Schwarzenberger - Urticaria, Immunobullous, Purpura Flashcards
1
Q
What is this?
A
- Urticaria: more of a blurred margin than in psoriasis plaques
- Should not generally see blisters, but you may see an extravasated blood cell
2
Q
What is urticaria?
A
- Rapid development of “hives”— evanescent (come and go in mins to hrs), itchy swellings of skin
- Inflam rxn in skin mediated by release of histamine (anti-histamine tx) and o/cytokines -> leakage from capillaries into dermis causing edema
- Allergic OR non-allergic in nature; lifetime prev of 20% -> may or may not have identifiable cause
- Wheals last a few hours before resolving; however, may get series of lesions over longer period of time
- May have associated angioedema (swelling of deeper dermis and subcu tissue) for up to 72 hours
3
Q
What are some of the associations with acute urticaria? Chronic?
A
-
Acute: <6 wks
1. Infections
2. Drugs: beta-lactam ABs, NSAIDs, aspirin, opiates, contrast media
3. Food
4. Inhalants
5. Stress
6. Systemic diseases -
Chronic: >6 wks -> majority no identifiable cause
1. Chronic infection
2. Rheum disorders
3. Auto-Abs to IgE receptor on mast cells
4
Q
What is this?
A
Angioedema
5
Q
What is angioedema?
A
- Occurs in 40% cases of urticaria in adults, and may be more frequent in food-induced urticaria
-
Typically involves face: lips, periorbital area, hands, and feet
1. Tongue, larynx, respiratory and GI tracts may be involved - Wheezing, difficulty breathing, abdominal pain, dizziness, low BP may be signs of anaphylactic rxn
-
Hereditary angioedema: rare condition with recurrent episodes of edema, abdominal pain
1. C1 inhibitor deficiency or dysfunction - Angioedema without urticaria often related to drug therapy -> ACEI’s
6
Q
What are physical urticarias?
A
- Forms of urticaria that are not immunologic and have a physical cause:
1. Dermatographism: response to scratching, rubbing, or stroking
2. Cold or heat urticaria
3. Delayed pressure urticaria: pressure sites
4. Solar urticaria: sunlight
5. Aquagenic urticaria: i.e., jumping into pool
6. Cholinergic urticaria: exercise, stress, and heat-induced
7
Q
How do you treat urticaria?
A
- Mainstay of treatment: antihistamines
1. Treatment must be ongoing
2. Prevents hives rather than making them resolve - May need several drugs or higher doses for chronic urticaria
- Other options: LT antagonists, H2-blockers
- AVOID SYSTEMIC STEROIDS: risk of rebound (only time these may be given is acute setting where pt took AB, and you knew this was the cause)
8
Q
What should you do if urticarial plaques last >24 hours?
A
- Consider possibility of urticarial vasculitis
- Biopsy is important to distinguish
9
Q
How common are cutaneous drug reactions?
A
- Cutaneous rxns to meds one of the most common dermatologic problems in hospitalized patients
1. 1-3% of inpatients experience a cutaneous adverse drug reaction - Many commonly used drugs have rates > 1%
- Many drug reactions are miserable; however, some are life threatening
10
Q
Who has increased risk of cutaneous drug reactions?
A
- Can happen to anyone, but increased risk with:
1. Increasing age
2. Female gender
3. Concomitant viral infections: EBV and HIV (e.g., you can get a rash when you give people with mono (EBV infection) penicillin)
11
Q
What are the common offenders in cutaneous drug reactions?
A
- Antibiotics
- Anticonvulsants
- Nonsteroidal anti-inflammatory drugs (NSAIDS)
12
Q
What are the most common cutaneous drug rashes?
A
- Variety of patterns, but:
1. 90% morbilliform or “maculopapular” rash
2. 5% urticarial - Morbilliform rash can be initial presentation of more serious rash, including toxic epidermal necrolysis, DRESS syndrome and serum sickness
13
Q
What is this?
A
- Morbilliform (maculopapular) rash: if you see this in a child, esp. if they are non-immunized, you should also think about measles
14
Q
What do you see here?
