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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_5192_Библиотеки_им_академика_М_И_Перельмана.pdf
Keratitis-ichthyosis-
deafness (KID)
syndrome
Erythrokeratodermia
variabilis
Progressive
symmetric
erythrokeratoderma
Acral peeling skin
syndrome
GJB2 (encodes connexin
26)
GJB3
GJB4 (encode connexin
31 GJA1 and 30.3)
LOR
GJB4
other unknown gene(s)
TGM5 AR Recurrent spontaneous painless
AD (nearly all
reported cases
are sporadic)
AD Birth/infancy Transient, variable,
AD or AR Infancy/
Birth/infancy Transient neonatal erythroderma;
childhood
erythematous, hyperkeratotic
plaques w/ well-demarcated,
borders on face and
extremities; follicular keratoses;
thickening of the skin with an
appearance of “coarse-grained
leather;” stippled palmoplantar
keratoderma
erythematous patches;
more stable, geographic,
hyperkeratotic plaques over
knees, elbows, Achilles tendons,
extremities, buttocks, and lateral
trunk; face and scalp often
spared; less common generalized
hyperkeratosis; palmoplantar
keratoderma in 50% of patients
Fixed, slowly progressive,
erythematous, hyperkeratotic
plaques with sharp, figurate
borders; on cheeks, over knees,
elbows, extremities, and rarely
trunk; palmoplantar keratoderma
common
superficial peeling on dorsal
hands and feet, followed by the
development of mild erythema;
resolves without scarring;
exacerbated by heat and humidity
Congenital
sensorineural
hearing
impairment;
progressive keratitis
with corneal
neovascularization
that may lead
to blindness,
conjunctivitis;
recurrent
mucocutaneous
infections, especially
with Candida
albicans; increased
susceptibility to
oral and cutaneous
squamous cell
carcinoma; nail,
hair, and dental
anomalies; cheilitis
Burning or stinging
sensation preceding
or accompanying
erythema
Nonspecific; acanthosis,
papillomatosis, and
follicular plugging
Nonspecific; may reveal
reduced lamellar
bodies in stratum
granulosum and reduced
keratinization
Nondiagnostic; acanthosis,
hyperkeratosis, and
prominent granular layer
Separation occurs
between the junction of
the stratum granulosum
and the stratum corneum
Genetic testing
4.15 Miscellaneous Pediatric Dermatologic Disorders
285
286
Table 4.24 Features of Selected Ichthyoses and Erythrokeratodermas—cont'd
Diagnosis Gene Inheritance Onset Primary Cutaneous Features
Congenital
hemidysplasia with
ichthyosisiform
erythroderma
and limb defects
(CHILD) syndrome
(Fig. 4.39)
Conradi-Hünermann-
Happle syndrome
(X-linked dominant
chrondrodysplasia
punctata) (Fig. 4.40)
Ichthyosis
follicularis-atrichiaphotophobia (IFAP)
syndrome
a
Also occasionally associated with CIE or intermediate LI/CIE phenotypes; a CIE-like phenotype is also seen in harlequin ichthyosis sur vivors.
b
Also occasionally associated with mild LI or intermediate LI/CIE phenotypes.
CGH, Comparative genomic hybridization; FISH, uorescence in situ hybridization; PPK, palmoplantar keratoderma.
Modied from Richard G, Ringpfeil F. Ichthyoses, erythrokeratodermas, and related disorders. In: Bolognia JL, Schaffer JV, Cerroni L, eds. Dermatology. 4th ed. Philadelphia: Elsevier; 2018:888–923.
NSDHL
(3b-hydroxysteroiddehydrogenase)
EBP (emopamil-binding
protein)
MBTPS2 XLR Birth Erythroderma, scaling, and follicular
XLD Birth
XLD Birth At birth, ichthyosiform
At birth, unilateral (right . left-
sided) erythema and waxy,
yellowish adherent scale on half
of the body (trunk/ extremities);
later, verrucous hyperkeratosis
of variable extent, with affinity for
skin folds
erythroderma (generalized, vs.
