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Schistosomiasis causes severe hepatic fibrosis, making it a global health issue. Moringa oleifera seed oil extract, which had antiparasitic, anti-inflammatory and antioxidant effects, was investigated as an alternative treatment. The 50 mice were divided into control, infected, praziquantel-treated, M. oleifera seed oil extract-treated and combined treatment groups. These treatments were examined for their effects on egg granulomas, hepatic enzymes, total protein, albumin, antioxidant enzymes and pro-inflammatory cytokines. M. oleifera seed oil and/or PZQ significantly reduced egg numbers, granuloma size and liver histopathology. M. oleifera seed oil reduced hepatic enzyme activity, increased total protein and albumin, and increased antioxidant enzyme activity while decreasing malondialdehyde. M. oleifera seed oil reduced the levels of pro-inflammatory cytokines. M. oleifera seed oil may treat schistosomiasis instead of PZQ due to its antifibrotic, immunomodulatory and schistosomicidal properties., (© 2024 John Wiley & Sons Ltd.)

Praziquantel (PZQ) is the standard treatment for schistosomiasis; however, it is poorly effective on immature and juvenile worms. The present study aimed to evaluate the therapeutic efficacy of praziquantel loaded-chitosan nanoparticles (PZQ-CSNPs) on the 25 days old juvenile Schistosoma mansoni worms compared to PZQ and chitosan nanoparticles (CSNPs). It was conducted on 60 Swiss albino mice, including 20 control and 40 experimental mice. The control groups included healthy uninfected and infected non-treated mice. The experimental groups included mice infected treated on the 25th day with 400 mg/kg PZQ, 30 mg/kg CSNPs, 100 mg/kg, and 400 mg/kg PZQ-CSNPs. The results revealed that PZQ-CSNPs (100, 400 mg/kg) gave the best results substantiated by a remarkable decrease in worm burden, egg count, granuloma count and size compared to the other treatments. Moreover, it induced severe deformations of worm morphology regarding oral and ventral suckers, tegument, spines distribution, and male gynaecophoric canal. Liver enzymes and oxidative stress markers were significantly decreased while antioxidant activities were increased compared to control and other treated groups. In conclusion, a single dose of PZQ-CSNPs had significant antischistosomal therapeutic effects during the early maturation phase., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests and this manuscript has not been submitted to any other journal in Egypt or abroad. Alexandria University's code of ethics and rules of academic integrity had been followed., (Copyright © 2024. Published by Elsevier Inc.)

Umbilical granuloma may be defined as a small mass of granulation tissue which develops at the base of the umbilicus after separation of the cord. It consists of true granulation tissue with fibroblast and abundant capillaries. Treatment options are chemical cauterization, electro cauterization and sometimes need surgical excision. Aims of this study were to develop a simple and feasible method for the treatment of umbilical granuloma with table salt (NaCl). This was a multi-center prospective type of observational study and conducted from January 2023 to March 2024 in the department of Pediatrics Surgery, Mymensingh Medical College Hospital, Mymensingh and other Private Hospitals of Mymensingh, Bangladesh. Total 66 patients were included among them 59(89.09%) cured and 7(10.6%) patients need other options. No complications and recurrence was seen in 3 months follow up. Treatment of umbilical granuloma with table salt (NaCl) is a simple, effective, low cost and feasible method.

Actinic granuloma (AG) is a rare dermatological condition with only a few dozen cases reported worldwide. Initially classified as a variant of granuloma annulare, it is now recognized as a distinct entity characterized by asymptomatic annular plaques in sun-exposed areas of the skin. The exact pathogenesis remains unclear, but it is believed to be an inflammatory response to sun damage, possibly involving injured elastic fibers. Numerous local and systemic therapeutic options exist, but no specific treatment guidelines have been established. We present a case of AG treated with intralesional application of triamcinolone acetonide in a 64-year-old male patient. We also discuss the most important clinical and histological characteristics and various treatment options.

Objectives: To report the presentation, treatment and outcome of dogs with granulomatous steatitis associated with total and ionised hypercalcaemia., Methods: Six dogs diagnosed with ionised and/or total hypercalcaemia and histologically diagnosed granulomatous steatitis were evaluated to determine the clinical signs, clinical findings, response to treatment and outcome. These cases were seen at different primary care and referral veterinary hospitals in the United Kingdom between 2019 and 2023., Results: No alternative aetiology to explain the total and/or ionised hypercalcaemia or steatitis was identified. The most common presenting signs were lethargy, anorexia or hyporexia, vomiting and polyuria/polydipsia. Other clinical signs included weight loss, discomfort and panting. Five out of the six dogs responded to prednisolone. Four dogs were alive at the time of writing, one dog was lost to follow-up and one dog died 2 weeks post-diagnosis., Clinical Significance: It is well-established that granulomatous disease can cause hypercalcaemia. In this case series we found granulomatous steatitis associated with total and/or ionised hypercalcaemia. Dogs diagnosed with granulomatous steatitis should have ionised calcium measured, which may prompt further diagnostics and treatment options. Dogs with hypercalcaemia should be evaluated for evidence of steatitis where more common differentials have been excluded., (© 2024 The Author(s). Journal of Small Animal Practice published by John Wiley & Sons Ltd on behalf of British Small Animal Veterinary Association.)

