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ETAS_09 ped derm

  1. 1. 9  Pediatric Dermatology Andrea L. Zaenglein, MDC o n t e n t s9.1 Neonatal Dermatology . . . . . . . . . . . . . . . . . . . . . . . . . 3139.2 Childhood Infectious Diseases . . . . . . . . . . . . . . . . . 3189.3 Pigmented Lesions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3209.4 Dermal Tumors and Disorders . . . . . . . . . . . . . . . . . . 3249.5 Vascular Lesions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3269.6 Genodermatoses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 331 Photosensitivity Disorders . . . . . . . . . . . . . . . . 331 a. Premature Aging Syndromes . . . . . . . . . . . . . 333 b. Disorders of Cornification . . . . . . . . . . . . . . . 335 c. Hereditary Palmoplantar Keratodermas . . . 339 d. Ectodermal Hypohidrotic Dysplasias . . . . . . 340 e. f. Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . 341 Hair Disorders of Pigmentation . . . . . . . . . . . . . . . 342 g. Blistering Disorders . . . . . . . . . . . . . . . . . . . . . 344 h. i. Tumor Suppressor Disorders . . . . . . . . . . . . . 345 j. Metabolic Disorders . . . . . . . . . . . . . . . . . . . . . 348 Immunodeficiency Syndromes . . . . . . . . . . . 349 k. l. Disorders of the Connective Tissue . . . . . . . 350 Pediatric Dermatology  311
  2. 2. Committed to Your Future For practice exam questions and interactive study tools, visit the Dermatology In-Review Online Practice Exam and Study System at by
  3. 3. 9.1  NEONATAL DERMATOLOGYSclerema Neonatorum • Very rare form of panniculitis u TIP • Premature infants with serious underlying disease a oststeroid panniculitis also P has needle-shaped clefts • Often fatal entity with little inflammation • Rapidly progressive, woody hardening of the skin within the first few days of life • Histopathology: Needle-shaped clefts within necrotic adipocytes with little surrounding inflammationSubcutaneous Fat Necrosis of the Newborn u TIP • Uncommon localized subcutaneous nodules in newborns aSFNN • More inflammation • Healthy infants • Milder disease • First weeks of life • More localized • May be associated with maternal cocaine use, hypothermia and • More calcification cardiac surgery • Less fibrous • Increase in incidence recently with use of hypothermia to reduce neonatal brain injury • Calcification common and its resolution may be associated PEA RL with a profound hypercalcemia w alcium levels should be C • Histopathology: Lymphocytes, giant cells and histiocytes followed until one month after all lesions have are common with needle-shaped clefts and fat necrosis, cleared calcificationPedal Papules of Infancy • Soft, non-tender papules located on the medial aspect of heel • Not associated with any systemic disorder. Do not interfere with ambulationAplasia Cutis Congenita (ACC) • Localized developmental defect involving variable skin thickness • Along developmental suture lines on the scalp (80–90%º trunk or extremities) • May rarely be associated with underlying bony abnormalities, skeletal abnormalities, brain malformations, cleft lip, syndactyly • Hair collar sign is a ring of dark, long hair at the periphery of ACC, encephalocele or other type of neural tube defect • Associated syndromes: – Bart’s syndrome (dystrophic epidermolysis bullosa with congenitala PEARL absence of skin) w o imaging D – Setleis’ syndrome (bitemporal aplasia cutis congentia, leonine facies, before biopsy absent eyelashes)Cutis Marmorata Telangectatica Congenita • Fixed, reticular, blanchable vascular patterning on extremities trunk, face. More common unilateral with sharp demarcation at midline • May be associated with limb atrophy or hypertrophy (most common), arterial stenosis, cardiac defects, limp length discepancies, glaucoma with periocular involvement, CNS abnormalities in rare, extensive disease • Adams-Oliver syndrome: CMTC with aplasia cutis congenita and limb defects Pediatric Dermatology  313
  4. 4. Nevus Sebaceus • Waxy orange-tan plaque with alopecia. Usually present from birth. Head and neck • Neoplasms associated: syringocystadenoma papilliferum, trichoblastoma. BCC 1% (Syringoscystadenoma papilliferum is the most common benign tumor according to a review of 596 cases (30/596). Trichoblastomas were identified in 28/596 cases.12 A subsequent report of 155 cases showed trichoblastoma rather than SCP as the most common tumor arising in NS13 • Nevus sebaceus syndrome - large or extensive nevus sebaceus with associated eye, skeletal, neurologic abnormalitiesAcute Hemorrhagic Edema of Infancy (Finkelstein disease) • Leukocytoclastic vasculitis. 30% IgA • Infants around 6 months of age (up to 3 years) • Hypersensitivity reaction thought to be a response to infection (vaccination or medication less common) • Large round, red - purpuric plaques involving the ears, cheeks and extremities • Associated with fever and tender edema of the hands, feet, ears and face • Self-limited in 4-20 days • No treatment Table 9-1. Cutaneous Signs of Spinal Dysraphism: in Midsacral Region  Any two or more findings at high risk for dysraphism Hypertrichosis Dimpling Skin tags Tails/pseudotails Lipomas Aplasia cutis Hemangiomas Dermoid cysts/sinuses Telangectasia, capillary malformations, and nevi less likely MRI if older than 6 months. Ultrasound may be done in those under 6 months (but not highly sensitive) Table 9-2. Transient Benign Neonatal Rashes Neonatal acne First 30 days Erythematous papules/pustules on cheeks, chin and forehead. (neonatal cephalic Lasts few months Malessezia species implicated. No treatment. Neutrophils pustulosis) with debris on smear Erythema toxicum 24h-72h Erythematous macules with central vesicle/pustules. Eosinophils neonatorum Resolves 2 weeks on smear. No treatment. Common in full term infants Transient neonatal At birth Small pustules with no underlying erythema. Collarette when pustular melanosis ruptured. Heals with hyperpigmented macule. More common in darkly pigmented neonates, up to 1%. Neutrophils on smear314  2011/2012 Dermatology In-Review l Committed to Your Future
  5. 5. Table 9-2. Transient Benign Neonatal Rashes (cont.)Seborrheic 2-4 weeks Irregular salmon-pink patches with waxy scaling in seborrheicdermatitis Resolves by 1 yr distribution (scalp, forehead, chest eyebrows, ears, intertriginous areas)Miliaria 1-2 weeks Erythematous fine, uniform papules (rubra prickly heat) to Resolves in 1-2 vesicles (crystallina sudamina) in intertriginous areas. Due to days occluded eccrine ductsSucking blisters Birth+ Usually solitary, oval noninflammatory bullae at site of neonate’s sucking, e.g., hand or wrist. Most common on wrist Table 9-3. Disorders with Milia Bazex syndrome milia, follicular atrophoderma, multiple BCCs, abnormal hair Rombo syndrome milia, vermicular atrophoderma, BCCs, tricheopitheliomas Epidermoysis bullosa Down syndrome Oro-facial-digital syndrome X-linked dominant Defect in CXORF5 Epstein pearls milia on mucosa Bohn nodules milia on palate Table 9-4. Diaper DermatitisType SymptomsIrritant Dermatitis Diaper covered surfaces, spares folds Chronic wetness, increased pH, diarrheaCandidal Dermatitis Bright red, moist patches with satellite pustules Intertriginous involvement or thrushSeborrheic Dermatitis Groin, scalp, intertriginous areas Salmon colored, waxy scaling patches and plaquesPsoriasis Well demarcated, pink plaques with minimal scale, creases involved Most common presentation of psoriasis in infantsAcrodermatitis Brown, orange crusted plaques with vesicles and bullaeEnteropathica/ Perineal, perioral areas and distal extremitiesZinc Deficiency 2° to low serum zinc level 1.) Premature infants: poor absorption, inadequate stores and increased zinc requirement 2.) Healthy infants: low breast milk zinc levels with normal maternal serum zinc level 3.) Acquired form: malabsorption and/or inadequate nutritional intake (i.e., TPN) 4.) Autosomal recessive inherited form: defect in intestinal zinc-specific transporter SLC39A4 that manifests when infant is weaned off breast milk (due to greater availability of zinc maternal breast milk than non- maternal source) Alkaline phosphatase (zinc dependent enzyme) also lowLangerhans Cell Yellowish-brown, crusted papules with petechiae in a seborrheic distributionHistiocytoses CD1+, S100+ Langerhans cells with comma-shaped or reniform nuclei.(Letterer-Siwe disease) Multisystem involvement may be presentJacquet’s Erosive Severe erosive papules, nodulesDermatitis May cause pain with urination Multifactorial etiology: yeast, irritant dermatitis and moisture. Hirschprung’s Pediatric Dermatology  315
