Incidence and risk factors for invasive fungal infections in patients initiating TNF-alpha inhibitors for inflammatory bowel disease and rheumatoid arthritis.

In a commercial claims database analysis, <0.5% of patients with inflammatory bowel disease or rheumatoid arthritis developed an IFI within one year of initiating TNF-alpha therapy. Histoplasmosis was the most common IFI type. Overall IFI incidence varied based on region, underlying conditions, and use of certain immunosuppressive medications.

Paradoxical and bimodal immune-mediated dermatological side effects of TNF-α inhibitors: A comprehensive review.

INTRODUCTION: Due to the increasing prevalence of immune-mediated diseases such as psoriasis, lichen planus, rheumatoid arthritis and inflammatory bowel disease, dermatologists have turned to new biologic drugs known as DMARDs (disease-modifying anti-rheumatic drugs) in recent years. AREAS COVERED: In this study, we evaluate the immune-mediated dermatological side effects of DMARDS by reviewing and analyzing previous peer-reviewed research on the effects of TNF-α inhibitors in the treatment of skin diseases, as well as adverse effects of these drugs and some of the main causes of these effects. EXPERT OPINION: DMARDs are very effective in improving control of the above diseases. TNF-α inhibitors are an important group of DMARDs that are widely used. The paradoxical adverse events (PAEs) associated with the use of TNF-α inhibitors are divided into three categories: true paradoxical, borderline paradoxical, and non-paradoxical. True PAEs include conditions for which TNF-α inhibitors are approved for treatment. Borderline PAEs are considered to occur with this class of drugs for which there is no definite approval but for which there is sufficient evidence. Although these events are rare, early recognition of the accused drug and appropriate decision-making may prevent progression of complications and irreversible side effects.

Loeffler's Endocarditis- A cause of endomyocardial fibrosis in a patient of juvenile idiopathic arthritis: A Case Report.

Endomyocardial fibrosis secondary to hyper-eosinophilic syndrome also known as Loeffler's Endocarditis is a rare cause of restrictive cardiomyopathy. If left untreated, it carries a very high morbidity and mortality rate. The case of a 20 years old girl, a known case of polyarticular juvenile idiopathic arthritis since the age of 13 years was reported at Federal Government Polyclinic Hospital, Islamabad on 14th May 2022. She presented with an acute history of shortness of breath and cough for two weeks. Her initial echocardiogram showed suspicion of Loeffler's Endocarditis, which is attributed to be an adverse effect of etanercept- a tumour necrosis factor (TNF) inhibitor, which she had been prescribed for her arthritis. The patient is currently being managed with high doses of steroids, therapeutic anticoagulation with rivaroxaban, carvedilol for tachycardia and mycophenolate mofetil as an immunosuppressant.

The predictors of paradoxical reactions, especially psoriasis, to biologic therapy-findings from the TReasure database: a 5-year follow-up study.

OBJECTIVES: The objectives of this study were to assess the clinical characteristics, predictive factors, and practical algorithms of paradoxical reactions (PRs), specifically paradoxical psoriasis (PP). METHODS: The TReasure database is a web-based prospective observational cohort comprised of patients with RA and SpA from 17 centres around Turkey since 2017. A cohort study and a case-control study nestled within the cohort were identified. RESULTS: In total, 2867 RA and 5316 SpA patients were evaluated. The first biologic agent was found to have caused PRs in 60% of the 136 patients (1.66%) who developed the PRs. The median time interval between the PRs and biological onset was 12 months (range 1-132 months, mean 21 months). The most common types of PP, constituting 92.6% of PRs, were pustular (60.3%) and palmoplantar (30.9%). Adalimumab (30.9%), infliximab (19%) and etanercept (17.4%) were the most common agents causing the PP. In the treatment of most PP patients (73.2%), switching biologic agents was favoured, with TNF inhibitor (TNFi) chosen in 46.03% and non-TNFi in 26.9% of cases. The three most frequently selected drugs were etanercept (24.6%), secukinumab (9.5%) and adalimumab (8.7%). Only 5.17% of patients who switched to another TNFi showed progression. The odds ratios (s) for SSZ, HCQ, and LEF use were significantly higher in RA controls than in PP patients (P = 0.033, OR = 0.15; P = 0.012, OR = 0.15; and P = 0.015, OR = 0.13, respectively). In the PP group with SpA, the number of smokers was significantly higher (P = 0.003, OR: 2.0, 95% CI: 1.05, 3.81). CONCLUSION: Contrary to expectations based on earlier research suggesting that paradoxical reactions develop with the class effect of biological agents, the response of patients who were shifted to another TNFi was favourable.

