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Clinical ShowCase™: Developing a Personalized Treatment Plan for a Patient with Sickle Cell Disease

Clinical Showcase Sickle Cell 

A recent study in Puerto Rico assessed trends among pediatric patients with 

 including regional tendencies, comorbidities, and common allergens.

, AD is known as the most frequent dermatologic disorder for children. 

, on the other hand, is an antigen-mediated, chronic esophageal disease known to impact 43 of every 100,000 pediatric patients in the US.

Flare-ups of EoE and AD can result from dietary and environmental factors, which is why they were seen as important to assess. The study was led by Vylma Velázquez MD, FAAP, FACAAI, from the Centro Medici Episcopal San Lucas.

“This pilot study attempts to identify and compare frequent allergies in pediatric patients with AD or EoE,” Velázquez and colleagues wrote. “The purpose is to provide physicians with more defined data on the relationship between allergies and these diseases in Puerto Rico and how to apply ambient exposure modifications and dietary restrictions to the Puerto Rican diet.”

The study involved reviewing the medical records of 138 patients in Ponce, Puerto Rico at a specific allergist/immunologist outpatient clinic. The investigators included patients who matched the following inclusion criteria:

RAST IgE-specific or epicutaneous allergy tests

Data assessed between December 2016 - 2021

The investigators assessed the presence of both qualitative and quantitative variables in study participants. They then compared the collected data to that of AD and EoE patients in the US.

The investigators found regarding comorbidities that AD patients showed statistical significance of allergic rhinitis presence compared to EoE, 30.4% and 72.7% respectively. They also noted clinical relevance of allergic conjunctivitis and asthma in both groups.

The research team reported that the allergies with the most statistical significance were nuts, peanuts, soya beans and walnuts, with prevalence in EoE patients versus AD patients. The most common allergens for AD patients were eggs at 36.0%, milk at 32.8%, and wheat at 16.8%. EoE patients’ most common food allergens were peanuts at 36.4%, soya beans at 27.3%, and eggs, almonds, nuts, and wheat with equal patient percentages of 18.2%.

Additionally, the investigators noted that among environmental allergies, the most statistically significant was cat allergy with prevalence in EoE patients compared to AD. AD patients’ most predominant allergies were to dust mites, yeast and dogs, and EoE patients’ most predominant were dust mites, cats, and pollen.

“When our data was analyzed and compared to that of the United States, atopic dermatitis showed the same trend as reported across the states. In contrast, the prevalence of sensitivities to the most common allergens were reported differently in our studies in patients with EoE. More patients of EoE will be evaluated to reassess food sensitivities and associated food exacerbations.”

The study, “Prevalence of allergies on Pediatric Patients with Atopic Dermatitis and Eosinophilic Esophagitis,” was presented at ACAAI 2022.

This article was published by our sister publication HCP Live.

Articles

New data presented at ACAAI 2022 observed various trends in allergies associated with eczema and eosinophilic esophagitis, comparing observed data with that of patients in the United States.

Frequent allergies in pediatric atopic dermatitis, eosinophilic esophagitis patients in Puerto Rico

At the American College of Rheumatology (ACR) Convergence 2022, Amit Golding, MD, PhD, medical officer for the US Food and Drug Administration (FDA), provided updates on recent FDA approvals for drugs and discussed how biosimilars are approved.

Golding outlined the 4 categories of similarity between adult and pediatric conditions. Different conditions show no overlap, dissimilar conditions contain slight overlap with significant differences, similar conditions show significant overlap with slight differences, and same conditions show significant overlap with no clear significant differences.

The first approval discussed by Golding was the use of belimumab IV (BENLYSTA; GlaxoSmithKline plc) for pediatric lupus nephritis in patients aged 5 to 17 years. Approval was based on established efficacy in adults and a successful study in pediatric patients. The pediatric dosage is 10 mg/kg in 2-week intervals for the first 3 doses, followed by 4-week intervals, matching the adult dosage.

