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Herpes simplex virus (HSV) encephalitis is a serious life-threatening complication of neonatal HSV infection that may result in irreversible neurologic sequelae. While neonatal HSV may be transmitted in the intrauterine, peripartum, and the postpartum periods, the majority of transmissions occur in the peripartum period from a mother with active HSV genital lesions during delivery. Infants with CNS HSV present with seizures, tremors, lethargy, and irritability. On physical examination, patients often have high-grade fever and bulging fontanelles. The majority of patients also have an active vesicular HSV rash during the course of the CNS disease. On imaging, neonates with HSV encephalitis often have temporal lobe encephalitis or diffuse encephalitis. The disease is suspected based on clinical manifestations and imaging. Unlike other HSV infections, serology is not very helpful to diagnose neonatal HSV infection given the presence of transplacentally acquired maternal IgG. PCR or viral culture are useful diagnostic techniques to confirm clinical suspicion. HSV encephalitis requires antiviral therapy with acyclovir
HSV-1 and HSV-2 are 2 of 8 human herpesviruses. They are large, enveloped double-stranded DNA viruses with an icosahedral capsid. While labial herpes is almost always caused by HSV-1, genital herpes may be caused by either HSV-1 or HSV-2. HSV is also one of the ToRCHHeS infections, which are infections that can be transmitted vertically from the mother to the infant during pregnancy. The infections corresponding with the ToRCHHeS are: ''Toxoplasma gondii'', Rubella virus, cytomegalovirus, Herpes, HIV, and syphilis.<br/>
'''Educational Objective:''' Neonatal encephalitis may be caused by herpes simplex virus (HSV). HSV transmission often occurs during the peripartum period from a pregnant woman who has active genital lesions. Herpes infection may cause a vesicular rash and temporal lobe encephalitis that results in seizures and high-grade fever.<br/>
'''References:''' Kimberlin DW. Neonatal herpes simplex infection. Clin Microbiol Rev. 2004;17(1):1-13.<br>
First Aid 2014 page 174
Patients with pancreatic cancer often present with a painless jaundice that results from compression of the bile duct by the mass in pancreatic head. Pancreatic adenocarcinomas account for 95% of pancreatic tumors; they arise from the exocrine cells of the pancreas. 75% of these cancers arise in the head of the pancreas. Mutations of the ''KRAS'' gene are present in 96% of patients with pancreatic adenocarcinomas. A curative pylorus-preserving Whipple procedure (pancreatoduodenectomy) may be performed for patients with localized disease at the time of diagnosis. Otherwise, patients who are not surgical candidates may benefit from palliative chemotherapy that improves quality of life and may gain modest benefit in survival. Pancreatic cancer has an extremely poor prognosis.
The patient in this vignette is being treated with 5-Fluorouracil (5-FU). 5-FU is a pyrimidine analogue indicated for a variety of solid adenocarcinomas, such as pancreatic adenocarcinoma and colorectal cancer. It is also indicated in topical form for actinic keratosis and basal cell carcinoma. Once introduced into a cell, 5-FU is converted to 5-FdUMP which then inhibits thymidylate synthase. Thymidylate synthase is the enzyme responsible for the synthesis of thymine nucleotides, which are essential for DNA synthesis. 5-FU can also be incorporated into newly synthesized RNA and thereby disrupt RNA synthesis. 5-FU acts only in S-phase of the cell cycle (when the genome is being replicated prior to cell division). Adverse reactions associated with 5-FU administration include bone marrow toxicity, oral ulcerations, photosensitivity, and anorexia.<br/>
'''Educational Objective:''' 5-FU is a fluorinated uracil anaologue indicated in several solid cancers. 5-FU inhibits thymidylate synthase, an enzyme essential for the synthesis of thymine nucleotides needed for DNA synthesis.<br/>
'''References:''' Beck A, Etienne MC, Chéradame S, et al. A role for dihydropyrimidine dehydrogenase and thymidylate synthase in tumour sensitivity to fluorouracil. Eur J Cancer. 1994;30A(10):1517-22.<br> Kaye SB. New antimetabolites in cancer chemotherapy and their clinical impact. Br J Cancer. 1998;78 Suppl 3:1-7.<br>
First Aid 2014 page 403<br>
Vincristine is an alkaloid that binds to β-tubulin dimers, thereby inhibiting the assembly of microtubules and blocking microtubule formation in the mitotic spindle (M-phase arrest). Because cancer cells divide more rapidly, there is a therapeutic window which allows vincristine to be used as a chemotherapeutic agent. Mitosis occurs after cells have duplicated their genomes in S phase. Thus, cells which are stalled in mitosis will appear to have doubled DNA content, as pictured in the flow cytometry plot below.
