A healthy 17-year-old girl with inflammatory acne had failed to respond to topical tretinoin, benzoyl peroxide, and oral minocycline. She was subsequently treated with oral isotretinoin at 0.5 mg/kg/d. Two days later, she developed fever, arthralgias, and progressive severe inflammatory lesions on the back, chest, shoulders, and sides of her face, many of which were ulcerated 

 The isotretinoin was discontinued, and she was started on oral prednisone at 1 mg/kg/d which was tapered over 4 months. She had a recurrence a week later and required 0.5 mg/kg/d of oral steroids which were tapered over the subsequent 2 months. She was also treated concurrently with oral doxycycline, which was continued for several months after the steroids were discontinued.

Acne fulminans (AF) is a rare and severe variant of inflammatory acne. It presents as an abrupt eruption of multiple large, painful, hemorrhagic, crusted nodulocystic lesions that rapidly undergo necrosis and ulceration and heal with scarring.

 Commonly involved areas include the face, upper chest, back, and shoulders. In rare cases, lesions may extend down to the thighs. The spectrum of disease ranges from skin-limited disease to systemic symptoms such as fever, malaise, arthralgias, bone pain, erythema nodosum, and painful splenomegaly.

 Laboratory abnormalities may also be noted.

The incidence of AF is unclear, with about 200 reported cases overall in the medical literature. It typically affects White adolescent boys with a prior history of acne, but there are also reports of this condition in adolescent females.

Common triggers for AF include the use of moderate- to high-dose isotretinoin to manage severe acne, anabolic steroids in bodybuilders, exogenous hormone administration, certain antibiotics, or spontaneous occurrence.

 The underlying etiologic mechanism is currently unknown, but it is posited to be the result of an inflammatory cytokine response to the massive immune reaction triggered by flaring inflammatory acne alone or the initiation of isotretinoin against 

 Classification systems are used to refer to the absence (AF-WOSS) or presence (AF-SS) of systemic symptoms.

The differential diagnosis of AF may include acne conglobata; rosacea fulminans; and synovitis, acne, pustulosis, hyperostosis, osteitis (SAPHO) syndrome.

 Acne conglobata presents with slow evolution of numerous inflammatory nodules into burrowing abscesses, painful nodules, and multiple polyporous comedones without systemic involvement. Rosacea fulminans is a severe, female-predominant variant of rosacea presenting with sudden onset of facial papules, pustules, cysts, and painful coalescing nodules with red-cyanotic centrofacial erythema.

SAPHO syndrome is a chronic disease often reported in women with a long lag time between cutaneous manifestations (besides acne, these include palmoplantar pustulosis) and the development of systemic manifestations, which may also include fever and weight loss. There is some thought that SAPHO syndrome and AF are on the same disease spectrum, possibly triggered by the same underlying process.

Because of the association with systemic symptoms, the workup should include the following

Complete blood count may reveal elevated white blood cell count with neutrophilia, anemia, and/or leukemic-type reaction.

Inflammatory markers including erythrocyte sedimentation rate and C-reactive protein level may be elevated.

Liver function tests may show transaminitis.

Elevated serum alkaline phosphatase may suggest underlying bone lesions.

Imaging such as x-rays of the extremities may reveal the presence of aseptic osteolytic lesions that can mimic osteomyelitis but have been shown to be culture negative.

Urine or serum human chorionic gonadotropin may be elevated in female patients.

There are no standardized guidelines for the management of AF. However, there are evidence-based recommendations, and it is best to involve a dermatologist early on to ensure an optimal outcome.

The mainstay of initial therapy is the early administration of systemic corticosteroids (prednisone or prednisolone) because of their strong anti-inflammatory and immunosuppressive properties. Corticosteroids can rapidly bring systemic AF symptoms under control, including fever and/or musculoskeletal manifestations. Recommended management includes prednisone at 0.5 to 1 mg/kg/d for up to 4 weeks or longer until lesions have healed before adding low-dose isotretinoin at 0.1 mg/kg/d.1 Subsequently, there should be overlap between corticosteroid therapy and isotretinoin to allow for slow tapering of the former with gradual increase in the latter. This may take 3 to 4 months and may be prolonged if the patient experiences flares with an increase in the isotretinoin dose. Case reports in the literature show patients are treated effectively with combination corticosteroid and retinoid therapy until they reach the maximum tolerated isotretinoin dose without flares.

