Comprehensive sub-chronic toxicological profiling of illegal artisanal small-scale mining-polluted river bodies in four regions of Ghana.

Rituximab-associated colitis, a rare toxicity that may occur following prolonged latency, has nonspecific features. We report a 42-year-old female with diffuse cutaneous systemic sclerosis and interstitial lung disease whose last rituximab infusion was 195 days before admission. She developed diarrhea and abdominal pain; initial computed tomography revealed no intra-abdominal focus. On day 12, colonoscopy revealed erosions and ulcers from the cecum to the descending colon; cytomegalovirus testing was negative. Symptoms persisted; repeat colonoscopy on day 20 confirmed multifocal ulceration, suggesting cytomegalovirus colitis or severe Crohn's disease. By day 27, computed tomography showed ascending colon thinning, descending colon thickening, and haustral loss like ulcerative colitis. High-dose prednisolone was initiated owing to the inflammatory bowel disease-like process. Although clinical symptoms and inflammatory markers were improved, follow-up computed tomography revealed free air and perforation, necessitating emergency subtotal colectomy with ileostomy. Histology demonstrated ulcers extending to the subserosa, and noncaseating granulomas in the mucosa and submucosa. Immunohistochemistry demonstrated CD3-positive, CD20-negative, and CD4-predominant lymphocytic infiltration. This case highlights that rituximab-associated colitis may mimic inflammatory bowel disease, show prolonged latency, and progress to perforation despite apparent biochemical improvement, warranting early biopsy and careful radiologic follow-up. Rituximab-associated colitis should be considered even months following anti-CD20 exposure.

Oral sarcoidosis: A systematic review of dental implications.

Sarcoidosis is a heterogenous disease of unknown etiology characterized by non-caseating granulomas. Disease prevalence and presentation vary significantly by ancestry and ranges from acute, self-resolving disease to severe, chronic disease. Following previous reports suggesting B cells in the development and pathogenesis of sarcoidosis, we present here results of single-cell RNA sequencing, supporting B cell involvement in sarcoidosis through altered immediate early response, rewiring of MAPK signaling, and ancestry-specific preferential expansion of B cell receptors. Peripheral blood mononuclear cells were obtained from individuals of African or European Ancestry (AA and EA, respectively) including 48 healthy controls, 59 sarcoidosis patients, and 28 systemic lupus erythematosus (SLE) patients. SLE samples were used as a disease control. Differential expression analysis highlighted many differentially expressed genes (DEGs) with almost 5x more in the AA sarcoidosis versus AA control group compared to the EA sarcoidosis versus EA control group. B cells had the most DEGs of all cell types and expression patterns were similar between ancestries, however, sarcoidosis had an opposite transcription pattern than SLE, demonstrating an alternative immune response to acute activation than that seen in a prototypical autoinflammatory disease. This trend was maintained when examining specialized B cell subsets, with the most pronounced effect in the AA sarcoidosis versus AA control comparison. Our results strongly support further investigation of the role of humoral immune response in sarcoidosis and the potential to highlight patient groups likely to benefit from existing B cell therapies.

Sarcoidosis (S) is a systemic inflammatory disease of unknown etiology characterized by the formation of noncaseating granulomas, multisystemic organ involvement, and T-cell activation at the site of granulomatous inflammation with the release of various chemokines and cytokines. In Russia, a large team of specialists in various fields has developed clinical guidelines. Primary diagnosis of S. requires comprehensive laboratory and instrumental studies, including imaging diagnostics, and treatment is recommended only in cases of disease progression and a life-threatening course. Symptoms of S. vary widely, from acute to asymptomatic. Spontaneous remissions occur in up to 70% of cases, but fibrosis may develop in 10-15%. Dangerous variants of S. include cardiac sarcoidosis, sarcoidosis of the nervous system, and sarcoidosis of the eyes. In stable cases, long-term use of alpha-tocopherol and pentoxifylline is possible. Systemic glucocorticosteroids are considered first-line treatment for progressive sarcoidosis, with a starting dose of at least 20 mg per day and a duration of at least 10- 12 months. However, this therapy is more often associated with relapses, and low doses and short courses more often lead to subsequent fibrosis. Second-line treatments include methotrexate, but also leflunomide, azathioprine, mycophenolate, and cyclophosphamide. Third-line treatments include adalimumab and infliximab, but they themselves can cause sarcoid reactions. In refractory and recurrent cases, efferent therapies are used. The authors invite readers to discuss the updated version of clinical guidelines, available on the website of the Russian Respiratory Society to continue working on them.

scRNA-seq based gene and cell dynamics behind the formation of the non-caseating granulomas.

