American College of Physicians - Connecticut Chapter 2009
- Best Oral Presentation: Harm Feringa
- Runner Up- Clinical Vignette: Shilpa Shetty
Fatal, fulminant cryoglobulinemia in ex-“skin-popper”
Ewa Kontny, M.D.; Victoria Costales, M.D.; Armin Sharokni, M.D.
Introduction: Essential mixed cryoglobulinemia is a disorder of circulating immunoglobulins and complement complexes that precipitate in cold temperatures. This can be associated with many disorders including multiple myeloma, lymphoproliferative disorders, connective tissue diseases, infection, and liver disease. Since the discovery of hepatitis C virus it was established that nearly 5% of patients with chronic hepatitis C develop the syndrome. Aberrant immune response to chronic Hepatitis C infection seems to be the culprit behind widespread vasculitic changes.
Case presentation: 54 year old male with past medical history of hepatitis C (and failed interferon treatment), alcohol abuse, pancreatitis, bipolar disorder and intravenous drug abuse presented with 4 weeks of progressive lower extremity swelling difficult to control with diuretics and bullous rash. Renal biopsy showed changes consistent with membranoproliferative glomerulonephritis. Despite aggressive treatment with hemodialysis, plasmapheresis and eventually rituximab, the patient became more confused, developed respiratory distress and died. Initially 2 sets of cryoglobulins were negative with the last set confirming the diagnosis.
Conclusion: Cryoglobulinemia associated with hepatitis C has a guarded prognosis. Acute mortality from essential mixed cryoglobulinemia is rare. If glomerulonephritis occurs in the course of disease, it is one of the worst prognostic signs with nearly 40% of patients suffering from fatal cardiovascular event, infection, or liver failure. Since many cases are associated with hepatitis C infection, it was noticed that clinical recovery is often dependent on antiviral treatment response (interferon alfa with ribavirin). Steroids offer complete remission in only about 7 % of cases. Plasmapheresis and cytotoxic agents have been used in anecdotal reports with variable response.
“Go With The Flow”- AML in Patient with No Peripheral Blood Smear Changes.
Ewa Kontny, M.D.; Dorothea Wild, M.D.
Introduction: Flow cytometric techniques are routinely utilized in clinical hematology. When cells pass through a laser beam the light that emerges from each cell as it flows through is captured and analyzed to report cellular characteristics. It can be especially helpful in cases like our patient with normal cell morphology on peripheral blood smear where diagnosis could be nailed only by immunophenotyping-technique offered by flow cytometry.
Case Presentation: The patient was a 87 years old white female with past medical history significant for hypertension, pulmonary hypertension and remote history of colon cancer. The patient had recently started seeing a hematologist for elevated platelets. For approximately 2 months she was taking 500 mg hydroxyurea daily until 3 days prior to admission when she was found to be mildly pancytopenic with a very low vitamin B12 level. Before her next follow up appointment patient presented to the hospital with complaints of fevers, chills and swelling with redness of the right sternoclavicular joint. CBC on admission revealed Hgb 8.3, Hct 23.9, WBC 1.8 with 46% granulocytes, 2% bands, 14% monocytes, 2% meta, 1% myelo, PLT 186, MCV 112.7, rouleaux noted. LDH 3170 (UNL-610), alk phosph 138 (UNL-127). Admission x-ray of the affected clavicle showed only degenerative changes. MRI showed edema surrounding the right sternoclavicular joint with bone marrow edema noted. CT-guided aspiration of the joint fluid did not show any gross pathologic findings. Patient’s swelling started to go down and she seemed to be doing well until 10-th day of the hospital stay when patient developed acute respiratory failure necessitating intubation and transfer to ICU. Repeat CT of the chest revealed new bilateral patchy airspace opacities imposed on interstitial lung disease and new left lower lobe infiltrate. Flow cytometry report came back with results showing approximately 20-25 % of circulating cells to be myeloblasts expressing CD34, dimCD33, CD117, CD13, MPO and HLADR, no lymphoid or monocytic markers. Given the history of myeloproliferative disease this could be evolution to acute myelogenous leukemia, FAB M1. Patient failed to wean from a ventilator, and her further hospital stay was complicated by essentially multiorgan failure. The patient eventually expired after comfort care extubation. Post mortem lung and bone marrow biopsy were consistent with acute leukemic process and leukemic infiltrate of the lungs.
