerous other autoimmune conditions
but often present in Sjögren's).
- Schirmer's test measures the production of
tears: a strip of filter paper is held inside
the lower eyelid for five minutes, and its
wetness is then measured with a ruler.
<5ml of liquid = Sjögren's syndrome.
Artificial tears, punctal plugs
into lacrimal ducts
mouth care, regular sips of
fluid, artificial saliva
topical cyclosporine or other
DMDs
awareness of lymphoma risk
- Initially joint inflammation
- Progresses to damage to joints.
- Inflammation, pain, deformity
- Mall joints affected (e.g. MCP and
PIP joints), but large joints can be
affected.
- Worse in the morning / before
exercise, improves with movement
during the day.
- There may be extra-articular
features (about 20% of cases).
These include fever, weight loss,
malaise, nodules, vasculitis,
anaemia, atlantoaxial subluxation
and others.
- Can be associated with Sjögren's
syndrome
- FBC : anaemia (chronic disease /
haemolytic)
- ESR : raised
- CRP : moderately raised
- RhF : raised in ~70% of cases (but also some
healthy people)
- Anti-citrullinated protein antibodies
- Anti-cyclic citrillunated peptides
- Anti-mutated citrullinate vimentin assay
- US, MR or isotope bone scans (early
changes)
- Radiographs of hands & feet (later changes)
:
- soft tissue swelling, juxta-articular
osteopenia, joint space narrowing →
periarticular erosions, subluxation,
deformity
- Steroids
- NSAIDs
- DMDs : methotrexate = antiproliferative (against folate
activity), azathioprine = antiproliferative (against purine
synthesis), sulphasalazine =
suppressive (against IL-1 &
TNF), penicillamine =
suppressive (against MΦs, T
cells, IL-1)
- Gold injections = uncertain
mechanism
- mAbs : infliximab = anti-TNF
cytokine, rituximab = antiCD20 on B lymphocytes
Rheumatoid
Arthritis
Graves’ Disease
The most common
autoimmune disorder (1152
per 100,000), but more
common in women (2% of all
women will get Grave’s
disease). Caused by
autoantibody IgG against the
TSH receptor.
All the signs and symptoms of
hyperthyroidism, including goitre,
exophthalmos (in 40% of cases, as
they have autoantibodies against the
ophthalmic muscles) and pre-tibial
myxoedema.
- TSH = low
- T3 & T4 = high
- anti-TSH receptor antibodies (TSHR-Ab)
- radio-iodine scans or thyroid biopsy =
rarely necessary
- beta-blocker (eg. propanolol)
- anti-thyroid drugs (eg.
carbimazole,
propylthiouracil)
- radio-active iodine treatment
(131I)
- thyroidectomy (partial)
organ-specific disease with
“indirect” treatments available
∴ systemic
immunosuppression not
justified
Hashimoto’s
Thyroiditis
An autoimmune condition in
which the thyroid itself is
attacked, resulting in
hypothyroidism with possible
bouts of hyperthyroid
symptoms.
- Hashimoto's thyroiditis is
All the signs and symptoms of
hypothyroidism.
Possible bouts of hyperthyroid
symptoms.
- Various autoantibodies may be present
- Low blood pressure
- Possible Addisonian crisis
- Hyperpigmentation
- Low steroid levels even after an
ACTH stimulation test.
interferon omega; transglutaminase;
aromatic acid carboxylase; GAD; HAI; 17
hydroxylase; 21 hydroxylase
against thyroid peroxidase, thyroglobulin
and TSH receptors, although a small
percentage of patients may have none of
these antibodies present.
- On gross examination, there is often
presentation of a hard goitre that is not
painful to the touch
Simply take T4 replacement
(levothyroxine)
often misdiagnosed as
depression, PMS, chronic
fatigue syndrome,
fibromyalgia and, less
frequently, as ED or
an anxiety disorder.
Addison’s
disease
Chronic underproduction of
steroid hormones by the
adrenal glands. Sometimes
(but not always) due to an
autoimmune problem.
Autoimmune adrenalitis is the
most common cause of
Addison's disease in the
industrialised world.
Autoimmune destruction of
the adrenal cortex is caused
Oral hydrocortisone to replace
the steroid hormones.
Replacement for other
steroids if needed.
Systemic Lupus
Erythematosus
by an immune reaction against
the enzyme 21-hydroxylase
- Associated with the HLA-DR2
and 3 genes.
