Gestational Trophoblastic Disease (GTD)

Types of GTD
Benign
•    Hydatidiform mole/molar pregnancy (complete or incomplete)
malignant
•    Invasive mole
•    Choriocarcinoma (chorioepithelioma)
•    Placental site trophoblastic tumor



    The term Gestational Trophoblastic Tumors  has been applied the latter three conditions
    Arise from the trophoblastic elements
    Retain the invasive tendencies of the normal placenta or  metastasis
    Keep secretion of the human chorionic gonadotropin (hCG)


Hydatidiform Mole
 (molar pregnancy)

Definition and Etiology
     Hydatidiform mole is a pregnancy characterized by vesicular swelling of placental villi and usually the absence of an intact fetus.
     The etiology of hydatidiform mole remains unclear, but it appears to be due to abnormal gametogenesis and fertilization
    In a ‘complete mole’ the mass of tissue is completely made up of abnormal cells
    There is no fetus and nothing can be found at the time of the first scan.

    In a ‘partial mole’, the mass may contain both these abnormal cells and often a fetus that has severe defects.
    In this case the fetus will be consumed ( destroyed) by the growing abnormal mass very quickly.  (shrink)



Incidence
•    1 out of 1500-2000 pregnancies in the U.S. and Europe
•    1 out of 500-600 (another report 1%) pregnancies in  some Asian countries.
•    Complete > incomplete
    Repeat hydatidiform moles occure in 0.5-2.6% of patients, and these patiens have a subsequent greater risk of developing invasive mole or choriocarcinoma
    There is an increased risk of molar pregnancy for women over the age 40

    Approximately 10-17% of hydatidiform moles will result in invasive mole
    Approximately 2-3% of hydatidiform moles progress to choriocarcinoma ( most of them are curable)





Clinical risk factors for molar pregnancy

Age (extremes of reproductive years)
                <15
                >40
           Reproductive history
                prior hydatidiform mole
                prior spontaneous abortion
           Diet
                Vitamin A deficiency
           Birthplace
                Outside North America( occasionally has this disease)




Cytogenetics
Complete molar pregnancy
Chromosomes are paternal , diploid
    46,XX in 90% cases
    46,XY in a small part

Partial molar pregnancy
Chromosomes are paternal and maternal, triploid.
    69,XXY   80%
    69,XXX or 69,XYY  10-20%





Comparative Pathologic Features of Complete and Partial Hydatidiform Mole

Feature                                                Complete Mole    Partial Mole
Karyotype                                  Usually diploid 46XX    Usually triploidy 69XXX most common. 
Villi                 All villi hydropin; no normal adjacent villi    Normal adjacent villi may be present
vessels             present they contain no fetal blood cells    blood cells
Fetal tissue                                             None present    Usually present
Trophoblast      Hyperplasia usually present to variable degrees    Hyperplasia mild and focal





Signs and Symptoms of Complete Hydatidiform Mole
•    Vaginal bleeding
•    Hyperemesis ( severe vomit)
•    Size inconsistent with gestational age( with no fetal heart beating and fetal movement)
•    Preeclampsia
•    Theca lutein ovarian cysts
Signs and Symptoms of Partial Hydatidiform Mole
•    Vaginal bleeding
•    Absence of fetal heart tones
•    Uterine enlargement and preeclampsia is reported in only 3% of patients.
•    Theca lutein cysts, hyperemesis is rare.


Diagnosis of hydatidiform mole
Quantitative beta-HCG
Ultrasound is the criterion standard for identifying both complete and partial molar pregnancies. The classic image is of a “snowstorm” pattern
    The most common symptom of a mole is vaginal bleeding during the first trimester
    however very often no signs of a problem appear and the mole can only be diagnosed by use of ultrasound scanning. (rutting check)
    Occasionally, a uterus that is too large for the stage of the pregnancy can be an indication.  
    NOTE:  Vaginal bleeding does not always indicate a problem!



Differential diagnosis
•    Abortion
•    Multiple pregnancy
•    Polyhydramnios




Treatment

 Suction dilation and curettage :to remove benign hydatidiform moles
   When the diagnosis of hydatidiform mole is established, the molar pregnancy should be evacuated.
    An oxytocic agent should be infused intravenously  after the start of evacuation and continued for several hours to enhance uterine contractility
•   
•    Removal of the uterus (hysterectomy) : used rarely to treat hydatidiform moles if future pregnancy is no longer desired. 

Chemotherapy with a single-agent drug
     Prophylactic (for prevention) chemotherapy at the time of or immediately following molar evacuation may be considered for the high-risk patients( to prevent spread of disease )



High-risk postmolar trophoblastic tumor
    Pre-evacuation uterine size larger than expected for gestational duration
    Bilateral ovarian enlargement (> 9 cm theca lutein cysts)
    Age greater than 40 years
    Very high hCG levels(>100,000 m IU/ml)
    Medical complications of molar pregnancy such as toxemia, hyperthyrodism and trophoblastic embolization (villi come out of placenta )
     repeat hydatidiform mole


Follow-up
    Patients with hudatidiform mole are curative over 80% by treatment of evacuation.
    The follow-up after evacuation is key necessary
    uterine involution, ovarian cyst regression and cessation of bleeding

    Quantitative serum hCG levels should be obtained every 1-2 weeks until negative for three consecutive determinations,
    Followed by every 3 months for 1 years.
    Contraception should be practiced during this follow-up period


Invasive mole
Definition
        This term is applied to a molar pregnancy in which molar villi grow into the myometrium or its blood vessels, and may extend into the broad ligament and metastasize to the lungs, the vagina or the vulva.








Common Sites for Metastatic
Gestational Trophoblastic Tumors


Site     Per cent
Lung     60-95
Vagina     40-50
Vulva/cervix    10-15
Brain     5-15
Liver     5-15
Kidney     0-5
Spleen     0-5
Gastrointestinal     0-5




Choriocarcinoma



Definition
        A malignant form of GTD which can develop from a hydatidiform mole or from placental trophoblast cells associated with a healthy fetus ,an abortion or an ectopic pregnancy.

