Transcript Chronic Blistering Dermatoses Part 2

Chronic Blistering Dermatoses
Part 2
and Nutritional Diseases
Adam Wray, D.O.
May 9, 2006
Pregnancy- Related Dermatoses
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Intrahepatic Cholestasis of Pregnancy
Polymorphic Eruption of Pregnancy
Herpes (pemphigoid) gestationis
Pruritic Urticarial Papules and Plaques of
Pregnancy (PUPPP)
Papular Dermatitis of Pregnancy
Pruritic Folliculitis of Pregnancy
Intrahepatic Cholestasis of
Pregnancy
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Generalized pruritus and jaundice
No primary skin lesions, secondary excoriations
Caused by cholestasis, occurs late in pregnancy,
resolves after delivery
Increased incidence of fetal comp.
0.5% of pregnancies
Tx: ursodeoxycholic acid more effective than Sadenosyl-L-methionine
Pruritic Urticarial Papules and
Plaques of Pregnancy (PUPP)
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First reported in 1979
Erythematous papules and plaques that
begin as 1-2 mm lesions within the
abdominal striae
Spread over the course of a few days to
involve the abdomen, buttocks, thighs
Upper chest, face, and mucous
membranes spared
PUPPP
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Primigravidas 75% of the time, usually
does not recur with subsequent
pregnancies
Begins late in third trimester and resolves
with delivery
May be associated with increase weight
gain
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More common in those carrying twins/triplets
PUPPP
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Histology:
perivascular infiltrate
in upper and mid
dermis, epidermis
normal
DIF negative
Tx: topical or oral
steroids
Papular Dermatitis of Pregnancy
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Controversial entity
Pruritic generalized eruption of 3-5 mm
erythematous papules surmounted by a small,
firm, central crust
May erupt at any time during pregnancy and
resolve with delivery
Marked elevation of 24 hr urine HCG
Tx: oral steroids, may recur in subsequent
pregnancies
Prurigo Gestationis (Besnier)
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Pruritic, excoriated
papules of the proximal
limbs and upper trunk
Onset is 20-34 weeks
gestation
Clears in postpartum
period and does not recur
Tx: topical steroids
Pruritic Folliculitis of Pregnancy
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2nd or 3rd trimester
Small follicular pustules scattered widely
over the trunk
May be a type of hormonally induced acne
Impetigo Herpetiformis
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Form of severe pustular psoriasis occurring in
pregnancy
Acute, usually febrile onset of grouped pustules
on an erythematous base
Begins in the groin, axillae, and neck
Increased WBC, hypocalcemia
Recurs with pregnancy, fetal death due to
placental insufficiency
Tx: prednisone 1mg/kg
Cicatricial Pemphigoid (Benign
Mucosal Pemphigoid)
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Vesicles which quickly rupture, leaving erosions
and ulcers with scarring
Primarily occur on mucous membranes,
conjunctiva (66%) and oral mucosa (90%)
Oral mucosa may be the only affected site for
years; desquamative gingivitis of buccal mucosa
Ocular complications: bilateral, flaccid vesicles
on conjuntivia, xerosis, symblepharon, and
blindness may result.
Generally confined to head and neck
Cicatricial Pemphigoid
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Tends to affect middle-aged to elderly women
2:1 female/male
Ddx; oral lichen planus (biopsy and IF)
Chronic disease that may lead to slowly
progressive shrinkage of the ocular mucous
membranes and blindness
Also occurs in pharynx, esophagus, larynx, nose,
penis, vagina, anal mucosa, deafness
Cicatricial Pemphigoid
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Cutaneous lesions in 25%; tense bullae
Bullae heal with or without scarring, occur on
the face, scalp, neck, and inguinal region and
extremities
Some pts may have antibodies targeted against
classic bullous pemphigoid antigens and should
be classified as “mucosal predominate bullous
pemphigoid”
Chronic course, pts health not usually affected
IgA antibodies may explain mucosal scarring
tendency
Cicatricial Pemphigoid
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Little tendency to remission (unlike bullous
pemphigoid)
Subtypes include types that target
basement membrane zone antigens
(laminin, glycoproteins,)
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Intracellular C-terminal domain of BP-180
Laminin 5 (antiepiligrin cicatricial pemphigoid)
Beta4 subunit of alpha6beta4 integrin
Cicatricial Pemphigoid
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Direct IF testing C3 and IgG at the lamina
lucida in 80-95%
Tx: mild cases topical steroids
(Temovate/Orabase), intralesional
triamcinolone every 2-4 weeks
Tx: Dapsone, prednisone, Azathioprine or
cyclophosphamide, cyclosporine, TCN
Epidermolysis Bullosa Acquisita
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Antibodies to Type VII collagen
Skin fragility, healing with scars
Bullous eruption, scaring, milia
Histo: epidermal necrosis, subepidermal blister,
dermal necrosis, lack of inflammation until
lesions become older.
