Group 1, Column 1 Flashcards
1
Q
Name the diagnosis.
- What is the most common associated malignancy?
- This is histologically identical to what three other things?
- How do you treat this?
A
Acanthosis nigricans
- Most common underlying malignancy is GI adenocarcinoma, especially with palmar involvement
- Derm path buzzword: epidermal papillomatosis
- Histologically identical to CARP, acrokeratosis verruciformis of Hopf and SK
- Can be treated with topical retinoids and AmLactin
2
Q
What are the four components of acne vulgaris?
A
- Abnormal follicular keratinization
- Sebum overproduction
- Propionibacterium acnes overgrowth
- Inflammation
3
Q
Topical retinoids downregulate which receptor?
A
TLR-2
P. acnes activates this on macrophages, causing inflammation and attracting neutrophils
4
Q
Describe key findings of actinic keratosis (AK).
- What kind of genetic damage/mutation has occurred?
A
- UVB causes AKs by inducing thymidine dimers and causing p53 mutations, impairing apoptosis
- Look for “flag sign” with overlying parakeratosis (looks pink) alternating with orthohyperkeratosis (looks blue)
- Rate of transformation to SCC: less than 0.1%
5
Q
What kinds of immune cells target the hair follicles in alopecia areata and where?
What type of cytokines are involved?
A
CD8+ T-cells attack bulb, involving type 1 cytokines (IL-2, IL-12, IFN-gamma and TNF-alpha)
6
Q
What is important to know about the prognosis of ophiasis pattern alopecia areata?
A
There is a poor prognosis.
7
Q
What is the opposite of ophiasis pattern?
A
Sisapho pattern
(This is basically ophiasis spelled backward.)
8
Q
What are the nail findings in alopecia areata?
A
- Regular (geometric) nail pitting
- Trachyonychia (or 20-nail dystrophy), where nails are sandpaper-like
9
Q
What findings on dermoscopy are classically seen with alopecia areata?
A
- Exclamation point hairs
- Perifollicular yellow dots
10
Q
What are other disease associations with alopecia areata?
A
- Atopy (a poor prognostic factor)
- Autoimmune thyroid
- Vitiligo
- SLE
- IBD
11
Q
What are classic histology findings in alopecia areata?
- What kind of inflammatory pattern is seen?
- What kind of hairs are present?
A
- Peribulbar lymphocytic infiltrate (“swarm of bees”)
- Catagen-telogen shift
- Increased miniaturized hairs (i.e., nanogen hairs)
12
Q
What does anagen mean?
- What proportion of hairs are in this phase?
- How long does this last?
- What medicine recreates this phase?
A
- Hair growth phase and determines length of hair
- 85% of hairs at any particular time
- Lasts 2-6 years (genetically determined)
- Minoxidil recreates anagen phase
13
Q
What does catagen mean?
- What happens to the hair in this phase?
- What proportion of hair are in this phase?
- How long does this last?
A
- Transitional phase after anagen
- The bulb regresses and the inner root sheath (IRS) is lost
- 2% of hairs at any particular time
- Lasts 2-4 weeks
14
Q
What does telogen mean?
- How long does this last?
- What proportion of hairs are in this phase?
A
“Telogen is tired and resting.”
- Resting phase
- Lasts 3 months
- 15% of hairs at any particular time
15
Q
Name the layers of the hair follicle from outer to inner.
A
16
Q
What is the gene implicated in atopic dermatitis?
A
Fillagrin mutations, causing alterations in the epidermal barrier
17
Q
Where is filaggrin located in the epidermal cell and in what layer of the epidermis?
- What does filaggrin do in the cell?
A
- In the keratohyalin granules of the stratum granulosum
- Filaggrin binds to intermediate filaments, also known as keratin filaments, causing structural integrity
18
Q
Is atopic dermatitis Th1 or Th2 mediated?
A
Th2
- Important in allergies, humoral immunity
- Think IL-4, IL-5, IL-6, IL-10, IL-13
19
Q
Name the Th1 cytokines.
A
- IL-2
- IL-12
- IFN-γ (downregulates Th2 pathway)
- TNF-α
Important in cell-mediated immunity, delayed-type hypersensitivity reactions
Think ACD, psoriasis
20
Q
Name the Th2 cytokines.
A
- IL-4
- IL-5
- IL-6
- IL-10
- IL-13
Important in allergies, humoral immunity
Think atopic dermatitis
21
Q
Name the diseases associated with Th1 cytokine profile.
A
- Allergic contact dermatitis
- Psoriasis
- Tuberculoid leprosy
- Cutaneous leishmaniasis
22
Q
Name the diseases associated with Th2 cytokine profile.
