The number of U.S. emergency department visits for acute pancreatitis associated with alcohol abuse, chronic pancreatitis history, and younger age was on the rise in recent years, an analysis of a nationally representative database has suggested.

Katarzyna Bialasiewicz/Thinkstock

Help your patients better understand pancreatitis and available tests and treatments by using AGA patient education materials, https://www.gastro.org/practice-guidance/gi-patient-center/topic/pancreatitis.

SOURCE: Garg SK et al. J Clin Gastroenterol. 2018 Apr 6. doi: 10.1097/MCG.0000000000001030.

The number of U.S. emergency department visits for acute pancreatitis associated with alcohol abuse, chronic pancreatitis history, and younger age was on the rise in recent years, an analysis of a nationally representative database has suggested.

Katarzyna Bialasiewicz/Thinkstock

Help your patients better understand pancreatitis and available tests and treatments by using AGA patient education materials, https://www.gastro.org/practice-guidance/gi-patient-center/topic/pancreatitis.

SOURCE: Garg SK et al. J Clin Gastroenterol. 2018 Apr 6. doi: 10.1097/MCG.0000000000001030.

The number of U.S. emergency department visits for acute pancreatitis associated with alcohol abuse, chronic pancreatitis history, and younger age was on the rise in recent years, an analysis of a nationally representative database has suggested.

Katarzyna Bialasiewicz/Thinkstock

Help your patients better understand pancreatitis and available tests and treatments by using AGA patient education materials, https://www.gastro.org/practice-guidance/gi-patient-center/topic/pancreatitis.

SOURCE: Garg SK et al. J Clin Gastroenterol. 2018 Apr 6. doi: 10.1097/MCG.0000000000001030.

A 46-year-old man presents to your clinic with hearing loss and ear fullness. He awoke with sudden and unexplained right-sided hearing loss with aural fullness 6 days prior to presentation and reports associated unilateral tinnitus and vertigo. He denies otorrhea and otalgia. Hearing on the left is otherwise preserved, and he has no prior otologic history. He denies inciting events. He has never experienced this before.

On examination, the auricles are normal, and there are no vesicular lesions. His ear canals are patent and without occluding cerumen. Tympanic membranes are translucent and intact without effusion or retraction. On tuning fork examination, Weber lateralizes to the left, and air conduction is greater than bone conduction bilaterally.


What is the most likely diagnosis?

A. Otitis media with effusion.

B. Ménière’s disease.

C. Ramsay Hunt syndrome.

D. Sudden sensorineural hearing loss.

E. Bell’s palsy.

F. Otosclerosis.

G. Benign paroxysmal positional vertigo.

This patient is presenting with sudden sensorineural hearing loss (SSNHL). There are approximately 4,000 new cases of SSNHL reported each year in the United States, and many primary care physicians will encounter this disorder.¹

Idiopathic SSNHL is an otolaryngology emergency, and recognition and prompt treatment is imperative to potentially salvage hearing and improve quality of life.² The rates of spontaneous recovery within the literature vary widely from 32% to 65%. However, this constitutes a significant portion of patients who still require the use of hearing aids. Recovery at lower frequencies occurs more commonly, and the rates of true spontaneous recovery are likely approximately one-third of all cases, with only 15% of patients who recover fully.³

Patients with SSNHL present to an otolaryngologist on average 55 days after symptom onset. Yet it is believed that the earlier the intervention, the more improved the recovery, especially if instituted within 1-2 weeks.⁴ Most patients, however, initially present to their primary care physicians.

The history and physical are particularly important to rule out other etiologies of hearing loss, including otitis media with effusion, acute otitis media, and cerumen impaction.

The onset and progression of SSNHL are unique, in that patients will experience near immediate unilateral hearing loss, typically with a normal ear examination. Aural pressure and tinnitus are frequently reported in SSNHL. In fact, ear fullness is the most common presenting symptom, and tinnitus is reported nearly universally. Dizziness or vertigo does not refute the diagnosis of SSNHL, as this occurs in 30%-40% of cases and is a negative prognostic factor, along with profound sensorineural loss, contralateral hearing impairment, and delayed treatment.^3,5

In 9 out of 10 patients with SSNHL, a precipitating factor or cause will never be identified, and approximately one-third of patients will spontaneously recover hearing.⁶

This has created controversial treatment options. Regardless, specialty guidelines advocate for early medical treatment with systemic corticosteroids within the first 14 days of symptom onset. Clinicians must be prepared to empirically and rapidly treat patients with suspected SSNHL without understanding the etiology and without conclusive audiologic or imaging data.

Other causes indeterminate of sudden hearing loss include autoimmune and Ménière’s disease; however, diagnosis and management of these disorders does not have the same urgency as that of SSNHL.

Otolaryngology follow-up for SSNHL is recommended to provide treatment options and counseling, monitor hearing thresholds, provide ongoing evaluation for hearing augmentation, and establish expert consultation to ensure there are no underlying causes.

Primary care providers need to institute the initial treatment recommendations, which include systemic steroids, potentially in combination with alternative treatment options. There is conflicting evidence on the efficacy of early high-dose steroid therapy in SSNHL. But, unfortunately, the alternative may include permanent unilateral deafness.⁷ The earlier the treatment, the better the outcomes, although oral steroids may contribute to significant improvement even at late presentation.⁴

Dosing recommendations vary, but include prednisone 1 mg/kg per day (maximum of 60 mg), methylprednisolone 48 mg/day, and dexamethasone 10 mg/day for 7-14 days prior to tapering. Examination and audiometry are ideally obtained at the time of symptom onset and immediately after treatment for full evaluation.

Evidence supports the use of intratympanic steroid injections after primary treatment failure, although there is increasing interest in combining transtympanic perfusion with oral steroids for primary treatment.^7,8 In a survey of otolaryngologists, 86% of respondents reported the concomitant use of intratympanic steroid injections for primary treatment.⁹ Of these, greater than 50% and 32% used steroid injections up to 1 month, and up to 3 months following the onset of symptoms, respectively.

There may be benefit with hyperbaric oxygen therapy, which is rarely used in the United States.⁶ There may be benefit with a low side effect profile in combining systemic steroids with antioxidants, such as vitamins A, C, and E.¹⁰

In summary, SSNHL is not uncommon; ear fullness and tinnitus are common and may represent the chief complaint. A high index of suspicion is necessary, and decisions are often made without full knowledge of the etiology. Conductive hearing loss should be ruled out on history and examination. Initial diagnostic workup includes formal audiometry with initiation of high-dose corticosteroid therapy, ideally within 2 weeks of symptom onset.

Consultation to otolaryngology or neurotology is important for ongoing discussions regarding potential recovery, hearing augmentation, and to ensure there is no underlying condition.
 

Dr. Shinn is with the department of otolaryngology–head and neck surgery at Vanderbilt University Medical Center in Nashville, Tenn. Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and he serves as third-year medical student clerkship director at the University of Washington. Contact Dr. Paauw at [email protected].

References

1. Otolaryngol Head Neck Surg. 2012;146(3 Suppl):S1-35.

2. JAMA Otolaryngol Head Neck Surg. 2018 Jun 21. doi: 10.1001/jamaoto.2018.1072.

3. Braz J Otorhinolaryngol. 2015 Oct-Sep;81(5):520-6.

4. Cureus. 2017 Dec;9(12):e1945.

5. JAMA Otolaryngol Head Neck Surg. 2018 Jun 21. doi: 10.1001/jamaoto.2018.0648.

6. Otolaryngol Clin North Am. 2008;41(3):633-49.

7. Curr Opin Otolaryngol Head Neck Surg. 2016 Oct;24(5):413-9.

8. Eur Arch Otorhinolaryngol. 2015 Oct;272(10):2777-82.

9. Ann Otol Rhinol Laryngol. 2018 Jul;127(7):481-2.

10. Audiol Neurotol. 2018 Jun 22;23(1):1-7.

A 46-year-old man presents to your clinic with hearing loss and ear fullness. He awoke with sudden and unexplained right-sided hearing loss with aural fullness 6 days prior to presentation and reports associated unilateral tinnitus and vertigo. He denies otorrhea and otalgia. Hearing on the left is otherwise preserved, and he has no prior otologic history. He denies inciting events. He has never experienced this before.

On examination, the auricles are normal, and there are no vesicular lesions. His ear canals are patent and without occluding cerumen. Tympanic membranes are translucent and intact without effusion or retraction. On tuning fork examination, Weber lateralizes to the left, and air conduction is greater than bone conduction bilaterally.


What is the most likely diagnosis?

A. Otitis media with effusion.

B. Ménière’s disease.

C. Ramsay Hunt syndrome.

D. Sudden sensorineural hearing loss.

E. Bell’s palsy.

F. Otosclerosis.

G. Benign paroxysmal positional vertigo.

This patient is presenting with sudden sensorineural hearing loss (SSNHL). There are approximately 4,000 new cases of SSNHL reported each year in the United States, and many primary care physicians will encounter this disorder.¹

Idiopathic SSNHL is an otolaryngology emergency, and recognition and prompt treatment is imperative to potentially salvage hearing and improve quality of life.² The rates of spontaneous recovery within the literature vary widely from 32% to 65%. However, this constitutes a significant portion of patients who still require the use of hearing aids. Recovery at lower frequencies occurs more commonly, and the rates of true spontaneous recovery are likely approximately one-third of all cases, with only 15% of patients who recover fully.³

Patients with SSNHL present to an otolaryngologist on average 55 days after symptom onset. Yet it is believed that the earlier the intervention, the more improved the recovery, especially if instituted within 1-2 weeks.⁴ Most patients, however, initially present to their primary care physicians.

The history and physical are particularly important to rule out other etiologies of hearing loss, including otitis media with effusion, acute otitis media, and cerumen impaction.

The onset and progression of SSNHL are unique, in that patients will experience near immediate unilateral hearing loss, typically with a normal ear examination. Aural pressure and tinnitus are frequently reported in SSNHL. In fact, ear fullness is the most common presenting symptom, and tinnitus is reported nearly universally. Dizziness or vertigo does not refute the diagnosis of SSNHL, as this occurs in 30%-40% of cases and is a negative prognostic factor, along with profound sensorineural loss, contralateral hearing impairment, and delayed treatment.^3,5

In 9 out of 10 patients with SSNHL, a precipitating factor or cause will never be identified, and approximately one-third of patients will spontaneously recover hearing.⁶

This has created controversial treatment options. Regardless, specialty guidelines advocate for early medical treatment with systemic corticosteroids within the first 14 days of symptom onset. Clinicians must be prepared to empirically and rapidly treat patients with suspected SSNHL without understanding the etiology and without conclusive audiologic or imaging data.

Other causes indeterminate of sudden hearing loss include autoimmune and Ménière’s disease; however, diagnosis and management of these disorders does not have the same urgency as that of SSNHL.

Otolaryngology follow-up for SSNHL is recommended to provide treatment options and counseling, monitor hearing thresholds, provide ongoing evaluation for hearing augmentation, and establish expert consultation to ensure there are no underlying causes.

Primary care providers need to institute the initial treatment recommendations, which include systemic steroids, potentially in combination with alternative treatment options. There is conflicting evidence on the efficacy of early high-dose steroid therapy in SSNHL. But, unfortunately, the alternative may include permanent unilateral deafness.⁷ The earlier the treatment, the better the outcomes, although oral steroids may contribute to significant improvement even at late presentation.⁴

Dosing recommendations vary, but include prednisone 1 mg/kg per day (maximum of 60 mg), methylprednisolone 48 mg/day, and dexamethasone 10 mg/day for 7-14 days prior to tapering. Examination and audiometry are ideally obtained at the time of symptom onset and immediately after treatment for full evaluation.

Evidence supports the use of intratympanic steroid injections after primary treatment failure, although there is increasing interest in combining transtympanic perfusion with oral steroids for primary treatment.^7,8 In a survey of otolaryngologists, 86% of respondents reported the concomitant use of intratympanic steroid injections for primary treatment.⁹ Of these, greater than 50% and 32% used steroid injections up to 1 month, and up to 3 months following the onset of symptoms, respectively.

There may be benefit with hyperbaric oxygen therapy, which is rarely used in the United States.⁶ There may be benefit with a low side effect profile in combining systemic steroids with antioxidants, such as vitamins A, C, and E.¹⁰

In summary, SSNHL is not uncommon; ear fullness and tinnitus are common and may represent the chief complaint. A high index of suspicion is necessary, and decisions are often made without full knowledge of the etiology. Conductive hearing loss should be ruled out on history and examination. Initial diagnostic workup includes formal audiometry with initiation of high-dose corticosteroid therapy, ideally within 2 weeks of symptom onset.

Consultation to otolaryngology or neurotology is important for ongoing discussions regarding potential recovery, hearing augmentation, and to ensure there is no underlying condition.
 

Dr. Shinn is with the department of otolaryngology–head and neck surgery at Vanderbilt University Medical Center in Nashville, Tenn. Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and he serves as third-year medical student clerkship director at the University of Washington. Contact Dr. Paauw at [email protected].

