The Role of Diverse Immune Cells in Sarcoidosis

Sarcoidosis is a systemic inflammatory disorder of unknown etiology characterized by tissue infiltration with macrophages and lymphocytes and associated non-caseating granuloma formation. The disease primarily affects the lungs. Patients suffering from sarcoidosis show a wide range of clinical symptoms, natural history and disease outcomes. Originally described as a Th1-driven disease, sarcoidosis involves a complex interplay among diverse immune cells. This review highlights recent advances in the pathogenesis of sarcoidosis, with emphasis on the role of different immune cells. Accumulative evidence suggests Th17 cells, IFN-γ-producing Th17 cells or Th17.1 cells, and regulatory T (Treg) cells play a critical role. However, their specific actions, whether protective or pathogenic, remain to be clarified. Macrophages are also involved in granuloma formation, and M2 polarization may be predictive of fibrosis. Previously neglected cells including B cells, dendritic cells (DCs), natural killer (NK) cells and natural killer T (NKT) cells were studied more recently for their contribution to sarcoid granuloma formation. Despite these advances, the pathogenesis remains incompletely understood, indicating an urgent need for further research to reveal the distinct immunological events in this process, with hope to open up new therapeutic avenues and if possible, to develop preventive measures.

Treatment of Idiopathic Granulomatous Mastitis: Combined Intralesional Steroid Injection with Topical Steroid Administration vs. Systemic (Oral) Steroid

BackgroundIdiopathic granulomatous mastitis (IGM)is characterized by non-caseating granuloma and microabscess formation limited to mammary gland lobules. It is a form of chronic mastitis of unknown pathogenesis. In this study, we aimed to compare the effectiveness of intralesional steroid injection with topical steroids versus systemic steroid therapy in the treatment of IGM. MethodsBetween June 2017 and December 2020, the patients were collected and assessed. IGM was diagnosed histopathologically by tru-cut biopsy in patients with breast mass, pain, and erythema with suspicion of IGM. Included in the study were one hundred and eleven patients who were diagnosed with IGMand who were treated with local or oral administration of corticosteroids, with at least 6 months of follow-up. The patients were divided into 2 groups: a local corticosteroid treatment group (LC, group 1, n=57); and a peroral corticosteroid treatment group (OC, group 2, n=54). Demographic characteristics, treatment responses, recurrence rates, side effects of the steroid, and the need for surgery were compared.ResultsWhile the rate of smoking was 12.3% in the LC group, was 20.4% in the OC group. There was no history of oral contraceptive use in either group of patients. Previous steroid use was significantly lower in the LC group (10.5%) compared to the OC group (55.6%) (p = 0.001). Previous antibiotic use was significantly lower in the LC group (75.4%) compared to the OC group (100%) (p = 0.001). When complete and partial responders were grouped as “responders,” 96.5% in the LC group and 75.9% in the OC group responded after the first course of treatment (p=0.001). 98.2% in the LC group and 87.0% in the OC group were complete responders after the third course of treatment (p=0.003). While 7% of the patients in the LC group had recurrence, 37% in the OC group had recurrence (p=0.001). Steroid-related side effects were lower in the LC group (no) compared to the OC group (11.1%) (p=0.010). Surgery was performed in 3.5% of the LC group, while surgery was performed in 57.3% of the OC group (p=0.001). ConclusionSteroid injection is an IGM treatment with proven efficacy, short response time, low recurrence rate, and lower need surgery. The treatment is easy to administer and minimizes the risk of systemic side effects. Even in clinically severe cases, we believe that steroid injection might be used as monotherapy, or in combination with other therapies, to improve treatment efficacy and create a transition to less aggressive treatments.