A week after stopping prednisone, the patient experienced a relapse of AF. Her condition responded to a second, lower-dose course of corticosteroids for 2 months and remained in remission without systemic medications. Several hypertrophic scars subsequently improved dramatically with topical steroids. Notably, her isotretinoin was not restarted.

Alternative treatments to the above regimen have been used in treatment-resistant patients. These agents include dapsone, immunosuppressants such as methotrexate or azathioprine, or biologic agents such as infliximab or etanercept. However, larger clinical trials that recommend the general use of these agents are unavailable. Antibiotic therapy is generally not recommended for AF.

The use of pulsed dye laser (585-595 nm) may be used to remove excess granulation tissue and reduce scarring.

 Because of the large lesions, multiple treatments are required. Scarring and hypopigmentation remain common complications.

Greywal T, Zaenglein AL, Baldwin HE, et al. Evidence-based recommendations for the management of acne fulminans and its variants. 

. 2017;77(1):109-117. doi:10.1016/j.jaad.2016.11.028

Zito PM, Badri T. Acne fulminans. In: StatPearls. StatPearls Publishing; 2022. Accessed November 7, 2022. 

http://www.ncbi.nlm.nih.gov/books/NBK459326/

Dall’oglio F, Puglisi DF, Nasca MR, Micali G. Acne fulminans. 

. 2020;155(6):711-718. doi:10.23736/S0392-0488.20.06711-5

Fakih A, Goens J, Grozdev I, Dangoisse C, Richert B. Acne fulminans induced by a low dose isotretinoin: case report and review of the literature. 

Gualtieri B, Tonini A, Panduri S, Chiricozzi A, Romanelli M. Acne fulminans associated with lymecycline intake: a case report. 

. 2018;11:403-405. doi:10.2147/CCID.S158925

Lee G, Ferri-Huerta R, Greenberg KB, Somers KE. Acne fulminans in a transgender boy after an increase in testosterone dosage. 

. 2022;21:32-34. doi:10.1016/j.jdcr.2021.11.029

Zimmermann P, Curtis N. Synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome - a challenging diagnosis not to be missed. 

. 2016;72(suppl):S106-S114. doi:10.1016/j.jinf.2016.04.030

Articles

A healthy 17-year-old girl with inflammatory acne had failed to respond to topical tretinoin, benzoyl peroxide, and oral minocycline. What's the diagnosis?

Worsening acne after isotretinoin treatment in an adolescent girl

A study of lisdexamfetamine dimesaylate (LDX) in children aged 4 to 5 years with attention-deficit/hyperactivity disorder (ADHD) found that the treatment reduced symptoms and was generally well tolerated compared with placebo.

The study’s 199 participants had baseline scores on the parent-reported ADHD Rating Scale-IVPreschool Version (ADHD-RS-IV-PS) and the Clinical Global Impression-Improvement (CGI-I) scale. Scores on these 2 scales, determined again at the end of the 6-week study period, provided the major end points for the trial. Most (175) of the participants had diagnoses of the combined ADHD subtype and CGI scores corresponding to “markedly ill.” Only 8 of the participants had used ADHD medications, such as atomoxetine, guanfacine, and methylphenidate, prior to being in the study.

Participants were divided into 2 groups. One group received LDX for 6 weeks and the other group received placebo. Some children received 5 mg of LDX or matching placebo while others received 10-, 20-, or 30-mg doses. At the end of the 6-week study period, CGI-I scores had improved in 41.7% of patients in the LDX group compared with 24.3% of patients in the placebo group. As for ADHD-RS-IV-PS, the LDX group did better than the placebo group with regard to inattention but not with regard to hyperactivity/impulsivity. Almost half the participants in the active group had adverse effects, usually mild. These adverse effects most often included decreased appetite and irritability.

