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New Directions in Targeted Therapeutic Approaches for Older Adults With Mantl...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck presented by Dr. Kami Maddocks, Professor-Clinical in the Division of Hematology and
Associate Division Director for Ambulatory Operations
The Ohio State University Comprehensive Cancer Center, will provide insight into new directions in targeted therapeutic approaches for older adults with mantle cell lymphoma.
STATEMENT OF NEED
Mantle cell lymphoma (MCL) is a rare, aggressive B-cell non-Hodgkin lymphoma (NHL) accounting for 5% to 7% of all lymphomas. Its prognosis ranges from indolent disease that does not require treatment for years to very aggressive disease, which is associated with poor survival (Silkenstedt et al, 2021). Typically, MCL is diagnosed at advanced stage and in older patients who cannot tolerate intensive therapy (NCCN, 2022). Although recent advances have slightly increased remission rates, recurrence and relapse remain very common, leading to a median overall survival between 3 and 6 years (LLS, 2021). Though there are several effective options, progress is still needed towards establishing an accepted frontline approach for MCL (Castellino et al, 2022). Treatment selection and management of MCL are complicated by the heterogeneity of prognosis, advanced age and comorbidities of patients, and lack of an established standard approach for treatment, making it vital that clinicians be familiar with the latest research and advances in this area. In this activity chaired by Michael Wang, MD, Professor in the Department of Lymphoma & Myeloma at MD Anderson Cancer Center, expert faculty will discuss prognostic factors informing treatment, the promising results of recent trials in new therapeutic approaches, and the implications of treatment resistance in therapeutic selection for MCL.
Target Audience
Hematology/oncology fellows, attending faculty, and other health care professionals involved in the treatment of patients with mantle cell lymphoma (MCL).
Learning Objectives
1.) Identify clinical and biological prognostic factors that can guide treatment decision making for older adults with MCL
2.) Evaluate emerging data on targeted therapeutic approaches for treatment-naive and relapsed/refractory MCL and their applicability to older adults
3.) Assess mechanisms of resistance to targeted therapies for MCL and their implications for treatment selection
Prix Galien International 2024 Forum ProgramLevi Shapiro
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- ADVANCES IN CARDIOLOGY: A NEW PARADIGM IS COMING
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- ETHICAL CHALLENGES IN LIFE SCIENCES
- Prix Galien International Awards Ceremony
- Video recording of this lecture in English language: https://youtu.be/lK81BzxMqdo
- Video recording of this lecture in Arabic language: https://youtu.be/Ve4P0COk9OI
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
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3. DEFINITION CHRONIC RHINOSINUSITIS
Chronic rhinosinusitis with and without Nasal polyposis:
> 12 weeks without complete resolution of symptoms
Inflammation of the nose and the
paranasal sinuses ≥2 symptoms;
• Nasal blockage/obstruction/congestion
• Nasal discharge
(anterior/posterior nasal drip)
• Facial pain/pressure
• Reduction or loss of smell
Endoscopic signs;1 or more;
• Polyps
• Mucopurulent discharge primarily from
middle meatus
• Edema/mucosal obstruction primarily in
middle meatus
CT changes
• Mucosal changes within the ostiomeatal
complex and/or sinuses
Sarbjit S. Saini. Middleton's 8th edition. European position paper on rhinosinusitis and nasal polyp 2012
4. CLASSIFICATION OF RHINOSINUSITIS
Diagnosis and Management of Rhinosinusitis: Highlights from the 2015 Practice Parameter
Recurrent acute rhinosinusitis (RARS) : ≥ 3 episode/year each lasting >7 day
5. EPIDEMIOLODY
Affects about 10 -15% of adults
CRS : significant effect on health-related quality of
life and is associated with substantial health care
and productivity costs.
Prevalence
• CRS without nasal polyp (CRSsNP) : 10.9%
• CRS with nasal polyps (CRSwNP) : 2-4 %
Zhang et al.J Allergy Clin Immunol 2017;140:1230-9
6. Zhang et al. Chronic rhinosinusitis in asia. J Allergy Clin Immunol 2017;140:1230-9.
7. CRS with Nasal polyps occur more frequently in
• Asthma patients with aspirin sensitivity
• Cystic fibrosis (children and adolescents)
• Churg-Strauss syndrome and Kartagener syndrome (situs inversus).
incidence of nasal polyps : higher in men > women
Sarbjit S. Saini. Middleton's 8th edition. European position paper 2012
EPIDEMIOLODY
8. DEVELOPMENTAL OF SINUSES
Sarbjit S. Saini. Middleton's 8th edition. European position paper 2012
paranasal sinuses are cavities
-partially present at birth : maxillary sinus
ethmoidal sinus
Frontal and sphenoid: later, complete pneumatization at mid to
late adolescence
9. The ostiomeatal complex : region for ventilation and drainage of
the maxillary ethmoidal and frontal sinuses
10. SINUS PHYSIOLOGY
The sinus cavities
• Air, pseudostratified, ciliated columnar epithelia with goblet cells.
