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Összefoglaló. A nekrotizáló sarcoid granulomatosis a granulomatosus pulmonalis angitisek közé tartozó, ritka kórkép. Egyesek a sarcoidosis variánsának, mások primer pulmonalis vasculitisnek tartják. A kórkép klinikai és patológiai jellegzetességeit két eset bemutatásával ismertetjük. A 20 éves nőbeteg sürgősséggel került pulmonológiai osztályra száraz köhögés, jobb oldali, mély belégzéssel összefüggő mellkasi fájdalom és láz miatt, a 63 éves férfi beteget pedig pneumoniát követő kontroll-mellkasröntgenfelvételen látott elváltozás kivizsgálása során észlelték. Az autoimmun panel vizsgálata, a mikrobiológiai tesztek mindkét betegnél negatívnak bizonyultak, a légzésfunkciós vizsgálat és a bronchoszkópos vizsgálat nem talált eltérést. A mellkas-CT-felvételen lágyrész-denzitású nodulusok látszottak egyoldali dominanciával, a folyamatot nem kísérte a hilusi nyirokcsomók szimmetrikus megnagyobbodása. A nodulusok szövettani vizsgálata vált indokolttá, melyet videoasszisztált torakoszkópos tüdőreszekciós mintavétellel biztosítottak. Mikroszkóposan a tüdőparenchymában gócos nekrózisokat, a környezetükben el nem sajtosodó epitheloid sejtes granulomatosus gócokat, az átfutó artériákban pedig granulomatosus arteritist láttak; a klinikai adatok figyelembevételével a tüdő nekrotizáló sarcoid granulomatosisa diagnózisát állították fel. A tüdőbetegség mindkét betegnél egy év alatt spontán regrediált. Az irodalom adatait és az eseteket összegezve, a tüdő nekrotizáló sarcoid granulomatosisában mikrobiológiai vizsgálatokkal nem igazolható tüdőfertőzés, és az immunológiai kivizsgálás sem tár fel szisztémás autoimmun betegséget; a diagnózis a klinikai kép és a képalkotó vizsgálatok alapján indikált szövettani vizsgálattal állítható fel. A betegség szteroidkezelésre jól reagál, de előfordul spontán regresszió is, az utóbbira láttunk példát. Bár az entitás átmenetet képez a nekrotizáló vasculitisek és a sarcoidosis között, egyre több érv szól amellett, hogy a sarcoidosis spektrumába tartozik. Orv Hetil. 2021; 162(38): 1541–1547. Summary. Necrotizing sarcoid granulomatosis is a rare entity currently classified as a subtype of granulomatous pulmonary angiitis. It is considered to be either a variant of sarcoidosis or a primary pulmonary angiitis. Two cases are demonstrated to present its clinical and pathological features. A 20-year-old female patient was admitted to the department of pulmonology with dry cough, right-sided chest pain during hyperventilation and fever. A 63-year-old male patient was observed with a right-sided lesion on chest X-ray after pneumonia. In both cases, autoimmune panel examination, microbiology tests, spirometry function test and bronchoscopy were unremarkable. Chest CT scans have revealed nodules with soft-tissue density without bilateral hilar lymphadenopathy. In order to clarify the diagnosis, video-assisted thoracoscopic resection (biopsy) was performed. Microscopically, parenchymal focal necrosis with adjacent to non-caseating granulomas and granulomatous angiitis were detected. In both cases, spontaneous remission occurred within a year. Histological examination – integrated with clinical data and radiological tests’ results – is the gold standard form of evaluation to confirm necrotizing sarcoid granulomatosis; furthermore, exclusion of pneumonia and autoimmune diseases are also required. The disease responds well to corticosteroids; moreover, spontaneous remission is often reported, as it happened in both cases. Necrotizing sarcoid granulomatosis is a transition between necrotizing vasculitides and sarcoidosis; although more and more evidence appears supporting the fact that necrotizing sarcoid granulomatosis may belong to the spectrum of sarcoidosis. Orv Hetil. 2021; 162(38): 1541–1547.

Background: There are similarities between the ophthalmic presentation of toxoplasmosis and sarcoidosis, and there are some concerns of immunosuppressive treatments for sarcoidosis, which may lead to T. gondii reactivation. We report a rare case with acute sarcoidosis (Heerfordt- Waldenström syndrome) with a history of ocular toxoplasmosis from the North of Iran. Case presentation: The patient was a 36-year-old woman with left painful eye and swollen parotid, right facial paresis, maculopapular rash in left eyebrow and erythema nodosa on both legs. Anti–Toxoplasma IgG antibody was positive, and IgM was not detectable. Radiographic findings on the chest revealed bilateral hilar lymphadenopathy. The initial treatment was sulfamethoxazole- trimethoprim to prevent the recurrence of retinal toxoplasmosis and corticosteroid and mycophenolate mofetil for sarcoidosis. The patient showed clinical and vision improvement without recurrences during three months follow-up. Discussion: Ophthalmological examinations and laboratory test to rule out toxoplasmosis could be considered in known cases of sarcoidosis particularly in ocular sarcoidosis status. To the best of our knowledge this is first report of co-morbidity of ocular toxoplasmosis / sarcoidosis from Iran and possibly the world.

