Group 2, Column 2 Flashcards
1
Q
Name the clinical finding/diagnosis.
- What is the typical symptom?
- How does this heal?
A
Atrophie blanche seen in livedoid vasculopathy.
- Burning pain along ankle prior to ulceration
- Painful ulcerations on lower legs +/- surrounding livedo reticularis
- Heal with atrophic hypopigmented scars
2
Q
What systemic disorders are classically associated with livedoid vasculopathy?
A
- Hypercoagulable disorders (e.g., Factor V Leiden, protein C deficiency, prothrombin mutations, hyperhomocysteinemia)
- Autoimmune conditions (SLE, scleroderma, APLS)
- Atherosclerosis and stasis
3
Q
What are the early and late histopathology findings of livedoid vasculopathy and atrophie blanche?
- What happens to the vessels?
- What happens to the epidermis?
A
- Segmental hyalinization (“pink-red crayon”) and thrombosis of small vessels in the upper and mid dermis
- Late stage with epidermal atophy and hyalinized vessels
4
Q
What are the treatment options for livedoid vasculopathy?
- First line?
- In recurrent/recalcitrant cases?
A
- Aspirin
- Pentoxyfilline
- Dipyridamole
- In recurrent or recalcitrant cases:
- Anticoagulants (warfarin, heparin, etc.)
- Oral steroids
5
Q
What labs should be obtained in suspected livedoid vasculopathy?
- What is part of the coagulopathy work up?
A
-
Coagulopathy workup
- Cryoglobulins
- Homocysteine
- Protein C and S
- Anti-thrombin III
- ANA
- Anti-cardiolipin antibody
- Factor V mutation
- Prothrombin mutation
6
Q
Name the diagnosis.
- What do early lesions look like? Late lesions?
- How is hair and sweat affected?
- What indicates persistent disease activity with respect to lesion appearance?
A
Plaque morphea (localized scleroderma)
- Begin as erythematous to violaceous patches on trunk and proximal extremities
- Evolve to indurated hyperpigmented or ivory plaques
- Often hairless and anhidrotic
- Violaceous border indicates persistent disease activity
7
Q
What is the most common subtype of morphea (localized scleroderma) in adults and in children?
A
- Plaque in adults
- Linear in children
8
Q
What is the suspected pathogenesis of morphea (localized scleroderma)?
- What cytokines are involved?
- What happens to vessels and the dermis?
A
- Genetic predisposition + environmental trigger
- Vascular injury leads to inflammation
- Triggers profibrotic Th2 cytokines (IL-4, IL-6 and TGF-beta)
- Fibroblast proliferation and collagen deposition
9
Q
What are classic triggers of morphea (localized scleroderma)?
- What types of infections?
- What are general iatrogenic causes?
A
- Infections with Borrelia spp. (in Europe and Japan mainly; Borrelia afzelii and Borellia garinii)
- Radiation
- Medications
- Trauma
10
Q
Name the diagnosis.
- What do early lesions look like? Late lesions?
- How is hair and sweat affected?
- What indicates persistent disease activity with respect to lesion appearance?
A
Plaque morphea (localized scleroderma)
- Begin as erythematous to violaceous patches on trunk and proximal extremities
- Evolve to indurated hyperpigmented or ivory plaques
- Often hairless and anhidrotic
- Violaceous border indicates persistent disease activity
11
Q
Name the diagnosis.
- in which population is this the most common subtype?
- What autoantibodies is most common in this condition?
- What are possible complications of this condition?
A
Linear morphea (localized scleroderma)
- Associated with significant morbidity (especially in kids, in whom it is the most common subtype)
- Look for linear distribution often along Blaschko’s lines
- Legs (#1 site) > arms > head/trunk
- Anti-ssDNA autoantibodies most common
- Undergrowth of limbs, joint restriction/contractures
12
Q
Name the diagnosis.
A
En coup de sabre
- Indentation of frontal, frontoparietal or parasagittal forehead or scalp
13
Q
Name the diagnosis.
- What is the other term for this condition?
- What are other associations with this condition?
A
Parry-Romberg syndome (a.k.a. progressive hemifacial atrophy)
- Unilateral atrophy of face involving dermis, subcutaneous tissue, muscle and bone
- Can be associated with epilepsy, headache, exophthalmos, cerebral atrophy, alopecia
14
Q
Name the diagnosis.
- What is the buzzword for this condition?
- What does the dermis look like on histology?
A
Atrophoderma of Pasini and Pierini
- Brownish-gray hyperpigmented oval, atrophic, well-demarcated plaques with sharp sloping borders (“cliff drop” edges)
- Begins as persistent single lesion with additional lesions over time
- Histology: significantly decreased dermal thickness compared to normal skin (biopsy at lesion edge)
15
Q
Name the diagnosis.
A
Necrobiosis lipoidica
- Yellow to red-brown atrophic to indurated plaques typically over pretibial areas; prominent telangiectasis, +/- ulceration
16
Q
Name the diagnosis.
A
Necrobiosis lipoidica
- Yellow to red-brown atrophic to indurated plaques typically over pretibial areas; prominent telangiectasis, +/- ulceration
17
Q
How can you tell the difference between morphea and systemic sclerosis on rheumatologic serologies?
A
- All forms of morphea lack anti-Scl70 (Topo I) and anti-centromere antibodies (in contrast to systemic sclerosis)
18
Q
What is the suspected pathogenesis of necrobiosis lipoidica?
- What happens to the vessels and dermis?
- What kind of inflammation occurs?
A
- Vascular compromise from immunodeposition in vessel walls or diabetes-related microangiopathic changes
- Subacute dermal ischemia leads to dermal collagen degeneration
- Secondary granulomatous inflammatory response
19
Q
What are the key histopathology findings of necrobiosis lipoidica?
- What is the special “sign” on biopsy?
- What is the inflammatory pattern and how is it arranged in the dermis?