IgG deposition on dermal side of salt-split
Associations: myeloma, granulomatous colitis,
diabetes, lymphoma, leukemia, amyloidosis, and
carcinoma
EBA
IgG on floor of blister, in contrast
to pemphigoid.
EBA criteria proposed in 1971 by
Roenigk
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1)
2)
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5)
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clinical lesions of EBA
adult onset
lack of a family hx of EB
exclusion of all other bullous dz
IgG at BMZ by DIF
blister beneath basal lamina
deposition of IgG beneath basal lamina
Epidermolysis Bullosa Acquisita
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Tx; unsatisfactory, steroids, dapsone,
colchicine, IV Immunoglobulin,
Cyclosporin
Dermatitis Herpetiformis
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Chronic, relapsing, severely pruritic dz
Grouped symmetrical, polymorphous,
erythematous-based lesions
May be papular, papulovesicular,
vesiculobullous, bullous, or urticarial
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Linear petechial lesions on palms, fingers
Pigmented spots over lumbosacral region
Itching and burning are intense
Spontaneous remissions lasting a week
Dermatitis Herpetiformis
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Laryngeal lesions 
hoarseness
Premenstrual flares
may occur
Oral iodides may flare
dz
Dermatitis Herpetiformis
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Very few patients with DH ever have diarrhea
although DH is associated with Gluten-sensitiveenteropathy (GSE)
87% of pts with DH and IgA deposits in the skin
are HLA-B8 positive (like GSE)
Gluten is a protein found in cereals except for
rice, oats, and corn
IgA antibodies are formed in the jejunum, may
deposit in the skin
Dermatitis Herpetiformis
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Associated with; Thyroid disorders, small
bowel lymphoma, non-Hodgkins
lymphoma
70-100% of pts have abnormalities of the
jejunal mucosa
Gluten-free diet decreases Dapsone dose
requirements after 3-4 months
Dermatitis Herpetiformis
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Ddx: pemphigoid, EM, scabies, contact
dermatitis, atopic dermatitis, eczema,
insect bites, pruigo nodularis
IgA in a granular pattern in the
dermal papillae in normal skin is
specific and pathognomonic for DH
Dermatitis Herpetiformis
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IgA deposits may be focal, so multiple
biopsies may be needed.
Deposits of the antibody are more often
seen in previously involved skin or normal
appearing skin adjacent to involved skin
Dermatitis Herpetiformis
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Equal male:female
Onset between 20 to 40 years
Tx: Dapsone 50-300mg daily (hemolytic
anemia, methemoglobinemia, check G6PD
prior to tx) monitor Hct,WBCs, LFTs
Tx: Sulfapyridine 0.5g QID to 2-4g/day
Gluten-free diet will decrease need for
meds or allow pt to go off them
Linear IgA Bullous Dermatosis
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Subepidermal blisters, a neutrophillic
infiltrate, circulating IGA antibasement
membrane zone antibody
Deposition of IgA antibody at the
dermoepidermal junction by direct IF
Linear IgA Bullous Dermatosis
Adult Form
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Acquired autoimmune blistering disease
Clinical pattern similar to dermatitis
herpetiformis, or with vesicles and bullae in a
bullous pemphigoid-like appearance
50% mucous membrane involvement
Oral and conjunctival lesions may be scarring
No association with enteropathy or with HLA-B8
Tends to remit over several years
Linear IgA Bullous Dermatosis
Adult Form
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Linear IgA dermatosis can occur as a druginduced disease:
Self-limited, less mucosal involvement, usually
does not have circulating autoantibody
IgA is usually deposited in the subbasal lamina
area
Vanco, Lithium, amiodarone, carbamazapine,
captopril, PCN, PUVA, lasix, dilantin, oxaprozin,
statins, tea tree oil, and others
Linear IgA Bullous Dermatosis
Adult Form
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Histo: papillary dermal microabscess with
neutrophils, subepidermal bullae may be seen
with neutrophils and eosinophils
Direct IF: homogeneous linear deposition of IgA
is present at the BMZ
Indirect IF: few will have circulating IgA
autoantibody with anti-BMZ specificity
On salt-split, deposition of IgA may be on the
roof, base, or a combination of both.