The purposes of this study are to propose an unsupervised anomaly detection method based on a deep neural network (DNN) model, which requires only normal images for training, and to evaluate its performance with a large chest radiograph dataset. We used the auto-encoding generative adversarial network (α-GAN) framework, which is a combination of a GAN and a variational autoencoder, as a DNN model. A total of 29,684 frontal chest radiographs from the Radiological Society of North America Pneumonia Detection Challenge dataset were used for this study (16,880 male and 12,804 female patients; average age, 47.0 years). All these images were labeled as “Normal,” “No Opacity/Not Normal,” or “Opacity” by board-certified radiologists. About 70% (6,853/9,790) of the Normal images were randomly sampled as the training dataset, and the rest were randomly split into the validation and test datasets in a ratio of 1:2 (7,610 and 15,221). Our anomaly detection system could correctly visualize various lesions including a lung mass, cardiomegaly, pleural effusion, bilateral hilar lymphadenopathy, and even dextrocardia. Our system detected the abnormal images with an area under the receiver operating characteristic curve (AUROC) of 0.752. The AUROCs for the abnormal labels Opacity and No Opacity/Not Normal were 0.838 and 0.704, respectively. Our DNN-based unsupervised anomaly detection method could successfully detect various diseases or anomalies in chest radiographs by training with only the normal images.

Immune checkpoint inhibitors (ICI) have been associated with several immune-related adverse events, including sarcoidosis-like reactions (SLR). SLR, which has a low prevalence but an increasing incidence, is similar to sarcoidosis in terms of histology, and clinical and radiological manifestations. The most commonly affected organs are hilar and mediastinal lymph nodes and skin. SLR is an exclusion diagnosis, so a lymph node biopsy can be useful to distinguish between tumor progression and SLR, particularly in tumors in which nodal involvement is very common. We performed a retrospective analysis of SLR in all cancer patients receiving ICIs in our institution between January 2016 and June 2020. Among the 1063 treated patients, seven experienced SLR, four of whom were symptomatic (cough, skin lesions, arthralgia), with time to onset ranging from 1.5 to 6.7 months after ICI initiation. All seven patients had bilateral hilar lymphadenopathy, and granulomatous reactions in five of the six patients with lymph node biopsies. SLR improved in all patients, including four patients who continued with ICI. Three patients received corticosteroids and/or stopped ICI therapy. Four of these patients had partial responses at the time SLR was identified. Management of SLR lacks a consensus recommendation, although corticosteroids and/or stopping the ICI are generally implemented. The potential consequences of stopping anticancer treatment should be taken into consideration, particularly in the absence of clear management recommendations.

Ocular sarcoidosis is diagnosed based on suggestive intraocular findings and systemic investigations. In this study, we assessed the clinical usefulness of systemic parameters in the diagnosis of ocular sarcoidosis. A retrospective study. This study included 79 cases (19 men, 60 women) with ocular sarcoidosis who visited Hokkaido University Hospital from 2011 to 2015 and were followed up for more than one year. The control group was 91 cases of other uveitis (38 men, 53 women). All cases underwent blood examination for the measurement of angiotensin-converting enzyme (ACE), Krebs von den Lungen-6 (KL-6), soluble interleukin-2 receptor (sIL-2R), and calcium (Ca) levels. Bilateral hilar lymphadenopathy (BHL) was also examined by plain chest X-ray and contrasting chest computed tomography (CT). The sensitivity for sIL-2R (76.4%) was higher than for ACE (37.7%), KL-6 (26.3%), and Ca (11.8%), although all showed high specificity: ACE (97.5%), KL-6 (96.2%), sIL-2R (93.8%), and Ca (95.1%). From these results, the Youden index of sIL-2R (0.70) was higher than that of ACE (0.35), KL-6 (0.26), and Ca (0.07). Imaging tests revealed better detection of BHL by contrasting chest CT (82.7%) than by plain chest X-ray (29.5%). The present findings indicate that the systemic parameters, particularly serum sIL-2R levels and BHL on contrasting chest CT, are useful biomarkers for the diagnosis of ocular sarcoidosis.

Background: Sarcoidosis is a chronic inflammatory disorder characterized by non-caseation granuloma. It is an inflammatory disorder of unknown etiology. Sarcoidosis has variable ocular presentations from anterior uveitis to rare venous occlusions. Case: We present a rare case of sarcoidosis with bilateral hilar lymphadenopathy and a compatible uveitis. Positive findings of mutton fat keratic precipitates, Koeppes nodule, posterior synechiae, trabecular meshwork nodules, Candle wax dripping sign, Branch retinal vein occlusion and choroidal granuloma in one eye supported the diagnosis of sarcoidosis. Elevated serum acetylcholine esterase and bilateral hilar lymphadenopathy also confirmed the diagnosis of sarcoidosis. Observation: The patient responded well to oral steroids and laser photocoagulation of the vein occlusion area. The patient developed complications of steroid like Herpes Zooster of abdomen and avascular necrosis of femur. Conclusion: Branch Retinal Vein Occlusion is a rare vascular complication in ocular sarcoidosis. Systemic steroids and laser for vein occlusion is mainstay of treatment. Physician must be aware of serious complications of steroid therapy, as seen in this case. Keyword: Sarcoidosis, Branch retinal vein occlusion, Steroids.

