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BACKGROUND The search for aesthetic non-surgical procedures is growing. The use of polymethylmethacrylate (PMMA) as a filling material in the nose represents one of the many options among these aesthetic procedures. Its use, however, can lead to complications. The treatment of these complications is often challenging. METHODS We performed a retrospective clinical analysis of the medical records of patients undergoing treatment of PMMA granulomas of the nose at a private clinic from January, 2015, to January, 2021. A short-pulsed neodymium-YAG (Nd:YAG) laser was applied intranasally or directly by cutaneous incision in the granulomas. Laser-tissue interaction heats the alloplastic material, fragments the product and creates cleavage paths, thereby facilitating the removal of PMMA, either by intercartilaginous removal or aspiration. RESULTS Twenty-seven patients were included in the study. All had a history of PMMA injection in the nose. All patients were treated with an intralesional pulsed 1064nm Nd:YAG laser. The material removed after laser-tissue interaction was sent for histopathological examination; this showed the presence of microparticles of exogenous material compatible with PMMA. The partial removal of the alloplastic material was shown to be effective in all cases. One patient developed a small blister in the nasal dorsum. Follow-up ranged from six to 47 months. CONCLUSIONS The use of intralesional Nd:YAG laser for the treatment of PMMA granulomas on the nose proved to be an effective and safe procedure with improvement of nasal shape, without compromising respiratory function. This technical option represents yet another alternative in the treatment of PMMA granuloma complications. J Drugs Dermatol. 2021;20(11): 1161-1166. doi:10.36849/JDD.6550.

Background Female genital tuberculosis (FGTB) causes infertility in a significant number of females. The immunological impact of tuberculosis on endometrium in infertile females has not been studied before. The present study was designed to evaluate markers related to infiltrating immune cells and implantation in endometrial aspiration from infertile females and correlate with conventional tests and polymerase chain reaction (PCR) for tuberculosis (TB). Methods It was a prospective cohort study with 385 patients out of which IHC was done in 306 over a period of 3 years from 2013 to 2016 in a tertiary care hospital. Women with infertility, 20–35 years of age, without history of pulmonary TB or intake of antitubercular therapy were included. Endometrial samples were subjected to PCR for TB along with microbiological and histological examination for TB. Immunohistochemistry for CD45, CD3, CD20, CD4, CD8, CD68, CD138, Interferon gamma, Interleukin 10 (IL-10) and implantation markers MUC1 and Notch 1 were done on the endometrial samples along with 25 control subjects. Results Conventional tests for tuberculosis like staining for acid fast bacilli (AFB), granuloma on histology or culture positivity were seen in 2.61% (6/306; 1.96% had granulomas, 1/306; 0.32% was AFB positive, 2/306; 0.6% were liquid culture positive). PCR was positive in 190/306 (62.09%). CD3, CD20, CD45, CD68, CD4, CD8 and CD 138 expressing infiltrating cells were not significantly related to PCR positive cases. Interferon gamma expressing lymphocytes were significantly higher (38.94%) in PCR positive endometria compared to 26.72% in the PCR negative (p = 0.04). Notch −1 expression correlated significantly with the occurrence of pregnancy. A trend towards high intensity expression of Notch1 was seen in PCR negative cases. MUC-1 expression did not correlate with pregnancy although interferon gamma expression was significantly related to low intensity MUC1 expression. Conclusions Immunohistochemical markers are not reliable tests in diagnosis of FGTB. Notch 1 expression though showing correlation with pregnancy has to be further evaluated with a panel of other implantation markers. Study funding Indian Council of Medical Research, New Delhi, India.

BRAF-inhibitors have emerged as a promising targeted therapy for malignancies with BRAF mutations, particularly metastatic melanoma. However, granulomatous reactions including sarcoidosis and sarcoid-like-reactions have been reported as a consequence of BRAF-inhibition. It is important to adequately characterise these granulomatous reactions including cutaneous manifestations and systemic involvement, in order to guide investigations and management. A literature review was conducted to characterise the spectrum of granulomatous reactions associated with BRAF-inhibitors - identifying 55 reactions affecting 51 patients, with 37 reactions limited to cutaneous involvement. Further, possible correlation with cancer response, mechanisms of granuloma formation, as well as a proposed workup and management approach for these granulomatous reactions are presented.

Intraocular tuberculosis has protean clinical manifestations and remains an important etiological differential for uveitis in an endemic region. A 27-year-old male presented with visual acuity of counting fingers close to face in right (OD) and 20/25 in left eye (OS). Examination revealed a choroidal granuloma in OS and healed serpiginous-like choroiditis in OD. Antitubercular therapy was started with systemic corticosteroids. Granuloma resolved completely; however, the patient presented with neuroretinitis and posterior scleritis, as first and second recurrence, respectively, within a oneyear period. These were managed with systemic corticosteroids and immunosuppressive therapy was added, after second recurrence. The patient responded well and maintains remission. This case presented a clinical challenge with distinct recurrence patterns of tubercular posterior uveitis in the same eye, which has not been reported before. Successful management entailed use of antitubercular therapy, corticosteroids, and immunosuppressive therapy in a step-ladder approach, resulting in preservation of vision and achieving long-term remission.

Abstract: Sarcoidosis is a worldwide inflammatory disorder of unknown etiology that is characterized by the formation of non-caseating immune granulomas in involved organs, most commonly in the lungs and eyes. Although clinical manifestations of sarcoidosis depend on the organs involved, the most common symptoms include fatigue, fever, weight loss, eye pain, dyspnea, and chest pain. Sarcoidosis usually undergoes spontaneous regression, yet its chronic form progressively threatens the involved organs through the induction of fibrotic damage. Despite decades of medical research, the etiology of sarcoidosis still remains unclear. Nevertheless, a combination of contributors, including genetic factors, environmental exposures, and microbial agents, is believed to trigger the inflammatory state observed in this disease. Furthermore, a highly polarized Th1 and Th17 response with diminished immunomodulatory mechanisms constitute the most significant immunological event associated with this disorder. Indeed, sarcoid granulomas, which consist of highly activated antigen-presenting cells (APCs) and lymphocytes, maintain a robust specialized niche to facilitate antigen presentation and exaggerated immune responses. Both the unknown etiology and multisystem nature of the disease have hampered the development of specific therapeutics and definitive diagnostic assays for sarcoidosis. Consequently, its diagnosis and treatment still represent a challenging task for clinicians. In this article, we aim to summarize contemporary findings of sarcoidosis and its etiology, pathogenesis, and treatment.

Background/Aims: Intestinal tuberculosis (ITB) is difficult to diagnose due to poor sensitivity of definitive diagnostic tests. ITB may be associated with concomitant pulmonary tuberculosis (PTB) which may remain undetected on chest X-ray. We assessed the role of contrast enhanced computed tomography (CECT) chest in detecting the prevalence of active PTB, and increasing the diagnostic yield in patients with suspected ITB. Methods: Consecutive treatment naïve patients with suspected ITB (n=200) who underwent CECT chest (n=88) and had follow-up duration>1 year were recruited in this retrospective study (February 2016 to October 2018). ITB was diagnosed in the presence of caseating granuloma, positive acid fast stain or culture for Mycobacterium tuberculosis on biopsy, presence of necrotic lymph nodes (LNs) on CT enterography or positive response to anti-tubercular therapy. Evidence of active tuberculosis on CECT-chest was defined as presence of centrilobular nodules with or without consolidation/miliary nodules/thick-walled cavity/enlarged necrotic mediastinal LNs. Results: Sixty-five of eighty-eight patients (mean age, 33.8±12.8 years; 47.7% of females) were finally diagnosed as ITB (4-caseating granuloma on biopsy, 12-necrotic LNs on CT enterography, 1-both, and 48-response to anti-tubercular therapy) and 23 were diagnosed as Crohn’s disease. Findings of active TB on CECT chest with or without necrotic abdominal LNs were demonstrated in 5 and 20 patients, respectively. No patient with Crohn’s disease had necrotic abdominal LNs or active PTB. Addition of CECT chest in the diagnostic algorithm improved the sensitivity of ITB diagnosis from 26.2% to 56.9%.Conclusions: Addition of CECT chest significantly improves the sensitivity for definite diagnosis in a patient with suspected ITB.

