Bullous and Vesicular Dermatoses Flashcards
1- A 31-year-old male presents with rash on his elbows, back of neck, and lower back x 3 months that is very itchy. He feels bloated and has occasional cramping abdominal pain. What is the next best step in management?
A. Referral to psychiatry
B. Start betamethasone 0.05% ointment BID to areas with rash on body for allergic contact dermatitis and have him stop using every topical he is currently using
C. Give a weight-based prednisone taper over 3 weeks starting at 1 mg/kg/day
D. Perform patch testing on his back with the NACS 80 series
E. Perform punch biopsy for H&E and DIF
Correct choice: E. Perform punch biopsy for H&E and DIF
Explanation: The patient may have dermatitis herpetiformis and thus punch biopsy for H&E and DIF is the next most appropriate step.
Allergic contact dermatitis should not be assumed in this patient with a rash that could be dermatitis herpetiformis especially in the setting of abdominal pains as the patient may have celiac disease. A referral to psychiatry is not appropriate.
2- Which bullous disorder is frequently associated with the ingestion of vancomycin?
A. Bullous pemphigoid
B. Pemphigus vulgaris
C. Pemphigus foliaceus
D. Linear IgA bullous dermatosis
E. Bullous lupus erythematosus
Correct choice: D. Linear IgA bullous dermatosis
Explanation: Linear IgA bullous dermatosis is frequently associated with vancomycin usually within 2 weeks of initiation.
3- A 55 year old male presented to clinic two months ago with the tense blisters seen here, mostly on the dorsal hands, elbows and knees. Some of the blisters heal with scarring. H+E biopsy showed a subepithelial blister with sparse lymphocytic infiltrate. DIF findings were linear deposits of IgG along the dermal-epidermal junction. IIF on salt-split skin showed antibody binding to only the dermal side of the split. After a one-month course of prednisone monotherapy showed no improvement, which of the following treatments would be most appropriate to initiate next?
A. Rituximab
B. Dapsone
C. Doxycycline and nicotinamide
D. Hydroxychloroquine
E. Daclizumab
Correct choice: B. Dapsone
Explanation: The clinical and pathological findings are consistent with a diagnosis of epidermolysis bullosa acquisita (EBA). EBA is notoriously difficult to treat and can be refractory to multiple interventions. Dapsone appears to have efficacy in multiple reported cases and is usually the first- line medication. While the other listed medications have also been reported to help in a few cases of EBA, dapsone remains the first-line medication, given its reported efficacy and safety profile.
4- Desmoglein 1 is the antigen in which of the following autoimmune diseases of the skin:
A. Pemphigus foliaceus
B. Bullous impetigo
C. Dermatitis herpetiformis
D. Bullous pemphigoid
E. Pemphigoid gestationis
Correct choice: A. Pemphigus foliaceus
Explanation: The antigen implicated in pemphigus foliaceus is Desmoglein 1. Desmoglein 1 is targeted in bullous impetigo, but this is an infectious condition, not an autoimmune disease. The antigen in dermatitis herpetiformis is transglutaminase 3. The antigens for both bullous pemphigoid and pemphigoid gestationis are BPAG1 and BPAG2.
- A- patient had antibodies to desmoglein 3, but no antibodies to desmoglein 1 or desmplakin. The likely diagnosis is:
A. Pemphigus vulgaris
B. Pemphigus foliaceous
C. Bullous pemphigoid
D. Dermatitis herpetiformis
E. Erythema multiforme
Correct choice: A. Pemphigus vulgaris
Explanation: The answer is pemphigus vulgaris, which typically has autoantibodies to desmoglein
3. While mixed forms of pemphigus can occur, the histology in this case confirmed pemphigus vulgaris. Pemphigus foliaceous has antigens to Dsg1. Bullous pemphigoid typically has antigens to BP180 and BP230. Dermatitis herpetiformis has antigens to transglutaminase 3.
6- Cicatricial pemphigoid antibodies directed against this are associated with high frequency of malignancy:
A. Laminin 5
B. Laminin 6
C. Beta4-integrin
D. BPAg1
E. BPAg2
Correct choice: A. Laminin 5
Explanation: Anti-laminin 5 cicatricial pemphigoid (CP) is also known as anti-epiligrin CP. Anti- epiligrin CP is associated with an increased frequency of internal adenocarcinomas. Laminin 5 is composed of three chains (heterotrimer), alpha3, beta3, gamma2. Antibodies are frequently directed against the alpha3 chain, and so cross-reactivity can be observed with laminin 6, as laminin 6 (alpha3beta1gamma1) has the alpha3 chain as well. Beta4-integrin antibodies have been associated with ocular CP. BPAg2 antibodies are seen in CP patients that have mucosal as well as skin disease.
7- A 67-year-old female presents for a bullous dermatosis. DIF shows linear IgA +/- C3 at the basement membrane zone. After stopping any potentially responsible medication, what is the most appropriate first-line therapy?
A. Cyclosporine
B. Dapsone
C. Prednisone
D. Mycophenolate mofetil
E. Topical calcineurin inhibitor
Correct choice: B. Dapsone
Explanation: The immunofluorescence staining pattern suggests linear IgA bullous dermatosis. The best treatment for this immunobullous disease is dapsone, after any possible offending agent has been stopped. Cyclosporine, prednisone, mycophenolate mofetil and topical calcineurin inhibitors are not first line therapies for linear IgA bullous dermatosis.
8- A patient presents with several blisters on her skin. A peri-lesional biopsy for direct immunofluorescence reveals intercellular IgA deposition. Which of the following is the best initial treatment?
