Physician editor: Christopher Sankey, MD, FACP
Deputy physician editor: Benjamin Galen, MD, FACP
Case 1: Anaphylaxis to mammalian meat mediated by hypersensitivity to alpha-gal
By Roula Altisheh, MD, ACP Resident/Fellow Member
A 66-year-old man with no allergic history presented with oropharyngeal angioedema, generalized urticaria, and wheezing. Symptoms resolved with epinephrine, diphenhydramine, and intravenous steroids, and he was discharged home. Two days later, he awoke with similar but more severe symptoms that prompted return to the hospital. Additional history revealed that he had eaten a cheeseburger the previous night and had received tick bites in rural Missouri in the preceding 3 months. Workup demonstrated elevated alpha-gal IgE level of 29.8 kU/L (reference range, <0.35 kU/L). Complement levels and results of other allergy testing were normal. He was advised to eliminate all mammalian meat from his diet, which resulted in successful amelioration of symptoms and no further episodes at 6-month follow-up.
This patient's diagnosis was anaphylaxis to alpha-gal (meat allergy), which has a unique history. In 2008, a number of patients in the United States were found to have IgE antibodies to a carbohydrate moiety on cetuximab, a monoclonal antibody against epidermal growth factor receptor used to treat colon cancer. Galactose-alpha-1,3-galactose (alpha-gal) was discovered to be the relevant epitope. Around the same time, urticaria, angioedema, or anaphylaxis was reported in patients 3 to 4 hours after consuming red meat. These patients had positive skin and serum IgE testing to mammalian meats and highly positive serum IgE to alpha-gal.
Studies have associated tick bites with mammalian meat allergy. It is thought that the bites from the Amblyomma americanum (lone star) tick can induce both IgE antibodies to tick proteins as well as alpha-gal. There are higher rates of IgE antibodies to alpha-gal present in serum specimens of patients in areas of the United States where this tick is more commonly found. Red-meat allergic reactions can be delayed and don't necessarily occur with every exposure. Exercise and tissue source of the meat can alter the time to reaction. In affected individuals, reactions to dairy, gelatin-containing vaccines, and bioprosthetics have been described.
Unlike protein-induced food allergies that begin in childhood, alpha-gal allergy is more prominent in adults. Treatment consists of avoiding known triggers and mammalian meat products. Desensitization is possible and is primarily used for patients requiring cetuximab therapy but is not routinely attempted for meat-allergic patients.
- Alpha-gal allergy (meat allergy) should be considered in patients with urticaria, angioedema, or anaphylaxis after consuming mammalian meat products.
- A history of lone star tick bite has been associated with the development of antibodies to alpha-gal.
Case 2: Rapidly progressive glomerulonephritis due to post-infectious IgA nephropathy
By Adam Merando, MD, ACP Member, and Kristin Knobloch, DNP, APRN, CCNS
A 65-year-old man was admitted to the ICU with septic shock due to bacterial pneumonia. He responded to vasopressors and broad-spectrum antibiotics. His sputum culture grew methicillin-sensitive Staphylococcus aureus. He improved clinically and was transferred to the general medical ward for further management. Afterward, it was noted that his creatinine level increased from normal to 3.4 mg/dL on hospital days 7 through 10. Urinary sediment did not demonstrate granular casts consistent with acute tubular necrosis, urinary and peripheral eosinophilia were absent, and creatinine did not respond to intravenous fluid challenge. Autoimmune evaluation did not demonstrate an underlying cause, and complement levels were normal. He subsequently developed oliguria and proteinuria (1.3 g/d), prompting renal biopsy. Crescentic IgA nephropathy was noted. He was started on cyclophosphamide therapy, but his condition ultimately progressed to requiring permanent hemodialysis.
This patient had rapidly progressive glomerulonephritis associated with IgA nephropathy, a type of glomerulonephritis characterized by deposition of IgA immune complexes in the mesangial cells of glomeruli with mesangial proliferation and crescent formation. IgA nephropathy is the most common form of glomerulonephritis in the world and can be a benign condition in up to 30% of patients with self-limited disease. It can present with hematuria, edema, hypertension, and progressive kidney injury. Common presentations are recurrent macroscopic hematuria after upper respiratory infection and persistent asymptomatic microscopic hematuria. IgA nephropathy is associated with chronic conditions such as HIV, hepatitis, and underlying autoimmune disease and can be associated with recent mucosal infection.
