Pediatric Blistering Diseases

MSU/Beaumont Health Dermatology Residency Program

Matthew Laffer, DO & Dustin Portela, DO PGY-4
Chelsea Duggan, DO & Peter Jajou, DO PGY-3
Sonam Rama, DO & Rachel Cetta, DO PGY-2

Steven Grekin, DO Program Director

Disclosures
• No conflicts of interest to disclose
Overview
• Infectious Disease
• Drug Related Disorders
• Hereditary Disorders
• Autoimmune Conditions
• Miscellaneous Disorders
INFECTIOUS
 Staphylococcus Scalded Skin Syndrome
• Clinical Presentation
• Fever, skin tenderness and erythema in groin folds, axillary regions, nose, that
leads to a generalized superficial exfoliative dermatitis and bullae
• +Nikolsky sign. Perioral crusting and fissuring

http://medlibes.com/entry/staphylococcal-scalded-skin-syndrome
Staphylococcus Scalded Skin Syndrome
• Pathogenesis
• Staphylococcus aureus group 2 phage (71) infects child at a distant site
• Exfoliative toxins/Epidermolytic toxins A and B (ET-A, ET-B) bind to desmoglein-1 
superficial bullae within the granular layer (subcorneal)
• ET is a unique serine protease that shows lock and key specificity to desmoglein -11-2
• Diagnosis
• Mainly clinical
• Culture of the bullae will be NEGATIVE. Must culture site of initial infection
• Treatment
• Supportive care: IVF!!
• Dicloxacillin
Bullous Impetigo
• Clinical Presentation
• Flaccid bullae which rupture and leave honey colored crust behind
• No surrounding erythema
• Can have systemic manifestations such as malaise, diarrhea

http://dermatologyoasis.net/bullous-impetigo-2/
http://www.adhb.govt.nz/newborn/TeachingResources/Dermatology/InfectiveLesions.htm
Bullous Impetigo
• Pathogenesis
• Often secondary to Staphylococci group 2 phage type 71 at the site of the lesion
• Exfoliative toxins A and B bind to desmoglein 1 forming superficial bullae within the
granular layer (subcorneal)
• Diagnosis
• Mainly clinical, but can culture site of infection
• Treatment
• Topical mupirocin
• There is no clear preference among systemic treatment: antistaphylococcal
penicillins (dicloxacillin), amoxicillin/clavulanate, cephalosporins (cephalexin), and
macrolides, although resistance rates to erythromycin are rising3
Bullous Tinea
• Clinical Presentation
• Tense multilocular bullae with surrounding erythema and scale often located
along the arch of the foot
• Common to see interdigital fungal involvement
• May serve as a portal of entry for superinfection and cellulitis

http://www.regionalderm.com/Regional_Derm/Tfiles/tinea_bullous.html http://www.regionalderm.com/Regional_Derm/Tfiles/tinea_bullous.html
Bullous Tinea
• Pathogenesis
• Most common dermatophyte: Trichophyton mentagrophytes
• Most commonly due to chronic disease that has not been treated or
incorrectly treated
• Diagnosis
• KOH scraping, fungal culture, biopsy4
• Treatment
• Topical antifungals
• If extensive, can use oral terbinafine up to 250 mg once daily for 2 weeks4
Eczema Herpeticum
• Clinical Presentation
• AKA Kaposi varicelliform eruption
• Itchy, umbilicated vesiculopustules that erupt in a disseminated pattern.
These often become hemorrhagic and crusted
• Seen in children with atopic dermatitis

http://www.pcds.org.uk/clinical-guidance/eczema-eczema-herpeticum
http://healthh.com/eczema-herpeticum/
Eczema Herpeticum
• Pathogenesis
• Reactivation of HSV 1 predominantly
• Other viruses indicated in literature: Coxsackie A 16, vaccinia, and varicella
zoster5
• Diagnosis
• Mainly clinical
• Tzanck smear, viral culture, direct fluorescent antibody, biopsy
• Treatment
• Acyclovir (10–15 mg/kg/day), intravenous or oral
• Oral valacyclovir has a higher bioavailability than oral acyclovir5
• In acyclovir resistant cases, can use foscarnet or cidofovir
Blistering Distal Dactylitis
• Clinical Presentation
• Tense vesicles filled with purulent fluid and surrounding erythema on the
dorsal surface of distal fingers and toes
• Can involve the proximal nail fold9

