Spongiosis and Spongiotic • What is ‘spongiosis’? – Intra-epidermal and Dermatitis intercellular edema • Widening of intercellular spaces between keratinocytes • Elongation of G.Peter Sarantopoulos, MD intercellular bridges UCLA Medical Center

Spongiosis vs. Spongiotic Spongiosis Dermatitis • ‘Spongiosis’ as a histologic concept (not a • Not everything ‘spongiotic’ is a diagnosis!) spongiotic dermatitis – Intra-epidermal edema accompanies many (if not all) inflammatory skin diseases to some degree • So-called ‘patterns of spongiosis’ • Important to distinguish spongiosis as… – Neutrophilic – The predominant histologic finding – Eosinophilic – A non-specific feature of other inflammatory – Follicular dermatoses (e.g. lichenoid/interface, vasculopathic, – Miliarial psoriasiform, etc) – Sometimes, there is overlap

Dermatitis with ‘Spongiosis’ Dermatitis with ‘Spongiosis’ *

Neutrophilic: Eosinophilic: Miliarial: Neutrophilic: Eosinophilic: Miliarial: Pustular psoriasis Pemphigus (precursor) M. Crystallina Pustular psoriasis Pemphigus (precursor) M. Crystallina Reiter’s syndrome Pemphigus vegetans M. Rubra Reiter’s syndrome Pemphigus vegetans M. Rubra IgA Pemphigus Bullous pemphigoid M. profunda IgA Pemphigus Bullous pemphigoid M. profunda Pemphigus herpetiformis Cicatricial pemphigoid Pemphigus herpetiformis Cicatricial pemphigoid Infantile acropustulosis Pemphigoid (herpes) Infantile acropustulosis Pemphigoid (herpes) AGEP gestationis Follicular: AGEP gestationis Follicular: Palmoplantar pustulosis Idiopathic eosinophilic Infundibulofolliculitis Palmoplantar pustulosis Idiopathic eosinophilic Infundibulofolliculitis SSSS spongiosis Atopic dermatitis (follicular SSSS spongiosis Atopic dermatitis (follicular lesions) lesions) Neisserial infections Allergic contact dermatitis Neisserial infections Allergic contact dermatitis Apocrine miliaria Apocrine miliaria Dermatophytoses Atopic dermatitis Dermatophytoses Atopic dermatitis Eosinophilic folliculitis Eosinophilic folliculitis Candidosis Arthropod dermatitits Candidosis Arthropod dermatitits Beetle dermatitis Ofuji’s Disease Beetle dermatitis Ofuji’s Disease (Paederus) Incontinentia pigmenti (Paederus) Incontinentia pigmenti Pustular contact Drug reactions Pustular contact Drug reactions dermatitis Autoeczematization (‘Id’) dermatitis Autoeczematization (‘Id’)

* Some overlap exists between what Dermatopathologists consider ‘spongiotic dermatitis’ and so-called patterns of spongiosis

1 Spongiotic Dermatitis Spongiotic Dermatitis

• Select entities commonly encountered in • Nummular eczema daily practice –Clinical: • Tiny / papulo- – Nummular eczema vesicles, may coalesce – Contact dermatitis to form coin-shaped patches, single or – Seborrheic dermatitis multiple • Dorsum of hands, – extensor forearms, lower legs / outer thigh, posterior trunk

Spongiotic Dermatitis Spongiotic Dermatitis

• Nummular eczema • Nummular eczema – Early lesions – spongiosis – Early lesions – spongiosis leading to vesiculation, leading to vesiculation, vesicles often contain vesicles often contain inflammatory cells (may inflammatory cells (may mimic Pautrier’s mimic Pautrier’s microabscesses!) microabscesses!) – Later lesions – progressive – Later lesions – progressive psoriasiform hyperplasia psoriasiform hyperplasia (less regular than allergic CD!)