- How does its histology compare with granuloma annulare?
- What immune cells are abundant? What stromal component is absent?
A
- “Square biopsy” sign
- Horizontally arranged (“layered”) palisaded granulomatous inflammation with horizontal tiers of degenerated collagen fibers and dermal sclerosis
- Process diffusely involves entire dermis (vs. GA which is mainly superficial)
- Lacks mucin
- Plasma cells and multinucleated giant cells are abundant
20
Q
What are the treatments for necrobiosis lipoidica?
- What are topical and systemic treatments?
- What does not affect disease course?
A
- Potent topical steroids and/or ILK (into inflammatory rim), TCIs
- Systemic treatments include PO steroids, colchicine, cyclosporine, TNF-alpha inhibitors and pentoxifylline for chronic/recalcitrant cases
- Note: none of these is borne out in the literature
- Glycemic control does not affect disease course
21
Q
What is the inheritance pattern and genetic mutation of NF-1?
A
- Autosomal dominant inheritance (but can occur as a sporadic mutation)
- Mutation of neurofibromin (NF1), a tumor suppressor gene that downregulates Ras activation
22
Q
What is another name for NF1?
A
von Recklinghausen’s disease
23
Q
What is the diagnostic criteria for NF1?
Hint: think of the mnemonic!
A
“CA NN OT FAI L2 B 1ST”
Must have >2 of the following:
- CA: CAfe-au-lait (six lesions)
- NN: Neurofibromas
- OT: OpTic glioma
- FAI: Freckles (Axillary, Inguinal)
- L2: Lisch nodules x 2
- B: Bone (sphenoid or tibial wing dysplasia)
- 1st: (affected 1st degree relative)
24
Q
Name the clinical finding and disease association.
A
Lisch nodules found in NF1
25
Name the diagnosis.
Hint: think of the mnemonic!
**NF1**
Must have \>2 of the following:
* **_CA: CAfe-au-lait (six lesions)_**
* NN: Neurofibromas
* OT: OpTic glioma
* FAI: Freckles (Axillary, Inguinal)
* L2: Lisch nodules x 2
* B: Bone (sphenoid or tibial wing dysplasia)
* 1st: (affected 1st degree relative)
26
Name the diagnosis.
Hint: think of the mnemonic!
**NF1**
**Axillary freckling is also called "Crowe's sign."**
Must have \>2 of the following:
* **CA: CAfe-au-lait (six lesions)**
* **NN: Neurofibromas**
* OT: OpTic glioma
* **FAI: Freckles (Axillary, Inguinal)**
* L2: Lisch nodules x 2
* B: Bone (sphenoid or tibial wing dysplasia)
* 1st: (affected 1st degree relative)
27
What is the **strong triple association** that includes **NF1**?
1. **NF1**
2. Juvenile xanthogranulomas (**JXGs**)
3. Juvenile myelomonocytic leukemia (**JMML**)
28
What is the inheritence pattern and genetic mutation (and its gene product) seen in **NF2**?
* **AD**
* Caused by mutations in **SCH gene** (encodes schwannomin/**merlin**)
29
What are the key cutaneous (2) and neurologic (1) findings in **NF2**?
* Where are the neurofibromas located, and how is this different than **NF1**?
* **Subcutaneous neurofibromas (overlying pigment/hair,** rather than _intradermal_ like in NF1; see photo)
* **Cafe au lait macules (two or fewer)**
* **Bilateral vestibular schwannomas (acoustic neuromas)**
30
What is the classic histopathology of **nevus sebaceus**?
* How is the epidermis affected? Follicles?
* What glands are present? (2)
* With what other condition is the histology similar to?
* Verrucous epidermis with malformed, dimunitive hairs
* **Lacks fully formed terminal hairs within lesion**
* **Sebaceous glands open directly onto skin surface**
* **Dilated apocrine glands**
* **Histology is similar to an epidermal nevus**
31
Name the diagnosis.
* What are the typically present along?
**Nevus sebaceus**
* Present **at birth** along **Blaschko's lines**
* Becomes more yellow and verrucous after puberty
* Scalp/face most common sites
* **Alopecia** of affected area
32
Name the diagnosis.
* What are they typically present along?
**Nevus sebaceus**
* Present **at birth** along **Blaschko's lines**
* Becomes more yellow and verrucous after puberty
* Scalp/face most common sites
* **Alopecia** of affected area
33
What **secondary adnexal neoplasms** are known to arise within **nevus sebaceus**?
* There are three of them.
1. **Trichoblastoma (#1)**
2. **SPAP (syringocystadenoma papilliferum)**
3. **BCC**
34
What is the other name for **nevus spilus**?
**Speckled lentiginous nevus**
35
Name the diagnosis.
* What is this also known as?
**Nevus spilus**
(**Speckled lentiginous nevus**)
* Homogeneous tan patch within which develops small pigmented macules and papules
* Presents within first year of life
36
What is the name of the condition where a **nevus spilus/speckled lentiginous nevus** is associated with **port-wine stains**?
* What other type of spots/nevi may also be found in this condition?
**Phakomatosis pigmentovascularis**
* May also have dermal melanocytosis (Mongolian spots) and nevus of Ota or Ito
37
Name the diagnosis.
* How does this differ from a **nevus spilus**?
**Agminated nevus**
* Presents in teenage years
* Cluster of nevi over a skin-colored background (rather than tan background in **nevus spilus**)
* Probably what Addison has on his neck
38
What is the most common form of **pemphigus** worldwide?
**Pemphigus vulgaris**
39
Which desmoglein plays a major role in **mucosal** epithelial adhesion?
* Where is this Dsg present in the epidermis and mucosal epithelium?
* If autoantibodies only targeted this Dsg, then where would blisters form?