A
- Atopic dermatitis
- Lepromatous leprosy
- Disseminated leishmaniasis
- Sezary syndrome
- Parasitic infections
23
Q
What is the classic histopathology of acute atopic dermatitis?
- What happens in the epidermis?
- What kind of inflammatory pattern and what immune cells are present?
A
- Prominent spongiosis
- Intraepidermal vesicles/bullae
- Perivascular lymphohistiocytic infiltrate with eosinophils
24
Q
What is the classic histopathology of chronic atopic dermatitis?
- What happens in the epidermis?
A
- Psoriasiform acanthosis with little spongiosis
25
What are the two most common genetic mutations in **BCCs**?
* ***PTCH* (chromosome 9q)**, most common
* p53 point mutations, second most common
26
List the (8) subtypes of **BCCs**
1. Nodular
2. Superficial
3. Morpheaform/sclerotic
4. Micronodular
5. Fibroepithelioma of Pinkus
6. Pigmented
7. Infundibulocystic
8. Basosquamous
27
List the genetic syndromes associated with multiple **BCCs**.
Hint: "**G**reen **B**erets **R**arely **B**uy e**X**tra **S**hoes"
"**G**reen **B**erets **R**arely **B**uy e**X**tra **S**hoes...but they get a lot of BCCs from being in the sun!"
* **G**orlin's
* **B**azex-Dupre-Christol
* **R**ombo
* **B**rooke-Spiegler
* **X**eroderma pigmentosum
* **S**chopf-Schulz-Passarge
28
What is the classic histology of **BCC**?
* What do the cells look like? How do they organize? How do they interact with the stroma?
* **Nests of basaloid and uniform cells** with high N:C ratio (i.e., **look blue**)
* **Peripheral palisading**
* At least focal epidermal connection
* **"Retraction spaces"** between epithelium and stroma
29
What is the chemotherapy used for inoperable or metastatic **BCC**?
**Vismodegib**, a hedgehog pathway inhibitor (and the first of its kind)
30
Describe **_candidal_ diaper dermatitis**.
* Are the intertriginous areas and scrotum involved?
* What does Candida look like on histology?
* Bright red patches with pustules and satellite papules with **possible intertriginous involvement, including the scrotum**
* May also have thrush
* Look for pseudohyphae and budding yeast on histology
31
What are the two most common causes of **cellulitis**?
**Group A beta-hemolytic strep (GAS)**
Followed by *S. aureus* (the most common cause in children)
32
What are the (3) antibiotics of choice for uncomplicated cases of **cellulitis**?
* Oral **cephalexin**, **dicloxacillin** or **clindamycin** for 10 days
33
What is the antibiotic of choice for **cellulitis** associated with decubitus or diabetic ulcers? (2 regimens)
* What kinds of bacteria must these antibiotics cover?
**Piperacillin-tazobactam (Zosyn) or ciprofloxacin-metronidazole (Flagyl)**
This covers GPs, GNs and anaerobes, as these ulcers tend to be polymicrobial.
34
What is the antibiotic of choice for **MRSA cellulitis**? (4)
* Bactrim
* Minocycline
* Doxycycline
* Clindamycin
35
State the one-liner for hypersensitivity reactions:
* Type I
* Type II
* Type III
* Type IV
* Type I: IgE-mediated (anaphylaxis)
* Type II: IgG-mediated cytotoxic (i.e., autoimmune hemolytic anemia, Goodpasture syndrome, myasthenia gravis)
* Type III: immune complex-mediated
* Type IV: delayed, cell-mediated
36
What is the most common cause of **allergic contact dermatitis** in the U.S. and the world?
* US: poison ivy
* Worldwide: nickel
37
What is the classic histology of **ACD**?
* What is the inflammatory pattern, and what cells are notably present in the dermis?
* Are necrotic keratinocytes present?
* Spongiotic dermatitis with **dermal eosinophils**
* **Lacks necrotic keratinocytes** (found in ICD)
38
What is the classic histology of **ICD**?
* What is the inflammatory pattern, and what cells are notably present in the dermis?
* Are necrotic keratinocytes present?
* Mild spongiosis
* **Scattered necrotic keratinocytes (in contrast with ACD)**
* Mild perivascular inflammation
* Probably not eosinophils (compared to ACD)
39
How do you discriminate between an **irritant and allergic** response on patch testing?
* Irritant reactions will fade between the first and second readings
* Allergic reactions will persist or progress
40
Name the diagnosis.
**Dermatofibroma**
41
Name the diagnosis.
**Dermatomyositis**
* Gottron's papules are over MCP joints
* Versus Gottron's sign (which is reddish scaling over knuckles, knees and elbows)
42
Name the diagnosis.