A. Azathioprine
B. Mycophenolate mofetil
C. Dapsone
D. Isotretinoin
E. Sulfapyridine
Correct choice: C. Dapsone
Explanation: A blistering dermatosis with DIF showing intercellular IgA deposition confirms the diagnosis of IgA pemphigus. Dapsone +/- oral steroids is considered first line treatment. The remaining answer choices are not first line treatment for IgA pemphigus.
9- Herpes gestationis is most commonly associated with which HLA?
A. HLA-DR3
B. HLA-B27
C. HLA-B51
D. HLA-DR9
E. HLA-DQ8
Correct choice: A. HLA-DR3
Explanation: HLA-DR3 is the most commonly found HLA association in herpes gestationis. HLA- DR4 is also found in addition to HLA-DR3 in about 50% of patients. There is nearly 100% incidence of anti-HLA antibodies patients affected by herpes gestationis. The remaining answer choices are not commonly associated with herpes gestationis.
10- What is the antigen for this disease?
A. Desmoglein 1
B. Corneodesmosin
C. Envoplakin
D. Col XVII
E. Laminin 5
Correct choice: D. Col XVII
Explanation: This is bullous pemphigoid. There is a tense blister as this is a subepidermal split. The antigen is BPAg1 and Col XVII (BPAg2). The DIF shows a linear IgG and C3 at the DEJ. On salt- split skin the IgG goes to the roof.
11- The predominant cleft in dermatitis herpetiformis is:
A. Dermal
B. Basement membrane zone
C. Basal keratinocytes
D. Suprabasal
E. Subcorneal/granular
Correct choice: B. Basement membrane zone
Explanation: Dermatitis herpetiformis, or Duhring’s disease, presents with very pruritic vesicles symmetrically on extensor surfaces. On histology it presents as suprapapillary vesicles with mostly neutrophils and inflammatory destruction of the basement membrane zone. Direct immunoflourescence shows granular deposition of IgA in the dermal papillae and along the basement membrane zone. The cleft in dermatitis herpetiformis is most commonly found in the basement membrane zone/subepidermal. The antigen is transglutaminase. The other answer choices listed are incorrect.
12- The direct immunofluorescence and indirect immunofluorescence for this dermatosis is:
A. DIF: linear IgA at the basement membrane zone, IIF: linear IgA at the basement membrane zone
B. DIF: granular IgA in dermal papillae, IIF: negative
C. DIF: negative, IIF: negative
D. DIF: granular IgG in dermal papillae, IIF:negative
E. DIF: linear IgG at the basement membrane zone, IIF: linear IgG at the basement membrane zone
Correct choice: A. DIF: linear IgA at the basement membrane zone, IIF: linear IgA at the basement membrane zone
Explanation: Linear IgA bullous dermatosis (LABD) typically presents with tense vesicles and bullae in a serpiginous or annular distribution. It typically presents 1-14 days after the offending medication, such as Vancomycin, B-lactams, ACE inhibitors, etc. Linear IgA presents histologically similar to dermatitis herpetiformis (DH) with neutrophils along the DEJ, but has linear IgA at the basement membrane zone on DIF and IIF. DIF: granular IgA in dermal papillae, IIF: negative describes DH . DIF: linear IgG at the basement membrane zone, IIF: linear IgG at the basement membrane zone can describe bullous pemphigoid, Epidermolysis Bullosa Acquisita.
13- Patients diagnosed with variegate porphyria have skin fragility and can have neurological issues. They have a defect in:
A. Protoporphyrinogen oxidase
B. Ferrochelatase
C. Porphobilinogen deaminase
D. Uroporphyrinogen III synthase
E. Uroporphyrinogen decarboxylase
Correct choice: A. Protoporphyrinogen oxidase
Explanation: Patients with variegate porphyria have photosensitivity and neurological issues, with flaccid skin that heals with crusting. They can also have a higher incidence of skin infection. They
have a defect in the protoporphyrinogen oxidase. Ferrochelatase deficiency is seen in Erythropoietic Protoporphyria. Porphobilinogen deaminase deficiency is seen in Acute Intermittent Porphyria. Uroporphyrinogen III synthase deficiency is seen in Congenital Erythropoietic Porphyria. Uroporphyrinogen decarboxylase deficiency is seen in Porphyria cutanea tarda and Hepato- erythropoietic porphyria.
14- Using the salt-split skin technique with direct immunofluorescence, epidermolysis bullosa acquisita will show linear deposition of complement in what position?
A. Roof of the split
B. Roof and floor of the split
C. Floor of the split
D. Neither the roof or floor of the split since IgA is the most common reactant
E. None of the above since the pattern is not linear
Correct choice: C. Floor of the split
Explanation: Epidermolysis bullosa acquisita (EBA) is a bullous disease of adults in which minor trauma (usually on the hands and feet) leads to blisters that heal with scaring. On histology there is classically a noninflammatory subepidermal split. The blister will immunostain with IgG on the floor of salt-split skin, as the antigen is type VII collagen. The other answer choices are incorrect.
15- Which of the following is NOT associated with a K1 mutation?
A. Ichthyosis Hystrix, Curth Macklin Type
B. Epidermolytic ichthyosis
C. Epidermal nevi with epidermolytic hyperkeratosis
D. Nonepidermolytic palmoplantar keratoderma
E. Ichthyosis bullosa of Siemens
Correct choice: E. Ichthyosis bullosa of Siemens
Explanation: Mutation in keratin 1 is associated with ichthyosis hystrix. Mutations in keratins 1/10 are associated with epidermolytic ichthyosis and epidermal nevi with epidermolytic hyperkeratosis. Mutations in keratins 1/16 are associated with nonepidermolytic palmoplantar keratoderma.
Reference: Reference: Dermatology In-Review. 2016-2017 ed. p20.