Lisdexamfetamine is converted to the less expensive dextroamphetamine, known to be effective for ADHD, so these results are expected. I do not like the trend of using stimulants to treat preschool-aged patients, even if they are effective, and suspect this study will be used to push for lowering the approved age for use. Also of note is the high incidence of adverse effects.

Childress AC, Lloyd E, Jacobsen L, Gunawardhana L, Johnson SA Jr, Findling RL. Efficacy and safety of lisdexamfetamine in preschool children with attention-deficit/hyperactivity disorder. 

Published online May 13, 2022. doi:10.1016/j.jaac.2022.03.034

Lisdexamfetamine dimesaylate was associated with reduced ADHD symptoms in children aged 4 to 5 years.

Lisdexamfetamine is effective in preschoolers with ADHD

Obesity in children and adolescents is a growing global public health concern. Recent data indicate that upward of 18.5% of children and adolescents in the United States have obesity.

 The Centers for Disease Control and Prevention and the American Academy of Pediatrics define obesity in individuals aged 2 to 20 years as a body mass index (BMI) equal to or above the 95th percentile of the percentile range on a specific BMI-for-age growth chart.

Given pathophysiological changes associated with a higher body proportion of fat in obesity, drug pharmacokinetics may be altered, and therefore, adjustments to medication dosing may be required.

 Furthermore, there is a risk of drug doses exceeding the recommended maximum amount if total body weight (TBW) is used for weight-based dosing of certain drugs.

However, because of the lack of pharmacokinetic studies of individual drugs in children and adolescents with obesity, there is limited guidance for determining whether drug dose adjustments are necessary. Evaluation of pharmacokinetic changes, drug properties, and patient factors are important considerations when determining optimal doses.

Given changes in body composition and physiology that occur in the setting of obesity, alterations in drug pharmacokinetics may result in therapeutic failure or toxicity (

 Children and adolescents with obesity have a higher proportion of body fat and changes in volume of distribution (Vd), although the direction and magnitude are difficult to predict. Vd is affected by physiological changes that occur in obesity, such as body mass, extracellular water, tissue perfusion, and proportions of lean and fat tissue.

Vd is typically larger for lipophilic medications because of distribution of the drugs into adipose tissues and is often altered for hydrophilic medications as well (ie, increased or decreased). Additionally, metabolism and clearance may be affected by obesity. It is thought that individuals with obesity may have changes in hepatic clearance and increased phase 1 and 2 reactions. Increased kidney size has been noted with higher TBW, leading to increased glomerular filtration rate.

 Collectively, these physiological and pharmacokinetic changes may require adjustments to the loading dose, dose interval, and time to reach steady state in certain medications.

Table 1. Pharmacokinetic Considerations in Obesity

ABW, adjusted body weight; CL, clearance; t½, half-life; Vd, volume of distribution.

Dosing in pediatric patients with obesity

Dosing regimens in pediatric patients are based on age, weight, and body surface area (BSA). Dosing based on weight and BSA is the most utilized method. However, in children and adolescents with obesity, this may lead to doses greater than the maximum dose for adults. Adjusted measures of weight have been developed to help accommodate these changes, including ideal body weight (IBW) and adjusted body weight (ABW) (

 The selection of a size description for dosing is often considered when the patient TBW is greater than 120% of the IBW and prevents excess doses or accumulation of medications.

 Lean body weight may be used for maintenance dosing. BSA using the Mosteller equation for individuals aged 1 month to 14 years may also be used for certaintreatments, such as chemotherapy.

 Patient-specific characteristics such as underlying organ function, illness severity, and extent of obesity must also be considered. Additionally, medication characteristics including Vd, lipophilicity, hydrophilicity, and therapeutic range should be evaluated. Collectively, these factors are useful for determining appropriate loading and maintenance dosing. If a loading dose is required in pediatric patients with obesity, TBW is typically used for lipophilic drugs, ABW for partially lipophilic drugs, and IBW for hydrophilic drugs.

Table 2. Body Composition Descriptions for Children

ABW, adjusted body weight; BMI, body mass index; BSA, body surface area; IBW, ideal body weight; TBW, total body weight.

The prespecific cofactor is medication specific.

