A report published in the New England Journal of Medicine describes the case of a 25-year-old woman who developed methemoglobinemia following the use of topical benzocaine. 

According to clinicians from the Miriam Hospital in Providence, RI, the patient presented with generalized weakness, fatigue, shortness of breath and skin discoloration. “Measurements of arterial blood gases included a partial pressure of arterial oxygen of 120 mmHg and a calculated oxygen saturation of 100%; however, when measured by CO-oximetry, the oxygen saturation was 67%. The percentage of methemoglobin was 44%,” the authors reported. 

The patient reported that the night before she presented to the emergency department, she had used large amounts of topical benzocaine to relieve a toothache. Topical benzocaine-containing products are available over-the-counter to provide temporary relief of pain due to minor irritation, soreness, or injury of the mouth and throat.  However, since 2006, the Food and Drug Administration has been alerting the public of the potential risk of methemoglobinemia associated with the use of these products; more than 400 cases have been reported to the Agency. In 2018, the FDA required manufacturers to make changes to the labeling indicating that only a small amount of product should be applied no more than 4 times per day. 

Signs of methemoglobinemia can develop quickly after use (within minutes to 1 or 2 hours) and can include pale, gray or blue colored skin, lips, and nail beds. Symptoms may also include headache, lightheadedness, confusion, shortness of breath, fatigue and tachycardia. Patients at increased risk for methemoglobinemia include those with breathing problems (ie, asthma, bronchitis, emphysema, smokers), heart disease, patients with certain inborn deficits (ie, glucose-6-phosphodiesterase deficiency, hemoglobin-M disease, NADH-methemoglobin reductase [diaphorase 1] deficiency, and pyruvate-kinase deficiency), and the elderly.

In this case, the patient was treated with intravenous methylene blue and eventually had complete resolution of her symptoms. “Methemoglobinemia can occur after exposure to a number of medications, including topical anesthetic agents such as benzocaine, through metabolic pathways that appear to vary from person to person, which may account for the unpredictability of this complication,” the authors concluded. 

For more information visit nejm.org.

A 27-year-old man presents with acute onset of an itchy rash on the extremities and trunk. He is in good health and does not take any oral medications or recreational drugs. He recently returned from a work-related trip where he drove to several different states. Examination reveals numerous erythematous papules on the extremities and trunk.

A recently published report described the case of a 57-year-old male who developed systemic lupus erythematosus precipitated by hydrochlorothiazide administration.

The patient, who had a past medical history significant for hypertension and hyperlipidemia, presented to the Emergency Department (ED) complaining of fevers, severe substernal chest pain, and dyspnea. His current medications included losartan 100mg daily, hydrochlorothiazide 25mg daily, aspirin 81mg daily, and atorvastatin 20mg daily.

Initial evaluation of the patient showed diffuse ST elevations as well as small pericardial effusion. Laboratory findings revealed that the patient was anemic, leukopenic, and had elevated inflammatory markers. The patient was treated with aspirin and nitroglycerin for a presumed acute coronary syndrome as well as prednisone for pericarditis.

Six months after presenting to the ED, the patient saw his primary care physician and reported experiencing fevers, fatigue, joint swelling and pain, morning stiffness, unintentional weight loss (40 pounds), decreased appetite, night sweats, and shortness of breath. Physical examination revealed a significantly reduced range of motion and swelling in the patient’s joints. Laboratory findings revealed anemia as well as leukopenia with persistent severe neutropenia.

Following an extensive workup with unremarkable findings and discussion about the patient’s clinical presentation, the study authors were led to a diagnosis of exclusion. “Although the patient had a negative ANA, his symptoms, physical examination, and additional blood work, particularly positive antihistone and anti-chromatin antibodies, were consistent with systemic lupus, most likely drug induced,” they reported. They added, “Hydrochlorothiazide was the most likely culprit of his presentation and was discontinued immediately.” At this time, a 1-month prednisone taper was initiated. 

At his 1-month follow-up visit, the patient’s anemia and leukopenia were significantly improved. At his 3-month follow-up visit, the patient’s inflammatory markers and anti-chromatin antibody levels were normalized, however, he complained of persistent arthralgias and laboratory tests revealed he was neutropenic. He was therefore initiated on hydroxychloroquine 200mg twice daily, which aided in improving his symptoms.

In this report, a rare case of hydrochlorothiazide-induced systemic lupus erythematosus as well as its management was discussed. “Based on our finding, hydrochlorothiazide should be considered a possible offending agent when a patient presents with symptoms suspicious of drug induced lupus,” the authors concluded.

Reference

Sosenko T, Pasula S, Brahmamdam R, Girnita D. When Chest Pain Reveals More: A Case of Hydrochlorothiazide-Induced Lupus Erythematosus. American Journal of Case Reports. 2019; 20:26-30.

Mr. C, a 30-year-old male with Crohn’s disease, presented to his clinician with symptoms of fatigue, lethargy, headaches, pallor, hair loss, irritability, and weakness. He states that these symptoms are significantly interfering with his productivity at work and with his family life at home.

Mr. C’s IBD was stable until 6 months ago, when he experienced an exacerbation and began a course of steroids with combination antibiotic therapy with ciprofloxacin and metronidazole. Shortly after initiation of this therapy, he began feeling fatigued, and in the following weeks, he developed hair loss, irritability, and increasingly frequent headaches. His clinician initiated treatment with oral iron supplementation but his symptoms continued to worsen.