Presentation, diagnosis, and treatment of a cerebellar tuberculoma: illustrative case

BACKGROUND Central nervous system (CNS) tuberculomas are a feared complication of tuberculosis (TB) infection. These lesions can present in varying manners and are associated with significant morbidity and mortality. Prompt diagnosis and treatment of the lesion and the underlying infection are critical in the care of these patients. The authors presented a case of a 45-year-old Yemeni immigrant presenting with a 3-month history of severe right temporo-occipital headaches with photophobia and night sweats. Imaging showed a rim-enhancing lesion in the right cerebellar hemisphere. OBSERVATIONS Laboratory tests were unremarkable and within normal limits. QuantiFERON testing was negative, ruling out latent TB infection. The patient received a suboccipital craniotomy, and resection of the cerebellar lesion showed caseating granuloma formation, which was positive for acid-fast bacilli and Fite stain. LESSONS CNS tuberculomas are an important differential to consider in patients with a history of primary TB, regardless of active disease or immunocompetent status. Resection of these lesions remains a viable treatment option that is safe and effective.

Hemophagocytic Lymphohistiocytosis in a Patient With Familial Mediterrean Fever and Miliary Tuberculosis: A Case Report

Hemophagocytic Lymphohistiocytosis (HLH) is a lethal complication of several infections especially viral origin. M.Tuberculosis infection can also lead HLH, yet it is an uncommon trigger. Considering role of increased cytokines in HLH, autoinflammatory conditions as Familial Mediterrean Fever (FMF) might contribute to development of it. Nevertheless, possible relationship between FMF and HLH has only suggested in some case reports. We present a case with FMF was admitted to hospital with the complaints of constitutional symptoms and chest pain regarding to recurrent pericarditis. On blood test, pancytopenia and elevated acute phase reactants were seen. FDG Positron Emission Tomography/Computed Tomography (FDG PET/CT) demonstrated positive FDG uptake sites on both right and left surrenal glands, visseral layer of pericard and reactive lymphadenomegalies at multipl mediastinal regions. Bone marrow biopsy revealed hemophagocytosis. Methylprednisolone treatment was initiated. Despite immunosupressive treatment, clinical and biochemical parameters deteriorated thus a thorax CT was executed. Findings were consistent with miliary tuberculosis (TB) infection. M.Tuberculosis was detected in blood culture and bronchoalveolar lavage culture material. Also bone marrow and surrenal biopsy material revealed necrotising caseating granuloma.

Unusual organ involvement in sarcoidosis: sarcoid myopathy and peritoneal sarcoidosis

Myopathy and peritoneal involvement are rare complications of sarcoidosis, and the latter can mimic malignancy with peritoneal dissemination. In this case, a patient with a history of polyarthritis and positive rheumatoid factor presented with proximal muscle weakness and abdominal pain. Biopsies of muscle and peritoneum revealed non-caseating granuloma suggesting sarcoidosis. Ocular and pulmonary involvement later developed and confirmed the diagnosis of sarcoidosis.

Clinical Significance of Caseating Granulomas Detected on Transrectal Ultrasound Biopsy of Prostate Gland: The Recommended Management

Introduction: The histopathological examination (HPE) findings of caseating granulomas from the transrectal ultrasound (TRUS) of prostate biopsy are rare. A high index of suspicion is necessary to diagnose a tuberculosis infection. Here, we present the clinical outcomes of patients and the practical management steps when encounter these findings. Methods: We conducted a retrospective analysis of three cases in a tertiary care centre and reviewed the available literature on the topic. Results: All patients were aged less than 55 years and were considered young adults. One patient presented with neurogenic systemic symptoms, and two patients presented with lower urinary tract symptoms. All patients had abnormal digital rectal examination findings that warranted a TRUS biopsy of the prostate. All biopsies reported caseating granuloma with multinucleated giant cells. Additional investigations led to the diagnosis of tuberculosis infections in two patients, and one patient was diagnosed as having non-specific granulomatous prostatitis. All patients were treated according to their specific diagnosis and recovered fully. Conclusion: The detection of caseating granuloma on prostate biopsy may lead to diagnoses of several conditions, either infective or non-infective in origin. Further investigation is mandatory to provide appropriate treatment.