Cardiac sarcoidosis is a rare but potentially life-threatening condition characterized by the formation of non-caseating granulomas in the myocardium. Clinical manifestations range from asymptomatic forms to atrioventricular blocks, ventricular arrhythmias, heart failure, and sudden cardiac death. Diagnostic work-up requires a multimodality approach combining advanced imaging, clinical criteria, and, when possible, histological confirmation. Immunosuppressive therapy remains the cornerstone of treatment, aimed at suppressing myocardial inflammation and preventing irreversible damage. Risk stratification for sudden cardiac death is crucial, and cardiac implantable electronic devices play a key role in selected patients. This review, structured in ten clinical questions, provides an overview of the epidemiology, clinical presentation, diagnostic criteria, differential diagnosis, therapeutic strategies, and risk stratification of cardiac sarcoidosis, in light of the most recent international guidelines and consensus documents.

Emerging diagnostic techniques in sarcoidosis: a path forward.

Bone sarcoidosis is a rare manifestation, reported in 1-15% of patients, and most often presenting as a multisystemic disease. Although it was historically described as predominantly affecting the phalanges (Perthes-Jüngling disease), axial involvement (spine, pelvis) is now recognized as frequent, most likely due to the increased use of MRI and PET-CT scans. This condition is often asymptomatic and discovered incidentally, but it can cause pain and disabling complications. Lesions can appear lytic, sclerotic, or mixed, with no specific radiological pattern. Definitive diagnosis relies on a bone or bone marrow biopsy demonstrating non-caseating granulomas and ruling out infection or malignancy. Treatment is not standardized and mainly relies on systemic glucocorticoids, with immunosuppressive agents added when necessary.

Systemic sarcoidosis can occur without pulmonary involvement and may present exclusively with extrapulmonary manifestations, thereby mimicking infections, autoimmune diseases, or malignancies. The case of a60-year-old female patient with pronounced cachexia (BMI 14 kg/m2), hypercalcemia, and multiorgan involvement is presented. Histology revealed non-caseating granulomas in gastric biopsies (granulomatous gastritis) as well as granulomatous interstitial nephritis with atubular proteinuria pattern on renal biopsy. Imaging revealed no evidence of pulmonary involvement. Markedly elevated serum angiotensin-converting enzyme and soluble interleukin‑2 receptor levels, together with cerebrospinal fluid and MRI findings, were consistent with neurosarcoidosis. As the disease progressed, posterior reversible encephalopathy syndrome developed, presenting with seizures and transient cortical blindness. An extensive differential diagnostic workup, particularly for lymphoma, tuberculosis, and systemic vasculitis, was negative. The clinical course was complicated by percutaneous endoscopic gastrostomy-associated Enterococcus faecium peritonitis and Candida albicans sepsis. After stabilization and infection control, high-dose corticosteroid therapy was initiated, resulting in partial improvement of renal function and neurological symptoms. This case highlights the diagnostic and therapeutic challenges of life-threatening, purely extrapulmonary sarcoidosis with renal, gastrointestinal, and neurological manifestations. Early histological confirmation, thorough exclusion of relevant differential diagnoses, and multidisciplinary management are essential, particularly in balancing immunosuppression with infection control.

