A 44-year-old Caucasian man presented to an outpatient clinic with a 2-month history of fatigue, night sweats, weight loss, loss of appetite, and mild abdominal discomfort. The patient did not have fever, chills, cough, nausea, vomiting, itching, urinary, or bowel symptoms. The patient had a past medical history significant for biopsy-proven sarcoidosis of the mediastinal lymph nodes, which was diagnosed 9 years prior. At that time, the patient had hilar lymphadenopathy seen on a routine chest radiography. The disease seemed inactive, as the patient never had symptoms related to sarcoidosis nor received treatment throughout the years. He also had a history of hypertension, hyperlipidemia, bipolar disorder, coronary artery disease with percutaneous coronary intervention performed a month prior to the current presentation, as well as a recently diagnosed type 2 diabetes mellitus. His regular home medications included amlodipine, metoprolol tartrate, lisinopril, lamotrigine, clopidogrel, metformin, rosuvastatin, and sildenafil. The patient denied any history of alcohol or tobacco use and stated that he used to work as a secretary.
On physical examination, the vital signs were normal. Body mass index was 37.2 kg/m2, and weight was 263 pounds. The general, lung, heart, and abdominal examinations were unremarkable, and no palpable lymphadenopathy was identified. A battery of laboratory tests were performed and revealed the following: alanine aminotransferase and aspartate aminotransferase levels were within normal limits; however, the alkaline phosphatase (ALP) and gamma-glutamyl transferase (GGT) levels were elevated (ALP = 258 U/L, reference = 38-126 U/L; GGT = 274 U/L, reference = 12-73 U/L). He was also found to have hyperbilirubinemia (total bilirubin was 1.7 mg/dL, reference = 0.0-1.3 mg/dL, and direct bilirubin was 0.7 mg/dL, reference = 0.0-0.3 mg/dL). The total protein, albumin, serum creatinine, and calcium levels were within normal limits. Further workup including ceruloplasmin, serum iron saturation, lactate dehydrogenase, serum angiotensin converting enzyme level, and erythrocyte sedimentation rate were normal. Alpha-1 antitrypsin antigen, a viral hepatitis panel, and anti-mitochondrial and anti-smooth muscle antibodies were negative. A slight elevation in beta2-microglobulin levels were noted (3.2 mg/L, reference = 0.8-2.34 mg/L).
Ultrasound examination of the abdomen was negative for common bile duct dilatation but showed a 3.5 x 4.1 cm abdominal mass at the head of pancreas. Computed tomography (CT) scan of the abdomen and pelvis with intravenous contrast demonstrated cirrhotic appearance of the liver with steatosis, with enhancing hepatic masses, splenomegaly, and multiple enlarged lymph nodes in the periaortic and portocaval areas. The largest lymph node was measured at 7.2 x 4.3 cm in diameter in the precaval area. There was, however, no visible pancreatic lesions, biliary duct dilatation, or gallbladder stones (Figure 1).
Histopathological examination of a transjugular liver biopsy showed expanded portal areas containing occasional granulomas with the majority of the granulomas appear non-necrotizing, with a few demonstrating central necrosis. Mild macrovascular steatosis and chronic inflammation is noted (Figure 2). Auramine-rhodamine and GMS stains was negative for acid-fast bacilli and fungal organisms. Staining for iron and immunoglobulin G4 was negative.
Evaluation for other etiologies of abdominal lymphadenopathy was performed to exclude malignancies and infectious granulomatous diseases. Infectious workup for granulomatous hepatitis was negative for Histoplasma, Bartonella, tuberculosis, and Coxiella burnetii (Q fever). An autoimmune workup including ANA, ANCA, immunoglobulin G4, complement C3, and complement C4 levels was performed and was unremarkable.
A provisional diagnosis of hepatic sarcoidosis and nonalcoholic steatohepatitis was procured based on the biopsy results. Unfortunately, at that time the patient refused steroid treatment as well as immunosuppressive therapy; however, he agreed to ursodeoxycholic acid 1500 mg daily to help with itching.
Two months later, the patient started to complain of excruciating pain in his lower back with radiation to his thighs and legs, in addition to diffuse joint pain. His loss of appetite and fatigue did not improve significantly, and he continued to lose weight. A whole body positron emission tomography-CT scan showed extensive hepatic uptake, hypermetabolic lymphadenopathy involving the chest, cervical, supraclavicular regions, upper abdominal, retroperitoneal, iliac chain, and inguinal lymph nodes, as well as numerous fluorodeoxyglucose-avid osseous lesions involving the thoracic and lumbar spine, left proximal humerus, left scapula, pelvis, and proximal right femur. There was a concern of metastatic bone disease given the widespread distribution of the lesions (Figure 3). Evaluation with spine, pelvis, and upper extremity, magnetic resonance imaging (MRI) showed multiple small marrow lesions involving the vertebral bodies in the thoracic and lumbar spine, with small spotty lesions noted in the sacrum, pelvis, hips, ribs, and humerus on the left. MRI of the brain showed no evidence of neurosarcoidosis. An ophthalmologist evaluated the patient, and ocular involvement was ruled out. The patient underwent a bone biopsy of the T12 vertebra, which revealed benign trabecular bone with replacement of the marrow space with numerous non-necrotizing granulomas and fibrosis consistent with diagnosis of vertebral sarcoidosis (Figure 4).
Of note, while this extensive workup was taking place, the patient developed a sudden onset of left flank pain and hematuria. There was a small left ureteric stone on abdominal imaging identified. He underwent laser lithotripsy and left ureteral stent placement.
The patient agreed to immunosuppression and was started on methotrexate 20 mg subcutaneously once weekly, folic acid 1 mg daily, and prednisone 5 mg daily as treatment for systemic sarcoidosis. However, 2 months later, he developed actinomycosis skin infection of the groin. Methotrexate was held, and he was treated with amoxicillin until the infection resolved. The patient was restarted on methotrexate. Two months after restarting methotrexate, the patient reported significant clinical improvement of his pain, loss of appetite, and has gained 40 pounds since the start of methotrexate. His liver enzymes improved significantly. A repeat positron emission tomography-CT scan demonstrated a decrease in the lymph nodes, bone, and hepatic lesions size.