  6. 6. Table 9-4. Diaper Dermatitis (cont.) Type Symptoms Granuloma Gluteale Red-purple, granulomatous nodules Infantum 2° local irritation, maceration and Candida (multifactorial) Allergic Contact Topical preparations (or foods rarely) Dermatitis Cystic Fibrosis Resembles zinc deficiency Pedal edema common FTT, HSM, infections, malabsorption Biotin Deficiency/Multiple Resembles zinc deficiency but affects all biotin dependent enzymes Carboxylase Deficiency Neonatal form: AR holocarboxylase synthetase – vomiting Juvenile form: AR biotinidase – optic atrophy and hearing loss All: seizures, (6 month of age), hypotonia, ataxia, lactic acidosis/ketosis, hyperammonemia, alopecia. TX: Biotin lifelong Atopic Dermatitis Increased incidence of diaper dermatitis in this group Perianal Streptococcal Bright red, well-defined erythema perianally and in creases disease Bullous Impetigo Flaccid bullae with honey colored crusts Miliaria Blocked eccrine ducts secondary to heat and humidity of diaper area. May be superficial, small, clear vesicles (miliaria crystalline) or small, erythematous papules/pustules (miliaria rubra/miliaria pustulosa) Scabies Lesions tend to be more nodular under diaper Kawasaki’s disease 2/3 pts present with confluent, tender erythema in the perineum. Later desquamates Congenital Syphilis Condylomata lata or generalized papulosquamous eruption of secondary syphilis may be present in diaper area Perianal Pseudoverrucous Erythematous flat-topped papules and nodules in children with chronic Papules and Nodules fecal incontinence Human Very severe erosive diaper dermatitis. May be complicated by secondary Immunodeficiency Virus bacterial and viral infectionsSystemic neurocutaneous melanosis = poor prognosis (50% develop leptomeningeal melanoma) Table 9-5. Neonatal Infections (TORCH) Infection Skin Findings Extracutaneous Findings Other Toxoplasmosis Nonspecific. Petechiae/ Neurologic sequelae, Acquired from cats rash blueberry muffin chorioretinitis, intracranial lesions calcification Rubella Extramedullary IUGR, microcephaly, Congenital heart hematopoesis: “cranberry chorioretinitis, HSM disease, cataracts, muffin”– “blueberry muffin” pneumonia. Deafness lesions, petechiae/purpura 50%. Most severe in first trimester Cytomegalovirus Blueberry muffin lesions IUGR, microcephaly Most reactivation and petechiae and chorioretinitis, of latent maternal thrombocytopenia, HSM, infection. Also in breast pneumonitis milk. Greatest risk with infection in first trimester. *Acyclovir not effective against CMV316  2011/2012 Dermatology In-Review l Committed to Your Future
  7. 7. Table 9-5. Neonatal Infections (TORCH) (cont.)Infection Skin Findings Extracutaneous Findings OtherHerpes Simplex Vesicles and scarring. Microcephaly, chorioretinitis, Majority HSV2, 85% Eroded bullae also sepsis, multi organ failure, acquired perinatally blueberry muffin lesions encephalitis, neurologic sequelae. 50%-75% mortality untreatedVaricella Cicatricial lesions Chorioretinitis, limb paresis Greatest risk in first 20 and hypoplasia. Neurologic weeks and eye abnormalitiesSyphilis early - Snuffles - Bone lesions, epiphysitis May be asymptomaticcongenital - Saddle nose can lead to Parrot at birth/ look normal at(0 to 2 years; - Skin lesions resemble pseudoparalysis birth. Infection throughmother usually acquired 2° syphilis- - Enlarged lymph nodes placenta usually afterhas early syphilis) morbilliform, papular, and spleen 4th month pustular - Neurosyphilis - Syphilitic pemphigus - Nephrotic syndrome (vesiculobullous lesions on and soles) - Rhagades (aka Parrot’s u TIPa lines) fissured or Be able to diffentiate early/late congenital syphi- depressed linear scars lis features that radiate around u TIP aBlueberry muffin lesions occur 2° to extra- orifices, perineum and med ullary hematopoesis (purpuric intertriginous areas macules and papules present within 1–2 days - Condylomata lata around of birth) present in 30% of neonates with anus and skin folds TORCH synd rome - toxoplasmosis, other - syphilis/bacterial sepsis, rubella, cmv and herpesSyphilis Stigmata and – Interstitial keratitis Cornea, bones, CNSlate congenital inflammatory foci – Perisynovitis( 2 years) - Hutchinson’s teeth (Clutton’s joints) - Mulberry molar – Gummas in long bones - Saddle nose and skull - Saber shins – CNS lesions (tabes - Higoumenaki’s sign dorsalis, generalized (unilateral thickening of paresis) inner 1/3 of clavicle)Candidiasis Monomorphous - Pneumonia, sepsis Appears about 12 papulovesicles-pustules occasionally hours after birth. More widespread common in low birth weight infantsStaph Scalded Diffuse tender erythema Excessive fluid loss, fever, Toxin (exfoliativeSkin syndrome and superficial blistering. conjunctivitis, rhinitis toxin), mediated. Group(Ritter’s disease) Flexural/ perioral pneumonia, endocarditis. II phage. Desmoglein 1 accentuation Mortality due to sepsis Pediatric Dermatology  317
  8. 8. 9.2 CHILDHOOD INFECTIOUS DISEASES Table 9-6. Exanthems, Enanthems and Other Eruptions Classic Etiology Extra- Complication Disease Exanthem Enanthem Designation Infectivity cutaneous Other Measles First Morbilliform Koplik spots blue- Paramyxovirus 3 C’s Cough, Pneumonia, (Rubeola) disease rash begins grey specks on ssRNA coryza, otitis media behind ears, erythematous conjunctivitis diarrhea, spreads (appear before Airborne high fever postinfections downward, not rash) buccal encephalomy- pruritic, lasts mucosa. Fades litis, vit. A can 4–7 days within 2–3 days decrease mor- after onset of rash tality esp. in malnourished Scarlet Second Sandpaper Strawberry tongue Group A Fever, sore Rx: PCN Fever disease rash, Pastia’s (white then red) β-hemolytic throat abrupt lines (accen- petechiae on streptococcus onset fever, School- aged tuation in palate (pyrogenic headache, children skin folds), exotoxin) vomiting, fall, winter, Circumoral malaise, sore spring pallor desqua- Airborne or throat mation as rash fomites fades after 4–5 days Rubella Third Confluent rose Erythema Togavirus Fever Teratogenic (German disease papules, which Petechiae on soft Respiratory, adenopathy congenital measles) begin centrally palate = adolescent, arthralgias rubella = mild prodrome: on face and Forscheimer’s spring suboccipital/ cataracts, malaise, cough, spread acrally spots ssRNA posterior deafness, fever with rapid auricular cardiac (PDA) fading Erythema Fifth “Slapped None Parvovirus B19 Arthritis or 1.) Aplastic Infectiosum disease cheeks” ssDNA virus arthralgias more crisis in sickle 1–4 days then (only ssDNA common in cell, other 5-15 year olds, generalized virus) adults hemolytic winter/spring lacy rash lasts anemia 4-9 days Respiratory, (GGPD def, Rash waxes blood, vertically spherocytosis wanes several from mother to thalassemia weeks with fetus 2.) Possible physical stimuli fetal, death all (temperature, 3 trimesters, sunlight) in 2nd 3.) Hydrops fetalis-fetal ascites, pleural and pericardial effusions Roseola Sixth disease After fever Red macules/ HHV 6 High fever for 3 1.) Palpebral Infanum declines, streaks on soft (HHV7) days edema = (Exanthem erythermatous palate (Nagayama dsDNA viruses Rash begins as Berliner’s sign subitum) rose-pink spots) fever ends 2.) most macules with (fever, fever common halo papules on rash, rash) complication trunk minimal, =seizures acrally rash resolves 1–2 days without desquamation318  2011/2012 Dermatology In-Review l Committed to Your Future
