Clinical implications of mast cell involvement in allergic conjunctivitis.

The conjunctiva is a common site for the allergic inflammatory response due to it being highly vascularized, having constant exposure to environmental pollutants and allergenic pollens and having a unique conjunctival associated lymphoid tissue. The primary morbidity of anterior surface conjunctival disorders that include allergic conjunctivitis and tear film disorders is associated with its high frequency of involvement rather than its severity, although the more chronic forms can involve the cornea and lead to sight-threatening conditions. Ocular allergy is associated with IgE-mediated mast cell activation in conjunctival tissue leading to the release of preformed mediators including histamine and proteases and subsequent de novo formation of lipid-derived mediators and cytokines that trigger a cascade of cellular and molecular events leading to extensive migration and infiltration of inflammatory cells to the ocular surface. The trafficking of neutrophils, eosinophils, and lymphocytes to the ocular surface is due to establishing various chemokine gradients (mainly CCL11, CCL24, CCL5, MCP-3, and MCP-4), cell surface expression of adhesion molecules (such as VCAM-1 the ligand for VLA-4), and leukocyte adhesion to vascular endothelium. The release of preformed mediators underlies the acute ocular surface response while the secondary influx of inflammatory cells leading to the recruitment and activation of eosinophils and the subsequent activation of Th2 and Th1 lymphocytes at the level of the conjunctiva reflects the late-phase reaction.

Complementary and alternative therapy (CAM) in the treatment of allergic rhinitis.

CAM is any therapeutic intervention that exists outside traditional allopathic medicine. The utilization in the US population is increasing up to 4 out of 10 patients in some surveys. Given this increasing prevalence, it is essential that clinicians have the resources to advise their patients in the utilizations, benefits, and potential harms of these alternative therapies. Recent literature was reviewed in regard to traditional Chinese medicine [TCM], acupuncture, homeopathy, and herbal therapy in the treatment of allergic rhinitis limited to randomized controlled trials. Several complementary treatment studies demonstrated statistically significant benefits to patients' quality of life and symptom scoring without providing duration of effect. Alternative therapy studies have revealed mixed results in regard to efficacy. Although the adverse effect profile is low, additional studies will be required to further promote integration into the standard of care for the routine treatment of allergic rhinitis.

Impact of mometasone furoate nasal spray on individual ocular symptoms of allergic rhinitis: a meta-analysis.

BACKGROUND: Intranasal corticosteroids (INSs) are a mainstay of treatment of allergic rhinitis (AR) nasal symptoms. The INS mometasone furoate nasal spray (MFNS) has well-documented efficacy and safety for the treatment and prophylaxis of nasal symptoms of seasonal AR (SAR) and for the treatment of nasal symptoms of perennial AR (PAR). Increasing interest has focused on whether INSs, including MFNS, may have beneficial effects on the ocular symptoms frequently associated with AR. METHODS: We performed a meta-analysis of 10 randomized, placebo-controlled trials of the efficacy of MFNS 200 mcg daily in relieving ocular allergy symptoms, including itching/burning, redness, and tearing/watering in both SAR and PAR. Four PAR studies and six SAR studies are included in the analysis. A fixed-effect inverse variance model was used to calculate weighted mean differences, 95% confidence intervals (CIs) for each comparison, and a combined overall treatment effect (Z) with P-value. RESULTS: In both analyses of SAR and PAR studies, including 3132 patients, all individual ocular symptoms were reduced in patients treated with MFNS. Overall treatment effect was significant for all three individual ocular symptoms in the SAR studies (Z = 9.18 for tearing, Z = 10.15 for itching, and Z = 8.88 for redness; P < 0.00001 for all) and in the PAR studies (Z = 5.94, P < 0.00001 for tearing; Z = 2.43, P = 0.02 for itching; and Z = 2.42, P = 0.02 for redness). CONCLUSIONS: Our findings add to the growing body of literature supporting the positive class effect of INSs, including MFNS, on ocular symptoms associated with SAR and PAR.

Clinical characteristics, diagnostic criteria and therapeutic outcomes in autoimmune optic neuropathy.