    Characterized by abnormal trophoblastic hyperplasia and anaplasia , absence of chorionic villi





Symptoms and signs
•    Bleeding
•    Infection
•    Abdominal swelling
•    Vaginal mass
•    Lung symptoms
•    Symptoms from other metastases





FIGO Staging System for Gestational Trophoblastic Tumors
Stage    Description
Ⅰ    Limited to uterine corpus
Ⅱ    Extends to the adnexae, outside the uterus, but limited to the genital structures
Ⅲ    Extends to the lungs with or without genital tract
Ⅳ    All other metastatic sites

    Substages assigned for each stage as follows:
    A:  No risk factors present
    B:   One risk factor
    C:  Both risk factors
    Risk factors used to assign substages:
    1.   Pretherapy serum hCG > 100,000 mlU/ml
    2.   Duration of disease >6 months





Diagnosis and evaluation
    Gestational trophoblastic tumor is diagnosed by rising hCG following evacuation of a molar pregnancy or any pregnancy event
    Once the diagnosis established the further examinations should be done to determine the extent of disease ( X-ray, CT,  MRI)


Treatment
    Nonmetastatic GTD
    Low-Risk Metastatic GTD
    High-Risk Metastatic GTD


Treatment of Nonmetastatic GTD

    Hysterectomy is advisable as initial treatment in patients with nonmetastatic GTD who no longer wish to preserve fertility
    This choice can reduce the number of course and shorter duration of chemotherapy.
    Adjusted single-agent chemotherapy at the time of operation is indicated to eradicate any occult metastases and reduce  tumor dissemination.

    Single-agent chemotherapy is the treatment of choice for patients wishing to preserve their fertility.
    Methotrexate(MTX) and Actinomycin-D are generally chemotherapy agents
    Treatment is continued until  three consecutive normal hCG levels have been obtained and two courses have been given after the first normal hCG level.



Treatment of Low-Risk Metastatic GTD

    Single-agent chemotherapy with MTX or actinomycin-D is the treatment for patients in this category
    If resistance to sequential single-agent chemotherapy develops, combination chemotherapy would be taken
    Approximately 10-15% of patients treated with single-agent chemotherapy will require combination chemotherapy with or without surgery to achieve remission


Treatment of High-Risk Metastatic GTD

    Multiagent chemotherapy with or without adjuvant radiotherapy or surgery should be the initial treatment for patients with high-rist metastatic GTD
    EMA-CO regimen formula is good choice for high-rist metastatic GTD
    Adjusted surgeries such as removing foci of chemotherapy-resistant disease, controlling hemorrhage may be the one of treatment regimen






EMA-CO Chemotherapy for poor Prognostic  Disease

Etoposide(VP-16)    100mg/M2    IV daily×2 days (over 30-45 minutes)
Methotrexate    100mg/M2    IV losding dose, then 200mg/M2 over 12 hours day 1
Actinomycin D    0.5mg    IV daily×2 days
Folinic acid    15mg IM or p.o. q 12 hours×4 starting 24 hours after starting methotrexate
Cyclophosphamide     600mg/M2    IV on day8
Oncovin (vincristine)    1mg/M2    IV on day8
(Repeat every 15 days as toxicity permits)



Prognosis
    Cure rates should approach 100% in nonmetastatic and low-risk metastatic GTD
    Intensive multimodality therapy has resulted in cure rates of 80-90% in patients with high-risk metastatic GTD


Follow-up After Successful Treatment
    Quantitative serum hCG levels should be obtained monthly for 6 months, every two months for remainder of the first year, every 3 months during the second year
    Contraception should be maintained for at least 1 year after the completion of chemotherapy. Condom is the choice.


Placenta Site Trophoblastic
Tumor (PSTT)
Definition
    Placenta Site Trophoblastic Tumor is an extremely rare tumor that arised from the placental implantation site
    Tumor cells infiltrate the myometrium and grow between smooth-muscle cells


Dignosis and treatment 
    Surum hCG levels are relatively low compared to those seen with choriocarcinoma.
    Several reports have noted a benign behavior of this disease. They are relatively chemotherapy-resistant, and deaths from metastasis have occurred.
    Surgery has been the mainstay of treatment

Cerebral Palsy

Outline

I. Definition
II. Incidence, Epidemiology and Distribution
III. Etiology
IV. Types
V.  Medical Management
VI. Psychosocial Issues
VII. Aging

   

Cerebral Palsy-Definition


•    Cerebral palsy is a symptom complex, (not a disease) that has multiple etiologies.

•    CP is a disorder of tone, posture or movement due to a lesion in the developing brain.

•    Lesion results in paralysis, weakness, incoordination or abnormal movement

•    Not contagious, no cure.

•    It is static, but it symptoms may change with maturation


       
       
       
Cerebral Palsy
Brain damage
Occurs during developmental period
Motor dysfunction
Not Curable
Non-progressive (static)
    Any regression or deterioration of motor or intellectual skills should prompt a search for a degenerative disease
Therapy can help improve function


Cerebral Palsy

•    There are 2 major types of CP, depending on location of lesions:
–    Pyramidal (Spastic)
–    Extrapyramidal
•    There is overlap of both symptoms and anatomic lesions.

•    The pyramidal system carries the signal for muscle contraction.

•    The extrapyramidal system provides regulatory influences on that contraction.

•    Types of brain damage

–    Bleeding
–    Brain malformation
–    Trauma to brain
–    Lack of oxygen
–    Infection
–    Toxins
–    Unknown

Epidemiology
•    The overall prevalence of cerebral palsy ranges from 1.5 to 2.5 per 1000 live births.
•    The overall prevalence of CP has remained stable since the 1960’s.
•    Speculations that the increased survival of the VLBW preemies would cause a rise in the prevalence of CP have proven wrong.
•    Likewise the expected decrease in CP as a result of
    C-section and fetal monitoring has not happened.
•    However, the prevalence of the subtypes has changed.
•    Due to the increased survival of very low birth weight preemies, the incidence of spastic diplegia has increased.
•    Choreoathetoid CP, due to kernicterus, has decreased.
•    Multiple gestation carries an increased risk of CP.


Distribution of the Types of CP

Types of Cerebral Palsy                             Frequency of Distribution
Nonspastic (extrapyramidal and mixed types)      23%
Spastic CP (total)                                               77%
Spastic Diplegia                                                  21%
Spastic Hemiplegia                                             21%
Spastic Quadriplegia                                           23%


Etiology
•    CP has multiple etiologies- many are still unknown
•    Since CP is not a single entity, recurrence risks depend on the underlying cause.
•    If there is a regression in skills, suspect a degenerative disease.
•    Most causes are prenatal- genetic, congenital malformations, metabolic, intrauterine infections, rather than perinatal or postnatal- birth asphyxia, hemorrhage, infarction, infections, trauma.

•    Much of the literature of the 1990’s was directed at the controversy re the role of asphyxia in the etiology of CP
–    Asphyxia implies poor gas exchange, low Apgars and neurologic depression during and soon after delivery.
–    Significant asphyxia is accompanied by acidosis.
–    Asphyxia is rarely the cause of CP in the term infant.
•    In one outcome study of 43,437 full term children, 150 had cerebral palsy. Only 9 of these cases were attributable to birth asphyxia.
•    34 had spastic quadriplegia and 71% of those cases had identifiable causes.
        53%- congenital disorders
        14%-birth asphyxia
        8%-CNS infections
   


•    Among the children with non quadriplegic cerebral palsy, congenital disorders appeared to account for  about 1/3 of the cases, and CNS infections accounted for 5%.



