Effect of galectin-3, IL-1, IL-6 and TNF-alpha on disease prognosis and mortality in COVID-19 patients.

INTRODUCTION: COVID-19 is a significant cause of morbidity and mortality. It is crucial to identify biomarkers that can aid in predicting patients' prognosis and mortality. This study evaluated the relationship between galectin-3 (Gal-3), interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) levels and the prognosis and mortality of COVID-19 patients. METHODOLOGY: The study included 69 COVID-19 patients (32 outpatients, 37 inpatients) and 19 healthy controls. Gal-3, IL-1, IL-6, and TNF-α levels in serum samples were measured using an ELISA test. RESULTS: In a comparison between the patient and healthy control groups, it was observed that the patient group had significantly higher levels of Gal-3, IL-6, and TNF-α. Comparison between the outpatient and inpatient groups revealed that the hospitalized patient group had significantly higher levels of IL-6 and TNF-α, while the Gal-3 levels were lower in this group. In the analysis of subgroups to assess disease severity, critical COVID-19 patients exhibited elevated levels of Gal-3 and IL-6 compared to those with severe COVID-19. Moreover, Gal-3 and IL-6 were identified as having predictive value for mortality in hospitalized patients, while both IL-6 and TNF-α demonstrated diagnostic accuracy across all patient groups. CONCLUSIONS: The study results indicate that the levels of IL-6 TNF-α play a crucial role in determining the hospitalization and mortality of COVID-19 patients. Additionally, it was observed that Gal-3 and IL-6 levels can be utilized to assess the severity of the disease and predict mortality in patients who require hospitalization.

Effects of Apelin-13 on auditory system in STZ-induced diabetic rats.

AIM: Damage to the auditory pathways is one of the complications of diabetes. The aim of this study was to investigate the potential therapeutic effects of apelin-13 in the auditory pathways of rats with experimentally induced diabetes by examining its effect on auditory brainstem responses, cochlear oxidative stress and inflammatory cytokines. METHODS: Thirty-two male Wistar albino rats were divided into four groups: sham control, diabetes, apelin and diabetes + apelin. A single dose of 45 mg/kg streptozotocin (STZ) was administered to induce diabetes. The apelin group received 50 µg/kg apelin-13 for seven days intraperitoneally (ip). At the end of the apelin and STZ applications auditory brainstem responses (ABR) was recorded. At the end of the experiment, cochlea was removed and biochemical analyzes were performed. RESULTS: In ABR recordings, the latencies of wave V in diabetic group were observed to be longer than those of the control, with the apelin treatment exhibiting a partial reversal of this situation, particularly at specific frequencies and intensity levels. Apelin treatment leads to a significant increase in total antioxidant status (TAS) and a reduction in total oxidant status (TOS) and oxidative stress index (OSI) in cochlea compared to diabetic groups. The levels of tumor necrosis factor-alpha (TNF-alpha) and interleukin 1-beta (IL-1 beta) in cochlear tissue were found to be significantly reduced in the apelin-treated group compared to the diabetic group. CONCLUSION: Apelin-13 may have a protective effect on the auditory system and may be proposed as a potential new therapeutic strategy for the management diabetic auditory impairment.

The Effects of Brodalumab on the Fungal Microbiome in Patients with Psoriasis.

The gut microbiota plays a critical role in immune system function, with dysbiosis linked to systemic inflammation, contributing to conditions like psoriasis and depression. Although biological treatments for severe psoriasis are known to impact gut bacteria, less is understood about their effects on fungi. This study aims to investigate fungal gut microbiota changes in psoriasis patients transitioning from TNF-α inhibitors to brodalumab. Fecal samples from 20 patients were analyzed using Illumina MiSeq sequencing of the ITS2 region of 18S rRNA. Microbial diversity was assessed through Bray-Curtis dissimilarity and the Shannon-Wiener index. Clinical outcomes were measured using clinical scores for psoriasis and depression severity, with statistical analysis performed via Wilcoxon signed-rank tests and PERMANOVA. Results showed that Ascomycota was the dominant fungal phylum in both treatment groups, with Saccharomyces, Penicillium, Candida, and Debaryomyces as prevalent genera. No significant changes occurred at the phylum level after switching to brodalumab, though minor genome-level variations were observed. Beta diversity analysis highlighted inter-patient variability, with no significant correlation between fungal composition and clinical outcomes. Despite improved clinical scores, the fungal gut microbiota remained largely stable, suggesting that brodalumab does not significantly alter fungal communities in psoriasis patients. Further research is needed for a comprehensive understanding.

