The Chinese proverb says “A journey of a thousand miles begins with a single step”. That single step was September 30, 2004 and it started a journey of 1,000 general pediatric cases. What an amazing journey it has been!

What started as a way of extending learning after a clinical encounter for residents and medical students, has really highlighted how there is something to learn from every clinical encounter. PediatricEducation.org shows how many other people can benefit from those encounters as well.

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Donna M. D’Alessandro and Michael P. D’Alessandro
Curators, PediatricEducation.org

Patient Presentation
An intern in her continuity clinic shared a teenage patient she had admitted to the inpatient floor with only facial swelling. “She really didn’t have anything else on physical exam, but her labs were off and she just didn’t look right,” he said. “That’s an odd one. Entire facial swelling, not just the eyes or a more localized edema? No other areas of body edema either?” asked the attending. “No nothing else really on physical exam. No specific rashes, no fever, no weight loss, no urinary or GI problems. Her hemoglobin was a little low as was her WBC count. UA was normal,” the intern said. “We’ll I’m thinking that if she is still in the hospital, then it isn’t straight forward. You must have all looked at renal or allergic disease with the swelling. A localized cancer doesn’t seem to fit and it doesn’t seem like something metastatic. Autoimmune problems and unusual infectious diseases most likely a virus are big categories, but there could be lots of things. Two diseases that have a wide range of presentations that sometimes don’t seem logical are EBV virus and SLE,” the attending remarked. “I talked with the intern this morning and their working diagnosis is SLE, but they are not sure. Viruses and EBV were negative. They are still in the process of evaluating her. They even did some test where they use snake venom,” she said. “That is why you need a rheumatologist and maybe even a couple of other specialists to help you when it is that specific. Just remember that some of your best differentials may come from the person with a wide viewpoint like a generalist, or even a radiologist or pathologist. These people don’t think of things by just one specialty. There are some really good specialists who also take that wide viewpoint too and can really help when things are not clear,” the attending stated. She went on, “I hope they figure it out soon so that she can start to get better. It’s hard not feeling well and not really knowing too.”

Discussion
Lupus erythematosus is one of the classic autoimmune diseases. Its presentations, evaluation and management can be challenging for even seasoned practitioners. Cutaneous lupus erythematosus as it implies involves the skin but can progress to systemic involvement. Systemic lupus erythematosus (SLE) usually involves multiple organ systems concurrently. Childhood (sometimes called juvenile) SLE is usually defined as occurring before age 18 years. Estimates are 15-20% of patients with SLE started having symptoms before age 18 years, with most occurring after age 10 years. Childhood SLE often has a more aggressive course and high incidence of end organ damage especially kidney disease.

As the presentations and problems can be diverse and there are other potential diagnoses, especially other autoimmune problems, professional groups have used criteria which can aid diagnosis, treatment and further research. Current criteria from Europe and the US (EULAR/ACR criteria) from 2019 include:

• ANA antibodies at a titre of ≥1:80 or HEp-2 cells or equivalent positive test (Must be present to diagnosis SLE) [Note: ANA antibodies are present in ~99% of patients with SLE. Anti ds-DNA and anti-Smith antibodies have good specificity for SLE.]
• If ANA is present then a variety of domains with different additive criteria are used and a total score of ≥10 or more is needed to make the diagnosis of SLE. There are caveats about how to apply the criteria as well.
• Domains evaluated include constitutional symptoms, hematologic, neuropsychiatric, mucocutaneous, serosal, musculoskeletal, renal, antiphosolipid antibodies, complement proteins and SLE-specific antibodies.

Neonatal lupus is not the same as SLE. Neonatal lupus is due to maternal antibodies crossing the placenta during gestation which then affect the fetus and neonate, especially cardiac, liver and hematological problems. As the autoantibodies wane, symptoms, if any, disappear with time. A review can be found here.

