Inflammatory skin disorders

Inflammatory skin disorders, also inflammatory skin diseases, are a significant part of dermatopathology. They lead to trepidation among pathologists that don't see lots of skin. Non-inflammatory skin disease is covered in dermatologic neoplasms and non-malignant skin disease.

Classification

• Bullous.
• Interface.
• Nodular & diffuse.
• Spongiotic.
• Vasculitis.
• Perivascular.
• Panniculitis.
• Psoriasiform.

Tabular comparison of inflammatory skin disease (adapted from Brinster):

Pattern	Key histologic feature	Subclassifications	Example	Image
Bullous	large "empty spaces"	-subcorneal -suprabasillar -subepidermal	-pemphigus foliaceus -pemphigus vulgaris -dermatitis herpetiformis	PV (WC)
Interface	inflammation at DE junction	-vacuolar (minimal) -lichenoid (band-like)	-erythema multiforme, SLE -lichen planus	VID (WC)
Nodular & diffuse	intradermal inflammatory infiltrate - nodular and/or diffuse	-neutrophic -lymphocytic -plasmic -eosinophilic -histocytic	-follicular occlusion triad, ruptured cyst/follicle -CTCL, reactive -plasma cell neoplasm, syphilis -eosinophilic cellulitis, Kimura disease -granuloma annulare, sarcoidosis, TB	CTCL (WC)
Spongiotic	small empty spaces between keratinocytes - can see squamous bridges (best seen at high power); +/- quasi-microvacuolar appearance	-acute -subacute -chronic	-poison ivy -nummular dermatitis -atopic dermatitis	severe (WC), mild (WC)
Vasculitis	inflammation of vessel wall/vessel was destruction	-small vessel -medium vessel -large vessel	-leukocytoclastic vasculitis -PAN -giant cell arteritis	EGPA (WC)
Perivascular	inflammation around vessels	-neutrophilic -lymphocytic -mastocytic -eosinophilic	-cellulitis -viral exanthem, Rx reaction -mastocytosis -insect bite, Rx reaction	DPLI (WC)
Panniculitis	inflammation of adipose tissue	-septal -lobular	-erythema nodosum, scleroderma panniculitis -erythema induratum, infection
Psoriasiform	epidermal thickening and long rete ridges	-regular -irregular	-psoriasis -lichen simplex chronicus	LSC (WC)

Notes:

• DE junction = dermal-epidermal junction.
• The "empty space" in bullous disease in situ is filled with fluid.

Non-specific patterns

Psoriasiform pattern

General

• Can be subclassified.

DDx:

• Psoriasis vulgaris (most common).
• Psoriatic arthritis.
• Drug-induced.
• Dermatomycosis (fungal infection).
• Others.

Microscopic

Features:

• Regular epidermal thickening - as very long rete ridges (described as "test tube-morphology") - key feature.
  • Epidermis between rete ridges thin ("thinning of suprapapillary plate").
• Parakeratosis.
• Thin/absent granular layer.
• Dilated blood vessels in superficial dermis.
• Neutrophil clusters (Munro microabscess).

Specific diseases

Seborrheic dermatitis

General

• Very common.

Microscopic

Features:

• Spongiosis (epidermal edema).
• Acanthosis (epidermal thickening).
• "Follicular lipping" = parakeratosis with neutrophils.
• Perivascular neutrophils and lymphocytes.

Lupus erythematosus

General

• A group of skin diseases - includes:
  • The systemic disease, systemic lupus erythematosus, that typically has multi-organ involvement.

Microscopic

Features - classic:

• Lymphocytic interface dermatitis.
• Basal layer vacuolization.
• Intradermal mucin.
• Thin epidermis.
• Compact stratum corneum.

DDx:

• Discoid lupus erythematosus.
• Drug reaction (drug-induced lupus erythematosus).
• Solar elastosis - may be confused with mucin; vacuolar interface dermatitis not present

Images

• 

  Vacuolar interface dermatitis with dermal mucin - low mag. (WC)

• 

  Vacuolar interface dermatitis with dermal mucin - intermed. mag. (WC)

• 

  Vacuolar interface dermatitis with dermal mucin - high mag. (WC)

• 

  Vacuolar interface dermatitis with dermal mucin - very high mag. (WC)

Discoid lupus erythematosus

General

• Typically self-limited and isolated.
  • It is not associated with systemic lupus erythematosus.