Application value of tissue tuberculosis antigen combined with Xpert MTB/RIF detection in differential diagnoses of intestinal tuberculosis and Crohn’s disease

Background The purpose of this study was to examine the value of Xpert MTB/RIF assay and detection of additional Mycobacterium tuberculosis complex (MTBC) species antigens from intestinal tissue samples in differentiating intestinal tuberculosis (ITB) from Crohn’s disease (CD). Methods Several clinical specimens of intestinal tissue obtained by either endoscopic biopsy or surgical excision were used for mycobacteriologic solid cultures,Xpert MTB/RIF assays, immunohistochemistry, and histological examinations. Four antigens (38KDa, ESAT-6, MPT64, and Ag85 complex) of MTBC in the intestinal tissue were detected by immunohistochemical analysis. Results The study included 42 patients with ITB and 46 with CD. Perianal lesions and longitudinal ulcers were more common in patients with CD, while caseating granuloma and annular ulcers were more common in patients with ITB. The positive rate of MTBC detected by Xpert MTB/RIF in intestinal tissues of patients with ITB was 33.33%, which was significantly higher than that in patients with CD and that detected using acid-fast staining smears. It was also higher than that detected by tissue MTBC culture, but the difference was not statistically significant. The positive MPT64 expression rate in patients with ITB was 40.48%, which was significantly higher than that observed in patients with CD. The sensitivity of parallelly combined detection of tuberculosis protein MPT64 and Xpert MTB/RIF in diagnosing ITB was 50.0%. Conclusions The detection of Xpert MTB/RIF in intestinal tissue is a rapid and useful method for establishing an early diagnosis of ITB. The detection of MTBC using Xpert MTB/RIF and MPT64 antigen in intestinal tissues has a definitive value in the differential diagnosis ofITB and CD. The combination of these two methods can improve the detection sensitivity.

Clinicopathological Study on TB Lymphadenopathy Case

Background: Tuberculosis in the form of pulmonary and extrapulmonary TB is common in developing countries like Bangladesh. Among extrapulmonary TB, lymphnode TB is still common in our setting. So, the objectives of the present study were to evaluate theclinicopathological findings among the lymphnode TB cases in our context. Materials and methods: This observational study was done from January 2017 to December 2019 among 300 lymphnode TB cases in a tertiary care hospital during a three-year study period. Patients were selected after obtaining informed written consent and clinical evaluation. Then enlarged lymphnodes were evaluated by FNAC or histopathology. If lymphnode TB features were found then the patients were included in our study.Other findings like metastasis, lymphoma or pyogenic lymphadenitis were excluded from this study. After collection, data was recorded and analyzed by Microsoft Excel. Results: Among 300 cases of TB lymphadenitis subjects were commonly within the age groups 11-20 years (Male 63 and female 51) and 21-30 years(male 45 and female 42) with amale: female ratioof 1.22:1. Regarding different clinical signs and symptoms,low grade fever was found in 21(7%) cases, local lymphnode pain and tenderness was found in 67 (22%) and 63(21%) of subjects. Discharging sinuses was present in 33(11%) patients, 35(12%) had history of weight loss, 39 (13%) had anorexia and 42(14%) had history of night sweats. Regarding locationof different lymph node areas, 125(41.67%) patients had deep cervical nodes, 65(21.67%) had supraclavicular lymph nodes, 60(20%) had lymph nodes in the posterior triangle 33 (11%) in jugulo-omohyoid and 17 (5.66%) in submandibular area. Among all cases, 83% cases showed bilateral and 17% showed unilateral involvement.Regarding nature of lymph nodes, firm, matted multiple lymphnodes were found in 130(43%) cases, single discrete nodes were found in 70(23.33%) cases, others were found as suppurative noded with single and multiple sinuses. Cytopathological and histopathological findings revealed caseating granuloma with epithelioid cell with Langerhans type giant cell was found in 220(73%) cases, caseating granuloma with epithelioid cell was found in 47(16%) epithelioid cell was found in 20(7%) cases and epitheliod cells with smear positive AFB was found in 13(4%) cases. Conclusion: TB lymphadenitis is still a common form of extrapulmonary tuberculosis and it has variable clinical and pathological presentations. Chatt Maa Shi Hosp Med Coll J; Vol.20 (1); January 2021; Page 77-80

