Resolution of multiorgan sarcoid-like reaction after treatment of renal cell carcinoma.

Sarcoid -like reactions (SLRs) can occur in several malignancies adjacent to primary tumour location or the draining lymph nodes. The presence of peritumoural and intratumoural SLR in patients suffering from renal cell carcinoma (RCC) has been reported in few instances. However, the association of RCC with SLR in spleen, liver and other organs in the absence of systemic sarcoidosis is very rare.We present an unusual case of a gentleman in his 30s, who presented with a lesion in the left kidney along with non-specific lesions (likely granulomatous) in liver, spleen and lungs. Partial Nnephrectomy specimen confirmed conventional/clear cell RCC. The histopathology revealed an extensive epithelioid granulomatous reaction affecting both peritumoural and intratumoural areas. Follow-up images demonstrated an almost complete resolution of lesions in the spleen, liver and lungs. Our case supports the hypothesis that non-caseating granulomas of SLR could be a manifestation of an immunologically mediated antitumour response.

Reevaluating Diagnosis of Sarcoidosis: Biopsy with Necrosis in Mycobacterial Endemic Areas.

BACKGROUND: Sarcoidosis is a multisystem inflammatory disease with a variable presentation. The most characteristic feature of sarcoidosis is nonnecrotizing granulomas. However, when sarcoidosis presents with rare organ involvement, and biopsy shows necrosis, the diagnosis becomes challenging. CASE PRESENTATION: Here, we present three cases of sarcoidosis with unusual organ involvement and biopsy findings of necrosis, leading to a delay in diagnosis and treatment. Case 1 was presented with lymphoreticular involvement within the intraparotid lymph node and genitourinary area. Biopsy from the epididymis showed necrosis, initially leading to treatment for tuberculosis (TB). Case 2 describes lymphoreticular involvement and cardiac symptoms. His cervical and bone marrow biopsies showed necrosis. Case 3's presentation was disseminated lymphadenopathy with hepatosplenomegaly, initially suspected as malignancy or TB. CONCLUSION: While biopsy plays a significant role in diagnosing sarcoidosis, the presence of necrosis alone should not lead to its exclusion.

Neurosarcoidosis manifesting as cavernous sinus syndrome in systemic sarcoidosis.

Neurosarcoidosis can manifest in various neurological presentations. The occurrence of cavernous sinus involvement in neurosarcoidosis is rare, which can complicate the diagnostic process. We present a case of neurosarcoidosis demonstrating progressively deteriorating right cavernous sinus syndrome in a woman in her 50s, affecting the oculomotor, abducens and the ophthalmic division of the trigeminal nerves. MRI demonstrated meningeal thickening along the lateral wall of the right cavernous sinus, and a pan-CT scan of the chest, abdomen and pelvis revealed disseminated sarcoidosis involving the lungs and the liver. Histopathological analysis of the liver lesion ultimately confirmed the diagnosis of sarcoidosis. This case underscores the significance of considering neurosarcoidosis as a potential cause of cavernous sinus syndrome. In such cases, early initiation of corticosteroid treatment, with or without steroid-sparing agents, is crucial to prevent disease progression and relapse.

Hypercalcaemia in gastrointestinal stromal tumour and sarcoidosis: a case report.

BACKGROUND: Hypercalcaemia is a common manifestation of sarcoidosis but is sparingly described in gastrointestinal stromal tumours (GISTs). We describe a case of acute kidney injury and hypercalcemia resulting from simultaneous diagnosis of GIST and sarcoidosis, the presentation of which has not yet been reported. CASE PRESENTATION: A 61-year-old male presented with acute kidney injury and hypercalcemia, with elevated 1,25-dihydroxyvitamin D levels. Investigations demonstrated a large gastric antral mass which was resected and proven to be GIST. Histopathology of incidentally found liver nodules revealed non-necrotising epithelioid granulomas consistent with concomitant sarcoidosis. The hypercalcemia was successfully treated with bisphosphonate therapy, resection of the GIST and a four month course of corticosteroids, which was truncated due to a mycobacterial infection. CONCLUSIONS: Our case report is the first to describe hypercalcemia due to GIST and biopsy-proven sarcoidosis, thereby raising the possibility of a common pathophysiological pathway relating the two entities. We review the literature describing the mechanisms of hypercalcaemia in GIST and the association between GIST and sarcoidosis.