**Desmoglein 3 (Dsg3)**
* Expressed in **lower portion of epidermis** and throughout **mucosal epithelium**
* If _only_ Dsg3 is targeted by autoantibodies, then _mucosal_ blisters form but **the skin is intact because of Dsg1**
40
What are the (3) autoimmune conditions that are associated with **pemphigus vulgaris**?
* **Myasthenia gravis**
* **Thymoma**
* **Autoimmune thyroiditis**
41
Name the diagnosis.
* Where are the most common sites for lesions?
**Pemphigus vulgaris**
* All patients have painful **oral erosions**
* Most common sites = **buccal and palatine** mucosa
42
Where does **desmoglein 1** play a major role in epithelial adhesion?
* Where does this Dsg occur in the epidermis and mucosal epithelium?
**Desmoglein 1 (Dsg1)**
* Expressed in **all levels of epidermis (top \> bottom)**
* **No significant role mucosal epithelial adhesion (Dsg3 does this)**
43
Name the diagnosis.
* What are the two "signs" that are positive in this condition?
**Pemphigus vulgaris**
* Flaccid vesicles/bulla easily rupture, erode and form crust
* Kodachromes are usually open erosions because vesicles/bulla rupture so easily
* Positive **Nikolsky and Asboe-Hansen signs**
44
What desmogleins are targeted in **mucosal-dominant pemphigus**? **Mucocutaneous pemphigus**?
* Mucosal-dominant pemphigus: Dsg3
* Mucocutaneous pemphigus: Dsg3 and Dsg1
45
Name the diagnosis.
* What areas are usually involved?
* What do early lesions look like? More developed lesions?
* This is thought to be a reactive phenonemon to what?
**Pemphigus vegetans**
* Usually involves intertriginous areas
* Early lesions are flaccid pustules that progress to erosions then ultimately vegetative plaques
* Reactive phenomenon to friction
46
Name the diagnosis.
* What areas are usually involved?
* What do early lesions look like? More developed lesions?
* This is thought to be a reactive phenonemon to what?
**Pemphigus vegetans**
* Usually involves intertriginous areas
* Reactive phenomenon to friction
* Early lesions are flaccid pustules that progress to erosions then ultimately vegetative plaques
47
**Neonatal** skin has what Dsg expression pattern?
* This is the same as what tissue in adults?
**Dsg3**
* The same expression pattern as **adult mucosa**
* *This is why neonates whose mothers have pemphigus foliaceus (anti-Dsg1 autoantibodies) are unaffected*
48
**Maternal** autoantibodies against **which desmoglein** can cross the placenta and cause **transient blistering of the infant**?
**Dsg3**
* **Neonatal skin has same Dsg expression pattern as adult mucosa**
* This is why neonates whose mothers have pemphigus foliaceus (anti-Dsg1 autoantibodies) are unaffected
49
What will DIF look like in **pemphigus vulgaris**?
* What immunoglobulin and complement is present?
* What part of the epidermis is most strongly stained?
* **Intercellular "chicken wire" staining** with IgG (100%) +/- C3
* Lower epidermis most strongly stained
50
What is the classic histopathology of **pemphigus vulgaris**?
* What is the earliest finding?
* What is the *buzzword*?
* What is present in the blister cavity?
* **Eosinophilic spongiosis** (earliest finding)
* **Suprabasilar acantholysis**
* ***"Tombstoning" of basal cells*** (vertically oriented basal keratinocytes attached to BMZ but not surrounding keratinocytes)
* Individual **rounded-up acantholytic keratinocytes within blister cavity**
51
What are the treatment options for **pemphigus vulgaris**?
* First line? Second line?
* For mild cases?
* What lab(s) can be used to monitor treatment response?
* First line: **oral steroids** (1 mg/kg/day) + **steroid-sparing immunosuppresive** (azathioprine most effective)
* Tetracycline + nicotinamide for mild cases
* Second line: plasmapheresis, IVIg, rituximab
* Monitor treatment response with IIF or ELISA levels
52
**Dsg1** is cleaved by what **bacterial toxin** in what two infection-related disorders?
**S. aureus exfoliatoxins**
* Seen in **bullous impetigo** and **SSSS**
53
Name the diagnosis.
* What is the classic distribution? Is the mucosae involved?
* What is the clinical exam *buzzword*?
**Pemphigus foliaceus**
* Well-demarcated transient **impetigo-like** **crusted erosions** on erythematous base
* Favors **seborrheic distribution**
* Look for ***"cornflake" scale***
* **Lacks mucosal involvement**
54
Name the diagnosis.
* What is the classic distribution? Is the mucosae involved
* What is the clinical exam *buzzword*?
**Pemphigus foliaceus**
* Well-demarcated tranient **impetigo-like** **crusted erosions** on erythematous base
* Favors **seborrheic distribution**
* Look for ***"cornflake" scale***
* **Lacks mucosal involvement**
55
What lab work can be used to **monitor treatment response** in **pemphigus vulgaris**?
* What is the substrate used?
* Which desmoglein do the autoantibodies target?
* **IIF**: assesses serum IgG against monkey esophagus substrate
* **ELISA**: assesses serum anti-Dsg1 and anti-Dsg3 IgG
56
What are autoantibodies targeting in **pemphigus foliaceus**?
**Dsg1**
57
What is the classic histopathology of **pemphigus foliaceus**?
* What is the earliest finding?
* Where in the epidermis does acantholysis occur?
* What cells are in the blister cavity?
* Eosinophilic spongiosis (early)
* Subcorneal acantholysis (granular layer \>\> midlevel epidermis)
* Look for acantholytic keratinocytes +/- neutrophils and eosinophils in blister cavity
58
**Pemphigus foliaceus** has identical histology findings with what three other disorders?
1. **Pemphigus erythematosis** (i.e., essentially lupus + PE)
2. **Bullous impetigo**
3. **SSSS**
59
What is the difference between **phototoxic** and **photoallergic** reactions?
* Which is more common?
* Which commonly occurs due to topical medications? Systemic medications?