Medication dosing adjustments in children and adolescents with obesity

Most data available to guide pediatric dosing recommendations are based on recommendations for adult patients with obesity.11 Given the limited published data to guide dosing in children and adolescents with obesity, attention should be given to dosing selected for individual medications (

). To prevent potential errors, the American Academy of Pediatrics recommends that patients’ weights are appropriate for the weight-based dosing regimen and that adult doses are not exceeded. The Pediatric Pharmacy Association supports the following empiric dosing considerations for pediatric patients13:

Fewer than 18 years of age and less than 40 kg: utilize weight-based dosing

Fewer than 18 years of age and greater than or equal to 40 kg: utilize weight-based dosing with adult maximum doses or total daily doses for the specific indication

Therapeutic drug monitoring as indicated to ensure effective and safe therapy

Table 3. Medication Dosing in Pediatric Obesity

ABW, adjusted body weight; H2, histamine2; IBW, ideal body weight; TBW, total body weight.

Given the continued rise of obesity in children and adolescents, thought should be given to dosing when selecting medications. Pathophysiologic changes associated with obesity can predict alterations in drug pharmacokinetics and pharmacodynamics, but consideration should be given to disease state and drug-specific properties. Therapeutic drug monitoring may also be of use where feasible to assess effectiveness and safety of dosing regimens. Future research should evaluate pediatric population pharmacokinetics/pharmacodynamics in children and adolescents with obesity.

Hales CM, Fryar CD, Carroll MD, Freedman DS, Ogden CL. Trends in obesity and severe obesity prevalence in US youth and adults by sex and age, 2007-2008 to 2015-2016. 

. 2018;319(16):1723-1725. doi:10.1001/jama.2018.3060

Ogden CL, Carroll MD, Lawman HG, et al. Trends in obesity prevalence among children and adolescents in the United States, 1988-1994 through 2013-2014. 

 2016;315(21):2292-2299. doi:10.1001/jama.2016.6361

Defining childhood weight status. Centers for Disease Control and Prevention. June 21, 2021. Accessed November 30, 2021. 

https://www.cdc.gov/obesity/childhood/defining.html

Nathan BM, Moran A. Metabolic complications of obesity in childhood and adolescence: more than just diabetes. 

. 2008;15(1):21-29. doi:10.1097/MED.0b013e3282f43d19

Kendrick JG, Carr RR, Ensom MHH. Pediatric obesity: pharmacokinetics and implications for drug dosing. 

. 2015;37(9):1897-1923. doi:10.1016/j.clinthera.2015.05.495

Sampson MR, Cohen-Wolkowiez M, Benjamin DK Jr, Capparelli EV, Watt KM. Pharmacokinetics of antimicrobials in obese children. 

. 2013;2(2):76-81. doi:10.5639/gabij.2013.0202.025

Xiong Y, Fukuda T, Knibbe CAJ, Vinks AA. Drug dosing in obese children: challenges and evidence-based strategies. 

. 2017;64(6):1417-1438. doi:10.1016/j.pcl.2017.08.011

Hanley MJ, Abernethy DR, Greenblatt DJ. Effect of obesity on the pharmacokinetics of drugs in humans. 

. 2010;49(2):71-87. doi:10.2165/11318100-000000000-00000

Callaghan LC. Prescribing in paediatric obesity: methods to improve dosing safety in weight-based dose calculations. 

2018;103(5):274-277. doi:10.1136/archdischild-2016-311491

Mulla H, Johnson TN. Dosing dilemmas in obese children. 

. 2010;95(4):112-117. doi:10.1136/adc.2009.163055

Ross EL, Heizer J, Mixon MA, et al. Development of recommendations for dosing of commonly prescribed medications in critically ill obese children. 

. 2015;72(7):542-556. doi:10.2146/ajhp140280

Mosteller RD. Simplified calculation of body-surface area. 

. 1987;317(17):1098. doi:10.1056/NEJM198710223171717

Matson KL, Horton ER, Capino AC; Advocacy Committee for the Pediatric Pharmacy Advocacy Group. Medication dosage in overweight and obese children. 