Hypoxic Ischemic Encephalopathy (HIE)
•    A clinical entity first described in 1976
•    Used interchangeably with Neonatal encephalopathy.
•    Asphyxia refers to the first minutes after birth (low Apgars and acidosis)
•    HIE signs and symptoms persist over hours and days that follow.

3 major lesions arise from HIE
•    Periventricular Leukomalacia (PVL) Typically seen in the premature infant
  a. Hemorrhagic PVL
  b. Ischemic PVL
•    Parasaggital Cerebral Injury
  Typically seen in the term infant
•    Selective (Focal) Neuronal Necrosis
  Seen in both term and premature infants





Periventricular Leukomalacia (PVL)

1.  Hemorrhagic PVL
•    Hemorrhage is associated with a collection of primitive cells between the ependyma and caudate that are programmed to “melt away” at 32-34 weeks gestation
•    They contain fragile capillaries that are easily damaged by hypoxia (lack of oxygen) and hypotension (drop in blood pressure).
•    When the blood pressure returns to normal, bleeding occurs because the preemie has underdeveloped autoregulation.
•    This bleeding may then rupture into the ventricle and/or parenchyma
•    Periventricular venous congestion (swelling) may then occur, and cause ischemia (lack of blood supply) and periventricular hemorrhagic infarction.
2. Ischemic PVL
•    An ischemic infarction or failure of perfusion usually to the watershed area surrounding the ventricular horns- “HIE white matter necrosis”.
•    Peak incidence occurs around 32 weeks
•    Larger infarcts may leave a cyst
•    Secondary hemorrhage can occur into theses cysts- “periventricular hemorrhage”.
•    PVL can extend into the internal capsule  and result in hemiplegia superimposed on diplegia.
•    Prenatal maternal ultrasound has detected lesions in the fetus at 28-32 weeks gestation, thus confirming that PVL can occur prenatally.


Parasaggital Cerebral Injury
•    Injury is related to vascular factors, especially in the parasaggital border zones that are more vulnerable to a drop in perfusion pressure and immature autoregulation.
•    The ischemic lesion results in cortical and subcortical white matter injury.
•    It is usually bilateral and symmetric.
•    The posterior aspect of the cerebral hemisphere especially the parietal occipital regions is more affected than the anterior.


Selective (Focal) Neuronal Necrosis (SNN)
•    Occurs in the glutamate sensitive areas in the basal ganglia, thalamus, brainstem and cortex.
•    The location of the focal necrosis, which show up as cystic lesions on MRI, depend on the stage of development of the infant’s brain at the time of the HIE.
–    For example, HIE at term often produces SNN in the basal ganglia since it is glutamate sensitive and very hypermetabolic at term. 

Types of Cerebral Palsy
Pyramidal   
•    Described as a Clasped knife response or
•    Velocity dependent increased resistance to passive muscle stretch
•    The spasticity can be worse when the person is anxious or ill.
•    The spasticity does not go away when the person is asleep.       
Extrapyramidal
•    Ataxia
•    Hypotonia
•    Dystonia
•    Rigidity
–    The tone may increase with volitional movement, or when the person is anxious
–    During sleep the person is actually hypotonic

  A.Pyramidal (Spastic)
•    Quadriplegia- all 4 extremities
•    Hemiplegia- one side of the body
•    Diplegia- legs worse than arms
•    Paraplegia- legs only
•    Monoplegia- one extremity



B. Extrapyramidal
Divided into Dyskinetic and Ataxic types

Dyskinetic
•    Athetosis- slow writhing, wormlike
•    Chorea- quick, jerky movements
•    Choreoathetosis- mixed
•    Hypotonia- floppy, low muscle tone, little movement

Ataxic CP
•    Results from damage to the cerebellum
•    Ataxia- tremor & drunken- like gait



Anatomy
Pyramidal
•    Lesion is usually in the motor cortex, internal capsule and/or cortical spinal tracts.
Extrapyramidal
•    Lesion is usually in the basal ganglia, Thalamus, Subthalamic nucleus and/or cerebellum.


Comparison of Symptoms

                                                   Pyramidal       Extrapyramidal
 Tone                                              increased    alternating
Type of tone                                       spastic    rigid
DTR’s                                            increased    normal to increased
Clonus                                              Present    occ. present
Contractures                                          early    late
Primitive Reflexes                             delayed      persistent
Involuntary movements                           rare    frequent




Medical Management
Growth
•    Persons with CP often have struggle to gain or maintain weight.
•    Failure to Thrive is a common problem.
–    Before diagnosing Failure to thrive, an accurate Body Mass Index must be obtained, but an accurate height is difficult to obtain in a person with severe contractures.
–    In such cases, arm span calculations may be used and a growth chart is available to determine percentiles standardized to age and gender.

Orthopedic Problems

•    Scoliosis
•    Hip Dislocations
•    Contractures
•    Osteoporosis

Oromotor Dysfunction
•    Especially common in persons with Extrapyramidal CP and Spastic quadriplegia
–    Language delay/Speech delays
–    Drooling
–    Dysphagia
–    Aspiration

Gastrointestinal Dysmotility
•    Delayed gastric emptying
•    Gastroesophageal reflux
–    Pain
–    Chronic aspiration
•    Constipation
These disorders are interrelated and compound one another.

Spasticity Management
Management of spasticity does not fix the underlying pathology of CP, but it may decreased the sequelae of increased tone.
•    Over time, the spasticity leads to:
–    musculoskeletal deformity
•    scoliosis
•    hip dislocation
•    contractures
–    Pain
–    Hygiene problems





Treatment of Spasticity
Medications
•    Valium
•    Dantrium
•    Baclofen
•    Clonidine
•    Clonazepam
•    BOTOX

Treatment of Dystonia
Medications-(None are very effective)
•    L-Dopa- drug of choice for certain disorders
•    Artane
•    Anticonvulsants-for intermittent and paroxysmal dystonia
•    Anti-spasticity medications-
•    Haldol or Reserpine- for choreoathetosis
•    Propranolol- for essential tremor
•    Clonazepam or Valium- for “rubral tremors”-(course tremors of the entire arm)
•    Valproic acid or clonazepam for action myoclonus- (large jerks with intentional movements)

Associated Problems
•    Mental Retardation
•    Communication Disorders
•    Neurobehavioral
•    Seizures
•    Vision Disorders
•    Hearing loss
•    Somatosensation (skin sensation, body awareness)




•    Temperature instability
•    Nutrition
•    Drooling
•    Dentition problems
•    Neurogenic bladder
•    Neurogenic bowel
•    Gastroesophageal reflux
•    Dysphagia
•    Autonomic dysfunction