• Cilia sweep mucus toward the ostial opening.
Obstruction ostia :
- mucous impaction → oxygenation → anaerobic condition →
purulent secretions → growth of bacteria
- air pressure →pain and pressure sensation
Sinonasal biofilms
• communities of bacteria >> mucus layer
• evasion of host defenses, decreased susceptibility to antibiotic therapy
A.T. Peters et al. Ann Allergy Asthma Immunol 2014;113:347-385
11. MICROBIOLOGY IN CRS
Children
• Aerobes:
Alpha-hemolytic streptococcus
(20.8%),
H. influenzae (19.5%)
S. pneumoniae (14.0%)
S. epidermidis (13.0%)
S. aureus (9.3%)
• Anaerobes: 8.0%
Adults
• Aerobes
Streptococcus species (21%)
H. influenzae (16%)
P. aeruginosa (16%)
S. aureus (10%)
M. catarrhalis (10%)
• Anaerobes:
Prevotella species (31%)
Fusobacterium species (16%)
A.T. Peters et al. Ann Allergy Asthma Immunol 2014;113:347-385
12. MICROBIOLOGY IN CRS
Nosocomial
• Gram-negative enteric species:
P. aeruginosa,
Klebsiella pneumoniae
Enterobacter species
Proteus mirabilis
Serratia marcescens
• Gram-positive cocci:
Streptococci, Staphylococci
CRSwNP
• Polymicrobial aerobic and
anaerobic flora
A.T. Peters et al. Ann Allergy Asthma Immunol 2014;113:347-385
13. CLINICAL MANIFESTATION
History
• Persistent cough, prolonged anterior and
posterior nasal drainage, congestion
• low-grade fever, irritability, and behavioral
difficulties
• Headache, especially in the frontal area, is a less
common
• Frequent URI or recurrent sinusitis
• Additional history should focus on identification
of any potential contributing factors
CRS in children. Pediatr Clin N Am 2013
14. NASAL & SINUS SYMPTOMS AND CHRONIC
RHINOSINUSITIS IN A POPULATION-BASED SAMPLE
15. CO-MORBID OF CRS
Pedro C. Avila GLOBAL ATLAS OF ALLERGIC RHINITIS AND CHRONIC RHINOSINUSITIS
Chapurin et al. Otolaryngol Head Neck Surg 2017
16. PREDISPOSING FACTORS TO RHINOSINUSITIS
A.T. Peters et al. Ann Allergy Asthma Immunol 2014;113:347-385
17. SIMILARITIES AND DIFFERENCES
IN PEDIATRIC VERSUS ADULT CRS
Diagnosis and Classifi cation of Chronic Rhinosinusitis with and Without Polyposis in Adults and Children 2014
19. CHRONIC RHINOSINUSITIS WITHOUT NASAL POLYP
Present chronic maxillary sinus
Local obstruction sinus , encourages bacterial growth ,
mucosal remodeling
Environmental triggers
• Pollution: carbon monoxide, nitrous dioxide, sulfur dioxide
• Irritants in air pollution: sulfur dioxide ozone and PM2.5
formaldehyde (indoor pollutant)
• Indoor dampness and mold exposure
• Active and secondhand cigarette smoking
20. Otolaryngol Head Neck Surg. 2018 Feb
• strong correlation between active and passive
cigarette smoke with the prevalence of CRS
• Pediatric patients exposed to secondhand smoke
appear to have particularly poor outcomes
21. Allergic/ nonallergic rhinitis
• Congestion interfere drainage, ↑secretion→ hypoxic and
acidosis leads to mucociliary dysfunction→ bacteria multiply
• CRS 36-60% have AR children, 40-84% in adult
• Test: SPT, specific IgE
Adenoid hypertrophy , Chronic adenoiditis
- Nearly 50% of CRS had adenoid hypertrophy while
<30% presented in ARS
CHRONIC RHINOSINUSITIS WITHOUT NASAL POLYP
22. Nasal polyps are edematous semitranslucent masses in the
nasal and paranasal cavities,
originating from the mucosal linings of the sinuses and
prolapsing into the nasal cavities.
