Clinical correlation of Clinical correlation of inflammatory skin inflammatory skin

lesionslesionsMary Jo Robinson, D.O.Mary Jo Robinson, D.O.

UMDNJ-SOMUMDNJ-SOMOct.3, 2007Oct.3, 2007

5 clinical keys to diagnosis5 clinical keys to diagnosis

• Type of lesions-very very important

• Region of body affected- also important

• Distribution of lesions-not that important

• Color-somewhat important

• Configuration/shape-less important

• Summary- pertinent history and complete skin examination is best key.

8 clinical diagnostic groups8 clinical diagnostic groups• Pustular-pustule• Vesicular bullous-vesicles or bullae• Papular mini-vesicular- vesicles less than

2 mm• Papulosquamous-scales• Papulonodular-non red nodule, no scale

or crust• Vascular dominant-red macule, papule or

nodule w/o epidermal changes• Pigmentary-brown, black, white or yellow

lesions• Tumor –large papules or nodules

>2000 clinical dermatologic diseases>2000 clinical dermatologic diseases

• Many with variety of presentations and tendency to change during the chronology of disorder

• Thus one disease can have a myriad of radically different presentations, ie. Lupus

100 most common dermatologic dzs100 most common dermatologic dzs

• Represent 85% of problems seen by practicing dermatologist

• But most do not need bx-acne, rosacea, seborrheic dermatitis , psoriasis, tinea corporis….diagnosed clinically w/o bx

• But atypical presentations of above and a subgroup of patients called “GOK” tend to get biopsies

So how does the pathologist So how does the pathologist correlate these clinical impressionscorrelate these clinical impressions??• Given the clinical impression

(macroscopic)try to subclassify into microscopic appearance

• Such as clinician describes scales, slide shows alternating parakeratosis and orthokeratosis= PRP

• Clinician describes pustules, slide shows collections of neutrophils in stratum corneum= pustular psoriasis

PustularPustular

• Microscopic• Collections of

neutrophils, eosinophils or lymphocytes in epidermis, follicle, sebaceous glands, etc

• Macroscopic• Pustular dermatosis

- impetigo-

folliculitis - acne

- Rosacea

- candidiasis

- Pustular

psoriasis

- Sweet’s

Generalized and intense Generalized and intense erythematous rash with pustuleserythematous rash with pustules

Palmoplantar pustulesPalmoplantar pustules

Macropustule Macropustule

Pustular Pustular psoriasis psoriasis

• Biopsy to exclude fungus, pustular drug, impetigo, superficial pemphigus, impetigo herpetiformis

• Should culture

Histology not specific, CC Histology not specific, CC necessary necessary

• Pustular psoriasis cannot be distinguished on histology from - acrodermatitis continua(pustular eruption on one of more fingers) - Reiter’s disease(arthritis, conjunctivitis, balanitis, pustular dermatosis)

- impetigo herpetiformis( pustular dermatosis of pregnancy assoc w/ hypocalcemia)

Papular minivesicularPapular minivesicular

• Microscopic• Epidermal

spongiosis w/ scale crust

• Macroscopic• Papular minivesicular

dermatitis- contact dermatitis- atopic dermatitis- scabies- dermatophytosis

- stasis dermatitis

- Grover’s

- Hailey Hailey

- Mucha-Habermann- Dermatitis

herpetiformis

Intensely pruritic rash of Intensely pruritic rash of elbows, knees, backelbows, knees, back

Early

Late

Floor of Floor of blisterblister

DIF granular IgA in dermal DIF granular IgA in dermal papillaepapillae

D/Dx DH via DIFD/Dx DH via DIF

• DIF DH- granular IgA

• Linear IgA dermatosis-linear IgAalso lack of gluten sensitive

enteropathy, no association w/HLA-B8 &DR-3 antigens, less response to dapsone tx

• Bullous pemphigoid-linear IgG

Dermatitis herpetiformisDermatitis herpetiformis

• clinically Grover’s, atopic dermatitis, scabies & Pityriasis lichenoides are always part of differential.

• Commonly due to intense pruritus of DH, a bx will come in as r/o scabies or atopic dermatitis

• Biopsy may often show only erosions or scale crusts

• Clinician should biopsy nonexcoriated, non-vesicular erythematous plaque or papule for best diagnosis

• d/dx of neutrophils in papillary dermis includes Bullous eruption of LE, mucous membrane pemphigoid, flea bites, leukocytoclastic vasculitis, linear IgA dermatosis.