Background: Sarcoidosis is a systemic inflammatory disease of unknown etiology that can affect virtually any organ. Löfgren syndrome, characterized by erythema nodosum, hilar lymphadenopathy, fever and polyarthritis, represents only 20-30% of the cases of sarcoidosis. Only 2- 10% of the cases feature hypercalcemia. Case: The case of a 42-year-old Hispanic woman with a history of erythema nodosum and three weeks of nausea, emesis, constipation, asthenia, adynamia, polydipsia, and somnolence, concomitant with hypercalcemia, but normal parathyroid hormone (PTH) and 25-hydroxyvitamin D has been presented. The initial diagnostic approach was based upon the suspicion of multiple myeloma or bone metastases; however, further findings of bilateral hilar lymphadenopathy, elevated serum angiotensin-converting enzyme (ACE) and a right inguinal lymphadenomegaly suggested an alternate diagnosis. Biopsy of the latter supported sarcoidosis as the diagnosis. She was successfully treated in the hospital with zoledronic acid and as an outpatient with immunosuppressive therapy. Persistence of a previously undisclosed symptom of oligomenorrhea led to the detection of hyperprolactinemia secondary to hypophyseal infiltration, refractory to immunosuppressive therapy but with an adequate response to cabergoline. Conclusion: This case strays from Löfgren Syndrome’s expected behavior, presenting a more progressive, multisystemic disease. This case report was written in adhThis case strays from Löfgren Syndrome’s expected behavior, presenting a more progressive, multisystemic disease. This case report was written in adherence to the CARE guidelines of 2013 to include information in it.erence to the CARE guidelines of 2013 to include information in it.

Sarcoidosis is a systemic granulomatous disease of unknown etiology. The outcome is quite variable and is mainly related to persistent inflammatory processes and the development of fibrosis. Many prognostic factors have been described, but the disease evolution is not yet entirely known. The nonthreatening course is characterized by spontaneous involution or stability after treatment withdrawal. Löfgren's syndrome is a subset within the spectrum of sarcoidosis phenotypes, composed of acute onset of fever, bilateral hilar lymphadenopathy, erythema nodosum and/or bilateral ankle periarticular inflammation/arthritis, specifically characterized by a self-limiting disease course. In contrast, advanced fibrotic sarcoidosis with pulmonary hypertension phenotype is correlated with a poor prognosis. Further studies are necessary to detail phenotypes to better understand the mechanisms of the disease and plan future clinical therapeutic studies.

Background As the outbreak of coronavirus disease 2019 (COVID-19) has progressed, computed tomography has emerged as an integral part of the diagnosis alongside reverse transcriptase–polymerase chain reaction assays. Frequently encountered imaging findings include peripheral airspace consolidations; bilateral ground-glass opacities; and, less commonly, cavitation. Hilar lymphadenopathy is a rarely reported finding in the setting of COVID-19. Case presentation A 73-year-old Caucasian woman presented to our hospital with fever and fatigue. She had a maximum body temperature of 102.3 °F with lymphopenia and thrombocytopenia. She was diagnosed with severe acute respiratory syndrome coronavirus 2 infection on the basis of a positive result from a reverse transcriptase–polymerase chain reaction of a nasopharyngeal swab sample. Contrast-enhanced chest computed tomography revealed multifocal, subpleural ground-glass opacities with nodular consolidations bilaterally. Computed tomography also demonstrated atypical bilateral hilar lymphadenopathy, a rarely reported imaging feature of COVID-19. Chest computed tomography 1 month before the presentation did not show focal consolidations or lymphadenopathy. This indicated that the findings were due to the patient’s severe acute respiratory syndrome coronavirus 2 infection. She received 5 days of oral hydroxychloroquine and experienced resolution of her symptoms. Conclusion Chest computed tomography has been used extensively to diagnose and characterize the distinguishing radiological findings associated with viral pneumonia. It has emerged as an integral part of the diagnosis of COVID-19 alongside reverse transcriptase–polymerase chain reaction assays. Clinicians must be aware of uncommon clinical and radiological findings in order to diagnose this entity. Hilar lymphadenopathy is commonly seen with fungal infections, mycobacterial infections, and sarcoidosis. An extensive literature review found that bilateral hilar lymphadenopathy has not been reported in the setting of COVID-19. More data are needed to establish the clinical impact of this novel finding.

Introduction Radiographic chest imaging is utilized in the workup of uveitis, with the purpose of diagnosing sarcoidosis. Sarcoidosis is an idiopathic systemic granulomatous inflammation which accounts for approximately 10% of uveitis. The prevalence of sarcoidosis and uveitis varies widely with geography and ethnicity. We studied the value of chest X-ray (CXR) in the evaluation of uveitis patients in the Western United States. The study was a retrospective chart review of 559 patients presenting to the Uveitis Department at University of Colorado between January 1, 2011 and July 31, 2017. Methods CXR and/or chest computerized tomography (CT) was obtained in patients with an unknown uveitic diagnosis. Presumed sarcoidosis was defined as the presence of bilateral hilar lymphadenopathy in a patient with uveitis. Age, race, and anatomic location of the uveitis were analyzed. Results The prevalence of sarcoidosis in our population was 4.3%. The discovery rate of sarcoidosis by CXR was 2.6%. Of 12 positive CXRs, 11 were in black patients. Our study identified five previously undiagnosed patients with sarcoidosis, four of whom were black. Conclusions CXR screening for sarcoid uveitis has a low yield in our population and is most likely to be positive in black patients. The prevalence of sarcoidosis is low in our study but not unlike the findings in similar demographic populations. Although chest CT scan is more sensitive than chest X-ray, the cost and radiation dose are greater; thus CT may not be indicated in low incidence populations.