Continue to page 2 to read an expert’s opinion on this case.

Ms. W has a 30-year history of hypertension and hyperlipidemia and an 8-year history of systolic dysfunction. She has persistent atrial fibrillation (AF) and an AICD for primary prevention. She was hospitalized for congestion following a 5-day river cruise. She seemed to have a good response to therapy with relief of her congestive symptoms; however, she reports persistent weakness and fatigue impacting her quality of life. She finds it taxing to do her errands and feels washed out by the middle of the afternoon. Her appetite is poor; she is eating smaller portions and has lost another 3 lbs. since the hospitalization. A recent colonoscopy was unrevealing. Last year her hemoglobin count was 11.4 g/dL and it is now 9.8. The echocardiogram prior to hospital discharge was notable for an ejection fraction (EF) of 24%.

Continue to page 2 to read an expert’s opinion on this case.

Trigger points are “symptomatic irritable foci in taut bands of a skeletal muscle or its fascia” and are the “hallmark physical examination signs of myofascial pain.”¹ Steroids and anesthetics are frequently used to inactivate tight muscular bands, leading to relief of nerve irritation and referred pain, and are typically delivered via ultrasound-guided injection into the trigger point. Although site injury is common, serious complications are rare.¹

A recent article by Soriano et al describes a case of a 30-year-old man who presented with chronic left hip pain from a work related injury. He had no family or personal history of periodic paralysis, muscle defects, or kidney disease. He was treated with trigger-point injection (TPI) consisting of methylprednisolone, bupivacaine, and epinephrine. A previous TIP had been effective in relieving his pain and he had experienced no adverse effects. The TPI was delivered to his left iliopsoas tendon and was administered under ultrasound guidance.

Initially, the patient experienced no complications. But approximately 12 hours following therapy, he awoke with shortness of breath and functional quadriplegia. However, his mental faculties remained intact and he did not experience chest pressure, vomiting, abdominal discomfort, or diarrhea. A summary of his workup is listed in Table 1.

Of note, the patient was in metabolic acidosis, with a base deficit of –7 (pH 7.31, HCO₂ 19 mmol/L, PCO₂ 38 mmHg). His serum potassium was 1.7 mmol/L, magnesium 2.1 mg/dL, calcium 9.8 mg/dL, and he had elevated creatinine kinase levels (523 IU/L).

Due to his diminished potassium levels, he received immediate “judicious potassium repletion,” consisting of a combined total of 150 milliequivalents of IV and PO KCl, which resolved his arrhythmias and muscular weakness within 2 hours. After 6 hours, his potassium showed normal levels (4.5 mmol/L). 

In their discussion of the case, the authors recommend several steps to determining the etiology of hypokalemia when it is not readily apparent. Although a 24-hour urine collection is the most accurate, it is not practical in the clinical setting, since patients require immediate repletion. For this reason, the urine potassium-to-creatinine ratio (U.K-Cr) from a single random sample provides comparable point-of-care information. A higher U.K-Cr value reflects renal potassium wasting, while values <1.5 meq/mmol creatinine (13 meq/g) are seen in transcellular potassium shifts, gastrointestinal losses, diuretic use, and poor intake. A trans-tubular potassium gradient (TTKG) gauges the renal potassium secretion by the cortical collecting duct.

In this patient, the U.K-Cr ratio was normal and did not reflect renal potassium wasting syndromes. These findings, coupled with rapid return to normal-high potassium levels following minimal repletion, suggest that the effect was “transient and redistributive,” possibly due to a “relative decrease in serum potassium secondary to transcellular shifting.”

The authors explain that the normal potassium distribution between cells and the extracellular fluid is primarily maintained by the Na-K-ATPase pump in the cellular membrane. In this case, they propose several hypotheses for the patient’s response to the TPI. (Table 2). They concluded that the diagnosis was hypokalemia secondary to TPI medications, after ruling out other possible etiologies.

The authors emphasize that the rapid onset of severe symptomatic hypokalemia “warrants urgent investigation and requires immediate treatment,” and that it is “critical to distinguish hypokalemia cause by redistribution from that caused by depletion.” They add that “judicious” early repletion “cannot be overstated,” and that ultimately, the primary pathology will “appropriately guide the clinician and enhance patient safety.”

References

1.      Soriano PK, Bhattarai M, Vogler CN, Hudali TH. A Case of Trigger-Point Injection-Induced Hypokalemic Paralysis. Am J Case Rep. 2017 Apr 26;18:454-457.

David Church, from the University of Cambridge Metabolic Research Laboratories in the United Kingdom, and colleagues report on the case of a 37-year-old female who presented to the emergency department after having collapsed. She had reported recurrent dizziness since the birth of her fifth child, and when symptomatic had recorded low capillary blood glucose. During her most recent pregnancy she had gestational diabetes, which was treated with insulin aspart, insulin glargine, and metformin.