* **Phototoxic:** common and predictable; occurs in **anyone** who receives enough drug and UVR; most commonly due to **systemic** medications
* **Photoallergic:** less common but more chronic; occurs only in **sensitized** patients (delayed-type hypersensitivity); most commonly due to **topical** photoallergens
60
Name the diagnosis.
* What are risk factors for this condition?
**Pitted keratolysis**
* Small crateriform/cribriform pits and foul odor
* Risk factors include hyperhidrosis and occlusion
61
What bacteria causes **pitted keratolysis**?
* What can it digest?
Caused by **Kytococcus sedentarius** **(a gram-positive bacteria)**
* Digests keratin in the stratum corneum
62
What are possible treatments for **pitted keratolysis**? (4)
* Topical **erythromycin**
* Topical clindamycin
* Mupirocin
* Azole antifungals
63
What is the classic histology of **pitted keratolysis**?
* What occurs in the stratum corneum?
* What is the name of the bacteria that causes this?
* Sharply demarcated, deep pits in stratum corneum with **gram-positive bacteria (Kytococcus sedentarius) at base of pits**
64
Name the diagnosis.
* What is found on histology?
* Where is the infiltrate? What is notably deposited in the dermis?
**Schamberg's disease**
* Cayenne-pepper purpura on the lower extremities that can extend; middle aged to older adults
* Histology: hemosiderin containing macrophages with RBC extravasation, endothelial swelling and perivascular lymphocytic infiltrate
65
Name the diagnosis.
* What is found on the palms and soles? The nails?
**Pityriasis rubra pilaris**
* Folliculocentric keratotic papules on erythematous base ("**nutmeg-grater**" papules)
* Papules coalesce into **orange to salmon-colored** plaques with "**islands of sparing**"
* **Orange-red waxy keratoderma** of palms and soles ("**sandal-like palmoplantar keratoderma [PPK]**")
* No nails pits (to differentiate from psoriasis)
66
Name the diagnosis.
* What is found on the palms and soles? The nails?
**Pityriasis rubra pilaris**
* Folliculocentric keratotic papules on erythematous base ("**nutmeg-grater**" papules)
* Papules coalesce into **orange to salmon-colored** plaques with "**islands of sparing**"
* **Orange-red waxy keratoderma** of palms and soles ("**sand-like PPK**")
* No nails pits (to differentiate from psoriasis)
67
What is the classic histopathology of **pityriasis rubra pilaris (PRP)**?
* What occurs in the stratum corneum?
* What occurs at and around the follicles?
* Alternating vertical and horizontal orthohyperkeratosis and parakeratosis (**"checkerboard pattern"**)
* **Follicular plugging**
* **"Shoulder parakeratosis"** (parakeratosis at edges of hair follicle orifice)
68
What are the treatments for **pityriasis rubra pilaris** (PRP)?
* **Acitretin**
* Isotretinoin
* High-dose vitamin A
* MTX
* TNF-alpha inhibitors (infliximab, adalimumab, etanercept)
* Phototherapy (_though note that this may cause flares, so phototesting is recommended_)
69
Name the diagnosis.
**Pityriasis rubra pilaris (PRP), _type IV_**
**a.k.a. circumscribed juvenile PRP**
70
Name the diagnosis.
* Where does this occur? What area is usually spared?
**Poikiloderma of Civatte**
* Reticular reddish-brown telangiectatic patches on neck (central submental region usually spared)
71
What are classic triggers of **polyarteritis nodosa (PAN)**?
* Diseases?
* Medications?
* Infections?
* **Hairy cell leukemia**
* **Hepatitis B**
* Autoimmune diseases
* Medications, including minocycline
* Infections, including streptococcal infection in children
(Thought to be immune-complex mediated)
72
Name the diagnosis.
* What other finding may this be associated with?
**Polyarteritis nodosa**
* Painful single or multiple **subcutaneous nodules** on lower extremities that **may ulcerate**
* +/- **livedo reticularis**
73
What are the two classic subtypes of **medium vessel vasculitis**?
1. **Polyarteritis nodosa (PAN)**
2. **Kawasaki disease**
74
What are systemic associations with **polyarteritis nodosa** (PAN)?
* What other vasculitis is it associated with?
* What arteries are affected in PAN?
* What can happen in the brain?
* What is the most common cause of death in PAN?
* **LCV**
* **Necrotizing arteritis of medium-sized arteries** (coronary, **renal,** celiac and mesenteric arteries) of subcutis and dermopannicular junction
* **Microaneurysms**, leading to thrombosis, ischemia and necrosis
* Can lead to HTN and **renal failure** (most common cause of death)
75
What are the treatment options for the _cutaneous-only_ subtype of **polyarteritis nodosa?**
* What should be considered in children?
* **ILK, NSAIDs and oral steroids** for 3-6 months, if severe skin involvement
* In children, consider **PCN** given Streptococcal association
76
What are the treatment options for the _multi-system form_ of **polyarteritis nodosa?**
* Cyclophosphamide + oral steroids
* MTX
* IVIg
* Need to treat the underlying infection, if present
77
What is the most common photosensitive dermatosis?
**Polymorphic light eruption (PMLE)**
78
What is the onset after _UVA_ exposure when **PMLE** classically occurs?
**Arises 1-4 days after _UVA_**
79
Name the diagnosis.
* What is the primary associated symptom?
**Polymorphous light eruption (PMLE)**
* Erythematous, itchy papules/vesicles/plaques on sun-exposed areas on sun-exposed areas (malar face, V of neck, outer arms, dorsal hands)
80
What is the classic histopathology of **polymorphous light eruption (PMLE)**?
* What occurs in the dermis?
* Where is the infiltrate located and what composes it?
* Marked papillary dermal edema
* Dense perivascular dermal lymphocytic inflammation
81
What type of hypersensitivity reaction is **PMLE**?