unilateral in CHILD syndrome)
with feathery, adherent scale
along Blaschko’s lines; erythema
resolves in first few months
of life (unlike CHILD syndrome)
and is replaced by follicular
atrophoderma along Blaschko’s
lines, most prominently on the
forearms and dorsal hands
hyperkeratosis; generalized
alopecia, including eyebrows and
eyelashes
Associated Clinical
Features
Ipsilateral skeletal
hemidysplasia
(hypoplastic limbs);
ipsilateral organ
hypoplasia;
ipsilateral alopecia;
may also see
stippled epiphyses/
chondrodysplasia
punctata (similar to
Conradi-HunermannHapple)
Unilateral cataracts;
stippled epiphyses/
chondrodysplasia
punctata seen
only during infancy;
asymmetric skeletal
abnormalities,
including scoliosis
and rhizomelic limb
shortening, but
less severe than
CHILD syndrome;
frontal bossing w/
macrocephaly; patchy
scarring alopecia
Growth retardation
and microcephly;
corneal opacities
and ulcerations;
photophobia;
vascularizing keratitis;
variable hearing
loss; nail dystrophy;
variable intellectual
impairment,
developmental
delay, seizures,
and structural
CNS anomalies;
genitourinary
anomalies and
skeletal anomalies
Histology and
Ultrastructural Features
Nonspecific; acanthosis,
papillomatosis, and
superficial perivascular
infiltrate
Nonspecific;
hyperkeratosis and focal
parakeratosis; may see
dystrophic calcification in
keratotic plugs
Follicular plugging
and hypoplastic
pilosebaceous structures
Ancillary Diagnostic
Studies
Genetic testing
Epiphyseal stippling on
X-ray only visible during
infancy; accumulation
of plasma cholesterol;
genetic testing
CHAPTER 4 • Pediatric Dermatology
Fig. 4.37 Lamellar ichthyosis phenotype of autosomal recessive congenital ichthyosis. Large plate-like scaling on the forehead and cheeks. This patient shows
moderate ectropion. (From Paller AS, Mancini AJ. Hereditary disorders
of cornication. In: Hurwitz Clinical Pediatric Dermatology: A Textbook of Skin
Disorders of Childhood and Adolescence. 5th ed. Philadelphia: Elsevier;
2016:95–118.)
4.15 Miscellaneous Pediatric Dermatologic Disorders
A
Fig. 4.38 Erythroderma, hypotrichosis, and areas with ichthyosis linearis circumexa. (From Pastore S, Gorlato G, Berti I, Barbi E, Ventura A. Successful induction of oral tolerance in Netherton syndrome. Allergol Immunopathol (Madr)
2012;40[5]:316–317.)
Fig. 4.39 CHILD syndrome. Unilateral erythema and scale with ipsilateral limb
defects. (From Baden HP, DiGiovanna JJ. Ichthyosiform dermatoses. In: Rimoin
DL, Pyeritz RE, Korf BR. Emery and Rimoin’s Principles and Practice of Medical
Genetics. 6th ed. Philadelphia: Elsevier; 2013.)
B
Fig. 4.40 Conradi-Hünermann syndrome. (A) Thick, psoriasiform scaling overlying erythema in a 1-month-old girl with the syndrome and chondrodysplasia
punctata. As the scaling desquamated, the underlying erythema along Blaschko’s
lines became more apparent. (B) The pattern of scale along Blaschko’s lines is
more evident in this neonate with Conradi-Hünermann syndrome. ( A, from Foley
CC, Paller AS, Irvine AD. Disorders of cornication (ichthyosis). In: Eicheneld LF,
Frieden IJ, eds. Neonatal and Infant Dermatology. 3rd ed. Philadelphia: Elsevier;
2015; B, from Paller AS. Ichthyosis in the neonate. In: Dyall-Smith D, Marks R,
eds. Dermatology at the Millennium. London: Parthenon Publishing Group; 1998,
with permission.)