Spongiotic Dermatitis Spongiotic Dermatitis

• Contact Dermatitis • Contact Dermatitis –Clinical: Irritant CD –Clinical: Allergic CD • Reactions vary – simple • Erythematous papules, erythema to purpura to small vesicles or eczematous to weeping plaques vesiculobullous • Lesions arise 12-48 hrs reactions following exposure to • Identified at sites of allergen, lesions often exposure extend beyond site of exposure

2 Spongiotic Dermatitis Spongiotic Dermatitis

• Contact Dermatitis • Contact Dermatitis – Spongiosis leads to – Spongiosis leads to intraepidermal vesicles intraepidermal vesicles – ‘Irritant’ often more marked – ‘Irritant’ often more marked changes, ballooning / changes, necrosis, possible neuts; ballooning/necrosis, varies with irritant possible neuts; varies with concentration irritant concentration – ‘Allergic’, spongiosis often – ‘Allergic’, spongiosis often with eos, persistent lesions with eos, persistent lesions often show scale crust with often show scale crust with © Weedon, Skin Pathology, 2002 regular psoriasiform regular psoriasiform hyperplasia hyperplasia

Spongiotic Dermatitis Spongiotic Dermatitis

• Contact Dermatitis • Seborrheic dermatitis – Spongiosis leads to –Clinical: intraepidermal vesicles • Erythematous, scaling – ‘Irritant’ often more marked papules and plaques, changes, sometimes with a ballooning/necrosis, greasy appearance possible neuts; varies with • Found upon irritant concentration ‘seborrheic’ areas – scalp, ears, eyebrows, – ‘Allergic’, spongiosis often eyelid margins, with eos, persistent lesions nasolabial areas often show scale crust with • Males, after puberty; regular psoriasiform common manifestation hyperplasia in AIDS

Spongiotic Dermatitis Spongiotic Dermatitis

• Seborrheic dermatitis • Seborrheic dermatitis – Acute / subacute - – Acute/subacute - spongiosis with scale crust spongiosis with scale crust – Later – psoriasiform – Later – psoriasiform epidermal hyperplasia epidermal hyperplasia – Lymphocytes, – Lymphocytes, macrophages, occasional macrophages, occasional neuts upon a mildly neuts upon a mildly edematous superficial edematous superficial papillary dermis papillary dermis – Note: folliculocentric scale – Note: folliculocentric scale crust favors SD over crust favors SD over psoriasis psoriasis

3 Spongiotic Dermatitis Spongiotic Dermatitis

• Seborrheic dermatitis • Seborrheic dermatitis – Acute/subacute - – Acute/subacute - spongiosis with scale crust spongiosis with scale crust – Later – psoriasiform – Later – psoriasiform epidermal hyperplasia epidermal hyperplasia – Lymphocytes, – Lymphocytes, macrophages, occasional macrophages, occasional neuts upon a mildly neuts upon a mildly edematous superficial edematous superficial papillary dermis papillary dermis – Note: folliculocentric scale – Note: folliculocentric scale crust favors SD over crust favors SD over psoriasis psoriasis

Spongiotic Dermatitis Spongiotic Dermatitis

• Pityriasis Rosea • Pityriasis Rosea – Vaguely undulating –Clinical: epidermis, ‘mounded’ • Oval, salmon-pink , usually lesions; initial scaly lessened granular layer plaque ‘herald patch’ – Focal spongiosis leads to often small vesicles, dyskeratotic • Trunk, neck, proximal cells seen at all levels of extremities; follow lines epidermis (> in ‘herald patch’) of cleavage – Pigment incontinence, • All ages; often 10 – 35 superficial pap-derm yo edema, rbc extrav, mild- mod lymph inflammation with macrophages

Spongiotic Dermatitis Spongiotic Dermatitis

• Pityriasis Rosea • Pityriasis Rosea – Vaguely undulating – Vaguely undulating epidermis, ‘mounded’ epidermis, ‘mounded’ parakeratosis, usually parakeratosis, usually lessened granular layer lessened granular layer – Focal spongiosis leads to – Focal spongiosis leads to small vesicles, dyskeratotic small vesicles, dyskeratotic cells seen at all levels of cells seen at all levels of epidermis (> in ‘herald epidermis (> in ‘herald patch’) patch’) – Pigment incontinence, – Pigment incontinence, superficial pap-derm superficial pap-derm edema, rbc extrav, mild- edema, rbc extrav, mild- mod lymph inflammation mod lymph inflammation with macrophages with macrophages

4 Spongiotic Dermatitis Spongiotic Dermatitis

• Pityriasis rosea • Don’t be fooled - spongiosis in and of itself – Neuts within parakeratotic mounds favors psoriasis is a non-specific finding – pitfall! – Mounded parakeratosis favors PR (over • Spongiosis may be identified as a part of acute/subacute eczema) any number of inflammatory skin disorders – Always consider drugs - wide range of drugs may show a PR-like eruption • Look for the predominant reaction pattern • Examples of overlap…

Don’t Be Fooled! Don’t Be Fooled!

