Diffuse Lymphocytic Infiltration Research Articles

Acute lymphoblastic leukemia with nephrogenic diabetes insipidus as the first symptom: a case report

BackgroundAcute lymphoblastic leukemia is the most common pediatric malignancy, characterized by fever, anemia, hemorrhage, and symptoms brought on by blasts infiltrating organs.Case presentationThis is a case report of a 9-year-old Asian patient with acute lymphoblastic leukemia who presented with polyuria alone as a presenting feature without any other clinical manifestation; primary renal disease or inherited metabolic disease was highly suspected. However, the water deprivation test and water deprivation pressurization test suggested nephrogenic diabetes insipidus, and the renal biopsy displayed diffuse lymphocytic infiltration in the renal interstitium. Bone marrow aspiration was performed immediately, and a comprehensive diagnosis of B-lymphoblastic leukemia was finally made.ConclusionsRenal infiltration with leukemic blasts mostly remains asymptomatic, but our case suggests that it can present with nephrogenic diabetes insipidus. This case fully demonstrates that the presentation of extramedullary infiltration in acute lymphoblastic leukemia is varied. When the patient has renal diabetes insipidus as the first symptom, the possibility of hematological tumor infiltration should be considered when finding the cause, and timely bone marrow cytology should be performed.

Heart transplantation under mechanical circulatory support for fulminant myocarditis: a Case Report

Fulminant myocarditis has been defined as the clinical manifestation of cardiac inflammation with rapid-onset heart failure and cardiogenic shock. We report on the case of a 17-year-old boy with hemodynamic derangement and cardiac arrest due to fulminant myocarditis. After about 2 h of intensive cardiopulmonary resuscitation, with 13 days of extracorporeal membrane oxygenation support, the patient finally bridged to orthotopic heart transplantation. The patient recovered uneventfully and was discharged 37 days after transplantation. The explanted heart revealed diffuse lymphocytic infiltration and myocyte necrosis in all four cardiac chamber walls confirming the diagnosis and identifying the underlying cause of fulminant myocarditis.

Chinese expert consensus on the pathological diagnosis of interstitial lung disease with transbronchial lung cryobiopsy specimens

Transbronchial lung cryobiopsy (TBLC) is an applicable technique that can provide a histologic diagnosis of interstitial lung disease(ILD). The general sample size of TBLC is much smaller than that of surgical lung biopsy (SLB), which raises more concerns about the procedure's diagnostic accuracy. A guiding consensus and guidelines on the pathological procedure of ILD with TBLC are required to better guide pathologists in diagnostic practice. The Respiratory Pathology Working Group of the Respiratory Physicians Branch of the Chinese Medical Doctor Association and the Thoracic Diseases Group of the Pathological Branch of the Chinese Medical Association, jointly organized by experts, have worked together to discuss and formulated the consensus. The consensus is based on literature review, clinical practice, collection of clinical issues, and discussion during a series of meetings. Experts approved the final proposed consensus with more than 70% of votes in favor (Delphi). The consensus summarized the delivery requirements, quality evaluation and artificial phenomena of TBLC specimens. It also proposed the diagnostic principles and procedures, types of ILD corresponding to major pathological changes, and major corresponding differential diagnoses of TBLC specimens. Finally, the consensus formed 14 recommendations for clinical diagnosis and multidisciplinary discussion.The recommendations are addressed as follows.Recommendation 1: We suggest that the TBLC clinical manipulators should observe and measure the size of the specimen in time. The specimen size should be greater than 5 mm in diameter, and multiple pieces(3 to 5 pieces)are recommended.Recommendation 2: Pathologists should record the number of blocks of tissue submitted for examination and the volume, color, and texture of each specimen. Evaluation of the proportion of alveolar parenchyma/airway components under the microscope, analysis of the type and distribution of lesions will facilitate making diagnostic suggestions.Recommendation 3: The size of TBLC specimens is significantly smaller than SLB and may not show sufficient features of ILD or secondary changes. It is more necessary to combine the evaluation of clinical changes and lesion distribution assessed by HRCT for a comprehensive diagnosis.Recommendation 4: Common microscopic artefacts of TBLC specimen are mass of red blood cells, proteinaceous fluid and fibrin exudation. In the absence of hemosiderin cells or clinical signs of hemoptysis symptoms, the diagnosis of pulmonary hemorrhagic disease should be considered with caution.Recommendation 5: TBLC is not a suggested diagnosis when the pathological changes are mainly located in the pleural or subpleural lung tissues, e.g., pleuroparenchymal fibroelastosis.Recommendation 6: The principle of pathological diagnosis of ILD in TBLC is consistent with SLB, with a description of the main pathological morphological change and a tendentious pathological diagnosis; if the lesion is not fully shown, only a pathological description is given.Recommendation 7: A well-sampled TBLC specimen may show patchy fibrosis and fibroblast foci in UIP, supporting a pathological diagnosis of a probable UIP pattern. TBLC may not display sufficient features of the distribution of subpleural and peripheral lung lesions in UIP, as well as secondary lesions.Recommendation 8: TBLC specimens show diffuse inflammation and fibrosis with well-preserved lung tissue structure, which may support a pathological diagnosis of NSIP; if the distribution of lesions and lung tissue structure are difficult to evaluate, it is recommended that a pathological diagnosis of fibrotic ILD or cellular ILD be made.Recommendation 9: TBLC specimens may show pathological features of NSIP accompanied by organization, but it is difficult to accurately evaluate the proportion of organization area. In this scenario, a descriptive diagnosis of NSIP accompanied by organization is suggested.Recommendation 10: It is recommended to diagnose organizing pneumonia if only distal airway organization is present in TBLC; in addition to organization, if pathological histology is accompanied by obvious interstitial fibrosis and lung tissue remodelling, granuloma formation, obvious neutrophil infiltration or accompanied with abscess formation, obvious eosinophil infiltration, tissue necrosis, hyaline membrane formation or vasculitis, secondary OP should be considered.Recommendation 11: It is recommended to diagnose acute fibrinous and organizing pneumonia (AFOP) if lesions on TBLC show features of organizing pneumonia and fibrin balls.Recommendation 12: A diagnosis of smoking-related ILD (RB-ILD or DIP) is suggested when a good sampling of TBLC shows a significant accumulation of histocytes or smoker's macrophages in the alveolar spaces, and without specific changes sufficient for other diagnoses. If the lesions are confined to the lumen of respiratory bronchioles and the immediate peribronchiolar airspaces, RB-ILD is supported; if the distribution is diffuse, DIP should be considered. If it is difficult to determine the distribution of the lesions, it is necessary to integrate clinical and chest CT imaging findings to differentiate RB-ILD from DIP.Recommendation 13: A well-sampled TBLC specimen can display the pathological features of DAD and then also support such a pathological diagnosis.Recommendation 14: Lymphoid interstitial pneumonia (LIP) should show diffuse lymphocyte infiltration and lymphoid follicle formation in the lung interstitium in TBLC specimens. It is recommended that chest CT imaging be combined to determine whether the lesion is diffuse to differentiate from other lymphoproliferative diseases.