Tuberculosis, a fatal infectious disease caused by Mycobacterium tuberculosis (M.tb), is difficult to treat with antibiotics due to drug resistance and short drug half-life. Phototherapy represents a promising alternative to antibiotics in combating M.tb. Exploring an intelligent material allowing effective tuberculosis treatment is definitely appealing, yet a significantly challenging task. Herein, an all-in-one biomimetic therapeutic nanoparticle featured by aggregation-induced second near-infrared emission, granuloma-targeting, and self-oxygenation is constructed, which can serve for prominent fluorescence imaging-navigated combined phototherapy toward tuberculosis. After camouflaging the biomimetic erythrocyte membrane, the nanoparticles show significantly prolonged blood circulation and increased selective accumulation in tuberculosis granuloma. Upon laser irradiation, the loading photosensitizer of aggregation-induced emission photosensitizer elevates the production of reactive oxygen species (ROS), causing M.tb damage and death. The delivery of oxygen to relieve the hypoxic granuloma microenvironment supports ROS generation during photodynamic therapy. Meanwhile, the photothermal agent, Prussian blue nanoparticles, plays the role of good photothermal killing effect on M.tb. Moreover, the growth and proliferation of granuloma and M.tb colonies are effectively inhibited in the nanoparticle-treated tuberculous granuloma model mice, suggesting the combined therapeutic effects of enhancing photodynamic therapy and photothermal therapy., (© 2024 Wiley‐VCH GmbH.)

Purpose of Review: The pathogenesis of granulomatous disease in common variable immunodeficiency (CVID) is still largely unknown, which hampers effective treatment. This review describes the current knowledge on the pathogenesis of granuloma formation in CVID and the biological basis of the current treatment options., Recent Findings: Histological analysis shows that T and B cells are abundantly present in the granulomas that are less well organized and are frequently associated with lymphoid hyperplasia. Increased presence of activation markers such as soluble IL-2 receptor (sIL-2R) and IFN-ɣ, suggest increased Th1-cell activity. Moreover, B-cell abnormalities are prominent in CVID, with elevated IgM, BAFF, and CD21low B cells correlating with granulomatous disease progression. Innate immune alterations, as M2 macrophages and neutrophil dysregulation, indicate chronic inflammation. Therapeutic regimens include glucocorticoids, DMARDs, and biologicals like rituximab., Summary: Our review links the biological context of CVID with granulomatous disease or GLILD to currently prescribed therapies and potential targeted treatments., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Granuloma formation is an uncommon and persistent skin inflammatory condition caused by the injection of dermal fillers. The exact cause of this reaction is not well understood, but it may be associated with irritating components or abnormal immune function. Treating granulomas can be difficult. However, recent research has shown that Janus kinase (JAK) inhibitors hold promise as a potential therapy for refractory granulomatous diseases., Objectives: The aim was to evaluate the efficacy and safety of tofacitinib as a treatment for granulomas secondary to filler injection and the possible mechanisms were discussed and summarized., Methods: This study focuses on three cases of patients who experienced granuloma formation after receiving filler injections and were subsequently treated with tofacitinib. The efficacy and safety of the treatment were evaluated using parameters such as photographs and monitoring for any adverse reactions. In addition, a literature review was conducted to explore the underlying mechanisms and potential effects of tofacitinib., Results: All three cases recovered from swelling and nodules without side effects through the off-label use of oral tofacitinib. Existing data review reveals some approaches for cutaneous granulomatous disorders like inhibiting macrophage activation and downregulation of the JAK-STAT pathway., Conclusion: This report emphasizes the effectiveness of JAK inhibitors in treating granulomas caused by filler injections. Recent advancements in understanding the underlying mechanisms of granulomatous reactions have paved the way for JAK inhibitors to be regarded as a promising treatment choice. However, further research is necessary to fully assess the safety and long-term effectiveness of using tofacitinib for granuloma treatment.