• May be an AD inheritance pattern with incomplete
penetrance
■
HLA-DR4 DRB1*0407 polymorphism present in
60%–70% of patients
• Seasonal variability in severity
■
Flares in spring and persists through summer
■
Improves in fall, but usually does not completely
remit in winter
• Intensely pruritic eruption on sun-exposed areas, though
covered skin may also be involved
■
Presents as papules and nodules that are frequently
excoriated and crusted
■
Progresses to eczematous plaques with lichenication;
secondary bacterial infection may occur
■
Dyspigmentation and scarring are common (vs.
polymorphous light eruption [PMLE])
• Actinic cheilitis is a characteristic feature
■
65%–85% of patients will have lip involvement with
pruritus, edema, scale, and crusting
■
Actinic cheilitis without other features may be seen in
10%–25% of children
287
288
Table 4.25 Selected Hereditary Palmoplantar Keratodermas (PPKs) With Known Genetic Basis
Type Gene Gene Product Synonyms Inheritance Onset Transgrediens Comments
Diffuse
Unna-Thost
(Fig. 4.41)
Vörner KRT1
Mal de Meleda SLURP-1 Secreted Ly6/Plaur
Greither KRT1 (in some
Mutilating
(Vohwinkel)
(Fig. 4.42)
Papillon-Lefèvre
syndrome
Naxos disease JUP Plakoglobin Diffuse NEPPK with woolly hair and
Focal
Striate type
Areata type
Richner-Hanhart
syndrome
Pachyonychia
congenita
Carvajal
syndrome
Howel-Evans
syndrome
AD, Autosomal dominant; AR, autosomal recessive; SCC, squamous cell carcinoma.
Modied from Krol AL, Siegel D. Keratodermas. In: Bolognia JL, Jorizzo JL, Schaffer JV. Dermatology. 3rd ed. Philadelphia: Elsevier; 2012:871–885.
KRT1
KRT6c
KRT9
families)
LOR (1
ichthyosis)
GJB2 (1
deafness)
CTSC Cathepsin C PPK with periodontitis AR Birth to early
DSG1
DSP
KRT1
KRT16
KRT6c
TAT Tyrosine amino-
KRT16
KRT6a
KRT17
KRT6b
DSP Desmoplakin Striate PPK with woolly hair and
RHBDF2/
IRHOM2
Keratin 1
Keratin 6c
Keratin 1
Keratin 9
domain-containing
protein-1
Keratin 1 Transgrediens and progrediens PPK AD Infancy Yes
Loricrin
Connexin 26
Desmoglein 1
Desmoplakin
Keratin 1
Keratin 16
Keratin 6c
transferase
Keratin 16
Keratin 6a
Keratin 17
Keratin 6b
Rhomboid 5,
drosophila, homolog
of 2/inactive
rhomboid protein 2
Nonepidermolytic PPK (NEPPK) AD 2–5 years,
Epidermolytic PPK (EPPK) AD 0–3 years No Clinically identical to diffuse NEPPK, but histology
Mal de Meleda AR 0–3 years Yes Atopic dermatitis; transgradiens PPK erythematous
Vohwinkel syndrome; keratoderma
hereditaria mutilans
cardiomyopathy
Wachters type, Brünauer-
Fuhs-Siemens type
Tyrosinemia type II, oculocutaneous
tyrosinemia
PC1, Jadassohn-Lewandowsky
type
PC2, Jackson-Lawler type PC2: steatocystoma multiplex and eruptive vellus hair
cardiomyopathy
Tylosis with esophageal cancer AD Childhood No Thick yellow PPK on weight-bearing areas (heels
AD Infancy Yes Honeycombed palmar PPK , pseudoainhum (esp.
AR Infancy No Woolly hair; arrhythmias and right ventricular
AD 4–10 years No Striate on palms and islands on feet; variable
AR Infancy (ocular)
AD Infancy to early
AR . AD
sometimes later
infancy
Early childhood
to adolescence
(skin)
childhood
Infancy No Woolly hair; dilated left ventricular
No Second most common type of diffuse PPK (after EPPK)
Yes, diffuse Transgradiens PPK w/ erythema/hyperhidrosis/
No Focal painful PPK on weight-bearing areas;
No PC1: more severe NEPPK
Diffuse, well-demarcated PPK w/ yellow hue;
hyperhidrosis
Histology w/ prominent orthokeratosis
shows epidermolytic hyperkeratosis
w/ fissures/hyperhidrosis/maceration/ horrible
odor/often infected; dystrophic nails
fifth finger – constriction bands → autoamputation),
starfish keratoses on the knuckles/ feet/
elbows/knees, linear keratoses on elbows/knees,
sensorineural deafness (connexin 26), and
generalized ichthyosis (loricrin)
terrible odor (soles . palms); pyogenic infections;
periodontitis/gingivitis → premature loss of
teeth, psoriasiform lesions on elbows/knees, and
pyogenic infections; dural calcification
cardiomyopathy develop during adolescence
phenotype
dendritic keratitis, corneal ulcers, and blindness
(ocular findings prior to skin findings); hyperkeratosis
of elbows/knees; developmental delay
cysts more common; natal teeth
cardiomyopathy (variable onset); occasionally skin
fragility, nail dystrophy, hypodontia
and balls of feet) starting in second decade
Significant risk for development of esophageal cancer
in third to fifth decade
CHAPTER 4 • Pediatric Dermatology
Fig. 4.41 Unna-Thost syndrome. (From Gehris RP, Ferris LK. Genodermatoses.
