Pyoderma gangrenosum (PG) is a rare, chronic neutrophilic dermatosis characterized by rapidly progressive, painful ulcers. It is frequently associated with systemic inflammatory conditions such as inflammatory bowel disease. The pathogenesis remains incompletely understood, and treatment of refractory cases poses a significant challenge. We present a 26-year-old woman diagnosed with PG, initially managed with systemic corticosteroids and ciclosporin. During follow-up, she developed gastrointestinal symptoms and was subsequently diagnosed with Crohn disease (CD). Despite treatment with azathioprine, infliximab and, later, ustekinumab, the patient experienced repeated flares of both PG and CD. Upon recurrence of PG lesions and CD exacerbation under ustekinumab therapy, systemic corticosteroids were reintroduced, and subcutaneous guselkumab, an interleukin (IL)-23 p19 inhibitor, was initiated. A rapid and sustained clinical response was observed following the second dose of guselkumab, with complete ulcer healing and tapering off corticosteroids. The patient has remained in complete remission from both PG and CD for over 2 years under guselkumab monotherapy. This case adds to the growing body of evidence supporting the use of IL-23 inhibitors, particularly guselkumab, in recalcitrant PG associated with systemic inflammatory comorbidities. Guselkumab may offer a promising therapeutic alternative in the management of treatment-resistant PG, especially in patients with coexisting CD.

Broad evidence confirms that AR (ICD J30.3) is a chronic disease with high prevalence among children and adults worldwide. Its consequences, both from a public health perspective and at the level of the individual patient, are often underestimated, and the condition is inadequately treated. In addition, AR is often related to comorbidities with additional impact on diseases-severity. Allergen provocation of the easily accessible nasal (nasal allergen provocation test: NPT) or conjunctival mucosa (conjunctival allergen provocation test: CPT) reproduces the allergen-dependent, IgE-mediated allergic reaction under controlled and standardized conditions. These measures are regarded as the diagnostic gold standard, particularly in cases of unclear results in primary allergological tests, enabling clinically relevant identification of the causative allergen. Approved test allergens are critical for ensuring the methodological quality of the NPT. However, their availability is increasingly limited, although adequate quantities of allergen solutions remain indispensable for high-quality nasal allergen testing. Unilateral allergen provocation has been established in the clinical routine for decades in Germany. However, scientific evidence for unilateral application of the test allergen is pending. International position papers differ from this recommendation. The CPT is a simple, safe, and well-tolerated measure. It is primarily used in perennial and, in selected cases, seasonal allergic conjunctivitis. This method is less commonly applied for vernal keratoconjunctivitis and atopic keratoconjunctivitis. It is primarily used to confirm the underlying allergen, particularly when establishing the indication for allergen immunotherapy (AIT). It can also be employed to monitor treatment effects such as e.g., AIT or pharmacotherapy. Although highly sensitive, the procedure of nasal ASA provocation remains a time-consuming procedure. While challenging in children, NPT provides clinically relevant additional diagnostic information on the causes of the allergic symptoms. Allergological diagnostic work-up also includes pulmonary assessment, particularly in patients with established asthma or symptoms suggestive of asthma. Both AAR and PNIF are applied as standard procedures for assessing the outcome of NPT in Germany. In individual cases, other rhinometric methods may also be used.

Background Acute severe ulcerative colitis (ASUC) affects up to 25% of patients with ulcerative colitis. Despite intravenous (IV) corticosteroids as first-line therapy, 30-40% require rescue treatment and up to 40% undergo colectomy within one year. Upadacitinib (UPA) has shown ability to induce rapid response in moderate-severe UC, but real-world data in ASUC remain limited. We aimed to describe outcomes of UPA initiation for ASUC across Mayo Clinic sites. Methods We conducted a descriptive study of 23 adults hospitalized with ASUC between 2022-2025 at Mayo Clinic. Patients with their first ASUC admission who were started on UPA were included. All patients received IV methylprednisolone (40-60 mg/day) within 24-48 hours of admission, followed by UPA initiation (inpatient or shortly after discharge). Clinical, laboratory, and treatment data were extracted from electronic medical records. Outcomes included colectomy during admission and colectomy within one year. Descriptive statistics were done using Microsoft Excel. Results Twenty-three patients received UPA (median age 35 years; 88% pancolitis; 4% PSC). Out of the 23, 18 were started on UPA during the ASUC admission. Before admission, 10 patients (43%) were receiving corticosteroids, three (13%) were on mesalamine, one (4%) on azathioprine, and 12 (52%) were on biologic therapy; four patients (17%) were already on lower dose UPA maintenance. The median number of prior advanced therapies was two (range 1-4). Admission labs showed a mean CRP of 56.3 mg/L (SD 44.9) and fecal calprotectin of 2521.9 µg/g (SD 783.9). Patients received IV corticosteroids for a mean of 3.7 days (SD 1.1), and UPA was initiated at a median of hospital day 3 (IQR 4). 2/18 patients (11.1%), who were started on UPA inpatient, required colectomy during admission. Of the 23 patients who received UPA during hospitalization or shortly after discharge, one year colectomy rate was 4/23 (17%). Conclusions In this cohort, initiation of UPA during hospitalization or shortly after discharge for ASUC was feasible and was associated with lower colectomy rates compared with published outcomes for patients treated with infliximab or cyclosporine, both during hospitalization (11.1% vs. 21% vs. 25%) and at one year (17% vs. 35% vs. 45%). These findings suggest that UPA may serve as an effective rescue option for hospitalized ASUC patients, particularly when rapid control of inflammation is needed. Larger prospective studies are warranted to confirm these observations and to define optimal timing, patient selection, and long-term safety in the ASUC setting.

