Rare and common manifestation of musculoskeletal and sinonasal sarcoidosis: A case report.

Sarcoidosis is a systemic granulomatous disease that can affect multiple organ systems. Although many sarcoidosis patients are asymptomatic, the variable clinical progression of symptomatic patients and the nonspecific presentation make diagnosis difficult in certain cases. Musculoskeletal and sinonasal involvement of sarcoidosis are uncommon manifestations, and they are often only seen in patients with widespread disease. Diagnosis of osseous sarcoidosis, sarcoid arthropathy, and sarcoid rhinosinusitis are typically based on a combination of clinical history, radiological findings, and pathologic specimens. Although there are classic image findings, such as lacelike honeycomb appearance of small bones of the hands or hilar/mediastinal lymphadenopathy, sole reliance on image findings for the diagnosis of sarcoidosis is unreasonable as many findings are nonspecific. However, failure to include sarcoidosis in the differential diagnosis often leads to a delay in recognition of musculoskeletal or sinonasal involvement and results in ineffective treatment plan. Even in patients with biopsy-proven sarcoidosis, some image findings in isolation that may represent granulomatous infiltrates are disregarded as nonspecific without raising the possibility of sarcoidosis due to its rare occurrence. Here we discuss a case of multisystemic sarcoidosis in a 42-year-old female with a constellation of classic and rare findings of biopsy-proven sarcoidosis.

DNA Methylation and Its Effects on TRIM29 Gene Expression in the Equine Sarcoid Tissue.

Sarcoids are the most frequently diagnosed dermatological tumour in horses. It is a disease that can affect various species of equids, such as donkeys, mules and zebras. This type of tumour can develop in all horse breeds, regardless of age and gender. Treatment options depend on many factors, such as the type of lesion, location, extent, owner preference and financial considerations. In the present study, we investigated the TRIM29 expression, the methylation status of its first exon and its involvement in the formation of equine sarcoids. Bisulfite sequencing PCR (BSP) was used to determine DNA methylation at CpG sites and real-time quantitative polymerase chain reaction (qPCR) was used to detect TRIM29 expression level. Our results showed that TRIM29 is significantly downregulated in lesional samples (FC = -3.72; p < 0.001). Furthermore, TRIM29 expression was significantly correlated (R = -0.73; p < 0.001) with hypermethylation of its specific CpG sites in the first exon of this gene. Our research has demonstrated that the identification of increased methylation of CpG sequences in horse sarcoids, along with the decreased expression of the TRIM29 gene, is an important step towards understanding the molecular mechanisms underlying the disease. These findings can serve in the future as a diagnostic biomarker for horse sarcoids and help in detecting the disease.

Can FDG-PET Imaging Identify Cardiac Sarcoidosis Disease Phenotypes?

PURPOSE OF REVIEW: Despite the scarcity of data, most guidelines have advocated for the treatment of cardiac sarcoidosis with corticosteroids. However, there is heterogeneity in disease presentation and response to treatment, which can make treatment challenging. The ability to identify disease phenotypes to allow for tailored therapy is therefore highly desirable. This review will seek to outline the disease phenotypes of cardiac sarcoidosis and the role that FDG-PET imaging can play in identifying these phenotypes to optimize disease diagnosis and treatment management. RECENT FINDINGS: FDG PET can identify cardiac sarcoidosis and is being increasingly used to monitor therapeutic response to immunosuppressive therapy, to follow treatment response after discontinuation of corticosteroid therapy, and to evaluate for disease relapse. Modern quantitative techniques using FDG PET imaging may allow for even better phenotypic disease characterization and the ability to track the response to immunosuppression more accurately. FDG PET currently plays an important role in cardiac sarcoidosis diagnosis. However, it also affords us the opportunity to offer insights into cardiac sarcoidosis disease phenotypes to better understand the underlying disease process and in the future may allows us to tailor therapies accordingly.

Arrhythmias in Cardiac Sarcoidosis: Management and Prognostic Implications.

Cardiac sarcoidosis (CS) is characterized by various arrhythmic manifestations ranging from catastrophic sudden cardiac death secondary to ventricular arrhythmia, severe conduction disease, sinus node dysfunction, and atrial fibrillation. The management of CS is complex and includes not only addressing the arrhythmia but also controlling the myocardial inflammation resultant from the autoimmune reaction. Arrhythmic manifestations of CS carry significant prognostic implications and invariably affect long-term survival in these patients. In this review, we focus on management of arrhythmic manifestation of cardiac sarcoidosis as well as risk stratification for sudden cardiac death in these patients.