References

1. Otolaryngol Head Neck Surg. 2012;146(3 Suppl):S1-35.

2. JAMA Otolaryngol Head Neck Surg. 2018 Jun 21. doi: 10.1001/jamaoto.2018.1072.

3. Braz J Otorhinolaryngol. 2015 Oct-Sep;81(5):520-6.

4. Cureus. 2017 Dec;9(12):e1945.

5. JAMA Otolaryngol Head Neck Surg. 2018 Jun 21. doi: 10.1001/jamaoto.2018.0648.

6. Otolaryngol Clin North Am. 2008;41(3):633-49.

7. Curr Opin Otolaryngol Head Neck Surg. 2016 Oct;24(5):413-9.

8. Eur Arch Otorhinolaryngol. 2015 Oct;272(10):2777-82.

9. Ann Otol Rhinol Laryngol. 2018 Jul;127(7):481-2.

10. Audiol Neurotol. 2018 Jun 22;23(1):1-7.

A 46-year-old man presents to your clinic with hearing loss and ear fullness. He awoke with sudden and unexplained right-sided hearing loss with aural fullness 6 days prior to presentation and reports associated unilateral tinnitus and vertigo. He denies otorrhea and otalgia. Hearing on the left is otherwise preserved, and he has no prior otologic history. He denies inciting events. He has never experienced this before.

On examination, the auricles are normal, and there are no vesicular lesions. His ear canals are patent and without occluding cerumen. Tympanic membranes are translucent and intact without effusion or retraction. On tuning fork examination, Weber lateralizes to the left, and air conduction is greater than bone conduction bilaterally.


What is the most likely diagnosis?

A. Otitis media with effusion.

B. Ménière’s disease.

C. Ramsay Hunt syndrome.

D. Sudden sensorineural hearing loss.

E. Bell’s palsy.

F. Otosclerosis.

G. Benign paroxysmal positional vertigo.

This patient is presenting with sudden sensorineural hearing loss (SSNHL). There are approximately 4,000 new cases of SSNHL reported each year in the United States, and many primary care physicians will encounter this disorder.¹

Idiopathic SSNHL is an otolaryngology emergency, and recognition and prompt treatment is imperative to potentially salvage hearing and improve quality of life.² The rates of spontaneous recovery within the literature vary widely from 32% to 65%. However, this constitutes a significant portion of patients who still require the use of hearing aids. Recovery at lower frequencies occurs more commonly, and the rates of true spontaneous recovery are likely approximately one-third of all cases, with only 15% of patients who recover fully.³

Patients with SSNHL present to an otolaryngologist on average 55 days after symptom onset. Yet it is believed that the earlier the intervention, the more improved the recovery, especially if instituted within 1-2 weeks.⁴ Most patients, however, initially present to their primary care physicians.

The history and physical are particularly important to rule out other etiologies of hearing loss, including otitis media with effusion, acute otitis media, and cerumen impaction.

The onset and progression of SSNHL are unique, in that patients will experience near immediate unilateral hearing loss, typically with a normal ear examination. Aural pressure and tinnitus are frequently reported in SSNHL. In fact, ear fullness is the most common presenting symptom, and tinnitus is reported nearly universally. Dizziness or vertigo does not refute the diagnosis of SSNHL, as this occurs in 30%-40% of cases and is a negative prognostic factor, along with profound sensorineural loss, contralateral hearing impairment, and delayed treatment.^3,5

In 9 out of 10 patients with SSNHL, a precipitating factor or cause will never be identified, and approximately one-third of patients will spontaneously recover hearing.⁶

This has created controversial treatment options. Regardless, specialty guidelines advocate for early medical treatment with systemic corticosteroids within the first 14 days of symptom onset. Clinicians must be prepared to empirically and rapidly treat patients with suspected SSNHL without understanding the etiology and without conclusive audiologic or imaging data.

Other causes indeterminate of sudden hearing loss include autoimmune and Ménière’s disease; however, diagnosis and management of these disorders does not have the same urgency as that of SSNHL.

Otolaryngology follow-up for SSNHL is recommended to provide treatment options and counseling, monitor hearing thresholds, provide ongoing evaluation for hearing augmentation, and establish expert consultation to ensure there are no underlying causes.

Primary care providers need to institute the initial treatment recommendations, which include systemic steroids, potentially in combination with alternative treatment options. There is conflicting evidence on the efficacy of early high-dose steroid therapy in SSNHL. But, unfortunately, the alternative may include permanent unilateral deafness.⁷ The earlier the treatment, the better the outcomes, although oral steroids may contribute to significant improvement even at late presentation.⁴

Dosing recommendations vary, but include prednisone 1 mg/kg per day (maximum of 60 mg), methylprednisolone 48 mg/day, and dexamethasone 10 mg/day for 7-14 days prior to tapering. Examination and audiometry are ideally obtained at the time of symptom onset and immediately after treatment for full evaluation.

Evidence supports the use of intratympanic steroid injections after primary treatment failure, although there is increasing interest in combining transtympanic perfusion with oral steroids for primary treatment.^7,8 In a survey of otolaryngologists, 86% of respondents reported the concomitant use of intratympanic steroid injections for primary treatment.⁹ Of these, greater than 50% and 32% used steroid injections up to 1 month, and up to 3 months following the onset of symptoms, respectively.

There may be benefit with hyperbaric oxygen therapy, which is rarely used in the United States.⁶ There may be benefit with a low side effect profile in combining systemic steroids with antioxidants, such as vitamins A, C, and E.¹⁰

In summary, SSNHL is not uncommon; ear fullness and tinnitus are common and may represent the chief complaint. A high index of suspicion is necessary, and decisions are often made without full knowledge of the etiology. Conductive hearing loss should be ruled out on history and examination. Initial diagnostic workup includes formal audiometry with initiation of high-dose corticosteroid therapy, ideally within 2 weeks of symptom onset.

Consultation to otolaryngology or neurotology is important for ongoing discussions regarding potential recovery, hearing augmentation, and to ensure there is no underlying condition.
 

Dr. Shinn is with the department of otolaryngology–head and neck surgery at Vanderbilt University Medical Center in Nashville, Tenn. Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and he serves as third-year medical student clerkship director at the University of Washington. Contact Dr. Paauw at [email protected].

References

1. Otolaryngol Head Neck Surg. 2012;146(3 Suppl):S1-35.

2. JAMA Otolaryngol Head Neck Surg. 2018 Jun 21. doi: 10.1001/jamaoto.2018.1072.

3. Braz J Otorhinolaryngol. 2015 Oct-Sep;81(5):520-6.

4. Cureus. 2017 Dec;9(12):e1945.

5. JAMA Otolaryngol Head Neck Surg. 2018 Jun 21. doi: 10.1001/jamaoto.2018.0648.

6. Otolaryngol Clin North Am. 2008;41(3):633-49.

7. Curr Opin Otolaryngol Head Neck Surg. 2016 Oct;24(5):413-9.

8. Eur Arch Otorhinolaryngol. 2015 Oct;272(10):2777-82.

9. Ann Otol Rhinol Laryngol. 2018 Jul;127(7):481-2.

10. Audiol Neurotol. 2018 Jun 22;23(1):1-7.

Andrew N. Wilner, MD, FAAN, FACP

Angels Neurological Centers

Abington, MA

Clinical History

A 37-year-old pregnant African American woman with a history of epilepsy and polysubstance abuse was found unresponsive in a hotel room. She had four convulsions en route to the hospital. In transit, she received levetiracetam and phenytoin, resulting in the cessation of the clinical seizures.

According to her mother, seizures began at age 16 during her first pregnancy, which was complicated by hypertension. She was prescribed medications for hypertension and phenytoin for seizures. The patient provided a different history, claiming that her seizures began 2 years ago. She denied taking medication for seizures or other health problems.

The patient has two children, ages 22 and 11 years. Past medical history is otherwise unremarkable. She has no allergies. Social history includes cigarette smoking, and alcohol and substance abuse. She lives with her boyfriend and does not work. She is 25 weeks pregnant. Family history was notable only for migraine in her mother and grandmother.

Physical Examination    

In the emergency department, blood pressure was 135/65, pulse 121 beats per minute, and oxygen saturation was 97%. She was oriented only to self and did not follow commands. Pupils were equal and reactive. There was no facial asymmetry. She moved all 4 extremities spontaneously. Reflexes were brisk. Oral mucosa was dry. She had no edema in the lower extremities.

Laboratories

Chest x-ray was normal. EKG revealed tachycardia and nonspecific ST changes. Hemoglobin was 11.1 g/dl, hematocrit 32%, white blood cell count 10,900, and platelets 181,000. Electrolytes were normal except for a low sodium of 132 mmol/l (135-145) and bicarbonate of 17 mmol/l (21-31). Glucose was initially 67 mg/dl and dropped to 46 mg/dl. Total protein was 6 g/dl (6.7-8.2) and albumin was 2.7 g/dl (3.2-5.5). Metabolic panel was otherwise normal. Urinalysis was positive for glucose, ketones, and a small amount of blood and protein. There were no bacteria. Blood and urine cultures were negative. Phenytoin level was undetectable. Urine drug screen was positive for cannabinoids and cocaine.

Hospital Course

Hypoglycemia was treated with an ampule of D50 and intravenous fluids. On the obstetrics ward, nurses observed several episodes of head and eye deviation to the right accompanied by decreased responsiveness that lasted approximately 30 seconds. The patient was sent to the electrophysiology lab where an EEG revealed a diffusely slow background (Figure 1).

Figure 1. Generalized Slowing

During the 20-minute EEG recording, the patient had six clinical seizures similar to those described by the nurses. These events correlated with an ictal pattern consisting of 11 HZ_sharp activity in the right occipital temporal region that spread to the right parietal and left occipital temporal regions (Figure 2). Head CT revealed mild generalized atrophy and an enlarged right occipital horn, but no acute lesions (Figure 3).

Figure 2. Partial seizure originating in right occipital temporal region

Figure 3. Mild generalized arophy, greater in right hemisphere

The patient was transferred to intensive care and received fosphenytoin. No further clinical and /or electrographic seizures were identified. The following day, an EEG revealed diffuse slowing without focal seizures (Figure 4). The patient gradually became more alert and cooperative over the next 24 hours. However, the next day no fetal heartbeat was detected. Labor was induced and a stillborn baby delivered. The pathology report indicated that the placenta was between the 5^th and 10^th percentile for gestational age.

Figure 4. Improved generalized slowing

Discussion

Status epilepticus is associated with significant morbidity and mortality (Claassen et al. 2002). This 37-year-old pregnant woman had an episode of focal status epilepticus with impaired awareness likely provoked by nonadherence to antiepileptic drugs (AEDs). Cocaine may have contributed to the episode of status epilepticus (Majlesi et al. 2010). The obstetric service did not diagnose preeclampsia.

The patient’s seizures started in the right occipital region, which was abnormal on neuroimaging. An MRI might have revealed more subtle structural abnormalities such as cortical dysplasia as the etiology of her epilepsy, but she refused the scan.

Women with epilepsy are at increased risk for adverse pregnancy outcomes such as preeclampsia, preterm labor, and stillbirth and should be considered high risk (MacDonald et al. 2015). Serum levels of AEDs such as lamotrigine, levetiracetam and phenytoin may decrease during pregnancy and contribute to breakthrough seizures. Accordingly, monthly measurements of serum levels of AEDs during the entire course of the pregnancy are strongly recommended. These measurements allow for a timely adjustment of AED doses to prevent significant drop in their serum concentrations and minimize the occurrence of breakthrough seizures. In the case of phenytoin, measurement of free and total serum concentrations are recommended. Supplementation with at least 0.4 mg/day to 1 mg /day of folic acid (and up to 4 mg /day) has been recommended (Harden et al. 2009a). Of note, there is no increase in the incidence of status epilepticus due to pregnancy per se (Harden et al. 2009b).

Although the patient survived this episode of status epilepticus, her fetus did not. Antiseizure drug nonadherence and polysubstance abuse probably contributed to fetal demise.

References

Claassen J, Lokin JK, Fitzsimons BFM et al. Predictors of functional disability and mortality after status epilepticus. Neurology. 2002;58:139-142.

Harden CL, Pennell PB, Koppel BS et al. Practice Parameter update: Management issues for women with epilepsy Focus on pregnancy (an evidence-based review): Vitamin K, folic acid, blood levels, and breastfeeding: Neurology 2009a;73:142-149.

Harden CL, Hopp J, Ting TY et al. Practice Parameter update: Management issues for women with epilepsy-focus on pregnancy (an evidence-based review): Obstetrical complications and change in seizure frequency. Neurology 2009b;50(5):1229-36.

MacDonald SC, Bateman BT, McElrath TF, Hernandez-Diaz S. Mortality and morbidity during delivery hospitalization among pregnant women with epilepsy in the United States. JAMA Neurol. 2015;72(9):981-988.

Majlesi N, Shih R, Fiesseler FW et al. Cocaine-associated seizures and incidence of status epilepticus. Western Journal of Emergency Medicine. 2010;XI(2):157-160.