Tx: Dapsone, topical steroids
Linear IgA Bullous Dermatosis
Childhood Form
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Chronic Bullous Disease of Childhood: acquired,
self-limited bullous disease
Onset by 2 or 3, remits by age 13
Bullae develop on erythematous or normal
appearing skin
Trunk, buttocks, genitalia, and thighs
Perioral and scalp lesions are common, oral
lesions not uncommon
Bullae arranged in a rosette or annular array
“cluster of jewels”
Linear IgA Bullous Dermatosis
Childhood Form
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Histo: subepidermal bullae filled with
neutrophils, eosinophils may predominate
Direct IF: linear deposition of IgA at the BMZ
Indirect IF: positive for circulating IgA antibodies
in 50%
Tx: Sulfapyridine or dapsone, topical steroids
In contrast to adults, children show increased
frequency of B8, DR3, and DQ2 HLA antigens.
Transient Acantholytic
Dermatosis
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Over age 50, strong male
predominace
Fragile vesicles, limited extent,
sparse, limited duration
Rapid crusting, keratotic
erosion <1cm
Usually chest, shoulder girdle,
and/or upper abdomen
Patients at strict bedrest
higher incidence.
Direct IF is negative
Tx: topical steroids,
isotretinoin, dapsone, PUVA
Nutritional Diseases
Andrews Chapter 22
Nutritional Diseases
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Caused by insufficiency or excess of dietary
essentials
Common in underdeveloped countries, infants
and children
Often pts have features of several disorders if
diet is generally restricted
Alcoholism is the main cause in developed
countries
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Postoperative pts, psychiatric pts (anorexia nervosa,
bulimia), surgical or inflammatory bowel dysfunction,
Crohn’s
Hypovitaminosis A
(Phrynoderma)
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Vitamin A: fat soluble found in milk, fish oil, liver,
eggs, and as carotenoids in plants
Common in children in developing world
Developed countries found in diseases of fat
malabsorption; Crohn’s, celiac, cystic fibrosis,
cholestatic liver disease, bowel bypass surgery
for obesity.
Vitamin A required for keratinization of mucosal
surfaces
Hypovitaminosis A
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Abnormal keratinization leads to increased
mortality from inflammatory disease of the gut
and lung ie; diarrhea and pneumonia
Phrynoderma or “toadskin” resembles
keratosis pilaris.
Keratotic papules over extremities and shoulders
arising from pilosebaceous follicles
Hypovitaminosis A
Ocular Findings
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Major cause of blindness in children in the
developing world!
Earliest finding is delayed adaptation to the dark
(nyctalopia)
Night blindness, xeropthalmia, xerosis corneae,
keratomalacia
Bitot’s Spots; circumscribed areas of xerosis
of the conjuctiva lateral to the cornea
Hypovitaminosis A
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Diagnosis: based on eye findings, serum
Vitamin A level.
Tx: 300,000 IU Vitamin A followed by the
recommended dietary requirement
Hypervitaminosis A
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Skin findings similar to side effects of Retinoid
therapy. Children are at greater risk as well as
dialysis patients.
Loss of hair and coarseness, loss of eyebrows,
exfoliation and pigmentation of skin, clubbing,
hepatosplenomegaly, anemia, increased LFTs,
pseudotumor cerebri with papilledema,
premature closure of epiphyses
Hypervitaminosis A
Adults
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Early signs are dryness of the lips and anorexia.
Followed by bone and joint pains, follicular
hyperkeratosis, brawny desquamation of the
skin, loss of scalp hair and eyebrows, dystrophy
of the nails.
Fatigue, myalgia, depression, anorexia, liver
disease
Birth defects with excess Vit A in
pregnancy
Vitamin D
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Deficiency of Vitamin D causes alopecia,
osteomalacia
Vitamin D overdose can cause
hypercalcemia and calcinosis.
Vitamin E Deficiency
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Most common in infants of low birth
weight
Peripheral edema, progressive
neuromyopathy, and ophthalmoplegia
Vitamin K Deficiency
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Dietary deficiency of vitamin K, a fat soluble
vitamin, does not occur in adults because it is
synthesized by bacteria in the large intestine
Liver and biliary disease, cystic fibrosis, and
anorexia nervosa causes deficiency
Drugs: coumadin, salicylates, cholestyramine,
and possibly cephalosporins
Vitamin K Deficiency
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Decrease in the vitamin K-dependent
clotting factor II, VII, IX, and X.