Background Sarcoidosis is a heterogeneous disease with high variability in natural history and clinical spectrum. The study aimed to reveal different clinical phenotypes of patients with similar characteristics and prognosis. Methods Cluster analysis including 26 phenotypic variables was performed in a large cohort of 694 sarcoidosis patients, collected and followed-up from 1976 to 2018 at Bellvitge University Hospital, Barcelona, Spain. Results Six homogeneous groups were identified after cluster analysis: C1 (n=47; 6.8%), C2 (n=85; 12.2%), C3 (n=153; 22%), C4 (n=29; 4.2%), C5 (n=168; 24.2%), and C6 (n=212; 30.5%). Presence of bilateral hilar lymphadenopathy (BHL) ranged from 65.5% (C4) to 97.9% (C1). Patients with Lofgren syndrome (LS) were distributed across 3 phenotypes (C1, C2, and C3). In contrast, phenotypes with pulmonary (PS) and/or extrapulmonary sarcoidosis (EPS) were represented by groups C4 (PS 100% with no EPS), C5 (PS 88.7% plus EPS), and C6 (EPS). EPS was concentrated in groups C5 (skin lesions, peripheral and abdominal lymph nodes, and hepatosplenic involvement) and C6 (skin lesions, peripheral lymph nodes, and neurological and ocular involvement). Unlike patients from LS groups, most patients with PS and/or EPS were treated with immunosuppressive therapy, and evolved to chronicity in higher proportion. Finally, the cluster model worked moderately well as a predictive model of chronicity (AUC=0.705). Conclusion Cluster analysis identified 6 different clinical patterns with similar phenotypic variables and predicted chronicity in our large cohort of patients with sarcoidosis. Classification of sarcoidosis into phenotypes with prognostic value may help physicians to improve the efficacy of clinical decisions.

Background The presence of histologically evident epithelioid granuloma is required for the diagnosis of sarcoidosis worldwide. The Japan Society of Sarcoidosis and Other Granulomatous Disorders 2015 diagnostic criteria (JSSOG 2015 criteria) includes “clinically proven diagnosis” (involvement of at least 2 of 3 systems confirmed solely by clinical assessment) because of the frequency of sarcoidosis with ocular, cardiac, and respiratory involvement in Japan and the difficulty of obtaining specimens. Here, we describe in detail the clinical presentation of clinically diagnosed sarcoidosis. Methods We enrolled 68 consecutive patients with clinically diagnosed sarcoidosis (12 men, 56 women) based on the JSSOG 2015 criteria who were treated at Jichi Medical University between December 2018 and January 2000. We analyzed age at diagnosis, organ involvement, and laboratory findings. Results Age at diagnosis was unimodal in women. Ocular, splenic, cardiac, and skin involvement, and hypercalcemia were observed in 95.6%, 8.8%, 7.4%, 5.9%, and 35.0% of patients, respectively. High serum lysozyme and soluble interleukin-2 receptor (sIL-2R) levels, bilateral hilar lymphadenopathy on chest radiography, high-grade atrioventricular block or fatal ventricular arrhythmia, and bundle branch block were found in 18.8%, 48.3%, 95.6%, 5.0%, and 10.0% of patients, respectively. Conclusions The age-specific distribution of clinically diagnosed sarcoidosis was similar to histologically diagnosed sarcoidosis in women, as previously reported. Rates of elevated serum lysozyme and sIL-2R levels were lower in this study than previously reported in histologically diagnosed patients in Japan.

Sarcoidosis is a granulomatous disease of unknown etiology. At present the best diagnostic imaging procedure to assess stage and activity of sarcoidosis is controversial. We report the case of a 50-year-old male admitted with a history of dyspnea and fatigue with past medical history negative for smoking, occupational and environmental risk factors. Physical examination, routine blood tests, and pulmonary function tests were normal except for hypercalciuria. A chest radiograph showed bilateral hilar lymphadenopathy. Single photon emission computed tomography and/or computed tomography (SPECT and/or CT) In-111 Octreotide (Octreoscan) scintigraphy confirmed morphologic involvement of bilateral hilar lymph nodes and a mediastinoscopy biopsy specimen provided diagnosis of pulmonary sarcoidosis (stage 0). This clinical case shows the effectiveness of In-111 Octreotide SPECT and/or CT in the early diagnosis of pulmonary sarcoidosis.

Heerfordt’s syndrome – the combination of facial palsy, parotid swelling, anterior uveitis and fever, is a rare manifestation of sarcoidosis. Here, we present case history of a patient with bilateral lower motor neuron facial nerve palsy, who was found to have bilateral parotid gland swelling and bilateral hilar lymphadenopathy. Computed tomography guided fine needle aspiration cytology from hilar lymph node findings were consistent with sarcoidosis. Subsequently, based on clinical features and cytological findings, the case was diagnosed as incomplete Heerfordt’s syndrome. Birdem Med J 2021; 11(1): 67-69

A case is presented of mucormycosis in a patient with acute myeloblastic leukemia following liver transplantation for Wilson’s disease. A 58-year-old female was admitted to the Department of Haematology with deterioration of her general condition, loss of appetite, tiredness and difficulty with mental contact for a few days. Blood and urine cultures for bacteria and fungus, galactomannan antigen were negative. Whole body computed tomography demonstrated bilateral hilar lymphadenopathy with necrotic lesions: splenomegaly with a hypodensive lesion 13 × 20 × 19 mm and lower pulmonary infiltrates suggested fungal etiology. Magnetic resonance imaging of the brain showed thickened meninges. Finally, mucormycosis was diagnosed. Treatment with amphotericin B lipid complex was started, resulting in an partial improvement of the general condition and decreased level of inflammatory markers. However, the patient’s condition continued to deteriorate, with sepsis etiology Escherichia coli, and despite the intensive managements she eventually died.