A
- Morbilliform drug eruption: multiple small, pink, itchy papules on trunk and pressure-bearing areas
- Spread over time to become confluent
- May be purpuric in dependent areas, esp. if pt is thrombocytopenic
15
Q
What is this rash? When will you get it?
A
-
Morbilliform drug reaction: usually starts 5-7 days after starting drug -> can also occur even a few days after drug is discontinued
1. Cell-mediated, T4 HS rxn -> have to become sensitized first, but this can happen during the drug course - Resolves spontaneously in one to two weeks, usually without complications
- Not uncommon to have sunburn-like peeling after resolution
- Anticonvulsants and ABs most common causes
16
Q
What are the most common causes of morbilliform drug reactions?
A
- Penicillins
- Cephalosporins
- Sulfonamides
- Anticonvulsants
17
Q
What is this? What are the most common causes?
A
-
Urticarial drug reaction: 2nd most common form of cutaneous drug reaction
1. Occur within minutes of exposure, and hives resolve within hours -
Most common causes:
1. Penicillins/cephalosporins
2. Aspirin
3. Latex
18
Q
What is an urticarial drug reaction?
A
- IgE-mediated, immediate hypersensitivity reactions (T1 HS)
- Requires prior exposure with antibody formation
- With re-exposure, antigen binds IgE on mast cells and basophils, inducing degranulation
19
Q
What is DRESS?
A
- Drug rash w/eosinophilia & systemic symptoms, aka, drug hypersensitivity syndrome
- Severe morbilliform drug reaction with eosinophilia and systemic illness (a little bit to very elevated IgE)
- Onset 2-6 weeks after exposure (happens late)
- Facial edema characteristic + fever, LAD, joint pain
1. Can be difficult to distinguish from viral infection - Multisystem involvement; liver common, and can be fatally involved (FULMINANT HEPATITIS)
- Persists weeks to months after drug stopped
20
Q
What’s up with this dude?
A
DRESS
21
Q
What drugs are most commonly implicated in DRESS? How is it treated?
A
- Drugs most commonly implicated:
1. Anticonvulsants
2. Antibiotics: sulfonamides, minocycline, erythromycin - Requires long-term treatment with corticosteroids
- Mortality up to 10% from fulminant hepatitis
22
Q
What is this? What are the common causes?
A
-
Fixed drug eruption: well circumscribed, red-brown plaque; often heals with hyperpigmentation
1. Recurs at same location following repeated exposure, and may blister
2. Commonly on genitals, lips, extremities -
Common causes:
1. Sulfonamides
2. NSAIDS
3. Laxatives
23
Q
What are SJS/TEN? Causes?
A
- Stevens-Johnson Syndrome/Toxic epidermal necrolysis: rare, but potentially life threatening spectrum of blistering skin diseases
- Precise pathophysiology unclear, but majority are drug-related
- Commonly implicated drugs:
1. Antibiotics: sulfonamides, penicillins, cephalosporins, quinolones
2. Anticonvulsants: phenobarbital, carbamazepine, lamotrigine
3. Allopurinol
4. NSAIDS (oxicam derivatives)
5. Nevirapine, Abacavir (HIV drugs)
6. Acetaminophen in children
24
Q
What is the difference between SJS and TEN?
A
- Considered a spectrum of same disease
- Skin and mucous membrane involvement usual in both
- Distinguished by % body surface area involved:
1.
- 10-15% BSA: overlap, and
- >15% BSA: TEN
25
Q
When do pts get SJS/TEN? What happens?
A
- Onset within 1-2 months of starting drug
- Starts with influenza-like, febrile prodromal illness
- Mucosal irritation, conjunctivitis, dysuria common
1. Mucosal involvement is hallmark - Skin starts with morbilliform rash or atypical, dusky target lesions -> may be painful or burning
1. Rash expands and skin starts peeling with full-thickness loss - Multisystem involvement
26
Q
What is this?
A
SJS/TEN (mucocutaneous involvement shown in attached image too)
27
Q
What is going on here?
A
- Sloughing of skin in SJS/TEN
28
Q
How do you manage SJS/TEN?