**Dermatomyositis (shawl sign)**
43
Name the diagnosis.
* What are three nail findings of these condition?
**Dermatomyositis**
* Ragged cuticles (Samitz sign)
* Nailfold telangiectasias
* Periungual erythema
44
Name the diagnosis.
**Dermatomyositis (heliotrope rash)**
45
Name the diagnosis.
**Dermatomyositis**
| (Ragged cuticles, a.k.a. "Samitz sign")
46
Name the diagnosis.
**Dermatomyositis**
* Gottron's sign (reddish scaling over knuckles, knees and elbows)
47
Name notable causes of **_drug-induced_ dermatomyositis**.
* **Hydroxyurea** (a chemotherapy for SCC and treatment for sickle cell disease; most common, \> 50% of cases)
* **Statins**
* Cyclophosphamide
* TNF-alpha inhibitors
48
Describe the classic muscle and activity problems in **dermatomyositis**.
* Symmetric proximal muscle weakness **without myalgias**
* Difficulty walking up stairs or brushing hair
49
Describe the classic skin findings of **dermatomyositis**.
Hint: think about face, chest and arms.
* Gottron's papules (lichenoid papules overlying knuckles)
* Gottron's sign (maculary erythema overlying joints)
* Facial erythema with malar involvement _AND melolabial involvement_ (versus lupus)
* Heliotrope sign (lid erythema and edema)
* Holster sign (erythema of lateral hips/thighs, see photo)
* V-sign/"shawl" sign
* Poikiloderma
50
Why does the **heliotrope sign** arise?
It is the result of inflammation of **underlying orbicularis oculi muscle** and NOT the skin.
51
What is **mechanic's hands of dermatomyositis** associated with?
Anti-synthetase syndrome
52
What are the notable nail changes of **dermatomyositis**?
* Ragged cuticles (Samitz sign)
* Proximal nail fold with dilated capillary loops, as well as other areas with vessel dropout
* Periungual erythema
53
What is one way to help differentiate **dermatomyositis** from lupus or psoriasis based on _pruritus_?
**Dermatomyositis is often very pruritic** (especially on the scalp), while the others are usually NOT
54
What are the associated malignancies of **dermatomyositis** in men and women?
* Lung and GI cancer most common in men
* Ovarian and breast most common in women
55
Name the findings of **anti-synthetase syndrome**.
Hint: think about clinical findings, symptoms and rheumatologic serologies.
* **Mechanics hands**
* **ILD** (pulmonary fibrosis)
* Antisynthetase autoantibodies (_Anti-Jo1_)
* Acute disease onset (myositis)
* Constitutional symptoms
* Raynauds
* Arthritis
56
Name the diagnosis.
* What is the buzzword for this diagnosis?
* In patients with which other skin conditions is this diagnosis seen?
**Eczema herpeticum**
* Monomorphic, umbilicated vesiculopapules or _punched-out ulcerations_
* Disseminated HSV (usually HSV-1) mainly seen in atopics, Darier, Hailey-Hailey
57
What is the classic histopathology of **dermatomyositis**?
* What is the inflammatory pattern? What is abundant in the dermis?
* Subtle vacuolar interface dermatitis
* Very abundant mucin
* Mild inflammation
58
What are the most common causes of **erythema multiforme**?
**HSV is by far the most common cause of EM (HSV-1 \> HSV-2) in general**
* HSV is the most common cause of EM minor
* Mycoplasma pneumoniae is the most common cause of EM major (simulates SJS)
59
Name the diagnosis.
**Erythema multiforme**
60
Describe the three zones of a typical target lesion of **EM**.
**Three zones**
1. A dusky, vesicular or necrotic center
2. Elevated, edematous pale surrounding ring
3. Outer rim of macular erythema
61
Describe the papular (elevated) atypical target lesion of **EM**.
**Only two zones, but is palpable**
* Note that _macular_ atypical lesions are seen in SJS/TEN but NOT EM
62
Describe the components of **EM minor**.
* Targetoid lesions (palpable)
* Minimal mucosal involvement
* No systemic symptoms
63
Describe the components of **EM major**.
* Target lesions (palpable)
* Severe mucosal involvement (mouth \> eyes \> genitals)
* **Systemic symptoms** (fever, arthralgias)
64
What infectious lab testing is often positive in **EM** patients?
**80%** have detectable HSV DNA by PCR in early erythematous papules or outer rim of targets
65
What is the classic histopathology of **EM**?
* What is the inflammatory pattern?
* Where is the inflammatory infiltrate?