Andrew N. Wilner, MD, FAAN, FACP

Angels Neurological Centers

Abington, MA

Clinical History

A 37-year-old pregnant African American woman with a history of epilepsy and polysubstance abuse was found unresponsive in a hotel room. She had four convulsions en route to the hospital. In transit, she received levetiracetam and phenytoin, resulting in the cessation of the clinical seizures.

According to her mother, seizures began at age 16 during her first pregnancy, which was complicated by hypertension. She was prescribed medications for hypertension and phenytoin for seizures. The patient provided a different history, claiming that her seizures began 2 years ago. She denied taking medication for seizures or other health problems.

The patient has two children, ages 22 and 11 years. Past medical history is otherwise unremarkable. She has no allergies. Social history includes cigarette smoking, and alcohol and substance abuse. She lives with her boyfriend and does not work. She is 25 weeks pregnant. Family history was notable only for migraine in her mother and grandmother.

Physical Examination    

In the emergency department, blood pressure was 135/65, pulse 121 beats per minute, and oxygen saturation was 97%. She was oriented only to self and did not follow commands. Pupils were equal and reactive. There was no facial asymmetry. She moved all 4 extremities spontaneously. Reflexes were brisk. Oral mucosa was dry. She had no edema in the lower extremities.

Laboratories

Chest x-ray was normal. EKG revealed tachycardia and nonspecific ST changes. Hemoglobin was 11.1 g/dl, hematocrit 32%, white blood cell count 10,900, and platelets 181,000. Electrolytes were normal except for a low sodium of 132 mmol/l (135-145) and bicarbonate of 17 mmol/l (21-31). Glucose was initially 67 mg/dl and dropped to 46 mg/dl. Total protein was 6 g/dl (6.7-8.2) and albumin was 2.7 g/dl (3.2-5.5). Metabolic panel was otherwise normal. Urinalysis was positive for glucose, ketones, and a small amount of blood and protein. There were no bacteria. Blood and urine cultures were negative. Phenytoin level was undetectable. Urine drug screen was positive for cannabinoids and cocaine.

Hospital Course

Hypoglycemia was treated with an ampule of D50 and intravenous fluids. On the obstetrics ward, nurses observed several episodes of head and eye deviation to the right accompanied by decreased responsiveness that lasted approximately 30 seconds. The patient was sent to the electrophysiology lab where an EEG revealed a diffusely slow background (Figure 1).

Figure 1. Generalized Slowing

During the 20-minute EEG recording, the patient had six clinical seizures similar to those described by the nurses. These events correlated with an ictal pattern consisting of 11 HZ_sharp activity in the right occipital temporal region that spread to the right parietal and left occipital temporal regions (Figure 2). Head CT revealed mild generalized atrophy and an enlarged right occipital horn, but no acute lesions (Figure 3).

Figure 2. Partial seizure originating in right occipital temporal region

Figure 3. Mild generalized arophy, greater in right hemisphere

The patient was transferred to intensive care and received fosphenytoin. No further clinical and /or electrographic seizures were identified. The following day, an EEG revealed diffuse slowing without focal seizures (Figure 4). The patient gradually became more alert and cooperative over the next 24 hours. However, the next day no fetal heartbeat was detected. Labor was induced and a stillborn baby delivered. The pathology report indicated that the placenta was between the 5^th and 10^th percentile for gestational age.

Figure 4. Improved generalized slowing

Discussion

Status epilepticus is associated with significant morbidity and mortality (Claassen et al. 2002). This 37-year-old pregnant woman had an episode of focal status epilepticus with impaired awareness likely provoked by nonadherence to antiepileptic drugs (AEDs). Cocaine may have contributed to the episode of status epilepticus (Majlesi et al. 2010). The obstetric service did not diagnose preeclampsia.

The patient’s seizures started in the right occipital region, which was abnormal on neuroimaging. An MRI might have revealed more subtle structural abnormalities such as cortical dysplasia as the etiology of her epilepsy, but she refused the scan.

Women with epilepsy are at increased risk for adverse pregnancy outcomes such as preeclampsia, preterm labor, and stillbirth and should be considered high risk (MacDonald et al. 2015). Serum levels of AEDs such as lamotrigine, levetiracetam and phenytoin may decrease during pregnancy and contribute to breakthrough seizures. Accordingly, monthly measurements of serum levels of AEDs during the entire course of the pregnancy are strongly recommended. These measurements allow for a timely adjustment of AED doses to prevent significant drop in their serum concentrations and minimize the occurrence of breakthrough seizures. In the case of phenytoin, measurement of free and total serum concentrations are recommended. Supplementation with at least 0.4 mg/day to 1 mg /day of folic acid (and up to 4 mg /day) has been recommended (Harden et al. 2009a). Of note, there is no increase in the incidence of status epilepticus due to pregnancy per se (Harden et al. 2009b).

Although the patient survived this episode of status epilepticus, her fetus did not. Antiseizure drug nonadherence and polysubstance abuse probably contributed to fetal demise.

References

Claassen J, Lokin JK, Fitzsimons BFM et al. Predictors of functional disability and mortality after status epilepticus. Neurology. 2002;58:139-142.

Harden CL, Pennell PB, Koppel BS et al. Practice Parameter update: Management issues for women with epilepsy Focus on pregnancy (an evidence-based review): Vitamin K, folic acid, blood levels, and breastfeeding: Neurology 2009a;73:142-149.

Harden CL, Hopp J, Ting TY et al. Practice Parameter update: Management issues for women with epilepsy-focus on pregnancy (an evidence-based review): Obstetrical complications and change in seizure frequency. Neurology 2009b;50(5):1229-36.

MacDonald SC, Bateman BT, McElrath TF, Hernandez-Diaz S. Mortality and morbidity during delivery hospitalization among pregnant women with epilepsy in the United States. JAMA Neurol. 2015;72(9):981-988.

Majlesi N, Shih R, Fiesseler FW et al. Cocaine-associated seizures and incidence of status epilepticus. Western Journal of Emergency Medicine. 2010;XI(2):157-160.

Andrew N. Wilner, MD, FAAN, FACP

Angels Neurological Centers

Abington, MA

Clinical History

A 37-year-old pregnant African American woman with a history of epilepsy and polysubstance abuse was found unresponsive in a hotel room. She had four convulsions en route to the hospital. In transit, she received levetiracetam and phenytoin, resulting in the cessation of the clinical seizures.

According to her mother, seizures began at age 16 during her first pregnancy, which was complicated by hypertension. She was prescribed medications for hypertension and phenytoin for seizures. The patient provided a different history, claiming that her seizures began 2 years ago. She denied taking medication for seizures or other health problems.

The patient has two children, ages 22 and 11 years. Past medical history is otherwise unremarkable. She has no allergies. Social history includes cigarette smoking, and alcohol and substance abuse. She lives with her boyfriend and does not work. She is 25 weeks pregnant. Family history was notable only for migraine in her mother and grandmother.

Physical Examination    

In the emergency department, blood pressure was 135/65, pulse 121 beats per minute, and oxygen saturation was 97%. She was oriented only to self and did not follow commands. Pupils were equal and reactive. There was no facial asymmetry. She moved all 4 extremities spontaneously. Reflexes were brisk. Oral mucosa was dry. She had no edema in the lower extremities.

Laboratories

Chest x-ray was normal. EKG revealed tachycardia and nonspecific ST changes. Hemoglobin was 11.1 g/dl, hematocrit 32%, white blood cell count 10,900, and platelets 181,000. Electrolytes were normal except for a low sodium of 132 mmol/l (135-145) and bicarbonate of 17 mmol/l (21-31). Glucose was initially 67 mg/dl and dropped to 46 mg/dl. Total protein was 6 g/dl (6.7-8.2) and albumin was 2.7 g/dl (3.2-5.5). Metabolic panel was otherwise normal. Urinalysis was positive for glucose, ketones, and a small amount of blood and protein. There were no bacteria. Blood and urine cultures were negative. Phenytoin level was undetectable. Urine drug screen was positive for cannabinoids and cocaine.

Hospital Course

Hypoglycemia was treated with an ampule of D50 and intravenous fluids. On the obstetrics ward, nurses observed several episodes of head and eye deviation to the right accompanied by decreased responsiveness that lasted approximately 30 seconds. The patient was sent to the electrophysiology lab where an EEG revealed a diffusely slow background (Figure 1).

Figure 1. Generalized Slowing

During the 20-minute EEG recording, the patient had six clinical seizures similar to those described by the nurses. These events correlated with an ictal pattern consisting of 11 HZ_sharp activity in the right occipital temporal region that spread to the right parietal and left occipital temporal regions (Figure 2). Head CT revealed mild generalized atrophy and an enlarged right occipital horn, but no acute lesions (Figure 3).

Figure 2. Partial seizure originating in right occipital temporal region

Figure 3. Mild generalized arophy, greater in right hemisphere

The patient was transferred to intensive care and received fosphenytoin. No further clinical and /or electrographic seizures were identified. The following day, an EEG revealed diffuse slowing without focal seizures (Figure 4). The patient gradually became more alert and cooperative over the next 24 hours. However, the next day no fetal heartbeat was detected. Labor was induced and a stillborn baby delivered. The pathology report indicated that the placenta was between the 5^th and 10^th percentile for gestational age.

Figure 4. Improved generalized slowing

Discussion

Status epilepticus is associated with significant morbidity and mortality (Claassen et al. 2002). This 37-year-old pregnant woman had an episode of focal status epilepticus with impaired awareness likely provoked by nonadherence to antiepileptic drugs (AEDs). Cocaine may have contributed to the episode of status epilepticus (Majlesi et al. 2010). The obstetric service did not diagnose preeclampsia.

The patient’s seizures started in the right occipital region, which was abnormal on neuroimaging. An MRI might have revealed more subtle structural abnormalities such as cortical dysplasia as the etiology of her epilepsy, but she refused the scan.

Women with epilepsy are at increased risk for adverse pregnancy outcomes such as preeclampsia, preterm labor, and stillbirth and should be considered high risk (MacDonald et al. 2015). Serum levels of AEDs such as lamotrigine, levetiracetam and phenytoin may decrease during pregnancy and contribute to breakthrough seizures. Accordingly, monthly measurements of serum levels of AEDs during the entire course of the pregnancy are strongly recommended. These measurements allow for a timely adjustment of AED doses to prevent significant drop in their serum concentrations and minimize the occurrence of breakthrough seizures. In the case of phenytoin, measurement of free and total serum concentrations are recommended. Supplementation with at least 0.4 mg/day to 1 mg /day of folic acid (and up to 4 mg /day) has been recommended (Harden et al. 2009a). Of note, there is no increase in the incidence of status epilepticus due to pregnancy per se (Harden et al. 2009b).

Although the patient survived this episode of status epilepticus, her fetus did not. Antiseizure drug nonadherence and polysubstance abuse probably contributed to fetal demise.

References

Claassen J, Lokin JK, Fitzsimons BFM et al. Predictors of functional disability and mortality after status epilepticus. Neurology. 2002;58:139-142.

Harden CL, Pennell PB, Koppel BS et al. Practice Parameter update: Management issues for women with epilepsy Focus on pregnancy (an evidence-based review): Vitamin K, folic acid, blood levels, and breastfeeding: Neurology 2009a;73:142-149.

Harden CL, Hopp J, Ting TY et al. Practice Parameter update: Management issues for women with epilepsy-focus on pregnancy (an evidence-based review): Obstetrical complications and change in seizure frequency. Neurology 2009b;50(5):1229-36.

MacDonald SC, Bateman BT, McElrath TF, Hernandez-Diaz S. Mortality and morbidity during delivery hospitalization among pregnant women with epilepsy in the United States. JAMA Neurol. 2015;72(9):981-988.

Majlesi N, Shih R, Fiesseler FW et al. Cocaine-associated seizures and incidence of status epilepticus. Western Journal of Emergency Medicine. 2010;XI(2):157-160.

Any economist could have predicted it: As the price of electronic cigarettes goes down, sales increase.

Price decreases for the three products available in 2012 were all significant: The average price per unit was down 48% for rechargeables by 2016, 14% for disposables, and 12% for prefilled cartridges. E-liquids were 9% cheaper by 2016, but that change did not reach significance, they noted.

“Overall, the increase in e-cigarette sales and decrease in price is consistent with previous studies demonstrating that e-cigarette sales are responsive to their own price changes. These trends suggest that, if e-cigarette prices continue to decrease, their sales may also continue to rise,” Dr. Wang and her associates wrote.

The data for the study came from the Nielsen Company and were based on retail sales at convenience stores; supermarkets; drug, dollar, and club stores; and military commissaries in the 48 contiguous states and Washington, D.C. One study limitation was the lack of data from tobacco/vape shops and the Internet.

[email protected]

SOURCE: Wang TW et al. Prev Chronic Dis. 2018;15:170555. doi: 10.5888/pcd15.170555.

Any economist could have predicted it: As the price of electronic cigarettes goes down, sales increase.

Price decreases for the three products available in 2012 were all significant: The average price per unit was down 48% for rechargeables by 2016, 14% for disposables, and 12% for prefilled cartridges. E-liquids were 9% cheaper by 2016, but that change did not reach significance, they noted.

