IgG4-related disease was only recently discovered, so its description, management, and new discov... more IgG4-related disease was only recently discovered, so its description, management, and new discoveries related to its etiology are rapidly evolving. Because IgG4 itself is a unique antibody which is intimately related to the diagnosis of the disease, the role of plasmablasts in the pathophysiology remains an active area of discussion. Recent studies have uncovered a possible role for CD4-positive cytotoxic T lymphocytes, T follicular helper cells, and M2 macrophages. The clinical presentation is variable and can be vague, as this disease affects many organs and new presentations are continuing to be described. The diagnosis depends on clinical and histopathological assessment. The mainstay of treatment is with glucocorticoids, but rituximab has recently shown promise. Monitoring disease activity using imaging modalities (including positron emission tomography) and serum markers is imperative, as relapses are common. IgG4-related disease spans many medical disciplines but is a treata...
This problem-based learning case focused on the approach to evaluation and management of a 5-year... more This problem-based learning case focused on the approach to evaluation and management of a 5-year old girl who was "always sick" with sinus infections. The discussion unfolds in a "real life" scenario, i.e., based on information available to the clinician initially and after the acquisition of laboratory data, and, ultimately, after sinus surgery. Emphasis is placed on the differential diagnosis of the patient's symptoms, discussion of the initial management strategy for chronic rhinosinusitis (CRS), evolution from acute rhinosinusitis to CRS, the prevalence of and differential diagnosis of nasal polyps in children, treatment considerations specific for CRS with nasal polyps, the significance of Pseudomonas aeruginosa sinus infection, the significance of an abnormal sweat chloride test in a young child with nasal polyposis, special considerations in children with CRS who have cystic fibrosis, treatment considerations after endoscopic sinus surgery, and, finally, prognostic factors that impact the outcomes of endoscopic sinus surgery. This problem-based learning case highlights many facets of managing refractory CRS in children.
Despite systemic sensitization, not all allergic individuals develop asthma symptoms upon airborn... more Despite systemic sensitization, not all allergic individuals develop asthma symptoms upon airborne allergen exposure. Determination of the factors that lead to the asthma phenotype in allergic individuals could guide treatment and identify novel therapeutic targets. We used segmental allergen challenge of allergic asthmatics (AA) and allergic nonasthmatic controls (AC) to determine whether there are differences in the airway immune response or airway structural cells that could drive the development of asthma. Both groups developed prominent allergic airway inflammation in response to allergen. However, asthmatic subjects had markedly higher levels of innate type 2 receptors on allergen-specific CD4(+) T cells recruited into the airway. There were also increased levels of type 2 cytokines, increased total mucin, and increased mucin MUC5AC in response to allergen in the airways of AA subjects. Furthermore, type 2 cytokine levels correlated with the mucin response in AA but not AC sub...
The inability to visualize airway smooth muscle (ASM) cells in vivo is a major obstacle in unders... more The inability to visualize airway smooth muscle (ASM) cells in vivo is a major obstacle in understanding their role in normal physiology and diseases. At present, there is no imaging modality available to assess ASM in vivo. Confocal endomicroscopy lacks the penetration depth and field of view, and conventional optical coherence tomography (OCT) does not have sufficient contrast to differentiate ASM from surrounding tissues. We have developed a birefringence microscopy platform that leverages the micro-organization of tissue to add further dimension to traditional OCT. We have used this technology to validate ASM measurements in ex vivo swine and canine studies, visualize and characterize volumetric representations of ASM in vivo, and quantify and predict ASM contractile force as a function of optical retardation. We provide in vivo images and volumetric assessments of ASM in living humans and document structural disease variations in subjects with mild asthma. The opportunity to li...
The Journal of Allergy and Clinical Immunology, Apr 30, 2008
Nasal endoscopy has been practiced by allergists since the early 1980s; however, allergists in ge... more Nasal endoscopy has been practiced by allergists since the early 1980s; however, allergists in general have not embraced endoscopic evaluation of patients with sinus disease, either before or after surgery. Allergists are in a unique position to render medical (as opposed to surgical) care of patients with sinusitis. There has been a growing realization that endoscopy is a valuable procedure for the evaluation and medical treatment of patients with difficult sinusitis. This has resulted in the need for a resource to allow allergists to understand the nature of endoscopic findings in patients with sinusitis, either preoperatively or postoperatively. This article introduces the findings at endoscopy that are common in patients with sinusitis, including those that may be seen after surgery. The findings include perforation of the septum, retained secretions, small surgical ostium caused by postoperative ostial stenosis, previous Caldwell Luc procedure, recirculation of mucus, hyperplastic nasal disease, synechiae, recurrent disease in previously unaffected sinuses, empty nose syndrome, frontal sinus disease, dental disease, and other, more complicated entities.
