Normal Complete Blood Cell Count Research Articles

Paenibacillus thiaminolyticus sepsis and meningoencephalitis in a 37-day old preterm infant

Introduction: The Paenibacillus genus consists of saprophytic organisms that are commonly associated with soil, water, plants, feces, and diseased insect larvae. Human infection is rare. This disease typically occurs in immunocompromised hosts, adults with a history of intravenous drug use, and hosts with prosthetic medical devices. There are a limited number of case reports describing Paenibacillus infections in neonates. This is the second published instance of pediatric meningoencephalitis caused by Paenibacillus thiaminolyticus in a preterm infant with intrauterine drug exposure. Case Report: A 37-day-old male infant with a history of prematurity of 33 weeks completed gestation presented to the Emergency Department for acute onset poor feeding, poor color, and unresponsiveness at home. Examination revealed cyanosis, apnea, and hypotonia. Vital signs were significant for hypotension and hypothermia. Initial labs revealed a metabolic acidosis, elevated C-reactive protein, normal complete white blood cell count, and a negative viral respiratory pathogen panel. Aerobic blood culture and cerebrospinal fluid (CSF) culture were positive for P. thiaminolyticus within 24 hours. Cranial ultrasound and magnetic resonance imaging revealed changes concerning for liquefactive meningoencephalitis. The infant was admitted to the neonatal intensive care unit (NICU) and ultimately discharged home on a “do not resuscitate/do not intubate” status and later died at 11 months of age. Conclusion: Paenibacillus species are common environmental organisms but can cause devastating disease in neonates. This is the second reported case of a preterm infant with P. thiaminolyticus infection and inutero drug exposure (IUDE), supporting that prematurity and IUDE may be risk factors for severe disease.

A PATIENT WITH KABUKI SYNDROME AND HYPOGAMMAGLOBULINEMIA DEVELOPS BURKITT LYMPHOMA

<h3>Introduction</h3> Kabuki syndrome (KS) is a rare genetic disorder characterized by congenital abnormalities, autoimmunity, intellectual disability, distinctive facial abnormalities, and hypogammaglobulinemia. <h3>Case Description</h3> A 24-year-old male with KS and hypogammaglobulinemia presented to the emergency department (ED) with lower back pain and extremity paralysis. His previous genetic diagnosis of KS had a heterozygous novel variant causing a premature translational stop signal p.Pro235Alafs*6 in the KMT2D gene. The patient also has a history of congenital heart disease, autoimmune cytopenias, and longstanding hypogammaglobulinemia on/off replacement immunoglobulin with baseline IgG 300-400 mg/dL, low IgA 10-20 mg/dL, normal IgM 50-60 mg/dL, normal lymphocyte subsets, and absent protein and polysaccharide vaccine responses consistent with common variable immunodeficiency. On arrival at the ED, spinal imaging revealed a compression fracture and underlying mass. Right-axillary and bone marrow biopsies confirmed Burkitt lymphoma. He was treated with chemotherapy, radiation, and replacement immunoglobulin. He has suffered from pneumonia, adenovirus, ileus<b>,</b> heart failure, and stroke. Routine immunologic testing performed at time of diagnosis revealed normal complete blood cell count, mild transaminitis from baseline (AST/ALT 61/71 U/L), baseline immunoglobulins, and normal lymphocyte subsets. <h3>Discussion</h3> While KS is a well-known cause of hypogammaglobulinemia, the authors have identified only two other published cases of Burkitt lymphoma in KS. This case emphasizes the importance of oncological screening and that routine immunologic testing of lymphocyte subsets and immunoglobulins may not have abnormalities from baseline in patients with active lymphoma. A mild transaminitis, however, might be concerning for malignancy in these patients.

Mass on the Floor of the Mouth in a Teenager.

Mass on the Floor of the Mouth in a Teenager.

Irritable Infant with Bilateral Leg Swelling.

Irritable Infant with Bilateral Leg Swelling.

Rash, Diaphoresis, Anorexia, and Loss of Motor Skills in a 10-month-old Boy.