A 21-year-old female presented with complaints of new-onset asymptomatic, erythematous plaques localized to the tattooed sites on her body. The patient had a history of psoriasis for the past three years. She initially had psoriatic plaques with a typical morphology in a generalized distribution present on the normal (nontattooed) skin which had resolved around three months ago. Around two months ago, she started developing erythematous plaques with minimal scaling localized to the tattooed sites. History revealed that the patient had gotten these tattoos two years ago. She did not recall any history of flare in psoriasis at the time of tattooing. Examination showed erythematous plaques localized to some areas of tattooed skin over the right forearm, leg, and left breast [Figure 1a-c]. Clinically, differential diagnoses considered were late-onset psoriatic koebnerization, granulomatous reaction secondary to tattoo ink, lichenoid tattoo reaction, and tattoo sarcoidosis.Figure 1: Cutaneous examination revealed decorative black ink tattoos with overlying erythematous plaques bearing fine whitish scales sharply confined to the tattooed areas over the right forearm (a), right leg (b), and left breast (c)Biopsy revealed a normal epidermis with dermal lymphohistiocytic infiltrate forming noncaseating granulomas with deposition of red pigment [Figure 2a and b].Figure 2: (a and b) Hist opathological examination of the affected area showed a normal epidermis with dermis displaying focal aggregates of lymphocytes, epithelioid histiocytes, and foreign body giant cells containing red tattoo pigment, findings consistent with foreign body granuloma (H and E, 40×) (a) and (H and E, 200×) (b). H and E = Hematoxylin and EosinANSWER: Granulomatous reaction secondary to tattoo ink Tattooing for cosmetic purposes has gained popularity in recent times. Cutaneous reactions to tattoos have generally been attributed to metallic salts used in the preparation of the pigment. Commonly reported reactions to tattoos can be divided into infections, allergic contact dermatitis to tattoo pigment, granulomatous reactions, lichenoid tattoo reaction, and localization of inflammatory skin conditions like psoriasis and eczema on the tattoo area.[1] Rarely, cutaneous skin conditions like pseudolymphomatous reactions and keratoacanthomas may develop. There have been a few case reports of exogenous pigments in the tattoo, inducing a sarcoidal granulomatous reaction presenting as a localized cutaneous disease or heralding systemic involvement.[2] Evolution of erythematous papules to scaly plaques localized to tattoo sites, presenting months to years after tattooing should raise suspicion of lichenoid reaction to tattoo, granulomatous reactions, and sarcoidal reactions.[3] These can be differentiated on the basis of histopathology. Multiple case reports of psoriasis showing isomorphic response localized to the tattoo sites with a delay of weeks to years after the tattooing process have also been reported. Most of these patients had a previous history of psoriasis, while a few were diagnosed with psoriasis after the appearance of koebnerization over tattoo sites.[4] Table 1 summarizes the clinical differentials in the above case along with the expected histopathological findings. Since our patient had a previous history of psoriasis, we had also kept the differential of late-onset koebnerization. However, there were no classical findings of psoriasis on histopathology. There was significant improvement within 4 weeks with topical mometasone furoate 0.1% cream. Steroids, laser therapy, and surgical excision have been considered in patients presenting with such tattoo.Table 1: Summarizes the clinical differentials in the above case along with the expected histopathological findingsIn suspected cases, especially in front of papulonodular lesions arising from a tattoo, it is important to perform an early diagnosis through histopathology. Key learning points Delayed Granulomatous Reactions to Tattoo PigmentsTattoo ink can incite granulomatous inflammation, often with noncaseating granulomas containing pigmentladen histiocytes—typically appearing months to years after tattooing. These reactions can mimic sarcoidosis and pose diagnostic challenges.Koebner Phenomenon in Psoriasis within TattoosIn individuals with psoriasis, Koebnerization can manifest at tattoo sites—even years after the procedure—resulting in psoriatic lesions localized to those areas.Therapeutic Approaches and Avoidance of Ink Dispersion InterventionsManagement often includes topical or systemic corticosteroids and, in some cases, antimalarials (e.g., hydroxychloroquine). Declaration of patient consent The authors certify that they have obtained all appropriate patient consent. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.

