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Sarcoidosis is an immune-mediated inflammatory disorder with unknown aetiology that is marked by non-caseating granulomas in affected organs. Pulmonary sarcoidosis is the most common manifestation, but gastrointestinal involvement, particularly in the small bowel, is exceedingly rare. While symptom-driven treatment guidelines that are steroid based are well established for pulmonary and few extrapulmonary manifestations (ie, cardiac, neurologic, renal), gastrointestinal sarcoidosis treatment is largely extrapolation with optimal management under investigation. Additionally, few works document small bowel obstruction related to small bowel sarcoidosis. We present a case of short-interval recurrent small bowel obstruction in a man in his sixties that revealed newly diagnosed sarcoidosis with suspected small bowel involvement who never underwent steroid therapy. The patient exhibited gastrointestinal symptoms, despite asymptomatic pulmonary disease and a course of prednisone may have reduced his risk of recurrence. We also review suggested gastrointestinal sarcoidosis treatment and surveillance guidelines with focus on the small bowel.

We report the case of a woman in her 30s who was referred to the ear, nose and throat department with sudden onset left-sided sensorineural hearing loss (SNHL), left anterior uveitis and erythematous lower limb lesions with bilateral pitting oedema. Based on her symptoms, an underlying inflammatory systemic disease was suspected. Autoantibodies were negative but an X-ray and high-resolution CT scan of the chest were suggestive of sarcoidosis, which was confirmed on endoscopic bronchial biopsy. Following treatment with a course of oral steroids, the patient’s hearing has improved but she still suffers from episodes of uveitis. While immune-mediated inner ear disorders are a recognised cause of SNHL, sarcoidosis is a very rare cause. This case demonstrates the importance of screening for systemic autoimmune aetiology in SNHL and highlights the importance of an effective multidisciplinary team in the diagnosis and management of these patients.

We present a case of a patient with a history of Blau syndrome, who presented with acute onset of widespread florid painful folliculitis rash, which was resistant to the treatment with multiple courses of antibiotics in the community. Despite of the negative skin swab and negative periodic acid-schiff (PAS)stain on the skin biopsy, clinical diagnosis was fungal folliculitis and patient responded well to the course of itraconazole.

We present a unique case of biopsy-proven necrotising sarcoidosis involving the central nervous system in a man in his 40s. The patient presented with a 2-week history of right-sided headache and diplopia. He had right trochlear and abducens nerve palsy, sensory blunting over V1 and V2 segment of right trigeminal sensory nerve and right sensory neural hearing loss. A contrast-enhanced MRI revealed an enhancing dural-based mass lesion in the petroclival area suggestive of probable meningioma. Surgical resection was attempted and intraoperative consultation with frozen section revealed granulomata. So, the lesion was biopsied and surgical intervention was terminated. A diagnosis of necrotising neurosarcoidosis was confirmed on histopathology. He was treated with steroids after excluding other causes of intracranial necrotising granulomas like tuberculosis and he clinically responded favourably. We report one of the very few case reports of histologically proven necrotising sarcoidosis involving the central nervous system mimicking petroclival meningioma.

Purpose To explore the clinical significance of anti-rabphillin-3A antibody for the differential diagnosis of lymphocytic panhypophysitis. Methods and results A 58-year-old Japanese man developed uveitis of unknown cause in 2017. In 2019, he became aware of polyuria. In August 2020, he noticed transient diplopia and was diagnosed with right abducens nerve palsy. At the same time, he complained of fatigue and loss of appetite. Head magnetic resonance imaging demonstrated enlargement of the pituitary stalk and pituitary gland, corresponding to hypophysitis. Hormone stimulation tests showed blunted responses with respect to all anterior pituitary hormones. Central diabetes insipidus was diagnosed on the basis of a hypertonic saline loading test. Taking these findings together, a diagnosis of panhypopituitarism was made. Computed tomography showed enlargement of hilar lymph nodes. Biopsies of the hilar lymph nodes revealed non-caseating epithelioid cell granulomas that were consistent with sarcoidosis. Biopsy of the anterior pituitary revealed mild lymphocyte infiltration in the absence of IgG4-positive cells, non-caseating granulomas, or neoplasia. Western blotting revealed the presence of anti-rabphilin-3A antibody, supporting a diagnosis of lymphocytic panhypophysitis. Because the patient had no visual impairment or severe uveitis, we continued physiological hormone replacement therapy and topical steroid therapy for the uveitis. Conclusion To the best of our knowledge, this is the first case of anti-rabphilin 3A antibody positive lymphocytic panhypophysitis comorbid with sarcoidosis, diagnosed by both pituitary and hilar lymph node biopsy. The utility of anti-rabphilin-3A antibody for the differential diagnosis of hypophysitis like this case should be clarified with further case studies.

Cardiac sarcoidosis is associated with a high mortality rate. Given multiple barriers to obtaining cardiac PET imaging, we suspect individuals with access to this imaging modality are not representative of the Sarcoid patient population, which in the United States are predominantly Black females.To evaluate the demographics of patients with cardiac PET access and the cost-effectiveness of cardiac PET/MR imaging relative to standard of care.This is a retrospective, observational study. The demographic information of patients with suspected cardiac sarcoidosis and cardiac PET/CT imaging within a national registry of sarcoidosis were reviewed (n = 4561). An individual-level, continuous, time-state transition model was used for the evaluation of long-term cost-effectiveness for the combined cardiac PET/MR compared to standard of care cardiac MR followed by cardiac PET/CT.Patients who underwent cardiac PET in the national registry had 88.35% higher odds of being male (p 0.001) and 43.82% higher odds of being White (p = 0.003) than their counterparts who did not have cardiac PET imaging. Combined cardiac PET/MR had overall lower total lifetime costs ($8761 vs $10,777) and overall improved expected quality of life-years compared to the standard of care (0.77 vs 0.69).The findings suggest that patients with access to cardiac PET/CT are not representative of the patient population most likely to have cardiac sarcoidosis in this limited study evaluation. Universal insurance coverage should be considered for Cardiac PET imaging as same day cardiac PET and MR imaging has potential long-term cost and quality of life benefit.

Sarcoidosis is a heterogeneous disease, which can affect virtually every body organ, even though lungs and intra thoracic lymph nodes are almost universally affected. The presence of noncaseating granulomas is the histopathological hallmark of the disease, and clinical picture depends on the organs affected. Data about interaction between sarcoidosis and comorbidities, such as cardiovascular and pulmonary diseases, autoimmune disorders, malignancy and drug-related adverse events are limited. Several lung conditions can be associated with sarcoidosis, such as pulmonary hypertension and fibrosis, making it difficult sometimes the differentiation between complications and distinctive pathologies. Their coexistence may complicate the diagnosis of sarcoidosis and contribute to the highly variable and unpredictable natural history, particularly if several diseases are recognised. A thorough assessment of specific disorders that can be associated with sarcoidosis should always be carried out, and future studies will need to evaluate sarcoidosis not only as a single disorder, but also in the light of possible concomitant conditions.Key messagesComorbidities in sarcoidosis are common, especially cardiovascular and pulmonary diseases.In the diagnostic workup, a distinction must be made between sarcoidosis-related complaints and complaints caused by other separate disorders. It can be very difficult to distinguish between complications of sarcoidosis and other concomitant conditions.The coexistence of multiple conditions may complicate the diagnosis of sarcoidosis, affect its natural course and response to treatment.