Adamantiades-Behçet's disease therapy: current treatment options and recommendations with regard to the COVID-19 pandemic.

Adamantiades-Behçet's disease (ABD) is a chronic, idiopathic, relapsing immune-mediate disease that may involve multiple organs. It is characterized by recurrent oral and genital ulcers, skin lesions, ocular, gastrointestinal, vascular, neurological and joint involvement. It can lead to significant morbidity and mortality. Due to its heterogeneity in clinical findings and physiopathology, its treatment can be various as ABD manifestations in different organs may differently respond to the same drug. The cornerstone of therapy for inducing remission is systemic corticosteroid, whereas immunomodulatory and immunosuppressive agents such as colchicine, azathioprine, cyclosporine-A, interferon-alpha, and cyclophosphamide are used as steroid-sparing agents and to prevent relapses. For aggressive, refractory or frequently relapsing cases, tumor necrosis factor (TNF) alpha inhibitors (infliximab, adalimumab, etanercept) have been reported beneficial. Herein, we describe our experience of 7 patients treated with TNF-alpha inhibitors with recommendations regarding treatment choice during the COVID-19 era.

[Genetically engineered biological agents in the treatment of uveitis in patients with ankylosing spondylitis (clinical observations)]. / Genno-inzhenernye biologicheskie preparaty v lechenii uveita pri ankiloziruyushchem spondilite (klinicheskie nablyudeniya).

The article describes clinical cases with effective use of some genetically engineered biological agents for arresting and preventing uveitis attacks, and discusses the potential usage of tumor necrosis factor (TNF)-alpha inhibitors and interleukin-17 inhibitors in the treatment of uveitis in patients with ankylosing spondylitis.

Pathological findings in central nervous system demyelination associated with infliximab.

BACKGROUND: Tumor necrosis factor alpha (TNF-alpha) inhibitors, such as infliximab, are commonly used to treat rheumatoid arthritis (RA) and other immune-mediated disorders. OBJECTIVE: To determine whether infliximab-associated central nervous system (CNS) demyelination can be differentiated from multiple sclerosis (MS). METHODS: We present a case of pathologically proven CNS demyelination in a patient treated with infliximab and describe clinical-radiographic-neuropathological findings. Putative mechanisms of TNF-alpha inhibitor-associated CNS demyelination are described. RESULTS AND CONCLUSION: Infliximab treatment is associated with CNS inflammatory demyelinating activity, which is histopathologically indistinguishable from MS.

Biologic Treatment in Elderly Patients With Psoriasis: A Systematic Review.

With our aging population, an increasing number of psoriasis patients are classified as elderly. However, psoriasis treatment in older adults can be challenging, given an increased number of comorbid conditions and immunosenescence. Biologic agents present a solution to this treatment dilemma because of their high efficacy and favorable tolerability. The objective of this systematic review was to summarize the findings of clinical trial and real-world studies exploring the safety and efficacy of biologic agents in elderly patients with moderate-to-severe psoriasis. We searched MEDLINE, Embase, the Cochrane Library, and clinical trial databases. Studies analyzing biologics for psoriasis were included if elderly patients were the main population of interest or were a separate subgroup in their analysis. Eighteen articles met inclusion criteria after screening. Across all biologic classes, efficacy for biologics between nonelderly adult patient and elderly patients was similar. Adverse events (AEs) and infections occured at a similar frequency between both groups. However, serious AEs were more common in the elderly. The available literature on the safety and efficacy of biologic agents in elderly patients supports the use of these agents in this population. However, serious AEs and discontinuation due to AEs were more common in older patients. As elderly patients have a higher burden of comorbid conditions and an increased baseline vulnerability for AE, physicians should continue to be prudent in screening before initiating biologics and monitor patients more closely as AEs tend to be more severe.

[Psoriasis therapy in pregnancy : Consultation of pregnant patients]. / Systemische Psoriasistherapie während der Schwangerschaft : Individuelle Beratung von schwangeren Patientinnen.

Systemic therapy of pregnant patients with psoriasis requires special attention and has to be adapted to disease activity throughout the pregnancy. With the approval of the first tumor necrosis factor alpha inhibitors for the treatment of these patients, a new range of options has to be discussed with the women. If the inflammatory presentation of the psoriasis demands systemic therapy, the decision for treatment should be made as early as possible, preferably before the onset of pregnancy.

The use of etanercept for treatment of toxic epidermal necrolysis when toxic shock syndrome is in the differential.