Sarcoidosis-associated pulmonary hypertension due to pulmonary arteries stenosis - a case report.

BACKGROUND: Sarcoidosis-associated pulmonary hypertension (SAPH) is listed in Group 5 of the clinical classification of pulmonary hypertension, due to its complex and multifactorial pathophysiology. The most common cause of SAPH development is advanced lung fibrosis with the associated destruction of the vascular bed, and/or alveolar hypoxia. However, a substantial proportion of SAPH patients (up to 30%) do not have significant fibrosis on chest imaging. In such cases, the development of pulmonary hypertension may be due to the lesions directly affecting the pulmonary vasculature, such as granulomatous angiitis, pulmonary veno-occlusive disease, chronic thromboembolism or external compression of vessels by enlarged lymph nodes. Based on the case of a 69-year-old female who developed SAPH due to pulmonary arteries stenosis, diagnostic difficulties and therapeutic management are discussed. CASE PRESENTATION: The patient, non-smoking female, diagnosed with stage II sarcoidosis twelve years earlier, presented with progressive dyspnoea on exertion, dry cough, minor haemoptysis and increasing oedema of the lower limbs. Computed tomography pulmonary angiography (CTPA) showed complete occlusion of the right upper lobe artery and narrowing of the left lower lobe artery, with post-stenotic dilatation of the arteries of the basal segments. The vascular pathology was caused by adjacent, enlarged lymph nodes with calcifications and fibrotic tissue surrounding the vessels. Pulmonary artery thrombi were not found. The patient was treated with systemic corticosteroid therapy and subsequently with balloon pulmonary angioplasty. Partial improvement in clinical status and hemodynamic parameters has been achieved. CONCLUSIONS: An appropriate screening strategy is required for early detection of pulmonary hypertension in sarcoidosis patients. Once SAPH diagnosis is confirmed, it is crucial to determine the appropriate phenotype of pulmonary hypertension and provide the most effective treatment plan. Although determining SAPH phenotype is challenging, one should remember about the possibility of pulmonary arteries occlusion.

Systemic Diseases and Heart Block.

Systemic diseases can cause heart block owing to the involvement of the myocardium and thereby the conduction system. Younger patients (<60) with heart block should be evaluated for an underlying systemic disease. These disorders are classified into infiltrative, rheumatologic, endocrine, and hereditary neuromuscular degenerative diseases. Cardiac amyloidosis owing to amyloid fibrils and cardiac sarcoidosis owing to noncaseating granulomas can infiltrate the conduction system leading to heart block. Accelerated atherosclerosis, vasculitis, myocarditis, and interstitial inflammation contribute to heart block in rheumatologic disorders. Myotonic, Becker, and Duchenne muscular dystrophies are neuromuscular diseases involving the myocardium skeletal muscles and can cause heart block.

Blau Syndrome: Challenging Molecular Genetic Diagnostics of Autoinflammatory Disease.

The aim of this study was to describe the clinical and molecular genetic findings in seven individuals from three unrelated families with Blau syndrome. A complex ophthalmic and general health examination including diagnostic imaging was performed. The NOD2 mutational hot spot located in exon 4 was Sanger sequenced in all three probands. Two individuals also underwent autoinflammatory disorder gene panel screening, and in one subject, exome sequencing was performed. Blau syndrome presenting as uveitis, skin rush or arthritis was diagnosed in four cases from three families. In two individuals from one family, only camptodactyly was noted, while another member had camptodactyly in combination with non-active uveitis and angioid streaks. One proband developed two attacks of meningoencephalitis attributed to presumed neurosarcoidosis, which is a rare finding in Blau syndrome. The probands from families 1 and 2 carried pathogenic variants in NOD2 (NM_022162.3): c.1001G>A p.(Arg334Gln) and c.1000C>T p.(Arg334Trp), respectively. In family 3, two variants of unknown significance in a heterozygous state were found: c.1412G>T p.(Arg471Leu) in NOD2 and c.928C>T p.(Arg310*) in NLRC4 (NM_001199139.1). In conclusion, Blau syndrome is a phenotypically highly variable, and there is a need to raise awareness about all clinical manifestations, including neurosarcoidosis. Variants of unknown significance pose a significant challenge regarding their contribution to etiopathogenesis of autoinflammatory diseases.

A case of renal sarcoidosis complicated by parotid gland and uterine lesions.