CHRONIC RHINOSINUSITIS WITH NASAL POLYP
Sarbjit S. Saini. Middleton's 8th edition.
23. Typical history : most prominent symptoms nasal obstruction
and discharge
Anosmia is a typical symptom for nasal polyps.
Viral infections : prolonged episodes of severely obstructed
nasal passages and colored secretions, with subsequent
bacterial infection.
Inhalant allergens do not cause polyps.
CHRONIC RHINOSINUSITIS WITH NASAL POLYP
Sarbjit S. Saini. Middleton's 8th edition.
24. Asthma
• CRSwNP frequently is found in association with asthma and
nonspecific bronchial hyperresponsiveness.
• medical or surgical treatment of CRSwNP may have a
favorable impact on the control of asthma.
CHRONIC RHINOSINUSITIS WITH NASAL POLYP
Sarbjit S. Saini. Middleton's 8th edition.
25. Aspirin sensitivity
• Samter’s triad : aspirin sensitivity,
corticosteroid- dependent asthma
nasal polyposis
• Aspirin sensitivity is suspected after a typical respiratory reaction.
15% of patients : aspirin- provoked asthma and rhinitis attack
Investigation : oral , bronchial or nasal provocation test
Aspirin-exacerbated respiratory disease (AERD)
- increased blood eosinophil counts
- increase of eosinophils in the nasal and bronchial mucosa
- Elevated cysteinyl-leukotriene concentrations in the tissue and urine
CHRONIC RHINOSINUSITIS WITH NASAL POLYP
Sarbjit S. Saini. Middleton's 8th edition.
26. Fungal disease
• Fungal sinusitis is currently divided into four primary categories:
• Acute/ fulminant
• Chronic/ indolent
• Fungus ball : mycetoma (unilateral, chronic maxillary sinusitis)
• Allergic fungal sinusitis; AFS (most common , associated nasal polyps)
Imaging studies (CT or MRI) may show
heterogeneous opacification,calcification in CT
hypointense signal onT2-weighted MRI
typical sinus : creamy or claylike secretions
CHRONIC RHINOSINUSITIS WITH NASAL POLYP
Sarbjit S. Saini. Middleton's 8th edition.
invasive
27. Fungi associated allergic fungal rhinosinusitis (AFS) :
predominantly dematiaceous family
• Aspergillus, Rhizopus,Alternaria, Curvularia, Bipolaris specifera,
AFS
- Atopic young hosts, nasal polyps
- Positive skin testing for fungus
- Elevated serum total IgE and fungus-specific IgG
Invasive forms
• indolent chronic, slowly destructive disease ,caused by Aspergillus flavus.
• fulminant acute, necrotizing form in immunocompromised hosts
caused by Aspergillus fumigatus
lethal within days , hematogenous dissemination
Treatment high-dose intravenous antifungal
CHRONIC RHINOSINUSITIS WITH NASAL POLYP
Sarbjit S. Saini. Middleton's 8th edition.
28. Cystic fibrosis
• Involvement of the nose and sinuses is common in patients with CF.
• no sinonasal complaints but detected in radiologic investigations.
Incidence of CRSwNP in CF varies (6-48%)
CF reported that 37% had CRSwNP.
50% of the children who present with CRSwNP have CF
affect bilateral paranasal cavities,
possibly causing facial deformities (hypertelorism )
Radiological signs bulging of the lateral nasal wall
erosion of the uncinate process
CHRONIC RHINOSINUSITIS WITH NASAL POLYP
Sarbjit S. Saini. Middleton's 8th edition.
29. Cystic fibrosis
• Predominant organisms
Pseudomonas aeruginosa, S. aureus, H. influenzae, and anaerobes.
• Suboptimal response to antimicrobial therapy
• Sinus surgery should only be performed in case of severe symptoms or
before lung transplantation.
• functional endoscopic sinus surgery (FESS) has decreased morbidity
of sinus surgery and reduced the recurrence of nasal polyposis in cystic
fibrosis.
CHRONIC RHINOSINUSITIS WITH NASAL POLYP
Sarbjit S. Saini. Middleton's 8th edition.
