Chapter 5: Allergic rhinitis.

Rhinitis is a symptomatic inflammatory disorder of the nose with different causes such as allergic, nonallergic, infectious, hormonal, drug induced, and occupational and from conditions such as sarcoidosis and necrotizing antineutrophil cytoplasmic antibodies positive (Wegener's) granulomatosis. Allergic rhinitis affects up to 40% of the population and results in nasal (ocular, soft palate, and inner ear) itching, congestion, sneezing, and clear rhinorrhea. Allergic rhinitis causes extranasal untoward effects including decreased quality of life, decreased sleep quality, obstructive sleep apnea, absenteeism from work and school, and impaired performance at work and school termed "presenteeism." The nasal mucosa is extremely vascular and changes in blood supply can lead to obstruction. Parasympathetic stimulation promotes an increase in nasal cavity resistance and nasal gland secretion. Sympathetic stimulation leads to vasoconstriction and consequent decrease in nasal cavity resistance. The nasal mucosa also contains noradrenergic noncholinergic system, but the contribution to clinical symptoms of neuropeptides such as substance P remains unclear. Management of allergic rhinitis combines allergen avoidance measures with pharmacotherapy, allergen immunotherapy, and education. Medications used for the treatment of allergic rhinitis can be administered intranasally or orally and include oral and intranasal H(1)-receptor antagonists (antihistamines), intranasal and systemic corticosteroids, intranasal anticholinergic agents, and leukotriene receptor antagonists. For intermittent mild allergic rhinitis, an oral or intranasal antihistamine is recommended. In individuals with persistent moderate/severe allergic rhinitis, an intranasal corticosteroid is preferred. When used in combination, an intranasal H(1)-receptor antagonist and a nasal steroid provide greater symptomatic relief than monotherapy. Allergen immunotherapy is the only disease-modifying intervention available.

Chapter 27: Approach to primary immunodeficiency.

Primary immunodeficiency diseases (PID) are inherited defects of the innate or adaptive arms of the immune system that lead to an increase in the incidence, frequency, or severity of infections. There may be defects in the adaptive arm of the immune system that include combined immunodeficiency and antibody deficiency syndromes or by abnormalities in innate immunity such as disorders of phagocytes, the complement pathway, or Toll-Like receptor (TLR) mediated signaling. Recurrent sinopulmonary infections with encapsulated bacteria such as Haemophilus influenza type B or Streptococcus pneumoniae may be characteristic of an IgG antibody deficiency or dysfunction. Frequent viral, fungal, or protozoal infections may suggest T lymphocyte dysfunction. Multiple staphylococcal skin infections and fungal infections may imply neutrophil dysfunction or the hyper-IgE syndrome, and recurrent neisserial infection is a characteristic manifestation of late complement component (C5-9, or the membrane attack complex) defects. Recurrent viral or pyogenic bacterial infections often without the presence of a significant inflammatory response suggest a defect in TLR signaling. Mycobacterial infections are characteristic of defects in interleukin (IL)-12, interferon (IFN) gamma, or their receptors. Screening of newborns for T-cell lymphopenia using a polymerase chain reaction to amplify T-cell receptor excision circles (TRECs), which are formed when a T cell rearranges the variable region of its receptor, serves as a surrogate for newly synthesized naïve T cells. Because of very low numbers of TRECs, severe combined immunodeficiency, DiGeorge syndrome, and other causes of T-cell lymphopenia have been identified in newborns.

Chapter 28: Classification of hypersensitivity reactions.