In: Schwarzenberger K, Werchniak AE, Ko CJ, eds. Requisites in Dermatology:
General Dermatology. Philadelphia: Elsevier; 2009:277–296.)
Fig. 4.42 Vohwinkel’s syndrome. Mutilating keratoderma. (From Gehris RP, Ferris LK.
Genodermatoses. In: Schwarzenberger K, Werchniak AE, Ko CJ, eds. Requisites in
Dermatology: General Dermatology. Philadelphia: Elsevier; 2009:277–296.)
• Actinic conjunctivitis can manifest as epiphora and
photophobia
• Biopsy of the lips commonly shows lymphoid follicle
formation and is a distinguishing feature
• Phototesting shows ↓ minimal erythema dose
in 60%
• Treatments: sun avoidance/photoprotection, NB-UVB
phototherapy in the spring can minimize ares, topical
corticosteroids, and short courses of oral prednisone may
help with ares; mainstay of treatment is thalidomide
• Often has a chronic course that continues into
adulthood
4.15 Miscellaneous Pediatric Dermatologic Disorders
Juvenile spring eruption
• Boys . girls; 5–12 years of age
• Triggered by UVA, UVB, and rarely visible light
• Thought to be a variant of PMLE
• Occurs in early spring with improvement through the
season
• Pruritic, skin-colored to pink edematous papules that can
progress to vesicles and crusting
■
Most common on the helical ears, but can affect the
hands or face
■
Lesions self-resolve in 1 week w/o scarring
• Treatment: sun avoidance and photoprotection; NB-UVB
phototherapy for a 4- to 6-week course at the beginning of
spring may prevent recurrence; topical and systemic
corticosteroids; oral antihistamines
• Lesions self-resolve in several weeks, but may recur each
spring; disease remits after puberty
Diaper dermatitis
• Peak incidence at 9 to 12 months
• Risk factors: contact with urine/feces, friction/maceration,
and 2° infection with bacteria and/or yeast
• Irritant contact dermatitis: erythema of convex surfaces,
but tends to spare the folds
• Seborrheic dermatitis: salmon-colored erythema in the
folds
• Allergic contact dermatitis: most often due to blue dye or
mercaptobenzothiazole in the elastic band
• Psoriasis: diaper area is often the presenting area in
infancy; may be due to koebnerization from irritant
contact; presents as well-demarcated erythema 1/– scale
• Candidiasis: beefy red erythema and pustulovesicular
“satellite” lesions
• Granuloma gluteale infantum: purple red nodules, often
appearing after use of high-potency topical steroids and/
or prolonged use of cloth diapers (nonabsorbent)
• Perianal pseudoverrucous papules and nodules: at
topped, wart-like papules and nodules appear in incontinent
patients as a form of severe irritant contact dermatitis
• Jacquet’s erosive dermatitis: severe erosive dermatitis
with ulcerated papules and nodules; presents more
pinpoint than other erosive diaper dermatoses
• Acrodermatitis enteropathica: similar to “erosive psoriasis”
of the diaper area; also affects perioral area
• Langerhans cell histiocytosis: severely erosive in the folds,
petechial papules
• Treatment:
■
Meticulous diaper hygiene with frequent diaper
changes and gentle cleansing, avoid packaged wipes
when possible
■
Application of thick barrier ointments
■
Low-potency topical steroid ointments (avoid in
granuloma gluteale infantum)
Juvenile plantar dermatosis
• Boys . girls
• May be worse in summer and cold weather
• Most likely represents a frictional irritant dermatitis
289
CHAPTER 4 • Pediatric Dermatology
• Erythematous, symmetrical, smooth red plaques, affecting
the plantar surfaces of the distal soles and toes, with
sparing of the web spaces
■
5% may have similar changes on ngertips
■
May be associated with hyperhidrosis (“sweaty sock
syndrome”)
• Treatments: cotton or super absorbent socks and avoidance
of occlusive footwear, absorbent foot powder, emollients,
and medium-/high-potency topical corticosteroids
Acropustulosis of infancy
• Onset is typically between birth and 2 years of age
■
Most common in black infants
• Etiology unknown; some cases a/w preceding scabies
infection
• Recurrent crops of vesiculopustules over the palms, soles,
and distal extremities
