Associations between occupational and environmental exposures and organ involvement in sarcoidosis: a retrospective case-case analysis

Background Sarcoidosis most commonly affects lungs and intrathoracic lymph nodes, but any other organ can be involved. In epidemiological studies, many occupational and environmental exposures have been linked to sarcoidosis but their relationship with the disease phenotype has barely been studied. Objective To investigate how occupational and environmental exposures prior to diagnosis relate to organ involvement in patients with sarcoidosis Methods We retrospectively studied patients seen at a sarcoidosis clinic between 2017 and 2020. Patients were included if they had a clinical presentation consistent with sarcoidosis and histologically confirmed epithelioid granulomas or had Löfgren syndrome. In a case–case analysis using multivariable logistic regression we calculated odds ratios (OR) of prespecified exposure categories (based on expert ascertainment) for cases with a given organ involvement versus cases without this organ involvement. Results We included 238 sarcoidosis patients. Sarcoidosis limited to pulmonary involvement was associated with exposure to inorganic dust prior to diagnosis (OR 2.11; 95% confidence interval [CI] 1.11–4.17). Patients with liver involvement had higher odds of contact with livestock (OR 3.68; 95% CI 0.91–12.7) or having jobs with close human contact (OR 4.33; 95% CI 1.57–11.3) than patients without liver involvement. Similar associations were found for splenic involvement (livestock: OR 4.94, 95% CI 1.46–16.1; close human contact: OR 3.78; 95% CI 1.47–9.46). Cardiac sarcoidosis was associated with exposure to reactive chemicals (OR 5.08; 95% CI 1.28–19.2) or livestock (OR 9.86; 95% CI 1.95–49.0). Active smokers had more ocular sarcoidosis (OR 3.26; 95% CI 1.33–7.79). Conclusions Our study indicates that, in sarcoidosis patients, different exposures might be related to different organ involvements—hereby providing support for the hypothesis that sarcoidosis has more than one cause, each of which may promote a different disease phenotype.

Bilateral leg swelling as the presenting symptom of Löfgren syndrome in a paediatric patient: a rare presentation of a rare paediatric disease

A 17-year-old previously healthy man presented with a 4-week history of progressive bilateral leg swelling with discomfort and erythema, but no signs of arthritis or erythema nodosum. An incidental finding of a query pulmonary nodule on chest X-ray prompted chest CT for further evaluation, revealing bilateral hilar and mediastinal lymphadenopathy. The patient then underwent endobronchial ultrasound and transbronchial needle aspiration biopsies of mediastinal lymph nodes. Biopsies and bronchoalveolar lavage samples were negative for microbiology, including mycobacterial culture. Pathology demonstrated non-caseating granulomas consistent with a diagnosis of sarcoidosis. Weeks later, he developed arthralgias of the left metacarpophalangeal joints and erythema nodosum and was diagnosed with Löfgren syndrome, a phenomenon rarely described in the paediatric population. This case highlights an approach to lower extremity swelling as well as hilar lymphadenopathy in the paediatric population. In addition, it emphasises the importance of multidisciplinary teamwork for accurate and timely diagnoses.

Löfgren Syndrome with Hypercalcemia and Neuroendocrinological Involvement: A Case Report

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.