16- The predominant location of the cleft in linear IgA is:
A. Dermal
B. Basement membrane zone
C. Basal keratinocytes
D. Suprabasal
E. Subcorneal/granular
Correct choice: B. Basement membrane zone
Explanation: Linear IgA bullous dermatosis is an autoimmune disorder that presents with tense blisters along red annular rings (like a string of pearls). Antibodies are found in the lamina lucida against LAD-1 antigen in anchoring filaments. The cleft in linear IgA would be found in the basement membrane zone/subepidermal with direct immunostaining IgA in a linear pattern at the dermal-epidermal junction. The other answer choices listed are incorrect.
17- This alcoholic patient presents with tense bullae. Direct immunofluorescence of a biopsy of perilesional skin shows IgG and C3 deposition along the basement membrane and H&E shows numerous eosinophils with a subepidermal cleft. Which of the following is the LEAST appropriate therapy for this patient?
A. Prednisone
B. Methotrexate
C. Doxycycline with niacinamide
D. Liberal topical BID application of clobetasol
E. Mycophenolate mofetiI
Correct choice: B. Methotrexate
Explanation: The correct answer is B; given that the patient is an alcoholic, methotrexate should be avoided. This patient has a diagnosis of bullous pemphigoid. Prednisone is typically first line and is tapered once control is achieved. There is data for the remainder of the treatments listed in bullous pemphigoid, but few comparing between the treatments.
18- A 29-year-old primigravida presents to you for a skin check in her 2nd trimester. On exam, you notice urticarial papules and plaques around the umbilicus and the rest of the body, with blisters in a polycyclic arrangement. You perform a biopsy for direct immunofluorescence. What pattern would you expect to see in 100% of patients with this condition?
A. Intercellular IgG and C3
B. Linear C3, occasionally IgG at basement membrane
C. Granular IgG and C3 at the basement membrane
D. Granular IgA at the basement membrane
E. Multiple immunoglobulins, complement, and fibrin at the junction
Correct choice: B. Linear C3, occasionally IgG at basement membrane
Explanation: Linear C3/IgG immunofluorescence pattern is seen in bullous pemphigoid and herpes gestationis. DIF shows linear C3, occasionally IgG at the basement membrane in 100% of patients with herpes gestationis. On histology, there is a subepidermal split similar to BP.
Reference: Reference: Dermatology In-Review. 2016-2017 ed. pg 426
19- Which is not caused by a sub-epidermal split:
A. Bullous pemphigoid
B. Cicatricial pemphigoid
C. Porphyria cutanea tarda
D. Epidermolysis bullosa acquisita
E. Fogo selvagem
Correct choice: E. Fogo selvagem
Explanation: The disease examples with a location of split below basal cells include: bullous pemphigoid, cicatricial pemphigoid, porphyria cutanea tarda, epidermolysis bullosa acquisita.
20- You are called to evaluate a patient with a new onset vesicular eruption that developed 7 days after starting intravenous vancomycin. What is the target antigen at the dermoepidermal junction?
A. Tansglutaminase 3
B. Alpha-6-beta-4 integrin
C. Desmocollin-1
D. LAD 97
E. BPAG1 (230 KD)
Correct choice: D. LAD 97
Explanation: Annular plaques with tense vesicles at the periphery (“string of pearls”) is typical of linear IgA bullous dermatosis. Antibodies are directed against the linear IgA disease antigen (LAD-1), 97-kDa portion of BPAG-2, which is localized to the lamina lucida.
21- This patient has intercellular IgA on DIF what is the most likely associated condition?
A. Malar rash
B. IgA monoclonal gammopathy
C. Positive ANA
D. Malignancy
E. Tuberculosis
Correct choice: B. IgA monoclonal gammopathy
Explanation: IgA pemphigus is associated with intercellular IgA and an IgA monoclonal gammopathy. There are two types, the SPD type and the IEN type.
22- This patient had antibodies to 180 kd antigen. The likely diagnosis is:
A. Bullous pemphigoid
B. Pemphigus vulgaris
C. Pemphigus foliaceous
D. Erythema multiforme
E. Bullous lichen planus
Correct choice: A. Bullous pemphigoid
Explanation: The answer is bullous pemphigoid, which shows a characteristic antibasement membrane antibody to Bp180. The target antigens in pemphigus vulgaris are usually desmoglein 1 and 3. The target antigen in pemphigus foliaceous is usually desmoglein 1. Erythema multiforme does not usually have a known target antigen. Bullous lichen planus also does not usually have a known target antigen; in contrast with lichen planus pemphigoides which also has a target antigen of Bp180.
23- Lichen planus pemphigoides has been associated with an antigen to which structure?
A. Type XVII collagen
B. Hemidesmosome plaque
C. Desmoglein 3
D. Desmoglein 1
E. Type VII collagen
Correct choice: A. Type XVII collagen
Explanation: Type XVII collagen, or BPag2 (180 kD) has been associated with LP pemphigoides. The hemisdesomosome plaque is also known as BPag1 (230 - kD), desmoglein 1 and 3 are antigens in pemphigus, and antibodies to Type VII collagen are found in epidermolysis bullosa aquisita and bullous lupus.
24- Anti-epiligrin (laminin 5) antibodies may be seen in:
A. Pemphigoid gestationis
B. Pemphigus vegetans
C. Fogo selvagem
D. Cicatricial pemphigoid
E. Paraneoplastic pemphigus
Correct choice: D. Cicatricial pemphigoid
Explanation: Patients with cicatricial pemphigoid have been reported to have anti-epiligrin (aka laminin-5 or laminin 332) antibodies. Patients with this target antigen might be at a higher risk of having an underlying malignancy. The target antigen in pemphigoid gestationis is most commonly BPAg2. The target antigen in pemphigus vegetans is most commonly Dsg 3. The target antigen in fogo selvagem is most commonly Dsg 1. Paraneoplastic pemphigus has many reported target antigens that belong to the plakin family.