1. Mike Hart-Matyas, MD, PhD* 2. Elizabeth Yen-Leng Foong, MD, MSc* 3. Amelia Kellar, MD, MSc* 4. Lucy Dong Xuan Li, HBSc, MD* 5. Hosanna Au, HBSc, MD, DipMEd*,† 1. *Department of Paediatrics, University of Toronto, Toronto, Ontario, Canada 2. †Division of Paediatric Medicine, Hospital for Sick Children, Toronto, Ontario, Canada A previously well 10-month-old boy presents with a 1-month history of a papular rash with interdigital desquamation, diaphoresis, and anorexia. These symptoms were preceded by a 3-day febrile illness with otitis media. He had weight loss of 1 kg and lost the ability to crawl and cruise during this period. The patient’s medical history was unremarkable. He was born at 41 weeks’ gestation by spontaneous vaginal delivery after an uneventful pregnancy. Developmentally he was previously sitting, cruising, and babbling. There were no known sick contacts. The family had traveled to Mexico 4 months before presentation, but the patient was well on return. On physical examination the boy’s temperature is 97°F (36.1°C), respiratory rate is 48 breaths/min, heart rate is 136 beats/min, and blood pressure is 111/63 mm Hg. His weight is 7.9 kg (5th percentile) and length is 72 cm (11th percentile). He is alert but irritable and unable to sit without tripoding. He has no cervical adenopathy and no oral changes. He is diaphoretic. He has a slight head lag with overall decreased tone and deep tendon reflexes in the upper and lower extremities that are difficult to elicit. There is an erythematous papular rash on the trunk, upper arms, buttocks, thighs, and dorsal hands, with interdigital desquamation. Laboratory testing from the emergency department reveals normal complete blood cell and differential counts and normal levels of electrolytes, liver enzymes, creatinine, and C-reactive protein. He is admitted to the hospital for further diagnostic evaluation and nutritional …

S1725 Case Report: Prostate Cancer Diagnosed on Rectosigmoid Biopsies in a Patient Presenting With Diarrhea

INTRODUCTION: Prostate cancer is the second most commonly diagnosed cancer in men worldwide. Despite the anatomic proximity, rectosigmoid involvement of prostate adenocarcinoma is rare. We present a case of metastatic prostate cancer diagnosed on rectosigmoid biopsies in a patient presenting with diarrhea and fecal urgency. CASE DESCRIPTION/METHODS: A 76-year-old male presented to clinic for evaluation of non-bloody diarrhea with associated fecal urgency. His medical history was significant for prostate adenocarcinoma diagnosed and treated nine years ago with prostatectomy, radiation, and androgen deprivation therapy (ADT). On current presentation, labs showed a normal complete blood cell count, TSH, and tissue transglutaminase IgA. Stool studies were negative for gastrointestinal pathogens. A colonoscopy was performed which demonstrated a normal terminal ileum, sigmoid diverticulosis, and mild radiation proctitis. Random colon biopsies showed changes consistent with collagenous colitis. Treatment for collagenous colitis was initiated, however, three months later the patient continued to have diarrhea as well as new onset abdominal pain, nausea, vomiting, and weight loss. Imaging showed sigmoid colon wall thickening, an ill-defined soft tissue mass in the pelvis, and lymphadenopathy. Flexible sigmoidoscopy revealed congested and erythematous mucosa beginning at 10cm from the anal verge with multiple clean based ulcerations. Targeted biopsies revealed a population of keratin positive cells with limited differentiation and positive PSA staining consistent with poorly differentiated adenocarcinoma of prostate origin, likely from lymphangitic spread. The patient was diagnosed with metastatic castrate-resistant prostate adenocarcinoma and started on ADT. DISCUSSION: Rectosigmoid involvement by prostate adenocarcinoma is rare and review of available literature suggests at least three potential routes of involvement including direct invasion through Denonvilliers’ fascia, lymphatic metastasis, and implantation after transrectal biopsy. Rectosigmoid involvement of prostate adenocarcinoma may present with symptoms including change in bowel habits, rectal urgency, lower gastrointestinal bleeding, and pelvic pain. The case presented here emphasizes the importance of including prostate adenocarcinoma on the differential diagnosis in men presenting with lower gastrointestinal symptoms and abnormal rectosigmoid mucosa on colonoscopy, especially in patients older than 65 years or with a history of prostate adenocarcinoma.Figure 1.: Congested and erythematous mucosa starting approximately 10 cm from the anal verge.Figure 2.: Rectosigmoid ulcerations with surrounding erythematous mucosa.Figure 3.: Ill-defined soft tissue mass in the peri-rectal region with lymphadenopathy.

Legal Briefs: Was This Case of Necrotizing Enterocolitis Preventable?