Purpura, hemorrhage, and ecchymosis.
Tx: 5 to 10 mg/day IM Vit K for 2-3 days
Vitamin B1 Deficiency
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Thiamine deficiency results in Beriberi
Edema, and peripheral neuropathy
Vitamin B2 Deficiency
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Riboflavin deficiency is seen
most often in alcoholics.
Phototherapy for neonatal
icterus, boric acid ingestion,
hypothyroidism,
chlorpromazine
Oral-ocular-genital
Syndrome: angular chelitis,
atrophic tongue, photophobia,
blepharitis, confluent
dermatitis of scrotum
Tx: 5mg Riboflavin qd
Vitamin B6- Pyridoxine
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Deficiency: occurs in uremia and cirrhosis
Seborrheic dermatitis, glossitis, chelitis,
conjunctivitis, confusion, neuropathy
Somnolence, confusion, and neuropathy
Excess: subepidermal vesicular
dermatosis, peripheral sensory neuropathy
Vitamin B12 Deficiency
Cyanocobalamin
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Absorbed through the distal ileum after binding
to gastric intrinsic factor in an acid ph.
Deficiency caused by: decreased intrinsic factor,
achlorhydria, malabsorption syndromes
(pancreatic, sprue)
Because of large body stores in adults,
deficiency occurs 3 to 6 years after onset of GI
disease!
Vitamin B12 Deficiency
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Glossitis, hyperpigmentation accentuated
in exposed areas resembling Addison’s
disease
Megaloblastic anemia, weakness,
paresthesias, ataxia
Tx: IM B12, neuro defects may not
improve
Folic Acid Deficiency
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Diffuse hyperpigmentation, glossitis,
chelitis, and megaloblastic anemia
Scurvy
Vitamin C Deficiency
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Most common vitamin deficiency dxd by
dermalologists
Elderly alcoholics and psychiatric pts
Scurvy
“The Four H’s”
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Hemorrhagic signs
Hyperkeratosis of the hair follicles
Hypochondriasis
Hematologic abnormalities
Scurvy
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Perifollicular petechiae and ecchymoses,
subungual, subconjunctival, intramuscular, and
intraarticular hemorrhage
“Corkscrew hairs”; hairshafts are curled in
follicles capped by keratotic plugs
Hemorrhagic gingivitis; bleeding gums, epistaxis,
anemia
Scurvy
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Dx: serum ascorbic acid level
Tx: ascorbic acid 1000mg qd x 1 week;
maintenance of 100 mg/day
Niacin Deficiency
Pellagra
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Nicotinic acid, vitamin B3,
niacin or its precursor
tryptophan is associated
with a diet entirely
composed of corn, millet
or sorghum
Other vitamin deficiencies
or malnutrition coexist
Most cases are alcoholics
in developed countries
Pellagra
Causes
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Carcinoid tumors, which divert tryptophan to
serotonin
Hartnup dz (impaired absorption of tryptophan)
Intestinal parasites esp; hookworm
GI diseases ie Crohn’s and GI surgery
IV alimentation
Anorexia nervosa
Meds; Isoniazid, azathioprine, 5-FU, Hydantoins
Pellagra
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Chronic disease affecting
GI tract, CNS, skin
“3 D’s”; diarrhea,
dementia, dermatitis
Dermatitis:
photosensative eruption,
perineal lesions,
thickening and
pigmentation over boney
prominences, seborrheic
dermatitis-like eruption
on face
Pellagra
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Photosensitive eruption
on face, neck, chest
(Casal’s necklace),
eruption may be vesicular
or bullous (wet pellagra)
After several phototoxic
events the skin shows
hyperpigmentation,
scaling, a copper hue
Scrotal and perineal
erosions, fissures, angular
cheilitis
Pellagra
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CNS and GI
symptoms may occur
without skin changes;
apathy, muscle
weakness,
paresthesias,
dizziness, psychosis
Disease is
progressive, majority
of pts die in 4-5 years
if untreated
Pellagra
Diagnosis and Treatment
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Diet: Animal proteins, eggs, milk,
vegetables
100mg nicotinamide qid
Skin lesions begin to resolve within 24
hours of tx
Alcoholism should be addressed and
treated
Biotin Deficiency
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Biotin is universally available and is produced by
intestinal bacteria
Deficiency is rare, can occur in short gut,
malabsorption, long term antibx, ingestion of
avidin (found in raw egg white), and valproic
acid treatment in children
Dermatitis is perioral; patchy, red, eroded lesions
on the face and groin. May resemble Zn
deficiency.
