Dermal Inflammation - Symptoms & Diagnosis PDF

Symptomatology and Dermal inflammation Charoen Choonhakarn, MD Division of Dermatology Departmet of Medicine Khon kaen University  Objectives of Dermal Inflammation Understand and able to use dermatologic terminology appropriately Able to de...

Symptomatology and Dermal inflammation Charoen Choonhakarn, MD Division of Dermatology Departmet of Medicine Khon kaen University  Objectives of Dermal Inflammation Understand and able to use dermatologic terminology appropriately Able to describe the skin lesions correctly Understand pathogenesis,clinical manifestations, natural history and principle of the treatments of the following skin disorders 1. Papulosquamous diseases 2. Urticaria 3. Alopecia 4. Acne 5. Erythema multiforme 6. Steven-Johnson syndrome 7. Toxic epidermal necrolysis  References 1. Fitzpatrick’s Dermatology in General Medicine :2 volumes 2. Bolognia; Dermatology : 2 volumes 3. Rook; Textbook of Dermatology : 4 volumes  Symptomatology Skin lesions** Itching Pain/burning Anesthesia How to diagnose skin disorders? 1. Skin lesions 2. Configuration 3. Location of the lesions 4. Distribution of the lesions Classification of skin lesions Primary skin lesions arise from previously normal skin classified morphologically as macules, papules, plaques, patches, nodules, tumors, wheals, cysts, vesicles, bullae or pustules Classification of skin lesions Secondary skin lesions lesions arise as a consequence of rupture, mechanical irritation, extension, invasion, normal and abnormal healing eg. erosion, ulcer, fissure, crust, scale, lichenification, excoriation, scar, keloid  Calcinosis Papule Wheal/flare Plaque  Vesicle Blister Scale Excoriation  Erosion Horn Ulcer Comedone Lichenification Fissure Callus, corn Crust  Keloid Scar Umbilication, Basal cell CA Umbilication, Molluscum Atrophy Sinus tract Burrow Sclerosis Pustule Telangiectasia Purpura Cyst  Configuration of skin disorders -Annular or arciform or polycyclic: tinea coporis, pityriasis versicolor, leprosy, psoriasis, subacute cutaneous lupus erythematosus (SCLE), granuloma annulare -Linear: excoriation, psoriasis, scabies -Zosteriform: herpes zoster -Iris or target: erythema multiforme -Herpetiform: herpes simplex  Configuration of skin disorders -Morbilliform: measles, drug eruption -Discrete -Confluent -Reticulate: livedo reticularis, lichen planus -Serpiginous: creeping eruption -Oval: nummular eczema, fixed drug eruption, psoriasis Livedo reticularis Morbiliform Serpiginous Target lesion  Color of the lesions Violaceous or purplish: discoid LE, Gottron’s papules in dermatomyositis, lichen planus, Kaposi’s sarcoma Green: Pseudomonas infection of nail Yellow: xanthoma, xanthelasma Black: melanoma, pigmented BCC, mole, seborrheic keratosis Hyperpigmented: melasma, pityriasis versicolor, postinflammatory hyperpigmentation White : vitiligo Hypopigmented: P. versicolor, P. alba, indeterminate or tuberculoid leprosy, postinflammatory hypopigmentation Red: psoriasis, cellulitis Green nail: Pseudomonas infection Black nodule: malignant melanoma Violaceous papules : Kaposi’s sarcoma Depigmentation: vitiligo Yellowish nodule: xanthoma  Scale Thick silvery scale: psoriasis Fine wrinkle scale: pityriasis versicolor Fish-like scale: ichthyosis Greasy scale: seborrheic dermatitis Collarette scale : pityriasis rosea Trailing scale: erythema annulare centrifugum Fine wrinkle scale: pityriasis versicolor Collarette scale : pityriasis rosea Trailing scale: erythema annulare centrifugum Fish-like scale: ichthyosis  Greasy scale: seborrheic dermatitis Thick silvery scale: psoriasis Location of the skin diseases Location of the skin diseases  Distribution of the lesions Along skin crease (Christmas tree pattern): pityriasis rosea, psoriasis, pityriasis lichenoides, Kaposi’s sarcoma Photodistribution: sparing areas( periorbital, nasolabial, below chin, flexural areas): drug