While right ventricular (RV) involvement is commonly observed in patients with cardiac sarcoidosis (CS), the utility of strain imaging to detect RV involvement is unclear. We aimed to investigate the association between RV free wall longitudinal strain (RVFWLS) and cardiovascular events in patients with CS.We studied 51 patients with CS who were diagnosed between 2012 and 2020. All patients underwent comprehensive echocardiographic evaluation, and RVFWLS was assessed using 2-dimensional speckle tracking echocardiography. The primary outcome was major adverse cardiovascular events (MACEs).During a median follow-up duration of 548 days, 11 patients exhibited MACEs. In the univariable Cox proportional hazards model, the baseline RVFWLS was associated with MACEs (hazard ratio: 1.29, p = 0.008). The addition of RVFWLS to the conventional echocardiographic parameters exhibited a significant incremental value associated with MACEs. Patients with reduced RVFWLS showed a higher prevalence of late gadolinium enhancement on cardiac magnetic resonance imaging in RV wall (p = 0.02) and trends toward higher prevalence of fluorodeoxyglucose uptake in RV (p = 0.06). A serial echocardiographic evaluation revealed that patients with events showed a worsening in RVFWLS, while others showed a trend toward improvement.Impaired RVFWLS at baseline was associated with MACEs in patients with CS. RVFWLS could be an important surrogate of disease activity and prognosis by detecting active RV involvement in CS.

Aims Although soluble interleukin 2 receptor (sIL‐2R) is a potentially useful biomarker in the diagnosis and evaluation of disease severity in patients with sarcoidosis, its prognostic implication in patients with cardiac sarcoidosis (CS) is unclear. We sought to investigate whether sIL‐2R was associated with clinical outcomes and to clarify the relationship between sIL‐2R levels and disease activity in patients with CS. Methods and results We examined 83 consecutive patients with CS in our hospital who had available serum sIL‐2R data between May 2003 and February 2020. The primary outcome was a composite of advanced atrioventricular block, ventricular tachycardia or ventricular fibrillation, heart failure hospitalization, and all‐cause death. Inflammatory activity in the myocardium and lymph nodes was assessed by 18F‐fluorideoxyglucose positron emission tomography/computed tomography. During a median follow‐up period of 2.96 (IQR 2.24–4.27) years, the primary outcome occurred in 24 patients (29%). Higher serum sIL‐2R levels (>538 U/mL, the median) were significantly related to increased incidence of primary outcome (P = 0.037). Multivariable Cox regression analysis showed that a higher sIL‐2R was independently associated with an increased subsequent risk of adverse events (HR 3.71, 95% CI 1.63–8.44, P = 0.002), even after adjustment for significant covariates. sIL‐2R levels were significantly correlated to inflammatory activity in lymph nodes (r = 0.346, P = 0.003) but not the myocardium (r = 0.131, P = 0.27). Conclusions Increased sIL‐2R is associated with worse long‐term clinical outcomes accompanied by increased systemic inflammatory activity in CS patients.

Patients with suspected cardiac sarcoidosis frequently undergo fluorodeoxyglucose (FDG)-positron emission tomography (PET)/computed tomography (CT) imaging to assess disease activity at baseline and after treatment initiation.This study investigated the effect of immunosuppressive therapy and biopsy status to achieve complete treatment response (CTR), partial treatment response (PTR), or no response (NR) on myocardial FDG-PET/CT.This study analyzed 83 patients with suspected cardiac sarcoidosis (aged 53 ± 1.8 years, 71% were male, 69% were White, 61% had a history of biopsy-confirmed sarcoidosis) who were treatment naive, had evidence of myocardial FDG at baseline, and underwent repeat PET imaging after treatment initiation. CTR was graded visually, and PTR/NR were measured both visually and quantitatively using the total glycolytic activity. Patients were also evaluated for the occurrence of death, sustained ventricular arrhythmias, and heart failure admissions.Overall, 59 patients (71%) achieved CTR/PTR (30%/41%) at follow-up scan (P = 0.04). Total glycolytic activity and visual estimate of PTR/NR had excellent agreement (κ = 0.86 [95% CI: 0.72-0.99]; P 0.0001). In patients receiving prednisone only, the highest rates of CTR/PTR were observed in patients initiated on moderate or high dose (P 0.01). In a regression model, moderate prednisone start dose (P = 0.03) was more strongly associated with achieving CTR/PTR than was high prednisone start dose. However, the latter patients were tapered faster between start dose and follow-up scan (P 0.01). After a median follow-up of 4.7 (IQR: 3.1-7.8) years, patients who were biopsy-proven (vs non-biopsy-proven; P = 0.029) and with preserved left ventricular function (P = 002) were less likely to experience major adverse cardiac events. Outcomes based on treatment response status (CTR vs PTR vs NR; P = 0.23) were not significantly different.Among patients with suspected sarcoidosis and evidence of myocardial inflammation, treatment response by serial FDG-PET was variable, but a favorable response was more common when using moderate-to-high intensity prednisone dose. Biopsy-proven individuals and those with preserved systolic function were less likely to experience adverse outcomes during follow-up.

Although sarcoidosis is an established cause of multiorgan dysfunction, acute presentation with thrombotic microangiopathy resulting in severe renal and hematological sequelae has not been reported. We describe the case of a patient presenting with hypercalcemia, pancreatitis, and acute renal failure, followed by microangiopathic hemolytic anemia. Although there were no significant respiratory symptoms, thoracic radiology and mediastinal lymph node biopsy results were in keeping with sarcoidosis as the underlying cause of this multisystem presentation. Corticosteroids were commenced with clinical and biochemical improvement. This novel case highlights the need to consider sarcoidosis as part of the differential diagnosis for unusual multiorgan presentations and for early multidisciplinary involvement in such cases to permit optimal treatment.

Sarcoidosis is a multiorgan granulomatous disease with a variable course.The purpose of this study is to identify the patients that are more likely to experience disease progression.A retrospective study in patients ≥18 years. Pulmonary function and radiological stage (Scadding criteria) were assessed at diagnosis, and at 1, 3 and 5 years. Sarcoidosis progression was established based on deterioration of radiological or pulmonary function (decrease ≥10% of FVC and/or ≥15% of diffusing capacity of the lung (DLCO).The sample included 277 caucasian patients [mean age, 50±13.6; 69.7% between 31-60 years; 56.3% men]. In total, 65% had stage II sarcoidosis, whereas only 8.3% had stage III/IV disease. Mean pulmonary function (FVC, FEVAt 3 years, a third of patients experienced sarcoidosis progression. Age was the only factor associated with disease prognosis.

BNT162b2 (Pfizer/BioNTech) is a coronavirus disease 2019 (COVID-19) vaccine containing nucleoside-modified messenger RNA encoding the severe acute respiratory syndrome coronavirus 2 spike glycoprotein. Recently, ocular complications of mRNA vaccines have been reported increasingly frequently. However, immunological adverse events due to mRNA vaccines in real-world settings are not fully known. We herein report the novel development of sarcoidosis manifested as uveitis, bilateral hilar lymphadenopathy, angiotensin-converting enzyme elevation, and epithelioid and giant cell granuloma formation in the lung soon after the first BNT162b2 injection and review the current literature, including three reported cases of sarcoid-like reaction following COVID-19 vaccination.

Objectives Oil Red O (ORO) positivity in bronchoalveolar lavage (BAL) fluid macrophages in the setting of e-cigarette, or vaping, product use–associated acute lung injury (EVALI) has been frequently requested by clinicians based on rare reports and subsequent US Centers for Disease Control and Prevention guidelines. The aim of this study was to determine the specificity of ORO staining in BAL specimens with disease states other than EVALI. Methods Consecutive BAL specimens (October-December 2019) were stained with ORO. The lipid-laden macrophage index (LLMI) was calculated for each case. Results We studied BAL samples from 50 patients. Indications for BAL were surveillance bronchoscopy for lung transplantation (27/50), suspected infection (12/50), sarcoidosis/suspected sarcoidosis (3/50), nodules or ground-glass opacities (3/50), hemoptysis (2/50), asthma or eosinophilic pneumonia (2/50), and idiopathic pulmonary fibrosis (1/50). ORO staining was seen in BAL fluid macrophages in 45 of 50 cases (focal in 18, moderate in 23, diffuse in 4); LLMI ranged from 0 to 218. Using a threshold of LLMI of 85 or higher as positive, ORO was positive in 7 of 50 (14%) cases (range, 85-218). Conclusions ORO staining in BAL fluid macrophages is not specific for EVALI. Even when an LLMI of 85 or higher is used as a threshold for positivity, ORO positivity occurs in a significant subset of non–vaping-related cases.

