3 Atopic Dermatitis Pruritis is the hallmark of AD “Itch that rashes” Eczematous eruption leads to lichenified dermatitisItching precedes the appearance of lesions
4 Atopic Dermatitis High level of IgE antibodies to House dust mites IgE bound to Langerhans cells in atopic skinFood 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 washingContact with irritating substances (wool, soaps, detergents, cigarette smokeContact allergyAeroallergensMicrobial agentsFoodStress
7 AD – 3 Stages Infantile 2 months to 2 years Childhood 2 years to 10 yearsAdultadolescence to adulthood
8 Infantile Atopic Dermatitis 60% of AD present in the first year of life, after 2 months of ageBegin as itchy erythema of the cheeksDistribution include scalp, neck, forehead, wrist, and extensorsMay 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 ruleWorsening 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 lesionsDistribution: 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 population70% develop hand dermatitis sometime in their livesCommon in women after birth of their 1st child, when increased exposure to soaps and water trigger disease
21 AD and Ichthysosis vulgaris Up to 50% of AD will have Ichthysosis vulgarisAutosomal dominantExcessive scaling most prominent on shinsWhite, 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 immunityVaccination 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 10IL-4 and IL-5 produce elevated IgE and eosinophiliaIL-10 inhibits delayed type hypersensitivityTh2 may be sensitive to house mites or grass pollen
27 ImmunologyMonocytes produces elevated amount of prostaglandin E2 (PGE2)PGE2 reduces gamma-interferon production, but not IL-4 from helper cells thereby enhancing the Th2 dominancePGE2 also directly enhances IgE production from B cells
29 ImmunologyLangerhans cells of AD patient stimulate helper T cells into Th2 phenotype without the presence of antigenLangerhans cells have IgE bound to their suface receptors. These IgE are associated with atopic antigens, such as house dust mites
35 Management Protect from scratching Adequate cleansing but not over bathing or rubbingGentle cleanserAnti-histamines, especially at nightBathing protocolFood 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)PUVACyclosporine
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 pruritusElidel good for “return eczema”Protopic good for severe casesProtopic can cause initial increase pruritus
43 Eyelid dermatitisWhen on one eye only, it is most frequently caused by nail polish, and usually affects the upper eyelidWhen both eyes are involved, consider mascara, eye shadow, eyelash cement, eyeline, etcIn 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 dermatitisIf 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 soapsPompholyx- tapioca vesicles, on sides of fingers, palms, and solesDifferentials – 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 buttocksIrritation caused by bacteria, change in the environment (moisture, lower PH, feces)Candida albicans secondary infection.
58 Juvenile plantar dermatosis Begins as a patchy symmetrical, smooth, red, glazed macules on the base of the great toesAffect 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 socksVirtually always resolve after puberty
61 Xerotic EczemaAka winter itch, nummular eczema, eczema craquele, and asteototic eczema.Anterior shins, extensor arms, and flankElderly person predisposed.Use of bath oils in bath water is recommended to prevent water lossMoisturizers – 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 modalitiesAutoimmune 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 AgammaglobulinemiaIsolated IgA DeficiencyCommon Variable ImmunodificiencyIsolated Primary IgM DeficiencyImmunodificiency with Hyper-IgMThymic HypoplasiaThymic Dysplasia with Normal Immunoglobulins (Nezelof Syndrome)
67 X-Linked Agammaglobulinemia Aka Bruton’s syndrome, sex-linked agammaglobulinemia.Appears after 3-6 month of lifeFrequent Strep and staph infection. Viral resistance intact.IgA, IgM, IgD, and IgE are absent in the serum. IgG present in small amountCell-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 differentiationProtein tyrosine kinase (PTK) gene deletion and point mutationMay develop leukemia, lymphoma, fatal encephalitis, pulmonary fibrosisTx: gamma globulin
69 Selective IgA Deficiency Most common immunoglobulin deficiencyUsually asymptomaticClinical manifestations 10-15%Sinopulmonary bacterial infectionsGiardia gastroenteritis1/3 with clinical disease develop autoimmune disordersSLE, Vitiligo, chronic mucocutaneous candidiasis, lipodystrophia centrifugalis abdominalis, ITPNo sexual predilection
70 Isolated IgA Deficiency Absence or marked reduction of serum IgA1:600 in white population, most are entirely well.Malignancy is increased in adult with IgA deficiency.
