Atopic Dermatitis, Eczema, and Noninfectious Immunodeficiency by n7YOgrT

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									Atopic Dermatitis, Eczema, and
Noninfectious Immunodeficiency
           Disorders
         Adam Wray, D.O.
         August 10, 2004
            Atopic Dermatitis
•   Aka atopic eczema
•   Aka infantile eczema
•   Aka flexural eczema
•   Aka disseminated neurodermatitis
•   Aka prurigo diathsique
          Atopic Dermatitis
• Pruritis is the hallmark of AD
• “Itch that rashes”
• Eczematous eruption leads to lichenified
  dermatitis
• Itching precedes the appearance of lesions
          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, cow’s milk
  represent up to 75% of positive test.
                 Atopic Dermatitis
• Triggering Factors
   –   Temperature change
   –   Sweating
   –   Excessive washing
   –   Contact with irritating
       substances (wool, soaps,
       detergents, cigarette smoke
   –   Contact allergy
   –   Aeroallergens
   –   Microbial agents
   –   Food
   –   Stress
            AD – 3 Stages
• Infantile
      2 months to 2 years
• Childhood
      2 years to 10 years
• Adult
      adolescence to adulthood
    Infantile Atopic Dermatitis
• 60% of 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 desquamate leading to erythroderma.
• Buttocks and diaper area frequently spared
Infantile Atopic Dermatitis
              • Partial or even
                complete remission in
                summer and relapse in
                winter are the rule
              • Worsening observed
                after immunizations
                and viral infections
    Infantile Atopic Dermatitis
• Most cases the symptoms will disappear
  toward the end of the second year.
• 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 sometime in their
  lives
   – Common in women after birth of their 1st child, when
     increased exposure to soaps and water trigger disease
          Cutaneous stigmata
• Dennie-Morgan fold
• Pityriasis alba
• Keratosis pilaris
• Hertoghe’s sign – thinning of the lateral
  eyebrows
• Keratosis punctata palmaris et plantaris
AD and Ichthysosis vulgaris
              • Up to 50% of AD will
                have Ichthysosis vulgaris
              • Autosomal dominant
              • Excessive scaling most
                prominent on shins
              • White, translucent,
                quadrangular scales on the
                extensor aspects of the
                arms and legs common
                with atopy
          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.
   – Secondary to reduced cell-mediated immunity
• Vaccination against smallpox is contraindicated in
  person with atopic dermatitis. Even when
  condition is in remission, widespread and even
  fatal vaccinia can occur.
Eczema herpeticum:
  typical vesicular
  lesions on the hand,
  around the eye, and on
  the face
              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 may be 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 allergy identification and dietary restrictions.
• Hydrate skin daily with moisturizers
             Management
• Topical steroid
• Wet compress of Burow’s solution such as
  Domeboro.
• Crude coal tar/liquor corbonis detergens
  (LCD)
• PUVA
• Cyclosporine
             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
            Elidel vs. Protopic
• Elidel good for mild      • Protopic good for
  cases                       severe cases
• Elidel doesn’t cause      • Protopic can cause
  initial increase pruritus   initial increase pruritus
• Elidel good for “return
  eczema”
            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, and usually affects
  the upper eyelid
• When both eyes are involved, consider
  mascara, eye shadow, eyelash cement,
  eyeline, etc
• In contrast, atopic dermatitis affects both
  upper and lower eyelid.
             Nipple eczema
• Painful fissuring, seen especially in nursing
  mothers
• Maybe an isolated manifestation of atopic
  dermatitis
• If persist more than 3 months, and/or
  unilateral, biopsy is mandatory to rule out
  Paget’s
              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)
• New research suggests use of oral retinoids
  for severe recalcitrant hand eczema
    Diaper (Napkin) Dermatitis
• Erythematous, papulovesicular dermatitis
  distributed over the lower abdomen,
  genitals, thighs, and the convex surfaces of
  the buttocks
• Irritation caused by bacteria, change in the
  environment (moisture, lower PH, feces)
• Candida albicans secondary infection.