Another approval was the use of ustekinumab SC (Stelara; Janssen Pharmaceuticals) for psoriatic arthritis in pediatric patients aged 6 to 17 years. The approval followed efficacy in adults and completed studies in pediatric patients with plaque psoriasis. A dosage based on weight is given 4 weeks after the initial dose, then every following 12 weeks.

Golding also discussed a study for secukinumab (COSENTYX; Novartis) for pediatric psoriatic arthritis and enthesitis-related arthritis. The study evaluated the treatment in pediatric patients aged 2 to under 18 years. In part 2 of the study, participants were randomized to secukinumab or placebo, with a primary endpoint of time to flare. 

Following the study, approval was given to the product. Adverse events were mild and matched the safety profile for secukinumab, and efficacy for reducing flare rate was proven.

In discussing biosimilars, Golding described them as treatments that are highly similar and with, “no clinically meaningful differences from the FDA approved reference product.” They use the same mechanisms for conditions of use, which have been previously approved for the reference product. Biosimilars should meet the standards of safety, purity, and potency.

To evaluate differences in products, Golding recommended analytical study. Golding also stated that a biosimilar should have similar efficacy and safety as the reference product, and that an assessment of immunogenicity should be conducted.

Golding, A. Pediatric rheumatology FDA update 2022 ACR Convergence November 14, 2022. Presented at: ACR Convergence 2022, Philadelphia, Pennsylvania. November 11 to November 14, 2022.

At ACR Convergence 2022, Amit Golding, MD, PhD, outlined drugs recently approved by the FDA, and discussed the requirements for biosimilars to meet approval. 

Updates on FDA drug approvals

Getting to know families and patients with diabetes has been a real privilege and honor in the scope of my practice. More than anything, you begin to realize that they have no option but to get up every day and face their diabetes, knock it down for the day, go to bed, and do it all over again. Whatever their effort was yesterday, they don’t really get to bank that and skate on the next day. They really have to do it all over again. Because of that, you don’t want any other members of the family, or they themselves to have to do that day after day.

Through antibody screenings, we want to prevent diabetes as much as possible. That is a complex endeavor. For decades we’ve been trying to cure diabetes, and for decades we’ve tried to prevent diabetes. The immune system has a definite mind of its own. I think of it like a military. A military has many divisions and doesn’t use just 1 division to come at you from 1 angle. With research, we are able to look at different ways that the immune system attacks the beta cell, and we have come up with various angles to try to prevent the immune system from attacking the beta cell from various angles. Thus far, unfortunately, we don’t have something widely available that prevents all the ways in which the immune system can attack the beta cell. We are definitely trying, but as yet nothing has been totally successful. It could be that in the future, there are going to be several different agents that will need to be used to shut down that attack.

Other ways that we think about how we can get a child to continue to have functioning beta cells is by infusing those cells or creating those cells. One of the challenges there is to, if we create those cells, we want to make sure that those cells can make insulin, but we don’t want them to make insulin all the time. Obviously, we only want them to make insulin when the blood sugar is at a certain level, and we want them to stop making insulin when the blood sugar starts to fall, just like our own insulin cells do in such a miraculous way all of the time. This has been a decades-long process, and the number of people who are dedicated to making this work are boundless. Many of them have diabetes or they know someone who has diabetes, and this is their life’s work and passion. We are so lucky to have them working day and night on this cause.

As they do that work, we still want the best quality of life for those patients we see and their families. We want them to be able to carry on playing softball and T-ball, going to school, going to parties, going on field trips, doing everything they want to do, and just incorporating diabetes into their lives. So, one of the exciting things we’ve witnessed as providers is technology evolving to help them do those things. Many of our patients here have not checked a finger-stick blood sugar level in a very long time, and they have not given themselves a shot in a very long time. They wear a continuous glucose sensor and an insulin pump, and over the past year to year and a half, those devices, the sensor and the pump, have been talking to one another and delivering insulin on an automated basis. That has provided a great improvement in glucose control for those patients. The complications that we mentioned earlier are becoming less common, and we love to see that.