Sarcoidosis is a systemic granulomatous disease characterized by non-caseating epithelioid cell granulomas. One of its immunological hallmarks is the differentiation of CD4 + naïve T cells into Th1/Th17 cells, accompanied by the release of numerous pro-inflammatory cytokines. The TL1A/DR3 signaling pathway plays a crucial role in activating effector lymphocytes, thereby triggering pro-inflammatory responses. The primary aim of this investigation was to scrutinize the impact of anti-TL1A monoclonal antibody on the dysregulation of Th1/Th17 cells and granuloma formation in sarcoidosis. Initially, the abnormal activation of the TL1A/DR3 signaling pathway in pulmonary tissues of sarcoidosis patients was confirmed using qPCR and immunohistochemistry techniques. Subsequently, employing a murine model of sarcoidosis, the inhibitory effects of anti-TL1A monoclonal antibody on the TL1A/DR3 signaling pathway in sarcoidosis were investigated through qPCR, immunohistochemistry, and Western blot experiments. The influence of anti-TL1A monoclonal antibody on granulomas was assessed through HE staining, while their effects on sarcoidosis Th1/Th17 cells and associated cytokine mRNA levels were evaluated using flow cytometry and qPCR, respectively. Immunofluorescence and Western blot experiments corroborated the inhibitory effects of anti-TL1A monoclonal antibody on the aberrant activation of the PI3K/AKT signaling pathway in sarcoidosis. The findings of this study indicate that the TL1A/DR3 signaling pathway is excessively activated in sarcoidosis. Anti-TL1A monoclonal antibody effectively inhibit this abnormal activation in sarcoidosis, thereby alleviating the dysregulation of Th1/Th17 cells and reducing the formation of pulmonary granulomas. This effect may be associated with the inhibition of the downstream PI3K/AKT signaling pathway. Anti-TL1A monoclonal antibody hold promise as a potential novel therapeutic intervention for sarcoidosis., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Rationale: Sarcoidosis is a granulomatous disorder of unclear cause notable for abnormal elevation of blood and tissue ACE1 (angiotensin converting enzyme 1) levels and activity. ACE1 regulates the renin-angiotensin-aldosterone system (RAAS), the terminal product of which is aldosterone, which selectively engages mineralocorticoid receptors to promote inflammation. Objectives: We sought to determine whether the RAAS promotes sarcoidosis granuloma formation and related inflammatory responses. Methods: Using an established ex vivo model, we first determined whether aldosterone was produced by sarcoidosis granulomas and verified the presence of CYP11B2, the enzyme required for its production. We then evaluated the effects of selective inhibitors of ACE1 (captopril), angiotensin type 1 receptor (losartan), and mineralocorticoid receptors (spironolactone, eplerenone) on granuloma formation, reflected by computer image analysis-generated granuloma area, and selected cytokines incriminated in sarcoidosis pathogenesis. Measurements and Main Results: Aldosterone was spontaneously produced by sarcoidosis peripheral blood mononuclear cells, and both intra- and extracellular levels steadily increased during granuloma formation. In parallel, peripheral blood mononuclear cells were shown to express more CYP11B2 during granuloma formation. Significant inhibition of sarcoidosis granulomas and related cytokines (TNFα, IL-1β, IFNγ, IL-10) was observed in response to pretreatments with captopril, losartan, spironolactone, or eplerenone, comparable to that of prednisone. Conclusions: The RAAS is intact in sarcoidosis granulomas and contributes significantly to early granuloma formation and to related inflammatory mediator responses, with important implications for clinical management.

Purpose: To report the treatment response of a case of tubercular choroidal granuloma and subretinal abscess with intravitreal anti-vascular endothelial growth factor (anti-VEGF) and moxifloxacin., Method: Retrospective interventional case report., Results: A 34-year-old man presented with bilateral choroidal granuloma and subretinal abscess in one eye. He was a known case of spinal tuberculosis and was on anti-tubercular therapy. Patient was successfully treated with intravitreal injection of anti-VEGF and moxifloxacin., Conclusion: Intravitreal anti-VEGF and moxifloxacin combination may be beneficial in tubercular choroidal granuloma and subretinal abscess.

Purpose: To report a case of disseminated TB presenting as ciliary body and thyroid mass lesions., Case Report: A 17-year-old male patient presented with a thyroid mass and blurring of vision in the left eye. A diagnosis of ciliary body granuloma was made. Although the Mantoux was negative, the HRCT chest showed evidence of miliary TB, and the fine needle aspiration cytology from the thyroid mass revealed AFB. On initiation of Antitubercular therapy(ATT), a paradoxical worsening of ciliary body granuloma was noted which resolved on starting steroids., Conclusion: Involvement of thyroid gland and ciliary body although rare in tuberculosis, may be the presenting feature of disseminated TB. Paradoxical reactions seen after initiation of ATT in these cases may respond well to oral steroids.

This study aimed to elucidate the regression process of ostium granulomas under the usage of intranasal steroid after primary endoscopic dacryocystorhinostomy (DCR). The authors retrospectively reviewed 57 patients (a total of 72 ostia) who had ostium granulomas after primary endoscopic DCR between 2011 and 2015. Topical intranasal steroid spray was applied in all the patients since postoperative day 1. Adjunctive intralesional triamcinolone acetonide injections were administered for extensive and large-sized granulomas that caused impending ostium blockage. Sequential regression of the ostium granulomas and success rates of DCR were assessed using endoscopic photos. The granulomas completely disappeared in 69 (95.8%) ostia, and the average time interval from the surgery to the disappearance was 6.9 ± 2.8 months. Anatomical and functional surgical success rates were 90.3% and 84.7%, respectively. Intralesional steroid injections for ostium granulomas did not alter the outcomes compared to topical intranasal steroid usage significantly (p = 0.445). In conclusion, we observed that, by continuing the usage of intranasal steroids, ostium granulomas disappear gradually at postoperative 6 months. The intranasal surgical manipulation of granulomas, which results in more mucosal cicatricial change and impedes patient satisfaction, can be successfully avoided., (© 2024. The Author(s).)

Abstract: This case emphasizes the value of meticulous observation and regular follow-up of patients receiving rifampicin therapy. The prognosis for complete improvement in renal function in such cases was excellent, with prompt recognition and discontinuation of rifampicin. Teaching patients about these possible adverse effects and encouraging immediate reporting of signs and symptoms are likely to be beneficial because acute kidney injury can manifest itself very quickly after rifampicin is started. Even if renal failure can happen with any dose of rifampicin, primary physicians must have awareness about patients on intermittent or irregular therapy and those who have previously used this medication. It is challenging to determine the prevalence of adverse reactions to common antibiotics where a state- or country-wide reporting system is absent. Along with withdrawal of the causative agent patients were treated with corticosteroids (0.5-1 mg/kg/day) for an average period of 4-12 weeks showing significant recovery of renal function., (Copyright © 2024 Copyright: © 2024 Indian Journal of Pharmacology.)