allergy, CNT disease Air-borne distribution: no sparing area : air-borne contact dermatitis Axillae, umbilicus, perineum, toe and finger webs: scabiasis Christmas tree pattern Photodistribution Photodistribution Maculopapular rash: (exanthematous) 1. drug eruption 2. autoimmune disease 3. systemic infection viral exanthem  Describe skin lesions Primary skin lesions Surface change or secondary lesion eg. scale, erosion Color Configuration for specific disease Location Distribution White reticular lesion : oral lichen planus Annular erythematous patchs : tinea corporis Target-like papules with central vesicles : erythema multiforme Papulosquamous disease 1. Eczema 2. Psoriasis 3. Pityriasis rosea Classification 3 stages 1. Acute-vesiculobullous,serum oozing 2. Subacute-crusting,scaly plaque 3. Chronic-lichenified, hyperkeratotic plaque  Eczema Endogenous Exogenous (contact) Atopic dermatitis Related to ultraviolet Seborrheic dermatitis Phototoxic CD Nummular dermatitis Photoallergic CD Dyshidrosis Not related to ultraviolet Prurigo nodularis Irritant CD Lichen simplex chronicus Allergic CD Stasis  Atopic dermatitis 3 phases 1. Infant : 2 months-2 years 2.Childhood : 3-11years 3.Adult : 12-30 years Atopic dermatitis, allergic rhinitis, asthma “Atopic march”  Atopic dermatitis ESSENTIAL FEATURES—Must be present: Pruritus Eczema (acute, subacute, chronic) -Typical morphology and age-specific patterns* -Chronic or relapsing history *Patterns include: 1. Facial, neck, and extensor involvement in infants and children 2. Current or previous flexural lesions in any age group 3. Sparing of the groin and axillary regions IMPORTANT FEATURES—Adding support to the diagnosis: Early age of onset Atopy : personal and/or family history, Ig E reactivity Xerosis  Atopic dermatitis Pathogenesis: complex interaction of 1. Skin barrier disruption: impaired filaggrin, reduced ceramide level, increased transepidermal water loss 2. Genetic: uncertain inheritance pattern (AD adult- 60% children with AD, both AD parents-81% AD children) 3. Environmental:infection (S.aureus, pityrosporum sp.),food,inhalants,season,clothing,stress 4. Immunologic factor: IgE, Th1, Th2, Th17 2. Seborrheic dermatitis greasy scale erythema on face, scalp (dandruff), chest wall, upper back, axillae and inguinal area Risk: HIV patient, stroke, facial palsy, parkinsonism 3. Dyshidrotic dermatitis (pompholyx) deep-seated vesicles (sago grain) on palm and sole Risk: nickle allergy, stress 4. Prurigo nodularis indurated, hyperkeratotic, excoriated papules on extremities 5. Lichen simplex chronicus lichenified plaque usually on ankels and knees 6. Stasis dermatitis brownish or purpuric scaly patch commonly located on medial side of ankles Risk: venous insufficiency 7. Asteatotic or xerotic dermatitis fish-like scale and cracking skin, usually on flank, thighs, and legs Risk: atopy, elder, ichthyosis, malnutrition 8. Nummular dermatitis Coin-shaped lesion, vary in size Id reaction: Autosensitization from pre-existing eczematous lesions presenting with generalized papulvesicles Nummular dermatitis with Id eruption  Contact dermatitis 1. Irritant contact dermatitis or phototoxic dermatitis 2. Allergic contact dermatitis or photoallergic dermatitis Differentiation between irritant and allergic contact dermatitis Feature Allergic Irritant Susceptibility Somebody Everybody Duration 7-14 d 0-2 d Remission after Slow Rapid discotinuing Symptoms Icthing ++++(early) +++ (late) Pain/burning ++ ++++ (early) Concentration of - High agent Stimulating agent Ag and T cell Keratinocytes Patch test Positive Negative  Allergic contact dermatitis Pathogenesis: Delayed,cell-mediated hypersensitivity -Langerhans cell (Ag-presenting cell) in epidermis -T cell (MHC class II) in lymph node - Sensitized T cells back to skin  Allergic contact dermatitis Lesion usually develop after 1-wk exposure to allergen, predominate itching Clinical: depend