What is the Lifespan for a Child with Holoprosencephaly?

Patient Presentation
A 2-year-old female came to clinic with her mother for her health supervision visit. She had semilobar holoprosencephaly with developmental delay, abnormal facial features, intermittent seizures that were well controlled with medication, nasogastric tube for supplemental feedings, constipation, various endocrinology issues, and was wheelchair bound. The mother vocalized that she felt she was getting more stressed as the children got older and their needs increased. Her Patient Health Quotient score was 2. The social history showed that the parents were married and had a 4 year old son as well who was playing in the room. Her father had an office job and provided care and was supportive at home. Her mother primarily cared for the children. They had some intermittent respite care from family members who would travel from 2 hours away.

The pertinent physical exam showed a non-communicative patient with weight in the 15%, length in the 25% and head in the 25%. The physical examination showed narrowed forehead and eyes with a more prominent nose. Her dentitia was okay but she already had some capped teeth. Her heart, lung and abdomen were normal. She was generally hypotonic. Her skin examination was normal.

The diagnosis of a child with holoprosencephaly and a mother who was probably depressed was made. The pediatrician discussed some potential options for the family including looking for consistent skilled nursing and respite care, potential preschool for her brother and referral for the mother’s depression. “I know that in the past you have wanted to care for the kids by yourself and you have done a great job, but you also need to take care of yourself,” the pediatrician began. “I know. But we thought that she would only be with us for a short time, and I love her, and I wanted to spend that with her and her brother. We really didn’t expect her to be with us and have so many problems,” the mother confided. “I can understand that, but she is still with us, and everyone in the family needs a healthy mom, especially you. Would it be okay if I try to work with one of the social workers to get you some home health care while you think about preschool for your son. The front office staff can also help scheduling you to see your own doctor soon about your possible depression. Can I do these things for you?” she asked. “I’m not sure about the preschool, but having some respite care so my son and husband can do some things together would be good. I think I might like to talk with my doctor too but I want to think some more before I do that,” she replied. “Okay, but I’m going to call you in a few days to check in and see what you have decided about preschool and your doctor after you have talked with your husband,” the pediatrician said.

Discussion
Holoprosencephaly (HPE) is a clefting problem of the brain. “[HPE] the result of incomplete or absent midline division of the embryonic forebrain into distinct cerebral hemispheres (prosencephalon) between the 18th and 28th day after conception.”

There are four distinct subtypes:

  • Alobar – both hemispheres are completely fused and are not separated into the left and right hemispheres. There is agenesis of the corpus callosum, arrhinencephaly and a single ventricle with fused thalami. Facial features are almost always affected.
  • Semilobar – the cerebral hemispheres are fused anteriorly but are separated posteriorly. There is agenesis or hypoplasia of the corpus callosum and the olfactory bulbs and tracts are usually absent. Facial features are often affected.
  • Lobar – the cerebral hemispheres are almost completely separated however the corpus callosum and olfactory lobes may be incompletely developed. Facial features may not be affected or are affected to a lesser degree.
  • Middle interhemispheric – occurs when the posterior frontal and parietal lobes are incompletely separated. This is the least severely affected form.

The prevalence of HPE is one in 10,000 to 100,000 live births depending on the study. In certain subtypes there is a female preponderance.

“Cyclopia a congenital malformation characterized by the presence of a single eye,…located in the middle of the face in the place normally occupied by the roof of the nose.” This is one of the severest malformations that can be seen in alobar HPE. Cyclopia is often seen in HPE but it can be seen with other congenital defects in about 1/3 of the cases.

Problems associated with HPE include:

  • Hydrocephalus
  • Seizures/epilepsy
  • Development delays including intellectual disability
  • Motor problems – hypotonia, dystonia or spasticity
  • Oral motor problems – problems with swallowing, dysphagia
  • Pulmonary problems – particularly aspiration
  • Gastrointestinal problems – gastroesophageal reflux, slow gastric emptying, constipation
  • Hypothalamic problems – abnormal sleep wake cycles, temperature dysregulation, diabetes insipidus, hypothyroidism, hypoadenocorticoism, growth hormone deficiency

Learning Point
In general and not surprisingly, more severe forms of HPE are correlated with higher morbidity and mortality. However within the subtypes there is a wide range of morbidity and mortality.

One study found that “…33% died within the first 24hr and 58% died within the first month, yet 29% survived the first year.” Another study found 57% with syndromic HPE died within 2 days of life, but 54% with isolated HPE lived longer than 1 year. A consortium group who manages and follows patients with HPE reports that the mean age of their patients was 4 years with 15% being between 10-19 years. Patients with alobar HPE have the highest mortality.