• Biopsy not necessary but demonstrates neutrophils
• Treatment: systemic antihistamines and high-potency
topical corticosteroids
• Typically resolves spontaneously by 3 years of age
Trichorhinophalangeal syndrome
• Mainly AD, TRPS1 gene
• Cone-shaped epiphyses of the phalanges
• Short stature
• Pear-shaped nose with a rounded tip, long philtrum; and
thin upper lip
• Sparse hair, with possible total alopecia, mainly in males
Nail-patella syndrome (onychoosteodysplasia; Fong disease)
• AD, LMX1B (encodes collagen synthesis transcription factor)
• Hypoplastic or absent nails, most often on the thumb,
sometimes ngers (esp. medial), with dystrophy typically
worse on the radial side
• Triangular lunula
• Bony abnormalities including hypoplastic or absent patellae,
radial head dysplasia, and posterior iliac “horns” (exostoses)
• Nephropathy, especially glomerulonephritis, sometimes
causing renal insufciency
• Lester iris (darker pigmentation of central iris)
MIDAS syndrome (also MLS or microphthalmia with linear skin defects)
• XLD, HCCS gene
• Microopthalmia (among other ocular defects), dermal
aplasia, sclerocornea
• Linear skin defects → aplasia cutis congenita (ACC)—mostly
red-brown Blaschkoid on the face and neck, limited to upper
body
• Can also get agenesis of corpus callosum, seizures,
intellectual disability, and cardiac arrythmias
H syndrome
• AR, SCL29A3 (nucleoside transporter)
• Hyperpigmentation, Hypertrichosis with induration and
varicose veins characteristically of the thighs sparing
knees, Hallux valgus with exion contracture of toes,
Hepatosplenomegaly, Heart abnormalities,
Hypogonadism, decreased Height, Hyperglycemia/DM
Cutaneous ndings in patients with
chromosomal abnormalities
• Down syndrome (trisomy 21): transverse palmar crease,
syringomas, elastosis perforans serpiginosa, transient
myeloproliferative disorder (often presents as
vesiculopustular eruption) autoimmune diseases including
alopecia areata, epicanthic folds, predisoposition to yeast
and fungal infections, hidradenitis suppurativa, and scrotal
tongue
• Turner syndrome (XO): cystic hygroma → webbed neck,
transient peripheral lymphedema, ↑ numbers of nevi (but
no increased melanoma risk), multiple pilomatricomas,
propensity towards keloid formation, nail dystrophy, and
low posterior hairline, coarctation of the aorta
• Noonan syndrome (AD, PTPN11): lower extremity
lymphedema, CALMs, multiple nevi, light/curly/rough
hair, hypertelorism, ulerythema ophryogenes, webbed
neck, lowered nuchal hairline, and low-set ears (note:
allelic with LEOPARD syndrome—both have pulmonic
stenosis)
• Cardio-facio-cutaneous (CFC) (AD, BRAF . KRAS):
generalized ichthyosis-like scaling, keratosis pilaris
including ulerythema ophryogenes, CALMs, many nevi,
sparse curly hair, cardiac including pulmonary stenosis
• Costello syndrome (AD, HRAS . KRAS): lax skin
especially of the hands and feet, periorofacial papillomas,
acanthosis nigricans, curly hair, unusual body odor and
heat intolerance, cardiac including pulmonary stenosis,
increased risk of rhabdomyosarcoma
• Klinefelter syndrome (XXY): ↑ varicosities, leg ulcers, ↓
body hair, marfanoid habitis, and gynecomastia
Cutaneous mastocytosis
• Childhood and adulthood types; most cases present
before 15 years of age
• Adults more likely than children to develop systemic
symptoms/disease
• c-KIT mutations (activating mutations typically, as
tyrosine kinase accounts for increased pigmentation of
mastocyotmas)
■
D816V activating mutation found in 42% of children
and adults
■
Of note, c-KIT encodes KIT (CD117) on mast cells;
stem cell factor is the ligand for KIT and essential for
survival of mast cells
• Childhood forms
■
Solitary mastocytoma
Usually occurs as single tan/yellow-tan plaque/
nodule with an overlying peau d’orange appearance
Most commonly seen on distal extremities
Generally self-resolves over 1 to 3 years
■
Urticaria pigmentosa (Fig. 4.43)
Most common presentation in children
290
Fig. 4.43 Multiple tan to brown lesions of urticaria pigmentosa. (From Tharp MD.
