SARS-CoV-2 (COVID-19) has been associated with numerous complications, including autoimmune and autoinflammatory diseases. The surge of cytokines following COVID-19 infection or vaccination has been proposed to contribute to immune dysregulation, which might subsequently give rise to an autoinflammatory syndrome. Adult-onset Still\'s disease (AOSD) is one of the rare autoinflammatory diseases characterized by a surge of cytokines. Although an association between COVID-19 vaccines and AOSD has been reported, an association with COVID-19 infection or nirmatrelvir/ritonavir remains very rare. In this case, we present a patient who developed AOSD after COVID-19 infection and subsequent treatment with nirmatrelvir/ritonavir. After the initial response to glucocorticoids, canakinumab was initiated, resulting in positive clinical outcomes.

Multiple sclerosis is a systemic autoimmune disease characterized by demyelination of nerves within the central nervous system. The prevalence of the disease is increasing. Cases with varying severity are observed. Multiple sclerosis is accompanied by severe osteoporosis, which may lead to fractures and may compromise patient mobility. The aim was to describe the case of a patient with multiple sclerosis who developed severe osteoporosis with multiple fractures. A female patient was diagnosed with multiple sclerosis at the age of 52. At the age of 63, she presented with a fracture of the right femur. She was treated surgically with total arthroplasty. Osteoporosis was diagnosed and treatment was initiated. Seven months later the patient fell upon the fractured leg and developed a periprosthetic femoral fracture. She was treated with open reduction and internal fixation. Thereafter, bisphosphonates were administered. The patient can now walk with difficulty, independently, without orthotic help. In this case report, we have presented a case of multiple sclerosis who developed severe osteoporosis with multiple fractures.

BACKGROUND: Late-onset capsule block syndrome (CBS) is a rare complication of cataract phacoemulsification and the implantation of a posterior chamber intraocular lens (PCIOL), which manifests six months to years after surgery. The hallmark of CBS is the formation of an opaque liquid substance between the implanted intraocular lens (IOL) and the posterior capsule. However, its pathogenesis remains unclear.
METHODS: A 64-year-old female patient with chronic angle-closure glaucoma (axis length < 21 mm) underwent trabeculectomy surgery combined with phacoemulsification and PCIOL. After a 4-year follow-up, a decline in visual acuity occurred in her right eye due to the location of opaque fluid in the visual axis and distension of the capsular bag. The initial course of action was to release the trapped fluid. Neodymium: yttrium-aluminum-garnet (Nd: YAG) laser capsulotomy could not be employed due to her non-dilating pupil and high extension of the posterior capsule. Subsequently, anterior capsule peeling and anterior segment vitrectomy surgery were performed. The depth of the anterior chamber (ACD), the distance between the face of the retro-IOL and the posterior capsule, the best-corrected visual acuity (BCVA), and the visual quality (VQ) were measured both before and after surgery. Inflammatory cytokine levels in the opaque substances (OS) trapped between the PCIOL and the posterior capsule were assessed using a flow cytometer and compared to normal statistical data in aqueous humor. After surgery, the patient experienced a significant improvement in BCVA and VQ. The distance between the face of the retro-IOL and the posterior capsule was on the verge of disappearing. However, ACD did not differ between pre- and post-operatively. Interleukin-8 (IL-8) and basic fibroblast growth factor (BFGF) concentrations were higher in the OS than in aqueous humor, especially in the former. However, the concentration of vascular cell adhesion molecule (VCAM) in the OS was lower than in aqueous humor.
CONCLUSIONS: Anterior segment vitrectomy surgery proved to be a successful treatment for late-onset CBS, presenting a challenging case. In the human lens, inflammatory cytokines originating from the opaque substances may contribute to abnormal metabolism in the sealed area, a consequence of late-onset CBS.