“Overall, the increase in e-cigarette sales and decrease in price is consistent with previous studies demonstrating that e-cigarette sales are responsive to their own price changes. These trends suggest that, if e-cigarette prices continue to decrease, their sales may also continue to rise,” Dr. Wang and her associates wrote.

The data for the study came from the Nielsen Company and were based on retail sales at convenience stores; supermarkets; drug, dollar, and club stores; and military commissaries in the 48 contiguous states and Washington, D.C. One study limitation was the lack of data from tobacco/vape shops and the Internet.

[email protected]

SOURCE: Wang TW et al. Prev Chronic Dis. 2018;15:170555. doi: 10.5888/pcd15.170555.

Any economist could have predicted it: As the price of electronic cigarettes goes down, sales increase.

Price decreases for the three products available in 2012 were all significant: The average price per unit was down 48% for rechargeables by 2016, 14% for disposables, and 12% for prefilled cartridges. E-liquids were 9% cheaper by 2016, but that change did not reach significance, they noted.

“Overall, the increase in e-cigarette sales and decrease in price is consistent with previous studies demonstrating that e-cigarette sales are responsive to their own price changes. These trends suggest that, if e-cigarette prices continue to decrease, their sales may also continue to rise,” Dr. Wang and her associates wrote.

The data for the study came from the Nielsen Company and were based on retail sales at convenience stores; supermarkets; drug, dollar, and club stores; and military commissaries in the 48 contiguous states and Washington, D.C. One study limitation was the lack of data from tobacco/vape shops and the Internet.

[email protected]

SOURCE: Wang TW et al. Prev Chronic Dis. 2018;15:170555. doi: 10.5888/pcd15.170555.

Case Report

A 31-year-old man presented to the dermatology clinic 1 day after mountain biking in the woods in Hartford County, Connecticut. He stated that he found a tick attached to his shirt after riding (Figure). Careful examination of the patient showed no signs of a bite reaction. The insect was identified via microscopy as the deer ked Lipoptena cervi.

Comment

Lipoptena cervi, known as the deer ked, is an ectoparasite of cervids traditionally found in Norway, Sweden, and Finland.¹ The deer ked was first reported in American deer in 2 independent sightings in Pennsylvania and New Hampshire in 1907.² More recently deer keds have been reported in Massachusetts, New York, Pennsylvania, and New Hampshire.³ In the United States, L cervi is thought to be an invasive species transported from Europe in the 1800s.^4,5 The main host is thought to be the white-tailed deer (Odocoileus viginianus). Once a suitable host is found, the deer ked sheds its wings and crawls into the fur. After engorging on a blood meal, it deposits prepupae that fall from the host and mature into winged adults during the late summer into the autumn. Adults may exhibit swarming behavior, and it is during this host-seeking activity that they land on humans.³

Following the bite of a deer ked, there are reports of long-lasting dermatitis in both humans and dogs.^1,4,6 One case series involving 19 patients following deer ked bites reported pruritic bite papules.⁴ The reaction appeared to be treatment resistant and lasted from 2 weeks to 12 months. Histologic examination was typical for arthropod assault. Of 11 papules that were biopsied, most (7/11) showed C3 deposition in dermal vessel walls under direct immunofluorescence. Of 19 patients, 57% had elevated serum IgE levels.⁴

In addition to the associated dermatologic findings, the deer ked is a vector of various infectious agents. Bartonella schoenbuchensis has been isolated from deer ked in Massachusettes.⁷ A recent study found a 75% prevalence of Bartonella species in 217 deer keds collected from red deer in Poland.⁵ The first incidence of Borrelia burgdorferi and Anaplasma phagocytophylum in deer keds was reported in the United States in 2016. Of 48 adult deer keds collected from an unknown number of deer, 19 (40%), 14 (29%), and 3 (6%) were positive for B burgdorferi, A phagocytophylum, and both on polymerase chain reaction, respectively.³

A recent study from Europe showed deer keds are now more frequently found in regions where they had not previously been observed.⁸ It stands to reason that with climate change, L cervi and other disease-carrying vectors are likely to migrate to and inhabit new regions of the country. Even in the current climate, there are more disease-carrying arthropods than are routinely studied in medicine, and all patients who experience an arthropod assault should be monitored for signs of systemic disease.

Case Report

A 31-year-old man presented to the dermatology clinic 1 day after mountain biking in the woods in Hartford County, Connecticut. He stated that he found a tick attached to his shirt after riding (Figure). Careful examination of the patient showed no signs of a bite reaction. The insect was identified via microscopy as the deer ked Lipoptena cervi.

Comment

Lipoptena cervi, known as the deer ked, is an ectoparasite of cervids traditionally found in Norway, Sweden, and Finland.¹ The deer ked was first reported in American deer in 2 independent sightings in Pennsylvania and New Hampshire in 1907.² More recently deer keds have been reported in Massachusetts, New York, Pennsylvania, and New Hampshire.³ In the United States, L cervi is thought to be an invasive species transported from Europe in the 1800s.^4,5 The main host is thought to be the white-tailed deer (Odocoileus viginianus). Once a suitable host is found, the deer ked sheds its wings and crawls into the fur. After engorging on a blood meal, it deposits prepupae that fall from the host and mature into winged adults during the late summer into the autumn. Adults may exhibit swarming behavior, and it is during this host-seeking activity that they land on humans.³

Following the bite of a deer ked, there are reports of long-lasting dermatitis in both humans and dogs.^1,4,6 One case series involving 19 patients following deer ked bites reported pruritic bite papules.⁴ The reaction appeared to be treatment resistant and lasted from 2 weeks to 12 months. Histologic examination was typical for arthropod assault. Of 11 papules that were biopsied, most (7/11) showed C3 deposition in dermal vessel walls under direct immunofluorescence. Of 19 patients, 57% had elevated serum IgE levels.⁴

In addition to the associated dermatologic findings, the deer ked is a vector of various infectious agents. Bartonella schoenbuchensis has been isolated from deer ked in Massachusettes.⁷ A recent study found a 75% prevalence of Bartonella species in 217 deer keds collected from red deer in Poland.⁵ The first incidence of Borrelia burgdorferi and Anaplasma phagocytophylum in deer keds was reported in the United States in 2016. Of 48 adult deer keds collected from an unknown number of deer, 19 (40%), 14 (29%), and 3 (6%) were positive for B burgdorferi, A phagocytophylum, and both on polymerase chain reaction, respectively.³

A recent study from Europe showed deer keds are now more frequently found in regions where they had not previously been observed.⁸ It stands to reason that with climate change, L cervi and other disease-carrying vectors are likely to migrate to and inhabit new regions of the country. Even in the current climate, there are more disease-carrying arthropods than are routinely studied in medicine, and all patients who experience an arthropod assault should be monitored for signs of systemic disease.

Case Report

A 31-year-old man presented to the dermatology clinic 1 day after mountain biking in the woods in Hartford County, Connecticut. He stated that he found a tick attached to his shirt after riding (Figure). Careful examination of the patient showed no signs of a bite reaction. The insect was identified via microscopy as the deer ked Lipoptena cervi.

Comment

Lipoptena cervi, known as the deer ked, is an ectoparasite of cervids traditionally found in Norway, Sweden, and Finland.¹ The deer ked was first reported in American deer in 2 independent sightings in Pennsylvania and New Hampshire in 1907.² More recently deer keds have been reported in Massachusetts, New York, Pennsylvania, and New Hampshire.³ In the United States, L cervi is thought to be an invasive species transported from Europe in the 1800s.^4,5 The main host is thought to be the white-tailed deer (Odocoileus viginianus). Once a suitable host is found, the deer ked sheds its wings and crawls into the fur. After engorging on a blood meal, it deposits prepupae that fall from the host and mature into winged adults during the late summer into the autumn. Adults may exhibit swarming behavior, and it is during this host-seeking activity that they land on humans.³

Following the bite of a deer ked, there are reports of long-lasting dermatitis in both humans and dogs.^1,4,6 One case series involving 19 patients following deer ked bites reported pruritic bite papules.⁴ The reaction appeared to be treatment resistant and lasted from 2 weeks to 12 months. Histologic examination was typical for arthropod assault. Of 11 papules that were biopsied, most (7/11) showed C3 deposition in dermal vessel walls under direct immunofluorescence. Of 19 patients, 57% had elevated serum IgE levels.⁴

In addition to the associated dermatologic findings, the deer ked is a vector of various infectious agents. Bartonella schoenbuchensis has been isolated from deer ked in Massachusettes.⁷ A recent study found a 75% prevalence of Bartonella species in 217 deer keds collected from red deer in Poland.⁵ The first incidence of Borrelia burgdorferi and Anaplasma phagocytophylum in deer keds was reported in the United States in 2016. Of 48 adult deer keds collected from an unknown number of deer, 19 (40%), 14 (29%), and 3 (6%) were positive for B burgdorferi, A phagocytophylum, and both on polymerase chain reaction, respectively.³

A recent study from Europe showed deer keds are now more frequently found in regions where they had not previously been observed.⁸ It stands to reason that with climate change, L cervi and other disease-carrying vectors are likely to migrate to and inhabit new regions of the country. Even in the current climate, there are more disease-carrying arthropods than are routinely studied in medicine, and all patients who experience an arthropod assault should be monitored for signs of systemic disease.

Women in the United States do not appear to be delaying pregnancy after a diagnosis of melanoma, despite general recommendations to wait at least 2 years to attempt pregnancy because it might increase the risk of recurrence or exacerbate disease, investigators reported in the Journal of Surgical Research.

A review of records from a large national health care database showed that women aged 18-40 years with melanoma who were not pregnant on the index date had a significantly higher rate of pregnancy within 2 years, compared with matched controls, reported Julie A. DiSano, MD, from Penn State University, Hershey.

“These results suggest that a diagnosis of melanoma may serve as an impetus for some families to begin childbearing or have additional children sooner than they otherwise would have,” they wrote.

The investigators also found, reassuringly, that women who became pregnant after a melanoma diagnosis were not at increased risk for requiring additional therapy for the malignancy, at least in the short term.

Although earlier studies suggested that women who were pregnant at the time of a melanoma diagnosis had worse prognoses when compared with women who were not pregnant at the time of diagnosis, more recent studies have indicated women who are pregnant when diagnosed have similar outcomes as nonpregnant women with the same disease stage, the investigators noted.

“What is unclear and difficult to study is the relationship between melanoma and subsequent pregnancy rates, and pregnancy on melanoma outcomes. Very little data exist to guide women and physicians as to the safety of pregnancy after a diagnosis of melanoma. As a result, there are no formal guidelines for physicians who wish to counsel their patients regarding pregnancy after melanoma, and it is unknown whether women receive any counseling at all,” they wrote.

To get a clearer picture of the link between melanoma and subsequent pregnancy, the investigators scanned the Truven Health MarketScan database and identified 11,801 women from 18-40 years with melanoma who were not pregnant on the index date, determined by the earliest claim for melanoma diagnosis or therapy.

Each patient was matched on a 1:1 basis with women who did not have a melanoma claim at any time; cases were matched with controls on the basis of year of index date, age at index date, state of residence, and pregnancy status in the 90 days before the index date.

The authors found that the rate of pregnancy within 2 years of the index date was 15.8% for cases, compared with 13.6% for controls (P less than .001).

They also found, however, that women who required postsurgical therapy, suggesting more advanced disease stage or early recurrence, had a significantly lower probability of becoming pregnant within the first 9 months after the index date (hazard ratio, 0.26; P = .003).

There were no significant differences in the rate of postsurgical treatment by pregnancy status at either 3, 6, 9, or 12 months after surgery (P less than .05 for each), or in a Cox regression model for all time points (HR, 0.68, P = .23).

SOURCE: DiSano JA et al. J Surg Res. 2018 Jun 16. doi: 10.1016/j.jss.2018.05.026.
 

Women in the United States do not appear to be delaying pregnancy after a diagnosis of melanoma, despite general recommendations to wait at least 2 years to attempt pregnancy because it might increase the risk of recurrence or exacerbate disease, investigators reported in the Journal of Surgical Research.

A review of records from a large national health care database showed that women aged 18-40 years with melanoma who were not pregnant on the index date had a significantly higher rate of pregnancy within 2 years, compared with matched controls, reported Julie A. DiSano, MD, from Penn State University, Hershey.

“These results suggest that a diagnosis of melanoma may serve as an impetus for some families to begin childbearing or have additional children sooner than they otherwise would have,” they wrote.

The investigators also found, reassuringly, that women who became pregnant after a melanoma diagnosis were not at increased risk for requiring additional therapy for the malignancy, at least in the short term.

Although earlier studies suggested that women who were pregnant at the time of a melanoma diagnosis had worse prognoses when compared with women who were not pregnant at the time of diagnosis, more recent studies have indicated women who are pregnant when diagnosed have similar outcomes as nonpregnant women with the same disease stage, the investigators noted.