The consortium authors conclude “[b]ecause most deaths occur within the first few days to weeks of life, even children with alobar HPE who survive the first month are likely to survive beyond infancy.” Therefore appropriate primary and speciality care with support of the family is important for the patients and families.

Questions for Further Discussion
1. What are the genetics of cleft lip and palate? A review can be found here
2. How are malformations of brain cortical development grouped? A review can be found here
3. What are NORD and OMIM and how can they help learn more about rare diseases?
4. What is the role of a primary care pediatrician for families with a rare disease? A review can be found here

Related Cases

To Learn More
To view pediatric review articles on this topic from the past year check PubMed.

Evidence-based medicine information on this topic can be found at SearchingPediatrics.com and the Cochrane Database of Systematic Reviews.

Information prescriptions for patients can be found at MedlinePlus for these topics: Brain Malformations and Craniofacial Abnormalities.

To view current news articles on this topic check Google News.

To view images related to this topic check Google Images.

To view videos related to this topic check YouTube Videos.

Sedano HO, Gorlin RJ. The oral manifestations of cyclopia. Review of the literature and report of two cases. Oral Surg Oral Med Oral Pathol. 1963;16:823-838. doi:10.1016/0030-4220(63)90321-9

Orioli IM, Amar E, Bakker MK, et al. Cyclopia: An epidemiologic study in a large dataset from the International Clearinghouse of Birth Defects Surveillance and Research. Am J Med Genet C Semin Med Genet. 2011;157C(4):344-357. doi:10.1002/ajmg.c.30323

Levey EB, Stashinko E, Clegg NJ, Delgado MR. Management of children with holoprosencephaly. Am J Med Genet C Semin Med Genet. 2010;154C(1):183-190. doi:10.1002/ajmg.c.30254

Kaliaperumal C, Ndoro S, Mandiwanza T, et al. Holoprosencephaly: Antenatal and postnatal diagnosis and outcome. Childs Nerv Syst ChNS Off J Int Soc Pediatr Neurosurg. 2016;32(5):801-809. doi:10.1007/s00381-016-3015-4

Author
Donna M. D’Alessandro, MD
Professor of Pediatrics, University of Iowa

What is the Long-term Outcome of ACL Repair?

Patient Presentation
A 17-year-old male came to clinic for his health supervision visit. He had been injured during the previous football season and had undergone left anterior cruciate ligament (ACL) repair and successful rehabilitation. He had been cleared by physical therapy and his orthopaedic surgeon to play competitive sports again and was looking forward to the next season. The past medical history was otherwise unremarkable and this was his only significant injury.

The pertinent physical exam showed a muscular male with normal vital signs, with no change in weight or height over the previous year. His physical examination was unremarkable except for a well-healed surgical scar.

The diagnosis of a healthy male with a previous ACL repair was made. The teen noted that he had been working very closely with his physical therapist and weight trainer at school. “I know that I can get hurt again because I’m a running back and have to cut in and out and speed up and slow down. But I’ve worked really hard and done everything I’ve been asked to do. I’m excited that I can play again and want to have a great season especially as I’m a senior now and won’t play in college. I’m good but not good enough for that level,” he said. The pediatrician recommended continuing to work with the trainer and do the exercises to keep his knee strengthened and his other balancing exercises. The pediatrician knew that after ACL repair the longer term outcome wasn’t great for athletes but didn’t know any specifics and decided to look up the question.

Discussion
The anterior cruciate ligament (ACL) “is an intra-articular but extrasynovial collagenous structure with limited healing capacity that originates in the posteromedial aspect of the lateral femoral condyle and crosses into anteromedially to insert anterior into the intercondylar eminence of tibial articular surface.” It plays an important part as a mechanoreceptor particularly as a proprioceptor. Its main role is to prevent excessive anterior tibial translation, limits varus/valgus stress when the knee is in full extension and some rotary movements of the knee.

There are ~120,000 surgeries per year mainly in the teenage and young adult population, with the number of injuries slowly increasing because of athletic opportunities and exposure. This is especially true for girls and young women who have increased risks because of hormones, genetic predisposition, narrower knee notch width and differences in cutting (e.g. change of direction) and landing biomechanics. Females have an increased risk per exposure at 3.8 vs 3.7 for males. Other risk factors for ACL injury include patella alta (high riding patella) or an increased tibial slope. For females the highest risk sports for ACL injury are soccer and basketball, while for males it is football and lacrosse. Potentially a multisport athlete over 4 years of a high school career could have up to 5-10% chance of having an ACL injury.