A Presentation of Neisseria meningitidis in a Patient Taking Adalimumab as Immunosuppressive Therapy for Hidradenitis Suppurativa.

Neisseria meningitidis is common within the human population. Most patients with N. meningitidis colonization are asymptomatic, but invasive disease can result in meningitis, fulminant septicemia, and disseminated intravascular coagulation. This case report describes a patient who presented with symptoms of sepsis and was later diagnosed with N. meningitidis. The cause of her infection was believed to be immunosuppression from adalimumab, which she was taking for systemic hidradenitis suppurativa.

Concomitant sarcoidosis, psoriasis, and eczema - immune patterns on the skin.

Sarcoidosis is a rare and elusive chronic inflammatory disease. It can manifest itself in any organ, but preferentially affects the lungs and the skin. Our case of an elderly woman with cutaneous and pulmonary sarcoidosis presented with exacerbated itchy, scaly skin changes to our department. The clinical and histopathological findings were consistent with sarcoidosis and eczematized psoriasis. The case represents a unique presentation of sarcoidosis with cutaneous involvement and poses diagnostic and therapeutic challenges due to overlapping clinical features and histology covering the three diagnoses. We discuss the immunological complexities underlying this overlap and resulting possible treatment options, highlighting the role of dermatology in systemic autoimmune diseases involving the skin and the need for pathophysiology-based tailored management approaches in these diseases.

Hailey-Hailey Disease Successfully Treated With Adalimumab: A Case Series.

Hailey-Hailey disease is an autosomal dominant disorder caused by a mutation in the ATP2C1 gene and characterized by recurrent blisters, erosions, and crust in intertriginous areas. Currently, there are no curative treatments for Hailey-Hailey disease, and therapeutic strategies are focused on controlling skin microbial colonization, infection, and inflammation. Recent efforts have aimed to find therapies that target the biochemical pathway involved in the pathogenesis of this disease. Several case reports indicate the use of different biological agents to achieve long-term remission in patients with recalcitrant Hailey-Hailey disease. Tumor necrosis factor-alpha inhibitors have been used to treat and maintain remission in recalcitrant Hailey-Hailey disease patients, but additional reporting and studies are required. In this case series, we report three cases of recalcitrant Hailey-Hailey disease whose lesions were successfully controlled with adalimumab.

Increased arterial stiffness in Crohn's disease: Prevalence, associated factors and impact of anti-TNF therapy.

INTRODUCTION: Recent studies have demonstrated the growing interest in cardiovascular risk in Crohn's disease (CD), the aim of our work is to highlight the need for research into the frequency of arterial stiffness (AS) and its link with certain associated factors, particularly those related to inflammation. MATERIALS AND METHODS: This was a cross-sectional observational study involving 118 patients with CD. Pulse wave velocity (PWV) measured by applanation tonometry was the criterion for calculating AS, the study also investigated the association of AS especially the indicators of inflammation, as well as the impact of anti-TNF alpha therapy on AS. RESULTS: The prevalence of AS, after adjustment for age and blood pressure level reached more than a quarter of patients compared to the cardiovascular risk which was low. The factors that were strongly associated with AS were age, systolic and diastolic blood pressure. Two parameters related to inflammation emerged as having a highly significant link after multivariate analysis: recurrence in the last year and length of disease with a p=0.008, and an OR of 5 and 9 successively. Patients treated with anti-TNF alpha had a significant reduction in PWV. CONCLUSION: The prevalence of AS reached more than a quarter of patients with CD, the duration and recurrence rate of CD appear to be factors linked to inflammation. Treatment with anti-TNF alpha seems to slow down PWV in these patients.

Long-term TNF-alpha therapy for preserving beta cell function in new onset type 1 diabetes: a case report.