We won’t ever drop our pursuit of a complete, 100% cure, but a lot of work is going on in a lot of avenues, and we hope it all works because that’s what we do, and that’s what we’re here to do. In the meantime, we’ll take care of these patients one by one and ensure that we do our best for them. They didn’t ask for this, and as soon as we can rid them of this burden, the better off they will all be, and we’ll all be very happy for them.

On occasion, diabetes can be a great pretender. A child might show up to your office just with complaints of abdominal pain, or with a complaint of fatigue. A child doesn’t always show up with classic symptoms of weight loss, increased thirst, and increased urination. If the complaint seemed vague, and you aren’t really sure what’s going on, but the child just has a bit of malaise, it is never a bad idea to get a finger stick for blood sugar and a urinalysis. The urinalysis will show you whether there are any ketones, and if the child’s spilling blood sugar. The glucose test will show you whether there’s any hyperglycemia. With those tools, you can rule out whether the abdominal pain, if there is such, is a product of ketosis. You can also see whether the blood sugar has been over 200 mg/dL and the child is spilling glucose in their urine, and obviously, the point-of-care glucose test shows you whether they are hyperglycemic. Those 2 simple points-of-care tests will give you a wealth of information and will essentially rule out new onset diabetes for you with each child who has vague complaints.

Videos

Dr Elaine M. Apperson shares diabetes prevention strategies and mitigating disease complications in the pediatric population as well as advice for health care practitioners managing the disease.

Approaching Prevention and Management of Diabetes

Nothing has been approved by the FDA to use as an intervention. When you monkey around with giving something that would alter, be an immune modulator, you better have some long-term data showing safety. We don’t have that yet. The idea most likely is that it’s going to look something like chemotherapy where you have multiple immune modulators at the same time to thwart the immune system’s attack. By the time you’re showing signs of elevated blood sugar, you’ve lost about 90% of your beta cell function. That doesn’t leave you a whole lot of room to operate. So by the time you’re requiring insulin and that sick, you’ve only got a small margin of working beta cells. We don’t have anything that is out on the market to do anything at stage 1 or 2. That’s why we keep working.

Even when they tried to transplant pancreatic cells from cadavers, the immune system would tear those up. The hard part was shutting down the immune system and the morbidity from that. With immunosuppressant drugs the outcomes were terrible, and the immune system would, even if you tried suppressing it, the cells would not thrive. Patients could go sometimes insulin free or with very reduced insulin for a few years, but overall, in general, it was not a successful endeavor.

Right now, to be honest, where we are with hooking up sensors to insulin pumps and automating those systems where the sensor tells the pump how much insulin to deliver every 5 minutes, and having the patient put in the amount of carbohydrates they eat and having the insulin pump be programmed with their insulin needs for carbohydrates and for high blood sugar, and have that happen, essentially automatically like an external pancreas, is our quasi cure. And the good thing about technology is that you can press stop, you can take it off, and you haven’t monkeyed around with your physiology internally. That’s where we are, essentially, and it’s producing great outcomes. Would it be nice to have a biological cure right away? Sure, but in the meantime, 75% or more of our patients are on a pump, a CGM [continuous glucose monitor], or both, and they do pretty well.

Elaine M. Apperson, MD, addresses early intervention and technologies for monitoring type 1 diabetes for disease management.

Monitoring Type 1 Diabetes

VTAMA (tapinarof cream, 1%; Dermavant Sciences) has shown positive results in children aged as young as 2 years with atopic dermatitis (AD), according to Dermavant Sciences.

Philip M. Brown, MD, JD, chief medical officer of Dermavant, said tapinarof has shown favorable results for safety, pharmacokinetics, and clinical improvement, along with a low incidence of adverse events.

There were 36 pediatric patients enrolled in the study aged 2 to 17 years old with an investigator's global assessment score of 3 or more during screening, implying moderate to severe AD. Patients underwent 4 weeks of treatment with tapinarof under maximal usage conditions.

The study evaluated the same 1% cream that is undergoing ADORING 1 and ADORING 2 pivotal trials and has been approved by the US Food and Drug Administration to treat plague psoriasis in adult patients.Dermavant plans to announce results from the trials in the first half of 2023.

