Microangiopathy in Ocular Sarcoidosis Using Fluorescein Gonio and Fundus Angiography from Diagnostic and Therapeutic Aspects

In this retrospective study, we investigated vascular abnormalities in sarcoidosis using fluorescein gonioangiography (FGA) to detect angle neovascularization (ANV), fundus fluorescein angiography (FFA), and pathological specimens from the aspects of microangiopathy. In 57 sarcoidosis patients, clinical data was reviewed by dividing the cases into three groups (Group I: histologically diagnosed; Group II: positive bilateral hilar lymphadenopathy (BHL); Group III: negative BHL). The FFA, FGA, and pathological examination data in the autopsy eyes and trabeculectomy specimens were investigated. FGA and FFA detected ANV (91%) and nodule-associated abnormalities (87%), respectively. No intraocular pressure (IOP) elevation was observed after continuous topical betamethasone, except in the steroid responder group. Maximum IOP had significant correlation with nodules in the angle (p = 0.02696) and visual field defect (p = 0.0151). Granulomas adjacent to blood vessels, including the Schlemm’s canal, and thickening of the retinal blood vessel wall caused occlusion of those vessels. Photocoagulation was required for retinal tears (14%) and the retinal blood vessel occlusion (7%). Suppression of IOP elevation via continuous topical betamethasone may be important to avoid irreversible outflow-route changes and optic-nerve damage, and the concept of microangiopathy in ocular sarcoidosis may be important for understanding the proper treatment of serious complications

Sarcoidosis and NOD1 variation with impaired recognition of intracellular Propionibacterium acnes

AbstractSarcoidosis is a systemic granulomatous disease of unknown etiology. NOD2 mutations have been shown to predispose to granulomatous diseases, including Crohn's disease, Blau syndrome, and early-onset sarcoidosis, but not to adult sarcoidosis. We found that intracellular Propionibacterium acnes, a possible causative agent of sarcoidosis, activated NF-κB in both NOD1- and NOD2-dependent manners. Systematic search for NOD1 gene polymorphisms in Japanese sarcoidosis patients identified two alleles, 796G-haplotype (156C, 483C, 796G, 1722G) and 796A-haplotype (156G, 483T, 796A, 1722A). Allelic discrimination of 73 sarcoidosis patients and 215 healthy individuals showed that the frequency of 796A-type allele was significantly higher in sarcoidosis patients and the ORs were significantly elevated in NOD1-796G/A and 796A/A genotypes (OR [95% CI]=2.250 [1.084, 4.670] and 3.243 [1.402, 7.502], respectively) as compared to G/G genotype, showing an increasing trend across the 3 genotypes (P=0.006 for trend). A similar association was found when 52 interstitial pneumonia patients were used as disease controls. Functional studies showed that the NOD1 796A-allele was associated with reduced expression leading to diminished NF-κB activation in response to intracellular P. acnes. The results indicate that impaired recognition of intracellular P. acnes through NOD1 affects the susceptibility to sarcoidosis in the Japanese population

Clinical Course and Changes in High-Resolution Computed Tomography Findings in Patients with Idiopathic Pulmonary Fibrosis without Honeycombing

<div><p>Some patients with idiopathic pulmonary fibrosis (IPF) do not have honeycombing on high-resolution computed tomography (HRCT) at their initial evaluation. The clinical course and sequential changes in HRCT findings in these patients are not fully understood. We reviewed the cases of 43 patients with IPF without honeycombing on initial HRCT from institutions throughout Japan. All patients were diagnosed with IPF based on a surgical lung biopsy. Multidisciplinary discussions were held five times between 2011 and 2014, to exclude alternative etiologies. We evaluated the sequential changes in HRCT findings in 30 patients with IPF. We classified these 30 patients into three groups based on their HRCT patterns and clarified the clinical characteristics and prognosis among the groups. The patterns of all 30 patients on initial HRCT corresponded to a possible usual interstitial pneumonia (UIP) pattern which was described in the 2011 International Statement. On long-term follow-up (71.0±38.7 standard deviation [SD] months), honeycombing was seen in 16 patients (53%, the HoneyCo group); traction bronchiectasis or cysts without honeycombing was observed in 12 patients (40%, the NoHoneyCo group), and two patients showed no interval change (7%, the NoChange group) on HRCT. The mean survival periods of the HoneyCo and NoHoneyCo groups were 67.1 and 61.2 months, respectively (p = 0.76). There are some patients with IPF whose conditions chronically progress without honeycombing on HRCT. The appearance of honeycombing on HRCT during the follow-up might not be related to prognosis.</p></div

Kaplan-Meier survival curves where honeycombing appeared on subsequent HRCT scans after initial evaluation (n = 16, blue line, the HoneyCo group), patients in whom honeycombing was not seen but traction bronchiectasis or cysts appeared on subsequent computed tomography scans after initial evaluation (n = 12, green line, the NoHoneyCo group), and patients with no change in HRCT findings after long-term follow-up (n = 2, yellow line, the NoChange group).

<p>Kaplan-Meier survival curves where honeycombing appeared on subsequent HRCT scans after initial evaluation (n = 16, blue line, the HoneyCo group), patients in whom honeycombing was not seen but traction bronchiectasis or cysts appeared on subsequent computed tomography scans after initial evaluation (n = 12, green line, the NoHoneyCo group), and patients with no change in HRCT findings after long-term follow-up (n = 2, yellow line, the NoChange group).</p

HRCT images of two patients with representative HRCT scans, showing reticular abnormalities and/or subpleural irregularities without honeycombing.

<p>HRCT images of two patients with representative HRCT scans, showing reticular abnormalities and/or subpleural irregularities without honeycombing.</p

Representative HRCT scans from the three patient groups.

<p>HoneyCo: Honeycombing became evident on HRCT scan. NoHoneyCo: Traction bronchiectasis or cysts became evident on HRCT scan. NoChange: No significant change in HRCT findings.</p

Baseline characteristics of patients with a UIP pattern or a probable UIP pattern based on histopathological criteria and a possible UIP pattern based on HRCT criteria without honeycombing.

<p>Baseline characteristics of patients with a UIP pattern or a probable UIP pattern based on histopathological criteria and a possible UIP pattern based on HRCT criteria without honeycombing.</p