* Are necrotic keratinocytes and eosinophils present?
* Prominent basal vacuolar change and spongiosis
* Moderately dense superficial dermal perivascular lymphohistiocytic infiltrate
* Necrotic keratinocytes
* Absent/rare eosinophils (as opposed to SJS/TEN)
66
Name the diagnosis.
**Granuloma annulare**
67
What is the classic histopathology for **granuloma annulare**?
* What is more abundant in the dermis?
* Are eosinophils present?
* Granulomas in the dermis
* Increased mucin
* Scattered eosinophils
68
Describe the three common histologic patterns of **GA**.
1. **Interstitial** (most common; 70% of cases): subtle, singly-arrayed histiocytes between collagen fibers intermixed with increased dermal mucin, perivascular eosinophils
2. **Palisaded granulomas** (25%)
3. **Sarcoidal pattern** (5%)
69
What is the classic histopathology of **HSV**?
* What are the epidermal changes? What is the buzzword for the keratinocyte change?
* What is the name of the viral inclusions seen within keratinocyte nuclei?
* **Intraepidermal vesicles** with **slate-gray enlarged keratinocytes (ballooning degeneration)** that are multinucleated
* +/- Cowdry A inclusions (eosinophilic) within nucleus
70
Name the diagnosis.
**HSV**
"Dew drops on a rose petal"
71
What do you use to treat **eczema herpeticum, neonatal HSV, or severe HSV in immunosuppressed**?
* What do you use in refractory cases?
* **First line: IV acyclovir**
* If acyclovir-resistant, use foscarnet or cidofovir
72
What constitutes **disseminated herpes zoster**?
* What patients tend to have this?
* What other organs may be affected when this occurs?
* **Dermatomal disease and \> 20 lesions outside** of the dermatome
* Seen in the immunosuppressed
* Increased risk of pneumonitis and encephalitis
73
Describe **Ramsey-Hunt syndrome**.
* What are the cause and clinical symptoms?
* Reactivation of varicella infection
* Geniculate ganglion of **CN VII** is affected
* Ipsilateral facial nerve paralysis
* Hearing loss
* Anterior 2/3 tongue taste loss
74
What is **Hutchinson's sign**?
* What is involved/affected?
* What does this raise special concern for?
* **Involvement of the side and tip of nose** with herpes zoster, indicating disease of **CN V1 (ophthalmic nerve)**
* Raises concern for **uveitis and vision loss**
75
Name the diagnosis.
**Bullous impetigo**
76
Name the diagnosis.
**Impetigo**
77
What is the pathophysiology of **bullous impetigo**?
* What are the toxins involved and desmoglein is targeted?
Phage group II (types 55 and 77) S. aureus --\> produce **exfoliatoxins A and B** --\> cleaves **desmoglein 1** --\> subcorneal/intragranular acantholysis
78
True or false?
**Streptococcal impetigo** can lead to **rheumatic fever**.
**False**
**_Only_ streptococcal pharyngitis** leads to rheumatic fever.
79
**Bullous _impetigo_** plus renal insufficiency or immunodeficiency can lead to what serious condition? Why?
**Staph scalded skin syndrome**
* Due to disseminated exfoliatoxin
80
**_Bullous impetigo_** has nearly identical histology with which other disorder because the target is the same?
**P. foliaceus**
Both involve cleavage of **desmoglein 1**
81
Name the diagnosis.
**Keloid**
82
What is the histopathology of **lentigo simplex**?
* What are the epidermal changes?
* Basal layer hyperpigmentation
* Elongated rete ridges with mild increased melanocyte density
83
What (6) conditions are associated with **multiple lentigines**?
1. LEOPARD
2. Carney complex (LAMB/NAME)
3. Peutz-Jeghers (especially oral/perioral)
4. Bannayan-Riley-Ruvalcaba (penile)
5. Cowden syndrome
6. Xeroderma pigmentosum
84
Name the diagnosis.
**Lentigo simplex**
85
Name the diagnosis.
**Lichen planus**
86
What are classic _viral_ triggers of **lichen planus**?
* **HBV** (oral or bullous LP)
* **HCV** (oral ulcerative/erosive LP)
87
Name the diagnosis.
**Lichen planus**
88
What are classic _contact allergen_ triggers of **LP**? (3)
* Mercury amalgam (tooth fillings; oral LP)
* Gold
* Copper
89
Name the diagnosis.
**Lichen planus**
90
What are classic triggers of **drug-induced LP**?
* **HCTZ (often photo-exacerbated)**
* Beta-blockers
* ACE inhibitors
* Antimalarials
* "Gold salts" (used for RA)
* Note that **ACE inhibitors, beta-blockers and gold salts** are also drug triggers of **pityriasis rosea**.