Vincristine is used in a variety of cancers including Wilms’ tumor, rhabdomyosarcoma, neuroblastoma, and non-Hodgkin's lymphoma. However, its use is particularly important in the treatment of Hodgkin’s lymphoma, where it is part of the MOPP protocol (Mustargen, Oncoverin/Vincristine, Procarbazine, and Prednisone). The most prominent adverse event associated with vincristine is neurotoxicity, such as peripheral neuritis and paralytic ileus. Vincristine is contraindicated in pregnant women and patients with demyelinating forms of Charcot-Marie-Tooth syndrome.
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<img src="http://static.wikidoc.org/1/13/Mitosis_Arrest_Figure_Explanation_copy.svg" style="width:600px">
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'''Educational Objective:''' Vincristine is an alkaloid that binds to β-tubulin dimers, thereby inhibiting the assembly of microtubules and blocking microtubule formation in the mitotic spindle (M-phase arrest).<br/>
'''References:''' First Aid 2014 page 405 +
The patient in this vignette is suffering from polycythemia vera and is being treated with hydroxyurea. Polycythemia vera (PV) is a myeloproliferative blood disorder in which the bone marrow produces red blood cells excessively. PV is caused by mutations in the ''JAK2'' gene, which renders erythroid precursors hypersensitive to erythropoietin (EPO). PV is more common in the elderly and may be symptomatic or asymptomatic. Common signs and symptoms include pruritus and severe burning pain in the hands or feet that is usually accompanied by a reddish or bluish discoloration of the skin. Pruritis is often exacerbated by exposure to warm water, such as when taking a shower or bath. On physical examination, splenomegaly is common due to erythrocyte trapping. The rapid turnover of erythrocytes in PV can lead to release of uric acid and gout in 20% of patients.
Treatment for PV includes regular aggressive phlebotomy to decrease blood count and the concentration of RBCs. Phlebotomy may be supplemented with pharmacologic therapy using pipobroman, hydroxyurea, busulfan, and ruxolitinib. Hydroxyurea inhibits ribonucleotide reductase and essentially starves erythrocyte precursors of necessary deoxynucleotides for DNA synthesis. Hydoxyurea is also indicated for sickle cell disease. Sickle cell disease is caused by a point mutation in the beta-globin chain of the hemoglobin tetramer, whereby glutamic acid is substituted for valine at position 6. Through unknown mechanisms, hydroxyurea administration increases the synthesis of fetal hemoglobin (HbF) in patients with sickle cell disease, which may replace the mutant beta-globin in sickle cell patients and thereby decrease sickling of RBCs. Notably, the efficacy and safety of hydroxyurea has also been variably studied for other disorders (eg. thalassemia intermedia, thalassemia major, and paroxysmal nocturnal hemoglobinuria, essential thrombocythemia, solid tumors, leukemia, and psoriasis).<br/>
'''Educational Objective:''' Hydroxyurea is a ribonucleotide reductase inhibitor indicated for polycythemia vera and sickle cell disease. Sickle cell disease is caused by a point mutation in the beta-globin chain of the hemoglobin tetramer, whereby glutamic acid is substituted for valine at position 6.<br/>
'''References:''' First Aid 2014 page 405
