SYSTEMIC LUPUS ERYTHEMATOSUS

Exams and Tests

The diagnosis of SLE is based upon the presence of at least 4 out of 11 typical characteristics of the
disease. The doctor will listen to your chest with a stethoscope. A sound called a heart friction rub or
pleural friction rub may be heard. A neurological exam will also be performed.

Tests used to diagnose SLE may include:

 Antibody tests, including:

o Antinuclear antibody (ANA) panel
o Anti-double strand (ds) DNA
o Antiphospholipid antibodies
o Anti-Smith antibodies
 CBC to show low white blood cells, hemoglobin, or platelets
 Chest x-ray showing pleuritis or pericarditis
 Kidney biopsy
 Urinalysis to show blood, casts, or protein in the urine

This disease may also alter the results of the following tests:

 Anti-SSA or -SSB antibodies

 Antithyroglobulin antibody
 Antithyroid microsomal antibody
 Complement components (C3 and C4)
 Coombs' test - direct
 Cryoglobulins
 ESR
 Rheumatoid factor
 RPR - a test for syphilis
 Serum globulin electrophoresis
 Serum protein electrophoresis

Treatment

There is no cure for SLE. Treatment is aimed at controlling symptoms. Your individual symptoms
determine your treatment.

Mild disease that involves a rash, headaches, fever, arthritis, pleurisy, and pericarditis does not need
much therapy.

 Nonsteroidal anti-inflammatory medications (NSAIDs) are used to treat arthritis and pleurisy.
 Corticosteroid creams are used to treat skin rashes.
 An antimalaria drug (hydroxychloroquine) and low-dose corticosteroids are sometimes used for
skin and arthritis symptoms.
You should wear protective clothing, sunglasses, and sunscreen when in the sun.

Severe or life-threatening symptoms (such as hemolytic anemia, extensive heart or lung

involvement, kidney disease, or central nervous system involvement) often require treatment by a
rheumatologist and other specialists.

 Corticosteroids or medications to decrease the immune system response may be prescribed to

control the various symptoms.
 Cytotoxic drugs (drugs that block cell growth) are used to treat people who do not respond well to
corticosteroids, or who are unable to stop taking corticosteroids without their symptoms getting
worse.

Possible Complications

Some people with SLE have deposits of antibodies in the cells (glomeruli) of the kidneys. This leads to a
condition called lupus nephritis. Patients with this condition may eventually develop kidney failure and
need dialysis or a kidney transplant.

SLE causes damage to many different parts of the body, including:

 Blood clots in the legs (deep vein thrombosis) or lungs (pulmonary embolism)
 Destruction of red blood cells (hemolytic anemia) or anemia of chronic disease
 Fluid around the heart (pericarditis), endocarditis, or inflammation of the heart (myocarditis)
 Fluid around the lungs (pleural effusions), damage to the lung tissue (interstitial lung disease)
 Pregnancy complications, including miscarriage and flare-up of SLA during pregnancy
 Stroke
 Severely low blood platelets (thrombocytopenia)
 Vasculitis, which may damage arteries anywhere in the body

Pathophysiology
SLE is a result of disturbed immune regulation that causes
an exaggerated production of autoantibodies. This immunoregulatory
disturbance is brought about by some combination
of genetic, hormonal (as evidenced by the usual onset during the
childbearing years), and environmental factors (sunlight, thermal
burns). Certain medications, such as hydralazine (Apresoline),
procainamide (Pronestyl), isoniazid (INH), chlorpromazine
(Thorazine), and some antiseizure medications, have been implicated
in chemical or drug-induced SLE.
In SLE, the increase in autoantibody production is thought to
result from abnormal suppressor T-cell function, leading to immune
complex deposition and tissue damage. Inflammation stimulates
antigens, which in turn stimulate additional antibodies,
and the cycle repeats.

Guillain-Barré syndrome (GBS) is a rare medical condition that affects the nerves outside the brain
and spinal cord. 

1. Peak ages: teens and adults > 55 yo

 2. Male:Female = 1.25:1

GBS Causes

Guillain-Barre syndrome is not hereditary or contagious. What causes GBS is not known; however, in about half of all
cases the onset of the syndrome follows a viral or bacterial infection, such as the following:

 Campylobacteriosis (usually from eating undercooked poultry)

 Flu (influenza), common cold

 Gastrointestinal viral infection

 HIV

 Infectious mononucleosis

 Porphyria (rare disease of red blood cells)

 Viral hepatitis

A small number of cases have been known to occur after a medical procedure, such as minor surgery.

Tests 
Three tests can confirm a diagnosis of Guillain-Barre syndrome.

Lumbar puncture (spinal tap)—The patient is given local anesthetic. Once the anesthetic has taken effect, a needle
is inserted between two lower (lumbar) vertebrae and a sample of cerebrospinal fluid is drawn. An elevated level of
protein without an increase in the number of white blood cells (WBCs) in the fluid is characteristic of GBS.

Electromyogram (EMG)—This is an effective diagnostic tool because it records muscle activity and can show the
loss of individual nerve impulses due to the disease's characteristic slowing of nerve responses.

Nerve conduction velocity (NCV)—This test is performed with EMG, and together, they are often referred to
as EMG/NCV studies. NCV records the speed at which signals travel along the nerves. These signals are
characteristically slowed in GBS, although the findings may evolve over several weeks.

Treatment

Plasmapheresis 
Patients diagnosed early in the course of the disease and those who are acutely ill often respond well to blood
plasma exchange (plasmapheresis). In this procedure, blood is withdrawn and passed through a series of filters that
separate the different types of blood cells. The blood cells are then suspended in donor or synthetic plasma and
returned to the patient's body. The patient's plasma is discarded.
Plasmapheresis is thought to remove the substances that damage myelin. It can shorten the course of GBS, alleviate
symptoms, and prevent paralysis.

Immunoglobulin 
Large doses of immunoglobin given intravenously can help shorten the duration of symptoms. This treatment is just
as effective as plasmapheresis. It often is preferred to plasmapheresis because it does not require insertion of a large
venous catheter.

Overall, about 70% of patients respond to plasmapheresis or immunoglobin. There is no evidence of additional
benefit from treatment with both procedures.

Medications 
Muscle and joint pain can be treated with over-the-counter analgesics such as aspirin. If necessary, stronger pain
medication (e.g., acetaminophen with hydrocodone) may be prescribed. Muscle spasms can be controlled with
relaxants such as diazepam (Valium®).

Unpleasant sensation problems, such as painful tingling, can be treated with tricyclic antidepressants or
anticonvulsants such as gabapentin (Neurontin®).

Corticosteroids, which often effectively treat the symptoms of autoimmune disorders, actually worsen Guillain-Barre
syndrome and should not be used. However, they often are used to treat CIDP.

Physical therapy 
Before recovery begins, caregivers move the patient's arms and legs to prevent stiffness. After symptoms subside,
the rehabilitation team will prescribe an active exercise routine to help regain muscle strength and independence.
Training with adaptive devices, such as a wheelchair or braces, give the patient mobility.

Hydrotherapy 
Whirlpool therapy (hydrotherapy) may help relieve pain and be useful in retraining the movement of affected limbs.

