Workup For Infectious Etiologies Research Articles

S2972 Disseminated Herpes Simplex Virus: A Diagnostic Enigma

Introduction: Disseminated Herpes Simplex Virus (HSV) is rare but is associated with up to 50% mortality, especially in immunocompromised patients and pregnant women in whom the diagnosis is often missed. In pregnant women, it can cause fulminant liver failure and can lead to fetal demise in some cases. We describe a case of disseminated HSV in a pregnant woman with no known active disease prior to pregnancy. Case Description/Methods: A 28-year-old healthy female presented at 26 weeks gestation with fever, chills and back pain. Initial labs were concerning for pyelonephritis and antibiotics were initiated. Despite broad spectrum antibiotics, she had persistent fever and workup for infectious etiology was broadened to include HIV, CMV, EBV, toxoplasma, syphilis, which were all negative. She developed worsening transaminases with AST 384 U/L and ALT 220 U/L. Viral hepatitis serologies and, due to her recent travel to Lyme endemic area, arbovirus serology was tested, which were all negative. She subsequently developed thrombocytopenia and worsening hypertension raising concern for HELLP syndrome and underwent emergent cesarean section. Postpartum course was complicated by persistent fevers and concern for chorioamnionitis; however, she continued to have worsening transaminases (AST 2632, ALT 1000). Computed tomography abdomen found numerous liver lesions concerning for abscesses or metastases. Liver biopsy found microvesicular steatosis consistent with HELLP syndrome. She developed worsening thrombocytopenia, coagulopathy (INR 2) and rising LDH, which was concerning for disseminated intravascular coagulation. She was started on plasma exchange and N-acetylcysteine. HSV PCR serology was tested which returned positive for HSV-2 and she was started on acyclovir. Lumbar puncture returned positive for HSV confirming disseminated HSV. Her course was complicated by encephalopathy that eventually improved and she was able to be discharged on a 21-day course of acyclovir. Transaminases and coagulopathy improved with treatment of disseminated HSV. Discussion: Disseminated HSV has a high mortality in pregnancy but can be missed due to the rarity of the condition. Early diagnosis and administration of acyclovir decreases mortality. A high index of suspicion is necessary, and it should remain in the differential diagnosis in pregnant and postpartum patients with acute hepatitis and even considered in patients with elevated transaminases without any overt history or skin lesions concerning for HSV as in this patient.

Do Not Miss MEN 1 Screening When Patients Are Newly Diagnosed With Pancreatic Neuroendocrine Tumor

Abstract Background: Multiple endocrine neoplasia type 1(MEN 1) is a rare genetic disorder characterized by the combined occurrence of parathyroid, pituitary, and duodeno-pancreatic neuroendocrine tumors (NETs) along with other characteristic tumors. Here, we present a patient with history of pancreatic NET who presented 2 years after her initial diagnosis with primary hyperparathyroidism and prolactinoma, consistent with MEN 1. Case Report: A 60-year-old African American woman was admitted to our hospital with nausea, vomiting and headache for a week. On presentation, she was found to be hypotensive and tachycardic, both responded to IV fluids. Workup for infectious etiology came back negative. Her physical exam was benign except for dry oral mucosa, dry skin and epigastric tenderness. Laboratory evaluation showed serum calcium 11.8 mg/dL (8.4 - 10.2 mg/dL), which prompted further work up. Her PTH level was 1,079 pg/ml (8.5 - 72.5 pg/ml), Phosphorus 2.1 mg/dL (2.3 - 4.7 mg/dL), and 25 Hydroxy Vitamin D 10.2 ng/ml (7.4 - 44.0 ng/ml). Additional history and review of her records revealed she was hospitalized 2 years earlier with nausea, vomiting and abdominal pain. Then she was found to have esophageal and gastric ulcers on EGD. Endoscopic ultrasound revealed an 8 mm hypoechoic lesion in the body of pancreas found to be a pancreatic NET on biopsy. She had elevated gastrin level of 470 pg/ml (0 - 115 pg/ml) and was diagnosed with a gastrinoma. She was discharged on a PPI and was lost to follow up. Patient had no significant family history. Given her past history and current presentation, we assessed her pituitary hormonal function which was unremarkable except for prolactin level of >1,000 ng/ml (post-menopausal 1.8 - 20.3 ng/ml). Pituitary MRI showed a 1.8 cm macroadenoma. The optic nerve and optic chiasm were normal. Based on her clinical presentation and radiologic findings, she was diagnosed with MEN 1. Her Calcium level trended down with IV hydration, and her presenting symptoms resolved. She was started on bromocriptine, pantoprazole and vitamin D and was discharged with out-patient appointments scheduled with gastroenterology and endocrinology clinics. Conclusion: This case highlights the importance of having a high index of suspicion to prompt screening for MEN 1 in patients newly diagnosed with a pancreatic NET. Early diagnosis and timely treatment of the associated disease conditions in MEN 1 can prevent significant morbidity and mortality associated with these conditions.

