Frontal swelling – An unusual presentation of sarcoidosis: A case report

Subcutaneous sarcoidosis is a rare, cutaneous expression of systemic sarcoidosis. It is observed as asymptomatic firm, nodules covered by normal-appearing skin, principally on the extremities, which show the typical histopathology appearance of non-caseating granulomas localized to the subcutaneous tissue. It may be associated with the early benign, hilar lymphadenopathy of sarcoidosis or with the later stages of progressive sarcoidosis. Here, we report a case of subcutaneous sarcoidosis, which presented as an asymptomatic, forehead swelling with involvement of skull bone and lung. We report this case since subcutaneous sarcoidosis on the face with involvement of skull bone is a rarity.

First Report of Two Cases of Löfgren’s Syndrome after SARS-CoV-2 Vaccination-Coincidence or Causality?

Sarcoidosis can present as an acute form or take a chronic course. One of the acute presentations is Löfgren’s syndrome (LS), consisting of the symptom triad of bilateral hilar lymphadenopathy, erythema nodosum, and ankle periarthritis. In addition, there are occasional reports of sarcoid-like reactions following drug exposures. Nevertheless, reports of sarcoidosis or LS after vaccination have not been published. Here, we report two cases of de novo LS in a temporal association with different vaccines against the new coronavirus SARS-CoV-2. One patient developed the first symptoms three days after the second vaccination (first vaccination ChadOx-1, Astra Zeneca; second vaccination CX-024414, Moderna); in the second patient, symptoms started 28 days after the first vaccination (ChadOx-1, Astra Zeneca). Both patients eventually required treatment with glucocorticoids. Both patients achieved clinical improvement with treatment. In conclusion, we report the first two cases of LS shortly after SARS-CoV-2 vaccination.

Mediastinal/hilar lymphadenopathy: A possibly overlooked variable in the classification of lung nodules

Background Clinical prediction models to classify lung nodules often exclude patients with mediastinal/hilar lymphadenopathy, although the presence of mediastinal/hilar lymphadenopathy does not always indicate malignancy. Herein, we developed and validated a multimodal prediction model for lung nodules in which patients with mediastinal/hilar lymphadenopathy were included. Methods A total of 359 patients with pulmonary nodules were considered for enrollment in the study. We developed and validated a logistic regression model including patients with mediastinal/hilar lymphadenopathy. Discrimination of the model was assessed by area under the operating curve. Goodness of fit was performed via the Hosmer-Lemeshow test, and a nomogram of the logistic regression model was drawn. Results There were 311 cases included in the final analysis. A logistic regression model was developed and validated. There were nine independent variables included in the model. The AUC of the training and validation sets was 0.93 (95% CI, 0.90–0.97) and 0.91 (95% CI, 0.85–0.98), respectively. In the validation set with or without mediastinal/hilar lymphadenopathy, the AUC was 0.95 (95% CI, 0.90–0.99) and 0.91 (95%CI, 0.87–0.95), respectively. The Hosmer-Lemeshow goodness-of-fit statistic was 0.22. A nomogram was drawn to visualize the model. Conclusions We developed and validated a multimodal risk prediction model for lung nodules with excellent discrimination and calibration, regardless of the inclusion of mediastinal/hilar lymphadenopathy. This broadens the application of lung nodule prediction models. Furthermore, the presence of mediastinal/hilar lymphadenopathy added value for predicting lung nodule malignancy, highlighting the importance of this variable in clinical practice.

Childhood Intra-Thoracic Tuberculosis Clinical Presentation Determines Yield of Laboratory Diagnostic Assays