“What is unclear and difficult to study is the relationship between melanoma and subsequent pregnancy rates, and pregnancy on melanoma outcomes. Very little data exist to guide women and physicians as to the safety of pregnancy after a diagnosis of melanoma. As a result, there are no formal guidelines for physicians who wish to counsel their patients regarding pregnancy after melanoma, and it is unknown whether women receive any counseling at all,” they wrote.

To get a clearer picture of the link between melanoma and subsequent pregnancy, the investigators scanned the Truven Health MarketScan database and identified 11,801 women from 18-40 years with melanoma who were not pregnant on the index date, determined by the earliest claim for melanoma diagnosis or therapy.

Each patient was matched on a 1:1 basis with women who did not have a melanoma claim at any time; cases were matched with controls on the basis of year of index date, age at index date, state of residence, and pregnancy status in the 90 days before the index date.

The authors found that the rate of pregnancy within 2 years of the index date was 15.8% for cases, compared with 13.6% for controls (P less than .001).

They also found, however, that women who required postsurgical therapy, suggesting more advanced disease stage or early recurrence, had a significantly lower probability of becoming pregnant within the first 9 months after the index date (hazard ratio, 0.26; P = .003).

There were no significant differences in the rate of postsurgical treatment by pregnancy status at either 3, 6, 9, or 12 months after surgery (P less than .05 for each), or in a Cox regression model for all time points (HR, 0.68, P = .23).

SOURCE: DiSano JA et al. J Surg Res. 2018 Jun 16. doi: 10.1016/j.jss.2018.05.026.
 

Women in the United States do not appear to be delaying pregnancy after a diagnosis of melanoma, despite general recommendations to wait at least 2 years to attempt pregnancy because it might increase the risk of recurrence or exacerbate disease, investigators reported in the Journal of Surgical Research.

A review of records from a large national health care database showed that women aged 18-40 years with melanoma who were not pregnant on the index date had a significantly higher rate of pregnancy within 2 years, compared with matched controls, reported Julie A. DiSano, MD, from Penn State University, Hershey.

“These results suggest that a diagnosis of melanoma may serve as an impetus for some families to begin childbearing or have additional children sooner than they otherwise would have,” they wrote.

The investigators also found, reassuringly, that women who became pregnant after a melanoma diagnosis were not at increased risk for requiring additional therapy for the malignancy, at least in the short term.

Although earlier studies suggested that women who were pregnant at the time of a melanoma diagnosis had worse prognoses when compared with women who were not pregnant at the time of diagnosis, more recent studies have indicated women who are pregnant when diagnosed have similar outcomes as nonpregnant women with the same disease stage, the investigators noted.

“What is unclear and difficult to study is the relationship between melanoma and subsequent pregnancy rates, and pregnancy on melanoma outcomes. Very little data exist to guide women and physicians as to the safety of pregnancy after a diagnosis of melanoma. As a result, there are no formal guidelines for physicians who wish to counsel their patients regarding pregnancy after melanoma, and it is unknown whether women receive any counseling at all,” they wrote.

To get a clearer picture of the link between melanoma and subsequent pregnancy, the investigators scanned the Truven Health MarketScan database and identified 11,801 women from 18-40 years with melanoma who were not pregnant on the index date, determined by the earliest claim for melanoma diagnosis or therapy.

Each patient was matched on a 1:1 basis with women who did not have a melanoma claim at any time; cases were matched with controls on the basis of year of index date, age at index date, state of residence, and pregnancy status in the 90 days before the index date.

The authors found that the rate of pregnancy within 2 years of the index date was 15.8% for cases, compared with 13.6% for controls (P less than .001).

They also found, however, that women who required postsurgical therapy, suggesting more advanced disease stage or early recurrence, had a significantly lower probability of becoming pregnant within the first 9 months after the index date (hazard ratio, 0.26; P = .003).

There were no significant differences in the rate of postsurgical treatment by pregnancy status at either 3, 6, 9, or 12 months after surgery (P less than .05 for each), or in a Cox regression model for all time points (HR, 0.68, P = .23).

SOURCE: DiSano JA et al. J Surg Res. 2018 Jun 16. doi: 10.1016/j.jss.2018.05.026.
 

SAN FRANCISCO—Chronic migraine is associated with increased age-related cortical thinning of some brain areas and decreased age-related cortical thinning in other areas, according to research presented at the 60th Annual Scientific Meeting of the American Headache Society. It remains uncertain whether these cortical changes are a cause or an effect of chronic migraine.

Age-related cortical integrity had not been explored in chronic migraine previously. To investigate this topic, Yohannes Woubishet Woldeamanuel, MD, Instructor in Neurology and Neurologic Sciences at Stanford University in California, and colleagues enrolled 30 patients with chronic migraine and 30 age- and sex-matched healthy controls into a study. All participants were right-handed. The mean age in the chronic migraine group was 40.5, and the male-to-female ratio was 1:4. Investigators obtained the duration of chronic migraine and lifetime migraine from participants with chronic migraine.

Suggested Reading

Chong CD, Dodick DW, Schlaggar BL, Schwedt TJ. Atypical age-related cortical thinning in episodic migraine. Cephalalgia. 2014;34(14):1115-1124.

Schwedt TJ, Berisha V, Chong CD. Temporal lobe cortical thickness correlations differentiate the migraine brain from the healthy brain. PLoS One. 2015 Feb 13;10(2):e0116687.

SAN FRANCISCO—Chronic migraine is associated with increased age-related cortical thinning of some brain areas and decreased age-related cortical thinning in other areas, according to research presented at the 60th Annual Scientific Meeting of the American Headache Society. It remains uncertain whether these cortical changes are a cause or an effect of chronic migraine.

Age-related cortical integrity had not been explored in chronic migraine previously. To investigate this topic, Yohannes Woubishet Woldeamanuel, MD, Instructor in Neurology and Neurologic Sciences at Stanford University in California, and colleagues enrolled 30 patients with chronic migraine and 30 age- and sex-matched healthy controls into a study. All participants were right-handed. The mean age in the chronic migraine group was 40.5, and the male-to-female ratio was 1:4. Investigators obtained the duration of chronic migraine and lifetime migraine from participants with chronic migraine.

Suggested Reading

Chong CD, Dodick DW, Schlaggar BL, Schwedt TJ. Atypical age-related cortical thinning in episodic migraine. Cephalalgia. 2014;34(14):1115-1124.

Schwedt TJ, Berisha V, Chong CD. Temporal lobe cortical thickness correlations differentiate the migraine brain from the healthy brain. PLoS One. 2015 Feb 13;10(2):e0116687.

SAN FRANCISCO—Chronic migraine is associated with increased age-related cortical thinning of some brain areas and decreased age-related cortical thinning in other areas, according to research presented at the 60th Annual Scientific Meeting of the American Headache Society. It remains uncertain whether these cortical changes are a cause or an effect of chronic migraine.

Age-related cortical integrity had not been explored in chronic migraine previously. To investigate this topic, Yohannes Woubishet Woldeamanuel, MD, Instructor in Neurology and Neurologic Sciences at Stanford University in California, and colleagues enrolled 30 patients with chronic migraine and 30 age- and sex-matched healthy controls into a study. All participants were right-handed. The mean age in the chronic migraine group was 40.5, and the male-to-female ratio was 1:4. Investigators obtained the duration of chronic migraine and lifetime migraine from participants with chronic migraine.

Suggested Reading

Chong CD, Dodick DW, Schlaggar BL, Schwedt TJ. Atypical age-related cortical thinning in episodic migraine. Cephalalgia. 2014;34(14):1115-1124.

Schwedt TJ, Berisha V, Chong CD. Temporal lobe cortical thickness correlations differentiate the migraine brain from the healthy brain. PLoS One. 2015 Feb 13;10(2):e0116687.

An allergic reaction is an exaggerated immune response that is known as a type I or immediate hypersensitivity reaction when provoked by reexposure to an allergen or antigen. Upon initial exposure to the antigen, dendritic cells bind it for presentation to helper T (T_H2) lymphocytes. The T_H2 cells then interact with B cells, stimulating them to become plasma cells and produce IgE antibodies to the antigen. When exposed to the same allergen a second time, IgE antibodies bind the allergen and cross-link on mast cells and basophils in the blood. Cross-linking stimulates degranulation of the cells, releasing histamine, leukotrienes, prostaglandins, and other cytokines. The major effects of the release of these mediators include vasodilation, increased vascular permeability, and bronchoconstriction. Leukotrienes also are responsible for chemotaxis of white blood cells, further propagating the immune response.¹

Effects of a type I hypersensitivity reaction can be either local or systemic, resulting in symptoms ranging from mild irritation to anaphylactic shock and death. Latex allergy is a common example of a type I hypersensitivity reaction. Latex is found in many medical products, including gloves, rubber, elastics, blood pressure cuffs, bandages, dressings, and syringes. Reactions can include runny nose, tearing eyes, itching, hives, wheals, wheezing, and in rare cases anaphylaxis.² Diagnosis can be suspected based on history and physical examination. Screening is performed with radioallergosorbent testing, which identifies specific IgE antibodies to latex; however, the reported sensitivity and specificity for the latex-specific IgE antibody varies widely in the literature, and the test cannot reliably rule in or rule out a true latex allergy.³

Allergic responses to latex in psoriasis patients receiving frequent injections with biologic agents are not commonly reported in the literature. We report the case of a patient with a long history of psoriasis who developed an allergic response after exposure to injection devices that contained latex components while undergoing treatment with biologic agents.

Case Report

A 72-year-old man presented with an extensive history of severe psoriasis with frequent flares. Treatment with topical agents and etanercept 6 months prior at an outside facility failed. At the time of presentation, the patient had more than 10% body surface area (BSA) involvement, which included the scalp, legs, chest, and back. He subsequently was started on ustekinumab injections. He initially responded well to therapy, but after 8 months of treatment, he began to have recurrent episodes of acute eruptive rashes over the trunk with associated severe pruritus that reproducibly recurred within 24 hours after each ustekinumab injection. It was decided to discontinue ustekinumab due to concern for intolerance, and the patient was switched to secukinumab. 

After starting secukinumab, the patient's BSA involvement was reduced to 2% after 1 month; however, he began to develop an eruptive rash with severe pruritus again that reproducibly recurred after each secukinumab injection. On physical examination the patient had ill-defined, confluent, erythematous patches over much of the trunk and extremities. Punch biopsies of the eruptive dermatitis showed spongiform psoriasis and eosinophils with dermal hypersensitivity, consistent with a drug eruption. Upon further questioning, the patient noted that he had a long history of a strong latex allergy and he would develop a blistering dermatitis when coming into contact with latex, which caused a high suspicion for a latex allergy as the cause of the patient's acute dermatitis flares from his prior ustekinumab and secukinumab injections. Although it was confirmed with the manufacturers that both the ustekinumab syringe and secukinumab pen did not contain latex, the caps of these medications (and many other biologic injections) do have latex (Table). Other differential diagnoses included an atypical paradoxical   psoriasis flare and a drug eruption to secukinumab, which previously has been reported.⁴

Based on the suspected cause of the eruption, the patient was instructed not to touch the cap of the secukinumab pen. Despite this recommendation, the rash was still present at the next appointment 1 month later. Repeat punch biopsy showed similar findings to the one prior with likely dermal hypersensitivity. The rash improved with steroid injections and continued to improve after holding the secukinumab for 1 month.

After resolution of the hypersensitivity reaction, the patient was started on ixekizumab, which does not contain latex in any component according to the manufacturer. After 2 months of treatment, the patient had 2% BSA involvement of psoriasis and has had no further reports of itching, rash, or other symptoms of a hypersensitivity reaction. On follow-up, the patient's psoriasis symptoms continue to be controlled without further reactions after injections of ixekizumab. Radioallergosorbent testing was not performed due to the lack of specificity and sensitivity of the test3 as well as the patient's known history of latex allergy and characteristic dermatitis that developed after exposure to latex and resolution with removal of the agent. These clinical manifestations are highly indicative of a type I hypersensitivity to injection devices that contain latex components during biologic therapy.

Comment

Allergic responses to latex are most commonly seen in those exposed to gloves or rubber, but little has been reported on reactions to injections with pens or syringes that contain latex components. Some case reports have demonstrated allergic responses in diabetic patients receiving insulin injections.^5,6 MacCracken et al⁵ reported the case of a young boy who had an allergic response to an insulin injection with a syringe containing latex. The patient had a history of bladder exstrophy with a recent diagnosis of diabetes mellitus. It is well known that patients with spina bifida and other conditions who undergo frequent urological procedures more commonly develop latex allergies. This patient reported a history of swollen lips after a dentist visit, presumably due to contact with latex gloves. Because of the suspected allergy, his first insulin injection was given using a glass syringe and insulin was withdrawn with the top removed due to the top containing latex. He did not experience any complications. After being injected later with insulin drawn through the top using a syringe that contained latex, he developed a flare-up of a 0.5-cm erythematous wheal within minutes with associated pruritus.⁵

Towse et al⁶ described another patient with diabetes who developed a local allergic reaction at the site of insulin injections. Workup by the physician ruled out insulin allergy but showed elevated latex-specific IgE antibodies. Future insulin draws through a latex-containing top produced a wheal at the injection site. After switching to latex-free syringes, the allergic reaction resolved.⁶

Latex allergies are common in medical practice, as latex is found in a wide variety of medical supplies, including syringes used for injections and their caps. Physicians need to be aware of latex allergies in their patients and exercise extreme caution in the use of latex-containing products. In the treatment of psoriasis, care must be given when injecting biologic agents. Although many injection devices contain latex limited to the cap, it may be enough to invoke an allergic response. If such a response is elicited, therapy with injection devices that do not contain latex in either the cap or syringe should be considered.