Pharmacologic Interventions:
1. Analgesics and muscle relaxants to control painful sensations and fasciculations.
Nursing Interventions:
1. Monitor respiratory status through vital capacity measurements, rate and depth of respirations, and breath
sounds.
2. Monitor level of muscle weakness as it ascends toward respiratory muscles. Watch for breathlessness while
talking which is a sign of respiratory fatigue.
3. Monitor the patient for signs of impending respiratory failure.
4. Monitor gag reflex and swallowing ability.
5. Position patient with the head of bed elevated to provide for maximum chest excursion.
6. Avoid giving opioids and sedatives that may depress respirations.
7. Position patient correctly and provide range-of-motion exercises.
8. Provide good body alignment, range-of-motion exercises, and change of position to prevent complications
such as contractures, pressure sores, and dependent edema.
9. Ensure adequate nutrition without the risk of aspiration.
10. Encourage physical and occupational therapy exercises to help the patient regain strength during
rehabilitation phase.
11. Provide assistive devices  as needed (cane or wheelchair) to maximize independence and activity.
12. If verbal communication is possible, discuss the patient’s fears and concerns.
13. Provide choices in care to give the patient a sense of control.
14. Teach patient about breathing exercises or use of an incentive spirometer to reestablish normal breathing
patterns.
15. Instruct patient to wear good supportive and protective shoes while out of bed to prevent injuries due to
weakness and paresthesia.
16. Instruct patient to check feet routinely for injuries because trauma may go unnoticed due to sensory
changes.
17. Urge the patient to maintain normal weight because additional weight will further stress monitor function.
18. Encourage scheduled rest periods to avoid fatigue.

Management / Initial orders

- Admit for close observation until maximum progression reached and then as required
- ABCs!
- Diet: high protein, high caloric +/- NG tube and dietary consult as required
- Activity: bed rest, HOB <30 degrees
- Vitals q1h-q4h
- Spinal cord testing BID initially then OD
- CBC, electrolytes, urea, creatinine, glucose, liver enzmes, INR/PTT, bilirubin
- Serum protein electrophoresis and quantitative immunoglobulins (BEFORE starting IVIg)
           - Anaphylaxis may occur more commonly in patients with IgA deficiency treated with IVIg
- Bedside spirometry (FVC/FEV1) BID-QID
- Cap gases daily and as required (see NOTE below)
- Pulse oximetry (see NOTE below)
- Telemetry / cardiac monitoring
- Initial ECG

Supportive treatments
- IV access with adequate hydration
- Foley catheter
- NG tube with feeds as required
- DVT prophylaxis: TED stockings and heparin 5000 units SC BID
- Nerve protectors to nerve pressure points to prevent sec. compression palsies
- OT / PT / swallowing consults
- Chest physiotherapy
- Pain control: NSAIDs or morphine, will usually require narcotics
- Aggressive bowel routine (lactulose or milk of magnesium PO 15-30 cc OD to BID, colace 100 mg PO
BID, dulcolax supp OD prn, fleet prn)
- Psychological / social suport

Pathophysiology
All forms of Guillain-Barre syndrome are due to an immune response to foreign antigens (such as
infectious agents or vaccines) that becomes mistargeted to host nerve tissues (a form of antigenic
mimickry). The targets of such immune attack are thought to begangliosides, which are complex
glycosphingolipids present in large quantities on human nerve tissues, especially in the nodes of
Ranvier. An example is the GM1 ganglioside, which can be affected in 20-50% of cases, especially
in those preceded by Campylobacter jejuni infections. Another example is the GQ1b ganglioside,
which is the target in the Miller-Fisher syndrome variant (see below).
The result of such autoimmune attack on the peripheral nerves is inflammation of myelin and
subsequent conduction block, leading to a rapidly evolving flaccid paralysis which is sometimes
accompanied by sensory or autonomic disturbances. However, in mild cases, axonal function
remains intact and recovery can be rapid if remyelination occurs. In severe cases, such as in the
AMAN or AMSAN variants (see below), axonal degeneration occurs, and recovery depends on
axonal regeneration. Recovery is much slower, and there is more residual damage. Recent studies
have shown that about 80% of patients have myelin loss, and the remainder have axon loss

Clinical variants
Although ascending paralysis is the most common form of spread in GBS, other variants exist.

 Miller-Fisher Syndrome (MFS) is a rare variant and manifests as a descending paralysis,

proceeding in the reverse order of the more common form of GBS. It usually affects the
ocular muscles first and presents as ophthalmoplegia, ataxia, and areflexia. Anti-GQ1b
antibodies are present in 90% of cases.
 Acute motor axonal neuropathy (AMAN) attacks motor nodes of Ranvier and is prevalent
in China and Mexico. The disease may be seasonal and recovery is rapid. Anti-GD1a
antibodies are present.
 Acute motor sensory axonal neuropathy (AMSAN) is similar to AMAN but also affects
sensory nerves with severe axonal damage. Recovery is slow and often incomplete.

Pathophysiology
  Post-infectious, immune mediated disease
 Most patients have infectious disease in weeks prior to onset.
 Many infectious agents thought to induce antibody production against specific gangliosides and
glycolipids that are distributed throughout the myelin in the peripheral nervous system.
 Campylobacter jejuni is most common associated organism.
 C. jejuni’s virulence based on specific antigens in its capsule that are shared with nerves.
 Immune responses directed against its capsular components produce antibodies that react with
myelin- demyelination.
 Lymphocytic infiltration of spinal roots and peripheral nerves
 Then, macrophage mediated multifocal stripping of myelin
 Then, defects in nerve impulse propagation
 Results in conduction block and flaccid paralysis of some degree
 Secondary axonal disruption and loss can result

Myasthenia gravis
Background
Myasthenia gravis (MG) is an acquired autoimmune disorder characterized clinically by weakness of
skeletal muscles and fatigability on exertion. Thomas Willis reported the first clinical description in 1672.

Incidence and Prevalence of Myasthenia Gravis

Myasthenia gravis affects approximately 2 out of every 100,000 people and can occur at any age. It is most common
in women between the ages of 18 and 25. In men, the condition usually develops between 60 and 80 years of age.

 Prevalence
o 50 to 400 cases per million
o Higher > 40 years
 Annual incidence: 2.5 to 20 per million
 Lifetime risk: 500 per million

Symptoms & Signs

 Weakness
o Variable: May increase through the day, or with prolonged physical
activity
o Onset: Often diplopia or ptosis 2° to extraocular muscle or levator
palpebrae weakness
 Most patients develop weakness in other muscles
 Ocular myasthenia
o Weakness remains limited to ocular muscles during entire
course of the illness
o Specific muscle groups
 Ocular
o Ptosis & Ophthalmoplegia
o Usually asymmetric & bilateral
o Pupils: Normal
o Rule out focal neural lesions
 III or VI nerve lesion; Internuclear ophthalmoplegia
 Especially when unilateral signs
 Bulbar
o Symptoms: Dysarthria, Dysphagia, Weak mastication
o Signs: Poor gag reflex & palate elevation; Weak tongue
o May result in aspiration pneumonia
o Considered life-threatening
 Usually an indication for rapidly-acting therapeutic
intervention
 Plasma exchange most commonly used
 Facial
o Frequency: > 95% of MG
o Reduced facial expression, or snarl with attempt to smile
o Distribution: Orbicularis oculi most common; Also
orbicularis oris
 Respiratory failure
o Considered life-threatening
o Usually due to Diaphragmatic and Intercostal muscle
weakness
 Strong indication for rapidly-acting therapeutic
intervention
 Pyridostigmine & Plasma exchange most commonly
used
o May be due to vocal cord paralysis1
 Vocal cords in adductor position: Produces stridor
 May require intubation
o Monitor with forced vital capacity
 Limbs & Trunk
o Typical
 Proximal > Distal
 Arms > Legs
 Symmetric
 o Weakness in selective areas
 Posterior neck (head ptosis)
 Triceps
 Quadriceps
 Occasionally: Distal musculature
 Differences from LEMS3
o LEMS never begins with ocular weakness
o LEMS usually has weakness in Legs > Arms
 Fatigue
o Induced by
 Repetitive muscle strength testing
 Prolonged tonic contraction
o Quantitation
 Timed upward gaze
 Forward arm abduction
 Muscle wasting: Uncommon, except when MG is chronic & untreated
 Deep tendon reflexes
o Usually preserved
o May be brisk in clinically weak muscles
 Sensory: Normal

Pathophysiology
Autoantibodies (immunoglobulin G [IgG]) develop against ACh nicotinic postsynaptic receptors for
unknown reasons, although certain genotypes are more susceptible. 2 

Cholinergic nerve conduction to striated muscle is impaired by a mechanical blockage of the binding site
by antibodies and, ultimately, by destruction of the postsynaptic receptor.