The patient in this vignette has developed hemorrhagic cystitis following cyclophosphamide administration. Chronic lymphocytic leukemia (CLL) is an indolent, slowly evolving hematopoetic malignancy that primarily affects the elderly. Because CLL is a slowly-growing malignancy that may not be clinically detectable for prolonged periods of time, chemotherapy is generally withheld until the patient is symptomatic. CLL is generally a B-cell leukemia that demonstrates CD20+ and CD5+. CLL may feature autoimmune hemolytic anemia, peripheral blood lymphocytosis, and the presence of smudge cells on peripheral blood smears (damaged leukocytes during the preparation of the smear). CLL may be treated using antineoplastic agents, such as cyclophosphamide. Cyclophosphamide is an alkylating agent that covalently cross-links guanine nucleotides at the N-7 nitrogen. Cyclophosphamide administration is associated with hemorrhagic cystitis that may take a few weeks to develop following after cyclophosphamide is started. A small portion of the original drug is metabolized to acrolein. Acrolein is toxic to the bladder urothelium and can, at least partly, lead to hemorrhagic cystitis. The high concentrations of acrolein may be prevented through the use of aggressive hydration and/or mesna. Mesna binds acrolein in the bladder, barring it from exerting its toxic effects. Cyclophosphamide itself is a carcinogen and may cause acute myeloid leukemia (AML) or transitional cell carcinoma of the bladder.<br/>
'''Educational Objective:''' Mesna may be administered along with cyclophosphamide to prevent hemorrhagic cystitis.<br/>
'''References:''' Korkmaz A, Topal T, Oter S. Pathophysiological aspects of cyclophosphamide and ifosfamide induced hemorrhagic cystitis; implication of reactive oxygen and nitrogen species as well as PARP activation. Cell Biol Toxicol. 2007.23(5):303-12.<br>
First Aid 2014 page 407 +
Ovarian cancer results from the malignant transformation of the ovarian epithelium. It is usually suspected in pre-menopausal women with enlarging ovarian sizes and post-menopausal women with a palpable adnexal mass. Risk for ovarian cancer is family history, increases with older age, nulliparity, and familial cancer syndromes caused by mutations of the ''BRCA1'' (chromosome 17q) and ''BRCA2'' (chromosome 13q). ''BRCA1'' and ''BRCA2'' normally encode nuclear proteins involved in DNA repair. On the other hand, oral contraceptive use, tubal ligation, pregnancy, and lactation are associated with a reduced risk for the development of ovarian cancer. Histopathological analysis of ovarian cancer may demonstrate any of 4 subtypes:
#Papillary serous: Most common. Characterized by presence of psammoma bodies. Usually markedly elevated serum CA-125 level
#Endometrioid: May be associated with endometriosis
#Mucinous: May be associated with pseudomyxoma peritonei. May be chemoresistant. Less associated with BRCA mutations or elevations in serum CA-125 level
#Clear-cell: Chemoresistant. Hobnail-shaped with clear cytoplasm.
Patients with ovarian cancer may have non-specific abdominal or pelvic symptoms, such as abdominal fullness and bloating, indigestion, early satiety, or pelvic pain. Physical examination may be unremarkable or may be significant for a palpable abdominal or pelvic mass, ascites, or Sister Mary Joseph's nodule (umbilical mass). In the minority of cases, ovarian cancer is associated with paraneoplastic syndromes, such as hypercalcemia, subacute cerebellar degeneration (presence of anti-Purkinje-cell antibodies), Leser-Trelat sign (sudden development of multiple seborrheic keratoses on trunk), and Trousseau's syndrome (migratory superficial thrombophlebitis). A transvaginal ultrasound is useful to confirm the presence of an ovarian mass and is more sensitive than CT scan. Although CA-125 measurement suffers from low sensitivity and specificity, it may be useful to confirm diagnosis, especially among post-menopausal women with palpable adnexal mass and serum CA-125 levels > 65 U/mL. CA-125 is also useful for follow-up and evaluation of response to therapy.