Summary Objective Vocal process granuloma (VPG) has a varied treatment success rate and may frustrate patients and physicians due to poor outcomes. There is still a lack of standard protocols to manage VPG. This study aimed to review the efficiency of a standardized low-dose laryngeal electromyographic (LEMG)-guided botulinum toxin A (BTA) injection in intractable vocal granulomas. Methods Twenty-four patients with intractable VPG were recruited. All patients underwent percutaneous LEMG-guided BTA injection on the thyroarytenoid-lateral cricoarytenoid muscle complex in an office setting. The injecting dose was standardized to 1 U in 0.1 mL normal saline at a time. We evaluated the treatment effect by measuring the lesion size with serial laryngoscope evaluations. Results The postinjection follow-up time varied from 3 to 23 months. Twenty-one patients (87.5%) experienced complete regression of the granuloma over 1–7 months (median 3 months). No major adverse effects were noted during the follow-up period. Conclusion For recalcitrant VPG, LEMG-guided low-dose BTA injection has the potential to be a safe, efficient, and effective treatment.

The aims of this study were to describe the trends in the behavior of pediatric CD during the last decade and to describe the seasonal variation of disease presentation.Patients under 18 years old and diagnosed between 2009 and 2019 were included. The clinical, endoscopic, histological, and laboratory data were collected from the medical records. We analyzed the trends of these parameters according to the year and season of diagnosis.654 patients were included in the study. The number of incident CD cases increased yearly. Patients diagnosed between 2015 and 2019 were younger at diagnosis (OR 2.53, p = 0.02), had more perianal diseases (OR: 2.30, p 0.0001) and more granulomas (OR: 1.61, p = 0.003), but fewer eosinophils (OR: 0.35, p 0.0001) and less chronic lymphoplasmacytic infiltrate (OR: 0.56, p = 0.008) as compared to the 2009-2014 cohort. There was fewer CD diagnosis during winter. Patients diagnosed in the fall had lower PCDAIs, less failure to thrive and less extensive digestive involvement. Colonic disease was significantly more frequent during summer and fall.The clinical and histological phenotype of CD has changed over time and there are important seasonal trends in the frequency and severity on disease behavior suggesting possible disease triggers.

Some cases of patients with IgA nephropathy diagnosed via kidney biopsy and antineutrophil cytoplasmic antibody (ANCA) positivity have been reported. This article describes a case series comprising patients with IgA nephropathy and ANCA positivity seen at a medical center in the city of São Paulo, Brazil, from 1996 to 2016. A total of 111 patients underwent diagnostic kidney biopsies for IgA nephropathy. Five were ANCA-positive at the time of diagnosis; their mean age was 45 ± 15.3 years and they were predominantly females with a mean proteinuria of 2.2 ± 0.9 g/day and a median serum creatinine level of 2.5 (2.0 - 8,6) mg/dL; all had hematuria. Four of the five were cANCA-positive (80%); all had normal serum C3 and C4 levels; and 80% were positive for ANA. One case presented an association with infection, but no associations were found with medication. One patient had granuloma and another had a collapsing lesion. This article describes the cases of five ANCA-positive patients (with predominantly cANCA positivity) submitted to diagnostic kidney biopsies for IgA nephropathy; one patient had a collapsing lesion, but progressed well. Resumo Alguns casos clínicos de biópsia renal diagnóstica de nefropatia por IgA em pacientes com títulos séricos positivos de anticorpo anticitoplasma de neutrófilos (ANCA) vêm sendo publicados. Descreve-se uma série de casos de nefropatia por IgA com ANCA positivo de centro único da cidade de São Paulo, Brasil, no período de 1996 a 2016. No período estudado, houve 111 pacientes com biópsia renal com diagnóstico de nefropatia por IgA; destes, 5 tinham ANCA positivo ao diagnóstico com média de idade de 45 ± 15,3 anos, predominando o sexo feminino, com média de proteinúria de 2,2 ± 0,9 g/dia, hematúria presente em 100% dos casos e mediana de creatinina sérica de 2,5 (2,0 - 8,6) mg/dL. O cANCA foi o padrão mais encontrado, em 4 dos 5 casos (80%), com os níveis séricos das frações de complemento C3 e C4 normais em todos e FAN positivo em 80% dos casos. Houve associação com infecções em um caso, mas sem associação com medicações. À microscopia óptica, um dos pacientes tinha granuloma e outro, lesão colapsante. Em resumo, descreve-se cinco casos de pacientes com biopsia renal diagnóstica de nefropatia por IgA com ANCA sérico positivo predominando cANCA, destacando um paciente desse grupo com microscopia óptica com lesão colapsante que, apesar disso, teve boa evolução.

The final stage of spine neoplasm diagnostics is histological examination. In order to obtain the tissue from neoplasm punction biopsy is used.Objective: to assess the efficacy of punctional biopsy with further pathohistological examination in patients with neoplasm in thoracic and lumbar spine.Methods: we analyzed 259 case histories of patients with pathological spine changes.Results: punction biopsy was made in 238 patients (89 %). In 30 (11 %) patients it was no effective because of the large amount of obtained material, in 27 (10 %) pathohistological diagnosis was not established. Pepeated biopsy was made in these cases. As a result at primary and secondary biopsies the diagnosis was confirmed in 95.5 %.Conclusions: punctional biopsy with pathohystological examination is integral part of diagnostic process at spine neoplasm. It allows to obtain enough material for studying (inspite of the dense of tissues) to decrease the risks of contamination of surrounded tissues. Such minimalinvasive method gives possibility to use it in patients with comorbidities. Most of primary spine cancer is represented by myeloma and malignant lymphoma. Episodic were cases of hondrosarcoma, osteosarcoma and fibrosarcoma, when the lesion was spread on one or two vertebrae. Most frequent non malignant lesions were haemangioma and eosino­philic granuloma. Metastatic disease were revealed in 74 (28 %) of patients and often appeared in cases of low grade cancer and adenocarcinoma., Заключительным этапом диагностики опухолевых заболеваний позвоночника является гистологическое исследование. Для получения ткани из очага поражения используют пункционную биопсию.Цель: оценить эффективность пункционной биопсии (с последующим патогистологическим исследованием) у пациентов с новообразованиями в грудном и поясничном отделах позвоночника.Методы: проанализировано 259 историй болезни пациентов с патологическими изменениями в позвоночнике.Результаты: пункционная биопсия выполнена всем больным. При этом у 30 (11 %) человек она оказалась неэффективной из-за небольшого количества полученного материала, а у 27 (10 %) не установлен патогистологический диагноз. Этим 57 (21 %) пациентам проведена повторная биопсия очага поражения. В результате первичной и вторичной биопсии у 95,5 % обследованных патоморфологически диагноз подтвержден.Выводы: пункционная биопсия с последующим патогистологическим исследованием является неотъемлемым этапом диагностического процесса при новообразованиях позвоночника. Она позволяет получить достаточное количество материала (независимо от плотности ткани) для изучения и уменьшить риск контаминации окружающих тканей. Малоинвазивность метода дает возможность использовать его у пациентов с тяжелыми сопутствующими соматическими патологиями. Большинство злокачествен­ных первичных поражений позвоночника представлены плазмоклеточной миеломой (миеломной болезнью) и злокачественной лимфомой; одиночными были случаи хондросаркомы, остеосаркомы и фибросаркомы, когда очаг поражения распространялся на один или два позвонка. Наиболее часто обнаружены такие доброкачественные поражения позвоночника, как гемангиома и эозинофильная гранулема. Метастатические изменения в позвоночнике выявлены у 74 (28 %) пациентов и чаще всего развивались в случае низкодифференцированного рака и аденокарциномы., Заключним етапом діагностики пухлинних захворювань хребта є гістологічне дослідження. Для отримання тканини з вогнища ураження використовують пункційну біопсію.Мета: оцінити ефективність пункційної біопсії (з подальшим патогістологічним дослідженням) у пацієнтів із новоутвореннями в грудному та поперековому відділах хребта.Методи: проаналізовано 259 історій хвороби пацієнтів із патологічними змінами в хребті.Результати: пункційну біопсію виконано всім хворим. При цьому в 30 (11 %) осіб вона виявилася неефективною через невелику кількість отриманого матеріалу, а у 27 (10 %) не встановлено патогістологічний діагноз. Цим 57 (21 %) пацієнтам проведено повторну біопсію вогнища ураження. У результаті первинної та вторинної біопсії у 95,5 % обстежених патоморфологічно діагноз підтверджений.Висновки: пункційна біопсія з наступним патогістологічним дослідженням є невід’ємним етапом діагностичного процесу в разі новоутворень хребта. Вона дозволяє отримати достатню кількість матеріалу (незалежно від щільності тканини) для вивчення та зменшити ризик контамінації прилеглих тканин. Малоінвазивність методу дає можливість використовувати його в пацієнтів із важкими супутніми соматичними патологіями. Більшість злоякісних первинних уражень хребта представлені плазмоклітинною мієломою (мієломною хворобою) і злоякісною лімфомою; поодинокими були випадки хондросаркоми, остеосаркоми та фібросаркоми, коли вогнище ураження поширювалося на один або два хребця. Найчастіше визначали такі доброякісні ураження хребта, як гемангіома й еозинофільна гранульома. Метастатичні зміни в хребті виявлено в 74 (28 %) пацієнтів і найчастіше розвивалися в разі низькодиференційованого раку й аденокарциноми.