http://www.cram.com/flashcards/bacterial-infections-of-the-skin-5578577 http://www.liveinternet.ru/journalshowcomments.php?jpostid=45192638&journalid=1693906&go=next&categ=0
Blistering Distal Dactylitis
• Pathogenesis
• Group A β-hemolytic Streptococcus, S. aureus, S. epidermidis are the
responsible organisms
• Diagnosis
• Rare, but mainly a clinical diagnosis. Can culture
• Treatment
• I&D
• Dicloxicillin or first generation cephalosporin (cephalexin)
Bullous Scabies
• Clinical Presentation
• Erythematous papules and burrows are seen in finger and toe webspaces,
nipples, axilla, male genitalia and the umbilicus
• Very pruritic leading to excoriations
• Must be considered in ddx for diaper rash ages 3-6 mon

http://www.jaad.org/cms/attachment/2005281640/2022604688/gr1.jpg

http://www.rash-pictures.com/images/4/455.jpg
Bullous Scabies
• Pathogenesis
• The adult scabies mite burrows within the stratum corneum resting in the
upper granular layer.
• Diagnosis
• Mineral oil scraping from burrow
• Treatment
• Permethrin, the recommended first-line agent; with two applications one
week apart
• Lindane has become unavailable due to concerns regarding neurotoxicity,
particularly in pediatric populations
Varicella Virus
• Clinical Presentation
• A congenital infection of the newborn
• Greatest risk at first 20 weeks gestation
• Presents as cicatricial erythematous vesicles with crust
• Chorioretinitis, cataracts, cortical atrophy, psychomotor retardation and
hypoplastic limbs

http://www.6minutes.com.au/news/features/vaccination-eliminates-congenital--varicella http://indianpediatrics.net/feb2010/feb-181.htm
Varicella Virus
• Pathogenesis
• Transplacental infection
• Maternal rash within 5 days before to 2 days after delivery, varicella-
associated antibodies are not transferred to the baby  severe rash6
• Diagnosis
• Clinical
• Can get viral titer to confirm
• Treatment
• Live attenuated vaccine has lowered incidence
• Acyclovir (10–15 mg/kg/day)
Herpes Simplex Virus
• Clinical Presentation
• Erythematous vesicles with erosions and scarring in a localized or
disseminated manner
• Temporal encephalitis

http://rickshawmag.com/tag/congenital/ http://www.ultramag50.com/page/321/
Herpes Simplex Virus
• Pathogenesis
• Results from fetus contact with active maternal genital herpes lesions during
delivery
• Majority HSV 2
• Diagnosis
• Clinical
• Can swab maternal lesions prior to delivery to check for viral shedding
• Treatment
• Acyclovir (10–15 mg/kg/day)
• Mothers with active HSV-2 genital lesions should have c-section
Drug Related
 Stevens Johnson Syndrome & Toxic
Epidermal Necrolysis
• Clinical Presentation
• Patients with fever, severe mucosal/conjunctival ulcerations and occasional GI
and/or GU involvement
• Dusky erythematous or purpuric macules, papules, patches or plaques 
flaccid bullae with epidermal detachment and necrosis
• +Nikolsky and +Asboe-Hansen seen in most cases

http://emedicine.medscape.com/article/1197450-clinical

http://www.bestonlinemd.com/stevens-johnson-syndrome-rare-but-serious-problem/
 Stevens Johnson Syndrome & Toxic
Epidermal Necrolysis
• Pathogenesis
• Almost always drug related, rarely infection (Mycoplasma pneumoniae most
common) or immunization
• Anticonvulsants (#1), antibiotics and non steroid anti-inflammatory drugs7
• Diagnosis
• Clinically, eruption begins 7-21 days after initiation of drug
• Bx: full epidermal thickness necrosis
• Treatment
• D/C offending agent!!
• Supportive care in ICU or Burn unit: IVF, wound care, electrolyte and
nutritional supplement
• IVIG
Acute Generalized Exanthematous Pustulosis
• Clinical Presentation
• An eruption of multiple sterile pustules with surrounding erythema,
appearing first on face and intertriginous areas, then spreading to trunk and
extremities
• Edema of the face and sometimes hands

http://www.e-ijd.org/article.asp?issn=0019-5154;year=2014;volume=59;issue=2;spage=210;epage=210;aulast=Shingade http://jamanetwork.com/journals/jamadermatology/fullarticle/423839
AGEP
• Pathogenesis
• Most frequently mentioned drugs antibiotics (beta lactams, macrolides); antifungal
agents (terbinafine and nystatin); anticonvulsants (carbamazepine and
phenobarbital) 8
• Diagnosis
• Mainly clinical
• Biopsy will show spongiosis with dermal eosinophilic and neutrophilic infiltrate and a
subcorneal pustule
• Part of subcorneal pustule differential diagnosis