Most ACL injuries are non-contact mechanisms (70-80%). Usually a deceleration, cutting, jumping or direct impact (e.g. fall) on the knee. Patients having difficulties describing what occurred, but often stating something like “the knee popped out of its socket,” or it “bent the wrong way” (i.e. hyperextended). On physical examination, risk factors which are more likely with an ACL injury include having a popping sensation during the trauma, the knee “giving way”, presence of continuous effusion and a positive anterior drawer test and/or Lachman test. There are also other tests such as the pivot shift test or lever test which can also be used to help determine on physical examination if the ACL is injured. The gold standard for determination though is magnetic resonance imaging of the knee. Prevention programs include strengthening, multiple different types of exercises and “proximal control” exercises to help with biomechanics.

As a reminder:
Anterior drawer test is performed, “[w]ith the patient in supine position, the hip and knee were flexed to 45 and 90 degrees respectively. While the foot [is] stabilized on the examination table and the hamstrings [are] relax[ed], frequent manual gentle antro-posterior forces [are] applied to the proximal tibia, and tibia antero-posterior displacement in flexed knee [is] measured. The degree of displacement was compared with normal side. Displacement of more than 6 mm comparing the opposite side with a soft end point [is] proposed as torn ACL”
“The Lachman test is carried out in relax supine position, the examiner bends the knee to about 15 degrees [with] slightly external rotation. Then, by stabilizing the femur with one hand and putting the other hand behind the proximal tibia at the level of joint line, and then the tibia is pulled forward. In normal response there should be a steady restraint to anterior movement. Anterior displacement of proximal tibia being felt by examiner thumb in a soft or mushy end point [is] associated with positive Lachman test.”

Learning Point
ACL repair surgery is very successful for patients with good rehabilitation. There are various surgical techniques for repair but treatment appears to be more successful if done within 3 months of injury which appears to prevent additional trauma.

However the long-term outlook may not be as good as one would hope. Up to “81% of athletes return to some sport, while 65% return to their pre-injury level, and 55% return to competitive sports. However, only 38% remained at the same level 2 years after ACL [repair].” Depending on the study, the sport, the particular position on a team, the level of competitiveness, and the amount of time after injury, even many highly trained professional athletes often had fewer games, competitive outcomes (games, assists, goals etc.) and career lengths. Long term problems after repair can include injury to contralateral ACL, osteoarthritis, pain or loss of motion. The loss of motion is often more problematic for patients because of loss of function. Once one ACL is injured there is an increased risk of a contralateral ACL injury (4-25x) within 2 years of surgery.

Questions for Further Discussion
1. What are potential complications of other soft tissue injuries?
2. What are potential complications of fractures? A review can be found here
3. What are indications for use of computed tomography or magnetic resonance imaging for orthopaedic injuries?
4. How are posterior cruciate ligament injuries or meniscal injuries diagnosed?

Related Cases

To Learn More
To view pediatric review articles on this topic from the past year check PubMed.

Evidence-based medicine information on this topic can be found at SearchingPediatrics.com and the Cochrane Database of Systematic Reviews.

Information prescriptions for patients can be found at MedlinePlus for this topic: Knee Injuries and Disorders

To view current news articles on this topic check Google News.

To view images related to this topic check Google Images.

To view videos related to this topic check YouTube Videos.

Kaeding CC, Leger-St-Jean B, Magnussen RA. Epidemiology and Diagnosis of Anterior Cruciate Ligament Injuries. Clin Sports Med. 2017;36(1):1-8. doi:10.1016/j.csm.2016.08.001

Dekker TJ, Rush JK, Schmitz MR. What’s New in Pediatric and Adolescent Anterior Cruciate Ligament Injuries? J Pediatr Orthop. 2018;38(3):185-192. doi:10.1097/BPO.0000000000000792

Sepulveda F, Sanchez L, Amy E, Micheo W. Anterior Cruciate Ligament Injury: Return to Play, Function and Long-Term Considerations. Curr Sports Med Rep. 2017;16(3):172-178. doi:10.1249/JSR.0000000000000356

Makhmalbaf H, Moradi A, Ganji S, Omidi-Kashani F. Accuracy of Lachman and Anterior Drawer Tests for Anterior Cruciate Ligament Injuries. Arch Bone Jt Surg. 2013;1(2):94-97.