The majority of patients require surgical debulking of the tumor followed by adjuvant chemotherapy to fully eradicate residual cancer cells. Chemotherapy often includes carboplatin and paclitaxel. Paclitaxel hyperstabilizes microtubules and inhibits the disassembly of the mitotic spindle (M-phase arrest). Paciltaxel may also be used in drug-eluting stents (DES) that are used in interventional cardiology for patients with myocardial infarction (MI). The use of antiproliferative agents, such as paclitaxel, prevents re-stenosis of a previously deployed stent via inhibition of intimal hyperplasia caused by vascular smooth muscle cells in the stented coronary artery.<br/>
'''Educational Objective:''' Paclitaxel is a chemotherapeutic agent that inhibits microtubule depolymerization. It is indicated for ovarian cancer and may be used in drug-eluting stents.<br/>
'''References:''' Cannistra SA. Cancer of the ovary. N Engl J Med. 2004;351:2519-29.<br>
First Aid 2014 page 405
The patient in this scenario presents with premature ovarian failure (POF), a primary ovarian defect characterized by depletion of ovarian follicle reserve before 40 years of age. Patients with POF might have primary amenorrhea, where menarche has been absent since birth, or secondary amenorrhea, where patients stop having menses before they reach the age of 40. The clinical signs and symptoms of POF are similar to those of menopause. Patients with POF typically present with hot flashes, fatigue, and facial flushing. Lab work-up also reveals a marked decrease in ovarian hormones, estrogen and progesterone, and a significant increase in pituitary hormones, LH and FSH, which are no longer regulated by feedback inhibition.<br/>
'''Educational Objective:''' Premature ovarian failure (POF) is a state of primary ovarian defect, which mimics menopause, before the age of 40. In POF, ovarian hormones are decreased, while pituitary hormones are increased due to an absence of feedback inhibition.<br/>
'''References:''' Beck-Peccoz P, Persani L. Premature ovarian failure. Orphanet J Rare Dis. 2006; 1:9. +
The patient in this scenario is most likely presenting with HELLP (hemolysis, elevated liver enzymes, and low platelets) syndrome. The disease is classically described as a complication of preeclampsia, despite a recent trend considering HELLP as one extreme on the pregnancy-related hypertensive disease spectrum. HELLP is a life-threatening condition that most commonly manifests in pregnant women between 32-34 weeks of gestation, classically those with diagnosed preeclampsia. Similar to this scenario, patients with HELLP syndrome present with right upper abdominal pain with non-specific symptoms, such as fatigue and nausea. The hepatic lesions (microthrombi and fibrin clots) associated with HELLP syndrome lead to obstruction of the circulation and liver swelling with tension of the Glisson capsule, causing abdominal pain. Serum haptoglobin is important for the detection of early hemolysis. Usually an elevation in liver enzymes precedes the decrease in platelets. Patients who are at 32 weeks gestation or more are usually recommended to deliver as soon as the diagnosis is made. The most common causes of mortality in patients with HELLP syndrome are intracranial hemorrhage and ARDS.<br/>
'''Educational Objective:''' Intracranial hemorrhage and ARDS are the most common causes of mortality in patients with HELLP syndrome.<br/>
'''References:''' Rath W, Faridi A, Dudenhausen JW. HELLP syndrome. J Perinat Med. 2000;28(4):249-60. <br>
Suarez B, Alves K, Senat MV, et al. Abdominal pain and preeclampsia: sonographic findings in the maternal liver. J Ultrasound Med. 2002;21(10):1077-83. +
The patient in this scenario has the classical presentation of iron deficiency anemia (IDA). Children are often asymptomatic but may present with fatigue, poor school performance, and pica (increased appetite for substances that are largely non-nutritive such as dirt, rocks, ice, and clay). Physical exam typically reveals tachycardia, impaired growth, skin and conjunctival pallor, spoon-shaped nails (koilonychia), and glossitis. Risk factors include prematurity, exclusive breastfeeding beyond 6 months not supplemented by iron-rich foods, early and/or excessive cow milk consumption, and maternal prenatal anemia.