Toxic shock syndrome (TSS) can sometimes mimic Steven Johnsons syndrome/toxic epidermal necrolysis (SJS/TEN). Tumor necrosis factor (TNF) alpha is thought to play a role in the pathogenesis of both TSS and SJS/TEN. Etanercept, a TNF-alpha inhibitor has been recently shown to treat and decrease mortality of SJS/TEN. We report a 51-year-old female with history of SJS presenting with painful skin and bullae 2 days following cystoscopy with botulinum toxin injection into the bladder. Due to initial concern for SJS/TEN, the patient was treated with 50 mg of subcutaneous etanercept. Punch biopsies were not consistent with SJS, and the patient fulfilled five out of five criteria for a confirmed case of TSS. The patient ultimately had a favorable outcome despite etanercept treatment. Ultimately, TNF-alpha antagonists are an emerging therapy to treat SJS/TEN, and are unlikely to worsen TSS prognosis. Given that etanercept can be used to successfully treat SJS/TEN and TNF-alpha levels are elevated in TSS, if a dermatologist chooses to treat TEN with etanercept, consideration of TSS on the differential should not necessarily exclude etanercept as a reasonable treatment option.

[Application of TNF-alpha inhibitors in treatment of uveitis associated with ankylosing spondylitis]. / Primenenie ingibitorov FNOα v terapii uveitov, assotsiirovannykh s ankiloziruiushchim spondilitom.

Uveitis is one of the most frequent extraskeletal manifestations of ankylosing spondylitis (AS). Despite iridocyclitis being the most prevalent form of uveitis in patients with AS, and the rareness of the involvement of posterior eye segments in the inflammatory process, the frequent exacerbation of the disease, a significant number of patients develop complications that lead to decrease of visual acuity. The review features theoretical prerequisites for application of tumor necrosis factor alpha (TNF-alpha) inhibitors: infliximab, adalimumab and etanercept. Literature data speaks for high efficacy of TNF-alpha inhibitors in prevention and arrest of uveitis onset in patients with AS.

Fungal Infections and New Biologic Therapies.

The development of biologic therapies targeting proinflammatory mediators has led to significant advances in the treatment of immune-mediated inflammatory diseases (IMIDs). Blocking undesired inflammatory effects also has the potential to disrupt the body's immune response and increase the risk for infections, including fungal infections. This review summarizes the published data on the frequency and risk for fungal infections among patients treated with biologics, with a focus on the newer therapies approved for use with IMIDs in the last 10 years. The use of biologics is associated with a small but important risk of fungal infections. Pneumocystis jirovecii pneumonia, histoplasmosis, and candidiasis are some of the most common fungal infections associated with biologics. Providers should be vigilant for fungal infection among patients taking biologics, be aware that biologic agents may alter the typical presentation of fungal infections, and take timely steps to diagnose and treat fungal infection to reduce resultant morbidity and mortality.

Protothecosis in hematopoietic stem cell transplantation: case report and review of previous cases.

Prototheca species are achlorophyllus algae. Prototheca wickerhamii and Prototheca zopfii cause human disease. In immunocompetent individuals, they cause soft tissue infections and olecranon bursitis, but in transplant recipients, these organisms can cause disseminated disease. We report a fatal case of disseminated P. zopfii infection in an hematopoietic stem cell transplant (HSCT) recipient with bloodstream infection and involvement of multiple soft tissue sites. We review all previous cases of protothecosis in HSCT reported in the literature. Protothecosis is uncommon after HSCT, but has a disseminated presentation that is frequently fatal. It is commonly misidentified as a yeast. Tumor necrosis factor-alpha inhibitors and contamination of central venous catheters may contribute to development of protothecosis. Optimal treatment approaches are yet to be defined. New agents such as miltefosine may be possible future therapies.

Effects of TNF-alpha inhibitors on circulating Th17 cells in patients affected by severe psoriasis.

Psoriasis was previously considered to be mostly a Th1 cell-related disorder, but Th17 cell has recently emerged as an important player in the pathogenesis of psoriasis. The Th17 immune pathway is increased in psoriatic patients, both in peripheral circulation and in skin lesions, and positively correlates with the Psoriasis Area and Severity Index. Anti-tumor necrosis factor alpha (TNF-α) agents, in addition to potent inhibition of TNF-α activity, are able to decrease IL-17 levels and Th17 cells in the skin and plasma of patients with moderate-to-severe psoriasis. We found a decrease in the median Th17 cell count in peripheral blood after 4 months' therapy with anti-TNF-α compared with baseline values, but the difference did not reach statistical significance, probably due to the small cohort size. Our data suggest that anti-TNF-α treatment for psoriasis is able to achieve a substantial Th17 cell count reduction in the peripheral blood of patients and that this decrease is significantly associated with an adequate response to biologic therapy, as previous studies in rheumatoid arthritis have shown.