Patients become symptomatic once the number of ACh receptors is reduced to approximately 30% of
normal. The cholinergic receptors of smooth and cardiac muscle have a different antigenicity than skeletal
muscle and are not affected by the disease.

The role of the thymus in the pathogenesis of myasthenia gravis is not entirely clear, but 75% of patients
with myasthenia gravis have some degree of thymus abnormality (eg, hyperplasia in 85% of cases,
thymoma in 15% of cases). Given the immunologic function of the thymus and the improvement in the
clinical condition of patients following thymectomy, the thymus is suspected to be the site of autoantibody
formation. However, the stimulus that initiates the autoimmune process has not been identified
Laboratory Studies
Anti-acetylcholine receptor antibody

This test is reliable for diagnosing autoimmune myasthenia gravis. The result of the test for the anti-AChR
antibody (Ab) is positive in 74% of patients.

 Results are positive in about 80% of patients with generalized myasthenia and in 50% of those
with pure ocular myasthenia.
 Thus, the anti-AChR Ab test result is frequently negative in patients with only ocular myasthenia
gravis.

False-positive anti-AChR Ab test results have been reported in cases of thymoma without myasthenia
gravis and in patients with Lambert-Eaton myasthenic syndrome, small cell lung cancer, rheumatoid
arthritis treated with penicillamine, and in 1-3% of the population older than 70 years.

Antistriated muscle (anti-SM) Ab 

This is another important test in patients with myasthenia gravis.

 It is present in about 84% of patients with thymoma who are younger than 40 years and less often
in patients without thymoma.
  Thus its presence should prompt a search for thymoma in patients younger than 40 years.
 In individuals older than 40 years, anti-SM Ab can be present without thymoma.

Thyroid function tests 

Thyroid function should be tested to evaluate for coexistent thyroid disease.

Anti-MuSK antibody 

About half of the patients who are AChR-ab negative (seronegative myasthenia gravis) may be positive
for muscle-specific receptor tyrosine kinase (MuSK) antibodies. They may represent a distinct group of
autoimmune myasthenia gravis, as they show some characteristics as a group that are different from
AChR-positive patients.9These individuals tend to have more pronounced bulbar weakness and may have
tongue and facial atrophy. They may have neck, shoulder and respiratory involvement without ocular
weakness. They are also less likely to respond to acetylcholine esterase inhibitors, and their symptoms
may actually worsen with these medications.10,11 

Antistriational antibodies

Serum from some patients with myasthenia gravis possesses antibodies that bind in a cross-striational
pattern to skeletal and heart muscle tissue sections. These antibodies react with epitopes on the muscle
protein titin and ryanodine receptors (RyR). Almost all patients with thymoma and myasthenia gravis and
half of the late-onset myasthenia gravis patients (onset >50 y) exhibit an antibody profile with a broad
striational antibody response. Striational antibodies are rarely found in AChR Ab negative patients. These
antibodies can be used as prognostic determinants in myasthenia gravis; as in all subgroups of
myasthenia gravis, higher titers of these antibodies are associated with more severe disease. 12

As it is often associated with thymoma in young patients with myasthenia gravis, the presence of titin/RyR
antibodies should arouse strong suspicion of thymoma in a young patient with myasthenia gravis.

Imaging Studies

 Chest radiograph
o Plain anteroposterior and lateral views may identify a thymoma as an anterior mediastinal
mass.
o A negative chest radiograph does not rule out a smaller thymoma, in which case a chest
CT scan is required.
 Chest CT scan is mandatory to identify thymoma in all cases of myasthenia gravis. This is
especially true in older individuals.

 MRI of the brain and orbits should not be obtained routinely. It is helpful when the diagnosis of
myasthenia gravis is not established and to rule out other causes of cranial nerve deficits. MRI
can evaluate for intraorbital or intracranial lesions, basal meningeal pathology, or multiple
sclerosis.

Procedures

 Electrodiagnostic studies can demonstrate a defect of neuromuscular transmission in 2 ways.

 o The first is by repetitive stimulation of a muscle at 2-3 Hz, also known as repetitive nerve
stimulation (RNS).
o The second is by performing single-fiber electromyography (SFEMG) and evaluating
neuromuscular block, jitter, and fiber density.
o SFEMG is more sensitive than RNS in myasthenia gravis. However, SFEMG is
technically more difficult and much more dependent on the experience and skill of the
testing physician.
o Thus RNS is the most frequently performed neurophysiological test of neuromuscular
transmission.
 Single-fiber electromyography: A concentric needle electrode or other monopolar and bipolar
needle electrodes record single motor unit potentials, but cannot discriminate individual muscle
fibers within the motor unit.
o The single-fiber needle, which has a small recording surface, allows recording from
individual muscle fibers.
o It can determine jitter (ie, variability of the interpotential interval between 2 or more single
muscle fibers of the same motor unit) and fiber density (ie, number of single-fiber action
potentials within recording radius of the needle).
o The following findings are suggestive of NMF transmission defect: increased jitter (with or
without impulse blocking) and normal fiber density.
o Examination of a weak muscle by SFEMG is more useful than RNS in demonstrating
abnormal neuromuscular transmission. In generalized myasthenia gravis, results of
SFEMG of the extensor digiti communis (EDC) are abnormal in 87% of patients.
Examination of a second muscle raises the sensitivity to 99%.
o In ocular myasthenia gravis, examination of the frontalis muscle is more useful than
examination of the EDC, since frontalis findings are abnormal in almost 100% of patients;
only approximately 60% of EDC findings are abnormal.
o Treatment with AChR inhibitors does not normalize SFEMG.
o SFEMG findings are abnormal in almost 100% of patients, while RNS findings are
abnormal in only 44-65%.
 Repetitive nerve stimulation (RNS): During low-frequency RNS (1-5 Hz), the locally available ACh
becomes depleted at all NMJs, and less is available for immediate release. This results in smaller
EPSPs.
o In patients without myasthenia gravis, all EPSPs exceed the threshold to generate an
action potential (ie, safety factor). No change in the summated compound muscle action
potential (CMAP) is noted.
o In patients with myasthenia gravis, the number of AChRs is reduced, lowering the safety
factor. During RNS, some EPSPs may not reach threshold and no action potential is
generated. This results in the decrement in the amplitude of the CMAP.
o In patients with myasthenia gravis, this decremental response usually has a maximum
decrement at the fourth or fifth response and then a tendency toward repair, as shown
below.