Discussion: The diagnosis of acute myelogenous leukemia (AML) is usually made by identification of leukemic blast cells. In our case, the morphology of the circulating white cells on the peripheral smear was normal, while flow revealed cells consistent with AML. Of note is that this patient likely suffered leukemic infiltrates of and signs and symptoms disrupted hematopoiesis. Pulmonary presentation is not very common-most often happens in FAB M5 leukemia-but as outlined in case report by Dr. Vlad pneumonia-like picture with subsequent respiratory failure can be a presenting complaint of some subset of patients with hematologic malignancies. 5 A high index of suspicion is necessary when approaching any older patient with non specific complaints and previous hematologic malignancy history treated with chemotherapy-even if typical features of acute malignancy are absent on peripheral blood smear.
Elusive anemia: A case report
Victoria Costales, MD, Ewa Konty MD, and Armin Shahrokni MD
Introduction: Anemia work-up involves excluding the most common causes like hypoproliferative disorders (e.g. iron deficiency, bone marrow failure), maturation disorders (drug-related, including alcohol and vitamin B12 or folate deficiency), or hemolysis/hemorrhage-related. Microscopic examination of the bone marrow is the gold standard for diagnosing primary or secondary hematologic disorders when clinical history, blood cell counts, peripheral smear or laboratory results are inconclusive. Thrombocytopenia can be drug- or infection-induced, part of the microangiopathic hemolytic syndromes or idiopathic. Bone marrow biopsy in thrombocytopenia is warranted when concomitant erythrocyte or leukocyte counts are abnormal. Bone marrow sampling allows for further testing such as cytogenetics, molecular studies, microbiologic cultures, immunohistochemistry and flow cytometry.
Case: The patient is a 75 year old Caucasian male with hypertension, hyperlipidemia, atrial fibrillation (not on Coumadin), and history left carotid stenosis s/p carotid endarterectomy who admitted for non-ST elevation myocardial infarction. He was anemic with a hemoglobin/hematocrit(H/H) of 8.5/25. He is an ex-smoker with no family history of heart disease or hematologic problems. Physical exam was remarkable for pale non-icteric sclera, no lymphadenopathy, a systolic murmur in right 2nd intercostals area, a soft, non-tender abdomen without distention or hepatosplenomegaly, guiaiac negative stool, and non-edematous extremities.
Fifteen months prior to presentation, the patient was admitted for bright red blood per rectum. Endoscopy showed Barrett’s esophagus and colonoscopy showed now bleed sources. In the subsequent months, the patient continued to have decreasing hemoglobin and hematocrit. Three months prior to presentation, the patient became thrombocytopenic with a macrocytic anemia. Work up of the anemia showed negative anti-cardiolipin antibodies, within normal limits C3, C4, SPEP, UPEP, and negative cryoglobulins. Immunoelectrophoresis showed no monoclonal component. Peripheral smear showed… Flow cytometry was normal. Bone marrow biopsy showed all cell lines with decreased megakaryocytes but otherwise no abnormalities. The patient was treated with a 2-week course of Prednisone 60 mg, with no effect. Three more subsequent BMBs were done which were all normal.
Discussion: The three major etiologies of anemia are decreased production of RBCs (bone marrow failure), increased destruction (intravascular/extravascular hemolysis), and blood loss. The patient’s four normal bone marrow biopsies rules out bone marrow failure. Multiple endoscopies showed no bleeding source. The differential diagnosis of hemolytic anemia is relevant to the patient’s diagnosis. Hemolytic anemias can be inherited or acquired. Hemolysis predominantly occurs either intravascularly or extravascularly. Inherited intravascular hemolytic anemias include hemoglobinopathies (hereditary spherocytosis) and enzymopathies (G6PD deficiency) while inherited extravascular disease familial hemolytic uremic syndrome. Acquired intravascular hemolysis is seen in paroxysmal nocturnal hemoglobinuria while acquired extravascular factors are involved in hemolytic anemias secondary to mechanical destruction, toxic agents, drugs, infectious causes and autoimmune.Hereditary hemolytic anemias are ruled out in the patient because the peripheral smear did not reveal spherocytes and elliptocytes. Among the acquired hemolytic anemias, mechanical destruction is ruled out because the patient does not have prosthetic heart valve. The patient does not take hemolysis-inducing medications. Infectious causes such as malaria and Shiga-toxin producing Escherichia coli are also ruled out. Autoimmune hemolytic anemia is also ruled out because of the patient’s negative cardiolipin antibodies (seen in systemic lupus erythematosus) and coombs negative test.
Conclusion: Despite a thorough investigation of anemia, including the gold standard bone marrow biopsy, the diagnosis can still be elusive. This is the case in our patient who is left transfusion dependent as his only therapeutic option.
Intravenous Immunoglobulin – An Effective Treatment of Chronic Inflammatory Demylinating Polyradiculoneuropathy
Divya Aggarwal, MD, Venkatesh Lakshminarayanan, MD, James B. Butler, MD
Griffin Hospital, Derby, Connecticut
Introduction Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an uncommon acquired disorder of peripheral nerves causing relapsing and remitting or progressive weakness and loss of sensation of limbs. Many clinical trials have been conducted in an effort to find a potential cure for this autoimmune debilitating illness.
