Atopic Dermatitis, Eczema, and Noninfectious Immunodeficiency Disorders Rick Lin, DO MPH July 15, 2003.

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, cow’s 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

• Hertoghe’s 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 Burow’s 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 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)

Diaper dermatitis

• Jacquet’s 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-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.

• 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-B-cell 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 Hyper-IgM

• 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.

• Omenn’s 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

• Good’s syndrome

• Deficient in cell mediated immunity and benign thymoma occurring simultaneously

• 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 are 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.

• Persistent granulomatous plaques on the leg of child with ataxia–telangiectasia.

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 Duncan’s 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

Job’s 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-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…