Backgrounds Trigeminal neuralgia (TGN) is a common pain syndrome of nervous system, despite about 90% patients who were refectory to medications could free from pain after microvascular decompression (MVD), some patients did experience recurrence. Objectives The study aimed to analyze clinical characteristics of patients with recurrent TN, recurrence factors of TN, and prognosis after re-do MVD. Methods Clinical data and at least 12 months follow-up of patients with recurrent TN who underwent re-do MVD in our hospital from 2005 to 2020 were collected and analyzed. Results 14 patients with recurrent TN were enrolled eventually, adhesive arachnoid membranes were found in all patients. Teflon granuloma was found in 10 patients, new neurovascular compression (NVC) in 3 patients, and Teflon displacement in 1 patient. Pain disappeared in 12 patients and relieved in 2 patients, but 4 patients experienced facial numbness and 1 patient suffered from incision infection after re-do MVC. No serious surgery-related complications and pain recurrences were recorded. Conclusions Teflon granuloma was the most common cause of TN recurrence in current study, new NVC was also a common cause, patients with recurrent TN could get satisfactory results from re-do MVD.

A 67-year-old man was admitted to our hospital with cough and fatigue. He had had long-term exposure to silica due to cement processing. Chest computed tomography showed bilateral centrilobular nodules, and hilar and mediastinal lymphadenopathy with calcification, suggesting chronic silicosis. Within a few months, these nodules enlarged, and bilateral patchy consolidations appeared. A lung biopsy revealed sarcoid-like granulomas with birefringent particles under polarized light without malignancy or infection. He was diagnosed with silicosis-associated sarcoid-like granulomatous lung disease, rather than sarcoidosis, according to the clinicopathological findings. His pulmonary manifestations improved after the discontinuation of silica exposure and combination therapy of corticosteroid and azathioprine.

A two-year-old full-term boy with a history of an intermittent exotropia presented to the pediatric ophthalmology clinic for routine follow-up. He was found to have a stable sensorimotor examination however dilated funduscopic examination of the right eye was significant for a dim foveal reflex with a new discrete, white, elevated retinal lesion superotemporal to the fovea with surrounding subretinal exudates. An examination under anesthesia (EUA) was performed two days later that revealed a subretinal posterior pole granuloma with hyperfluorescence and late leakage from the lesion without telangiectatic vessels on fluorescein angiography. A repeat EUA one month later demonstrated an increase in surrounding subretinal and overlying intraretinal fluid. The patient was started on topical 1% prednisolone with a presumed diagnosis of Toxocara granuloma. At EUA, three months later, the subretinal and intraretinal fluid had resolved. The topical steroids were tapered, and the patient continues to be followed closely.

Asthma and its heterogeneity change with age. Increased airspace neutrophil numbers contribute to severe steroid-resistant asthma exacerbation in the elderly, which correlates with the changes seen in adults with asthma. However, whether that resembles the same disease mechanism and pathophysiology in aged and adults is poorly understood. Here, we sought to address the underlying molecular mechanism of steroid-resistant airway inflammation development and response to corticosteroid (Dex) therapy in aged mice. To study the changes in inflammatory mechanism, we used a clinically relevant treatment model of house-dust mite (HDM)-induced allergic asthma and investigated lung adaptive immune response in adult (20–22 wk old) and aged (80–82 wk old) mice. Our result indicates an age-dependent increase in airway hyperresponsiveness (AHR), mixed granulomatous airway inflammation comprising eosinophils and neutrophils, and Th1/Th17 immune response with progressive decrease in frequencies and numbers of HDM-bearing dendritic cells (DC) accumulation in the draining lymph node (DLn) of aged mice as compared with adult mice. RNA-Seq experiments of the aged lung revealed short palate, lung, and nasal epithelial clone 1 (SPLUNC1) as one of the steroid-responsive genes, which progressively declined with age and further by HDM-induced inflammation. Moreover, we found increased glycolytic reprogramming, maturation/activation of DCs, the proliferation of OT-II cells, and Th2 cytokine secretion with recombinant SPLUNC1 (rSPLUNC1) treatment. Our results indicate a novel immunomodulatory role of SPLUNC1 regulating metabolic adaptation/maturation of DC. An age-dependent decline in the SPLUNC1 level may be involved in developing steroid-resistant airway inflammation and asthma heterogeneity.

PET/CT scans are frequently used in the initial workup of suspicious lesions but not all that lights up on a PET is cancerous. We wish to discuss a case of silicone-induced granuloma mimicking malignancy and the role of other imaging modalities for further workup.

We herein report an unusual case of granulomatosis with polyangiitis (GPA) in a 65-year-old man in whom relapsed disease manifested as an anterior cheek nodule. Magnetic resonance imaging indicated the differential diagnoses of the subcutaneous nodule in the patient's anterior cheek to be inflammatory granulomatous lesions with GPA, malignancy, or infectious disease. A histopathological examination ruled out malignancy and infectious diseases, and necrotizing vasculitis was suspected. The subcutaneous nodule was successfully treated using rituximab, suggesting that it was associated with GPA, secondary to vasculitis. Clinicians should be aware of the possibility of such a rare manifestation of GPA.

