Pathology of Common Dermatitides & Dermatoses Mark R. Wick, M.D.

“Papulosquamous” Dermatitides n Defined by clinical attributes, as slightly elevated papular eruptions with scaling n These diseases include spongiotic, lichenoid, and psoriasiform dermatitides from a pathological perspective n Defined by clinical attributes, as slightly elevated papular eruptions with scaling n These diseases include spongiotic, lichenoid, and psoriasiform dermatitides from a pathological perspective

n 1.Spongiotic dermatitides ä Contact dermatitis ä Eczema (atopic dermatitis) ä Superficial mycoses (dermatophytoses) ä Seborrheic dermatitis (acute/subacute) ä Pityriasis rosea ä Selected cases of secondary syphilis n 2.Lichenoid dermatitides ä Lichen planus ä Lichen simplex chronicus (“neurodermatitis”) ä Lupus erythematosus (discoid or systemic) ä Dermatomyositis n 3.Psoriasiform dermatitides ä Psoriasis vulgaris ä ANY CHRONIC SPONGIOTIC DERMATITIS n 1.Spongiotic dermatitides ä Contact dermatitis ä Eczema (atopic dermatitis) ä Superficial mycoses (dermatophytoses) ä Seborrheic dermatitis (acute/subacute) ä Pityriasis rosea ä Selected cases of secondary syphilis n 2.Lichenoid dermatitides ä Lichen planus ä Lichen simplex chronicus (“neurodermatitis”) ä Lupus erythematosus (discoid or systemic) ä Dermatomyositis n 3.Psoriasiform dermatitides ä Psoriasis vulgaris ä ANY CHRONIC SPONGIOTIC DERMATITIS “Papulosquamous” Dermatitides: Common Representative Examples

SPONGIOTIC DERMATITIDES

Spongiotic Dermatitides: General Histologic Features n 1.Variable parakeratosis: retention of nuclei in superficial cornified epidermal cells n 2. Spongiosis : Presence of edema fluid between individual epidermal cells, which may progress to formation of vesicles (microscopic intraepidermal “blisters”) n 3. Inflammation in the epidermis and dermis, with perivascular dermal accentuation. It is usually chronic in nature ( i.e., featuring lymphocytes and histiocytes), but small numbers of neutrophils & eosinophils may also be observed n 1.Variable parakeratosis: retention of nuclei in superficial cornified epidermal cells n 2. Spongiosis : Presence of edema fluid between individual epidermal cells, which may progress to formation of vesicles (microscopic intraepidermal “blisters”) n 3. Inflammation in the epidermis and dermis, with perivascular dermal accentuation. It is usually chronic in nature ( i.e., featuring lymphocytes and histiocytes), but small numbers of neutrophils & eosinophils may also be observed

n 1. Allergic Contact Dermatitis : Eosinophils in the epidermis n 2. Seborrheic Dermatitis: Accentuation of parakeratosis around hair follicle ostia, with or without neutrophils n 3. Pityriasis rosea: Extravasation of red cells in the epidermis n 4. Dermatophytoses: Neutrophils in the epidermis, along with intracorneal PMNs; fungi are visible with the GMS stain n 5. Syphilis: Spirochetes in epidermis with the Warthin-Starry/Steiner silver stains n 1. Allergic Contact Dermatitis : Eosinophils in the epidermis n 2. Seborrheic Dermatitis: Accentuation of parakeratosis around hair follicle ostia, with or without neutrophils n 3. Pityriasis rosea: Extravasation of red cells in the epidermis n 4. Dermatophytoses: Neutrophils in the epidermis, along with intracorneal PMNs; fungi are visible with the GMS stain n 5. Syphilis: Spirochetes in epidermis with the Warthin-Starry/Steiner silver stains Spongiotic Dermatitides: Histologic Nuances