The original Gell and Coomb's classification categorizes hypersensitivity reactions into four subtypes according to the type of immune response and the effector mechanism responsible for cell and tissue injury: type I, immediate or IgE mediated; type II, cytotoxic or IgG/IgM mediated; type III, IgG/IgM immune complex mediated; and type IV, delayed-type hypersensitivity or T-cell mediated. The classification has been improved so that type IIa is the former type II and type IIb is antibody-mediated cell stimulating (Graves Disease and the "autoimmune" type of chronic idiopathic urticaria). Type IV has four major categories: type IVa is CD4(+)Th1 lymphocyte mediated with activation of macrophages (granuloma formation and type I diabetes mellitus); type IVb is CD4(+)Th2 lymphocyte mediated with eosinophilic involvement (persistent asthma and allergic rhinitis); type IVc is cytotoxic CD8(+) T lymphocyte with involvement of perforin-granzme B in apoptosis (Stevens-Johnson syndrome and toxic epidermal necrolysis); type IVd is T-lymphocyte-driven neutrophilic inflammation (pustular psoriasis and acute generalized exanthematous pustulosis). Some diseases have multiple types of immunologic hypersensitivity.

Increased expression of the chemokine CCL23 in eosinophilic chronic rhinosinusitis with nasal polyps.

BACKGROUND: Chronic rhinosinusitis (CRS) is a heterogeneous chronic disease characterized by local inflammation of the sinonasal tissues. The pathogenesis of CRS remains controversial, but it has been associated with the accumulation of various immune and inflammatory cells in sinus tissue. OBJECTIVES: The objective of this study was to investigate the expression of the chemokine CCL23, which is known to bind to CCR1 and recruit monocytes, macrophages, and dendritic cells, in patients with CRS. METHODS: We collected nasal tissue from patients with CRS and control subjects. We assayed mRNA for CCL23 by using real-time PCR and measured CCL23 protein by means of ELISA, immunohistochemistry, and immunofluorescence. RESULTS: CCL23 mRNA levels were significantly increased in nasal polyps (NPs) from patients with CRS with nasal polyps (CRSwNP; P < .05) compared with inferior turbinate and uncinate tissue from patients with CRS or control subjects. CCL23 protein levels were also increased in NPs, although these levels were not statistically significant. Immunohistochemical analysis revealed CCL23 expression in mucosal epithelial cells and inflammatory cells, but accumulation of CCL23(+) inflammatory cells occurred only in NPs. Immunofluorescence data showed CCL23 colocalization with eosinophil cationic protein-positive eosinophils. The concentration of CCL23 in NPs positively correlated with the concentration of eosinophil cationic protein, suggesting that eosinophils are major CCL23-producing cells in NPs. Finally, we found that CCL23 protein levels were significantly increased in NPs from patients with CRSwNP with aspirin sensitivity. CONCLUSION: Overproduction of CCL23 in NPs might contribute to the pathogenesis of eosinophilic CRSwNP through the recruitment of CCR1(+) inflammatory cells, including monocytes and macrophages, and the amplification of local inflammation.

Impulse oscillometry in the evaluation of diseases of the airways in children.

OBJECTIVE: To provide an overview of impulse oscillometry and its application to the evaluation of children with diseases of the airways. DATA SOURCES: Medline and PubMed search, limited to English language and human disease, with keywords forced oscillation, impulse oscillometry, and asthma. STUDY SELECTIONS: The opinions of the authors were used to select studies for inclusion in this review. RESULTS: Impulse oscillometry is a noninvasive and rapid technique requiring only passive cooperation by the patient. Pressure oscillations are applied at the mouth to measure pulmonary resistance and reactance. It is employed by health care professionals to help diagnose pediatric pulmonary diseases such asthma and cystic fibrosis; assess therapeutic responses; and measure airway resistance during provocation testing. CONCLUSIONS: Impulse oscillometry provides a rapid, noninvasive measure of airway impedance. It may be easily employed in the diagnosis and management of diseases of the airways in children.

Pediatric-onset mastocytosis: a long term clinical follow-up and correlation with bone marrow histopathology.