BACKGROUND: Sarcoidosis is a systemic disease that can affect multiple organs. While pulmonary sarcoidosis is most commonly observed, renal sarcoidosis occurs less frequently. We herein report a case of sarcoidosis with an exceptionally rare distribution including renal lesions. CASE PRESENTATION: A 51-year-old Japanese female was referred because of bilateral parotid swelling and renal dysfunction. Computed tomography scan showed the swelling of bilateral kidneys, parotid glands, and uterus. Ga scintigraphy also showed remarkable accumulation in these organs. Renal biopsy and cytological evaluations of parotid gland and uterus were performed and she was diagnosed as sarcoidosis of these organs. Treatment was initiated with prednisolone 40 mg/day and then renal dysfunction subsequently improved. In addition, the swelling of parotid glands and uterus improved and Ga accumulation in each organ had disappeared. CONCLUSION: This is a first case of renal sarcoidosis complicated by parotid glands and uterus lesions. Pathological findings and the reactivity observed in Ga scintigraphy indicated the presence of lesions in these organs.

[Hepatosplenic sarcoidosis: description of a case at the University hospital center of Brazzaville, Congo]. / Sarcoïdose à localisation hépatosplénique : description d'un cas au Centre hospitalier universitaire de Brazzaville, Congo.

Sarcoidosis is a multisystem inflammatory disease of unknown etiology. The isolated extrapulmonary form is rare. We report the case of hepatosplenic sarcoidosis in a 29-year-old female patient.It is a patient with no notable medical history, who was seen in consultation for repeated epistaxis. Clinical examination noted nodular hepatomegaly associated with signs of portal hypertension and splenomegaly. Sedimentation rate, alkaline phosphatase, serum angiotensin converting enzyme, aminotransferases were high. Histological examination of the spleen and liver biopsy noted granulomatous inflammatory infiltration without cancerous lesion or tonsil stones.This picture is comparable with sarcoidosis, despite the absence of PET scans. The main challenge remains the differential diagnosis with other granulomatoses. Corticosteroid therapy is the first-line treatment, and after splenectomy the patient has achieved clinical and biological stability.

Stroke associated with sarcoidosis: A systematic review of reported cases.

BACKGROUND: Sarcoidosis can be associated with stroke. Whether granulomatous vasculitis directly causes stroke in patients with sarcoidosis remains unclear. This systematic review aims to consolidate reports of concurrent sarcoidosis and stroke. METHODS: Medline and Embase were searched for terms encompassing sarcoidosis and stroke with a censoring date of March 25, 2023. Cases were reviewed by two authors, with the inclusion criteria: biopsy-confirmed systemic sarcoidosis, stroke confirmed by imaging or pathology, clinical description of individual patient history, and English language publications. RESULTS: Of 1628 articles screened, 51 patients from 49 articles were included (65% male, mean age 41 years). Seventy-one percent of strokes were ischemic and 29% were hemorrhagic. Lesions were supratentorial in 78% of cases, infratentorial in 34%, and multifocal in 45%. Presenting symptoms were variable, with the most common being headache (38%) followed by weakness (35%). 10 patients had recurrent strokes. Stroke was the presenting symptom of sarcoidosis in 65%. 21 patients had brain biopsies. The most common neuropathologic findings were perivascular (33%) or intramural (33%) non-caseating granulomas. On imaging, 32 patients had findings suggestive of neurosarcoidosis, including 35% with evidence of meningeal enhancement. 63% of patients were treated with corticosteroids and/or other immunomodulatory therapy, with varying clinical improvement. CONCLUSIONS: Stroke associated with sarcoidosis generally follows trends in stroke incidence, with infarction being more common than hemorrhage and male sex carrying a higher risk. Most patients were diagnosed with sarcoidosis during or following their stroke episode. Brain biopsy infrequently shows clear granulomatous vasculitis.

Anti-TL1A monoclonal antibody modulates the dysregulation of Th1/Th17 cells and attenuates granuloma formation in sarcoidosis by inhibiting the PI3K/AKT signaling pathway.

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

Air pollution and incident sarcoidosis in central Pennsylvania.

