Dermatologic Update

From the 20th Annual Las Vegas Postgraduate Pediatric Conference: Advances in Pediatrics, presented by the American Academy of Pediatrics, California Chapter 2

Robert Sidbury, MD, MPH, Assistant Professor, Chief, Dermatology Program, Division of Dermatology, Department of Pediatrics, Seattle Children’s Hospital, University of Washington School of Medicine, Seattle

Educational Objectives

The goals of this program are to improve diagnosis and treatment of pediatric dermatologic diseases and to examine current recommendations on vitamin D from a dermatologic and pediatric perspective.

1.   List the similarities and differences between atopic dermatitis (AD) and psoriasis.

2.   Explain how to clinically differentiate AD from psoriasis.

3.   Discuss the process whereby steroid use thins skin and enumerate measures for avoiding thinning.

4.   Describe the issues associated with exposure to the sun and vitamin D supplementation.

5.   Identify the health states recently linked to vitamin D deficiency.

Faculty Disclosure

In adherence to ACCME Standards for Commercial Support, Audio-Digest requires all faculty and members of the plan­ning committee to disclose relevant financial relationships within the past 12 months that might create any personal con­flicts of interest. Any identified conflicts were resolved to ensure that this educational activity promotes quality in health care and not a proprietary business or commercial interest. For this program, Dr. Sidbury and the planning committee re­ported nothing to disclose.

Acknowledgments

Dr. Sidbury spoke at 20th Annual Las Vegas Postgraduate Pediatric Conference: Advances in Pediatrics, presented April 16-19, 2009, by the American Academy of Pediatrics, California, Chapter 2. The Audio-Digest Foundation thanks Dr. Sidbury and the American Academy of Pediatrics, California, Chapter 2 for their cooperation in the production of this program.

The Yin and Yang of Atopic Dermatitis and Psoriasis

Similarities: both diseases  —  common; associated with Th1 and Th2 inflammatory cytokines; cause unknown; T-cell-mediated; frequently found on elbows and knees; steroid-responsive; systemic therapy  —  used after failure of topical treatment; cyclosporine most effective and fastest-acting; oral prednisone used as last resort due to rebound after discontinuation of treatment (administer for 2-3 wk, then taper off while reintroducing topical treatment)

Differences: psoriasis  —  life-long condition; atopic dermatitis (AD)  —  one form of eczema; improves somewhat each year and resolves by school age; warn parents to expect occasional disease spikes; parents often attribute flares to food allergies (possible, but more likely due to waxing and waning of disease)

Diagnostic dilemma: may see features of AD and psoriasis in one child; rare to have both conditions; AD typically itches, while psoriasis typically does not

Associated conditions: atopic triad  —  eczema, asthma, hay fever; atopic march  —  eczema as baby, asthma as child, hay fever as adult; progression through all 3 does not always occur, but baby with AD at increased risk for asthma; therefore, counsel parents about eliminating tobacco smoke and dust mites in home; psoriatic arthritis  —  uncommon in children

Atopic Dermatitis

Triggers: allergies  —  can be relevant; however, speaker finds most issues resolve without dietary changes when ap­propriate skin care regimen followed; causes of flares (in order of importance)  —  changes in bathing and moistur­izing regimen; seasonal changes in humidity; bacterial infection; allergies; vaccination (due to stimulation of immune system)

Risk for infection: children with AD experience repeated superinfection with Staphylococcus aureus (unusual with psoriasis)

Innate immunity: cathelicidins  —  antimicrobial peptides; do not require previous exposure (not memory cell depen­dent); study found low levels in children with eczema; levels normal or up-regulated in children with psoriasis

Eczema herpeticum: widespread herpetic infection in child with AD; appearance different from S aureus infection; characterized by “punched out” or crater-like erosions and vesicles; S aureus infection superimposed on herpes infection can make diagnosis difficult; examine periphery for discrete focal herpetic lesions; parents experienced with S aureus infections in child may notice “something is different” (eg, fever, lack of appetite)