Fixed oil from the Caatinga palm Syagrus coronata with effect on Complete Freund's Adjuvant (CFA)-induced arthritis.

Syagrus coronata, a native palm tree in the Caatinga domain, produces fixed oil (ScFO) used therapeutically and dietary by Northeast Brazilian communities. This study evaluated its anti-inflammatory potential of CFA-induced arthritis and its effect on behavioral parameters. In the acute model, ScFO at 25, 50, and 100mg/kg showed edematogenic effects similar to indomethacin at 4mg/kg (p > 0.05). In the arthritis model, 100mg/kg ScFO treatment was comparable to indomethacin (4mg/kg) (p > 0.05). TNF-α and IL-1β levels were significantly reduced in ScFO-treated groups at 25, 50, and 100mg/kg, and the indomethacin group (4mg/kg) versus the positive control (p > 0.05). Radiographs showed severe soft-tissue swelling and bone deformities in the control group, while the 100mg/kg ScFO group had few alterations, similar to the indomethacin group. Histopathological analysis revealed intense lymphocytic infiltration in the control group, mild diffuse lymphocytic infiltration in the indomethacin group, and mild lymphoplasmacytic infiltration with focal polymorphonuclear infiltrates in the 100mg/kg ScFO group. Behavioral analysis showed improved exploratory stimuli in ScFO and indomethacin-treated mice compared to the positive control (p > 0.05). ScFO demonstrated anti-inflammatory effects in both acute and chronic arthritis models, reducing edema and pro-inflammatory cytokines, and improved exploratory behavior due to its analgesic properties.