Other Treatments
•    Casting
•    Therapeutic Electrical Stimulation
•    Patterning: Doman-Delacato- (not recommended)
•    Selective Dorsal Rhizotomy
•    Massage
•    Hyperbaric Oxygen
•    Acupuncture



Adult Concerns
Medical
•    Routine Healthcare Maintenance
•    Sequelae of Spasticity
•    Orthopedic Issues
•    Pain Management
•    Neurogenic Bowel and Bladder
•    Prevention of Chronic Aspiration Management of Gastroesophageal Reflux & Complications
–    Barrett’s esophagus
–    Esophageal strictures
–    Esophageal/stomach cancer

Psychosocial

Transition from Pediatric to Adult services
Independence
    Work
    Home
Relationships
Guardianship
End of life

Toni Benton, M.D.
Continuum of Care Project
UNM HSC School of Medicine


DOWNLOAD THIS POWERPOINT  PRESENTATION

Acute and Chronic Sinusitis

Objectives
•    Be knowledgeable of the causes of and risk factors associated with sinusitis
•    Differentiate acute from chronic sinusitis
•    Evaluate patients by history, physical exam, appropriate laboratory and imaging studies, and when indicated screen patients for allergy
•    Prescribe appropriate medication regimens for acute and chronic sinusitis
•    Know of the relationships between upper airway (rhinosinusitis) and lower airway disease (asthma)




Rhinosinusitis May be Better Term Because
•    Allergic or nonallergic rhinitis nearly always precedes sinusitis
•    Sinusitis without rhinitis is rare
•    Nasal discharge and congestion are prominent symptoms of sinusitis
•    Nasal mucosa and sinus mucosa are similar and are contiguous



Development of Sinuses
•    Maxillary and ethmoid sinuses present at birth
•    Frontal sinus developed by age 5 or 6
•    Sphenoid sinus last to develop, 8-10


Physiologic Importance of Sinuses
•    Provide mucus to upper airways
–    Lubrication
–    Vehicle for trapping viruses, bacteria, foreign material for removal
•    Give characteristics to  voice
•    Lessen skull weight
•    Involved with olfaction


Sinusitis
•        4 paranasal sinuses, each lined with pseudostratified     ciliated columnar epithelium and goblet cells
–    Frontal   
–    Maxillary
–    Ethmoid
–    Sphenoid

 Ostiomeatal Complex
•    Ostiomeatal complex is that area under the middle meatus (airspace) into which the anterior ethmoid, frontal and maxillary sinuses drain
•    Posterior ethmoids drain into the upper meatus
•    Ostiomeatal complex is the functional relationship between the space and the ostia that drain into it


Viral Rhinosinusitis
•    Most upper respiratory infections are viral
•    Short lived, last less than 10 days
•    Sinus mucosa as well as nasal mucosa is involved
•    Most will clear without antibiotics
•    Treatment: decongestants, nasal lavage, rest, fluids


Classification of Bacterial Sinusitis
•    Acute bacterial sinusitis- infection  lasting 4 weeks, symptoms resolve completely (children 30 days)
•    Subacute bacterial sinusitis- infection lasting between 4 to 12 weeks,  yet resolves completely (children 30-90 days)
•    Chronic sinusitis- symptoms lasting more than 12 weeks (children >90 days)
•    Some guidelines add treatment failure + a positive imaging study


Recurrent Acute Bacterial Sinusitis
•    Episodes lasting fewer than 4 weeks and separated by intervals of at least 10 days during which the patient is totally asymptomatic
•    3 episodes in 6 months or 4/year


Acute Sinusitis Imposed on
Chronic Sinusitis
•    Patients with chronic, low grade symptoms experience increase  in mucous flow, change in viscosity or color, or secretions
•    Treated
•    New symptoms resolve but chronic symptoms continue


Differentiating Sinusitis from Rhinitis
Sinusitis
Nasal congestion
Purulent rhinorrhea
Postnasal drip
Headache
Facial pain
Anosmia
Cough, fever


Rhinitis
Nasal congestion
Rhinorrhea clear
Runny nose
Itching, red eyes
Nasal crease
Seasonal symptoms



Road to Bacterial Sinus Infections
•    Obstruction of the various ostia
•    Impairment in ciliary function
•    Increased viscosity of secretions
•    Impaired immunity
•    Mucus accumulates
•    Decrease in oxygenation in the sinuses
•    Bacterial overgrowth



Pathogenesis of Nasal Obstruction
•    Viral upper respiratory infections
–    Daycare centers
•    Allergic and nonallergic stimuli
•    Immunodeficiency disorders
–    Immunoglobulin deficiency (IgA, IgG)
•    Anatomic changes
–    Deviated septum, concha bullosa, polyps



Allergic Stimuli Causing Rhinosinusitis
•    Pollens
–    Tree, grass, weeds
•    House dust mite
•    Animal danders
–    Cat, dog, mice, gerbil, other animals with fur
•    Molds
•    Allergic foods and beverages


Nonallergic Stimuli Causing Rhinosinusitis
•    Tobacco smoke
•    Perfumes
•    Cleaning solutions
•    Potpourri
•    Burning candles
•    Cosmetics
•    Car exhaust, diesel fumes
•    Hair spray
•    Cold air
•    Dry air
•    Changes in barometric pressure
•    Auto exhaust
•    Gas, diesel fuel
•    Nonallergic foods
•    Nonallergic beverages


Causes of Ciliary Dysfunction
•    Immotile cilia syndrome
•    Prolonged exposure to cigarette smoke
•    Common cold viruses causing URI
•    Increased viscosity of mucus
•    Medications
–    First generation antihistamines (non sedating do not affect)
–    Anticholinergics
–    Aspirin
–    Anesthetic agents
–    Benzodiazepines


Diseases Slowing Ciliary Function
•    Allergic and nonallergic rhinitis
•    Rhinosinusitis
•    Aging rhinitis
•    Cystic fibrosis
•    Any disease causing obstruction, crusting of the mucosa


Causes of Mechanical Obstruction
•    Deviated nasal septum
•    Concha bullosa
•    Foreign body
•    Nasal polyps
•    Congenital atresia
•    Lymphoid hyperplasia
•    Nasal structural changes found in Downs syndrome



Vasculitides, Autoimmune and Granulomatous Diseases
•    Churg-Strauss vasculitis
•    Systemic lupus erythematosis
•    Sjogren’s syndrome
•    Sarcoidosis
•    Wegener granulomatosis


Other Predisposing Conditions
•    Physical trauma
•    Scuba diving
•    Foreign body
•    Cleft palate
•    Dental disorders
•    Any patient with chronic fatigue, fever, general malaise/aching or headaches should be evaluated for sinusitis


Acute Bacterial Sinusitis
•     Usually begins with viral upper respiratory illness
•    Symptoms initially improve, but then …
•    Symptoms become persistent or severe
•    Persistent… 10-14 days but fewer than 4 weeks
•    Severe…temperature of 102°, purulent nasal discharge for 3-4 days, child appears ill
•    Disease clears with appropriate medical treatment


Physical Findings
•    Mucopurulent nasal discharge
–    Highest positive predictive value
•    Swelling of nasal mucosa   
•    Mild erythema
•    Facial pain (unusual in children)
•    Periorbital swelling


Objectives of Treatment of Acute Bacterial Sinusitis
•    Decrease time of recovery
•    Prevent chronic disease
•    Decrease exacerbations of asthma or other secondary diseases
•    Do so in a cost-effective way!


