Cynthia H. Ho

2-year-old girl with pancytopenia due to vitamin B12 (cobalamin) deficiency.

Case A 2-year-old girl of Mexican and Spanish descent came to our hospital with her mother for 2 weeks of pallor and fatigue. She was born full term to parents who were first cousins. Past medical history was unremarkable, and development was appropriate. Diet was balanced and unrestricted. Growth parameters were appropriate. She appeared well nourished but with obvious pallor. Liver and spleen were not palpable. Neurologic examination was unremarkable. Laboratory tests revealed pancytopenia with white blood cell count of 2.9 × 10 3 /μL, haemoglobin of 4.8 g/dL, platelets of 98 × 10 3 /μL, mean corpuscular volume of 94 fL and red cell distribution width of 43%. Additional serum tests showed lactate dehydrogenase of 3128 U/L (normal 90‐220), total bilirubin 1.2 mg/dL (normal 0‐1) and direct bilirubin 0.3 mg/dL (normal 0‐0.3). On review of the peripheral blood smear, macrocytosis and hypersegmented neutrophils were seen. The differential diagnosis of macrocytosis in infants and children is shown in Table 1. The finding of megaloblastic anaemia, defined by hypersegmented neutrophils in the peripheral blood, raised concern for a problem with deoxyribonucleic acid (DNA) synthesis during red blood cell production. Therefore, serum levels of vitamin B12 (cobalamin) and folate were obtained. Vitamin B12 was 45 pg/mL (normal 211‐911), and folate was 14 ng/mL. Urine dipstick showed 30 mg/dL protein. DNA mutation analysis revealed a homozygous mutation of the amnionless gene (AMN) consistent with ImerslundGrasbeck syndrome (IGS, megaloblastic anaemia 1; OMIM #261100). Our patient was treated with intramuscular vitamin B12 injections. At a clinic visit 2 months later, serum vitamin B12 level was 384 pg/mL. The patient is now a healthy and thriving 6-year-old girl. She continues to have mild proteinuria (30‐ 100 mg/dL) without evidence of impaired glomerular function.

BITTER BOTTLE GOURD (LAGENARIA SICERARIA) TOXICITY

BACKGROUND Bottle gourd (Lagenaria siceraria) is an edible plant in the Cucurbitaceae family. When extremely bitter, ingestion of bottle gourd can cause rapid onset diarrhea, vomiting, gastrointestinal bleeding, and hypotension due to release of a substance named cucurbitacin. OBJECTIVE Our aim was to increase physician awareness of cucurbitacin poisoning in order to facilitate accurate diagnosis and appropriate management. CASE REPORT Five adult patients presented with nausea, vomiting, and diarrhea within 5 to 25 min of ingesting cooked bitter bottle gourd. One patient developed severe diarrhea, hematemesis, and hypotension requiring hospitalization. All patients improved within a few days with intravenous fluids and proton pump inhibitors. To our knowledge, this is the first reported group of patients with toxicity due to ingestion of bottle gourd in the United States (US). CONCLUSIONS Physicians should be suspicious of cucurbitacin toxicity in patients who present with symptoms within minutes of ingestion of a plant in the Cucurbitaceae family. Patients should be asked if the plant tasted unusually bitter. The most common symptoms include diarrhea and hematemesis. More than half of patients develop hypotension. There is no known antidote for bottle gourd poisoning; treatment is supportive. Proton pump inhibitors should be given to patients with gastrointestinal mucosal injury.

Hypersegmented Neutrophils in an Adolescent Male With Heatstroke.

