Hematologic side effects of biologics and kinase inhibitors used in rheumatologic diseases: a review of the current evidence.

Treatment options for various rheumatologic diseases have been limited until the introduction of biologic agents and kinase inhibitor therapy in recent decades. Since their arrival, they have steadily been integrated into routine management. Given their wide use and overall successful outcomes, it becomes increasingly pertinent for clinicians to readily identify their side effects. Their effects can involve multiple organ systems, including hematologic. This review aims to identify and classify the range of hematologic effects associated with individual biologics and kinase inhibitors used for treatment of rheumatologic diseases.

Pharmacogenetics of therapies in rheumatoid arthritis: An update.

Rheumatoid arthritis (RA) is a systemic autoimmune inflammatory arthritis. Despite many treatment advances, achieving remission or low-disease activity in RA remains challenging, often requiring trial and error approaches with numerous medications. Precision medicine, particularly pharmacogenomics, explores how genetic factors influence drug response in individual patients, and incorporates such factors to develop personalized treatments for individual patients. Genetic variations in drug-metabolizing enzymes, transporters, and targets may contribute to inter-individual differences in drug efficacy and toxicity. Advancements in molecular sequencing have allowed rapid identification of such variants, including single nucleotide polymorphisms (SNPs). This review highlights recent major findings in the pharmacogenetics of therapies in RA, focusing on key genes and SNPs to provide insights into current trends and developments in this field.

Role of PET/CT in diagnosing and monitoring disease activity in rheumatoid arthritis: a review.

Rheumatoid Arthritis (RA) is a systemic inflammatory disorder that commonly presents with polyarthritis but can have multisystemic involvement and complications, leading to increased morbidity and mortality. The diagnosis of RA continues to be challenging due to its varied clinical presentations. In this review article, we aim to determine the potential of PET/CT to assist in the diagnosis of RA and its complications, evaluate the therapeutic response to treatment, and predict RA remission. PET/CT has increasingly been used in the last decade to diagnose, monitor treatment response, predict remissions, and diagnose subclinical complications in RA. PET imaging with [18F]-fluorodeoxyglucose ([18F]-FDG) is the most commonly applied radiotracer in RA, but other tracers are also being studied. PET/CT with [18F]-FDG, [18F]-NaF, and other tracers might lead to early identification of RA and timely evidence-based clinical management, decreasing morbidity and mortality. Although PET/CT has been evolving as a promising tool for evaluating and managing RA, more evidence is required before incorporating PET/CT in the standard clinical management of RA.

Chimeric antigen receptor T cell therapy for the treatment of systemic rheumatic diseases: a comprehensive review of recent literature.

Systemic rheumatoid diseases (SRDs) are autoimmune and inflammatory disorders that affect multiple organ systems, impacting patients' quality of life, and survival rates. Standard treatment requires continuous drug therapy and immunosuppression. Chimeric antigen receptor (CAR) T cell therapy has the potential to target and eliminate pathologically activated immune cells and re-establish tolerance in organs affected by dysregulated immunity, making them a promising treatment option for autoimmune diseases. In autoimmune diseases, CAR T cells have the advantage of being able to kill B cells effectively without the need for an accessory cell type. Additionally, CAR T cells targeting CD19 have shown promise in comprehensive B cell aplasia, preserving pre-existing humoral immunity, and specifically eliminating pathogenic B cells. CAR T cell therapy's limited use in SRDs is due to its inability to effectively target the various autoreactive lymphocytes present. Researchers are developing a universal CAR T cell therapy that detects and targets autoreactive lymphocytes using major epitope peptides, though further studies are required. Moreover, adoptive transfer of CAR-Tregs has shown promise for effectively reducing inflammation and treating autoimmunity. Through this exploration, the authors hope to provide a comprehensive understanding of the current state of research on this topic, identify areas for further study, and promote the advancement of CAR T cell therapy as a treatment option for SRDs.

The Ominous Aspergillus With Cancer of Blood Vessels: A Case of Invasive Aspergillosis and Epithelioid Angiosarcoma of the Lung.

Invasive aspergillosis occurs in the setting of risk factors such as severe or prolonged neutropenia, defects in cell-mediated immunity, and receipt of immunosuppressive therapy, particularly in patients with graft-versus-host disease (GVHD). Pulmonary epithelioid angiosarcomas (EASs) are rare malignant vascular tumors that are aggressive, frequently metastatic, and associated with a poor prognosis. We describe these two rare conditions occurring concurrently.

Octreotide as a novel agent for the management of bronchorrhea in mechanically ventilated patients: A case series and review of literature.

Excessive bronchial secretions pose a challenge in mechanically-ventilated patients and may prolong the time to extubation, increasing the risk for pneumonia. Octreotide, a somatostatin analog, has been used to decrease bronchial secretions especially for the symptomatic management of patients with lung cancer. We describe three patients in the form of a case series and discuss effect of octretotide on bronchial secretions and management of bronchorrhea in the intensive care unit. Similar to reports of its utilization in palliative care in patients with lung cancer, we observed a clinically significant decrease in the rate of bronchial secretions.