- SLE most often harms the
heart, joints, skin, lungs,
blood vessels, liver, kidneys,
and nervous system. The
course of the disease is
unpredictable, with periods
of illness (called flares)
alternating with remissions.
- SLE occurs 9 times more
often in women than in men.
- It is both a type 2 and a type
3 hypersensitivity reaction
- The main cause of death is
from cardiovascular disease
due to accelerated
atherosclerosis.
- The most common presenting
symptom is joint pain, followed by
butterfly rash.
- Ulcers
- Stillbirth / miscarriage
- Photosensitivity of the skin
- Chest pain when taking a deep
breath
- Fatigue
- Fever with no other cause
- General discomfort, uneasiness, or
ill feeling (malaise)
- Hair loss
- Mouth sores
- Sensitivity to sunlight
- Skin rash - a "butterfly" rash in
about half people with SLE.
- Swollen lymph nodes
- Anti-nuclear autoantibodies, specifically
autoantibodies to double stranded DNA.
These are 70% specific for SLE.
- You may also get anti Ro and anti La forms
of anti-nuclear antibodies.
- Treated mainly with
immunosuppression
- Cyclophosphamide,
corticosteroids and other
immunosuppressant’s.
- The treatment of SLE
involves preventing flares and
reducing their severity and
duration when they occur.
- DMD’s used to reduce the
frequency and duration of
flares include methotrexate
and azathioprine.
- Recently a new drug for the
treatment of SLE has become
available, belimumab.
Coeliac disease
Crohn’s disease
- Coeliac disease is an
autoimmune disorder of the
small intestine that occurs in
genetically predisposed
people of all ages from
infancy onward.
- Can be screened for, so a lot
of people are diagnosed
while asymptomatic.
- It is thought to affect 1% of
the population in the UK.
- It is caused by an immune
reaction to gliadin, a protein
found in wheat and other
common grains. This protein
is modified by an enzyme
(tissue transglutaminase),
and the immune system then
cross reacts with the small
bowel tissue, causing
inflammation.
- NOTE: this is different from a
wheat allergy!
- Linked with the HLA-DQ2
allele.
- The aetiology of Crohn’s
disease is not well
understood. It is known to be
an immune disorder, but it is
theorised that the immune
reaction is against the gut
flora, and the damage to the
gut itself is an unfortunate
side effect.
- It may not be classified as an
autoimmune disorder as the
reaction is triggered by non
self-antigens (theoretically),
- Pain and discomfort in the digestive
tract.
- Chronic constipation and diarrhoea
- Failure to thrive
- Anaemia
- Malabsorption
- Steatorrhoea
- Weight loss
- Anti-gliadin & anti-endomysial
autoantibodies
- Anti-transglutaminase antibodies to the
enzyme tissue transglutaminase (tTG) are
found in an overwhelming majority of
cases, and this is the most common test for
coeliac disease.
- The gold standard test is a small bowel
biopsy, and this is usually done for
everyone with a positive serological test.
Gluten free diet is the only
long term treatment, and
symptoms should begin to
improve following the start of
a gluten fre diet. It can take up
to a year for the bowel to
recover, so patients may still
be symptomatic during this
time.
If a patient does not improve
on a gluten free diet (possibly
because they do not stick to
the diet, or because the
intestine is so badly damaged
that it cannot heal properly),
then the patient may be given
immunosuppressants such as
azathioprine.
Patchy, cobblestone appearance to
the GIT mucosa due to transluminal
skip lesions.
- The patient may present with
abdominal pain, diarrhoea (may be
bloody), vomiting and weight loss.
- The gold standard test is colonoscopy and a
biopsy analysis.
- Under a microscope, biopsies of the
affected colon may show mucosal
inflammation, characterized by focal
infiltration of neutrophils, a type of
inflammatory cell, into the epithelium. This
typically occurs in the area overlying
lymphoid aggregates. These neutrophils,
along with mononuclear cells, may
infiltrate the crypts, leading to
inflammation (crypititis) or abscess (crypt
abscess). Granulomas, aggregates of
- There is no cure for Crohn’s
disease, and remission may
not be possible.
- Smoking is BAD FOR
CROHN’S DISEASE! Stopping
smoking is one of the best
treatments (if people do
smoke).
- Acute treatment uses
medications to treat any
infection (normally
antibiotics) and to reduce
inflammation (normally
but it usually treated as
though it were.