Sarcoidosis is a chronic granulomatous disease predominantly affecting the lungs and inducing significant morbidity and elevated mortality rate. The etiology of the disease is unknown but may involve exposure to an antigenic agent and subsequent inflammatory response resulting in granuloma formation. Various environmental and occupational risk factors have been suggested by previous observations, such as moldy environments, insecticides, and bird breeding. Our study investigated the association of air pollution with diagnosis of sarcoidosis using a case-control design. Penn State Health electronic medical records from 2005 to 2018 were examined for adult patients with (cases) and without (controls) an International Classification of Disease (ICD)-9 or -10 code for sarcoidosis. Patient addresses were geocoded and 24-hr residential-level air pollution concentrations were estimated using spatio-temporal models of particulate matter <2.5 µm (PM2.5), ozone, and PM2.5 elemental carbon (EC) and moving averages calculated. In total, 877 cases and 34,510 controls were identified. Logistic regression analysis did not identify significant associations between sarcoidosis incidence and air pollution exposure estimates. However, the odds ratio (OR) for EC for exposures occurring 7-10 years prior did approach statistical significance, and ORs exhibited an increasing trend for longer averaging periods. Data suggested a latency period of more than 6 years for PM2.5 and EC for reasons that are unclear. Overall, results for PM2.5 and EC suggest that long-term exposure to traffic-related air pollution may contribute to the development of sarcoidosis and emphasize the need for additional research and, if the present findings are substantiated, for public health interventions addressing air quality as well as increasing disease surveillance in areas with a large burden of PM2.5 and EC.

The co-occurrence of sarcoidosis and anti-PLA2R-associated membranous nephropathy in a patient with underlying genetic susceptibility.

BACKGROUND: Sarcoidosis is a multisystemic inflammatory disease, characterized by the presence of non-caseating, epithelioid granulomas. Glomerular disease in patients with sarcoidosis is rare and membranous nephropathy (MN) is cited as the most common. The association between the two diseases remained unclear. This article reported a case of co-occurrence of sarcoidosis and anti-PLA2R-associated MN, to provide a possible relationship between these two entities. CASE PRESENTATION: A 61-year-old Chinese Han woman with a history of sarcoidosis was admitted to our hospital for nephrotic syndrome. Her sarcoidosis was diagnosed according to the adenopathy observed on the computed tomography scan and the biopsy of lymph nodes. The MN presented with nephrotic syndrome with a PLA2R antibody titer of 357RU/ml, and the final diagnosis was based on a renal biopsy. The patient's sarcoidosis was remitted after treatment with prednisone. One year later MN was diagnosed, and she was treated with prednisone combined with calcineurin inhibitors, based on a full dose of renin-angiotensin system (RAS) inhibitor. The patient's sarcoidosis had been in remission while the MN was recurrent, and her renal function deteriorated to end-stage renal disease 6 years later due to discontinuation of immunosuppression. A genetic test led to the identification of the HLA-DRB1*0301 and HLA-DRB1*150 genes associated with both sarcoidosis and MN, which provides a new possible explanation of the co-occurrence of these two diseases. CONCLUSION: This case suggested for the first time a potential genetic connection between idiopathic MN and sarcoidosis which needs further studies in the future.

Occupational exposures and sarcoidosis: a rapid review of the evidence.

BACKGROUND: Sarcoidosis is a rare, multisystem, inflammatory condition associated with the formation of granulomas. Diagnosis can be challenging because of non-specific symptoms complicating epidemiological investigations of its aetiology. Despite research efforts, a review of the current state of the evidence is needed. AIMS: To assess the evidence for an association between occupational exposures and the development of sarcoidosis. To determine if workers in any occupation are at a greater risk of developing sarcoidosis. METHODS: This rapid review follows the methodology suggested by the World Health Organization. Two electronic databases were systematically searched until April 2022. The methodological quality of the studies was critically appraised, and a best-evidence approach was used to synthesize the results. RESULTS: Titles and abstracts of 2916 articles were screened, with 67 full-text articles reviewed for eligibility. Among the 13 studies eligible for this review, none were of high quality (i.e. low risk of bias). Six studies exploring the association between sarcoidosis and a range of occupations and exposures, and one previous systematic review were of low quality reporting inconsistent findings. Six studies examined the risk of sarcoidosis associated with occupational silica exposure, two of which were of acceptable quality. Overall, the study methodologies and results were inadequate to support causal relationships. CONCLUSIONS: There is limited evidence of acceptable methodological quality to assess the risk of sarcoidosis associated with occupational exposures. There is a growing body of research examining occupational exposure to silica and sarcoidosis. Additional high-quality confirmatory research is needed.