New treatment guidelines for SLE from the American College of Rheumatology became available in 2025. “Hydroxychloroquine should be standard therapy for all people with SLE unless contraindicated.” Glucocorticoids are to be used for initial treatment and flares with tapering as soon as possible. Other commonly used medications include azathioprine, cyclophosphamide, calcineurin inhibitors and a variety of biological medications. SLE can go into remission and also recur. Therefore ongoing daily treatment with these medications can be tapered or stopped in the right circumstances, but patients need to be monitored. Likewise life- or organ-threatening disease may require intense, prolonged treatment. Ten-year survival rates are very high (90% +) and often are related to the intensity of the kidney disease the patient has.

Learning Point
Problems associated with SLE are due to its inflammatory or thrombotic tendencies. However it is important to note, that the treatment drugs can cause side effects which can be the same or similar to the disease itself. Living with any disease can also have problems that may overlap with the disease itself. For example, painful joints may decrease activity, which can cause overall deconditioning which can cause fatigue. Depression can be caused by living with SLE, SLE disease itself, or some of the drugs used to treat it. This highlights how difficult it can be to diagnose and manage problems associated with SLE.

While the “classic” SLE presentation of malar rash, joint pain and fever is what is taught, in childhood SLE, patients frequently present with fever, fatigue and arthritis. SLE can have a variety of presentations and problems with which to manage. Unexplained fever, arthritis with rash, cytopenias, neurological disease and kidney disease should have SLE considered as a possible diagnosis. Below are some of the presentations and problems associated with SLE. Those with an asterisk are part of the EULAR/ACR criteria.

• Constitutional
  • *Fever
  • Fatigue
  • Weight loss
• Hematologic
  • *Autoimmune hemolysis
  • *Leukopenia
  • *Thrombocytopenia
  • Lymphadenopathy
  • Splenomegaly
  • Thrombosis of various organs
• Neuropsychiatric
  • *Delirium
  • *Psychosis
  • *Seizure
  • Cognitive deficits
  • Chorea
  • Encephalopathy
  • Headache
  • Mood disorders
  • Transverse myelitis
  • Stroke
  • Cranial nerve problems
  • Peripheral nerve problems
    • Paresthesia
    • Guillain-Barre syndrome
    • Myasthenia-like syndrome
• Mucocutaneous
  • *Alopecia, non-scaring
  • *Acute cutaneous lupus = malar or butterfly rash over nasal bridge and cheeks
  • *Subacute cutaneous lupus – photosensitive
  • *Discoid lupus
  • *Oral ulcers (usually painless)
  • Nasal ulcers
  • Bullae
  • Cutaneous vasculitis
  • Chilblains
  • Erythema nodosum
  • Gangrene
  • Palpable purpura
• Serosal
  • *Pericardial effusion
  • *Acute pericarditis
  • *Pleural effusion
  • Endocarditis
  • Myocarditis
  • Cardiac tamponade
  • Peritonitis
• Musculoskeletal
  • *Joint involvement both large and small
  • Polyarteritis/arthralgia
• Renal
  • *Proteinuria
  • *Renal biopsy with specific diagnostic criteria
    • Glomerulonephritis
    • Interstitial nephritis
  • Nephrotic syndrome
  • Hypertension
• Antiphosolipid antibodies
  • *Anti-cardiolipin antibodies
  • *Anti-β2GP1 antibodies
  • *Lupus anticoagulant
• Complement proteins
  • *Low C3 and/or low C4
• SLE-specific antibodies
  • *Anti-dsDNA antibody
  • *Anti-Smith antibody
• Other lab testing
  • DAT (Coomb’s) positive
  • Dilute Russell’s Viper Venom Time
• Endocrine
  • Diabetes mellitus
  • Hypothyroid
• Gastroenterology
  • Bowel (enteritis)
  • Hepatitis
  • Pancreatitis
  • Hepatomegaly
  • Splenomegaly
• Ocular
  • Dry eyes
  • Eyelids – edema, erythema, ecchymosis
  • Conjunctivitis, scleritis, keratitis, uveitis
  • Retinopathy and choroid changes
  • Optic nerve neuropathy or neuritis
  • Papilledema

Questions for Further Discussion
1. What are the criteria for diagnosing juvenile idiopathic arthritis?
2. What is in the differential diagnosis of limp? A review can be found here
3. What are indications for a renal biopsy?