Löfgren's syndrome is an acute form of sarcoidosis that is characterised by articular symptoms, erythema nodosum and bilateral hilar lymphadenopathy. This syndrome is rare in Japan. We report a 62-year-old Japanese woman with Löfgren's syndrome and describe the articular manifestations as evaluated by multiple imaging modalities. Musculoskeletal ultrasound, magnetic resonance imaging and positron emission tomography-computed tomography findings indicated periarticular and subcutaneous inflammation. These imaging modalities facilitated the diagnosis of Löfgren's syndrome and helped differentiate from other rheumatic diseases.

Introdução: a sarcoidose é uma granulomatose sistêmica de etiologia desconhecida, que se pode ma- nifestar de forma aguda como síndrome de Löfgren em 20 %-50 % dos indivíduos, a qual, não obstante ter um curso benigno, exige uma vigilância e acompanhamento cuidadosos dos doentes. Esta síndrome caracterizada pela tríade eritema nodoso, linfadenopatias hilares bilaterais e poliartralgia ou poliartrite, não carece de confirmação histológica para o diagnóstico e é mais prevalente em mulheres caucasianas até aos 35 anos de idade. Apresenta bom prognóstico e pode ter resolução espontânea das queixas no primeiro ano após o aparecimento. Caso Clínico: os autores apresentam o caso clínico de uma doente de 20 anos que recorreu ao serviço de urgência com lesões nodulares, avermelhadas e dolorosas nos membros inferiores, acompanhadas de mal-estar geral e gonalgias bilaterais com compromisso funcional. Constataram-se linfadenopatias e hilares bilaterais e elevação da enzima conversora da angiotensina sérica. Conclusão: a doente teve resposta favorável a um ciclo curto de corticoterapia e analgesia com anti-inflamatórios não esteroides.

Background: Sarcoidosis is a multisystem, chronic granulomatous disease of unknown etiology. The clinical course of sarcoidosis is punctuated with remission and relapses, which is unpredictable. Materials and Methods: This was a retrospective observational study in which case records of all patients with a confirmed diagnosis of sarcoidosis attending the outpatient department of pulmonary medicine department between January 2014 and December 2018 were evaluated. The diagnosis of sarcoidosis was confirmed by demonstration of noncaseating granuloma in cytopathology or histopathology along with a compatible clinical picture. Mantoux test, serum angiotensin-converting enzyme (ACE) levels, serum calcium, and 24-h urinary calcium were done. Results: Sarcoidosis was found to be more common in females. Cough, breathlessness, fever, and fatigue were the predominant symptoms. Mantoux was negative in 95.83%, raised serum ACE was seen in 65.83%, hypercalcemia in 10.83%, and hypercalciuria in 30.0% of patients, respectively. Chest radiograph revealed that 14.17% of patients presented with Stage 1, 52.50% of patients with Stage 2, 15.83% of patients with Stage 3, and 17.50% of patients with Stage 4. Mediastinal lymphadenopathy was seen in contrast-enhanced computed tomography chest in 93.33%, septal thickening with nodularity in 61.67% and fibrosis in 25.83%. Corticosteroids were started in 97.5% patients and 24.17% patients relapsed after stopping or tapering corticosteroids. Conclusion: Sarcoidosis is a common cause of bilateral hilar lymphadenopathy and interstitial lung diseases. Relapses are frequent after stopping corticosteroids, so patients should be followed up actively after stopping treatment.

Sarcoidosis is an autoimmune multisystem granulomatous disorder of unknown aetiology, which mainly affects the adults in the age group of 20–39 years. The disease can affect any organ in the body but mainly presents as bilateral hilar lymphadenopathy, pulmonary infiltrates, cutaneous lesions, ocular manifestations and arthropathy. Lofgren’s syndrome is an uncommon initial presentation of sarcoidosis which is recognised by the classical triad of acute arthritis, erythema nodosum and bilateral hilar lymphadenopathy. We describe a newly diagnosed case of sarcoidosis who presented as Lofgren’s syndrome. Acute sarcoid arthritis should be kept as one of the differential diagnoses for patients presenting with acute arthritis and skin lesions; and chest X-ray should be considered to rule out bilateral hilar lymphadenopathy in these patients. Early suspicion and identification of classical clinical features are essential to establish early diagnosis.

Introduction Thymic clear cell carcinoma is the most uncommon subtype of thymic carcinoma, with 20 cases reported worldwide. Case description We present the case of a 61-year-old female with dyspnoea and chest pain for 2 days. Computed tomography (CT) angiography showed pulmonary thromboembolism and the existence of mediastinal and bilateral hilar lymphadenopathy, the largest infracarinal with an inferior axis of 25 mm, and also, micronodules on the left pulmonary parenchyma. The patient was admitted for aetiological assessment and underwent anticoagulant therapy. After a month, she had an ischaemic stroke, the sequelae of which proved to be fatal. The autopsy showed a mass in the superior-anterior mediastinum, with dimensions of 11×8×6 cm, corresponding to a thymus signet ring cell primary carcinoma. The immunohistochemistry study revealed that this mass was positive for AE1/AE3, CK5/6 and CK7. Conclusion The clinical, morphological and immunophenotypic diversity of this tumour makes its diagnosis a difficult multidisciplinary challenge, which requires a high level of clinical knowledge and accurate imaging and histological investigation. Learning points Thymic clear cell carcinoma is a very rare entity with an aggressive and nonspecific clinical behaviour.There are no defined diagnostic criteria, although diagnosis could be established with histologic/cytology analysis.There are no clear guidelines for treatment, which can include highly invasive surgery and chemotherapy or radiation therapy.