INTRODUCTION Sarcoidosis is a chronic granulomatous disease that develops with non-caseified granuloma formation. Galectin-3 is a multifunctional protein operating in biological processes such as fibrosis, angiogenesis, and immune activation. PURPOSE This study evaluates the levels of serum galectin-3 and TGF-beta in sarcoidosis patients to determine a possible correlation with clinical findings. MATERIAL AND METHOD Forty-four biopsy-proven sarcoidosis patients followed in a single centre and 41 age and sex-matched healthy volunteers were included in the study. The levels of serum galectin-3 and TGF-beta were evaluated by ELISA method. RESULTS Among the 44 sarcoidosis patients, 13(29.5%) were male and 31(70.5%) were female. The average patient age was 47.4 and the average disease duration was 3.2 years. The level of serum galectin-3 was found to be the same as in the control group and had no significance statistically (p=.977). No correlation was determined between the level of serum galectin-3 and clinical and laboratory findings of sarcoidosis (p>.05). The level of serum TGF-beta was found to be higher in the sarcoidosis patients when compared to that of the control group (p=.005). While a correlation was found between serum TGF-beta and enthesitis, sacroiliitis, and arthralgia (p=.006, p=.034, p=.02), no correlation was determined on the other clinical and laboratory findings (p>.05). CONCLUSION While the level of serum galectin-3 was determined to be normal in sarcoidosis patients, a high level of serum TGF-beta was found. These findings show that TGF-beta may play an important role in sarcoidosis pathogenesis and the formation of granuloma.

Pulmonary sarcoidosis is a multisystem disease characterized by sarcoid granulomas, vasculitis, and degrees of necrosis with unknown etiology. This article discusses the pathophysiology of sarcoidosis and its medical and nursing management. A case presentation highlights some long-term concerns with this chronic disease.

Necrobiosis lipoidica (NL) is a chronic granulomatous idiopathic disorder. It usually presents as yellow-brown, atrophic, telangiectatic plaques with an elevated violaceous rim, typically in the pretibial region of both extremities with and without ulceration [1, 2]. There are few reported cases of childhood-onset NL in atypical locations. We report a case of type 1 diabetic 13-year-old girl who developed yellow atrophic plaque with telangiectasia on the extensor aspect of her upper arm.

Objective The aim of this retrospective study was to review the clinical data and outcomes of patients that suffered ectopic cilium (EC). Animals studied One hundred and twelve dogs from multiple private practices in France, with a clinical diagnosis of EC were included in the study. Results The mean age of affected dogs was 2.3 years. There were 64 females and 48 males. The most represented breeds were the Shi Tzu, the French Bulldog, the English Bulldog and the Chihuahua. Eleven dogs were affected bilaterally. The upper eyelid was implicated in 93.5% of the cases, with the median portion being the most affected. No statistical difference was observed between the right and the left eye. EC were associated with distichiasis in 50% of the cases. Pigmentation of the conjunctiva at the point of exit of the EC was present in 58% of the cases. EC were short in 75% and long in 25% of the cases. Corneal complications were statistically associated with short EC. The corneal lesions associated with EC were keratitis (94%), corneal granuloma (0.8%), corneal fibrosis (2.7%), corneal degeneration (0.8%), superficial corneal ulcer (68.7%), deep corneal ulcer (8%) and perforating corneal ulcer (0.8%). The surgeries which consisted of the removal of the hair follicle was successful in 88.4% of the cases. Conclusion EC is a rare condition which can be treated successfully by the removal of the hair follicles. It must be suspected in cases of corneal lesions unresponsive to medical treatment.

The differential diagnosis of intestinal tuberculosis and Crohn’s disease is a difficult task for most specialists due to their high similarity in clinical manifestations, instrumental diagnosis and histological pattern.The aim: to consider the clinical and diagnostic features of intestinal tuberculosis and Crohn’s disease, to show the role of various methods of their diagnosis (CT of the abdominal cavity, CT-enterography, colonoscopy with biopsy).A clinical example shows a case illustrating the difficulties of diagnosing intestinal tuberculosis, initially diagnosed as Crohn’s disease. The features of the course, complex diagnosis and treatment of intestinal tuberculosis and its complications during immunosuppression are demonstrated. At the first stage of treatment, the patient’s data related to CT of the chest organs, colonoscopy and histological examination of biopsy samples were incorrectly interpreted. As a result, a wrong diagnosis of Crohn’s disease was made, and immunosuppressive therapy was prescribed that provoked a generalization of the existing tuberculosis process. Subsequently, repeated surgical interventions were performed for complications of intestinal tuberculosis – perforation of tuberculous ulcers, peritonitis. Based on the analysis of the literature data and our own observation, it is shown that granulomatous inflammation in the study of intestinal biopsies doesn’t always allow us to make a clear diagnosis, first of all, there are intestinal tuberculosis and Crohn’s disease in the differential diagnostic series. The use of histobacterioscopy according to Ziehl – Neelsen, the study of fecal matter by luminescent microscopy, as well as molecular genetic methods for detecting DNA MTB allow us to verify the diagnosis. If Crohn’s disease is misdiagnosed as intestinal tuberculosis, then the prescribed anti-tuberculosis therapy can cause harm and lead to a delay in the underlying disease treatment. The reverse misdiagnosis is potentially more dangerous: if tuberculosis is misdiagnosed as Crohn’s disease, then the appointment of immunosuppressive therapy can lead to the generalization of tuberculosis and the development of fatal complications.

Mycoplasma bovis, the most important primary pathogen in the family Mycoplasmataceae, causes pneumonia, arthritis, otitis media, and mastitis in cattle. Histopathologic pulmonary changes associated with M. bovis infection have been characterized as suppurative-to-caseonecrotic bronchopneumonia; infection in other organs has been reported in only a few studies that examined caseonecrotic endocarditis and suppurative meningitis. Granulomatous lesions associated with M. bovis infection have been reported only rarely. We studied the granulomatous inflammation associated with M. bovis infection in several organs of 21 Japanese Black cattle. M. bovis was detected by isolation and loop-mediated isothermal amplification methods; other bacteria were detected using culture on 5% blood sheep agar and a MALDI-TOF MS Biotyper. Tissues were examined by histopathology and by immunohistochemistry (IHC) using anti– M. bovis, anti-Iba1, anti-iNOS, and anti-CD204 antibodies. All 21 cases, which included 2 cases of meningitis-meningoencephalitis, 8 cases of endocarditis, and 11 cases of bronchopneumonia, had caseonecrotic granulomatous inflammation associated with M. bovis infection. The IHC for macrophages revealed a predominance of iNOS-labeled (M1) macrophages in the inner layer of the caseonecrotic granulomas associated with meningitis-meningoencephalitis, endocarditis, and bronchopneumonia in Japanese Black cattle naturally infected with M. bovis.

Foreign body granulomas from sutures are more common among non-absorbable sutures compared to absorbable sutures and have been reported as a postoperative complication in a variety of medical fields. However, only a few cases of delayed foreign body reaction have been reported and addressed with orthopedics. We present a patient with systemic lupus erythematosus who developed an infectious suture granuloma that extended to the entire Achilles tendon and was induced by nonabsorbable sutures that were used for open Achilles tendon repair 20 years before. This granuloma was resistant to antibiotic treatment and drainage and required surgical intervention. The tumor was marginally resected, and the continuity of the Achilles tendon was preserved. Histopathological examination detected many suture materials surrounded by xanthochromic necrotic lesions and the lesion was diagnosed as a foreign body granuloma. At 1 year after the operation, the patient did not exhibit exacerbation of infection or recurrence of the tumor, and she became able to walk by herself. To the best of our knowledge, this represents the first report of an infectious delayed foreign body granuloma in autoimmune disorder patient after open Achilles tendon repair. Surgical intervention should be considered, as treatment with conservative therapy such as antibiotics may be difficult.