• Treatment
• Resolves in 1-2 weeks with d/c of drug
• Can use topical steroids for symptomatic relief
 Bullous Fixed Drug Eruption
• Pathogenesis: Lesions appear 1-2 weeks after first exposure. Found
anywhere on the body. With re-administration of the drug, lesions recur
at the same site.
• Clinical Presentation: Sharply circumscribed erythematous to violaceous
patches with central vesicles and bullae
 Bullous Fixed Drug
• Causes: Sulfa, NSAIDs, Tetracyclines,
Aspirin, Acetaminophen,
Metronidazole
• Histopathology: Superficial and deep
interstitial and perivascular infiltrate
with lymphocytes. There may be
necrotic keratinocytes in the
epidermis and dermal melanophages
• Treatment: Discontinue offending
agent
Hereditary Bullous Disorders
Epidermolysis Bullosa
• Four main types based on cleavage zones
• Epidermolysis Bullosa Simplex
• Blistering in epidermis within basal keratinocytes
• Junctional Epidermolysis Bullosa
• Blistering within laminia lucida
• Dystrophic Epidermolysis Bullosa
• Blistering in the dermis/ sublamina densa
• Kindler Syndrome
Ioffreda M. Histology of the skin. 31 Jul. 2016. http://plasticsurgerykey.com/histology-of-the-
• Multiple cleavage planes possible skin/

• All types characterized by skin fragility and blister formation with

mechanical traction
Epidermolysis Bullosa Simplex (EBS)
• EBS is mainly associated with autosomal dominant inheritance
• Exceptions: EBS with muscular dystrophy, EBS with pyloric atresia, and EBS-
autosomal recessive type
• Subtypes with mutations in Keratins 5 and 14 (located in basal
keratinocytes)
• Dowling-Meara
• Onset at birth
• Herpetiform, widespread bullae
• Mucosal involvement
• Confluent palmoplantar keratoderma
• Early death
• Classic clumped tonofilaments seen on EM
• Weber-Cockayne (localized)
• Palmoplantar bullae in childhood
• Koebner (generalized) Intong LR, Murrell DF. Inherited epidermolysis bullosa: new
diagnostic criteria and classification. Clin Dermatol. 2012 Jan-
Feb;30(1):70-7. doi: 10.1016/j.clindermatol.2011.03.012.
• Generalized bullae at birth
• Heal without scarring
• Mucosal involvement
Epidermolysis Bullosa Simplex (EBS)
• Keratin 5/14 subtypes continued:
• EBS with mottled pigmentation
• mainly associated with KRT 5 mutation
• Autosomal recessive EB Sprecher E. Epidermolysis bullosa simplex. Dermatol
Clin. 2010 28(1): 23-32. doi: 10.1016/j.det.2009.10.003.
• Mutation in KRT 14 or occasionally BPAG1
• Subtypes with mutations in Plectin (links filaments to the plasma
membrane and crosslinks hemidesmosomal proteins)
• EBS with muscular dystrophy
• EBS with pyloric atresia
• EBS ogna type
• Acral blistering, generalized bruising
Junctional Epidermolysis Bullosa (JEB)
• Autosomal recessive inheritance
• Enamel hypoplasia is linked with multiple types of JEB
• Subtypes
• JEB non-Herlitz type
• Laminin 5 or BPAG2 mutation
• Bullae heal with atrophic scarring, may also have scarring alopecia and nail dystrophy
• Normal lifespan
• Condition improves over time
• JEB Herlitz type
• Laminin 5 mutation
• Diffuse non-healing bullae
• Early death
• Perioral granulation tissue
• JEB with pyloric atresia
• Integrin α6β4 mutation Intong LR, Murrell DF. Inherited epidermolysis bullosa: new diagnostic criteria and classification. Clin Dermatol. 2012 Jan-Feb;30(1):70-7.
doi: 10.1016/j.clindermatol.2011.03.012.
Dystrophic Epidermolysis Bullosa (DEB)
• All caused by mutation in collagen VII
• Recessive DEB:
• Hallopeau-Siemens:
• Severe bullae that heal with scarring
• Mitten deformity
• Fatal squamous cell carcinomas
• Non-Hallopeau- Siemens:
• Localized to acral prominences
• Less severe than above
• Dominant DEB:
• Cockayne- Touraine Intong LR, Murrell DF. Inherited epidermolysis bullosa: new diagnostic criteria and classification. Clin Dermatol. 2012 Jan-
Feb;30(1):70-7. doi: 10.1016/j.clindermatol.2011.03.012.
• Bullae on extremities
• Resolve with milia and scarring
• Pasini variant
• Hypopigmented perifollicular papules
Epidermolysis Bullosa Continued