Medicinal mushrooms have long been used in traditional medical systems, yet their ophthalmic relevance has only recently been explored. This narrative review provides, to our knowledge, an integrative mapping of medicinal mushroom-derived bioactive compounds in ophthalmology, with particular emphasis on their level of evidence across different ocular diseases. A structured search of PubMed, Scopus, Google Scholar and ScienceDirect (2001-2026) was conducted to identify experimental, clinical, and mechanistic studies addressing antioxidant, anti-inflammatory, immunomodulatory, neuroprotective and antifibrotic pathways in ocular tissues. The findings reveal a marked heterogeneity in evidence levels. A limited subset of fungal-derived compounds - primarily antimicrobial and immunomodulatory agents such as β-lactam antibiotics, cyclosporine A, and mycophenolate mofetil - are supported by high-level clinical evidence (Level 1), while emerging evidence (Level 2) is available for compounds such as Isaria cicadae in dry eye disease and Ganoderma lucidum in age-related macular degeneration. In contrast, the majority of medicinal mushrooms - including Pleurotus spp., Hericium erinaceus, Wolfiporia extensa, and Polyporus umbellatus - remain supported mainly by preclinical studies and traditional use (Level 5 evidence). Experimental data indicate that mushroom-derived polysaccharides and triterpenoids can modulate oxidative stress, inflammation, intraocular pressure, fibrosis, and neuronal survival. Additional compounds demonstrate potential in glaucoma, cataract, and retinal disorders through multitarget mechanisms. Overall, medicinal mushrooms represent a promising but still under-validated therapeutic resource in ophthalmology. The observed disparity between traditional use, experimental evidence, and clinical validation highlights a significant translational gap, underscoring the need for standardized formulations and well-designed clinical trials to enable evidence-based integration into ophthalmic practice.

Haemophagocytic Lymphohistiocytosis (HLH) causes life-threatening hyperinflammation and has conventionally been treated with glucocorticoids plus additional immunosuppression such as ciclosporin and anakinra. We describe the case of a 47-year-old female who presented to a DGH with HLH secondary to both Systemic Lupus Erythematosus (SLE) and Covid infection. Her disease relapsed despite an initial response to first-line treatment including glucocorticoids, ciclosporin, intravenous immunoglobulins (IVIG) and conventional doses of anakinra. She subsequently responded to a higher dose of anakinra, resulting in sustained remission. This case illustrates the potentially life-saving difference between conventional and higher anakinra doses in severe HLH- an observation that is consistent with other reported cases of HLH with different triggers. We argue, therefore, for high-dose anakinra to be used first-line in refractory HLH, given the high mortality of the disease, while also carefully monitoring for infections post-interleukin-1-blockade. This adds weight to the shifting national treatment paradigm in this direction.

Backgorund/Objectives: Respiratory diseases represent a substantial global health burden and require effective localised pulmonary delivery strategies, particularly for poorly water-soluble therapeutic molecules. Nanoparticle-based drug delivery systems, especially those manufactured using microfluidics, have emerged as promising approaches to overcome pulmonary barriers, enhance local drug retention, and reduce systemic side effects. Among these nanocarriers, solid lipid nanoparticles (SLNs) and solid hybrid nanoparticles (SHNs) combine biocompatibility with controlled release and improved formulation stability. Methods: In this study, SLNs and lipid-chitosan SHNs were developed using microfluidic technology as candidate platforms for pulmonary drug delivery, with Cyclosporine A (CyA) used as a model hydrophobic cyclic peptide. Nanocarriers were produced using 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and cholesterol as lipids, with low-molecular-weight chitosan incorporated to obtain hybrid systems. Physicochemical properties were evaluated using dynamic light scattering (DLS) and ζ potential measurements, while morphology and structural organisation were investigated using transmission electron microscopy (TEM), Fourier-transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), and differential scanning calorimetry (DSC). Results: The microfluidic approach enabled the production of nanoparticles with controlled sizes below 200 nm, narrow size distributions, and good reproducibility. In addition, the SHNs exhibited a positive surface charge, high encapsulation efficiency (~80%), and good colloidal and thermal stability. In vitro release studies showed an initial burst release followed by sustained CyA release, reaching approximately 94% cumulative release within 6 h. The Korsmeyer-Peppas model was used as the standard kinetic model. No blank nanoparticles were used as controls in the EE and release assay. Conclusions: Overall, these findings support further investigation of microfluidic-produced lipid and hybrid nanoparticles as candidate platforms for pulmonary drug delivery.