BACKGROUND: Type 1 diabetes mellitus (T1D) is an autoimmune disease caused by destruction of pancreatic islet beta-cells. There is significant residual beta-cell function, measured through circulating C-peptide, present at the time of T1D diagnosis but this subsequently decreases with time. Higher residual beta-cell function at diagnosis associates with better glycaemic control and less glucose variability, and later in the disease course with less hypoglycaemia, lower glucose variability and fewer microvascular complications. There is therefore value in preserving residual beta cell function in new onset T1D Immunotherapeutic agents can protect residual beta-cell function in type 1 diabetes. However, clinical trials of such agents, whilst demonstrating C-peptide preservation in short term studies, have yet to be taken forward into routine clinical care due to concerns around safety and long-term efficacy. Here we report the case of a gentleman with newly diagnosed T1D whose glycaemic control and insulin requirement improved whilst on a five year infusion programme of infliximab, a monoclonal antibody against TNF-alpha, for colitis. CASE PRESENTATION: A 52-year-old White Caucasian man was diagnosed with T1D in August 2018. Glucose was 25.6 mmol/L, HbA1c was 98mmol/mol and GAD antibodies were strongly positive. HbA1c marginally improved to 91mmol/mol following initiation of insulin detemir 5 units at night and 1:10 g of insulin aspart (November 2018). In June 2019, he developed rectal bleeding and abdominal pain. Following colonoscopy, he was diagnosed with "indeterminate colitis" and commenced on 6-weekly infusions of 400-450 mg infliximab. Thus far, he has received 32 doses and achieved colitis remission. Following infliximab initiation there was increased frequency of mild-moderate hypoglycaemia and he was gradually weaned off and discontinued detemir in June 2020. Since then, HbA1c improved from 57mmol/mol in August 2019 to 52mmol/mol in April 2022, remaining stable at 51mmol/mol. His most recent HbA1c is 54mmol/mol in February 2024. His c-peptide was 550pmol/L in October 2022 and 442pmol/L in February 2024, suggesting well-preserved beta-cell function almost 6 years post-diagnosis. CONCLUSIONS: Our patient's improvement in glycaemic control can be explained by immunomodulation and C peptide preservation from infliximab. With the growing focus on type 1 diabetes disease modulation and working towards an 'insulin free T1D', our findings strengthen the evidence base for the repurposing of and long-term treatment with anti-TNF-α agents to preserve beta-cell function in new onset T1D.

Current Practices and Emerging Therapies to Optimize Heart Failure Management in Cardiac Sarcoidosis: A Systematic Review.

Cardiac sarcoidosis (CS) is a distinctive manifestation of sarcoidosis, a multisystemic inflammatory disorder that is characterized by non-necrotizing granulomas. CS can lead to arrhythmias, heart failure (HF), and sudden cardiac death. The diagnosis of CS involves imaging in the form of a two-dimensional echocardiogram, cardiac magnetic resonance imaging (MRI), an 18-fluoro-deoxyglucose positron emission tomography (FDG-PET) scan, and an endomyocardial biopsy. Treatment of CS entails corticosteroids, immunosuppressive agents, monoclonal antibodies, and, in advanced cases, heart transplantation (HTx). This systematic review follows Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines, focusing on HF in sarcoidosis patients. Eligibility criteria include recent (2019-2024) research papers on sarcoidosis-induced heart failure, excluding other causes. The databases searched were PubMed, Google Scholar, and ScienceDirect. From 36,755 initial articles, 2,060 remained after filtering, and 17 were selected for quality assessment. Based on quality assessment, 11 studies were included in the final review. In CS, a variety of treatment strategies can be implemented. Corticosteroids are the first-line therapeutic options, and in the majority of cases, they are very successful in controlling the disease progression. Immunosuppressive agents like methotrexate and azathioprine are used to avoid long-term steroid use. Both corticosteroids and immunosuppressives act by reducing inflammation and preventing myocardial scarring. Biological agents like infliximab and adalimumab prevent disease progression by targeting specific inflammatory pathways and are used in refractory cases. Regular HF management drugs like angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), sodium-glucose transport protein 2 (SGLT2) inhibitors, beta-blockers, and diuretics help in optimizing cardiac function. In severe cases, a left ventricular assist device (LVAD) may be required. The ultimate treatment for end-stage CS is HTx, which has to be supplemented with a strong, individualized regimen of glucocorticoids and immunosuppressives to avoid graft rejection and to control sarcoidosis. Due to a lack of standard protocols for management and limited knowledge about CS, the ideal treatment of HF is still a matter of debate. Hence, further research and clinical trials need to be performed to optimize patient outcomes.