Biopsy is required for definitive diagnosis of IgA nephropathy. Progressive disease is atypical, with about 30% of patients progressing to renal failure over 20 to 25 years of disease activity. Therapy is targeted at reducing proteinuria, and when progressive and severe, immunosuppressant agents and hemodialysis support may be required. Rapidly progressive glomerulonephritis should be considered in hospitalized patients who develop progressive renal dysfunction in the setting of hematuria and proteinuria in the absence of granular casts or other evidence on microscopy of acute tubular necrosis.
- IgA nephropathy is the most common form of glomerulonephritis in the world and can range in severity from self-limited disease to rapidly progressive glomerulonephritis and end-stage renal disease.
- IgA nephropathy commonly presents as recurrent macroscopic hematuria after upper respiratory infection and persistent asymptomatic microscopic hematuria.
Case 3: Typhoid fever
By Arfaa Ali, MD, ACP Resident/Fellow Member, and Phil Fung, MD, ACP Member
A 36-year-old woman presented with a 2-day history of fever, chills, and epigastric abdominal pain. She was a refugee from Uganda and had immigrated to the United States 3 weeks before admission. She was diagnosed with malaria prior to traveling and was treated with intravenous quinine therapy. Vital signs on her current presentation revealed a temperature of up to 39.4°C and a heart rate of 96 beats/min. On physical examination, she exhibited epigastric tenderness and splenomegaly. Laboratory results showed leukopenia, normocytic anemia, and elevated aminotransferase levels. Results of malaria smear, urine and stool cultures, and lumbar puncture were unremarkable. HIV test results were negative. The patient's blood cultures ultimately returned positive for Salmonella typhi. She was treated with a 2-week course of ceftriaxone therapy. Her laboratory abnormalities resolved by the completion of treatment, and she was discharged to an acute rehabilitation facility.
This patient's diagnosis was typhoid fever, a severe illness that typically presents with fever and abdominal pain. It can also be accompanied by a characteristic rash consisting of flat, rose-colored spots. Patients with typhoid fever may exhibit a classic sign of fever with associated relative bradycardia known as “Faget sign” or sphygmothermic dissociation. Splenomegaly is seen in only 5% to 10% of cases, and 60% to 80% have positive blood cultures for Salmonella. Transmission most commonly occurs by ingestion of contaminated food or water.
Approximately 5,700 cases of typhoid fever in the United States are reported annually by the CDC, 75% of which were acquired during international travel. There are roughly 21.5 million cases worldwide each year, mostly in developing nations. Treatment options include fluoroquinolones, ceftriaxone, and azithromycin, although resistance is increasing for these therapies and treatment should be based on antibiotic sensitivity information when available. Up to 20% of untreated patients die of complications of typhoid fever. Vaccination should be considered for travelers to endemic regions at least 1 to 2 weeks prior to departure.
- Typhoid fever should be considered in patients with suggestive symptoms who have recently traveled to Salmonella typhi-endemic areas in Southcentral Asia, Southeast Asia, and Southern Africa.
- The clinical manifestations of typhoid fever can include fever, abdominal pain, relative bradycardia, and rash.
Case 4: Opiate-induced leukoencephalopathy
By Adam Merando, MD
A 47-year-old man with active intravenous heroin use presented after a witnessed fall from his bed in a correctional facility. He reported no other medication or drug use before admission. He demonstrated signs of acute opioid intoxication, including miosis, respiratory depression, and confusion. He responded to naloxone injection with improvement in mentation and maintenance of his airway. Several hours later, his systolic blood pressure was noted to be greater than 200 mm Hg and was accompanied by a recurrent alteration in mental status. A CT of the head was negative for acute hemorrhage, and MRI of the brain demonstrated findings of posterior symmetric white-matter changes suggestive of posterior leukoencephalopathy.
The patient was treated with antihypertensive therapy and had gradual improvement in his blood pressure and encephalopathy. Additional evaluation, including a lumbar puncture, was negative for infection. Urine toxicology was positive for opiates and negative for cocaine, amphetamines, and phencyclidine. He was presumed to have taken an illicit opiate during his incarceration preceding his symptoms. His blood pressure improved throughout his hospital course, and by hospital day 3 his mental status normalized.