Treatment of Acute Sinusitis
•    Antihistamines recommended if allergy present
–    Oral or topical
•    Decongestants
–    Oral or topical
•    Antibiotic when indicated (bacteria)
•    Nasal irrigation
•    Guaifenesin 200-400 mg q4-6 hrs
•    Hydration

Decongestants
•    Topical nasal sprays (limit use to 3-7 days)
–    Phenylephrine
–    Oxymetazoline
–    Naphthazoline
–    Tetrahydrozoline
–    Zylometazoline
•    Topical nasal spray (unlimited daily use)
–    Ipatropium
•    Oral
–    Pseudoephedrine 30-60 mg
–    Phenylephrine 2-4 times/day

Treatment of Acute,
Uncomplicated Sinusitis

Antibiotic may not be indicated
Many are viral
Benefit of antibiotics are only moderate
Weigh factors of cost, side effects, antibiotic resistance, and antibiotic reactions

Antibiotics for Acute Bacterial Sinusitis
•    Amoxicillin 500 mg tid for 10-14 days
–    First line choice in most areas
–    Local differences in antibiotic resistance occur
•    Where beta-lactanase resistance is an issue
–     Amoxicillin/clavulanate
–    Cefuroxime
–    Cefpodoxime
–    Cefprozil



Additional Antibiotics for Acute
Bacterial Sinusitis
•    Amoxicillin should be considered because of its efficacy, low cost, side-effect profile, and narrow spectrum (45-90 mg/kg/d in children; 500 mg tid or qid in adults for 10 to 14 days)
•    If penicillin-allergic clarithromycin  or azithromycin
•    Erythromycin does not provide adequate coverage
•    Trimethoprim/suflamethoxazole and erythro/sulfisoxazole have significant pneumococcal resistance


Nasal Irrigation
•    Commercial buffered sprays
•    Bulb syringe
–    1/4 tsp of salt to 7 ounces water
•    Waterpik with lavage tip
–    1 tsp salt to reservoir
•    Disposable enema bucket
–    2 tsp salt, 1 tsp soda per quart of water

•    Washes away irritants
•    Moistens the dry nose
•    Waterpik with nasal irrigator
•    Ceramic irrigators
•    Enema bucket with normal saline and soda
–    “Hose-in-the-nose”-- $2.50


•    With enema bucket/hose….
–    Add 2 teaspoons of salt and 1 tsp of baking soda to a quart of warm water
–    Over tub, sink, or in shower lean over, head tilted slightly downward and to side place hose in upper nostril (fluid may return from either nostril or through mouth) run in 1/2 solution. Turn head to opposite side and repeat process.
–    Use once, twice daily or as often as needed


When Medical Therapy for Acute Bacterial Sinusitis Fails…
•    Assess for chronic causes
–    Identify allergic and nonallergic triggers
•    Allergy testing, nasal smears for eosinophilia
–    Consider other medical conditions associated with sinusitis
–    Rhinolaryngoscopy
–    Imaging studies
        Sinus x-rays
        CT scanning (limited, coronal views)


Sinus Transillumination
•    Helpful in older children and adults
•    Normal transillumination decreases chance of pus in the sinus
•    No light reflex suggests mucopurulent material or thickening of nasal mucosa
•    Inexpensive screening tool

•    Have patient sit at your eye level in darkened room (the darker the better)
•    Let eyes get accustomed to dark
•    Place bright light (transilluminator) over inferior orbital ridge to look at maxillary sinuses, under superior orbital rim for frontal sinuses
•    Look at palate for presence/absence of transilluminated light


Rhinoscopy Aids in Diagnosing
•    Nasal polyps
•    Septal deviation
•    Concha bullosa
•    Eustachian tube dysfunction
•    Causes of  hoarseness
•    Adenoid hyperplasia
•    Tumors

MRI Imaging
•    Not used for imaging suspected acute sinusitis
•    Suspected fungal sinusitis
•    Suspected tumors


Bacteria Involved in Acute
Bacterial Sinusitis
•    Streptococcus pneumoniae     30%
•    Haemophilus influenza        20%
•    Moraxella catarrhalis        20%
•    Sterile                30%



Rational for Starting Rx with Amoxicillin
•    In the absence of risk factors, i.e. attendance in daycare center, recent antibiotics, age younger than 2…
•    80% of patients will respond to amoxicillin
•    Give Rx for 5 days with a refill -- if responding treat for 10 to 14 days, if not, switch to another


Reasons to Use Alternative Antibiotics
•    No response to amoxicillin within 3-5 days
•    Recent treatment with amoxicillin for other causes
•    Symptoms present for more than 30 days
•    Recurrent sinus infections


Secondary Antibiotics for Acute Sinusitis
•    Cefdinir (Omnicef)
•    Cefuroxime (Ceftin)
•    Cephpodoxime (Vantin)
•    Azithromycin
•    Clarithromycin



Optimal Duration of Antibiotics

Give antibiotic until patient free of symptoms then add 7 days



Chronic Sinusitis
•    Symptoms present longer than 8 weeks or 4/year in adults or 12 weeks or 6 episodes/year in children
•    Eosinophilic inflammation or chronic infection
•    Associated with positive CT scans
•    Poor (if any) response to antibiotics


Quality-of-Life Issues
•    Fatigue
•    Concentration
•    Nuisance
•    Sleep disturbance
•    Emotional well being
•    Social interactions

•    Missing school/work
•    Halitosis       
•    Decreased production
•    Impaired studying
•    Sniffing/snorting
•    Blowing nose



Sx of Chronic Sinusitis
•    Nasal discharge
•    Nasal congestion
•    Headache
•    Facial pain or pressure
•    Olfactory disturbance
•    Fever and halitosis
•    Cough (worse when lying down)



Conditions Causing Chronic Sinusitis
•    Allergic and nonallergic rhinitis
•    Uncorrected anatomic conditions
•    Ciliary dyskinesia
•    Cystic fibrosis
•    Tumors
•    Immunodeficiency disorders
–    IgA, IgM
•    Granulomatous diseases