  9. 9. Table 9-6. Exanthems, Enanthems and Other Eruptions (cont.) Classic Etiology Extra- ComplicationDisease Exanthem Enanthem Designation Infectivity cutaneous OtherPapular- Purpuric Erythema Parvovirus Flu-like Peaks spring/Purpuric macules and Palatal erosions ssDNA virus symptoms summer inGloves and papules acrally. Intraoral young adultsSocks Sharp demarc- apththaesyndrome ation along ankle and wrists, resolves in 2 weeksHand Foot Macules progress Vesicles on oral Coxsackie A16, 12–24 hours of Resolvesand Mouth to gray, football- mucosa, oral virus fever, anorexia, spontaneously,disease shaped vesicles/ lacerations ssRNA malaise, abdomi- 1 week pustules on a red picornovirus nal pain, myo- base on dorsal carditis, hands/feet/groin pneumonia, encephalitisMononucleosis Young Morbilliform EBV Triad: Fever, Ampicillin/ children/ rash on trunk, dsDNA LAD, sore amoxicillin = adolescents upper extremi- herpes virus throat; malaise, florid rash ties, spread to headache, HSM entire body, Periorbital edema Varicella Chicken “Tear drop” VZV dsDNA 1.) Fever, malaise Penumonitis pox vesicles on red herpes virus 2.) Pneumonia more severe base centrally (esp. in immuno- and common Late fall, necrotic or compromised) in adults winter, crusted lesions. spring Do not give Congenital All stages aspirin = Reye’s varicella = 1–14 yr old simultaneously syndrome hypoplastic limbs, scars, ocular, CNS diseaseToxic Shock Adolescent/ Scarlatiniform Staph aureus High fever, vom- Sourcessyndrome young adults rash that later TSS toxin-1 iting hypoten- include: desquamates, Also sion, diarrhea Tampons erythema, Streptococcal multisystem fail- Wounds edema, ure, strawberry palms, soles tongue, conjunc- tival hyperemiaGianotti-Crosti 1–6 yr. old Flesh colored Unknown Mild LAD /HSM Resolves insyndrome to red lichenoid low grade fever few weeks - Any season Possibly HepB,(Papular acro- papules or pap- months EBV associateddermatitis of ulovesicles on Avoid steroidchildhood) face, buttocks, creams as may extremities make rash (spares trunk) worse Pediatric Dermatology  319
  10. 10. Table 9-6. Exanthems, Enanthems and Other Eruptions (cont.) Classic Etiology Extra- Complication Disease Exanthem Enanthem Designation Infectivity cutaneous Other Kawasaki’s Mucocutaneous Generalized Strawberry Unknown 4 of 5 Criteria: Cardiac aneu- disease lymph node polymorphous tongue 1.) Fever 5 days rysm in 19% syndrome exanthem Dry, red mucosa 38.3° C Tx: ASA + IVIG Groin/ 2.) almoplantar P 80–90 mg/ Winter/ palmoplantar erythema, kg/d spring erythema edema, des- Cardiovascular 6 mo-6 yrs quamation of complications Early findings tips of digits are most sig- erythematous 3.) Conjunctivitis nificant causes desquamating 4.) trawberry S of long term peripheral tongue/red morbidity/ eruption fissured lips mortality 5.) Cervical (Leading cause adenopathy of acquired heart disease in children) -Echo at base- line Henoch- Palpable None Unknown Joint pain Glomerulo- Schonlein purpuric papules Abdominal pain nephritis purpura and macules on Nephritis with IgA vasculitis extensor surfaces hematuria and buttocks Unilateral Pink macules, None Presumed viral Fever, conjunc- Spontaneous laterothoracic papules tivitis, diarrhea, resolution in exanthem confluent rhinopharyngitis 4-6 wks unilaterally in lymphadenopa- (Asymmetric axillae, arm, thy Young children periflexural trunk, (22 months) exanthem) may spread bilaterally9.3  PIGMENTED LESIONSFreckles (Ephelides) • Light brown even bordered macules in sun exposed areas • More prominent in summer/childhoodLentigines • Well defined tan-brown macules (bigger than freckles) with increased numbers of epidermal melanocytes Table 9-7. Syndromes with Lentigines LEOPARD syndrome AD Lentigines, EKG abnormalities, ocular hypertelorism, (Multiple lentigines (PTPN11 pulmonic stenosis, abnormal genitalia, retarded growth, syndrome) including gene defect) deafness. Allelic with Noonan syndrome Moynahan syndrome Peutz-Jeghers syndrome AD Mucosal lentigines, intestinal polyps. (STK11/LKB1 GI adenocarcinoma, breast, pancreatic, endometrial ca gene defect) Carney complex AD Lentigines, myxomas, blue nevi, psammomatous mela- (LAMB/NAME syndrome) (PRKAR1A notic schwannomas, multiple endocrine abnormalities gene) (pigmented nodular adrenocortical disease g Cushing, tes- ticular tumors320  2011/2012 Dermatology In-Review l Committed to Your Future
  11. 11. Table 9-7. Syndromes with Lentigines (cont.) Centrofacial lentiginosis AD MR, Mitral valve stenosis, seizures, sacral hypertrichosis, (Touraine syndrome) unibrow, high palate, absence of middle incisors, neural tube defect, psychiatric disorder, dwarfism, endocrine abnormalities Bannayan-Zonana AD Penile lentigines, macrocephaly, lipomas and hemangiomas syndrome/ Bannayan- PTEN Riley-Ruvalcaba Laugier-Hunziker Perioral lentiginosis and pigmented nail/streaks syndromeCafé au Lait Macules • Uniformly pigmented tan to brown macules • At birth or acquired • Multiple café au lait macules are associated with many genodermatoses Table 9-8. Syndromes Associated with Multiple Cafe au Lait Macules Albright syndrome Bannayan-Riley-Ruvalcaba syndrome Bloom syndrome Cardiofaciocutaneous syndrome Ectrodactyly-Ectodermal Dysplasia Clefting syndrome Epidermal Nevus syndrome Fanconi Aplastic Anemia Johanson-Blizzard syndrome (VBR1 gene, nasal alar hypoplasia, hypothryroidism, congenitial deafness, pancreatic achylia) Maffucci syndrome McCune-Albright syndrome* Morquio syndrome Mucosal Neuroma syndrome Neurofibromatosis* Niemann-Pick syndrome Proteus syndrome Ring Chromosome syndrome* Russell-Silver syndrome Watson syndrome* (pulmonic stenosis, CALM, perineal freckling) Westerhof syndrome (hereditary congenitial hypopigmented and hyperpigmented macules) *Known to be associated. The rest are possibly associated.Congenital Nevi • Melanocytic nevi present at birth or within the first year u TIP • Approximately 1% of the population a MRI of brain for GCMN to rule out neurocutaneous melanosis Pediatric Dermatology  321
  12. 12. • Larger lesions may have cobblestoned, verrucous surface and hypertrichosis. Risk of melanoma very low: – Small congenital nevi: less than 1.5 cm in diameter – Medium congenital nevi: 1.5 – 20 cm in diameter – Large or giant congenital nevi (GCMN): greater than 20 cm or 10% body surface area • Risk of melanoma in GCMN is approximately 4.5-10% often by 5 years of age. Axial lesions have greatest risk • GCMN overlying the spinal column and skull or multiple satellite lesions can be associated with neurocutaneous melanosis (symptoms of increased cranial pressure, spinal cord compression or leptomeningeal melanoma) • Symptomatic neurocutaneous melanosis = poor prognosis (50% develop leptomeningeal melanoma) • MRI to rule-out CNS involvementCommon Acquired Nevi and Atypical Nevi • Appear in first decade of life • Genetic predisposition and sun exposure • Sun protection counseling • Atypical appearing nevi should be biopsied • Clark’s nevus – variegated color, 5mm, irregular shape, marker for increased melanoma riskMelanoma • Lifetime risk 1:70 • Prepubertal children only 0.3-0.4% of all melanomas in patients less than 20 years of age • More common in fair skin, blond/ red hair, blue eye patient • African-Americans more likely to have palm/sole, nailbed, mucosal melanoma Table 9-9. Clinical Signs of Melanoma A Asymmetry Two halves do not look alike B Border irregularity Notched, scalloped, irregular edges C Color changes Any changes – red, blue/ black, white D Diameter 6mm Not applicable to congenital nevi E Enlargement Changes in size • Increased risk of melanoma in children with: – Familial melanoma gene (a tumor suppressor gene p16 or CDKN2A, a cyclin dependent kinase inhibitor, located on 9p21). Also elevated risk of pancreatic ca – Xeroderma pigmentosum (2000X greater frequency) – FAMM syndrome (familial atypical mole/melanoma)/dysplastic nevus syndrome – Giant congenital nevi and neurocutaneous melanosis • Sun protection counseling, clinical suspicion and early detection importantSpitz Nevi (Epithelioid Cell and/or Spindle Cell Nevomelanocytic Nevi) • Subtype of melanocytic nevus, first 2 decades (although 1/3 occur in adults) • Eruptive smooth dome topped tan-pink papule on the face or neck • Pigmented and atypical variants are described (i.e.,: Pigmented Spindle Cell Nevus of Reed)322  2011/2012 Dermatology In-Review l Committed to Your Future