Microscopic

Features:

• Lymphocytic interface dermatitis with basal layer vacuolation and keratinocyte apoptosis.
• Deep dermal lymphocytes.
• Basket weave stratum corneum.
• Dermal mucin.
• Thick dermal-epidermal basement membrane.

DDx:

• Lupus erythematosus.

Image:

• DLE (dermpedia.org).

Dermatomyositis

For the muscle manifestations see: Neuromuscular_pathology#Dermatomyositis.

General

• Complement mediated disease - membrane attack complex.
• Usually middle age.
• Associated skin rash is common.
  • May precede or follow muscle pathology.
• Associated with malignancy in approximately 10% of cases.

Clinical:

• Jo-1 +ve.

Gross

• Have lesions on the knuckles - Gottron's papules.

Microsopic

Features:

• Vacuolar interface dermatitis (lymphocytic inflammation at the dermal-epidermal junction).
• +/-Loss of rete ridges.

DDx:

• Lupus.

Lichen planus

Should not be confused with lichen planus-like keratosis.

• Abbreviated LP.

General

• An oral pathology - classically.
• May be seen where the sun don't shine - penis, vulva and vagina.

Etiology:

• Autoimmune disease, T-cell–mediated.

Clinical:

• 6 Ps: pruritic (itchy), purple, polygonal, planar papules and plaques.

Note:

• Clinically, lichen planus and lichen sclerosus are similar. The main difference is lichen planus involves mucous membranes.

Gross

• Wickham striae = white lines/dots.
  • Due to hypergranulosis.

Microscopic

Features:

• Loss of basal cells (stratum basale) -- key feature.
• Loss of rete ridges/formation of pointed rete ridges "sawtoothing".
• Interface dermatitis (lymphocytes at dermal-epidermal junction).
• Hypergranulosis; stratum granulosum thickened (grossly seen as "Wickham stria" = white lines).
• Hyperkeratosis; stratum corneum thickened.
• Necrotic basal cell in dermis = colloid bodies = Civatte bodies.
  • Pink bodies approximately the size of a keratinocyte.

Notes:

• Hyperkeratosis and hypergranulosis are not seen in erythema multiforme.
• Colloid bodies = cytoid bodies = Civatte bodies = hyaline bodies = apoptotic bodies.
  • DDx: systemic lupus erythematosus, lichen planus, and graft-versus-host disease.

DDx:

• Bullous disease, subepithelial vesicular.
• Lichenoid keratosis (lichen planus-like keratosis) - parakeratosis prominent, no oral mucosal involvement.
• Fungal infection.
• Lichenoid drug reaction - unusual body site affected, separated clinically.
• Lichenoid actinic keratosis - basal atypia, solar elastosis.

Images

• 

  Lichen planus - intermed. mag. (WC/Nephron)

• 

  Lichen planus - low mag. (WC/Nephron)

Stains

• PAS-D or PAS-F to exclude a fungal infection.

Sign out

FORESKIN, CIRCUMCISION:
- LICHEN PLANUS.

VULVA, LEFT POSTERIOR FOURCHETTE, BIOPSY:
- COMPATIBLE WITH LICHEN PLANUS.

Micro

The sections show skin with a lymphoplasmacytic interface dermatitis, basal cell loss, hypergranulosis, hyperkeratosis, loss of the rete ridges and Civatte bodies.

The epidermis matures to the surface. No significant nuclear atypia is identified.

Fungal organisms are not identified with a PAS-D stain.

Lichen sclerosus

Main article: Lichen sclerosus

Microscopic

Features:

• Subepithelial fibrosis - key feature.

Psoriasis

General

• Chronic skin condition +/- systemic involvement:
  • Arthritis, i.e. psoriatic arthritis.
  • Myopathy.
  • Enteropathy, e.g. inflammatory bowel disease.
  • Syondylitic joint disease (spondylos = vertebrae).

• Other considerations:
  • Drug-induced psoriasis.