Patients with IDA usually require several months of oral iron supplementation. Iron is absorbed in the duodenum as ferrous (Fe<sup>2+</sup>) iron. At physiological pH, ferrous iron is readily oxidized into ferric (Fe<sup>3+</sup>) iron, which is not as readily absorbed by the duodenum as ferrous iron. ''In vivo'', however, the acidity present in the stomach allows the absorption of iron in the form of ferrous iron in the duodenum. The use of proton pump inhibitors, or other drugs that decrease gastric acidity may reduce the absorption of iron in the duodenum due to the decreased availability of ferrous iron.<br/>
'''Educational Objective:''' Ferrous iron is absorbed in the GI tract mostly at the level of the duodenum.<br/>
'''References:''' <br>Cheng TL. Iron deficiency anemia. Pediatr Rev. 1998;19(9):321-2.
First Aid 2014 page 335 +
Tropical sprue is an intestinal disease of unknown etiology, most likely a manifestation of an infectious process. The most common regions of distribution are the Caribbeans, South America, and India. Patients with tropical sprue frequently present with chronic diarrhea and steatorrhea. Other findings associated with tropical sprue, such as fatigue, weight loss, abdominal colics, glossitis, angular stomatitis, anemia, and hypoproteinemia, are often also indicative of malabsorption. The disease is diagnosed endoscopically, displaying features of inflammation involving the entire small bowel as opposed to celiac sprue that is usually confined to the proximal small bowel. Histologically, variable villous atrophy (partial, subtotal, total) may be observed.<br/>
'''Educational Objective:''' Patients with tropical sprue have inflammation of the entire small bowel with variable villous atrophy.<br/>
'''References:''' Baker SJ. Tropical sprue. Br Med Bull. 1972;28(1):87-91. +
Acute lymphoblastic leukemia (ALL) is the most common childhood malignancy, accounting for approximately 30% of all cancers in patients younger than 14 years of age. It is a clonal lymphoid stem cell disease. The classical presentation of patients with ALL includes fatigue, recurrent infections, bony pain, weight loss, easy bruisability, petechiae, dyspnea on exertion, and hepatosplenomegaly. t(12;21) translocation is the most common chromosomal anomaly in childhood leukemias and is exclusively found in patients with Pre-B-ALL (approximately 25% of these patients). The translocation generates TEL-AML1 (ETV6-RUNX1) fusion gene, which is associated with a more favorable prognosis as evidenced by a significantly lower relapse rate. Evaluation of this and other prognostic markers helps in selecting low toxicity versus high toxicity therapies.<br/>
'''Educational Objective:''' The t(12;21) translocation is a good prognostic marker in cases of acute lymphoblastic leukemia.<br/>
'''References:''' Romana SP, Mauchauffé M, Le coniat M, et al. The t(12;21) of acute lymphoblastic leukemia results in a tel-AML1 gene fusion. Blood. 1995;85(12):3662-70.<br>
Borkhardt A, Cazzaniga G, Viehmann S, et al. Incidence and clinical relevance of TEL/AML1 fusion genes in children with acute lymphoblastic leukemia enrolled in the German and Italian multicenter therapy trials. Associazione Italiana Ematologia Oncologia Pediatrica and the Berlin-Frankfurt-Münster Study Group. Blood. 1997;90(2):571-7. +
Neonatal lupus is a relatively rare disease of the newborn characterized by cutaneous lesions and third-degree heart block, along with dilated cardiomyopathy, hepatobiliary disease, and hematological abnormalities. Although cutaneous lupus lesions often appear several days later, patients may develop lesions immediately after birth. The lesions are typically described similarly to those described in this patient, showing annular erythema with central clearing and raised red borders. Classically, congenital third-degree (complete) heart block begins in utero and persists antenatally. On ECG, third-degree heart appears as a complete dissociation between the P waves and the QRS complexes. The presence of heart block has been attributed to fibrosis of the AV node region. Patients usually require pacemaker placement, and if left untreated, the majority of patients die.