Candida overgrowth of lesions occurs
Biotin
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Alopecia including loss of eyebrows and
eyelashes
Neuro: depression, lethargy, paresthesias
Infants: hypotonia, lethargy seizures,
developmental delays
Inherited form: detecting organic aminoaciduria
with 3-hydroxyisovaleric acid
Tx: 10mg Biotin qd Skin lesions resolve rapidly,
but neuro damage may be permanent
Zinc Deficiency
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Inherited or Aquired
Inherited: Acrodermatitis enteropathica
Premies at risk due to inadequate body
zinc stores
Weaning from breast milk precipitates
clinical zinc deficiency
Parental nutrition without adequate zinc
content may contribute
Zinc
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Acquired: alcoholics, bowel disease,
anorexia, AIDS
Zinc requirements increase with metabolic
stress
Diets containing mainly cereal grains are
high in phytate, which binds zinc, Middle
East, North Africa
Zinc
Dermatitis
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Pustular and bullous, acral and perioral
Patchy, red, dry, scaling with exudation
and crusts. Angular cheilitis and
stomatitis
Nail dystrophy, alopecia
Diarrhea, growth retardation, CNS
Histo: vacuolation of the keratinocytes of
the upper stratum malpighii
Zinc Deficiency
Diagnosis and Treatment
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Characteristic skin findings, acral or perioral
dermatitis
Chronic diaper rash with diarrhea in an infant
should lead to evaluation for zinc deficiency
Diagnosis: low serum zinc, alkaline phosphatase
Tx: zinc sulfate 1-2 mg/kg/day
Tx: acrodermatitis enteropathica is lifelong and
recommend 3mg/kg of Zn. Caution: may lead to
low serum copper levels
Essential Fatty Acid Deficiency
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Lbw infants, bowel disease, alimentation, cystic
fibrosis
Dermatitis similar to zinc def : xerosis, EFA’s
constitute 25% of the fatty acids of the stratum
corneum
Widespread erythema, intertriginous weeping
eruption, infection, alopecia
Decrease in linoleic acid and an increase in
palmitoleic and oleic acids
EFA Deficiency
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Ratio of eicosatrienoic acid to arachidonic
acid of >0.4 is diagnostic
Tx: Intralipid 10% IV
Iron Deficiency
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Common in menstruation
Mucocutaneous; glossitis, angular chelitis,
pruritus, telogen effluvium
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Plummer-Vinson syndrome:
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microcytic anemia, dysphagia, glossitis
(middle aged women) thin lips, narrow
mouth, koilonychia in 50%
Post-cricoid esophageal web
Iron Deficiency
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Diagnosis: serum iron (Fe+)
Tx: iron sulfate 325 mg tid
Selenium Deficiency
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IV alimentation, poor soil selenium
content, lbw infants
Children: hypopigmentation of skin and
hair (psuedoalbinism), leukonychia
Cardiomyopathy, muscle pain, elevated
muscle enzymes (cpk)
Tx: 3 ug/kg/day selenium
Protein-energy Malnutrition
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Spectrum of diseases: marasmus,
kwashiorkor, and marasmic kwashiorkor
Endemic in developing world
Marasmus; def of protein and calories,
children < 60% of IBW without edema
Kwashiorkor; protein def, 60-80% of IBW
with edema or hypoproteinemia
Marasmus/ Kwashiorkor
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Cystic fibrosis, dietary restrictions
Marasmus: skin is dry, wrinkled, loose
“Monkey facies”; due to lose of buccal fat
pad, no edema
Kwashiorkor; edema, potbelly, hair and
areas of skin are hypopigmented, hair is
red, gray to white
Kwashiorkor
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Africans call them “Red Children”
“Flag Sign”; alternating bands of pale and
dark hair along a single strand correspond
to periods of good and poor nutrition
“Mosaic skin”; areas of
hyper/hypopigmentation resemble peeling
paint
Carotenemia and Lycopenemia
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Excessive ingestion of : carrots, oranges,
squash, spinach, turnips, corn, beans, butter,
eggs, pumpkins, sweet potatoes, papaya
Yellowish discoloration of skin, palms, soles,
central face
Carotenemia occurs in vegetarians
Lycopenemia; red foods, beets, tomatoes, chili
beans (flatulence), berries leads to reddish
discoloration of skin aka “K.C. Chiefs’
syndrome