Gross and Histopathological Study of Postscabietic Nodules

Background: Nodular postscabietic scabies refer to the persistent intermittent signs of scabies that are seen in active and post-treatment period that might last for months. The spectrum of clinico-morphological ranges that can be observed with sarcoptic nodules is broad, and most of the entity's criteria can be elicited histopathologically and pathologically. The management of such nodules may be a challenge. They are commonly treated through local application of corticosteroids or injection of corticosteroids to nodules but the response to treatment is less than clent and relapses are very frequent. The objective of this study was to illuminate which of these features prevail and which ones fade in scarred sites which undergo postscabietic nodule development. The time span between August 2021 to May 2022 was allowed to collect samples from patients with (1-60) years old and full of scabies burrows who visit teaching hospitals and private dermatology clinics in Kut, Wasit Province, Iraq. Treat groups were split into 30 females, and 20 males; with persistent itchy nodular lesions of scabies demonstrated clinically and histopathologically. Everity grade scabies was evaluated by the number of lesions and rated it as severity of itching. Long-term treatment with topical glucocorticoids for 14 days in every age. Tissue from the blisters of patient was obtained after medication. The specimens were washed, fixed and cut to 4-5 µm and stained with H&E. The staining allowed us to observe the fragments of tissues under light microscope with different magnification power. We have observed excessive males and the prevalence of SCABies were more in a young adult group in comparison with other age groups. It was found that lesions with wiry projections tended to persist for two weeks to 52 weeks and the number of nodules had varied from one to fourteen lesions. Examination of Histopathological slide showing acanthosis in 80, histolymphocytic infiltration in 76, and eosinophilia in 100 of total cases in the whole period. After the scabitic nodule loop, the body experiences a hypersensitivity reaction. From the three hundred cases examined microscopically, most (80%) of them were found to be characterized by acanthotic epidermis and diffuse dense dermal lymphocytic infiltration. Neutrophilic reaction, epithelioid-granulomatous inflammation and eosinophilia have been diagnosed in 76 % sight upon while 100 % of other nodules have shown eosinophilia.

Primary Cutaneous Acral CD8-Positive Lymphoproliferative Disorder: A Case Report With Nonacral Presentation.

In this study, we describe a patient of primary cutaneous acral CD8-positive lymphoproliferative disorder located in a nonacral region. A 65-year-old male presented with an ill-defined lesion of rubbery consistency and a maximum diameter of 2.5 cm localized in the right thigh. Histologically, it was composed of a diffuse dermal infiltration of medium-sized atypical lymphocytes that expressed CD3, CD8, and TIA-1. In addition, a characteristic paranuclear positivity with CD68 was observed. During the follow-up, the patient had a recurrence of the disease in the abdomen with a lesion showing similar morphology and phenotype. To our knowledge, < 20 patients of primary cutaneous acral CD8-positive lymphoproliferative disorder with a nonacral presentation have been described in English literature. Although rare, its identification is essential to differentiate it from other T-cell lymphoma that express CD8 and cytotoxic markers, and whose clinical courses are very aggressive.

Diffuse Lymphocytic Infiltration Syndrome (DILS) as a Mode of Revelation of HIV: On a Case

Diffuse Lymphocyte Infiltration Syndrome (DILS) is a rare condition observed in HIV patients, characterized by infiltration of CD8+ T lymphocytes in several organs. In this article, a case of revelation of HIV infection is presented, diagnosed following bilateral parotidomegaly associated with DILS. The patient, aged 60, presented a progressive deterioration in general condition, significant asthenia, weight loss, and local symptoms including bilateral parotid swelling, cervical lymphadenopathy, and intermittent fever. Investigations revealed HIV-1 seropositivity, lymphocytosis with high T-CD8+ levels, salivary gland enlargement on imaging, and benign lymphoepithelial lesions on parotid biopsy. The diagnostic criteria for DILS were met, highlighting the importance of salivary gland involvement in this syndrome. Treatment with HAART resulted in significant regression of symptoms. In summary, DILS represents a multisystem complication of HIV, requiring appropriate management including antiretroviral treatment to improve patient prognosis.

A 35-year-old male with Waldenstrom Macroglobulinemia

Waldenstrom macroglobulinemia is one type of non- Hodgkin lymphoma that presents with a wide range of clinical features mainly due to secretion of the IgM paraprotein and infiltration of lymphoplasmacytic cells. Patients with Waldenstrom macroglobulinemia may experience fatigue, unexplained weight loss, enlarged lymph nodes, abdominal swelling, weakness, nose bleeding, blurring of vision etc. Waldenstrom macroglobulinemia is a disease of elderly individuals. The median age at diagnosis is 65 years, with a slight male predominance. We reported a case of a 35-yearold male who presented with fever, abdominal pain, loose motion and epistaxis. Examination revealed cervical and inguinal lymphadenopathy with hepatosplenomegaly. Investigation revealed diffuse lymphocyte infiltration on bone marrow study . Protein electrophoresis showed monoclonal gammopathy with high serum IgM level. On the basis of clinical features and investigation reports finally we diagnosed that, this was a rare case of Waldenstrom macroglobulinemia in a young patient. The patient was transfused 5 units of whole blood and was treated following standard treatment protocol with dexamethasone, Bortezomib and G-CSF. Unfortunately, patient died 3 weeks after initiation of treatment. J Bangladesh Coll Phys Surg 2023; 41(4): 325-328