Patients with sarcoidosis experience fatigue and excessive daytime sleepiness (EDS). However, the underlying pathomechanism is unclear. Studies suggested undiagnosed obstructive sleep apnea (OSA) to be an important contributor, but reliable data on prevalence and impact of OSA in sarcoidosis are scarce.71 adult patients with sarcoidosis, 1-to-1 matched to 71 adult controls according to sex, age, and body mass index were included. Participants underwent structured interviews (including Epworth Sleepiness Scale [ESS], Fatigue Assessment Scale [FAS], and Functional Outcome of Sleep Questionnaire [FOSQ-30]) and level-3 respiratory polygraphy. OSA was defined as apnea-hypopnea index ≥ 5 events/h. Prevalence of OSA was assessed and possible risk factors for OSA in sarcoidosis were investigated.Mild OSA (AHI ≥ 5 events/h) was prevalent in 32 (45%) sarcoidosis patients vs 22 (31%) controls (The risk for mild OSA is 2.5-fold higher in sarcoidosis patients compared with matched controls. OSA seems not to be the reason for increased sleepiness or fatigue in sarcoidosis. Risk factors such as body mass index, sex, neck circumference, and NoSAS score can be used to screen for OSA in sarcoidosis patients.Registry: ClinicalTrials.gov; Name: Obstructive Sleep Apnoea in Sarcoidosis (OSASA); URL: https://clinicaltrials.gov/ct2/history/NCT04156789?V_2=View; Identifier: NCT04156789.Roeder M, Sievi NA, Schneider A, et al. The prevalence of obstructive sleep apnea in sarcoidosis and its impact on sleepiness, fatigue, and sleep-associated quality of life: a cross-sectional study with matched controls (the OSASA study).

OBJECTIVE: To investigate 18F-FDG PET/CT findings of tuberculous lymphadenitis and analyze the causes of misdiagnosis. METHOD: Between 2013 and 2021, a retrospective review was conducted on 22 patients at Jiangxi Provincial People’s Hospital Affiliated with Nanchang University who had lymph node tuberculosis confirmed by histology or clinical investigation. Subjective judgment and quantitative analysis were adopted. RESULTS: Out of 22 patients, 14 are male and 8 are female. The average age was 55.5 years (55.5±12.4). The most common site of lymph node tuberculosis (LNTB) is the mediastinum (41.5%), followed by the neck (24.4%) and the abdominal cavity (21.9%). Half of the patients have more than one site affected. More than half of LNTB patients (54.5%) are concurrent with other types of TB, especially PTB. Among the 41 biggest affected lymph nodes, the average maximum diameter, minimum diameter, SUVmax and the lesion SUVmax/SUVmean liver ratio are 22.04±8.39, 16.93±6.75, 9.72±5.04 and 6.72±3.60, respectively. There is a poor correlation coefficient of 0.236 between the FDG uptake and the size of the biggest affected lymph node. Patients who are concurrent with no other TB have the significantly higher FDG uptake than patients who are concurrent with other TB (12.42 vs 8.02) (p = 0.005). Among these cases, 6 cases (27.3%) are accurately diagnosed with LNTB, all of which have pulmonary tuberculosis as a complication. However, 16 cases (72.7%) are misdiagnosed as lymphoma (50%), sarcoidosis (13.6%), and lymph node metastasis (9%). CONCLUSIONS: This study demonstrates that 18F-FDG PET/CT is very useful in detecting LNTB because tuberculous granulomas show significant levels of glucose uptake. It proves to be an effective method for revealing lesion extent and discovering additional lesions that morphological imaging is missed. However, 18F-FDG PET/CT is not able to reliably distinguish LNTB from lymphoma, sarcoidosis, and metastatic lymph nodes. Nonetheless, 18F-FDG PET/CT allows for the selection of the most optimal biopsy location, and thus has potential to detect early treatment response and distinguish between active and inactive lesions.

Sarcoidosis is a systemic inflammatory disease of unknown etiology, which can affect almost any organ. Cardiac involvement determines the prognosis of the affected individuals. Its prevalence in patients with extracardiac sarcoidosis with the absence of cardiac symptoms remains unclear. Cardiac magnetic resonance (CMR) provides excellent diagnostic accuracy in the detection of heart involvement by sarcoidosis.We sought to determine the prevalence of cardiac sarcoidosis in asymptomatic individuals with newly diagnosed extracardiac sarcoidosis using CMR.We prospectively evaluated 55 consecutive patients including 23 women with newly diagnosed extracardiac sarcoidosis who underwent contrast-enhanced CMR and had no symptoms of heart disease. The mean (standard deviation) age of patients was 43 (11) years. The presence of myocardial late gadolinium enhancement (LGE) of non-ischemic etiology on CMR examination was considered diagnostic for cardiac sarcoidosis.In 3 (6%) patients, the LGE pattern consistent with cardiac sarcoidosis was detected. In all patients, preserved left ventricular systolic regional and global function was present, and in none of them, the elevation of blood biomarkers of myocardial injury or overload was found.Our study suggests that the prevalence of cardiac involvement in patients with newly diagnosed extracardiac sarcoidosis and no symptoms of heart disease is very low as assessed by CMR. However, CMR may be considered as part of routine evaluation of patients with extracardiac sarcoidosis due to its higher diagnostic yield in comparison with echocardiography and electrocardiography, respectively.

Background: Cardiac sarcoidosis (CS) predisposes to sudden cardiac death (SCD). Guidelines for implantable cardioverter defibrillators (ICDs) in CS have been issued by the Heart Rhythm Society in 2014 and the American College of Cardiology/American Heart Association/Heart Rhythm Society consortium in 2017. How well they discriminate high from low risk remains unknown. Methods: We analyzed the data of 398 patients with CS detected in Finland from 1988 through 2017. All had clinical cardiac manifestations. Histological diagnosis was myocardial in 193 patients (definite CS) and extracardiac in 205 (probable CS). Patients with and without Class I or IIa ICD indications at presentation were identified, and subsequent occurrences of SCD (fatal or aborted) and sustained ventricular tachycardia were recorded, as were ICD indications emerging first on follow-up. Results: Over a median of 4.8 years, 41 patients (10.3%) had fatal (n=8) or aborted (n=33) SCD, and 98 (24.6%) experienced SCD or sustained ventricular tachycardia as the first event. By the Heart Rhythm Society guideline, Class I or IIa ICD indications were present in 339 patients (85%) and absent in 59 (15%), of whom 264 (78%) and 30 (51%), respectively, received an ICD. Cumulative 5-year incidence of SCD was 10.7% (95% CI, 7.4%–15.4%) in patients with ICD indications versus 4.8% (95% CI, 1.2%–19.1%) in those without (χ 2 =1.834, P =0.176). The corresponding rates of SCD were 13.8% (95% CI, 9.1%–21.0%) versus 6.3% (95% CI, 0.7%–54.0%; χ 2 =0.814, P =0.367) in definite CS and 7.6% (95% CI, 3.8%–15.1%) versus 3.3% (95% CI, 0.5%–22.9%; χ 2 =0.680, P =0.410) in probable CS. In multivariable regression analysis, SCD was predicted by definite histological diagnosis ( P =0.033) but not by Class I or IIa ICD indications ( P =0.210). In patients without ICD indications at presentation, 5-year incidence of SCD, sustained ventricular tachycardia, and emerging Class I or IIa indications was 53% (95% CI, 40%–71%). By the American College of Cardiology/American Heart Association/Heart Rhythm Society guideline, all patients with complete data (n=245) had Class I or IIa indications for ICD implantation. Conclusions: Current ICD guidelines fail to distinguish a truly low-risk group of patients with clinically manifest CS, the 5-year risk of SCD approaching 5% despite absent ICD indications. Further research is needed on prognostic factors, including the role of diagnostic histology. Meanwhile, all patients with CS presenting with clinical cardiac manifestations should be considered for an ICD implantation.