Cartilage hypoplasia syndrome is a primary immunodeficiency disease characterized by short stature, hypoplastic hair and a variable degree of immunodeficiency. Noninfectious cutaneous granulomas represent an uncommon yet well-recognized manifestation within the spectrum of primary immunodeficiency diseases. However, cutaneous granulomas as a manifestation of cartilage-hair hypoplasia syndrome, are extremely rare. We present a case of a middle-aged man with cartilage hypoplasia syndrome featuring cutaneous granulomas, manifesting as chronic, extensive and deep cutaneous ulcers. The patient was treated with anti-TNF-alpha adalimumab with partial improvement. Our case underscores the broad spectrum of clinical manifestations associated with cartilage hypoplasia syndrome and adds new evidence to the potential therapeutic efficacy of anti-TNF-alpha drugs in its treatment., (© 2024 Australasian College of Dermatologists.)

Background: Mesotherapy is a popular cosmetic procedure for localized delivery of substances. However, due to the lack of standardized processes, there are potential risks of adverse reactions. Granulomas formation is one of the chronic reactions which impose significant physical and mental burdens on patients., Objectives: The aim of this analysis is to evaluate the safety and feasibility of combining intense pulsed light (IPL) with intralesional corticosteroids for treating noninfectious granulomas after mesotherapy., Methods: This retrospective observational case series included patients who suffer from noninfectious granulomas after mesotherapy and received combination of IPL and intralesional corticosteroids treatment between October 2021 and December 2022 at Peking University Shenzhen Hospital, Shenzhen, China. The process and effect were analyzed and summarized., Results: Among the seven patients, five expressed extreme satisfaction with the efficacy, while two was slightly satisfied. The physicians believed that all patients had shown significant improvement. No adverse reactions or recurrences were observed during follow-up., Conclusion: Based on this analysis, the application of the combined treatment in patients suffering from noninfectious granuloma due to mesotherapy demonstrates good clinical efficacy and safety, making it worth considering as a treatment option., (© 2024 The Authors. Journal of Cosmetic Dermatology published by Wiley Periodicals LLC.)

Ethnopharmacological Relevance: "Snow-white waterlily" (Nymphaea candida) dried flower possesses various efficacy in Uighur medicine such as reducing fever and nourishing the liver, anti-inflammatory and cough relieving, moistening the throat and quenching thirst., Aim of the Study: Polyphenols are characteristic component of N. candida as well as its quality markers, and the purpose of this study was to conduct investigations into anti-inflammatory, antitussive, antipyretic, and analgesic activities of the polyphenol-enriched fraction from N. candida (NCTP) in order to validate the traditional efficacy of this plant., Materials and Methods: The polyphenols in NCTP were analyzed by HPLC, and an acute oral toxicity study was conducted for NCTP. The anti-inflammatory activities of NCTP were evaluated using xylene induced ear edema, capillary permeability, cotton pellet granuloma, and carrageenan-induced rat paw edema, of which multiple biochemical indices were measured in carrageenan-induced rat paw edema such as prostaglandin E2 (PGE2), cyclooxygenase-2 (COX-2),5-lipoxygenase (5-LOX), interleukin-6 (IL-6), interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione (GSH) activities; the analgesic activities were investigated using acetic acid writhing, hot plate test, and formalin test; the anti-tussive and antipyretic effects were tested by ammonia induced cough in mice and yeast-induced fever respectively., Results: NCTP with LD50 of 5222 mg/kg was low toxicity and safety. NCTP (200 mg/kg) could significantly reduce ear swelling and capillary permeability by 30.63% and 31.37%, respectively. NCTP revealed 15.76% inhibiting activities in cotton pellet granuloma in mice at a dosage of 200 mg/kg. Furthermore, NCTP (50, 100, and 200 mg/kg) substantially decreased carrageenin-induced paw edema in rats between 1 and 5 h, and NCTP could decrease PGE2, 5-LOX, COX-2 levels as well as IL-6, IL-1β, TNF-α activities compared with the control group; NCTP could decrease MDA contents in carrageenin-induced rise, and increase SOD and GSH activities. Furthermore, the dose-dependent inhibition effect of NCTP on pain was revealed in the hot plate experiment. In addition to reducing the amount of writhes brought on by acetic acid, NCTP (50, 100, and 200 mg/kg) significantly inhibited pain latency against both stages of the formalin test. Moreover, NCTP (50, 100, 200 mg/kg) showed the better antitussive activities in mice in a dose-dependent manner. In the yeast-induced pyrexia test, dosages of 50, 100, and 200 mg/kg resulted in a statistically significant drop in rectal temperature., Conclusion: The experimental results proved the analgesic, anti-inflammatory, anti-tussive and antipyretic activities of the polyphenol-enriched fraction from N. candida, and supported the traditional use of this plant as well., Competing Interests: Declaration of competing interest All authors disclosed no relevant relationships, and confirm that there are no known conflicts of interest associated with this publication and there has been no significant financial support for this work that could have influenced its outcome., (Copyright © 2024. Published by Elsevier B.V.)