Sarcoidosis, a rare inflammatory multisystemic disease more prevalent among females, is characterised by noncaseating granulomas affecting organs like the lungs, liver, lymph nodes, skin, and eyes. Diagnosis is through exclusion, ruling out infections, malignancies, and environmental factors. It involves an inflammatory response in a genetically susceptible host. Clinical presentations range from asymptomatic to organ failure, including skin lesions, ocular manifestations, and neurological involvement. Granuloma formation is the pathological hallmark, and chest radiograph using Scadding staging is common for the diagnosis of pulmonary sarcoidosis. A rare case of splenic involvement in sarcoidosis is presented in a 50-year-old diabetic, hypertensive, and hypothyroid female. She reported significant weight loss, decreased appetite, generalised weakness, bilateral knee and ankle pain, fever, dry cough, chest pain, exertional breathlessness, neck swelling, and maculopapular lesions on her upper limbs. Examination revealed palpable cervical lymph nodes (1.5×1 cm) and hepatosplenomegaly. Investigations showed microcytic hypochromic anaemia, hypokalaemia, elevated alkaline phosphatase, and bilateral hilar lymphadenopathy on chest X-ray. Tests for tuberculosis and connective tissue disorders were negative. Elevated serum calcium and angiotensin-converting enzyme (ACE) levels, along with noncaseating granulomas on lymph node and skin biopsies, confirmed sarcoidosis. Computed tomography (CT) scans revealed hepatomegaly with liver and spleen lesions and enlarged lymph nodes in the mediastinum, bilateral axillae, para aortic, aorto-caval, and bilateral inguinal locations. The patient received symptomatic treatment, followed by oral steroids and methotrexate with folic acid supplementation. She improved symptomatically and was discharged with instructions for regular follow-up. Prompt identification of sarcoidosis is crucial, as it often goes undetected, its closest mimic being tuberculosis. Treatment starts with steroids and may include immunosuppressive or anti-tumour necrosis factor (anti-TNF) alpha agents, significantly benefiting the patient.

BACKGROUND Sarcoidosis, a rare multisystem disease characterized by non-caseating granulomas, affects the gastrointestinal system in less than 1% of cases, mainly involving the gastric antrum. Most cases are asymptomatic and are discovered incidentally during endoscopy; fewer than 1% of patients present with symptoms such as gastroesophageal reflux disease (GERD), dyspepsia, or bleeding. The relationship between gastric sarcoidosis and GERD is not well understood, posing diagnostic and treatment challenges that are not fully addressed in the current literature. This report describes a case of incidentally discovered gastric sarcoidosis presenting as GERD that improved without immunosuppressive therapy. To facilitate management, we propose an algorithm for managing GERD symptoms in the context of gastric sarcoidosis. CASE REPORT A 48-year-old man with pulmonary sarcoidosis - in remission for 7 years - presented for endoscopic evaluation of GERD and nonspecific chest pain. Vital signs, physical examination, and routine laboratory results, including a cardiac workup, were unremarkable. Upper gastrointestinal endoscopy revealed grade A esophagitis and a 6-mm antral papule. Histopathologic examination of the biopsy specimen revealed non-caseating granulomas consistent with gastric sarcoidosis. The patient's symptoms improved with escalated proton pump inhibitor therapy; immunosuppression was not required. Rheumatology consultation recommended no additional treatment, given his clinically quiescent disease and improvement in GERD symptoms. CONCLUSIONS This case highlights the diagnostic uncertainty of GERD in the presence of gastric sarcoidosis and emphasizes the importance of personalized, multidisciplinary management.

Pericardial effusion is a fatal and life-threatening condition. If it is not addressedthoroughly, complications such as constrictive pericarditis may occur. Etiologies ofpericardial effusion varied and one of the most common etiologies is tuberculosis.Other etiologies include inflammation, malignancy or other autoimmune disordersuch as sarcoidosis. Sarcoidosis is a diagnosis of exclusion and is confirmed bybiopsy result that showed non-caseating epitheloid-cell granuloma, with no otherorganism or particles. Epidemiology of sarcoidosis in Japan is 1-2 case per 100.000patients, with the peak incidence between the age of 20 to 39 years old. We reporteda case of 37 years old woman presented to our emergency department withshortness of breath and signs of pericardial tamponade. She was previously healthywith no other significant past medical. She was first treated as a case ofextrapulmonary tuberculosis and shown no improvement with anti-tuberculosismedications. Several work ups were then done in search of other etiologies of herpericardial effusion. A biopsy form one of her abdominal lymph nodes wasperformed, which pathologically revealed sarcoidosis. She was placed oncorticosteroid and methotrexate with improvement of symptoms. One monthfollowed up showed complete resolution of her pericardial effusion.