o Any decrement over 10% is considered abnormal.
o Patients with myasthenia gravis rarely have a decremental response in a clinically normal
muscle. Thus, testing a proximal weak muscle gives a better yield than testing a
technically easier unaffected distal muscle. Testing a facial muscle (orbicularis oculi) is
useful since most patients suffer from eyelid weakness or ptosis.
o The most common employed stimulation rate is 3 Hz.
 o Several factors can affect RNS results.
 Lower temperature increases the amplitude of the CMAPs. Patients with
myasthenia gravis may report clinically significant improvement in cold
temperatures. Typically they report worsening of ptosis in bright sunlight or on a
warm day. Therefore maintaining a constant and perhaps higher-than-ambient
temperature during RNS testing is important to bring out abnormalities of NMJ
function. Temperature of skin overlying the tested muscle should be at least
34°C.
 Administration of AChE inhibitors prior to the testing may mask the abnormality
and should be avoided for at least 1 day prior to testing (even longer for long-
acting agents).
o Posttetanic potentiation and posttetanic exhaustion
 A tetanic contraction of muscle is followed by 2 distinct phases: for the first 2
minutes after tetanic contraction, posttetanic potentiation occurs; this is followed
by posttetanic exhaustion, which lasts an additional 15 minutes.
 During posttetanic potentiation, accumulation of calcium inside the terminal axon
causes enhanced mobilization and release of ACh, which overcomes the
reduced number of AChR at the NMJ and results in larger EPSPs with additional
recruitment of muscle fibers, resulting in a larger CMAP.
 In myasthenia gravis, this potentiation may normalize RNS.
 In the posttetanic exhaustion phase, the NMJ is less excitable and even fewer
EPSPs reach threshold. Thus, some patients with an equivocal abnormality on
RNS during resting phase may show clear-cut abnormality during the posttetanic
exhaustion phase.
 Tetanic contraction of the muscle can be achieved by electrical stimulation of the
nerve at a rate of 50 per second lasting for 20-30 seconds. However, this is
painful. Voluntary contraction of the muscle for 10 seconds at the maximum force
can achieve the same goal without discomfort and is preferred.
 Pharmacological testing (edrophonium or Tensilon test) for the diagnosis of myasthenia gravis
o In patients with myasthenia gravis, the number of AChR at the NMJ is low. This results in
a decreased number of interactions between ACh and its receptor. ACh released from
motor nerve terminals is metabolized by AChE.
o Pharmacological inhibition of AChE increases ACh concentration at the NMJ, improving
the chance for interactions between ACh and its receptor. Edrophonium (Tensilon) is a
short-acting AChE inhibitor that improves muscle weakness in patients with myasthenia
gravis.
o Evaluate weakness (eg, ptosis, partial or complete ophthalmoplegia, and forced hand
grip) before and after administration of Tensilon. Blinding of both the examiner and the
patient increases the validity of the test.
o Sinus bradycardia due to excessive cholinergic stimulation of the heart is a serious
complication. An ampule of atropine should be available at the bedside or in the clinic
room while performing the test.
o To perform the test, a test dose of 0.1 mL of 10 mg/mL edrophonium solution is
administered. If no response and no untoward effects are noted, remainder of the drug
(0.9 mL) is injected.
o While interpreting this test, it is important to remember that these drugs can improve
weakness in diseases other than myasthenia gravis, such as amyotrophic lateral
sclerosis, poliomyelitis, and some peripheral neuropathies.
Medication

 Acetylcholinesterase inhibitors: neostigmine and pyridostigmine can improve muscle function by

slowing the natural enzyme cholinesterase that degradesacetylcholine in the motor end plate; the
neurotransmitter is therefore around longer to stimulate its receptor. Usually doctors will start with a
low dose, e.g. 3x20mg pyridostigmine, and increase until the desired result is achieved. If taken 30
minutes before a meal, symptoms will be mild during eating. Side effects, like perspiration and
diarrhea can be countered by adding atropine. Pyridostigmine is a short-lived drug with a half-life of
about 4 hours.

 Immunosuppressive drugs: prednisone, cyclosporine, mycophenolate
mofetil and azathioprine may be used. It is common for patients to be treated with a combination of
these drugs with a cholinesterase inhibitor. Treatments with some immunosuppressives take weeks
to months before effects are noticed. Other immunomodulating substances, such as drugs that
prevent acetylcholine receptor modulation by the immune system, are currently being researched

Plasmapheresis and IVIG

If the myasthenia is serious (myasthenic crisis), plasmapheresis can be used to remove the putative
antibody from the circulation. Also, Intravenous immunoglobulins (IVIG) can be used to bind the
circulating antibodies. Both of these treatments have relatively short-lived benefits, typically measured in
weeks.

Surgery
Main article:  thymectomy

Thymectomy, the surgical removal of the thymus, is essential in cases of thymoma in view of the potential
neoplastic effects of the tumor. However, the procedure is more controversial in patients who do not show
thymic abnormalities. Although some of these patients improve following thymectomy, some patients
experience severe exacerbations and the highly controversial concept of "therapeutic thymectomy" for
patients with thymus hyperplasia is disputed by many experts and efforts are underway to unequivocally
answer this important question.

MANAGEMENT 
Patients who report neurological signs or symptoms require a through review of family history, illnesses, systems,
medications and behaviors. Inspect and measure the palpebral apertures of patients with positional lid anomalies.

In office tests for the optometrist include:

1. asking the pertinent history

2. testing the pupils

3. assessing the orbicularis function by asking the patient to squeeze their eyelids shut while you attempt to open
them forcibly

4. attempt to elicit diplopia by eliminating the occlusive effects of ptosis

5. attempt to elicit superior rectus or levator fatigue by asking the patient to sustain upgaze while you observe for
unexpected eyelid droop

6. attempt to elicit the Cogan's lid twitch sign by asking the patient to look into downgaze for an extended period,
then to gaze up

7. apply an ice pack to the eyelid for five to 15 minutes, reevaluating the ptosis and/or ocular motility for improved
position following the ice packs removal

8. ask the patient to close their eyes for 30 minutes (sleep test), reevaluating the ocular motility and/or ptosis for
improved position upon awakening. Diagnosis may also be assisted by evaluating old photographs for appearance.

The quintessential method of diagnosing MG is the endrophonium hydrochloride (Tensilon) injection test. An
additional laboratory test used for diagnosing MG is the acetylcholine antibody receptor test. Medical management
of MG should be handled by the neurologist or neuro-ophthalmologist.

Myasthenia Gravis Complications

Myasthenic crisis is a medical emergency that develops when muscles that control breathing become severely
weakened. This condition may lead to acute respiratory failure and patients often require a respirator to assist
breathing during the crisis. Other complications that may develop include choking, food aspiration, and pneumonia.

Factors that can trigger complications in patients with myasthenia gravis include illness (e.g., viral respiratory
infection), surgery, corticosteroid use that is tapered too quickly, overexertion (especially in hot weather), pregnancy,
and emotional stress.

2-36. MYASTHENIA GRAVIS

a. Definition. Myasthenia Gravis is an autoimmune disorder affecting the neuromuscular transmission of

impulses in the voluntary muscles of the body. In normal individuals, transmission of impulses from the
nerve to the motor end plate of the muscle is accomplished by the transmitter substance acetylcholine.

(1) Acetylcholine is released at the nerve ending and moves to the muscle end plate, causing muscle
contraction.

(2) Acetylcholine is then broken down into acetate and choline by the substance cholinesterase.

(3) In myasthenia gravis, one of three physiological abnormalities may exist:

(a) There may be too much cholinesterase present, and acetylcholine is destroyed too quickly.

 (b) There may be too little acetylcholine released from the nerve fiber, resulting in inadequate
depolarization of the motor end plate.
(c) The motor end plate is not sensitive to the action of acetylcholine.

b.     Signs and Symptoms.

(1) Diplopia (double vision).

(2) Ptosis (dropping of one or both eyelids).

(3) Abnormal muscle weakness; characteristically worse after effort and improved by rest.

(4) Sleepy, mask-like facial expression with difficulty smiling.

(5) Speech weakness (high-pitched nasal voice).

(6) Difficulty swallowing.

(7) Choking, aspiration of food.

c.      Medical and Nursing Management.

(1) Primary drug therapy (anticholinesterase drugs to enhance the action of acetylcholine at the
myoneural junction).

(a) Drug must be given exactly on time to control symptoms.

(b) After initial medication adjustments are made, patient learns to take his medication according to
his/her needs.

(2) Patient needs explicit instructions regarding medications.

Actions.

Reasons for timing.

Dosage adjustment.

Symptoms of overdosage and actions to take should crisis occur.

(d)

(3) Have mealtimes coincide with peak effect of anticholinergics, when ability to swallow is best.

(4) Obtain medic alert bracelet signifying that patient has myasthenia gravis.

(5) Wear an eyepatch over one eye (alternating from side to side) if diplopia occurs.

(6) Control factors which lead to fatigue.

 (7) Emphasize importance of avoiding contact with individuals with colds or respiratory infections, since
these conditions could be devastating to the myasthenic patient.