An Unusual Presentation of Neurosarcoidosis in a 64-Year-Old Man: A Case Report.

Sarcoidosis is a multisystem granulomatous disorder with an unknown etiology that typically involves the lungs, skin, and lymph nodes, with neurological involvement being relatively rare. We discuss a case of neurosarcoidosis in a 64-year-old man who initially presented with unexplained cognitive impairment, insomnia, hyponatremia, paresthesias, and weight loss and later developed uveitis, diplopia, and dysphagia. Ultimately, findings of hilar and mediastinal lymphadenopathy on chest computed tomography (CT) resulted in bronchoscopy, which led to the diagnosis. This case highlights a rare presentation of sarcoidosis with an unusual constellation of symptoms. We discuss the difficulty involved in diagnosing this disorder as well as its highly variable course.

Focal inflammatory neuropathies.

This chapter focuses on neuropathies that present with focal involvement of nerve roots, plexus, and/or peripheral nerves associated with autoimmune and inflammatory mechanisms that present with focal involvement of nerve roots, plexus and/or peripheral nerves. The clinical presentation, diagnosis, and treatment of focal autoimmune demyelinating neuropathies, focal nonsystemic vasculitic disorders (diabetic and nondiabetic radiculoplexus neuropathies, postsurgical inflammatory neuropathy, and neuralgic amyotrophy), and focal neuropathies associated with sarcoidosis and bacterial and viral infections are reviewed.

Feline Facial Spindle Cell Tumors in 29 Cats: Histomorphological and Immunohistochemical Characterization.

Soft tissue tumors/sarcomas (STSs) in felines, encompassing a variety of mesenchymal tumors with similar histomorphological features, present diagnostic challenges due to their diverse cellular origins and the overlap with other tumor types such as feline sarcoid. This study aimed to delineate the clinical, histomorphological, and immunohistochemical characteristics of 34 feline facial spindle cell tumors affecting 29 cats, including testing for bovine papillomavirus type 14 (BPV14), the virus causing feline sarcoids. Only five out of 12 tumors previously diagnosed as feline sarcoids based on histomorphology were confirmed by PCR for BPV14, underscoring the importance of comprehensive diagnostic approaches to accurately distinguish between STSs and feline sarcoids. This study shows that most facial spindle cell tumors were compatible with peripheral nerve sheath tumors (PNSTs) based on positive immunohistochemical staining for Sox10 and other immunohistochemical markers such as GFAP, NSE, and S100. Some of these tumors displayed as multiple independent masses on the face or as erosive and ulcerative lesions without obvious mass formation, an atypical presentation and an important highlight for general practitioners, dermatologists, and oncologists. This study also describes periadnexal whorling of neoplastic cells as a novel histomorphologic finding in feline facial PNSTs and emphasizes Sox10 as a useful complementary immunohistochemical marker for the diagnosis of facial PNST in cats, providing valuable insights for veterinary pathologists.

Recommencement of atezolizumab with associated pulmonary sarcoid-like reaction.

An 81 year old male with Child-Pugh A cirrhosis and metastatic hepatocellular carcinoma (HCC) treated with 3-weekly atezolizumab and bevacizumab developed a pulmonary sarcoid-like reaction (SLR) after 5 months. Atezolizumab, an immune checkpoint inhibitor, was identified as the likely culprit. He was treated with prednisolone, resulting in improvement, and was successfully rechallenged with both atezolizumab and bevacizumab.

Peri-Operative Outcomes Associated With the Placement of Implantable Cardioverter-Defibrillators in Patients With Sarcoidosis: A Nationwide Database Analysis.

