Atopic Dermatitis, Eczema, and

Noninfectious Immunodeficiency
Disorders
Rick Lin, DO MPH
July 15, 2003

Atopic Dermatitis

Aka atopic eczema

Aka infantile eczema
Aka flexural eczema
Aka disseminated neurodermatitis
Aka prurigo diathsique

Atopic Dermatitis
High level of IgE antibodies to House dust
mites
IgE bound to Langerhans cells in atopic
skin
Food exacerbates symptoms in some
patients: eggs, peanuts, cows milk
represent up to 75% of positive test.

Atopic Dermatitis
Pruritis is the hallmark of AD
Eczematous eruption leads to lichenified
dermatitis
Itching precedes the appearance of lesions

Infantile Atopic Dermatitis

60% of case AD present in the first year of
life, after 2 months of age
Begin as itchy erythema of the cheeks
Distribution include scalp, neck, forehead,
wrist, and extensors
May become desquamate leading to
erythroderma.

Infantile Atopic Dermatitis

Most cases the symptoms will disappear
toward the end of the second year.
The role of food allergy in infantile and
childhood atopic dermatitis has been
clarified
Egg, peanut, milk, wheat, fish, soy, and
chicken may exacerbate infantile AD

Involvement of the cheeks is characteristic of the infantile pattern of AD.

Childhood Atopic Dermatitis

Characterized by less acute lesions
Distribution: antecubital and popliteal
fossae, flexor wrist, eyelids, and face.
Severe atopic dermatitis involving more
than 50% of body surface area is associated
with growth retardation.

Adult Atopic Dermatitis

Distribution: antecubital and popliteal
fossae, the front side of the neck, the
forehead, and area around the eyes.
Atopic individuals are at greater risk of
developing hand dermatitis than are the rest
of the population
70% develop hand dermatitis some times in
their lives

Cutaneous stigmata

Dennie-Morgan fold
Pityriasis alba
Keratosis pilaris
Hertoghes sign thinning of the lateral
eyebrows
Keratosis punctata palmaris et plantaris

Vascular Stigmata
Headlight sign perinasal and periorbital
pallor
White dermographism blanching of the
skin at the site of stroking with a blunt
instrument cause edema and obscure color
of underlying vessels.

Infection
Staph aureus 90% of chronic lesions
Eczema herpeticum generalized herpes
simplex infection. Young children usually.
Vaccination against smallpox is
contraindicated in person with atopic
dermatitis. Even when condition is in
remission, widespread and even fatal
vaccinia can occur.

Immunology
T helper cell type 2 (Th2) dominance
Th2 produces IL-4, 5, and 10
IL-4 and IL-5 produce elevated IgE and
eosinophilia
IL-10 inhibits delayed type hypersensitivity
Th2 maybe sensitive to house mites or grass
pollen

Immunology
Monocytes produces elevated amount of
prostaglandin E2 (PGE2)
PGE2 reduces gamma-interferon
production, but not IL-4 from helper cells
thereby enhancing the Th2 dominance
PGE2 also directly enhances IgE production
from B cells

Immunology
Langerhans cells of AD patient stimulate
helper T cells into Th2 phenotype without
the presence of antigen
Langerhans cells have IgE bound to their
suface receptors. These IgE are associated
with atopic antigens, such as house dust
mites

Differential Diagnosis

Seb Derm
Contact dermatitis
Nummular eczema
Scabies
Psoriasis

Histology
Spongiotic dermatitis
Lichen simplex chronicus
Eosinophiles may be seen

Management
Protect from scratching
Adequate cleansing but not over bathing or
rubbing
Gentle cleanser
Anti-histamines, especially at night
Bathing protocol
Food allergies concerns and dietary restrictions.
Hydrate skin daily with moisturizers

Management
Topical steroid
Wet compress of Burows solution such as
Domeboro.
Crude coal tar/liquor corbonis detergens
(LCD)

Management
Topical FK506 (Tacrolimus) is
dramatically beneficial in SEVERE atopic
dermatitis
95% showed good improvement in Alaiti
and Rusicka study in JAAD 1998, Archive
1999

Regional Eczema

Ear eczema
Eyelid dermatitis
Nipple eczema
Hand eczema
Diaper dermatitis
Infectious eczematoid dermatitis
Juvenile plantar dermatosis

Ear Eczema
Most frequently caused by seborrheic or
atopic dermatitis
Staph, Strep, or Psoeudomonas
Earlobe is pathognomonic of nickel allergy

Eyelid dermatitis
When on one eye only, it is most frequently
caused by nail polish
When both eyelids are involved, consider
mascara, eye shadow, eyelash cement,
eyeline, etc

Nipple eczema
Painful fissuring, seen especially in nursing
mothers
Maybe an isolated manifestation of atopic
dermatitis
If persist more than 3 month, and/or
unilateral, biopsy is mandatory to rule out
Pagets

Hand eczema
Spongiosis histologically
Irritant hand dermatitis- seen in
homemakers, nurses. Resulting from
excessive exposure to soaps
Pompholyx- tapioca vesicles, on sides of
fingers, palms, and soles
Differentials Bullous Tinea, id, allergic
contact dermatitis

Treatment

Barrier
Moisturizer
Systemic Corticosteroids
Phototherapy UVA, PUVA, Radiotherapy
(Grenz Ray)

Diaper dermatitis

Jacquets erosive diaper dermatitis

Pseudoverrucous papule and nodules
Graduloma gluteal infantum
Irritation caused by bacteria, change in the
environment (wet, lower PH, feces)
Candida albicans are secondary infection.