**Delayed (type IV) hypersensitivity reaction**
82
What is the treatment for **polymorphous light eruption (PMLE)**?
* First line? Second line?
* What type of UVR causes **PMLE**?
* What can be done for prophylaxis? (2)
* **Photoprotection (first line)**: broad-spectrum sunscreens that **block UVA** (**avobenzone, titanium dioxide and zinc oxide**)
* Topical or oral steroids
* Antimalarial prophylaxis
* Prophylactic phototherapy in the early spring
83
Is **PMLE** caused by UVA or UVB?
**UVA**
84
Name the (6) subtypes of **porokeratosis**.
* Which three classically affect the palms/soles?
* What is the name of the subtype that looks like a nevus comedonicus of the palm/sole? What does histology show?
1. **Porokeratosis of Mibelli:** onset in infancy/childhood; **extremities**; large **circinate plaques** with keratotic borders
2. **Disseminated superficial actinic porokeratosis (DSAP)**: numerous brown-red macules with keratotic borders on sun-exposed areas
3. **Linear porokeratosis**: onset in newborns; linear lesions following Blaschko lines; highest SCC risk
4. **Punctate porokeratosis**: onset in adolescence; small, "seed-like papules" on palms/soles; no SCC risk
5. **Porokeratosis palmaris, plantaris, et disseminata (PPPD)**: onset childhood/teens; initially of palms/soles
6. **Porokeratotic eccrine ostial and dermal duct nevus**: looks like nevus comedonicus of palm/sole (see photo); **histology shows abundant cornoid lamellae arising from acrosyringium**
85
Name the diagnosis.
* When is classic onset?
* What part of body is usually involved?
**Porokeratosis of Mibelli**
* Onset in infancy or childhood
* **Extremities**
* **Large circinate plaque** with keratotic border
86
Name the diagnosis.
* When is classic onset?
* What part of body is usually involved?
**Disseminated superficial actinic porokeratosis (DSAP)**
* Onset in middle age
* Numerous brownish-red macules with keratotic borders in sun exposed areas
* Most common on legs
87
What is the classic histology of **porokeratosis**?
* What is notable about the stratum corneum and granular layer?
* How may the epidermis otherwise appear?
* **Cornoid lamella** (angled column of parakeratosis with underlying hypogranulosis and dyskeratotic cells)
* Between two cornoid lamellae, the epidermis may otherwise appear atrophic, hyperplastic, normal or BLK-like
88
What syndromes are seen in association with **port-wine stains**? (6)
1. **Maffucci Syndrome**
2. **Klippel-Trenaunay**
3. **Sturge-Weber**
4. **Blue Rubber Bleb**
5. Kasabach-Merritt
6. Proteus
89
Describe the clinical course of a **port-wine stain**.
* When is its onset?
* How does it progress over time?
* Do they resolve?
* **Present at birth**
* **Does not rapidly enlarge** (because it is a malformation and NOT a neoplasm), unlike infantile hemangiomas
* **Tend to persist** and become more verrucous over time
90
Are **port-wine stains** GLUT-1 positive or negative?
**GLUT-1 _NEGATIVE_**
91
Name the diagnosis.
**Port-wine stain**
92
Name the diagnosis.
* What are other skin findings?
* What areas are classically afected?
**Porphyria cutaneous tarda (PCT)**
* Skin findings include: fragility, vesicles, bullae, **erosions, milia, scarring, hyperpigmentation, hypertrichosis** in photodistributed areas (dorsal hands/forearms)
* **Classic photo is hemorrhagic blisters on dorsal hands**
93
Name the diagnosis.
* What are other skin findings?
* What areas are classically affected?
**Porphyria cutaneous tarda (PCT)**
* Skin findings include: fragility, vesicles, bullae, **erosions, millia, scarring, hyperpigmentation, hypertrichosis** in photodistributed areas (dorsal hands/forearms)
* **Classic photo is hemorrhagic blisters on dorsal hands**
94
What enzyme is affected in **porphyria cutanea tarda (PCT)**?
**Decreased _hepatic uroporphyrinogen decarboxylase (UROD)_**
95
What are classic triggers of **porphyria cutanea tarda**?
* What dietary habits?
* What hormone?
* What infections?
* **Alcohol abuse**
* **Hemochromatosis, high iron/red meat diets**
* **Estrogen**
* Hepatitis C
* HIV
96
Describe the classic histology findings of **porphyria cutanea tarda (PCT)**?
* What is inside the blister cavity?
* What occurs in the epidermis?
* What *buzzword* may be found in the blister cavity and epidermis?
* **Cell poor subepidermal bulla** with "**festooning" of dermal papillae**
* ***"Caterpillar bodies"*** (pink BMZ material in blister cavity and epidermis; click on photo)
97
What is classically seen on DIF of **porphyria cutanea tarda (PCT)**?
* What is deposited (4) and in what pattern?
* Where is it deposited? (2)
**IgG, IgM, fibrinogen and C3 _linearly_ along BMZ AND in superficial dermal vessels**
98
What is the treatment for **porphyria cutanea tarda**?
* What is the classic treatment?
* What things should be avoided?
* What medications could be given?
* **Phlebotomy**
* Avoid precipitating factors (alcohol, estrogen)
* Photoprotection/sun avoidance
* Low-dose hydroxychloroquine
* Defasirox (iron reducer)
99
Name the diagnosis.
* How do you describe the normal skin at the margin of the lesion?
* What are common sites? What about during pregnancy?
**Pyogenic granuloma**
* Rapidly growing, exophytic, and **hemorrhagic papule with *epidermal collarette***
* Common sites: **gingiva (pregnancy),** lips, digits
100
Name the diagnosis.
* How do you describe the normal skin at the margin of the lesion?
* What are common sites? What about during pregnancy?
**Pyogenic granuloma**
* Rapidly growing, exophytic, and **hemorrhagic papule with epidermal collarette**
* Common sites: **gingiva (pregnancy)**, lips, digits
101
What are notable associations with **pyogenic granuloma**?