An allergic reaction is an exaggerated immune response that is known as a type I or immediate hypersensitivity reaction when provoked by reexposure to an allergen or antigen. Upon initial exposure to the antigen, dendritic cells bind it for presentation to helper T (T_H2) lymphocytes. The T_H2 cells then interact with B cells, stimulating them to become plasma cells and produce IgE antibodies to the antigen. When exposed to the same allergen a second time, IgE antibodies bind the allergen and cross-link on mast cells and basophils in the blood. Cross-linking stimulates degranulation of the cells, releasing histamine, leukotrienes, prostaglandins, and other cytokines. The major effects of the release of these mediators include vasodilation, increased vascular permeability, and bronchoconstriction. Leukotrienes also are responsible for chemotaxis of white blood cells, further propagating the immune response.¹

Effects of a type I hypersensitivity reaction can be either local or systemic, resulting in symptoms ranging from mild irritation to anaphylactic shock and death. Latex allergy is a common example of a type I hypersensitivity reaction. Latex is found in many medical products, including gloves, rubber, elastics, blood pressure cuffs, bandages, dressings, and syringes. Reactions can include runny nose, tearing eyes, itching, hives, wheals, wheezing, and in rare cases anaphylaxis.² Diagnosis can be suspected based on history and physical examination. Screening is performed with radioallergosorbent testing, which identifies specific IgE antibodies to latex; however, the reported sensitivity and specificity for the latex-specific IgE antibody varies widely in the literature, and the test cannot reliably rule in or rule out a true latex allergy.³

Allergic responses to latex in psoriasis patients receiving frequent injections with biologic agents are not commonly reported in the literature. We report the case of a patient with a long history of psoriasis who developed an allergic response after exposure to injection devices that contained latex components while undergoing treatment with biologic agents.

Case Report

A 72-year-old man presented with an extensive history of severe psoriasis with frequent flares. Treatment with topical agents and etanercept 6 months prior at an outside facility failed. At the time of presentation, the patient had more than 10% body surface area (BSA) involvement, which included the scalp, legs, chest, and back. He subsequently was started on ustekinumab injections. He initially responded well to therapy, but after 8 months of treatment, he began to have recurrent episodes of acute eruptive rashes over the trunk with associated severe pruritus that reproducibly recurred within 24 hours after each ustekinumab injection. It was decided to discontinue ustekinumab due to concern for intolerance, and the patient was switched to secukinumab. 

After starting secukinumab, the patient's BSA involvement was reduced to 2% after 1 month; however, he began to develop an eruptive rash with severe pruritus again that reproducibly recurred after each secukinumab injection. On physical examination the patient had ill-defined, confluent, erythematous patches over much of the trunk and extremities. Punch biopsies of the eruptive dermatitis showed spongiform psoriasis and eosinophils with dermal hypersensitivity, consistent with a drug eruption. Upon further questioning, the patient noted that he had a long history of a strong latex allergy and he would develop a blistering dermatitis when coming into contact with latex, which caused a high suspicion for a latex allergy as the cause of the patient's acute dermatitis flares from his prior ustekinumab and secukinumab injections. Although it was confirmed with the manufacturers that both the ustekinumab syringe and secukinumab pen did not contain latex, the caps of these medications (and many other biologic injections) do have latex (Table). Other differential diagnoses included an atypical paradoxical   psoriasis flare and a drug eruption to secukinumab, which previously has been reported.⁴

Based on the suspected cause of the eruption, the patient was instructed not to touch the cap of the secukinumab pen. Despite this recommendation, the rash was still present at the next appointment 1 month later. Repeat punch biopsy showed similar findings to the one prior with likely dermal hypersensitivity. The rash improved with steroid injections and continued to improve after holding the secukinumab for 1 month.

After resolution of the hypersensitivity reaction, the patient was started on ixekizumab, which does not contain latex in any component according to the manufacturer. After 2 months of treatment, the patient had 2% BSA involvement of psoriasis and has had no further reports of itching, rash, or other symptoms of a hypersensitivity reaction. On follow-up, the patient's psoriasis symptoms continue to be controlled without further reactions after injections of ixekizumab. Radioallergosorbent testing was not performed due to the lack of specificity and sensitivity of the test3 as well as the patient's known history of latex allergy and characteristic dermatitis that developed after exposure to latex and resolution with removal of the agent. These clinical manifestations are highly indicative of a type I hypersensitivity to injection devices that contain latex components during biologic therapy.

Comment

Allergic responses to latex are most commonly seen in those exposed to gloves or rubber, but little has been reported on reactions to injections with pens or syringes that contain latex components. Some case reports have demonstrated allergic responses in diabetic patients receiving insulin injections.^5,6 MacCracken et al⁵ reported the case of a young boy who had an allergic response to an insulin injection with a syringe containing latex. The patient had a history of bladder exstrophy with a recent diagnosis of diabetes mellitus. It is well known that patients with spina bifida and other conditions who undergo frequent urological procedures more commonly develop latex allergies. This patient reported a history of swollen lips after a dentist visit, presumably due to contact with latex gloves. Because of the suspected allergy, his first insulin injection was given using a glass syringe and insulin was withdrawn with the top removed due to the top containing latex. He did not experience any complications. After being injected later with insulin drawn through the top using a syringe that contained latex, he developed a flare-up of a 0.5-cm erythematous wheal within minutes with associated pruritus.⁵

Towse et al⁶ described another patient with diabetes who developed a local allergic reaction at the site of insulin injections. Workup by the physician ruled out insulin allergy but showed elevated latex-specific IgE antibodies. Future insulin draws through a latex-containing top produced a wheal at the injection site. After switching to latex-free syringes, the allergic reaction resolved.⁶

Latex allergies are common in medical practice, as latex is found in a wide variety of medical supplies, including syringes used for injections and their caps. Physicians need to be aware of latex allergies in their patients and exercise extreme caution in the use of latex-containing products. In the treatment of psoriasis, care must be given when injecting biologic agents. Although many injection devices contain latex limited to the cap, it may be enough to invoke an allergic response. If such a response is elicited, therapy with injection devices that do not contain latex in either the cap or syringe should be considered.

An allergic reaction is an exaggerated immune response that is known as a type I or immediate hypersensitivity reaction when provoked by reexposure to an allergen or antigen. Upon initial exposure to the antigen, dendritic cells bind it for presentation to helper T (T_H2) lymphocytes. The T_H2 cells then interact with B cells, stimulating them to become plasma cells and produce IgE antibodies to the antigen. When exposed to the same allergen a second time, IgE antibodies bind the allergen and cross-link on mast cells and basophils in the blood. Cross-linking stimulates degranulation of the cells, releasing histamine, leukotrienes, prostaglandins, and other cytokines. The major effects of the release of these mediators include vasodilation, increased vascular permeability, and bronchoconstriction. Leukotrienes also are responsible for chemotaxis of white blood cells, further propagating the immune response.¹

Effects of a type I hypersensitivity reaction can be either local or systemic, resulting in symptoms ranging from mild irritation to anaphylactic shock and death. Latex allergy is a common example of a type I hypersensitivity reaction. Latex is found in many medical products, including gloves, rubber, elastics, blood pressure cuffs, bandages, dressings, and syringes. Reactions can include runny nose, tearing eyes, itching, hives, wheals, wheezing, and in rare cases anaphylaxis.² Diagnosis can be suspected based on history and physical examination. Screening is performed with radioallergosorbent testing, which identifies specific IgE antibodies to latex; however, the reported sensitivity and specificity for the latex-specific IgE antibody varies widely in the literature, and the test cannot reliably rule in or rule out a true latex allergy.³

Allergic responses to latex in psoriasis patients receiving frequent injections with biologic agents are not commonly reported in the literature. We report the case of a patient with a long history of psoriasis who developed an allergic response after exposure to injection devices that contained latex components while undergoing treatment with biologic agents.

Case Report

A 72-year-old man presented with an extensive history of severe psoriasis with frequent flares. Treatment with topical agents and etanercept 6 months prior at an outside facility failed. At the time of presentation, the patient had more than 10% body surface area (BSA) involvement, which included the scalp, legs, chest, and back. He subsequently was started on ustekinumab injections. He initially responded well to therapy, but after 8 months of treatment, he began to have recurrent episodes of acute eruptive rashes over the trunk with associated severe pruritus that reproducibly recurred within 24 hours after each ustekinumab injection. It was decided to discontinue ustekinumab due to concern for intolerance, and the patient was switched to secukinumab. 

After starting secukinumab, the patient's BSA involvement was reduced to 2% after 1 month; however, he began to develop an eruptive rash with severe pruritus again that reproducibly recurred after each secukinumab injection. On physical examination the patient had ill-defined, confluent, erythematous patches over much of the trunk and extremities. Punch biopsies of the eruptive dermatitis showed spongiform psoriasis and eosinophils with dermal hypersensitivity, consistent with a drug eruption. Upon further questioning, the patient noted that he had a long history of a strong latex allergy and he would develop a blistering dermatitis when coming into contact with latex, which caused a high suspicion for a latex allergy as the cause of the patient's acute dermatitis flares from his prior ustekinumab and secukinumab injections. Although it was confirmed with the manufacturers that both the ustekinumab syringe and secukinumab pen did not contain latex, the caps of these medications (and many other biologic injections) do have latex (Table). Other differential diagnoses included an atypical paradoxical   psoriasis flare and a drug eruption to secukinumab, which previously has been reported.⁴

Based on the suspected cause of the eruption, the patient was instructed not to touch the cap of the secukinumab pen. Despite this recommendation, the rash was still present at the next appointment 1 month later. Repeat punch biopsy showed similar findings to the one prior with likely dermal hypersensitivity. The rash improved with steroid injections and continued to improve after holding the secukinumab for 1 month.

After resolution of the hypersensitivity reaction, the patient was started on ixekizumab, which does not contain latex in any component according to the manufacturer. After 2 months of treatment, the patient had 2% BSA involvement of psoriasis and has had no further reports of itching, rash, or other symptoms of a hypersensitivity reaction. On follow-up, the patient's psoriasis symptoms continue to be controlled without further reactions after injections of ixekizumab. Radioallergosorbent testing was not performed due to the lack of specificity and sensitivity of the test3 as well as the patient's known history of latex allergy and characteristic dermatitis that developed after exposure to latex and resolution with removal of the agent. These clinical manifestations are highly indicative of a type I hypersensitivity to injection devices that contain latex components during biologic therapy.

Comment

Allergic responses to latex are most commonly seen in those exposed to gloves or rubber, but little has been reported on reactions to injections with pens or syringes that contain latex components. Some case reports have demonstrated allergic responses in diabetic patients receiving insulin injections.^5,6 MacCracken et al⁵ reported the case of a young boy who had an allergic response to an insulin injection with a syringe containing latex. The patient had a history of bladder exstrophy with a recent diagnosis of diabetes mellitus. It is well known that patients with spina bifida and other conditions who undergo frequent urological procedures more commonly develop latex allergies. This patient reported a history of swollen lips after a dentist visit, presumably due to contact with latex gloves. Because of the suspected allergy, his first insulin injection was given using a glass syringe and insulin was withdrawn with the top removed due to the top containing latex. He did not experience any complications. After being injected later with insulin drawn through the top using a syringe that contained latex, he developed a flare-up of a 0.5-cm erythematous wheal within minutes with associated pruritus.⁵

Towse et al⁶ described another patient with diabetes who developed a local allergic reaction at the site of insulin injections. Workup by the physician ruled out insulin allergy but showed elevated latex-specific IgE antibodies. Future insulin draws through a latex-containing top produced a wheal at the injection site. After switching to latex-free syringes, the allergic reaction resolved.⁶

Latex allergies are common in medical practice, as latex is found in a wide variety of medical supplies, including syringes used for injections and their caps. Physicians need to be aware of latex allergies in their patients and exercise extreme caution in the use of latex-containing products. In the treatment of psoriasis, care must be given when injecting biologic agents. Although many injection devices contain latex limited to the cap, it may be enough to invoke an allergic response. If such a response is elicited, therapy with injection devices that do not contain latex in either the cap or syringe should be considered.

SAN FRANCISCO—Unmet treatment needs among migraineurs receiving oral prescription medications include therapies to reduce nausea and disturbed sleep, according to a study described at the 60th Annual Scientific Meeting of the American Headache Society. The population also has unmet needs for therapies that provide pain freedom and rapid onset of action.