Lifelong concerns: propensity for dryness of skin; rash with excessive washing and drying of skin; hyperirritancy (eg, to wool clothing); increased risk for infections of skin; smallpox vaccination  —  contraindicated by history of eczema; case history documents incident in which child with eczema exposed via father’s vaccination (received be­fore military deployment); child nearly died of smallpox

Treatment considerations: inflammation (treat with topical steroids); superinfection; Staphylococcus carriage; basic skin care; special considerations  —  food allergies; primary immunodeficiency

Topical steroids: can treat through superinfection while administering either topical or oral antibiotics; treat eczema herpetica before using topical steroids; potency  —  no stronger than Class VI on face (emollients or over-the-counter hydrocortisone for babies); 0.1% triamcinolone ointment on body; vehicle  —  ointment preferred over cream (more efficient for getting steroid molecule into skin); empower parents to avoid thinning of skin

Precautions and concerns: periocular use  —  avoid when possible; if necessary, use weakest formulation or nonsteroi­dal agent; reported incidence of adverse periocular or ocular effects rare; hypothalamus-pituitary-adrenal (HPA) axis suppression  —  rare; smaller infants with wider involvement at greatest risk; cancer  —  no documented link

Reducing risks of steroid use: describe natural history of thinning of skin; no refills; mandatory breaks in application, rather than limits (eg, daily use for 1 wk, then skip 1 wk); touch test  —  if skin dyspigmented but normal to touch (with eyes closed) and not itching, means area in healing process (ie, not eczema); moisturize instead of applying steroids; thinning skin  —  begins with broken blood vessels and progresses to papery skin (reversible); ultimately be­comes stretch mark or stria (nonreversible scar)

Superinfection: culture skin and nares; mupirocin if localized; cephalexin (pending culture) if not localized

Carrier state: for recurrent superinfection, suggest bleach bath; if parents balk, compare to swimming pool with chlorine; avoid “double-dipping” into moisturizer (container of, eg, petroleum jelly, becomes culture dish for in­fectious organism)

Emollients and barriers: ointments preferred over creams, creams preferred over lotions (but order of preference may be reversed in hot and/or humid weather); barriers  —especially important for infants; apply before meals and after post-meal washing of face

Psoriasis

Characterization: described as hyperproliferative; whereas it generally takes 30 days to shed layer of skin, plaque of psoriasis takes 4 days (extremely rapid turnover); locations  —  umbilicus; intergluteal cleft; concha of ears; Koebner phenomenon  —  skin disease (psoriasis and others) induced by minor trauma

Treatment: determined by extent of disease and impact on patient; topical steroids  —  need strong formulation, as plaque presents significant barrier to treatment; calcipotriene (eg, Dovonex)  —  vitamin D analogue; can be used for therapeutic trial to distinguish between psoriasis and eczema (improves psoriasis, but not eczema); tazarotene  —variation of tretinoin (eg, Retin A); tar  —  acceptable therapeutic option

Inverse psoriasis (pityriasis rosea): confluent plaques in axilla or groin; easily missed, as constant moisture pre­vents scaliness in these locations; differential diagnosis includes intertrigo and seborrheic dermatitis

Nail psoriasis: not just pitting; oil spot discoloration; nail bed erythema; subungual debris (often mistaken for ony­chomycosis); linked with psoriatic arthritis (especially with inflammation on distal pad and proximal nail folds, and nail dystrophy)

Scalp psoriasis: usually characterized by sharp demarcation and silvery scale; some presentations referred to as tinea amiantacea due to resemblance to fungal infection; check for lymphadenopathy (associated with tinea, but not with psoriasis); treat with shampoos, topical steroids, oils (eg, Derma-Smoothe), and foams

Widespread disease: discrete dewdrop plaques; consider streptococcal infection

New systemic therapies: mostly injected or infused biologic agents; speaker does not recommend (expensive and as­sociated with many adverse side effects)

Vitamin D Deficiency: Current Recommendations

Questions: is vitamin D deficiency epidemic, or should definition of deficiency be adjusted? does vitamin D really affect as many health states as purported (ie, is it another false panacea)? if vitamin D deficiency as widespread as purported, why not supplement orally (and avoid health risks associated with exposure to sun)?