Background: Erythema Nodosum (EN) is the most common skin manifestation in sarcoidosis and has often been associated with a good prognosis. Objectives: To compare the clinical characteristics and treatment-related features in patients with sarcoidosis according to whether or not EN was seen as a presenting symptom at the time of diagnosis. Methods: A 20-year single-center retrospective study was performed. The following two groups were identified: one group with EN as one of the presenting symptoms at the time of diagnosis of sarcoidosis (EN group) and a second group without EN as a presenting symptom at diagnosis (non-EN group). The clinical characteristics and treatment modalities were collected from the medical records. Results: A total of 122 patients (31 in the EN group, 91 in the non-EN group) were included. Radiological stages of pulmonary disease were significantly lower in the EN group. Articular involvement was more common in the EN group (p = 0.001), whereas other systemic organ involvements (p = 0.025), especially neurological involvement (p = 0.036), were significantly more common in the non-EN group. In the EN group, a higher percentage of patients were managed without systemic therapy (71.0% vs. 54.9%) and spontaneous remission was more frequent (25.0% vs. 14.1%), however, this wasn’t statistically significant. Study limitations: Retrospective design. Conclusions: The lower radiological stage of pulmonary sarcoidosis and lower frequency of systemic organ involvement in patients with EN augment the prognostic value of EN highlighted in the literature. However, this study couldn’t confirm that the patients with EN would need less systemic therapy in the course of their disease.

BRAF-inhibitors have emerged as a promising targeted therapy for malignancies with BRAF mutations, particularly metastatic melanoma. However, granulomatous reactions including sarcoidosis and sarcoid-like-reactions have been reported as a consequence of BRAF-inhibition. It is important to adequately characterise these granulomatous reactions including cutaneous manifestations and systemic involvement, in order to guide investigations and management. A literature review was conducted to characterise the spectrum of granulomatous reactions associated with BRAF-inhibitors - identifying 55 reactions affecting 51 patients, with 37 reactions limited to cutaneous involvement. Further, possible correlation with cancer response, mechanisms of granuloma formation, as well as a proposed workup and management approach for these granulomatous reactions are presented.

To review the current literature regarding cochlear implantation in patients with retrocochlear pathologies and extract speech perception scores between 6 months and 1 year after surgery.PubMed/MEDLINE, Embase and Cochrane CENTRAL via Ovid, CINAHL Complete via Ebsco, and Web of Science.The review was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Search strategies included keywords and subject headings to maximize retrieval and reflect cochlear implants and retrocochlear pathologies. Patients with previously resected vestibular schwannoma (VS) were excluded.There were 2,524 abstracts screened against inclusion criteria, and 53 studies were included, with individual data available for 171 adult patients. Pathologies included were either observed or irradiated VS (previously operated tumors were excluded) (n = 99, 57.9%), superficial siderosis (n = 39, 22.8%), neurosarcoidosis (n = 11, 6.4%), and previous central nervous system or skull base radiation (n = 22, 12.9%). Mean (standard deviation) postoperative consonant-nucleus-consonant (CNC) word scores were 45.4% (24.2) for observed VS, 44.4% (20.8) for irradiated VS, 43.6% (21.0) for superficial siderosis, 89.5% (3.0) for neurosarcoidosis, and 30.0% (30.2) in patients with previous central nervous system or skull base irradiation. Irradiated compared with observed VS had similar postoperative CNC word scores (effect size, 0.06; p = 0.71). Age, sex, maximal tumor dimension, and neurofibromatosis type 2 status did not significantly impact cochlear implant performance in patients with VS. Eighty-two percent of patients with reported device usage were daily users, and overall, 82% of cases benefitted from cochlear implantation.Cochlear implantation in patients with concomitant retrocochlear pathology generally results in improved speech discrimination scores sustained over time.

We present a case of a 7-year-old Afro-Caribbean girl presenting with rapidly progressive bilateral sensorineural hearing loss. She was found to have an elevated Angiotensin converting enzyme (ACE) and mediastinal lymphadenopathy containing non-caseating granulomas with multinucleate giant cells, in keeping with sarcoidosis. Cranial imaging demonstrated labyrinthitis. She underwent urgent bilateral cochlear implantation with rehabilitation of hearing sufficient to restart education within 1 month.

Sarcoidosis is a systemic granulomatous disease mainly affecting the lungs and hilomediastinal lymph nodes. It is characterized by non-caseating epithelioid cell granulomas in lymph nodes and lungs. Our study aimed to evaluate and compare T, B and NK cell subsets in the alveolar compartment, lymph nodes and the bloodstream simultaneously in the same patients to elucidate the immune responses associated with the development and progression of sarcoidosis. A secondary aim was to evaluate the distribution of CD45RA-expressing cells in the different anatomical compartments. Patients suspected to have sarcoidosis and who underwent bronchoscopy with bronchoalveolar lavage (BAL), lung-draining lymph node (LLN) biopsy by EBUS-TBNA and peripheral blood (PB) sampling were included in the study. They were monitored at the Regional Referral Centre of Siena University Hospital and the Respiratory Diseases Unit of Perugia Hospital. Multicolour flow cytometry analysis through FASCLyric was performed to assess T, B and NK cell subsets. Thirty-two patients (median age (IQR) 57 (52–58) years) were consecutively and prospectively enrolled. Machine learning analysis created a model which selected CD56dim16bright, CD8, Tfc, Th17, Th12, Tfh17, Tfh2, TcemRA, ThemRA, T naïve, Tc naïve, Breg, CD1d+CD5+, Th-reg, Tfh, Th1 and CD4 cells with an accuracy of 0.9500 (kappa 0.8750). Comparative analysis found 18 cell populations that differed significantly between the three anatomical compartments. The bloodstream was enriched in ThemRA (p = 0.0416), Tfh2 (p = 0.0189), Tfh17 (p = 0.0257), Th2 (p = 0.0212), Th17 (p = 0.0177), Th-naïve (p = 0.0368), CD56dimCD16bright (p < 0.0001), CD8 (p = 0.0319), TcemRA (p < 0.0001) and Tfc cells (p = 0.0004) compared with the alveolar compartment, while Th-reg were lower in PB than BAL (p = 0.0329). The alveolar compartment was enriched in Breg (p = 0.0249) and CD1d+CD5+ (p = 0.0013) with respect to LLN samples and PB. Conversely, Tfh (p = 0.0470), Th1 (p = 0.0322), CD4 (p = 0.0486) and Tc-naïve (p = 0.0009) were more abundant in LLN than in BAL and PB. It has been speculated that changes in the relative contents of PB cells could be related to changes in production and to the selective redistribution of PB cells to granulomatous foci. This study further supports the fact that sarcoidosis is multisystemic in nature. However, the low level of immune cells in peripheral blood of patients with sarcoidosis is concerning. A re-expression of CD45RA on CD4+ and CD8+ cells could result in a reduction in peripheral immune activity. Thus, changes in the spectrum of the bloodstream may reflect both pathogenic and compensatory processes.