on stage of lesion, acute-vesicles, subacute-scaly plaque, chronic-lichenified plaques Common allergens: nickle, rubber, fragrance, formaldehyde Confirmation: Patch test Patch test (allergic CD)  Irritant contact dermatitis -Occur within hours or days after exposure -Depend on concentration of chemical agents -Clinical: burn-like lesion ( high conc.) or dry, scaly plaque with fissure ( low conc.) -Usually seen in person with chronic exposure to water -Paederus dermatitis from chemical substance in Rove beetle presenting with vesicles or pustules  Eczema treatment -Wet compression (acute) -Topical corticosteroids (acute, subacute, chronic) -Antihistamines -Intralesional corticosteroids (chronic) -Keratolytics eg. salicylic or urea (chronic) -Systemic corticosteroids -Emollients -Avoidance : contact dermatitis -Advice  Psoriasis vulgaris Chronic inflammatory disease, not cure, genetic influence Common association: metabolic syndrome Clinical features: 1.Skin: well-demarcated erythematous plaques with silvery scale on trunk, scalp, extremities 2.Nail: pits, oil spots,oncholysis, subungual hyperkeratosis  Psoriasis vulgaris Unknown exact etiology 1. Alteration of cell kinetics of keratinocytes (311 vs 36 hr) 2. CD8+ T cells 3. Cytokines from Th1, Th17 4. Environmental factor: physical trauma (Koebner phenomenon), drugs, stress, infection, alcohol ingestion Current model of psoriasis pathogenesis Lynde CW, et al. JAAD 2014;71:141-50. Cytokine environment regulates CD4+ T-cell differentiation into functional subsets Lynde CW, et al. JAAD 2014;71:141-50.  Precipitating factors 1. Trauma “Koebner phenomenon” 2. Infection esp. Streptoccous infection, HIV 3. Stress 4. Drug eg. chloroquine, beta-blocker, lithium, NSAIDs, steroid withdrawal (pustular psoriasis) 5. Alcohol drinking, smoking  Classification 1. Chronic plaque; “psoriasis vulgaris” 2. Guttate; papule 3. Erythrodermic; diffuse 4. Pustular; localized or generalized 5. Inverse; flexural area 6. Nail; oil spot, pits, subungual hyperkeratosis, onycholysis 7. Arthritis/enthesopathy Chronic plaque type Extensor aspects Guttate type Erythrodermic psoriasis Pustular type, generalized Palmoplantar pustular psoriasis Inverse psoriasis  Pits / Oil spot / Subungual hyperkeratosis Leukonuchia Pustular nails  Psoriasis treatment Mild: PASI or BSA 30% Systemic agents eg. methotrexate, cyclosporine, acitretin, biologics Phototherapy: UVA or UVB  Pityriasis rosea -Age 10-35 years, male = female -Course: 6-8 weeks -Unknown etiology: infectious agents:HHV-7, sometimes HHV-6 -DDX; -PR-like drug eruption eg. barbiturates, captopril, gold, metronidazole, clonidine, bismuth -Secondary syphilis  Clinical features -Round or oval erythematous papules or plaques with collarette scale -Herald patch or primary medallion or mother patch: 50-90% -Trunk along skin creases “Christmas tree” -Itching 75% -Prodome: fever, malaise, arthralgia, lymphadenopathy -Rx: topical steroids, antihistamine, acyclovir Christmas tree pattern Herald patch Collarette scale  Urticaria Definition: appearance of wheal and/or angioedema Wheal: 1. Central swelling of variable size surrounded by a reflex erythema 2. Itching, sometimes burning 3. Fleeting nature, returning to normal appearance, usually within 1-24 hr Angioedema: 1. Sudden, pronounced swelling of the lower dermis and subcutis 2. Frequent mucous membrane 3. Resolution slower than for wheal and can take up to 72 hr Urticaria Angioedema Classification  Acute urticaria 2/3 of urticaria Causes: contact, insect bite (papular urticaria), drugs, foods, viral infection of upper respiratory tract 20-30% progress to chronic urticaria  Chronic urticaria Causes: idiopathic, infections (viral hepatitis, Helicobacter pylori,parasites), physical, systemic diseases (SLE,neoplasm) Chronic spontaneous urticaria (CSU) - Chronic persistent - Chronic intermittent Inducible urticaria - Dermographism, cold, delayed