Adalimumab as treatment for neurosarcoidosis: A case series.

Sarcoidosis is a disease characterized by non-caseating granulomas that can involve the central nervous system as neurosarcoidosis. This challenging disease is currently managed with high dose steroids, and sometimes the addition of infliximab. Other TNA-alpha inhibitors have not been studied as rigorously. We discovered ten neurosarcoidosis patients who were on an alternative TNA-alpha inhibitor, adalimumab. Eight patients had a positive response clinically and radiographically to adalimumab.

Should Histoplasmosis be Screened for Before Initiation of Tumour Necrosis Factor Alpha Inhibitors?

Histoplasmosis is a soil-based dimorphic fungus endemic to the Midwest and Southeastern United States and is responsible for infection through inhalation of conidia. Infection is usually asymptomatic, as the fungal growth is contained by formation of granulomas. However, dissemination can occur in immunocompromised hosts due to the lack of optimal activity of interferon gamma, tumour necrosis factor alpha (TNF-alpha) and interleukin-17. There is a significant overlap between the symptomatology of histoplasmosis and granulomatosis with polyangiitis (GPA). We report a case of a 48-year-old female who presented with high-grade fever, worsening generalised weakness and tachycardia. She had a previous history of bilateral cavitary lung lesions for which she was evaluated at an outside facility. As her entire infectious investigation was negative and found to be positive for antineutrophil cytoplasmic antibody (ANCA), a diagnosis of GPA was made, and she was initiated on rituximab infusions 7 weeks prior to her presentation to our facility. Repeat infectious investigations at our facility were positive for (1-3)-ß-D-glucan test and urine histoplasma antigen. Prompt discontinuation of rituximab and initiation of systemic antifungal therapy led to clinical improvement. Based on this experience, we highlight the association of histoplasma with ANCA positivity along with the importance of closely monitoring these patients for possible clinical worsening after the initiation of TNF-alpha inhibitors, despite the negative infectious work-up. Also routine screening or pre-emptive therapy for histoplasmosis before the initiation of TNF-inhibitors is not recommended. LEARNING POINTS: Histoplasmosis is associated with ANCA positivity.Despite the negative investigations for histoplasmosis and criteria for GPA being met, patients should be closely monitored for possible clinical worsening after the initiation of immunosuppressive therapy, especially TNF-alpha inhibitors.Current guidelines are not recommending routine screening or pre-emptive therapy for histoplasmosis before initiation of TNF-alpha inhibitors.

Facial Hyperpigmentation: A Rare Side Effect of Adalimumab.

This report describes a case of facial hyperpigmentation in a patient with Crohn's disease receiving adalimumab, a tumor necrosis factor (TNF)-alpha inhibitor. The onset of hyperpigmentation coincided with adalimumab administration, and its discontinuation resulted in significant improvement. Histopathological findings suggest a postinflammatory process at the dermo-epidermal junction. However, the precise mechanism remains unclear.

A retrospective analysis of mortality risk and immunosuppressive therapy for Stevens-Johnson Syndrome and toxic epidermal necrolysis syndrome using the TriNetX research network.

Stevens-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN) exist on a spectrum of autoimmune conditions which cause epidermal detachment and keratinocyte necrosis. Due to the rare incidence of these conditions, a dramatic heterogeneity in treatment algorithms exists. To better appreciate pharmacologic immunosuppressive therapies' impact on survival, the authors queried a multi-institutional data network. Data for this study was extracted from TriNetX Research Network, a platform that contains ICD-9/ICD-10 coding data from a consortium of international healthcare organizations. Seventy-one institutions were queried to identify adult patients diagnosed with SJS, TEN or SJS-TEN Overlap. Cohorts were created based on the therapy received: systemic steroids (SS), diphenhydramine (DH), cyclosporine (CS), intravenous immunoglobulin (IVIG), tumor necrosis factor alpha inhibitors (TNFαi), or a combination of treatments. Cohorts were then propensity matched with patients who received supportive care. Patients who only received one of the above treatments showed no significant reduction in 90-day mortality. Patients who received CS or IVIG as part of their multitherapy showed a significantly increased risk of death when compared to supportive care (CS: RR = 1.583, 95% CI [1.119, 2.240]; IVIG: RR = 2.132, 95% CI [1.485, 3.059]). Despite their frequent utilization, this study's analysis suggests that none of these therapies confer significant 90-day mortality survival over supportive care alone. These results highlight the heterogeneity of therapies and emphasize the need for critical prospective appraisal of their outcomes in SJS and TEN.