25- You are rotating through a children’s hospital this month, and are called to see an inpatient consult, a 12-year-old girl with severe oral and genital ulcerations and trouble breathing. A direct immunofluorescence shows IgG and C3 intercellular and linear/granular at the dermoepidermal junction. Indirect immunofluorescence on rat bladder shows intercellular IgG. What malignancy is most commonly associated with this condition in children?
A. Chronic lymphocytic leukemia
B. Sarcoma
C. Non-Hodgkin’s lymphoma
D. Castelman’s disease
E. Thymoma
Correct choice: D. Castelman’s disease
Explanation: Castleman’s disease is the most common malignancy association with paraneoplastic pemphigus in children. The disease occasionally remits with treatment of the tumor. IIF, best on rat bladder, shows intercellular IgG. Respiratory failure in these patients can lead to death.
The other listed tumors are associated with paraneoplastic pemphigus in adults
26- What is the antigen in this disease?
A. BPAg1
B. Desmoglein 3
C. Desmoplakin
D. Plakoglobin
E. Envoplakin
correct choice: A. BPAg1
Explanation: This is bullous pemphigoid which is due to antibodies to BPAg1 and BPAg 2. It is a subepidermal blister. Pemphigus vulgaris is due to antibodies to desmoglein 3. Paraneoplastic pemphigus is due to antibodies to many proteins the most common being envoplakin and periplakin.
27- this is due to a mutation in what gene?
A. AKT1
B. LEMD
C. PORCN
D. It is a sporadic mutation
E. ABCC6
Correct choice: C. PORCN
Explanation: This is Goltz syndrome which is a XLD mutation in the PORCN gene in the wnt pathway. The photo shows the associated aplasia cutis congenita. LEMD3 is mutated in Buschke- Ollendorff. Proteus is due to a sporadic mutation in AKT1. PXE is due to a mutation in ABCC6
28- What is the most common complication of this condition?
A. Atrial fibrillation
B. Hallucinations
C. Sepsis
D. Death
E. Symblepharon
Correct choice: E. Symblepharon
Explanation: This is TEN which is most commonly due to a drug. The patients start with tender skin that progresses to blisters with epidermal sloughing. The mucosal surfaces are also involved. The most common complication is symblepharon and dry eyes.
29- What is the target antigen?
A. Collagen 7
B. Laminin 5
C. BPAg2
D. Keratin 1 and 10
E. Envoplakin
Correct choice: A. Collagen 7
Explanation: This is epidermolysis bullosa acquisita which is like dystrophic EB but in adults. It is due to autoantibodies to the NC-1 domain of collagen 7 (the amino terminus). There is a subepidermal split. On DIF there is linear IgG and C3 in an Userrated pattern at the DEJ. On salt- split skin it goes to the floor as compared to bullous pemphigoid where it goes to the roof.
30- What is a common cause of this condition?
A. Infection
B. Sunlight
C. Lupus
D. Atypical keratinocytes
E. Nail polish
Correct choice: E. Nail polish
Explanation: This is contact dermatitis on the eyelids which is commonly caused by nail polish. The malar rash in lupus, which is of autoimmune etiology, is usually not on the eyelids.
31- A 10 y/o child presents with oral ulcerations and a polymorphous eruption of targetoid lesions and flaccid bullae on her body. Histology shows suprabasilar acantholysis with dyskeratotic and necrotic keratinocytes. DIF shows IgG and C3 intracellularly and linear/granular at the DEJ.
A. Genitourinary
B. Gastrointestinal
C. Neurologic
D. Lymph nodes
E. Respiratory
Correct choice: D. Lymph nodes
Explanation: Per the clinical and histopathologic description, this child is presenting with paraneoplastic pemphigus. Paraneoplastic pemphigus can resemble severe erythema multiforme with oral ulcerations, pemphigus vulgaris, or even bullous/cicatricial pemphigoid. Skin lesions can be polymorphous with erythematous papules, lichenoid lesions, targetoid lesions, flaccid or tense bullae. Histology would show suprabasilar acantholysis and dyskeratotic keratinocytes with basal vacuolar change. IIF shows tntercellular IgG on rat bladder. The most common underlying cause of paraneoplastic pemphigus in a child is Castleman’s disease, which affects lymph nodes. Carcinomas of the GI, GU, respiratory, and neurologic systems are significantly less likely to cause paraneoplastic pemphigus in children.
32- Which of the following is FALSE regarding epidermolysis bullosa acquisita?
A. Mucous membrane involvement does not occur
B. IIF on salt-split skin shows binding to the dermal side of split
C. DIF shows linear deposition of IgG along the BMZ
D. The autoantigen is Type VII collagen
E. A subepidermal split is seen histologically
Correct choice: A. Mucous membrane involvement does not occur
Explanation: Epidermolysis bullosa acquisita (EBA) is an autoimmune subepidermal bullous disorder of the skin and mucous membranes. The disease results from the production of immunoglobulin G (IgG) antibodies against type-VII collagen, a major component of anchoring
filaments in the dermal-epithelial junction. The disease has two major forms of presentation: the classical (non-inflammatory) type and the inflammatory type. Classical EBA is mainly characterized by the following features: development of non-inflammatory tense blisters on trauma- prone areas, multiple milia cysts, minimal or no inflammation findings on histopathology. Alternatively, inflammatory EBA is defined by widespread inflammatory blistering eruptions and a neutrophil-rich inflammatory infiltrate on standard histopathology. In both cases, specialized immunopathological findings are further required to establish an accurate diagnosis.