pressure, solar, heat, vibratory Special types - Cholinergic, contact, aquagenic, adrenergica  Adrernergic urticaria Cholinergic urticaria Cold urticaria Dermographism Dermographism Cold urticaria Heat urticaria Ice cube test Papular urticaria hypersensitivity reaction to the bites of mosquitoes, fleas, bedbugs, and other insects Individual papules may surround a wheal and display a central punctum Urticarial vasculitis urticaria that persist for > 24 hr Appear hyperpigmentation after healing  Mechanism 1. Immunologic IgE-meadiated (type I) 2. Non-immunologic Direct mast cell degranulation eg. opiate, plymyxin B, radiocontrast media Arachidonic acid metabolism eg. aspirin, NSAIDs Urticaria pathogenesis  Diagnosis algorithm for urticaria Urticaria Angioedema Recurrent unexplained fever? ACE inhibitor treatment? Joint/bone pain? Malaise? History + - - + Auto-inflammatory Average hive Remission after HAE or AAE? disease? duration >24 hours? stop? + - + - - + - + Diagnostic tests Signs of vasculitis in Are symptoms biopsy? inducible? + - - + Provocation test - + Chronic Chronic Acquired/ Urticarial HAE I–III ACE-inhibitor spontaneous inducible hereditary AID vasculitis AAE induced AE Treatment urticaria urticaria Interleukin-1 Histamine and other Mast Cell Mediators Bradykinin AAE = acquired angioedema due to C1-inhibitor deficiency; ACE = angiotensin converting enzyme AE = angioedema; AH = antihistamine; AID = auto-inflammatory disease; HAE = hereditary angioedema. Zuberbier T, et al. Allergy 2014;69:868–87.  Recommended diagnostic test Spontaneous Routine Extended diagnostic diagnostic tests tests Acute urticaria None None Chronic CBC,ESR or CRP Autologous serum skin test, urticaria Test for infectious diseases ( H. pylori, HBV, HCV), Thyroid function and antibodies, Pseudoallergen- free diet for 3 weeks, Skin biopsy, ANA  Recommended diagnostic test Inducible Routine diagnostic tests Extended diagnostic tests Acquired cold Cold provocation (ice cube Differential blood count, for 20 mins) ESR, CRP, cryoproteins Delayed pressure Pressure test (0.2-1.5 None kg/cm2 for 10-20 mins Heat Heat provocation None Solar UV and visible light of Rule out other light- different wavelengths induced dermatosis Dermographic Elicit dermographism Differential blood count, ESR, CRP  Recommended diagnostic test Other Routine diagnostic tests Extended urticaria diagnostic tests Aquagenic Wet cloths at body temp for None 20 mins Cholinergic Exercise and hot bath None provocation Contact Prick test read after 20 mins None Exercise- According to history exercise None induced test with/without food  Management Identification and elimination of underlying causes Avoidance or elimination of the eliciting stimulus Inhibition of mast cell mediators  Inhibition of mast cell mediators 1st generation H1antihistamines for acute urticaria (chlorpheniramine, hydroxyzine) 2nd generation or non/less-sedating H1antihistamines (cetirizine, levocetirizine, loratidine, desloratidine, rupatadine, bilastine, fexofenadine) considered as first-line treatment for chronic urticaria Dose-dependent, good safety profiles  Erythema multiforme (EM) Typical targets: 2 mucosal involvement (eyes, mouth, genitalia, perianal area, urethra) Stevens-Johnson syndrome Stevens-Johnson syndrome Stevens-Johnson syndrome Overlap SJS/TEN TEN with spots TEN with spots TEN without spots  SJS/TEN Drug-induced: antibiotics eg.sulfonamide, anticonvulsants (carbamazipine,HLA-B*1502), allopurinol (HLA-B*5801), NSAIDs Infection: herpes infection, mycoplasma HIV infection dramatically increases the risk Predisposing disorder: autoimmune disease eg. SLE Malignancy: lymphoma  SJS/TEN Mortality rate - SJS: 5-15%, TEN: 30-35% Fever Mucous membrane: 1-3 days before skin eruption Nikolsky’s sign: positive GI and RS: profuse diarrhea, respiratory distress  Treatment of SJS/TEN No generally accepted regimens or treatment guideline Identification/elimination