Nsaids Linked to IgA-Mediated Hypersensitivity Vasculitis and Purpura Fulminans-Like Eruption.

Background: IgA vasculitis and hypersensitivity reactions following exposure to non-steroidal anti-inflammatory drugs (NSAIDs) are very rarely associated with purpura fulminans (PF). The latter is a coagulation event characterised by decreased levels of protein C and a rapidly progressive purpuric rash, often leading to ischaemia, amputations and death. Case summary: A previously healthy 66-year-old man presented with a vasculitic rash and abdominal pain following exposure to naproxen (NSAID), which quickly deteriorated to purpura fulminans-like eruption and skin necrosis, mainly involving the face and hands. The presence of IgA sediments on skin biopsy and decreased levels of complement as well as protein C pointed to an immune-mediated inflammatory process. Dramatic clinical escalation with immediate risk to organs and life required an aggressive and broad-spectrum therapeutic approach in an intensive care setting. Clinical improvement and complete reconstitution of protein C were achieved following plasma exchange with fresh frozen plasma (FFP) and immunosuppression with glucocorticoids with no persistent organ damage. Conclusions: This rare case illustrates the catastrophic cross links between NSAIDs, IgA-mediated hypersensitivity vasculitis and purpura fulminans-like syndrome. A high index of suspicion is required for the evaluation of environmental exposures such as drugs and infections in patients with vasculitis and/or purpura. A rapid and comprehensive therapeutic approach should be implemented to avoid multi-organ damage, amputations and death. Complete avoidance of the offending agent is key for future prevention of recurrence. LEARNING POINTS: This case illustrates a rare cross link between a commonly used drug (NSAIDs) and severe, life-threatening hypersensitivity reactions (IgA vasculitis and purpura fulminans-like eruption).These events require a high index of suspicion and emphasise the importance of considering environmental exposures such as drugs in the immediate diagnosis of both conditions.In addition to long-term drug avoidance, early and aggressive interventions are required to avoid organ damage, amputations or death.

The association between adrenal adenoma size, autonomous cortisol secretion and metabolic derangements.

OBJECTIVE: Autonomous cortisol secretion (ACS) is common in patients with adrenal incidentalomas (AI). ACS is associated with increased cardiovascular morbidity and mortality. Data regarding the association between radiological characteristics of adrenal adenomas, their hormonal functionality and metabolic outcomes, are scarce and inconclusive. In this study, we aim to delineate the association between radiological characteristics of AI, ACS and metabolic status. METHODS: A cross-sectional study of 77 patients with AI who underwent a comprehensive hormonal evaluation. Radiological assessments were performed by an independent radiologist blinded to the clinical and hormonal phenotype of each case. Linear regression models were used to evaluate the association between post dexamethasone suppression test (DST) cortisol levels, metabolic indices and radiological measurements. RESULTS: Mean maximal adenoma diameter was greater in patients with versus without ACS (20.35 ± 6 vs. 27.09 ± 9.3 mm, respectively, p < .01). Maximal adenoma diameter was found to be positively and linearly correlated with post-DST morning cortisol levels across their entire range (R = .474, p < .01). Linear correlations between maximal adenoma diameter and indices of glycemic control showed a correlation coefficient (R) of .481 and .463 for fasting plasma glucose (FPG) and haemoglobin A1c (HbA1c), respectively, p < .01. When analysis included only patients with ACS, an R = .584 and R = .565 was observed for FPG and HbA1c, respectively (p < .01 for both). The association between maximal adenoma diameter and both FPG and post-DST morning cortisol intensified in patients with metabolic syndrome. CONCLUSION: There is a quantitative positive mild correlation between AI size and both cortisol autonomy and metabolic parameters.

The Quantitative Relationship Between Autonomous Cortisol Secretion, Dysglycemia and the Metabolic Syndrome.

OBJECTIVE: Autonomous cortisol secretion (ACS) is the most common endocrine abnormality in the evaluation of adrenal incidentalomas. The categorization of ACS is derived from a 1 mg dexamethasone suppression test (DST). Impaired DST is associated with several metabolic derangements. In this study we analyzed the association between post-DST cortisol level, analyzed as a continuous parameter, and indices of glycemic metabolism. METHODS: We prospectively collected data of 1,976 patients evaluated for adrenal incidentalomas in a large tertiary medical center between December 1, 2017, and August 31, 2019. Seventy-three patients completed the evaluation process. Post-DST cortisol levels were analyzed for correlation with various metabolic parameters, including fasting plasma glucose (FPG) and hemoglobin A1c (HbA1c) among the general cohort and for subgroups stratified by the number of metabolic syndrome (MS) criteria. RESULTS: Post-DST cortisol demonstrated a linear association with FPG and HbA1c across its entire cortisol range (R = 0.51 and 0.41, respectively; P≤.01). The association between post-DST cortisol and FPG was strengthened with an increased number of metabolic syndrome criteria. Patients with 4 MS criteria show a stronger association (R = 0.92) compared to patients with only a single criterion (R = 0.509). Furthermore, mean post-DST cortisol levels increased as the number of MS criteria accumulated. CONCLUSION: Post-DST cortisol should be viewed as a continuous parameter in risk stratification algorithms for the development of MS and particularly dysglycemia.

Centrobin regulates centrosome function in interphase cells by limiting pericentriolar matrix recruitment.

The amount of pericentriolar matrix at the centrosome is tightly linked to both microtubule nucleation and centriole duplication, although the exact mechanism by which pericentriolar matrix levels are regulated is unclear. Here we show that Centrobin, a centrosomal protein, is involved in regulating these levels. Interphase microtubule arrays in Centrobin-depleted cells are more focused around the centrosome and are less stable than the arrays in control cells. Centrobin-depleted cells initiate microtubule nucleation more rapidly than control cells and exhibit an increase in the number of growing microtubule ends emanating from the centrosome, while the parameters of microtubule plus end dynamics around the centrosome are not significantly altered. Finally, we show that Centrobin depletion results in the increased recruitment of pericentriolar matrix proteins to the centrosome, including γ-tubulin, AKAP450, Kendrin and PCM-1. We propose that Centrobin might regulate microtubule nucleation and organization by controlling the amount of pericentriolar matrix.