33- A biopsy for DIF is negative. IIF is positive for IgG antibodies directed against monkey esophagus. Which of the following is true regarding the diagnosis?
A. The primary target antigen is desmoglein 1
B. It is associated with bronchiolitis obliterans
C. There are no FDA-approved treatments
D. A positive DIF would show intercellular and linear IgG & C3 along the BMZ
E. Autoantibody titers correlate with disease activity
Correct choice: E. Autoantibody titers correlate with disease activity
Explanation: IIF positivity for IgG antibodies directed against monkey esophagus is diagnostic of pemphigus vulgaris (PV). Autoantibody titers correlate with PV disease activity and can be monitored to assess response to therapy. It is important to keep in mind that DIF biopsies may be falsely-negative in PV, so IIF studies are important in the diagnostic approach. The primary target antigen in PV is desmoglein 3 > 1. Paraneoplastic pemphigus (PNP) is associated with bronchiolitis obliterans, and a positive DIF would show intercellular and linear IgG & C3 along the BMZ. The best IIF substrate for PNP is rat bladder transitional epithelium. Lastly, rituximab is FDA-approved for the treatment of pemphigus vulgaris.
34- A 70 y/o male presents to clinic with several well-demarcated denuded areas of skin. A punch biopsy is performed and shows IgG and C3 on the roof of a salt-split skin. Which of the following medications is most likely to appear in his medication list?
A. Metformin
B. Levodopa
C. Vildagliptin
D. Glipizide
E. Insulin
Correct choice: C. Vildagliptin
Explanation: This clinical and histopathologic description above describes a diagnosis of bullous pemphigoid. The question indicates that this is a medication-induced case. Several studies in the past few years have indicated dipeptidyl peptidase-IV inhibitors (gliptins) as a cause of drug- induced bullous pemphigoid. Out of the medications in the class, Vildagliptin is one of the most common causes. Metformin, Glipizide, and Insulin are widely used medications in the treatment of diabetes but haven’t been recognized as common causes of drug induced BP.
Though there has been a link established between bullous pemphigoid and Parkinson’s disease, levodopa has not been identified as a cause of drug-induced BP.
35 -Drugs that are associated with the exacerbation of pemphigus foliaceus include :
A. Captopril
B. Metoprolol
C. Fluconazole
D. Calcium channel blockers
E. Statins
►A
Pemphigus foliaceus is a form of pemphigus with superficial blisters. The autoantibodies are against Dsg1. Medications associated with the exacerbation of pemphigus foliaceus is sulfhydryl groups such as captopril, penicillamine and piroxicam. Metroprolol can exacerbate psoriasis.
36 -An elderly gentleman with a history of hypertension and a thymoma, presents to the Emergency Room with oral and conjunctival erosions and hemorrhagic bullae on his hands and feet. These finds are seen in:
A. Cicatricial pemphigoid
B. Sweet”s syndrome
C. Toxic epidermal necrolysis
D. Paraneoplastic pemphigus
E. Erythema multiforme
►D
Paraneoplastic pemphigus is usually associated with cancers of lymphoid origin, including lymphoma, leukemia, thymomas, Castleman”s tumor. Clinically, this condition may present with intractable staomatitis, severe painful oral and conjunctival erosions.
37- A child develops an allergic reaction at the site of an influenza vaccine. To which of the following substances may she be allergic to?
A. Lanolin
B. Thimerosol
C. Ethylenediamine dichloride
D. Triclosan
E. Gluteraldehyde
►B
Thimerosol is a preservatives in vaccines such as the influenza, tetanus, and diphtheria vaccines. It is also found in antitoxins and immunoglobulins. Thimerosol is a mercury-containing organic compound. Lanolin is from the sebum of sheep. Ethylenediamine dichloride is a stabilizer in topical creams, medicines, dyes, insecticides, and fungicides and was previously found in nystatin cream. Triclosan is an antibacterial agent found in soap, shampoo and mouthwash. Gluteraldehyde is a cold sterilizing solution used for medical and dental equipment.
38- Gallstones are associated with:
A. Erythropoietic protoporphyria
B. Hepatoerythropoietic porphyria
C. Variegate porphyria
D. Coproporphyria
E. Harderoporphyria
►A
Gallstones and liver failure can complicate erythropoietic protoporphyria.
39- Antibodies against type VII collagen are seen in:
A. Epidermolysis bullosa simplex
B. Pemphigus erythematosus
C. Cicatricial pemphigoid
D. Epidermolysis bullosa acquisita
E. Bullous pemphigoid
►D
Type VII collagen is present in the basement membrane of stratified squamous epithelia in the anchoring fibrils. It is the target antigen in several blistering disease including epidermolysis bullosa acquista, bullous lupus erythematosus. Mutated collagen 7 occurs in dominant and recessive dystrophic epidermolysis bullosa.
40- The dimethylglyoxime test is used to detect the presence of:
A. Gold
B. Silver
C. Mercury
D. Nickel
E. Latex
►D
1% dimethylglyoxime is added to to the metal. If a red precipitate forms, there is >1:10000 nickel content.
41 -Characteristic eosinophilic abscesses are seen in:
A. Bullous drug
B. Pemphigus vegetans
C. Herpes gestationis
D. Incontinentia pigmenti
E. Paraneoplastic pemphigus
►B
Eosinophilic abscesses with minimal to no spongiosis in a hyperplastic epidermis are characteristic of pemphigus vegetans.
Circulating autoantibodies to type XVII collagen are most characteristic of which disease?