A 14-year-old male presented to the hospital after syncope during football practice on a hot summer day. On examination, temperature was 40.41C (104.71F) and heart rate was 180 beats per minute. He was unresponsive, intubated, and cooled in the pediatric intensive care unit. Laboratory values revealed acute kidney injury and ischemic hepatitis. Complete blood count showed a white blood cell count of 17!10/L, hemoglobin of 14.8 g/L, platelet count of 395!10/L, and mean corpuscular volume of 83.8 fL (normal, 81.4 to 91.9 fL). Peripheral blood smear showed hypersegmented neutrophils with “botryoid” nuclei (Supplemental Fig. 1 Supplemental Digital Content 1, http://links.lww.com/JPHO/A98). Hypersegmented neutrophils are classically seen with folate (vitamin B9) orcobalamin (vitamin B12) deficiency. These morphologic changes of the neutrophil nucleus occur due to impaired DNA synthesis from inadequate substrate or impaired replication from a toxin or medication effect. Arrest of nuclear maturation, impaired cell division, and unbalanced cell growth results in characteristic large cells with immature nuclei with relative cytoplasmic maturity. Red blood cell macrocytosis often accompanies hypersegmented neutrophils and can be seen in hypothyroidism, alcohol abuse, uremia, and myelodysplastic syndromes. Hypersegmented neutrophils without red blood cell macrocytosis, as in our patient, has been described in patients with hyperthermia, uremia, and concurrent megaloblastic and microcytic anemia from combined folate and/ or cobalamin deficiency along with iron deficiency or thalassemia. As the finding of hypersegmented neutrophils preceeds macrocytosis, neutrophil hypersegmentation without macrocytosismay represent early cobalamin and folate deficiency.1 The term “botryoid” refers to nuclei that appear like a cluster of grapes around a stem.2 Botryoid nuclei have been described in patients with hyperthermia due to cocaine and methamphetamine use,3 malignant hyperthermia, neuroleptic malignant syndrome,4 and autoimmune disorders such as rheumatoid arthritis, psoriatic arthritis, and systemic sclerosis.5 In comparison, the multilobed nuclei in cobalamin and folate deficiency appear disorganized. The pathogenesis of botryoid nuclei in hyperthermia has not been clearly elucidated. Hyperthermia may activate the intrinsic signaling pathway that initiates apoptosis since pyknosis, nuclear condensation in the setting of irreversible cell death, is seen in neutrophils in response to hyperthermia.6 In addition, microtubular decomposition may play a role.7 In vitro experiments have shown that radially segmented neutrophils are induced by applying heat.8 Botryoid changes in >50% of neutrophils on a peripheral blood smear may be sufficient to diagnose heatstroke.2 Fewer than 50% botryoid neutrophils is suggestive of heatstroke. Clinicians should be aware that hyperthermia can cause hypersegmented neutrophils so as to avoid unnecessary evaluations for other etiologies. Our patient’s mental status and renal function improved with cooling and intravenous fluids. He was extubated on the first day of hospitalization. Subsequent peripheral blood smears showed resolution of hypersegmented neutrophils by the second hospital day. He was discharged home after 3 days without any complications.

Paracetamol-induced ductal closure in a 5-month-old infant.

Recently, we cared for a 5-month-old baby boy born at 28 weeks gestation with a 1.9-mm patent ductus arteriosus (Fig 1). The parents were counselled regarding the plan for percutaneous device closure and asked to return 2 weeks later. Surprisingly, on repeat echocardiogram, the ductus arteriosus had closed. As spontaneous ductal closure is unusual past the newborn period, we questioned the parents about the events in the preceding 2 weeks. The parents reported administering paracetamol 12 mg/kg/dose twice daily for 4 days because of fussiness and nasal congestion. In premature infants during the newborn period, indomethacin or ibuprofen are first-line agents utilised for ductal closure. In patients with contraindications to non-steroidal anti-inflammatory drugs, paracetamol at 15 mg/kg/dose every 6 hours for 48 hours has been used effectively as a second-line agent. Previous authors have suggested that paracetamol works by acting at the peroxidase segment of prostaglandin synthetase and inhibits activity. To the best of our knowledge, our case is the first reported case of ductal closure associated with paracetamol outside of the newborn period. Further studies are needed to elucidate the role of paracetamol for ductal closure beyond the neonatal period.

