Reduced expression of chemoattractant receptors by polymorphonuclear leukocytes in Hyper IgE Syndrome patients.

Hyper IgE Syndrome (HIES) is a rare genetic disorder, characterized by elevated serum IgE levels and reduced inflammatory responses to bacterial infections. This leads to dermatitis, recurrent lung infections and "cold abscesses". Recently, progress was made in HIES research, when mutations in STAT3 were found in the autosomal dominant form of HIES, and impaired responses of T helper 17 cells were reported. However, the causes for reduced inflammatory responses in these patients were not fully elucidated. In view of studies that indicated that polymorphonuclear leukocytes (PMN) of HIES patients are defective in their chemotactic properties, we asked if the PMN of these patients have reduced expression of receptors for chemoattractants. To analyze this possibility, we focused on fMLP and ELR(+)-CXC chemokines - which are essential for mounting acute inflammatory responses - and determined the coding sequences and expression levels of their corresponding receptors: FPR (for fMLP) as well as CXCR1 and CXCR2 (the receptors for ELR(+)-CXC chemokines). The analyses of these receptors in HIES patients indicated that their coding sequences were intact and normal. However, the percentages of PMN that expressed FPR, CXCR1 and CXCR2 were significantly lower in HIES patients. In addition, lower expression levels per cell were denoted for CXCR1 in PMN of the patients. A cumulative score that was calculated for the three chemoattractant receptors together indicated that in some of the patients there were prominent reductions, of up to approximately 50% in the overall expression of the receptors (indicated by % positive cells and mean expression levels per cell). In addition, we asked whether deregulation of PMN activities in HIES may result from binding of IgE to corresponding receptors on HIES PMN. Our findings indicate that this is probably not the case, because similarly to normal PMN, the cells of HIES patients did not express notable levels of the IgE receptors FcvarepsilonRI and FcvarepsilonRII. Together, these results provide novel information on the expression of key determinants in PMN migration in HIES, suggesting that a defect in the expression of chemoattractant receptors may lead to impaired chemotaxis found in HIES patients, and to decreased inflammatory responses.

Local corticosteroid treatment of eyelid and orbital xanthogranuloma.

PURPOSE: To demonstrate the efficacy of local corticosteroid therapy for the treatment of eyelid and orbital xanthogranuloma in adults. METHODS: The authors performed a retrospective chart review of 6 patients receiving local triamcinolone acetonide (40 mg/ml) injections for the treatment of eyelid and orbital xanthogranuloma at the University of Michigan. All patients underwent diagnostic biopsy before treatment. The effects of this therapy on symptoms and signs of the disease were assessed. RESULTS: All 6 patients had eyelid swelling or nodularity and 5 had yellow discoloration of their eyelids. All lesions involved the eyelids and anterior orbit and 5 were present bilaterally. Biopsy revealed necrobiotic xanthogranuloma in 4 patients and adult-onset xanthogranuloma in 2 patients. Triamcinolone acetonide was administered intralesionally as series of 2 to 25 injections. Local control was obtained in all 6 cases, with the reduction of symptoms and signs of the disease in 5 cases. Two patients with necrobiotic xanthogranuloma had development of non-Hodgkin lymphoma. Average follow-up of patients whose treatment was not truncated by systemic chemotherapy was 52 months (range, 30 to 86 months). No complications occurred as a result of this treatment. CONCLUSIONS: Intralesional injection of triamcinolone acetonide is an effective, safe treatment for orbital xanthogranuloma in adults. This modality avoids the side effects associated with systemic corticosteroid or cytotoxic agent therapy.

Local corticosteroid treatment of eyelid and orbital xanthogranuloma.