In this retrospective study, we investigated vascular abnormalities in sarcoidosis using fluorescein gonioangiography (FGA) to detect angle neovascularization (ANV), fundus fluorescein angiography (FFA), and pathological specimens from the aspects of microangiopathy. In 57 sarcoidosis patients, clinical data was reviewed by dividing the cases into three groups (Group I: histologically diagnosed, Group II: positive bilateral hilar lymphadenopathy (BHL), Group III: negative BHL). The FFA, FGA, and pathological examination data in the autopsy eyes and trabeculectomy specimens were investigated. FGA and FFA detected ANV (91%) and nodule-associated abnormalities (87%), respectively. No intraocular pressure (IOP) elevation was observed after continuous topical betamethasone, except in the steroid responder group. Maximum IOP had significant correlation with nodules in the angle (p = 0.02696) and visual field defect (p = 0.0151). Granulomas adjacent to blood vessels, including the Schlemm&rsquo, s canal, and thickening of the retinal blood vessel wall caused occlusion of those vessels. Photocoagulation was required for retinal tears (14%) and the retinal blood vessel occlusion (7%). Suppression of IOP elevation via continuous topical betamethasone may be important to avoid irreversible outflow-route changes and optic-nerve damage, and the concept of microangiopathy in ocular sarcoidosis may be important for understanding the proper treatment of serious complications.

Objective To analyse the clinical patterns of sarcoidosis triggered by immune checkpoint inhibitors (ICIs) in patients with cancer. Patients and methods The ImmunoCancer International Registry is a big data–sharing multidisciplinary network from 18 countries dedicated to evaluating the clinical research of immune-related adverse events related to cancer immunotherapies. Results We identified 32 patients with biopsy-proven sarcoidosis. Underlying cancer included mainly melanoma (n = 24). Cancer immunotherapy consisted of monotherapy in 19 cases (anti-PD-1 in 18 and ipilimumab in 1) or combined ipilimumab + nivolumab in 13. The time median interval between initiation of ICI and sarcoidosis diagnosis was 3 months (range, 2–29 months). The use of combined ICI was associated with a shorter delay in developing sarcoidosis symptoms. The disease was symptomatic in 19 (59%) cases with mostly cutaneous, respiratory and general symptoms. The organs involved included mainly the mediastinal lymph nodes (n = 32), the lungs (n = 11), the skin (n = 10) and the eyes (n = 5). Pulmonary computed tomography studies showed bilateral hilar lymphadenopathy in all cases. There was no severe manifestation. Specific systemic therapy was required in only 12 patients (37%): oral glucocorticoids in 9, and hydroxychloroquine in 3. ICIs were held in 25 patients (78%) and definitively discontinued in 18 (56%) patients. Seven patients continued ICI treatment with a second flare in one case. In six additional patients, an ICI was reintroduced with no harm, and sarcoidosis relapsed in one of them. Conclusion Our study shows that ICI-related sarcoidosis seems to have a specific profile, possibly more benign than that of idiopathic sarcoidosis, and does not necessarily imply ICI discontinuation.

Objective To present a patient with sarcoidosis-induced hypercalcemia who responded to methotrexate (MTX). Methods The described case includes clinical and biochemical reports. Results A 65-year-old woman presented with bilateral hilar lymphadenopathy and pulmonary nodules. Her calcium and phosphorous levels were 11.4 mg/dL and 3.5 mg/dL, respectively. Blood levels of 25-hydroxyvitamin D and parathyroid hormone were 68 nmol/L and 23 pg/dL, respectively. A diagnosis of sarcoidosis was confirmed by a lymph node biopsy that revealed non-caseating granulomas. Prednisone therapy was efficacious in normalizing the calcium level. However, hypercalcemia recurred when the prednisone dosage was tapered to below15 mg daily. Following initiation of MTX at 15 mg/week, prednisone levels were successfully titrated to 3 mg daily. After a temporary withdrawal of MTX therapy, calcium levels increased dramatically to 17 mg/dL. Conclusion MTX can be used as treatment for sarcoidosis-induced hypercalcemia. Abbreviations MTX methotrexate PTH parathyroid hormone TNF tumor necrosis factor

A 40‐year‐old man with bilateral hilar lymphadenopathy in chest X‐ray and the λ‐sign in gallium‐67 scintigraphy was subsequently diagnosed with systemic sarcoidosis according to the findings of bronchoalveolar lavage and histopathological examinations of transbronchial lung biopsies. Identifying the λ‐sign could be a valuable clue to the early diagnosis of sarcoidosis., The λ‐sign strongly suggests the diagnosis of sarcoidosis because all reported patients with the λ‐sign were subsequently diagnosed as having sarcoidosis. Identifying the λ‐sign with gallium‐67 scintigraphy could be a valuable clue to the early diagnosis of sarcoidosis.

Idiopathic acute eosinophilic pneumonia is a rare and potentially life-threatening condition that is defined by bilateral pulmonary infiltrates and fever in the presence of pulmonary eosinophilia. It often presents acutely in previously healthy individuals and can be difficult to distinguish from infectious pneumonia. Although the exact etiology of idiopathic acute eosinophilic pneumonia remains unknown, an acute hypersensitivity reaction to an inhaled antigen is suggested, which is further supported by recent public health risks of vaping (electronic cigarette) use and the development of lung disease. In this case, a patient with a year-long history of vaping in conjunction with tetrahydrocannabinol cartridge use who was diagnosed with idiopathic acute eosinophilic pneumonia with associated bilateral hilar lymphadenopathy is described.