Author
Donna M. D’Alessandro, MD
Professor of Pediatrics, University of Iowa

What Does Non-Verbal Mean?

Patient Presentation
A 6-year-old male came to clinic for his health supervision visit and to establish care as he had recently moved to the area. He had autism spectrum disorder and needed to have multiple specialist consultations initiated for continuing care and therapy. He was already enrolled in school and his individualized education plan was being carried out to his parent’s satisfaction. His father described him as pretty compliant with activities but he still was fairly rigid about routines, clothing and choices of foods. “He’s non-verbal most of the time, but in certain circumstances he will talk but that is rare,” he described his son. He continued, “the speech therapist is working with him to try to get him to talk more, but he prefers to communicate by signing, drawing or just not interacting. Sometimes he just has a tantrum too.” The mother described several events where the child seemed to be very anxious too. The past medical history was positive for autism in a maternal cousin.

The pertinent physical exam showed a healthy boy with growth parameters 50-75%. Blood pressure and vision screenings could not be accomplished because of uncooperation. The boy did not speak or try to communicate with the physician but did maintain good eye contact throughout most of the visit. He did not appear anxious during the visit but more curious. The rest of his physical examination was normal.

The diagnosis of a healthy boy with autism spectrum disorder and possible selective mutism or other language disorder was made. The pediatrician offered, “I’m certainly not a specialist in autism or language disorders, but we have a regional children’s hospital nearby that has specialists. I’d like to refer you there for more evaluation, particularly about the language issue. I know that many of the behaviors and problems you are seeing can be caused by more than 1 thing and maybe it is not just the autism. Now that he is a little older, it might be easier to figure some of this out and he was evaluated when he was 4 years old. He’s already 2 years older and can help us more to understand him better. Sometimes there are other treatments too available for some of the other problems. I’ll put in the referrals for the children’s hospital, the local speech therapist and the ophthalmologist so we can check his vision properly. I also have a couple of dentists in the area who are excellent with children and used to children with some special needs too.”

Discussion
Children can be non-verbal for many reasons with most just not wanting to talk in a given situation for a short period of time (e.g. angry with a person, scared to give a speech at school, etc.). Children may have the ability to communicate verbally but for some reason it is physically impaired for a period of time.

Selective mutism (SM) “… is characterized by an individual’s consistent failure to speak in social situations in which there is an expectation to speak (e.g., at school), despite speaking in other situations.” The lack of speech cannot be due to discomfort speaking in a given language (i.e. a person learning a new language) or be due to another developmental condition or communication disorder. It must occur for at least 1 month. The prevalence rate ranges depending on the group studied. In a general population setting about 0.7% has been cited. Symptoms generally appear between 2-4 years. Children usually will not speak in a public or semi-public setting and are more likely to speak at home. The cause is felt to be multifactorial with an interplay between genetics (there is increased rate of relatives with SM, anxiety and social phobia), temperament (more common in persons who avoid unfamiliar situations), environment (more common in immigrant children, where the problem is out of proportion to the language acquisition or may occur in both languages) and development (more common in children with motor delays, speech or language delays, and cognitive delays). Treatment currently is using treatments for anxiety including cognitive behavioral therapy and pharmacotherapy with selective serotinin reuptake inhibitors. SM usually resolves but there may be persistent communication disorders, psychiatric and academic problems even into adulthood. SM is highly comorbid with Social phobia. Social phobia is “marked fear or anxiety about one or more social situations, in which [the person is] exposed to possible scrutiny by others. The anxiety must be expressed in peer settings and be expressed by behaviors such as “crying, tantrums, freezing, clinging, and failure to speak.”

A child who is consistently non-verbal may have an intellectual disability that impairs their ability to communicate verbally. This does not mean they cannot communicate in other non-verbal means or through assistive devices. Cerebellar mutism syndrome is another type of mutism that “is characterized by delayed onset mutism/reduced speech and emotional lability after cerebellar or 4th ventricle tumor surgery in children….The mutism is always transient, but recovery …may be prolonged. Speech and language may not return to normal, and other deficits of cognitive, affective and motor function often persist.”

Learning Point
Autism Spectrum Disorder (ASD) is a social communication disorder estimated to affect about 2% of children in the United States. There are problems with social-emotional reciprocity, non-verbal communication and developing and maintaining social relationships. People with ASD usually have some type of restricted or repetitive behaviors, interests and/or activities.

