Case 20 – A 1-month-old girl with failure to thrive

A 1-month-old white girl is sent to the emergency room by her pediatrician for failure to thrive. She was born at full term, weighing 2.72 kg (6 lb), via spontaneous vaginal delivery with no complications. She was discharged to home with her mother and has been feeding well; she takes 3-4 ounces of formula every 2-3 hours. Her parents deny any emesis, fevers, or diarrhea, although her mother notes frequent foul-smelling loose stools. Family history is unremarkable. She lives with her parents and four siblings. She is afebrile with normal vital signs. Her weight is 3.3 kg (7.3 lb) (<5th percentile), length is 50 cm (19.7 in) (<5th percentile), and head circumference is 37 cm (14.6 in) (at 10th percentile). She is cachetic but interactive. The remainder of her examination is unremarkable.

What is the definition of failure to thrive (FTT)?

The term FTT may be attributed to a child who meets any of the following criteria:

1. Has weight <5th percentile for age and sex
2. Has depressed weight for height
3. Has a rate of weight gain that causes a decrease across two or more major percentile lines over time
4. Has a rate of daily weight gain less than expected for age

What are the two types of FTT?

Organic causes of FTT include:

1. Abnormal loss of calories
2. An abnormal need for calories
3. Failure to ingest an appropriate number of calories
4. Failure to metabolize

Most cases of FTT are due to nonorganic causes, typically psychosocial factors.

What organic causes of FTT should be considered in patients <6 months old?

1. Cystic fibrosis
2. Gastroesophageal reflux
3. HIV infection
4. Inborn errors of metabolism
5. Milk-protein intolerance
6. Perinatal or postnatal infections
7. Renal tubular acidosis

While in the hospital the patient feeds well, but despite adequate caloric intake, she fails to gain weight. What tests should be included in the initial work-up of this patient’s cause of FTT?

Malabsorption must be considered when a patient fails to gain weight despite feeding well. Initial screening studies for malabsorption include:

1. Serum electrolytes, albumin, and total protein
2. Stool exam for Clostridium difficile, ova, and parasites and stool cultures for bacterial pathogens
3. Stool exam for occult blood, leukocytes, reducing substances, and pH
4. Urinalysis and culture

What is the most likely diagnosis in this patient, and how should it be confirmed?

Since this patient is a white person with a history of FTT, malabsorption, and foul-smelling stools, cystic fibrosis must be considered. The next step in the work-up of this patient should be a sweat chloride test, which is the gold standard for the diagnosis of cystic fibrosis.

How should this patient’s malabsorption be treated?

The mainstay of treatment for pancreatic insufficiency in cystic fibrosis is pancreatic enzyme replacement. In addition, patients should receive supplementation of fat-soluble vitamins (vitamins A, D, E, and K).

By Jessica Kagen Hart, Resident, Department of General Pediatrics, Children’s Hospital of Philadelphia; in association with Le TT, Schabelman E, Shivaram A, and Klein J, eds: First Aid Cases for the USMLE Step 2 CK. New York: McGraw-Hill, 2007.

Case 19 – A 27-year-old woman with fever and cough

A 27-year-old woman presents to her physician because of 5 days of fever and cough. She has no significant past medical history but has been “fighting colds” for the past 3 months, which she attributed to the winter season. She began having low-grade fevers as well as a dry cough 5 days ago. She has also become increasingly short of breath over the past 2 days. Her temperature is 38.7°C (102°F), heart rate is 110/min, respiratory rate is 24/min, blood pressure is 110/70 mm Hg, and oxygen saturation is 90% on room air. Physical examination reveals pallor and oral thrush. Lung auscultation is significant for bilateral crackles and rhonchi throughout. The remainder of her examination is unremarkable. She lives with her husband, who is HIV-positive but is currently asymptomatic. She has no pets and no recent travel history. X-ray of the chest reveals diffuse bilateral interstitial infiltrates.

What is the most likely diagnosis?

The patient’s respiratory symptoms, oral thrush, and radiographic findings are most concerning for Pneumocystis carinii pneumonia (PCP) (now called Pneumocystis jiroveci). PCP is an important cause of pneumonia in immunocompromised hosts and is a leading cause of opportunistic infection, morbidity, and mortality in patients with HIV. The fact that this patient’s husband is HIV positive makes her chance of also being HIV positive very likely.

What is the next step in diagnosis?

