The Paradoxical Induction of Crohn's Disease Following Treatment of Psoriatic Arthritis With Etanercept

Introduction: While psoriasis, psoriatic arthritis, and Crohn's Disease (CD) all share a common central pathogenesis pathway and a wide overlap of treatment regime, discrepancies still exist and are highlighted by the variability in the effectiveness of certain immunomodulating agents. Etanercept, for example, has been shown to be ineffective in CD due to its inability to induce T-cell apoptosis in the intestinal mucosa. Case: We describe the case of a 37-year-old man with a 20-year history of psoriatic arthritis. The patient presented with abdominal pain, watery diarrhea with mild hematochezia, and a reported 24-pound unintentional weight loss over the past five months. Of note, the patient began treatment with etanercept five months earlier after discontinuation of infliximab for his psoriatic arthritis symptoms. Colonoscopy with terminal ileum intubation revealed active colitis and intestinal biopsy results showed marked ulcerations and non caseating granulomas, indicative of CD. Etanercept was subsequently discontinued and the patient was started on ustekinumab, leading to remission of both his psoriatic arthritis and new onset CD. Discussion: Because the concurrent existence of psoriatic arthritis and IBD is becoming increasingly appreciated in recent literature, healthcare providers should have a high index of suspicion in patients with psoriasis and psoriatic arthritis presenting with unusual intestinal symptoms. Etanercept is intestinally inactive and should be used in caution in patients with psoriasis and psoriatic arthritis, as it may unmask underlying CD in this predisposed patient population. Dermatologists should also be aware of recent studies suggesting that etanercept directly contributes to the development of CD by altering the inflammatory cytokine milieu. Lastly, ustekinumab was successful in relieving our patient's cutaneous, joint, and gastrointestinal symptoms and may be considered an effective treatment option in patients suffering from both psoriasis and CD or the paradoxical induction of one disease entity secondary to treatment of the other

The Safe Management of Acne Vulgaris in Lupus Erythematosus: A Systematic Review with Evidence-Based Treatment Recommendations

To date, there have been no studies that have specifically investigated which medications can and cannot be safely used to treat acne vulgaris in patients who have lupus erythematosus (LE). These patients require a highly individualized treatment approach, as the use of certain acne medications may exacerbate LE symptomology, such as photosensitivity and hypercoagulability. In this systematic review, we examine safety outcomes associated with commonly prescribed oral acne medications, specifically in the context of LE. A literature search, conducted on PubMed/MEDLINE, revealed 146 studies, of which 13 met the criteria. We assigned a level of evidence to each study and sought to determine evidence-based recommendations for each class of drug; each recommendation was then assigned a corresponding grade. There were very few high-quality studies available on this topic. Although we determined recommendations based on the existing literature, the grading was occasionally unfavorable due to the low-quality nature of the evidence supporting the recommendation. However, our recommendation against the use of combined oral contraceptive pills and in favor of spironolactone for the treatment of acne, in the setting of LE, received a satisfactory grading (grade A). While no definitive recommendations for the treatment of acne in LE can be made based on the existing quality and quantity of studies available, this article aims to provide a comprehensive overview and analysis of oral acne medication safety in patients with LE, while emphasizing the immense need for higher quality studies and distinct acne treatment guidelines for this vulnerable patient population

The Inflammasome Signaling Proteins ASC and IL-18 as Biomarkers of Psoriasis

Inflammasome activation in the innate immune response plays a role in the pathogenesis of psoriasis largely due to the increased levels of pro-inflammatory cytokines. However, the precise role of inflammasomes in psoriasis (Ps) and psoriatic arthritis (PsA) is largely undefined. To establish the reliability of inflammasome signaling proteins as diagnostics and predictive biomarkers of clinical severity in this disease population, serum from healthy donors and patients with Ps/PsA were analyzed for the protein expression of caspase-1, apoptosis-associated speck-like protein containing a caspase-recruitment domain (ASC), interleukin (IL)-1β and IL-18 levels to determine cut-off points, positive and negative predictive values, and receiver operator characteristic (ROC) curves. Our data revealed that ASC and IL-18 proteins were significantly higher in the Ps group when compared to healthy controls. The area under the curve (AUC) for ASC was 0.9224 with a cut-off point of 321.8 pg/ml, while IL-18 had an AUC of 0.7818 and a cut-off point of 232.1 pg/ml. In addition, levels of IL-18 had a statistically significant linear correlation with that of ASC with an adjusted R squared of 0.2566, indicating that approximately 25% of IL-18 levels could be explained by ASC levels in serum. Our findings indicate that ASC and IL-18 play a significant role in the inflammatory response associated with the pathology of Ps. These inflammasome proteins appear to be key biomarkers in determining diagnoses in this patient population