BackgroundSarcoidosis is an inflammatory disease characterized by the formation of granulomas, which involve the heart in up to 25% of patients. Cardiac sarcoidosis can lead to life threatening arrhythmias and heart failure. While corticosteroids have been used as a treatment for over 50 years, they are associated with hypertension, diabetes, and weight gain, further increasing cardiovascular risk. Interleukin-1 (IL-1) is the prototypical proinflammatory cytokine that works to activate the nuclear transcription factor NF-kB, one of the targets of glucocorticoids. IL-1 also plays an important role also in the pathophysiology of heart disease including atherosclerosis, myocardial infarction, and myocarditis.MethodsBuilding on a network of research collaborators developed in the Cardiac Sarcoidosis Consortium, we will investigate the feasibility and tolerability of treatment of CS with anakinra at two National Institute of Health Clinical and Translational Science Award (CTSA) hubs with expertise in cardiac sarcoidosis. In this pilot study, up to 28 patients with cardiac sarcoidosis will be recruited to compare the administration of an IL-1 blocker, anakinra, 100 mg daily on top of standard of care versus standard of care only for 28 days and followed for 180 days. Utilizing surrogate endpoints of changes in systemic inflammatory biomarkers and cardiac imaging, we aim to determine whether IL-1 blockade with anakinra can combat systemic and cardiac inflammation in patients with cardiac sarcoidosis.DiscussionThe current trial demonstrates an innovative collaborative approach to clinical trial development in a rare, understudied disease that disproportionately affects females and minorities.Trial RegistrationThe trial was registered prospectively with ClinicalTrials.gov on July 12, 2019, identifier NCT04017936.

BACKGROUND: Inborn errors of immunity (IEI) are rare diseases, which makes diagnosis a challenge. A better description of the initial presenting manifestations should improve awareness and avoid diagnostic delay. Although increased infection susceptibility is a well-known initial IEI manifestation, less is known about the frequency of other presenting manifestations.OBJECTIVE: We sought to analyze age-related initial presenting manifestations of IEI including different IEI disease cohorts.METHODS: We analyzed data on 16,486 patients of the European Society for Immunodeficiencies Registry. Patients with autoinflammatory diseases were excluded because of the limited number registered.RESULTS: Overall, 68% of patients initially presented with infections only, 9% with immune dysregulation only, and 9% with a combination of both. Syndromic features were the presenting feature in 12%, 4% had laboratory abnormalities only, 1.5% were diagnosed because of family history only, and 0.8% presented with malignancy. Two-third of patients with IEI presented before the age of 6 years, but a quarter of patients developed initial symptoms only as adults. Immune dysregulation was most frequently recognized as an initial IEI manifestation between age 6 and 25 years, with male predominance until age 10 years, shifting to female predominance after age 40 years. Infections were most prevalent as a first manifestation in patients presenting after age 30 years.CONCLUSIONS: An exclusive focus on infection-centered warning signs would have missed around 25% of patients with IEI who initially present with other manifestations.

Currently tuberculosis is considered as a group of diseases united by one etiological factor. The pathogenesis of certain localizations of tuberculous inflammation, in particular peritoneum tuberculosis, hasn’t been sufficiently studied. The role of cytokine mechanisms in the development of the disease and the elaboration of non-sterile immunity requires further experimental studies, in particular the creation of a reproducible model on laboratory animals.The aim: to study the effect of TNF-α on the development of tuberculosis of the serous coat of the abdominal cavity, as well as to evaluate the possibility of modeling tuberculous peritonitis in laboratory animals using infliximab.Materials and methods. The studies were conducted on 18 male rabbits, which were simulated peritoneal tuberculosis by intra-abdominal administration of a suspension of Mycobacterium tuberculosis. 10 rabbits of the experimental group were intravenously injected with an infliximab solution and an iron (III) hydroxide sucrose complex intraperitoneally a day before infection.Results. In the control group of animals, tuberculosis either didn’t develop, or in a third of cases it affected only the pulmonary parenchyma, while proliferative processes prevailed. On the contrary, in animals with inactivated TNF-α, in 100 % of observations, tuberculous peritonitis was detected with associated lung damage and the predominance of alterative caseous processes.Conclusion. The created model of tuberculous peritonitis shows the leading role of TNF-α in the activation of macrophages, as well as in attracting cells to the site of infection. This is the primary signal necessary for the formation and stability of granulomas since the neutralization of this cytokine leads to a loss of control over the infection and the destruction of the granuloma with the development of destructive tuberculosis in the serous coat of the abdominal cavity.

A granuloma, a pathologic hallmark of tuberculosis (TB), is a complex cellular structure that develops at the site of Mycobacterium tuberculosis (Mtb) infection and is comprised of different immune cell types. Severe pulmonary TB in humans is characterized by the presence of heterogeneous granulomas, ranging from highly cellular to solid/non-necrotic and necrotic lesions, within the lungs. The host-Mtb interactions within the granulomas dictate the containment of Mtb infection or its progression into a necrotic, cavitary disease. However, the immune environment in various granulomas is poorly understood. The myeloid-derived suppressor cells (MDSCs) are key immune cells that regulate the protective versus permissive host responses against Mtb infection. However, their contexture within the lung granulomas remains unclear. In this study, using single and multiplex immunohistochemical staining, we analyzed the distribution of MDSCs, macrophages, CD4+ T cells and their immunometabolic and effector function states in the solid/non-necrotic and necrotic granulomas in patients with active pulmonary TB. We found increased MDSCs with elevated expression of immunosuppressive molecules in the solid/non-necrotic granulomas. In contrast, cells in the solid and necrotic granulomas produced similar levels of IL-6 and IL-10. Our findings suggest that MDSCs are present in solid/non-necrotic granuloma, which may play an essential role in the progression into a necrotic lesion, thus exacerbating disease pathology and transmission.

The objectives are to precisely identify the cells that incite the formation of lesions that are generally known as "pulse granuloma" or "hyaline ring granuloma" that occur mostly in the oral cavity, in the lungs, in and around the gastrointestinal tract, and other sites, and to suggest an alternative name for these lesions that accurately reflects their etiology. Critical review of the medical and dental literature was undertaken, and the microscopic appearances of granuloma-inciting cells depicted in the literature and seen in our practices were compared with seeds and their contents originating from a variety of leguminous and non-leguminous plants. Sections of selected seeds were examined microscopically before and after digestion with saliva and alpha amylase and subsequent routine processing and staining with H&E, PAS, and iodine. Pre- and post-digestion slides were examined with polarized light. The morphology of the granuloma-inciting cells is identical to the storage cells present in seeds from a variety of leguminous and non-leguminous plants. The cells that trigger the formation of "pulse granulomas"/"hyaline ring granulomas" are storage cells that are derived from ingested seeds of leguminous and non-leguminous plants. The terms "pulse," "legume," and "lentil," which have been applied to these cells, are misnomers. Our findings indicate that the terms "pulse granuloma" and "hyaline ring granuloma" are not appropriate descriptors of these lesions. We recommend that they be replaced by "seed storage cell granuloma," a term that now accurately reflects the etiology of these lesions.

Localized inflammatory or reactive overgrowths are quite more common clinical findings on human gingiva. Most of the lesions are benign and innocuous though some have potency to transfer in to a malignant lesion. These types of lesions are difficult to identify clinically as their appearance are quite similar so only Histopathological evaluation can detect their identity. In this case report we displayed a case of Peripheral Ossifying Fibroma in maxillary anterior tooth region in 32 year old female patient along with clinical, Histopathological evaluation along with present and future treatment details. Peripheral ossifying fibroma (POF) is usually a fibromatic, non neoplastic enlargement of the gingiva which shows areas of calcification or ossification. Synonyms for POF include Peripheral cementifying fibroma, Peripheral fibroma with calcification, Calcifying or ossifying fibrous epulis and Calcifying fibroblastic granuloma. Keywords: Gingival overgrowth, Ossifying fibroma, Peripheral ossifying fibroma, Peripheral cementifying fibroma

Exposure to particulate matter pollutant PM2.5 diminishes the immune response to mycobacterial antigens relevant to contain the infection in the granuloma, thus leading to reactivation of latent bacilli. The present study was therefore designed based on the hypothesis that exposure to PM2.5 affects the granuloma formation and reactivation of latent mycobacterial bacilli contained in the granuloma. For the sampling of PM2.5, based on initial standardisations, Teflon filter was selected over the quartz filter. Two different approaches were used to study the effect of PM2.5 on the human PBMC granuloma formed by Mycobacterium bovis BCG at multiplicity of infection (MOI) 0.1. In the first approach, granuloma formed in the presence of PM2.5 was loosely packed and ill-defined with significant downregulation of dormancy-associated mycobacterial genes, upregulation of reactivation-associated rpfB gene along with a significant increase in TNFα level without any change in the bacterial load in terms of CFUs. In the second approach, preformed human PBMC granuloma using M. bovis BCG was treated with PM2.5 that resulted in the disruption of granuloma architecture along with downregulation of not only dormancy-associated genes but also reactivation-associated rpfB gene of mycobacterial bacilli recovered from granuloma. However, there was no significant change in the host cytokine levels. Therefore, it can be inferred that PM2.5 can modulate the granuloma formation in vitro as well as mycobacterial gene expression in the granuloma with a possible role in the reactivation of latent bacilli.