A 28 1/7 week gestational age male infant with a birthweight of 1,280 g was born to a 23-year- old gravida 3, para 0-0-2-0 woman. The pregnancy was uneventful until the night before delivery when she developed preterm labor. She received 1 dose of betamethasone 8 hours before delivery. She also received 3 doses of penicillin for unknown group B Streptococcus status. Artificial rupture of membranes occurred a few hours before birth and the amniotic fluid was clear. The birth was via normal spontaneous vaginal delivery. The placenta appeared grossly normal, but subsequent pathologic examination showed mild chorioamnionitis. The infant’s Apgar scores were 8 at 1 minute and 9 at 5 minutes of age. The infant was clinically stable and treated with continuous positive airway pressure. The infant had a normal complete blood cell (CBC) count and was started on antibiotics because of preterm labor. The infant also received intravenous fluids at 80 mL/kg per day. On day 1, caffeine was initiated and phototherapy was started because the infant’s bilirubin was 8.1 mg/dL (138.5 μmol/L). At that time, the infant’s weight was down 11% from birthweight. On day 2, a percutaneous intravenous central catheter (PICC) was placed. On day 3, the infant’s weight loss was down 13% from birthweight and his sodium was 151 mEq/L (151 mmol/L) with a blood urea nitrogen of 30 mg/dL (10.7 mmol/L). The infant was started on trophic breast milk feedings of 1.5 mL every 3 hours. With the intravenous fluids being infused at 122 mL/kg per day, the total volume of fluids was 154 mL/kg per day. The infant did not receive probiotics. As the feedings increased, the volume infused diminished. The plaintiff neonatologist thought that the infant should have had his hydration status better managed to prevent dehydration and that it was inappropriate …

Frequency of polycythemia in individuals with normal complete blood cell counts according to the new 2016 WHO classification of myeloid neoplasms.

Polycythemia vera (PV) is a disorder characterized by clonal proliferation of myeloid cells and increased red blood cell mass. Recently, the revised 2016 WHO classification of myeloid neoplasms decreased the threshold levels of hemoglobin and hematocrit for the diagnosis of PV. However, the new proposed cutoffs have remarkable overlap with the normal reference values reported and the clinical impact of these new cutoffs has not been widely assessed in the general population. We retrospectively examined 248839 patients with presumptively normal complete blood cell results, consecutively obtained in an outpatient setting. The proportion of men with Hb >165g/L was 5.99%, Hct>49% was 2.4%, and Hb >165g/dL or Hct>49% was 6.48%, while the proportion of women with Hb >160g/L was 0.22%, Hct>48% was 0.11%, and Hb >160g/L or Hct>48% was 0.28%. The isolated use of the proposed Hb/Hct levels as a definer of polycythemia may lead to a substantial increase in unnecessary diagnostic tests. In cases with borderline levels of hemoglobin, the diagnostic workup of PV should only be indicated in the presence of clinical and/or laboratorial features associated with MPN.

A case of myeloproliferative neoplasm with a normal complete blood cell count: A novel problem of the JAK2 era.

The present study reported a case of a myeloproliferative neoplasm (MPN) in a patient with a normal complete blood cell count. Bone marrow biopsy showed bone marrow hyperplasia, an elevated megakaryocyte count, megakaryocytic dysplasia and pleomorphic changes, multiple megakaryocyte clusters and focal reticulin fiber hyperplasia. Furthermore, genetic analysis revealed that the patient was positive for the JAK2-V617F mutation, and negative for the JAK2 exon 12 and 13 mutations and the BCR-ABL (p210) fusion gene. The patient's condition was basically stable and at the time of writing, the patient remained in a stable condition with no specific symptoms of disease. The present study also analyzed the diagnostic and clinical features of MPNs, and a literature review was performed. MPN with a normal complete blood cell count is a rare disease, and attention should be focused on this entity in the clinic.

A nine-week-old girl with fever and seizures.