. 2017;22(1):81-83. doi:10.5863/1551-6776-22.1.81

Zempsky WT, Bhagat PK, Siddiqui K. Practical challenges-use of paracetamol in children and youth who are overweight or obese: a narrative review. 

. 2020;22(5):525-534. doi:10.1007/s40272-020-00417-z

Kramer NM, Gazelka HM, Thompson VH, Batsis JA, Swetz KM. Challenges to safe and effective pain management in patients with super obesity: case report and literature review. 

. 2018;55(3):1047-1052. doi:10.1016/j.jpainsymman.2017.11.005

Kyler KE, Wagner J, Hosey-Cojocari C, Watt K, Shakhnovich V. Drug dose selection in pediatric obesity: available information for the most commonly prescribed drugs to children. 

. 2019;21(5):357-369. doi:10.1007/s40272-019-00352-8

Atyia SA, Smetana KS, Tong MC, Thompson MJ, Cape KM, May CC. Evaluation of dexmedetomidine dosing in obese critically ill patients. 

. 2021;8971900211021578. doi:10.1177/08971900211021578

Fukuchi H, Nakashima M, Araki R, et al. Effect of obesity on serum amiodarone concentration in Japanese patients: population pharmacokinetic investigation by multiple trough screen analysis. 

. 2009;34(3):329-336. doi:10.1111/j.1365-2710.2008.00987.x

Wells M, Goldstein L. The utility of pediatric age-based weight estimation formulas for emergency drug dose calculations in obese children. 

 2020;1(5):947-954. doi:10.1002/emp2.12099

Richard AA, Kim S, Moffett BS, Bomgaars L, Mahoney D Jr, Yee DL. Comparison of anti-Xa levels in obese and non-obese pediatric patients receiving treatment doses of enoxaparin. 

 2013;162(2):293-296. doi:10.1016/j.jpeds.2012.07.047

Lewis TV, Johnson PN, Nebbia AM, Dunlap M. Increased enoxaparin dosing is required for obese children. 

. 2011;127(3):e787-e790. doi:10.1542/peds.2010-0746

Moffett BS, Teruya J, Petit C. Heparin dosing in obese pediatric patients in the cardiac catheterization laboratory. 

. 2011;45(7-8):876-880. doi:10.1345/aph.1Q090

Taylor BN, Bork SJD, Kim S, Moffett BS, Yee DL. Evaluation of weight-based dosing of unfractionated heparin in obese children. 

. 2013;163(1):150-153. doi:10.1016/j.jpeds.2012.12.095

Caraco Y, Zylber-Katz E, Berry EM, Levy M. Carbamazepine pharmacokinetics in obese and lean subjects. 

 1995;29(9):843-847. doi:10.1177/106002809502900902

Li ZR, Wang CY, Zhu X, Jiao Z. Population pharmacokinetics of levetiracetam: a systematic review.

 2021;60(3):305-318. doi:10.1007/s40262-020-00963-2

Lexicomp. Pediatric Lexi-Drugs Online, Hudson, Ohio: LexiComp Inc. Updated November 1, 2021. Accessed November 25, 2021.

Donoso AF, Ulloa VD, Contreras DE, Arriagada SDS. Childhood obesity: pharmacokinetics considerations for drugs used in the intensive care unit. 

. 2019;117(2):e121-e130. doi:10.5546/aap.2019.eng.e121

Natale S, Bradley J, Nguyen WH, et al. Pediatric obesity: pharmacokinetic alterations and effects on antimicrobial dosing. 

. 2017;37(3):361-378. doi:10.1002/phar.1899

Zheng Y, Liu SP, Xu BP, et al. Population pharmacokinetics and dosing optimization of azithromycin in children with community-acquired pneumonia.

. 2018;62(9):e00686-18. doi:10.1128/AAC.00686-18

Smith MJ, Gonzalez D, Goldman JL, et al. Pharmacokinetics of clindamycin in obese and nonobese children. 

. 2017;61(4):e02014-16. doi:10.1128/AAC.02014-16

United Kingdom Paediatric Intensive Care Society Sedation

, Analgesia and Neuromuscular Blockage Working Group. Consensus guidelines for sustained neuromuscular blockade in critically ill children.