This patient was diagnosed with a heroin-induced leukoencephalopathy. Reversible posterior leukoencephalopathy syndrome, also known as posterior reversible encephalopathy syndrome (PRES), is a condition of reversible vasogenic edema without signs of infarction on neuroimaging. It typically involves headache, encephalopathy, visual symptoms, and seizures and may involve alterations in autoregulation of cerebral blood flow. PRES has been described with acute drug intoxication, including ethanol, cocaine, 3,4-methylenedioxymethamphetamine (MDMA) and heroin. Prescription medications such as certain antiepileptic, antineoplastic, and immunosuppressant agents have also been implicated in cases of PRES, as have eclampsia and autoimmune disease.
Treatment is aimed at identifying and reversing underlying causes and targeting strict control of blood pressure to prevent seizures and control encephalopathy. Patients with recurrent seizures or status epilepticus may require at least short-term antiepileptic medications. Neuroimaging abnormalities usually resolve in days to weeks. However, there are reports of progressive lesions that can cause irreversible damage and leukomalacia.
- Reversible posterior leukoencephalopathy syndrome, also known as PRES, can cause altered mental status associated with elevated blood pressure and visual symptoms.
- PRES has been described with acute illicit drug intoxication, prescription medications, and some systemic medical diseases; treatment entails removal of the causative agent, blood pressure control, and monitoring for seizure activity.
Case 5: Active pulmonary infection with Mycobacterium tuberculosis
By Hiral Choksi, MD, ACP Member
A 41-year-old Vietnamese man who immigrated to the United States 25 years ago presented with fever of 2 weeks' duration. Two days prior to admission he noticed a nonproductive cough. His last visit to Vietnam was approximately 10 years ago. He reported no sick contacts, had never been incarcerated, and did not recall ever having a skin test for tuberculosis. Vital signs on admission revealed a temperature up to 38°C and a heart rate of 94 beats/min. Physical examination was unremarkable, and his lungs were clear to auscultation. A CT scan of the chest on admission showed right apical and superior segment right lower-lobe consolidation with ground-glass opacities. He was started on antibiotics for possible community-acquired pneumonia and placed in airborne isolation. HIV testing and urine antigens for Legionella pneumophila and Streptococcus pneumoniae were all negative. Three negative sputum acid-fast bacilli (AFB) smears were obtained, after which he underwent bronchoscopy with lavage AFB smear, which also was negative. He was discharged home to complete treatment for community-acquired pneumonia with oral antibiotics.
Four days after discharge, this patient's interferon-gamma release assay (IGRA) serum test returned positive, and he was referred to the health department for latent tuberculosis treatment. Three weeks after discharge, he presented back to the hospital with chest pain. At that time, his health department appointment had not yet occurred and he had not been started on any medications for tuberculosis. Repeated chest radiograph showed a new right upper-lobe cavitation (Figure 1), and he was placed back into airborne isolation. Repeat AFB smears were positive, and treatment was initiated with isoniazid, rifampin, ethambutol, and pyrazinamide. The original AFB sputum and bronchial lavage cultures were positive for Mycobacterium tuberculosis 5 weeks after being obtained.
This patient had acute pulmonary infection with M. tuberculosis. This case highlights important differences between AFB smear testing and culture for M. tuberculosis. AFB sputum specimens should be collected at 8- to 24- hour intervals, with at least 1 specimen collected in the early morning. If necessary, sputum can be “induced” with nebulized hypertonic saline. AFB smears have a sensitivity of 50% to 80% for active pulmonary tuberculosis, which is increased by serial testing (typically 3 smears). The utility of AFB smear testing is primarily as a public health intervention to assess the infectivity of an individual and not for the diagnosis of M. tuberculosis infection. All AFB smears must be sent for culture, the diagnostic gold standard, since the organism demonstrates slow growth and often takes up to 6 weeks to grow in sufficient quantity. Interferon-gamma release assays are surrogate markers of M. tuberculosis infection and are used as diagnostic tools for latent infection. Positive IGRA results are not diagnostic for acute infection, and negative results do not rule out active infection with M. tuberculosis. Bronchoscopy is reserved for unsuccessful attempts to obtain adequate sputum samples, negative studies in high clinical suspicion for active tuberculosis (as was the case for our patient), consideration of alternative diagnoses, and urgent need for diagnostic information.
- Active M. tuberculosis is a microbiologic diagnosis, and sputum AFB smears have inadequate sensitivity to rule out active pulmonary infection. In cases with a high pretest probability, repeated testing and/or bronchoscopy may be required.
- All AFB samples must be sent for mycobacterial culture and followed up, given the potential for growth after up to 6 weeks of incubation.