General overview of the Risk factors, Pathogenesis, and Combined treatments for Hashimoto's Thyroiditis (HT)

In regions of the world where iodine is abundant, Hashimoto's thyroiditis, also known as Hashimoto's disease or autoimmune thyroiditis, is the most prevalent cause of hypothyroidism. It is a chronic inflammation of the thyroid gland. It is characterized by autoimmune-mediated thyroid gland destruction, which results in progressive thyroid failure, either with or without goiter formation. In young to middle-aged women, Hashimoto's thyroiditis typically starts as a painless, diffuse, firm thyroid gland enlargement that progresses to hypothyroidism. Many people don't initially exhibit hypothyroidism, and some don't even have a goiter or may have an atrophic thyroid gland. Hashimoto's thyroiditis (HT), also known as chronic autoimmune thyroiditis, is an inflammatory condition that is characterized by parenchymal atrophy, fibrosis, and diffuse lymphocytic infiltration. being the main source of primary hypothyroidism in regions with adequate iodine. With the help of various criteria, such as physical examination, blood tests for thyroid hormone levels (TSH is low, T3 and T4 are tall, for example), serum cholesterol and triglycerides, blood glucose, and radioactive iodine uptake, it is possible to distinguish between infections and clutter. According to estimates from several thyroid disease studies, 42 million persons in India are estimated to have the ailment. The pathogenesis causes, risk factors and combination therapy linked to Hashimoto's thyroiditis are discussed in this review study.

Pityriasis Lichenoides et Varioliformis Acuta pada Wanita Dewasa dengan Bakteriuria Asimptomatik: Sebuah Pemicu Lain?

Introduction: Pityriasis Lichenoides et Varioliformis Acute (PLEVA) is a rare and benign inflammatory skin disease. This acute form is distinguished from the milder chronic condition, Pityriasis Lichenoides Chronica (PLC). The etiology of PLEVA itself remains unclear, although it has been associated with infection as a trigger.Case: Here, we present the case of a 34-year-old woman who presented with abrupt, generalized, pruritic skin eruptions for two months.Case Discussion: The eruptions started as red scaly papules and vesicles and resolved as hyperpigmentations. She denied having any previous dermatological diseases, routine medications, or vaccinations. On examination, she showed generalized multiple hyperpigmented macules, scaly papules, and vesicles over the trunk, extremities, and face, with erosions and crusts in several areas. Eosinophilia and asymptomatic bacteria were found in her urinalysis. A skin biopsy showed diffuse lymphocytic infiltration in the dermal/epidermal junction and perivascular region, with parakeratosis and lymphocyte exocytosis. While the pathogenesis of PLEVA itself remains unclear, a triggering factor of inflammatory reaction, such as infection, may contribute to the development of the disease.Conclusion: Asymptomatic bacteriuria is associated with inflammatory responses, and thus, it can be one of many possibilities. More studies are needed to confirm this association with PLEVA. Due to the lack of a clear pathogenesis and the benign nature of the disease, this rare entity may present difficulties in diagnosis and therapy

Unilateral conjunctival concretions associated with chronic inflammation and tear instability.

