The Elusive Sarcoidosis, an Eight-Year Journey to the Diagnosis of Sarcoidosis: A Case Report.

We present a unique case of a patient coming to our internal medicine clinic with intermittent diffuse lymphadenopathy and non-specific symptoms for the past eight years. Initially, the patient was thought to have carcinoma of unknown primary origin, given the abnormalities seen in her imaging. The diagnosis of sarcoidosis was also dismissed, given that the patient had not responded to steroids with negative laboratory support. The patient was referred to several specialists, and only after a pulmonary biopsy was a non-caseating granuloma revealed after multiple prior failed biopsies. The patient was placed on infusion therapy and responded positively. This case demonstrates a challenging diagnosis and treatment which emphasizes the importance of considering alternative treatments if the initial therapy fails.

Exome Sequencing Reveals Genetic Variability and Identifies Chronic Prognostic Loci in Chinese Sarcoidosis Patients.

Background: Sarcoidosis is an inflammatory disease characterized by non-caseating granuloma formation in various organs, with several recognized genetic and environmental risk factors. Despite substantial progress, the genetic determinants associated with its prognosis remain largely unknown. Objectives: This study aimed to identify the genetic changes involved in sarcoidosis and evaluate their clinical relevance. Methods: We performed whole-exome sequencing (WES) in 116 sporadic sarcoidosis patients (acute sarcoidosis patients, n=58; chronic sarcoidosis patients, n=58). In addition, 208 healthy controls were selected from 1000 G East Asian population data. To identify genes enriched in sarcoidosis, Fisher exact tests were performed. The identified genes were included for further pathway analysis using Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG). Additionally, we used the STRING database to construct a protein network of rare variants and Cytoscape to identify hub genes of signaling pathways. Results: WES and Fisher's exact test identified 1,311 variants in 439 protein-coding genes. A total of 135 single nucleotide polymorphisms (SNPs) on 30 protein-coding genes involved in the immunological process based on the GO and KEGG enrichment analysis. Pathway enrichment analysis showed osteoclast differentiation and cytokine-cytokine receptor interactions. Three missense mutations (rs76740888, rs149664918, and rs78251590) in two genes (PRSS3 and CNN2) of immune-related genes showed significantly different mutation frequencies between the disease group and healthy controls. The correlation of genetic abnormalities with clinical outcomes using multivariate analysis of the clinical features and mutation loci showed that the missense variant (rs76740888, Chr9:33796673 G>A) of PRSS3 [p=0.04, odds ratio (OR) = 2.49] was significantly associated with chronic disease prognosis. Additionally, the top two hub genes were CCL4 and CXCR4 based on protein-protein interaction (PPI) network analysis. Conclusion: Our study provides new insights into the molecular pathogenesis of sarcoidosis and identifies novel genetic alterations in this disease, especially PRSS3, which may be promising targets for future therapeutic strategies for chronic sarcoidosis.

Muscular sarcoidosis in the eyes of 18 F-FDG PET/CT.

PURPOSE: The aim of this study was to determine the frequency, symptoms, activity and pattern of muscle sarcoidosis, correlation with laboratory parameters, and to assess its therapy response with 18 F-FDG PET/CT. METHODS: Study included 90 patients with biopsy confirmed sarcoidosis and symptoms/biochemical/imaging findings suggestive of active disease. The exclusion criteria were: presence of cancer or other diseases that resemble sarcoidosis on PET/CT (Wegener syndrome, tuberculosis, aspergillosis), and the glucose level being greater than 11 mmol/L. All patients were screened for muscle sarcoidosis with 18 F-FDG PET/CT examination. Follow-up examination was done 1 year after the baseline in order to evaluate therapy response. RESULTS: Disease was very rare and present in only 7/90 patients. Most of the patients had polysymptomatic disease, while muscle pain was less frequent, present only in one-third of the patients. The disease was usually present in the lower limbs, upper limbs, and skeletal striated muscles. The most common pattern of disease was nodular. Disease activity estimated with SUVmax was not in correlation with the ACE findings, creatine kinase, and aldolase levels (p > 0.05). Follow-up PET/CT revealed complete remission in one patient and partial remission in two. CONCLUSION: 18 F-FDG PET/CT can be useful in asymptomatic young patients with nodular pattern of disease, who have easily relapsing form of disease. It can help in further management of these patients and can affect prognosis of the disease, since most of the laboratory parameters in this entity are within normal limits.

Lupus Pernio in Chronic Sarcoidosis.

Lupus pernio (LP) is characterized by the association between insidious purpuric or purplish blue lesions localized in the nose, cheeks, lips, and ears and swelling of the fingers and toes. We report a case of chronic sarcoidosis with lupus pernio in a 34-year-old male. The diagnosis of sarcoidosis was made on the basis of clinical data and imaging results and confirmed by skin biopsy, which showed numerous epithelioid granulomas surrounded by a non-caseous inflammatory crown. Treatment with prednisolone was started. It is important to make an early diagnosis to avoid a delay in treatment and worsening of the functional and psychological prognosis.

Safety and efficacy of abatacept in patients with treatment-resistant SARCoidosis (ABASARC) - protocol for a multi-center, single-arm phase IIa trial.