• Clinical response to dapsone can be used as confirmatory test

• 2/3 pts have asymptomatic celiac –like disease on jejunal bx & endomysial antibodies

VesiculobullousVesiculobullous

• Microscopic• Epidermal or

subepidermal vesicle(<10mm)

• Bullae(>10 mm)

• Macroscopic• Burn• Erythema

multiforme• Pemphigus vulgaris• Dermatitis

herpetiformis• Herpes simplex• Bullous pemphigoid• Contact dermatitis• Fixed drug

eruptions

Firm bullae w/ erosions, Firm bullae w/ erosions, crusts, papules and whealscrusts, papules and wheals

• groin, axillae, forearms, oral

• Intertriginous to generalized

• Pink to red

Histopathology Histopathology

DIF linear IgGDIF Salt split skin IgG

Type IV collagen present along Type IV collagen present along base of blisterbase of blister

EBA - collagen along roof of blister

Bullous pemphigoidBullous pemphigoid

• Histology- epidermal spongiosis

• Rete ridge pattern preserved

• Subepidermal blister

• Early bullae will have many eosinophils

• Clinician should biopsy erythematous skin with early bullae

• Perilesional skin should be biopsied for DIF

Histologic d/dxHistologic d/dx

• Spongiotic arthropod assault

• Herpes gestationis• Porphyria cutanea

tarda• Erythema

multiforme• Dermatitis

herpetiformis

• Linear IgA bullous dermatosis

• Epidermolysis bullosa

• Bullous lichen planus

• Bullous drug eruption

• Bullous LE

Pruritic vesiculopustular disease Pruritic vesiculopustular disease of trunk and proximal extremitiesof trunk and proximal extremities

Note the vesicles start clear and then fill with white creamy pus, then erosions form

HistologyHistology

• Subcorneal pustules to bullae with neutrophilic infiltrate w/ sparse to moderate numbers of eosinophils

IgA pemphigusIgA pemphigus

• Presented case is SPD type (subcorneal pustular dermatosis)

• Resemble SPD/Sneddon- Wilkinson, pemphigus foliaceous

• Second clinical type is IEN type (interepidermal neutrophilic bullae)

• Annular erythema with peripheral vesicular eruption

IEN typeIEN type

Intraepidermal pustules of neutrophils and some eosinophils

IgA DIFIgA DIF• Intercellular IgA deposits• SPD form shows antibodies to

desmocollin-1• Some cases of IEN form antibodies to

desmoglein1• Both have serum antibodies to IgA

epithelial cell surfaces by IFA• Differentiates from Pemphigus foliaceus

which has IgG epithelial cell surface

Papulosquamous Papulosquamous

• Microscopic• Confluent

orthokeratosis, parakeratosis or alternating OK/PK sometimes with minimal serum

• Macroscopic• Lichen planus• Psoriasis • Lupus erythematosus• Pityriasis rosea• Seborrheic dermatitis• Solar keratosis• Scaly dermatophytosis• Ichthyosis• Mycosis fungoides• Pityriasis rubra pilaris

ClinicalClinical

• Scaly • Large scale(flakes)

> 1mm size= large scale dz(psoriasiform)

• Small scales< 1 mm size=small scale dz(pityriasis)

• Shiny compact scalescompact scale

dz (lichenoid)

HistopathologyHistopathology

• Large scale usually psoriasiform

may be spongiotic, interface vacuolar or interface

• Small scale usually spongiotic, but may be interface vacuolar or interface

• Compact scale usually interface but spongiotic or interface vacuolar may be seen

Plaques with overlying scale Plaques with overlying scale and erythematous borders and erythematous borders

IgG, complement band at base of epidermis on IF

Lupus erythematosusLupus erythematosus

• Annular to plaques• Photosensitive distribution• Scales• Atrophy/scarring(late)• Follicular plugging(late)• Dermal edema &/or mucin deposits• Telangiectases• Lichenoid to sup & deep pv lymph

infiltrate

Follicular pluggingFollicular plugging

Polymorphous autoimmune Polymorphous autoimmune diseasedisease

• primary changes at epidermal dermal interface including hair follicle

• Vacuolar change

• BM thickening –chronic cases PAS

• Compact Orthokeratosis

• Loss of rete ridges late

• Necrotic keratinocytes occasionally

Stage of disease affects Stage of disease affects histologyhistology

• Early – maculopapular more superficial sparse inflammation, lichenoid and may be neutrophilic

• Later smudging subtle to progress to more obvious vacuolar

• Then plaque stage shows dermal mucin and adnexal inflammation

• Late- scarring, atrophy, melanophages

Histologic D/DXHistologic D/DX• Seborrheic dermatitis- early forms w/

pyknotic neutrophils @ follicular ostia, later chronic forms more spongiosis

• Actinic keratosis- interface changes due to solar damage, check the follicular ostia, no interface change there? It is not DLE

• Lichen planus• PMLE- no atrophy, no foll. plugging, no

fibrosis• Rosacea –central face especially, but more

vascular than LE & assoc clinically w/ flushing, perifollicular infl, no mucin

Flat topped violaceous Flat topped violaceous papules w/ shiny scalepapules w/ shiny scale

Histology Histology

Lichen planusLichen planus• Compact orthokeratosis

• If rubbed, parakeratosis &/or hypertrophic

• Acanthosis with jagged sawtoothed rete ridges

• Focal wedge-shaped hypergranulosis that is more prominent next to acrosyringium