30. CRS IN SYSTEMIC VASCULITIS
Granulomatosis with polyangiitis
Three of the following criteria
• renal involvement
• positive histopathology
• upper airway involvement
• laryngotracheobronchial involvement
• pulmonary involvement
• ANCA positive
31. A.T. Peters et al. Ann Allergy Asthma Immunol 2014;113:347-385
CHRONIC RHINOSINUSITIS AND IMMUNE DEFICIENCY
Candidate for immunological evaluation in
chronic/recurrent RS
• Failure of treatment despite of appropriate treatment
- At least 2 serious sinus infections
• Recurrence within 1 month after discontinuation of antibiotic therapy
• Recurrence/persistent of CRS after sinus surgery
• Associated with other recurrent respiratory tract infections e.g.
bronchitis, pneumonia, bronchiectasis
32. Immunodeficiency
Humoral immune deficiency: Predominantly Antibody deficiency
: Specific antibody deficiency (SAD)
Selective IgA deficiency
Common variable immunodeficiency (CVID)
IgG subclass deficiency
A.T. Peters et al. Ann Allergy Asthma Immunol 2014;113:347-385
CHRONIC RHINOSINUSITIS AND IMMUNE DEFICIENCY
33. PIDS AND CRS
PIDs with CRS: 842 predominantly antibody deficiencies children
Int J Pediatr Otorhinolaryngol. 2006 Sep;70(9):1587-92
34. PIDS AND CRS
Prevalence of common PIDs in adult patients with CRS
at an academic institution
Peters AT. GLOBAL ATLAS OF ALLERGIC RHINITIS AND CHRONIC RHINOSINUSITIS
Am J Rhinol Allergy 2015;29:115-118
42. ENDOTYPING OF CRS
Concept ‘‘distinct’’ endotypes in patients with CRS is misguided
• defined by absolute presence or absence of eosinophils, cytokine,
other specific marker.
Robust expression of any of these markers can serve as an aid for
guiding therapeutic decisions.
Gurrola and Borish. J Allergy Clin Immunol 2017;140:1499-508.
44. PATHOPHYSIOLOGY IN CRSSNP
Deficiencies in epithelial immune barrier function and the production of
antimicrobial proteins
Two main defensive strategies
1. Nonspecific phase
• Mucus and its contents: lysozyme and defensins
• VEGF: promote nasal epithelial cell growth and inhibit apoptosis.
2. Innate and adaptive immune response
•Innate immune system : phagocytosis of microorganisms by neutrophils,
monocytes and macrophages.
• Adaptive immunity reacts on antigen presentation through formation of immune
products (Th1&Ab).
Sarbjit S. Saini. Middleton's 8th edition
46. PATHOPHYSIOLOGY IN CRSWNP
highest concentrations of IL-5, eosinophil cationic protein (ECP) , were
found in polyp tissue in subjects with nonallergic asthma and aspirin
sensitivity.
Eosinophil recruitment is mediated mainly by the chemokines RANTES and
eotaxins, in cooperation with IL-5.
Treatment :
anti-IL-5 monoclonal antibodies
- Eosinophil apoptosis and decreased eosinophil-infiltrated polyp tissue
Topical glucocorticosteroids
- Expression of VCAM-1 in polyps, eotaxin and IL-5
- marked reduction of tissue eosinophils.
Sarbjit S. Saini. Middleton's 8th edition
47. PATHOPHYSIOLOGY IN CRSWNP
upregulation of GATA3 : Upregulation ofTh2 cytokines •
Downregulation of Foxp3
Downregulation of regulatoryT cells (Tregs)
Nasal polyps (large quantities B lymphocytes and plasma cells)
upregulated of B cell–activating factor of the TNF family (BAFF)
Sarbjit S. Saini. Middleton's 8th edition
48. PATHOPHYSIOLOGY IN CRSWNP
Role of Staphylococcus aureus Enterotoxins (SAEs)
S. aureus may form biofilms & enterotoxins with superantigenic activity
• modify the functions of T and B cells, eosinophils, inflammatory cells.
S. aureus enterotoxin :
- Th2-polarized eosinophilic inflammation
- impairment of T regulatory function, secrete multiclonal IgE production
IgE antibodies to SAEs : local eosinophilic inflammation
IgE antibodies to Staphylococcal enterotoxins : increase in local total IgE ,
increases risk asthma.