• Treatment:
• Day to day management includes avoiding mechanical trauma, loose clothing,
non-adhesive dressings, bleach baths
• Prompt treatment of secondary infections
• Close monitoring for squamous cell carcinoma development
• Multispecialty involvement
• Dystrophic Epidermolysis Bullosa Research Association of America (DEBRA)
• http://www.debra.org/research-trials
• Information on the latest stem cell transplant, protein replacement and gene therapies
that are currently being tested
Kindler Syndrome
• Rare autosomal recessive inherited subtype of epidermolysis bullosa
• Usually caused by a loss of function mutation in the gene FERMT1 (KIND1)
• Encodes a protein kindlin-1, involved in keratinocyte adhesion
• Characteristics:
• Congenital blistering
• Trauma induced skin fragility
• Atrophic/wrinkled skin
• Photosensitivity
• Poikiloderma
• Palmoplantar hyperkeratosis
• Pseudosyndactyly
• Periodontal disease Image: Youssefian L, Vahidnezhad H, Uitto J. Kindler Syndrome. 2016 Mar 3 [Updated 2016 Dec 1]. In: Pagon RA,

•
Adam MP, Ardinger HH, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle;
Phimosis 1993-2017. Available from: https://www.ncbi.nlm.nih.gov/books/NBK349072/

• Pseduoainhum
Kindler Syndrome

• Histology:
• Atrophic epidermis Burch JM, Fassihi H, Jones CA, Mengshol SC, Fitzpatrick JE, McGrath

•
JA. Kindler SyndromeA New Mutation and New Diagnostic
Vacuolar changes at basement membrane Possibilities. Arch Dermatol. 2006;142(5):620-624.
doi:10.1001/archderm.142.5.620

• Sparse infiltrate
• Decreased immunostaining of anti-kindlin-1 antibody
• Treatment:
• Need multidisciplinary team (dentist, urologist, ophthalmologist)
• Skin protection from trauma and sun
• Close monitoring early actinic keratosis and squamous cell carcinomas
• Prompt treatment of secondary infections
• Blistering improves with age, but poikiloderma is progressive
Bullous Congenital Icthyosiform
Erythroderma (BCIE)
• AKA Epidermolytic Hyperkeratosis or Epidermolytic Ichthyosis
• Autosomal dominant inheritance
• Gene defect in Keratins 1 (KRT1) and 10 (KRT10)
• Expressed in spinous and granular layer of epidermis
• Presents with diffuse erythema at birth in addition to vesicles and erosions
• Overtime has less erythema and more verrucous plaques, especially over
flexural areas
• Other characteristics:
• Malodorous plaques
• Palmoplantar keratoderma (KRT1)
• Nail dystrophy
Images: Sung JY. Oh SW, Kim SE, Kim SC. Mild phenotype of epidermolytic hyperkeratosis mimicking
ichthyosis bullosa of Siemens is related to specific mutation in 2B domain of KRT1 . J Dermatol Sci. 2013
Jun;70(3):220-2. doi: 10.1016/j.jdermsci.2013.03.001.
Bullous Congenital Icthyosiform
Erythroderma (BCIE)
• Histology:
• Acanthosisis, hyperkeratosis
• Expanded granular layer
Image: Sung JY. Oh SW, Kim SE, Kim SC. Mild phenotype of epidermolytic hyperkeratosis mimicking ichthyosis
• Large keratohyalin granules bullosa of Siemens is related to specific mutation in 2B domain of KRT1 . J Dermatol Sci. 2013 Jun;70(3):220-2. doi:
10.1016/j.jdermsci.2013.03.001.

• Vacuolar change and intracellular edema at spinous/granular layers

• Clumped keratin filaments seen on electron microscopy
• A patient with epidermal nevi with above histology changes may have a
postzygotic mutation and are at risk for having a child with BCIE.
• Treatment:
• Mainly supportive, wound care and emollients for blistering
• Use of antiseptic soap to decrease bacterial colonization
• Oral or topical retinoids can be of benefit
Incontinentia Pigmenti (Bloch-Sulzberger
Syndrome)
• Inherited X-linked dominant
• usually lethal in males
• Gene mutation of NEMO (NF-kB essential modulator); also known as IKBKG gene
• Normal function is to protect against apoptosis
• Four stages follow the lines of Blaschko
• Vesiculobullous lesions
• Neonatal period
• Verrucous and hyperkeratotic lesions
• 2-6 months
• Hyperpigmented patches
• Toward the end of infancy Image: Zafeiriou DI, Vargiami E, Hatzidimitriou