Sarcoidosis (SA) is a granulomatous disorder, which mostly affects the lungs. Its clinical characteristics resemble tuberculosis (TB), but its treatment is different. The etiology of SA is unknown; however, mycobacterial antigens were proposed as environmental factors in its development. Due to previously revealed immunocomplexemia with mycobacterial antigens in the blood of our SA but not TB patients, and in the search for biomarkers for differential diagnosis of the two disorders, we studied the phagocytic activity of monocytes from both patients’ groups with flow cytometry. With the use of this method, we also analyzed the occurrence of receptors for IgG (FcγR) and complement components (CR) at the surface of these monocytes, responsible for phagocytosis of immunocomplexes. We revealed a higher phagocytic activity of monocytes in both disorders, but an increased frequency of monocytes with FcγRIII (CD16) and decreased with CR1 (CD35) receptor in the blood of SA vs. TB patients. With regard to our other genetic study on FcγRIII variants in SA and TB, this may account for the decreased clearance of immunocomplexes and different immune responses in the two diseases. Thus, the presented analysis not only sheds light on the pathomechanisms of SA and TB but may also support their differential diagnosis.

Silicosis is one of the most important occupational respiratory diseases worldwide, hence the importance of making a correct diagnosis. Diagnosis is commonly based on radiological findings according to the ILO International Classification of Radiographs of Pneumoconioses and occupational exposure. High-resolution computed tomography is indicated for differential diagnosis. This article presents two cases with an initial diagnosis of silicosis that ended up being diagnosed as sarcoidosis and siderosis, respectively. The first case was a 42-year-old male who worked as a crushing operator in an underground copper and molybdenum mine for 22 years. He had a history of exposure to silicon dioxide and was asymptomatic. X-rays did not distinguish silicosis or siderosis, but histological findings (open lung biopsy) allowed for a diagnosis of sarcoidosis. The second case was a 50-year-old male who had worked as a welder in a molybdenum filter plant, an open pit mine since 2013; he spent the previous 20 years as a welder in an underground copper mine, with exposure to silicon dioxide and was symptomatic. The first radiograph showed opacities that were compatible with pulmonary silicosis. A subsequent high-resolution computed tomography and lung biopsy showed a pattern of pulmonary siderosis. Due to the similarities in the radiographs of these three diseases, greater emphasis must be placed on the differential diagnosis, for which a complete occupational and clinical history is important in order to provide clues for the performance of complementary tests to avoid misdiagnosing.

We described nailfold videocapillaroscopy (NVC) findings and estimated the prevalence of serum anti-nuclear (ANA) and extractable nuclear antigen autoantibodies (ENA) in a cohort of sarcoidosis patients, comparing them with adequate healthy controls (HCs) and with primary Raynaud’s phenomenon patients (PRPs). NVC findings were also correlated with the occurrence of autoantibodies, current treatment, laboratory parameters, variables of lung function and whole-body imaging data. Twenty-six patients with sarcoidosis were assessed through NVC, laboratory parameters, pulmonary function tests, chest-X ray and 18- fluorodeoxyglucose positron emission tomography/computed tomography. The NVC parameters and ANA/ENA dosage were recorded also in 30 PRPs and 30 HCs. Sarcoidosis patients showed a higher rate of capillary dilations and nonspecific abnormalities and a lower mean capillary absolute number than PRPs and HCs (p p p

Thymic stromal lymphopoietin (TSLP), long known to be involved in Th2 response, is also implicated in multiple inflammatory dermatoses and cancers. The purpose of this study was to improve our understanding of the expression of TSLP in the skin of those dermatoses. Lesional specimens of representative immune-related dermatoses, including lichen planus (LP), discoid lupus erythematosus (DLE), eczema, bullous pemphigoid (BP), psoriasis vulgaris (PsV), sarcoidosis, and mycosis fungoides (MF), were retrospectively collected and analyzed by immunohistochemistry. Morphologically, TSLP was extensively expressed in the epidermis of each dermatosis, but the expression was weak in specimens of DLE. In a semiquantitative analysis, TSLP was significantly expressed in the epidermis in LP, BP, eczema, PsV, sarcoidosis, and MF. TSLP expression was higher in the stratum spinosum in LP, eczema, BP, PsV, and MF and higher in the stratum basale in sarcoidosis and PsV. Moreover, we found positive TSLP staining in the dermal infiltrating inflammatory cells of BP, PsV, and sarcoidosis. Our observation of TSLP in different inflammatory dermatoses might provide a novel understanding of TSLP in the mechanism of diseases with distinctly different immune response patterns and suggest a potential novel therapeutic target of those diseases.

Sarcoidosis is a granulomatous disorder. Rarely, malignancy is accompanied by a granulomatous reaction. This retrospective study addressed whether cancer can masquerade as sarcoidosis.TriNetX identified 1029 newly diagnosed cases of sarcoidosis between October 2015 and September 2020, of whom 50 had a subsequent diagnosis of malignancy.In 36 cases, the malignancy was unrelated to sarcoidosis. In 7 cases, the diagnosis of sarcoidosis delayed the eventual cancer diagnosis by a range of 1 month to 2 years. In 7 cases, the subsequent diagnosis of cancer might have been related to the therapy for sarcoid.Cancer masquerading as sarcoidosis is very rare occurring in 7 (0.7%) of our 1029 cases. In no case was lung cancer masquerading as sarcoidosis. Searching for occult malignancy in patients with a known diagnosis of sarcoidosis is rarely indicated.

Cardiac sarcoidosis (CS) is a nonischemic cardiomyopathy (NICM) characterized by infiltration of noncaseating granulomas involving the heart with highly variable clinical manifestations that can include conduction abnormalities and systolic heart failure. Cardiac resynchronization therapy (CRT) has shown significant promise in NICM, though little is known about its efficacy in patients with CS.To determine if CRT improved cardiac remodeling in patients with CS.We retrospectively reviewed all patients with a clinical or histological diagnosis of CS who underwent CRT implantation at the Mayo Clinic enterprise from 2000 to 2021. Baseline characteristics, imaging parameters, heart failure hospitalizations and need for advanced therapies, and major adverse cardiac events (MACE) were assessed.Our cohort was comprised of 55 patients with 61.8% male and a mean age of 58.7 ± 10.9 years. Eighteen (32.7%) patients had definite CS, 21 (38.2%) had probable CS, while 16 (29.1%) had presumed CS, and 26 (47.3%) with extracardiac sarcoidosis. The majority underwent CRT-D implantation (n = 52, 94.5%) and 3 (5.5%) underwent CRT-P implantation with 67.3% of implanted devices being upgrades from prior pacemakers or implantable cardioverter defibrillators. At 6 months postimplantation there was no significant improvement in ejection fraction (34.8 ± 10.9% vs. 37.7 ± 14.2%, p = .331) or left ventricular end-diastolic diameter (58.5 ± 10.2 vs. 57.5 ± 8.1 mm, p = .236), though mild improvement in left ventricular end systolic diameter (49.1 ± 9.9 vs. 45.7± 9.9 mm, p .0001). Within the first 6 months postimplantation, 5 (9.1%) patients sustained a heart failure hospitalization. At a mean follow-up of 4.1± 3.7 years, 14 (25.5%) patients experienced a heart failure hospitalization, 11 (20.0%) underwent cardiac transplantation, 1 (1.8%) underwent left ventricular assist device implantation and 7 (12.7%) patients died.Our findings suggest variable response to CRT in patients with CS with no overall improvement in ventricular function within 6 months and a substantial proportion of patients progressing to advanced heart failure therapies.