Mast cell disease. In: Callen JP, Jorizzo JL, Zone JJ, Piette WW, Rosenbach MA,
Vleugels RA, eds. Dermatological Signs of Systemic Disease. 5th ed. Philadelphia:
Elsevier; 2017:370–376.)
Multiple light brown to red-brown macules and
papules, which can occur anywhere; start on trunk;
spare palms/soles/face
Pruritus and ushing may be seen; blistering
(bullous mastocytosis) in about one fourth patients
Symptoms improve by early adolescence, and skin
lesions often resolve
Patients with more lesions are more likely to have
systemic symptoms
Diarrhea, abdominal pain are most common
symptoms
Anaphylaxis is rare, but possible
■
Diffuse cutaneous mastocytosis
Inltrated, red-brown, leathery plaques with peau
d’orange appearance that can involve large areas of
body
Skin lesions frequently blister → erosions
↑ Incidence of systemic symptoms and progression
to systemic mastocytosis
Can also occur in adults, although rarely
• Adult Forms
■
Reddish-brown macules/papules: occur on trunk/
proximal extremities; ↑ in # over time; hyperpigmented;
most common presentation in adults
4.15 Miscellaneous Pediatric Dermatologic Disorders
■
Telangiectasia macularis eruptiva perstans: telangiectatic
macules and patches with no hyperpigmentation
• Darier’s sign (local erythema or urticarial wheal after
friction or rubbing) is present in all forms; more
pronounced in childhood forms due to increased
numbers of mast cells
• Systemic manifestations commonly occur in the systemic
mastocytoses (e.g., indolent systemic mastocytosis, mast
cell leukemia, and aggressive systemic mastocytosis)
■
Prognosis is poor for many of these disorders
■
Symptoms include skeletal lesions, bone marrow
involvement, hepatosplenomegaly, lymphadenopathy,
GI symptoms (diarrhea, abdominal pain, nausea/
vomiting, and GI hemorrhage), and mixed organic
brain syndrome
• On histology, mast cell inltrates are seen in the dermis of
lesional skin
■
Eosinophils and hyperpigmentation of the basal layer
may be present
■
Stains: toluidine blue, Giemsa, Leder, tryptase, and
CD117 (kit) antibodies
■
Bone marrow biopsy should be performed when
considering systemic disease, especially in adults
• Serum tryptase may be elevated but is often normal;
urinary histamine and histamine metabolites
(1,4-methylimidazole acetic acid and
N-methylimidazoleacetic acid) may be detectable
• Treatment:
■
Avoid mast cell degranulators (e.g., alcohol,
anticholinergics, nonsteroidal anti-inammatory drugs
[NSAIDs], aspirin, opiates including morphine and
dextromethorphan, polymyxin, and systemic
anesthetics)
■
Antihistamines (H1 and H2 antagonists), topical/
systemic steroids, topical calcineurin inhibitors, oral
cromolyn (best treatment for associated GI
symptoms), PUVA/UVA1, intramuscular epinephrine,
and imatinib (in some with systemic mastocytosis—
e.g., those who have FIP1L1-PDGFRA gene
rearrangement)
Neutrophilic eccrine hidradenitis of childhood
• Acute onset, painful palmoplantar papules and
nodules in children (6 months to 15 years)
• May be associated with chemotherapy or idiopathic
■
Pseudomonas hot foot syndrome is a variant due to