Diaper dermatitis - complications
• Jacquet’s erosive diaper dermatitis
  – Punched out ulcers/erosions with elevated
    borders
• Pseudoverrucous papule and nodules
• Granuloma gluteal infantum
Jacquet’s diaper dermatitis with eroded nodules on the labia
Granuloma gluteale infantum
           Diaper Dermatitis
• Ddx: Napkin psoriasis, seborrheic
  dermatitis, atopic dermatitis, langerhans cell
  histiocytosis, tinea cruris, allergic contact
  dermatitis, acrodermatitis enteropathica,
  biotin deficiency, congenital syphillis
• Treatment: prevention
     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
Juvenile plantar
dermatosis
           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.
  Hormone Induced Dermatoses
• Autoimmune progesterone dermatitis – urticaria,
  urticarial paplues, papulovesicular lesion, or
  eythema multiforme. Appear 5-10 days before
  menses. Oophorectomy, danazol, and tamoxifen
  are treatment modalities
• 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-Bar’s 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 Bruton’s syndrome, sex-linked
  agammaglobulinemia.
• Appears 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 in 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-B-
  cell to B-cell differentiation
• Protein tyrosine kinase (PTK) gene deletion
  and point mutation
• May develop leukemia, lymphoma, fatal
  encephalitis, pulmonary fibrosis
• Tx: gamma globulin
       Selective IgA Deficiency
• Most common immunoglobulin deficiency
• Usually asymptomatic
• Clinical manifestations 10-15%
   – Sinopulmonary bacterial infections
   – Giardia gastroenteritis
• 1/3 with clinical disease develop autoimmune
  disorders
   – SLE, Vitiligo, chronic mucocutaneous candidiasis,
     lipodystrophia centrifugalis abdominalis, ITP
• No sexual predilection
      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 cell dysfunction evident
            Common Variable
            Immunodeficiency
• Increased risk of autoimmune disorders
  – Vitiligo, alopecia areata, vasculitis
• Increased incidence of lymphoma
  – 400 fold increase risk in female patients
Isolated Primary IgM Deficiency
• Eczematous dermatitis presents in 1/5 of
  patients with this condition
• Predisposition to bacterial infection
• Defect in maturation of IgM producing
  plasma cell.
  Immunodificiency with Hyper-
              IgM
• Low or absent IgG, IgE, and IgA level. Normal or
  elevated IgM and IgD
• 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.
• Tx: IVGG, and allogenic bone marrow transplant
          Thymic Hypoplasia
• DiGeorge anomaly, aka III and IV pharyngeal
  pouch syndrome
• Facies: notched and low-set ears, micrognathia,
  shorten philtrum, hypertelorism
• Congenital absence of the parathyroid, thymus,
  and abnormal aorta
• Hpocalcemia is the first sign
• Aortic and cardiac defects are the most common
  cause of death
• Deletions within proximal long arm of
  chromosone 22
Noninfectious, persistant cutaneous granulomas in a patient with
DiGeorge Syndrome. The granulomas are indistinguishable
clinically from cutaneous granulomas associated with other
immunodeficiencies.
 Thymic Dysplasia with Normal
      Immunoglobulins
     (Nezelof Syndrome)
• Faulty development of thymus gland
• Autosomal recessive
• Thymus is present but underdeveloped; 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.
  – Most common in Amish and Finns
  – May have “doughy” skin secondary to
    degenerated elastic tissue
  – Increased risk of non-Hodgkin’s lymphoma and
    basal cell carcinomas
 Miscellaneous T-Cell Deficiencies
• Omenn’s syndrome
  – AR
  – Mimics GVHD
  – exfoliative erythroderma, eosinophilia,
    recurrent infection, hypogammaglobulinema,
    diarrhea, hepatosplenomegly, alopecia
  – Early death by 6 months
  – 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
• Good’s syndrome
• Deficient in cell mediated immunity and
  benign thymoma occurring simultaneously
• Deficiency of B and pre-B cells is striking
• Thymectomy does not affect the
  immunodeficiency
         Ataxia-Telangiectasia
           (Louis-Bar’s S.)