Case report A 72 year old male presented with progressive weakness of both legs two weeks after receiving vaccine for tetanus and pneumonia. The patient first noticed a cold sensation in the hands along with numbness and “wet sensation” in the legs. He was initially diagnosed with Guillaine Barre syndrome after spinal tap and nerve conduction studies. However, weakness in all the four limbs continued to progress over the next three months.
On physical examination, the patient was alert and oriented to time, place and person. Attention, concentration, language, fund of knowledge and memory appeared intact. Cranial nerves 2-12 were intact. Motor tone was intact in all extremities. Power was 4/5 proximally and distally in all groups of both upper extremities. In lower extremities, motor strength was 4/5 in all groups except for ankle dorsiflexion which was 3/5 bilaterally. No atrophy or fasciculation was noted. There was loss of vibratory perception below the knees and a marked reduction in distal proprioception. Pain and temperature sensation was impaired in all four extremities in a glove and stocking manner. Tendon reflexes were 1 plus at the level of biceps but absent at all other sites. Cerebellar signs were negative. The gait was wide-based and ataxic, complicated by partial foot drops. He ambulated with the help of a walker. There was no family history of neuromuscular disease and no relevant medical history.
Nerve conduction studies showed reduced sural, radial and median sensory amplitudes and velocity, absent F-waves, and bilateral motor conduction block in median, ulnar, tibial and peroneal nerves. Routine laboratory investigation was normal. CSF disclosed elevated protein content (2.26g/dl) and a normal cell count.
He was treated with approximately 30 gm intravenous immunoglobulin (IVIG) for a total of five doses. Negative inspiratory flow was monitored every day. After 5 days of IVIG, motor strength improved in all extremities and deep tendon reflexes were positive. Numbness was less pronounced but pain sensation loss remained the same. Sensory and motor nerve conduction studies showed minor differences but no significant change compared to previous study. He was discharged on a maintenance dose of 20 mg Prednisone daily.
Conclusion This case illustrates the role of IVIG in remission and initial improvement in CIDP. IVIG (Gamunex) has been approved by the US FDA as a first line treatment for CIDP to improve neuromuscular impairment and for maintenance therapy to prevent relapse after the success of Immune Globulin Intravenous efficacy (ICE) trial.
A case of TB, exploring the risk factors.
Matxalen Amezaga, Armin Shahrokni, Seema D’souza.
INTRODUCTION: Tuberculosis is an infection caused by mycobacterium tuberculosis complex microorganisms that remains the most common infectious cause of death in adults worldwide. Approximately eight million new TB cases occur each year, and about three million infected patients die. About one third of the world population is estimated to be infected with tuberculosis. The epidemiology of TB varies around the world with less than 25 cases per 100,000 inhabitants in the United States. In 2008 TB rate declined 3.8% from 2007 to 4.2 cases per 100,000 populations in the US. Foreign born person and racial/ethnic minorities continue to bear a disproportionate burden of TB disease in the US. In 2008, the TB rate in foreign-born persons in the United States was 10 times higher than in US-born persons. Blacks had the highest number of TB cases among US-born persons. California, Florida, New York and Texas combined contributed to almost half of TB cases in 2008. Reactivation TB represents 90% of adult cases in the non HIV infected population. The most common symptoms of active TB are cough, malaise, fever and sputum production; more than 65% of patients will have an abnormal CXR. Once TB is diagnosed standard therapy with Isoniazide, Rifampin, Ethambutol and Pyrazinamide should be started and infection control measures established.
CASE: The patient is a 45 year old male with a history of uncontrolled diabetes mellitus type 2, HTN and tobacco abuse for 30 years who presented to the ER with sudden onset of pleuritic left sided chest pain not associated with physical exertion, daily morning productive clear/white cough for the past year, which he attributed to smoking and 20 pounds weight loss for the past 6 months. He denied any SOB, palpitations, syncope, diaphoresis, hemoptisis, fever or chills. He was adopted and his family history is unknown. He denied alcohol or drug abuse. He used to work for the US army in Kentucky and Alabama and was exposed to a person with tuberculosis 5 years ago. His is married and had multiple extramarital sexual contacts. His has 2 cats and has no history of recent travels. His vitals signs and physical exam on admission were normal. His WBC was 11,400 cells/mm2 with 55% granulocytes, 31.3% lymphocytes, Eosinophyles 5.4%; H/H 11.1/34.1, MCV 65.4 and RDW 16.7. His BMP and LFT’s were normal. Cardiac work-up for ACS was negative. ANA was negative, ERS was 4. His HBA1C was 10.2. HIV test was negative. CXR showed focal opacity in left midlung with relative lucency and questionable cavitation. CT scan of the chest without IV contrast showed multiple cavitary lesions in the left lung in upper and lower lobes with air-fluid levels and thickened walls with innumerable lung nodules within the adjancent left upper and lower lobes with tree bud configuration, small left pleural effusion, very small few right lung nodules and single subpleural cyst right lung apex. AFB smears and sputum cultures came back positive for mycobacterium tuberculosis and the patient was started on Isoniazide, Rifampin, Ethambutol and Pyrazinamide.