In 2017, investigators conducted the Migraine in America Symptoms and Treatment (MAST) study, which focused on migraine symptoms, current treatment patterns, and the assessment of unmet treatment needs. Richard B. Lipton, MD, Edwin S. Lowe Chair in Neurology at Albert Einstein College of Medicine in the Bronx, New York, and colleagues examined MAST data to empirically characterize the patterns of poorly controlled migraine and assess corresponding rates of migraine-related disability.

A Survey of American Migraineurs

The MAST survey data were obtained from a general US population sample of migraineurs age 18 and older. Migraineurs were identified using a validated migraine symptom screen based on modified ICHD-3b criteria. Eligible participants had an average of at least one headache day per month during the previous three months.

Respondents provided information about sociodemographics and medication use and responded to a 13-item battery evaluating headache burden and response to medication. The items on the battery were derived from a review of relevant literature, clinician input, and interviews with migraine patients. Participants provided frequency data for each item on a five-point scale ranging from “1) Never” to “5) All or Nearly All of the Time.” To measure construct validity for the scale, the investigators assessed moderate to severe disability for each respondent using the Migraine Disability Assessment Scale (MIDAS).

To determine the underlying structure of unmet treatment needs, Dr. Lipton and colleagues conducted Exploratory Factor Analysis (EFA) among the subset of respondents currently using oral acute prescription medications. They assessed the internal consistency for the derived factors using Cronbach’s alpha. Mean factor scores (range, 1 to 5) were calculated by summing item responses for each factor and dividing by the number of items loading on that factor. The researchers used Mantel-Haenszel Chi Square Test for Trend to evaluate the relationship between mean factor score and rates of moderate to severe migraine-related disability.

Treatment May Act Too Slowly

Among 15,133 respondents meeting inclusion criteria, 3,930 reported current use of acute oral prescription headache medication (mean age, 45.0, 73.6% women, 81.6% Caucasian). Injection and nasal spray medication users were eliminated from the sample. The most commonly endorsed needs were “severe headache attacks come on very rapidly” (52.8%), “attacks reach peak intensity in less than 30 minutes” (50.4%), “severe headache presents upon awakening” (40.9%), and “the return of pain within 24 hours after initial pain relief” (38.6%). EFA identified the following four unmet needs: nausea interference, disturbed sleep, rapid onset, and lack of pain freedom. Internal consistency exceeded acceptable levels for all factors except disturbed sleep. MIDAS disability increased in a clear linear pattern with increasing mean factor scores.

Suggested Reading

Blumenfeld AM, Aurora SK, Laranjo K, Papapetropoulos S. Unmet clinical needs in chronic migraine: Rationale for study and design of COMPEL, an open-label, multicenter study of the long-term efficacy, safety, and tolerability of onabotulinumtoxinA for headache prophylaxis in adults with chronic migraine. BMC Neurol. 2015;15:100.

Lipton RB, Buse DC, Serrano D, et al. Examination of unmet treatment needs among persons with episodic migraine: results of the American Migraine Prevalence and Prevention (AMPP) Study. Headache. 2013;53(8):1300-1311.

SAN FRANCISCO—Unmet treatment needs among migraineurs receiving oral prescription medications include therapies to reduce nausea and disturbed sleep, according to a study described at the 60th Annual Scientific Meeting of the American Headache Society. The population also has unmet needs for therapies that provide pain freedom and rapid onset of action.

In 2017, investigators conducted the Migraine in America Symptoms and Treatment (MAST) study, which focused on migraine symptoms, current treatment patterns, and the assessment of unmet treatment needs. Richard B. Lipton, MD, Edwin S. Lowe Chair in Neurology at Albert Einstein College of Medicine in the Bronx, New York, and colleagues examined MAST data to empirically characterize the patterns of poorly controlled migraine and assess corresponding rates of migraine-related disability.

A Survey of American Migraineurs

The MAST survey data were obtained from a general US population sample of migraineurs age 18 and older. Migraineurs were identified using a validated migraine symptom screen based on modified ICHD-3b criteria. Eligible participants had an average of at least one headache day per month during the previous three months.

Respondents provided information about sociodemographics and medication use and responded to a 13-item battery evaluating headache burden and response to medication. The items on the battery were derived from a review of relevant literature, clinician input, and interviews with migraine patients. Participants provided frequency data for each item on a five-point scale ranging from “1) Never” to “5) All or Nearly All of the Time.” To measure construct validity for the scale, the investigators assessed moderate to severe disability for each respondent using the Migraine Disability Assessment Scale (MIDAS).

To determine the underlying structure of unmet treatment needs, Dr. Lipton and colleagues conducted Exploratory Factor Analysis (EFA) among the subset of respondents currently using oral acute prescription medications. They assessed the internal consistency for the derived factors using Cronbach’s alpha. Mean factor scores (range, 1 to 5) were calculated by summing item responses for each factor and dividing by the number of items loading on that factor. The researchers used Mantel-Haenszel Chi Square Test for Trend to evaluate the relationship between mean factor score and rates of moderate to severe migraine-related disability.

Treatment May Act Too Slowly

Among 15,133 respondents meeting inclusion criteria, 3,930 reported current use of acute oral prescription headache medication (mean age, 45.0, 73.6% women, 81.6% Caucasian). Injection and nasal spray medication users were eliminated from the sample. The most commonly endorsed needs were “severe headache attacks come on very rapidly” (52.8%), “attacks reach peak intensity in less than 30 minutes” (50.4%), “severe headache presents upon awakening” (40.9%), and “the return of pain within 24 hours after initial pain relief” (38.6%). EFA identified the following four unmet needs: nausea interference, disturbed sleep, rapid onset, and lack of pain freedom. Internal consistency exceeded acceptable levels for all factors except disturbed sleep. MIDAS disability increased in a clear linear pattern with increasing mean factor scores.

Suggested Reading

Blumenfeld AM, Aurora SK, Laranjo K, Papapetropoulos S. Unmet clinical needs in chronic migraine: Rationale for study and design of COMPEL, an open-label, multicenter study of the long-term efficacy, safety, and tolerability of onabotulinumtoxinA for headache prophylaxis in adults with chronic migraine. BMC Neurol. 2015;15:100.

Lipton RB, Buse DC, Serrano D, et al. Examination of unmet treatment needs among persons with episodic migraine: results of the American Migraine Prevalence and Prevention (AMPP) Study. Headache. 2013;53(8):1300-1311.

SAN FRANCISCO—Unmet treatment needs among migraineurs receiving oral prescription medications include therapies to reduce nausea and disturbed sleep, according to a study described at the 60th Annual Scientific Meeting of the American Headache Society. The population also has unmet needs for therapies that provide pain freedom and rapid onset of action.

In 2017, investigators conducted the Migraine in America Symptoms and Treatment (MAST) study, which focused on migraine symptoms, current treatment patterns, and the assessment of unmet treatment needs. Richard B. Lipton, MD, Edwin S. Lowe Chair in Neurology at Albert Einstein College of Medicine in the Bronx, New York, and colleagues examined MAST data to empirically characterize the patterns of poorly controlled migraine and assess corresponding rates of migraine-related disability.

A Survey of American Migraineurs

The MAST survey data were obtained from a general US population sample of migraineurs age 18 and older. Migraineurs were identified using a validated migraine symptom screen based on modified ICHD-3b criteria. Eligible participants had an average of at least one headache day per month during the previous three months.

Respondents provided information about sociodemographics and medication use and responded to a 13-item battery evaluating headache burden and response to medication. The items on the battery were derived from a review of relevant literature, clinician input, and interviews with migraine patients. Participants provided frequency data for each item on a five-point scale ranging from “1) Never” to “5) All or Nearly All of the Time.” To measure construct validity for the scale, the investigators assessed moderate to severe disability for each respondent using the Migraine Disability Assessment Scale (MIDAS).

To determine the underlying structure of unmet treatment needs, Dr. Lipton and colleagues conducted Exploratory Factor Analysis (EFA) among the subset of respondents currently using oral acute prescription medications. They assessed the internal consistency for the derived factors using Cronbach’s alpha. Mean factor scores (range, 1 to 5) were calculated by summing item responses for each factor and dividing by the number of items loading on that factor. The researchers used Mantel-Haenszel Chi Square Test for Trend to evaluate the relationship between mean factor score and rates of moderate to severe migraine-related disability.

Treatment May Act Too Slowly

Among 15,133 respondents meeting inclusion criteria, 3,930 reported current use of acute oral prescription headache medication (mean age, 45.0, 73.6% women, 81.6% Caucasian). Injection and nasal spray medication users were eliminated from the sample. The most commonly endorsed needs were “severe headache attacks come on very rapidly” (52.8%), “attacks reach peak intensity in less than 30 minutes” (50.4%), “severe headache presents upon awakening” (40.9%), and “the return of pain within 24 hours after initial pain relief” (38.6%). EFA identified the following four unmet needs: nausea interference, disturbed sleep, rapid onset, and lack of pain freedom. Internal consistency exceeded acceptable levels for all factors except disturbed sleep. MIDAS disability increased in a clear linear pattern with increasing mean factor scores.

Suggested Reading

Blumenfeld AM, Aurora SK, Laranjo K, Papapetropoulos S. Unmet clinical needs in chronic migraine: Rationale for study and design of COMPEL, an open-label, multicenter study of the long-term efficacy, safety, and tolerability of onabotulinumtoxinA for headache prophylaxis in adults with chronic migraine. BMC Neurol. 2015;15:100.

Lipton RB, Buse DC, Serrano D, et al. Examination of unmet treatment needs among persons with episodic migraine: results of the American Migraine Prevalence and Prevention (AMPP) Study. Headache. 2013;53(8):1300-1311.

The treatment of multiple myeloma has been revolutionized in the past few decades, with the introduction of numerous novel drug classes that have more than doubled median survival times. The immunomodulatory drug (IMiD), lenalidomide, forms the backbone of the majority of treatment paradigms, first receiving US Food and Drug Administration approval in 2006 for use in combination with dexamethasone in previously treated patients with multiple myeloma. Since then, approved indications for lenalidomide in multiple myeloma have continued to expand.

Most recently, on February 22, 2017, lenalidomide was approved for use as maintenance therapy following autologous stem cell transplant (ASCT), making it the first and only treatment available in this setting. This approval was based on 2 randomized, controlled trials that evaluated the efficacy and safety of lenalidomide in more than 1,000 patients in this setting and demonstrated a significant advantage in progression-free survival (PFS) compared with patients receiving placebo.

CALGB 100104¹ and IFM 2005-02² were randomized, double-blind phase 3 trials conducted at 47 locations across the United States and 78 centers in France, Belgium, and Switzerland, respectively. In the CALGB trial, eligible patients were 18-70 years of age, with a European Cooperative Oncology Group (ECOG) performance status of 0 or 1, symptomatic disease requiring treatment (Durie-Salmon stage ≥1), and who received any induction therapy of 2-12 months duration. In the IFM trial, eligible patients were younger than 65 years, with multiple myeloma that had not progressed in the interval between first-line ASCT, performed within the previous 6 months, and randomization, and who had normal liver function tests and blood cell counts.

In CALGB 100104, after undergoing ASCT, 460 patients were randomly assigned to lenalidomide (starting at a dose of 10 mg/day) or placebo between day 100 and day 110 after transplantation. In IFM 2005-02, after undergoing ASCT, 614 patients were randomized 1:1 to receive either consolidation treatment with lenalidomide (at a dose of 25 mg/day on days 1-21 of each 28-day cycle for 2 cycles) followed by maintenance with lenalidomide (10 mg/day for the first 3 months, increasing to 15 mg if tolerated), or the same consolidation treatment followed by maintenance therapy with placebo.

The primary endpoint of CALGB 100104 was time to progression (TTP) and lenalidomide was associated with a significantly longer TTP. Median PFS was also improved by around 15 months (hazard ratio [HR], 0.38; P < .001). In a more recent long-term PFS analysis, median PFS was 5.7 years in the lenalidomide arm compared with 1.9 years with placebo, a difference of 3.8 years (HR, 0.38).³

The primary endpoint for IFM 2005-02 was PFS and lenalidomide maintenance therapy resulted in a significant improvement in PFS in both the originally published study (18-month PFS advantage) and long-term follow-up. The most recent PFS analysis demonstrated a PFS of 3.9 years for lenalidomide, compared with 2 years for no maintenance, a difference of 1.9 years (HR, 0.53). Although the studies were not powered for an overall survival (OS) endpoint, a descriptive analysis showed a median OS of 9.3 years, compared with 7 years in CALGB 100104, and 8.8 years compared with 7.3 years in IFM 2005-02.

In a meta-analysis of data pooled from these 2 studies and a third randomized trial (GIMEMA-RVMM-PI-209),⁴ which was presented at the 2016 annual meeting of the American Society of Clinical Oncology, maintenance therapy with lenalidomide following frontline treatment with high-dose melphalan and ASCT reduced the risk of death by 26% compared with placebo or no maintenance therapy, prompting suggestions that lenalidomide become standard of care in this setting.