In the study, tapinarof was tolerated by patients even in areas of sensitive skin. There was also minimal to no systemic exposure confirmed for patients with up to 90% body surface area (BSA) affected. The mean BSA in the study was 43%.

AD affects over 26 million people in the United States alone and is most common in pediatric patients. Up to 30% of children worldwide are afflicted with AD, experiencing red, swollen, cracked skin.

AD frequently causes itching leading to sleep disturbances and fatigue that makes children inattentive at school. The visibility and discomfort of AD could also lead to social and emotional distress.

Tapinarof is currently the top branded topical treatment for plague psoriasis. Adverse events include contact dermatitis, nasopharyngitis, folliculitis, itching, headache, and influenza. 

The full results on the effects of tapinarof in pediatric AD will likely be presented at a future medical meeting, according to Dermavant.

Dermavant announces highly favorable results from pediatric maximal usage study of VTAMA® (tapinarof) cream, 1% in atopic dermatitis.Dermavant. November 8, 2022. Accessed November 15, 2022.

https://www.dermavant.com/dermavant-announces-compelling-results-from-pediatric-maximal-usage-study-of-vtama-tapinarof-cream-1-in-atopic-dermatitis/

Dermavant Sciences recently announced positive results for VTAMA (tapinarof cream, 1%) for treatment of atopic dermatitis in children aged as young as 2 years.

VTAMA effective against pediatric atopic dermatitis

The US Food and Drug Administration (FDA) has been tackling the drug shortage through its Drug Shortage Staff (DSS), which was outlined by Hyun Son, PharmD, at the American College of Rheumatology (ACR) Convergence 2022.

The DSS is an office within the FDA made to manage and resolve drug shortage situations, bringing safe and effective drugs to patients. Tasks of the DSS include creating short- and long-term strategies to combat drug shortages, making decisions that fully account for risks and benefits, and distributing information.

Key communication occurs between the DSS and other groups to manage drug shortages. The DSS receives information on disruptions to drug distribution from manufacturers, and provides shortage information to pharmacists, patients, providers, researchers, and other US agencies. Important information is also exchanged between the DSS and international authorities.

According to Son, early notification is key to preventing and mitigating drug shortages. Products should be prioritized if they are medically necessary, with the risks and benefits of the drugs considered. The DSS works to maintain availability while minimizing risks to patients and works with firms to address problems.

Son discussed the “FDA toolbox,” a set of guidelines the DSS follows when managing drug shortages. These include making other suppliers aware of potential shortage concerns, encouraging firms to look at demand and supply, and maintaining regulatory discretion.

The FDA toolbox also outlines expedited review of company proposals, listing proposals such as new manufacturing site, increased expiry date, new raw material source, and changes in specifications. Changes in importation from other countries was also discussed, using triamcinolone hexacetonide injection as an example.

According to Section 506C of the Federal Food, Drug, and Cosmetic Act and FDA regulations, manufacturers must notify the FDA of permanent discontinuation of a drug or interruption of manufacturing that will cause a supply disruption. This notification should come at least 6 months in advance regardless of market share and is not limited to medically necessary products.

Notifications that must be sent to the DSS include plans for upgrades, manufacturing issues, raw material batch failures, and product quality issues. Individuals in the public marketplace can also send the DSS notifications on shortages through their public email, drugshortages@fda.hhs.gov.

The DSS also receives information on current inventory, production plans, and distribution data from manufacturers. This data is used to estimate the supply gap, and has led to many prevented drug shortages, including over 150 in 2020.

The drug supply chain as outlined by Son went from suppliers, to manufacturers, to wholesalers, to pharmacies and hospitals, and to patients and health care providers. Interruptions generally occur at the wholesale level.

In 2011, shortages peaked at 251, then decreased through 2016. In 2020, there were 43 new shortages. Son noted that these shortages could occur for months or years depending on precipitating events.

While the FDA works closely with manufacturers to address problems, it cannot require a company to make a drug, a company to make more of a drug, or how much a drug is distributed. Instead, the FDA can require notifications by manufacturers on supply disruptions, delays, discontinuations, and certain manufacturing changes.