S2745 Thinking Outside the Box: Is This Really NASH?

INTRODUCTION: Nonalcoholic steatohepatitis (NASH) is a diagnosis of exclusion and an alternative diagnosis should always be sought. We present a patient with features of portal hypertension and possible sepsis, concerning for decompensated NASH cirrhosis. He was eventually diagnosed with a hemophagocytic syndrome-associated variant of intravascular large B-cell lymphoma on autopsy. CASE DESCRIPTION/METHODS: A 64-year-old Caucasian male with metabolic syndrome presented with a 2-month history of fatigue, fevers, and 20-pound weight loss. Initial work-up was notable for an elevated AST (65 IU/L) and high total bilirubin (2 mg/mL; direct 1.3 mg/mL). Albumin was 3.2 g/dL, INR was 1.0 and platelets were 48,000 cells/mL. CT imaging showed mild hepatosplenomegaly with no ascites. He had no known history of liver disease or alcohol use. He was referred to the liver clinic for possible chronic liver disease and portal hypertension, thought to be from NASH. At the time of presentation, he was febrile (101.8 °F), tachycardic (105 bpm), and hypotensive. Besides hepatosplenomegaly, there were no other stigmata of chronic liver disease on exam. Admission labs were unchanged except an increase in total bilirubin (4 mg/mL) and a high ferritin (2400 ng/ml). Work-up for infectious etiologies, autoimmune liver serologies and drug toxin screen were unrevealing. He met 5 out of 8 criteria to diagnose hemophagocytic lymphohistiocytosis (HLH) including fever, splenomegaly, cytopenia, increased ferritin, and absent NK cell function. A PET scan showed uptake in the bone marrow, liver, spleen and lymph nodes. The patient rapidly declined clinically and died from respiratory failure. Autopsy showed diffuse involvement of the liver, spleen, bone marrow, lymph nodes and several other organs by intravascular large B-cell lymphoma (IVBCL). DISCUSSION: Our case emphasizes the importance of considering a broad differential in patients with thrombocytopenia and hepatosplenomegaly, even if typical risk factors for liver cirrhosis are present. Hematological malignancies should be strongly considered in the differential especially if patients present with B symptoms. Hemophagocytic syndrome-associated variant of IVBCL, the so-called ‘Asian variant’, is a rare and aggressive form of diffuse large B cell lymphoma. A prompt diagnosis is crucial, given its life-threatening potential and possibility of recovery with institution of therapy early in the course of the disease.Figure 1.: The cut sections of the liver looked relatively normal and did not show any gross evidence of cirrhosis.Figure 2.: Histology of the liver, which shows intravascular infiltration of tumor cells.

SUN-327 Hypercalcemia and Hypoglycemia Due To EBV-Associated Lymphoma

Background: Hypercalcemia is uncommon in HIV infection but can occur in the setting of lymphoma. We describe a patient with HIV with hypercalcemia and hypoglycemia due to an initially undetected EBV-associated lymphoma. Clinical Case: A 32-year old Caucasian male with recent diagnosis of HIV was admitted for HIV arthropathy and sepsis, and found to have hypercalcemia (Ca 10.7mg/dL, n 8.9-10.2mg/dL; ionized Ca 6.1mg/dL, n 4.6-5.7mg/dL). PTH was suppressed (<10pg/mL, n 12-72pg/mL). PTH-independent causes of hypercalcemia were unremarkable for humoral hypercalcemia of malignancy (PTHrP 0.2pmol/L, n <2.0pmol/L), vitamin D toxicity (24-hydroxyvitamin D 41ng/mL, n 30-80ng/mL), granulomatous disorders (1,25-dihydroxyvitamin D 24.8pg/mL, n 19.9-79.3pg/mL; quantiferon negative), hyperthyroidism, and adrenal insufficiency. Renal function was normal and there was no thiazide, lithium, calcium, or vitamin A use. Serum protein electrophoresis (PEP) showed hypogammaglobinemia consistent with immunodeficiency. Urine PEP was negative for immunoglobulin light chains. Hypercalcemia was initially attributed to HIV with immobilization and calcium level was expected to normalize with antiretroviral therapy. Workup for infectious etiology was negative, his arthralgia and overall clinical status improved, and he was discharged. Three days later, he was readmitted for altered mental status and anemia. He was hypoglycemic, which was new on readmission, and required dextrose-containing IV fluids in addition to tube feeds to keep his serum glucose within normal range. Work up was negative for insulinoma (C peptide 0.48ng/mL, n 0.81-5.3ng/mL; glucose 31mg/dL) but IGF-2 to IGF-1 ratio was elevated at 4.57 which was suggestive of IGF-2-mediated tumor-associated hypoglycemia. Persistent leukocytosis and type B lactic acidosis also suggested an underlying malignancy. Bronchoscopy, bone marrow biopsy, and CSF cytology were negative for malignancy. CSF was positive for EBV (77,100 copies/mL). CT imaging showed liver lesions and biopsy led to the diagnosis of high-grade B-cell lymphoma. He was started on chemotherapy. Hypoglycemia resolved 10 days later, as did the lactic acidosis. Hypercalcemia was treated with pamidronate with return to normal levels. Conclusion: Hypercalcemia in an HIV patient warrants diligent workup. Hypercalcemia in lymphomas are often attributed to elevated 1,25-dihydroxyvitamin D. A possible explanation for normal 1,25-dihydroxyvitamin D observed in our patient is the effect of antiretroviral therapy on accelerated catabolism of vitamin D. Hypoglycemia may be due to IGF-2 production by tumor and malignancy-related glucose consumption via glycolytic pathway with lactic acid production. Literature on concurrent hypercalcemia and hypoglycemia with B-cell lymphoma is sparse and, to our knowledge, occurrence in the setting of HIV has not been reported.