A
- Critical step is identifying and stopping the offending drug
- Patients need aggressive supportive care -> mgmt in burn unit appropriate where available
- Need for multidisciplinary care: skin care + specialty intervention for eyes, mucous membranes and OB/GYN
- High risk of infection -> aggressive wound care
-
Treatment w/systemic steroids INC mortality
1. Short window if you catch early where these might work as prevention - Do NOT put these people on prophylactic ABs
- Use of IV immunoglobulin may have benefit
- Mortality remains high
- Typically heal up just fine, but may have some pigmentary changes
29
Q
What is going on here?
A
- SJS/TEN: vaginal involvement
30
Q
What are some examples of blistering conditions that are not autoimmune in nature?
A
- Coma blister: ischemic, pressure blister
- Bullous impetigo: from superficial staph or strep infections -> can be pretty intense, and provoke biopsy for autoimmune disease
- Edema blister: from hydrostatic pressure alone
- Bullous smalll vessel cutaneous vasculitis
- Bullous fixed drug reaction
- Exuberant bug bites in pts w/leukemia: children with leukemia and adults with CLL -> might help you pick up a leukemia
- Bed bug bites
- Cutaneous mastocytoma: localized collection of mast cells
- Epidermolysis bullosa: several different variations, but genetic and structural, not immunologic -> babies who are born with eroded skin
31
Q
What is this?
A
- Coma blister: ischemic, pressure blister
32
Q
What is this?
A
- Bullous impetigo: from superficial staph or strep infections -> can be pretty intense, and provoke biopsy for autoimmune disease
33
Q
What is this?
A
- Edema blister: from hydrostatic pressure alone
34
Q
What is this?
A
Bullous smalll vessel cutaneous vasculitis
35
Q
What is this?
A
Bullous fixed drug reaction
36
Q
What is this?
A
- Exuberant bug bites in pts w/leukemia: children with leukemia and adults with CLL -> might help you pick up a leukemia
37
Q
What is this?
A
Bed bug bites
38
Q
What is this?
A
- Cutaneous mastocytoma: localized collection of mast cells
39
Q
What is this?
A
- Epidermolysis bullosa: several different variations, but genetic and structural, not immunologic -> babies who are born with eroded skin
40
Q
What are the characteristics of the autoimmune bullous diseases as a group?
A
- Uncommon chronic skin conditions caused by devo of auto-Abs against various skin proteins
- Usually affect older individuals
- Unknown etiology, but probs some sort of epigenetics -> genetic predisposition + an envo trigger
- Source of significant morbidity and, potentially, mortality
41
Q
When should you suspect an autoimmune blistering disease?
A
- Patients with unexplained:
1. Blisters
2. Erosions on skin
3. Erosions or pain in mucous membranes: can even be diagnosed by dentists due to mucosal lesions
4. Itchy rash that doesn’t respond to “usual” treatments
42
Q
What are the 3 autoimmune blistering diseases?
A
- Bullous pemphigoid and variants
- Pemphigus vulgaris and variants
- Dermatitis herpetiformis
43
Q
What is epidermolysis bullosa acquisita?
A
- A less common autoimmune bullous disease with Ab’s to collagen 7 (affecting adherence of dermis to epidermis)
44
Q
What is bullous pemphigoid?
A
- 4-14 cases per million/year; women > men
- Affects older persons: age 68-82 or older
- Usually no obvious trigger, but rarely caused by medications
- Auto-Abs to hemidesmosomes in basal cells: target Ags are BP 180 and BP 230 proteins
- Tons of eosinophils is a hallmark (often line the BM even before blistering) -> you can also get these with a drug reaction.
45
Q
What is this?
A
Bullous pemphigoid
46
Q
What do you see here?
A
- Bullous pemphigoid: separation of epidermis from dermis, with eosinophilic infiltrate
- Tons of eosinophils is a hallmark (often line the BM even before blistering) -> you can also get these with a drug reaction
47
Q
What do you see here?
A
- Bullous pemphigoid: IgG and C3
- Remember: the point of IF is to look for the characteristic Ab subtype (IgG, IgM, etc.).