Related Cases

Disease: Lupus

Symptom/Presentation: Edema

Specialty: General Pediatrics | Infectious Diseases | Rheumatology

Age: Teenager

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: Lupus

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.

Aringer M, Costenbader K, Daikh D, et al. 2019 European League Against Rheumatism/American College of Rheumatology Classification Criteria for Systemic Lupus Erythematosus. Arthritis & Rheumatology. 2019;71(9):1400-1412. doi:10.1002/art.40930

Mann MP, Sage AM, McKinnon E et al. Childhood Systemic Lupus Erythematosus: Presentation, management and long-term outcomes in an Australian cohort. Lupus. 2022;3(2):246-255. doi:10.1177/09612033211069765

Curtiss P, Walker AM, Chong BF. A Systematic Review of the Progression of Cutaneous Lupus to Systemic Lupus Erythematosus. Front Immunol. 2022;13:866319. doi:10.3389/fimmu.2022.866319

Chandwar K, Aggarwal A. Systemic Lupus Erythematosus in Children. Indian J Pediatr. 2024;91(10):1032-1040. doi:10.1007/s12098-023-04833-0

Nikolaidou A, Gianni T, Sandali A, Toumasis P, Benekos K, Tsina E. Ocular manifestations of Juvenile Systemic Lupus Erythematosus: a systematic review. Eye (Lond). 2025;39(6):1056-1069. doi:10.1038/s41433-025-03664-x

Sammaritano LR, Askanase A, Bermas BL, et al. 2025 American College of Rheumatology (ACR) Guideline for the Treatment of Systemic Lupus Erythematosus. Arthritis Care Res (Hoboken). Published online November 3, 2025. doi:10.1002/acr.25690

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

Patient Presentation
An 8-year-old male came to clinic for his well child visit. He was being treated for strabismus and amblyopia with glasses and patching. His mother said he was mainly compliant with the glasses but wasn’t very much with the patching as he didn’t like looking different than his friends. She had tried multiple methods to try to increase compliance, and reported about 2 hours of patch use/day. “He likely is going to need surgery and I just don’t want to do that,” she said. “I read about some of these vision therapies but he won’t use the patch so I don’t think he’ll do the therapy either. Is there something else?” she asked.

The pertinent physical exam revealed a healthy male with normal vital signs who was growing at the 50%. His physical examination was normal. The diagnosis of a healthy male with vision problems was made. “I’m not the right person to give you all the options; that needs to be his ophthalmologist. But I think there are eye drops that are sometimes used instead of the patching that you can ask them about next week at his appointment. The vision therapies are newer, and again I don’t know much about them. They are certainly not so revolutionary that the studies are being highlighted by the professional organizations and media outlets. I suspect any benefit is probably modest, but again ask the eye doctor next week,” she counseled. “I’ll also give you some ideas how to get him to use the patch.”

Discussion
Amblyopia is a neurodevelopmental visual disorder that is usually monocular but sometimes binocular that has a decrease in visual acuity where there are problems with visual processing but where no organic cause can be identified. Functionally, amblyopia is widely defined based on visual acuity (VA) where there is a “…difference of two or more Snellen’s or logarithm of the minimum angle of resolution (log MAR) lines in BCVA [best-corrected visual acuity] between the normal and amblyopic eye in cases of unilateral amblyopia. For bilateral amblyopia, BCVA should be less than 6/12.” Amblyopia is extremely common with a prevalence between 1-6% in the pediatric age range and 1.43-5.64% in adults. It is classified as mild, moderate or severe based on BCVA, and also classified into refractive, strabismic or stimulus deprivation. Theoretically, the normal and amblyopic eyes have visual images that are mismatched, and the brain suppreses the weaker eye’s image leading to poor acuity in the amblyopic eye. Problems that arise because of amblyopia include “…reduced contrast sensitivity, poor spatial localization, poor stereovision, and foveal crowding.”