BACKGROUND/AIMS: Autoimmune optic neuropathy (AON) is characterised by chronically progressive or recurrent visual loss associated with serological or cutaneous evidence of autoimmunity, without a defined systemic autoimmune illness. It may improve with large doses of corticosteroids alone, or in combination with immunosuppressive agents. The aim was to determine the relative effectiveness of various therapeutic regimens in AON. METHODS: All patients in this study fulfilled these criteria: (1) multiple attacks in one eye or attacks in both eyes (at least three total attacks); (2) a minimum of 12 months of neuro-ophthalmic follow-up; (3) serological abnormalities or skin biopsy changes consistent with AON; (4) no diagnosis of a defined collagen vascular disease or neurological autoimmune disease throughout follow-up, with the exception of one patient, later shown to be shown to be neuromyelitis optic antibody positive. RESULTS: Nine cases were found (female = 7, male = 2, ages 8-74). One case received corticosteroids alone, the others received corticosteroids in combination with methotrexate/gammaglobulin (n = 1), methotrexate (n = 1), gammaglobulin (n = 1), chlorambucil (n = 2), cyclophosphamide (n = 1) and azathioprine/chlorambucil (n = 1), and one received multiple combinations of agents. Criteria for diagnosis are proposed. CONCLUSION: As AON is quite rare, no formal recommendation can be made regarding its best therapy, although there is a suggestion that chlorambucil, although potentially toxic, may yield long-term remission.

Diagnosis and management of adult onset Still's disease.

BACKGROUND: Adult onset Still's disease (AOSD) is a rare systemic inflammatory disorder of unknown aetiology that is responsible for a significant proportion of cases of fever of unknown origin and can also have serious musculoskeletal sequelae. OBJECTIVE: To assess and synthesise the evidence for optimal diagnosis and management of AOSD. METHODS: The key terms, adult onset Still's disease, AOSD, adult Still's disease, ASD, Still's disease were used to search Medline (1966-2005) and PubMed (1966-2005) for all available articles in the English language. Clinically relevant articles were subsequently selected. Bibliographies, textbooks, and websites of recent rheumatology conferences were also assessed. RESULTS: Data on diagnosis and treatment of AOSD are limited in the medical literature and consist mainly of case reports, small series, and modest scale retrospective studies. Diagnosis is clinical and requires exclusion of infectious, neoplastic, and other autoimmune diseases. Laboratory tests are non-specific and reflect heightened immunological activity. Treatment comprises non-steroidal anti-inflammatory drugs, corticosteroids, immunosuppressive drugs (methotrexate, leflunomide, gold, azathioprine, cyclosporin A, cyclophosphamide), and intravenous gammaglobulin. The recent successful application of biological agents (anti-tumour necrosis factor, anti-interleukin (IL)1, anti-IL6), often in combination with traditional immunosuppressive drugs, has been very promising. CONCLUSIONS: AOSD often poses a diagnostic and therapeutic challenge and clinical guidelines are lacking. The emergence of validated diagnostic criteria, discovery of better serological markers, and the application of new biological agents may all provide the clinician with significant tools for the diagnosis and management of this complex systemic disorder.

Animal models of allergic and inflammatory conjunctivitis.

Allergic eye diseases are complex inflammatory conditions of the conjunctiva with an increasing prevalence and incidence. The diseases are often concomitant with other allergic diseases such as allergic rhinitis, atopic dermatitis and allergic asthma. Despite the disabling and prominent symptoms of ocular allergies, they are less well studied and further insights into the molecular basics are still required. To establish new therapeutic approaches and assess immunological mechanisms, animal models of ocular allergies have been developed in the past years. The major forms of allergic ocular diseases, seasonal and perennial allergic conjunctivitis, vernal and atopic keratoconjunctivitis and giant papillary conjunctivitis, each have different pathophysiological and immunological components. In contrast to these distinct entities, the current animal models are based on the sensitization against a small number of allergens such as ovalbumin, ragweed pollen or major cat allergens and consecutive challenge. Different animal species have been used so far. Starting with guinea-pig models of allergic conjunctivitis to assess pharmacological aspects, new models including rats and mice have been developed which mimic major features of ocular allergy. The presently preferred species for the investigation of the immunological basis of the disease is represented by murine models of allergic conjunctivitis. In the future, combined ocular, nasal and aerosolic challenges with allergens may provide a model of allergy that encompasses simultaneously the target organs eye, nose and airways with conjunctivitis, rhinitis and asthma.