Pseudomonas in swimming pools or hot tubs
• Neutrophilic inltration around eccrine glands on
histopathology
291
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5
Infectious Diseases
Ali Alikhan and Thomas L.H. Hocker
CONTENTS LIST
5.1 VIRAL DISEASES
5.2 HIV/AIDS DERMATOLOGY
5.3 BACTERIAL INFECTIONS
5.4 FUNGAL DISEASES
5.5 PARASITES AND OTHER CREATURES
5.1 VIRAL DISEASES
I. Human papillomavirus (HPV)
• Double-stranded DNA virus that infects skin and
mucosal epithelial cells n warts and malignancies (e.g.,
cervical cancer and squamous cell carcinoma [SCC])
■
Capsid
Contains DNA
Composed of L1 (major structural protein) and L2
(minor structural protein)—important for binding/
entering epithelial cells
■
HPVs are species-specic and require fully
differentiated squamous epithelia for their life cycle
Productive infection/hyperproliferation can only be
accomplished if virus infects basal layer keratinocytes;
early proteins (E1–E7) are responsible for DNA
replication and keratinocyte immortalization;
late proteins (L1–L2) are expressed in supercial
epidermis and encode structural proteins required
for virion formation
E1 and E2 genes are rst to be expressed at strata
basale and spinosum—control transcription of other
genes 1 replication of viral DNA (using host cell
machinery)
E4 protein disrupts cytokeratin network n
koilocytosis
E5, E6, and E7 genes allow viral replication above
stratum basale n amplication
♦ E6 and E7 decrease host immune response (e.g.,
TLR-9 and IL-8)
♦ E6 and E7 in high-risk mucosal subtypes are
oncoproteins
E6 n ubiquitin-mediated p53 destruction n g
apoptosis/h replication/h mutations
E7 binds RB n loss of inhibition of E2F
transcription factor n h expression of genes
important for DNA replication
More supercial epidermal layers have higher L1
and L2 levels; complete virus observed in granular
layer and above
Host response is primarily cell-mediated in nature,
along with help from the innate immune system
(e.g., TLR-3 and TLR-9)
■
Genus a (most of the mucosal and cutaneous HPV
types) and b (epidermodysplasia verruciformis [EV]-
associated HPV types) account for most known types
• Typically spread via sexual contact or skin-to-skin/
fomite contact; HPV DNA found in normal skin and
perilesional skin
• Most warts resolve in 1 to 2 years without treatment
• Cutaneous manifestations of HPV infection
■
Common warts: hyperkeratotic papules with pinpoint
black dots (thrombosed capillaries), most commonly
on ngers, dorsal hands/elbows/knees; usually HPV-1,
-2, -4, -27, and -57 (HPV-57 can cause 10 nail
dystrophy)
■
Palmar/plantar warts: thick/deep endophytic papules
with black dots on palms/soles
Myrmecia refers to anthill appearance of some
plantar warts; mosaic refers to coalescence of several
warts on plantar surfaces
HPV-1, HPV-2, -4, -27, and -57
Histology: “church spire” papillomatosis 1
hyperkeratosis, acanthosis (with elongated rete
ridges), hypergranulosis, koilocytosis (granular
layer); h dermal vessels
■
Flat/plane warts: light pink/brown, soft/smooth,
slightly raised, occasionally linear at-topped papules
on dorsal hands/face
More common in children; adult women ..