The authors note that the patient had early-morning hypoglycemia and postprandial hyperglycemia. The patient had high circulating insulin during hypoglycemia. An insulin assay was performed and serum anti-insulin immunoglobulin G concentration was 171 mg/L; insulin autoimmune syndrome was diagnosed. The patient was fitted with continuous glucose monitoring (CGM) with a hypoglycemia alarm, and was prescribed frequent low-glycemic index carbohydrate meals. Prednisone was commenced as significant hypoglycemia continued, and rituximab was given to reduce anti-insulin antibodies. After six weeks, repeat CGM demonstrated intermittent hypoglycemia and sustained daytime hyperglycemia. There were reductions in total insulin, anti-insulin antibody concentration, and antibody-bound insulin over the following months. Hypoglycemia was rare and postprandial hyperglycemia had improved by six months.

“We show that B-cell depletion with rituximab induces a sustained reduction in anti-insulin antibodies, circulating insulin, and the frequency of hypoglycemia,” the authors write.

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J. Csomor, M.D., from the 1st Medical Faculty Charles University and Central Military Hospital in the Czech Republic, and colleagues described the case of a 57-year-old woman admitted for total thyroidectomy for thyroid goiter, during which she received a single dose of propofol. After a cholecystectomy in 2006 she had an attack of mild biliary pancreatitis.

The researchers write that the thyroidectomy was performed without complications; however, the patient developed severe abdominal pain with nausea and vomiting at 12 to 15 hours after surgery. Acute pancreatitis was confirmed, without pathology in the biliary tract. The patient was transferred to the intensive care unit and was administered standard intensive therapy. The patient suffered from hemorrhagic shock on the 20th day of hospitalization, with evidence of a ruptured spleen. The patient died of progressive multiple organ failure and septic shock 90 days after admission to the hospital. A biliary form of acute pancreatitis was unlikely based on findings including normal repeated liver function tests and no dilation of the patient’s intrahepatic biliary tract or common bile duct after endoscopic papillotomy. The researchers concluded that the acute pancreatitis was drug-induced.

“Acute pancreatitis as an adverse drug (propofol) reaction is extremely rare,” the authors write. “In our case report, we have focused on this possible complication of propofol. It is possible that cases of drug-induced acute pancreatitis are under-recognized.”

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Colleen Croy, Pharm.D., from the Medical University of South Carolina Medical Center in Charleston, and colleagues describe the case of a 22-year-old man who presented with a swollen tongue and dysphagia. Eight days earlier he had noticed and extracted a pimple on the fifth digit of his right hand; the hand had become infected after pimple extraction. The patient was admitted for cellulitis and initiated treatment with intravenous clindamycin. Three days later, vancomycin was added to the regimen. After five days on intravenous clindamycin, including two of these days also on intravenous vancomycin, the patient was discharged on an unknown dose of oral clindamycin.

The patient presented the next day with a fever and worsening rash. The rash next spread to the mucus membranes of the tongue. After admission for management of the acute skin eruption and persistent cellulitis, the patient’s rash was classified as acute generalized exanthematous pustulosis secondary to clindamycin therapy, based on rash presentation, time course, lack of eosinophilia, elevated liver enzymes,and skin biopsy. The patient was treated with oral diphenhydramine and oral famotidine for symptomatic therapy. Intravenous linezolid was started to treat the active cellulitis.

“This case highlights the importance of responding to an adverse drug reaction, identifying the reaction, and identifying the causative agent,” the authors write.

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Ulcerative colitis (UC) is a chronic condition that affects greater than 900,000 Americans and is also prevalent worldwide.¹ In patients with UC, ulceration and inflammation of the colon leads to episodes of relapsing and remitting flares, making lifelong maintenance therapy necessary.^1,2 Symptoms of UC often include abdominal pain and discomfort, rectal urgency, diarrhea containing blood, and tenesmus.² Patients may also experience weight loss and feelings of fatigue.¹ Diagnosis of UC requires both clinical evaluation as well as confirmation of the disease via colonoscopy and biopsy.²

Treatment of UC involves diet modification, initiation of medications, and surgical intervention, if necessary.¹ Pharmacologic therapy of mild to moderate UC typically begins with orally or rectally administered mesalamine.² Mesalamine, which is structurally similar to aspirin, decreases inflammation via inhibition of cyclooxygenase (COX) 1 and 2 enzymes. Because significant systemic absorption occurs with mesalamine, drug allergies are important to consider when treating a patient.

Not only is the literature regarding the cross-reactivity between aspirin and mesalamine lacking, but published evidence about the relationship is also conflicting.² Some research suggests that cross-reactivity between aspirin and mesalamine does not occur, while other reports state that a test dose should be administered in patients with a history of aspirin hypersensitivity prior to initiation of mesalamine. In a recent article published by Heath et al, a successful desensitization protocol was described in a patient that required mesalamine therapy who had a history of hypersensitivity to aspirin and nonsteroidal anti-inflammatory (NSAID) drugs.

Case Report: A Patient With Chronic UC

Presenting Complaint: A 33-year old woman with a history of drug hypersensitivity to NSAIDs and aspirin presented for management of her chronic UC with mesalamine.² Her active, moderate colitis involved the entire colon and she stated that she experienced predominant rectal symptoms. Upon ingestion of aspirin as a child, she reported occurrence of urticaria and laryngeal angioedema requiring intubation. Additionally, the patient more recently experienced diffuse pruritus and edema upon administration of ibuprofen and naproxen. Assessment of the patient eliminated the possibility of infectious causes.