Neonatal lupus is responsible for 80 to 95% of all cases of congenital complete heart block diagnosed in utero or in the neonatal period. The characteristic skin rash, the maternal history consistent with systemic lupus erythematosus (autoimmune disease characterized by joint paints, malar rash, and photosensitivity in an African-American patient), and the congenital heart block makes the diagnosis of neonatal lupus very likely. Neonatal lupus (NL) results from the transplacental passage of maternal anti-SSA/Ro and/or anti-SSB/La antibodies. The presence of anti-Ro-antibodies is considered the most significant risk factor for the development of neonatal lupus. Most infants with complete heart block have a mother with anti-SSA/Ro and anti-SSB/La antibodies, and screening for those antibodies may prevent the patient's condition by administration of systemic corticosteroids, which has demonstrated efficacy in improving outcomes in neonatal lupus.<br/>
'''Educational Objective:''' Neonatal lupus (NL) results from the transplacental passage of maternal anti-SSA/Ro and/or anti-SSB/La antibodies. The presence of anti-Ro-antibodies is considered the most significant risk factor for the development of neonatal lupus. Neonatal lupus is a relatively rare disease of the newborn characterized by cutaneous lesions and third-degree heart block, along with dilated cardiomyopathy, hepatobiliary disease, and hematological abnormalities.<br/>
'''References:''' Finkelstein Y, Adler Y, Harel L, Nussinovitch M, Youinou P. Anti-Ro (SSA) and anti-La (SSB) antibodies and complete congenital heart block. Ann Med Interne. 1997;148(3):205-8.<br>
Lee LA. Neonatal lupus erythematosus: clinical findings and pathogenesis. J Investig Dermatol Symp Proc. 2004;9:52-6.<br>
Lee LA. Neonatal lupus. clinical features and management. Paediatr Drugs. 2004;6(2):71-8.<br>
First Aid 2014 page 425<br>
Friedreich's ataxia (FRDA) is an autosomal recessive neurodegenerative disease characterized by a transcription defect caused by GAA trinucleotide repeats in the ''Frataxin'' gene on the long arm of chromosome 9. The defect of the ''Frataxin'' gene results in a deficient frataxin protein, an iron-binding protein, in the mitochondria and a reduction of overall mitochondrial metabolism. The hallmark of FRDA is a CNS and PNS disease with involvement of the heart, skeleton, and endocrine system. FRDA affects children aged 9-16 years old, and patients usually die before they reach 40 years of age. Neurological manifestations of FRDA include dysarthria, staggering gait ("clumsy" children) and dysmetria of the extremities due to involvement of the spinocereballar tissue, weakness of the lower extremities due to involvement of the corticospinal tracts, loss of vibratory and priopioceptive sensation due to involvement of the dorsal columns, areflexia, stocking-and-glove type sensory neuropathy, and positive Babinski sign. Other clinical features include hypertrophic cardiomyopathy, which may be the first manifestation of the disease and is often the cause of death. Hypertrophic cardiomyopathy may be suggested on physical examination by the presence of an S4 gallop, a low-pitched sound present late in diastole that immediately precedes S1. Skeletal abnormalities usually include scoliosis, kyphoscoliosis, and pes cavus of the feet. Approximately 20% of individuals with FRDA develop carbohydrate intolerance, and 10% develop diabetes mellitus. Diabetes mellitus is usually a late manifestation of the disease and may be due to either insulin-dependence or glucose intolerance without insulin dependence. Although the association is clear, the exact pathogenesis for the association of diabetes mellitus and FRDA is poorly understood.<br/>
'''Educational Objective:''' Friedreich's ataxia (FRDA) is an autosomal recessive neurodegenerative disease characterized by a transcription defect caused by GAA trinucleotide repeats in the ''Frataxin'' gene on the long arm of chromosome 9. The hallmark of FRDA is a CNS disease with involvement of the heart, skeleton, and endocrine system. Diabetes mellitus is usually a late manifestation of FRDA<br/>
'''References:''' Schoenle EJ, Boltshauser EJ, Baekkeskov S, et al. Preclinical and manifest diabetes mellitus in young patients with Friedreich's ataxia. no evidence of immune process behind the islet cell destruction. Diabetologia. 1989;32:378-81.<br>
Gonzalez-Cabo P, Palau F. Mitochondrial pathophysiology in Friedreich's ataxia. J Neurochem. 2013; 126 Suppl 1:53-64.<br>
Koeppen AH. Friedreich's ataxia: pathology, pathogenesis, and molecular genetics. J Neurol Sci. 2011; 303(1):1-12.<br>
First Aid 2014 page 468
Digitalis has been tested in several RCTs and there’s a general consensus that it does not improve mortality, but it decreases hospitalizations and reduces healthcare costs.<br/>
'''Educational Objective:''' <br/>
'''References:''' +
Aortic injuries carry a high mortality rate and are immediately fatal in an estimated 80%–90% of all cases. Evaluation for mediastinal hematoma, and by inference a major vascular injury, is the main goal of the initial chest radiograph as shown above. Acute traumatic aortic injuries are considered to be surgical emergencies, and patients should undergo repair immediately especially if they are hemodynamically unstable as is the case here.<br/>
'''Educational Objective:''' <br/>
'''References:''' +
Maternal physiological changes in pregnancy are the normal adaptations that a woman undergoes during pregnancy to better accommodate the embryo or fetus. They are physiological changes, that is, they are entirely normal, and include cardiovascular, hematologic, metabolic, renal and respiratory changes that become very important in the event of complications.