Infectious eczematoid dermatitis

Vesicular, pustular, or cursted
Ulceration and superficial infection may be
present
Treatment involve the removal of irritant
and antibiotic treatment.

Juvenile plantar dermatosis

Begins as a patchy symmetrical, smooth, red,
glazed macules on the base of the great toes
Affect age 3 to puberty.
Symmetrical lesions on weight bearing area
toxic sock syndrome caused by repeated
maceration of the feet by occlusive shoes and
nonabsorbent synthetic socks
Virtually always resolve after puberty

Xerotic Eczema
Aka winter itch, nummular eczema, eczema
craquele, and asteototic eczema.
Anterior shins, extensor arms, and flank
Elderly person predisposed.
Use of bath oils in bath water is
recommended to prevent water loss
Moisturizers urea or lactic acid.

Nutritional Deficiency Eczema

Localized, thickened pattern with scaling
patches.
Exacerbated by nutritional deficiency

Hormone Induced Dermatoses

Autoimmune progesterone dermatitis urticaria,
urticarial paplues, papulovesicular lesion, or
eythema multiforme. Appear 5-10 days before
menses
Autoimmune estrogen dermatitis a cyclic skin
disorder with variable morphologies. Exacerbate
premenstrually or occur only immediately before
the menses. Treatment with tamoxifen maybe
effective.

Immunodeficiency Syndromes

X-Linked Agammaglobulinemia
Isolated IgA Deficiency
Common Variable Immunodificiency
Isolated Primary IgM Deficiency
Immunodificiency with Hyper-IgM
Thymic Hypoplasia
Thymic Dysplasia with Normal Immunoglobulins
(Nezelof Syndrome)

Immunodeficiency Syndromes
Purine Nucleoside Phosphorylase
Deficiency
Miscellaneous T-Cell Deficiencies
Severe Combined Immunodeficiency
Disease (SCID)
Thymoma with Immunodeficiency
Ataxia-Telangiectasia (Louis-Bars S.)
Wiskott-Aldrich Syndrome

Immunodeficiency Syndromes

X-Linked Lymphoproliferative Syndrome

Chronic Granulomatous Disease
Myeloperoxidase Deficiency
Leukocyte Adhesion Molecule Deficiency
Chediak-Higashi Syndrome
Hyperimmunoglobulinemia E Syndrome
Complement Deficiency
Graft-Versus-Host Disease

X-Linked Agammaglobulinemia
Aka Brutons syndrome, sex-linked
agammaglobulinemia.
Appear after 3-6 month of life
Frequent Strep and staph infection. Viral
resistance intact.
IgA, IgM, IgD, and IgE are absent in the serum.
IgG present with small amount
Cell-mediated immunity intact. T lymphocytes
are normal, B cells are completely lacking

X-Linked Agammaglobulinemia
Defect lies in the maturation block in pre-Bcell to B-cell differentiation
Protein tyrosine kinase (PTK) gene deletion
and point mutation
May develop leukemia, fatal encephalitis,
resporatory

Isolated IgA Deficiency

Absence or marked reduction of serum IgA
1:600 in white population, most are entirely
well.
Malignancy is increased in adult with IgA
deficiency.

Common Variable
Immunodificiency

Aka acquired hypogammaglobulinemia

HLA marker B8 and DR3 are affected
Recurrent sinopulmonary infections
B cells present but not terminally
differentiated
T cells dysfunction evident

Isolated Primary IgM Deficiency

Eczematous dermatitis presents in 1/5 of
patient with this condition
Predisposition to bacterial infection
Defect in maturation of IgM producing
plasma cell.

Immunodificiency with HyperIgM

Low or absent IgG, IgE, and IgA level. Normal or
elevated IgM and IgD
IVGG, and allogenic bone marrow transplant
X-linked form caused by mutation or deletion of
Xq26.3-27.1 region, which encodes a ligand of
CD40, gp39
Gp39-CD40 interaction signals for Ig isotype
switching.

Thymic Hypoplasia
DiGeorge anomaly, aka III and IV pharyngeal
pouch syndrome
Facies: notched, low-set ears, micrognathia,
shorten philtrum, hypertelorism
Congenital absence of the parathyroid, thymus,
and abnormal aorta
Hpocalcemia is the first sign
Aorteic and cardiac defects are the cause of death
Deletions within proximal long arm of
chromosone 22

Thymic Dysplasia with Normal

Immunoglobulins
(Nezelof Syndrome)
Faulty development of thymus gland
Autosomal recessive
Thymus is present but under developed, no
cardiac abnormalities.
Contrast to DiGeorge syndrome.