Case 3: Jaundice, Pallor, and Failure to Thrive in a 7-week-old Infant

1. Brigid O’Brien, DO* 2. Brittany Middleton, MD* 3. Erica Cua, MD* 4. Alex Resnick, MD* 5. Cynthia H. Ho, MD*,† 1. Departments of *Pediatrics and 2. †Internal Medicine, University of Southern California Medical Center, Keck School of Medicine, Los Angeles, CA A 7-week-old African-American boy is brought to the hospital by a social worker after law enforcement responded to a report of domestic violence between his parents. History from the social worker is limited. She states that the infant is fussy but has tolerated a bottle of infant formula. On physical examination, his weight is 3.7 kg (<5th percentile), length is 55 cm (25th percentile), and head circumference is 39 cm (25th-50th percentile). Vital signs are: temperature 98.2°F (36.8°C), heart rate 159 beats/min, blood pressure 75/51 mm Hg, and respiratory rate 36 breaths/min. The baby is thin, jaundiced, and pale but is alert and cooing. He appears severely dehydrated, with delayed capillary refill of 3 seconds. There is no rash, petechiae, or organomegaly. Laboratory evaluation shows total bilirubin of 15.2 mg/dL (259.98 μmol/L) and conjugated bilirubin of 0.5 mg/dL (8.55 μmol/L). Complete blood cell count reveals a white blood cell count of 7,600/μL (7.6 x 109/L), hemoglobin of 7.6 g/dL (76 g/L), hematocrit of 22.6% (0.226), platelet count of 251 × 103/μL (251 x 109/L), mean corpuscular volume of 84.7 μm3 (84.7 fL), and red cell distribution width of 18.3%. Urinalysis is negative for blood, leukocyte esterase, nitrites, and reducing substances. Urine and blood cultures are obtained. The newborn screening result is checked and is negative for congenital hypothyroidism but reveals homozygous sickle hemoglobin (Hgb SS) consistent with sickle cell disease (SCD). Additional evaluation leads to the cause of his pallor and jaundice. The infant was hospitalized for failure …

Raised in Darkness: A 7-Month-Old With Nystagmus From Severe Visual Deprivation

Child neglect is the most common form of child maltreatment and accounts for 60% of all cases reported to child protective services. Whereas physical and emotional neglect account for a quarter of the reported cases of child neglect, educational neglect accounts for half of the cases. We describe a 7-month-old infant with several manifestations of physical and emotional neglect including excessive quietness, failure to thrive, global developmental delay, and a gastric lactobezoar. In addition, our patient had a fine, lateral nystagmus likely due to being kept in the dark for long periods. To our knowledge, this is the first reported case of acquired nystagmus due to visual deprivation from child neglect.

Hyperglycemic Hyperosmolar State During Induction Chemotherapy for Acute Lymphoblastic Leukemia

Abstract We present the case of a 16-year-old boy who presented with fatigue, polyuria, and polydipsia while on chemotherapy for his relapsed acute lymphoblastic leukemia (ALL). Blood gas examination confirmed the diagnosis of hyperosmolar hyperglycemic state. The etiology for his hyperglycemia was most likely a result of oral glucocorticoid therapy combined with asparaginase therapy—both are a cornerstone of induction chemotherapy for ALL. The patient was aggressively rehydrated with saline, and medications were administered to correct his hyperkalemia. He was then slowly brought to euglycemia with a continuous infusion of insulin. Although hyperosmolar hyperglycemic state is rare during the treatment of ALL, frontline providers should be aware of this diagnosis because of the significant risk of hypovolemic shock and death if correction of hyperglycemia occurs prior to complete fluid resuscitation.