BACKGROUND: Pediatric onset mastocytosis usually presents as urticaria pigmentosa; and less often as diffuse cutaneous mastocytosis. While the literature indicates that disease often resolves, there has been a move to more aggressive therapy for mastocytosis early in life. We addressed the long term prognosis of pediatric-onset disease by examining 17 children with mastocytosis which we had reported on in 1989 [1]. PROCEDURE: We successfully contacted 15 of these patients and data was collected regarding their clinical status. Original bone marrow specimens were re-stained, re-examined, and correlated with disease outcome using consensus criteria. Three of five patients with persistent disease underwent repeat bone marrow biopsies. RESULTS: There was complete regression of disease as defined by cutaneous findings and symptoms (clinical disease severity) in 10 of 15 patients (67%). Three patients had major (20%) and two had partial regression of disease (13%). Repeat marrow examinations on three patients with persistent disease documented systemic mastocytosis based on marrow findings in one patient who had partial regression of disease and was the only patient with initial morphologic evidence of systemic disease. Of the remaining two patients, one demonstrated partial regression and the other major regression of disease; and neither had evidence of systemic mastocytosis. CONCLUSION: This study demonstrates that initial bone marrow biopsies were prognostic in that those without evidence of systemic disease experienced disease regression; and that the long term prognosis for children managed symptomatically with mastocytosis is highly encouraging.

Pediatric mastocytosis: routine anesthetic management for a complex disease.

BACKGROUND: Pediatric mastocytosis consists of a spectrum of clinical variants characterized by increased numbers of resident mast cells in various organ systems. Mast cells are instrumental in mediating anaphylaxis and patients with mastocytosis are at risk to develop provoked and unprovoked episodes of anaphylaxis. METHODS: We examined perianesthetic records of patients with pediatric mastocytosis who were anesthetized for diagnostic and surgical procedures from 1993 to 2006. In addition, we conducted a literature review of the anesthetic experience in pediatric mastocytosis. RESULTS: Twenty-two patients with pediatric mastocytosis, with a median age of 3.2 yr (range, 6 mo-20 yr) at the time of the procedure, were anesthetized for 29 diagnostic and surgical procedures. All variants of the disease are represented in this series. Most patients had a history of flushing, pruritus, gastro-esophageal reflux diseases, and abdominal pain; one patient had a history of spontaneous anaphylaxis. Routine anesthetic techniques were used and, despite the complexity of the disease, the perioperative courses were uncomplicated and without serious adverse events. CONCLUSIONS: We reviewed the main features of pediatric mastocytosis, its anesthetic and perioperative implications, and describe a practical approach to the anesthetic management of pediatric patients with the disease. Although many drugs used routinely in anesthesia reportedly caused mast cell degranulation, deviations from routine anesthesia techniques are not necessarily warranted. However, an understanding of the anesthetic implications of the disease and meticulous preparation to treat possible adverse events are advised.

Acoustic rhinometry in the practice of allergy.

OBJECTIVE: To provide a comprehensive practical overview of the use of acoustic rhinometry in the practice of allergy. DATA SOURCES: An all-inclusive PubMed search was conducted for articles on acoustic rhinometry that were published in peer-reviewed journals, between 1989 and 2006, using the keywords acoustic rhinometry, allergic rhinitis, and nasal provocation testing. STUDY SELECTION: The expert opinion of the authors was used to select studies for inclusion in this review. RESULTS: Acoustic rhinometry is a sound-based technique used to measure nasal cavity area and volume. It has been validated by comparison to measurements with computed tomography and magnetic resonance imaging. Acoustic rhinometry requires minimal patient cooperation and may be used in adults, children, and infants. It is used by medical practitioners to diagnose and evaluate therapeutic responses in conditions such as rhinitis and to measure nasal dimensions during allergen provocation testing. Acoustic rhinometry also provides a visual reflection of the nasal response to therapy, which may be useful in increasing compliance to prescribed medications. CONCLUSIONS: Acoustic rhinometry is a safe, noninvasive, objective, and validated measure of nasal obstruction that appears to be of practical use in the diagnosis and management of inflammatory diseases of the upper airways.