Dural-Based Metastatic Malignant Melanoma Masquerading as Meningiomata: A Diagnostic Challenge

Despite both clinical and radiographic examination, metastases from malignant melanomas can be susceptible to misdiagnoses, particularly when they are found in uncommon locations. We report on an unsettling case of a 38-year-old woman who presented to neurosurgery with worsening neurological symptoms. Upon magnetic resonance imaging, the patient was found to have two sizeable dural-based lesions and underwent subsequent resection of the larger mass. Although the results of the pathohistological examination and immunohistochemistry staining were suspicious for metastatic malignant melanoma, an incorrect diagnosis of atypical meningioma was rendered due to the patient’s age and lack of melanoma history. After the patient’s condition continued to clinically deteriorate, dermatology was ultimately consulted and a more comprehensive work-up was carried out, revealing the correct and exceedingly rare diagnosis of dural-based metastatic melanoma of unknown primary. This case underscores the importance of an interdisciplinary diagnostic approach; one which employs comprehensive histopathologic evaluation, judiciously selected immunohistochemical staining, and thorough physical examination

Acidification changes affect the inflammasome in human nucleus pulposus cells

BACKGROUND: Interleukin (IL)-1β is involved in the pathology of intervertebral disc degeneration. Under normal conditions, IL-1β is present in cells in an inactive form (pro-IL-1β). However, under pathological conditions, pro-IL-1β is turned into its active form (IL-1β) by the inflammasome, a multi-protein complex of the innate immune response that activates caspase-1. Under conditions of degeneration, the disc experiences an environment of increased acidification. However, the implications of acidification on the innate immune response remain poorly explored. METHODS: Here we have studied how pH changes in human nucleus pulposus cells affect inflammasome activation by immunoblot analysis of protein lysates obtained from nucleus pulposus cells that were exposed to different pH levels in culture. RESULTS: In this study, we have found that in nucleus pulposus cells, with increased acidification, there was a decrease in inflammasome activation consistent with lower levels of active IL-1β. However, this effect at a pH of 6.5, the lowest pH level tested, was abrogated when cells were treated with IL-1β. CONCLUSIONS: Taken together, these findings suggest that the inflammatory response through IL-1β experienced by the human disc is not initiated in nucleus pulposus cells when the stimulus is acidification. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12950-016-0137-0) contains supplementary material, which is available to authorized users

Insurance delays in the approval of biologic medications for patients with psoriasis and psoriatic arthritis

Biologics are the most effective treatment for moderate-to-severe psoriasis. Insurance approval and need for prior authorization continue to be a barrier to care for many patients with psoriasis and psoriatic arthritis. We sought to determine whether race/ethnicity, insurance type, and provider specialty affect biologic approval times. Records from the University of Miami Health System were reviewed, and 101 patients were included. Need for a prior authorization was significantly associated with long waits (p = 2.4 x 10(-5)). We did not identify a significant difference in wait times between non-Hispanic Whites and non-Whites. The average wait time for biologic approval for Whites was 29.7 days and for non-Whites was 27.2 days. Biologics were approved the same day for 23.7% of HMO carriers, 11.5% of PPO carriers, 63% of Medicare carriers, and 40% of Medicaid carriers (p < 0.001). There was no difference in the biologic type prescribed based on insurance type. Medicaid (p < 0.05) and the need for prior authorization (p = 2.4 x 10(-5)) significantly predicted approval wait time in our multilinear regression model. Patients with Medicare had the shortest wait time with a mean of 7.3 days. Medicaid patients waited a mean of 11.3 days. Private insurance patients waited the longest, regardless of whether they had a PPO (37 days) or HMO (41.3 days)