INTRODUCTION: Sarcoidosis is a granulomatous systemic disease that becomes chronic in approximately one third of affected patients resulting in quality of life and functional impairment. Immunosuppressive drugs other than steroids represent alternative therapeutic options, but side effects like liver and bone marrow toxicity or increased susceptibility to infections limit their use. Pathophysiological studies in sarcoidosis patients demonstrate altered regulatory T-cell functions with a reduced expression of CTLA-4 (CD152) and prolonged inflammation. Therefore, interfering with CTLA-4 using abatacept might be a therapeutic option in sarcoidosis similar to rheumatoid arthritis therapy. METHODS/DESIGN: This is a multicenter prospective open-labeled single arm phase II study addressing the safety of abatacept in sarcoidosis patients. 30 patients with chronic sarcoidosis requiring immunosuppressive therapy beyond 5 mg prednisolone equivalent will be treated with abatacept in combination with corticosteroids for one year in two centers.The primary endpoint is the number and characterization of severe infectious complications under treatment with abatacept.Secondary endpoints are the rate of all infections, patient-related outcomes (assessed by questionnaires), lung function and immunological parameters including alveolar inflammation assessed by bronchoaveolar lavage. DISCUSSION: This is the first trial of abatacept in patients with sarcoidosis. It is hypothesized that administration of abatacept is safe in patients with chronic sarcoidosis and can limit ongoing inflammation. Patients' wellbeing is assessed by established questionnaires. Immunological work-up will highlight the effect of abatacept on inflammatory pathways in sarcoidosis. TRIAL REGISTRATION: The trial has been registered at the German Clinical Trial Registry (Deutsches Register Klinischer Studien, DRKS) with the identity number DRKS00011660.

Hybrid Imaging in Head and Neck Sarcoidosis.

Abstract: To determine the prevalence of head and neck sarcoidosis (HNS) and evaluate the role of hybrid molecular imaging in HNS. Between 2010 and 2018, 222 patients with chronic sarcoidosis and presence of prolonged symptoms of active disease were referred to FDG PET/CT. Active disease was found in 169 patients, and they were all screened for the presence of HNS. All patients underwent MDCT and assessment of the serum ACE level. Follow-up FDG PET/CT examination was done 19.84 ± 8.98 months after the baseline. HNS was present in 38 out of 169 patients. FDG uptake was present in: cervical lymph nodes (38/38), submandibular glands (2/38), cerebrum (2/38), and bone (1/38). The majority of patients had more than two locations of disease. After FDG PET/CT examination, therapy was changed in most patients. Fourteen patients returned to follow-up FDG PET/CT examination in order to assess the therapy response. PET/CT revealed active disease in 12 patients and complete remission in two patients. Follow-up ACE levels had no correlation with follow-up SUVmax level (ρ = -0.18, p = 0.77). FDG PET/CT can be useful in the detection of HNS and in the evaluation of the therapy response. It may replace the use of non-purposive mounds of insufficiently informative laboratory and radiological procedures.

Hybrid Imaging in Evaluation of Abdominal Sarcoidosis.

OBJECTIVE: To determine the prevalence of abdominal involvement, distribution pattern and evaluate role of hybrid molecular imaging in patients with abdominal sarcoidosis. METHODS: Between January 2010 and December 2011, 98 patients with chronic sarcoidosis and presence of prolonged symptoms or other findings suggestive of active disease were referred to FDG PET/CT examination. Active disease was found in 82 patients, and they all were screened for the presence of abdominal sarcoidosis on FDG PET/CT. All patients also underwent MDCT and assessment of serum ACE level. Follow up FDG PET/CT examination was done 12.3±5.4 months after the baseline. RESULTS: Abdominal sarcoidosis was present in 31/82 patients with active sarcoidosis. FDG uptake was present in: retroperitoneal lymph nodes (77%), liver (26%), spleen (23%), adrenal gland (3%). Majority of patients had more than two locations of disease. Usually thoracic disease was spread into the extrathoracic localizations, while isolated abdominal sarcoidosis was present in 10% of patients. After first FDG PET/CT examination therapy was changed in all patients. Eleven patients came to the follow up examination where SUVmax significantly decreased in the majority of them. Three patients had total remission, three had absence of abdominal disease but discrete findings in thorax and others had less spread disease. ACE levels did not correlate with SUVmax level. CONCLUSION: FDG PET/CT can be a useful tool for detection of abdominal sarcoidosis and in the evaluation of therapy response in these patients. Awareness of the presence of intra-abdominal sarcoidosis is important in order to prevent long-standing unrecognized disease.

FDG PET/CT in bone sarcoidosis.

BACKGROUND: Bone sarcoidosis is rare manifestation of disease usually accompanied with pulmonary involvement. Until today, exact prevalence of bone sarcoidosis is not known, since reported prevalence varies widely depending on the studied population and the used diagnostic techniques. OBJECTIVE: To determine the prevalence of bone involvement and distribution pattern in active chronic sarcoidosis by using FDG PET/CT. METHODS: Between January 2010 and December 2011, 98 patients with chronic sarcoidosis and presence of prolonged symptoms or other findings suggestive of active disease were referred to FDG PET/CT examination. Active disease was found in 82 patients, and they all were screened for presence of bone sarcoidosis on FDG PET/CT. All patients also underwent MDCT and assessment of serum ACE level. RESULTS: Bone sarcoidosis was present in 18/82 patients with active sarcoidosis. FDG uptake in bones was focal in 8 (44.4%), diffuse in 6 (33.3%) and both diffuse and focal in 4 (22.2%) patients. CT indicated bone abnormalities only in 5% patients. Osseous involvement was present in: pelvis (61.1%), vertebrae (44.4%), ribs (27.8%) and bone marrow (16.7%). Some patients had two or more locations of disease. Follow-up FDG PET/CT showed normal findings in two patients, same localization of active disease in four patients and progression of disease in one. CONCLUSION: In patients with active chronic sarcoidosis 22% of patients had osseous abnormalities on FDG PET/CT that mostly were not detected on CT.