. 2007;17(9):881-887. doi:10.1111/j.1460-9592.2007.02313.x

Amador N, Guizar JM, Malacara JM, Pérez-Luque E, Paniagua R. Sympathetic activity and response to ACE inhibitor (enalapril) in normotensive obese and non-obese subjects. 

. 2004;35(1):54-58. doi:10.1016/j.arcmed.2003.08.010

. January 27, 2010. https://www.pharmacypracticenews.com/Opinion/Article/01-10/Immunoglobulins-and-Obesity/14546

Erstad BL, Barletta JF. Drug dosing in the critically ill obese patient: a focus on medications for hemodynamic support and prophylaxis. 

. 2021;25(1):77. doi:10.1186/s13054-021-03495-8

Amy L. Kiskaddon, PharmD, MBA, BCPPS, discusses how medication doses need to be adjusted for pediatric patients with obesity.

Pediatric obesity presents complexities in medication dosing

A digitally delivered sleep strategy (ie, an app) based on cognitive behavioral therapy (CBT) approaches can reduce childhood sleep problems. This was the finding of a pilot study that investigators conducted after first determining in a preliminary pilot study that new tools are needed to address pediatric sleep problems.

In the first study, about three-fourths (74%) of 218 participants (or their parents) reported sleep problems, usually mild (40.7%) or moderate (24.7%). Participants in the first study were aged 18 years or younger. Parents most often sought help for these problems by consulting their pediatrician (62%), a book (57%), a friend/family member (48%), a sleep consultant (41%), or web search (36%). Almost one-third (30%) of participants indicated the solution they tried did not produce meaningful improvements. Although only 8% of parents found their child’s sleep problems severely distressing, 41% termed them moderately distressing. Sleep problems also were associated with significant monetary costs.

In a second pilot study, investigators enrolled 11 families with sleep problems to receive the mobile app, DrLullaby, which includes pediatric versions of CBT protocols for insomnia, such as sleep restriction, stimulus control, relaxation strategies, worry time, cognitive restructuring, maintenance, and relapse prevention along with training and behavioral management techniques for parents. Participant families were assigned various informational modules depending on the child’s specific sleep problems, with the expectation of completing 1 module each week for 6 to 10 weeks. Each module is linked to more detailed reading materials about the desired changes and instructions on how to implement them. Participants also completed a weekly sleep distress scale and a daily sleep log.

DrLullaby was associated with improvements in key sleep behaviors, including time to fall asleep (72.7%), total time asleep (54.5%), and time awake (63.6%). These figures represent a mean 31.3% and 75.6% change from baseline for time to fall asleep and time awake, respectively, along with a mean improvement of 1 hour and 3 minutes compared with baseline for total time asleep. In addition, the collective distress scale score fell by 35%.

This is a small study of 11 children, 10 of whom were not infants (ages not specified), so it is not known whether the results will stand up. However, it may be worth looking into further; 6 to 8 weeks of treatment would cost $20 to $30. Some of the authors of the study are affiliated with the company that makes the app, suggesting potential conflicts of interest.

Tedford SE, Romano L, Gozal D, Medalie L. Digital solutions for sleep problems in children: a pilot study. 

 2022;57(8):1914-1920. doi:10.1002/ppul.25402

A digital sleep strategy may reduce sleep problems for children.

Need more sleep? Digital solutions show promise

Children with type 1 diabetes (T1D) have similar bone mineral density (BMD) levels to children without the disease, according to findings from a cross-sectional, case-control study conducted in an outpatient clinic in India. However, those with T1D had lower vitamin D levels than their peers without T1D, the study results showed.

Study participants were 37 children with T1D (mean age of 10 years) who require insulin to maintain normal blood glucose level and 37 children without T1D (mean age of 9.7 years). All participants underwent dual-energy x-ray absorptiometry scan of the lumbar spine and measurements of various bone health parameters, such as serum osteocalcin level, deoxypyridinoline level, serum vitamin D level, phosphorus and calcium levels, and alkaline phosphatase level.