  13. 13. Halo Nevus (Sutton’s Nevus) • Melanocytic nevus with a halo of white depigmentation evenly surrounding it. Eventually, nevus disappears followed slowly by repigmentation • May occur with blue nevi, Spitz nevi, neurofibromas, melanoma • Typically appear in older childhood on the trunk • A halo nevus may appear in the setting of vitiligo as well • Full skin exam to rule out concurrent melanomaSpeckled Lentiginous Nevus (Nevus Spilus) • Tan brown regularly bordered macule with melanocytic nevi arising with it • Rare melanoma arising in nevus component of SLN • Associations include phakomatosis pigmentovascularis (nevus spilus and nevus flammeus), phakomatosis pigmentokeratotica (nevus spilus and organoid nevus and hemiatrophy, neurologic deficits) • Generalized nevus spilus associated with nevus anemicus and primary lymphedema • 2% of populationBlue Nevus • Melanocytic nevus characterized by dark blue papule • Acquired or congenital melanocytic lesion • 3 types: common blue nevus, cellular blue nevus and combined blue nevus • Multiple epitheloid blue nevi associated with LAMB syndrome (Carney complex)Becker’s Melanosis • Typically large, light brown to tan macules with or without an increased amount of darker hair growing within it • Most common location on the shoulders, upper chest or back of teenaged boys • Usually, unilateral and may be associated with an underlying arrector pili smooth muscle hamartoma “pseudo Darier’s sign” • Increased melanin in epidermis, not increased melanocytesEpidermal Nevi • Hamartomas of epidermal structures • Typically present at birth, but may arise later, even into adulthood • Many of the larger lesions follow the lines of Blaschko • Epidermal nevus syndrome consists of systematized epidermal nevusNevus Sebaceous (of Jadassohn) • Yellowish-orange pebbly plaque with no hair • Usually solitary • Scalp (face and neck) • Occasional mutations in PATCHED gene associated • Commonly gives rise to benign and, very rarely, malignant tumors. Growths usually occur after puberty • Syringocystadenoma papilliferum and trichoblastoma. Basal cell carcinoma, sebaceous epithelioma, hidradenoma, syringoma, metaplastic synovial cysts Pediatric Dermatology  323
  14. 14. Nevus of Ota (Oculodermal melanocytosis/ Nevus fuscoceruleus ophthalmaxillaris) • Deep blue macular pigmentation involving trigeminal nerve (V1, V2) distribution • Most common in the Japanese population and women (5:1) • Underlying mucosa, conjunctiva and tympanic membranes may be pigmented • Color may darken with menses and age • Responds to laser therapy • Rarely, melanoma can arise within nevus of ota (choroid is most common site)Nevus of Ito (Nevus fuscoceruleus acromoidal toideus) • Same as nevus of Ota but in a lateral supraclavicular or lateral brachial nerves distribution • Other conditions with dermal melanocytosis include: Incontentia pigmenti, Naegeli Franceschetti-Jadassohn (keratin 14 mutation, palmar/plantar hypohidrosis, hyperkeratoses, reticular pigmentation, poor dentition, no dermatoglyphics), dermatopathia pigmentosa reticularis (KRT 14 mutation, triad generalized reticulate hyperpigmentation, noncicatricial alopecia, onychodystrophy; adermatoglyphia, PPK, hypo/hyperhidrosis) and macular amyloidosisAcquired Dermal Melanocytoses (Acquired bilateral nevus of Ota-like macules) • Hori nevus • Unresponsive to laser • Late adolescence/adulthoodAngiofibromas • Uniform flesh colored to red papules over nose and cheeks • Multiple lesions associated with tuberous sclerosis, MEN type 1, Cowden, Birt-Hogg-DubeConnective Tissue Nevi • Present at birth or in early childhood • Collagenomas may be autosomal dominant inherited • “Shagreen patch” of tuberous sclerosis is a type of connective tissue nevus (collagenoma) • Eruptive lesions symmetrically distributed over the back beginning in adolescence • Elastomas in Buschke-Ollendorf syndrome (LEMD3 gene) (dermatofibrosis lenticularis disseminata) are symmetric and associated with osteopoikilosisNeurofibromas • Single or multiple in association with neurofibromatosis.9.4 DERMAL TUMORS AND DISORDERSChildhood Fibromatoses Infantile Digital Fibroma • Typically arise during the first year of life • High recurrence rate with surgery, spontaneous regression • Painless nodules that spare the thumb and great toe • Pathognomonic small, round, red perinuclear intracytoplasmic PAS + inclusion bodies in the proliferating fibroblasts on histopathology, thought to be aggragates of actin Fibrous Hamartoma of Infancy • Generally present at birth on the upper trunk and in the genital region • No recurrence after excision324  2011/2012 Dermatology In-Review l Committed to Your Future
  15. 15. Fibromatosis Colli• Affects the lower sternocleidomastoid muscle• May arise secondary to birth trauma• Spontaneous remissionInfantile Myofibromatosis (Congenital Generalized Fibromatosis)• Both a localized and generalized form• Generalized form has visceral involvement• Eighty percent of the mortality is secondary to lung, GI and CNS involvement, failure to thrive and infectionJuvenile Hyaline Fibromatosis• Mutations in gene encoding capillary morphogenesis protein 2• Onset in early childhood with the development of multiple soft tumors affecting the face, extremities and scalp • Disfigurement with flexion contractures, hypertrophic gums and osteolytic bone lesions can occur• Treatment in all forms is by local excisionDermoid Cysts• Along embryonic fusion planes, usually noticeable at birth• Most commonly around the eyes and at the nasal root• Cysts are lined by stratified squamous epithelium and may contain appendageal elements, including hair and teeth• A CT or MRI should be done prior to excision to rule out intracranial extension and bony defectsMastocytosis• Accumulation of mast cells in the skin and other organs • Clinically, several forms exist 1.) Solitary mastocytoma • One to two fuzzy bordered tan to brown macules/patches • History of welting up 2.) Urticaria pigmentosa • Typically presents in early childhood. 50% of cases occurring before 6 months of age • Few to numerous macules, papules, nodules and vesicles with variable tan to grey pigmentation • Pruritus, diarrhea, shortness of breath, joint pains and fatigue variably present • Urtication upon stroking (Darier’s sign) is usually positive • Mast cell degranulators must be avoided in extensive cases to prevent possible anaphylaxsis: – Aspirin, alcohol, opiates, polymyxin B, quinine, scopolamine, amphotericin B and tubocurarine 3.) Diffuse cutaneous mastocytosis • Diffuse involvement of the entire skin surface • Orange color often present with vesicles and bullae at sites or urtication. Peau d’orange skin changes 4.) Telangectasia macularis eruptiva perstans • Very uncommon in childhood • Rarely, mast cell or other leukemias may develop in systemic mastocytosis • Treatment with antihistamines, both H1 and H2 blockers, PUVA and corticosteroids, oral cromolyn for GI symptoms Pediatric Dermatology  325