Clinical

• Auspitz sign = pin-point bleeding on removal of scale.
• Koebner phenomenon = lesions form at site of trauma.

Common locations:

• Knees, elbows, scalp, glans penis.

Microscopic

Features:

• "Regular" acanthosis + long rete ridges (psoriasiform hyperplasia).
  • "Regular" (psoriasiform change) = rete ridges are of similar length and thickness.
• Parakeratosis.
• Dilated vessels in superficial dermis (give rise to Auspitz sign).
• Spongiform pustules = PMNs in stratum spinosum.
• PMNs in parakeratotic stratum corneum (Munro microabscess).
• Thinning of the suprapapillary plate.
  • The epidermis between rete ridges is thinner than in the normal adjacent skin - key feature.

DDx:

• Dermatomycosis (fungal infection).
• Drug reaction.

Note:

• Dermatophytosis = ring worm; dermatophystosis != dermatomycosis.

Images

www:

• Psoriasis - low mag. (ucsf.edu).

Stains

• PASD stain -ve for fungal organisms.

Sign out

SKIN LESION, LEFT ARM, PUNCH BIOPSY:
- SKIN WITH ACANTHOSIS, HYPERKERATOSIS, FOCAL PARAKERATOSIS, PROMINENT
  DILATED VESSELS IN THE SUPERFICIAL DERMIS, SUPERFICIAL SPONGIFORM PUSTULES.
- MILD NONSPECIFIC PERIVASCULAR INFLAMMATION.
- NEGATIVE FOR FUNGAL ORGANISMS WITH PAS STAINING.

COMMENT:
The findings are compatible with psoriasis.  

Micro

The sections show skin with regular psoriasiform change, hyperkeratosis, focal parakeratosis, prominent dilated vessels in the superficial dermis, superficial clusters of intraepidermal neutrophils (spongiform pustules) and thinning of the suprapapillary plate is present. A few perivascular inflammatory cells are present.

There is no epidermal necrosis. Eosinophils are not apparent. The lymphocytes do not have significant atypia.

Lichen striatus

General

Features:

• Benign, self-limited.

Clinical:

• Linear rash usu. on lower extremity.
• Associated with atopy, lichen sclerosus.
• Children.

Clinical image:

• LS (perridermatology.com).

Microscopic

Features:

• "Ball and glove" pattern:
  • Rete ridges (glove) surround nexts of lymphocytes (ball).
• Hyperkeratosis.
• Parakeratosis.

DDx:

• Lichen planus.

Images:

• Lichen striatus (dermpathdiagnostics.com).
• Lichen striatus (drmihm.com).

Lichen aureus

General

• Rare.

Clinical:

• Plaques + minimal scale - erythematous/golden.

Microscopic

Features:

• Lymphocyte-predominant perivascular pattern.
  • May have features suggestive of vacuolar interface pattern.
• Fibrosis of superficial papillary dermis.

Images:

• Lichen aureus (cdlib.org).

Granuloma faciale

General

• Considered a vasculitis.

Microscopic

Features:

• Neutrophilic vasculitis - often subtle:
  • Neutrophils within blood vessel walls.
  • Vessels destruction (fibrinoid necrosis or nuclear dust).
• Mixed inflammatory superficial dermal infiltrate.
  • Eosinophils, neutrophils, plasma cells, histiocytes.
• Lesion separated from the (normal) epidermis (Grenz zone).

DDx of chronic fibrosing leukocytoclastic vasculitis:

• Granuloma faciale.
• Erythema elevatum diutinum - lacks Grenz zone.
• Inflammatory pseudotumour.

Image:

• Granuloma faciale (dermatlas.med.jhmi.edu).

Atopic dermatitis

• AKA atopic eczema, AKA infantile eczema.

General

• Very common - especially in children.
  • Most children outgrow the condition.

Microscopic

Features:

• Spongiotic dermatitis.

DDx:

• Spongiotic dermatitides.

Images

• 

  Mild spongiotic dermatitis - high mag. (WC)

• 

  Mild spongiotic dermatitis - very high mag. (WC)

Sweet syndrome

General

• Uncommon.