Son stated that shortages in 2020 were mainly because of COVID-19. To combat the pandemic, the DSS has continued early outreach to manufacturers. The FDA has also posted guidance on COVID-19 and has granted Emergency Use Authorizations to certain drugs.

Efforts have also been made to assist manufacturers during a shortage, such as expedited approvals to increase production and temporary extended use of distributed lots near expiration. According to Son, these efforts prevented 199 shortages in 2020.

Industry can also support the prevention and mitigation of drug shortages. This involves placing safeguards to combat vulnerabilities of their supply chain and early communication about possible shortages. When a shortage is unavoidable, shortage information can be posted on the FDA website.

The FDA has also introduced the CARES Act, which requires prioritized risk management plans (RMPs) from manufacturers of drug products that are life-supporting, life-sustaining, or made to prevent debilitating conditions. RMPs allow strategies to be implemented which can prevent supply disruptions.

Son, H. FDA: Pediatric Update. Presented at: ACR Convergence 2022, Philadelphia, Pennsylvania. November 11 to November 14, 2022.

At ACR Convergence 2022, Hyun Son, PharmD, discussed the role of the FDA’s Drug Shortage Staff in preventing and mitigating drug shortages. 

How the FDA prevents drug shortages 

A majority of patients say their physicians’ technology is so bad, they would rather skip an appointment than wade through the scheduling process.

 that fall short of patient expectations, said they report “What patients really want from healthcare.” San Mateo, California-based automation company 

 surveyed 1,005 patients in March this year and published 

“Our survey data shows that when care is difficult to access, many patients simply don’t go to the doctor,” Notable Head of Research Carle Falk said in a 

. “People aren’t skipping doctor visits because they’re confused about test results or worried about a procedure. They’re avoiding medical visits because the appointment-booking process is confusing and takes far too much time and effort.”

The company said legacy digital scheduling programs fall short because they require 

 and schedule intervention. That process creates patient hassles that limit access because health systems have challenges filling their support services jobs.

63% said their provider’s digital tools don’t meet expectations.

61% said they have skipped going to the doctor because of scheduling hassles.

70% of patients tried online scheduling in the past year but were redirected to a phone call.

30% of patients said they have not used digital services in the past year to book appointments, fill out forms, or pay bills.

41% of patients have switched providers due to a poor digital experience.

75% of patients would rather complete intake paperwork online.

Meanwhile, patients reported their waiting times are going up, even as more technology in integrated to streamline visit registration and intake.

Notable recommended a three-step process for physicians, executives, and IT support staff to change their digital interfaces with patients:

Complete a current state assessment on current digital tools and how patients feel about them.

Start by improving patient intake. Notable said “seamless patient intake is non-negotiable for patients.”

Improve patient and caregiver experiences with intelligent automation.

This article was published by our sister publication Medical Economics. 

Tech company surveys patients who say online experience with doctors’ offices is not great.

Use technology to make it easier for patients to schedule appointments

A Sleep Number study utilized smart bed technology to evaluate 

 parameters in children. Previous studies of the pediatric population are limited and those that have assessed sex differences in sleep parameters have yielded mixed results.

Vidhya Chellamuthu, M Tech, Sleep Number Labs, and investigators performed an ecologically-valid study in order to characterize overnight sleep parameters by age and sex. Data were collected from the large sample population for over 2 years.

Bedtime, wake time, bedtime/wake time variability, sleep duration, restful sleep duration, percent restful sleep, restless sleep duration, and percent restless sleep were included as sleep outcomes. The study endpoints were collected from January 2018-October 2021.

The investigation included 22,920 individuals between the ages of 5-17 years who were stratified into 3 separate age groups: youth (5–10 years, n=4272); preadolescent (11–13 years, n=5718); and adolescent (14–17 years, n=15,970). Relationships between sexes were observed within age groups and on an annual basis from ages 8-17.

The application of adaptive threshold to motion levels detected events of restless sleep and then attributed to the rest of the endpoint data gathered from the Sleep IQ technology featured in the smart bed platform. Investigators noted that this investigation period included the COVID-19 pandemic, school days, holidays, and weekends.