Background: Idiopathic aseptic facial granuloma (IAFG) is an underrecognized pediatric skin disease, currently considered within the spectrum of rosacea. It usually manifests as a solitary, reddish, asymptomatic nodule on the cheek that resolves spontaneously., Methods: Retrospective and descriptive observational study of 43 pediatric patients with a clinical diagnosis of IAFG, followed between 2004 and 2022, at two general hospitals in Argentina., Results: IAFG predominated in girls (65%) and the average age of onset was about 6 years. A single asymptomatic nodule was seen in 79% of patients. The most common localization was the cheek (58%) followed by lower eyelids (41%). Family history of rosacea was present in 16% of patients. A concomitant diagnosis of rosacea and periorificial dermatitis was made in 14% and 9% of our population, respectively. Past or present history of chalazia was detected in 42% of the children. IAFG diagnosis was mainly clinical (88% of cases). Oral antibiotics were the most common indicated treatment (84%). Complete healing was achieved by the majority, but 18% of those with eyelid compromise healed with scars., Conclusions: IAFG is a benign pediatric condition that physicians should recognize in order to manage correctly. We herein refer to a particular morphologic aspect of IAFG lesions affecting the lower eyelids, where nodules adopt a linear distribution and have a higher probability of involute leaving a scar. Also, we consider that the concomitant findings of rosacea, periorificial dermatitis and chalazia in our patients, reinforce the consideration of IAFG within the spectrum of rosacea., (© 2024 Wiley Periodicals LLC.)

Granulomatosis with polyangiitis (GPA) is a pauci-immune small vessel vasculitis characterised by neutrophil-mediated vasculitis and granuloma. The presence of intracranial parenchymal space-occupying lesions is rarely seen in GPA patients. In this manuscript, we report a case of GPA with granuloma of the fourth ventricle accompanied by obstructive hydrocephalus. Treatment with glucocorticoids (GCs) and multiple immunosuppressants cyclophosphamide (CYC), mycophenolate mofetil (MMF), and rituximab (RTX) showed poor efficacy in this case. After removal of the granuloma by craniotomy, GPA relapsed within 3 months. Under the premise of GC and MMF treatment combined with intrathecal injection of dexamethasone (DXM) and methotrexate (MTX), the intracranial granuloma gradually shrank, and the patient's general condition was alleviated, showing that this is an effective treatment method. Key Points • To date, there are few reports of granulomatous vasculitis combined with granuloma of the fourth ventricle, and our case is the second. • In this case, multiple immunosuppressants and rituximab were ineffective treatments, and the intracranial granuloma was effectively controlled by intrathecal injection of dexamethasone (DXM) and methotrexate (MTX). • Based on this report, it can be suggested that intrathecal injection is effective in treating patients with GPA and central nervous system involvement, but large-scale sample studies are needed., (© 2023. The Author(s), under exclusive licence to International League of Associations for Rheumatology (ILAR).)

Candidal granuloma is an uncommon type of deep chronic cutaneous candidiasis. Candida albican is the most common causative pathogen for candidal granuloma. We report herein the original case of a 69-year-old Chinese woman presented with a 3-year of painful cutaneous lesion on the back of left hand. Physical examination revealed a 4 × 5 cm large infiltrative reddish plaque with unclear boundaries. The yellow-white crusts were observed on the uneven surface of plaque. Histopathological examination of biopsy tissue revealed that yeast cells and the horizontal section of hyphae in the dermis by hematoxylin eosin staining and periodic acid-Schiff staining. Finally, the pathogen was identified as Candida parapsilosis by mycological examination and molecular identification. The patient was treated with itraconazole oral 200 mg twice daily combined with topical terbinafine hydrochloride cream for 2 months. The lesions were fully resolved and no recurrence was observed. Since the cutaneous infection caused by C. parasilosis were rarely reported, we also reviewed all 11 cases of cutaneous infection caused by C. parapsilosis in the PubMed. Our study highlighted that chronic unilateral infiltrated plaques or ulcers should be aware of the occurrence of fungal granuloma including candidal granuloma especially in immunocompromised patients., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

We read with great interest the article by Oyeniran E et al. on "Isolated optic disc granuloma as a presenting sign of sarcoidosis." We would like to share our experience with a similar optic nerve head granuloma secondary to sarcoidosis in the absence of any systemic symptoms and no evidence of signs of periocular/intraocular inflammation. However, our case was refractory to oral steroids and methotrexate and required intravitreal dexamethasone implants and mycophenolate mofetil.

Schistosomiasis afflicts approximately 120 million individuals globally. The hepatic pathology that occurs due to egg-induced granuloma and fibrosis is commonly attributed to this condition. However, there is currently no efficacious treatment available for either of these conditions.Our study aimed to investigate the potential antifibrotic and antiparasitic properties of different doses of gallic acid (GA) in experimental schistosomiasis mansoni. In addition, we investigated the outcomes of co-administering it with the standard anti-schistosomiasis treatment, praziquantel (PZQ).In experiment I, Schistosoma mansoni- infected mice were administered GA at doses of 10, 20, or 40 mg/kg. Their effectiveness was evaluated through parasitological (worm and egg loads, granuloma number and diameter), pathological (fibrosis percentage and H-score of hepatic stellate cells (HSCs)), and functional (liver enzymes) tests. In experiment II, we investigated the optimal dosage that yielded the best outcomes. This dosage was administered in conjunction with PZQ and was evaluated regarding the parasitological, pathological, functional, and immunological (fibrosis-regulating cytokines) activities.Our findings indicate that the administration of 40 mg/kg GA exhibited the highest level of effectiveness in experiment I. In experiment II, it exhibited lower antiparasitic efficacy in comparison to PZQ. However, it surpassed PZQ in other tests. It showed enhanced outcomes when combined with PZQ.In conclusion, our findings reveal that GA only slightly increased the antischistosomal activity of PZQ. However, it was linked to decreased fibrosis, particularly when administrated with PZQ. Our pilot study identifies GA as a natural antifibrotic agent, which could be administered with PZQ to mitigate the development of fibrosis.