The cross-over between ASD and other problems can make it difficult to discern if the problem is primary, comorbid or two or more different issues. For example, specific language impairment or social pragmatic communication disorder have many of the same difficulties with language and symptoms begin at the same age as many patients with ASD. Children with intellectual disabilities may have social or language impairments similar to ASD. Similarly, anxiety disorders can occur in children with ASD or be a separate entity such as generalized anxiety disorder and reactive attachment disorder

Two studies (1998 and 2000) cite ~7% of patients with SM also having ASD. A 2018 retrospective study found 63% of children with SM had ASD. These 2018 authors felt that the large difference was partially because they are an autism referral center. Their research showed an overlap between SM and ASD and also intellectual disabilities. In the 2018 study, SM symptoms occurred outside the home in 100% of families but only 5% inside the home. For those with symptoms in both locations, 4 of the 5 patients also had ASD.

Questions for Further Discussion
1. What resources are available in your community for children with speech or language disorders?
2. Explain how the theory of how cognitive behavior therapy helps for anxiety disorders?

Related Cases

To Learn More
To view pediatric review articles on this topic from the past year check PubMed.

Evidence-based medicine information on this topic can be found at SearchingPediatrics.com and the Cochrane Database of Systematic Reviews.

Information prescriptions for patients can be found at MedlinePlus for this topic: Speech and Communication Disorders.

To view current news articles on this topic check Google News.

To view images related to this topic check Google Images.

To view videos related to this topic check YouTube Videos.

Andersson CB, Thomsen PH. Electively mute children: An analysis of 37 Danish cases. Nord J Psychiatry. 1998;52(3):231-238. doi:10.1080/08039489850139157

Kristensen H. Selective mutism and comorbidity with developmental disorder/delay, anxiety disorder, and elimination disorder. J Am Acad Child Adolesc Psychiatry. 2000;39(2):249-256. doi:10.1097/00004583-200002000-00026

Hua A, Major N. Selective mutism. Curr Opin Pediatr. 2016;28(1):114-120. doi:10.1097/MOP.0000000000000300

Steffenburg H, Steffenburg S, Gillberg C, Billstedt E. Children with autism spectrum disorders and selective mutism. Neuropsychiatr Dis Treat. 2018;14:1163-1169. doi:10.2147/NDT.S154966

Simms MD. When Autistic Behavior Suggests a Disease Other than Classic Autism. Pediatr Clin North Am. 2017;64(1):127-138. doi:10.1016/j.pcl.2016.08.009

Catsman-Berrevoets CE. Cerebellar mutism syndrome: Cause and rehabilitation. Curr Opin Neurol. 2017;30(2):133-139. doi:10.1097/WCO.0000000000000426

Author
Donna M. D’Alessandro, MD
Professor of Pediatrics, University of Iowa

What Are Indications for Dermatological Light Treatment?

Patient Presentation
A 7-year-old female came to clinic for a rash. She had dry, reddened skin on her forearms, wrists and knees for the past week. She had tried some lotion once without improvement. She had no new exposures to sunscreen, insect repellent, hygiene or laundry products, etc. Her mother also asked to have her “unicorn star” looked at as some of her classmates had been teasing her about it. The “star” was a small red spot in the center of her forehead. The mother said the lesion had been there for a long time and perhaps had gotten slightly bigger. The past medical history showed seasonal allergic rhinitis and atopic dermatitis.

The pertinent physical exam showed a healthy female with normal vital signs and growth parameters in the 10-50%. Her examination was non-contributory except for her skin examination. She had dry, slightly reddened skin along both forearms, wrists and the extensor surfaces of her fingers. She had similar findings on the extensor surfaces of her knees and upper calves. On her forehead she had a 2 mm slightly raised, papule that was bright red. Magnification using an otoscope shows some very small “spider-like” vessels radiating an additional ~2 mm from the lesion. There was no perceptible halo around the lesion. No other lesions were noted.

The diagnosis of atopic dermatitis and a small spider telangectasia were made. The pediatrician recommended standard atopic dermatitis treatment be restarted. “The unicorn star is something we call a telangectasia. They usually don’t cause any problems but for some people they are a cosmetic problem,” she said. “They can be treated by a dermatologist, usually with laser or some kind of light treatment. I don’t know all about it, but I can send you to the dermatologist to talk about it including the risks and benefits of the treatment,” she continued. The girl piped up, “But I like my star!” “I know you do and so do I, but I think I want to talk with the doctor about the choices we have now and maybe in the future,” her mother responded.