Sarcoidosis is a systemic autoimmune disease that is associated with the development of non-caseating granulomas. The disease especially affects the lymph nodes, lungs, skin and eyes. It is an infrequent but not rare disease, especially in northern Europe, the United States and India. Sarcoidosis affects more women and is diagnosed between the ages of 30 and 50. Etiopathogenically, it is closely linked to environmental factors, especially occupational exposures. Clinically, it stands out for a wide variety of presentation phenotypes (casual diagnosis, involvement of a single organ or systemic presentation). The diagnosis of sarcoidosis is complex and requires the integration of clinical, analytical, radiological, and histolopathogical data carried out by multidisciplinary clinical units. The evolution of the disease is variable, as is the indication for systemic treatment, based on the use of corticosteroids as first-line option, the use of immunosuppressants as second-line therapy, and anti-TNF agents in severe and/or refractory cases.

Sarcoidosis often involves the liver. However, primary hepatic sarcoidosis confined to the liver without evidence of systemic involvement is rare. We report the case of a 37-year-old man with hepatic sarcoidosis who initially presented with elevated liver enzymes and suspicious cirrhotic nodules on computed tomography. The patient had cirrhosis but did not have portal hypertension. Based on the initial histopathologic finding of chronic granulomatous inflammation and the common clinical characteristics of sarcoidosis, he was initially diagnosed with primary biliary cholangitis, and his daily dosage of ursodeoxycholic acid was increased to 900 mg. After 14 months of treatment, his total serum bilirubin concentration was 10.9 mg/dL (upper normal limit, 1.2 mg/dL). Additionally, a transjugular liver biopsy revealed multiple noncaseating granulomas. He was diagnosed with primary hepatic sarcoidosis involving the lungs, heart, spleen, kidneys, and skin. Treatment with methylprednisolone was initiated. Two weeks later, he was started on azathioprine, and the dose of steroid was simultaneously reduced. These findings indicate the importance of including hepatic sarcoidosis as a possible diagnosis in patients with elevated liver enzymes or cryptogenic cirrhosis.

The treatment of sarcoidosis remains uncertain, despite 70 years of study. The conventional approach is to initiate corticosteroids in individuals who require treatment. The position of more aggressive regimes is unknown.Recent recognition that many patients will require prolonged therapy, and the observation that corticosteroids lead to overt and insidious toxicities, have led to suggestions that steroid-sparing medications be used earlier in the management of sarcoidosis. Individuals with poor prognostic features, designated as 'high-risk' sarcoidosis may, especially benefit from a broader palette of therapeutic options in the initial treatment regimen. An even more aggressive approach, known as 'top-down' or 'hit-hard and early' therapy has emerged in the fields of gastroenterology and rheumatology in the past 15 years, on the premise that highly effective early control of inflammation leads to better outcomes. These regimens typically involve early initiation of biologic therapies.For certain subpopulations of sarcoidosis patients, 'top-down' therapy could be helpful. Severe pulmonary sarcoidosis, neurosarcoidosis, cardiac sarcoidosis and multiorgan sarcoidosis are phenotypes that may be most relevant for revised therapeutic algorithms. Precision medicine approaches and randomized trials will be necessary to confirm a role for top-down therapy in the routine management of sarcoidosis.

PURPOSE OF REVIEW: Sarcoidosis is a chronic multisystemic inflammatory disease of unknown aetiology with a wide range of highly variable clinical manifestations and unpredictable disease course. Sarcoidosis patients may present with specific organ-related symptoms involving functional impairments, and less specific symptoms. The decision whether and when to treat a sarcoidosis patient with pharmacotherapy depends on two major factors: risk of organ failure and/or death and impairment of quality of life. This decision is complex and not standardized. RECENT FINDINGS: Glucocorticoids (GCs) are recommended as initial treatment, when needed. Subsequent GC-sparing alternatives frequently follow. Comorbidities or adverse drug reactions (ADRs) from drugs used in sarcoidosis treatment are sometimes very hard to differentiate from symptoms associated with the disease itself, which may cause diagnostic dilemmas. An ideal approach to minimalize ADRs would involve genetic screening prior to prescribing certain 'high-risk drugs' and therapeutic drug monitoring during treatment. Pharmacogenomic testing aims to guide appropriate selection of medicines, with the potential of reducing unnecessary polypharmacy while improving clinical outcomes. SUMMARY: A multidisciplinary approach to the management of sarcoidosis may avoid unnecessary ADRs. It is important to consider the possibility of drug-induced damage in sarcoidosis, especially if the clinical situation deteriorates after the introduction of a particular drug.

PET has emerged as method to determine the location and extent of disease activity in sarcoidosis. As most clinicians do not routinely utilize PET in the management of sarcoidosis, an understanding of the imaging technique is needed to comprehend the impact that PET abnormalities have on diagnosis, prognosis, and treatment.Although PET can detect inflammation because of sarcoidosis throughout the body, it is most often utilized for the diagnosis of cardiac sarcoidosis for which it may provide information about prognosis and adverse events. Whenever PET is combined with cardiac magnetic resonance (CMR), clinicians may be able to increase the diagnostic yield of imaging. Furthermore, PET abnormalities have the potential to be utilized in the reduction or augmentation of therapy based on an individual's response to treatment. Although various biomarkers are used to monitor disease activity in sarcoidosis, an established and reproducible relationship between PET and biomarkers does not exist.PET has the potential to improve the diagnosis of sarcoidosis and alter treatment decisions but prospective trials are needed to define the role of PET while also standardizing the performance and interpretation of the imaging modality.

Recently, the European Respiratory Society (ERS) developed new international guidelines for the treatment of sarcoidosis. This manuscript attempts to distill the ERS Sarcoidosis Treatment Guidelines to a manageable format that can be easily used by practitioners.The ERS Sarcoidosis Treatment Guidelines addressed the treatment of pulmonary, skin, cardiac, neurologic, and sarcoidosis-associated fatigue. Therapeutic drug dosing and treatment algorithms for these conditions were also addressed. Glucocorticoids were the initial recommended treatment for these conditions except for sarcoidosis-associated fatigue where a pulmonary exercise program or a neurostimulant was initially suggested. Because of the risk of glucocorticoid side-effects, the Guidelines recommended early consideration of glucocorticoid-sparing therapy including certain antimetabolites and two specific tumor necrosis alpha antagonists: infliximab and adalimumab.The ERS Sarcoidosis Treatment Guidelines used a rigorous GRADE (Grading of Recommendations, Assessment, Development and Evaluations) methodology to update treatment recommendations for this condition. This manuscript summarizes the Guideline findings in practical terms for clinicians. Suggested algorithms and treatment dosing recommendations are provided.

Pyroptosis is commonly induced by the gasdermin (GSDM) family and is accompanied by the release of inflammatory cytokines such as IL-1β and IL-18. Recently, increasing evidence suggests that pyroptosis plays a role in respiratory diseases. This review aimed to summarize the roles and mechanisms of pyroptosis in inflammation-related respiratory diseases. There are several pathways involved in pyroptosis, such as the canonical inflammasome-induced pathway, non-canonical inflammasome-induced pathway, caspase-1/3/6/7/GSDMB pathway, caspase-8/GSDMC pathway, caspase-8/GSDMD pathway, and caspase-3/GSEME pathway. Pyroptosis may be involved in asthma, chronic obstructive pulmonary disease (COPD), lung cancer, acute lung injury (ALI), silicosis, pulmonary hypertension (PH), and tuberculosis (TB), in which the NLRP3 inflammasome-induced pathway is mostly highlighted. Pyroptosis contributes to the deterioration of asthma, COPD, ALI, silicosis, and PH. In addition, pyroptosis has dual effects on lung cancer and TB. Additionally, whether pyroptosis participates in cystic fibrosis (CF) and sarcoidosis or not is largely unknown, though the activation of NLRP3 inflammasome is found in CF and sarcoidosis. In conclusion, pyroptosis may play a role in inflammation-related respiratory diseases, providing new therapeutic targets.