A 12-year-old male eclectus parrot ( Eclectus roratus ) was referred for evaluation of coelomic distention. Computed tomography and blood work revealed coelomic effusion with free coelomic mineral-attenuating material and elevations in the bile acids and aspartate aminotransferase activity, respectively. Coelomic effusion was consistent with macrophagic inflammation with abundant intracellular lipids. Initial treatment with meloxicam resulted in minimal patient improvement. Disseminated xanthogranulomatous inflammation was suspected based on imaging and diagnostic laboratory results, which were consistent with those previously reported. Biopsy samples of liver tissue and intracoelomic masses confirmed this diagnosis. Treatment was initiated with prednisolone 1 mg/kg/d for 6 months, followed by 0.5 mg/kg/d for 3 months. Clinical improvement was assessed based on owner evaluation, plasma bile acid concentrations, and repeated computed tomographic scans. After 2 months of treatment, the owner reported improved behavior and appetite; this persisted throughout treatment and when the bird was reexamined 17 months following the cessation of steroid therapy. Bile acid concentrations were normal 10 months after the prednisolone therapy was discontinued. Diagnostic imaging showed minimal coelomic effusion 10 months after the last prednisolone dose was administered, with improved ventilation of the air sacs and static to improved dystrophic mineral foci. This report describes the antemortem diagnosis and treatment of disseminated coelomic xanthogranulomatous disease in a psittacine species, with an observed measurable therapeutic response.

Introduction: Tuberculosis can involve any organ in the body including ocular tissue of which the uveal tissue is most commonly infected. Choroidal involvement ranges from choroidal tubercles to granulomas. This is one of the few cases of a solitary choroidal granuloma with no other systemic symptoms in an immunocompetent child., Method: A case report., Results: A 12-year-old female, presented with diminution of vision in the left eye for a month. The anterior segment of her left eye was normal. A fundus examination revealed an isolated orangish-yellow choroidal mass, 4 DD in size, involving the posterior pole with overlying subretinal exudation. CT scan of the thorax showed large pulmonary, cervical and pancreatic lymph nodes, along with lytic lesions of the thoracic vertebrae. Excision biopsy of the cervical lymph nodes showed caseating granulomas with no e/o malignancies on histopathology. The patient was started on anti-tubercular therapy. Six months after the treatment, the lesion had reduced in size and her vision had improved., Conclusion: Isolated choroidal tuberculomas can be present in eyes with little associated ocular inflammation and no other symptoms of systemic tuberculosis. High suspicion, early diagnosis and rapid initiation of medication are important for the treatment of ocular and systemic tuberculosis., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Schistosomiasis is a serious tropical disease. Despite extensive research into the etiology of liver fibrosis, effective therapeutic options remain limited. This study aims to assess the effectiveness of auranofin in treating hepatic granuloma and fibrogenesis produced by Schistosoma (S.) mansoni eggs. Auranofin is a gold complex that contains thioglucose tetraacetate and triethylphosphine. Eighty BALB/c male mice were divided into four groups (n=20/group): negative control (GI), positive control (GII), and early (GIII) and late (GIV) treatment groups with oral auranofin according to beginning of treatment 4th week and 6th week post-infection. Mice were infected subcutaneously in a dose of 60±10 cercariae/mouse. Worm counts, egg loads, and oogram patterns were determined. Biochemical, histological, and immunostaining of interleukin-1β (IL-1β), Sirtuin 3 (SIRT3), and smooth muscle actin (SMA) were assessed. GIII showed a significant decrease in the total S. mansoni worm burden and ova/gram in liver tissue (with reduction percent of 63.07% and 78.26%, respectively). Schistosomal oogram patterns, immature and mature ova, also showed a significant decrease. The reduction in granuloma number and size was 40.63% and 48.66%, respectively, in GIII, whereas in GIV, the reduction percent was 76.63% and 67.08%. In addition, the degree of fibrosis was significantly diminished in both treated groups. GIV showed significant reduction in IL-1β and SMA expression and increase in SIRT3 expression. These findings reveal how auranofin suppresses the development of liver fibrosis. Therefore, it is crucial to take another look at auranofin as a prospective medication for the treatment of S. mansoni egg-induced hepatic granuloma and consequent fibrosis.