Purine Nucleoside Phosphorylase

Deficiency
Greatly reduced T-Cell counts, depressed
cell mediated immunity
B cells and antibody formation intact
Mutation on 14q13
Usually died of overwhelming viral
infection

Miscellaneous T-Cell
Deficiencies
Cartilage-hair hypoplasia syndrome, AR, patient
with short-limbed dwarfism, fine sparse,
hypopigmented hair, defective cell mediated
immunity.
Omenns syndrome, AR, mimic GVHD,
exfoliative erythroderma, eosinophilia, recurrent
infection, hypogammaglobulinema, diarrhea,
hepatosplenomegly, early death by 6 month.
Inefficient and abnormal generation of T-Cell
receptor.

SCID: Severe Combined

Immunodeficiency Disease
Severe impairment of humoral and cellular
immunity
Triad of Moniliasis of the oropharynx and
skin, intractable diarrhea, and pneumonia.
Overwhelming viral infection is the cause
of death.
Deficiency or total absence of circulating
lymphocytes

Thymoma with
Immunodeficiency
Goods syndrome
Deficient in cell mediated immunity and
benign thymoma occurring simultaneously
Thymectomy does not affect the
immunodeficiency

Ataxia-Telangiectasia
(Louis-Bars S.)
Distinctive telangiectasia in bulbar conjuctiva and
flexural suraces of the arm developing during the
5th year of age
Telangiectasia occurs on butterfly are of the face,
palate, ear, and exposed skin. Caf au lait patches,
and Graying hair also present.
Cerebellar ataxia is the first sign of this syndrome,
beginning in the second year of life.
Choreic and athetoid movement present.

 Persistent granulomatous
plaques on the leg of child
with ataxiatelangiectasia.

Wiskott-Aldrich Syndrome
Triad: chronic eczematous dermatitis resemble
AD, increase suseptibility to infections (OM), and
thrombocytopenia purpura/hepatoslpenomegly
Death by age 6
Accelerated IgA, IgM and IgE synthesis
T-cell decline in numbers and activity
Xp11 gene mutation. Codes for WASP protein
which reorganize cytoskeleton

X-Linked Lymphoproliferative
Syndrome
Aka Duncans disease
Inability to control Epstein-Barr virus
infection.
Pt normal until develop infectious Mono.
Xq26 abnormailty
B-cell lymphoproliferative disease with
acquired hypoglobulinemia.

Chronic Granulomatous Disease

Recurring purulent and granulomatous
infections involving long bones, lymphatic
tissue, liver, skin, and lung.
Deficient in one of the component of
NADPH-oxidase complex, which generates
superoxide.
Leads to inability to destroy bacteria per
radical mechanism

Chronic Granulomatous Disease

65% of cases are the X-linked form, lacks
the subunit of cytochrom b 558(gp91-phox)
Female carrier has mixed and normal and
abnormal cells thus shows an intermediate
phenotype.

Leukocyte Adhesion Molecule

Deficiency
Autosomal recessive
Recurrent bacteria and fungal infections and
pus formations as a result of a block of
leukocyte migration
Faulty complexing of the CD11 and CD18
integrins
Death occurs in first 4 years of life unless
bone marrow transplant is undertaken.

Chediak-Higashi Syndrome
Progressively degenerative, fatal, familial disease
of young children
Partial oculocutaneous albinism, cutaneous and
intestinal infections early in childhood
Ocular albinism is accompanied by nystagmus and
photophobia.
Defect in the gene LYST, resulting in defective
vascular transport to and from the lysosome

Hyperimmunoglobulinemia E
Syndrome
Consists of atopic-like eczematous
dermatitis, recurrent pyogenic infection,
high lever of IgE, elevated IgD, IgE
antistaph antibodies, and eosinophilia.
Face is consistently involved. Begin early
in life (2 month to 2 years)
Lesions resemble prurigo
Keratoderma of the palms and soles

Jobs syndrome
Subset of HIE.
Mainly affect girls with red hair, freckles,
blue eyes, and hyperextensible joints. Cold
abscesses occur.

Graft-Versus-Host Disease
Immunocompetent cells are intor duced as
graft or blood transfusion to host who is
unable to reject the graft cell.
Most commonly after bone marrow
transplant.
Begins between 4-5th weeks after transplant.
Result in exfoliative erythroderma.

Early, chronic graft-versus-host reaction with widespread, almost

confluent hyperpigmented lichenoid papules and toxic epidermal
necrosis-like appearance on knee

Late, chronic graft-versus -host reaction

with hyperpigmented sclerotic plaques
on the back

Acute graft-versus-host reaction with vivid palmar erythema

Graft-versus-host reaction with early, chronic, diffuse,

widespread lichenoid changes of lips

Acute erosions of the buccal mucosa in graft-versushost reaction

Graft-versus-host reaction; acute basal cell hydropic

degeneration with interepidermal necrotic keratinocytes

Graft-versus-host reaction; early chronic hyperkeratosis

and hypergranulosis, irregular acanthosis, cytoid body
and basal cell hydropic degeneration reminiscent of
lichen planus

End of Lecture