Chronic pruritic dermatitis and peripheral eosinophilia in a 42-year-old man.

Chronic pruritic dermatitis with or without accompanying peripheral eosinophilia can be caused by a vast array of underlying disorders broadly classified as allergic/immunologic, infectious, or neoplastic. An organized and thorough work up is crucial in order to arrive at a definitive diagnosis enabling appropriate treatment. We present the case of a 42-year-old man with a history of chronic pruritic dermatitis and peripheral eosinophilia in a patient-oriented, problem-solving format including the clinical presentation, physical findings, results of pertinent lab/radiologic studies, differential diagnosis, and final diagnosis with discussion.

Eosinophilic esophagitis: review of nonsurgical treatment modalities.

Eosinophilic esophagitis (EoE) is a clinicopathological condition characterized by the combination of upper gastrointestinal symptoms such as dysphagia and even food impaction in association with histological findings of >15 eosinophils/high-powered field found in endoscopic biopsy specimens. EoE is considered an atopic disease with food and aeroallergen sensitivity. Current treatment options include elemental and elimination diets and topical corticosteroids. This study was designed to provide a review of the literature on the nonsurgical treatment modalities for EoE to understand the therapeutic challenges. A Medline and PubMed search was conducted using the key words eosinophilic esophagitis and treatment. EoE guidelines, randomized controlled trials, case studies, and evidence-based treatment articles in the English literature were selected. EoE patients can have symptomatic and pathological resolutions with dietary modifications and topical swallowed corticosteroids with continued therapy. However, these effects are not long-lasting and adverse reactions, both local and systemic, are possible. Newer targeted therapies using monoclonal antibodies against interleukin-5 (IL-5) appear to be well tolerated but various studies have not consistently shown symptomatic or histological improvement. Current therapies for EoE including specific diets and topical corticosteroids have shown only short-term symptomatic relief. Biological therapies such as anti-IL-5 agents are still under investigation. Long-term effects of treatments are not known and studies regarding safety of these therapies and specific dosing regimens are needed. Therapies targeting the molecules involved in the pathogenesis of EoE may be future options. Treatment should be individualized with careful consideration of patient's age, allergen sensitivity, lifestyle, and compliance.

Increased stress-induced generation of reactive oxygen species and apoptosis in human keratoconus fibroblasts.

PURPOSE: To determine whether keratoconus (KC) corneal fibroblast cultures have increased reactive oxygen species (ROS) production and are more susceptible to stress-related challenges. METHODS: Normal (n = 9) and KC (n = 10) stromal fibroblast cultures were incubated in either neutral- or low-pH conditions, with or without hydrogen peroxide. Catalase activities were measured with a fluorescent substrate assay. Superoxide and ROS/reactive nitrogen species (RNS) productions were determined with an amine-reactive green-dye assay and 2',7'-dichlorodihydrofluorescein diacetate (H2DCFDA) dye assay, respectively. Cell viability was analyzed by a dye-exclusion assay. Caspase 3 activity was measured by a fluorochrome inhibitor of caspase (FLICA) assay. A cationic (green) dye was used to measure the mitochondrial membrane potential (delta psi m). RESULTS: KC fibroblasts had increased superoxide and ROS/RNS production (6.2-fold, P < 0.001 and 1.8-fold, P < 0.001, respectively) and catalase activity (P < 0.01) with higher concentrations of H2O2 compared with normal cultures (P = 0.16). After a low-pH stress challenge, KC fibroblasts maintained higher ROS/RNS levels (3.3-fold, P < 0.02), showed higher caspase-3 activity (7.5-fold, P < 0.02) and decreased delta psi m (2.6-fold, P < 0.04), and had decreased cell viability (37%, P < 0.005 vs. 20%, P < 0.27) compared with normal fibroblasts. CONCLUSIONS: Under identical conditions, KC fibroblasts had increased basal generation of ROS/RNS and were more susceptible to stressful challenges (low-pH and/or H2O2 conditions) than were normal fibroblasts. In addition, the stressed KC fibroblasts possessed characteristics similar to those found in the intact KC corneas (increased catalase activity, ROS production, and apoptosis). These properties may play a role in the pathogenesis of KC.

Accumulation of mitochondrial DNA damage in keratoconus corneas.

PURPOSE: To determine whether keratoconus (KC) corneas have more mitochondrial (mt)DNA damage than do normal corneas. METHODS: Thirty-three normal corneas and 34 KC corneas were studied. Immunohistochemistry for mitochondria-encoded cytochrome c oxidase (complex IV) subunit 1 (CO-Iota) and porins was performed. Total DNA was isolated and mtDNA genome amplified by either long-extension-polymerase chain reaction (LX-PCR) or short-extension-PCR (SX-PCR). LX-PCR mtDNA was digested with restriction enzymes to confirm full-length mtDNA amplicon. SX-PCR mtDNA was probed by Southern blot analysis. The T414G mutation was analyzed by peptide nucleic acid directed clamping PCR. Real-time PCR measured the ratio of mtDNA to nuclear (n)DNA. RESULTS: KC corneas had decreased CO-Iota in areas of corneal thinning. LX-PCR mtDNA digested with restriction enzymes showed expected size bands except for PstI, which showed two additional bands in some KC corneas (2/18). By both LX-PCR (7.4 +/- 3.8 vs. 4.3 +/- 2.7, P < 0.04) and SX-PCR (5.5 +/- 0.55 vs. 2.4 +/- 2.0, P < 0.006), KC corneas had an increased number of smaller-sized bands (representing mtDNA deletions/mutations) compared with normal corneas. Southern blot analysis of SX-PCR products confirmed their mtDNA origin. The T414G mutation was not detected in either KC or normal corneas. KC corneas showed a trend of lower mtDNA-to-nDNA ratio (26%, P < 0.7) than did normal corneas. CONCLUSIONS: KC corneas exhibit more mtDNA damage than do normal corneas. The previously reported increased oxidative stress and altered integrity of mtDNA may be related to each other and may be important in KC pathogenesis.