Learning Point
The treatment goal is to reduce the acuity differences between the eyes and maintain the improved vision. Most treatments focus on monocular therapy. Treatment at an earlier age has better outcomes than older ages. Patients who are successfully treated still need monitoring.

Potential treatment options include:

• Refractive correction
  • Considered first line treatment
  • 27-32% overall improvement
  • Initially often done alone for several weeks before using other treatments. Also used as combined treatment
• Patching
  • Considered second line treatment
  • Can be used alone or often in combined treatment
  • Up to 70% respond to occlusion (including using cycloplegic penalization – see below)
  • Some studies cite continued amblyopia after refractive correction and patching at 50% of patients
  • Number of patching hours depends on the patient. Studies have shown that shorter time periods may be as effective as longer time periods, but compliance was not objectively measured in at least one major study
  • Preferred patch is a direct skin patch
  • Often needs weaning off the patch after clinically improved VA
• Cycloplegic penalization
  • A cycloplegic drug is instilled in the normal eye to blur its vision and make patient use the amblyopic eye
  • Also considered second line treatment
  • Can be used alone or often in combined treatment
  • Up to 70% respond to occlusion (including using cycloplegic penalization – see below)
  • Can be good in patients with allergies to the patches, non-compliant patients or those with patching failures
• Bangerter filters
  • A filter is attached to glasses and degrades the visual acuity
  • Used as treatment or maintenance therapy after patching or penalization
• Surgery
  • Not a direct treatment, but a treatment for strabismus which can cause amblyopia
  • Corrects visual axis obstruction or misalignment
  • Botulinum toxin can also be used for muscle alignment successfully in some populations
• Other novel therapies
  • These have fewer outcome studies available, potentially high rates of non-compliance with treatment, or limited outcome measures, but do have some data that could be helpful for some patients
  • Liquid crystal glasses
    • Provide intermittent occlusion where crystals in the glasses rapidly alternate between clear and occluded
  • Perception therapy
    • Binocular therapy
    • Idea to improve perception of the visual images
  • Visual display therapy which may include videogame play
    • Binocular therapy
    • Main idea is for visual stimuli to be presented to both eyes and then the eyes have to work together to complete a task
  • Drug treatments
    • Examples include Levo-dopa, Citicoline, Donepezil, and Selective serotonin reuptake inhibitors
    • Main idea is to improve brain plasticity so other treatments may have improved outcomes
    • “…[M]ore randomized trials with larger sample sizes and longer periods of follow-up are required to substantially prove or disprove the benefits of these drugs”

Questions for Further Discussion
1. How good is photoscreening for vision problems in young children? A review can be found here
2. How can you increase compliance for use of glasses? A review can be found here
3. What are potential complications of contact lens use?

Related Cases

Disease: Amblyopia | Strabismus | Vision Impairment and Blindness

Symptom/Presentation: Blurred Vision

Specialty: Ophthalmology

Age: School Ager

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: Amblyopia and Eye Movement 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.

Bui Quoc E, Kulp MT, Burns JG, Thompson B. Amblyopia: A review of unmet needs, current treatment options, and emerging therapies. Survey of Ophthalmology. 2023;68(3):507-525. doi:10.1016/j.survophthal.2023.01.001

Chaturvedi I, Jamil R, Sharma P. Binocular vision therapy for the treatment of Amblyopia – A review. Indian J Ophthalmol. 2023;71(5):1797-1803. doi:10.4103/IJO.IJO_3098_22

Kaur S, Sharda S, Aggarwal H, Dadeya S. Comprehensive review of amblyopia: Types and management. Indian J Ophthalmol. 2023;71(7):2677-2686. doi:10.4103/IJO.IJO_338_23

Chen DML, Han S, Summers A, et. al. Interventions for improving adherence to amblyopia treatments in children. Cochrane Database of Systemic Reviews 2025 (7). Art. No.: CD015820.