  16. 16. Juvenile Xanthogranulomas • Yellowish to orange papules typically erupt within the first year of life • Solitary lesions are most common; but multiple, nodular, plaque and giant forms are described • Extracutaneous ocular lesions most common (0.4%) with multiple lesions – Eye lesions usually occur within the first 2 years of life – Glaucoma, uveitis, hyphema, or heterochromia iridis • Multiple lesions are associated with NF-1 and CML Benign Cephalic Histiocytosis • Reddish yellow papules on the head, neck and upper trunk • Asymptomatic and no visceral involvement • Appear around 18 months of age • Boys are affected twice as often as girls • Spontaneous resolution occurs over several years • Histologically, the histiocytic infiltrate is S100/CDIa negative Langerhans’ Cell Histiocytoses (Letterer-Siwe-Disease, Eosinophilic Hranuloma, Hand- Schuller-Christian Disease) • Spectrum of diseases characterized by Langerhans’ cell proliferation • Extent and number of organ systems involved determine prognosis • Skin findings include yellow to brown, crusted papules often purpuric or hemorrhagic in a seborrheic distribution – CD1+, S100+ Langerhans’ cells with comma-shaped nuclei – A Tzank smear of vesicles may aid in diagnosis • Oral mucosal and gingival lesions can occur affecting dentition, alveloar bone loss with “floating” teeth on x-ray • Bone most commonly involved, tends to occur in older children and adults, as does pulmonary disease • Diabetes insipidus may result when the skull involved • Lymph node, bone marrow and liver disease may also occur Congenital Self-healing Reticulohistiocytosis (Hashimoto-Pritzker Disease) • Benign end of the spectrum with solitary to numerous red-brown to pink papules/ papulovesicles and small nodules present in the newborn period • Lesions resolve spontaneously over weeks to months • Systemic involvement must be ruled out • Follow up for years as late occuring eosinophilic granuloma reported9.5  VASCULAR LESIONS The nomenclature used for vascular birthmarks has been simplified over the last several years.The newer classification scheme is based on the distinction between vascular malformations,which are hamartomas or developmental mistakes, and vascular tumors, which are characterizedby a phase of marked cellular hyperplasia and subsequent involution. Vascular malformations aresubdivided into different types depending on the vessel(s) involved (i.e., capillary, venous, lym-phatic, or arteriovenous).326  2011/2012 Dermatology In-Review l Committed to Your Future
  17. 17. Table 9-10. Vascular Tumors and Malformations Vascular Tumors Vascular Malformations Hemangioma of Infancy Capillary Rapidly Involuting Congenital Venous Hemangioma (RICH) Noninvoluting Congenital Arterial Hemangioma (NICH) Arteriovenous Pyogenic Granuloma Lymphatic Kaposiform Hemangioendothelioma Tufted Angioma Combined VascularCapillary Vascular Malformation (Port Wine Stain) • Area innervated by the cutaneous sensory nerve V1 may have associated ipsilateral ophthalmic and/or meningeal anomalies (Sturge-Weber syndrome) • V2 alone may be associated with ocular problems, such as glaucoma, but not usually meningeal anomalies • If, in addition to Vl, the areas innervated by V2 and V3 are also involved, the patient runs a greater risk of CNS involvement • On the extremities, this is known as the Klippel-Trenuanay syndrome or the Parkes-Weber syndrome • Soft tissue hypertrophy is frequently seen in association with, but independent of, a capillary or more complex vascular malformation • CM/AVM syndrome caused by RASA 1 gene mutationNevus Simplex (Stork Bites, Salmon Patches, Nevus Flammeus Neonatorum) • V-shaped distribution on central forehead, nuchal region common. Less commonly on eyelids, upper lip, scalp, overlying spineLymphatic Malformations (Cystic Hygroma, Lymphangioma Circumscriptum andLymphangioma Simplex) • Do not undergo a rapid proliferative phase • Grow as the child grows; may become focally thickened • May be macrocystic or microcystic • Associated with proteus syndrome, Klippel Trenaunay-Weber syndromePhakomatosis Pigmentovascularis Type 1 – PWS + nevus flammeus + epidermal nevus Type 2 – PWS + nevus flammeus + dermal melanocytosis +/- nevus anemicus Type 3 – PWS + nevus flammeus + nevus spilus +/- nevus anemicus Type 4 – PWS + nevus flammeus + dermal melanocytosis + nevus spilus +/- nevus anemicus (associated findings an include ocular abnormalities, choroidal melanoma and hemi-hyper- c trophy of the limbs, visual vascular anomalies) • Example of twin spotting Pediatric Dermatology  327
  18. 18. Hemangiomas • Often not seen at birth but become apparent within the first weeks of life • Undergo a rapid proliferative phase over the first 3-9 months (up to 18 months) • Then shrink or involute over several years • Most resolve by 10 years of age (50% by 5 yrs and 70% by 7 yrs) • Treatment: Intralesional or systemic corticosteroids, surgical intervention, pulsed dye laser, vincristine, or alpha-interferon (which can cause spastic diplegia, permanent side-effect), propranolol, timolol • Lesions prone to cause functional impairment typically located in the periorbital region, and near the nose or mouth • Life-threatening complications can occur with visceral lesions • Laryngeal involvement in beard distribution • Ulceration in the anogenital region SACRAL Syndrome •  pinal dysraphism, congenital cutaneous, renal and urological anomalies associated with S hemagiona of lumbosacral localization PELVIS Syndrome •  erineal hemagioma, external genital malformations, lipomyelomeningocele, vesicorenal P abnormalities, imperforate anus and skin tag PHACE Syndrome •  osterior fossa malformations (Dandy Walker most common), facial hemangiomas, arterial P abnormalities, coarctation of the aorta, eye abnormalities, and sternal nonunion or supraumbilical raphe Diffuse Neonatal Hemangiomatosis • Patient’s prognosis is dependent upon which organ systems are involved • Mortality in severely affected infants may occur secondary to liver disease, gastrointestinal bleeding, neurological problems, heart failure and respiratory compromise Maffucci’s Syndrome • Defect in PTH/PTHRP type I receptor • Progressive growth of vascular hamartomas and enchondromas • Approximately 1/3 of patients develop malignancies including chondrosarcomas, fibrosarcomas, angiosarcomas, gliomas and teratomas Blue Rubber Bleb Nevus Syndrome • Compressible, rubbery blue-red masses (venous malformations) • Painful, +/- increased sweat over lesion • Often associated with similar gastrointestinal lesions. GI bleeding, resulting in anemia, intussuception Noninvoluting Congenital Hemangioma (NICH) • Plaque-like with a pink or purple color and prominent overlying coarse telangiectasias and peripheral pallor • Mix of high and low flow • Grows proportionally or expands slowly • Biopsy: Thin-walled channels that are lined by plump endothelial cells and one or more layers of pericytes. GLUT1 negative • Treatment: Surgical excision328  2011/2012 Dermatology In-Review l Committed to Your Future
  19. 19. Rapidly Involuting Congenital Hemangioma (RICH) • Pink-red to bluish-red often large vascular tumor with characteristic pale halo • Multifocal variants described. Prenatal diagnosis by ultrasound • Can be associated with transient coagulopathy due to localized intravascular coagulation, high output cardiac failure • Biopsy: Small capillary lobules separated by abundant collagen. Prominent draining channels. GLUT 1 negative • Involute spontaneously, rapidly within 1 year. May have residual atrophic skin Multiple Cutaneous and Mucosal Venous Malformations (VMCM) • AD • Due to activating mutations in receptor for tyrosine kinase, TIE2 • Venous malformations involving skin, mucosa, ? GI tract. Maxillary, mandibular deformity can occur Capillary Malformation -Arteriovenous Malformation • Due to mutation in gene encoding p120-Ras GTPase-activating protein (RASA1) • Capillary malformations: small, multifocal often with blanched halo, randomly distributed (single CVM less common) associated with AVM or AV fistula Parkes-Weber Syndrome • Due to mutation in gene encoding p120-Ras GTPase-activating protein (RASA1) • Capillary malformation with underlying multiple, fast flow micro-AVFs (arteriovenous fistulas)/ AVM in association with soft tissue and skeletal hypertrophy of the affected limb Multifocal Lymphangioendotheliomatosis with Thrombocytopenia (MLT) • Hundreds of cutaneous reddish- brown