Cryptococcal meningitis associated with interleukin-17 inhibitor use for psoriasis.

Invasive fungal infection is a rare but serious potential consequence of biologic therapy. Herein, we report a case of cryptococcal meningitis in an otherwise immunocompetent patient receiving ixekizumab for the treatment of severe plaque psoriasis. We also discuss the relevant immunologic role of interleukin-17, the potential for synergistic effects when transitioning biologic therapies, and clinical considerations when treating patients with such medications. To the best of our knowledge, this is the first case of cryptococcal meningitis reported in a patient treated with ixekizumab.

BAPoma presenting as an incidental scalp papule: case report, literature review, and screening recommendations for BAP1 tumor predisposition syndrome.

OBJECTIVE: BRCA1-associated protein 1 (BAP1) tumor predisposition syndrome (BAP1-TPDS) is associated with an increased risk for aggressive cancers. BAP1-inactivated melanocytic tumors (BIMTs) are observed in 75% of BAP1-TPDS, often presenting as early as the second decade of life. These lesions may serve as a predictive marker to identify patients who carry germline BAP1 mutations and thus are at higher risk of developing associated cancers. Early diagnosis for these malignancies is crucial for curative treatment. METHODS: We report a patient who presented with an incidental scalp papule for which biopsy was consistent with a BIMT. A review of literature was conducted by accessing the PubMed database to delineate present knowledge of BIMTs, assess recommendations for screening of germline BAP1 mutations, and evaluate cancer surveillance strategies for BAP1-TPDS associated cancers. RESULTS: Consensus in literature indicates that genetic evaluation should be encouraged in patients presenting with multiple BIMTs or a new BIMT with significant family history of BAP1-TPDS related cancers. If positive for a germline BAP1 mutation, cancer surveillance should be recommended for early diagnosis and timely intervention. CONCLUSIONS: Further workup should be encouraged in patients who meet the proposed screening criteria for germline BAP1 mutations. Patients could benefit from cancer surveillance for earlier diagnosis, management, and improved outcomes.

Penile calciphylaxis with extragenital gangrene.

Penile calciphylaxis is a rare cause of penile gangrene and is typically associated with multiple comorbidities, most commonly diabetes mellitus and hyperparathyroidism. It demonstrates a high mortality rate of 64% and is seen almost exclusively in patients with end-stage renal disease on hemodialysis. Underreporting of this disease likely occurs, contributing to a paucity of data and lack of formal therapeutic guidelines and approved treatments. Conflicting guidance exists regarding effective treatment strategies, with most formal literature existing in the form of case reports. Herein, we describe a 44-year-old man with end-stage renal disease on hemodialysis who presented with a 2-month history of nonhealing wounds on his penis and lower extremities.

Comparative profile of refractory status epilepticus models following exposure of cholinergic agents pilocarpine, DFP, and soman.

Status epilepticus (SE) is a medical emergency with continuous seizure activity that causes profound neuronal damage, morbidity, or death. SE incidents can arise spontaneously but mostly are elicited by seizurogenic triggers. Chemoconvulsants such as the muscarinic agonist pilocarpine and, organophosphates (OP) such as the pesticide diisopropylfluorophosphate (DFP) and, the nerve agent soman, can induce SE. Pilocarpine, DFP, and soman share a common feature of cholinergic crisis that transitions into a state of refractory SE, but their comparative profiles remain unclear. Here, we evaluated the comparative convulsant profile of pilocarpine, DFP, and soman to produce refractory SE and brain damage in rats. Behavioral and electrographic seizures were monitored for 24 h after exposure, and the extent of brain injury was determined by histological markers of neuronal injury and degeneration. Seizures were elicited rather slowly after pilocarpine as compared to DFP or soman, which caused rapid onset of spiking that swiftly developed into persistent SE. Time-course of SE activity after DFP was comparable to that after soman, a potent nerve agent. Diazepam controlled pilocarpine-induced SE, but it was ineffective in reducing OP-induced SE. All three agents produced modestly different degrees of neuronal injury and neurodegeneration in the brain. These results reveal distinct convulsant and neuronal injury patterns following exposure to cholinergic agonists, OP pesticides, and nerve agents. A battery of SE models, especially SE induced by cholinergic agents and other etiologies including epilepsy and brain tumors, is essential to identify novel anticonvulsant therapies for the management of refractory SE.