Evaluation of Chronic Sinusitis
•    CT or MRI scanning
–    Anatomic defects, tumors, fungi
•    Allergy testing
–    Inhalants, fungi, foods
•    Sinus aspiration for cultures
–    Bacterial
–    Fungal
•    Immunoglobulins



Treatment of Chronic Sinusitis
•    Nasal steroid spray
•    Guafenesin
•    Decongestants
•    Steam inhalation
•    Nasal  irrigation
•    Antibiotics with exacerbations



Bacteria Involved in Chronic Sinusitis Role of Viruses is Unknown
•    Streptococcus pneumoniae    
•    Haemophilus influenza       
•    Moraxella catarrhalis
•    Staph aureus       
•    Coagulase negative staphylococcus
•    Anerobic bacteria

               

Transition of Bacteria Rom Acute to Chronic Sinusitis
•    In one study, while initial aspirates showed strep pneumoniae, H. influenzae, and M catarrhalis, subsequent cultures showed Porphyromonas, Peptostreptococcus, and aerobic organisms found to be increasingly resistant to antibiotics
Sinus Aspiration and Culture
•    Correlation of routine nasal culture and sinus culture are poor
•    Endoscopically guided aspiration of cultures from medial meatus do correlate with sinus culture

   
Recommendations Made for Antibiotic Prophylaxis in ABS
•    Has not been evaluated as has its use in otitis media
•    Increasing evidence of antibiotic resistance is an issue
•    May be tried in chronic or recurrent disease


Complications of Sinusitis
•    Orbital
–    Diplopia, proptosis
–    Periorbital erythema, swelling
•    Bone
–    Periosteal abscesses
•    Brain
–    Intracranial abscesses causing neurologic symptoms



The Sinusitis-Asthma Connection
•    Mechanism is not understood
•    Evidence is compelling
•    Failure to control upper airway inflammation leads to suboptimal asthma control
•    Correcting the rhinosinusitis results in better asthma control


Indications for Referral
•    Allergy testing, possible immunotherapy
•    Sinus aspiration for bacterial culture
•    Surgical intervention
–    Correct obstructive process
–    Drain sinus abscesses
–    Consideration to remove nasal polyps


Indications for Hospitalization
•    Acutely ill child or adult with high fever, severe head pain
•    Suspected sphenoid sinusitis
•    Anytime complications of eye, bone or intracranial structures are present


The Recommendations
    The recommendations cited are those proposed by a task force of the American Academy of Pediatrics in consultation with other groups regarding the evaluation, diagnosis, and treatment of patients aged 1-21 years with sinus disease…expert opinion was used when insufficient data could be found. 

Recommendation 1
The diagnosis of acute bacterial sinusitis is based on clinical criteria with patients presenting with URI symptoms that are either persistent or severe.

Recommendation 2a
•    Imaging studies are not necessary to confirm a diagnosis of clinical sinusitis in children younger than 6 years (older than age 6 years is controversial)
•    Children with persistent symptoms (>10 days, < 30 days) predicted abnormal radiographs 80% of the time
•    Children < 6 symptoms predicted 88% of the time
•    Normal x-ray suggests ABS is not present
   

Recommendation 2b
•    CT scans of the paranasal sinuses should be reserved for:
–    Patients in whom surgery is being considered as a management strategy
–    Patients who do not respond to medical regimes which include adequate antibiotic use
–    Assisting in diagnosis of anatomical changes interfering with airflow or drainage



Recommendations for CT Scans
•    Patients presenting with complications of sinusitis
–    Neurologic symptoms, diplopia, periorbital or facial swelling with or without erythema
•    Patients with sinus symptoms accompanied by severe, boring, mid-head pain
–    Rule out sphenoid sinusitis


Recommendation 3
•    Antibiotics are recommended for the management of acute bacterial sinusitis to achieve a more rapid clinical cure
•    Patients must meet requirements of persistent or severe disease
•    Response improved with doses >Minimal Inhibition Concentration 



No EB Recommendations Found for Use of Adjunctive Therapy in ABS, May be Helpful
•    Nasal saline irrigation
•    Oral decongestants
•    Oral or nasal antihistamines
•    Topical decongestants
•    Mucolytic agents
•    Topical steroids



Summary
•    Acute and chronic sinusitis is one of the most common diseases treated in family practice
•    It is important to treat sinusitis aggressively to prevent chronic symptoms or development of serious complications
•    The underlying causes of chronic sinus disease should be sought out and corrected


Harold H. Hedges, III, M.D.
Private Practice
Little Rock Family Practice Clinic
Little Rock, Arkansas

and

Susan P. Pollart, M.D.
Associate Professor of Family Medicine
University of Virginia Health System
Charlottesville, Virginia

Medical Management of Nasal Polyposis

Background
► The term nasal polyposis comprises all types of nasal polyps which emerge as blue-gray protuberances in the area of
 the ethmoid bone,
 middle meatus,
 nose and
 middle turbinate


► Nasal polyposis
 characterized by eosinophil inflammation,
 accompanied by acetylsalicylic intolerance in up to 25% of cases
► 40% of cases of nasal polyposis are associated with intrinsic asthma
► Samter’s triad (nasal polyps, aspirin allergy, and asthma)
► Associations have also been described between Churg-Strauss syndrome (a form of eosinophilic immunovasculitis) and eosinophilic nasal polyposis
► Nasal polyps

 represent edematous semitranslucent masses in the nasal and paranasal cavities
 mostly originating from the mucosal linings of the sinuses and prolapsing into the nasal cavities.
► Several hypotheses regarding the underlying mechanisms including
  chronic infection,
 aspirin intolerance,
 alteration in aerodynamics with trapping of pollutants,
 epithelial disruptions,
 epithelial cell defects/gene deletions (CFTR gene), and
 inhalant or food allergies.
Anatomy

► Histologically polyps are characterized by
 edema or fibrosis,
 reduced vascularization,
 reduced number of glands and
 nerve endings in the presence of often damaged epithelium

Pathophysiology
► In the majority of nasal polyps, eosinophils comprise more than 60% of the cell population.
► Besides eosinophils, mast cells and activated T cells are also increased.
► An increased production of cytokines/chemokines like granulocyte/macrophage colony-stimulating factor, IL-5, RANTES and eotaxin contribute to eosinophil migration and survival.
► Increased levels of IL-8 can induce neutrophil infiltration.
► Increased expression of VEGF and its upregulation by transforming growth factor-[beta] contribute to edema and increased angiogenesis in nasal polyps.
► Transforming growth factor-[beta] modulate fibroblast function
  eosinophil infiltration and stromal fibrosis.
► Other mediators like albumin, histamine and immunoglobulins IgE and IgG are also increased in nasal polyps.