Only 3 children with T1D (8%) had a low BMD level compared with none in the control group. However, serum 25-hydroxyvitamin D (25[OH]D) level was significantly lower in the T1D group than in the control group, and serum-intact parathyroid hormone level was substantially higher. Bone mineral content was similar in the 2 groups, as were all other bone turnover variables.

Children with T1D have enough to worry about; it is reassuring we can cross BMD off the list (at least in childhood). Vitamin D supplementation has been called into question recently but given the elevated parathyroid hormone levels seen in the study results, it seems worth reconsidering.

Kumar RA, Kumar CGD, Sahoo J. Evaluation of bone mineral density in children with type 1 diabetes: a cross-sectional case–control study.

. 2022;2(1):9-13. doi:10.25259/JPED_1_2022

A study found similar bone mineral density between children with and without type 1 diabetes.

Type 1 diabetes and low bone mineral density are not a common combination

Alex, an 18-year-old male, presented to the emergency department with a 4-day history of paranoia, agitation, and disorganized behavior. He had no psychiatric history or prior mental health contact and no known medical conditions.

Alex was admitted to the psychiatry unit due to agitation and violent behavior in the context of new-onset psychosis. In the week leading up to his hospitalization, he had attempted to assault family members and punched holes in the walls. He believed that his father had hacked into his bank account and had been responsible for starting the COVID-19 pandemic. Alex had been sleeping approximately 4 hours per night. Concerned about his escalating agitation, his parents called for EMS to take him to the hospital to be evaluated. Alex had been working out regularly, using pre-workout supplements and occasional marijuana. He had no previous mental status changes, functional decline, or psychiatric contact.

On examination, he appeared afraid and was posturing and yelling loudly. He had no visible lesions, track marks, or skin rashes. Overall, his physical examination was unremarkable. He was tachycardic to 110 bpm, with a temperature of 101 °F and blood pressure within normal limits.

Due to sudden new-onset mental status changes, a workup for reversible causes of mental status change was performed. A CT scan of his head was unremarkable, and laboratory testing was negative for infectious etiologies, malignancy, or thyroid disease. Urine toxicology was positive for marijuana. Alex was seen by internal medicine and psychiatry in the emergency department, from where he was medically cleared, and subsequently admitted to the psychiatry unit on an involuntary basis owing to psychosis and violent behavior.

The differential for new-onset psychosis in an adolescent is broad and can be divided into psychiatric and nonpsychiatric causes. Psychiatric illnesses that present with psychotic symptoms include depression or bipolar disorder, schizophrenia, schizoaffective disorder, and brief psychotic illness. Alex’s presentation is less typical of primary psychotic illness because it had an abrupt onset. Other differentials include metabolic abnormalities, infectious etiologies, malignancy, and substance use (

Table 1. Differential Diagnosis

Upon admission to the inpatient psychiatry unit, Alex was started on oral risperidone due to his level of distress regarding his psychosis. On day 2 of hospitalization, the inpatient psychiatry team spoke with him and his mother and screened him for possible ingestions or changes in behavior. For the past 4 months, Alex had been working out regularly and had begun using a pre-workout supplement powder containing caffeine, branched-chain amino acids, vitamins, and minerals. Two weeks before presentation, he had begun dry scooping (consuming without diluting in water) pre-workout supplement, which is a trend on Tik-Tok. He was consuming up to 2 scoops at a time, which equals 800 mg caffeine. He had used marijuana socially for the previous 3 years, but neither his frequency of use nor supplier had changed during the previous year.

One month after hospitalization, Alex’s mother reported that he had no periods of disorganized thoughts, anger, or paranoia. After discharge, he had stopped all supplements, marijuana, caffeine, and risperidone. At a 3-month follow-up visit, both he and his mother denied that he was having mood or psychotic symptoms. Alex’s cannabis use may have been a contributing factor, but because he had been using cannabis 1 to 2 times per month for 3 years before presentation and there had been no changes in the frequency and quantity of his use or in his supplier, we felt that his psychosis was attributable to dry scooping the pre-workout supplement.