• Hypopigmentation and atrophic lesions V, Kyriazi M. Incontinentia pigmenti: A Skin,

Brain, and Eye Matter. J. Pediatr. 2013;
163(5):1520. DOI:10.1016/j.jpeds.2013.06.029
• Early adulthood
Image: Batson R, Keeling BH, Diaz LZ.
Incontinentia Pigmenti. J. Pediatr. 2016;
176:218-218. DOI:
10.1016/j.jpeds.2016.05.081
Incontinentia Pigmenti (Bloch-Sulzberger
Syndrome)
• Other characteristics:
• Alopecia
• Pegged teeth
• Eye abnormalities
• Nail dystrophy
• Seizures Tsai WC, Cheng YW, Chen CC, Hung PL. Two cases of cerebrovascular accidents in neonates
• Delayed development with incontinentia pigmenti. Pediatr Neurol. 2015 Sep;53(3):e7-9. doi:
10.1016/j.pediatrneurol.2014.11.012

• Histology
• Vesicular stage: Eosinophilic spongiosis with intraepidermal bullae
• Verrucous stage: Hyperkeratosis, acanthosis, and dyskeratotic cells
• Hyperpigmented stage: Pigment incontinence
• Hypopigmented stage: Atrophic epidermis with loss of adnexal structures
• Treatment:
• Multispecialty coordination (Neurology, dentistry, ophthalmology, geneticist)
• Early ophthalmologic screenings for infants for retinopathy and strabismus evaluation
• Prompt referral to neurology if any CNS abnormality
 Linear IgA Bullous Dermatosis of
Childhood
• Immune-mediated, subepidermal, vesiculobullous dermatosis with clinically
unique features in children. Also called “chronic bullous disease of childhood”
• Epidemiology: Mean age of 4.5 years
• Autoantigen: 97 kDa Ag (LAD-1/LABD97)
• Histology: subepidermal bullae with neutrophils in dermal papillae
• DIF: linear IgA (+/- C3) deposition at BMZ
• Treatment: dapsone (first line) 1-2 mg/kg or sulfapyridine. Second line agents
include; oral corticosteroids, colchicine, and nicotinamide.
• Childhood disease remits within 2-4 years
Linear IgA Bullous Dermatosis of
Childhood
Clinical: Annular and herpetiform bullae
with preference for flexural areas of
lower trunk, extensors, thigh, and
groin. “Crown of Jewels” configuration.

http://escholarship.org/
uc/item/1379s6t6/1.jpg
 Dermatitis Herpetiformis
• Cutaneous manifestation of gluten sensitivity, (90% of DH patients have gluten-sensitive
enteropathy, 20% have intestinal symptoms of celiac disease)
• F>M in children. HLA-DQ2 (strongest association)
• Autoantigen: epidermal transglutaminase (TG-3), tissue transglutaminase (endomysial)
• Chronic pruritic erythematous grouped papules/vesicles on elbows, knees, and buttocks.
Excoriations of vesicles common.
• Associated with gluten-sensitive enteropathy (wheat, barley, rye). NOT in rice, corn, oats
• Labs: anti-gliadin (DH)/anti-endomysial (celiac disease)
• Associations: Increased risk of enteropathy-associated T cell lymphoma (refer to GI),
Hashimoto’s thyroiditis, insulin dependent diabetes mellitus.
• Treatment: Dapsone (skin improvement 24-48 hrs) 0.5 mg/kg, gluten-free diet
 Dermatitis Herpetiformis

http://www.pcds.org.uk/ee/images/made/ee/images/uploads/clinical/DH_2_800_600_70_http:www.pcds.org.ukeeassetsimgwatermark.gif_0_0_80_r_b_-5_-5_.jpg

http://www.humpath.com/IMG/jpg/d_herpetiformis_40xhe2.jpg

Histology: neutrophilic microabscesses in dermal papillae

DIF (normal appearing skin): granular IgA > C3 in dermal papillae
Bullous Systemic Lupus Erythematosus
• Rare blistering eruption that consists of vesicles and bullae. Clinically may look like
BP or EBA with histopathology usually resembling DH. May be more common in
African Americans.
• Antigen: Type VII collagen
• Clinical: Non-inflamed bullae/vesicles (hx of SLE usually)
• Based on 5 main criteria: (1) acquired vesiculobullous eruption, (2) subepidermal
bullae with neutrophils, (3) DIF with linear or granular deposition of IgG (+/- IgA,
IgM, etc), (4) type VII antibodies, (5) response to dapsone
• Should also fulfill criteria for American College of Rheumatology for SLE ( positive
ANA, decreased complement, anemia, leukopenia, proteinuria, thrombocytopenia,
elevated ESR may be seen).
• Treatment: Dapsone, PO corticosteroids, anti-malarials, azathioprine,
mycophenolate mofetil
Bullous Systemic Lupus Erythematosus
Histology: subepidermal bullae
neutrophils in dermal papillae
(similar to DH)
DIF/SSS: Linear IgG, IgM,IgA, C3,
fibrinogen at BMZ, dermal side
(SSS)