A. Epidermolysis bullosa accquisita
B. Herpes gestationis
C. Pemphigus vulgaris
D. Pemphigus foliacious
E. Paraneoplastic pemphigus
►B
Type XVII collagen or BPAG2 is a transmembrane protein found in the hemidesmosome. Autoantibodies to type XVII collagen are important in the pathogenesis of cicatricial pemphigoid, bullous pemphigoid, and herpes gestationis.
43 -Patients with this disorder may develop exaggerated reactions to insect bites:
A. Chronic lymphocytic leukemia
B. Bullous pemphigoid
C. Lupus erythematosus
D. Atopic dermatitis
E. Incontinentia pigmenti
►A
Patients with chronic lymphocytic leukemia may develop exaggerated reactions to insect bites, including bullous reactions.
- What is the enzyme defect in Gunther’s disease?
A. Porphobilinogen deaminase
B. Uroporphyrinogen synthetase III
C. Uroporphyrinogen decarboxylase
D. Ferrochetalase
E. Protoporphyrinogen oxidase
►B
Gunther’s disease (also known as congenital erythropoietic porphyhria) is caused by a defect in uroporphyrinogen synthetase III, the enzyme which responsible for the conversion of hydroxymethylbilane to uroporphyriogen III. Patients present with red teeth and immediate photosensitivy during infancy. There is severe photophobia and late skin manifestations include mutilating scarswith scarring alopecia, and sclerodermoid changes.
-Which pair is incorrect?
A. Desmoglein 1 : 160 kDa
B. Desmoplakin I : 250 kDa
C. Type VII collagen : 290 kDa
D. Type XVII collagen: 180 kDa
E. Envoplakin : 190 kDa
►E
Envoplakin is 210 kDa. Periplakin is 190 kDa.
46- A 20-year-old female presents with an allergic contact dermatitis to a perfume containing Lily of the valley. What is the causative allergen?
A. Cinnamic acid
B. Vanillin
C. Hydroxycitronellal
D. Atranorin
E. Evernic acid
►C
The main allergen in Lily of the valley, which is found in perfumes, soaps, cosmetics, eye cream and aftershaves, is hydroxycitronellal (synthetic). Cinnamic acid and vanillin are present in Balsam of Peru, while atranorin and evernic acid are allergens in oak moss absolute.
47- Bullous pemphigoid antigen 1 (BPAg1) is a member of this family:
A. Cadherin
B. Integrin
C. Intermediate filament
D. Plakin
E. Selectin
►D
The plakin family includes desmoplakin I and II, BPAg1, envoplakin, periplakin.
48 -In the liver, the rate limiting step in the porphyria pathway is mediated by the enzyme:
A. Ferrochetalase
B. ALA dehydratase
C. ALA synthase
D. Uroporphyrinogen decarboxylase
E. Porphobilinogen deaminase
►C
ALA synthase mediates the first and rate-limiting step in the heme synthesis pathway. This step occurs in the mitochondria and allows for the conversion of Succinyl coA + glycine to delta aminolevilinic acid.
49- Which steriod screening agent should be used when an allergic contact dermaititis is suspected to hydrocortisone?
A. Glutaral
B. Tixocortol-21-pivalate
C. Budesonide
D. Hydrocortisone-17-butyrate
E. Benzalkonium chloride
►B
Tixocortol-21-pivalate is a group A steroid and screens for allergies to hydrocortisone, prednisone, and methylprednisolone. Budesonide screens for groups B and D steroids, and hydrocortisone-17- butyrate screens for group D steroids.
50- Common causes of drug-induced linear IgA:
A. Vancomycin
B. Penicillin
C. Cephalosporins
D. Captopril
E. All of these answers are correct
►E
Linear IgA disease that is induced by drugs is most commonly secondary to vancomycin. Other implicated drugs include other antibiotics and captopril.
- A- patient has desquamative lesions around the mouth and is diagnosed with antiepiligrin cicatricial pemphigoid. The autoantibodies are:
A. Anti-L-332 IgG autoantibodies
B. Anti-32 autoantibodies
C. Anti-IgM autoantibodies
D. Anti-332 autoantibodies
E. Anti-45 IgG autoantibodies
►A
Cicatricial pemphigoid affects the mucous membrane and genital areas. Anti-L-332 IgG autoantibodies are very specific for antiepiligrin cicatricial pemphigoid.
52- The vector of fogo selvagem may be:
A. Triatoma
B. Simulium
C. Cimex
D. Ornithodorus
E. Mus
►B
Fogo selvagem is considered to be an endemic form of pemphigus foliaceus, first described in Brazil, in rural areas where Simulium (black fly) is often found. Subsequently, other rural South American areas have had clusters of affected patients.
– Patients with latex allergy are LEAST LIKELY to develop a reaction to:
A. Cashew
B. Avocado
C. Chestnut
D. Banana
E. Kiwi
►A
Although rare, cross-reactivity in latex-allergic patients has been demonstrated to banana, kiwi, avocado, passion fruit, and chestnut. Cross-reaction to cashew has NOT been reported.
54- Which pair is incorrect?
A. Wrinkle-resistance : formaldehyde
B. Chewing gum : colophony
C. Parabens : artichokes
D. Glyceryl thioglycolate : acid permanent wave
E. Permethrin : chrysanthemum
►C
Wrinkle-resistant clothing is treated with formaldehyde. Chewing gum contains rosin (colophony). Parabens are preservatives. Artichokes are a member of the family Asteraceae (formerly Compositae). Glyceryl thioglycolate and methylchloroisothiazolinone are found in acid permanent wave products. Permethrins are synthetic pyrethroids that are similar to pyrethrins derived from the Asteraceae family. Permethrins can cross-react with allergy to chrysanthemums.