• Colloid bodies- more prominent in lower epidermis

Dermis in LPDermis in LP

• lichenoid lymphohistiocytic infiltrate fills papillary dermis, is dense and close to base of epidermis

• Coarse collagen bundles

• No mucin, no edema

D/Dx of lichenoid lesionsD/Dx of lichenoid lesions• Lichenoid photodermatitis-sup & deep w/

spongiosis• Lichenoid solar keratosis-atypical budding

w/ alternating ok/pk• Lichenoid LE-vacuolar change prominent,

dermal mucin, may be tough call• Lichen aureus-pigmented purpuric

dermatosis, hemosiderin macrophages• MF- epidermotropism, lamellar fibrosis• LPLK- usually solitary, peripheral SK/SL

Papulonodular Papulonodular

• Microscopic• Scale crust and

spongiosis are ABSENT

• Acanthosis, dermal deposits or inflammation are PRESENT

• Macroscopic• Prurigo nodularis• Granuloma annulare• Amyloidosis• Sarcoid • Acne• Follicular cysts• Arthropod assaults• Lymphocytoma cutis• Polyarteritis nodosa

Grouped 1-2 mm flesh colored to Grouped 1-2 mm flesh colored to pink papules in arcuate pink papules in arcuate

distribution on extremitiesdistribution on extremities

Clinical d/dxClinical d/dx• Sarcoid

• Lichen planus

• Urticaria pigmentosa

• Papular mucinosis

• Tinea corporis

• Necrobiosis lipoidica

• Rheumatoid nodule

• Foreign body

• Granulomatous rosacea

Granuloma annulare Histology Granuloma annulare Histology

D/Dx palisading granulomaD/Dx palisading granuloma

• Granuloma annulare• Rheumatoid nodules• Necrobiosis

lipoidica• Churg-Strauss

granulomatosis• Lupus miliaris

disseminatus facei

• Bovine collagen injections

• Actinic granuloma• Foreign body

granuloma• Infectious

granuloma

Vascular dominantVascular dominant• Microscopic• Proliferations of

blood vessels • Or perivascular

inflammatory infiltrate w/ no epidermal changes

• Redness, macular or papular erythema

• Wheals • purpura

• Macroscopic• Urticarial vasculitis• Macular papular

erythema• Vasculitis• Gyrate erythema• Schamberg’s• telangiectasia

Hemangiomas• Kaposi’s

Purpura as a clinical cluePurpura as a clinical clue• Non-purpuric

complete blanching with application of pressure, no extravasated rbc’s in dermis

• Sunburn, urticaria, macular papular erythema, erythema nodosum, fixed drug, gyrate erythemas

• Purpuricresidual erythema

persists with pressureecchymosis and

petechiae • Leukocytoclastic

vasculitis, septic vasculitis, pigmented purpura, dysproteinemic purpura, thrombocytopenic purpura

Bright red to brown red purpuric Bright red to brown red purpuric papules lower extremitiespapules lower extremities

Histology Histology

Endothelial cell swelling, angiocentric neutrophilic inflammation with nuclear dust, fibrin in vessel walls, extravasated erythrocytes

Henoch-Schoenlein purpura-IgA Henoch-Schoenlein purpura-IgA mediated in kids(beta strept)mediated in kids(beta strept)

PigmentaryPigmentary• Microscopic• Pigment containing

macrophages in upper dermis

• decreased or increased number of melanocytes in epidermis

• Of dermis with collections of histiocytic foams cells in dermis fibrosis

• Macroscopic • Lichen sclerosus• Vitiligo• Lentigo• Xanthelasma• Lupus erythematosus• Morphea• Tinea versicolor• Melanocytic nevus• Basal cell carcinoma,

pigmented• Seborrheic keratosis• Dermatofibroma

White to yellow linear plaques White to yellow linear plaques with violaceus to erythematous with violaceus to erythematous

halohalo

Histology linear morpheaHistology linear morphea

TumorTumor

• Microscopic• neoplastic

proliferation of cells• epidermal• Dermal• Melanocytic• other

• Macroscopic • Mycosis fungoides• Kaposi sarcoma• Melanoma • Basal cell

carcinoma• Seborrheic

keratosis• Sebaceous

hyperplasia• Etc.

15 top inflammatory skin lesions 15 top inflammatory skin lesions submitted to pathologysubmitted to pathology

• Arthropod assault• Erythema multiforme• Fixed drug• Granuloma annulare• Jessner’s/

lymphocytoma cutis• Lesion• Lichen planus• Leukocytoclasitc

vasculitis

• Mycosis fungoides/ parapsoriasis

• Polymorphous light eruption

• Psoriasis• Scleroderma/morphea• Urticaria• vasculitis

ReferencesReferences • Bolognia, Jorizzo & Rapini,

Dermatology, 2003:Elsevier, www.dermtext.com

• McKee, et.al. ,Pathology of the Skin with Clinical Correlations, 3rd ed. 2005:Elsevier.

• Bozzo P & Miller RC Clinical Dermatology and Dermatopathology: A Dynamic Interface series of ASCP lectures.