DISCUSSION: The global incidence of TB appears to be declining since 2003. Poverty, HIV and drug resistance are major contributors factors to the prevalence of TB in the world. Poorly controlled diabetes as well as heavy smoking increases the relative risk of reactivation of tuberculosis. In 2008 among persons with TB with an HIV test result, 10.7% were infected with HIV. MDR TB represents 1% of the TB population affecting disproportionately foreign-born persons. The recommended length of drug therapy is 6-9months. In 2005 83% of patients for whom less or 1 yea of treatment was indicated completed therapy within 1 year, which is bellow the target set by the Health People 2010. There are different risks factors for TB and the disproportion of TB rates in the populations in the US, might be explained by the low knowledge concerning Tb transmission and curability in the high risk population that may translate into low levels of care seeking among those with TB symptoms and results in increased transmission or deaths due to late diagnoses. Different strategies must been included in the control of TB starting from physician and patient education, infection control measures, screening of high risk population and use of DOT.
Unexpected Right Ventricular Mass in a Patient with Pulmonary Embolism and Antiphospholipid Syndrome
Yumi Koh, D.O., Harm H.H. Feringa, M.D., Ph.D., Joseph Gnanaraj, M.D.
Introduction: Intra-cardiac ventricular masses are uncommon and often discovered incidentally. The differential diagnosis of intra-cardiac masses includes thrombi, infectious masses and neoplastic masses, such as myxomas, lipomas, teratomas, sarcomas and metastases. We present an unusual case of right ventricular mass discovered in a patient with pulmonary embolism and antiphospholipid syndrome.
Case Presentation: A 37-year old female presented with symptoms of unresolving cough, shortness of breath, fever and yellow productive sputum for 10 days. Her past medical history was unremarkable, except for smoking. Computed tomography angiogram showed a subsegmental pulmonary embolus in the right lower lobe and extensive bilateral pulmonary infiltrates and consolidation. The patient was started on intravenous unfractionated heparin for the pulmonary embolus and on intravenous azithromycin and ceftriaxone for the pneumonia. A transthoracic and transesophageal echocardiogram was obtained to evaluate for a potential cardiac embolic source. The echocardiograms revealed a mobile round mass with stalk, measuring 1.75 by 1.54 cm in diameter. The mass was attached to the right ventricular wall with no ventricular outflow gradient. Cardiac magnetic resonance imaging confirmed a mobile mass measuring 2.3 by 1.4 cm, seen in the middle of the right ventricular cavity in between the papillary muscles. On cine MRI sequences, the mass had signal intensity similar to that of the myocardium. On inversion recovery delayed gadolinium contrast sequences with long (500-550 ms) TI, the mass exhibited low signal intensity compared to the myocardium, suggestive of thrombus. The patient was taken up for surgery for mass resection because of the possibility of dislodgement. The histopathological examination defined the mass as thrombus. Grocott and Sandiford stains were negative for organisms. Laboratory tests for hypercoagulability were positive for lupus anticoagulants.
Discussion: We described a rare case of right ventricular thrombus in a hypercoagulable patient with pulmonary embolism. Our case demonstrates that intraventricular cardiac masses, although rare, should be suspected in patients presenting with pulmonary embolism and hypercoagulable state. Echocardiography is often used as first-line diagnostic test for the evaluation of a cardiac embolic source. Although echocardiography can characterize structural abnormalities, it has limited value in tissue differentiation of cardiac masses. Our case illustrates that the signal intensity of cardiac masses evaluated by cardiac MRI can suggest the underlying type. Cardiac MRI may therefore be a promising tool in characterizing intraventricular cardiac masses and be potentially helpful in clinical decision-making.
Prevention of Peripheral Arterial Disease with Calcium Channel Blockers in Patients with Hypertension: A Meta-analysis of Randomized Trials.