Discussion
Spider telangiectasia or spider angiomas have a central red lesion with radiating dilatation of the distal, end vasculature that resemble arachnid appendages. They are common lesions (up to 38% in one study of children, and 60% in pregnant women), often solitary or < 3 lesions, and usually benign. Multiple lesions are characteristic of chronic liver disease. They can disappear over time (especially pregnancy related ones) but may not. The cause of these vascular lesions is unknown. Treatment is often not necessary, but laser treatments, fine needle electrocautery or electrodissection can be used.

Learning Point
Although the principals of LASER (i.e. light amplification by the simulated emission of radiation) was discussed by Einstein in the 1920s, the 1950s and 1960s saw the birth of the fundamentals of the technology with Nobel and other prizes being given for this work. Gordon Gould coined the phrase “LASER.”

Medical uses of light treatment comes in many different forms including the phototherapy for newborn jaundice commonly used in pediatrics, or light boxes for seasonal affective disorder. They have many uses within the surgical theaters. See the PubMed search below for a breadth of these indications.

The field of lasers and other similar light technologies has rapidly expanded with new indications, technologies, and increased distribution of the light devices into medical and other health related locations (e.g. spas). Basic treatment for dermatological conditions includes a light source of various wavelengths that is applied for various amounts of time during an individual treatment, and multiple treatments may be necessary. Different light treatment devices are applied in a single discrete location, multiple discrete locations or in a larger area by application of a predetermined scanning pattern. The skin area may also be given pretreatments such as mild dermabrasion and or localized photosensitizing drugs to assist with the treatment efficacy. The light sources are not necessarily a laser device but can include light emitting diodes or intense pulsed light devices. The term laser is often used by laypersons and health care providers as a generic term for such light based dermatological treatments.

Possible problems include pain during treatment or afterwards, burn, scarring, pigmentary changes, hair changes, infection, etc. Problems are more common when used by persons with less training using the light treatment devices.

Light based treatment indications includes:

  • Hemangiomas or other blood vessel lesions such as spider telangectasias
  • Acne – effective for inflammatory acne not comedomal
  • Verrucae
  • Scar treatment
  • Epilation
  • Pigment removal – e.g. tatoos, unwanted melanin
  • Photorejuvenation
  • Actinic keratosis or chelitis
  • Non-melanotic skin cancer
  • Sebaceous hyperplasia
  • Rosacea

Questions for Further Discussion
1. How do you use light therapy for seasonal affective disorder? A review can be found here
2. What are types of true laser devices used by dermatologists?

Related Cases

To Learn More
To view pediatric review articles on this topic from the past year check PubMed.

Evidence-based medicine information on this topic can be found at SearchingPediatrics.com and the Cochrane Database of Systematic Reviews.

Information prescriptions for patients can be found at MedlinePlus for this topic: Vascular Diseases

To view current news articles on this topic check Google News.

To view images related to this topic check Google Images.

To view videos related to this topic check YouTube Videos.

Hersant B, SidAhmed-Mezi M, Bosc R, Meningaud JP. Current indications of low-level laser therapy in plastic surgery: A review. Photomed Laser Surg. 2015;33(5):283-297. doi:10.1089/pho.2014.3822

Paasch U, Schwandt A, Seeber N, Kautz G, Grunewald S, Haedersdal M. New lasers and light sources – Old and new risks? J Dtsch Dermatol Ges J Ger Soc Dermatol JDDG. 2017;15(5):487-496. doi:10.1111/ddg.13238

Benedetto AV. What’s New in Cosmetic Dermatology. Dermatol Clin. 2019;37(1):117-128. doi:10.1016/j.det.2018.08.002

Ozog DM, Rkein AM, Fabi SG, et al. Photodynamic Therapy: A Clinical Consensus Guide. Dermatol Surg Off Publ Am Soc Dermatol Surg Al. 2016;42(7):804-827. doi:10.1097/DSS.0000000000000800

Kwon E-KM, Seefeldt M, Drolet BA. Infantile hemangiomas: An update. Am J Clin Dermatol. 2013;14(2):111-123. doi:10.1007/s40257-013-0008-x

Samant H, Kothadia JP. Spider Angioma. In: StatPearls. Treasure Island (FL): StatPearls Publishing; 2019. http://www.ncbi.nlm.nih.gov/books/NBK507818/. Accessed September 3, 2019.

Laser. In: Wikipedia. 2019. https://en.wikipedia.org/w/index.php?title=Laser&oldid=912216041. Accessed September 3, 2019.

Author
Donna M. D’Alessandro, MD
Professor of Pediatrics, University of Iowa