History and Physical Exam
► Diagnosis is based on finding of pale-gray, semitranslucent, round or bag-shaped mucosal protrusions from the sinuses into the nasal cavity, filled with gelatinous or watery masses.

► Polyps originating from the middle and superior turbinates may be seen in more severe disease, and those from the inferior turbinate are extremely rare.
► Most nasal polyps arise from
 the clefts of the middle nasal meatus and ethmoidal cells, prolapsing into the nose,
 with some polyps originating in the maxillary, sphenoid, or frontal sinuses
► The typical history is
 a “cold” that persisted over months or years,
 nasal obstruction and discharge prominent symptoms.
► With time
  hyposmia or anosmia develop, and
 additional complaints such as the feeling of a “full head” are present.
► Anosmia is a typical symptom for nasal polyps, differentiating it from chronic sinusitis without polyposis,
  may serve as a valid marker to estimate the duration and extent of disease.
► Whereas chronic sinusitis is often associated with headache and facial pain, nasal polyposis itself rarely causes pain despite the fact that most of the sinuses, including the frontal sinuses, are opacified.
► Because nasal polyps may represent a part of a systemic disease, adequate questions and further investigations may be necessary.
► Asthma and other lung diseases, aspirin sensitivity, Churg-Strauss syndrome, inhalant allergies, and CF must be considered.
► With the introduction of rigid endoscopes into daily practice, nasal polyps are now discovered in earlier stages than they were 10 years ago.
► Although anterior rhinoscopy may detect large polyps, it is not considered sufficient to exclude polyps. Especially for the differential diagnosis, an endoscopic investigation of the nose after topical decongestion is necessary.

Endoscopic Staging System for Nasal Polyposis 

Score   
0    No polyps present
1    Polyps confined to middle meatus
2    Polyps beyond middle meatus (reaching inferior turbinate or medial to middle turbinate)
3    Polyps almost or completely obstructing nasal cavity

Radiological Evaluation
► CT scan with coronary sections is performed, with special reference to mucosal structures and the delicate anatomy of the sinuses.  
► A CT scan is mandatory before sinus surgery may be considered, and CT must be available during surgery to inform the surgeon about anatomic variations.
► In addition, magnetic resonance imaging (MRI) may be helpful for the diagnosis of fungal disease and tumor or if intracranial extension of disease is suspected.

Differential Diagnosis
Nasal obstruction may also be caused by
 turbinate hypertrophy,
 chronic rhinosinusitis, or
 adenoid hypertrophy.
 Although nasal polyps have a characteristic appearance when investigated by nasal endoscopy, inverting papillomas and
 occasionally benign or malignant tumors or even meningoencephaloceles may be mistaken for nasal polyps.
 Any unilateral obstruction, nose bleeding, or crusting should be intensively investigated.

The objectives of medical management of nasal polyposis
► 1) to eliminate nasal polyps and rhinitis symptoms,
► 2) to reestablish nasal breathing and olfaction, and
► 3) to prevent recurrence of nasal polyps.

Available Treatments for sinusitis, chronic obstruction
► Sinus ventilation and drainage
► Management of allergies
► Saline irrigation
► Mucolytics
► Antihistamines
► Leukotrienes
► Corticosteroids
► Topical corticosteroids
► Decongestants
► Topical decongestants

Sinus ventilation and drainage
 Oral hydration
 Saline sprays
 Humidification
 Decongestants
 Mucolytics

Management of allergies
► Allergen avoidance
 history or positive skin prick tests
►  Saline irrigation
► Antiinflammatory therapy
► Antihistamine
► Leukotriene Receptor Antagonists
► Decongestant

Saline irrigation
► Increase mucociliary flow rates
► Brief vasoconstrictive effect
► Mechanically rinse
► Adding baking soda
 Alkaline medium leads to thinning of mucus
 An acidic medium creates a more viscous (gel) mucus
Mucolytics
► Guaifenesin
► High doses are required for obtaining an effect on mucous
 Emesis and abdominal pain

Antihistamine
► Inhibition of histamine receptor
► Ineffective in relieving chronic nasal congestion
► First-generation antihistamines
 Anticholinergic
► adverse effects such as drowsiness
► Leads to drying of secretions

Second-generation antihistamines
► Higher affinity to histamine receptors and increased potency
► No anticholinergic effect
► Cetirizine
 Block other mediator release such as that of leukotrienes and kinins
 Inhibit monocyte and lymphocyte chemotaxis
 Beneficial in the treatment of chronic congestion
Leukotriene
► More potent than histamine in triggering nasal allergic inflammation
► Leukotriene Receptor Antagonists
 Effective in allergic rhinitis
 Beneficial effects for the indication of chronic rhinosinusitis
Corticosteroid
► Inmunomodulator
 Stabilize mast cells
 Block formation of inflammatory mediators
 Inhibit chemotaxis of inflammatory cells
► Short courses of systemic corticosteroids
 Tx severe nasal mucosal congestion in allergic patients
► Only glucocorticosteroids (steroids) have a proven effect on the symptoms and signs of nasal polyps.
► Topically applied steroids are the therapeutic modality that has been best studied in controlled trials.
 reduces rhinitis symptoms,
 improves nasal breathing,
 reduces the size of polyps and the recurrence rate, but it has a negligible effect on the sense of smell and on any sinus pathology.
► Topical steroids can, as long-term therapy, be used alone in mild cases, or combined with systemic steroids/surgery in severe cases.
► Systemic steroids, which are less well studied, have an effect on all types of symptoms and pathology, including the sense of smell. This type of treatment, which can serve a "medical polypectomy," is only used for short-term improvement due to the risk of adverse effects.
► Contraindications
 Diabetes
 Peptic ulcer disease
 Glaucoma
 Severe hypertension
 Advanced osteoporosis
Topical corticosteroids
► Improve patency of the ostiomeatal complex
 reduction in mucosal swelling
► Inhibit both immediate and late-phase reactions to antigenic stimulation (After 7 days of treatment)
► 90% of patients with allergic rhinitis will experience improvement
► Common adverse effects
 nasal irritation, mucosal bleeding, and crusting
 propylene glycol contained in the preparations
► Alleviated by switching to a aqueous delivery system
► Concomitant nasal saline used lessen or eliminate the adverse effects
Decongestants
► vasoconstriction of dilated mucosal blood vessels (α-adrenergic agonists)
► symptomatic relief of nasal congestion
► No therapeutic efficacy for the treatment of sinusitis
Topical Decongestants
► Phenylephrine & oxymetazoline
► Rhinometric analysis
 Rebound vasodilation as early as 3 days
► Rhinitis medicamentosa
 after 10 days to 2 weeks