BACKGROUND: High mobility group box-1 (HMGB1) is an endogenous danger signal that mediates activation of the innate immune response including NLR pyrin domain containing 3 (NLRP3) inflammasome activation and proinflammatory cytokine release. Although HMGB1 and NLRP3 have been implicated in the pathophysiology of seizures, the correlation between HMGB1 and NLRP3 expression has not been determined in children with febrile seizures (FS). To explore the relationship between extra-cellular HMGB1 and NLRP3 in children with FS, we analyzed serum HMGB1, NLRP3, caspase-1, and proinflammatory cytokines in patients with FS.
METHODS: Thirty children with FS and thirty age-matched febrile controls were included in this study. Blood was obtained from the children with FS within 1 h of the time of the seizure; subsequently, the serum contents of HMGB1, NLRP3, caspase-1, interleukin (IL)-1β, interleukin (IL)-6, and tumour necrosis factor-α (TNF-α) were determined by enzyme-linked immunosorbent assay. The Mann‒Whitney U test was used to compare serum cytokine levels between FS patients and controls. Spearman\'s rank correlation coefficient was calculated to detect significant correlations between cytokine levels.
RESULTS: Serum levels of HMGB1, NLRP3, caspase-1, IL-1β, IL-6, and TNF-α were significantly higher in FS patients than in febrile controls (p < 0.05). Serum levels of HMGB1 were significantly correlated with levels of NLRP3 and caspase-1 (both, p < 0.05). Serum levels of caspase-1 were significantly correlated with levels of IL-1β (p < 0.05). Serum levels of IL-1β were significantly correlated with levels of IL-6 and TNF-α (p < 0.05).
CONCLUSIONS: HMGB1 is up-regulated in the peripheral serum of FS patients, which may be responsible, at least in part, for the increased expression of NLRP3 and Caspase-1. Increased expression of caspase-1 was significantly associated with elevated serum levels of IL-1β. Given that activated Caspase-1 directly regulates the expression of mature IL-1β and positively correlates with activation of the NLRP3 inflammasome, our data suggest that increased levels of peripheral HMGB1 possibly mediate IL-1β secretion through the activation of the NLRP3 inflammasome in children with FS. Thus, both HMGB1 and NLRP3 might be potential targets for preventing or limiting FS.

Psoriasis is a chronic, autoimmune, papulosquamous skin disorder, characterized by the formation of drop-like papules and silvery-white plaques surrounded by reddened or inflamed skin, existing predominantly on the scalp, knees and elbows. The characteristic inflammation and hyperproliferation of keratinocytes in psoriasis is regulated by progranulin (PGRN), which suppresses the expression and release of inflammatory cytokines, such as TNF-α.
In this study mutation analysis of the PGRN gene was performed by extracting the genomic DNA from blood samples of 171 diagnosed psoriasis patients and controls through standard salting-out method, followed by amplification and sequencing of the targeted region of exon 5-7 of PGRN gene.
Three single nucleotide polymorphisms, rs25646, rs850713 and a novel point mutation 805A/G were identified in the PGRN gene with significant association with the disease. The variant alleles of the polymorphisms were significantly distributed among cases and controls, and statistical analysis suggested that the mutant genotypes conferred a higher risk of psoriasis development and progression. Multi-SNP haplotype analysis indicated that the CAA (OR = 8.085, 95% CI = 5.16-12.66) and the CAG (OR = 3.204, 95% CI = 1.97-5.21) haplotypes were significantly associated with psoriasis pathogenesis.
These findings demonstrate that polymorphisms in PGRN might act as potential molecular targets for early diagnosis of psoriasis in susceptible individuals.

Adult-onset Still\'s disease (AOSD) is a rare systemic inflammatory disease that involves the excessive production of proinflammatory cytokines. Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening immune-mediated disorder that can be primary or secondary to malignancy, infections, and autoimmune diseases. We present an interesting case of a young female with adult-onset Still\'s disease that commenced during pregnancy. Whole-body fluorodeoxyglucose (FDG)-positron emission tomography (PET)/computed tomography (CT) scan showed diffuse uptake in the spleen and bone marrow with widespread lymphadenopathy. During the delayed diagnostic process to exclude lymphoproliferative malignancy, she developed severe HLH/macrophage activation syndrome (MAS) with multiorgan failure. In this case report, we described the challenges faced during the diagnosis of AOSD. We also highlighted the importance of using clinical criteria to aid in the early diagnosis and management of AOSD patients and the role of FDG-PET/CT scans in patients with AOSD. Additionally, we discussed the management aspects for patients with macrophage activation syndrome.