(8) Instruct patient to inform dentist of myasthenia condition since Novocaine is usually poorly tolerated.

(9) Instruct patient to rest at frequent intervals and avoid fatigue. d. Management of the Crises of
Myasthenia.

(1) Myasthenic crisis may result from natural deterioration of the disease, emotional upset, upper
respiratory infection, surgery, or steroid therapy.

(2) Patient may be temporarily resistant to anticholinesterase drugs or need increased dosage.

(3) Cholinergic crisis may result from overmedication with anticholinergic drugs.

(4) Patient must be placed in an intensive care unit for continuous monitoring of the patient's respiratory
status.

(5) Provide ventilatory assistance, endotracheal intubation, mechanical ventilation, if required.

(6) Administer appropriate medications, as determined by patient's status and cause of the crisis.

(7) Support patient's fluid and nutritional needs, as ordered and indicated by patient's condition.

(8) Give continued psychological support during crisis period, as patient is still alert.

DIAGNOSES

• Impaired gas exchange, related to ineffective breathing pattern

and muscle weakness

• Risk for aspiration, related to difficulty swallowing

• Fatigue, related to increased energy needs from muscular

involvement

Sjogren's Syndrome
Common eye and mouth tests are
 Schirmer test--This test measures tears to see how the lacrimal gland is working. It can be done in two ways: In
Schirmer I, the doctor puts thin paper strips under the lower eyelids and measures the amount of wetness on the paper after
5 minutes. People with Sjogren's usually produce less than 8 millimeters of tears. The Schirmer II test is similar, but the
doctor uses a cotton swab to stimulate a tear reflex inside the nose.
 Staining with vital dyes (rose bengal or lissamine green)--The tests show how much damage dryness has
done to the surface of the eye. The doctor puts a drop of a liquid containing a dye into the lower eye lid. These drops stain
on the surface of the eye, highlighting any areas of injury.
 Slit lamp examination--This test shows how severe the dryness is and whether the outside of the eye is inflamed.
An ophthalmologist (eye specialist) uses equipment that magnifies to carefully examine the eye.
 Mouth exam--The doctor will look in the mouth for signs of dryness and to see whether any of the major salivary
glands are swollen. Signs of dryness include a dry, sticky mouth; cavities; thick saliva, or none at all; a smooth look to the
tongue; redness in the mouth; dry, cracked lips; and sores at the corners of the mouth. The doctor might also try to get a
sample of saliva to see how much the glands are producing and to check its quality.
 Salivary gland biopsy of the lip--This test is the best way to find out whether dry mouth is caused by Sjogren's
syndrome. The doctor removes tiny minor salivary glands from the inside of the lower lip and examines them under the
microscope. If the glands contain lymphocytes in a particular pattern, the test is positive for Sjogren's syndrome.

 Routine blood tests--The doctor will take blood samples to check blood count and blood sugar level, and to see
how the liver and kidneys are working.
 Immunological tests--These blood tests check for antibodies commonly found in the blood of people with
Sjogren's syndrome. For example:
Antithyroid antibodies are created when antibodies migrate out of the salivary glands into the thyroid gland. Antithyroid
antibodies cause thyroiditis (inflammation of the thyroid), a common problem in people with Sjogren's.
Immunoglobulins and gamma globulins are antibodies that everyone has in their blood, but people with Sjogren's usually
have too many of them.
Rheumatoid factors (RFs) are found in the blood of people with rheumatoid arthritis, as well as in people with Sjogren's.
Substances known as cryoglobulins may be detected; these indicate risk of lymphoma.
Similarly, the presence of antinuclear antibodies (ANAs) can indicate an autoimmune disorder, including Sjogren's.
Sjogren's antibodies, called SS-A (or SS-Ro) and SS-B (or SS-La), are specific antinuclear antibodies common in people
with Sjogren's. However, you can have Sjogren's without having these ANAs.
 Chest x ray--Sjogren's can cause inflammation in the lungs, so the doctor may want to take an x ray to check
them.
 Urinalysis--The doctor will probably test a sample of your urine to see how well the kidneys are working.

Treatment of Sjogren's Syndrome:

Treatment of Sjogren's syndrome focuses on decreasing symptoms. Dry eyes may be helped by using artificial tears, or
medication to stimulate tear production (e.g. Restasis). Lacriserts (pellet placed in eyelid) is another treatment for dry eyes.
Drinking water, gum-chewing, or the use of saliva substitutes help dry mouth. Salagen and Evoxac are two prescription
medications which stimulate saliva flow. Moisturizers can be used for dry skin conditions associated with Sjogren's syndrome.
Lubricant jelly can treat vaginal dryness.
Anti-inflammatory drugs (e.g. NSAIDs, steroids) and immunosuppressants may be prescribed.

 Moisture replacement therapies

 Dry eye treatments
 o Artificial tears
o Eye ointment
o Propyl methylcellulose (Lacriserts)
o Punctal occlusion surgery (closing eye drainage ducts)
o Collagen plugs - temporary because they gradually dissolve
o Silicon plugs - permanent but can be removed.
o Cauterization - permanent closing.
o Avoid winds
o Humidifier
o Quit smoking
o Avoid cigarette smoke
o Care using mascara
 Dry mouth treatments
o Natural saliva stimulation - if you are still producing some saliva
o Chewing gum
o Sucking hard candy
o Frequent sips of water
o Saliva stimulants
o Saliva substitute
o Mouth lubricants
o Lip balms - for dry or cracked lips
 Oral hygiene - helps prevent mouth infectins.
o Brushing teeth
o Rinsing
o Flossing
o Regular dental checkups
o Avoid sugar
o Fluoride supplements
 Dry skin treatments
o Heavy moisturizing creams
o Brief showers
o Moisturizing soap
o Pat skin dry
o Moisturize after bathing
o Humidifier
o Topical corticosteroids - for itching
 o Sunscreen - for sun sensitivity
o To avoid sunburn
 The treatment options that are available to better manage the symptoms associated with dry mouth,
including:
o Saliva substitutes
o Saliva stimulants
o Interferon-alpha
o Good oral hygiene practices
o Lifestyle modifications
 The treatment options that are available to better manage dry eye symptoms, including:
o Artificial tears
o Methylcellulose inserts
o Eye ointments
o Muscarinic agonist drugs
o Immunomodulatory drugs
o Autologous serum drops
o Lifestyle modifications
o Punctual occlusion surgery

I. Etiology

A. Environmental stimulus triggers autoimmune reaction directed at exocrine

glands
B. Postulated triggers: CMV and EBV
C. Association with HLA-DR haplotype
D. B-Lymphocyte mediated exocrine gland destruction

Aka: Sjogren's Syndrome, Sjogren Syndrome, Keratoconjunctivitis Sicca, Dry Eye Syndrome

Risk factors

Although anyone can develop Sjogren's syndrome, it typically occurs in people with one or
more known risk factors. These include:

 Having a rheumatic disease. It's common for people who have Sjogren's

syndrome to also have a rheumatic disease such as rheumatoid
arthritis, lupus, scleroderma or polymyositis.
 Being female. Women are nine times as likely as men are to have Sjogren's
syndrome.
 Being a certain age. Sjogren's syndrome is usually diagnosed in people
older than 40.
 Having a family history of Sjogren's. Sjogren's syndrome sometimes runs
in families.

 Fatigue
  Insomnia
 Lupus
 Rheumatoid arthritis
 Pathophysiology
 Salivary, lacrimal, and other exocrine glands become infiltrated with CD4+ T cells and with some
B cells. The T cells produce inflammatory cytokines (eg, IL-2, interferon-γ). Salivary duct cells
also produce cytokines, eventually damaging the secretory ducts. Atrophy of the secretory
epithelium of the lacrimal glands causes desiccation of the cornea and conjunctiva. Lymphocytic
infiltration and intraductal cellular proliferation in the parotid gland cause luminal narrowing and in
some cases formation of compact cellular structures termed myoepithelial islands; atrophy of the
gland can result. Dryness and GI mucosal or submucosal atrophy and diffuse infiltration by
plasma cells and lymphocytes may cause symptoms (eg, dysphagia).