Rationale Sarcoidosis with cardiac involvement can be associated with serious life-threatening arrhythmias and an increased risk of sudden cardiac death. Implantable cardiac defibrillators (ICDs) have been used for primary and secondary prevention of sudden death in patients with cardiac sarcoidosis (CS). Post-ICD placement complications have been shown to be higher in patients with CS. However, data comparing postoperative ICD complications among sarcoidosis patients with the general population is limited. Here, we evaluated the association of postoperative complications with implantable cardioverter-defibrillators in sarcoidosis.  Methods Using the NIS database, we identified cases of adults aged ≥ 18 years undergoing surgical placement of implantable cardioverter-defibrillators between 2010 and 2019. Using ICD-9 and ICD-10 codes, we identified patients with sarcoidosis. In all statistical analyses, we applied weights provided by HCUP to produce results representative of national estimates. We compared categorical and continuous covariates in the baseline characteristics using the chi-square test and analysis of variance, respectively. We employed multivariable logistic and linear regression to compare binomial and continuous outcomes to assess differences in mortality rates. Results We analyzed 114073 patients during the study period. Of these, 1012 (0.9%) had sarcoidosis and were found to be significantly younger and female compared to patients without sarcoidosis (56.4 ±11.5 years vs. 65.6 ± 13.9 years, p <0.001) and (39.4% vs. 28.3%, p<0.001) respectively. Further, patients with sarcoidosis were more likely to be African American (45% vs. 16.3%), have private insurance (45.4% vs. 23.8%), and less likely to have Medicare (34.9% vs. 60.9%). Overall, post-ICD placement complications such as lead complications (4.2% vs. 6.9%, p = 0.03), post-procedure hemorrhage (4.1% vs. 5.5%, p=0.048), and requirement for transfusion (2.3% vs. 4.4%) were less likely in patients with sarcoidosis. Regarding post-ICD placement inpatient mortality, sarcoidosis was not associated with any difference (OR: 0.71, 95% CI 0.18-2.88 p=0.634). Conclusions Placement of implantable cardioverter-defibrillators in patients with sarcoidosis is a safe procedure and is associated with significantly lower rates of lead complications, post-procedure hemorrhage, and requirement for transfusion. This is of great importance as it is known that patients with underlying sarcoidosis are predisposed to developing more cardiac complications.

A randomized placebo-controlled double-blinded study comparing oral and subcutaneous administration of mistletoe extract for the treatment of equine sarcoid disease.

BACKGROUND: Equine sarcoids (ES) are the most common cutaneous tumors in equids. Systemic treatment options are sparse. Subcutaneous (SC) injections of Viscum album extract (VAE) demonstrate efficacy as a systemic treatment directed against ES. OBJECTIVES/AIM: To critically assess the therapeutic efficacy of orally administered VAE. ANIMALS: Forty-five ES-affected, privately owned, 3-12 year-old horses. METHODS: A 3-armed randomized placebo-controlled, double-blinded study was conducted in a double-dummy design. Horses were subjected to oral administration and SC injections of either VAE or placebo (VAE oral/placebo SC, VAE SC/placebo oral, placebo oral/placebo SC) over a 7-month treatment period. Primary endpoint was the change of baseline of a composite index of ES number and ES area after 14 months. Second endpoint was the clinical response. RESULTS: No statistically significant difference in the composite endpoint between the 3 study arms was found. The primary endpoint showed 4 (27%) horses in the VAE oral group with complete ES regression, 3 (21%) in the VAE SC injection group, and 2 (13%) in the placebo group. The clinical response revealed complete or partial regression in 6 horses of the oral VAE group (40%), 4 of the SC injection group (29%), and 4 of the placebo group (25%). Direct comparison of oral VAE and placebo showed an odds ratio, stratified for prognosis of 2.16 (95%-CI: 0.45-10.42) and a P-value of 0.336. CONCLUSION AND CLINICAL IMPORTANCE: Oral administration of VAE is well tolerated. No statistically significant difference in the effectiveness of systemic VAE versus placebo against ES was found.

Sarcoid-like reaction of the orbit in diffuse large B-cell lymphoma.

Sarcoid-like reaction (SLR) has been reported in patients with solid tumor malignancies, lymphomas, and patients receiving immunotherapy. SLR is often incidentally found during positron emission tomography/computed tomography scans as hilar and/or mediastinal lymphadenopathy. SLR has also been found in the lung, spleen, bone marrow, and skin. Biopsy of these lesions shows noncaseating granulomas. When systemic criteria are not met for sarcoidosis, these noncaseating granulomas are termed SLR. We present the first case in the literature of a case of orbital SLR in a patient with concomitant diffuse large B-cell lymphoma and inverted papilloma of the maxillary sinus. This case highlights the importance of including malignancy in the differential for the presence of a noncaseating granuloma in the orbit.

Gastric sarcoidosis diagnosed with endoscopic ultrasound.