Sarbjit S. Saini. Middleton's 8th edition
49. ROLE OF STAPHYLOCOCCUS AUREUS ENTEROTOXINS (SAES)
Zhang et a. J Allergy Clin Immunol2017;140:1230-9.
52. PATIENT EVALUATION IN CRSSNP
Evaluation
• Character,severity,duration and course of disease
• Comorbid illnesses,underlying pathologic condition
• Earlier management attempts
Anterior rhinoscopy
hyperemia and swelling of the inferior turbinates, septum deformities
purulent secretions from the sinuses (middle meatus).
Endoscopy
Rigid scope after nasal decongestion (rapid and easy)
evaluate middle meatus and ostiomeatal complex, posterior nasal
structures, nasopharynx.
Sarbjit S. Saini. Middleton's 8th edition
53. PATIENT EVALUATION IN CRSSNP
Standard sinus radiographs
• diagnosis of acute frontal or maxillary sinusitis
• do not provide additional information over history alone.
Ultrasound imaging: may be used in pregnant women
CT
- define extent of the disease, anatomic abnormalities, and changes in the
ostiomeatal complex and evaluation of orbital or cerebral complications
MRI: fungal sinusitis and extension into brain
Nasal cultures:
• infections resistant to treatment
• immunocompromised hosts
• HIV,CMT recipients,DM, ICU patients
Sarbjit S. Saini. Middleton's 8th edition
54. PATIENT EVALUATION IN CRSWNP
Diagnosis of CRSwNP : rigid nasal endoscopy
CT scan with coronal sections
- extent of disease within the sinuses
- mucosal structures and anatomy of the sinuses
CT scan
before sinus surgery is considered about anatomic variations.
MRI scan : for the diagnosis of fungal disease or tumor or
intra- cranial extension of disease.
Sarbjit S. Saini. Middleton's 8th edition
55. PATIENT EVALUATION IN CRSWNP
Nasal endoscopy : confirm diagnosis ,exclude other diseases
• Turbinate hypertrophy, concha bullosa,CRSsNP, adenoid hypertrophy
Unilateral obstruction,nose bleeding,or crusting
• Papillomas,benign or malignant tumors, meningoencephaloceles
Nasal polyps
• Asthma, aspirin sensitivity,Churg-Strauss syndrome,CF, other lung disease
SPT for inhalant allergens, cytologic examination of nasal secretions for
eosinophils, and a blood sample for an eosinophil
Endoscopically guided microbiology from the middle meatus or biopsy
Sarbjit S. Saini. Middleton's 8th edition
57. ENDOTYPING OF CHRONIC RHINOSINUSITIS
CRS: inflammatory processes
high and variable expression of immune and inflammatory markers.
Inflammatory endotype based on microarray-based detailed analyses
Distinct endotypes or phenotypes in patients with CRS
- Presence or absence of eosinophils
- Cytokine, any other specific marker
Robust expression of any of these markers can aid for guiding therapeutic
Gurrola and Borish. J Allergy Clin Immunol 2017;140:1499-508.
60. A.T. Peters et al. Ann Allergy
Asthma Immunol 2014;113:347-385
CHRONIC
RHINOSINUSITIS
WITHOUT
NASAL POLYP
61. A.T. Peters et al. Ann Allergy
Asthma Immunol 2014;113:347-385
CHRONIC
RHINOSINUSITIS
WITH
NASAL POLYP
62. TREATMENT
Jivianne T. Lee Atlas of Endoscopic Sinus and Skull Base Surgery, Chapter 7, 47-63
Primary objectives of CRS medical therapy
• Treat infection : antibiotics
• Reduce inflammation : Topical or oral corticosteroids,
antihistamines
leukotriene modifiers
• Improve ventilation : Saline irrigations
Decongestants
Mucolytics
63. TREATMENT
Medical Therapy for Chronic Rhinosinusitis: Antibiotics
• Antibiotics are indicated to treat acute exacerbations , persistent
purulent drainage
• Eradication of infection : sinus aeration and adequate mucociliary
clearance.
• Macrolides : anti-inflammatory with antibacterial effects.