LICHENOID DERMATITIDES

Lichenoid Dermatitides: General Histologic Features n 1.Damage to basal epidermal keratinocytes, with secondary “vacuolar” (clear-cell) change in their cytoplasm n 2.Infiltrate of lymphocytes + plasma cells in a “band” beneath the epidermis, with or without direct involvement of the dermoepidermal junction n 3.Death of keratinocytes near the stratum basalis, with formation of “cytoid” bodies n 4.Variable atrophy or hyperplasia (acanthosis) of the epidermis n 1.Damage to basal epidermal keratinocytes, with secondary “vacuolar” (clear-cell) change in their cytoplasm n 2.Infiltrate of lymphocytes + plasma cells in a “band” beneath the epidermis, with or without direct involvement of the dermoepidermal junction n 3.Death of keratinocytes near the stratum basalis, with formation of “cytoid” bodies n 4.Variable atrophy or hyperplasia (acanthosis) of the epidermis

n 1. Lichen Simplex Chronicus : Vertical striation of collagen surrounding the rete ridges, in the papillary dermis n 2. Lichen planus: Irregular “sawtooth” hyperplasia of the epidermis with irregular thickness of the stratum granulosum and a lack of parakeratosis n 3. Lupus erythematosus/Dermatomyositis: Atrophy of the epidermis with thickening of the epidermal basement membrane; LE also shows dermal mucin deposition n 1. Lichen Simplex Chronicus : Vertical striation of collagen surrounding the rete ridges, in the papillary dermis n 2. Lichen planus: Irregular “sawtooth” hyperplasia of the epidermis with irregular thickness of the stratum granulosum and a lack of parakeratosis n 3. Lupus erythematosus/Dermatomyositis: Atrophy of the epidermis with thickening of the epidermal basement membrane; LE also shows dermal mucin deposition Lichenoid Dermatitides: Histologic Nuances

PSORIASIFORM DERMATITIDES

Psoriasiform Dermatitides: General Histologic Features n 1.Regular acanthosis of the epidermis, but with suprapapillary thinning n 2.Parakeratosis and/or orthokeratosis n 3.Variable acute inflammation, especially involving the epidermis & stratum corneum (“Munro” & “Kogoj” microabscesses) n 4.Perivascular chronic dermal inflammation n 5.Papillary dermal hypervascularity n 1.Regular acanthosis of the epidermis, but with suprapapillary thinning n 2.Parakeratosis and/or orthokeratosis n 3.Variable acute inflammation, especially involving the epidermis & stratum corneum (“Munro” & “Kogoj” microabscesses) n 4.Perivascular chronic dermal inflammation n 5.Papillary dermal hypervascularity

n 1.There are NO specific markers of psoriasis vulgaris; Munro & Kogoj microabscesses may be seen in other diseases as well, particularly in chronic dermatophytoses n 2.“Suggestive” histologic features of acute or subacute spongiotic dermatitis are usually ABSENT in their chronic forms, yielding microscopic images which simulate that of psoriasis closely. Resulting differential diagnosis includes psoriasis, chronic eczema, chronic dermatophytosis, and chronic contact dermatitis n 1.There are NO specific markers of psoriasis vulgaris; Munro & Kogoj microabscesses may be seen in other diseases as well, particularly in chronic dermatophytoses n 2.“Suggestive” histologic features of acute or subacute spongiotic dermatitis are usually ABSENT in their chronic forms, yielding microscopic images which simulate that of psoriasis closely. Resulting differential diagnosis includes psoriasis, chronic eczema, chronic dermatophytosis, and chronic contact dermatitis Psoriasiform Dermatitides: Histologic Nuances

PRIMARY ACQUIRED BULLOUS DISEASES OF THE SKIN

Primary Acquired Bullous Diseases of the Skin n Pemphigus vulgaris n Bullous Pemphigoid n Epidermolysis bullosa acquisita n Dermatitis herpetiformis n Pemphigus vulgaris n Bullous Pemphigoid n Epidermolysis bullosa acquisita n Dermatitis herpetiformis