91
What is the classic histopathology of **LP**?
* How are the granular layer and rete ridges affected?
* What are the special cells found in the superficial dermis?
* Are eosinophils and parakeratosis present?
* **Wedge-shaped hypergranulosis**
* **Saw-toothed rete ridges**
* Apoptotic keratinocytes of basal layer with some falling into superficial dermis (eosinophilic, a.k.a. ***civatte or colloid bodies***)
* **Usually lacks eosinophils and parakeratosis** (except drug-induced LP)
* "Shaggy" fibrinogen along BMZ
92
Name the diagnosis and nail finding.
**Lichen planus (dorsal pterygium)**
* Can also see 20-nail dystrophy (trachyonychia; children \>\> adults) in LP
93
Name the diagnosis.
**Livedo reticularis**
94
What inherited genetic mutation raises risk for **familial melanoma**?
* What syndromes is this seen in? (2)
* What tumor suppressor genes are involved? (2)
Inherited **CDKN2A mutations**
Seen in **FAMMM syndrome**, **dysplastic nevus syndrome**
* Tumor suppressor genes **p14 (via p53)** and **p16 (via Rb)** stop working
95
Name the diagnosis.
**Melanoma**
96
Name the four subtypes of **melanoma**.
1. Superficial spreading
2. Nodular
3. Lentigo maligna
4. Acral lentiginous
97
What is the most common subtype of **melanoma**?
**Superficial spreading**
98
What are factors associated with a poor prognosis for **melanoma**?
* Some are clinical and some are histologic
Clinical:
* Ulceration
* Lymph node or visceral metastasis
* Head/neck/trunk location
Histologic:
* Breslow \> 1 mm
* Increased mitotic rate
99
Name this clinical sign.
* What condition is this seen in?
* **Hutchinson's sign**: extension of pigment from the nail bed, matrix, and nail plate to the adjacent cuticle and/or nail folds
* Seen in nail matrix lesions of **acral lentiginous melanoma**
100
What are indications for **sentinel lymph node biopsy**?
* **Breslow \> 1 mm** (which is why you want a biopsy at least 1 mm deep)
* **Ulcerated**
* **\>/= 1 mitosis**
101
Name the diagnosis.
**Discoid lupus**
(Chronic cutaneous lupus erythematosus, CCLE)
* Red macules and plaques develop scale, **atrophy and scarring**
* **Central hypopigmentation**
* **Peripheral hyperpigmentation**
102
Name the diagnosis.
**Discoid lupus**
(Chronic cutaneous lupus erythematosus, CCLE)
* Red macules and plaques develop scale, **atrophy and scarring**
* **Central hypopigmentation**
* **Peripheral hyperpigmentation**
103
Name the diagnosis.
**Discoid lupus**
(Chronic cutaneous lupus erythematosus, CCLE)
* Red macules and plaques develop scale, **atrophy and scarring**
* **Central hypopigmentation**
* **Peripheral hyperpigmentation**
104
Name the diagnosis.
* What is there an increased risk for?
* What part of the body is favored in this condition, compared with another similar condition?
**Hypertrophic (verrucous) lupus erythematosus**
* **Thick, hyperkeratotic and verrucous scaling plaques** with indurated border
* **Increased risk of SCC**
* **Favors upper half of body** (versus hypertrophic LP, which favors lower half)
* Usually accompanies typical discoid lupus lesions
105
Name the diagnosis.
* What can trigger this?
**Chilblains lupus erythematosus**
* Red or dusky purple papules and plaques on **fingertips, rims of ears**, heels and **toes**
* **Precipitated by cold, moist climates but can persist year-round**
* Note: Chilblains can occur by itself (without lupus)
106
Name the diagnosis.
* This looks similar to what other condition?
**Tumid lupus erythematosus**
* Edematous, indurated, erythematous, often **annular or arcuate plaques without epidermal change**
* Favors face and trunk
* Similar in appearance to **Jessner's lymphocytic infiltrate** (see photo)
107
What is the classic histopathology of **discoid lupus**?
* What happens in the epidermis?
* What is the inflammatory pattern?
* Where is the infiltrate and what composes it?
* Is follicular plugging present?
* What is present in the stroma?
* **Epidermal atrophy**
* **BMZ thickening**
* **Vacuolar interface dermatitis**
* **Follicular plugging**
* Superficial and deep **perivascular and periadnexal lymphohistiocytic inflammation** with plasma cells
* **Mucin** deposition
* **DIF: Lupus band test positive** (IgG and complement deposits at DEJ)
108
What is the suspected pathogenesis of **subacute cutaneous lupus erythematosus (SCLE)**?