adult men
HPV-3, -10, -28, and -29
Histology: alternating orthokeratosis/parakeratosis, mild
papillomatosis, hypergranulosis, acanthosis, koilocytosis
(granular/upper spinous layer; “bird’s eyes”)
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CHAPTER 5 • Infectious Diseases
■
Butcher’s warts: extensive lesions on hands in meat/
sh-handlers; HPV-7 and HPV-2
■
Ridged warts retain normal dermatoglyphics—
HPV-60; pigmented variant is more common in
Japan
■
EV: genetic disorder in which host has susceptibility to
genus b HPV types (HPV-3, -5, -8, -9, -12, -14, -15,
-17, -19–25, -36–38, -47, -49)
Autosomal recessive inheritance—mutations in
TMC6 (EVER1) and TMC8 (EVER2) (encode
transmembrane proteins in endoplasmic reticulum,
which interact with Zn transporter 1 n g Zn
intracellularly n g Zn-associated transcription
factors)
Acquired form may be seen in HIV
HPV types 5 and 8 can n Actinic keratoses and SCC
(generally patients $30 years old in sun-exposed
areas; .30% of patients will develop SCC)
Generalized polymorphic papules (generally at
wart-like appearance (dorsal hands, neck, face,
and extremities), but also scaly, pink macules or
hypopigmented, guttate macules/patches, and
seborrheic keratosis-like lesions on forehead/neck/
trunk)
Some cases have extensive and conuent warts n
generalized verrucosis
Histology: at wart-like architecture 1 large cells w/
perinuclear halos and blue-gray granular cytoplasm
(Fig. 5.1)
■
WHIM syndrome: autosomal dominant, primary
immunodeciency caused by a CXCR4 mutation—
warts, hypogammaglobinemia, infections (bacterial),
and neutropenia (2° to myelokathexis)
■
WILD syndrome: warts, immunodeciency,
lymphedema, and dysplasia (anogenital)
■
Treatments: destructive (cryotherapy, electrodessication
and curettage, scissors/shave removal, laser [pulsed dye
laser or CO
and salicylic acid preparations), immunomodulatory/
antiviral (diphenylcyclopropenone, cidofovir gel, and
intralesional immunotherapy [e.g., Candida]), 5-FU
(topically w/ salicylic acid usually or intralesional),
intralesional bleomycin
]/photodynamic therapy (PDT), cantharidin,
2
• Mucosal/genital manifestations of HPV infection
■
Genital warts (condyloma acuminata)
Most common sexually transmitted disease
Occur on external genitals/perineum/perianal/groin/
mons/vagina/urethra/anal canal
Smooth, sessile, raised, skin-colored to brown
lobulated papules
HPV-6, HPV-11, HPV-16, HPV-18, HPV-31, HPV-33,
and HPV-45
Condylomata plana (at cervical warts) best seen w/
acetic acid n whitening
Most cases resolve spontaneously within 2 years
Risk factors: sexual intercourse at young age, # of
sexual partners, and men who have sex with men
(MSM)
Circumcision n g risk HPV transmission
May n cervical cancer
♦ Most common scenario 5 persistent cervical
infection with high-risk HPV type (HPV-16,
HPV-18, HPV-31, HPV-33, and HPV-45)
♦ Immunosuppression (e.g., HIV1) can h risk
Histology: epidermal hyperplasia, koilocytosis
(should be seen in stratum spinosum too),
papillomatosis (less severe and more rounded than
in common warts), and parakeratosis
Treatments: destructive (cryotherapy, tricyclic
antidepressants [higher concentrations], electrosurgery,
scissors/shave removal, laser [CO
podophyllotoxin/podophyllin), immunomodulatory/
antiviral (imiquimod, sinecatechins, intralesional
immunotherapy, and cidofovir gel/intralesional)
HPV vaccines: contain L1 major capsid protein
(self-assembles into virus-like particles n allow for
development of immunity without any harm
because they do not contain DNA)
♦ Three types: quadrivalent (Gardasil; HPV-6, -11,
-16, and -18), bivalent (Cervarix; HPV-16 and
-18), and 9-valent (Gardasil 9; HPV-6, -11, -16,
-18, -31, -33, -45, -52, and -58)
♦ Best to use before sexually active—FDA-approved
for females and males $9 years old
■
Bowenoid papulosis: multiple brown papules/smooth
plaques on genitals/perineum/perianal that are high-grade
]/PDT, and
2
Hypergranulosis
Bluish keratinocytes
Fig. 5.1 Epidermodysplasia verruciformis histology—note the blue-gray cytoplasm of the keratinocyctes. (From Rapini RP. Viral, rickettsial, and chlamydial diseases.
In: Rapini RP, ed. Practical Dermatopathology. 3rd ed. Philadelphia: Elsevier; 2021:209–220.)
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