The differences were compared between age groups and sex groups based on the weekly mean of each endpoint. The team determined comparisons between groups using Cohen's d effect size (d) and 1-way ANOVA or 2-sample t test, with α=0.05.

A significant difference between age groups was revealed in the analyses for each sleep endpoint with the most meaningful demonstrations occurring in sleep duration, bedtime, and restful sleep duration.

Age groups differed significantly in their relationships with wake time, percent restful sleep, bedtime/wake time variability, restless sleep duration, and percent restless sleep, though their effect sizes were lower.

Across all age groups, females experienced signficantly greater sleep duration, restful sleep duration, and percent restful sleep when compared to the males in their age group. They also showed higher percent restful sleep duration, earlier bedtime, and earlier wake time in the annual analysis.

However, bedtime and wake time shifted later with age regardless of sex.

"The data support previous pediatric caregiver-report studies showing declines in sleep duration, restful sleep (which may serve as a proxy for slow wave sleep), restless sleep duration, and percent restless sleep; later bedtimes; and increased bedtime-wake time variability with increasing age," investigators concluded. "Across all age groups, females experienced greater sleep duration, greater restful sleep duration, and earlier bedtimes than males."

The study, "Age and sex differences in overnight sleep parameters in children and adolescents" was included in data from the 

International Pediatric Sleep Association (IPSA) Congress 2022.

New data from the International Pediatric Sleep Association (IPSA) Congress 2022 used smart bed technology that revealed consistent findings to previous studies.

Large-scale data collected from smart bed technology show sleep differences in pediatric groups

You are asked to evaluate an African American boy aged 4 years with a birthmark on his back and right arm. He is healthy with normal growth and development.

Lines of Blaschko are thought to represent pathways of epidermal migration and proliferation during fetal development.

 They differ from dermatomes that represent areas of skin innervated by a single nerve. Lines of Blaschko are usually invisible unless genetic mutations result in mosaicism that alters the pigmentation, proliferation, and/or differentiation of epidermal cells.

 The lines are visible and present in S-shaped, V-shaped, or even U-shaped patterns.

 They are usually seen on either the scalp, face, trunk, and/or limbs.

Genetic mosaicism can occur due to chromosomal abnormalities such as a nondisjunction event that takes place before zygote formation (meiosis) or after a postzygotic event (mitosis). In both cases, cells will have three copies of a chromosome, leading to trisomy. To create a diploid zygote, the embryo undergoes trisomic rescue where one of the chromosomes in the trisomy is lost to form a diploid cell. However, not all the cells will have one chromosome from each parent after trisomic rescue. Instead, some cells will be heterodisomic or isodisomic. The result is at least 2 different cell lines present in an individual derived from 1 zygote. In our patient’s case, these 2 cell lines may have differing amounts of melanocytes present which can give rise to different skin lesion phenotypes such as hyperpigmentation or hypopigmentation.

 The resulting phenotype is known as Blaschko lines. In addition to hyperpigmentation and hypopigmentation, Blaschko lines can sometimes be seen as warty or inflamed before becoming hyperpigmented.

Another type of mosaicism that can cause Blaschko lines is through epigenetics and termed as lyonization.

 This occurs in females where one X-chromosome in somatic cells is inactivated. In some cases, lyonization could lead to a manifesting heterozygote in the form of Blaschko lines.

: When looking at the patient’s findings, he presents with hypopigmented macules since birth. A diagnosis that can be associated with this symptom is tuberous sclerosis. However, tuberous sclerosis presents with characteristic ash-leaf spots that differ from the swirls and delineation nature of Blaschko lines.

 Other cutaneous findings in tuberous sclerosis include facial angiofibromas, periungual fibromas, hypomelanotic macules, and connective tissue nevi. Compared to Blaschko lines forming through errors of cell migration in embryogenesis, tuberous sclerosis is caused by mutations in tuberous sclerosis complex (TSC).

 This mutation leads to activation of the mTOR signaling pathway that decreases melanocyte production leading to the hypopigmented macules seen in patients with tuberous sclerosis.