Harm Feringa, Usha Emani, Miraude Adriaensen, Afrooz Ardestani, Shilpa Shetty, William Pearson
Background: Peripheral atherosclerotic disease (PAD) affects more than 30 million people worldwide. PAD is associated with increased cardiovascular morbidity and mortality and is recognized as a major health burden. Hypertension is a strong risk factor for the development of PAD. Animal studies have suggested that calcium channel blockers (CCB) can prevent the development of atherosclerosis. The effect of CCB for the primary prevention of PAD in hypertensive patients, however, is not well known.
Aim: This study sought to evaluate the effect of CCB treatment for the primary prevention of PAD in patients with hypertension.
Methods: We searched the published literature (MEDLINE, the Cochrane Central Register of Controlled Trials and EMBASE) for trials published after 1990 reporting the effect of CCB on the development of PAD. Criteria for inclusion included a study duration of more than 6 months, the use of a randomized control group not receiving CCB, and the availability of outcome data on PAD. We conducted a meta-analysis with random and fixed effect models to combine and summarize the results of these studies.
Results: Of 2,006 potentially relevant studies, a total of 7 studies (65,925 patients) met our inclusion criteria. Patients randomized to the control group received either placebo or active treatment with ACE-inhibitors, beta-blockers or diuretics. In patients receiving CCB, 535 out of 24,678 (2.2%) developed PAD versus 1,249 out of 39,833 (3.1%) in the control group. CCB treatment was associated with a risk reduction of 25% for the development of PAD (95% confidence interval CI 33% to 17%, p<0.001). In the subset of 6 studies with 64,511 participants taking dihydropyridines vs control, dihydropyridines were associated with a risk reduction of 26% for the development of PAD (95% CI 33% to 18%, p<0.001).
Conclusion: Based on the results of this study, calcium-channel blockers appear to be effective in the prevention of PAD in patients with hypertension.
Monoclonal Gammopathy of Unknown Significance (MGUS) presenting as recurrent hypoglycemia
Introduction: The insulin autoimmune syndrome, also termed Hirata Syndrome is characterized by hypoglycaemic episodes, elevated insulin levels and positive insulin antibodies. It is the third leading cause of hypoglycemia in Japan, but has been very rarely described in the non-Asian population. In the western population most patients develop the disease in association with treatment with sulfhydryl-containing medications. We report an interesting case of insulin autoimmune syndrome in a Caucasian patient with MGUS.
Case Presentation: An 82 year old female with a history of hypoglycemia which was thought to be secondary to an insulinoma presented to the ER complaining of weakness and a low blood sugar of 45 inspite of frequent snacking and proglycem. She also complained of a couple of episodes of nausea, vomiting and diarrhea. She had a past medical history significant for hypertension, dyslipidemia, lumbar disc prolapse, left adrenal nodule (ruled out for pheochromocytoma), GERD, TIA and presumed non localized insulinoma (due to high insulin levels and hypoglycaemic episodes). There was a family history of diabetes and thyroid cancer in her sister. Her medications included aggrenox, atenolol, spironolactone and proglycem. On physical examination her BP was 120/80, pulse 79, temperature 97.2F. The rest of the physical examination was essentially normal. Her proglycem was continued and she was started on a 5% dextrose drip. Evaluation of hypoglycaemia included an MRI of the abdomen which was negative for any mass lesions. C peptide levels were elevated (6.7 ng/ml) and insulin levels were also elevated (18 uIU/ml). Anti insulin antibodies were checked and were also found to be high (81%). On Serum electrophoresis the patient was noted to have monoclonal gammopathy characterised as IgG lambda (0.37 G/DL). She was treated with steroids to which she responded well with resolution of her recurrent hypoglycemic episodes.
Conclusion: Insulin autoimmune syndrome is a rare cause of hypoglycemia in the western population. Although there is some evidence indicating a genetic predisposition and linking this disease to HLA – DR4 in Japanese patients, most cases are associated with use of sulfhydryl- containing medications with a few reported cases occurring after use of the dietary supplement alpha lipoic acid. We propose that that the insulin antibodies detected in our patient are secondary to plasma cell dyscrasia. One should consider plasma cell dyscrasia induced insulin antibodies as a cause of recurrent hypoglycemia, particularly in elderly patients in whom an insulinoma is less likely as it may spare the patient an unnecessary pancreatic surgical procedure.
Idiopathic Immune thrombocytopenia after withdrawal from Interferon treatment: A Case Report
Neetu Nebhwani M.D, Joseph K Lim , M.D.
Introduction: Mild thrombocytopenia is a common adverse effect of recombinant Interferon, with most patients experiencing a mild reduction in platelet count. Interferon may lower platelet count via either bone marrow suppression secondary to decreased TPO synthesis or Immune –mediated platelet destruction. Recombinant alpha interferon, a common treatment for chronic viral disease, has immunomodulatory properties and can induce or exacerbate autoimmune diseases. Despite the common occurrence of mild thrombocytopenia, severe life threatening thrombocytopenia is uncommon, although cases have been reported of the same. Here in we report a case of patient with chronic Hepatitis C on interferon therapy presented as an Idiopathic thrombocytopenia purpura like syndrome within 1 month of withdrawing the Interferon.