• A recent evidence- based review recommended against the use of
intravenous antibiotics for uncomplicated CRS
A.T. Peters et al. Ann Allergy Asthma Immunol 2014;113:347-385
64. Jivianne T. Lee Atlas of Endoscopic Sinus and Skull Base Surgery, Chapter 7, 47-63
Medical Therapy for Chronic Rhinosinusitis: Antibiotics
• Amoxicillin 50 - 90 mg/kg/day
• Amoxicillin-clavulanate : cover B-lactamase organisms,H influenzae
• Alternative : quinolones or clindamycin with a 2nd or 3rd gen cephalosporins
65. LONG TERM MACROLIDE THERAPY FOR
CHRONIC RHINOSINUSITIS
• Clinical studies showing beneficial effects are quite limited.
• These studies do not clearly differentiate effects in CRSsNP or CRSwNP
Roxithromycin 150mg/d 12 wk – change from
baseline at 12 wk
Azithromycin 500 mg/d 3 d then 200mg/wk
11 wk – no significant
67. Seresirikachornet al.: Predicting Success of Low-Dose Macrolides.Laryngoscope 129:July 2019
• Treatment CRS did not favorable LDMs in improvement of outcomes.
• Data showed no difference between the effects of LDMs and placebo.
• Forest plots from the RCTs did not show the benefit of LDMs therapy.
68. TREATMENT
Jivianne T. Lee Atlas of Endoscopic Sinus and Skull Base Surgery, Chapter 7, 47-63
Medical Therapy for Chronic Rhinosinusitis: Anti-inflammatory
69. TOPICAL STEROID
CRSwNP and CRSsNP: Use INS (sprays and aerosols) (StrRec,A)
• Reduce symptoms of blockage, rhinorrhea, occasionally hyposmia
• Recurrent within weeks to months of discontinuation of treatment.
Children:
• no RCTs evaluating the effect of INSs in children with CRS.
• Treatment as allergic rhinitis (efficacy and safety of INSs).
- Mometasone fuorate 2 yr
-Fluticasone propionate 4 yr
A.T. Peters et al. Ann Allergy Asthma Immunol 2014;113:347-385
70. SYSTEMIC GLUCOCORTICOID
CRSsNP
short course of oral steroids for treatment of (Rec, C)
CRSwNP
short-term treatment with oral steroids (decreases polyp size and
alleviates symptoms.(StrRec,A)
• medical polypectomy
• Prednisolone 30 mg/day then stepwise reducing dose
during a 14 - 20 days
A.T. Peters et al. Ann Allergy Asthma Immunol 2014;113:347-385
71. TREATMENTS OF CRS
Anti-IgE :Omalizumab for treatment of CRSwNP
Annals of Otology, Rhinology & Laryngology 2017, Vol. 126(11) 739 –747
• prospectively SNOT-22 and the ACQ-7 scores
• Omalizumab (n =13) or Surgery (n = 24)
• significant decrease in total nasal endoscopic polyp scores after 4,16 weeks
• effective for severe CRSwNP comparative after surgery
-Anti-IgE therapy reduces nasal polyp score in patients with severe comorbid
asthma T. Bidder.Rhinology 56-1: 42-45, 2018
72. omalizumab is an effective treatment for CRSwNP
improvements are greater with eosinophilic disease.
Significant reduction of polyp size and QOL ,reduced need for surgery
1: 147 - 153, 2018 http://doi.org/10.4193/RHINOL/18.077
Gevaert P. Omalizumab is effective in allergic and nonallergic patients with nasal polyposis and
asthma. J. Allergy Clin. Immunol. 2013;131:110–116. doi: 10.1016/j.jaci.2012.07.047.
73. IMMUNOTHERAPY
Am J Rhinol allergy 28, 145–150, 2014; doi: 10.2500/ajra.2014.28.4019)
• Weak evidence to support use of immunotherapy
• Adjunctive treatment in CRS patients .
74. TREATMENTS OF CRS
Anti-Cytokine therapy :treatment of CRSwNP
Annals of Otology, Rhinology & Laryngology 2017, Vol. 126(11) 739 –747
- efficacy therapy in patients with CRSwNP.
- anti-IL-5 (reslizumab and mepolizumab) and anti-IL-4/IL-13 (dupilumbab)
- Reduce nasal polyp size, reduce need for surgery in CRSwNP patients
J AllergyClin Immunol 2017;140:1024-31.
75. JAMA. 2016;315(5):469-479. doi:10.1001/jama.2015.19330
Tsetsos N. antibodies for the treatment of chronic rhinosinusitis with nasal polyposis. Rhinology. 2018;56:11–21.