Exacerbated inflammatory responses to harmful stimuli can lead to significant pain, edema, and other complications that require pharmacological intervention. Abietic acid (AA) is a diterpene found as a significant constituent in pine species, and evidence has identified its biological potential. The present study aimed to evaluate abietic acid's antiedematogenic and anti-inflammatory activity in mice. Swiss mice (Mus musculus) weighing 20-30 g were treated with AA at 50, 100, and 200 mg/kg. The central nervous system (CNS) effects were evaluated using open-field and rotarod assays. The antinociceptive and anti-inflammatory screening was assessed by the acetic acid and formalin tests. The antiedematogenic activity was investigated by measuring paw edema induced by carrageenan, dextran, histamine, arachidonic acid, and prostaglandin, in addition to using a granuloma model. The oral administration of abietic acid (200 mg/Kg) showed no evidence of CNS effects. The compound also exhibited significant antiedematogenic and anti-inflammatory activities in the carrageenan and dextran models, mostly related to the inhibition of myeloperoxidase (MOP) activity and histamine action and, to a lesser extent, the inhibition of eicosanoid-dependent pathways. In the granuloma model, abietic acid's effect was less expressive than in the acute models investigated in this study. In conclusion, abietic acid has analgesic and antiedematogenic activities related to anti-inflammatory mechanisms., (© 2023 Wiley-VHCA AG, Zurich, Switzerland.)

Purpose: Tuberculosis (TB) is a chronic disease caused by Mycobacterium tuberculosis ( MTB ) that remains a major global health challenge. One of the main obstacles to effective treatment is the heterogeneous microenvironment of TB granulomas. This study aimed to investigate the potential of a hypoxic remission-based strategy to enhance the outcome of tuberculosis treatment when implemented in combination with ultrasound., Methods: A PLGA nanoparticle (LEV@CAT-NPs) loaded with levofloxacin (LEV) and catalase (CAT) was fabricated by a double emulsification method, and its physical characteristics, oxygen production capacity, drug release capacity, and biosafety were thoroughly investigated. The synergistic therapeutic effects of ultrasound (US)-mediated LEV@CAT-NPs were evaluated using an experimental mouse model of subcutaneous tuberculosis granuloma induced by Bacille Calmette-Guérin ( BCG ) as a substitute for MTB ., Results: LEV@CAT-NPs exhibited excellent oxygen production capacity, biosafety, and biocompatibility. Histological analysis revealed that ultrasound-mediated LEV@CAT-NPs could effectively remove bacteria from tuberculous granulomas, significantly alleviate the hypoxia state, reduce the necrotic area and inflammatory cells within the granuloma, and increase the penetration of dyes in granuloma tissues. The combined treatment also reduced the serum levels of inflammatory cytokines (eg, TNF-α, IL-6, and IL-8), and significantly downregulated the expression of hypoxia-inducible factor 1α (HIF-1α) and vascular endothelial growth factor (VEGF). These results suggested that the synergistic treatment of ultrasound-mediated LEV@CAT-NPs effectively eradicated the bacterial infection and reversed the hypoxic microenvironment of tuberculous granulomas, further promoting tissue repair., Conclusion: This study provides a non-invasive and new avenue for treating refractory tuberculosis infections. The potential role of regulating hypoxia within infected lesions as a therapeutic target for infection deserves further exploration in future studies., Competing Interests: The authors declare no competing interests in this work., (© 2023 Hu et al.)

Fish tank granuloma has traditionally been associated with Mycobacterium marinum. We report the case of a 54 old-year woman that worked in a freshwater fish pet store and developed a skin ulcer in a hand finger with a suppurative granuloma secondary to Microbacterium paraoxydans. This is a bacterial fish pathogen, rarely observed in human infections. Identification was performed by colony morphology and MALDI-TOF. She evolved satisfactorily after receiving a sequential treatment with beta-lactams and linezolid. To our knowledge, it is the first known description of this type.

Aseptic facial granuloma is a rare pediatric disease, presenting with asymptomatic facial nodules on the cheeks or the eyelids and may represent a form of granulomatous rosacea in children. In this retrospective case series, 12 children with aseptic facial granuloma were treated with oral macrolides (erythromycin or roxithromycin) resulting in a healing of the lesions within a mean treatment time of 5.25 months with no recurrences. The treatment was mainly well tolerated. Oral macrolides may be effective in the treatment of patients with aseptic facial granuloma., (© 2023 The Authors. Pediatric Dermatology published by Wiley Periodicals LLC.)