The perception of dyspnea in patients with mild asthma.

BACKGROUND: Airway function, as assessed by standard spirometry, and the intensity of dyspnea reported by asthmatic patients correlate poorly. OBJECTIVE: This study tests the following two hypotheses: (1) that measures of the tendency of a patient to somatize will reduce the variation in the report of dyspnea not explained by airway function; and (2) that plethysmography is a better tool with which to estimate the degree of dyspnea associated with asthma. DESIGN: A prospective laboratory study carried out over one study session. PARTICIPANTS: Forty asthmatic subjects who had withheld bronchodilator (BD) therapy overnight. INTERVENTIONS: We performed spirometry, plethysmography, and an assessment of dyspnea (ie, modified Borg scale) on all subjects before and after they received BD therapy. Standard questionnaires pertaining to psychological state and trait were administered as well. RESULTS: The change in specific airway conductance with BD therapy correlated with a decline in the Borg score (r = 0.47; p = 0.007). By contrast, neither spirographic measures nor measures of static lung volumes correlated. Correlation with the Borg scale score was not improved by adding indexes of either somatization or psychological state or trait. CONCLUSION: The relief of dyspnea reported by patients with mild asthma after BD therapy is related to dilatation of the central airways.

Neuro-ophthalmic manifestations of sarcoidosis: clinical spectrum, evaluation, and management.

OBJECTIVE: To familiarize the reader with the neuro-ophthalmic manifestations of sarcoidosis. MATERIALS AND METHODS: All patients underwent systemic evaluations (chest radiograph, magnetic resonance imaging and/or computed tomography, serum angiotensin-converting enzyme level, and gallium scan). Histologic confirmation was preferred (11 of 15 patients underwent biopsy, ten of whom [82%] had positive biopsies, and four refused). Otherwise, the diagnosis of clinical sarcoidosis was based on laboratory evaluation. RESULTS: We report our experience with 15 patients who had neuro-ophthalmic manifestations of sarcoidosis other than optic neuropathy or chiasmal disease. Eight of 15 (53%) did not have known sarcoidosis at the time of presentation. Thirteen of 15 (87%) patients demonstrated lesions consistent with sarcoidosis on magnetic resonance imaging of the brain. Treatment with corticosteroids and/or other immunomodulatory agents was necessary in all cases. CONCLUSIONS: Neuro-ophthalmic manifestations of sarcoidosis are rare. They may be the presenting signs of otherwise occult disease. Suspicion and inclusion in the differential are a key to establishing the diagnosis. A strategy for the detection and evaluation of these cases is presented.

The effects of stress, anxiety, and outdoor temperature on the frequency and severity of Raynaud's attacks: the Raynaud's Treatment Study.

It was expected that stress and anxiety would be related to Raynaud's phenomenon (RP) attack characteristics when mild outdoor temperatures produced partial or no digital vasoconstriction. Hypotheses were that in warmer temperature categories, compared to those below 40 degrees F, higher stress or anxiety would be associated with more frequent, severe, and painful attacks. The Raynaud's Treatment Study recruited 313 participants with primary RP. Outcomes were attack rate, severity, and pain. Predictors were average daily outdoor temperature, stress, anxiety, age, gender, and a stress-by-temperature or an anxiety-by-temperature interaction. Outcomes were tested separately in multiple linear regression models. Stress and anxiety were tested in separate models. Stress was not a significant predictor of RP attack characteristics. Higher anxiety was related to more frequent attacks above 60 degrees F. It was also related to greater attack severity at all temperatures, and to greater pain above 60 degrees F and between 40 degrees and 49.9 degrees F.

Asthma outcome changes associated with use of the leukotriene-receptor antagonist zafirlukast.