Rare Scar Sarcoidosis: A Dermatologic Masquerader

Infiltration of sarcoid granuloma in old cutaneous scars is one of the uncommon cutaneous manifestations of sarcoidosis. Here we report the case of a 32-year-old female who presented with swelling and irritation in a 9-month-old appendicectomy scar. An incisional scar biopsy was done and it revealed non-caseating granuloma. On query she had inflammatory polyarthritis and persistent dry cough for last two months. High resolution CT (HRCT) revealed right paratracheal, both hilar, paraaortic, and subcarinal lymphadenopathy with pulmonary nodular densities in both lung fields. FNAC from mediastinal node revealed non-caseating granuloma consistent with sarcoidosis. Successful regression of cutaneous inflammation was achieved using a course of oral steroids, hydroxychloroquine and methotrexate. The incidence of scar sarcoidosis is rare and therefore not well-understood. However, inflammatory alterations in preexisting scars may be important indicators of disease onset. J Enam Med Col 2020; 10(2): 122-125

Bilateral Adrenal Adenomas Attributed to Extrapulmonary Mycobacterium Tuberculosis

Introduction: Adrenal infections are rare, with the Mycobacterium tuberculosis (MTB) being the most common causative agent in the developing world. MTB usually spreads to the adrenal glands hematogenously where it may be clinically manifested years after systemic infection. Here, we present a case of bilateral adrenal MTB infection associated with MTB peritonitis. Case Presentation: A 46-year-old male, from Ecuador, without significant medical history and no medical follow-up presented to the emergency room with a two-week history of abdominal pain, nausea, diarrhea, and significant weight loss. He denied fever, cough, or night sweats. No smoking, alcohol, or illicit drug use. He works as a construction worker without a history of sick contacts. Vital signs were stable, with abdominal distension and fluid shifting dullness on exam. Blood work revealed leucocyte count of 5.58K (4-11K), INR 1.2 (0.9–1.1), Sodium 132 mEq/L (136–145 mEq/L) with albumin 3.3 mg/dL (3.5–5.2 mg/dL), total bilirubin level, 1.3 mg/dL (0–1.2 mg/dL), and AST and alkaline phosphatase levels, 73 U/L (0–40 U/L) and 186 U/L (40–129 U/L) respectively. Computerized tomography (CT) of the abdomen showed large ascites, omental nodularity, calcified gall bladder, bilateral adrenal nodules, and multiple abdominal lymphadenopathies. Chest CT revealed right apical reticulonodular densities. A diagnostic paracentesis revealed an exudative effusion with serum ascites albumin gradient of 0.7, and negative acid fast bacilli (AFB) and adenosine deaminase enzyme. Ascitic cellular analysis was negative for malignant cells. AFB blood and sputum cultures were negative, though Quantiferon gold test was positive and a skin tuberculin test was 13x13mm. Tumor markers CA19-9, CEA, and alpha-fetoprotein came back negative. Additionally, serum aldosterone, plasma metanephrines, DHEA-S, AM Testosterone, ACTH, and morning cortisol levels were normal. The patient had a negative 1-mg dexamethasone suppression test. Positron emission tomography (PET) scan showed a hypermetabolic left adrenal mass (4.9x3.2 cm) and nodular peritoneum with no fluorodeoxyglucose (FDG) uptake in the enlarged abdominal lymph nodes. Peritoneal biopsy analysis revealed non-caseating granuloma positive for MTB. The adrenal biopsy was not performed given the extensive intra-abdominal disease. The patient was started on anti-MTB treatment (Isoniazid, rifampicin, pyrazinamide, and ethambutol) with significant clinical improvement and a slight decrease in the adrenal masses following abdominal imaging. Conclusion: Extrapulmonary MTB should be part of a differential diagnosis for bilateral adrenal masses. Adrenal glands could be infected by a variety of pathogenic microorganisms either by direct contact or hematogenous dissemination. A high index of suspicion is required for the diagnosis of MTB in patients with atypical presentation.