Diagnosis of intra-thoracic tuberculosis (ITTB) in children is difficult due to the paucibacillary nature of the disease, the challenge in collecting appropriate specimens, and the low sensitivity of smear microscopy and culture. Culture and Xpert MTB/RIF provide higher diagnostic yield in presumptive TB in adults than in children. Current study was designed to understand poor yield of diagnostic assays in children. Children with presumptive ITTB were subjected to gastric aspirates and induced sputum twice. Samples were tested by Ziehl-Neelsen stain, Xpert MTB/RIF-assay, and MGIT-960 culture. Subjects were grouped as Confirmed, Unconfirmed, and Unlikely TB, and classified as progressive primary disease (PPD, lung parenchymal lesion), and primary pulmonary complex (PPC, hilar lymphadenopathy) on chest X-ray. Of children with culture-positive TB 51/394 (12.9%), culture-negative TB 305 (77.4%), and unlikely TB 38 (9.6%), 9 (2.3%) were smear positive, while 95 (24.1%) were Xpert-MTB/RIF positive. Xpert-MTB/RIF detected 40/51 culture confirmed cases (sensitivity 78.4% and NPV 96.3%). Culture was positive in more children presenting as PPD (p < 0.04). In culture-negative TB group, Xpert positivity was seen in 31% of those with PPD and 11.9% in those with PPC (p < 0.001).Conclusion: Xpert-MTB/RIF improved diagnosis by 2-fold and increased detection of MDR-TB. Both liquid culture and Xpert-MTB/RIF gave higher yield in children with lung parenchymal lesions. Children with hilar lymphadenopathy without active lung parenchymal lesions had poor diagnostic yield even with sensitive nucleic acid amplification tests, due to paucibacillary/localized disease, suggesting possible utility of invasively collected samples in early diagnosis and treatment.

Transcriptomics of bronchoalveolar lavage cells identifies new molecular endotypes of sarcoidosis

Sarcoidosis is a multisystem granulomatous disease of unknown origin with a variable and often unpredictable course and pattern of organ involvement. In this study we sought to identify specific bronchoalveolar lavage (BAL) cell gene expression patterns indicative of distinct disease phenotypic traits.RNA sequencing by Ion Torrent Proton was performed on BAL cells obtained from 215 well characterised patients with pulmonary sarcoidosis enrolled in the multicenter Genomic Research in Alpha-1 Antitrypsin Deficiency and Sarcoidosis (GRADS) study. Weighted Gene Co-expression Network Analysis (WGCNA) and non-parametric statistics were used to analyse genome wide BAL transcriptome. Validation of results was performed using a microarray expression data set of an independent sarcoidosis cohort (Freiburg, Germany (n=50)).Our supervised analysis found associations between distinct transcriptional programs and major pulmonary phenotypic manifestations of sarcoidosis including TH1 and TH17 pathways associated with hilar lymphadenopathy, TGFB1 and MTOR signaling with parenchymal involvement, and IL7 and IL2 with airway involvement. Our unsupervised analysis revealed gene modules that uncovered four potential sarcoidosis endotypes including hilar lymphadenopathy with increased acute T cell immune response; extraocular organ involvement with PI3 K activation pathways; chronic and multiorgan disease with increased immune response pathways; and multiorgan with increased IL-1 and IL-18 immune and inflammatory responses. We validated the occurrence of these endotypes using gene expression, pulmonary function tests and cell differentials from Freiburg. Taken together our results identify BAL gene expression programs that characterise major pulmonary sarcoidosis phenotypes and suggest the presence of distinct disease molecular endotypes.

Acute arthritis, skin rash and Lofgren’s syndrome

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.

An Orbital Mass Partially Responsive to Steroid

A 68 year old woman presented with a progressively enlarging orbital mass. MRI of her brain and orbits was consistent with an orbital pseudotumor. Although there was some improvement in the patient’s pain and the size of the mass, it did not fully resolve.The patient had a biopsy demonstrate non-caseating granulomatous inflammation. A chest X-ray and CT chest demonstrated bilateral hilar lymphadenopathy. Further examination and interviewing of the patient revealed several months of joint paints and lower extremity nodules. The patient was diagnosed with orbital sarcoidosis and was started on methotrexate by a rheumatologist

Use of immune checkpoint inhibitors in cancer patients with pre-existing sarcoidosis

Aim: To evaluate adverse events in cancer patients with pre-existing sarcoidosis receiving immune checkpoint inhibitors (ICIs). Patients & methods: We retrospectively reviewed cancer patients with sarcoidosis who underwent treatment with ICI to determine frequency of sarcoidosis flares. Results: 32 patients with sarcoidosis received ICIs The median time to ICI initiation was 7 years (range: 1 month to 51 years). One patient (3%) with a 20-year remote history of sarcoidosis developed a clinically symptomatic exacerbation after three doses of atezolizumab, with hilar lymphadenopathy, subcutaneous nodules, arthritis and uveitis. Atezolizumab was discontinued and prednisone initiated. She had a fluctuating course with two additional flares. Conclusion: Frequency of flares in patients with a remote history of sarcoidosis who receive ICIs is low.