Past Treatment Regimen: Although oral and rectal mesalamine was indicated initially, treatment with azathioprine and prednisone was chosen given the patient’s allergy history.² After 3 months of therapy, the patient reported worsening of abdominal symptoms, therefore her azathioprine dose was increased. The patient’s symptoms persisted despite an increase in medication dosage as well as the addition of hydrocortisone enemas to her therapy, therefore infliximab 5mg/kg per infusion was initiated. The patient reported that her symptoms continued despite increased therapy. A colonoscopy was performed and revealed “backwash ileitis, cecal patch inflammation, and mucosal healing of midportions of the colon but with a dominant residual proctosigmoiditis.” Orally administered enteric-coated budesonide was initiated at this time. The authors noted that “rectal symptoms persisted, and she was believed to be receiving maximal medical treatment with the exception of not having tried oral or rectal mesalamine.” Because she did not want to pursue surgical intervention at the time, she was referred to the allergy clinic for desensitization to mesalamine. 

German aristocrat Karl Friedrich Hieronymus Freiherr von Münchhausen (1720–1797) was famous for telling highly exaggerated stories of unusual feats, travels, and adventures. In 1786, these tales were fictionalized and published in The Surprising Adventures of Baron Munchausen, by Rudolf Erich Raspe.¹ The medical profession “has since borrowed the name of this famous raconteur to describe a group of individuals whose complaints are fabricated, but nonetheless so convincing that patients are subjected to needless hospitalizations, diagnostic tests, and even surgery.”¹ The syndrome was formally described in 1951 by Richard Asher, a British physician.²

While the term “Munchausen syndrome” is still commonly used, formal DSM-5 diagnosis is “factitious disorder (FD) imposed on self”³ (in contrast to factitious disorder imposed on another, such as a child or other dependent, which is sometimes called “Munchausen by proxy”). Unlike patients who malinger, those with FD are not seeking financial gain, housing, medications, or time off from work. Falsified symptoms can be medical or psychiatric in nature.³

The estimated prevalence of FD in hospitalized patients ranges from 0.5% to 0.8%, with a prevalence of up to 6% to 8% on psychiatric units.⁴ However, these may be conservative estimates, since patients with FD are commonly misdiagnosed with medical conditions, somatoform disorders, or malingering.⁴

While FD can involve an array of conditions, it often involves movement disorders that are difficult to distinguish from organic disease.⁵ A recent article by Zittel et al describes “the novel constellation of a FD presenting as a supposedly genetically confirmed hereditary disease manifesting with abnormal movements.” The authors present this case because of the increasing diagnostic role of genetic testing “in all areas of medicine, including rare and unusual conditions.”

Case Report: A Patient with Pseudo-dopa-responsive Dystonia

Presenting complaint: The patient, a 42-year-old nurse, presented with complaints of increased muscle tone in her back muscles and the right side of her body starting in adolescence. Her symptoms had no diurnal fluctuations and had onset in adolescence. She also noted intermittent muscle twitches. She reported developing impaired coordination and fine motor skills and hemihypesthesia in her late thirties, and she was granted early retirement.

Current treatment regimen: Since her father was reported to also have increased muscle tone. Dopa-responsive dystonia was suspected and genetically confirmed at another institution (according to the patient’s report). Treatment with dopaminergic medication was initiated, which alleviated her symptoms. In response to her “genetically confirmed dopa-responsive dystonia,” she received levodopa 1100mg and pramipexole 0.18mg per day. 

A 50-year-old woman presents with a painful lesion on the inside of her upper lip. She has had similar lesions on an intermittent basis over the past several years in this location and on her tongue and buccal mucosa. The lesions heal without scarring. Medical history is negative for systemic disease, and the patient reports no antecedent fever or arthralgia.

While Hymenoptera stings have been previously associated with cases of beekeeper’s arthritis (arthritis that closely mimics osteoarthritis), there have been no documented reports of a link between Hymenoptera venom and the development of psoriatic arthritis. This case, published in the journal Annals of Allergy, Asthma, and Immunology, reports on a patient who developed psoriatic arthritis shortly after being stung multiple times by wasps. 

The patient, a 46-year-old man, presented to the hospital with asymmetric pain in multiple joints which began 10–12 days after he was stung by multiple wasps (6–8 stings). He had tried several medications to relieve the pain (acetaminophen, tramadol, meloxicam), but these agents did not improve his symptoms, and eventually the joint pain was severe enough for him to become wheelchair bound. Apart from psoriasis, he had no other medical, social, or family history that could be attributed to his symptoms.  Physical and laboratory examination revealed the following:

• Blood pressure: 128/72mmHg
• Pulse: 90/min
• Respiratory rate: 20/min
• Oral temperature: 37.2 °C
• Bilateral shoulder, left knee, right wrist swelling (warm and tender to palpitation)
• Erythrocyte sedimentation rate: 74mm/h (range: <17mm/h for males)
• C-reactive protein: 24mg/L (range: <1mg/L)
• Rheumatoid factor: 15 IU/mL (range: <15 IU/mL)
• Antinuclear antibody, anti-double-stranded DNA, HLA-B27, anticyclic citrullinated peptide, CBC, metabolic panel, serum protein electophoresis: all negative
• Aspiration of fluid from affected joints: unsuccessful
• Radiography of joints: normal

Among pain management clinicians, the use of tramadol, a centrally-acting synthetic opioid analgesic, has increased in popularity, as it is perceived to be a safer option for analgesia. However, a previous study has shown that compared to codeine, tramadol was linked to a 3-fold increase in the risk of hypoglycemia requiring hospitalization within the first 30 days of use.  This case, published in Pain Physician Journal, highlights the first known case of rebound hypoglycemia in a patient with type 1 diabetes after tramadol use.