Saponins alleviate intestinal inflammation and regulate intestinal metabolic disorders induced by dextran sulfate sodium: TNF-α protein action.

Intestinal inflammation is a common feature of many digestive diseases, and intestinal metabolic disorders further aggravate the pathological state. The aim of this study was to investigate the regulatory effect of saponins on TNF-α protein and its effect on intestinal metabolism in the model of intestinal inflammation induced by sodium dextran sulfate. Through cell culture and biochemical detection, appropriate cell lines were selected to simulate intestinal inflammatory environment, induce inflammatory response, observe cell morphological changes and growth status, and evaluate the protective effect of TNF-α protein on cells. The level of TNF-α protein was quantitatively determined by biochemical assay, and the effect of saponins on its secretion and activity was investigated. Saponin treatment can restore the expression of intestinal metabolism-related enzymes and improve metabolic disorders. Therefore, by regulating the expression of TNF-α protein and its signaling pathway, saponins show a alleviating effect on intestinal inflammation and help restore intestinal metabolic balance.

Immunological Biomarkers in Autism Spectrum Disorder: The Role of TNF-Alpha and Dependent Trends in Serum IL-6 and CXCL8.

BACKGROUND: Autism spectrum disorder (ASD) has seen a rise in prevalence, and the immune system's role in brain development is increasingly recognized. This study investigates the relationship between immune dysregulation and ASD by examining serum concentrations of interleukin 6 (IL-6), interleukin 8 (CXCL8), and tumor necrosis factor alpha (TNF-alpha) in children. METHODS: Serum samples from 45 children with ASD and 30 controls, aged 2 to 12 years, were analyzed using electrochemiluminescence, chemiluminescent microparticle immunoassay, and chemiluminescent immunoassay. ASD symptoms were assessed using the Autism Spectrum Rating Scale (ASRS) and Social Communication Questionnaire (SCQ). RESULTS: No significant correlation was observed between CXCL8 levels and ASD. IL-6 levels showed a trend toward elevation in boys with ASD. TNF-alpha levels were significantly higher in children with ASD under 5 years compared to older children and controls, though no correlation with symptom severity was found. CONCLUSIONS: TNF-alpha may be a potential biomarker for early ASD detection, especially in younger children. Further research on larger cohorts is needed to understand the role of immune dysregulation in ASD.

The Value of C-Reactive Protein and Peritoneal Cytokines as Early Predictors of Anastomotic Leak after Colorectal Surgery.

OBJECTIVES: The aim of this study was to evaluate the accuracy of serum C-reactive protein (CRP) and intraperitoneal CRP, interleukin-6, and tumor necrosis factor-alpha in early diagnostics of anastomotic leakage in the first 4 postoperative days after colorectal surgery. METHODS: Between January 2023 and June 2023, one hundred patients with colorectal carcinoma were operated on with primary anastomosis. Ten patients had anastomotic leak (10%). RESULTS: Based on serum CRP, a patient with a leak will be detected with a 78% probability on postoperative day 3 with values above 169.0 mg/L and on postoperative day 4 with values equal to 159.0 mg/L and above. Intraperitoneal CRP values greater than 56 mg/L on the fourth postoperative day indicate a 78% probability of a diagnosis of leakage. An anastomotic leak will be detected with a 70.0% probability based on an IL-6 value on the first day, at a cut-off value of 42,150. The accuracy of TNF-alpha in predicting anastomotic leak in the first two days is 70% at values higher than 78.00 on the first and 58.50 on the second postoperative day. CONCLUSION: In this study serum CRP proved to be the most accurate in predicting anastomotic dehiscence after colorectal surgery.

Anti TNF-Alpha Treatment Improves Microvascular Endothelial Dysfunction in Rheumatoid Arthritis Patients.