Haile Tazeze,1 Solomon Mequanente,2 Dereje Nigussie,3 Belete Legesse,4 Eyasu Makonnen,2,4 Teklie Mengie5 1Department of Pharmacy, Kidus Petros TB Specialized Hospital, Addis Ababa, Ethiopia; 2Department of Pharmacology & Clinical Pharmacy, School of Pharmacy, College of Health Science, Addis Ababa University, Addis Ababa, Ethiopia; 3Ethiopian Public Health Institute, Addis Ababa, Ethiopia; 4Center for Innovative Drug Development & Therapeutics Trial in Africa (CDT-Africa), College of Health Science, Addis Ababa University, Addis Ababa, Ethiopia; 5Department of Pharmacy, College of Health Science, Debre Tabor University, Debre Tabor, EthiopiaCorrespondence: Teklie Mengie P.O.Box:272, Debre Tabor, 6300, EthiopiaTel +251910111531Email tekliepharm@gmail.comBackground: Traditionally Aloe trigonantha leaf is used for the treatment of different diseases. However, there were no in vivo studies which prove its claimed use for wound healing and anti-inflammatory activity. Therefore, the present study aimed at evaluating the in vivo wound healing and anti-inflammatory effects of the leaf gel of the plant in rats.Methods: The leaf gel powder of the Aloe trigonantha was prepared after the gel gets lyophilized. It was evaluated for wound healing activity topically by incorporating it in a simple ointment base at a concentration of 5% (w/w) and 10% (w/w). Excision and incision models were used for wound healing activity in rats. For the excision wound model, wound contraction and period of epithelialization were evaluated, while wound tensile strength was evaluated using an incision wound model. A Xylene-induced ear edema model and cotton pellet-induced granuloma model were used for anti-inflammatory study. The leaf gel powder of Aloe trigonantha was given orally at a dose of 100, 200, and 400 mg/kg in both models of anti-inflammatory studies. An anti-inflammatory effect was measured by reduction of ear edema weight and reduction of wet exudate and dry granuloma weight in both of xylene-induced ear edema and cotton pellet-induced granuloma models, respectively.Results: Treatment of wounds with ointment containing 5% and 10% (w/w) of the gel exhibited a significantly increased wound contraction rate, shorter epithelialization time, and higher skin breaking strength (p< 0.05) compared to controls. Aloe trigonantha leaf gel powder also produced dose-dependent significant reductions (p< 0.05) of inflammation compared to control in both models.Conclusion: Data obtained from this study collectively indicated that Aloe trigonantha is a potential wound-healing and anti-inflammatory agent in rat models of wound and inflammation which provides evidence for the traditional claim.Keywords: Aloe trigonantha, wound healing, anti-inflammatory, granuloma model, ear edema model

Background Granulomatous amoebic encephalitis (GAE) is an infrequent and fatal infectious disease worldwide. Antemortem diagnosis in this condition is very difficult because clinical manifestations and neuroimaging are nonspecific. Case presentation A 60-year-old Japanese woman was admitted with a chief complaint of left homonymous hemianopsia. Brain-MRI showed extensive necrotizing lesions enhanced by gadolinium, in the right frontal lobe, right occipital lobe, and left parietal lobe. Epithelioid granulomas of unknown etiology were found in the biopsied brain specimens. Shotgun metagenomic sequencing using a next-generation sequencer detected DNA fragments of Balamuthia mandrillaris in the tissue specimens. The diagnosis of granulomatous amoebic encephalitis was confirmed using an amoeba-specific polymerase chain reaction and immunostaining on the biopsied tissues. Conclusions Shotgun metagenomics is useful for the diagnosis of central nervous system infections such as GAE wherein the pathogens are difficult to identify.

The evidence of an association between diabetes and latent tuberculosis infection (LTBI) remains limited and inconsistent. Thus, the study aims to delineate the role of diabetes in activation of latent tuberculosis infection. Murine model of latent tuberculosis and diabetes was developed, bacillary load and gene expression of resuscitation promoting factors (rpfA-E) along with histopathological changes in the lungs and spleen were studied. Treatment for LTBI [Rifampicin (RIF) + Isoniazid (INH)] was also given to latently infected mice with or without diabetes for 4 weeks. Diabetes was found to activate latent tuberculosis as the colony forming unit (CFU) counts were observed to be > 104in lungs and spleen. The gene expression ofhspXwas downregulated and that ofrpfBandrpfDwas observed to be upregulated in latently infected mice with diabetes compared to those without diabetes. However, no significant reduction in the CFU counts was observed after 4 weeks of treatment with RIF and INH. Diabetes helps in the progression of LTBI to active disease mainly through altered expression of resuscitation promoting factorsrpfBandrpfD, which can serve as important targets to reduce the shared burden of tuberculosis and diabetes.

Use of stem cells to treat various diseases in dermatology has been of interest. Conditioned media with the growth factors secreted from stem cells has been used as a topical agent. We report a case of foreign body granulomas that appeared days after dermal injection of the conditioned media mimicking scars at all injection sites.

Hypersensitivity pneumonitis (HP) is an inflammatory and/or fibrotic disease of the lung parenchyma and terminal bronchioles caused by an allergic reaction to inhaled antigens. The immune response following antigen exposure results in lymphocytic inflammation as well as granuloma formation.The typical histologic pattern of HP consists of cellular interstitial pneumonia, cellular bronchiolitis, and epithelioid cell granulomas. The additional presence of fibrosis has a significant impact on the course as well as the prognosis of the disease and represents a therapeutic approach. Therefore, a classification into a non-fibrotic and a fibrotic phenotype is proposed.The diagnosis of HP is made by high-resolution computed tomography (HRCT) of the lung, evaluation of possible antigen exposure, and bronchoscopy with bronchoalveolar lavage and, if necessary, forceps biopsy. If the diagnosis is inconclusive, transbronchial cryobiopsy or surgical lung biopsy may need to follow. A multidisciplinary board is critical in making the diagnosis.