The patient, a 71-year-old female with a history of hypertension and type 1 diabetes, presented to the pain clinic with complaints of pain in her right buttock and right lateral leg discomfort. Using a visual analog scale, she rated the pain a 6 out of 10 and reported joint stiffness, paresthesia, and right leg pain as additional symptoms. The patient had tried several interventions (ie, bed rest, NSAIDs, aqua therapy, exercise/walking, heat) to reduce the symptoms before she was referred to the pain clinic by her general practitioner. Her current list of medications included an antihypertensive agent as well as Novolog (5 units prandial) and glargine (10 units nightly); no prior hospitalizations for severe hypoglycemia were reported in the past 36 years the patient was on insulin therapy.

Physical examination of the patient revealed “positive right lumbosacral neural tension and a positive Fortin’s finger sign test on the right sacroiliac joint (SIJ) and gluteal area.” Magnetic resonance imaging (MRI) was performed and showed “multilever lumbar degeneration with severe canal stenosis at L3-L5 and foraminal stenosis at L2-4.”  Several differential diagnoses were considered including right SIJ dysfunction, right sciatic nerve compression, osteoarthritis, and neurogenic claudication. The patient, who was opioid-naive, was initiated on tramadol 50mg three time daily as needed for her pain and was scheduled for right sacroiliac joint diagnostic and therapeutic block.

The next day, the patient began treatment with tramadol and after her second dose (taken before dinner at 6pm) noticed that her glucose level after dinner was 70mg/dL; glucose level pre-dinner was 93mg/dL. To boost her levels, she ate a cookie but three hours later she was hypoglycemic with a glucose level of 51mg/dL. She continued to eat and drink hoping to raise her levels but by 1:15am, her glucose level had dropped to 42mg/dL. After consuming two cups of orange juice, she remained hypoglycemic with a glucose level of 56mg/dL. She continued to consume the orange juice, drinking another four glasses until her glucose finally reached 80mg/dL just after 3am. 

While the antibiotic ciprofloxacin has been used for over 25 years, there is limited information on the potentially serious interaction that may occur when it is given with the antipsychotic agent clozapine. This case, published in Case Reports in Psychiatry, is the first to describe a fatal outcome with such an interaction.

The patient, a 28-year-old community-dwelling female with severe intellectual disability, was brought to the emergency department after experiencing two episodes of feeling faint without an obvious cause. The patient had a history of behavioral issues that were consistent with schizophrenia. Her medications included:

• Clozapine dissolving tablets 100mg twice daily
• Bupropion XL 150mg daily in the AM
• Escitalopram 10mg once daily in the AM
• N-acetylcysteine 1200mg twice daily
• Memantine 10mg twice daily
• L-thyroxine (for hypothyroidism)
• Famotidine (for gastroesophageal reflux)
• Fish oil, aspirin (for dyslipidemia)
• Fluticasone, levocetirizine (for seasonal allergies)

No changes in her medications were reported by the house staff who brought her to the ED; the patient had limited verbal abilities and her medication supplies were controlled by the staff. Physical examination only indicated tachycardia and tachypnea but without respiratory distress. The patient was uncooperative with any further testing so she was discharged with a prescription for lorazepam 1mg every 6 hours to treat her anxiety.

The next day, the patient was taken to an outpatient lab for testing where the following abnormalities were noted:

• White blood cell count: 14.7 with 84.1% neutrophils
• Nonfasting glucose: 179mg/dL
• Creatinine: 1.5mg/dL
• CO₂: 16mmol/L
• Urinalysis: trace bacteria with 3–4 WBC per high power field

A diagnosis of urinary tract infection (UTI) was made and the patient was started on ciprofloxacin 500mg twice daily that night. Two days later, the patient collapsed and emergency services were unable to resuscitate her; postmortem examination revealed a clozapine level of 2,900ng/mL (femorally) and 24,300ng/mL (hepatically). Acute drug toxicity was listed as the cause of death.

Published in The Journal of Clinical Hypertension, this unusual case reports on a gastroenterologist who suffered repeated episodes of malignant hypertension brought on while he performed a medical procedure common to his practice.

The patient, a middle-aged gastroenterologist, presented to the hospital with orthostatic hypertension and an erythematous rash on his neck. His past medical history included well-controlled hypertension and impaired fasting glucose, however in the previous weeks he had been repeatedly hospitalized for hypertensive crises. During these episodes he would experience searing “hot poker” occipital headache, face flushing, and neck rash, and an increase in his blood pressure (BP) to >170/120mmHg; these episodes occurred while performing endoscopy and would resolve once the procedure was completed. Over a period of three weeks, the patient was hospitalized seven times with BP values sometimes reaching over 230/130mmHg. 