* **UVR-induced apoptosis releases high levels of nuclear antigens** (Ro, La, DNA)
* **Reduced clearance of apoptotic cells** leads to loss of immune tolerance
* Release of pro-inflammatory cytokines and production of ANAs (especially **anti-Ro/La auto-Ab**)
109
What are genetic associations with **SCLE**?
* **HLA-B8 (strongest association)**, HLA-DR3
* **Hereditary complement deficiencies** (especially those involving the early intrinsic pathway: C1q/r/s, C2 and C4)
110
What _two_ autoimmune diseases are strongly associated with **anti-Ro/SS-A autoantibodies**?
1. Sjogren syndrome
2. Subacute cutaneous lupus erythematosus (SCLE)
111
Name the diagnosis.
* What are the two clinical variants of this condition?
* What parts of the body are usually involved?
**SCLE**
* May occur as two clinical variants:
* **Papulosquamous SCLE** (psoriasiform plaques)
* **Annular SCLE** (scaly polycyclic annular plaques with central clearing)
* Involves sun-exposed areas of **lateral face (central face spared), V-chest, upper back,** neck and extremities
* **Arthritis/arthralgias** is most common systemic finding (up to 70%)
112
Name the diagnosis.
* What are the two clinical variants of this condition?
* What parts of the body are usually involved?
**SCLE**
* May occur as two clinical variants:
* **Papulosquamous SCLE** (psoriasiform plaques)
* **Annular SCLE** (scaly polycyclic annular plaques with central clearing)
* Involves sun-exposed areas of **lateral face (central face spared), V-chest, upper back,** neck and extremities
* **Arthritis/arthralgias** is most common systemic finding (up to 70%)
113
Name the diagnosis.
* What are the two clinical variants of this condition?
* What parts of the body are usually involved?
**SCLE**
* May occur as two clinical variants:
* **Papulosquamous SCLE** (psoriasiform plaques)
* **Annular SCLE** (scaly polycyclic annular plaques with central clearing)
* Involves sun-exposed areas of **lateral face (central face spared), V-chest, upper back,** neck and extremities
* **Arthritis/arthralgias** is most common systemic finding (up to 70%)
114
What rheumatologic serologies are found in **SCLE**?
* Also, what else might be abnormal on CBC?
* **Anti-Ro/SS-A (75% - 90%)**
* **Anti-La/SS-B (30% - 40%)**
* ANA (60% - 80%): speckled/particulate pattern
* Leukopenia (20%)
115
What is the classic histopathology of **SCLE**?
Hint: Think about its findings regarding the corneum, epidermis, dermatitis pattern, and whether mucin, eosinophils and follicular plugging are present.
* Compact hyperkeratosis
* **Prominent epidermal atrophy**
* **Vacuolar interface dermatitis** with pigment incontinence
* Perivascular and periadnexal lymphoid aggregates of the superficial dermis with scattered plasma cells
* **Mucin deposition**
* Lacks eosinophils and follicular plugging
* DIF: Positive lupus band test in 60 - 80%
116
What are the first and second line treatments for **SCLE**?
* First line: **TCS, antimalarials (hydroxychloroquine-quinacrine; requires annual eye exams)** and sun protection
* Second and third line: **oral retinoids (acitretin, isotretinoin)**, dapsone, methotrexate, mycophenolate mofetil
117
What are the most important implicated drugs of **drug-induced SCLE**?
* **HCTZ (most common; same as drug-induced LP)**
* **Terbinafine**
* **Griseofulvin**
* **Calcium channel blockers**
* ACE inhibitors
* TNF-alpha inhibitors (most commonly etanercept)
Think HCTZ, oral antifungals and CCBs.
118
Name the diagnosis.
* Are the lesions usually present at birth?
* What is this condition the result of?
* The baby should be evaluated for what other serious congenital condition?
**Neonatal lupus erythematosus**
* Lesions arise within first weeks of life but not at birth
* Photosensitivity
* Periorbital erythema = **"raccoon eyes"**
* **Annular, polycylic erythematous plaques with central clearing** and raised red border, fine scale favoring head and neck (looks similar to SCLE)
* **Resolves without scarring but with dyspigmentation and telangiectasias by around 6 months old**
* Result of transplacental passage of anti-Ro/SS-A autoantibodies, which can lead to **congenital third-degree heart block**
119
Name the diagnosis.
* What other parts of the body are classically involved with this rash?