55- Gap junctions consist of:
A. Laminin
B. Plectin
C. Uncein
D. Filagrin
E. Connexins
►E
Gap junctions are protein channels that allow for communcation between cells. A connexon of one cell is joined to that of an adjacent cell to form an intercellular channel consisting of 12 connexin subunits. Each intercellular channel provides a channel that interconnects the cytoplasm of the apposed cell directly and permits the passage of ion and other small molecules between adjacent cells. These protein channels that make up the gap junctions consist of two hemi-channels or connexons. One connexon resides in the membrane of one cell and it aligns and joins the connexon of the neighboring cell, forming a continuous aquaeous pathway by which these ions and small molecules can freely pass from one cell to the other. Each hemi channel or connexon consist of six proteins ( hexamer) called connexins.
56- This is derived from Myroxylon pereirae:
A. Thimerosol
B. Aniline dyes
C. Balsam of Peru
D. Colophony
E. Thiuram
►C
Balsam of Peru is derived from the Myroxylon pereriae tree. Thimerosal is a questionable cause of allergic contact dermatitis; it is found in vaccines and contact lens solutions.
57- Which pair is incorrect?
A. Dermatitis herpetiformis : granular IgA
B. Lichen planus : linear C3
C. Bullous pemphigoid : linear C3
D. Systemic lupus erythematosus : linear IgG
E. IgA pemphigus: intercellular IgA
►B
The colloid bodies in lichen planus can trap IgM and C3; this can be seen on DIF as “globs.” There is no linear pattern.
58- Patients with epidermolysis bullosa acquisita have:
A. A defect in plectin
B. A defect in collagen XVII
C. Antibodies to collagen XVII
D. Antibodies to collagen VII
E. A defect in laminin 5
►D
Epidermolysis bullosa acquisita (EBA) classically presents in adulthood as noninflammatory trauma-induced bullae that heal with scarring, especially on the hands and feet. Histology shows a subepidermal blister (usually pauci-inflammatory); DIF shows linear IgG at the basememt membrane; salt-split skin shows antibodies at the “floor”. Patients have antibodies to type VII collagen.
59- Antibodies to which antigen are most likely responsible for this disease?
A. Bullous pemphigoid antigen II
B. Desmoglein I
C. Desmocollin
D. Keratin 5
E. Plakoglobin
►A
The clinical appearance of tense bullae and urticarial plaques is suggestive of bullous pemphigoid. Bullous pemphigoid antigen II is a transmembrane protein in the hemidesmosome. Antibodies to this antigen are pathogenic in bullous pemphigoid.
60 -Patients with Duhring’s disease are most likely to have:
A. Mutations in plectin
B. Mutations in laminin 5
C. Mutations in transglutaminase I
D. Antibodies to transglutaminase 3
E. Antibodies to BPAg2
►D
Duhring’s disease is also known as dermatitis herpetiformis. Antibodies are found to transglutaminase 3, and the direct immunofluorescent studies show granular IgA and C3 in the dermal papillae. Mutations in plectin are found in EBS with muscular dystrophy. Mutations in laminin 5 are found in patients with JEB,Herlitz type. Mutations in transglutaminase I are found in pateints with lamellar ichthyosis and non bullous congenital ichthyosiform erythroderma.
61- Direct immunofluorescent studies in chronic bullous disease of childhood is most likely to show:
A. Iga depostion in the superficial blood vessels
B. Linear IgG at the basement membrane
C. Linear IgA at the basement membrane
D. Granular IgG
E. Linear C3 at the basement membrane
►C
Chronic bullouse disease of childhood is believed to be a variant of linear IgA bullous disease, since disease are characterized by antibodies to the 97kDa antigen that is a part of BPAg2. Children present with extremely pruritic blisters in circular arrangements. Pathology shows a subepidermal bullae with neutrophils at the dermo-epidermal junction; the DIF shows IgA deposition at the basement membrane in a linear fashionl.
62- The primary autoantigen in pemphigoid gestationis is
A. Desmoplakin
B. BPAG1
C. BPAG2
D. Plakoglobin
E. Anchoring fibrils
►C
Herpes gestationsis is an autoimmune blistering disorder of pregnancy. It is characterized by urticarial plaques and tense bullae. Antibodies to BPAG2 are thought to form as a result of an aberreant response to MHC antigens on the placenta. The maternal health is generally not affected, but infants are more commonly born premature. Remission is common following delivery, but it may recur with OCP’s, menstruation, and subsequent pregnancies.
63- Papillary dermal deposits of IgA and a papillary dermal infiltrate of neutrophils is diagnostic of:
A. Sweet’s syndrome
B. Leukocytoclastic vasculitis
C. Dermatitis herpetiformis
D. Linear IgA dermatosis
E. Bullous pemphigoid
►C
Dermatitis herpetiformis is an uncommon chronic, pruritic papulovesicular dermatitis occurring most commonly in young to middle-aged adults. Common sites of predilection include the buttocks, elbows, knees, scapula and scalp. Typical histologic features include accumulation of neutrophils at the tips of dermal papillae, sometimes admixed with eosinophils. Direct immunoflorescence (DIF) reveals granular deposits of IgA within the dermal papillae. As the name implies, linear IgA disease is characterized by linear IgA deposition along the basement membrane zone with DIF in 100% of cases. The pattern of direct immunoflorescence in bullous pemphigoid is linear C3 deposition at the dermoepidermal junction in nearly 100% of cases and IgG in 65-95% of cases. Sweet’s syndrome is not characterized by a pattern with DIF. Under light microscopy, a dense perivascular infiltrate of neutrophils is seen assuming a bandlike pattern throughout the papillary dermis associated with prominent dermal edema. Leukocytoclastic vasculitides are characterized by a perivascular neutrophilic infiltration with karyorrhexis, leukocytoclasis, fibrinoid degeneration, and endothelial swelling.