Delayed‐onset Thrombocytopenia in a Pediatric Burn Patient

A 14-year-old boy presented with 36% total body surface area (TBSA) flame burns to his face, neck, and torso. On presentation to the hospital, he was endotracheally intubated for possible inhalation injury. Fluid-responsive shock was managed with Lactated Ringer’s solution and albumin. Pain and agitation were managed with opiates and benzodiazepines. Aztreonam and clindamycin were started due to concern of septic shock in the setting of a history of penicillin allergy. Thermal burns are a significant cause of injury. Prehospital care involves cooling the burn with cool (but not cold) running water and covering the burn with nonadherent dressings (cling wrap) to minimize heat loss. At the hospital, initial resuscitation includes fluid resuscitation using the Parkland formula, airway protection for patients with concern for inhalation injury, pain control, and transfer to an intensive care unit. He underwent multiple escharotomies, debridements, and skin grafts during the first 2 weeks of hospitalization. His burns were dressed with topical silver sulfadiazine prior to skin debridement on day #11 (Fig. 1). He was started on vancomycin when he was found to have clindamycin-resistant Streptococcus pneumoniae on respiratory culture. During his hospitalization, he developed thrombocytopenia at day #3 with a platelet nadir of 137 3 10/L at day #3 followed by normalization of the platelet count by day #6. The most common causes of thrombocytopenia in a pediatric patient with severe burn injury include burn-induced thrombocytopenia, sepsis, disseminated intravascular coagulation (DIC), drug-induced thrombocytopenia, heparin-induced thrombocytopenia (HIT), and post-transfusion purpura (PTP) (Supporting Information Table I). Burn-induced thrombocytopenia is the most common immediately after injury. Our patient’s thrombocytopenia followed by normalization within a week is consistent with the presentation of burn-induced thrombocytopenia. DIC and sepsis were unlikely since our patient was well-appearing and clinically improving at the onset of thrombocytopenia. On day #13, he underwent split-thickness skin grafting of the torso. On the same day, his platelet count again started to decline despite improvement in his wounds and resolution of pneumonia. By day #19, he had developed severe thrombocytopenia with a platelet count of <5 3 10/L. Microscopic examination of his blood smear revealed absence of platelets and normal red and white blood cell morphology. Severe thrombocytopenia, defined as platelet count <50 3 10/L, is unusual in a patient with burn-induced thrombocytopenia or sepsis. Therefore, other etiologies such as PTP, drug-induced thrombocytopenia, thrombocytopenia due to viral infection, HIT, and ITP were considered. PTP occurs 7–10 days after blood product transfusion. However, our patient did not receive his first transfusion until day 20. Drug-induced thrombocytopenia is typically associated with recovery of the platelet count 1 week after discontinuation of the offending agent. We considered several medications such as vancomycin and sulfa drugs (specifically, silver sulfadiazine); none of the medications were temporally related to the thrombocytopenia as illustrated in Fig. 1. HIT was unlikely since thrombocytopenia typically develops 5–10 days after exposure to heparin in patient who has not been previously exposed to heparin and recovers by 1 week after discontinuation of heparin. Our patient was not receiving heparin at the time of onset of thrombocytopenia. In addition, platelet counts in HIT rarely drop below 20 3 10/L. Therefore, ITP was our primary concern. Platelet transfusion was given on day #21 since thrombocytopenia. A 1-hr post-transfusion platelet count showed no change in platelet count. Intravenous immunoglobulin (IVIG) (0.8 g kg) was given for suspected ITP and heparin was discontinued. Antibody analysis was negative for HIT. Platelet transfusions are usually avoided in ITP unless a patient develops severe bleeding. However, our patient was given platelets since his severe thrombocytopenia was preventing routine wound care including dressing changes and debridement. In a patient with unexplained thrombocytopenia, platelet count should be assessed 1 hr after transfusion, since a platelet count refractory to transfusion may suggest immune-mediated platelet destruction. Refractoriness to platelet transfusion raised concern for drug-induced thrombocytopenia or allo-immunization from exposure to RBC antigens from previous transfusions. However, the time course made drug-induced thrombocytopenia unlikely and no allo-antibodies were identified by our blood bank.