Nailfold capillaroscopy is a non-invasive investigation, which allows for the study of the microvasculature (anatomical and functional). Rheumatoid arthritis (RA) is associated with a high risk of cardiovascular atherosclerotic diseases, with endothelial dysfunction (macrovascular and microvascular) representing the first step in atherosclerosis development. The aim of this study is represented by the assessment of microvascular endothelial dysfunction in RA patients by means of nailfold capillaroscopy and to assess its evolution after a period of 12 months of anti TNF-alpha treatment. The study included 70 consecutive patients with RA and 70 healthy subjects, matched for age and gender, as the control group. Rheumatoid factor, anti-cyclic citrullinated peptide antibodies, serum TNF-α, C reactive protein, and erythrocytes sedimentation rate were evaluated in all patients, but in controls, only rheumatoid factor, serum TNF-α, C reactive protein, and erythrocytes sedimentation rate were measured. The RA activity was measured by DAS28. Nailfold capillaroscopy was carried out in all patients and controls, determining the baseline nailfold capillary density (Db), nailfold capillary density during reactive hyperemia (Dh), and nailfold capillary density after venous congestion (Dc). Data were presented as mean ± standard deviation. Statistical analysis was performed using ANOVA and Pearson's correlation, with p < 0.05 being statistically significant. Db, Dh, and Dc were lower in RA patients than in controls (p < 0.0001), correlating with RA activity and TNF-α (p < 0.05). After 12 months of anti TNF-α treatment, microvascular endothelial dysfunction improved (p < 0.0001). Microvascular endothelial dysfunction can be assessed by nailfold capillaroscopy, with anti TNF-α medication contributing to its improvement.

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.

Insulin Resistance in Women Correlates with Chromatin Histone Lysine Acetylation, Inflammatory Signaling, and Accelerated Aging.

BACKGROUND: Epigenetic changes link medical, social, and environmental factors with cardiovascular and kidney disease and, more recently, with cancer. The mechanistic link between metabolic health and epigenetic changes is only starting to be investigated. In our in vitro and in vivo studies, we performed a broad analysis of the link between hyperinsulinemia and chromatin acetylation; our top "hit" was chromatin opening at H3K9ac. METHODS: Building on our published preclinical studies, here, we performed a detailed analysis of the link between insulin resistance, chromatin acetylation, and inflammation using an initial test set of 28 women and validation sets of 245, 22, and 53 women. RESULTS: ChIP-seq identified chromatin acetylation and opening at the genes coding for TNFα and IL6 in insulin-resistant women. Pathway analysis identified inflammatory response genes, NFκB/TNFα-signaling, reactome cytokine signaling, innate immunity, and senescence. Consistent with this finding, flow cytometry identified increased senescent circulating peripheral T-cells. DNA methylation analysis identified evidence of accelerated aging in insulin-resistant vs. metabolically healthy women. CONCLUSIONS: This study shows that insulin-resistant women have increased chromatin acetylation/opening, inflammation, and, perhaps, accelerated aging. Given the role that inflammation plays in cancer initiation and progression, these studies provide a potential mechanistic link between insulin resistance and cancer.

Long-term outcomes of infliximab treatment in neuro-Behcet syndrome: A single-center retrospective study.

INTRODUCTION: Behcet's syndrome is a rare inflammatory disorder characterized by oral and genital ulcers, skin lesions, and uveitis. It exhibits a higher prevalence along the historic Silk Road. Neuro-Behcet syndrome (NBS) affects the central nervous system and poses significant morbidity and mortality risks. Infliximab, a TNF-alpha antagonist, has shown potential in NBS management, although the current evidence is mainly derived from case series due to the lack of randomized controlled trials. OBJECTIVE: This retrospective study aimed to evaluate the disease outcomes during the first and second years following infliximab treatment in NBS patients experiencing attacks despite prior conventional immunosuppressive therapy. The study also sought to investigate the safety profile and adverse effects associated with infliximab. METHODS: Fifty-three NBS patients were examined, with 22 receiving infliximab as either monotherapy or in combination with other therapies. Retrospective analysis was conducted on demographic data, clinical characteristics, and treatment responses. Treatment efficacy was measured using the Expanded Disability Status Scale (EDSS) modified for NBS. The study adhered to the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) checklist guidelines. RESULTS: Among the study cohort, 60.4% had parenchymal NBS, and 39.6% had nonparenchymal NBS. Treatment with infliximab resulted in remission or disease stabilization in 95% of patients after one year and 68.7% after 2 years. Relapse rates were 4.5% at 1 year and 18.7% at 2 years, with disease progression observed in two cases. Adverse effects were primarily mild to moderate, with no reports of serious adverse events. CONCLUSION: Infliximab exhibited efficacy in achieving remission or stabilization in NBS patients, maintaining a favorable safety profile. The timing of infliximab treatment may prevent the accumulation of disability and hinder disease progression. Nonetheless, future prospective studies are necessary to confirm these findings and refine treatment strategies for this complex condition.