48
Q
What is this?
A
- Bullous pemphigoid: often starts with very itchy, urticarial rash
- May be confused for a drug reaction
49
Q
What are these from?
A
- Bullous pemphigoid: blisters are tense and may or may not have surrounding erythema
- Usually symmetrically distributed: clue that this is not poison ivy
- Get successive crops of these over periods of time
- Mucous membranes involved in less than 20%
50
Q
What is this?
A
Bullous pemphigoid
51
Q
What is this?
A
- Mucous membrane pemphigoid, a BP variant
- Scarring eye involvement; can lead to blindness
- Oral lesions
- +/- skin lesions
52
Q
What is this?
A
Bullous pemphigoid
53
Q
What is this?
A
- Gestational pemphigoid or “herpes gestationis,” a BP variant
- BP arising in pregnant women, usually during 2nd trimester
- Can be associated with preterm labor or low weight-for-gestational age baby
1. Mostly managed as high-risk OB pts
2. Baby can be born with some blistering too, but this is usually not long-term (from mom’s IgG) - Remits postpartum, but can recur in successive pregnancies
54
Q
How do you diagnose BP?
A
-
Skin biopsy (from normal skin close to the blister) for routine studies and direct immunofluorescence (DIF) studies
1. DIF shows a band of IgG and C3 at the dermal-epidermal junction (see attached) - May or may not find antibodies in the blood
56
Q
What is pemphigus vulgaris?
A
- Affects 1-10 per million worldwide
1. INC incidence in persons of Mediterranean or Ashkenazi Jewish descent - Affects all ages; mean onset 50-60; men = women
- May have genetic susceptibility
- Auto-Abs to part of desmosomes: target Ag -> desmoglein 1 and 3
57
Q
Describe the histo and IF in pemphigus vulgaris.
A
-
Histology: “row of tombstones”
1. Intraepidermal split (within epidermis)
2. Acantholysis: individual cells lose attachment
3. Basal layer (BM) stays intact -
Immunofluorescence: intercellular (netlike — b/t keratinocytes)
1. IgG and C3 -> targeting desmogleins 1 & 3
58
Q
What is this?
A
-
How pemphigus vulgaris starts: clinically often starts with painful erosions in the mouth or gums
1. Can’t drink anything acidic, and can be very painful
59
Q
What are the clinical manifestations of PV?
A
- Blisters may or may not be seen on skin
1. If present, blisters flaccid and easily broken - Lesions most common on head, chest, back, and intertriginous areas -> erosions can be painful
- Mucous membrane involvement may be extensive, involving all mucosa, larynx, esophagus, conjunctiva (often starts here)
- Can get scarring and conjunctival involvement (but not as bad as mucous membrane BP, which can lead to blindness)
60
Q
How do you diagnose and treat PV?
A
-
Diagnosis: skin biopsy (right at the edge, where there is active inflam, but still some skin), direct immunofluorescence
1. Can identify circulating antibodies in blood almost always, and can follow serially to assess disease progress quantitatively -
Treatment: needs long-term tx with steroids, immunosuppressives
1. Can be fatal without treatment—up to 70%
2. Rituximab has been used in some patients, stopping the disease before it even really gets started -> this drug is unbelievably expensive
66
Q
How do DH patients present?
A
- Pts present with intensely itchy rash; may or may not see vesicles
- Distribution symmetric: elbows, buttocks, knees, scalp and neck
- Mucosal involvement very rare
70
Q
What type of purpura is this? Be specific.
A
- Non-palpable purpura
-
Petechiae: small, <3 mm red or purple dots
1. Usually on dependent areas of body
2. Generally painless - Spots don’t blanche, so there are extravasated blood vessels in the skin
73
Q
What are the two types of causes of petechiae?
A
- Platelet related: low platelets or platelet dysfunction
- Non-platelet related: things that increase capillary fragility or allow them to leak
74
Q
How can scurvy cause this?
A
- Need Vitamin C to maintain integrity of capillaries
1. Remember: petechiae can be a result of platelet problems OR things that INC capillary fragility - Petechiae almost always around hair follicles in scurvy
1. Get corkscrew hairs too, and easily bleeding, pliable gums
75
Q
What are ecchymoses? What generally causes these?