Conjunctival concretions are small yellow-white subconjunctival spots that can be asymptomatic for years and are an incidental finding on routine ophthalmic examination.[1,2] The etiologies are chronic vernal conjunctivitis, severe atopic keratoconjunctivitis, and post-trachomatous changes.[1–5] The concretions are located within the conjunctival recesses layered by epithelium and are made up of cell debris and phospholipids.[3,4] Case Report A 24-year-old-female presented with chronic irritation and redness in the right eye for 1 year. Systemic evaluation was unremarkable with no immunosuppressive disorders. Her symptoms were intermittently associated with discharge. Her vision was 20/20 in both eyes. Everted upper and lower eyelids of the right eye showed multiple concretions scattered beneath the tarsal conjunctiva, more in the upper eyelid, protruding through the conjunctiva at two focal points [Fig. 1]. There was diffuse congestion in the tarsal conjunctiva with a normal lid margin appearance. The left eyelid had neither congestion nor concretions. There was no ocular surface staining with fluorescein dye, but the exposed concretions showed fluorescein uptake. Dry eye workup revealed a tear break-up time of 7.8 s with normal tear secretion in the right eye, whereas tear breakup and secretion was normal in the left eye. She gave an antecedent history of a vegetative object falling into her right eye while driving a bike. The ocular symptoms developed 1 month after that trauma. She was using topical lubricants and antibiotic ointment over the eyelid margin for the meibomitis. Because of unilateral presentation and young age, two concretions were removed on slit lamp using a sterile 26-gauge needle under topical anesthesia and sent for tissue processing.Figure 1: (a) Everted right upper eyelid of the 24-year-old female shows scattered numerous concretions in the tarsal conjunctiva, fewer in the lower eyelid (d). (b) Gomori methenamine silver stain (100×) shows presence of fungal elements within the concretions (higher magnification in inset), which are also seen on gram stain (e, 400×) as empty round and vertical spaces. (c and f) Left upper and lower eyelids show normal tarsal conjunctivaThe histopathologic examination of concretions revealed eosinophilic homogenous amorphous material containing fungal elements, which were Gomori methenamine silver stain positive [Fig. 2]. The deepest sections (till the last tissue section) also contained numerous fungal hyphae, which ruled out contamination. Due to atypical histopathologic findings of concretions, a superficial conjunctival incision biopsy containing tarsal conjunctiva, concretions, and a thin sliver of tarsus was taken at 4 mm from the upper eyelid margin. The incision biopsy showed scattered amorphous, acellular eosinophilic hyaline-like material and diffuse lymphocytic infiltration in the substantia propria. The amorphous material had a rim of conjunctival epithelium suggestive of concretions embedded within the pseudoglands of Henle. The periphery of the concretions had a slight basophilic appearance. The concretions were negative for von Kossa stain, Alcian blue, and Congo red but were red on Masson trichrome stain, suggesting cell debris and keratin to be one of the constituents. Alcian blue was focally positive in the conjunctival epithelium at the location of goblet cells. She was started on tablet fluconazole 150 mg once a week for 3 weeks along with 1% itraconazole eye ointment into the eye twice a day. Her symptoms resolved with a reduction in the conjunctival concretions’ number and conjunctival congestion.Figure 2: (a) Everted right upper eyelid with highlighted biopsied part. (b and c) Incisional biopsy from the upper tarsal conjunctiva shows diffuse subepithelial lymphocytic infiltration along with eosinophilic hyaline-like material deposits (c, at 200×). Masson trichrome (d), Congo red (e), and Alcian blue (f) were negative for amyloid and mucopolysaccharide depositsTear film instability and reduced tear production have been reported in patients with conjunctival concretions, where 51% of asymptomatic patients with conjunctival concretions have reduced tear break-up time.[3] The current case had reduced tear break-up time in the eye with concretions. An interesting finding in the current case was the presence of fungal elements, which can be explained by the possible entrapment of organic body containing fungus 1 year back. The organic material dissolved away, but the fungal elements caused persistent chronic inflammation, which resulted in the formation of concretions. This case reports the possibility of having unilateral concretions secondary to chronic inflammation with degenerative changes. Declaration of patient consent The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed. Financial support and sponsorship Hyderabad Eye Research Foundation, Hyderabad. Conflicts of interest There are no conflicts of interest.

Necrose gordurosa perirrenal bilateral em cervo sambar (Rusa unicolor)

ABSTRACT: The gross and histopathological findings of perirenal fat necrosis in a sambar deer (Rusa unicolor) are described in a 6-year-old female deer that was necropsied after showing severe apathy, weight loss, recumbency, and death. At post-mortem examination, two large white to yellow, irregular, and encapsulated masses involving both kidneys were observed. Microscopically, these masses consisted of fat tissue presenting multifocal to coalescing areas of necrosis, diffuse infiltration of lymphocytes, macrophages, occasional plasma cells, and multinucleated giant cells. Multifocally, the necrotic sites were replaced by mineralization and fibrosis. The described condition has not been reported in deer and the exact mechanisms of development of perirenal fat necrosis remain to be determined. Massive fat necrosis has been reported in other animal species such as dogs, cats, pigs, goats, cattle, and whales (Balaena mysticetus). It is usually an incidental finding during post-mortem examination that needs to be differentiated from neoplasms originating from the adipose tissue, kidneys and adrenals, and disorders resulting from pancreatitis and obesity.

Dermoscopic Features of Lichenoid Pseudovesicular Papular Eruption of the Nose (LiPEN): A Rare Entity.

Dermoscopic Features of Lichenoid Pseudovesicular Papular Eruption of the Nose (LiPEN): A Rare Entity.

Focal Myositis with CD8+T-Cell predominance: an Inflammatory Myositis Mimicking a Soft Tissue Neoplasm