CASE PRESENTATION A nine-week-old girl presented to the emergency department with a 12 h history of fever and a 1 min generalized tonic-clonic seizure. Review of systems was otherwise negative. Her two-year-old sister experienced a fever and oropharyngeal ulcers two weeks before. On physical examination, she was febrile to 39.2°C rectal, but with otherwise normal vital signs. She was well-appearing and her examination was normal, including the neurological examination. Blood, urine and cerebrospinal fluid (CSF) specimens were obtained, and intravenous ceftriaxone, vancomycin and acyclovir were started. Laboratory investigations showed a normal complete blood cell count and transaminase levels. CSF examination revealed 55 white blood cells/μL (51% monocytes, 37% lymphocytes, 12% neutrophils), 7 red blood cells/μL, normal protein (0.35 g/L) and normal glucose (2.9 mmol/L). An electroencephalogram revealed active epileptiform activity over the right centroparietal regions. She was admitted to the pediatric ward and underwent magnetic resonance imaging of her head, which revealed multifocal nonenhancing lesions in the subcortical white matter of the right precentral gyrus, right cingular gyrus, right corticospinal tract, as well as the right internal capsule and thalamus (Figure 1). Bacterial cultures were without growth and antibiotics were discontinued after 48 h. CSF herpes simplex virus (HSV) 1 and HSV 2 polymerase chain reaction (PCR) (LightCycler 2.0 HSV 1/2 qualitative kit [Roche Diagnostics, Canada]) and enterovirus PCR were also negative. Repeat lumbar puncture and blood testing were performed on hospital day 3. DIAGNOSIS Both the CSF and blood samples obtained on hospital day 3 returned positive results for HSV-1 using PCR, confirming a diagnosis of HSV encephalitis. Extracted DNA from the initial CSF was re-tested using a different laboratory-developed HSV 1 and HSV 2 quantitative realtime PCR assay at another reference laboratory. In retrospect, the initial CSF specimen was positive for HSV 1 (2,675 copies/mL) using this assay, as were the second CSF specimen (21,905 copies/mL) and the blood sample (12,089 copies/mL).

Impressive Blood Pressure and Heart Rate Response After Percutaneous Renal Denervation in a Woman With Morbid Obesity and Severe Drug‐Resistant Hypertension

Resistant hypertension is a growing problem in the United States and around the world. Although its pathophysiology is multifactorial and poorly understood, it is invariably associated with increased renal sympathetic activation and central sympathoexcitation. 1–3 Sympathetic nervous system (SNS) regulation is complex and several mechanisms modulate its activity, 4–6 with accumulating evidence pointing to the kidney as a key contributor. The kidney, through efferent and afferent sympathetic fibers, acts as both a generator and a recipient of sympathetic signals. 7 A great deal of basic research 8–11 has pointed out for decades that efferent fibers can modulate sodium and fluid retention by the kidney, control renin release and plasma renin activity, and regulate renal blood flow. On the other hand, afferent fibers can transfer signals generated by mechanoreceptors and chemoreceptors in the kidney to the brain and sequentially modulate heart rate (HR), heart function, and peripheral resistance. 9,10 Recent advances in technology made it possible to percutaneously approach and interrupt transvascularly the sympathetic fibers coursing in the adventitia of the renal artery. A first-in-man study, 12 using a single tip radiofrequency ablation catheter, suggested impressive reductions in office blood pressure (OBP), sustained and improved over time. Other follow-up studies demonstrated similar results, with durable long-term blood pressure (BP) reduction, 13–15 although all published data consistently indicate that response varies among patients. Some patients demonstrate adequate response, some partial response, and some no response at all. 16 It is therefore important to focus our research on response indicators in order to better tailor our therapies. In this brief article we describe a case with impressive BP response early on after sympathetic renal denervation using a multi-electrode ablation catheter. The patient had clinical evidence of sympathetic activation, ie, persistently high BP and HR despite the use of multiple drugs including sympatholytics. CASE The patient was a 52-year-old morbidly obese (body mass index = 43.4 kg/m 2 ) woman with a history of smoking of more than 30 years and uncontrolled severe drug-resistant hypertension diagnosed more than 5 years prior to presentation. She also had a history of hypothyroidism and received levothyroxin replacement therapy, being eythyroid at last follow-up. Extensive workup for secondary causes of hypertension had been negative. On presentation, the patient was treated with 6 antihypertensive medications as follows: olmesartan 40 mg, chlorthalidone 25 mg, nifedipine 60 mg, bisoprolol 15 mg, and eplerenone 50 mg once a day and clonidine 0.15 mg 3 times a day. Systolic OBP was consistently >160 mm Hg despite use of a multidrug regimen and she was referred for renal denervation. During baseline evaluation, office systolic and diastolic OBP were 223 mm Hg and 131 mm Hg, respectively. HR was 97 beats per minute and 24-hour ambulatory BP monitoring (ABPM) averaged 178/102 mm Hg. Laboratory results showed normal complete blood cell count and chemistry, and glomerular filtration rate was estimated at 93 mL/min/1.73 m 2 . Target organ damage was indicated by an albumin to creatinine ratio of 101 mg/g, while findings from transthoracic echocardiography revealed concentric left ventricular hypertrophy (left ventricular mass indexed for body surface area equal to 148.6 g/m 2 ).