to bluish-purple vascular papules to nodules. Present at birth • Severe GI bleeding ( hemetesis and melena ), thrombocytopenia • Biopsy: Dilated vessels in dermis and subcutis lined by hobnailed endothelial cells that formed intraluminal papillary projections. GLUT1 negative, CD31 positive, LYVE-1 positive • Treatment: systemic corticosteroids, interferon, vincristine Kaposiform Hemangioendothelioma • A distinct vascular anomaly • Associated with Kasabach-Merritt syndrome, a consumptive coagulopathy with high-output cardiac failure due to sequestration of platelets and large volumes of intravascular fluid Angiokeratomas A dilatation of the superficial vessels with overlying hyperkeratosis of the epidermis They do not blanch. Six types exist: 1.) Solitary or multiple angiokeratomas. Occur typically on lower extremity following trauma 2 .) Angiomakeratoma circumscriptum. Usually begin in infancy/early childhood. Females affected 3 times more often than males. No tendency to spontaneously involute 3 .) Angiokeratoma of Mibelli. Occurs on the extremities more often in girls during late childhood. Lesions on hands and feet may be associated with acrocyanosis, chillblains or frostbite with abnormal immunoglobulin levels 4 .) Angiokeratoma of Fordyce is characterized by angiokeratomas occuring on the scrotum or labia. Generally, onset begins in adulthood but may occur in adolescence. Can be associ- ated with varicocele, hernia, prostatitis, bladder or epidiymal tumors, LGV, or thrombophlebitis Pediatric Dermatology  329
  20. 20. 5 .) Angiokeratoma Corporis Diffusum or Fabry’s syndrome X-linked recessive disorder associ- ated with the intracellular accumulation of ceramide trihexosidase secondary to a defect in the enzyme a-galactosidase. Lesions appear during puberty, generally in clusters in the ilio- sacral region, umbilicus, scrotum, buttocks, thorax, and thighs. Little hyperkeratosis is visible. They characteristically appear on the vermillion border of lower lip. (See genodermatoses) 6 .) Fucosidosis has disseminated angiokeratomas similar to those in Fabry’s syndrome sec- ondary to deficiency of α-L-fucosidaseCutis Marmorata • Common transient mottling present on extremities of children and young womenLivedo Reticularis • Fixed vascular reticulated patterning • Associated with autoimmune diseases, rheumatic fever, neurologic disorders, drug, neoplasms, vasculitis, infection, metabolic disorders, hematologic diseases, pancreatitis, and cryoglobulinemia • Syndromal associations include: Sneddon’s syndrome (livedo reticularis, cerebrovascular accidents, antiphospholipid antibodies), Antiphospholipid antibody syndrome, Churg- Strauss syndrome and HomocystinuriaMacrocephaly Capillary Malformation • Formally M-CMTC • Cutis marmorata, nevus flammeus, infantile hemangiomas, CMTC, capillary malformation • Asymmetric somatic growth • CNS and neurological abnormalitiesCutis Marmorata Telangiectatica Congenita • A vascular anomaly that is usually present at birth and improves with age • A segmental reticular, blue-red mottling of the skin • Some cases appear to be due to dilated capillaries and veins • Can be distinguished from “physiologic” cutis marmorata of the newborn by simply warming the infant. The reticulated pattern will disappear in “physiological” cutis marmorata • Can have associated limb discrepancies, PDA, arterial stentosis and glaucoma (MR)Diffuse Phlebectasia (Brockenheimer’s Syndrome) • Synonymous for extensive venous vascular malformationSpider Angiomas (Nevus araneus) • Central arteriole with peripheral branches • Very common • May regress spontaneouslyAngioma Serpiginosum • Red, vascular macules in a linear distribution • Typically begins in childhood on the lower extremity and buttocks in females (90%) • Histologic examination reveals dilated capillaries in the upper dermisHereditary Hemorrhagic Telangiectasia (Osler-Weber-Rendu disease) • Autosomal dominant, endoglin and ALK1 gene mutations330  2011/2012 Dermatology In-Review l Committed to Your Future
  21. 21. • Multi-organ telangiectasias/AVMs • Usually presents with recurrent epistaxsis • Cutaneous lesions generally begin in 3rd decade and consist of slightly raised telangiectasias that are typically found on mucosal surfaces, palms and soles, and under the nails • Respiratory and gastrointestinal tracts, liver, brain, retina, and bladderAtaxia-Telangiectasia (Louis-Bar Syndrome) • hAlpha-fetoprotein levels in mother • ATM gene (codes for protein in DNA repair) mutation • Triad of cerebellar (2nd–3rd year of life) ataxia, oculocutaneous telangiectasias (3–6 years old) and respiratory infections beginning early childhood •  Autosomal recessive and heterozygous carriers have a higher risk of malignancy, especially breast cancer in females • Ovarian dysgenesis, insulin-resistant diabetesMicrocystic lymphatic malformation (Lymphangioma Circumscriptum) • Localized lymphatic malformation characterized by superficial clear or hemorrhagic vesicles and flesh colored papules (“frog spawn” appearance) • Histologically characterized by deep-seated, thick-walled vesicles • Commonly, they are located on the shoulders, neck, axilla, tongue, and mucous membranes • Recurrences are common post-excisionLymphedema • Congenital or acquired • Milroy’s disease is an autosomal dominant form of lymphedema that typically presents in adolescence. Due to a deject in FLTA gene, encoding a vascular endothelial growth factor receptor-3 • Feet and legs are most affectedAuriculotemporal Syndrome (Frey’s Syndrome) • Hyperhidrosis with cutaneous flushing in the distribution of the auriculotemporal nerve upon gustatory or olfactory stimulation9.6  GENODERMATOSESa. Photosensitivity Disorders Xeroderma Pigmentosum (XP) The genes implicated in XP are involved in the repair of UV induced DNA damage (nucleo-tide excision repair). UV irradiation induces specific types of DNA damage, primarily, cyclobutanepyrimidine dimers (CPDs) and 6–4 photoproducts. These are associated with skin cancer. Thedefects in nucleotide excision repair seen in XP involve all aspects of DNA repair; including recog-nizing damaged DNA (XPA and XPE), unwinding the coiled DNA to allow repair (helicases, XPBand XPD), and repairing the localized damaged DNA (endonucleases, XPF and XPG). De Sanctis-Cacchione Syndrome • AR • Subtype of XPD • XP, mental deficiency, progressive neurologic deterioration, dwarfism and gonadal hypoplasia Pediatric Dermatology  331
  22. 22. Cockayne Syndrome • AR • Defective excision-repair, cross-complementing group 8 gene (ERCC8) - CS Group A: ERCC8, defective excision repair - CS Group B: ERCC6 • Photosensitivity, mental retardation and cachetic dwarfism • “Wizened” appearance, “bird-headed” facies, “Mickey Mouse” ears • Cataracts, deafness, pigmentary retinopathy, dental caries. Skeletal, GU and endocrine abnormalities as well. Early death from pneumonia •  CS is not associated with skin cancer • XP/CS overlap present (complementation groups B,D and G) Table 9-11. Complementation Groups Gene Function Physical FindingsA Defective AR DeSanctis- Most severe variant. nucleotide Cacchione Photosensitivity excision repair: syndrome with variable to Initial step of severe neurologic binding abnormalities/ defective DNA growth delay/ encodes DNA deafness damage binding protein (DDBI)B DNA Helicase AD Overlap with Photosensitivity DNA excision- Cockayne (XP) with repair cross- syndrome XP/CS pigmentary complementing and retinopathy and (ERCC3) gene trichothiodystrophy basal ganglia defect calcification (CS)C Defective Most common At great risk nucleotide in Europeans/ for skin cancer (endonuclease) worldwide (melanoma) Rare excision repair: neurological Binding to ssDNA symptoms to allow stable repairD DNA Helicase AR Overlap with Poikiloderma, ERCC2 DNA repair Trichothiodystrophy early skin cancer, gene (PIBIDS) and XP/CS photo ocular damage, decreased intelligence, neurological impairment (later onset)E Defective AR Mildest skin/eye nucleotide photosensitivity. No excision repair: neurologic changes Enzyme that cleaves pyramidineF Endonuclease AR Occurs primarily in Mild ERCC4 gene Japanese patients photosensitivity, though rare freckling, rare skin cancer. No neuro/ocular abnormalities332  2011/2012 Dermatology In-Review l Committed to Your Future