Abstract Introduction/Objective FM is a rare self-limiting T-cell rich lesion arising within muscles of young adults as a solitary lesion and can be confused with a variety of neoplastic/inflammatory conditions or lymphoma. Here we describe a rare T-cell rich variant of FM with CD8 predominance. Methods/Case Report A 51-year-old female presented with two-month history of left trapezius swelling. MRI showed an enhancing tumor within the muscle, suspicious of sarcoma, less likely myeloma. Results (if a Case Study enter NA) Biopsy showed diffuse infiltration of small lymphocytes in a fibrotic background and atrophic skeletal muscle. These lymphocytes stained positive for CD2, CD3, CD7, CD8, CD5 (partial), TIA1 (partial), CD43, CD57 and negative for CD4, CD30, CD56, CD57, granzyme B, perforin, BCL-6, BCL-2, Pax5, TCL1, and CD56. Ki-67 was (&amp;lt;10%) with few background CD20+ B cells. By flow cytometry, the CD8+ T-cells co-express CD2, CD3, CD7, with dim CD5 expression. TCR gene rearrangement study by PCR showed no clonal TCR Gamma gene rearrangement. Conclusion FM is extremely rare with only 22 cases well-described in the literature, all predominantly composed of CD4+ T-cells, clinically concerning for low-grade sarcomas, as inflammatory myofibroblastic tumor, inflammatory leiomyosarcoma, or liposarcoma. Careful analysis is essential for correct diagnosis. Mimics include other causes of myositis, such as polymyositis and inclusion body myositis. Depending on the extent of lymphocytic infiltrate, gene rearrangement studies might be necessary to rule out clonality. Recognition of this rare entity with excellent prognosis is crucial to provide appropriate management and avoid unnecessary, aggressive procedures.

Cecal Reduction of Brachyspira and Lesion Severity in Laying Hens Supplemented with Fermented Defatted ‘Alperujo’

Antimicrobial resistance demands the development of therapeutic alternatives such as prebiotics, probiotics, and nutraceuticals. The aim of this study was to assess the antimicrobial proprieties of the nutraceutical fermented defatted “alperujo”, derived from olive oil production, in a laying hen farm (n = 122,250) endemic with avian intestinal spirochetosis (Brachyspira spp.). Part of the batch (n = 1440) was divided into six groups of 240 hens each that included 80 or 108-week-old laying hens, supplemented with 0%, 2%, or 6% fermented defatted ‘alperujo’ for a month. At the end of the experiment, eight hens from each group were autopsied and cecal content was subjected to (i) Brachyspira culture and species identification by PCRs, and (ii) direct DNA extraction and Brachyspira qPCR. Furthermore, the ceca were processed for histopathology. Microbiological isolation revealed B. pilosicoli and B. hyodysenteriae co-infection in all groups. The 80-week-old hen group 2% supplemented showed a reduction in the cecal Brachyspira content (qPCR) compared with non-supplemented hens. Cecal histopathology showed a diffuse mild infiltration of lymphocytes, plasma cells, and heterophils; and hyperplasia of the gut-associated lymphoid tissue hyperplasia which decreased in severity in 80-week-old supplemented hens. The reduction in Brachyspira colonization and the severity of the lesions observed in supplemented hens highlights a potential protective function against avian intestinal spirochetosis.

P42 Primary Sjogren’s Syndrome (pSS) in a seronegative adolescent female with family history of BehÇet’s disease: A challenging disease to diagnose Case-based discussion