Specific diagnosis of PCP requires documentation of the organism in respiratory specimens. Conventional stains such as toluidine blue O, methenamine silver, or Giemsa can be used to identify the organism. Immunofluorescent staining is the most common technique currently in use.

What is the most appropriate management for this patient?

Trimethoprim-sulfamethoxazole (TMP-SMX), which acts by inhibiting folic acid synthesis, is considered the drug of choice for all forms of pneumocystosis. Therapy is continued for 14 days in non-HIV-infected patients and for 21 days in persons infected with HIV. In patients with severe PCP, corticosteroids given in conjunction with anti-Pneumocystis therapy, decreases the incidence of mortality and respiratory failure.

What findings would one expect to see on high-resolution computed tomography (HRCT)?

A patchy or nodular ground-glass appearance is the most common finding of PCP on HRCT. HRCT has a high sensitivity for PCP among HIV-positive patients.

What prophylactic therapy should this patient use for her condition?

Indications for prophylaxis of PCP in HIV-positive patients include:

1. History of PCP
2. CD4 cell count <200/mm³
3. History of oropharyngeal candidiasis

Oral trimethoprim-sulfamethoxazole (TMP-SMX) is the preferred prophylactic regimen. Other options include pentamidine, dapsone, and atovaquone. Oral TMP-SMX is also useful in preventing toxoplasmosis and bacterial infections.

By Jessica Kagen Hart, Resident, Department of General Pediatrics, Children’s Hospital of Philadelphia; in association with Le TT, Schabelman E, Shivaram A, and Klein J, eds: First Aid Cases for the USMLE Step 2 CK. New York: McGraw-Hill, 2007.

Case 18 – A 60-year-old man with significant bleeding

A 60-year-old man presents to the emergency department complaining of a persistent nosebleed. His nose began bleeding spontaneously about 3 hours ago, and he has not been able to get it to stop despite direct pressure and ice packs. He denies trauma, blood disorders, cancer, or a family history of hematologic or oncologic problems. He has gastroesophageal reflux disease, for which he recently increased his dose of cimetidine, and atrial fibrillation, for which he takes metoprolol and warfarin. His temperature is 37.0°C (98.6°F), blood pressure is 120/80 mm Hg, heart rate is 90/min, and respiratory rate is 10/min. Physical examination is notable for crusted blood around his left nasal ala and slowly oozing bright red blood from his left nostril. He also has small conjunctival hemorrhages and a large bruise on his knee. The remainder of his physical examination is unremarkable, including a regular heart rate and rhythm and normal chest, abdominal, and neurologic examinations. Laboratory tests show:

WBC count: 6000/mm³
Hemoglobin: 13.5 g/dL
Hematocrit: 40%
Platelet count: 350,000/mm³
International Normalized Ratio: 12.5
Prothrombin time: Normal

What conditions should be included in the differential diagnosis?

The differential diagnosis of clinically significant hemorrhage includes trauma and disorders of hemostasis, specifically problems with platelet quantity (thrombocytopenia) and quality or clotting factor deficiency. Inherited (hemophilia, von Willebrand’s disease) and acquired (hematologic malignancy, bone marrow dysfunction, liver disease, medication, autoimmune) diseases may have identical clinical presentations, albeit frequently in different patient populations.

What is the most likely diagnosis?

This patient has clinically significant, persistent bleeding (epistaxis and other hemorrhagic phenomena) in the context of an International Normalized Ratio (INR) of 12.5 while receiving warfarin therapy. Although he may have an underlying malignancy or inherited bleeding disorder, his entire clinical presentation can be explained by his medications. Cimetidine inhibits the cytochrome P450 (CYP450) system of drug metabolism (a hepatic enzymatic system that metabolizes drugs for excretion), and warfarin is metabolized by this system. Thus, a recent increase in cimetidine dosage in a patient who takes warfarin could easily lead to dangerously high warfarin levels, evidenced in this patient by severe bleeding and a high INR.

What other risk factors are associated with this condition?

Medications and other compounds that induce the CYP45 system include:

1. Alcohol
2. Barbiturates
3. Carbamazepine
4. Dexamethasone
5. Griseofulvin
6. Phenytoin
7. Quinidine
8. Rifampin

Medications and other compounds that inhibit the CYP45 system include:

1. Cimetidine
2. Clarithromycin
3. Erythromycin
4. Grapefruit juice
5. Isoniazid
6. Ketoconazole
7. Ritonavir

What is the most appropriate management for this patient?