Microscopic

Features:

• Nodular and diffuse pattern - neutrophils predominant - without pus.

DDx rips:

• Rheumatoid neutrophilic dermatitis.
• Bowel-associated dermatosis-arthritis syndrome (BADAS).
• Pyoderma gangrenosum.
• Sweet syndrome.

Image:

• Sweet syndrome (cdlib.org).

Granuloma inguinale

Not to be confused with granuloma annulare.

• Previously known as donovanosis.

General

• Infection caused by Klebsiella granulomatis - Gram-negative, rod-shaped bacteria.
  • Used to be known as Calymmatobacterium granulomatis.

Location:

• Penis.
• Vulva.

Clinical:

• Sexually transmitted.
• Nodule or papule developing into a painless ulcer in the inguinal region.
• No lymphadenopathy (unlike syphilis).

Microscopic

Features:

• Donovan bodies - key feature:
  • Rod-shaped bodies within histiocytes.

DDx:

• Syphilis.

Image:

• Granuloma inguinale - crappy image (microblog.me.uk).

Stains

• Giemsa stain - highlights organisms.

Pyoderma gangrenosum

Main article: Pyoderma gangrenosum

Necrobiotic xanthogranuloma

• Abbreviated NXG.

Main article: Necrobiotic xanthogranuloma

DDx for pattern

Spongiotic dermatitides

DDx:

• Atopic dermatitis.
• Contact dermatitis.
• Stasis dermatitis.
• Seborrheic dermatitis.
• Nummular dermatitis.
• Spongiotic drug eruption.

Psoriasiform dermatitides

Regular psoriasiform dermatitis

DDx:

• Psoriasis vulgaris.
• Dermatophyte infection.
• Pityriasis rubra pilaris.

Irregular psoriasiform dermatitis

• Lichen simplex chronicus.

Interface dermatitides

Vacuolar interface dermatitides

DDx:

• Erythema multiforme.
• Lichen sclerosus.
• Fixed drug eruption.

Others:

• Graft versus host disease.
• Dermatomyositis.
• Systemic lupus erythematosus.
• Morbillifrom viral exanthem.

Additional:

• Phototoxic dermatitis.
• Acute radiation dermatitis.
• Erythema multiforme-like drug eruption.
• Lichen sclerosis et atrophicus.
• Erythema dyschromicum perstans (ashy dermatosis).

Super lame mnemonic Danny G & SLE:

• Dermatomyositis, GVHD, SLE, Lichen sclerosus, Erythema multiforme.

Lichenoid interface dermatitides

DDx:

• Lichen planus
• Mycosis fungoides.
• Discoid lupus erythematosus.
• Lichenoid drug eruption.
• Fixed drug eruption.

Additional:

• Lichen planus-like keratosis.
• Lichenoid actinic keratosis.
• Lichen nitidus.
• Pigmented purpuric dermatosis.
• Lichen amyloidosis.
• Pityriasis lichenoides chronica.
• HIV dermatitis.
• Syphilis.
• Urticaria pigmentosa.
• Chronic graft versus host disease.

Bullous disease

Main article: Bullous disease

Subcorneal bullous disorders

DDx with acantholysis:

• Pemphigus foliaceus.
• Bullous impetigo.
• Staphylococcal scalded skin syndrome.

DDx without acantholysis:DDx:

• Subcorneal pustular dermatosis (Sneddon-Wilkinson disease).
• Pustular psoriasis.
• Pustular drug eruption (acute generalized exanthematous pustulosis).

Suprabasilar bullous disorders

DDx:

• Pemphigus vulgaris.
• Hailey-Hailey disease (benign familial pemphigus).
• Darier disease.
• Grover disease (transient acantholytic dermatosis).

Memory device - PhD + Grover = Pemphigus vulgaris, Hailey-Hailey, Darier, Grover.

Subepidermal bullous disorders

DDx:

• Bullous pemphigoid.
• Cicatricial pemphigoid.
• Porphyria cutanea tarda.
• Epidermolysis bullosa acquista.
• Dermatitis herpetiformis.
• Linear IgA disease.

Others:

• Insect bite.
• Coma blister.
• Bullous systemic lupus erythematosus.