Introduction/BackgroundSjogren’s Syndrome (SS) is heterogenous chronic autoimmune disease with symptoms ranging from organ-specific to variable non-specific systemic features. It is a rare disease in childhood and can be very difficult to diagnose, especially in seronegative patients, with the absence of any specific diagnostic investigation or criteria. We are presenting a seronegative juvenile Primary Sjogren’s syndrome (pSS) patient with all the challenges we had to confirm the diagnosis and a highlight on the role of MDT as the most sensitive tool.Description/MethodA 14-year-old female patient was first referred to our Paediatric and adolescent rheumatology department at the age of 10 with history of recurrent bilateral painful parotid swellings since the age of 3 with absence of ANA, RF, Anti-SSA-Ro and Anti-SSB-La antibodies repeatedly. From 2016 till 2019 she was under the care of ENT with recurrent complicated bilateral ear infections. Episodes tend to occur every 2-3 weeks and last between a few days to 2 weeks. Her events were associated with fever, fatigue, shivering, joint and leg pain, cervical lymphadenopathy, infrequent folliculitis, and headaches. No history to indicate mouth or eye dryness or significant repeated ulcers. Both of our patient’s mother and maternal grandmother have Behçet’s disease. Further blood investigation only showed mild hypergammaglobulinemia with mildly elevated ESR and CRP, normal LFT, U&Es, complements, muscle enzymes and thyroid function. HIV serology was negative and serum IgG4 subclass was normal. Many USSs confirmed parotitis. Parotid gland biopsy was not specific and indicated chronic parotitis with diffuse infiltration of mature lymphocytes, periductal lymphocytic inflammation and exocytosis of lymphocytes into the ductal epithelium. Focus score nearly reaching 50 cells. Plasma cell staining ruled out IgG4 related disease. Ophthalmic assessment ruled out eye involvement by the appearance of her eyes. The Oral Medicine Team confirmed the appearance of dry mucosa with minimal salivary flow from the parotid ducts, though it has not been subjectively reported to cause any problem before. Failed trial of colchicine, never been off-prednisolone for at least the last 2 years, tried Methotrexate which resulted in significant but not full improvement. Now she is on azathioprine and Hydroxychloquine, but still reporting flares. Escalation in treatment is required though there are some concerns about previous medication compliance, the actual severity of symptoms reported and the lack of current suitable accommodation.Discussion/ResultsDiagnosing pSS is quite challenging especially in seronegative patients due to the possibility of other non-autoimmune diseases causing recurrent parotid gland swellings, especially Recurrent Juvenile Idiopathic Parotitis with very young age of onset. With the persistence of symptoms and lack of an underlying infection, our patient ended up having a parotid biopsy. This was generally not specific, with a focus score close to the 50 mononuclear cells required as evidence of exocrine inflammation. This further added to the challenge of confirming an underlying autoimmune disease. Nine years into the disease course, our patient was confirmed to have objective evidence of dry mucosa and decreased salivary flow from the parotid ducts. This shows how important it is to assess salivary and lacrimal gland dysfunction in a child with suspected pSS, despite the absence of typical xerophthalmia and xerostomia. Considering the non-typical features (sero-negativity and the non-specific histopathology findings), our patient clinical picture was discussed in an MDT meeting including ENT, Histopathology and Rheumatology and the diagnoses of pSS was confirmed. The chronicity of the disease, significant improvement of the flare frequency and severity while on immunosuppressants, the reoccurence of significant flares when the patient was off-treatment (personal decision), and the objective evidence of poor salivary flow all supported the diagnosis of pSS later in the disease course. This case shows us how the typical adult features of pSS should not be strictly applied to the juvenile form of the disease. It also highlights the importance of having an MDT as the most sensitive available tool to confirm the diagnosis.Regarding lack of subjective full response, how do you think we can prove this objectively and what would be the most appropriate next step in treatment escalation?Key learning points/ConclusionA high index of suspicion is crucial to reach the diagnosis and to avoid irreversible damage in children with SS.Quadrable sero-negativity should not be looked at as an absolute exclusion criterion of juvenile pSS.Exclusion of other more common and diverse causes of parotitis is crucial.The typical adult features of SS should not be strictly applied to the juvenile form of the disease.MDT approach is the most sensitive tool to diagnose SS.When there is no subjectively reported ophthalmic or oral dryness, we would advocate sending suspected children of pSS for formal assessment of it- we understand the age-related challenges.Considering its rarity, we need to improve the general awareness of the juvenile form of the disease among the population and the medical practitioners.

Focal cerebritis with vasculitis mimicking a high-grade glioma

Cerebritis is an inflammatory reaction in the brain which can be localized or diffuse and can be secondary to various etiologies like granulomatous demyelinating infections, vasculitis or neoplastic. Identifying the aetiology is very essential for the proper treatment. We report a case of 24 years male patient, who came with a history of headaches for 3 months. CT scan revealed intra-axial hypodense lesion suggesting high-grade glioma, which on histopathological examination revealed reactive gliosis with diffuse lymphocytic infiltrate and perivascular lymphocyte collection.

Fas/FasL and Complement Activation are Associated with Chronic Active Epstein-Barr Virus Hepatitis.

Chronic active Epstein-Barr virus hepatitis (CAEBVH) is a rare and highly lethal disease characterized by hepatitis and hepatomegaly. This study aimed to investigate the clinicopathological features and pathogenic mechanisms of CAEBVH. Ten patients with confirmed Epstein-Barr virus hepatitis infection were enrolled. The clinicopathological characteristics of these patients were summarized and analyzed. Flow cytometry was utilized to detect peripheral blood immune cell phenotypes and whole exome sequencing was used to explore pathogenic genetic mechanisms. Lastly, immunohistochemical staining was employed to verify pathogenic mechanisms. Clinical features observed in all Epstein-Barr virus hepatitis patients included fever (7/10), splenomegaly (10/10), hepatomegaly (9/10), abnormal liver function (8/10), and CD8+ T cell lymphopenia (6/7). Hematoxylin and eosin staining revealed lymphocytic infiltration in the liver. Positive Epstein-Barr virus-encoded small RNA in-situ hybridization (EBER-ISH) of lymphocytes of liver tissues was noted. Whole exome sequencing indicated that cytotoxic T lymphocytes and the complement system were involved. The expression of CD8, Fas, FasL, and Caspase-8 expression as well as apoptotic markers was enhanced in the Epstein-Barr virus hepatitis group relative to the controls (p<0.05). Lastly, Complement 1q and complement 3d expression, were higher in CAEBVH patients relative to controls (p<0.05). CAEBVH patients developed fever, hepatosplenomegaly, and lymphadenopathy. Histopathological changes were a diffuse lymphocytic sinusoidal infiltrate with EBER-ISH positivity. Fas/FasL and complement activation were involved in CAEBVH patients.