Alex developed substance-induced psychosis in the setting of dry scooping a pre-workout supplement, a trend circulating on TikTok. Pre-workout supplements are sold over the counter and used to enhance anaerobic exercise performance by decreasing fatigue and increasing endurance.

These supplements contain caffeine, amino acids, B vitamins, and other additives. Case reports and review articles have implicated caffeine as a trigger for psychosis,

 and we believe this resulted in Alex’s presentation.

Only 8% of TikTok videos involving pre-workout supplements show people consuming the supplements according to the instructions.

 Cases of cardiac strain and arrhythmia secondary to pre-workout supplement use have been reported,

 but to our knowledge, this is the first report of a person who developed pre-workout supplement–induced psychosis. Overall, the regulation of these supplements is limited, and active ingredients can vary. Due to ease of access, uncertainty of ingredients, and the possible physical and mental health consequences of use, physicians, teachers, and family members should consider counseling young adults on the risks of pre-workout supplement use. We had discussions with Alex and later with him and his mother and recommended talking about social media trends with physicians during routine health maintenance visits.

In addition to dry scooping pre-workout supplements,

 there are many other potentially dangerous trends circulating on TikTok. The “Benadryl challenge” encourages viewers to take at least 12 tablets of Benadryl (a total of more than 300 mg) and stay awake to hallucinate,

 and there have been numerous reports of adolescents requiring hospitalization afterwards.

 L-tyrosine, an over-the-counter amino acid, has been promoted on TikTok as a “natural Adderall” to improve energy and focus.

 Videos also encourage the use of 5-HTP, a naturally occurring amino acid the body uses to create serotonin, to curb appetite and improve sleep and mood.

 Some TikTok users also encourage the consumption of large quantities of nutmeg to induce hallucinations.

 for other TikTok trends that may impact adolescent mental health. Although some social media trends may decrease the stigma surrounding mental health through discussion and normalization, many trends may promote self-diagnosis and self-treatment.

Table 2. Dangerous TikTok Trends 

As the use of social media sites becomes increasingly common among teenagers, health care providers must be aware of the potential spread of misinformation via these sites. TikTok in particular is an algorithm-based platform where users share brief videos with keywords, or hashtags. “Fitness and sports” is now the fourth most popular hashtag.

 Within this category, people share tips on diet and exercise, like dry scooping pre-workout supplements, weight-loss changes, meal plans, and related matters. Rapid and accessible dissemination of information, opinions, and trends through social media platforms may result in the spread of misinformation, self-diagnosis, and self-treatment.

 Some worrisome trends include supplement use as the primary treatment for mental health conditions

 and the promotion of unrealistic body standards.

 On the other hand, these trends offer an opportunity for providers to engage adolescents and decrease the stigma around mental health.

When dealing with this population, it is important to remain up to date on trends likely to impact them. With new-onset personality and behavioral changes, supplement use should remain on the differential. Providers should educate family members on social media trends and exposure and offer appropriate treatment and support for this demographic.

1. Beckner ME, Pihoker AA, Darnell ME, et al. Effects of multi-ingredient preworkout supplements on physical performance, cognitive performance, mood state, and hormone concentrations in recreationally active men and women. 

. 2022;36(9):2493-2501. doi:10.1519/JSC.0000000000003660

2. Wang HR, Woo YS, Bahk W-M. Caffeine-induced psychiatric manifestations: a review. 

. 2015;30(4):179-182. doi:10.1097/YIC.0000000000000076

3. Nelson Chow. Dry scooping and other dangerous pre-workout consumption methods: a quantitative analysis. Presented at: American Academy of Pediatrics Annual Meeting; October 9, 2021; Lynbrook, NY.

4. Wang SSY. Pre-workout supplement induced cardiac ischemia in a young female. 

. 2020;38(2):187-191. doi:10.1080/02640414.2019.1689598

5. Minhaj FS, Leonard J. Dangers of the TikTok Benadryl challenge. 

. 2021;38(1). https://www.contemporarypediatrics.com/view/dangers-of-the-tiktok-benadryl-challenge

6. Scott C. Updated: Most dangerous, foolish, mean Tiktok trends and challenges. Parentology. Published online July 26, 2021.

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