Sarcoid-like granulomatosis (SLG) reaction caused by immunotherapy remains poorly understood. This study aims to investigate the outcome of patients with cancer and SLG associated with immunotherapy.Between April 2016 and June 2020, 434 patients with immunological adverse events were screened from the ImmunoTOX assessment board of Gustave Roussy, an academic cancer centre in France. Among them, 28 patients had SLG associated with immunotherapy (SLG cohort) and 406 patients had other immunological adverse events (control cohort). Clinical characteristics and outcome of patients were compared from SLG and control cohort.The SLG cohort consisted of 28 patients, 14 women and 14 men, with the median (range) age of 56.5 (28.7-75.3) years. Patients in the SLG cohort with sarcoidosis were asymptomatic (only radiographical finding) in 13 (46.4%) cases; otherwise, the most frequent symptoms were dyspnoea in 8 (28.6%) patients and cough in 5 (17.8%) patients. The computerised tomography scan found sarcoidosis localisations in mediastinal or peri-hilar thoracic lymph nodes in 26 (92.9%) patients, and lung parenchymal involvement was found in 14 (50.0%) patients. The radiographic Scadding stages for sarcoidosis classification were distributed in stages 0, I, II, III and IV in 2 patients (7.1%), 13 patients (46.4%), 11 patients (39.3%), 1 patient (3.6%) and 1 patient (3.6%), respectively. Compared with patients with other immunological toxicities (cohort control), patients with sarcoidosis presented most frequently with melanoma (75.0% versus 21.9% of patients; p 0.001) and more often received combined therapies of anti-programmed cell death 1 plus anti-cytotoxic T-lymphocyte antigen 4 protein (46.4% versus 12.6% of patients; p = 0.002). Patients with sarcoidosis had an improved overall survival (OS); the median OS was not reached in the SLG cohort and 40.4 months in the control cohort, hazard ratio = 0.232 (95% confidence interval: 0.086-0.630) (p = 0.002).Sarcoidosis-like reactions in patients receiving immunotherapy were reported as non-severe immunological reactions in most cases and were correlated with improved OS. SLG should not be misdiagnosed as tumour progression in patients receiving immunotherapy treatment for cancer.

Eosinophilic granulomatosis with polyangiitis (EGPA), formerly called Churg-Strauss syndrome, is a rare chronic necrotizing eosinophilic granulomatous inflammatory disease characterized by eosinophil-rich granulomatous inflammation and small- to medium-size vessel vasculitis associated with bronchial asthma and eosinophilia, which is positive for anti-neutrophil cytoplasmic antibody (ANCA) in approximately 50-70% of cases. We report a case of a 23-year-old woman was admitted to our hospital because of a of small vesicles on both lower limbs and a 4-month history of small scattered skin rash with pruritus V6 on both lower limbs four-month history of scattered skin rash with pruritus. Laboratory data from peripheral blood revealed leukocytosis, eosinophilia, thrombocytosis, hyperfibrinolysis, and mild renal injury. Her ANCA was negative, and the skin pathological examination showed granuloma lesions with eosinophils, while elevated eosinophils were also found in the bone marrow. EGPA was diagnosed. On the other hand, the patient had 2-year-long rhinosinusitis, 9-month-long nephrotic syndrome, and 1-month-long dry cough, which might be a type of asthma. With steroid therapy followed by systemic immunomodulatory therapy, the patient's symptoms were relieved. Our case report and literature review highlight the importance of recognizing cough variant asthma as an initial presenting symptom of EGPA, providing an opportunity for early diagnosis and treatment to reduce the risk of further disease progression and morbidity.

Granulomas Hialinizantes são lesões pulmonares fibrosantes raras, de etiologia ainda desconhecida. A apresentação é em geral de uma doença benigna, sendo os pacientes assintomáticos ou apresentando queixas torácicas vagas. Se apresentam, nos exames radiológicos, sob a forma de múltiplos nódulos pulmonares, que podem simular várias condições, particularmente metástases hematogênicas. Paciente do sexo feminino, assintomática, ao realizar pré-operatório para retirada em lesão maligna em dorso nasal foi evidenciada pela radiografia de tórax presença de opacidades em seguimentos dos lobos superiores bilaterais e calcificações em seguimento do lobo inferior direito pulmonar, de variados tamanhos, sugerindo a hipótese de metástase pulmonar. O diagnóstico confirmatório, realizado após segmentectomia pulmonar esquerda, por meio de análise histopatológica, evidenciou lesões benignas, firmando o diagnóstico de Granuloma Hialinizante Pulmonar, e excluindo a causa metastática. Até onde sabemos, esta é uma condição pouco conhecida, não sendo mencionada na maioria dos livros-texto que abordam radiologia pulmonar, frequentemente causando grandes dificuldades diagnósticas, tanto em termos radiológicos como anatomopatológicos.

Haemophagocytic lymphohistiocytosis (HLH) is a lethal complication of several infections, especially viral origin. Mycobacterium tuberculosis infection can also lead to HLH, yet it is an uncommon trigger. Considering the role of increased cytokines in HLH, autoinflammatory conditions, such as familial Mediterranean fever (FMF), might contribute to its development. Nevertheless, the possible relationship between FMF and HLH has been suggested only in some case reports. We present a case of FMF who admitted to the hospital with consitutional symptoms and chest pain regarding to recurrent pericarditis. On a blood test, pancytopenia and elevated acute phase reactants were seen. Fluorine-18 fluorodeoxyglucose (FDG) positron emission tomography/computed tomography demonstrated positive FDG uptake sites on both the right and left surrenal glands, the visceral layer of pericard, and reactive lymphadenomegalies at multiple mediastinal regions. Bone marrow biopsy revealed haemophagocytosis. Methylprednisolone treatment was initiated. Despite immunosuppressive treatment, clinical and biochemical parameters deteriorated; thus, a thorax computed tomography was executed. Findings were consistent with miliary tuberculosis infection. M. tuberculosis was detected in blood culture and bronchoalveolar lavage culture material. Also, bone marrow and surrenal biopsy material revealed necrotising caseating granuloma.

Dirofilariasis is a vector-borne disease that is present worldwide. This report describes a giant subconjunctival granuloma which mimics scleritis, caused by D. immitis. A 60-year-old man was referred with the complaints of irritation, redness, and swelling at the medial part of the right eye. He was living in Izmir province located in western Turkey. Slit-lamp examination showed a firm, immobile mass measuring 13.0 x 5.0 x 5.0 mm with yellowish creamy color. The mass was completely removed surgically under local anesthesia mainly for diagnosis. Histopathology revealed typical morphological features of a filarioid nematode in favor of Dirofilaria as characterized by the external smooth cuticular surface, cuticular layer, muscle layer, and intestinal tubule. Molecular study was performed using DNA isolated from paraffin-embedded tissue sections of the worm. PCR amplification and then DNA sequence analysis of cytochrome c oxidase subunit 1 (cox1) gene fragment confirmed that the worm was D. immitis. It is suggested that this may represent the first human case of D. immitis occurring in subconjunctival granuloma in Turkey. Although rare, D. immitis caused by ocular dirofilariasis in humans should be considered.

Cutaneous eruptions associated with hemophagocytic lymphohistiocytosis (HLH) have been reported in 6%-63% of patients. Clinical findings of these skin lesions vary widely and include maculopapular rashes, ulcers, and violaceous nodules. Corresponding histologic findings are also variable and are considered nonspecific. We report the case of a 4-year-old boy who initially developed a widespread popular-pustular rash 2 weeks after his 12-month measles, mumps, and rubella vaccinations. These resolved with scarring then recurred following his 24-month vaccinations. Multiple skin biopsies were negative for infectious organisms and showed a granulomatous infiltrate with perforation and necrobiosis. The differential diagnosis included perforating granuloma annulare, infection, or rheumatoid nodules. At the age of 4, he developed fever, hepatosplenomegaly, pancytopenia and other laboratory abnormalities, requiring hospitalization. A number of studies were performed including biopsies of bone marrow and liver. Molecular testing revealed 2 mutations in UNC13D known to be associated with familial HLH. His prior cutaneous lesions were likely caused by immune dysregulation exacerbated by immunizations because of underlying familial HLH. This case illustrates the importance of recognizing an unusual cutaneous manifestation of a rare disease to arrive at an earlier diagnosis in a pediatric patient. Although cutaneous eruptions usually develop concurrently with other systemic symptoms of HLH, preceding unusual skin lesions may be the first indication of this rare disease.