This review provides an update on recent advances in the diagnosis, pathogenesis, clinical presentation, histopathological findings, and treatment approaches for antineutrophil cytoplasmic antibody (ANCA) vasculitis-associated interstitial lung disease (AAV-ILD) with a focus on literature published in the last 3 years.Although there is no validated definition of AAV-ILD, which contributes to some of the heterogeneity seen in study results, there has been an increasing number of publications in recent years on this topic. Most patients with AAV-ILD have MPO-ANCA vasculitis, and this association appears to reduce their 5-year-survival to 60-66% (Sun et al. BMC Pulm Med 21(1), 2021, Maillet et al. J Autoimmun 106, 2020). Median age of diagnosis ranges from mid-60 s to mid-70 s (Ando et al. Respir Med 107(4), 2013), Kagiyama et al. BMJ Open Respir Res 2(1):1-9, 2015, Hozumi et al. Lung 194(2):235-42, 2016, Liu et al. Chest 156(4):715-23, 2019, Maillet et al. J Autoimmun 106, 2020, Wurmann et al. Sarcoidosis Vasc Diffuse Lung Dis 37(1):37-42, 2020, Watanabe et al. BMC Pulm Med 19(1), 2019). Computed tomography (CT) chest imaging for patients with AAV-ILD often shows a usual interstitial pneumonia (UIP) or nonspecific interstitial pneumonia (NSIP) pattern (12-58% and 13-61%, respectively) (Sun et al. BMC Pulm Med 21(1), 2021, Maillet et al. J Autoimmun 106, 2020, Wurmann et al. Sarcoidosis Vasc Diffuse Lung Dis 37(1):37-42, 2020, Watanabe et al. BMC Pulm Med 19(1), 2019, Baqir at al. Sarcoidosis Vasc Diffuse Lung Dis Off J WASOG 36(3):195-201, 2019). Additionally, lung biopsies typically do not demonstrate active inflammation, or capillaritis, questioning whether these patients should be treated with either immunotherapy or anti-fibrotic therapy, or both (Hozumi et al. Lung 194(2):235-42, 2016, Liu et al. Chest 156(4):715-23, 2019, Kitching at al. Nat Rev Dis Prim 6(1):71, 2020, Tanaka et al. Respir Med 106(12):1765-70, 2012). Besides immunosuppressive treatments, recent advances in anti-fibrotic therapy may offer patients with progressive AAV-ILD an alternative and/or more effective and individualized treatment option.

Abstract: Sarcoidosis is a worldwide inflammatory disorder of unknown etiology that is characterized by the formation of non-caseating immune granulomas in involved organs, most commonly in the lungs and eyes. Although clinical manifestations of sarcoidosis depend on the organs involved, the most common symptoms include fatigue, fever, weight loss, eye pain, dyspnea, and chest pain. Sarcoidosis usually undergoes spontaneous regression, yet its chronic form progressively threatens the involved organs through the induction of fibrotic damage. Despite decades of medical research, the etiology of sarcoidosis still remains unclear. Nevertheless, a combination of contributors, including genetic factors, environmental exposures, and microbial agents, is believed to trigger the inflammatory state observed in this disease. Furthermore, a highly polarized Th1 and Th17 response with diminished immunomodulatory mechanisms constitute the most significant immunological event associated with this disorder. Indeed, sarcoid granulomas, which consist of highly activated antigen-presenting cells (APCs) and lymphocytes, maintain a robust specialized niche to facilitate antigen presentation and exaggerated immune responses. Both the unknown etiology and multisystem nature of the disease have hampered the development of specific therapeutics and definitive diagnostic assays for sarcoidosis. Consequently, its diagnosis and treatment still represent a challenging task for clinicians. In this article, we aim to summarize contemporary findings of sarcoidosis and its etiology, pathogenesis, and treatment.

Interstitial lung disease (ILD) is a parenchymal lung disease and restrictive disorder that presents as diffuse infiltrative shadows. The initial diagnosis of ILD is important because management strategies depend on the disease pathogenesis. Connective-tissue disease (CTD)-associated ILD including rheumatoid arthritis (RA), systemic sclerosis (SSc) requires a thorough evaluation of chronic respiratory symptoms such as non-productive cough and exertional dyspnea, as well as physical findings. Moreover, myeloperoxidase-positive anti-neutrophilic cytoplasmic antibody (MPO-ANCA)-associated vasculitis with ILD also shows disease progression. In CTD-associated ILD, the first-line treatment is anti-inflammatory drugs such as prednisolone or immunosuppressants. In hypersensitivity pneumonitis (HP), detailed environmental history-taking is crucial. Therefore, systematic standardized questionnaires are needed. However, the causative antigens are often not identified in daily clinical practice. When an antigen is identified or suspected, the first action is avoidance. If antigen avoidance does not contribute to clinical improvement, anti-inflammatory drugs such as prednisolone might be introduced. Regarding sarcoidosis, while most patients do not require treatment for lung involvement, some need anti-inflammatory drugs or immunosuppressants. Additionally, steroid treatment should be considered for the critical status of extrapulmonary sarcoidosis including cardiac, neurogenic and ocular sarcoidosis. Once starting treatment for ILD, multi-dimensional approaches are applied, including symptom tracking, chest imaging, pulmonary function test (PFT), and 6-min walking test. Recently, the concept of progressive-fibrosing interstitial lung disease (PF-ILD) has been proposed as a new disease entity. The definition of PF-ILD includes symptom progression, PFT decline, and extension of chest high-resolution computed tomography (HRCT) findings. This mini-review describes the background, definition, clinical characteristics, management, and challenges of PF-ILD.

We aimed to determine the prevalence and clinical characteristics of self-reported hyperthyroidism in patients with sarcoidosis.A national registry-based study investigating 3836 respondents to the Sarcoidosis Advanced Registry for Cures questionnaire in the period between June 2014 and August 2019 was conducted. This registry is generated from a web-based questionnaire that is self-reported by patients with sarcoidosis. We compared patients with sarcoidosis who had hyperthyroidism with those who did not. We used multivariate logistic regression analysis to study the association between hyperthyroidism and different cardiac manifestations in patients with sarcoidosis.Three percent of the study respondents self-reported having hyperthyroidism and were generally middle-aged Caucasian women. Compared with patients without hyperthyroidism, patients with hyperthyroidism had more sarcoidosis-related comorbidities (59% vs 43%, P = .001) and more steroid-related comorbidities (56% vs 44%, P = .01), but there was no difference in the sarcoidosis-specific treatments they received, which included corticosteroids. Patients with hyperthyroidism reported sarcoidosis involvement of the heart (26.6% vs 14.9%, P = .005), kidneys (14.9% vs 8%, P = .033) and sinuses (17.7% vs 10.2%, P = .030) more frequently. Cardiac manifestations that were more frequently reported in patients with hyperthyroidism included atrial arrhythmias (11.3% vs 6.3%, P = .046), ventricular arrhythmias (17.2% vs 7.5%, P.001), congestive heart failure (10.4% vs 5%, P = .017), and heart block (9.4% vs 4.7%, P = .036).Hyperthyroidism is infrequent in patients with sarcoidosis but is potentially associated with different cardiac manifestations. We suggest considering routine screening for hyperthyroidism in patients with sarcoidosis, especially in those with cardiac involvement. Further studies are needed to investigate the impact of identifying and treating hyperthyroidism in patients with sarcoidosis.