Key Clinical Message: Endoscopic ultrasonography (EUS) is crucial in diagnosing gastrointestinal sarcoidosis, especially when patients exhibit refractory abdominal symptoms. Our case highlights the significance of considering sarcoidosis in such cases and emphasizes the utility of EUS for accurate diagnosis and guiding appropriate treatment. Abstract: Gastrointestinal sarcoidosis is a rare and challenging manifestation of sarcoidosis that often presents with nonspecific abdominal symptoms, making diagnosis a complex process. We report the case of a 46-year-old African American female who experienced chronic epigastric abdominal pain, recurrent nausea, vomiting, and diarrhea for 15 years. Despite extensive investigations, including multiple biopsies, she was misdiagnosed with cyclic vomiting syndrome. Subsequently, an endoscopic ultrasound (EUS) revealed prominent lymph nodes and gastric granulomas, leading to a diagnosis of GS. This case underscores the importance of considering sarcoidosis in patients with refractory abdominal symptoms and highlights the utility of EUS in diagnosing this rare condition.

Sarcoid-like reaction and hypothyroidism induced by PD-1 inhibitor treatment in metastatic renal cell carcinoma: a case report and literature review.

BACKGROUND: Pembrolizumab is among the approved treatments for a variety of cancer types, including clear cell renal cell carcinoma (ccRCC). It has contributed to enhancing the prognosis of renal cell carcinoma. However, it is essential to be aware of the numerous potential immune-related side effects associated with its use. CASE PRESENTATION: A 69-year-old patient with a history of metastatic renal cell carcinoma has been undergoing treatment with Pembrolizumab, an immune checkpoint inhibitor. The medication has led to the development of a sarcoid-like reaction, initially misinterpreted as cancer recurrence and progression. Additionally, the patient has experienced new-onset hypothyroidism, which has been attributed to the immunotherapy. CONCLUSION: Clinicians, including oncologists, endocrinologists, and radiologists, should maintain a high level of suspicions and awareness regarding the potential adverse events associated with newly introduced immunotherapies like pembrolizumab. This knowledge is crucial for the accurate diagnosis and appropriate management of patients receiving these treatments.

Pulmonary Adverse Events in Cancer Immunotherapy: Case Studies of CT Patterns.

Immune-checkpoint inhibitors have profoundly changed cancer treatment, improving the prognosis of many oncologic patients. However, despite the good efficacy of these drugs, their mechanism of action, which involves the activation of the immune system, can lead to immune-related adverse events, which may affect almost all organs. Pulmonary adverse events are relatively common, and potentially life-threatening complications may occur. The diagnosis is challenging due to the wide and non-specific spectrum of clinical and radiological manifestations. The role of the radiologist is to recognize and diagnose pulmonary immune-related adverse events, possibly even in the early stages, to estimate their extent and guide patients' management.

Immune checkpoint blockade induced sarcoid-like reaction mimicking progression of disease in a patient with microsatellite instable colorectal cancer: case report and review of the literature.

Background: Oncologists are prescribing checkpoint inhibitors with greater frequency, and an awareness of and ability to recognize immune-related adverse events (irAEs) is a key part of the safe administration of these drugs. Case Description: Herein, we report the case of a 26-year-old male diagnosed with de novo metastatic right-sided colon cancer to the liver, with tumor immunohistochemistry demonstrating loss of MSH2 and MSH6, and a pathogenic mutation in MSH2 identified on germline testing, consistent with Lynch Syndrome. The patient received first-line treatment with pembrolizumab. Following 7 months of immune checkpoint blockade (ICB), new pulmonary findings on routine imaging were felt to be concerning for disease progression, despite ongoing excellent clinical status, disease control in the liver, and stable tumor markers. An endobronchial biopsy of one of the mediastinal lymph nodes demonstrated granulomatous inflammation consistent histologically with sarcoidosis, and a diagnosis of sarcoid-like reaction (SLR) secondary to immunotherapy was established. Pembrolizumab was discontinued, and the patient continued active monitoring off of active therapy, with durable cancer control. After 8 months of watchful waiting, new hepatic lesions and increasing abdomino-pelvic lymphadenopathy were identified on imaging, concerning for progression of disease. Inguinal lymph node biopsy demonstrated findings consistent with ongoing SLR. The patient remains with durable cancer control, now 24 months since receipt of ICB. In addition, he remains asymptomatic of the SLR. Conclusions: This case highlights the propensity of SLRs to imitate progression of disease, and the importance of awareness of this adverse effect, to prompt appropriate investigation and management.