http://www.ijpd.in/articles/2016/17/2/images/IndianJPaediatrDermatol_2016_17_2_139_172468_f1.jpg
 Epidermolysis Bullosa Acquisita
• Rare, acquired, subepidermal immune-mediated bullous disease with antibodies directed against
Type VII collagen (290 kDa)

• Rarest subepidermal bullous diseases in Western Europe (may be more common in Korean/Asian and
African-American populations)

• Treatment: Unsatisfactory and difficult to treat. Dapsone and prednisolone may be of benefit for the
childhood form.
 Epidermolysis Bullosa Acquisita
Non-inflammatory bullae with fragile skin in areas easily
traumatized (elbows, hands, knees, toes).

Heals with scarring +/- mucous membrane involvement.

Childhood EBA overlaps with childhood BP and linear IgA

bullous dermatosis.

Systemic diseases may occur in association (inflammatory

bowel disease, SLE, RA, thyroiditis, and DM).

http://dermaamin.com/site/images/clinical-
pic/e/epidermolysis_bullosa_acquisita/epidermolysis_bullosa_acquisita11.jpg
 Epidermolysis Bullosa Acquisita
Histology: subepidermal separation without acantholysis,
variable infiltrate (neutrophils or non-inflammatory)

https://www.researchgate.net/profile/Michael_Camilleri/publication/
24177073/figure/download/fig5/AS:277351515607040@1443137162
174/Figure-7-Immunoglobulin-deposition-on-the-base-of-sodium-
chloride-induced-split-human.png

DIF/IIF: linear IgG (-/+ C3, fibrinogen, IgA, IgM) at BMZ, binds
dermal side of SSS (floor)

http://dermaamin.com/site/images/histo-
pic/e/epidermolysis-bullosa-acquisita/epidermolysis-
bullosa-acquisita4.jpg
 Bullous Pemphigoid
• Rarely occurs in children
• Autoantigen: BPAG2 (collagen XVII) 180 kDa-NC16A domain, BPAG1 230kDa, cytoplasmic
plaque protein
• Clinical
• IIF: SSS shows binding to epidermal side of split (roof)
• Treatment: Oral/topical corticosteroids, steroid-sparing (azathioprine, mycophenolate
mofetil) tetracycline +/- nicotinamide, dapsone.
 Bullous Pemphigoid
Often with initial urticarial lesions which evolve
into tense bullae, +/- pruritus.

Individual lesions in infants and older children look like

elderly but sites of involvement may vary.

Infants-bullae first appear acrally, then generalize

(including face). Involvement of the genital region and
other mucosal sites may occur in children.

http://clinicalgate.com/wp-content/uploads/2015/03/c00024_f024-002-9781455708413.jpg
 Bullous Pemphigoid
Histology: subepidermal bulla with
eosinophils and lymphocytes in papillary
dermis, +/- neutrophils

http://plaza.umin.ac.jp/pathol2/photo-
library/system/data/image_data/11348999517711.jpg