* What about medications?
* **Trauma**
* **Pregnancy**
* **OCPs**
* **Oral retinoids**
* **Indinavir (HIV protease inhibitor)**
* EGFR-inhibitors (lung cancer therapy)
102
Describe the histological findings of **pyogenic granuloma**.
* What is this also known as?
* What happens to the vessels and RBCs?
* What is the dermis packed with?
* What may be seen in the epidermis circumscribing the lesion?
* Also known as a **lobular capillary hemangioma**
* **Well-circumscribed, lobular** proliferation of small capillaries with **RBC extravasation**
* Dermis with solidly packed endothelial cells, ectatic vessels
* Epidermal collarette common; erosion, crust, impetigo
103
What is the other term for **pyogenic granuloma**?
**(Eruptive) Lobular capillary hemangioma**
104
What are the **medications** implicated in **drug-induced sarcoidosis?**
* Patients with what viruses taking what drugs?
* **Hepatitis C patients on treatment (IFN-alpha, ribavirin)**
* HIV patients on HAART
* Other meds: TNF-alpha inhibitors, vemurafenib and ipilimumab (both for melanoma), alemtuzumab (leukemias/lymphomas)
105
What is the suspected pathogenesis of **sarcoidosis**?
* What immune cells are involved?
* What MHC class is involved?
* What cytokines are involved?
* Genetic predisposition + unknown antigen trigger
* **MHC class II on monocytes** binds to unknown antigen and **activates CD4+ Th1 cells**
* Increased IL-2, interferon-gamma, TNF-alpha and monocyte chemotactic factor (MCF)
* Monocytes enter peripheral tissues and form **granulomas**
106
Patients with **cutaneous sarcoidosis** should be worked up with what other studies? (3)
1. **CXR**
2. **PFTs**
3. **Regular eye exams**
107
Name the diagnosis.
* What special physical exam finding may be found?
* What areas of the body does this have a predilection for?
**Sarcoidosis**
* Look for red-brown or erythematous papules and plaques with **"apple jelly" color with diascopy** (especially in light skinned patients)
* Predilection for face (especially lips and nose)
108
Name the diagnosis.
* What special physical exam finding may be found?
* What areas of the body does this have a predilection for?
**Sarcoidosis**
* Look for red-brown or erythematous papules and plaques with **"apple jelly" color** with diascopy (especially in light skinned patients)
* Predilection for **face** (especially **lips and nose)**
109
Name the diagnosis.
* What special physical exam finding may be found?
* What areas of the body does this have a predilection for?
**Sarcoidosis**
* Look for red-brown or erythematous papules and plaques with **"apple jelly" color** with diascopy (especially in light skinned patients)
* Predilection for **face** (especially **lips and nose)**
110
What are notable **non-cutaneous** complications of **sarcoidosis**?
* What might occur in the chest cavity?
* Eyes?
* Blood?
* Kidneys?
* Lung disease (**"honeycombing" of lung**, fibrosis, bronchiectasis)
* **Hilar and/or paratracheal lymphadenopathy**
* **Anterior uveitis**
* **Hypercalcemia due to calcitriol synthesis by sarcoidal granulomas**
* **Nephrocalcinosis** due to hypercalcemia
111
Describe the histopathology of **sarcoidosis**.
* What is the dermis packed with?
* What type of granulomas are involved?
* What special "bodies" may be found within granulomas?
* Superficial and deep dermis packed with nodules of **well-formed, non-caseating "naked epithelioid granulomas"**
* ****Lacking significant inflammatory ring
* **Asteroid bodies** (star shaped eosinophilic inclusions of collagen) and **Schaumann bodies** (basophilic calcium and protein inclusions) are commonly seen within granulomas
112
What tests can be performed when suspecting **sarcoidosis**?
* What "historical" test could be used?
* What imaging or testing could be obtained?
* What lab work could be obtained?
* **Kveim-Siltzbach test** (mostly historical; injection of suspension of sarcoidal spleen into the skin leads to granuloma formation at injection site)
* **CXR or CT - chest** (hilar/paratracheal lymphadenopathy)
* **PFTs** (restrictive lung disease pattern)
* **Increased angiotensive converting enzyme (ACE) level** (useful for monitoring response to therapy)
* **Increased ESR**
113
What is the **_first line_** treatment for **systemic sarcoidosis?**
**AND**
What is the most effective treatment option for **chronic skin involvement?**
* First line: **oral prednisone** for systemic involvement +/- TCS/ILK for skin involvement
* Most effective treatment for chronic skin involvement: **HCQ or CQ**
114
Name the (6) major **granulomatous dermatitides**.
1. **Sarcoidosis**
2. **Classic granuloma annulare (GA)**
3. **Necrobiosis lipoidica**
4. **Cutaneous Crohn's disease**
5. **Rheumatoid nodule**
6. Annular elastolytic giant cell granuloma (AEGCG)
115
Name the diagnosis.
**Spitz nevus**
* Most commonly present as pink papules on the face/scalp of a child
116
Name the diagnosis.
**Spitz nevus**
* Most commonly present as pink papules on the face/scalp of a child
117
What is the suspected pathogenesis of a **Spitz nevus**?
* What genetic mutation is suspected?
* What is the name of the recently described subset of atypical epithelioid **Spitz nevi**, and what mutation do they have?
* **HRAS** mutations/**11p gains**
* No *BRAF* mutations (usually)
* There is also a recently described subset of **atypical epithelioid Spitz nevi** with loss of ***BAP-1*** **tumor suppressor gene ("BAPomas," which have *BRAF* mutations)**
118
What is the classic histopathology of a **Spitz nevus**?
* How does the overall lesion and epidermis appear from the lowest magnification?
* How are the cells in nests arranged? What occurs around nests?
* What do the cells in the nests look like in terms of their cytoplasm and nucleoli?