We present the case of a 28-year-old Caucasian female with common variable immunodeficiency (CVID... more We present the case of a 28-year-old Caucasian female with common variable immunodeficiency (CVID) since age 5 who had a long history of hospitalizations for unexplained fevers and pulmonary infiltrates. The patient developed mild lymphocytosis 7 ...
The American Journal of Surgical Pathology, May 1, 2011
Eosinophilic angiocentric fibrosis (EAF) is an uncommon tumefactive lesion of the orbit and upper... more Eosinophilic angiocentric fibrosis (EAF) is an uncommon tumefactive lesion of the orbit and upper respiratory tract of unknown etiology. The condition is characterized histologically by concentric layers of fibrosis around small-caliber arteries and a mixed inflammatory infiltrate dominated by eosinophils. After the serendipitous observation of an elevated serum concentration of IgG4 in 1 patient with EAF, we investigated the hypothesis that EAF is an IgG4-related systemic disease. We retrospectively identified 5 EAF cases from our files. Demographic, clinical, and serological data were reviewed, and the histologic features and tissue IgG4 staining patterns were examined on biopsies from each case. Patients (2 male, 3 female) ranged in age from 31 to 82 years (mean, 56 y). The extent of disease varied from isolated involvement of the nasal cavity or the lacrimal gland to multicentric disease affecting the sinuses, nasal tract, and lower respiratory tract. The duration of symptoms ranged from 6 months to >20 years. The demographic features of the patients and disease extent were consistent with previously published reports of EAF, except for involvement of the lower respiratory tract in 1 case. Four of the 5 cases showed concentric perivascular fibrosis surrounding small-caliber vascular channels, embedded in an inflammatory infiltrate composed of lymphocytes, plasma cells, and eosinophils. One lacrimal gland biopsy showed a periductal inflammatory infiltrate, and 2 cases showed a storiform pattern of fibrosis. The index case had a serum IgG4 concentration of 1490 mg/dL (normal, 8 to 140 mg/dL). IgG4-positive plasma cells were identified in biopsies from 4 of the 5 cases. The numbers of IgG4-positive plasma cells ranged from 43 to 118 per high-power field, and the IgG4:IgG ratios ranged from 0.68 to 0.97. Neither IgG4-bearing nor IgG-bearing plasma cells were identified in 1 patient, whose longstanding disease was characterized principally by concentric perivascular fibrosis. Our data suggest that EAF is part of the spectrum of IgG4-related systemic disease.
IgG4-related disease was only recently discovered, so its description, management, and new discov... more IgG4-related disease was only recently discovered, so its description, management, and new discoveries related to its etiology are rapidly evolving. Because IgG4 itself is a unique antibody which is intimately related to the diagnosis of the disease, the role of plasmablasts in the pathophysiology remains an active area of discussion. Recent studies have uncovered a possible role for CD4-positive cytotoxic T lymphocytes, T follicular helper cells, and M2 macrophages. The clinical presentation is variable and can be vague, as this disease affects many organs and new presentations are continuing to be described. The diagnosis depends on clinical and histopathological assessment. The mainstay of treatment is with glucocorticoids, but rituximab has recently shown promise. Monitoring disease activity using imaging modalities (including positron emission tomography) and serum markers is imperative, as relapses are common. IgG4-related disease spans many medical disciplines but is a treata...
This problem-based learning case focused on the approach to evaluation and management of a 5-year... more This problem-based learning case focused on the approach to evaluation and management of a 5-year old girl who was "always sick" with sinus infections. The discussion unfolds in a "real life" scenario, i.e., based on information available to the clinician initially and after the acquisition of laboratory data, and, ultimately, after sinus surgery. Emphasis is placed on the differential diagnosis of the patient's symptoms, discussion of the initial management strategy for chronic rhinosinusitis (CRS), evolution from acute rhinosinusitis to CRS, the prevalence of and differential diagnosis of nasal polyps in children, treatment considerations specific for CRS with nasal polyps, the significance of Pseudomonas aeruginosa sinus infection, the significance of an abnormal sweat chloride test in a young child with nasal polyposis, special considerations in children with CRS who have cystic fibrosis, treatment considerations after endoscopic sinus surgery, and, finally, prognostic factors that impact the outcomes of endoscopic sinus surgery. This problem-based learning case highlights many facets of managing refractory CRS in children.
Despite systemic sensitization, not all allergic individuals develop asthma symptoms upon airborn... more Despite systemic sensitization, not all allergic individuals develop asthma symptoms upon airborne allergen exposure. Determination of the factors that lead to the asthma phenotype in allergic individuals could guide treatment and identify novel therapeutic targets. We used segmental allergen challenge of allergic asthmatics (AA) and allergic nonasthmatic controls (AC) to determine whether there are differences in the airway immune response or airway structural cells that could drive the development of asthma. Both groups developed prominent allergic airway inflammation in response to allergen. However, asthmatic subjects had markedly higher levels of innate type 2 receptors on allergen-specific CD4(+) T cells recruited into the airway. There were also increased levels of type 2 cytokines, increased total mucin, and increased mucin MUC5AC in response to allergen in the airways of AA subjects. Furthermore, type 2 cytokine levels correlated with the mucin response in AA but not AC sub...