Case Report: A 58 y/o old male with history of chronic Hepatitis C infection with treatment failure on Interferon and Ribavirin presented with 2 days of easy bruisability, gum bleeding and mouth sores on 5/13/07. He denied any fever, chills, night sweats, any recent viral illness, travel, sick contacts, and no blood in stools or urine. His past medical history includes Chronic hepatitis C infection , genotype 1 and stage 2 on liver biopsy who is non responder to standard IFN plus ribavirin , and is now non responder to PEG-IFN plus Ribavirin which was discontinued on 4/27/07. Socially patient was a heavy alcohol abuser in the past and IV drug abuser as well. At the time of admission, vitals were stable, and physical examination revealed wet purpura with mucosal hemorrhage on left lower gum and pharynx and central tongue, left gum and buccal mucosa were also involved. Patient also had scattered non blanching petehiae. Rest of the physical examination was within normal limits. Labs at the time of admission showed WBC of 4.1, Hematocrit of 42 % and platelet count was undetectable. Most recent platelet count was 135 on 3/19/07. Peripheral smear was not notable for platelets, and no schitocytes were visualized. Further work up for hemolysis and DIC were negative. Extensive evaluation for thrombocytopenia was undertaken including viral studies for HIV, Hepatitis B, EBV, and CMV which were negative. CT scan of chest, abdomen and pelvis was done which did not demonstrate any evidence of lymphoma. Platelet associated IgG antibody were negative. Bone marrow biopsy was deferred at this point and patient was empirically started on IV solumedrol and he was also given 2 doses of WinRho? (Rho (D) immune globulin). During the Hospital course patient’s platelet increased to 34 confirming the response to the treatment with solumedrol and WinRho? and our suspicion about the ITP.
Discussion:Severe thrombocytopenia is being described in patients who are treated with Interferon and Ribavirin for hepatitis C. In this patient we saw profound thrombocytopenia secondary to Idiopathic thrombocytopenic purpura which decreased platelet levels to undetectable requiring hospitalization. Although the underlying trigger for this event remains unclear, suspecting that an idiopathic immune –mediated event following PEG-IFN withdrawal may have been a contributing factor although this has not been established definitively, and this would be considered an exceedingly rare and reportable observation in literature.
Refractory Hypoxia: Think outside the box!
Introduction: Patent foramen ovale is a congenital cardiac lesion that can persist in adulthood affecting approximately 25% of the adult population. Its recognition, evaluation and treatment have attracted increasing interest as the importance and frequency of its implication in several pathologic conditions, but its mechanism has still not been clarified completely.
Case report: A 63 year old female presented to the hospital with chief complaint of progressive shortness of breath, weight gain, BL LE edema, orthopnea and PND. Patient’s past medical history includes Breast Ca sp lumpectomy and chemotherapy with Adriamycin, radiation therapy, OSA, Atrial fibrillation on Coumadin, Cardiomyopathy, sp AICD placement, hypothyroidism, COPD on home O2. Other ROS were noncontributory. Physical exam (PE) revealed chronically ill appearing white female in acute distress. Vitals: BP 94/60, pulse 66 irreregular, RR: 20, Lungs: Crackles at bases, Heart: S1 S2+, 2/6 systolic murmur, Extremities 3+ edema BL, rest physical exam being unremarkable. EKG: AtrialFibrillation? with no ischemic changes, CXR:cardiomegaly, no acute process. Labs BUN: 42, Cr: 1.8, Potassium: 5.8, BNP: 305, INR: 4.82, CBC and LFTs WNL. Patient was admitted to telemetry floor with probable diagnosis of biventricular heart failure in setting of cardiomyopathy with poor left ventricular function. Patient did well with IV lasix and was also started on dobutamine drip for marginal BP and poor LV function. Over the due course of hospital stay patient had multiple unexplained episodes of hypoxemia, 86% on 5L nasal canula, most of the times asymptomatic. ABG showed respitory alkalosis with hypoxemia, Pulmonary thromboembolism was ruled out with a negative VQ scan and negative lower limbs Doppler. Because of worsening hypoxemia patient was transferred to ICU and was intubated; echocardiogram with saline contrast showed right to left intracardiac shunting with mild pulmonary HTN. Patient was transferred to another hospital for further cardiac intervention. Transesophageal echocardiogram (TEE) demonstrated dilated LV with an EF of 35%, severe dilatation of right sided chambers, mild pulmonary HTN and evidence of patent foramen ovale with an atrial septal aneurysm and no valvular vegetations. Cardiac catherization confirmed the TEE findings and also demonstrated the regurgitant jet of severe tricuspid regurgitation with a structurally normal tricuspid valve which caused the reversal of flow through the shunt. Cardiothoracic surgery was consulted and patient was taken to operating room where she underwent tricuspid valve repair, closure of patent foramen ovale and intraaortic balloon pump placement which was weaned off in 2 days. Post repair TEE demonstrated closure of foramen ovale and absence of shunt at the atrial level with resolution of patient’s hypoxemia. Also there was significant improvement in the LVEF of approximately 45%.