Paraneoplastic granulomatous disease occurs in approximately 7.3% of patients with non-Hodgkin lymphoma, most commonly among patients with chronic lymphocytic leukemia (CLL). These lesions are often reported to appear similar to sarcoidosis in clinical presentation and under light microscopy. However, comprehensive descriptions of the cytomorphologic characteristics of these paraneoplastic granulomas are lacking, and the mechanisms involved in their formation remain ill-defined. Noninfectious dermal granulomatous reactions have also been reported in many primary immunodeficiencies, including common variable immune deficiency and ataxia-telangiectasia. We present a case of noninfectious CD8+ predominant granulomatous dermatitis with ocular involvement occurring in the setting of CLL and marked hypogammaglobulinemia. Based on the analysis of shared factors in patients with primary immunodeficiencies and CLL, we conclude that the presence of pan-humoral immunodeficiency could itself be a risk factor for developing a CD8+ lymphogranulomatous reaction. This report and associated discussion evince that CD8+ predominant granulomatous reactions, distinct from sarcoidosis, may represent a previously unappreciated segment of the paraneoplastic granulomas observed in hematologic malignancies.

This study was carried out to evaluate the anti-inflammatory activity of flavonoid (Rutin 20 mg/kg) on each (carrageenan-induced paw edema)acute inflammation and (cotton pellet granuloma) chronic inflammation and, effect of Rutin on some hematological, biochemical and histopathological examination in guinea pigs induced by inflammation. A total of eighteen male guinea pigs were categorized into three groups, six pigs on all group. Group one as non-treated control, they given 5% carboxymethyl cellulose orally for seven days. Group two received single dose orally (20mg/kg) Rutin for seven days. Group three received (10mg/kg) Indomethacin orally for seven days. By injecting of 0.1ml of carrageenan suspension in saline into the sub-planter superficies of the right hind paw, the acute inflammation (edema) was induced in all experiment guinea pigs one hour after compounds taken. Then estimated the volume of paw edema immediately after carrageenan injection through one, two, three and four hours by using a plethysmograph system(VGO Basile, Italy). The results indicated that, Rutin (20 mg/kg body weight) showed significant lowered (P

Background Suture granuloma with hydronephrosis after abdominal surgery is extremely rare. We herein report a successfully treated case of suture granuloma with hydronephrosis caused by ileostomy closure after rectal cancer surgery. Case presentation A 63-year-old male underwent laparoscopic low anterior resection with covering ileostomy. Two months after primary operation, ileostomy closure was performed with two layered hand-sewn suture (Albert–Lembert method) using absorbable suture. In that operation, marginal blood vessels in the mesentery were ligated with silk suture. The patient had remained in remission with no evidence of tumor recurrence, however, 2 years and 5 months after primary surgery, a contrast-enhanced computed tomography (CT) scan showed a mass-forming lesion on the right external iliac artery (43 × 26 mm) and hydronephrosis. Positron emission tomography/computed tomography (PET/CT) showed a mass-forming lesion without high accumulation, which obstructed the right ureter. Recurrence could not be ruled out due to the rapid appearance of tumor and hydronephrosis in the short-term period. Thus, the patient underwent laparotomy. The tumor located in the mesentery near the anastomosis of ileostomy closure and it was strongly adherent to the retroperitoneum, which obstructed the right ureter. The adhesion between the tumor and ureter was carefully dissected and tumor resection with partial small bowel resection was then performed with preservation of the ureter using ureteral stents. Pathological examination of the tumor revealed fibrous proliferation of foreign body granuloma. In the resected tumor, sutures with foreign giant cells were found. Therefore, we diagnosed the tumor as silk suture granuloma, which was caused by the silk suture used to ligate blood vessels of the mesentery at the ileostomy closure. The patient remained well with no evidence of tumor recurrence as 5 years after the primary operation of rectal cancer. Conclusions Suture granuloma is a rare surgery-related complication in the postoperative surveillance of patients with colorectal cancer. If suture granuloma mimicking local recurrence is a differential diagnosis, it would be important to consider to avoid unnecessary extended resection.

A 2‐year‐old male desexed Ragdoll cat with a 1‐year history of sneezing and nasal discharge presented with a large subcutaneous cervical mass, identified as the right medial retropharyngeal lymph node on computed tomography (CT). A right orbital mass, destructive sino‐nasal cavity disease and multiple pulmonary nodules were also identified. Aspergillus felis was cultured from the lymph node. After treatment with posaconazole and liposomal amphotericin B the lymph node enlargement and orbital mass resolved but left frontal sinus involvement and pulmonary lesions persisted despite additional caspofungin therapy. The cat was euthanized 14 months after diagnosis with dysphagia and chronic progressive exophthalmos. A meningeal granuloma with intravascular fungal hyphae was identified at post‐mortem and A felis was cultured from the left frontal sinus and a right retrobulbar fungal granuloma. This case demonstrates that disseminated disease is a possible sequel to invasive fungal rhinosinusitis caused by A felis in cats.

Part 2 of this series on granulomatous diseases focuses on skin biopsy findings. Whereas the first part treated noninfectious conditions (metabolic disorders and tumors, among other conditions), this part mainly deals with various types of infectious disease along with other conditions seen fairly often by clinical dermatologists.

The faultless seal of the anastomosis is an important aspect of abdominal surgery but opportunities to make a histological evaluation of human intestinal anastomosis sites are rare. This retrospective study examined 30 anastomoses that had been resected following complications or postmortem; the aim was to describe the histological changes at various stages of healing ranging from 4 days to 3.5 years post-surgery. Anastomosis dehiscence showed features of extensive mucosal necrosis and bad submucosal apposition. Old healed anastomoses continued to have chronic inflammatory cells and muscular discontinuity with areas of intervening fibrosis. It would be useful to underst and more about how the intraluminal contents are propelled through this scarred area

This series of 2 articles on dermatopathologic diagnoses reviews conditions in which granulomas form. Part 1 clarifies concepts, discusses the presentation of different types of granulomas and giant cells, and considers a large variety of noninfectious diseases. Some granulomatous diseases have a metabolic origin, as in necrobiosis lipoidica. Others, such as granulomatous mycosis fungoides, are related to lymphomas. Still others, such as rosacea, are so common that dermatologists see them nearly daily in clinical practice.

Rationale: Our current understanding of tuberculosis (TB) pathophysiology is limited by a reliance on animal models, the paucity of human TB lung tissue, and traditional histopathological analysis, a destructive two-dimensional approach that provides limited spatial insight. Determining the three-dimensional (3D) structure of the necrotic granuloma, a characteristic feature of TB, will more accurately inform preventive TB strategies. Objectives: To ascertain the 3D shape of the human tuberculous granuloma and its spatial relationship with airways and vasculature within large lung tissues. Methods: We characterized the 3D microanatomical environment of human tuberculous lungs by using micro computed tomography, histopathology, and immunohistochemistry. By using 3D segmentation software, we accurately reconstructed TB granulomas, vasculature, and airways in three dimensions and confirmed our findings by using histopathology and immunohistochemistry. Measurements and Main Results: We observed marked heterogeneity in the morphology, volume, and number of TB granulomas in human lung sections. Unlike depictions of granulomas as simple spherical structures, human necrotic granulomas exhibit complex, cylindrical, branched morphologies that are connected to the airways and shaped by the bronchi. The use of 3D imaging of human TB lung sections provides unanticipated insight into the spatial organization of TB granulomas in relation to the airways and vasculature. Conclusions: Our findings highlight the likelihood that a single, structurally complex lesion could be mistakenly viewed as multiple independent lesions when evaluated in two dimensions. In addition, the lack of vascularization within obstructed bronchi establishes a paradigm for antimycobacterial drug tolerance. Lastly, our results suggest that bronchogenic spread of Mycobacterium tuberculosis reseeds the lung.