Mice with Genetic Modifications in Prothrombin Limiting Activation Cleavage Events to Meizothrombin Survive to Adulthood, but Exhibit Alterations in Hemostasis and Thrombus Formation

AbstractAbstract 496Thrombin-mediated proteolysis is the central event not only of hemostasis and thrombosis but also in distinct physiological and pathological contexts such as development, inflammation, cancer biology, and cardiovascular disease. The proteolytic conversion of prothrombin to α-thrombin (fIIa) by the prothrombinase complex occurs through two possible pathways: i) the inactive intermediate termed prethrombin 2, or ii) the proteolytically active two-chain intermediate termed meizothrombin (fIIaMZ). fIIaMZ, unlike fIIa, retains the γ-carboxyglutamic acid-rich gla domain and two kringle domains of prothrombin and has distinct catalytic properties relative to fIIa that could be biologically meaningful in vivo, including a diminished capacity to cleave fibrinogen and a significantly increased capacity to activate protein C in the presence of thrombomodulin. Here, the endogenous prothrombin gene was modified in mice to better explore the properties of fIIaMZin vivo and to test the hypotheses that mice carrying a mutant form of prothrombin with a terminal activation product of fIIaMZ will: 1) develop to term and survive to adulthood despite an altered hemostatic profile; and 2) exhibit significantly dampened inflammatory responses due to enhanced protein C activation. In order to limit cleavage events to the single site yielding fIIaMZ, alterations were introduced into the endogenous prothrombin gene resulting in three amino acid substitutions (R157A, R268A, and K281A) located at the P1 positions of potential fXa or autocatalytic cleavage sites. Unlike prothrombin-null mice, mice homozygous for these mutations (hereafter referred to as fIIMZ mice) were found to be present at weaning age and viable into adulthood. Furthermore, unlike mice with a major deficit in either clotting function (e.g., fibrinogen-null) or platelet function (e.g., Gαq-null), fIIMZ females were capable of successfully carrying a litter to term. However, analysis of over 700 progeny generated from crosses of heterozygous fIIMZ/WT mice revealed that only about half of the number homozygous fIIMZ mice expected, based on Mendelian transmission rates, were observed in weaning-age offspring. Complementary studies suggest that the fraction of fIIMZ offspring that fail are lost primarily in utero, but occasional post-partum failures were observed associated with hemorrhagic events. Successful adult fIIMZ mice were found to have similar prothrombin mRNA levels and equivalent fII protein expression to fIIWT mice. Furthermore, fIIMZ animals exhibited normal complete blood cell counts and predictably normal thrombin times, but prolonged PTs and aPTTs. Thrombin generation assays revealed a prolonged time to peak thrombin production, but no significant difference in peak thrombin levels. Consistent with these findings, tail bleeding times in fIIMZ mice were significantly prolonged. None of the fIIMZ mice assayed achieved hemostasis within the 10 minute observation window, whereas fIIWT mice all stopped within 2 minutes of challenge. More sophisticated comparative studies of thrombus formation in mesenteric arterioles following FeCl3 injury using a real-time intravital microscopy approach established that the time to first thrombus formation in fIIMZ mice was almost twice that of wildtype animals. The majority of the fIIMZ mice failed to occlude the injured vessel within a 25 min observation window, whereas all fIIWT mice successfully formed occlusive thrombi with a mean time of 12.5 minutes. In summary, site-directed alterations of the endogenous prothrombin gene in mice leading to a terminal prothrombin activation product of meizothrombin were found to be compatible with development, growth to adulthood and reproductive success, albeit with modified hemostatic function. Based on the catalytic properties of fIIaMZ favoring protein C activation, studies are underway to compare APC generation in control and fIIMZ mice and explore the theory that physiological and pathological inflammatory responses will be dampened in fIIMZ mice. Disclosures:No relevant conflicts of interest to declare.