A
- Larger, non-palpable areas of purpura (>5 mm)
1. More likely reflect ABNORMALITIES IN COAGULATION, rather than platelet defects
a. Can be hyper-or hypocoagulable -> too much bleeding or too much clotting
2. Can get both platelet and bleeding abnormalities, but simplified for learning - Can be on any areas of body
- May/may not be painful, tender
77
Q
What is this?
A
- Solar purpura: due to sun damage
- Could be a complication of use of topical steroids chronically
- See this in older patients on their forearms
78
Q
What do you see here?
A
- Multifactorial purpura -> thrombocytopenia + trauma
- Linear purpura (=vibex) on upper arm due to blood pressure cuff in thrombocytopenic patient
79
Q
What is this?
A
- Multifactorial purpura
- Steroid-induced atrophy, actinic damage, trauma from pneumatic compression device
82
Q
What is this?
A
Hypergammaglobulinemic Purpura of Waldenström
84
Q
What are these?
A
- Palpable purpura in Henoch-Schönlein syndrome
- Syndrome in children (also adults) in which you get vasculitis associated with joint and abdominal pain
1. Often follows viral infection in kids (more benign)
2. Risk of kidney infection in adults
3. See IgA around the blood vessel - Inflammatory things tend to have less sharp border
- Cutaneous vasculitis can be seen in many settings: malignancy, autoimmune, drug reactions
85
Q
How are palpable purpura different than bland petechiae/ecchymoses?
A
- Associated with inflammation in the blood vessels
- Remember: no blood vessels in the epidermis
86
Q
What do you see here?
A
Inflammation of the superficial vessels in HSP
90
Q
What are these?
A
Palpable purpura from small vessel vasculitis
91
Q
What do you see here?
A
- Palpable purpura from small vessel vasculitis
- Can get little erosions the further down you go into the skin
- The primary lesions are up higher, and the lower lesion is a secondary change
92
Q
What do you see here? Why does it look like this?
A
- Small vessel involvement in a patient with Lupus
- Thicker skin here, so less obvious vasculitis
93
Q
What happened here?
A
- Leukocytoclastic vasculitis in a patient with myelodysplasia
- Vasculitis can be a hallmark of progression to leukemia
94
Q
What do you see here?
A
Meningococcemia (acute)
95
Q
What are these? From?
A
- Palpable purpura from leukocytoclastic vasculitis
96
Q
What do you see?
A
- Palpable purpura from leukocytoclastic vasculitis
97
Q
What happened here?
A
- Vasculitis, like drug eruptions, affect dependent areas in hospitalized patient
- Always look at weight-bearing areas (pressure)
99
Q
What could this be from?
A
- Mixed-size vasculitis: Churg-Strauss in this case
- May see nodules, ulcers (because vasculature further down in the dermis)
102
Q
What does this IF stain show?
A
- IgA staining in HSP: notice the concentration around blood vessels (VASCULITIS)
103
Q
What is this? What may have caused it?
A
- Livedo reticularis from medium-size vasculitis
- From polyarteritis nodosa, in this case (see attached image for histo)
- Not going to see palpable purpura necessarily, but see livedo (vascular network in the skin enhanced due to stasis of the blood vessels)
- Venous congestion, and also small nodules here
104
Q
What type of skin manifestation might this cause?
A
- Livedo reticularis from medium-size vasculitis: vascular network in the skin enhanced due to stasis of the blood vessels
- Can also small nodules here
107
Q
What is this?
A
-
Purpura fulminans: widespread retiform purpura
1. Ischemic necrosis following the vascular network - From DIC, in this case
- Not round, not smooth -> borders are very jagged
108
Q
Are these bruises?
A
- NO
- Case from cocaine -> predisposition to hyper-coagulation from a fungus (Levamisole) the drug is cut with (can recur)
- See attached histo image of THROMBOSES deep in the dermis
110
Q
What do you see here?
A
Histo of deep dermis thromboses (retiform purpura)