In patients with either severe bleeding or an INR >20 (risk factor for intracranial hemorrhage), immediate cessation of warfarin and CYP450 inhibitors is crucial. This patient should also receive nasal packing, as well as admission for observation and serial neurologic exams (for intracranial hemorrhage monitoring), INR assessments, and hemoglobin levels. Finally, this patient should be counseled to use a different histamine blocker for his gastroesophageal reflux disease, such as ranitidine, to avoid this complication in the future.

By Brian Ash, MD, Resident in Anesthesia and Perioperative Care, University of California, San Francisco Medical Center; in association with Le TT, Schabelman E, Shivaram A, and Klein J, eds: First Aid Cases for the USMLE Step 2 CK. New York: McGraw-Hill, 2007.

Case 17 – A 29-year-old woman with substance dependence

A 26-year-old G7P3 woman at 34 weeks’ gestation presents to the emergency department because she feels she is beginning to experience contractions and does not have an obstetrician to consult. On examination her pupils are dilated and she appears agitated and nervous. She then changes her mind and says she does not want further evaluation because it has been too long since her last “smoke.” She is adamant about needing to leave right away. Upon further questioning, she states that if she does not get to smoke soon, she will become very sleepy and depressed, and will have intense food cravings. She has been in inpatient drug rehabilitation twice but always relapses back to her drug of choice. She is currently living at a halfway house, is on welfare, and does not have custody of any of her 3 children. “They will probably take this one away from me, too,” she adds as she begins to cry. She says she used to be able to get high for $10 per day, but now it costs up to $100 per day. She affords her habit by trading drugs and money for sex; she has not been tested for HIV or other sexually transmitted diseases in recent memory.

What is the most likely diagnosis?

Cocaine dependence. This patient exhibits the classic signs of addiction: she has tolerance for the drug (requires more to achieve the same effect), and experiences withdrawal symptoms without it. She has continued to use cocaine despite the negative consequences it brings, and she has been unable to bring herself to stop using despite many attempts. Smoking cocaine results in feelings of euphoria and heightened energy, while depression, hunger, and sleepiness are symptoms of withdrawal. The criteria for substance dependence can be remembered using the mnemonic WITHDrawIT:

1. Withdrawal
2. Interest or important activities given up or reduced
3. Tolerance
4. Harm (physical and psychosocial) with continued use
5. Desire to cut down or control use
6. Intended time/amount of use exceeded
7. Time spent obtaining/using the substance is increased

What behavioral changes are associated with cocaine use?

Behavioral changes may include:

1. Blunting of feelings
2. Decreased appetite
3. Euphoria and increased energy
4. Heightened anxiety, irritability, or anger
5. Hypervigilance and heightened alertness
6. Impaired judgment
7. Increase in sexual excitement and spontaneous ejaculation
8. Increased risk for psychosis
9. Increased self-confidence
10. Interpersonal sensitivity

What physical changes are associated with cocaine use?

Physical changes may include:

1. Chest pain and/or arrhythmias due to vasospasm in coronary arteries
2. Confusion, seizures, stupor, or coma
3. Diaphoresis or chills
4. Dilated pupils
5. Increased pulse and blood pressure due to vasoconstriction
6. Muscle weakness, dystonia, or dyskinesia
7. Nausea or vomiting
8. Psychomotor slowing or agitation
9. Respiratory depression
10. Weight loss

What are the risks of cocaine use to the patient’s unborn child?

Since cocaine readily crosses the placenta and is metabolized slowly in fetuses, they can be exposed to significant levels of cocaine for long periods. Because of its vasoconstrictive properties, cocaine use increases the risk of fetal hypoxia and abruptio placentae.
In humans the most common consequences of cocaine abuse during pregnancy include premature birth, lower birth weight, respiratory distress, bowel infarctions, cerebral infarctions, reduced head circumference, and increased risk of seizures. Behaviorally, these newborns show an increased degree of tremulousness, crying, and irritability, and are overreactive to environmental stimuli. Within a month of birth these behaviors recover dramatically, but never to normal levels. It is important to remember that cocaine can be found in breast milk up to 60 hours after the last use.

By Kristen Vierregger, University of Pennsylvania School of Medicine, Class of 2008; in association with Le TT, Schabelman E, Shivaram A, and Klein J, eds: First Aid Cases for the USMLE Step 2 CK. New York: McGraw-Hill, 2007.