Index of Suspicion

Index of Suspicion

Pancytopenia, mucositis, and hepatotoxicity after intralesional methotrexate injection in a patient treated with peritoneal dialysis

A case of methotrexate toxicity from intralesional treatment of squamous cell carcinoma of the hands in a peritoneal dialysis patient is reported. A 68-year-old Caucasian man receiving peritoneal dialysis for end-stage renal disease complained to his primary care physician of shortness of breath, mouth and hand sores, nausea, and general malaise. Four days before his office visit, the patient received 25 mg of methotrexate intralesionally for refractory squamous cell carcinoma of his hands. The patient had several pustular lesions on both hands. On admission, the patient had a normal complete blood cell count and elevated liver enzyme levels. On hospital day 3, the patient's white blood cell count was 1,300 cells/μL, platelet count was 134,000 platelets/μL, hemoglobin value was 12.4 g/dL, and hematocrit was 37%. Folic acid 1 mg i.v. every six hours and leucovorin 10 mg/m(2) (20 mg) i.v. every six hours was initiated. His serum methotrexate concentration was 0.03 μmol/L on hospital day 6. The leucovorin dosage was increased to 200 mg i.v. every six hours. Platelets were administered, and the patient was switched to four-hour treatments of high-flux membrane hemodialysis for two consecutive days. The patient was discharged on hospital day 14. Mild mucositis was still present, but the patient had improved substantially and was discharged to a rehabilitation facility. A 68-year-old peritoneal dialysis patient who was treated with 25 mg of intralesional methotrexate for squamous cell carcinoma of the hands developed pancytopenia, mucositis, and hepatotoxicity as a result of systemic absorption and prolonged elimination.

Liver Transplantation for Massive Hepatic Lymphangiomatosis in a Child

Liver Transplantation for Massive Hepatic Lymphangiomatosis in a Child

Picture of the Month—Quiz Case

A PREVIOUSLY HEALTHY 6-YEAR-OLD BOY PREsented to the emergency department (ED) with 2 weeks of progressive right leg pain and a limp. He reported pain only when bearing weight or with extension of his right knee, although his parents noted he had been waking from sleep in pain. He denied a history of trauma and had not experienced joint swelling or erythema. He had not had fever, weight loss, or recent infections and confirmed normal voiding patterns. Our patient saw his pediatrician for this same concern 3 days before our evaluation and was found to have a minimally elevated erythrocyte sedimentation rate and normal lower extremity plain radiographs. In the ED, he was wellappearing and afebrile with normal vital signs for age. He held his right knee in mild flexion and refused to ambulate secondary to pain. The findings of a physical examination confirmed a full range of motion of the right hip and ankle. No joint instability, deformity, or swelling of his leg was noted, although he had mild swelling and tenderness over his right posterior iliac crest. Laboratory results were significant for C-reactive protein, 2.2 mg/L (to convert to nanomoles per liter, multiply by 9.524), erythrocyte sedimentation rate, 30 mm/h, and normal complete blood cell count with a normal manual differential cell count. Plain radiographs of the hip and right femur were obtained. (Figure 1) What is your diagnosis?

Juvenile xanthogranuloma with hematological dysfunction treated with 2CDA‐AraC

Juvenile xanthogranuloma was diagnosed in two infants aged 8 and 2 months with skin lesions, hepatosplenomegaly, and pancytopenia. Disease control was not achieved with first-line vinblastine-steroid-VP16 combination therapy. Two courses of 2-chlorodeoxyadenosine (2CDA) (0.3 mg/kg) and cytosine arabinoside (AraC) (1 g/m(2)) were then administered for 5 days and were followed, after hematological recovery, by maintenance therapy. Both patients had normal complete blood cell counts and no signs of JXG, respectively, 31 and 24 months after diagnosis.

Hypokalemic Paralysis and Rhabdomyolysis Secondary to Acquired Immunodeficiency Syndrome Enteropathy

