A 45-year-old never-smoking male of Danish origin, without any medical history, was referred acutely to our emergency department with abdominal pain, vomiting, and jaundice. He denied alcohol use and had no predisposition to cancer, pulmonary, or gastrointestinal (GI) diseases. As a gardener, he had no relevant occupational exposures. During the last 4 weeks, he had suffered from a lack of appetite, dull pain in the right upper abdominal quadrant, and had an unintended weight loss of 10 kg. He denied any respiratory symptoms, change in bowel habits, melena, or fever.
At physical examination, he was chronically ill with a body mass index of 18, jaundice and abdominal pain on palpation of the upper abdominal quadrant. Pulmonary and cardiac auscultation was normal and no exanthema was present.
Laboratory tests showed leucopenia of 2.50x109/L (3.50-8.80x109/L) and increased liver enzymes tests with alanine transaminase of 441 IU/L (10-70 IU/L), alkaline phosphatase of 194 IU/L (35-105 IU/L), bilirubin of 196 micromol/l (5-25 micromol/L), and lactate dehydrogenase of 218 U/L (105-205 U/L). Pancreas amylase, gamma-glutamyl transferase, C-reactive protein, haemoglobin, thrombocyte concentration, calcium, and creatinine were within normal limits. Because of the liver involvement, hepatitis was suspected, but serology test for Hepatitis A, B, C, HIV, and Leptospirosis were negative. There were normal immunoglobulin subgroups and autoimmunological tests, including anti-nuclear and anti-neutrophil cytoplasmic antibodies, which were negative. However, an increased blood angiotensin-converting enzyme (ACE) above 88 U/L (8-53 U/L) was observed.
Lung function tests showed normal ventilation and diffusion parameters with forced expiratory volume in 1 second (FEV1) of 4.4l, corresponding to 102% of predicted; forced vital capacity (FVC) of 5.7l, corresponding to 105% of predicted; and lung diffusion of carbon monoxide (DLCO) corresponding to 85% of predicted. Total lung capacity was not measured.
Because of the biochemical signs of hepatitis, an abdominal sonography was performed, uncovering lymphadenopathy in the lever hilus. The patient underwent computer tomography (CT) of thorax and abdomen, which revealed lesions in the pancreas, bilateral pulmonary nodular infiltrates, as well as mediastinal and intraabdominal lymphadenopathy (Figs. 1-3).
As metastatic cancer was suspected, a whole-body 18 flour-deoxyglucose positron emission tomography (18-FDG PET) scanning was performed, presenting multiple pathological lesions in lungs, pancreas, lymph nodes, and bones (Fig. 4).
A sonography-guided lever biopsy showed non-caseating granulomatous inflammation. The patient underwent further invasive procedures: bronchoscopy with transbronchial biopsy (TBB), bronchoalveolar lavage (BAL) with flowcytometry, endobronchial ultrasound (EBUS) with transbronchial needle aspiration (TBNAB) biopsy, and a bone marrow biopsy. None of the pathological tests revealed any malignant findings. Bronchoscopy was without any macroscopic abnormalities. BAL flowcytometry uncovered an overall lymphocytic inflammation with a proportion of 51%, an increased CD4/CD8 ratio of 5.4 without any eosinofilia or neutrofilia. Pathological evaluation of the samples from the TBBs demonstrated non-caseating granulomas and EBUS-TBNAB from the mediastinal lymph nodes showed unspecific fibrosis. Microbiological tests from the bronchoscopy specimens did not reveal any respiratory infection (no growth of bacteria in cultivation, negative tuberculosis tests including cultivation, negative PCR tests concerning Legionella pneumophila, Mycoplasma pneumonia, Chlamydia psittaci et pneumoniae, and Pneumocystis jirovecii).
We considered the following differential diagnoses: metastatic malignancy with unknown primary tumour, liver diseases (hepatitis, both infectious and autoimmune, biliary cirrhosis, and primary sclerosing cholangitis), infectious diseases (leptospirosis, AIDS, and tuberculosis), and autoimmune systemic diseases.
Based on the composite findings (increased blood ACE, various FDG metabolic active lesions in the PET-scanning, non-caseating inflammation in liver biopsy and TBBs, lymphocytic inflammation with increased CD4/CD8 ratio in BAL) and exclusion of other diseases capable of producing a similar pathological and clinical picture, a diagnosis of systemic sarcoidosis was well established.
The patient was treated with systemic prednisolone (0.5 mg/kg/day=37.5 mg/day), slowly tapering every third week (25 mg/day for 3 weeks, then 12.5 mg for 3 weeks), until a fixed dose of 7.5 mg prednisolone/day was reached. Three weeks into the treatment, blood tests showed normalised ACE and liver function parameters. At present we follow him in our respiratory outpatient clinic and plan to fully taper steroids according to the disease activity.
CT Thorax showing bilateral pulmonary nodular infiltrates.