Thrombolytic Therapy in the Oldest Old: Successful Alteplase Administration in a 105-Year-Old Female With Ischemic Stroke.

The elderly have a higher incidence of ischemic stroke along with higher mortality and morbidity compared to their younger counterparts. However, though studies have included people >85 or 90 years of age, there haven't been reports of many individuals above 100 years of age. Among the oldest old, the oldest age studied for alteplase administration is possibly 101 years. We present a case of a 105-year-old woman with a medical history of a cerebrovascular accident in 2018 for which she received thrombolytic therapy with residual slurred speech and mild dysphagia. She was brought in from her nursing facility for worsening of slurred speech and right facial droop that began two hours before presentation to the emergency department. She was found to have aphasia, left-sided gaze preference, and upper motor neuron dysfunction of her right arm associated with drift. Her National Institutes of Health Stroke Scale (NIHSS) score at presentation was 17. An urgent CT scan of the head was performed that did not show any evidence of acute bleeding. CT angiogram of brain and neck was unremarkable with no evidence of high-grade stenosis, aneurysm, occlusion, or dissection. With the negative CT findings, the patient received thrombolytic therapy with alteplase. She was monitored in the intensive care unit for 24 hours after alteplase administration with neurological checks every one hour. The repeated CT head after 24 hours was negative for any hemorrhage. She was discharged after two days of hospital admission and her NIHSS score on the day of discharge was 4. Our patient was 105 years old, which is arguably one of the oldest ages to receive alteplase. Her NIHSS score improved considerably and she did not suffer from hemorrhagic complications.

Iatrogenic Pneumocephalus Resolved by Oxygen Therapy.

Iatrogenic pneumocephalus and dural puncture are some causes of headache following cervical epidural injection. A 50-year-old woman presented with a sharp headache at the base of her skull following a cervical epidural injection for chronic neck pain. It was not relieved by lying down and was associated with nausea, vomiting, and photophobia without fever or neck rigidity. Neurological examination failed to show any abnormalities. A head CT scan showed newly evident pneumocephalus in the ventricular system and the extra-axial subarachnoid space within the sulci of the right frontal lobe. Oxygen supplementation was started with the help of a non-rebreather mask connected to 15 liters of oxygen and was slowly down titrated to room air. Repeat CT scan of the head after 48 hours showed complete resolution of the intracranial pneumocephalus. Normobaric oxygen therapy via a non-rebreather mask and a high-flow nasal cannula is effective for the treatment of intracranial pneumocephalus.

Possible Aripiprazole-Induced Hypothermia: An "Icy" Side Effect?

Antipsychotics are a widely used class of drugs. They have been frequently associated with temperature dysregulation, especially hyperthermia. Hypothermia is also a rare but very serious side effect associated with these drugs. We present a case of possible aripiprazole-induced hypothermia with normothermia achieved after its discontinuation. An 81-year-old woman was brought into the emergency room with hypotension, hypothermia, and bradycardia. She was initially managed with intravenous fluids, external rewarming, and broad-spectrum antibiotics. Blood cultures and workup for infection returned negative with a low procalcitonin. Workup for endocrinopathy was also negative. She needed a Bair Hugger™ (3M, Maplewood, MN) to keep her temperature above 36 °C even after her other vital signs had normalized. Finally, her aripiprazole was held with the suspicion that it was causing hypothermia. Following this, her temperature improved and remained stable throughout even after discharge. Since hypothermia can be life-threatening, after ruling out common causes, clinicians should consider aripiprazole-induced hypothermia in these patients and the drug should be promptly discontinued.

Nontuberculous Mycobacterial Infection Mimicking Inflammatory Tenosynovitis: A Real Head Scratcher.

Nontuberculous mycobacterial tenosynovitis is a rare entity that is often misdiagnosed as bacterial or inflammatory tenosynovitis. We present a case of a 64-year-old man who presented with pain and swelling of his right wrist for several weeks. Magnetic resonance imaging (MRI) of his right upper extremity showed findings consistent with prominent tenosynovitis in the right extensor digitorum tendon sheath. Surgical debridement showed reactive histopathology with negative Gram stain, culture, and acid-fast bacilli stain; after which, steroids were started along with methotrexate and hydroxychloroquine, which was later changed to anti-tumor necrosis factor (anti-TNF) therapy. Due to minimal improvement, repeat operative debridement was done showing macroscopic rice bodies with pathology revealing chronic granulomatous inflammation with necrosis. However, repeated infectious work-up remained negative. After his symptoms progressed to involve his right index finger, his tenosynovium was sampled again, which was positive for acid-fast bacilli (AFB) staining for rare mycobacterial organisms, with cultures growing faint transparent colonies that were sent to the state laboratory for speciation. He was started on empiric therapy with clarithromycin, ethambutol, and rifampin following which his wound fully healed. This case illustrates the insidious course of nontuberculous mycobacteria (NTM) tenosynovitis leading to delayed diagnosis along with unwarranted treatments that could be harmful. Open tissue biopsy is important in the context of a lack of clinical response to common treatment modalities, in the absence of an alternative diagnosis with a similar clinical picture.