Epidemiology

Historical perspective: phytoplankton generate vitamin D from sun exposure, as do most vertebrates; according to theory of evolution, humans originated in Africa; change in baseline pigmentation occurred as humans migrated to less sunny climates; lighter pigmentation may have been driven by need for more vitamin D; rickets  —  became prevalent in 18th and 19th centuries, when humans began living in more industrialized areas; cured by exposure to sun and supplementation; milk fortification  —  began in 1930s and reduced prevalence of rickets (people also en­couraged to get more exposure to sun; no concurrent rise in rate of skin cancer); in 1950s, case of infantile hyper­calcemia resulting from fortified milk in United Kingdom (UK) led to ban on fortification in UK

Deficiency: 1,25 dihydroxyvitamin D [1,25(OH)2D]  —  active molecule; half-life too short for measurement of level; 25 hydroxyvitamin D [25(OH)D]  —  storage molecule; longer half-life; measured to determine vitamin D level; physiologic definitions  —  derived from observation that supplementing deficient patients leads to leveling off of compensatory hyperparathyroidism (ie, parathyroid hormone level drops as vitamin D level rises); <20 ng/mL 25(OH)D determined to be deficient; 20 to 30 ng/mL, insufficient; >30 ng/mL, sufficient; by these definitions, 1 billion people worldwide with low vitamin D stores; no consensus on optimal levels; current recommended levels based on bone health; requirements for brain, skin, and nerve health unknown; laboratory tests  —  imperfect; lack standardization

Vitamin D and pediatrics: deficiency linked to increased risk for respiratory infection and eczema; maternal vitamin D deficiency linked to increased risk for asthma in children; deficiency and/or absorption issues implicated in pathophysiology of many other diseases (eg, HIV, cystic fibrosis, chronic renal disease); impact on calcium absorp­tion also important

High-risk populations: elderly; obese; pregnant; individuals with granulomatous disease; those in equatorial regions generally not deficient, but cultural practices (eg, wearing burka) can limit exposure to sun; large percentage of His­panic and black children in Boston found to be insufficient or deficient; 48% of preadolescent white girls in Maine found to be insufficient or deficient at end of winter, and 20% remain so by end of summer; 32% of medical stu­dents, residents, and doctors at Boston hospital found deficient, despite adequate diet and supplementation

Reasons for low levels: insufficient dietary intake (few foods rich in vitamin D; requires 1 qt of milk to fulfill daily requirement); lack of supplementation; aberrant metabolism; sun protection

Sources of vitamin D: sun  —  exposure converts vitamin D precursor (7-dehydrocholesterol; generated by body) to vitamin D₃; acted upon by liver; passes to kidney; produces active molecule; dietary intake  —  acted upon by liver and follows same route

UV rays: only UV-B range generates vitamin D; also responsible for sunburn (reason dermatologists cautious about suggesting exposure to sun for obtaining adequate vitamin D); 1 minimal erythematous dose (MED; enough to make skin turn pink) produces 20,000 IU of vitamin D, equivalent to 200 glasses of milk (ie, sun more efficient source of vitamin D than diet)

General health: vitamin D deficiency associated with multiple sclerosis (MS) and many cancers; almost every cell line has vitamin D receptor; vitamin D-resistant rickets  —mutation in receptor; cannot be overcome by increasing natural or supplemental levels

Supplementation issues: excess produced via exposure to sun does not lead to vitamin D intoxication (gets photo­metabolized), whereas toxicity possible with dietary supplementation; vitamin D₂ vs D₃  —  molecules almost iden­tical; most supplements contain D₂ (acceptable), although D₃ considered more active form

Macrophages: recently discovered to produce active 1,25(OH)₂D, independently from liver and kidneys; also pro­duce antimicrobial peptides; reduced levels of these peptides (eg, in AD and psoriasis) increase risk for infection; may have implications for susceptibility to tuberculosis in blacks