of the offending drug Supportive measures: the mainstay of therapy Active therapy “disease-modifying agent” No controlled therapeutic trials because of infrequent and life-threatening disease Require complex treatment and individually adapted care Alopecia Cyclic phases of hair growth 3 phases 1. Anagen (growing phase): 2-6 yrs, 85-90% of hair on the scalp 2. Catagen (atrophy phase): 2-3 weeks, 1% 3. Telogen (resting phase): 1-3 months, 10-15% 4. Exogen (shedding phase): hair shedding  Hair -Each follicle: 10-20 times of hair growth cycle in a lifetime -Hair color: melanocytes, eumelanin and pheomelanin -Type of hair: 1.Lanugo 2.Vellus eg. face 3.Intermediate 4.Terminal hair  Hypertrichosis Lanuginosa Acquisita Sudden appearance of long, fine, non- pigmented lanugo hairs Face and ears Most common: CA lung and colon AIDS, thyrotoxicosis, porphyria cutanea tarda Medications; cyclosporin, phenytoin  Hair -Highest density on scalp ~ 100,000 -Distribute throughout the integument, except: palms, soles and portion of genitalia -Highest density of follicles: scalp-1135/cm2 at birth and 615 third decade -Normal hair follicle 100,000/head in brown/black hair 10% greater in blondes 10% less in redheads -Hair growth 0.37 mm/day -Hair loss 100/day  Alopecia Hair breakage How many ? Acquired or congenital ? Duration Site Associated symptom Previous illness or postpartum Blood loss or operation Underlying disease Drugs Family history  Physical examination Characteristic alopecia Scalp : scale, crust, scar, inflammation, mass, exclamation mark hair, black dot appearance Hair pull Hair count Hair pluck Microscopic examination  Evaluation Pull test – Grasps ̴ 50–60 hairs and tugs them from proximal to distal end, 4 areas – Positive: > 2 hairs in > 1 area or 10% in 1 area – Examined with light microscope Blunt ends: hair breakage Club hairs: telogen hair  Evaluation Forcible hair pluck Trichogram – Proportion of anagen to catagen and telogen hairs – Grasp 25–50 hairs with a needle holder close to the scalp and plucked sharply in the direction of the hair – The proximal ends are place on a glass slide in a drop of water and covered with a cover slip Telogen hair Anagen hair  Trichogram evaluation Telogen count 10-25% =normal > 25-35% =suspicious-highly suspicious for telogen effluvium  Alopecia Localized Diffuse Nonscarring Scarring Nonscarring Scarring - Alopecia areata - DLE - AT, AU - DLE - Trichotillomania - Kerion - 2o syphilis - Trauma - 2o syphilis - Folliculitis -Anagen effluvium - Surgical scar - Tinea capitis - LPP -Telogen effluvium - Androgenetic - Trauma -Androgenetic - Tumor DLE, discoid lupus erythematosus LPP, lichen planopilaris (frontal fibrosing alopecia) AT, alopecia totalis AU, alopecia universalis  Anagen /telogen effluvium 1. Telogen effluvium diffuse alopecia with gradually progress 2. Anagen effluvium diffuse alopecia with rapid course  Telogen effluvium Sudden conversion of anagen  telogen hairs Often related to external causes, reverse when remove exogenous stimuli HPT: positive Trichogram: increase telogen hair > 25% May copresent with AGA  complicate diagnosis and treatment Scalp biopsy: differentiating from diffuse AA, AGA ChronicTE triggers may be difficult to identify.(esp in women between the ages of 30-60 years)  Telogen effluvium Sudden onset of Triggering massive shedding Ongoing massive events (bag sign) shedding 2-3 mo Acute TE Chronic TE TFT, CBC, ferritin, iron study, VDRL, ANA, BUN, Cr, LFT > 6 mo Improve within 6 mo after triggering event Stimulus persist > 6 mo or after withdrawal from suspected causal Primary/idiopathic Acute TE Causes of telogen effluvium  Treatment Remove cause Ferritin level < 40 ng/dl  iron supplement Thyroid condition 2% or 5% minoxidil solution  Anagen effluvium Disturbance of hair follicle matrix cells Interrupt anagen phase Hair falls out 7–14 days after the initiating event without entering catagen or