  23. 23. Table 9-11.  Complementation Groups (cont.) Gene Function Physical Findings G Endonuclease AR Overlap with Mild skin changes. human homolog XP/CS No skin cancer. of the yeast RAD2 Neuro/ocular gene abnormalities with XP/CS only Variant POLH gene: AR? About 1/3 of all Variable Normal DNA repair pts with XP. Most photosensitivity rate, but defective common in Japan with no postreplication neurological repair abnormality Trichothiodystrophy (Tay Syndrome, BIDS, IBIDS, PIBIDS) • Defective DNA repair involving the ERCC2/XPD (and rarely ERCC3/XPB) • AR • Photosensitivity (+/-), overlap with XPD (XPB) • Icthyosis (+/-), erythrodermic or eczematous, may present as collodian baby •  Brittle hair, sulphur deficient trichoschisis (“tiger tail” alternating bands of light and dark) • Intellectual impairment • Decreased fertility • Short stature • Variable nail abnormalities, cataracts, recurrent infection, microcephaly, hypogammaglobulinemia and hypogonadismb. Premature Aging Syndromes Hutchinson-Gilford Progeria Syndrome • AD • Defect in lamin A gene, a nuclear envelope protein • Markedly premature aging, prominent vein, sclerodermoid changes • Early growth retardation, cardiac disease, osteoporosis, alopecia, loss of subcutaneous fat, midface hypoplasia with micronathia • Urinary hyaluronic acid •  Death may occur in childhood, most commonly from coronary artery disease Werner Syndrome (Adult Progeria) • AR u TIP • Chronic leg ulcerations a • Urinary hyaluronic acid “you‘ 2 old” RECQL “2” re •  Defect in RECQL2 gene (encodes DNA helicase) • Scleroderma-like skin changes extremities, wizened facies with beaked nose, short stature, slender limbs and stocky trunk, cataracts, subcutaneous calcification, premature arteriosclerosis, diabetes mellitus u TIP Rothmund-Thomson Syndrome a ypoplastic or absent H • AR thumbs, has only 4 fingers, • RECQL4 gene defect (encodes DNA helicase) RECQL-”4” • Poikiloderma, photosensitivity, sparse hair, atrophic nails Pediatric Dermatology  333
  24. 24. • Short stature, juvenile zonular cataracts, annular pancreas, abnormal dentition, cryptorchidism, hypogonadism, osteoporosis • Increased malignancy: basal cell carcinoma, squamous cell carcinoma, osteogenic sarcoma Ataxia-Telangiectasia (Louis-Bar Syndrome) • AR • ATM gene defect (Milder AT-like syndrome due to MREII gene defect). High rate of chromosomal breakage and sensitivity to ionizing radiation • Oculocutaneous telangiectases, cafe-au-lait spots, sclerodermatous skin changes • Cerebellar ataxia by one year of age, later seizures, choreoathetosis • Increased malignancy: leukemia and lymphoma. Also increased risk of malignancy in heterozygotes carriers especially: breast cancer Bloom Syndrome • AR MNEMONIC •  LM gene defect (RecQ protein-like-3 DNA helicase) Increased B BLOOM sister chromatid exchange and increased spontaneous chromo- B Butterfly rash somal breakage/rearrangement L Lymphoma/leukemia • Prenatal onset growth deficiency, photosensitivity, midfacial O HypOgonadism O telangiectasia, dyspigmentation, prominent ears and nose, café- M Infertility IgM, IgA au-lait macules, hypertrichosis • Increased malignancy (leukemia, lymphoma, SCC, adenocarcinoma) • Skeletal/GU abnormalities. NIDDM, acanthosis nigricans Fanconi Anemia • AR • At least 7 different complimentation groups (i.e., FANCA, FANCB…). Increased chromosomal breakage/rearrangement • All marrow elements are usually affected, resulting in anemia, leukopenia, and thrombocytopenia • Hyperpigmentation/café-au-lait spots, easy bruisabilty. Congenital heart/GU malformations. Skeletal radial ray defects (aplasia of the radius, thumb hypoplasia) • Increased leukemia in both homo and heterozygotes Dyskeratosis Congenita (Zinsser-Engman-Cole Syndrome) • XR • Dyskerin gene defect (DKC1). Increased chromosomal breakage/rearrangement/TERC gene (AD cases) •  oikilodermatous skin changes, nail dystrophy, premalignant leukoplakia of the oral mucosa, P lacrimal duct atresia with constant tearing •  Absent fingerprints • Mental retardation, deafness, testicular atrophy. Thrombocytopenia and anemia. Increased infection • Malignancy in mucosal leukoplakia/skin, Hodgkin disease, pancreatic adenocarcinoma • Female carriers may have limited skin involvement and pulmonary complications; increased risk of malignancy334  2011/2012 Dermatology In-Review l Committed to Your Future
  25. 25. c. Disorders of Cornification Ichthyosis Vulgaris (IV) • AD • Homozygous and heterozygous mutation in fillagrin gene •  Fine scales on extensor surfaces, hyperlinear palms/soles. Flexures uTIP spared a etention hyperkeratoses: R • Not present at birth, onset after 3 months, face usually spared IV, LI, EKV • Assoc: atopy and keratosis pilaris • Histology: retention hyperkeratosis with decreased/absent granular layer, EM: abnornal keratohyaline granules X-linked Ichthyosis • XR •  Defect in steroid sulfatase gene (arylsulfatase C), fetal DHEAS • Contiguous gene deletion syndrome may result in Kallman syndrome and XLR chondrodysplasia punctata • Brown scales, “dried mud,” scales • Not present at birth, appears within few weeks of life. Nonlyonized • Neck involvement prominent, face/palms/soles spared • Assoc: Asymptomatic corneal opacities (50%), cryptorchidism (20%) with increased testicular cancer, prolonged labor in mothers of affected sons • Histo: Compact hyperkeratosis with normal granular layer Epidermolytic Hyperkeratosis (Congenital Bullous Ichthyosiform Erythroderma) • AD • Keratin 1 and 10 • Bullae at birth with evolution into odorous verrucous plaques, ridgelike skin markings flexural involvement, dystrophic nails • Localized: Ichthyosis hystrix/Epidermal nevus with EHK. Localized forms may affect germline making offspring at risk for generalized EHK • Histo: Hyperkeratosis with upper dermal vacuolar and clumped keratin proteins, EM: clumped keratinfilaments • Mauserung sign - scales shed in full thickness leaving denuded base Ichthyosis Bullosa of Siemens • AD • Keratin 2e defect • Erythema and blistering at birth. At risk for sepsis, protein/fluid losses. Brown thickened hyperkeratotic plaques with shallow erosions, extremities trunk Lamellar Ichthyosis (LI) • AR • Transglutaminase 1 defect (type 1), ABCA12 gene defect (type 2) (copper binding protein) •  Coarse dark scales, thick palms/soles, prominent flexural involvement •  Collodion baby, ectropion, eclabion, alopecia Congenital Ichthyosiform Erythroderma (Nonbullous Congenital Ichthyosiform Erythroderma) • AR •  Defects in transglutaminase-1 gene, 12R-lipoxygenase gene (ALOX12B), and the lipoxy- genase-3 gene (ALOXE3) Pediatric Dermatology  335