Past studies have shown the sex-related difference in the efficacy of cardiac resynchronization therapy (CRT). However, the data for cardiac sarcoidosis (CS) are limited.The purpose of this study was to assess the sex-related prognostic differences in CS patients with CRT.This multicenter CS survey included 430 patients (295 females) who met the diagnostic criteria for CS. Patients were divided into those treated with primary CRT or upgraded CRT from the pacemaker (CRT group; n = 73) and others (control group; n = 357). Sex differences in the incidence of all-cause death, heart failure (HF) death including heart transplantation, ventricular arrhythmia events (VAEs) (sudden death, appropriate device therapy), cardiac adverse events (CAEs) (HF death, VAEs), changes in serum brain natriuretic peptide (BNP) levels, and left ventricular ejection fraction (LVEF) over the follow-up period were analyzed.During median follow-up of 5.2 years, males, but not females, in the CRT group had significantly worse all-cause mortality than patients in the control group (P.001). In the CRT group, there was no significant sex-related difference in the incidence of HF death; however, females had significantly better VAE- and CAE-free survival than males (P = .033 and P = .008, respectively). Multivariate analysis of the CRT group showed that female sex (hazard ratio 0.37; 95% confidence interval 0.15-0.89; P = .02 and P = .6) independently predicted freedom from CAEs. During follow-up, BNP levels were significantly improved in all groups. LVEF was maintained in females with CRT.In CS patients with CRT, HF death-free survival was similar between sexes. However, females exhibited better VAE- and CAE-free survival than males.

A decline in lung function is the basis of the definition of progressive fibrosing interstitial lung disease. This study aimed to evaluate the epidemiology and clinical relevance of lung function decline in sarcoidosis.This retrospective observational study was conducted at a general sarcoidosis clinic. Lung function decline was defined as a relative 24-month decline in the percentage of predicted forced vital capacity (%FVC) of ≥10% or the percentage of predicted diffusion capacity for carbon monoxide (%DLco) of ≥15%. The frequency of lung function decline and its associations with the subsequent 24-month change in lung function and survival time were analyzed.Of the 201 patients, 14 (7.0%) exhibited a 24-month decline in %FVC of ≥10% and 28 (16.6%) exhibited a 24-month decline in %DLco of ≥15%. A 24-month decline in lung function was not associated with a subsequent 24-month lung function decline. Eleven patients died during the median observational time of 148.3 months; 4 of the 11 deaths were associated with sarcoidosis. A 24-month decline in lung function was associated with worse survival even after the adjustment for composite physiological index (CPI) and pulmonary hypertension (PH): 24-month decline in %FVC ≥10%, hazard ratio (HR) adjusted for CPI = 21.8, HR adjusted for PH = 19.3 and 24-month decline in %DLco ≥15%, HR adjusted for PH = 6.74.A 24-month decline in lung function can be a risk factor for mortality in sarcoidosis irrespective of CPI and PH.

Cardiac sarcoidosis (CS) frequently leads to ventricular tachycardia (VT), which is often refractory to antiarrhythmic and/or immunosuppressive medications and requires catheter ablation. We conducted a systematic review and meta-analysis to evaluate the role of catheter ablation in patients with refractory VT undergoing catheter ablation. We searched PubMed, Embase, and Scopus databases from their inception to December 31, 2021 with search terms "cardiac sarcoidosis" AND "electrophysiological studies OR ablation." Fifteen studies were ultimately included for evaluation. Patient demographics, VT mapping, and acute and long-term procedural outcomes were extracted. A total of 15 studies were included in our meta-analysis, with a total of 401 patients, of whom 66% were male, with ages ranging from 39 to 64 years. A total of 95% of patients were on antiarrhythmics and 79% of patients were on immunosuppressants. Left ventricular ejection fraction ranged from 35% to 49% and procedure duration ranged from 269 to 462 minutes. Ablation was reported using both irrigated and nonirrigated catheter tips. A total of 25% of patients (84/339) underwent repeat ablation. Acute procedural success was achieved in 57% (161/285). Procedure complications occurred in 5.7% (17/297) procedures. VT recurrence after first ablation was 55% (confidence interval 48% to 63%, 213/401); VT recurrence after multiple ablations was 37% (81/220). The composite end point of death, heart transplant, and left ventricular assist device implantation was 21% (confidence interval 14% to 30%, 55/297). In conclusion, catheter ablation is a useful modality in patients with CS with refractory VT. However, patients with CS presenting with refractory VT after undergoing VT ablation carry a poor prognosis.

To clarify the proportion of ocular sarcoidosis with severe, refractory, and prolonged inflammation and their association with ocular complications and visual prognosis.Multicenter, retrospective, longitudinal cohort study.Three hundred and twenty-three eyes of 164 patients (45 men; 119 women) with ocular sarcoidosis who visited Hokkaido University Hospital and Yokohama City University Hospital from 2010 to 2015. We newly defined severe, refractory, and prolonged inflammation in ocular sarcoidosis, and investigated their proportions, ocular complications and final visual acuity from medical records of our sarcoidosis patients.The eyes with severe inflammation numbered 72/323 (22.3%), with refractory inflammation, 80/323 (24.8%), and with prolonged inflammation, 91/323 (28.2%). The number of eyes having neither severe, refractory, nor prolonged inflammation (defined as none) was 114/323 (35.3%). The numbers of eyes that reached irreversible visual dysfunction were 6/72 (8.3%) of those with severe inflammation, 10/80 (12.5%) with refractory inflammation, 12/91 (13.2%) with prolonged inflammation, and 4/114 (6.2%) with none. As complications, cataract (62.2%), glaucoma (28.5%), epiretinal membrane (24.1%), cystoid macular edema (22.6%), vitreous hemorrhage (2.8%), choroidal atrophy (2.5%), macular degeneration (1.2%), macular hole (0.9%) and retinal detachment (0.3%) were identified. Among them, secondary glaucoma (16 eyes) and macular degeneration (4 eyes) were major complications related to irreversible visual dysfunction.Although most of the patients with ocular sarcoidosis had a relatively good visual prognosis, some developed severe, refractory, and/or prolonged inflammation related to the development of ocular complications, that resulted in poor visual prognosis.

PurposeAlpha-melanocyte stimulating hormone (α-MSH) is known to have anti-inflammatory effects. However, the anti-inflammatory properties of α-MSH on normal bronchial epithelial cells are largely unknown, especially in the context of in vitro sarcoidosis models.MethodsWe evaluated the anti-inflammatory effects of α-MSH on two different in vitro sarcoidosis models (lung-on-membrane model; LOMM and three-dimensional biochip pulmonary sarcoidosis model; 3D-BSGM) generated from NBECs and an in vivo sarcoidosis mouse model.ResultsTreatment with α-MSH decreased inflammatory cytokine levels and downregulated type I interferon pathway genes and related proteins in LOMM and 3D-BSGM models. Treatment with α-MSH also significantly decreased macrophages and cytotoxic T-cells counts in a sarcoidosis mice model.ConclusionOur results confirm the direct role of type I IFNs in the pathogenesis of sarcoid lung granulomas and highlight α-MSH as a potential novel therapeutic agent for treating pulmonary sarcoidosis.Graphical Abstract

Sarcoidosis is a variable, multisystem granulomatous disease, which can affect many organs including the lungs, lymph nodes, and eyes. It is difficult to differentiate sarcoidosis and tuberculosis because of their similar clinical and pathological features.This study aimed to describe a sarcoidosis case with typical ocular and systemic manifestations combined with suspected tuberculosis infection.A 30-year-old Chinese man, initially diagnosed with tuberculosis, presented with typical ocular sarcoidosis during antituberculosis therapy. The ocular surface, anterior chamber, anterior chamber angle, ciliary body, vitreous, optic disc, and lacrimal gland of the patient all exhibited manifestations of sarcoidosis, although optic disc involvement has rarely been reported. Typical ocular sarcoidosis manifestations and positive responses to corticosteroid therapy of the patient helped us reach the diagnosis of systemic sarcoidosis. The patient was followed up for 48 months and showed significant improvement of miliary nodules and lymph nodes in both lungs. However, the appearance of uveitis in the right eye persisted because of nonadherence to steroid treatment.This case shows the importance of ophthalmic evaluation in the diagnosis and management of sarcoidosis and supports a possible role of Mycobacterium tuberculosis in the pathogenesis of sarcoidosis.