**Acute cutaneous lupus (ACLE)**
* **Most strongly associated with systemic lupus erythematosus (SLE)** of all cutaneous subtypes
* Malar erythema ("butterfly rash") for hours to weeks after sun exposure
* Classically involves the nasal bridge and bilateral malar eminence
* **Sparing melolabial folds (in contrast to facial erythema of dermatomyositis)**
* May develop scaling, papules, erosions, **poikiloderma**
* May be accompanied by generalized photodistributed eruption of the **V-neck, upper back, extremities but _classically sparing the knuckles_ (unlike dermatomyositis)**
120
Name the diagnosis.
* What other parts of the body are classically involved with this rash?
**Acute cutaneous lupus (ACLE)**
* **Most strongly associated with systemic lupus erythematosus (SLE)** of all cutaneous subtypes
* Malar erythema ("butterfly rash") for hours to weeks after sun exposure
* Classically involves the nasal bridge and bilateral malar eminence
* **Sparing melolabial folds (in contrast to facial erythema of dermatomyositis)**
* May develop scaling, papules, erosions, **poikiloderma**
* May be accompanied by generalized photodistributed eruption of the **V-neck, upper back, extremities but _classically sparing the knuckles_ (unlike dermatomyositis)**
121
What is the classic histopathology of **acute cutaneous lupus erythematosus** (ACLE)?
Hint: think about what the dermatitis pattern is and where/what the infiltrate is.
* **Vacuolar interface dermatitis**
* **_Sparse_ perivascular lymphocytic infiltrate limited to upper dermis**
* Dermal edema
* DIF: Positive lupus band test
122
Name the diagnosis.
* What autoantibody is involved?
* What parts of the body may be involved with this rash?
* What is the treatment?
**Bullous SLE**
* **Anti-type VII collagen autoantibodies (same as EBA)**
* **Widespread, symmetric eruption of dense, subepidermal bullae on erythematous-to-urticarial base**
* Involves both **sun-exposed and non-exposed areas, including the mucosa**
* Patients must meet ACR criteria for SLE to term it bullous SLE
* **Treat with dapsone**
123
Name the diagnosis.
* What autoantibody is involved?
* What parts of the body may be involved with this rash?
* What is the treatment?
**Bullous SLE**
* **Anti-type VII collagen autoantibodies (same as EBA)**
* **Widespread, symmetric eruption of dense, subepidermal bullae on erythematous-to-urticarial base**
* Involves both **sun-exposed and non-exposed areas, including the mucosa**
* Patients must meet ACR criteria for SLE to term it bullous SLE
124
What is the classic histopathology of **bullous SLE**?
* What occurs at the DEJ?
* What is found on DIF?
* **Subepidermal bullae with neutrophils at DEJ and dermal papillae**
* DIF: granular to linear deposition of IgG, IgM, IgA and/or C3 along BMZ (also called "a full house")
125
What laboratory testing is notable in **bullous SLE**?
* What is found on salt-split skin testing?
* An ELISA tests for what autoantibodies?
* Is ANA positive?
* **Dermal reactivity (i.e., floor pattern)** on salt-split skin
* ELISA: autoantibodies to **type VII collagen (same as EBA)**
* **ANA positive**
126
What is the treatment of choice for **bullous SLE**?
* A quick response differentiates it from what other condition?
**Dapsone**
* **Dramatic response within 1-2 days**, differentiating bullous SLE from EBA
127
What are the general ACR criteria for diagnosis of **systemic lupus erythematosus (SLE)**?
Hint: think about the clinical, immunologic and serologic features, as well as a biopsy of a specific organ.
Need to satisfy **four items** (at least one clinical and one immunological item) OR have biopsy-proven nephritis compatible with SLE in the presence of ANA or anti-dsDNA antibodies
* Malar or discoid rash
* Photosensitivity
* Oral ulcers
* Arthritis
* Serositis (pleuritis, pericarditis)
* Renal disorder (proteinuria, cellular casts)
* Neurologic disorders (seizures, psychosis)
* -cytopenias
* Anti-DNA, Anti-Sm, antiphospholipid antibodies (i.e., anti-cardiolipin, lupus anticoagulant, false positive RPR)
* ANA
128
How should pregnant women with **systemic lupus erythematosus** be managed in terms of medicine and clot prophylaxis?
* Continue with **hydroxychloroquine** and **low-dose steroids**
* Consider azathioprine
* Anticoagulation for antiphospholipid syndrome (APLS)
129
What laboratory testing is seen in **systemic lupus erythematosus**?