Update on non-infectious uveitis treatment: anti-TNF-alpha and beyond.

Non-infectious uveitis (NIU) encompasses a range of conditions marked by inflammation within various layers of the eye. NIU is a significant contributor to irreversible vision loss among the working-age population in developed countries. The aim of treating uveitis is to manage inflammation, prevent its recurrences and to restore or salvage vision. Presently, the standard treatment protocol for NIU involves initiating corticosteroids as the primary therapeutic agents, although more aggressive approaches and steroid sparing agent may be necessary in certain cases. These advanced treatments option include synthetic immunosuppressants like antimetabolites, calcineurin inhibitors and alkylating agents. For patients who exhibit an intolerance or resistance to corticosteroids and conventional immunosuppressive therapies, biologic agents have emerged as a promising alternative. Notably, among the biologic treatments evaluated, TNF-α inhibitors, anti-CD20 therapy and alkylating agents have shown considerable efficacy. In this review, we delve into the latest evidence surrounding the effectiveness of biologic therapy and introduce novel therapeutic strategies targeting immune components as potential avenues for advancing treatment of NIU.

How comparative studies can inform treatment decisions for Crohn's disease.

INTRODUCTION: As new therapies for the treatment of Crohn's disease (CD) are approved, there is an increasing need for evidence that clarifies their positioning and sequencing. AREAS COVERED: Comparative effectiveness research (CER) aims to inform physicians' decisions when they choose which intervention (drug or treatment strategy) to administer to their patients. Pragmatic head-to-head trials represent the best tools for CER, but only a few have been published in the IBD field. Network meta-analyses can point toward the superiority of one drug over another, but they do not reflect everyday clinical practice. Finally, real-world evidence complements that coming from head-to-head trials and network meta-analyses, assessing the real-life effectiveness of therapeutic interventions. EXPERT OPINION: There is insufficient evidence to create a definitive therapeutic algorithm for CD, but some general considerations can be made. Anti-TNF-α agents seemingly represent the most 'sustainable' first-line choice, considering benefit-harm ratio and costs; vedolizumab, ustekinumab, and risankizumab may be considered as first-line choice when safety issues become prominent. In the event of pharmacodynamic failure, out-of-class swap is to be preferred - possibly with anti-IL23p19 as the best option, with unclear data regarding upadacitinib positioning; a second anti-TNF-α could be considered, as a second choice, after pharmacokinetic failure.

Pediatric cutaneous Crohn disease: A case series of 89 patients and review.

BACKGROUND: Cutaneous (or "Metastatic") Crohn disease (CCD) is a rare and underrecognized disease characterized by cutaneous granulomatous inflammation. We describe patient demographics, clinical characteristics, histology, and treatment of 89 pediatric cases of CCD, including 78 previously reported and 11 new cases seen at four academic institutions. We emphasize the efficacy of biologic mono- and dual therapy. METHODS: PubMed identified cases using keywords including "metastatic Crohn disease" and "cutaneous Crohn disease". Patients were identified by retrospective review of the electronic health record including histopathologic diagnosis consistent with CCD. Chart review collected demographic, clinical, and histologic data. RESULTS: Most pediatric patients with CCD are male 55% (49/89), present with edema (73/89, 82%) and erythema (47/89, 53%) of the genitals (33/49, 67%), and have intestinal Crohn disease (69/89, 78%). Oral corticosteroids (53/75, 71%) and metronidazole (29/75, 39%) are the most frequently prescribed medications. Of the 17 patients treated with tumor necrosis factor (TNF)-blockade, 94% (16/17) had partial or total clearance. Ustekinumab resulted in clearance of cutaneous disease in two patients (2/3, 67%) and partial clearance in one patient (1/3, 33%). Two cases achieved total clearance with the use of dual biologic therapy defined as the use of two biologic therapies with differing mechanisms of action or the use of a biologic therapy and small molecule inhibitor. CONCLUSIONS: TNF blockade is an effective treatment for pediatric CCD, and interleukin-12/23 inhibitors may be similarly effective. Consideration of dual biologic therapy may be useful in pediatric patients requiring discordant therapies for their intestinal and cutaneous CD.