Multiple problems may be encountered during the diagnosis of sarcoidosis: at first diagnose sarcoidosis in an appropriate clinical setting, secondly, identify any manifestation to be linked to sarcoidosis at diagnosis work-up and during evolution; thirdly, recognize "danger" in sarcoidosis and parasarcoidosis syndromes, and finally, diagnose sarcoidosis recovery. Diagnosis is often delayed as presentation may be diverse, non-specific, or atypical. Diagnosis of sarcoidosis is based on three criteria: a compatible presentation; evidence of non-caseating granulomas and exclusion of any alternative diagnosis. However, even when all criteria are fulfilled, the probability of sarcoidosis diagnosis varies from definite to only possible depending upon the presence of more or less characteristic radio-clinical and histopathological findings and on the epidemiological context. Bilateral hilar lymphadenopathy and/or diffuse lung micronodules mainly along lymphatics are the most frequent highly suggestive findings. Evidence of granulomas relies on superficial biopsies of clinically suspected lesion when present or most often by bronchial endoscopy. The diagnosis of sarcoidosis may be difficult in absence of thoracic or skin manifestations and may require the benefit of hindsight before being definitive. Differential diagnoses, mainly tuberculosis, must be considered. The diagnosis of events during evolution relies on serial clinical, pulmonary function, radiographic evaluation and on extrapulmonary manifestations work-up, including electrocardiogram and blood biology. Affected organs need to be related to sarcoidosis using an appropriate diagnostic assessment instrument. To declare the recovery of sarcoidosis, all manifestations must have disappeared spontaneously or after 3-5 years post-treatment without relapse.

Sarcoidosis is a systemic multisystem inflammatory disease of unknown etiology. The disease is characterized by formation of non-caseating granulomas. The most common presentation is bilateral hilar lymphadenopathy and lung infiltration, but the disease is very heterogeneous, with an unpredictable clinical course. Musculoskeletal manifestations are common. Bone involvement is less frequent, and usually occurs in patients with chronic multisystem course of the disease. They are most commonly found in the phalanges of hands and feet, and are usually bilateral. The skull, long bones, ribs, pelvis, and axial skeleton may also be affected. Osseous involvement may be asymptomatic but in some cases can cause a severe disability. Imaging techniques are important for diagnosis. Radiological investigations revealed sclerotic or destructive lesions (involving also joints), cystic and punched out lesions and cortical abnormalities. Biopsy is required for differential diagnosis with respect to malignancy. Treatment is a part of systemic therapy and is not needed in all cases. Glucocorticoids and TNF-a antagonists are used for management.

We herein report a 55-year-old woman who presented with erythema and bilateral hilar lymphadenopathy 4 months prior to the detection of pancreatic lesions on an ultrasound. A skin biopsy showed evidence of sarcoidosis. The largest lesion in the tail of the pancreas was hypoechoic on endoscopic ultrasonography (EUS). The lesion was initially iso-enhanced on contrast enhanced-EUS (CE-EUS) but subsequently became hypoenhanced. The lesion revealed heterogeneous components of both soft and hard tissue on EUS elastography. She was ultimately diagnosed with pancreatic sarcoidosis based on the presence of noncaseating granulomas seen on pancreatic tissue retrieved through an EUS-guided fine needle aspiration biopsy.

Löfgren's syndrome (LS), first described in 1946 by Swedish Professor of Medicine Sven Löfgren, is a clinically distinct phenotype of sarcoidosis. Patients typically experience an acute disease onset, usually with fever, and characteristic symptoms of bilateral hilar lymphadenopathy, erythema nodosum, and/or bilateral ankle arthritis or periarticular inflammation. LS patients are well documented to have a good prognosis, which is especially true for HLA-DRB1*03+ individuals. The presence of this allele correlates closely with an accumulation of clonal CD4+ T-cell populations in the lung, suggestive of local antigen recognition. Moreover, LS differs markedly from “non-LS” sarcoidosis regarding immune cell activation, differentiation, and regulation, which may influence clinical outcome and spontaneous disease resolution.This review offers an overview of the clinical characteristics, genetic background, and immunological characteristics of LS, as well as patient management, and reflections on future scientific challenges, emphasizing the concept of LS as a disease in its own right.

Key Clinical Message We report a rare case of an immunocompetent patient with Mycobacterium avium complex (MAC) disease in which bilateral hilar lymphadenopathy developed during anti‐MAC treatment. This case indicates that Propionibacterium acnes would be present and might be a cause of sarcoidosis even in patients with MAC.

Musculoskeletal manifestations in the context of sarcoidosis are frequently observed. The rheumatologist regularly encounters this disease in clinical practice. In the present review, we aim to give a current overview of the manifestations and treatments relevant to the practicing rheumatologist. The most frequently encountered manifestation is Lofgren's syndrome, which is characterized by bilateral ankle periarthritis, bilateral hilar lymphadenopathy, and erythema nodosum and has an excellent prognosis. Chronic arthropathy most commonly manifests as oligoarthritis, which sometimes hampers its differentiation from spondylarthropathies, especially when sacroiliitis, enthesitis or dactylitis are simultaneously present. Isolated vertebral granulomas are rare and require infectious and malignant disorders to be excluded, since there are no specific imaging findings that are exclusively found in vertebral sarcoidosis. The presence of granulomas in skeletal muscle is common in muscle biopsies, whereas clinically overt myopathy is present in only around 1-2% of patients. Therapeutic responses vary among the different clinical phenotypes. Non-steroidal anti-inflammatory drugs and low to medium dose glucocorticoids are the first-line therapy for musculoskeletal manifestations and often lead to adequate disease control in acute sarcoidosis. When these are ineffective or not tolerated, steroid-sparing agents are increasingly used in chronic sarcoidosis. Evidence for all medications used in sarcoid-related arthritis is comparatively scant. When supplementing vitamin D, the possible development of hypercalcemia, even at standard doses, needs to be considered; the optimal therapeutic levels for the prevention of medication-induced osteoporosis in sarcoidosis have not been firmly established.