During pregnancy the plasma volume increases by 50% and the red blood cell volume increases only by 20-30%. Consequently, the hematocrit decreases on lab value; this is not a true decrease in hematocrit, however, but rather due to the dilution.
The glomerular filtration rate (GFR) commonly increases by 50%, returning to normal around 20 weeks postpartum, therefore there’s a decrease in blood urea nitrogen (BUN) and creatinine. TSH will be normal while total T3 and T4 may increase as a result of high estrogen levels.<br/>
'''Educational Objective:''' <br/>
'''References:''' +
The patient presents has severe sepsis – fever and cloudy urine. The cloudy urine indicates that UTI is the possible source of the infection. Complications of severe sepsis include: multi-organ dysfunction such as hypotension, encephalopathy, disseminated intravascular coagulation (DIC) and renal insufficiency. You need to differentiate between DIC and Thrombotic Thrombocytopenic Purpura (TTP).
DIC is a consumptive coagulopathy i.e., it consumes the entire coagulation factors along with platelets. Hence, PT and PTT are elevated and fibrinogen is decreased in DIC but not in TTP. The intravascular thrombi in DIC are fibrin thrombi – the lysis of this lead to increased D-dimer and Fibrin Split Products. TTP is a consumptive thrombocytopenia, and is composed of platelet thrombi not fibrin – so, D-dimer is usually normal in TTP. Severe sepsis can resemble TTP. A full clinical picture should be considered in decision making. The source of sepsis should be sought and ruled out in suspected cases before making a diagnosis of TTP.
Educational Objective: Complications of severe sepsis include: hypotension, encephalopathy, DIC, e.t.c. Both disseminated intravascular coagulation and thrombotic thrombocytopenic purpura have similar presentation. In DIC, there is elevated PT, PTT, D-dimer, and fibrin split products.<br/>
'''Educational Objective:''' <br/>
'''References:''' +
The patient in this scenario is suffering from hairy leukoplakia, a white patch on the side of the tongue with a corrugated or hairy appearance. Hairy leukoplakia can be distinguished from oral candidiasis by the fact that candidiasis causes lesions which can be sloughed off by scraping leaving an area of inflammation, whereas leukoplakia cannot. Hairy leukoplakia is caused by Epstein-Barr virus (EBV) and is most commonly seen in HIV-infected patients. As a benign lesion, it does not require treatment but it typically responds to acyclovir therapy. The presence of hairy leukoplakia may indicate a high degree of immunocompromise. Hairy leukoplakia should also be distinguished from idiopathic leukoplakia, a premalignant lesion of oral squamous cell carcinoma, seen in smokers and in patients that chew tobacco. Both these lesion cannot be scraped off.<br/>
'''Educational Objective:''' Hairy leukoplakia is caused by EBV and is seen in patients with HIV/AIDS.<br/>
'''References:''' First Aid 2014 page 169 +
Sickle cell anemia (SCA) is an autosomal recessive genetic disorder caused by a missense mutation of the β-globin gene (substitution of the normal hydrophilic glutamic acid (GTG) with a hydrophobic valine (GAG) at the 6th position of the β-globin chain). Since valine on different globin chains has the capacity to dock complementary sites, the hydrophobic motif caused by the missense mutation in the deoxygenated HbS tetramer allows the polymerization of HbS by binding 2 hemoglobin molecules at the level of the mutated β-1 and β-2 chains. Binding of these molecules produces polymer nuclei that grow and disrupt the cellular morphology, resulting in cellular dehydration and oxidative stress. The presence of 3 factors determine the rate and severity of Hbs polymerization: Hb deoxygenation, intracellular HbS concentration, and presence of fetal hemoglobin (HbF) in the RBC.