DiseaseAutoantibody Target(s) n Pemphigus vulgarisPlakoglobin-130kD complex in epidermal desmosomes n PemphigoidBP antigen in the lamina lucida of the epidermal BMZ n EpidermolysisEBA antigen in sub-lamina bullosa acquisitadensa zone of epidermal BMZ n DermatitisDermal papillary collagen (& herpetiformis gliadin/endomysial proteins) DiseaseAutoantibody Target(s) n Pemphigus vulgarisPlakoglobin-130kD complex in epidermal desmosomes n PemphigoidBP antigen in the lamina lucida of the epidermal BMZ n EpidermolysisEBA antigen in sub-lamina bullosa acquisitadensa zone of epidermal BMZ n DermatitisDermal papillary collagen (& herpetiformis gliadin/endomysial proteins) Primary Acquired Bullous Disorders of the Skin: Models of Autoimmune Disease

n 1. Pemphigus vulgaris-- Intraepidermal blisters, centered in the suprabasal region; sparse mixed acute & chronic inflammation n 2. Pemphigoid-- Subepidermal blisters, filled & undermined by PMNs, eosinophils, & lymphocytes n 3. EBA-- Essentially identical to pemphigoid n 4. Dermatitis herpetiformis-- Dense regional dermal infiltrates of PMNs, most notable in upper dermal papillae & within blisters n 1. Pemphigus vulgaris-- Intraepidermal blisters, centered in the suprabasal region; sparse mixed acute & chronic inflammation n 2. Pemphigoid-- Subepidermal blisters, filled & undermined by PMNs, eosinophils, & lymphocytes n 3. EBA-- Essentially identical to pemphigoid n 4. Dermatitis herpetiformis-- Dense regional dermal infiltrates of PMNs, most notable in upper dermal papillae & within blisters Primary Acquired Bullous Disorders of the Skin: Histologic Features

DiseaseDIF Pattern PemphigusIntercellular labeling for IgG, IgM, C’3 in epidermis Pemphigoid/EBALinear labeling of epidermal BMZ for IgG, IgM, C’3; collagen type IV in blister floor in BP & in blister roof in EBA DermatitisInterrupted linear/granular herpetiformislabeling of epidermal BMZ for IgA, C’3 DiseaseDIF Pattern PemphigusIntercellular labeling for IgG, IgM, C’3 in epidermis Pemphigoid/EBALinear labeling of epidermal BMZ for IgG, IgM, C’3; collagen type IV in blister floor in BP & in blister roof in EBA DermatitisInterrupted linear/granular herpetiformislabeling of epidermal BMZ for IgA, C’3 Primary Acquired Bullous Disorders of the Skin: Direct Immunofluorescence

SELECTED VASCULAR ABNORMALITIES OF THE SKIN

Leukocytoclastic Vasculitis: Pathologic Features n Synonymous with “small vessel vasculitis,” “hypersensitivity vasculitis,” or “Zeek’s vasculitis.” May be associated with underlying collagen vascular disease, Henoch-Schoenlein disease, or malignancy. Microscopic diagnosis is based on: ä Neutrophilic infiltration of small venules in dermis, with karyorrhectic basophilic nuclear “dust” in interstitium ä Extravasation of erythrocytes in the dermis ä Fibrinoid change in vessel walls is often seen but not diagnostically necessary n Synonymous with “small vessel vasculitis,” “hypersensitivity vasculitis,” or “Zeek’s vasculitis.” May be associated with underlying collagen vascular disease, Henoch-Schoenlein disease, or malignancy. Microscopic diagnosis is based on: ä Neutrophilic infiltration of small venules in dermis, with karyorrhectic basophilic nuclear “dust” in interstitium ä Extravasation of erythrocytes in the dermis ä Fibrinoid change in vessel walls is often seen but not diagnostically necessary

Urticarial Reactions: Microscopic Features n Principal histologic alteration is dermal edema, relating to “leakiness” of capillaries in the corium during reactions featuring local hyperhistaminosis n Dermal collagen bundles are splayed apart, by seemingly empty spaces n Variable numbers of eosinophils and neutrophils are seen around dermal venules & capillaries n Urticarial vasculitis is defined histopathologically as an “amalgam” of urticaria and leukocytoclastic vasculitis n Principal histologic alteration is dermal edema, relating to “leakiness” of capillaries in the corium during reactions featuring local hyperhistaminosis n Dermal collagen bundles are splayed apart, by seemingly empty spaces n Variable numbers of eosinophils and neutrophils are seen around dermal venules & capillaries n Urticarial vasculitis is defined histopathologically as an “amalgam” of urticaria and leukocytoclastic vasculitis