Diabetes
Mellitus type 1
Associated with the HLA-DR4
and 3 genes.
- Autoimmune destruction of
the pancreas, usually onsets
in childhood.
- It has an incidence of
between 8 and 17 per
100,000 in the UK
- It is a polygenic disease, and
may be dominant, recessive
or new onset.
- The most influential gene,
IDDM1, is located in the MHC
class II region on Ch6, at
region 6p21.
- The classical symptoms are
polyuria, nocturia, weight loss,
polyphagia (increased hunger) and
polydipsia (increased thirst)
- Untreated, type 1 diabetes is fatal.
- Diabetic ketoacidosis is the most
deadly complication of DM1
macrophage derivatives known as giant
cells, are found in 50% of cases and are
most specific for Crohn's disease.
aminosalicylate antiinflammatory drugs and
corticosteroids).
- Medications used to treat
the symptoms of Crohn's
disease include 5aminosalicylic acid (5-ASA)
formulations, prednisone,
immunomodulators such as
azathioprine (given as the
prodrug for 6mercaptopurine),
methotrexate, infliximab,
adalimumab, certolizumab
and natalizumab.
Hydrocortisone should be
used in severe attacks of
Crohn's disease.
Type 1 diabetes can be distinguished from
type 2 by autoantibody testing - glutamic
acid decarboxylase autoantibodies (GADA),
islet cell autoantibodies (ICA), insulinomaassociated (IA-2) autoantibodies, and zinc
transporter autoantibodies (ZnT8) are
present in individuals with type 1 diabetes,
but not type 2. The C-peptide assay, which
measures endogenous insulin production,
can also be used.
- Supplemental insulin
- Islet or pancreas transplant
- Cyclosporine A, an
immunosuppressive agent,
has apparently halted
destruction of beta cells (on
the basis of reduced insulin
usage), but its nephrotoxicity
and other side effects make
it highly inappropriate for
long-term use.
- The risk of a child developing
type 1 diabetes is about 10%
if the father has it, about 10%
if a sibling has it, about 4% if
the mother has type 1
diabetes and was aged 25 or
younger when the child was
born, and about 1% if the
mother was over 25 years old
when the child was born. If
one individual of a pair of
monozygotic twins has DM1
then there is a 50% chance of
the other twin having it.
Guillain–Barré
syndrome
- This is an acute
polyneuropathy affecting the
peripheral nervous system.
- It typically begins as
weakness in the hands and
feet, and advances rapidly up
the body, so that within a
day or two the patient is
completely paralysed.
- It can be life threatening if
the respiratory muscles are
affected or if the autonomic
nervous system is involved.
- It is usually (but not always)
triggered by an infection.
- Six subtypes of Guillain-Barré
syndrome exist, but you do
not really need to know
these for the exams.
- This autoimmune condition
targets the nerve tissues due
to molecular mimicry.
- The most common preceding
infection is Campylobacter
Jejuni, but others are
possible.
- The most common symptom is
symmetrical weakness that usually
affects the lower limbs first, and
rapidly ascends towards the trunk.
- Often this will lead to involving the
respiratory muscles, which can be
life threatening.
- The demyelination that can occur
causes the majority of the
symptoms.
- This is a purely peripheral nerve
disorder, and does not cause
damage to the brain or spinal cord.
- The diagnosis is usually made via nerve
conduction studies and examination of the
CSF.
- The nerve conduction studies may show
prolonged distal latencies, conduction
slowing, conduction block, and temporal
dispersion of compound action potential in
demyelinating cases.
- Patients often demonstrate areflexia
(complete loss of the deep tendon
reflexes).
- About 80% of patients have myelin loss
(which means they can rapidly recover by
simply remyelinating the nerves.
- The other 20% have axonal loss, which
takes far longer to recover from.
- The diagnosis of GBS depends on findings
such as rapid development of muscle
paralysis, areflexia, absence of fever, and a
likely inciting event. Cerebrospinal fluid
analysis (through a lumbar spinal puncture)
and electrodiagnostic tests of nerves and
muscles (such as nerve conduction studies)
are common tests ordered in the diagnosis
of GBS.
- With prompt treatment by
intravenous immunoglobulins
or plasmapheresis, together
with supportive care, the
majority will recover
completely.
- Most patients require
hospitalisation, and about 30%
require ventilator assistance.