Discussion: Workup in the above mentioned case revealed that the shunt physiology displayed was due to the regurgitant jet from the right ventricle aiming directly at the patent foramen ovale. This case illustrates the importance of consideration of broad differential diagnosis in cases of refractory hypoxemia and is intriguing because patient presented with signs associated with right to left shunt but near to normal pulmonary vasculature pressures, which is usually not the case. Also cases have been described where patient have normal pulmonary pressures with postpneumectomy or dilated aortic root2 and usually present with platypnea-orthodeoxia syndrome, not persistent systemic hypoxemia as our patient did.
A case of Bone Metastasis from occult Hepatocellular Carcinoma
Karthikeyan Kandavelou, Neetu Nebhwani and Marya K. Chaisson
Department of Medicine, Griffin Hospital, Derby, CT 06418
Introduction: Hepato-cellular carcinoma (HCC) is one of the most common malignancies worldwide, presenting with high incidence in regions where there is high prevalence of viral hepatitis, especially hepatitis B. HCC is usually diagnosed based on the typical Computed Tomographic CT appearance of hypervascular liver lesion and elevated serum AFP. Typical presentation of patients with HCC is right upper quadrant pain, upper gastrointestinal bleeding, hepatomegaly, jaundice and weight loss. HCC generally tends to metastasize late in its course. Common sites of metastasis of HCC are lungs, lymph nodes, adrenal glands and bones including the skull. HCC has a very aggressive clinical course with a mean survival of <1 year if left untreated. Here we report an unusual case of occult HCC diagnosed after biopsy of a metastasized mass on the left pedicle of L1 vertebra.
Case Report: HCC was an accidental finding in this 63 year old gentleman who presented to our Emergency Department with Pneumonia. The unresolved right lobar consolidation initiated the workup for lung mass which led to the identification of isolated lytic lesion on the L1 vertebra. Malignancy work up showed an increase in Alpha Feto Protein (AFP), which raised the question of carcinoma of testicular origin. Subsequent ultrasound of the testes showed no evidence of mass lesions. Initial CT scan did not show any significant hepatic lesions. No significant activity in the liver was noticed on the PET scan. Pathological studies of the CT guided bone biopsy from the lumbar vertebra were suggestive of HCC which prompted the need for a CT scan performed with hepatic mass protocol. This showed multipe small, indeterminate lesions without a significant mass to suggest the presence of hepatic malignancy.
Discussion: The three different routes of the spread of HCC are: hematogenous, lymphatic embolization and direct extension to neighboring structures. Hematogenous spread to lungs is the most common route and direct infiltrating metastasis is the least common. A retrospective study of 482 patients with HCC, 65 of them (13.48%) had extrahepatic metastases to the lungs (53.8%), the bones (38.5%), and the lymph nodes (33.8%). Naturally, patients with extrahepatic metastasis have more advanced disease, with a median survival time of 7 months (range 1-59 months) and a survival rate of 24.9%. The case we report here presented an unusual course of HCC. But the failure of the initial work up to detect the primary malignancy required a more aggressive work up.
Menetrier’s Disease: A case report
Palak Shah M.D , Neetu Nebhwani M.D
Ménétrier's disease (hypertrophic gastropathy) is a rare cause of protein-losing enteropathy in adults and children. First described by Ménétrier in 1888, the disease is characterized by hypertrophic gastric folds and hypoalbuminemia. Histologically, there is expansion of surface mucous cell with absence of parietal cells resulting in achlorhydria and increased mucus production. Although the cause of this pathology is unknown, transforming growth factor Alfa (TGF – α), a mitogenic signaling molecule of epidermal growth factor receptor (EGF-R), might be playing a role in the etiology. Also, it is shown to have some association with CMV or H. pylori infection of the stomach. The disease carries an increased risk of subsequent gastric cancer, as high as 2–15% of lifetime risk. Here, we present a rare case of Menetrier’s Disease.