What is amyotrophic lateral sclerosis?

Amyotrophic lateral sclerosis (ALS), sometimes called Lou Gehrig's disease, is a rapidly progressive, invariably
fatal neurological disease that attacks the nerve cells (neurons) responsible for controlling voluntary muscles. The
disease belongs to a group of disorders known as motor neuron diseases, which are characterized by the gradual
degeneration and death of motor neurons.

Incidence:

Approx 1 in 54,400

Worldwide, ALS occurs in 1 to 3 people per 100,000. In the vast majority of cases — 90 to 95 percent
— doctors don't yet know why ALS occurs. About 5 to 10 percent of ALS cases are inherited.

Early signs and symptoms of ALS include:

 Difficulty lifting the front part of your foot and toes (footdrop)

 Weakness in your leg, feet or ankles

 Hand weakness or clumsiness

 Slurring of speech or trouble swallowing

 Muscle cramps and twitching in your arms, shoulders and tongue

The disease frequently begins in your hands, feet or limbs, and then spreads to other parts of your
body. As the disease advances, your muscles become progressively weaker until they're paralyzed. It
eventually affects chewing, swallowing, speaking and breathing.

Cause

Researchers are studying several possible causes of ALS, including:

 Gene mutation. Various genetic mutations can lead to inherited forms of ALS, which appear
nearly identical to the non-inherited forms.

 Chemical imbalance. People who have ALS typically have higher than normal levels of
glutamate, a chemical messenger in the brain, around the nerve cells in their spinal fluid. Too much
glutamate is known to be toxic to some nerve cells.

 Disorganized immune response. Sometimes a person's immune system begins attacking

some of his or her body's own normal cells, and scientists have speculated that this may trigger the
process that results in ALS.

 Protein mishandling. There's evidence that mishandled proteins within the nerve cells can
lead to a gradual accumulation of abnormal forms of these proteins in the cells, eventually causing the
nerve cells to die.

Diagnostic Tests and Exam

Amyotrophic lateral sclerosis is difficult to diagnose early because it may appear similar to several
other neurological diseases. Tests to rule out other conditions may include:

 Electromyogram. This test measures the tiny electrical discharges produced in muscles. A

fine wire electrode is inserted into the muscles that your doctor wants to study. An instrument records
the electrical activity in your muscle as you rest and contract the muscle. Generally, this test is mildly
uncomfortable.

 Nerve conduction study. For this test, electrodes are attached to your skin above the nerve
or muscle to be studied. A small shock, which may feel like a twinge or spasm, is passed through the
nerve to measure the strength and speed of nerve signals.

 MRI. Using radio waves and a powerful magnetic field, MRI can produce detailed images of
your brain and spinal cord. It involves lying on a movable bed that slides into a tube-shaped machine
that makes loud thumping and banging noises during operation. Some people feel uncomfortable in
the confined space.

 Blood and urine tests. Analyzing samples of your blood and urine in the laboratory may help
your doctor eliminate other possible causes of your signs and symptoms.

 Muscle biopsy. If your doctor believes you may have a muscle disease rather than ALS, you
may undergo a muscle biopsy. In this procedure, a small portion of muscle is removed while you're
under local anesthesia and is sent to a lab for analysis.

Therapy

 Physical therapy. A physical therapist can recommend low-impact exercises to maintain your
cardiovascular fitness, muscle strength and range of motion as long as possible, helping you preserve
a sense of independence. Regular exercise can also help improve your sense of well-being.

 Occupational therapy. An occupational therapist can help you become accustomed to a

brace, walker or wheelchair and may be able to suggest devices such as ramps that make it easier for
you to get around.

 Speech therapy. Because ALS affects the muscles you use to speak, communication becomes
an issue as the disease progresses. A speech therapist can help teach adaptive techniques to make
your speech more clearly understood or help you explore alternative methods of communication, such
as an alphabet board or simple pen and paper. Later in the disease, a speech therapist can
recommend devices such as speech synthesizers and computer-based equipment that may help you
communicate. Ask your therapist about the possibility of borrowing or renting these devices.

Medications
The drug riluzole (Rilutek) is the first and only medication approved by the Food and Drug
Administration for slowing ALS. The drug appears to slow the disease's progression in some people,
perhaps by reducing levels of glutamate — a chemical messenger in the brain that's often present in
higher levels in people with ALS.

2-34. AMYOTROPHIC LATERAL SCLEROSIS

a.  Definition. Amyotrophic lateral sclerosis (ALS) is a progressive, incapacitating, and fatal disease of
unknown cause. It is characterized by loss of motor neurons in the anterior horns of the spinal cord and
lower brain stem. Amyotrophic lateral sclerosis is commonly known as Lou Gehrig's Disease.

b Signs and Symptoms.

(1) Symptoms vary, depending upon the location of affected motor neurons.
(2) Progressive weakness and atrophy of muscles of arms, trunk, or legs.
(3) Progressive difficulty in speaking and swallowing, speech may be nasal and unintelligible.
(4) Excessive drooling.
(5) Muscle twitching.
(6) Mental facilities are not affected.
(7) Death usually occurs 3-5 years after onset.

c. Medical and Nursing Management

(1) Objective--to support the patient and improve quality of life.

(2) Instruct the patient to perform active exercises and range of motion exercises to strengthen uninvolved
muscles and prevent disuse atrophy.
(3) Utilize braces, splints, canes, etc., to keep patient mobile as long as possible.
(4) Assist the patient to prevent complications that may result from symptoms.
(a) Keep suction apparatus at bedside, as aspiration is a constant danger.      
(b) Instruct patient to drink and eat in an upright position with the neck flexed.        
(c) Use soft cervical collar if patient has difficulty holding head up.
(d) Give semi-soft foods. Avoid easily-aspirated pureed foods and mucous producing foods (milk).
(e) Keep in mind that patient may have frequent outbursts of laughing and crying.
(f)   Develop communication system when speech is lost.

(5) Give patient and family compassionate and caring support.

(a) Allow expressions of feelings and frustrations about losses and eventual outcome.
(b)   Remember that the patient is alert and retains vision, ocular movement, intelligence, and
consciousness even though he/she is paralyzed.
(c)    Advise patient's family of helping services of ALS Society of America.

I. Epidemiology

A. Prevalence: 5-7 per 100,000 worldwide

B. Gender: More common in men by ratio of 1.5 to 1
C. Ages affected: 50 to 70 years old
 II. Etiology

A. Idiopathic in most cases

B. Autosomal dominant inheritance in 5-10% of cases

I. Management

A. Riluzole 50 mg bid
1. Anti-glutamate properties
2. Only modest effect at best (extended life 3 months)
3. Best effect if used early
4. Very expensive ($700/month)
B. Vitamin E and Vitamin C
1. Shown effective in rats but not proven in humans
C. Immunosuppressants not effective or indicated
D. Treat at ALS center
1. Physical Therapy
2. Occupational Therapy
3. Dietitian
4. Neurologist
E. Symptomatic treatment
1. Progressive Pseudobulbar palsy
2. Spontaneous laugh (Tricyclic Antidepressants)

Pathophysiology

The weakness and atrophy of ALS results from progressive degeneration of motor neurons in the spinal

cord, brain stem, and motor cortex. As anterior horn cells (motor neurons whose cell bodies reside in the

anterior horn of the spinal cord) die, the muscle fibers they innervate become weak, fasciculate, and

eventually atrophy. Sometimes neighboring axons from other anterior horn cells will sprout collateral

branches to innervate the isolated muscle fibers, but these anterior horn cells are destined to eventually die

as well. Why the motor neurons begin to die is still unknown. Recent evidence, however, have implicated

glutamate excitotoxicity, free radical toxicity, and mitochondrial dysfunction as possible mechanisms, and

this is an area of active research.