- Subsequent treatment
consists of attempting to
reduce the body's attack on
the nervous system, either by
plasmapheresis, filtering
antibodies out of the blood
stream, or by administering
intravenous immunoglobulins
(IVIg), to neutralize harmful
antibodies and inflammation
causing disease. These two
treatments are equally
effective and a combination of
the two is not significantly
better than either alone.
Glucocorticoids have not been
found to be effective in GBS.
Multiple
Sclerosis
- MS is also known as
disseminated sclerosis or
encephalomyelitis
disseminate.
- It is an inflammatory disease
that leads to destruction of
the myelin sheaths in the
brain and spinal cord.
- It is postulated (not known
for certain) that MS is due to
autoimmune destruction of
the myelin producing
schwann cells.
- MS has an uncertain natural
history, and the prognosis is
very difficult to ascertain
with any accuracy. In
general, women have a
better prognosis than men.
- A better prognosis is also
likely in people who develop
the disease when they are
young, those who initially
experienced few attacks and
those whose symptoms
disappear completely
between attacks.
- There is a possible link
between MS and vitamin D,
as MS is less common in
people living on or near the
equator, regardless of their
genealogical heritage. People
that move to a new area of
- The symptoms of MS include both
physical and neurological problems.
- The symptoms (especially
symptoms occurring once the
disease is more progressed) can
occur either in isolated attacks or
building up in a progressive
manner.
- Symptoms may disappear
completely in between attacks, but
unfortunately with repeated
attacks, neurological damage
occurs that is irreversible.
- 85% of people improve after an
attack, but the other 15% gradually
worsen over time with no periods
of recovery.
- Features required for diagnosis are
progressive weakness in legs and often
arms, and areflexia (the absence of deep
tendon reflexes)
- MS is diagnosed based on the clinical
picture (signs and symptoms) and some
test results.
- It is impossible to predict when an attack
will occur, but they rarely occur more than
twice per year.
- It is known, however, that some things
(springtime, viral infections etc) can
increase the risk of a flare up.
- There is no cure for MS, so
treatment is mainly based
around ameliorating attacks
and delaying progression.
- Unfortunately, many of the
drugs used to treat MS have
rather nasty side effects, so
many people pursue
alternative treatments.
the world before the age of
15 acquire that regions risk
of MS, and moving may be of
benefit to older people as
well.
Wegener's
granulomatosis
- This disease is now known as
Granulomatosis with
polyangiitis. It is a systemic
autoimmune disorder that
involves both granulomatosis
and polyangiitis.
- It is a form of vasculitis that
affects small and medium
blood vessels.
- Granulomatosis with
polyangiitis is part of a larger
group of vasculitic
syndromes, all of which
feature an autoimmune
attack by an abnormal type
of circulating antibody
termed ANCAs
(antineutrophil cytoplasmic
antibodies) against small and
- In general, rhinitis is the first sign in
most patients.
- Other signs include decreased
kidney function and chronic renal
failure, upper airway disease, ENT
(ear, nose and throat) damage,
pulmonary disease, joint problems,
skin nodules and occasionally
sensory neuropathy.
- c-ANCA (antineutrophil cytoplasmic
antibodies)
- Granulomatosis with polyangiitis is usually
suspected only when a patient has had
unexplained symptoms for a long period of
time. Determination of Anti-neutrophil
cytoplasmic antibodies (ANCAs) can aid in
the diagnosis, but positivity is not
conclusive and negative ANCAs are not
sufficient to reject the diagnosis.
Cytoplasmic-staining ANCAs that react with
the enzyme proteinase 3 (cANCA) in
neutrophils are associated with Wegener's.
- If the patient has renal failure or cutaneous
vasculitis, a biopsy is obtained from the
kidneys.
- Without treatment, life
expectancy is only around 5
months.
- Steroids increase this to 8
months
- Cyclophosphamide and
newer immunosuppressive
drugs have led to a 5 year
survival rate of 87%.
- In general, treatment is
initially corticosteroids and
oral cyclophosphamide,
although the
cyclophosphamide can be
given IV.
- Once the patient is in
remission, treatment is
usually changed from
cyclophosphamide to
medium-size blood vessels.
Apart from Wegener's, this
category includes Churg–
Strauss syndrome and
microscopic polyangiitis.
azathioprine or
methotrexate, as these are
less toxic.
- Rituximab has also recently
been approved to treat the
condition.
Learn the following table regarding Crohn’s disease and ulcerative colitis!