* What are the special "bodies" present in the epidermis?
* What should occur as you go from the superficial to deep dermis?
* What is allowable in the superficial dermis?
* **Symmetric and circumscribed**
* **Epidermal hyperplasia**
* Large junctional nests with **clefting** around entire nest
* Parallel, vertically-oriented nests ("bananas on a tree") that have vertically-oriented melanocytes
* **Kamino bodies** (pink clumps of **BMZ material [collagen IV] within epidermis**)
* "Spitzoid" cytology (large epithelioid/spindled cells with abundant **pink-purple [amphophilic] cytoplasm** and prominent **lilac-colored nucleoli [versus cherry-red nucleoli in melanoma]**)
* Dermal component **"matures" with depth** **(reduction in density and cell size)**
* **Superficial mitoses allowable**
119
What is the classic histopathology of a **Spitz nevus**?
* How does the overall lesion and epidermis appear from the lowest magnification?
* How are the cells in nests arranged? What occurs around nests?
* What do the cells in the nests look like in terms of their cytoplasm and nucleoli?
* What are the special "bodies" present in the epidermis?
* What should occur as you go from the superficial to deep dermis?
* What is allowable in the superficial dermis?
* **Symmetric and circumscribed**
* **Epidermal hyperplasia**
* Large junctional nests with **clefting** around entire nest
* Parallel, vertically-oriented nests ("bananas on a tree") that have vertically-oriented melanocytes
* **Kamino bodies** (pink clumps of **BMZ material [collagen IV] within epidermis**)
* "Spitzoid" cytology (large epithelioid/spindled cells with abundant **pink-purple [amphophilic] cytoplasm** and prominent **lilac-colored nucleoli [versus cherry-red nucleoli in melanoma]**)
* Dermal component **"matures" with depth** **(reduction in density and cell size)**
* **Superficial mitoses allowable**
120
What is the classic histopathology of a **Spitz nevus**?
* How does the overall lesion and epidermis appear from the lowest magnification?
* How are the cells in nests arranged? What occurs around nests?
* What do the cells in the nests look like in terms of their cytoplasm and nucleoli?
* What are the special "bodies" present in the epidermis?
* What should occur as you go from the superficial to deep dermis?
* What is allowable in the superficial dermis?
* **Symmetric and circumscribed**
* **Epidermal hyperplasia**
* Large junctional nests with **clefting** around entire nest
* Parallel, vertically-oriented nests ("bananas on a tree") that have vertically-oriented melanocytes
* **Kamino bodies** (pink clumps of **BMZ material [collagen IV] within epidermis**)
* "Spitzoid" cytology (large epithelioid/spindled cells with abundant **pink-purple [amphophilic] cytoplasm** and prominent **lilac-colored nucleoli [versus cherry-red nucleoli in melanoma]**)
* Dermal component **"matures" with depth** **(reduction in density and cell size)**
* **Superficial mitoses allowable**
121
What immunostains would be positive in a **Spitz nevus?** (4)
* **S100A6+**
* **p16+**
* **Note: p16+ is frequently lost/diminished in atypical Spitz tumors and Spitzoid melanomas**
* S100+
* Melan-A+
122
Name the disease with this histology.
* How are the cells arranged?
**Spitz nevus**
* Nests of cohesive spindled and epithelioid melanocytes with clefts between the nests and a hyperplastic epidermis
123
Name the infections that cause **sporotrichoid** spread.
**"No SALT"**
**No**cardia
**S**porotrichosis
**A**typical mycobacteria
**L**eishmaniasis
**T**ularemia
124
Name the disease.
* In whom is this classically seen?
**Sporotrichosis**
* Multiple ascending ulcerated nodules or subcutaneous abscesses
* Most frequently in gardeners, farmers, veterinarians
125
Name the diagnosis.
* In whom is this classically seen?
**Sporotrichosis**
* Multiple ascending ulcerated nodules or subcutaneous abscesses
* Most frequently in gardeners, farmers, veterinarians
126
What is the treatment for **sporotrichosis**? (3)
* What is the treatment of choice?
* What can be used in disseminated disease?
* **Itraconazole (treatment of choice)**
* **SSKI** (potassium iodide oral solution)
* Amphotericin B in disseminated disease
127
Name the diagnosis.
* What is the other name for this condition?
* What is the *buzzword* descriptor for these lesions?
* What areas of the body are favored?
**Sweet's syndrome (acute febrile neutrophilic dermatosis)**
* **Tender/burning**, red, well-demarcated, expanding, ***edematous/"juicy"* papules and plaques**
* Favors **head/neck and arms**
* Can have **oral lesions**
* May be vesiculobullous, pustular or targetoid
128
What is another name of **Sweet's syndrome**?
**Acute febrile neutrophilic dermatosis**
129
Name the diagnosis.
* What is the *buzzword* descriptor for these lesions?
* What areas of the body are favored?
**Sweet's syndrome (a.k.a. acute febrile neutrophilic dermatosis)**
* **Tender/burning,** red, well-demarcated, expanding, **edematous/*"juicy"* papules and plaques**
* Favors **head/neck and arms**
* Can have **oral lesions**
* May be vesiculobullous, pustular or targetoid
130
Name the triggers of **Sweet's syndrome.**
* Infections?
* Cancers?
* Diseases?
* Drugs?
* Other triggers?
* Infections: mainly **Streptococcus,** yersiniosis
* Cancer: **AML** plus other hematologic and solid malignancies
* **IBD**
* Drugs: **G-CSF, GM-CSF, ATRA, TMP/SMX, minocycline, OCPs,** furosemide, hydralazine
* Other: autoimmune CTDs, **pregnancy,** HIV, HCV
131
What are extracutaneous features of **Sweet's syndrome** (acute febrile neutrophilic dermatosis)?
* Clinical findings?
* Symptoms?
* Lab finding?
* What about the HPI?
