Diagnostic Challenges in Neuro-Psychiatric Systemic Lupus Erythematosus: A Case of a Patient With Psychosis Secondary to Lupus Cerebritis in the Setting of a Steroid Taper.

Systemic lupus erythematosus (SLE) is an autoimmune condition whereby autoantibodies target systemic tissues, causing manifestations of inflammation and tissue damage. Neurologic inflammation in SLE can cause an array of neuropsychiatric (NP) symptoms, including headaches, depression, seizures, demyelinating conditions, mania, and psychosis. Patients treated for SLE are often on anti-inflammatory regimens, including high-dose steroids, which can independently precipitate psychosis. Steroid-induced psychosis (SIP) and lupus cerebritis (LC) are two distinct conditions that patients with SLE may have but often have overlapping presentations, which present a challenge for clinicians. Accurately differentiating between SIP and LC in an emergency setting is crucial for directing appropriate management and preventing potential complications. A clear timeline of the history of symptoms can help narrow down the cause. Diagnostic tools, mainly MRI patterns, can further clarify and indicate the presence of LC. We present a case of a 19-year-old African American female with a history of one steroid-induced psychotic episode five months prior in the setting of SLE who developed subsequent psychosis while on a steroid taper. MRI imaging elucidated a diagnosis of LC rather than a second SIP episode. There are few, if any, case reports that describe a patient with past SIP with a subsequent flare of cerebritis with psychotic symptoms. Strategic approaches to differentiating SIP from LC in the setting of SLE can lead to improved patient outcomes, follow-up care, and an overall understanding of the neuropsychiatric complexities of SLE.

Diagnosis of Marfan Syndrome Following Progressive Myopia and Secondary Lens-Induced Angle Closure Crisis.

Marfan syndrome (MFS) is a well-described genetic connective tissue disease that heightens the risk of cardiovascular, ocular, pulmonary, and other emergencies in affected individuals. The wide range of phenotypic presentations, spanning from mild, chronic, and asymptomatic to acute and life-threatening, can pose challenges in diagnosing MFS when disease manifestations are subtle. We report a pathogenetic variant of MFS characterized by subtle systemic findings that was identified only after the patient presented with visual changes and pain associated with angle closure, despite a medical history indicating other pathologies linked to this condition. This case underscores the importance of recognizing the varied and sometimes subtle clinical features of MFS. Vigilance in identifying the constellation of findings associated with MFS can enhance its diagnosis and treatment outcomes by enabling appropriate and timely referrals for prophylactic evaluation and care to address potentially life-threatening complications.

Unilateral conjunctival Classic Kaposi Sarcoma following a COVID 19 booster.

Purpose: We describe a case of Classic Kaposi's sarcoma in a functionally monocular patient following a COVID19 vaccine booster and provide compelling evidence that suggests the booster was a relevant co-factor in the initiation of the disease process. Observations: The patient presented with red, irritated conjunctival area described as "bubbling" in her right eye. While her past medical history includes hypercholesterolemia and hypertension, she had no history of a compromised immune system. Her ophthalmologic history is more complex including treatment for glaucoma. The patient has 20/20 uncorrected vision OD and LP OS. Due to her ocular co-morbidities, the patient initially received interferon alpha 2-B qid for 6 weeks. However, topical therapy failed to decrease the size of the conjunctival lesions. After referral to Radiation Oncology, the right eye/orbit was treated with electron beam therapy for 1 month which caused a marked decrease in the size and vascularity of the conjunctival lesions. A slow improvement continued during followup. Conclusion and importance: In that the vaccine booster preceded the cancer, it appears etiologic to the appearance of Kaposi's sarcoma. The patient's monocular vision and glaucoma complicated her treatment. This case expands on current concepts of cofactors needed for the development of Kaposi's sarcoma in that vaccine booster administration was relevant to tumor progression and both clinical and mechanistic evidence is presented to support this hypothesis.

Phosphosulindac (OXT-328) prevents and reverses chemotherapy induced peripheral neuropathy in mice.

Background: Chemotherapy-induced peripheral neuropathy (CIPN), a side effect of chemotherapy, is particularly difficult to treat. We explored whether phosphosulindac (PS), a modified NSAID, could treat CIPN. Methods: CIPN was induced in male C57BL/6 J mice by paclitaxel, vincristine or oxaliplatin. Mechanical allodynia was measured with the von Frey test and cold allodynia with the acetone test. To determine the preventive effect of PS, it was administered 2 days before the induction of CIPN. Mouse Lewis lung carcinoma xenografts were used to determine if PS altered the chemotherapeutic efficacy of paclitaxel. Cultured cell lines were used to evaluate the effect of PS on neuroinflammation. Results: Treatment with each of the three chemotherapeutic agents used to induce CIPN lowered the mechanical allodynia scores by 56 to 85% depending on the specific agent. PS gel was applied topically 3x/day for 16-22 days to the hind paws of mice with CIPN. This effect was dose-dependent. Unlike vehicle, PS returned mechanical allodynia scores back to pre-CIPN levels. PS had a similar effect on paclitaxel-induced CIPN cold allodynia. Sulindac, a metabolite of PS, had no effect on CIPN. PS significantly prevented CIPN compared to vehicle. Given concomitantly with paclitaxel to mice with lung cancer xenografts, PS relieved CIPN without affecting the anticancer effect of paclitaxel. The enantiomers of PS were equally efficacious against CIPN, suggesting the therapeutic suitability of the racemate PS. There were no apparent side effects of PS. PS suppressed the levels of IL-6, IL-10, CXCL1, and CXCL2 induced by paclitaxel in a neuroblastoma cell line, and macrophage activation to the M1 proinflammatory phenotype. Conclusion: Topically applied PS demonstrated broad therapeutic and preventive efficacy against CIPN, preserved the anticancer effect of paclitaxel, and was safe. Its anti-CIPN effect appears to be mediated, in part, by suppression of neuroinflammation. These data support further evaluation of topical PS for the control of CIPN.

A natural product biflavonoid scaffold with anti-tryptase activity.

Tryptase is a serine protease that is released from mast cells during allergic responses. Tryptase inhibitors are being explored as treatments for allergic inflammation in the skin and respiratory system, most notably asthma. Here we report direct tryptase inhibition by natural product compounds. Candidate inhibitors were identified by computational screening of a large (98,000 compounds) virtual library of natural product compounds for tryptase enzymatic site binding. Biochemical assays were used to validate the predicted anti-tryptase activity in vitro, revealing a high (four out of six) success rate for predicting binding using the computational docking model. We further assess tryptase inhibition by a biflavonoid scaffold, whose structure-activity relationship is partially defined by assessing the potency of structurally similar analogs.