• Infectious – • Infectious – – Fungal infections – Fungal infections (dermatophytoses) often (dermatophytoses) often mimic the histologic mimic the histologic features of psoriasis features of psoriasis – Some infections may show – Some infections may show marked spongiosis as well marked spongiosis as well – even forming marked – even forming marked vesiculation vesiculation – A PAS with diastase stain – A PAS with diastase stain can quickly lead you to the can quickly lead you to the diagnosis and save the diagnosis and save the patient additional time and patient additional time and morbidity morbidity

Don’t Be Fooled! Don’t Be Fooled!

• Infectious – • Psoriasiform – Fungal infections –Psoriasis, early psoriasis (dermatophytoses) often may show spongiosis mimic the histologic associated with lymphocyte features of psoriasis exocytosis – Some infections may show marked spongiosis as well – Established psoriasis seen – even forming marked on the palms and soles vesiculation may show spongiosis – – A PAS with diastase stain making a distinction from can quickly lead you to the allergic contact dermatitis diagnosis and save the difficult patient additional time and – Erythrodermic psoriasis morbidity may also show spongiosis

5 Don’t Be Fooled! Don’t Be Fooled!

• Psoriasiform • Psoriasiform –Psoriasis, early psoriasis –Psoriasis, early psoriasis may show spongiosis may show spongiosis associated with lymphocyte associated with lymphocyte exocytosis exocytosis – Established psoriasis seen – Established psoriasis seen on the palms and soles on the palms and soles may show spongiosis – may show spongiosis – making a distinction from making a distinction from allergic contact dermatitis allergic contact dermatitis difficult difficult – Erythrodermic psoriasis – Erythrodermic psoriasis may also show spongiosis may also show spongiosis

Don’t Be Fooled! Don’t Be Fooled!

• Vasculopathic • Vasculopathic – Erythema annulare – Erythema annulare centrifugum (EAC), centrifugum (EAC), characteristic annular, characteristic annular, erythematous lesion may erythematous lesion may show a fine scale inside the show a fine scale inside the advancing edge advancing edge – Histology shows – Histology shows spongiosis, parakeratosis spongiosis, parakeratosis and an underlying and an underlying superficial perivascular superficial perivascular lymphocytic inflammation, lymphocytic inflammation, often with a ‘coat-sleeve’ often with a ‘coat-sleeve’ appearance appearance

Spongiotic Dermatitis Spongiotic Dermatitis

• Vasculopathic • Vasculopathic – Pruritic urticarial papules – Pruritic urticarial papules and plaques of pregnancy and plaques of pregnancy (PUPPP), aka polymorphic (PUPPP), aka polymorphic eruption of pregnancy eruption of pregnancy – Epidermal changes, to – Epidermal changes, to include spongiosis and include spongiosis and parakeratosis with parakeratosis with exocytosis of inflammatory exocytosis of inflammatory cells may be seen in up to cells may be seen in up to 1/3 of cases 1/3 of cases – Lymphocytic vasculitis with – Lymphocytic vasculitis with varying admixture of varying admixture of eosinophils and variable eosinophils and variable edema of the superficial edema of the superficial papillary dermis papillary dermis

6 Spongiotic Dermatitis Spongiotic Dermatitis

• Vasculopathic • Interface/lichenoid – Pruritic urticarial papules and plaques of pregnancy – Erythema multiforme, early (PUPPP), aka polymorphic lesions may show intra- eruption of pregnancy and intercellular – Epidermal changes, to intraepidermal edema include spongiosis and parakeratosis with (spongiosis) exocytosis of inflammatory cells may be seen in up to 1/3 of cases – Lymphocytic vasculitis with varying admixture of eosinophils and variable edema of the superficial papillary dermis

Clinical History

• 54 yo woman is seen by her Dermatologist complaining of an itching, burning rash • Physical exam showed a morbilliform rash on the lower extremities and trunk • Further questioning revealed that the patient had recently changed one of her blood pressure medications

Drug Eruption Sources

• Drug eruptions are one of the more Weedon, Skin Pathology. Churchill Livingstone, 2002 commonly biopsied inflammatory skin McKee, Pathology of the Skin, Elsevier-Mosby, 2005 lesions Additional micrographs from personal collection

– Drug eruptions may show a wide range of Questions/comments: [email protected] histologic patterns – Spongiosis with eosinophils is a common pattern • Any number of medications may incite a rash

7