Mnemonic DELPHI:

• Dermatitis herpetiformis.
• Epidermolysis bullosa acquisita.
• Bullous lupus erythematosis.
• Pemphigoid, bullous.
• Herpes gestationis - rare autoimmune bullous dermatosis of pregnancy, not related to HSV.
• Linear IgA disease.

Dermatitides with perivascular inflammation

Lymphocytes

Lymphocytes (tightly cuffed):

• Infections.
• Medications.
• Malignancy.
• Vitiligo (with absent melanocytes).
• Scleroderma/morphea.

Lymphocytes & plasma cells +/-eosinophils:

• Erythema chronicum migrans (Lyme disease).

Lymphocytes (not tightly cuffed):

• Viral exanthems.
• Drug eruptions.

Lymphocytes & eosinophils:

• Drug reaction.
• Insect bite.
• Dermatophyte infection.

A simple memory device - 6 Ls:

• Lymphoma.
• Pseudolymphoma (cutaneous lymphoid hyperplasia, lymphocytoma cutis).
• Lupus erythematosus.
• Lymphocytic infiltrate of Jessner / tumid lupus erythematosus.
• Polymorphous light eruption.
• Lyme disease.

Neutrophils

DDx:

• Cellulitis.
• Neutrophilic eccrine hidradenitis (idiopathic palmar-plantar hidradenitis)

With eosinophils:

• Urticaria.

Eosinophils

DDx:

• Hypersensitivity reaction/drug reaction.
• Insect bite.
• Bullous pemphigoid, urticarial.

Mast cells

• Mastocytosis.

Vasculitis

Main article: Vasculitides

General DDx:

• Infection.
• Autoimmune.
• Malignancy.
• Toxic (medications).

Small vessel:

• Small vessel leukocytoclastic vasculitis (LCV).

Medium vessel:

• Polyarteritis nodosa.
• Wegener's granulomatosis.

Medium vessels often with small vessel involvement:

• Churg-Strauss syndrome.
• Microscopic polyangiitis.
• Mixed cryoglobulinemia.
• Connective tissue diseases.

Large vessel:

• Giant cell arteritis.

Nodular and diffuse dermatitides

Neutrophils

With pus (suppurative)

Neutrophils only:

• Follicular occlusion triad.
• Ruptured cyst/follicle.

Neutrophils and eosinophils:

• Halogenoderma.
• Blastomycosis-like pyoderma (pyoderma vegetans) - due to bacterial infection, usu. S. aureus.

Without pus

With vasculitis:

• Neutrophils only: see vasculitides.
• Mixed infiltrate: granuloma faciale, erythema elevatinum diutinum.

Without vasculitis:

• Sweet syndrome.
• Pyoderma gangrenosum.
• Rheumatoid neutrophilic dermatitis.
• Bowel-associated dermatosis-arthritis syndrome.

Lymphocytes

• Reactive lymphoid hyperplasia - may be due to drugs.
• Lymphoid malignancy.

Plasma cells

• Inflammation.
• Plasma cell neoplasms.
• Infections:
  • Syphilis - lichenoid/psoriasiform pattern.
  • Chancroid.
  • Granuloma inguinale.
  • Lymphogranuloma venereum.

Eosinophils

• Eosinophilic cellulitis (Wells syndrome).
  • Insect bites.
• Hypereosinophilic syndrome (HES).
• Angiolymphoid hyperplasia with eosinophilia (ALHE).
• Kimura disease.

Histiocytes

Granulomatous

Sarcoidal

• Sarcoidosis - have few lymphoid cells around them; thus called "naked granulomas".

Tuberculoid

• Tuberculosis.
• Tertiary syphilis - usu. abundant plasma cells.
• Cutaneous leishmaniasis.

Palisaded granumolas

Blue granuloma:

• Granuloma annulare.
• Wegener granulomatosis.
• Rheumatoid vasculitis.

Red granuloma:

• Rheumatoid nodule.
• Necrobiosis lipoidica.
• Necrobiotic xanthogranuloma.
• Churg-Strauss syndrome.

See also

• Dermatopathology.
• Non-malignant skin disease.

External links

• Dermatopathology mnemonics (dermpathmd.com).