Refractory multisystemic sarcoidosis, a diagnosis and treatment challenge: a case report.

BACKGROUND: Sarcoidosis is a multisystemic granulomatous disease of unknown origin. It is characterized by abnormal activation of lymphocytes and macrophages with the formation of granulomas. Most cases have asymptomatic pulmonary involvement. In case of symptoms, they have an excellent response to glucocorticoid therapy. We present a case of sarcoidosis with multi-organ involvement, refractory to multiple treatments including biological. Partial remission was achieved in it. CASE PRESENTATION: We report an interesting case of a 38-years-old Spanish woman treated by Heerfordt's syndrome (uveitis, parotiditis, fever and facial palsy) plus pulmonary hiliar adenopathy. A sarcoidosis diagnosis was confirmed by lung biopsy. She was initially treated with an 8 weeks course of medium dose oral glucocorticoids and tapered over 8 weeks with improvement. After the suspension of glucocorticoids a relapse occurs with severe ocular involvement and suspicion of neurological involvement. The patient received multiple lines of treatment with poor response. Finally, after the combination of cyclophosphamide with infliximab, the uveitis resolved, improving the neurological symptoms. CONCLUSIONS: Sarcoidosis is a benign disease in most cases. In a small percentage of cases behaves aggressively, requiring early diagnosis and immunosuppressive treatment to avoid sequelae. An adequate immunosuppressive therapy based on Anti TNF drugs should be started to minimize damage and improve the quality of life.The choice of treatment depends on the type and severity of the disease.

Food groups associated with immune-mediated inflammatory diseases: a Mendelian randomization and disease severity study.

BACKGROUND/OBJECTIVES: Immune-mediated inflammatory diseases (IMIDs) are prevalent diseases. There is, however, a lack of understanding of the link between diet and IMIDs, how much dietary patterns vary between them and if there are food groups associated with a worsening of the disease. SUBJECTS/METHODS: To answer these questions we analyzed a nation-wide cohort of n = 11,308 patients from six prevalent IMIDs and 2050 healthy controls. We compared their weekly intake of the major food categories, and used a Mendelian randomization approach to determine which dietary changes are caused by disease. Within each IMID, we analyzed the association between food frequency and disease severity. RESULTS: After quality control, n = 11,230 recruited individuals were used in this study. We found that diet is profoundly altered in all IMIDs: at least three food categories are significantly altered in each disease (P < 0.05). Inflammatory bowel diseases showed the largest differences compared to controls (n ≥ 8 categories, P < 0.05). Mendelian randomization analysis supported that some of these dietary changes, like vegetable reduction in Crohn's Disease (P = 2.5 × 10-10, OR(95% CI) = 0.73(0.65, 0.80)), are caused by the disease. Except for Psoriatic Arthritis and Systemic Lupus Erythematosus, we have found ≥2 food groups significantly associated with disease severity in the other IMIDs (P < 0.05). CONCLUSIONS: This cross-disease study demonstrates that prevalent IMIDs are associated to a significant change in the normal dietary patterns. This variation is highly disease-specific and, in some cases, it is caused by the disease itself. Severity in IMIDs is also associated with specific food groups. The results of this study underscore the importance of studying diet in IMIDs.

Genome-wide pathway analysis identifies VEGF pathway association with oral ulceration in systemic lupus erythematosus.

BACKGROUND: Systemic lupus erythematosus (SLE) is a genetically complex rheumatic disease characterized by heterogeneous clinical manifestations of unknown etiology. Recent studies have suggested the existence of a genetic basis for SLE heterogeneity. The objective of the present study was to identify new genetic variation associated with the clinically relevant phenotypes in SLE. METHODS: A two-stage pathway-based approach was used to identify the genetic variation associated with the main clinical phenotypes in SLE. In the discovery stage, 482 SLE patients were genotyped using Illumina Human Quad610 microarrays. Association between 798 reference genetic pathways from the Molecular Signatures Database and 11 SLE phenotypes was tested using the set-based method implemented in PLINK software. Pathways significantly associated after multiple test correction were subsequently tested for replication in an independent cohort of 425 SLE patients. Using an in silico approach, we analyzed the functional effects of common SLE therapies on the replicated genetic pathways. The association of known SLE risk variants with the development of the clinical phenotypes was also analyzed. RESULTS: In the discovery stage, we found a significant association between the vascular endothelial growth factor (VEGF) pathway and oral ulceration (P value for false discovery rate (P FDR) < 0.05), and between the negative regulation signaling pathway of retinoic acid inducible gene-I/melanoma differentiation associated gene 5 and the production of antinuclear antibodies (P FDR < 0.05). In the replication stage, we validated the association between the VEGF pathway and oral ulceration. Therapies commonly used to treat mucocutaneous phenotypes in SLE were found to strongly influence VEGF pathway gene expression (P = 4.60e-4 to 5.38e-14). Analysis of known SLE risk loci identified a strong association between PTPN22 and the risk of hematologic disorder and with the development of antinuclear antibodies. CONCLUSIONS: The present study has identified VEGF genetic pathway association with the risk of oral ulceration in SLE. New therapies targeting the VEGF pathway could be more effective in reducing the severity of this phenotype. These findings represent a first step towards the understanding of the genetic basis of phenotype heterogeneity in SLE.