* **Fever**
* **Leukocytosis**
* **Arthralgias**
* **Ocular involvement**
* Malaise
* Preceding URI or flu-like symptoms
132
What lab abnormalities are seen with **Sweet's syndrome** (acute febrile neutrophilic dermatosis)? (3)
* **Leukocytosis** with neutrophilia and bandemia
* **ESR and CRP** elevation
133
What are the classic histological findings of **Sweet's syndrome**?
* What occurs in the dermis? What cells are abundant?
* What is generally not present?
* **Diffuse dermal neutrophilic infiltrate** with karyorrhexis (fragmentation of nuclei) + massive **papillary dermal edema**
* Generally **lacks LCV**
134
What is the treatment for **Sweet's syndrome** (acute febrile neutrophilic dermatosis)?
* Hint: there are several of them.
* Systemic steroids (**prednisone 0.5-1.0 mg/kg daily for 4-6 weeks**)
* SSKI (potassium iodide oral solution)
* Dapsone
* Colchicine
135
What is the classic histopathology of a **syringoma**?
* What do the sweat ducts look like?
* What is inside the lumen of the sweat ducts? What is lining the inside of them?
* What does the surrounding stroma look like?
* Where in the dermis is the lesion?
* **Paisley-tie pattern of tadpole or comma-shaped sweat ducts** lined by a thin two cell layer of cuboidal cells
* **Eosinophilic cuticle** within sweat ducts
* **Amorphous sweat** within lumen
* **Surrounding sclerotic stroma**
* Confined to **upper half of dermis**
136
Name the diagnosis.
* Where is this typically found?
* In what patients is this associated with?
**Syringomas**
* Translucent-skin colored papules on **periorbital region (eyelids #1),** trunk, genitals
* Associated with **females, Asians, Down syndrome**
137
What are the important **autoantibodies** and **cytokines** associated with **scleroderma** (systemic sclerosis)?
* Think of three anti-nuclear antibodies
* **Anti-centromere, anti-Scl70 (anti-topoisomerase I) and anti-RNA polymerase antibodies**
* Profibrotic Th2 cytokines and growth factors (especially **TGF-beta**)
138
Describe **CREST Syndrome**.
* **C**alcinosis cutis
* **R**aynaud's phenomenon
* **E**sophageal dysmotility
* **S**clerodactyly
* **T**elangiectasias
139
Name the diagnosis.
* What is the initial presenting sign in 50% of cases?
**Scleroderma (systemic sclerosis)**
* Skin thickening of fingers of hands extending proximal to MCP joints
* Note in photo the **pitting edema of digits** (the initial presenting sign in 50% of cases)
140
Name the diagnosis.
* What is this finding called?
**Scleroderma (systemic sclerosis)**
This finding is called **sclerodactyly**.
141
Name the diagnosis.
* What is this physical exam finding?
**Scleroderma (systemic sclerosis)**
* This is called **microstomia**.
142
What are **extracutaneous** findings of **scleroderma** (systemic sclerosis)?
* What occurs in the lungs, heart, esophagus and kidneys?
* What is the most common cause of death?
* **Interstitial lung disease** (pulmonary disease is most common cause of death; screen with high-res CT - chest and PFTs)
* **Restrictive cardiomyopathy**
* **Esophageal dysmotility**
* **Scleroderma renal crisis** (help avoid by giving ACE inhibitors)
143
Name the diagnosis.
* What is the size cut off for this diagnosis?
* Where on the body do lesions mostly occur?
**Small plaque parapsoriasis**
* Hyperpigmented or yellowish red scaling patches, round to oval in configuration, with sharply defined, regular borders
* **Lesions should be smaller than 5 cm**
* Can be hypopigmented
* Mostly occurs on trunk
144
Name the diagnosis.
* What is the size cut off for this diagnosis?
* Where on the body do lesions mostly occur?
**Small plaque parapsoriasis**
* Hyperpigmented or yellowish red scaling patches, round to oval in configuration, with sharply defined, regular borders
* **Lesions should be smaller than 5 cm**
* Can be hypopigmented
* Mostly occurs on trunk
145
Name the diagnosis.
* What is the size cut off for this diagnosis?
* Where on the body do lesions mostly occur?
**Small plaque parapsoriasis**
* Hyperpigmented or yellowish red scaling patches, round to oval in configuration, with sharply defined, regular borders
* **Lesions should be smaller than 5 cm**
* May be hypopigmented
* Mostly occurs on trunk
146
Name the diagnosis.
* What is the size cut off for this diagnosis?
* Where on the body do lesions mostly occur?
**Large plaque parapsoriasis**
* Large brown-red, ovoid or irregular plaques with minimal scale
* Usually asymptomatic or minimally pruritic
* **"Bathing suit" distribution**
* **Lesions should be at least 5 cm**
* Resembles **patch stage MF** (and can progress to MF)
147
Name the diagnosis.
* What is the size cut off for this diagnosis?
* Where on the body do lesions mostly occur?
**Large plaque parapsoriasis**
* Large brown-red, ovoid or irregular plaques with minimal scale
* Usually asymptomatic or minimally pruritic
* **"Bathing suit" distribution**
* **Lesions should be at least 5 cm**
* Resembles **patch stage MF** (and can progress to MF)
148
Name the diagnosis.
* What is the size cut off for this diagnosis?
* Where on the body do lesions mostly occur?
**Large plaque parapsoriasis**
* Large brown-red, ovoid or irregular plaques with minimal scale
* Usually asymptomatic or minimally pruritic
* **"Bathing suit" distribution**
* **Lesions should be at least 5 cm**
* Resembles **patch stage MF** (and can progress to MF)
149
What is the rare but important clinical progression of (large plaque) **parapsoriasis** that we worry about?
**Progression to cutaneous lymphoma**
150
What are the treatment options for **parapsoriasis**? (2)
* Topical steroids
* Phototherapy
