Epidermal growth factor receptor (EGFR) is a cell surface molecule and member of the ErbB family of receptor tyrosine kinases. Its activation leads to proliferation, antiapoptosis, and metastatic spread, making inhibition of this pathway a compelling target. In recent years, an increasing number of clinical trials in the management of solid malignancies have become available indicating the clinical efficacy of anti-EGFR monoclonal antibodies and oral small molecule tyrosine kinase inhibitors (TKIs). This review addresses frequently used EGFR inhibitors, summarizes clinical efficacy data of these new therapeutic agents, and discusses their associated toxicity and management.
4932 Eosinophilia as a marker of Strongyloides infection Aisha Zaidi, Nagendra Natarajan, Vivek R. Sharma Background: Peripheral blood eosinophilia can be categorized into secondary, clonal and idiopathic types. Secondary eosinophilia can occur due to parasitic infections, allergic or vasculitic conditions, drugs and malignancies. Presence of cytogenetic, histologic and molecular evidence of myeloid malignancy differentiates clonal from idiopathic type. Usually the first step in evaluation of eosinophilia is to exclude secondary causes. Complete work up to exclude secondary causes include careful and extensive review of travel history, medication list, physical examination, chest radiography, multiple stool oval and parasite testing, and serological testing for suspected pathogens (strongyloides stercolaris). Strongyloides infection is a particularly important secondary cause of eosinophilia that requires timely diagnosis and treatment to avoid life-threatening complications (hyperinfection syndrome) from interventions (corticosteroids) for treating the eosinophilia. We report a case highlighting this issue including the fact that such parasitic infection can occur in patients living in the United States (US) who have never traveled outside the country. Abstract: A 66 year old male with multiple comorbities including coronary artery disease, Chronic obstructive pulmonary disease, and stroke was evaluated in the hematology clinic for persistent eosinophilia. He has lived in the US his entire life and did not give any history of travel or change in his medication regimen. He had an itchy urticarial rash on the dorsal surface of his hands but denied any gastrointestinal symptoms. During his initial visit his CBC showed a white blood cell count of 8300 cells/mm3, with 28% eosinophils (Absolute eosinophil count of 2300). His hemoglobin was 13.5 mg/dl with an MCV 100.2 and the platelet count was 202,000 cells/mm3. Extensive work up including multiple stool ova and parasite testing, computed tomography of chest, abdomen and pelvis, cosyntropin test for adrenal insufficiency was unrevealing. His Bone Marrow evaluation revealed mild eosinophilia without dysplastic changes. Fluorescence in situ hybridization performed using tricolor probes targeting SCFD2/FIP1L1, LNX/CHIC2 and PDGFRA was normal. All interphase nuclei examined were negative for a deletion of LNX/ CHIC2 or rearrangement of PDGFRA often seen in association with hypereosinophilic syndrome/chronic eosinophilic leukemia or systemic mastocytosis. Finally, serological testing for strongyloides using ELISA that was ordered as part of the initial workup came back showing strongly positive IgG titer (3.84 ref > 2.11 is positive). He was treated with Ivermectin 200 mcg/kg/day for two days. At his 8 week follow up visit he had complete resolution of eosinophilia. He will be followed by serology within six months as Eosinophilia due to Strongyloidiasis is notoriously prone to fluctuations and may be absent in 20% of the patients with microscopically confirmed infection. Conclusion: This case highlights the importance of diagnosing asymptomatic or minimally symptomatic cases of strongyloides. Even though it is uncommon, it can be found in patients living in certain parts of the US especially the southeastern states. Diagnosis of asymptomatic cases is vital as it eliminates the risk of subsequent hyperinfection should the host's immunity be suppressed for example by corticosteroids used for treating the secondary eosinophilia. Disclosures: No relevant conflicts of interest to declare.
Contrary to most animals which are capable of obtaining ascorbic acid (vitamin C) by metabolizing glucose, humans require an exogenous source of vitamin C. It is a water-soluble vitamin found in various foods, including citrus fruits (oranges, lemons, grapefruit), green vegetables (peppers, broccoli, cabbage), tomatoes, and potatoes. It is essential for growth and repair of tissues, particularly blood vessels. Deficiency of vitamin C is relatively rare; the third National Health and Nutrition Examination Survey (NHANES III, 1988-1994) found approximately 13% of the US population to be vitamin C deficient. Smoking cigarettes lowers the amount of vitamin C in the body, so smokers are at a higher risk of deficiency. Additionally, alcoholics, the elderly, patients with psychiatric disorders and individuals who experience social isolation are also at risk. Symptoms can manifest after 3 months of deficient intake of vitamin C -containing foods. Since ascorbic acid is required for collagen synthesis, deficiency usually manifests with bleeding gums, ecchymoses, petechiae, coiled hairs and hyperkeratosis. Diagnosis can be established when plasma levels of vitamin C fall below 0.2mg/dl. There are currently no evidence based guidelines for supplementation once low levels are detected. We describe a case of a 33 year old Caucasian female seen in our clinic for easy bruising of 10 years duration. She would wake up in the morning with bruised arms and legs without any inciting trauma. She denied prolonged bleeding after dental extractions, frequent nose bleeds, menorrhagia any genitounrinary or gastrointestinal blood loss. Her exam revealed ecchymoses on her arms and legs with no evidence of perifollicular hemorrhage or gingival hyperplasia. Workup including CBC, Coagulation profile and Von Willibrand factor levels were all within normal limits. She had a vitamin C level of 0.1mg/dl. She was subsequently advised to increase vitamin C intake through fruits and vegetable and was started on vitamin C supplementation with 500mg twice a day for four weeks. Her repeat vitamin C level on her one month follow up was noted to be 1.9mg/dl. She noticed complete resolution of her symptoms. This case illustrates the fact that vitamin C deficiency should be excluded in adults presenting with bruising. It also offers a supplementation regimen that resulted in improvement of clinical symptoms as well as laboratory value normalization. Disclosures: No relevant conflicts of interest to declare.
e17019 Background: Chronic Lymphocytic Leukemia is a lymphoproliferative disorder which can have variable course from being indolent to aggressive. Reported annual incidence of Chronic Lymphocytic Leukemia is 3:100000. The most common manifestation is Lymphadenopathy and Leptomeningeal involvement is very rare with only a few reported cases in literature. Methods: This is an observational case report. Results: We report a case of 57 year old White male who presented with CNS disease as his first manifestation of CLL. He reported a 6 week history of cognitive decline with inability to perform complex tasks, difficulty with calculations, word finding trouble, progressive clumsiness of right arm and leg and a weight loss. MRi revealed Left sided Leptomeningeal enhancement. As part of his work up; patient received LP, PET scans, Infectious and autoimmune studies and eventually brain biopsy which initially showed Lymphocytic predominance.On further review by NIH immunohistochemical stains for CD5, CD20 and CD23 were positive on the leptomeningeal and parenchymal lymphocytes. His bone marrow showed CLL involvement both morphologically and immunophenotypically by means of flow cytometric analysis. He was started on treatment with High dose methotrexate and Rituximab and showed remarkable improvement in his cognitive function by the completion of his second cycle. His bone marrow repeat biopsy showed complete remission and no involvement of lymphoma. Conclusions: CLL is an indolent disease and direct CNS invasion is extremely rare. Our case becomes unique in terms of its presentation. It highlights the importance of timely diagnosis and management of leptomeningeal disease in CLL can lead to resolution of neurologic symptoms.
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