Beyond his hypertension diagnosis, which had been managed with a single drug, no other significant medical history could explain these episodes. During observation in the hospital, it was noted that the patient’s BP increased whenever he rotated his neck to the left, which he did during endoscopy as it was necessary for him to rotate and extend his neck to view the video monitors during the procedure. Comprehensive laboratory work-up as well as imaging did not provide any additional answers for the patient’s condition. The patient was ultimately stabilized on amlodipine and labetolol, however he continued to have breakthrough episodes, which eventually led him to retire from his practice.

After extensive evaluation ruled out other etiologies, the authors speculate “that repetitive neck rotation and fixation positions while performing endoscopy led to baroreceptor failure in the gastroenterologist.” Baroreflex failure is a rare condition that occurs “after damage to the carotid baroreceptors by neck trauma, surgery or radiation,” however the cause may also be unknown.  As this occupational link has not been addressed in previous literature, the authors caution that clinicians performing endoscopy should be “mindful of workplace ergonomics.” 

Reference:

1. Kram, Michael MD, Voaklander, Rebecca MD, Siegel H Jerome MD, Rph. Recurrent Hypertensive Crises in an Endoscopist: A Possible Occupational Link. The Journal of Clinical Hypertension. DOI: 10.1111/JCH.12842.

High-intensity statin therapy is often prescribed for patients with significant coronary disease, however it can be a risk factor for rhabdomyolysis development, particularly for elderly patients. This case, published in the Journal of Pharmacy Practice, reports on a patient whose nonadherence to medication instructions, coupled with his age and high dose, resulted in statin-induced rhabdomyolysis, suggesting that clinicians may want to avoid or use caution when prescribing aggressive statin therapy to patient over the age of 75.

The patient, a 91-year-old man, was admitted to the hospital with reported leg weakness and muscle pain that had been occurring for the past 10 days. His medical history included hyperlipidemia, type 2 diabetes, hypertension, chronic heart failure with a reduced ejection fraction and non-ST-segment elevation myocardial infarction (nSTEMI), which occurred four months prior to this admission. His medication list included the following:

— Atorvastatin 40mg/day 
— Furosemide 40mg in the AM and 20mg in the PM
— Lisinopril 10mg/day
— Pantoprazole 40mg/day 
— Clopidogrel 75mg/day
— Aspirin 81mg/day 
— Metoprolol succinate 25mg/day 
— Nitroglycerin 0.4mg SL as needed for angina
— Potassium chloride 20mEq in the AM, 10mEq in the afternoon
— Ophthalmic multivitamin twice daily

Four months prior to admission the patient was started on atorvastatin 80mg daily following his diagnosis of nSTEMI, but was instructed to reduce the dose to 40mg daily at a follow-up appointment one month later. The patient, however, did not follow these instructions. At a follow-up appointment (11 days before admission), he was again told to reduce the dose after he began to complain of back and hip pain. His symptoms, however, continued to worsen which eventually led to his admission for rhabdomyolysis.

Published online in JAMA Internal Medicine, this case describes a “teachable moment” for clinicians regarding the potentially fatal impact an incorrect Lyme disease diagnosis can have for a patient desperate to find an answer for her chronic symptoms.

The patient, a 45-year-old female, presented to the emergency department with high fever (103° F), diffuse pruritic rash, and nausea. Her medical history included neurological and gastrointestinal complaints for which she received many medical opinions but no clear diagnosis. Prior to her admission, she sought the care of a “Lyme-literate doctor” who diagnosed her with chronic Lyme disease and babesiosis based on tests conducted in a lab which specialized in Lyme testing, albeit the tests had not been validated through serologic studies. Based on these results (with no evidence of Lyme disease rash), the physician decided to treat the patient with multiple antibiotics (doxycycline and minocycline initiated 3 months prior to admission; trimethoprim-sulfamethoxazole initiated 5 weeks prior to admission).

Laboratory work-up at the time of admission revealed the following:

— Eosinophilia: 5000/uL
— Aspartate transaminase: 205 U/L
— Alanine transaminase: 581 U/L
— Alkaline phosphatase: 561 U/L
— Total bilirubin: 9.9mg/dL
— Lyme enzyme immunoassay, babesia antibody testing, blood smear: all negative

Based on the appearance of her rash as well as the high-grade fever, eosinophilia, and liver injury, the clinicians diagnosed her with drug reaction with eosinophilia and systemic symptoms (DRESS), most likely due to one of the antibiotics she was prescribed for her chronic Lyme diagnosis. The patient was treated with methylprednisolone (escalating doses up to 4mg/kg/d) which led to gradual improvement; she was discharged after 2 weeks and was continued on steroids (tapering the dose) for the next 6 months. Cognitive behavioral therapy was recommended to address her chronic fatigue and pain.

Published in the American Journal of Case Reports, this case study highlights a rare adverse effect of a commonly used antibiotic and brings to light the importance of evaluating the possibility of drug-induced hepatotoxicity in a patient with liver injury of unknown etiology.

The patient, a 74-year-old woman, was being treated with ciprofloxacin for a urinary tract infection (UTI), but on day 4 of treatment she experienced nausea and vomiting which was attributed to a “high dose”; therapy was discontinued on day 5. After discontinuing the drug, she continued to experience nausea, fatigue, weakness, and anorexia for the next two months. Her symptoms continued to worsen at which point she was admitted to the hospital for evaluation.