Stevens-Johnson syndrome is a rare, serious disorder in which your skin and mucous membranes
react severely to a medication or infection. Often, Stevens-Johnson syndrome begins with flu-like
symptoms, followed by a painful red or purplish rash that spreads and blisters, eventually causing the
top layer of your skin to die and shed.

Pathophysiology
An idiosyncratic, delayed hypersensitivity reaction has been implicated in the pathophysiology of Stevens-
Johnson syndrome. Certain groups of patients appear more susceptible to develop Stevens-Johnson
syndrome than the general population. The slow acetylators, patients who are immunocompromised, and
patients with brain tumors undergoing radiotherapy with concomitant antiepileptics are among those at
most risk. The slow acetylators are incapable of achieving complete detoxification of reactive drug
metabolites. Such metabolites can act as haptens that interact with host tissues rendering them to be
antigenic. Antigen presentation and production of tumor necrosis factor alpha (TNF-alpha) by the local
tissue dendrocytes results in the recruitment and augmentation of T-lymphocytes' proliferation and
enhances the cytotoxicity of the other immune effector cells.  The activated CD8+ lymphocytes, in turn,
can induce epidermal cell apoptosis via several mechanisms, which include the release of granzyme B
and perforin. Apoptosis of the keratinocytes can also take place as a result of ligation of their surface
death receptors with the appropriate molecules. Those can trigger the activation of the caspase system
leading to DNA disorganization and cell death. Apoptosis of the keratinocytes can be mediated via direct
interaction between the cell-death receptor Fas and its ligand. Both can be present on the surfaces of the
keratinocytes. Alternatively, activated T-cells can release soluble Fas ligand and interferon-gamma, which
induces Fas expression by the keratinocytes. Once apoptosis ensues, the dying cells provoke recruitment
of more chemokines; this can perpetuate the inflammatory process, which leads to extensive epidermal
necrolysis.

Etiology
Medications appear to be the most common cause of Stevens-Johnson syndrome and have
been implicated in as many of 60% of cases studied.5 Short courses of sulfonamide,
aminopenicillin, quinolone, and cephalosporin drugs all increase risk of Stevens-Johnson
syndrome.8 Longer-term therapy with anticonvulsant agents, oxicam, nonsteroidal
antiinflammatory drugs (NSAIDs), or allopurinol has also been named as a possible cause of
Stevens-Johnson syndrome.8 Even some chemicals, such as silver nitrite present in a wound
dressing, have been implicated.9 Although many medications have been blamed, some 
drugs administered for prodromal viral syndromes might have been falsely accused of
causing Stevens-Johnson syndrome.

Stevens-Johnson syndrome also has been linked to herpes simplex virus, mycoplasma
bacterial species, and measles vaccine.10 Neoplasms and collagen diseases have also been
pointed out as possible causes.5 However, in up to half of cases, no known cause can be
found.5

KAWASAKI DISEASE

I. Definitions and pathophysiology

A. aka "Mucocutaneous lymph node syndrome"

B. A multisystem vasculitis
C. Incidence limited to children

II. Clinical features

A. Epidemiology
1. 50% occurs before 2.5 y; 35% 2.5-5y, rare >10y
2. Most common in kids of Asian or African descent
 3. Male > Female
4. Fatal in 0.5% of cases, more likely to be fatal in boys and pts < 3yo
B. Presents with fever, usually > 5d
C. Usually tachycardic; may have mildly prolonged PR interval, TWI or flattening,
and nonspecific ST changed.
D. Labs: usually have high WBC w/left shift, high platelet counts, high ESR and
CRP; sterile pyuria and albuminuria sometimes noted
E. Can cause coronary vasculitis and aneurysms with fatal complications
F. Other cardiac abnormalities reported: AR, MR, conduction system dysfunction,
myocardial dysfunction, and myocardial fibrosis
G. Diagnostic criteria--Need fever x > 5d & four of the following, w/o evidence of
other cause for the sx. If coronary aneurysms are documented, only 3 of the
following are required for dx:

1. Conjunctival injection (bilateral, nonexudative)

2. Oropharyngeal lesions (red or cracked lips, strawberry tongue, or injected
mucosae)
3. Erythematous rash (usually "blotchy")
4. Erythema, edema, or desquamation of hands or feet
5. Cervical lymphadenopathy (50-75% of pts)

III. Treatment

A. ASA--continue until all lab abnormalities are resolved

B. Intravenous Immune Globulin (IVIG)--helps reduce symptoms & risk of
coronary aneurysms, but can cause fever, chills, hypotension, and rarely,
hemolytic anemia
C. Corticosteroids
1. 39 pts with Kawasaki's randomized to methylprednisolone 30mg/kg IV;
all pts also received ASA and were randomized to receive IVIG.
Compared with the ASA-IVIG-alone group, the ASA-IVIG-steroid group
had sig. shorter mean duration of fever (1.0 vs. 2.4d) and mean
duration of hospital stay (1.9 vs. 3.3d) (J. Peds. 142:611, 2003--abst)
2. In a meta-analysis of 8 randomized studies of corticosteroids vs.
placebo in pts with Kawasaki's disease, incidence of coronary artery
aneurysms was sig. lower in corticosteroid recipients (OR 0.55); only 3
of these studies included IVIG as part of standard therapy, though
steroids were found to be beneficial in an analysis of just those three
studies as well (Peds. 116:989, 2005--JW)
 3. In a study in 178 pts with Kawasaki disease, all of whom were treated
with IVIG, randomized to prednisolone 2mg/kg/d vs. placebo until
temperature and CRP were normal, there was no sig. diff. in prevalence
of coronary artery abnormalities at 1mo, though prednisolone group
had sig. faster resolution of fever and high CRP (J. Peds. 149:336, 2006--
JW)
4. In a study in in 199 children with Kawasaki disease and fever for 10d
randomized to methylprednisolone 30mg/kg IV x 1 vs. placebo (all
received IVIG + ASA), there were no sig. diffs. at 1wk or 5wks in various
measures of coronary disease though IV steroid recipients had shorter
initial hospitalization stays (NEJM 356:659, 2007--JW)
D. Follow-up echocardiography recommended by AHA (as of 2004) 6-8wks after
initial presentation and again 6-12mos later; however, the latter was not likely
to show abnormalities in pts whose first f/u echo was normal in one
retrospective study (Am. J. Cardiol. 88:328, 2001--AFP)
Kawasaki disease (mucocutaneous lymph node syndrome) is a form of vasculitis identified by an acute febrile illness
withmultiple systems affected.