DIF: linear C3 and IgG at BMZ

http://www.pcds.org.uk/download/2208
Pemphigus
• Group of autoimmune blistering diseases of the skin and mucous
membranes
• Includes:
• Vulgaris:
• potentially fatal disease, can be seen in newborns (neonatal pemphigus) but rare.
• Foliaceous:
• more superficial and less severe than PV
• Endemic (Fogo selvagem)
• Drug Induced:
• sulfhydryl group containing drugs are common offenders
• Parneoplastic:
• less commonly due to an underlying malignancy in children
• IgA:
• characteristic histologic deposit
Pemphigus Vulgaris (PV)
• Rare in pediatric patients, but can be
seen in the newborns (neonatal
pemphigus) whose mothers have
pemphigus vulgaris.
• Due to passive transfer of maternal IgG
to fetus
• Autoantibody:
• Desmoglein 3 (mucosal)
• Desmoglein 1 (mucocutaneous)
• Clinical
• vesicles and erosions trunk and
extremities, mucosal involvement
uncommon in neonatal form, (+)
Nikolsky and Asboe-Hansen sign
PV
• Histology
• “tomb stone row” suprabasal
split with acantholytic
keratinocytes (possible follicular
involvement), perivascular
lymphocytes and eosinophils
• DIF: intercellular IgG4 > C3,
netlike pattern in epidermis
• IIF: monkey esophagus,
correlates with disease severity
• Prognosis and Treatment
• Self resolving within weeks
 Pemphigus Foliaceous (PF)
• Endemic (fogo selvagem) is more
common in pediatric patients
• Seen in rural Brazil after a bite from black fly
(Simulium nigrimanum)
• Sporadic PF is rare in children, but
if present, shows a dramatic
pattern of crusted plaques and
erosions with an arcuate, circinate,
or polycyclic morphology on the
face and scalp.
• Autoantibody:
• Desmoglein 1
• Clinical
• Crusted plaques and erosions in polycyclic
distribution on face and scalp
 PF
• Histology
• Subcorneal acantholysis with
acantholytic cells seen on blister roof
(cling-ons), neutrophils can be seen in
blister cavity (resembling impetigo)
• DIF : same as PV, however, more
pronounced in upper layers
• IIF : best substrate is guinea pig
esophagus
• Treatment:
• First line: Systemic corticosteroids
• Steroid-sparing therapies reported:
Azathioprine, mycophenolate mofetil,
IVIG, plasmapheresis, methotrexate,
cyclophosphamide
• Biologics: Rituximab
Drug Induced Pemphigus
• Particularly rare in children.
• Sulfhydryl group containing medicines are implicated, most common
being penicillamine and captopril.
• Sulfhydryl groups thought to interact with the sulfhydryl groups in desmogleins 1
and 3, thus modifying the antigenicity of the desmoglein.
• Clinical:
• Initially, a nonspecific morbilliform, annular, or urticarial eruption may be seen,
eventually evolving after a variable latency period into the blistering process.
• Treatment:
• Removal of offending agent if known
• Corticosteroids if necessary
 Parneoplastic Pemphigus
• General:
• In adults, commonly due to underlying malignancy (non-Hodgkin’s lymphoma most common)
• In children, the most common causes include:
• Castleman’s disease
• Giant lymph node hyperplasia
• Benign giant lymphoma
• Sarcoma
• Autoantibody:
• desmoglein 3, periplakin, envoplakin, desmoplakin ½, BPAG1, plectin, 170 kDa Ag, rarely desmoglein 1
• Clinical
• Intractable stomatitis, ocular involvement common, bullous or lichenoid lesions
Parneoplastic Pemphigus
• Histology
• suprabasilar acantholysis, ± v acuolar basal layer
damage associated with lichenoid dermal
lymphocytic infiltrate, and necrotic keratinocytes
• DIF : intercellular + linear IgG/C3 along BMZ
• IIF : intercellular IgG, best substrate is rat bladder
epithelium
• Prognosis & Treatment
• Poor prognosis; respiratory failure due to
bronchiolitis obliterans more common
• Treatment of malignancy, palliative
immunosuppression
 IgA Pemphigus
• Blistering disease with intraepidermal IgA deposits
• Two types: Subcorneal pustular dermatosis (SPD) &
Intraepidermal neutrophilic type (IEN)
• There is no difference in the clinicopathologic features
and prognosis of the disease between adults and
children
• Autoantibody:
• desmocollin 1 (SPD), ± desmoglein 1/3 (IEN)
• Clinical
• SPD: serpiginous vesicles or pustules; may be associated
with underlying IgA gammopathy
• IEN: flaccid pustules and bullae involving intertriginous
locations which enlarge forming annular or polycyclic
(sunflower-like) arrangement
• Histology
• intraepidermal pustule or vesicles containing neutrophils, no
acantholysis
• DIF: intercellular IgA deposition
• IIF: (+) in 50%, intercellular IgA
• Treatment: Dapsone, oral corticosteroids
 Herpes Gestationis
• Aka Pemphigoid gestationis (PG), is an autoimmune bullous dermatosis of pregnancy.
• Common in the 2nd or 3rd trimester, or immediately postpartum
• Neonatal disease is observed in up to 10% of children born to mothers with PG.
• Autoantibody
• anti-BPAG2 (BP180, NC16A site)
• Clinical:
• Erythematous urticarial or vesicular rash, but yellowish plaques on erythematous base and frank bullae
have also been reported.
• Cutaneous lesions in the newborn are due to a passive transfer of Ig.
• Fetal risks:
• prematurity & small for gestational age in 20%, also, a borderline increase in the rate of
spontaneous abortions has also been reported
• Histology:
• papillary dermal edema resulting in subepidermal bulla with eosinophil rich infiltrate, ± keratinocyte
necrosis, perivascular infiltrate
• DIF: linear C3 deposition ± IgG at basement membrane
• IIF: epidermal base (roof of blister like BP)
• Treatment:
• The disease is generally mild and resolves spontaneously in the course of days to weeks after onset.
 Subcorneal Pustular Dermatosis
• Aka Sneddon-Wilkinson
• Etiology still unknown, but certain associations
have been seen including a benign monoclonal
IgA gammopathy and pyoderma
gangrenosum
• Clinical
• annular or polycyclic lesions, usually commencing in
the flexures, with hallmark superficial (subcorneal)
sterile pustules Treatment: Dapsone
• Has a cyclic course, as the pustules resolve they are
replaced by superficial scaling and then new
pustules form again
• Histology
• Perivascular inflammatory infiltrate with neutrophils and
occasional eosinophils.
• Neutrophils migrate through the epidermis, without
forming spongiform pustules, to collect beneath the
stratum corneum in subcorneal pustules
 Chilblains
• Abnormal inflammatory response to cold, damp, non-freezing
conditions
• Common in the UK and northwestern Europe, particularly in
those whose homes lack central heating
• Unknown pathogenesis, but thought to have a vascular origin
• Clinical:
• lesions are red-purple and usually macular, papular
or nodular
• develop symmetrically on acral skin, in particular the
fingers and toes, but can occur elsewhere
• Histology:
• Nonspecific, consisting of dermal edema plus a
superficial and deep lymphohistiocytic infiltrate
(mainly T cells) with peri-eccrine accentuation
• Treatment:
• Adequate clothing and avoidance of cold, damp
conditions are important preventive measures, as
are keeping feet dry and avoidance of smoking.
• In a Double-blind, placebo-controlled trial, nifedipine
(20 to 60 mg daily) was found to be efficacious for
the treatment of pernio
Phytophotodermatitis
• Pathogenesis: A phototoxic eruption, commonly caused by a topical
or oral photosensitizing agent followed by exposure to UVR.
• Members of 2 plant families are common causes: Apiaceae and
Rutaceae. The common photosensitizer is furocoumarins.
• Clinical presentation: Random configurations of erythema, edema
and bullae after sun exposure.
Phytophotodermatitis
Erythema Multiforme
• Clinical Presentation: Typical target lesions with at least three distinct
zones. There is usually a central bullae and the lesion resembles a
target.
• Pathogenesis: Occurs in predisposed individuals, often in the setting
of HSV or Mycoplasma Pneumonia infection.
• Histopathology: Spongiosis and focal vacuolar degeneration of basal
keratinocytes with dermal edema and a perivascular infiltrate of
mononuclear leukocytes and T lymphocytes
Erythema Multiforme
Bullous Mastocytosis
• Some infants with urticaria pigmentosa or diffuse cutaneous
mastocytosis may develop bullous lesions
• Thought to be due to increased mast cell serine proteases
• Often resolves by age 3-5y
• Manage as you would for other child mastocytoses with increased
attention to wound care for eroded lesions
Diffuse cutaneous mastocytosis with the
formation of vesicles and bullae