71 Common Variable Immunodificiency Aka acquired hypogammaglobulinemiaHLA marker B8 and DR3 are affectedRecurrent sinopulmonary infectionsB cells present but not terminally differentiatedT cell dysfunction evident
72 Common Variable Immunodeficiency Increased risk of autoimmune disordersVitiligo, alopecia areata, vasculitisIncreased incidence of lymphoma400 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 conditionPredisposition to bacterial infectionDefect 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 IgDX-linked form caused by mutation or deletion of Xq region, which encodes a ligand of CD40, gp39Gp39-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 HypoplasiaDiGeorge anomaly, aka III and IV pharyngeal pouch syndromeFacies: notched and low-set ears, micrognathia, shorten philtrum, hypertelorismCongenital absence of the parathyroid, thymus, and abnormal aortaHpocalcemia is the first signAortic and cardiac defects are the most common cause of deathDeletions 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 glandAutosomal recessiveThymus is present but underdeveloped; no cardiac abnormalitiesContrast to DiGeorge syndrome
81 Purine Nucleoside Phosphorylase Deficiency Greatly reduced T-Cell counts, depressed cell mediated immunityB cells and antibody formation intactMutation on 14q13Usually died of overwhelming viral infection
82 Miscellaneous T-Cell Deficiencies Cartilage-hair hypoplasia syndromeAR, patient with short-limbed dwarfism, fine sparse, hypopigmented hair, defective cell mediated immunity.Most common in Amish and FinnsMay have “doughy” skin secondary to degenerated elastic tissueIncreased risk of non-Hodgkin’s lymphoma and basal cell carcinomas
83 Miscellaneous T-Cell Deficiencies Omenn’s syndromeARMimics GVHDexfoliative erythroderma, eosinophilia, recurrent infection, hypogammaglobulinema, diarrhea, hepatosplenomegly, alopeciaEarly death by 6 monthsInefficient and abnormal generation of T-Cell receptor.
86 SCID: Severe Combined Immunodeficiency Disease Severe impairment of humoral and cellular immunityTriad 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 syndromeDeficient in cell mediated immunity and benign thymoma occurring simultaneouslyDeficiency of B and pre-B cells is strikingThymectomy 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 ageTelangiectasia 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 lostFacial skin becomes atrophic and sclerotic early onPoikilodermaSinopulmonary infections in 80%Defects in cell mediated immunityMost 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 boysTriad: chronic eczematous dermatitis resemble AD, increase suseptibility to infections (OM), and thrombocytopenia purpura/hepatosplenomeglyDeath by age 6Accelerated IgA, IgM and IgE synthesisT-cell decline in numbers and activityXp11 gene mutation. Codes for WASP protein which reorganize cytoskeletonBone 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 diseaseInability to control Epstein-Barr virus infection.Pt normal until develop infectious Mono.Necrotic hepatitis and exanthem are commonXq26 abnormailtyB-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 mechanismPatients 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 radicalsStaph. AureusSerratia
99 Chronic Granulomatous Disease Screening test: Nitroblue tetrazolium (NBT) reduction assayNBT is normally yellow80-90% of normal leukocytes reduce NBT during phagocytosis to insoluble precipitate, turning it blueOnly 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 recessiveNecrotic ulcerations resembling pyoderma gangrenosumFrequent skin infections, mucositis, and otitisPoor wound healingDelayed separation of the umbilical cordFaulty complexing of the CD11 and CD18 integrinsDeath 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 recessiveAbnormal pigmentation with silvery hairPhotophobiaPartial oculocutaneous albinism, cutaneous and intestinal infections early in childhoodOcular 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 melanosomeCauses 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 expressivityConsists 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 prurigoKeratoderma 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 jointsCold 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