Her past medical history included hypertension, dyslipidemia, gastroesophageal reflux disease, and hypothyroidism. At the time of hospital admission, she was taking simvastatin 20mg daily, pantoprazole 20mg daily, and levothyroxine 75mcg daily; she denied herbal supplement use, acetaminophen use, or prior liver disease. 

— Laboratory work-up showed the following:
— Aspartate transaminase (AST): 1106
— Alanine transaminase (ALT): 789
— Alkaline phosphatase (ALP): 338
— Total bilirubin (TBIL): 2.75
— Albumin: 2.6
— Hemoglobin: 11.6
— White blood cells: 4700
— Platelets: 142000

Testing also revealed she had a UTI at which point she was given ciprofloxacin again for the next three days. Given the patient’s report of anorexia and low fluid intake, her abnormal liver transaminases were attributed to dehydration and hypoperfusion. She was discharged on day 3 following a small improvement in liver enzymes, however over the next six days, the patient developed new-onset vomiting and jaundice.

Physical examination showed bilateral pedal edema and icterus; labs indicated liver enzymes were again elevated (AST 1263, ALT 870, ALP 496, TBIL 8.9). Since statins are often implicated in hepatotoxicity cases, the patient was taken off simvastatin. Extensive workup, including screening for viral serologies (hepatitis, cytomegalovirus), autoimmune panels, and imaging (abdominal CT scan, ultrasound, magnetic resonance cholangiopancreatography), was found to be unremarkable; liver biopsy indicated cholestatic hepatitis of unclear etiology. After a small drop in her liver enzymes (despite rising bilirubin), the patient was discharged and instructed to follow up with a gastroenterologist.

Fueled by social media, food challenges have become a trendy new fad, that in some cases, can go from fun to fatal very quickly. The Cinnamon Challenge is one example of this, where young adults posted YouTube videos of themselves swallowing a tablespoon of ground cinnamon in 60 seconds without drinking, leading to numerous calls to Poison Control Centers. In this case, published in the Journal of Emergency Medicine, a food challenge with ghost peppers leads to a potentially life-threatening situation that could have easily been misinterpreted as indigestion after a spicy meal.

The patient, a 47-year-old male, presented with severe abdominal and chest pain subsequent to violent retching and vomiting. Before arriving at the ER, the patient had been at a restaurant where he consumed a hamburger that included ghost pepper puree as part of a food challenge; following ingestion he began to experience severe pain and burning in his mouth. Ghost peppers are considered the hottest chili peppers in the world with a measured ‘heat” of >1,000,000 Scoville heat units. After ingesting this meal, forceful retching and vomiting followed at which point the patient started to feel severe chest pain and abdominal pain.

Examination revealed the following:

• Epigastric tenderness to palpitation
• Blood pressure: 174/106mmHg
• Heart rate: 106 beats/min
• Respiratory rate: 18 breaths/min
• Oxygen saturation: 96% on room air
• Temperature: 36.3 Cº
• White blood cell count: 15.7 x 10³/µL
• Hemoglobin: 15.1g/dL
• Hematocrit: 43.4%
• Platelet count: 221 x 10⁹/L
• Creatinine: 1.14mg/dL
• Liver function tests: normal

To help with the patient’s discomfort, he was given a “GI cocktail” that included viscous lidocaine and liquid Maalox, as well as pantoprazole IV and hydromorphone.  While initial review of the chest X-ray by the ER physician was negative, a review by the radiologist showed “evidence of subcutaneous emphysema, a subtle left apical pneumothorax, poor aeration of the base of the left lung, and suspected pneumomediastinum.”

Significant strides have been made in the treatment of hepatitis C virus (HCV) with the introduction of direct-acting antiviral agents (DAAs), however there is limited data on how to treat patients who have failed treatment with multiple DAAs. This case, published in the Journal of Clinical Pharmacy and Therapeutics, discusses a patient with a 20-year-long HCV infection that was finally cured after failing treatment with five different HCV regimens.

The patient, a 60-year-old white woman, had been diagnosed with HCV genotype 1a in 1995 and had been unsuccessfully treated with five different treatment regimens.  These included:

1. Interferon for 24 weeks: null responder
2. Interferon + ribavirin for 48 weeks: null responder
3. Pegylated-interferon + ribavirin for 20 weeks: null responder (discontinued due to leukopenia)
4. Pegylated-interferon + ribavirin + telaprevir for 9 weeks: partial responder (discontinued after detectable viral load of 5830 IU/mL at 4 weeks and 5470 IU/mL at 9 weeks)
5. Simeprevir + sofosbuvir for 12 weeks: partial responder

Genotypic resistance testing was conducted after she had failed her fourth regimen; testing showed resistance to telaprevir and boceprevir with resistance-associated variants V36M and R155K.