PURPOSE: To demonstrate the efficacy of local corticosteroid therapy for the treatment of eyelid and orbital xanthogranuloma in adults. METHODS: We performed a retrospective chart review of six patients receiving local triamcinolone acetonide (40 mg/mL) injections for the treatment of eyelid and orbital xanthogranuloma at the University of Michigan. All patients underwent diagnostic biopsy prior to treatment. The effects of this therapy on symptoms and signs of the disease were assessed. RESULTS: All six patients complained of eyelid swelling or nodularity, and five had yellow discoloration of their eyelids. All lesions involved the eyelids and anterior orbit, and five were present bilaterally. Biopsy revealed necrobiotic xanthogranuloma in four patients and adult-onset xanthogranuloma in two patients. Triamcinolone acetonide was administered intralesionally as series of two to 25 injections. Local control was obtained in all six cases, with the reduction of symptoms and signs of the disease in five cases. Two patients with necrobiotic xanthogranuloma developed non-Hodgkin's lymphoma. Average follow-up of patients whose treatment was not truncated by systemic chemotherapy was 52 months (range, 30 to 86 months). No complications occurred as a result of this treatment. CONCLUSION: Intralesional injection of triamcinolone acetonide is an effective, safe treatment for orbital xanthogranuloma in adults. This modality avoids the side effects associated with systemic corticosteroid or cytotoxic agent therapy.

Ocular manifestations of inflammatory bowel disease.

Extraintestinal manifestations of inflammatory bowel disease (IBD) occur in one third of patients. Ocular complications are infrequent, occurring in less than 10% of cases, but can be associated with significant morbidity, including blindness. Ocular complaints are often nonspecific; clinical relevance may not be appreciated by patient or physician and, thus, be misdiagnosed. Evaluation of the eye should be a routine component in the care of patients with IBD. Clinicians must be aware of the spectrum of ocular symptoms and know that these complaints may precede a diagnosis of ulcerative colitis (UC) or Crohn's disease (CD). We review ocular pathology in IBD to alert clinicians to the diverse, at times confusing, spectrum of eye disorders associated with these diseases. Clinical manifestations include blurred vision, teary, burning or itchy eyes, ocular pain, photophobia, conjunctival or scleral hyperemia, loss of visual acuity, and possible blindness. Many patients are unaware that IBD has a risk of eye complications and, therefore, patient education is vital.

Factors affecting visual outcomes after small-incision phacoemulsification in diabetic patients.

PURPOSE: To examine the factors affecting visual outcome after phacoemulsification and evaluate the use of preoperative visual potential in assessing the visual prognosis in diabetic patients. SETTING: Department of Ophthalmology, University of Texas Medical Branch, Galveston, Texas, USA. METHODS: In a retrospective chart review of 1345 consecutive patients who had uneventful small-incision phacoemulsification, operated eyes from 106 diabetic and 55 nondiabetic control patients were selected. Data on demographics, level of retinopathy, perioperative glycosylated hemoglobin (HbA(Ic)), surgical duration, preoperative best corrected visual acuity (BCVA), and visual potential were collected. RESULTS: The age, sex, preoperative BCVA, and visual potential in the diabetic and control eyes were comparable. Throughout the postoperative period, BCVA was worse of the diabetic group. At 1 year, BCVA was 20/40 in 82.1% of the diabetic group and 94.7% of the control group (P =.01). The most important factors affecting postoperative BCVA included coexisting diabetes and preoperative level of retinopathy. No correlation was found between perioperative and postoperative BCVA. Diabetic patients were less likely than control patients to achieve a BCVA better than or equal to the preoperative visual potential at 4 years (hazard ratio 0.6; 95% confidence interval, 0.4-0.9; P =.011). Patients with nonproliferative diabetic retinopathy were nearly 5 times less likely (P =.023) and patients with proliferative diabetic retinopathy 30 times less likely (P <.0001) to achieve a postoperative BCVA of 20/40 than diabetic patients without retinopathy. CONCLUSIONS: Although uneventful small-incision phacoemulsification improved visual acuity in diabetic patients, this group had an overall worse visual outcome than nondiabetic patients. The most important predictors of visual outcome were coexisting diabetes and the extent of preoperative retinopathy. Methods used to assess preoperative visual potential provided a reasonable estimate of postoperative BCVA in diabetic patients. Given the inverse association between the level of retinopathy and visual outcome, it may be better to perform cataract extraction in diabetic patients during earlier stages of retinopathy.