Patient CRS with refractory to INS, subcutaneous dupilumab to mometasone
furoate nasal spray compared with mometasone alone reduced endoscopic
nasal polyp burden after 16 weeks
76. TREATMENT: CRSWNP WITH AERD
Avoidance of aspirin and other NSAIDs
• Prevent exacerbations but does not prevent progression of disease.
• Selective COX-2 inhibitors (celecoxib, rofecoxib)
Aspirin desensitization
• relapse of risk in case of noncompliance
• gastrointestinal side effects
Leukotriene receptor antagonists
Oral and/or topical glucocorticosteroids
• effective but they cause side-effects in long- term usage.
Sarbjit S. Saini. Middleton's 8th edition
77. TREATMENT: CRSWNP WITH AFRS
Antifungals are indicated only for invasive forms of sinus mycosis
or in immuno- compromised patients.
Surgical intervention and use systemic and long-term topical
corticosteroids are recommended.
Follow up : Total serum IgE
• increase in total serum IgE >> need of recurrent surgical
intervention.
Sarbjit S. Saini. Middleton's 8th edition
78. SURGERY
Removing mucosal disease > involved bone ethmoid sinuses and sinus ostia
- Restore sinus ventilation and drainage by opening the key areas
- Preserve sinus mucosa
- Reduce symptoms, increase the quality of life, decrease morbidity
A.T. Peters et al. Ann Allergy Asthma Immunol 2014;113:347-385
79. SURGERY IN CHILDREN
If refractory medical management : Adenoidectomy
• Remove infection reservoir, biofilms
• < 7 years with asthma >> prefer FESS
Maxillary antral irrigation
• clear secretion & infection
• provide culture material
Balloon sinuplasty
• Benefit to irrigation
• Combination with adenoidectomy
Sarbjit S. Saini. Middleton's 8th edition
80. FUNCTIONAL ENDOSCOPIC SINUS SURGERY
(FESS)
Standard procedure
• Indication : patients resistant to medical treatment.
• Complications
-severe bleeding, orbital trauma and cerebrospinal fluid leaks
-meningitis or cerebral damage
Extensive postoperative care and follow-up
prevent recurrent nasal polyp regrowth.
Decrease morbidity of sinus surgery
Sarbjit S. Saini. Middleton's 8th edition
81. Jivianne T. Lee Atlas of Endoscopic Sinus and Skull Base Surgery, Chapter 7, 47-63
82. US CLINICAL GUIDELINES ON CHRONIC RHINOSINUSITIS IN CHILDREN
History
3 months of at least 2 of the following symptoms purulent rhinorrhea,
nasal obstruction, facial pressure/pain, or cough
Nasal Endoscopy
Nasal endoscopy :mucosal edema, purulent drainage or nasal polyps
Imaging
CT showing ostiomeatal complex or sinus edema
MRI : concern for intracranial or intraorbital complications of sinusitis
Cultures
Endoscopically guided middle meatal cultures : non responded to
empiric therapy within 72 hours, severe illness
Current Allergy and Asthma Reports (2019) 19: 14
83. US CLINICAL GUIDELINES ON CHRONIC RHINOSINUSITIS IN CHILDREN
EVIDENCE-BASED RECOMMENDATIONS FOR MANAGEMENT
Current Allergy and Asthma Reports (2019) 19: 14
Nasal saline irrigation • First line treatment option
Nasal steroid spray • First line treatment option
• limited evidence in pediatric population
Oral antibiotics • First line treatment option
• Amoxycillin, Amox/clav, Cephalosporin
• Clindamycin for suspicious of anaerobes
• 3rd gen + clindamycin
• Duration 20 days is superior to 10 days
Surgical management • Adenoidectomy +/- Functional Endoscopic
Sinus Surgery(FESS)
84.
85. COMPLICATIONS
Children and adolescents
Orbital complications
- effect ethmoid , frontal sinus
- first sign : reddish swelling medial upper eyelid (cellulitis),
subperiostial abscess, intraorbital or eyelid abscess.
Orbital phlegmona
-Immediate hospitalization : surgical care ,IV antibiotic
-Lead to a thrombosis of the cavernous sinus, intracranial
infection and complete loss of vision
86. COMPLICATIONS
Adult
Empyema frontal sinus : meningitis, an epidural or subdural brain abscess.
Osteomyelitis of frontal bone
Recurrent episodes of meningitis
Fungal disease : penetrate bony structures and the orbit,cheek, and brain.
Pyomucocele