Tharp, MD. Mastocytosis in Dermatology 3rd Ed. Bolognia J et al. Elsevier 2012 p 1996
 Porphyria
• Inherited or acquired disordes due to enzyme deficiency causing
increased production of photosensitizing porphyrins or their precursors
during heme synthesis
Table from: Photosensitivity and Photoreactions in Hurwitz Clinical Pediatric Dermatology,
Mancini AJ, Paller AS. Elsevier 2011. p 449
Porphyria
• Congenital Erythropoeitic Porphyria (CEP) [AR]
• Onset in infancy through 1st decade
• Extreme photosensitivity, hypertrichosis, erythrodontia
• Erythropoeitic Porphyria [AD]
• Onset between 1-4yo
• Photosensitivity with burning, gallstones, hepatic damage
• Hepatoerythropoetic Porphyria [AR]
• Usually manifest before 2 years of age
• Dark urine is most common initial finding
• Acute Intermittent Porphyria [AD]
• No skin findings
• Neurologic and psychiatric findings with abdominal pain
Friction Blisters
• Occur most commonly on the soles and heels.
• Caused by repeated friction
• Blistering occurs just below the stratum granulosum
Burns and Scalds
• Can be accidental or intentional (child abuse)
• Careful history and physical examination with care to note child caregiver
interactions
• In inflicted wounds there is often a delay in seeking care from the time of
injury
• Look for lesions in various stages of healing
Raimer SS, Raimer-Goodman L, Raimer BG. Skin Signs of Abuse in Dermatology 3rd Ed.
Bolognia J et al. Elsevier 2012 p 1523
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