A new class of asthma drugs modifying the leukotriene pathway was introduced in 1996. The authors investigated outcome changes associated with use of the leukotriene-receptor antagonist zafirlukast. The study group included patients with asthma (12-64 yr), most with mild-to-moderate, persistent asthma, who had at least two zafirlukast prescriptions within 90 days after the start of zafirlukast treatment. Zafirlukast treatment was associated with reductions in occurrence of outpatient visits, emergency department visits, inpatient stays, and prescriptions for short-acting beta-adrenergic agonists in the next six months (all P < .05). A 12-month pre- and post-zafirlukast treatment comparison in a smaller group of patients and a classification of patients into three mutually exclusive outcome groups (increase, decrease, or no change in outcome events) verified the majority of the findings. A cost analysis from a third-party perspective indicated that costs of zafirlukast treatment were more than offset by cost savings associated with the reductions in outcome events.

Complementary medicine for the allergist.

The objective of this article is to provide a historical overview of the present state of complementary and alternative medicine (CAM) in the treatment of atopic disorders. The evolution of medicine in the United States has been in flux with the advent of newer technologies, new designs in managed care, and integrating the cultural differences into a complex multidisciplinary health care delivery process. There have been several herbal modalities that contain various anti-allergy and asthma components with effects on bronchodilation, congestion, pulmonary function tests, and antagonism of asthma mediators such as histamine and PAF, corticosteroid levels, and clearance of mucus. In the field of allergy, asthma, and immunology, the popularity of CAM is more widespread than other common chronic medical problems. Overall, CAM use has created a $15-billion-a-year industry in dietary supplements alone. This has been especially fueled by the deregulation of the "herbal" industry by the congressional passage of the Dietary Supplement Health and Education Act of 1994. It would appear that our specialty would clearly benefit from expanding its knowledge base about these entities because "allergies" are high on the list of patients seeking CAM. This will prepare us to better coordinate the future possibilities and to "doctor" (i.e., teach) our patients about the risks and benefits of these modalities.

Therapeutic targets in allergic eye disease.

The objective of this article is to provide an overview of the present state of treatment of ocular allergy. Immuno-ophthalmology arose in the portion of this past century when investigators uncovered the uniqueness of the lens proteins and that it could induce an immunological response otherwise know as phacoanaphylaxis. Further studies have shown many similarities between the eye and other organ systems, but one of the most profound problems was the spring "catarrh" that involved the eyes and nose, i.e., rhinoconjunctivitis. Treatment over the past 10 years has expanded with the better understanding of the allergic response at the conjunctival surface. Allergen immunotherapy remains a cornerstone of treatment. In fact, the very first report of the use of immunotherapy in 1911 "measured the patient's resistance during experiments ... of pollen extracts to excite a conjunctival reaction" (Noon L, and Cantar BO, Lancet 1572-1573, 1911).

Allergic and immunologic disorders of the eye. Part II: ocular allergy.

Allergy affects more than 15% of the world population, and some studies have shown that up 30% of the US population has some form of allergy. Most of these patients have various target organs for their allergies, and most have ocular involvement. The ocular component may be the most prominent and sometimes disabling feature of their allergy. Some are affected for only a few weeks to months, whereas others have symptoms that last throughout the year. The seasonal forms may present to clinical allergists, whereas the more chronic forms may present to ophthalmologists. Thus, in the second of this 2-part review series (Part I: Ocular Immunology appeared in the November issue of the Journal), an overview is provided of the spectrum of ocular allergy that ranges from acute seasonal allergic conjunctivitis to chronic variants of atopic keratoconjunctivitis. With a better understanding of the immunologic mechanisms, we now can develop better treatment approaches and design further research in intervention of allergic eye diseases.

Allergic and immunologic disorders of the eye. Part I: immunology of the eye.

Immuno-ophthalmology evolved during the 20th century as a subspecialty linking ophthalmologists and immunologists. This emerging subspecialty has focused on the use of immunology to better understand and treat ocular disorders. To help the allergist/clinical immunologist better appreciate the growing field of immuno-ophthalmology, this 2-part review series (Part II: Ocular Allergy will appear in the December issue of the Journal) will provide an overview of the impact that immunology has had on our understanding and treatment of allergic and immunologic eye diseases. The current review will focus on mechanisms by which mast cells, T cells, eosinophils, cytokines, and other inflammatory constituents contribute to the unique features of eye disease and their link to allergic responses that occur in other organs of the body.