After the infection with COVID-19, pyoderma gangrenosum worsened and further led to necrosis following pyogenic osteomyelitis. Infection is a major exacerbating factor in pyoderma gangrenosum.

Cryptococcal meningitis (CM) is a central nervous system disease caused by a novel Cryptococcus infection that leads to subacute or chronic inflammatory changes in the nervous system. In this study, we present the case of a woman aged 72 years with CM and severe cognitive impairment and disabilities. The cognitive assessment indicated that, although her cognitive function was impaired, especially executive function, it largely improved after receiving anti-infectious and repetitive transcranial magnetic stimulation, which can alter the membrane potential of the cortical nerve cells by triggering long-term potentiation and depression, modulating and releasing hormones, reducing the level of neuroinflammatory and peripheral blood cytokines, promoting nerve regeneration and synaptic remodeling, and changing the activity of the neural circuitry of the dorsolateral prefrontal cortex. We argue that this case provides a novel method of treatment for patients with CM in conjunction with cognitive impairments.

Elderly people are at high risk of suffering from infection and being affected by severe forms of disease because their immunosystem suffers from aging. The alteration of normal immune functions causes the increase of pro-inflammatory cytokines which can expose these people to increased risk of developing pathologies as cancer, diabetes, and/or arthritis. Some supplements could be helpful for restoring normal immune functions. We conducted a case-control study to evaluate the efficacy of a supplement containing Sambucus nigra, zinc, tyndallized Lactobacillus acidophilus (HA122), arabinogalactans, vitamin D, vitamin E, and vitamin C to improve the inflammatory levels (IL-6 and CRP) and to modulate the lymphocytes growth. Additionally, we analyzed wellness by self-questionnaire. This study had two control group: a young group and an elderly one. Our study showed that treating elderly patients with the supplement for 30 days improved IL-6, CRP, and lymphocytes levels; the result was independent from the dosage of the supplements used. Elderly patients, despite the improvement, were not able to reach the same conditions of young patients; however, most of the patients (>70%) claimed to “feel better” after the use of the supplement. The use of this supplement should be considered at a low dosage for a prolonged period to reduce inflammation and modulate immune senescence in patients over 60 years old.

This study aimed to investigate the effect of CD36 rs1761667 gene polymorphisms on the expression of CD36 and inflammatory cytokines and the progression of Parkinson\'s disease (PD).
A total of 138 patients with PD (60 men and 78 women) and 132 healthy controls (48 men and 84 women) from a northern Han Chinese population were enrolled in this case-control study. Polymerase chain reaction-restriction fragment length polymorphism was used to detect the CD36 rs1761667 genotype. An enzyme-linked immunosorbent assay was used to determine the expression of CD36, interleukin (IL)-6, IL-1β, and tumor necrosis factor (TNF)-α in the plasma.
The frequency of the rs1761667 AA genotype was significantly higher in patients with PD than that in healthy controls, suggesting AA genotype to be a risk factor for PD. When compared with those in healthy controls, CD36 levels were significantly lower in patients with PD, whereas IL-6, IL-1β, and TNF-α levels were significantly higher in patients with PD. Furthermore, GA and AA carriers with PD showed lower levels of CD36, and GG, GA, and AA carriers showed higher levels of IL-6, IL-1β, and TNF-α than those in healthy controls. In the PD patient group, AA and GA carriers had lower expression levels of CD36 than GG carriers did, and CD36 levels were lower in AA carriers than in GA carriers. Conversely, AA carriers had elevated expression levels of IL-6 compared with that of GG and GA carriers. Logistic regression analysis revealed that IL-6, IL-1β, and TNF-α levels were risk factors for PD in a northern Han Chinese population.
The CD36 rs1761667 AA genotype may increase susceptibility to PD and the expression of inflammatory cytokines.