A 36 year-old male with no significant past medical history presented with lower extremity numbness, gait instability, and urinary and bowel retention of 4 weeks onset. Spine MRI revealed diffuse oedema of cervicothoracic spinal cord with several solid enhancing intramedullary lesions, suggestive of metastases. The 18F-FDG PET/CT performed to identify the primary malignancy demonstrated mild hypermetabolic foci within the cervicothoracic cord, as well as a mildly hypermetabolic bilateral hilar lymphadenopathy and a mildly hypermetabolic pulmonary nodule, suggestive of sarcoidosis versus metastasis. The diagnosis of sarcoidosis was supported by identifying non-caseating granuloma in the biopsy of the pulmonary nodule. The patient responded well to steroid-therapy, with the symptoms being resolved within 3 weeks.

A 71-year-old woman with a history of left lower lobe lobectomy 4 years ago for adenocarcinoma of the lung presented with new mediastinal and bilateral hilar lymphadenopathy on surveillance imaging, suspicious for disease recurrence. She underwent an endobronchial ultrasound-guided transbronchial needle aspiration of the lymph nodes and histology yielded non-necrotizing epithelioid granulomas with no evidence of malignancy. A diagnosis of sarcoid-like reaction associated with lung adenocarcinoma was made. The significance of this rare condition is discussed.

Sarcoidosis is a multi-system disease with neurological involvement being one of the more rare manifestations. We report a case of a patient who presented with the lateral medullary syndrome and panuveitis as her initial manifestation of sarcoidosis. The patient’s course was further complicated by renal involvement. Lacrimal gland and renal biopsies showed noncaseating granulomas without evidence of infection, establishing the diagnosis. Intracranial vertebral artery involvement was confirmed by brain imaging. Bilateral hilar lymphadenopathy with upper lobe predominant nodules on chest imaging was consistent with asymptomatic pulmonary involvement. Systemic steroid therapy is indicated for treatment of ocular sarcoidosis, with standard stroke management indicated for the treatment of lateral medullary syndrome.

A 73-year-old man was hospitalized with complaints of general malaise, limb muscle weakness and weight loss progressing in 6 months. Ca, ACE, lysozyme, sIL-2R, vitamin 1.25 D was high in the blood test. Bilateral hilar lymphadenopathy on CT were not recognized, and CD4/CD8 ratio increased by bronchoalveolar lavage. In the 67Ga-citrate scintigraphy, accumulation was observed on the thigh and shoulder to the upper arm bilaterally. A muscle biopsy was performed from the right femoris muscle where the gadolinium contrast effect in the T1 weighted image was observed. As muscle biopsy revealed non-toxic epithelial cell granulomas, he was diagnosed as muscle sarcoidosis. Even if bilateral hilar lymphadenopathy is not observed, muscle sarcoidosis should be considered in patients developed with hypercalcemia and limb muscle weakness.

The patient was an 81-year-old woman. At age 73, she developed difficulties in climbing stairs and swallowing, and became unable to open bottles at age 74. She had been walking with a cane since age 76. Accidental chest X-ray findings showed bilateral hilar lymphadenopathy at age 78. Angiotensin converting enzyme (ACE) was elevated. Lymphocyte proliferation was prominent in bronchoalveolar lavage fluid. Sarcoidosis was suspected, but she was followed without treatment due to lack of respiratory symptoms. She became unable to walk without assistance at age 80 and visited our hospital with a complaint of gait disturbance at age 81. Moderate diffuse muscle atrophy in extremities was evident. Muscle weakness of finger flexion and knee extension were remarkable. The muscle involvement pattern was similar to sporadic inclusion body myositis (sIBM). However, radiographically, rectus femoris and semitendinosus muscles are selectively preserved. This radiogaphic finding was consistent with chronic sarcoid myopathy (CSM). We reached a final diagnosis of CSM based on the presence of granulomas in the muscle biopsy specimen, BHL in fluorodeoxyglucose positron-emission tomography, the previous finding of elevated ACE, and bronchoscopy results. In conclusion, CSM is a treatable disease and should thus be differentiated from sIBM. This should not be done solely based on clinical findings, but instead, muscle biopsy should be performed. Moreover, muscle selectivity may be useful in distinguishing between CSM and sIBM.

To review the role of high resolution chest computed tomography (HRCT) in ocular sarcoidosis in a high TB endemic population.This was a retrospective study.Out of 140 cases, 54 had ocular sarcoidosis, while 86 cases had ocular tuberculosis. Abnormal HRCT findings was noted in 52 cases (96.3%) of ocular sarcoidosis compared with 55 cases (64.7%) of ocular tuberculosis (p = 0.001). Mediastinal lymphadenopathy was the most common finding in both groups (p = 0.544). Hilar lymphadenopathy and fissural nodules were significantly seen in ocular sarcoidosis (p = 0.001). Necrosis was seen in three cases of ocular sarcoidosis. In nearly half of the cases, it was not possible to differentiate between sarcoidosis and tuberculosis on HRCT.HRCT is a useful diagnostic tool in ocular sarcoidosis. Bilateral hilar lymphadenopathy and fissural nodules are significant findings in ocular sarcoidosis. A confident diagnosis of ocular sarcoidosis is made by the amalgamation of results of clinical, radiologic, and other laboratory investigations.