Temperature Acclimation Alters the Thermal Tolerance and Intestinal Heat Stress Response in a Tibetan Fish Oxygymnocypris stewarti

Numerous studies have shown that thermal tolerance and intestinal heat resistance are strongly associated with temperature acclimation. However, few reports have successfully conducted similar research on fishes from the Qinghai–Tibetan Plateau, an area that is facing the threat of climate warming. Therefore, the present study determined the growth, thermal tolerance, and intestinal heat stress (exposure to 30°C) responses in juveniles of a Tibetan fish, Oxygymnocypris stewarti, acclimated to three temperature levels (10°C, 15°C, and 20°C, named as T10, T15, and T20, respectively) for 30 days. The fastest growth was recorded in the T15 group. At 1°C/30 min heating rate, the critical thermal maximum (CTMax) ranged from 31.3°C to 32.3°C, and the lethal thermal maximum (LTMax) ranged from 31.8°C to 32.6°C among the three acclimation temperatures. According to the results of thermal tolerance tests, the heat stress temperature was set to 30°C. When the water temperature reached 30°C, the expression of the intestinal heat shock protein 70 (HSP70) gene as well as the intestinal microbiome and histology of experimental fish were monitored at 0, 2, 6, and 12 h. The expression of HSP70 reached the highest level at 2 h in all three temperature treatments. The histological analysis showed damage to intestinal cells, including diffuse infiltration of lymphocytes, villi epithelial cell swelling, decrease of intestinal villi length, and cytoplasmic light staining at 2 h in all three temperature treatments. In terms of the intestinal microbiome, phyla Proteobacteria and Firmicutes dominated the treatments at each monitored time in the T10 and T15 groups and at 0 h in T20 group, while phyla Fusobacteria, Proteobacteria, and Cyanobacteria were dominant in treatments at 2, 6, and 12 h in the T20 group. The overall results indicated that acclimation temperature could affect the growth, thermal tolerance, and intestinal heat stress response of O. stewarti juveniles. As the first report on intestinal heat stress response associated with temperature acclimation in a Tibetan fish, this study will help to understand the potential effects of climate change on highland fishes.

TOPOGRAPHIC RELATIONSHIPS OF MORPHOLOGICALLY HETEROGENEOUS ORGANS IN REACTIONS TO DEPLETED URANIUM

Annotation: Researches of the effect of radionuclides on the human body remain relevant up to date. Their effect of penetrating the body is characterized by involvement of numerous systems of human body. The causal significance of the effects of depleted uranium exposure has not been specifically defined, however, people who live in zones of armed conflict, as well as armed forces personnel, had health problems of "unknown origin", and with remote symptomatic etiology. The risk of possible exposure is also may appear when manufacture of nose spikes for armor piercers and atomic energetics products. In view of these perspectives, depleted uranium, which used in various types of weapons, has been considered as the cause of complaints. Acute uranium intoxication is appeared in polytropic effect that is apparently depended on the resistance of the body. Getting into the internal milieu, depleted uranium exhibits radiation effect of exposure followed by alpha particles radiation. Long-term consequences after oral incorporation of depleted uranium with drinking water are matters of particular interest. The study purpose is defined by assessing of morphofunctional state of the trachea and thyroid gland, united by topographic proximity and different by morphological heterogeneity, upon one month after a single oral incorporation of an aqueous solution of depleted uranium oxides. General histological and histochemical staining methods on thin paraffin slices have been performed for studying on morphological and functional state of the trachea and thyroid gland The results of the morphological and statistical analysis of the trachea wall upon staining with hematoxylin and eosin revealed changes in the structural components that determined deformation of its functionality a month after oral incorporation of an aqueous solution of depleted uranium oxides. Morphological diagnosis was characterized by a change thickness of the epithelial layer, its multi-rowed structure, the cellular composition of the epithelium, and the loss of special organelles. Modifying effect of depleted uranium is also extended to the glandular epithelium with exposure of secretory segments hypertrophy and excretory ducts. There was revealed the diffuse lymphocyte infiltration of the tracheal membranes and formation of lymph nodules. Histochemical analysis of hormone formation in the thyroid gland has demonstrated a change in the ratio of follicles according to the degree of iodization of colloid amino acids with accurate predomination of non-iodized amino acids of irregular shape with accurate smaller diameter against target parameters, with flat or low cubic epithelium, indicating a decrease of gland functionality. The bioeffect of depleted uranium, independently from organ implementation and tissue organization, was prolonged indicating a functional inability.