1. Atopic Dermatitis, Eczema, and Noninfectious Immunodeficiency Disorders
Adam Wray, D.O.
August 10, 2004

2. Atopic Dermatitis Aka atopic eczema Aka infantile eczema
Aka flexural eczema
Aka disseminated neurodermatitis
Aka prurigo diathsique

3. Atopic Dermatitis Pruritis is the hallmark of AD “Itch that rashes”
Eczematous eruption leads to lichenified dermatitis
Itching precedes the appearance of lesions

4. 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.

5. 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

7. AD – 3 Stages Infantile 2 months to 2 years Childhood
2 years to 10 years
Adult
adolescence to adulthood

8. 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

9. Infantile Atopic Dermatitis
Partial or even complete remission in summer and relapse in winter are the rule
Worsening observed after immunizations and viral infections

10. 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

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

12. 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.

14. 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

16. Adult with atopic dermatitis that favors the face and neck

17. Cutaneous stigmata Dennie-Morgan fold Pityriasis alba
Keratosis pilaris
Hertoghe’s sign – thinning of the lateral eyebrows
Keratosis punctata palmaris et plantaris

18. Note the Dennie–Morgan lines and central facial pallor.

21. 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

22. 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.

23. 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.

24. Eczema herpeticum: typical vesicular lesions on the hand, around the eye, and on the face

25. 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

27. 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

29. 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

31. Differential Diagnosis
Seb Derm
Contact dermatitis
Nummular eczema
Scabies
Psoriasis

33. Histology Spongiotic dermatitis Lichen simplex chronicus
Eosinophiles may be seen

35. 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

36. Management Topical steroid
Wet compress of Burow’s solution such as Domeboro.
Crude coal tar/liquor corbonis detergens (LCD)
PUVA
Cyclosporine

37. 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

38. Elidel vs. Protopic Elidel good for mild cases
Elidel doesn’t cause initial increase pruritus
Elidel good for “return eczema”
Protopic good for severe cases
Protopic can cause initial increase pruritus

40. Regional Eczema Ear eczema Eyelid dermatitis Nipple eczema Hand eczema
Diaper dermatitis
Infectious eczematoid dermatitis
Juvenile plantar dermatosis

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

43. 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.

44. 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

47. 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

48. Smoking as in palmoplantar pustulosis, may be a cofactor

50. Treatment Barrier Moisturizer Systemic Corticosteroids
Phototherapy – UVA, PUVA, Radiotherapy (Grenz Ray)
New research suggests use of oral retinoids for severe recalcitrant hand eczema

51. 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.

54. Diaper dermatitis - complications
Jacquet’s erosive diaper dermatitis
Punched out ulcers/erosions with elevated borders
Pseudoverrucous papule and nodules
Granuloma gluteal infantum

55. Jacquet’s diaper dermatitis with eroded nodules on the labia

56. Granuloma gluteale infantum

57. 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

58. 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

59. Juvenile plantar dermatosis

61. 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.

63. 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.

64. 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)

65. 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

66. 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

67. 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

68. 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

69. 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

70. 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.

71. 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

72. Common Variable Immunodeficiency
Increased risk of autoimmune disorders
Vitiligo, alopecia areata, vasculitis
Increased incidence of lymphoma
400 fold increase risk in female patients

73. Leukocytoclastic vasculitis on the legs of a girl with common variable immunodeficiency . Autoimmune disorders show a significant increase in frequency.

74. 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.

75. 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 Xq region, which encodes a ligand of CD40, gp39
Gp39-CD40 interaction signals for Ig isotype switching.
Tx: IVGG, and allogenic bone marrow transplant

76. Extensive, recalcitrant warts in an adult with hyperimmunoglobulinemia M syndrome.

77. Painful oral ulceration in a patient with hyperimmunoglobulinemia M syndrome

78. 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

79. Noninfectious, persistant cutaneous granulomas in a patient with DiGeorge Syndrome. The granulomas are indistinguishable clinically from cutaneous granulomas associated with other immunodeficiencies.

80. 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

81. 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

82. 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

83. 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.

86. 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

87. 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

88. 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.

90. 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

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

92. 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

93. The boy was successfully treated with bone marrow transplantation, and his dermatitis virtually cleared owing to the T-cell engraftment

94. Petechiae and ecchymoses in a young boy with WAS

95. 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.

96. 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

97. 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.

98. Chronic Granulomatous Disease
Myeloperoxidase producing bacteria characteristically cause infections because their destruction requires generation of oxygen free radicals
Staph. Aureus
Serratia

99. 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

100. Swollen, erythematous draining inguinal lymphadenopathy related to Staphylococcus aureus infection in a boy with chronic granulomatous disorder

101. 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.

102. 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.

103. 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

104. 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

105. Light microscopic examination of hair shows giant melanosomes in patients with Chédiak–Higashi syndrome.

106. 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

107. Coarse faces with scattered small staphylococcal pustules on a 9-year-old boy with hyperimmunoglobulin E syndrome.

108. Job’s syndrome AKA Buckley Syndrome Subset of HIE.
Mainly affect girls with red hair, freckles, and blue eyes.
Hyperextensible joints
Cold abscesses occur.

109. Infant with hyperimmunoglobulin E syndrome shows several erythematous, slightly purulent ‘cold’ abscesses on the forehead and scalp.

110. 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.

111. Early, chronic graft-versus-host reaction with widespread, almost confluent hyperpigmented lichenoid papules and toxic epidermal necrosis-like appearance on knee 

112. Late, chronic graft-versus -host reaction with hyperpigmented sclerotic plaques on the back

113. Acute graft-versus-host reaction with vivid palmar erythema 

114. Graft-versus-host reaction with early, chronic, diffuse, widespread lichenoid changes of lips

115. Acute erosions of the buccal mucosa in graft-versus-host reaction

116. Graft-versus-host reaction; acute basal cell hydropic degeneration with interepidermal necrotic keratinocytes 

117. Graft-versus-host reaction; early chronic hyperkeratosis and hypergranulosis, irregular acanthosis, cytoid body and basal cell hydropic degeneration reminiscent of lichen planus

118. Screening laboratory tests for a patient with recurrent cutaneous infections (including staphylococcal) where there is suspicion of a primary immunodeficiency

119. End of Lecture…