Case Report: A 38 year old male presented with c/o chronic epigastric burning pain, which was relieved by food intake and antacids. Additionally, he exhibited anasarca and weight gain, which were successfully treated with Lasix. He was also prescribed anatacids and protein supplements for albumin level of 1.8 gm/dl. He had no nausea, vomiting, dysphagia, and denied any diarrhea, constipation, blood per rectum or melena. The patient had no significant past medical or surgical history. No family history of colon cancer, polyp, IBD or celiac disease. The patient smoked and drank alcohol occasionally. On physical examination the patient was found to be thin, although not malnourished, rest of examination was not significant. On laboratory data, he recorded total protein level of 5.6 gm/dl and albumin level of 3.2 gm/dl and mild iron deficiency anemia. RPR and H.pylori antibody were negative. CT scan of abdomen and pelvis which was done to rule out pelvis mass had revealed questionable thickening of small bowel, jejunum and sigmoid colon. EGD showed erythmatous gastric body and fundus with hypertrophic folds, whereas esophageal mucosa and gastric antrum were grossly normal. Biopsy specimen of gastric body and fundus revealed reactive gastropathy with foveolar hyperplasia, which was consistent with Ménétrier's Disease. Antipariental cells and anti-Intrinsic factor antibodies were negative, Gastrin level was checked and H.Pylori antibody was rechecked. Patient was given Octreotide Injections, antacids and protein supplements. Patient is doing well with medical treatment at this point, so surgical treatment is deferred.
Conclusion: Menetrier’s disease, although rare, should be included as a differential for clinical presentation of epigastric pain, edema and hypoalbuminemia. The characteristic feature is hypertrophic gastric folds. Treatment for the patients with Ménétrier disease includes supportive treatment with antacid, protein supplements and H.pylori eradication. Also, Octreotide - a somatostatin analog and Cetuximab – which is an EGF- R blocker, can be effective treatment options in some patients. When condition does not respond to medical treatment, surgical treatment such as partial gastrectomy should be considered. This not only improves quality of life by giving symptomatic relief and preventing loss of protein, but it also reduces the risk of gastric carcinoma.
Clostridium difficile bacteremia: Yet another anecdote
Shilpa Bhardwaj M.D, Neetu Nebhwani M.D
Introduction: Clostridium difficile is an anaerobic gram positive rod which is known to be the main cause of antibiotic associated diarrhea and pseudo membranous colitis. While this bacteria is commonly isolated from stool specimens of infected patients, it is extremely uncommon to grow it in blood. However, there are sporadic case reports that have documented its growth in blood cultures, usually from patients who are acutely ill with severe ongoing disease processes. The present case is another such anecdotal episode of culturing C.difficile in blood.
Case presentation: We report a case of a 77 year old male who presented to the emergency department at Griffin Hospital in December 2008. At the time of admission patient had diarrhea and chills but denied fever, nausea, vomiting, blood in stools and urine. The patient had a past medical history of rectal cancer status post chemotherapy and resection, coronary artery disease status post CABG and hypertension. Also, he had been admitted 2 weeks ago for neutropenic fever after a cycle of chemotherapy and was discharged on Augmentin and Ciprofloxacin. On admission this time, B.P was 80/40 and temp of 97.3 F. Physical examination was normal except for an old ejection systolic murmur. Patient had elevated BUN, creatitnine with a white count of 8.8. The patient was aggressively resuscitated and admitted to intensive care unit. After the initial day, he remained hemodynamically stable. The patient was still on Augmentin and Ciprofloxacin during this admission which was discontinued because of diarrhea. He was pancultured to rule out any occult infection. Stool specimens for isolating Clostridium difficile were sent considering present complaints of diarrhea in the setting of recent antibiotic use. As expected, the patient grew Clostridium difficile in stool. However, much to our surprise one set of blood cultures was positive for Clostridium difficile as well. At the same time, his white count trended up and peaked at 17.5 during his stay. The patient was also mounting a moderate fever of 100.1 F during this time. He was started on Flagyl along with aggressive hydration and he responded well. He became afebrile and the white count trended back to normal. The patient had a total hospital stay of ten days.
Discussion: It is well known that gut is the main site of colonization for C. difficile. The anecdotal bacteremias that have been described thus far have usually had gut as the source of infection. Most case reports are from patients who have abscesses or sustained serious wounds and injuries. C. difficile has been reported to be isolated from both immunocompetent and immunocompromised patients. Unlike most reported cases of C. difficile bacteremia, this case does not show an extremely high white count, which could be due to the neutropenic state of the patient. The possibility of this culture being a result of contamination cannot be ruled out, yet, this seems like a curious case probing for many unanswered questions like the predictors of the risk of developing fulminant C. difficile bacteremia as well as successful treatment outcomes in immunocomprominsed patients.