Chronic Lupus Erythematosus (aka discoid LE)

Figure: Damage to basal layer of epidermis can see vacuoles within basal keratinocytes as a result of damage. Can see dramatically thickened basement membrane here.

Discoid Lupus much more skin limitied. Very rarely progresses to systemic disease. See post-inflammatory hypopigmentation.

Perivascular lymphocytes

Above: Mucin production collagen bundles here are separated by mucin.

Test q: Histologic features of Lupus Erythematosus include: interface vacuoles and focal epidermal atrophy

Interface Dermatitis w/lichenoid (band-like) inflammation Lichen Planus Chronic but self-limiting disease Multiple, symmetric lesions on extremities (especially wrists) Pruritic, purple, polygonal papules Oral mucosal involvement common (see right) oral lesions have lacy, white pattern. Dense band-like lymphocytic infiltrate hugs epidermis Epidermal changes: Hyperkeratosis Wedge-shaped hypergranulosis

Saw-toothed basal layer Thickening of granular layer Individual necrotic keratinocytes (circled)

Test q: A 40y/o woman goes to her dentist who notes that she has 0.2 to 1.5cm scattered, white, reticulated areas on the buccal mucosa. The woman says that these lesions have been present for one year. She also has some 0.3-cm purple, pruritic papules on each elbow. A biopsy specimen of a skin lesion shows a bandlike infiltrate of lymphocytes at the dermalepidermal junction as well as degeneration of basal keratinocytes. The most likely diagnosis is: Lichen planus.

Above: Lichen Planus Interface dermatitis, so damage to the basal layer of keratinocytes due to attack by lymphocytes. Circle necrotic keratinocytes. See band-like infiltrate of lymphocytes. Thickening of epidermis increase in granular layer.

Bullous Dermatosis: Bullae and vesicles are primary clinical manifestations Bullae = large blisters; vesicles = tiny blisters Diagnostic categories based on level of split in epidermis Subcorneal (beneath SC), intraepidermal or subepidermal Diseases caused by Ig deposition i.e. autoimmune diseases Pemphigus Vulgaris: Presents in the 4th-6th decades, M=F Autoimmune blistering disease IgG against desmoglein 3 in desmosomes Desmosomes hold epithelial cells together loss of cell adhesion within the epidermis
Test q: In pemphigus vulgaris, IgG autoantibodies are directed against: Desmosomes REPEATED x2

Variants: pemphigus vegetans and foliaceus Flaccid, fragile bullae Oral mucosa involvement (typically ruptures before you see it clinically)

Pemphigus vulgaris.
Intraepidermal, suprabasilar blister with tombstone basal layer Mixed dermal inflammatory infiltrate, often with eosinophils Intraepidermal: looks like this blister is under the whole epidermis, but note the one layer of cells left underneath. The rest makes up the roof of the blister.

Above: In the base of the blister is one layer of the epidermis. The rest makes up the roof of the blister.

Above: Pemphigus Vulgaris Immunofluoresence

Bullous Pemphigoid: Generally affects elderly patients Bullae on extremities, intertriginous areas, abdomen and oral mucosa (1/3 pts) Autoimmune disease IgG against hemidesmosome proteins Hemidesmosomes bind epidermis to basement membrane Subepidermal blistering process blisters have more strength because of more material in the roof. Blisters are tense and stay intact longer (as compared to fragile blisters of PV, described above). Tense bullae

Above: Bullous Pemphigoid. Subepidermal blister without tombstones or acantholysis. No epidermis in the base of the blister.

Above: Blister contains edema fluid and eosinophils.

Bullous Pemphigoid: Immunofluorescence. IgG bound to hemidesmosome located in basement membrane.

Dermatitis Herpetiformis Vesicular dermatosis not bullous rd th 3 and 4 decades, M>F Pruritic, burning vesicles, especially on extensor surfaces of extremities Strongly associated with celiac disease everyone w/DH either has Celiac disease or sub-clinical Celiac disease. Responds to gluten free diet (like celiac) IgA deposited in dermal papillae of skin

Incredibly itchy patients will scratch blisters before you ever see them in clinic.