Macrolide
► Antiinflamatory effect
► Accumulate in inflammatory cells >100X higher than concentrations in extracellular fluid
Macrolide Inmunomodulator effect
► Macrolide antibiotics targets cytokine production
 Decreased IL-5, IL-8, GM-CSF, TGF-β, IL-6, IL-8, TNF-ɑ
► Reduced expression leukocyte adhesion molecules
► Accelerate neutrophil apoptosis
► Impaired neutrophil oxidative burst
► Decrease secretion and improve mucociliary clearance
► Inhibited release of elastase, protease, phospholipase C, and eotaxin A by P aeruginosa
Macrolide
► Long-term, low-dose macrolides for treatment of CRS (primarily in Japan)
► Clarithromycin is the macrolide most studied in CRS
► Azithromycin lack studies in CRS
► Long term use is 3-12 month
Anti-Inflammatory Effect of Macrolides
► Hashiba and Baba (1996) studied 45 adult patients with chronic sinusitis, 44% of whom had had previous sinus surgery. 
► They were treated with 400 mg/day clarithromycin (CAM) for 8 or 12 weeks. 
► Improvement in symptoms and rhinoscopic findings were noted in 71.1% of the patients at the end of the treatment period. 
► The study demonstrated the slow onset of macrolide therapy.
 After 2 weeks of treatment only 5 % of patients indicated improvement,
 after 4 weeks 48% were improved,
 after 8 weeks 63% were improved and after 12 weeks 71% were improved. 
It concluded that CAM was as effective as EM. 
► A study of nasal polyps with chronic sinusitis was presented by Ichimura et al in 1996. 
► Treatment with 150 mg RXM per day for at least 8 weeks showed reduction in nasal polyps by 52%.  With the addition of astelin (azelastine) 1 mg twice daily, an inhibitor of mediator release, another 20 patients were evaluated.
► Azelastine augmented the rate of improvement to 68% compared to RXM alone but result wasn’t significant. 
► Smaller polyps were more likely to decrease in size, but some larger polyps also markedly decreased in size.
Short course of systemic corticosteroids in sinonasal polyposis A double-blind, randomized, placebo-controlled trial with evaluation of outcome measures
► Hissaria et al (EBM A)
 the efficacy of a short course of oral prednisolone in ameliorating the symptoms of sinonasal polyposis,
 reducing mucosal inflammation assessed by means of nasendoscopy and magnetic resonance imaging (MRI).
► Subjects with symptomatic endoscopically diagnosed sinonasal polyposis received 50 mg of prednisolone daily for 14 days or placebo.
► Outcome was quantified using
 the modified 31-item Rhinosinusitis Outcome Measure questionnaire,
 physician's assessment,
 nasendoscopy with photography, and
 MRI.
► There were 20 subjects in each treatment group.
Short course of systemic corticosteroids in sinonasal polyposis A double-blind, randomized, placebo-controlled trial with evaluation of outcome measures
► Only the prednisolone-treated group showed significant improvement in nasal symptoms (P < .001).
► The Rhinosinusitis Outcome Measure score improved in both groups, but the prednisolone-treated group had significantly greater improvement than the placebo group (P < .001).
► Objectively, there was significant reduction in polyp size, as noted with nasendoscopy (P < .001) and MRI (P < .001), only in the prednisolone-treated group.
► The outcome measures correlated with each other; the highest level of correlation was between the objective measures of nasendoscopy and MRI (R2 = 0.76, P < .001).
Short course of systemic corticosteroids in sinonasal polyposis A double-blind, randomized, placebo-controlled trial with evaluation of outcome measures
► There were no significant adverse events.
► This trial clearly establishes clinically significant improvement in the symptoms and pathology of sinonasal polyposis with a short course of systemic corticosteroids.
► MRI scanning and quantitative nasendoscopic photography are objective and valid tools for assessing the outcome of treatment in this condition.
► A 14-day course of 50 mg of prednisolone is safe and effective therapy for symptomatic nasal polyposis.
Randomised controlled study evaluating medical treatment vs surgical treatment in addition to medical treatmentof nasal polyposis
► Blomqvist et al (2001)  (EBM B) compared the effect of medical treatment versus combined surgical and medical treatment on olfaction, polyp score, and symptoms in nasal polyposis.
► They evaluated thirty-two patients with nasal polyposis and symmetrical nasal airways were randomized to unilateral endoscopic sinus surgery after pretreatment with oral prednisolone for 10 days and local nasal budesonide bilaterally for 1 month.
► Postoperatively, patients were given local nasal steroids (budesonide). Patients were evaluated with nasal endoscopy, symptom scores, and olfactory thresholds.
► They were followed for 12 months.
► They found that the sense of smell was improved by the combination of local and oral steroids. Surgery had no additional effect.
Randomised controlled study evaluating medical treatment vs surgical treatment in addition to medical treatmentof nasal polyposis
► Symptom scores improved significantly with medical treatment alone, but surgery had additional beneficial effects on nasal obstruction and secretion.
► After surgery,
 the polyp score decreased significantly on the operated side but remained the same on the unoperated side.
 Twenty-five percent of the patients were willing to undergo an operation also on the unoperated side at the end of the study.
► They concluded that medical treatment seems to be sufficient to treat most symptoms of nasal polyposis.
 When hyposmia is the primary symptom, no additional benefit seems to be gained from surgical treatment. If nasal obstruction is the main problem after steroid treatment, surgical treatment is indicated.

Effect of anti-fungal nasal lavage with amphotericin B on nasal polyposis
► Fungus has also been considered to be involved in the development of AFS, though there is no consensus on its involvement or in the use of amphotericin B rinses to aid with nasal polyposis.  
► Richetti et al (2002) looked into amphotericin B nasal rinses as a possible adjuvant for the treatment of nasal polyposis and stated that a direct effect on the integrity of the cell membrane could not be excluded. 
► Weschta et al (2004) compared the effects of amphotericin B versus control nasal spray on chronic rhinosinusitis in a double-blind, randomized clinical trial. 
► Patients with chronic rhinosinusitis were administered 200 μL per nostril amphotericin B (3 mg/mL) or saline nasal spray 4 times daily over a period of 8 weeks.
► The response rate, defined as a 50% reduction of pretreatment computed tomography score, was the primary outcome variable.
► Additional outcome variables included a symptom score, a quality of life score, and an endoscopy score.
► They found that nasal amphotericin B spray in the described dosing and time schedule was ineffective and deteriorated patient symptoms.

Conclusions
► Nasal polyposis is a multifactorial disease with several different etiological factors.
► Although antibiotics are used for infectious complications of nasal polyposis, only glucocorticosteroids (steroids) have a proven effect on the symptoms and signs of nasal polyps. 
► Macrolides may play a role in the future in management of nasal polyps but further studies must be conducted in this area.
Camysha Wright, MD,MPH
Jing Shen,MD
University of Texas Medical Branch
Department of Otolaryngology