The safety profile of lenalidomide in this setting was similar to that previously described in other studies. The most frequently reported adverse events (AEs), across both studies, were neutropenia, thrombocytopenia, leukopenia, anemia, upper respiratory tract infection, bronchitis, nasopharyngitis, cough, gastroenteritis, diarrhea, rash, fatigue, asthenia, muscle spasm, and pyrexia. The most common grade 3/4 AEs included neutropenia, thrombocytopenia, and leukopenia. AEs were generally most common in the first 6 months of treatment and subsequently declined in frequency over time or remained stable.

The prescribing information carries warnings and precautions about embryo-fetal toxicity, hematologic toxicity, venous/arterial thromboembolic events, secondary primary malignancies, hepatotoxicity, allergic reactions, tumor lysis syndrome, and thyroid disorders.⁵ Given its teratogenic effects, lenalidomide is only available through a restricted program under a risk evaluation mitigation strategy.

Patients with neutropenia should be monitored for signs of infections, patients advised to look for signs of bleeding or bruising, and weekly complete blood count performed for the first 2 cycles, on days 1 and 15 of cycle 3 and every 4 weeks thereafter.

Action should be taken to try to reduce the risk of venous and arterial thromboembolic events where possible and thrombophylaxis is recommended, based on the assessment of the underlying risk. Since lenalidomide can increase the risk of secondary primary malignancies, each case should be evaluated for risk-to-benefit ratio.

Liver enzymes should be monitored periodically and treatment interrupted upon their elevation, resuming at a lower dose if levels return to baseline values. Patients who have a history of grade 4 rash following thalidomide treatment should not receive lenalidomide. If grade 2-3 skin rash occurs, treatment interruption or discontinuation should be considered and lenalidomide should be discontinued in the event of angioedema, grade 4 rash, exfoliative or bullous rash, or if Stevens-Johnson syndrome or toxic epidermal necrolysis are suspected.

Patients with high tumor burden prior to treatment are at highest risk of tumor lysis syndrome and should be monitored closely and appropriate precautions taken, and thyroid function should be measured before and during lenalidomide treatment to address potential thyroid disorders. Lenalidomide is marketed as Revlimid by Celgene Corporation.

The treatment of multiple myeloma has been revolutionized in the past few decades, with the introduction of numerous novel drug classes that have more than doubled median survival times. The immunomodulatory drug (IMiD), lenalidomide, forms the backbone of the majority of treatment paradigms, first receiving US Food and Drug Administration approval in 2006 for use in combination with dexamethasone in previously treated patients with multiple myeloma. Since then, approved indications for lenalidomide in multiple myeloma have continued to expand.

Most recently, on February 22, 2017, lenalidomide was approved for use as maintenance therapy following autologous stem cell transplant (ASCT), making it the first and only treatment available in this setting. This approval was based on 2 randomized, controlled trials that evaluated the efficacy and safety of lenalidomide in more than 1,000 patients in this setting and demonstrated a significant advantage in progression-free survival (PFS) compared with patients receiving placebo.

CALGB 100104¹ and IFM 2005-02² were randomized, double-blind phase 3 trials conducted at 47 locations across the United States and 78 centers in France, Belgium, and Switzerland, respectively. In the CALGB trial, eligible patients were 18-70 years of age, with a European Cooperative Oncology Group (ECOG) performance status of 0 or 1, symptomatic disease requiring treatment (Durie-Salmon stage ≥1), and who received any induction therapy of 2-12 months duration. In the IFM trial, eligible patients were younger than 65 years, with multiple myeloma that had not progressed in the interval between first-line ASCT, performed within the previous 6 months, and randomization, and who had normal liver function tests and blood cell counts.

In CALGB 100104, after undergoing ASCT, 460 patients were randomly assigned to lenalidomide (starting at a dose of 10 mg/day) or placebo between day 100 and day 110 after transplantation. In IFM 2005-02, after undergoing ASCT, 614 patients were randomized 1:1 to receive either consolidation treatment with lenalidomide (at a dose of 25 mg/day on days 1-21 of each 28-day cycle for 2 cycles) followed by maintenance with lenalidomide (10 mg/day for the first 3 months, increasing to 15 mg if tolerated), or the same consolidation treatment followed by maintenance therapy with placebo.

The primary endpoint of CALGB 100104 was time to progression (TTP) and lenalidomide was associated with a significantly longer TTP. Median PFS was also improved by around 15 months (hazard ratio [HR], 0.38; P < .001). In a more recent long-term PFS analysis, median PFS was 5.7 years in the lenalidomide arm compared with 1.9 years with placebo, a difference of 3.8 years (HR, 0.38).³

The primary endpoint for IFM 2005-02 was PFS and lenalidomide maintenance therapy resulted in a significant improvement in PFS in both the originally published study (18-month PFS advantage) and long-term follow-up. The most recent PFS analysis demonstrated a PFS of 3.9 years for lenalidomide, compared with 2 years for no maintenance, a difference of 1.9 years (HR, 0.53). Although the studies were not powered for an overall survival (OS) endpoint, a descriptive analysis showed a median OS of 9.3 years, compared with 7 years in CALGB 100104, and 8.8 years compared with 7.3 years in IFM 2005-02.

In a meta-analysis of data pooled from these 2 studies and a third randomized trial (GIMEMA-RVMM-PI-209),⁴ which was presented at the 2016 annual meeting of the American Society of Clinical Oncology, maintenance therapy with lenalidomide following frontline treatment with high-dose melphalan and ASCT reduced the risk of death by 26% compared with placebo or no maintenance therapy, prompting suggestions that lenalidomide become standard of care in this setting.

The safety profile of lenalidomide in this setting was similar to that previously described in other studies. The most frequently reported adverse events (AEs), across both studies, were neutropenia, thrombocytopenia, leukopenia, anemia, upper respiratory tract infection, bronchitis, nasopharyngitis, cough, gastroenteritis, diarrhea, rash, fatigue, asthenia, muscle spasm, and pyrexia. The most common grade 3/4 AEs included neutropenia, thrombocytopenia, and leukopenia. AEs were generally most common in the first 6 months of treatment and subsequently declined in frequency over time or remained stable.

The prescribing information carries warnings and precautions about embryo-fetal toxicity, hematologic toxicity, venous/arterial thromboembolic events, secondary primary malignancies, hepatotoxicity, allergic reactions, tumor lysis syndrome, and thyroid disorders.⁵ Given its teratogenic effects, lenalidomide is only available through a restricted program under a risk evaluation mitigation strategy.

Patients with neutropenia should be monitored for signs of infections, patients advised to look for signs of bleeding or bruising, and weekly complete blood count performed for the first 2 cycles, on days 1 and 15 of cycle 3 and every 4 weeks thereafter.

Action should be taken to try to reduce the risk of venous and arterial thromboembolic events where possible and thrombophylaxis is recommended, based on the assessment of the underlying risk. Since lenalidomide can increase the risk of secondary primary malignancies, each case should be evaluated for risk-to-benefit ratio.

Liver enzymes should be monitored periodically and treatment interrupted upon their elevation, resuming at a lower dose if levels return to baseline values. Patients who have a history of grade 4 rash following thalidomide treatment should not receive lenalidomide. If grade 2-3 skin rash occurs, treatment interruption or discontinuation should be considered and lenalidomide should be discontinued in the event of angioedema, grade 4 rash, exfoliative or bullous rash, or if Stevens-Johnson syndrome or toxic epidermal necrolysis are suspected.

Patients with high tumor burden prior to treatment are at highest risk of tumor lysis syndrome and should be monitored closely and appropriate precautions taken, and thyroid function should be measured before and during lenalidomide treatment to address potential thyroid disorders. Lenalidomide is marketed as Revlimid by Celgene Corporation.

The treatment of multiple myeloma has been revolutionized in the past few decades, with the introduction of numerous novel drug classes that have more than doubled median survival times. The immunomodulatory drug (IMiD), lenalidomide, forms the backbone of the majority of treatment paradigms, first receiving US Food and Drug Administration approval in 2006 for use in combination with dexamethasone in previously treated patients with multiple myeloma. Since then, approved indications for lenalidomide in multiple myeloma have continued to expand.

Most recently, on February 22, 2017, lenalidomide was approved for use as maintenance therapy following autologous stem cell transplant (ASCT), making it the first and only treatment available in this setting. This approval was based on 2 randomized, controlled trials that evaluated the efficacy and safety of lenalidomide in more than 1,000 patients in this setting and demonstrated a significant advantage in progression-free survival (PFS) compared with patients receiving placebo.

CALGB 100104¹ and IFM 2005-02² were randomized, double-blind phase 3 trials conducted at 47 locations across the United States and 78 centers in France, Belgium, and Switzerland, respectively. In the CALGB trial, eligible patients were 18-70 years of age, with a European Cooperative Oncology Group (ECOG) performance status of 0 or 1, symptomatic disease requiring treatment (Durie-Salmon stage ≥1), and who received any induction therapy of 2-12 months duration. In the IFM trial, eligible patients were younger than 65 years, with multiple myeloma that had not progressed in the interval between first-line ASCT, performed within the previous 6 months, and randomization, and who had normal liver function tests and blood cell counts.

In CALGB 100104, after undergoing ASCT, 460 patients were randomly assigned to lenalidomide (starting at a dose of 10 mg/day) or placebo between day 100 and day 110 after transplantation. In IFM 2005-02, after undergoing ASCT, 614 patients were randomized 1:1 to receive either consolidation treatment with lenalidomide (at a dose of 25 mg/day on days 1-21 of each 28-day cycle for 2 cycles) followed by maintenance with lenalidomide (10 mg/day for the first 3 months, increasing to 15 mg if tolerated), or the same consolidation treatment followed by maintenance therapy with placebo.

The primary endpoint of CALGB 100104 was time to progression (TTP) and lenalidomide was associated with a significantly longer TTP. Median PFS was also improved by around 15 months (hazard ratio [HR], 0.38; P < .001). In a more recent long-term PFS analysis, median PFS was 5.7 years in the lenalidomide arm compared with 1.9 years with placebo, a difference of 3.8 years (HR, 0.38).³

The primary endpoint for IFM 2005-02 was PFS and lenalidomide maintenance therapy resulted in a significant improvement in PFS in both the originally published study (18-month PFS advantage) and long-term follow-up. The most recent PFS analysis demonstrated a PFS of 3.9 years for lenalidomide, compared with 2 years for no maintenance, a difference of 1.9 years (HR, 0.53). Although the studies were not powered for an overall survival (OS) endpoint, a descriptive analysis showed a median OS of 9.3 years, compared with 7 years in CALGB 100104, and 8.8 years compared with 7.3 years in IFM 2005-02.

In a meta-analysis of data pooled from these 2 studies and a third randomized trial (GIMEMA-RVMM-PI-209),⁴ which was presented at the 2016 annual meeting of the American Society of Clinical Oncology, maintenance therapy with lenalidomide following frontline treatment with high-dose melphalan and ASCT reduced the risk of death by 26% compared with placebo or no maintenance therapy, prompting suggestions that lenalidomide become standard of care in this setting.

The safety profile of lenalidomide in this setting was similar to that previously described in other studies. The most frequently reported adverse events (AEs), across both studies, were neutropenia, thrombocytopenia, leukopenia, anemia, upper respiratory tract infection, bronchitis, nasopharyngitis, cough, gastroenteritis, diarrhea, rash, fatigue, asthenia, muscle spasm, and pyrexia. The most common grade 3/4 AEs included neutropenia, thrombocytopenia, and leukopenia. AEs were generally most common in the first 6 months of treatment and subsequently declined in frequency over time or remained stable.

The prescribing information carries warnings and precautions about embryo-fetal toxicity, hematologic toxicity, venous/arterial thromboembolic events, secondary primary malignancies, hepatotoxicity, allergic reactions, tumor lysis syndrome, and thyroid disorders.⁵ Given its teratogenic effects, lenalidomide is only available through a restricted program under a risk evaluation mitigation strategy.

Patients with neutropenia should be monitored for signs of infections, patients advised to look for signs of bleeding or bruising, and weekly complete blood count performed for the first 2 cycles, on days 1 and 15 of cycle 3 and every 4 weeks thereafter.

Action should be taken to try to reduce the risk of venous and arterial thromboembolic events where possible and thrombophylaxis is recommended, based on the assessment of the underlying risk. Since lenalidomide can increase the risk of secondary primary malignancies, each case should be evaluated for risk-to-benefit ratio.

Liver enzymes should be monitored periodically and treatment interrupted upon their elevation, resuming at a lower dose if levels return to baseline values. Patients who have a history of grade 4 rash following thalidomide treatment should not receive lenalidomide. If grade 2-3 skin rash occurs, treatment interruption or discontinuation should be considered and lenalidomide should be discontinued in the event of angioedema, grade 4 rash, exfoliative or bullous rash, or if Stevens-Johnson syndrome or toxic epidermal necrolysis are suspected.

Patients with high tumor burden prior to treatment are at highest risk of tumor lysis syndrome and should be monitored closely and appropriate precautions taken, and thyroid function should be measured before and during lenalidomide treatment to address potential thyroid disorders. Lenalidomide is marketed as Revlimid by Celgene Corporation.