In March 2015, she presented to her clinic to initiate a sixth course of therapy at which point her baseline workup was as follows:

• Viral load: 995,810 IU/mL
• Fibrosis stage F4 (diagnosed with compensated cirrhosis in 2012)
• AST: 115 IU/L
• ALT: 124 IU/L
• INR: 1.0
• AFP: 19.8ng/mL
• CrCl >70mL/min

She was not co-infected with HIV or hepatitis B and had no other significant medical history; adherence to previous regimens was found to be excellent. Taking into account previous treatment failures,clinicians started her on ledipasvir/sofosbuvir without ribavirin (due to possible prior intolerance) for a 24 week period.

Montelukast is a leukotriene receptor antagonist used in the treatment of asthma and allergic rhinitis. It works by inhibiting the actions of leukotriene D4 at its receptors, thereby disrupting the inflammatory process associated with these conditions. However, in this case report, published in the American Journal of Therapeutics, a patient experiences angioedema after starting treatment with montelukast, prompting clinicians to question whether this leukotriene inhibitor is at the center of this hypersensitivity reaction.

The patient, a 52-year old man, presented to the emergency department with dysphagia, shortness of breath, and wheezing; he also reported a “drowning feeling” which he experienced when lying down. His medical history included allergies and asthma but he denied experiencing similar symptoms before; he also denied any abdominal pain, nausea, vomiting, diarrhea, rash or pruritus. Further questioning revealed that the patient was not on angiotensin-converting enzyme inhibitors, nor had he changed his eating habits or used any new soaps recently.  A week prior to presentation, he visited his primary care physician who prescribed montelukast as a treatment for his allergies. 

Patient work-up in the emergency department showed the following:

• Heart rate: 115 beats/minute
• Respiratory rate: 23 breaths/minute
• Oxygen saturation: 95% on room air
• Physical exam: respiratory distress; tongue: midline and fully mobile; uvula: symmetric without edema
• Lab test: unremarkable
• Nasopharyngolaryngoscopy: mucosa overlying arytenoids and aryepiglottic folds; redundant and edematous

To treat his symptoms, the patient was started on famotidine 20mg twice daily, diphenhydramine 25mg every 6 hours, and dexamethasone 8mg every 8 hours and was kept overnight for observation. The following day, a repeat nasopharyngolaryngoscopy indicated significantly reduced supraglottic angioedema. Once his symptoms had improved, the patient was discharged with a prescription for methylprednisolone dose pack as well as an antihistamine. Follow-up showed no recurrence of symptoms.

Angioedema associated with montelukast use appears to be a rare side effect given that only one other report of a possible link has been found in the literature. In this case, the authors believe the drug was the cause of the patient’s angioedema as removal of the agent led to a reversal in symptoms with appropriate management. Based on this information, the authors scored this adverse reaction as a 6 on the Naranjo scale. Given the “perplexing nature” of this event, the authors conclude that “physicians should be aware of the life-threatening angioedema, which could occur from montelukast use.” 

References

1. Gill, Dalvir MD; Mann, Kamalpreet BSc; Wani, Lubna MD. Montelukast-Induced Angiodema. American Journal of Therapeutics. 2016; doi: 10.1097/MJT.0000000000000499

Venlafaxine, a serotonin and norepinephrine reuptake inhibitor (SNRI) is used in the treatment of major depressive disorder, generalized anxiety disorder, social anxiety disorder, and panic disorder. Generally, side effects of venlafaxine include reduced libido and arousal, similar to other antidepressants known to inhibit serotonin reuptake. This report, published in the Journal of Clinical Psychopharmacology, discusses the first documented case of a female patient who experienced a venlafaxine-associated increase in libido which required therapy change for her depression and anxiety.

The patient, a 32-year-old woman, had a history of depression and panic attacks which began after the birth of her first child. At that time she was prescribed escitalopram (which caused her to have blurry vision) and then later buspirone and paroxetine, neither of which had an appreciable effect. With supportive therapy, her depression remitted without medication but reoccurred after her second child was born. This time, the patient’s depression was persistent and was complicated by military deployment; she was prescribed sertraline which initially proved to be beneficial. In addition to depression, upon her return from active duty, the patient suffered from subthreshold posttraumatic stress symptoms and intermittent panic attacks (2–4/month). Sertraline was continued, however after the birth of her third child, she became poorly responsive to the drug.

Symptoms of depression continued to persist including passive suicidal thinking; she also indicated a reduction in libido. The decision was made to increase the sertraline to the maximum dose in addition to continued use of clonazepam 0.25mg as needed for panic attacks. At follow-up, almost 2 months later, she reported no substantial improvement and was cross-tapered from sertraline to venlafaxine. One month later, the patient reported an improvement in mood and a reduction in panic attacks, however bilateral galactorrhea, mastalgia and a large increase in libido (desire for sex multiple times/day) also occurred. The patient indicated she was not pregnant nor had she breastfed for quite some time, menstruation was regular and she denied any headaches or visual changes. Her other medications included albuterol, budesonide/formoterol, fexofenadine, fluticasone, pseudoephedrine, and omeprazole. Lab results (during her luteal phase) showed the following:

Beta HCG: negative
TSH, free T3 and T4: normal
Prolactin: 12.1ng/mL (normal)
Follicle-stimulating hormone: 2.3mIU/mL (normal)
Luteinizing hormone: 2.6mIU/mL (normal)
Complete blood count: normal
Metabolic panel: normal
Liver function: normal
Renal function: normal
Brain magnetic resonance imaging (with and without contrast): normal