Ixekizumab in the treatment of moderate-to-severe plaque psoriasis: Patient adherence, satisfaction, and preferences.

Ixekizumab is a humanized monoclonal antibody that exhibits its immunomodulatory effects by binding to interleukin 17A (IL-17A), a proinflammatory cytokine. It was approved for the treatment of plaque psoriasis by the Food and Drug Administration in 2016. Ixekizumab has demonstrated superiority in clinical trials against etanercept, with no significant difference in the side effect profile. The chronicity of psoriasis requires continual treatment to achieve disease clearance. Many factors may affect adherence to treatment including patient satisfaction, patient preferences, medication cost, and medication side effects. Limited data on patient adherence, satisfaction, and preference exists in formal literature. Often, surrogate measures must be used to extrapolate information regarding these measures. In this narrative review, we describe patient adherence, satisfaction, and preferences via both direct and surrogate measures as they relate to ixekizumab treatment for moderate-to-severe plaque psoriasis.

Diffuse dermal angiomatosis of the breast.

Diffuse dermal angiomatosis of the breast can be a painful, irritating, and persistent inflammatory condition. It tends to present in middle age and is associated with a number of risk factors, mainly relating to tissue hypoxia. There are no standard treatment guidelines, and current treatment focuses on mitigating tissue hypoxia by addressing atherosclerosis through lifestyle changes and medical and/or surgical intervention. Herein, we present a case of diffuse dermal angiomatosis of the breast, describing the condition and current treatment approaches and the likelihood that this diagnosis is more common than previously believed.

Histone deacetylase-1 (HDAC1) is a molecular switch between neuronal survival and death.

Both neuroprotective and neurotoxic roles have previously been described for histone deacetylase-1 (HDAC1). Here we report that HDAC1 expression is elevated in vulnerable brain regions of two mouse models of neurodegeneration, the R6/2 model of Huntington disease and the Ca(2+)/calmodulin-dependent protein kinase (CaMK)/p25 double-transgenic model of tauopathic degeneration, suggesting a role in promoting neuronal death. Indeed, elevating HDAC1 expression by ectopic expression promotes the death of otherwise healthy cerebellar granule neurons and cortical neurons in culture. The neurotoxic effect of HDAC1 requires interaction and cooperation with HDAC3, which has previously been shown to selectively induce the death of neurons. HDAC1-HDAC3 interaction is greatly elevated under conditions of neurodegeneration both in vitro and in vivo. Furthermore, the knockdown of HDAC3 suppresses HDAC1-induced neurotoxicity, and the knockdown of HDAC1 suppresses HDAC3 neurotoxicity. As described previously for HDAC3, the neurotoxic effect of HDAC1 is inhibited by treatment with IGF-1, the expression of Akt, or the inhibition of glycogen synthase kinase 3ß (GSK3ß). In addition to HDAC3, HDAC1 has been shown to interact with histone deacetylase-related protein (HDRP), a truncated form of HDAC9, whose expression is down-regulated during neuronal death. In contrast to HDAC3, the interaction between HDRP and HDAC1 protects neurons from death, an effect involving acquisition of the deacetylase activity of HDAC1 by HDRP. We find that elevated HDRP inhibits HDAC1-HDAC3 interaction and prevents the neurotoxic effect of either of these two proteins. Together, our results suggest that HDAC1 is a molecular switch between neuronal survival and death. Its interaction with HDRP promotes neuronal survival, whereas interaction with HDAC3 results in neuronal death.