Hint: think about how it affects a CBC with diff, complement levels, inflammatory markers, UA, as well as autoantibodies (5)
* Hemolytic anemia (Coombs positive)
* -Cytopenias
* Decreased total complement levels (CH50)
* Increased inflammatory markers (CRP, ESR)
* Proteinuria, hematuria
* Anti-C1q Ab (associated with severe SLE nephritis)
* ANA (99%)
* Anti-dsDNA (60%; highly specific)
* Anti-Smith (10% - 30%; highly specific)
* Anti-histone (seen in drug-induced SLE)
130
What is the treatment for **mild SLE** _without_ visceral involvement?
**Hydroxychloroquine + NSAIDs**
131
What is the treatment for **moderate-to-severe SLE** _without_ renal involvement?
**Prednisone + steroid-sparing agent (e.g., azathioprine, MTX or MMF)**
132
What is the treatment for **severe SLE** _with_ renal involvement?
**High dose prednisone + pulsed IV cyclophosphamide or MMF**
133
What is the treatment for **moderate-to-severe and recalcitrant SLE**?
**Rituximab** or **belimumab**
134
How long after drug initiation does **drug-induced lupus** classically occur?
* How long does it take to resolve?
* Onset is **usually \> 1 year** after drug initiation
* Typically resolves **within 4 - 6 weeks of stopping the drug**
135
What rheumatologic serologies characterize **drug-induced SLE**? (2)
* **Positive anti-histone** antibody (\> 95%)
* **Negative dsDNA** antibody
136
What are the most important implicated drugs for **drug-induced lupus**?
Hint: for high risk medications, think about the heart.
* **High risk: procainamide, hydralazine**
* Medium to low risk: methyldopa, isoniazid, D-penicillamine, minocycline, TNF-alpha inhibitors
137
In children, what are the most common causes of **urticaria**?
* Viral
* Idiopathic
* Infectious (UTI, URI, GI infection)
* Allergic (foods, meds, environmental allergens)
* Physical stimuli (pressure, solar, cold)
* Arthropod bite reactions ("papular urticaria")
* Malignancy (most commonly lymphoma)
138
What are the most common causes of **acute urticaria**?
* **Idiopathic (#1)**
* **URIs (#2)**
* Drugs (**beta-lactams** most common)
139
What are different types of **physical urticaria**?
* Dermatographism
* Delayed pressure
* Heat-induced
* Cold ("ice cube test" for primary cold contact urticaria, PCCU)
* Cholinergic (exercise, hot bath, emotions)
* Adrenergic (reproduced by norepinephrine injection)
* Solar
* Aquagenic (associated with cystic fibrosis)
140
How can **urticaria** and **urticarial vasculitis** be distinguished?
Hint: think about lesion duration, specific associated symptoms and histology.
* Any given urticarial lesion **lasts \< 24 hours**
* **Urticarial vasculitis (UV) lesions last \> 24 hours**
* **UV burns/hurts and leaves behind bruises** rather than itches (like urticaria)
* **UV shows mild LCV** +/- eosinophils
141
Name the diagnosis (these lesions have been present for _\> 24 hours_).
* What are associated symptoms, lab findings and treatments for this?
* What broad family of diseases is associated with this diagnosis?
**Urticarial vasculitis**
* **Pain/burning** \> itch (unlike acute urticaria)
* Usually **chronic**
* **Angioedema in one-third of patients**
* **Arthralgias (50%)**, GI issues (20%), asthma (20%)
* Increased ESR, decreased complement, (+) ANA
* **Treat with NSAIDs (first line)**, colchicine, dapsone, MTX, steroids
* Associated with **autoimmune CTDs**
142
What is the classic histopathology of **urticaria**?
* **Superficial dermal edema**
* Vasodilation
* Scant perivascular and **interstitial infiltrate** seen in lesions at least an hour old
* **Predominantly neutrophils** ( \> eosinophils, lymphocytes)
143
What kind of testing can be performed for **acute and recalcitrant chronic urticaria**?
Hint: think about specific allergy testing and blood work, including antibody testing.
* For acute urticaria:
* Radioallergosorbent (**RAST**) test (20% false negative rate)
* **Skin prick** (intradermal) test
* For recalcitrant chronic urticaria
* CBC with diff
* ESR/CRP
* **Anti-thyroid Ab**, TFTs
* Anti-FcεRI and anti-IgE Ab
144
What is the treatment of **urticaria**?
* What oral and topical medications can be used?
* What can be used in recalcitrant cases?
* What should be avoided?
* **First-line treatment = H1 antihistamines (cetirizine [Zyrtec], diphenhydramine [Benadryl])**
* Recalcitrant cases: doxepin, PO steroids, montelukast, phototherapy, colchicine, dapsone, omalizumab
* Soothing lotions (pramoxime, menthol)
* Avoidance of triggers
* Avoid aspirin, NSAIDs and opiates