: Waardenburg syndrome is a genetic condition that affects the skin through genetic mutations in the MITF gene. When MITF is genetically altered, it has been shown to affect melanocytes, leading to hypopigmentation of the skin.

 A key difference between Waardenburg syndrome and Blaschko lines is that Waardenburg syndrome not only affects the skin, but also affects ears, eyes, and hair through genetic mutations in SOX 10, EDN3, EDNRB, and PAX312. Patients can have congenital hearing loss, different colored irises, and a patch of white hair above their forehead known as “white forelock."

 Depending on what genes are affected, Waardenburg Syndrome can be further differentiated into Types I-Types IV. Types I and II have an autosomal dominant inheritance while Types III and IV have an autosomal recessive inheritance.

: Another diagnosis that can lead to hypopigmented macules as a cutaneous finding includes Piebaldism, an autosomal dominant inherited condition. Piebaldism results when genes, KIT and SNIA2, are mutated.

KIT2 is an important signaling protein of melanocytes during embryogenesis. It activates the Ras/MARK pathway which contributes to production of melanin.

 SIAD2 is crucial to neural crest cell production which helps produce melanocytes.

 When either of these proteins are mutated, melanocyte production is decreased and hypopigmented macules can be seen on exam. In contrast to Blaschko lines, the hypopigmented areas are symmetrical on each side of the body.

 In addition to hypopigmentation, Piebaldism shares the “white forelock” characteristic seen in Waardenburg syndrome.

: Nevus depigmentosus, or achromic nevus, is a congenital skin condition seen at birth or during changes in development. Patients present with a serrated, unilateral, pale patch of skin that remains stable over time and does not cross the midline.

 Genetic mosaicism can lead to nevus and thereby cause a decreased production of melanocytes or even decreased production in melanin.

 There are 3 variants of Nevus depigmentosus: Isolated (solitary patch), Segmental (patch following Blaschko lines), and Systematized (swirled areas of skin).

 In 50% of patients diagnosed with Nevus depigmentosus, the discolored patch of skin is isolated.

 This single, isolated patch distinguishes nevus depigmentosus from the many lines of Blaschko all over our bodies.

Genetic mosaicism can be tested prenatally through amniocentesis from the uterus or chorionic villus sampling from the placenta. Furthermore, a karyotype can be done after birth to detect any chromosomal abnormalities if present. When a child presents with cutaneous lesions at birth, he or she can be evaluated based on history, presentation, and initial differential diagnoses listed above. Our patient was diagnosed with hypopigmented Blaschko lines by looking at the delinear presentation of the lines, characteristics of pigmentation, and their location.

Although not required, for patients that wish to treat hyperpigmented Blaschko lines, they have the option to be treated with laser or topical hydroquinone and sunscreen. The treatment for patients with hypopigmented Blaschko lines is the option to use cosmetic cover up, pigmentary tattoos, dermabrasion, and phototherapy.

Our patient’s mother was worried about the lesions on her son’s back which were present since birth so she brought the patient in to be evaluated. The patient was noted to have hypopigmented Blaschko macules on the midline of his back and extensor surface of his right arm. Furthermore, the patient had an MRI brain/spine done with no abnormal findings. In light of his normal growth and development and MRI findings, we were able to reassure his mother that he would continue to grow and develop normally.

When caring for patients with lesions similar to our patient, it is important to thoroughly educate these patients on the causes behind Blaschko lines. We must also be mindful to understand the role that these lesions may play on the emotional and mental health of our patient.

Alkhowailed, Mohammad S et al. “Clinical Approach to Linear Hyperpigmentation: A Review Article.” 

Clinical, cosmetic and investigational dermatology

 vol. 14 23-35. 8 Jan. 2021, doi:10.2147/CCID.S280819

, 26 Aug. 2021, https://www.pcds.org.uk/clinical-guidance/blaschkos-lines.

Di Lernia, Vito. “Linear and whorled hypermelanosis.” 