telogen Causes: chemotherapy, radiation, toxins, heavy metal, severe malnutrition Once the initiating trigger is removed, the hair usually regrows after around 120 days Anagen effluvium  Alopecia areata Non-cicatricial alopecia Hair-specific autoimmune disease, with genetic factors involved in disease susceptibility and severity together with environmental factors T-lymphocyte interaction with follicular antigens (autoantigens) Chronic relapsing nature  Alopecia areata Clinical: patches of alopecia without scarring or inflammation of scalp, HPT+ “ exclamation mark hair or black dots” Alopecia totalis Alopecia universalis  Diffuse variant: widespread thinning or may primarily affect the top of the head  Trichotillomania “Hair pulling madness” Rx : Psychiatist, Chloripramine  Secondary syphilis 1. Moth-eaten 2.Diffuse syphilitic 3. Mixed type Dx: looking for other signs eg. mucous patch, condyloma lata, rash Ix : VDRL Rx: Benzathine penicillin 2.4 mu IM Roseola syphilitica  Condyloma lata Mucous patches  Androgenetic alopecia Male pattern and female pattern hair loss Androgen-dependent: dihydrotestosterone – Conversion of scalp terminal hairs into miniaturized vellus hairs – Progressive decline in anagen duration, an increase in telogen duration Genetic predisposition: polygenic The frequency and severity increase with age Androgenetic alopecia  Pathogenesis-AGA MPHL – Increase 5α-reductase activity and DHT levels – DHT : miniaturized hair – Genetic predisposition FPHL – More complex etiology – Androgen-related combined with genetic sensitivity – Recommend W/U ferritin and TSH to rule out TE – Irregular periods and/or other signs of androgen excess  free and total testosterone, DHEA-S  Treatment MPHL – Minoxidil (2% and 5%) and finasteride (1 mg) – Hair transplantation FPHL – 2% and 5% topical minoxidil – Oral contraceptives (to suppress ovarian androgen production), spironolactone (antiandrogen) or finasteride therapy – Finasteride higher daily doses of 2.5 and 5 mg (can improve FPHL)  Tinea capitis Endothrix “Black dot” Ectothrix Localized scarring alopecia Cause: -discoid lupus erythematosus -folliculitis (suppurative or fungus) -tumor -operative scar -cyst Acne Vulgaris  Acne One of the most common dermatologic disorder 33% at some time between ages of 15-44 years, primarily adolescents Profound effect on the physical, psychological, and social wellbeing of patients Impaired self-image, self-esteem Increased depression, anxiety, suicidal thoughts and attempts Effective treatment can prevent psychological distress and physical scarring  Pathogenesis of acne 1. Sebum production Androgen (end-organ hyperresponse) Severity 2. Hypercornification of follicular epithelium Microcomedones 3. Cutibacterium acnes Release chemotactic factor, complement activation 4. Release of inflammatory mediators into the skin -IL-1α up-regulation with linoleic deficiency -Synthesis of TNF-α and IL-1β through TLR-2 -Autocrine and paracrine mechanism by activating AP-1 C. acnes  Type of acne Non-inflammatory Microcomedone (acne precursor) Open comedone ("blackhead") Closed comedone ("whitehead") Inflammatory Papules, Pustules Cysts, Nodules Sequelae Dyspigmentation Scarring How should acne be managed? Aim: reduce the presence and impact of symptoms including psychosocial sequelae Importance: acne duration and inflammation correlate to the degree of scarring Evaluation: treatment needs to be continued for at least 6-8 weeks before changing or adding other treatments  Acne treatment Drugs Mechanism Benzoyl peroxide Antimicrobial Weakly comedolytic Topical retinoids Comedolytic Anti-inflammatory Systemic/ topical antibiotics Antimicrobial Anti-inflammatory Oral contraceptives Sebosuppressive Systemic retinoids Comedolytic Anti-inflammatory Sebosuppressive Indirectly antimicrobial Thiboutot D, et al. J Am Acad Dermatol 2009;60:s1-50. Eichenfield LF, et al. Semin Cutan Med Surg 2010;29:13-6.