Research

Multiple sclerosis: no large randomized controlled clinical trials; above 35° latitude, UV-B rays filtered out by ozone (vitamin D production prevented); prospective observational studies show risk for MS reduced significantly in pro­portion to incremental increases in 25(OH)D; animal models support these findings

Neoplasia: breast, prostate, lung, and colon cancer, as well as cancer cell lines, show relationship between vitamin D and increased apoptosis, angiogenesis, and carcinogenesis

Risk for cardiovascular disease: effects renin and self-regulation of blood pressure

Diabetes: 1960s study  —  newborns in Finland given 2000 IU vitamin D during first year of life; by age of »30 yr, huge reduction seen in rate of type 1 diabetes

Problems with research: most studies epidemiologic, and therefore prone to bias and confounding (eg, experience with hormone replacement therapy); need to be circumspect with interpretation of data

Recommendations for supplementation: currently, 400 IU per day (may be “woefully” inadequate); toxicity “prob­ably” not expected with <10,000 IU per day

Melanoma: sun exposure known to cause skin cancer; however, most melanomas (especially aggressive types) occur in sun-protected areas; also, facial melanomas correlated with best survival rates have most solar elastosis (histo­logic marker for sun damage)

Atopic dermatitis: keratinocytes can make active vitamin D and generate antimicrobial peptides; worsening of AD in winter typically linked to use of heaters and decreased humidity, but may be related to decreased levels of vita­min D; frequent skin infections in children with AD may be related to vitamin D deficiency and lack of antimicro­bial peptides; in speaker’s pilot trial of vitamin D supplementation for AD, unknown at outset whether treatment group would benefit (equipoise); 80% of patients receiving vitamin D improved, compared to 17% of patients re­ceiving placebo

Suggestions: risk-stratify patients; if recommending sunscreen, also discuss vitamin D awareness and balance mes­sage with one about prudent exposure to sun; consider checking vitamin D levels; most experts recommend supple­mentation of 200 to 400 IU per day, but likely inadequate (speaker takes 1000 IU daily)

Suggested Reading

Boguniewicz M et al: MAS063DP is effective monotherapy for mild to moderate atopic dermatitis in infants and children: a mul­ticenter, randomized, vehicle-controlled study. J Pediatr 152:854, 2008; Breneman D et al: Intermittent therapy for flare preven­tion and long-term disease control in stabilized atopic dermatitis: a randomized comparison of 3-times-weekly applications of tacrolimus ointment versus vehicle. J Am Acad Dermatol 58:990, 2008; Callen J et al: A systemic review of the safety of topical therapies for atopic dermatitis. Br J Dermatol 156:203, 2007; Gordon CM et al: Prevalence of vitamin D deficiency among healthy adolescents. Arch Pediatr Adolesc Med 158:531, 2004; Holick MF: Vitamin D deficiency. N Engl J Med 357:266, 2007; Holick MF et al: Vitamin D2 is as effective as vitamin D3 in maintaining circulating concentrations of 25-hydroxyvitamin D. J Clin Endocrinol Metab 93:677, 2008; Krakowski AC et al: Topical therapy in pediatric atopic dermatitis. Semin Cutan Med Surg 27:161, 2008; Krakowski AC et al: Management of atopic dermatitis in the pediatric population. Pediatrics 122:812, 2008; Munger KL et al: Serum 25-hydroxyvitamin D levels and risk of multiple sclerosis. JAMA 296:2832, 2006; Ong PY et al: Atopic dermatitis. Clin Allergy Immunol 16:355, 2002; Ong PY et al: Endogenous antimicrobial peptides and skin infections in atopic dermatitis. N Engl J Med 347:1151, 2002; Osborne JE et al: Vitamin D and systemic cancer: is this relevant to malignant melanoma? Br J Dermatol 147:197, 2002; Paller AS et al: Etanercept treatment for children and adolescents with plaque psoria­sis. N Engl J Med 358:241, 2008.