To the Editor We read with interest the review by Maniar and Tolan1 on rhabdomyolysis secondary to primary human immunodeficiency virus (HIV) infection in the recent issue of Infectious Diseases in Clinical Practice. Despite the thorough review, they failed to mention hypokalemia as an uncommon but recognized cause of rhabdomyolysis. A 37-year-old man was referred from the prison service with a few days' history of worsening generalized body weakness, loss of appetite, profuse diarrhea, vomiting, abdominal pain, and significant weight loss. The diarrhea had started 3 months before this admission. The diarrhea was typically voluminous and occasionally contained fresh blood. The patient was diagnosed as having HIV infection 3 years previously during routine checks for all new inmates. He was not referred to the hospital for further evaluations because he was scheduled to be repatriated back to his country. On examination, he was malnourished and cachectic. Neurological examination showed generalized hypotonia, generalized power weakness (Medical Research Council grade 2/5), and absent reflexes. There were no obvious mucocutaneous manifestations of acquired immunodeficiency syndrome (AIDS). The rest of the examinations was unremarkable. Blood investigations showed normal complete blood cell counts and normal liver function test results, except for mildly elevated serum alanine transferase of 97 μ/L. Renal function test results showed severe hypokalemia of 1.4 mmol/L (normal range [NR], 3.6-5.1 mmol/L) with sodium of 132 mmol/L (NR, 136-144 mmol/L), urea of 7.9 mmol/L (NR, 2.9-7.1 mmol/L), creatinine level of 102 mmol/L (NR, 53-115 mmol/L), and bicarbonate of 17.9 mmol/L (NR, 22-32 mmol/L). Creatine kinase (CK) was also elevated at around 2000 IU/L (NR, 40-200 IU/L) with a CK-MB of 15 IU/L. Thyroid function test result was normal. Spot urine potassium level was 3.99 mmol/L (NR, 25-150 mmol/L). Urine microscopy was normal. The electrocardiogram showed nonspecific ST- and T-wave abnormalities but surprisingly without the changes of hypokalemia. The clinical impression was rhabdomyolysis secondary to hypokalemia as a result of potassium loss from the gastrointestinal tract. The serum CK subsequently peaked at 23,000 IU/L. The patient was initially started on intravenous fluids, potassium replacement, and antibiotics (ciprofloxacin 400 mg BID). Stool microscopy showed Cryptosporidium cysts and Candida albicans. His treatment was later changed to intravenous spiramycin and fluconazole. Subcutaneous octreotide was added because there was no improvement in the stool output. CD4 counts were markedly reduced (32 cells/μL). Antiretroviral therapy with Combivir and indinavir was commenced, and this led to a marked reduction in stool output. As a result, there was an improvement in the serum potassium leading to marked improvement in power. He was able to mobilize without much assistance and was discharged back to the prison service with further follow-up. Patients with AIDS experienced many complications, and intractable diarrhea is a common gastrointestinal manifestation. This is often caused by parasitic infections but can also be caused by the HIV itself. It can be quite debilitating, and the resultant dehydration, metabolite disturbances, and malabsorption can lead to significant morbidity.2 Among the many manifestations of HIV infection, rhabdomyolysis is less common compared with the gastrointestinal manifestations. Rhabdomyolysis can occur via immune-mediated myocyte injuries or more commonly secondary to the toxic highly active antiretroviral medications.1 Other medications either legal or illicit as highlighted by Maniar and Tolan1 can also cause rhabdomyolysis. Our patient was not using any of these medications and had not been exposed to any highly active antiretroviral therapy. We cannot be certain whether the diarrhea in our patient was secondary to the Cryptosporidium or the HIV because we did not perform an endoscopy and biopsy. However, regardless of the underlying etiology, hypokalemia is a known complication of chronic diarrhea. Hypokalemia is a well-recognized cause of rhabdomyolysis.3 In our setting, such manifestation is commonly caused by periodic hypokalemic paralysis secondary to thyrotoxicosis or renal tubular acidosis.4,5 Despite the prevalence of diarrheal disorders among patients with HIV/AIDS, it is surprising that rhabdomyolysis secondary to hypokalemia had not been previously reported. Therefore, it is important for clinicians to be aware of this association. In addition, severe hypokalemia can be associated with fatal cardiac arrhythmias. In conclusion, our case highlights that the intractable diarrhea with resultant hypokalemia associated should be included as a cause of rhabdomyolysis. Shir Kiong Lu, MBChB, MRCP Aza Zetty Feroena Jamaludin, MBChB, MRCP Nallathamby Rajendran, MBBS, FRCP Vui Heng Chong, MRCP, FAMS Department of Medicine Raja Isteri Pengiran Anak Saleha Hospital Brunei Darussalam [email protected]