A 12-Year-Old Boy With Dyspnea, Hypertension, Hematuria, and Proteinuria

Case: A 12-year-old boy presented to the emergency department with progressive dyspnea for 1 week and bilateral periorbital edema for 1 day. On review of systems, he reported an upper respiratory tract infection 1 week before the onset of dyspnea. A review of vital signs showed a temperature of 99.8°F (37.7°C), heart rate of 99 beats/min, blood pressure of 167/117 mm Hg, respiratory rate of 22 breaths/min, and oxygen saturation of 99% on room air. In addition to periorbital edema, the patient appeared to have worsening dyspnea when he was placed supine. The patient’s admission laboratory values revealed the following: sodium, 142 mmol/L; potassium, 4.4 mmol/L; chloride, 112 mmol/L; bicarbonate, 20 mmol/L; blood urea nitrogen, 11 mg/dL; creatinine, 0.63 mg/dL; and a normal complete blood cell count except for a hemoglobin level of 9.8 g/dL. Urinalysis with microscopy showed trace amounts of blood with 6 to 10 red blood cells (RBCs) per high-power field and 100 mg/dL of protein. Chest radiograph revealed pulmonary edema (Fig 1). FIGURE 1 Chest radiograph showing pulmonary vascular congestion. Question: What is the significance of hematuria and proteinuria in this patient with hypertension and pulmonary edema? Discussion: Hematuria and proteinuria, along with hypertension, are highly suggestive of glomerulonephritis (GN).1 Assessment of RBC morphology may help determine whether hematuria is glomerular or nonglomerular in origin. Intact urinary RBCs suggest an anatomic urinary tract lesion or trauma, whereas dysmorphic RBCs and RBC casts suggest glomerular hematuria. A fresh urine specimen should be analyzed under the microscope promptly because RBC casts disintegrate within 1 hour of voiding. In patients with suspected GN, the amount of proteinuria should be quantified to assess the severity of GN. Nephrotic-range proteinuria in children is defined as >40 mg/m2 per hour, >3 g/1.73 m2/day, or >50 mg/kg per day of …

A 9-Year-Old Girl With Poor Weight Gain and Postprandial Vomiting

Question: A 9-year-old girl presented with epigastric pain, postprandial vomiting, anorexia, and poor weight gain for 6 months. On examination, she was less than the fifth percentile for height, weight, and body mass index. An esophagogastroduodenoscopy (EGD) report from 3 months before arrival to our hospital revealed erythematous gastric mucosa with ulcerations and edema of the pyloric canal. She was treated for Helicobacter pylori and cytomegalovirus (CMV) without improvement. Laboratory results showed the following: White blood cell count 4.4 10/L (27.3% neutrophils, 64% lymphocytes, 6.6% monocytes, 1.4% eosinophils, 0.7% basophils), hemoglobin 9.5 g/dL, mean corpuscular volume 82 fL, red cell distribution width 24.2%, platelet count 556 10/L, total protein 4.7 g/dL, and albumin 2.5 g/dL. Review of records showed negative anti-neutrophil cytoplasmic antibodies, anti-Saccharomyces cerevisiae antibodies (ASCA), and tissue transglutaminase immunoglobulin (Ig)G and IgA. Serum total IgA levels were normal. Upper gastrointestinal series showed thickened gastric folds and narrowing of the pyloric canal (Figure A). Repeat EGD showed erythematous and friable mucosa, superficial ulcerations, and nodularity (Figure B–E). Friability, ulceration, and scarring of the prepyloric area and pylorus were appreciated; therefore, the duodenum was not able to be visualized. Colonoscopy was unremarkable. Histologic sections of the gastric biopsy specimens are shown in Figures F–I. What is the diagnosis? Look on page 905 for the answer and see the Gastroenterology web site (www.gastrojournal.org) for more information on submitting your favorite image to Clinical Challenges and Images in GI.