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

Patient Presentation
A pediatrician stopped her adolescent medicine colleague in the hallway for a quick consultation. “I have a young adult coming to see me who is a trans male. In their notes from the last visit, I saw that they had asked about a breast binder but I don’t know if that was done and if not, where I can send them or get more information for them,” she asked. “We can work with them in the adolescent clinic to get them measured and fitted. A couple of our nurses are trained to do that, and then they usually give them the resources to have them ordered, or sometimes some of the local non-profit agencies have them for low cost or free. I don’t know if any of the agencies do now, but the nurses will know. What time is the patient coming? I can have one of the nurses come over to your clinic if they want us to do the fitting,” the specialist offered. “They are coming late afternoon and I’ll ask them. They are also using oral contraceptives for pregnancy prevention and menstrual suppression and I’m very comfortable with that,” she said. “You know you can always ask me about any gender-related health issues you might not know about or don’t feel comfortable with. All of us working in the adolescent clinic can help, or we can refer the patient to other services, ” the specialist stated. “That’s why I stopped you. I knew I could ask and learn something. Helps me take better care of patients,” she said.

Discussion
Transgender and gender-diverse (TGD) youth in the US are estimated to be 300,000 or 1.4-2% of youth in the US. These numbers are for youth who identify as transgender or a gender identity that is different from their assigned sex at birth (ASAB). “However, the number of gender-diverse youth or youth whose gender expression does not confirm to societal expectations is estimated to be as high as 10% among U.S. high school students.” Among US adults, 1.4 million (0.6%) adults identify as transgender in a nationwide telephone survey.

TGD youth are or can be at increased risk for a variety of health problems including:

• Bone health – low dietary calcium, risk for bone loss
• Lifestyle – obesity, decreased activity
• Mental health – self-harm, suicidal ideation or attempts, depression, anxiety, eating disorders, substance use
• Sexual health – future fertility loss, pregnancy, sexually transmitted infections
• Social – bullying/harassment, discrimination, violence including sexual assault or dating violence, socioeconomic disparity including homelessness

Gender affirming care (GAC) is a broad term that is not synonymous with gender transition care. In GAC, “”…the goal (…) is to partner with TGD people to holistically address their social, mental and medical health needs and well-being while being respectfully affirming their gender identity.” GAC may include transition-related care such as puberty blockers, gender-affirming hormones (…), mental health support, and /or a range of therapies, including surgery.” GAC is not unlike the care pediatricians and other professionals provide to all patients in their practices, which would be compassionate, inclusive, holistic, and effective care. For any professional, there are limits to one’s knowledge and experience, so when this occurs professionals seek answers themselves or consult specialists who can manage and treat the patient, or partner with the professional to manage the patient.

Gender identity begins as early as 2 years and continues throughout childhood, adolescence and into young adulthood. The trajectory of gender identity is impossible to predict, and children and youth commonly explore their gender identity. Some people experience gender dysphoria but others may not. Some research “…suggests that the majority of prepubertal youth with gender dysphoria will ultimately identify as cisgender adolescents and adults, whereas postpubertal youth with gender dysphoria are more likely to continue experiencing gender dysphoria through adolescent and adulthood.” Late adolescence and adulthood can also be times where TGD identities also emerge.

Some terminology

• Gender identity – a person’s own felt sense of their gender (female, male, both, neither)
• Transgender/cisgender/nonbinary
  • Transgender – a person whose gender does not align with their ASAB
  • Cisgender – a person whose gender does align with their ASAB
  • Nonbinary – a person whose gender is neither strictly female or male, and exists along or outside of the spectrum of gender identity
• Gender expression – the way a person presents their gender to others
• Sexual orientation – the gender(s) to whom a person is sexually attracted such as gay, straight, bisexual, lesbian. This is distinct from gender identity
• Gender dysphoria – the distress a person experiences when their gender identity is not in alignment with their experience of their body or other’s perception of them
• Transition – “the process whereby an individual makes changes to their gender expression, physical body, name or pronouns for their lived gender role to align more closely with their gender identity”

Learning Point
Most care provided to TGD is the same care providers give to all of their patients. There may be some legal restrictions on specific types of care for TGD. Some specific care that TGD patients may need includes:

• Welcoming environment for all children, youth and young adults
  • Use of preferred name and pronouns has been shown to decrease depression, suicidal ideation and suicidal behaviors. Include this information in electronic medical record if the youth agrees, ASAB also needs to be recorded as some health risks are based on this
  • Inclusive physical space including signage and gender neutral bathrooms if possible
• History and physical examination
  • History taking using non gendered language
  • Appropriate confidentiality
  • Standard history for all youth including social, mental and sexual health histories
  • History includes youths’ experience with their gender identity such as social transitioning, gender dysphoria, family and community support
  • Trauma informed care sensitivity
  • Standard physical examination including monitoring for pubertal changes
• Body contours
  • Breast binding
    • To flatten the chest using breast binders, tight sports bras, or ace wraps
  • Male genital contouring
    • Tucking
      • To move the testicles and penis posteriorly or into the inguinal canals
    • Packing
      • To use devices to create the appearance of a penis such as socks, clothing, pouches, packers, etc.
    • Reversible, recommended to be used only for intervals of time
• Body hair
  • Referrals for body hair removal through lasers/electrolysis, depilatory, threading, waxing, etc.
  • Reversible or permanent
• Speech therapy/Voice training
  • Assistance in utilizing their voice that is more consistent with their gender identity
  • Reversible
• Hormonal therapy
  • Pregnancy prevention and menstrual suppression
    • Usually provided as part of general adolescent care
    • Reversible
  • Pubertal suppression – gonadotropin-releasing hormone analogues
    • May need referral to specialist or multidisciplinary clinic
    • Reversible
  • Exogenous gender affirming hormones – testosterone or estrogen
    • May need referral to specialist or multidisciplinary clinic
    • Most effects are considered irreversible, but some may be reversible
  • Fertility preservation
    • May need referral to specialist or multidisciplinary clinic
• Surgical intervention
  • These procedures may be performed at the age of majority, and need referral to a surgeon
  • Creation of desired anatomy
  • Removal or undesired organs
  • Modification of anatomy
• Sexual health
  • Routine sexual health screening and treatment
  • Pregnancy prevention and menstrual suppression
• Mental health
  • Therapy referrals for mental health or other social problems, including facilitating discussions of gender identity and exploration
• Social support
  • Health care providers are good supports for youth
  • Help assist identity disclosure to family or others
  • Provide support, education and mental health referrals for family members who may face challenges in accepting their child’s gender identity. As with all people, parental support has significant positive effects on TGD
  • Referral for legal services

Questions for Further Discussion
1. What resources do you have in your community for TGD?
2. What if any legal restrictions on treatment exist for TGD in your location?
3. How do you screen for substance abuse and what resources are available in your location?

Related Cases

Disease: Teen Health | Teen Development | Teen Mental Health | Teen Sexual Health

Symptom/Presentation: Health Maintenance and Disease Prevention

Specialty: Adolescent Medicine | Obstetrics / Gynecology | Nephrology / Urology | Social Services

Age:Young Adult

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: Teen Health, Teen Development and Teen Sexual Health.

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.

Voss, RV, Simons S. Supporting the Health of Transgender and Gender-Diverse Youth in Primary Care Settings. Prim Care Clin Office Pract. 2021:48;259-270.

Hodax JK, Crouch JM. Sethness JL. et. al. Strategies for Providing Gender-Affirming Care for Adolescents in the Primary Care Setting. Pediatr Ann. 2023;52(12);e442-e449.

Salvetti B, Gallagher M, Schapiro NA, Daley AM. Prioritizing Gender-Affirming Care for Youth: The Role of Pediatric-Focused Clinicians. Journal of Pediatric Health Care. 2024;38(2):253-259. doi:10.1016/j.pedhc.2023.12.006

Ho T, Ricklefs C. Healthcare for Sexual and Gender Minority Adolescents. Primary Care: Clinics in Office Practice. 2024;51(4):675-688. doi:10.1016/j.pop.2024.05.007

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