Sarcoid heart disease and imaging.

Cardiac sarcoidosis (CS) can mimic any cardiomyopathy due to its ability to manifest with a variety of clinical presentations. The exact prevalence of CS remains unknown but has been reported ranging from 2.3% to as high as 29.9% among patients presenting with new onset cardiomyopathy and/or atrioventricular block. Early and accurate diagnosis of CS is often challenging due to the nature of disease progression and lack of diagnostic reference standard. The current diagnostic criteria for CS are lacking in sensitivity and specificity. Here, we review the contemporary role of advanced imaging modalities such as cardiac magnetic resonance imaging and positron emission tomography/computed tomography imaging in diagnosing and prognosticating patients with CS.

Sarcoid-like reaction in malignant melanoma exacerbated with pembrolizumab therapy case report.

Sarcoid Like Reaction (SLR) is a localized non-caseating epithelioid granulomatous reaction seen secondary to certain immunotherapies and malignancies. Invasive melanoma, while being associated with onset of sarcoidosis, has not shown to directly induce SLR in the literature. We present the case of a 68-year-old male with malignant melanoma, who was found to have SLR prior to starting immunotherapy, which worsened while on pembrolizumab. This case highlights the challenge of distinguishing between drug-induced SLR and melanoma-induced SLR, and the implications in terms of management.

First report of Besnoitia bennetti in Irish donkeys: an emerging parasitic disease in Europe.

BACKGROUND: This is the first report of Besnoitia bennetti in donkeys in Ireland. B. bennetti, an apicomplexan protozoan parasite specific to equids, is an emerging pathogen in Europe. This parasite forms chronic intracytoplasmic cysts in cells of the mesenchymal lineage, mainly fibroblasts, in the skin, sclera and mucosa. Clinical signs in affected equine hosts vary from mild to severe debilitating disease. Little is known of the phylogeny, epidemiology or transmission of B. bennetti infection in donkeys, mules or horses. CASE PRESENTATION: Two cases of besnoitiosis in donkeys are presented. Both donkeys were born and raised in theSouthwest of Ireland. The first case was a 2.5-year-old donkey that had a suspect sarcoid removed, while the second case,a 2-year-old donkey, had a biopsy of nodular dermatitis of the muzzle. Diagnosis was made by histopathology and the parasite species, B. bennetti, was confirmed by PCR followed by sequencing and microsatellite analysis. Both donkeys had high antibody titres against Besnoitia spp. Small (0.5 mm) scleral, conjunctival and dermal cysts over the muzzle were subsequently observed in both animals. Treatment with trimethoprim sulfadiazine for 30 days did not lead to clinical resolution. The findings are compared to the cases of besnoitiosis in donkeys reported in the past 10 years throughout Europe. CONCLUSIONS: Besnoitiosis should be considered as a differential diagnosis for chronic skin disease particularly in cases of cutaneous masses, non-pruritic dermatitis, and dermatitis that is not responsive to treatment in donkeys and other equids. Future studies are needed to investigate the prevalence of the disease in Irish donkeys, the spread of the disease and the potential impact on the health and welfare of the donkeys.

Löfgren Syndrome: A Mosaic of Sarcoidosis Phenotypes.

Sarcoidosis is an autoimmune multisystemic granulomatous disease with an unknown etiology. Löfgren syndrome (LS), an infrequent initial presentation of acute sarcoidosis, is characterized by the classic triad of acute arthritis, erythema nodosum (EN), and bilateral hilar lymphadenopathy (BHL). The presence of this triad offers high diagnostic specificity for sarcoidosis, eliminating the need for a confirmatory biopsy. Typically, LS follows a predictable, self-limiting clinical course. However, atypical presentations require early suspicion and closer monitoring. This case report highlights an unusual clinical manifestation of LS, marked by an incomplete presentation with acute panniculitis and joint lesions in the absence of EN. Acute sarcoidosis should be considered among the differential diagnoses when these clinical manifestations are present, and chest radiography should be performed to rule out BHL. In atypical cases, the disease course becomes less predictable, as exemplified in our case, where recurrence of the disease may occur, necessitating consistent monitoring.