• Distinctive telangiectasia in bulbar conjuctiva and
  flexural suraces of the arm developing during the
  5th year of age
• Telangiectasia occurs on butterfly area of the face,
  palate, ear, and exposed skin. Café 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.
         Ataxia-Telangiectasia
• Progeric changes seen in 90%
  – Subcutaneous fat is lost
  – Facial skin becomes atrophic and sclerotic early on
• Poikiloderma
• Sinopulmonary infections in 80%
  – Defects in cell mediated immunity
  – Most common cause of death is bronchiectasis with
    respiratory failure
• Persistent granulomatous
  plaques on the leg of child
  with ataxia–telangiectasia.
     Wiskott-Aldrich Syndrome
• Exclusively in boys
• Triad: chronic eczematous dermatitis resemble
  AD, increase suseptibility to infections (OM), and
  thrombocytopenia purpura/hepatosplenomegly
• 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
• Bone marrow transplant is tx of choice
Petechiae and ecchymoses in a young boy with WAS
    X-Linked Lymphoproliferative
             Syndrome
•   Aka Duncan’s disease
•   Inability to control Epstein-Barr virus infection.
•   Pt normal until develop infectious Mono.
•   Necrotic hepatitis and exanthem are common
•   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
• Patients develop granulomas as a compensatory
  effort to confine organisms
Chronic Granulomatous Disease
• 65% of cases are the X-linked form, lacks
  the subunit of cytochrome b 558(gp91-
  phox)
• Female carrier has mixed, normal and
  abnormal cells thus shows an intermediate
  phenotype.
 Chronic Granulomatous Disease
• Myeloperoxidase producing bacteria
  characteristically cause infections because
  their destruction requires generation of
  oxygen free radicals
  – Staph. Aureus
  – Serratia
Chronic Granulomatous Disease
• Screening test: Nitroblue tetrazolium (NBT)
  reduction assay
  – NBT is normally yellow
  – 80-90% of normal leukocytes reduce NBT
    during phagocytosis to insoluble precipitate,
    turning it blue
  – Only 5-10% of leukocytes from patients with
    CGD are able to reduce NBT during
    phagocytosis
  Leukocyte Adhesion Molecule
          Deficiency
• Autosomal recessive
• Necrotic ulcerations resembling pyoderma
  gangrenosum
• Frequent skin infections, mucositis, and otitis
• Poor wound healing
• Delayed separation of the umbilical cord
• Faulty complexing of the CD11 and CD18
  integrins
• Death occurs by 2 years of life unless bone
  marrow transplant is undertaken.
A minor scratch from his sister evolved during the subsequent weeks
into a large ulcer on the arm of a boy with leukocyte adhesion
disorder.
    Chediak-Higashi Syndrome
• Autosomal recessive
• Abnormal pigmentation with silvery hair
• Photophobia
• Partial oculocutaneous albinism, cutaneous
  and intestinal infections early in childhood
• Ocular albinism is accompanied by
  nystagmus and photophobia.
• Parental consanguinity common
    Chediak-Higashi Syndrome
• Defect in the gene LYST, resulting in
  defective vesicular transport to and from the
  lysosome and melanosome
  – Causes the “giant” intracytoplasmic granules
    found within leukocytes, melanocytes, hair
    shafts, renal tubular cells, CNS neurons, and
    other tissues
   Hyperimmunoglobulinemia E
          Syndrome
• Autosomal dominant with variable expressivity
• Consists of atopic-like eczematous dermatitis,
  recurrent pyogenic infection, high level 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
             Job’s syndrome
• AKA Buckley Syndrome
• Subset of HIE.
• Mainly affect girls with red hair, freckles,
  and blue eyes.
• Hyperextensible joints
• Cold abscesses occur.
    Graft-Versus-Host Disease
• Immunocompetent cells are introduced 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-versus-
host 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…

								
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