Idiopathic granulomatous mastitis (IGM) is a rare inflammatory condition of the breast with unknown etiology, primarily affecting women of childbearing age. IGM commonly presents with culture-negative abscesses, often leading to significant scarring, hyperpigmentation, and deformation of the affected breast. Breast cancer and tuberculosis are important differential diagnoses. IGM is confirmed by the presence of non-caseating granulomas and microabscesses on histopathological examination. The literature mainly consists of case studies, and there is no evidence-based treatment. A regional multidisciplinary collaboration group was formed in Stockholm. The purpose of this collaboration was to develop a guideline to assist physicians in the investigation and management of patients with suspected IGM. A literature search was conducted in NCBI Pubmed and thirty relevant studies were included. Flowcharts were developed for the investigation and treatment of IGM. Investigation includes wound bacterial cultures, DNA sequencing (for fungi and bacteria), core needle biopsy, blood tests and skin punch biopsy. Ultrasound-guided drainage is recommended for abscesses, and surgery should be avoided. An initial treatment option when diagnosis has been established consists of daily application of topical group III corticosteroids for 2-3 weeks. Second-line therapy involves a combination of oral corticosteroids and methotrexate for 1-2 months, followed by a tapering of corticosteroids, with continuation of methotrexate monotherapy for an additional six months. Due to the complexity and suffering associated with IGM, patients should be managed by a team of specialists with a specific interest in the condition.The EUBREAST Network has an upcoming IGM registry study, which is expected to provide valuable insights into the understanding and management of this condition.

Sarcoidosis is a granulomatous inflammatory disease primarily affecting the lungs. Central nervous system involvement is rare, occurring in approximately 5-10% of cases. Isolated lesions of the cranial nerve, particularly affecting the trigeminal nerve, are even less common. These lesions can closely resemble more well-known tumors, such as trigeminal schwannomas, meningioma, and multiple sclerosis, which can complicate diagnosis when a solitary mass in Meckel's cave is the initial finding. We report a case of a 45-year-old white man who presented with several months of right facial discomfort and numbness in the mandibular (V3) distribution consistent with trigeminal neuralgia. Magnetic resonance imaging of the brain revealed an avidly contrast-enhancing lesion in the right Meckel's cave along the trigeminal nerve. The patient underwent a skull base surgical exploration and resection. Histopathological, immunohistochemistry, and infectious screening of the resected tissue demonstrated noncaseating granulomas with no evidence of neoplastic or infectious etiologies. Lab work of angiotensin-converting enzyme levels and inflammatory markers were within normal limits. Importantly, the patient had presented with isolated trigeminal neurological symptoms, and thoracic abnormalities of mediastinal and hilar calcified lymph nodes with perilymphatic nodules were discovered only during the postoperative systemic evaluation prompted by the histopathological diagnosis. The patient started high-dose corticosteroid therapy following the operation, and his trigeminal pain and neurological symptoms improved substantially; he remained stable for the entirety of the 12-month follow-up duration. This case highlights the diagnostic challenges of trigeminal nerve lesion. There are no specific imaging features on magnetic resonance imaging that reliably distinguish neurosarcoidosis from tumors such as schwannomas or meningiomas. Therefore, neurosarcoidosis should be included in the differential diagnosis of contrast-enhancing Meckel's cave masses, even in patients without known systemic sarcoidosis. Tissue biopsy can be invaluable in determining inflammatory lesions and preventing overly aggressive resections. Once diagnosed, neurosarcoidosis is typically managed with high-dose corticosteroids and follow-up, often leading to symptom improvement. Timely histological confirmation and collaborative, multidisciplinary management are essential for achieving correct diagnosis and favorable outcomes.