SCA is thus characterized by the abnormal presence of rigid, sickle-shaped RBC. The abnormal RBCs obstruct capillaries and restrict blood flow to an organ, resulting in ischemia, pain, necrosis, and organ damage. Clinical manifestations of SCA are usually not present until the concentration of HbF diminishes beyond infancy. The child in this vignette is suffering from dactylitis, which is often described as the presenting symptom of sickle cell disease. Hand-foot-syndrome due to dactylitis causes painful swelling of the hands and/or feet; it usually affects young children < 3 years of age. Patients eventually develop more complications from vaso-occlusive crises: acute chest syndrome (hypoxia-driven, pneumonia-like illness with fever, respiratory symptoms, and infiltrates on chest x-ray due to vaso-occlusion and/or infections), avascular necrosis of bone, acute abdomen (mesenteric vessel occlusion), splenic disease (splenic sequestration, hyposplenism, and autosplenectomy), renal disease (papillary necrosis), aplastic crises with parvovirus B19 infection, priapism, severe osteomyelitis (commonly due to ''S. aureus'' but classically associated with ''Salmonella spp.''), and finally cerebrovascular events (ischemic strokes). SCA is common in Africa and some regions of the Middle East. Diagnosis of SCA is usually by hemoglobin electrophoresis or chromatography. Treatment includes chronic hydroxyurea therapy that increases the concentration of HbF, provides symptomatic relief, and decreases the frequency and intensity of complications. Patients do not regularly require transufsions as patients with β-thalassemia do, but acute transfusions in SCA may only be required for acute exacerbations of anemia, severe acute chest syndrome, stroke, and in cases of multiorgan failure. Bone marrow transplant is the only curative treatment for patients with SCA.
It is important to distinguish different terms that are related to sickle cell anemia:
*Sickle cell disease: A general term that refers to all genotypes that cause the clinical syndrome
*Sickle cell anemia (HbSS): SCD that is specifically caused by homozygous β<sup>s</sup> allele
*Sickle cell trait: Heterozygous mutation of the β-globin gene. Individuals do not have symptoms of sickle cell disease
*Hemoglobin SC disease (HbSC disease): Co-inheritance of β<sup>s</sup> and β<sup>c</sup> alleles with moderate severity of symptoms
*HbS/β-thalassemia: Inheritance of β<sup>s</sup> with a β-thalassemia allele. Clinically, manifestations are similar to SCA<br/>
'''Educational Objective:''' Sickle cell anemia (SCA) is an autosomal recessive genetic disorder caused by a missense mutation of the β-globin gene (substitution of the normal hydrophilic glutamic acid (GTG) with a hydrophobic valine (GAG) at the 6th position of the β-globin chain).<br/>
'''References:''' Rees DC, Williams TN, Gladwin MT. Sickle-cell disease. Lancet. 2010;376:2018-31.<br>
Stuart MJ, Nagel RL. Sickle-cell disease. Lancet. 2004; 364(9442):1343-60.<br>
First Aid 2012 page 386
Pituitary enlargement and hyperpigmentation following bilateral adrenalectomy is called Nelson’s syndrome. The cause of pituitary enlargement is loss of feedback by adrenal glucocorticoids following the adrenalectomy. The tumour is aggressive and is treated by surgery or pituitary radiation.<br/>
'''Educational Objective:''' <br/>
'''References:''' +