Signs and symptoms:

Stage I – Acute Febrile Phase (First 10 days)
 The child appears severely ill and irritable.
 Major diagnostic criteria established by the Centers for Disease Control and Prevention (CDC) are as
follows:
a. High, spiking fever for 5 days or more.
b. Bilateral conjunctival injection.
c. Oropharyngeal erythema, “Strawberry “ tongue, or red dry lips.
d. Erythema and edema of hands and feet, periungal desquamation.
e. Erythematous generalized rash.
f. Cervical lymphadenopathy greather than 0.6 inch (1.5cm)
 Pericarditis, myocarditis, cardiomegaly, heart failure, and pleural effusion.
 Other associated findings include meningitis, arthritis, sterile pyuria, vomiting, and diarrhea.
Stage II – Subacute Phase (Days 11 to 25)
 Acute symptoms of stage I subside as temperature returns normal. The child remains irritable and anorectic.
 Dry, cracked lips with fissures.
 Desquamation of toes and fingers.
 Coronary thrombus, aneurysm, myocardial infarction, and heart failure.
 Thrombocytosis peaks at 2 weeks.
Stage III – Convalescent Phase (Until sedimentation rate and platelet count normalize)
 The child appears well.
 Transverse grooves of fingers and toenails (Beau’s lines).
 Coronary thrombosis, aneurysms may occur.
Diagnostic evaluation:
 The diagnostic of Kawasaki disease is based on clinical manifestations. The CDC requires that fever and
four of the six other criteria listed above in stage I be demonstrated.
 Electrocardiogram, echocardiogram, cardiac catheterization, and angiocarddiography may be required to
diagnose cardiac abnormalities.
 Although there are no specific laboratory tests, the following may help support diagnosis or rule out other
disease.
1. CBC – leukocytosis during acute stage.
2. Erythrocytes and hemoglobin – slight decrease.
3. Platelet count – increased during second to fourth week of illness.
4. IgM, IgA, IgG, and IgF – transiently elevated.
5. Urine – protein and leukocytes present.
6. Acute phase reactants (ESR, C-reactive protein, alpha I antitrypsin) are elevated
during the acute phase.
7. Myocardial enzyme levels (serum CK-MB) suggest MI if elevated.
8. Liver enzymes (AST, ALT) – moderately elevated.
9. Lipid profile – low high density lipoprotein and high triglyceride level.
Pharmacologic interventions:
 Immune globulin (gamma globulin) I.V. therapy – IVGG (2g/kg/day) is initiated during stage I in one 8 to 10
hour infusion to reduce the incidence of coronary artery abnormalities.
 Aspirin therapy
 Thrombolytic therapy may be required during stages I, II, or III.
Nursing Interventions:
Monitoring
1. Monitor pain level and child’s response to analgesics.
2. Institute continual cardiac monitoring and assessment for complications; report arrhythmias.
1. Take vital signs as directed by condition; report abnormalities.
2. Assess for signs of myocarditis (tachycardia, gallop rhythm, chest pain).
3. Monitor for heart failure (dyspnea, nasal flaring, grunting, retractions, cyanosis, orthopnea,
crackles, moist respirations, distended jugular veins, edema).
1. Closely monitor intake and output, and administer oral and I.V fluids as ordered.
2. Monitor hydration staus by checking skin turgor, weight, urinary output, specific gravity, and
presence of tears.
3. Observe mouth and skin frequently for signs of infection.
Supportive care
1. Allow the child periods of uninterrupted rest. Offer pain medication routinely rather than as needed during
stage I. Avoid NSAIDS if the child is in aspirin therapy.
2. Perform comfort measures related to the eyes.
 Conjunctivities can cause photosensitivity, so darken the room, offer sunglasses.
 Apply cool compress.
 Discourage rubbing the eyes.
 Instill artificial tears to soothe conjunctiva.
3. Monitor temperature every 4 hours. Provide sponge bath if temperature above normal.
4. Perform passive range of motion exercises every 4 hours while the child is awake because movement may
be restricted.
5. Provide quiet and peaceful environment with diversional activities.
6. Provide care measures for oral mucous membrane.
 Offer cool liquids like ice chips and ice pops.
  Use soft toothbrush only.
 Apply petroleum jelly to dried, cracked lips.
7. Provide skin measures to improve skin integrity.
 Avoid use of soap because it tends to dry skin and make it more likely to breakdown.
 Elevate edematous extremities.
 Use smooth sheets.
 Apply emollients to skin as ordered.
 Protect peeling of skin, observe for signs of infection.
8. Offer clear liquids every hour when the child is awake.
9. Encourage the child to eat meals and snack with adequate protein.
10. Infuse I.V fluids through a volume control device if dehydration is present, and check the site and amount
hourly.
11. Explain all procedures to the child and family.
12. Encourage the parents and child to verbalize their concerns, fears, and questions.
13. Practice relaxation techniques with child, such as relaxation breathing, guided imagery, and distraction.
14. Prepare the child for cardiac surgery or thrombolytic therapy if complications develop.
K

Pathophysiology
KD is a systemic vasculitis manifested by relatively prolonged fever, rash, conjunctivitis, mucous membrane changes,
cervical lymphadenopathy, and changes in hands and feet. The most serious complication of this unique illness is the
development of an acute coronary artery vasculitis with dilatation or aneurysm formation. Initially, KD was considered
just to be a self-limiting, benign condition. However, subsequent reports suggest that up to 2% of patients die from
coronary abnormalities, and 20% to 25% of untreated patients develop coronary artery aneurysms (CAAs) or ectasia.
In addition, KD may lead to myocardial infarction, sudden death, and ischaemic heart disease. [13]
In the early phase of the disease, there is development of oedema and neutrophil infiltration in the coronary arterial
wall, with a rapid transition to mononuclear cells. [14] This is followed by local production of matrix metalloproteinases
that cause destruction of the internal elastic lamina and media, with progress to fibrous connective tissue
replacement of the intima and media, leading to aneurysm formation, scarring, and stenosis. [15] The standard
treatment for KD, intravenous immunoglobulin, neutralises circulating antibodies through anti-idiotypic antibodies and
downregulates these inflammatory events.
Reports are available from children with KD who did not develop coronary abnormalities during the acute phase of
the disease and died years later due to unrelated causes. Autopsies performed on these children demonstrated
coronary artery intimal thickening and medial fibrosis. [16]
15. eep the family informed about progress and reinforce stages and prognosis.

Pathophysiology and Etiologic Considerations

The pathologic hallmark of Kawasaki disease is a generalized vasculitis that is most severe in the
extraparenchymal sections of medium-sized musculoelastic arteries, especially the coronary
arteries. The primary cause of death is myocardial infarction due to acute thrombosis of inflamed
coronary arteries. Coronary artery stenosis can occur and result in death years after the acute
illness. Aneurysms can occur in any major artery. Phlebitis occurs but is not of clinical
significance.

An initial mixed neutrophil and mononuclear cell infiltrate into arterial walls and rapidly give
way to a predominantly mononuclear cell presence. In severe cases, edema and smooth muscle
necrosis occur in the media, with inflammation also seen in the intima and adventia
(panarteritis). Elastin and collagen fibers become fragmented such that structural integrity of the
vessel wall is lost, leading to aneurysm. [5] Fibrosis and intimal proliferation occur over time,
causing vessel walls to become stiff and stenotic. Luminal occlusion may occur by stenosis or
thrombosis. [6]

The mononuclear infiltrate consists of activated T cells (CD8 cytotoxic and suppressor T cells
more than CD4 helper T cells), macrophages and IgA-producing plasma cells. [1,7,8] The
immune system is highly activated in Kawasaki Disease, with extensive production of many
cytokines: interleukins (IL)1, 2, 4, 6, 8, and 10; tumor necrosis factor a, interferon y, and
solulable IL-2 receptor. Endothelial cells are activated with up-regulation of leukocyte adhesion
molecules and other surface markers. There is systemic polyclonal activation of B cells with
increased antibody production of all classes. Antiendothelial cells and other autoantibodies have
been reported, but their precise roles, if any, in pathogenesis remain unclear. The accumulated
evidence suggests that immune cascades triggered in Kawasaki disease lead to autoimmune
vascular damage that is mediated by cytokine-induced expression of various endothelial cell
surface antigens (i.e., receptor proteins). [1,9]

The initiating etiology of Kawasaki disease remains unknown. Many organisms and exposures
(e.g., chemical, heavy metals) have been offered up over the years, only to become discarded
after subsequent studies. Recent theories that superantigen-producing microbes were causative
also now seem unlikely. IgA-plasma cells infiltrating coronary artery walls are oligoclonal,
consistent with response to a conventional antigen. [10] The process likely represents a post-
infectious inflammatory state. The rarity of the disease in young infants and adults suggests a
relatively ubiquitous infection may initiate the process. The disease likely is not new. Infantile
polyarteritis nodosa, which appears identical to Kawasaki disease histopathologically and
clinically, was recognized as early as 1871. [1,11]