DH Histologic Features- Subepidermal vesicles

Neutrophilic microabscess

Test q: A 35y/o female presents w/small vesicles on extremeties. The rash is extremely pruritic. She also has been diagnosed w/celiac disease. Diagnosis: Dermatitis herpetiformis REPEATED x2 Test q: A person w/dermatitis herpetiformis should avoid what food substance: gluten. Test q: A 35y/o man has had an outbreak of pruritic lesions over the extensor surface of the elbows and knees during the past month/ He has a history of malabsorption that requires him to eat a special diet, but he has had no previous skin problems. On phys exam, the lesions are 0.4-0.7cm vesicles. A 3mm punch biopsy of one of the lesions over the elbow is performed. Microscopic exam of the biopsy specimen shows accumulation of neutrophils at the tips of dermal papillae and formation of small blisters due to separation at the dermo-epidermal junction. Immunofluorescence studies performed on this specimen show granular deposits of IgA localized to tips of dermal papillae. Lab studies show serum anti-gliadin antibodies. Which of the following is the most likely diagnosis? Dermatitis herpetiformis.

DH Immunofluorescence. IgA deposits recruit in neutrophils.

Test q: Neutrophilic microabscesses and fluffy IgA deposits on basement membrane anchoring febrils are characteristic of: Dermatitis herpetiformis.

Infections and Infestations: Dermatophytosis: AKA: Tinea (capitis scalp, corporis body, barbae beard area, cruris groin, pedis foot), ringworm Dermatophytes infect outer keratin layer of skin

Dermatophytosis

Above: Tinea corporis expanding, annular, erythematous plaque w/elevated, scaly border. Annular because dermatophytes start in a small area and grow outwards = ring.

Dermatophyte Infection: Histologic Features: Hyperkeratosis Parakeratosis Neutrophils in keratin Hyphae in keratin Difficult to see on H&E Organisms grow in the stratum corneum do not go down into epidermis at all.
Test q: Neutrophils in the stratum corneum are a common feature in: Psoriasis and dermatophytosis. Test q: A 25y/o male joins a gym and works out regularly. He develops a pruritic rash on his feet which shows white centers w/a red, scaly border. A diagnostic stain would be: PAS stain.

PAS stain demonstrating hyphae

Shows fungal hyphae/spores very clearly but only in s. corneum.

Warts (verrucae): Benign neoplasms caused by human papillomavirus (HPV) >60 subtypes Certain subsets associated w/squamous cell carcinoma Common Common wart (verruca vulgaris) Plantar/palmar wart - caused by diff HPV subtypes Genital wart (condyloma acuminatum) Flat wart Occur at any age Self-limited Verruca Vulgaris: Histologic Features Histology similar across all the different subtypes. Papillomatosis projections of epidermis Acanthosis thickening of epidermis Tortuous vessels within papillae KEY FEATURE = Koilocytes. Have clear area within cytoplasm due to viral particles present.

Molluscum Contagiosum: Common especially in children Dome-shaped papules with a central keratinfilled crater Easily spread through contact DNA poxvirus Histologic Features: large, bright pink viral inclusions. Molluscum body: eosinophilic cytoplasmic inclusion in upper layers of epidermis.

Test q: A 35y/o man has noted a bump on his upper trunk for the past 6wk. On phys exam, there is a solitary 0.4cm flesh-colored nodule on the upper trunk. The dome-shaped lesion is umbilicated, and a curd-like material can be expressed from the center. This material is smeared on a slide, and Giemsa stain shows many pink, homogenous, cytoplasmic inclusions. The lesion regresses over the next 2mo. Which of the following infectious agents most likely produced this lesion? Molluscum contagiosum

Impetigo: Common superficial infection Staphylococcus or streptococcus Exposed surfaces Characteristic honey-colored crust Histologic Feature: Subcorneal pustule A lot of neutrophils in the stratum corneum can see gram positive cocci here.

Infestations: Scabies (Sarcoptes scabiei)

Above: The scabies mite.

Scabies feces.

Linear burrows.

Scabies like to burrow underneath the stratum corneum. Find them on the penis and web spaces of the fingers. Figure: Scabies organism underneath the stratum corneum. Scabies feces underneath?

Herpesvirus infections: HSV-1 Cold sores, fever blisters Oral infection most common Cutaneous blistering eruption, usually linear HSV-2 Genital herpes VZV varicella zoster Chicken pox
Figure: Germline mutation: born w/one mutated allele and one wildtype allele. During life, youll have hits from viruses, chemicals, other environmental factors and you will lose the wildtype allele. Called LOH (loss of heterozygosity) uncontrolled proliferation.

Figure: Herpes infects keratinocytes see multinucleated cells (circled one has 10-15 nuclei)