The inability to visualize airway smooth muscle (ASM) cells in vivo is a major obstacle in unders... more The inability to visualize airway smooth muscle (ASM) cells in vivo is a major obstacle in understanding their role in normal physiology and diseases. At present, there is no imaging modality available to assess ASM in vivo. Confocal endomicroscopy lacks the penetration depth and field of view, and conventional optical coherence tomography (OCT) does not have sufficient contrast to differentiate ASM from surrounding tissues. We have developed a birefringence microscopy platform that leverages the micro-organization of tissue to add further dimension to traditional OCT. We have used this technology to validate ASM measurements in ex vivo swine and canine studies, visualize and characterize volumetric representations of ASM in vivo, and quantify and predict ASM contractile force as a function of optical retardation. We provide in vivo images and volumetric assessments of ASM in living humans and document structural disease variations in subjects with mild asthma. The opportunity to li...
The Journal of Allergy and Clinical Immunology, Apr 30, 2008
Nasal endoscopy has been practiced by allergists since the early 1980s; however, allergists in ge... more Nasal endoscopy has been practiced by allergists since the early 1980s; however, allergists in general have not embraced endoscopic evaluation of patients with sinus disease, either before or after surgery. Allergists are in a unique position to render medical (as opposed to surgical) care of patients with sinusitis. There has been a growing realization that endoscopy is a valuable procedure for the evaluation and medical treatment of patients with difficult sinusitis. This has resulted in the need for a resource to allow allergists to understand the nature of endoscopic findings in patients with sinusitis, either preoperatively or postoperatively. This article introduces the findings at endoscopy that are common in patients with sinusitis, including those that may be seen after surgery. The findings include perforation of the septum, retained secretions, small surgical ostium caused by postoperative ostial stenosis, previous Caldwell Luc procedure, recirculation of mucus, hyperplastic nasal disease, synechiae, recurrent disease in previously unaffected sinuses, empty nose syndrome, frontal sinus disease, dental disease, and other, more complicated entities.
We present the case of a 28-year-old Caucasian female with common variable immunodeficiency (CVID... more We present the case of a 28-year-old Caucasian female with common variable immunodeficiency (CVID) since age 5 who had a long history of hospitalizations for unexplained fevers and pulmonary infiltrates. The patient developed mild lymphocytosis 7 ...
The American Journal of Surgical Pathology, May 1, 2011
Eosinophilic angiocentric fibrosis (EAF) is an uncommon tumefactive lesion of the orbit and upper... more Eosinophilic angiocentric fibrosis (EAF) is an uncommon tumefactive lesion of the orbit and upper respiratory tract of unknown etiology. The condition is characterized histologically by concentric layers of fibrosis around small-caliber arteries and a mixed inflammatory infiltrate dominated by eosinophils. After the serendipitous observation of an elevated serum concentration of IgG4 in 1 patient with EAF, we investigated the hypothesis that EAF is an IgG4-related systemic disease. We retrospectively identified 5 EAF cases from our files. Demographic, clinical, and serological data were reviewed, and the histologic features and tissue IgG4 staining patterns were examined on biopsies from each case. Patients (2 male, 3 female) ranged in age from 31 to 82 years (mean, 56 y). The extent of disease varied from isolated involvement of the nasal cavity or the lacrimal gland to multicentric disease affecting the sinuses, nasal tract, and lower respiratory tract. The duration of symptoms ranged from 6 months to >20 years. The demographic features of the patients and disease extent were consistent with previously published reports of EAF, except for involvement of the lower respiratory tract in 1 case. Four of the 5 cases showed concentric perivascular fibrosis surrounding small-caliber vascular channels, embedded in an inflammatory infiltrate composed of lymphocytes, plasma cells, and eosinophils. One lacrimal gland biopsy showed a periductal inflammatory infiltrate, and 2 cases showed a storiform pattern of fibrosis. The index case had a serum IgG4 concentration of 1490 mg/dL (normal, 8 to 140 mg/dL). IgG4-positive plasma cells were identified in biopsies from 4 of the 5 cases. The numbers of IgG4-positive plasma cells ranged from 43 to 118 per high-power field, and the IgG4:IgG ratios ranged from 0.68 to 0.97. Neither IgG4-bearing nor IgG-bearing plasma cells were identified in 1 patient, whose longstanding disease was characterized principally by concentric perivascular fibrosis. Our data suggest that EAF is part of the spectrum of IgG4-related systemic disease.
Uploads
Papers by Daniel Hamilos