Background: Common salt is a safe, effective and cheap home-made remedy for umbilical granuloma. The aim of this scoping review is to identify and summarize the available evidence and examine the research conducted on salt treatment for umbilical granuloma., Methods: A literature search was performed in the second week of September, 2022 using Google scholar, PubMed, MEDLINE and EMBASE databases using the keywords 'umbilical granuloma' and 'salt treatment' to identify all English articles pertaining to salt treatment for umbilical granuloma. Tables were made to summarize the methodological characteristics, results and the dosage regimens of salt used by different authors. The Cochrane Collaboration's tool was used for assessing risk of bias in RCTs. The indexing statuses of the journals publishing these studies were also noted. The overall efficacy with the use of common salt was calculated by adding the success rates mentioned in each study., Results: Twenty-four articles (2 systematic reviews, 6 Randomized Controlled Trials, 11 prospective cohort studies, 1 case control study, 3 retrospective case series and 1 case report) were included. An overall 93.91% success rate (1033/1100) was seen with common salt application, without any reports of complications/recurrences., Conclusion: Topical application of common salt for umbilical granulomas is simple, effective and inexpensive. This scoping review provides a broader outlook at the existing level of evidence and may help in planning interventional comparative studies, so that recommendations can be formulated. It also highlights a lack of properly designed randomized controlled trials on this topic., Level of Evidence: I., Competing Interests: Conflicts of interest None., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objectives: This study aimed to describe catheter tip granuloma (CTG) formation in a patient on ultralow-dose, low-concentration morphine via intrathecal (IT) drug delivery system (IDDS) and to review literature for reports of IT granuloma formation and association with drug type, drug dose, and drug concentration., Materials and Methods: This review describes diagnosis and management of a patient with CTG on ultralow-dose, low-concentration morphine. PubMed data base search was conducted from January 1990 to July 2021 for original articles on CTG formation in humans getting intrathecal analgesics. Data were extracted on indications for IDDS, time to detect CTG, and type of drug/s with drug doses and concentrations. Percentages and average with range for age, sex, duration of infusion, drug doses, and drug concentrations were calculated., Results: We describe CTG formation and spinal cord compression with worsening of sensorimotor deficits in a patient receiving intrathecal morphine at ultralow dose (0.6 mg/d) and low concentration (1.2 mg/mL), which is the lowest reported morphine dose associated with CTG in the literature. Our literature review shows all IT drugs have the potential for granuloma formation, and there is no drug with granuloma-inhibiting effect., Conclusions: There is no drug, dose, or concentration that has granuloma-sparing effect. It is imperative to maintain vigilance for potential CTG in all patients with IDDS. Routine monitoring and prompt evaluation for any unexplained symptoms or change in neurologic status from baseline is critical in early detection and treatment of CTG., (Copyright © 2023 International Neuromodulation Society. Published by Elsevier Inc. All rights reserved.)

Infections caused by members of the mycobacterium tuberculosis complex [MTC] and nontuberculous mycobacteria [NTM] can induce widespread morbidity and mortality in people. Mycobacterial infections cause both a delayed immune response, which limits rate of bacterial clearance, and formation of granulomas, which contain bacterial spread, but also contribute to lung damage, fibrosis, and morbidity. Granulomas also limit access of antibiotics to bacteria, which may facilitate development of resistance. Bacteria resistant to some or all antibiotics cause significant morbidity and mortality, and newly developed antibiotics readily engender resistance, highlighting the need for new therapeutic approaches. Imatinib mesylate, a cancer drug used to treat chronic myelogenous leukemia [CML] that targets Abl and related tyrosine kinases, is a possible host-directed therapeutic [HDT] for mycobacterial infections, including those causing TB. Here, we use the murine Mycobacterium marinum [Mm] infection model, which induces granulomatous tail lesions. Based on histological measurements, imatinib reduces both lesion size and inflammation of surrounding tissue. Transcriptomic analysis of tail lesions indicates that imatinib induces gene signatures indicative of immune activation and regulation at early time points post infection that resemble those seen at later ones, suggesting that imatinib accelerates but does not substantially alter anti-mycobacterial immune responses. Imatinib likewise induces signatures associated with cell death and promotes survival of bone marrow-derived macrophages [BMDMs] in culture following infection with Mm. Notably, the capacity of imatinib to limit formation and growth of granulomas in vivo and to promote survival of BMDMs in vitro depends upon caspase 8, a key regulator of cell survival and death. These data provide evidence for the utility of imatinib as an HDT for mycobacterial infections in accelerating and regulating immune responses, and limiting pathology associated with granulomas, which may mitigate post-treatment morbidity., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Cleverley et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Sarcoidosis is a multisystemic disease, characterised by histopathologic presence of non-necrotising granulomas, primarily affecting the lungs (>90%). We present three cases predominantly characterised by uncommon extrapulmonary manifestations of sarcoidosis, where only one had pulmonary involvement. We describe three female patients, between the second and third decades of life, whose sarcoidosis was a diagnostic challenge due to their atypical extrapulmonary manifestations, from which we highlight: livedo reticularis and painful subcutaneous nodules with uncommon localisation, size and histology, being the first reported case of extensive subcutaneous nodules triggered by intramuscular penicillin; extensive symptomatic and refractory osseous involvement; and dispersed erythema nodosum affecting the entire body surface. All three patients required third-line treatment (antitumour necrosis factor agents) to achieve significant clinical and imagiological improvement. Through this case series, we highlight the importance of considering the rare and atypical presentations of sarcoidosis to avoid diagnostic delays and serious repercussions on the patient's prognosis., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

A 54-year-old male presented with a three-year history of bilateral upper eyelid and peri-orbital swelling and adult-onset asthma. Histopathology of a left orbital biopsy showed lymphoid follicles with foamy macrophages and Touton giant cells. Clinical, histological and radiological features were consistent with adult-onset asthma and periocular xanthogranuloma. Treatment with rituximab led to a complete clinical and radiological remission. Nine years later, his condition relapsed with a biopsy of the left orbit and lacrimal gland demonstrating features of IgG4-related disease and adult-onset asthma and periocular xanthogranuloma. Immunohistochemistry showed increased numbers of IgG4+ plasma cells (290 per high power field) and an elevated IgG4+/IgG+ plasma cell ratio of 480%. Involvement by both disorders in the orbit and ocular adnexa of a single patient has not previously been reported in the literature, to the best of our knowledge, and suggests a possible aetiologic or pathophysiologic association.