Cardiac sarcoidosis (CS) is a rare and complex disease that requires a multidisciplinary approach for diagnosis and treatment. The diagnosis of CS can be confirmed by histological examination of non-caseating granulomas in cardiac or extracardiac tissue, along with supportive clinical and imaging findings. Symptoms are often non-specific, and the yield of endomyocardial biopsy is low due to the patchy nature of cardiac involvement-thus, many cases are not straightforward to diagnose, especially when pulmonary or extracardiac features are absent. Modern non-invasive imaging modalities have unique strengths in assessing the myocardium's structure, function, perfusion, inflammation and fibrosis-abnormalities of all these features exist in CS in varying degrees and can be integrated to assist in the diagnosis. Echocardiography is universally used as the initial imaging test when CS is suspected and provides information on cardiac structure and function, but is limited by inadequate tissue characterisation and differentiation from other infiltrative or restrictive cardiomyopathies. Positron emission tomography (PET) and cardiovascular magnetic resonance (CMR) have good accuracy in diagnosing CS. With current tissue characterisation techniques, such as T1 and T2 parametric mapping, CMR imaging can detect subclinical or early CS. While CMR has better overall prognostic utility for arrhythmic risk and cardiac mortality, fluorodeoxyglucose (FDG)-PET is superior in monitoring disease activity and guiding anti-inflammatory therapy. Hybrid FDG-PET/CMR imaging is a newer, complementary approach that is being increasingly used in centres of excellence. It combines the unique strengths of both modalities, thereby achieving superior sensitivity and specificity.

Sarcoidosis is a systemic disease that causes noncaseating granulomas in multiple organs, primarily affecting the respiratory tract, eyes, skin, and heart. Although it also occurs in the liver, it is difficult to distinguish it from well-differentiated hepatocellular carcinoma based on imaging diagnosis alone. Here, we report a case in which it was difficult to distinguish it from well-differentiated hepatocellular carcinoma, but the diagnosis was made after surgical resection.

Sarcoidosis is an inflammatory granulomatous disease that affects people worldwide and can involve virtually any organ but most commonly the lungs and thoracic lymph nodes. The cause of sarcoidosis remains unknown, but occupational and environmental exposures, genetic background, and ethnicity are likely contributors to disease development. Recent immunological studies, including single-cell RNA sequencing and spatial transcriptomics, have increased our understanding of disease pathogenesis. Diagnosing sarcoidosis is often challenging due to the lack of a diagnostic gold standard and the remarkable variability in clinical presentation. Accordingly, the diagnosis requires the presence of compatible clinical and radiological features along with histopathological evidence of noncaseating granulomas and exclusion of other granulomatous diseases. The differential diagnosis includes infection, drug-induced granulomatosis, inborn error of immunity, vasculitis and malignancies. Sarcoidosis often resolves spontaneously, but it is not a benign disease. Up to one-third of patients develops chronic or progressive disease, which carries an increased risk of organ failure or death. Treatment is not always required, but is clearly indicated for progressive pulmonary disease, symptomatic cardiac or central nervous system involvement, and significantly impaired quality of life. Treatment aims to decrease symptom burden and preserve organ function. Corticosteroids have been considered first-line treatment for decades, but their long-term use is associated with substantial toxicity. Recently, methotrexate was found to be equally effective as prednisone as first-line treatment in pulmonary sarcoidosis. The identification of novel pathways involved in disease pathogenesis has suggested JAK inhibitors and mTOR inhibitors as potential therapies. More efficacious and better tolerated therapies are urgently needed; however, the rarity of the disease, its heterogeneous clinical course and the lack of prognostic biomarkers make it difficult to design and implement clinical trials of novel therapies.

Work-up in patients with retinal vasculitis: A systematic review and meta-analysis: International Uveitis Study Group (IUSG) Retinal Vasculitis Study (ReViSe) Report 2.