Cavitating Lung Nodule and Lytic Spinal Lesions in an Adolescent Male

A previously healthy 17-year-old boy from northern New Brunswick presented to his local physician with a six-week history of mid-thoracic back pain and a 4 kg weight loss. There was no history of trauma, fever or night sweats; the review of systems was otherwise normal. He had no recent travel outside of the province, no recent infectious contacts, took no medications and his immunizations were up to date. He was a nonsmoker and denied illicit drug use. A brief exposure to his grandfather with suspected tuberculosis 12 years earlier was noted. Physical examination revealed a tall, thin and well-looking adolescent male. His vital signs, including temperature, were normal. His head and neck examinations were unremarkable. Tactile fremitus was noted over his left upper lung fields, but on auscultation, air entry was good bilaterally with no adventitious sounds. His cardiac and abdominal examinations were normal. There was no tenderness on palpation of the spine or paraspinal muscles. His neurological examination was normal. Initial laboratory results included a normal complete blood cell count and an absolute neutrophil count. The erythrocyte sedimentation rate was elevated at 60 mm/h. Serology tests for antinuclear antibody, perinuclear anticytoplasmic antibody and circulating antineutrophil cytoplasmic antibody were negative. A nuclear bone scan demonstrated an increased uptake in the sacrum and mid-thoracic spine, further defined on computed tomography (CT) scan as a lytic right-sided S1/S2 sacral lesion involving adjacent soft tissue. A large lytic lesion of T9 was also seen, as well as a cavitating 3 cm diameter lung lesion in the left upper lobe of the lung, surrounded by minimal alveolar infiltrate. No hilar adenopathy was present. The patient was referred to the IWK Health Centre (Halifax, Nova Scotia) for further evaluation. Over the course of investigations, a mild nonproductive cough developed. Further studies noted normal serum quantitative immunoglobulin levels, a normal sweat chloride test and a negative tuberculin skin test. An oxidative burst assay of neutrophil function was normal. An open sacral biopsy was performed revealing neutrophilic and eosinophilic infiltrates, but no dysplasia or malignancy. Gram, Kinyoun and Calcofluor stains for bacteria, mycobacteria and fungi were negative. Routine bacterial and mycobacterial cultures were negative. Pathology noted the rim of a granuloma in one section. Two weeks later, a repeat CT scan documented rapid disease progression despite the indolent symptoms. The lytic T9 lesion had extended into T10 with increased soft tissue swelling and rim enhancement (Figure 1), and there were increased infiltrates around the pulmonary cavitation. Mycobacterial and fungal cultures of the biopsy material remained negative. Nucleic acid amplification tests for mycobacteria were negative from the biopsy. Figure 1) Coronal computed tomography image before the computed tomography-guided vertebral biopsy and the thoracoscopic lung biopsy. An intermediate window-level setting depicts both the spine and lung lesions. The lytic T9 lesion, the left paraspinal soft tissue ... In pursuit of a firm diagnosis, both a T9 CT-guided needle biopsy and thoracoscopic excisional lung biopsy of the cavitation were performed. Necrotizing granulomas were seen in the tissue from both sites. What is the diagnosis?

Cardiomyopathy Associated With Ephedra‐Containing Nutritional Supplements

with both S3 and S4 gallops. The lungs were clear, and extremities were without edema. The remainder of the results of the physical examination were normal. Laboratory findings included normal complete blood cell count, serum chemistry, and liver function test results. Serum ferritin and thyroid function test findings were normal. Immunologic testing for Toxoplasma species, Lyme disease, and Ehrlichia species were negative. Chest radiography showed cardiomegaly, and electrocardiography revealed sinus tachycardia. Two-dimensional echocardiography demonstrated left ventricular dysfunction with severe global hypokinesia and an estimated left ventricular ejection fraction (LVEF) of 10% to 15%. Right heart catheterization revealed a pulmonary capillary wedge pressure of 24 mm Hg and mild pulmonary hypertension. Left heart catheterization revealed an LVEF of 10% with severe global hypokinesia, a left ventricular end-diastolic pressure of 7 mm Hg, and a left dominant coronary system with normal coronary arteries. Right ventricular biopsy revealed minimal changes and probable idiopathic cardiomyopathy. The patient was advised to stop taking the ephedra-containing dietary supplement, and medical treatment was started with aspirin, a b-blocker, and an angiotensin-converting enzyme inhibitor, with subsequent symptom improvement. The patient could not tolerate spironolactone therapy because of hyperkalemia. Repeat echocardiography performed 3 years later showed marked improvement in left ventricular systolic function, with an estimated LVEF of 45% to 50%.