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Hewedy, E. , Hassan, A. , Salah, E. , Sallam, F. , Dawood, N. , Al-Bakary, R. , & Al-Sharnoby, H. (2013). Clinical and ultrastructural study of nevus depigmentosus. 

Jindal, Rashmi et al. “Ash-leaf spots or naevus depigmentosus: a diagnostic challenge.” 

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Jun Yi Wong, Daniel. “Achromic Naevus.” 

, 2013, https://dermnetnz.org/topics/achromic-naevus.

Kouzak, Samara Silva et al. “Cutaneous mosaicisms: concepts, patterns and classifications.” 

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, U.S. National Library of Medicine, 18 Aug. 2020, https://medlineplus.gov/genetics/condition/piebaldism/#resources.

Senner, Sonja, et al. “Linear Patterns of the Skin and Their Dermatoses.” 

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, 22 June 2015, https://rarediseases.org/rare-diseases/waardenburg-syndrome/.

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You are asked to evaluate an African American boy aged 4 years with a birthmark on his back and right arm. He is healthy with normal growth and development. What's the diagnosis?

Congenital hypopigmented macules on a healthy child 

 in the United States, but the 50 states have different per capita spending and rates of increase.

“Varied Health Spending Growth Across US States Was Associated With Incomes, Price Levels, and Medicaid Expansion, 2000-19,” was published in August in 

 per person across the 50 states and Washington, D.C., up to the year before the COVID-19 pandemic.

Researchers aimed to illuminate “changes in health spending during a period with substantial changes in health policy at the state and federal levels,” including the Affordable Care Act (ACA) of 2010 and its provisions for Medicaid expansion after 2014.

“Official state-specific spending estimates that date back to 2014 are not recent enough to enable analyses that consider newer policies or changing state characteristics,” the study said. “In addition, structural, legal, economic, and demographic features vary across US states and types of payers, resulting in substantial variation in health spending across states and payers that is challenging to interpret.”

In 2014, residents of Utah had the lowest annual spending per person at $5,982, while Alaskans spent the most, $11,064 per person per year. Five years later, those states retained their ranks at lowest and highest amounts – $7,250 a year for Utah residents, $14,500 for Alaska residents, according to the analysis.

Primary data came from sources including the U.S. Centers for Medicare & Medicaid Services, the American Hospital Association, the U.S. Commerce Department’s Bureau of Economic Analysis, and the Medical Expenditure Panel Survey.

In 2019, Medicare as a percentage of total health spending ranged from 9% in Alaska, to 30% in Florida.

Medicaid as a percentage of total health spending ranged from 10% of total health spending in South Dakota, to 26% of total health spending in Washington, D.C.

Private insurance as a percentage of total health spending ranged from 25% in West Virginia to 49% in Washington, D.C.

Out-of-pocket payments as a percentage of total health spending ranged from 12% in Washington, D.C., to 42% in Alaska.

Researchers noted the expansion of Medicaid “had a complex relationship with state spending growth.” But emerging trends about the effects of the ACA show increased state and national spending is associated with increased 

, especially for financially disadvantaged patients.

Researchers analyzed spending categories including hospitals, physicians/clinics, nursing facilities, home health, dental, pharmaceutical, and other professional spending categories. In all states, hospitals and physician and clinical services received the most from health care spending per person.

Hospital spending, as a percentage of total health spending, ranged from 35% in New Jersey to 51% in South Dakota.

Physician and clinical services, as a percentage of total health spending, ranged from 16% in Vermont to 30% in Alaska.

There were six non-health-system factors tested to explain variation in health spending per person. They accounted for 77.2% of variation in state per capita health spending from 2000 to 2019:

Behaviors such as physical activity levels and smoking (8%)

For income and regional prices, wealthiest states with the highest prices had the highest estimated per capita spending, while lower income states had lower spending, despite having greater need for health care “because of systematically worse health.”

The researchers noted 22.8% of spending was left unexplained. “This finding calls for a reexamination of possible factors underlying the often piecemeal, state-specific approach to addressing the rising cost and uneven quality of health care,” the study said.

This article was published by our sister publication Medical Economics.

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