Perfusion Imaging in Autoimmune Encephalitis.

Encephalitis is characterized by inflammation of brain tissue and has various infectious and noninfectious causes. CSF analysis and MRI usually reveal inflammatory changes although sometimes brain imaging may be normal. Autoimmune encephalitis is caused by antibodies against neuronal synaptic receptors, surface proteins, or intracellular proteins. In this case report, we present a 65-year-old female who presented with a fall and altered mental status. Workup for infectious etiologies was negative and MRI of the brain displayed focal restricted diffusion with corresponding T2-FLAIR hyperintensity involving gray matter structures, making the diagnosis unclear. CT perfusion of the brain demonstrated increased cerebral blood volume and cerebral blood flow in the left parietooccipital gray matter, with corresponding normal mean transit time. Following treatment failure with acyclovir, antibiotics, and steroids, the patient was found to be positive for GAD65 antibodies and diagnosed with autoimmune encephalitis. Symptoms markedly improved with plasmapheresis. Autoimmune encephalitis rarely causes restricted diffusion and this is the first case report to describe corresponding hyperperfusion on CT perfusion study.

SARCOIDOSIS PRESENTING WITH MASSIVE SPLENOMEGALY IN A CHILD WITH A HISTORY OF IRIDOCYCLITIS AND SENSORINEURAL DEAFNESS

Childhood sarcoidosis is a rare multisystemic disorder that can have variable clinical presentations. A triad of skin, eye, and joint involvement is common in children younger than 5 years; however, pulmonary disease is more common in older children, similar to adults. The authors report the case of a 10-year-old girl who presented solely with massive splenomegaly. Her history was significant for iridocyclitis and unilateral sensorineural deafness at 6 and 7 years of age, respectively. A gallium scan showed diffuse splenic uptake, and the pathology of the spleen was consistent with a noncaseating granuloma, with no evidence of malignancy. A work-up for infectious etiology was unremarkable. This case demonstrates that the challenge in diagnosing sarcoidosis in young children stems from its ability to present in several unique clinical scenarios. It also reinforces the importance of tissue evaluation and the exclusion of other differential diagnoses, such as lymphoma, to confirm the diagnosis of sarcoidosis.

Enthesitis-related arthritis in Kikuchi–Fujimoto disease

Histiocytic necrotizing lymphadenitis or Kikuchi-Fujimoto disease (KFD) is a rare, benign and self-limiting disorder that characteristically presents with fever and cervical lymphadenopathy. Articular manifestations in the form of arthralgias are common but frank arthritis is distinctly rare and dactylitis has not been reported yet. Herein, we describe a young boy who presented with arthritis and dactylitis as the initial manifestation of KFD. A 14-year-old boy presented with a two-week history of fever, generalized lymphadenopathy and asymmetric polyarthritis, enthesitis and dactylitis of the toes. Two years earlier he presented with arthritis of the knee and ankle joints, which lasted for 12 months. However, he had been asymptomatic for one year. Investigations revealed anemia, leukopenia and raised acute phase reactants. Work-up for infectious etiology, systemic lupus erythematosus and leukemia and lymphoma was negative. Excision biopsy of the cervical lymph node confirmed KFD. Fever, lymphadenopathy and leukopenia dissipated with nonsteroidal anti inflammatory drug therapy, but the arthritis persisted. A trial of methotrexate led to the resolution of the arthritis.