  26. 26. • Fine scaling overlying generalized erythema with flexures involved, hyperkeratotic palms and soles, hair and nails may be affected. Loss of eyebrows/eyelashes. Mental and growth retardation. Decreased life expectancy • Collodian baby (90% present as collodin baby) Triglyceride Storage Disease with Impaired Long-Chain Fatty Acid Oxidation (Dorfman-Chanarin Syndrome or Neutral Lipid Storage Disease) • AR •  CGI-58 gene defect • Fine scaling on erythroderma. May present as collodion baby • Ectropion, cataracts, myopathy and central neuropathy. Fatty liver/hepatosplenomegaly • No fasting ketonemia •  Histo: Lipid laden vacuoles in keratinocytes and granulocytes - “Jordan’s anomaly” • Neutral lipid storage disease without myopathy due to PNPLA2 gene defect Harlequin Fetus • AR • ABCA 12 gene defect (copper binding protein), absent lamellar granules • Markedly thick, restrictive diamond-shaped plate-like scales, severe ectropion with bulging eyes, eclabion • Death within one week usually secondary to respiratory difficulty and sepsis • Tx: Isotretinoin may prolong survival Restrictive Dermopathy • AR • LMNA gene defect or ZMPSTE24 gene defect • Tight, restrictive adherent skin at birth associated with fixed, pinched facies. Skeletal anomalies and flexion contractures are present along with pulmonary hypoplasia and cardiac defect. Universally lethal • Histo: Markedly thin dermis with decreased/absent elastin and collagen Erythrokeratoderma Variabilis (Mendes da Costa Syndrome) (EKV) • AD • GJB3, which encodes the gap junction protein, connexins 31 and 30.3 • GJB4 gene mutation for EKV with erythema gyratum repens • Hyperkeratotic plaques on face and extremities, transient erythematous migratory patches, hypertrichosis Progressive Symmetric Erythrokeratodermia • AD • Loricrin gene mutation • Symmetric progressive erythrokeratodermia in the first year, some overlap with Vohwinkel syndrome, and EKV Netherton Syndrome • AR (almost all female) • SPINK5 gene defect encoding serine protease inhibitor, LEKT1 • Triad – Ichthyosis linearis circumflexa (CIE or psoriasiform erythroderma may also be seen) – Trichorrhexis invaginata (bamboo hair) g eyebrow hair most common site – Atopy (AD, anaphylactic readiness to foods)336  2011/2012 Dermatology In-Review l Committed to Your Future
  27. 27. • Decreased granular and spinous layers (increased drug absorption i.e.,: tacrolimus) • Failure to thrive, hypernatremic dehydration, recurrent infections, growth retardation Keratitis, Ichthyosis and Deafness Syndrome (KID Syndrome) • AD • Heterozygous defects in connexin-26 gene – GJB2 gene • Progessive vascularized keratitis, congenital sensiorneural hearing loss, hyperkeratotic skin lesions and increased SCC/skin infections Sjogren-Larsson Syndrome • AR • Mutation in gene encoding fatty aldehyde dehydrogenase • Pruritic velvety ichthyosis as infant, hair/nails normal • Mental retardation by age 2–3 years old, spasticity, retinal “glistening white dots,” photophobia Refsum Disease (Phytanic acid storage disease or Heredopathia atactica polyneuritiformis) • AR • Defect in gene encoding phytanoyl-CoA hydroxylase • Infantile form: PEX1 or PEX2 gene defect • Unable to metabolize phytanic acid • Fine scaling, thickened palms and soles, yellow nevi • Retinitis pigmentosa, night blindness, ataxia, peripheral polyneuritis, deafness, anosmia, cardiomyopathy, epiphyseal dysplasia, bilateral fourth metatasal shortening CHILD Syndrome (Congenital Hemidysplasia with Ichthyosiform Erythroderma and Limb Defects) • XD • NSDHL gene defect encodes 3B-hydroxysteroid dehydrogenase • Unilateral ichthyotic erythroderma (may follow Blaschko’s lines) with ipsilateral hypomelia/ webbing. Face spared • Multisystem ipsilateral defects including cardiac atrial defects, lung hypoplasia, structural genitourinary abnormalities Chondrodysplasia Punctata (CPXR or C-H-Happle Syndrome) • XR • Arylsulfatase E deficiency • Ichthyosis, hypogonadism, and anosmia in contiguous gene syndrome (with X-linked ichthyosis and Kallmann syndrome) • Facial hypoplasia, hypoplasia of distal phalanges, growth and mental retardation XD Chondrodysplasia Punctata (Conradi-Hunermann Syndrome) • XD • EBP gene defect (delta(8)-delta(7) sterol isomerase emopamil-binding protein) • Whorled/linear, egg shell-like ichthyosis and erythroderma along Blaschko’s lines, follicular atrophoderma, “orange peel” skin, and scarring alopecia • Failure to thrive. Flat facies. Tracheal stenosis/calcification. Stippled and punctate calcification sternum/ribs/scapula. Eye/kidney/CNS abnormalities • Acquired cases described as “stippled epiphyses” with maternal vitamin K deficiency on X-ray and wafarin teratogenicity Rhizomelic Chondrodysplasia Punctata • AR • Peroxisomal disorders Pediatric Dermatology  337
  28. 28. – Type 1: PEX7 gene defect – Type 2: DHAPAT – Type 3: alkyl-DHAP synthetase • Diffuse fine scaling, erythema, and alopecia • Dwarfism. Punctate chondral calcifications and epiphyseal dysplasia in infancy, cleft vertebrate. Respiratory compromise. Abnormal CNS, death in infancy AD Chondrodysplasia Punctata • Diffuse ichthyosis and erythema • “Koala bear” facies. Milder skeletal defects, asymmetric epiphyseal stippling Acrokeratosis Verruciformis of Hopf • AD • ATP2A2 gene mutation (allelic to Darier disease) • Warty, keratotic papules on dorsal hands and feet, extensor forearms and knees Darier Disease (Keratosis Follicularis) • AD • ATP2A2, Gene encoding SERCA2 Ca(2+)-ATPase • Keratotic malodorous papules or painful erosions in seborrheic distribution, palmar pits, “cobblestoning” of mucous membranes, red or white longitudinal streaking of nails with distal V notching. Neuropsychiatric disturbances • Segmental variants described • Histo: Acantholysis with corps ronds and corps grains Hailey-Hailey Disease (Benign Chronic Pemphigus) • AD • ATP2C1 gene mutation • Onset in 3rd to 4th decade • Moist eroded bullae and vesicles, crusted, usually in intertriginous areas, worse with heat, friction, sunlight, infection. Longitudinal white streaks on nails • Histo: “dilapidated brick wall” Pachyonychia Congenita • AD – Type 1 (Jadasshon-Lewandowsky) caused by defect in Keratins 6a and 16 – Type 2 (Jackson-Lawler) caused by defect in Keratins 6b and 17 • Thick hyperkeratotic nails, palmoplantar keratoderma, hyperhidrosis, keratotic papules intraoral and on extremities • Type 1 is associated with oral leukokeratosis not pre-malignant • Type 2 is associated with steatocystoma multiplex, epidermal inclusion cysts and amyloid deposition, cataracts, microphthalmia, and natal teeth Steatocystoma Multiplex • AD • Defect in the Keratin 17 gene • Numerous cysts may be associated with nail dystrophy, natal teeth Nail-Patella Syndrome • AD • LMX1B gene defect • Hypoplastic or aplastic nails (fingers toes), triangular or absent lunulae338  2011/2012 Dermatology In-Review l Committed to Your Future
  29. 29. • Hypoplastic or absent patella, elbow abnormalities, small joint hyperextensibility, renal disease, glaucoma and other ophthalmologic abnormalitiesd. Hereditary Palmoplantar Keratodermas Table 9-12. Hereditary Palmoplantar KeratodermasDisease Inheritance Defect Clinical CharacteristicsEpidermolytic PPK AD Keratin 9 Sharply demarcated PPK. May(Vorner) be associated with knuckle padsNonepidermolytic PPK AD Keratin 1 or 16 PPK with focal oral, genital,(Unna-Thost) follicular keratoses (see Pachy­ onychia congenita). Mosaic Keratin 16 mutation = Unilateral palmoplantar verrucous nevusPPK with deafness AD Defect in gene encoding PPK, progressive high-frequency connexin-26 (type 1) sensioneural deafness Mitochondrial tRNA serine point mutation in MTTS1 gene (type 2) onepidermolytic N AD Keratins 16 or 1 Nonepidermolytic PPK palmplantar with focal oral, genital keratoderma and follicular lesionsVohwinkel syndrome AD GJB2 gene encoding PPK with honeycomb- classic (Kerato­­ derma connexin-26 appearance; “starfish-shaped”hereditaria mutilans) keratoses over dorsal joints of hands and feet and later constricting bands that may cause autoamputation (pseudo- ainhum); linear keratotic plaques on knees, progressive, bilateral sensorineural deafnessStriated Palmoplantar AD Gene defect encoding Linear hyperkeratotoic plaquesKeratoderma desmoglein 1 (type 1) and palm to finger. Onset in teens or desmoplakin 1 (type 2) later. MF keratin 1Tylosis with Esophageal AD Unknown Nonepidermolytic PPK withCancer (Howel-Evans esophageal carcinoma, oralsyndrome) leukoplakiaKnuckle Pads AD Unknown Assoc. with epidermolytic palmoplantar keratoderma (keratin 9)/Dupuytren contracturesAcrokeratoelastoidosis AD Unknown Yellow, hyperkeratotic nodules on palms/soles. Histo: disorganized elastic fibers and hyperkeratosisKeratosis Punctata AD Unknown Hyperkeratotic palms/soles withPalmaris et Plantaris pits along creases Mal de Meleda AR SLURP1 gene mutation Erythematous PPK over with transgrediens dorsally, elbows and knees, perioral erythema, hyperhidrosis, lichenoid plaques, brachydactyly Pediatric Dermatology  339