64- Bullous lesions are most often seen in:
A. Congenital syphilis
B. Primary syphilis
C. Secondary syphilis
D. Tertiary syphilis
E. All of these answers are correct
►A
Congenital syphilis, can occasionally present with bullae. There are rare case reports of secondary syphilis having bullae however, this is much less common than congenital syphillis.
65- Which association is incorrect?
A. Epidermolysis bullosa acquisita : inflammatory bowel disease
B. Dermatitis herpetiformis : small bowel lymphoma
C. Paraneoplastic pemphigus : Castleman‟s
D. Herpes gestationis : menopause
E. Porphyria cutanea tarda : hemochromatosis
►D
Herpes gestationis is an immunoblistering disease of pregnancy. Unlike pruritic urticarial papules and plaques of pregnancy, it recurs with successive pregnancies. It is associated with Grave’s disease and choriocarcinoma.
- A- 35 year-old dentist presents with tingling in his fingertips. What allergen is most likely to cause this dermatitis?
A. Methyl methacrylate
B. Paraphenylenediamine
C. Colophony
D. Thiuram mix
E. Ethylenediamine dihydrochloride
►A
Methyl methacrylate is found in synthetic resins, dentures, artificial, nail adhesives, and acrylic bone cement. This allergen may penetrate through the gloves to the fingertips and most often affects the first three fingers. In addition to dermatitis, it also causes a peripheral neuropathy.
67- Which of the following agent(s) has been most effective in treating severe ocular cicatricial pemphigoid?
A. Cyclophosphamide
B. Mycophenolate mofetil
C. Cyclophosphamide + corticosteroids
D. Cyclosporin
E. Azathioprine
►C
Cicatricial pemphigoid is a heterogeneous group of subepithelial blistering diseases involving the mucous membranes and skin. The treatment of cictracial pemphigoid is predicated upon the extent, severity, and location of disease. Most regimens used are empiric and are based on clinical experience. With severe ocular involvement, most experts recommend aggressive treatment with the combination of cyclophosphamide and steroids.
c
68- What is the antigen found in the variant of cicatrical pemphigoid that is as sociated with internal malignancies?
A. BPAg1
B. BPAg2
C. Type VII collagen
D. Epiligrin
E. Keratins 5 & 14
►D
Individuals with anti-epiligrin cicatricial pemphigoid are thought to be at an increased risk for solid internal malignancies.
69- Dermatitis herpetiformis presents as grouped papules and vesicles symmetrically and is associated with:
A. HLA-DQ2
B. HLA-Dw2
C. HLA-3 and HLA-4
D. HLA-DR3
E. HLA23Q
►A
Dermatitis herpetiformis is associated with HLA-DQ2 and has a positive IgA granular pattern in the dermal papilla on direct IF and a negative indirect IF.
70- Which of the following concerning Degos’ Disease is true?
A. After undergoing multiple stages, it resolves without scarring
B. It affects women more than men
C. Gatrointestinal involvement is a poor prognosis
D. Glucocorticoids are standard of treatment
E. Lab results indicate a low plasma fibrinogen level and decreased platelet aggregation
►C
Dego’s Disease (Malignant Atrophic Papulosis): It most frequently affects men and is a potentially fatal obliterative arteritis. After undergoing multiple stages, the patient is left with varicelliform scars. Later, anemic infarcts involve the intestines to produce acute abdominal symptoms of epigastric pain, fever, and hematemesis. Death is usually due to fulminating peritonitis caused by multiple perforations of the intestines. GI involvement is a poor prognosis. Lab results indicate a
high plasma fibrinogen level and increased platelet aggregation. Administration of corticosteroids has not been beneficial.
71- Paraneoplastic pemphigus:
A. Is characterized by a pathognomonic 250 kDa antigen
B. Is most often seen in association with lung cancer
C. Remits with excision of the neoplasm
D. May be caused by a benign neoplasm
E. All of these answers are correct
►D
Paraneoplastic pemphigus can be caused by lymphoma as well as other malignancies. It can also be secondary to benign thymomas and Castleman’s disease. Numerous antigens have been found, including desmoplakin I and II. Desmoplakin I and II may be antigenic in Stevens-Johnson syndrome. It may not remit after treatment of the neoplasm.
-Which neoplasm is the most common cause of paraneoplastic pemphigus?
A. Thymoma
B. CLL
C. Castleman’s disease
D. Retroperitoneal sarcoma
E. Non-Hodgkin’s lymphoma
►E
All of the above have been associated with paraneoplastic pemphigus with non-Hodgkin’s lymphoma being the most common. Castlemans’s disease is most common in children with paraneoplastic pemphigus.
73- Which of the following is true of herpes gestationis?
A. Demonstrates antibodies to the C-terminal domain of BPAg2
B. Has higher frequency in females with HLA-DQ2
C. Is associated with Grave’s disease
D. Usually occurs in the first trimester of pregnancy
E. Shows subepidermal bullae mostly with neutrophils
►C
Herpes gestationis is associated with Grave’s disease. It is more common with patients with HLA- DR3 and DR4 and most often occurs between 4-7 months of pregnancy. The antibodies are against the NC 16-A portion of BPAg2. Histology shows subepidermal bullae with mostly eosinophils.
74- In penicillamine-induced pemphigus, the split is most often:
A. Subcorneal
B. Intraspinous
C. Suprabasal
D. Intraepidermal and subepidermal
E. Subepidermal
►A
Penicillamine is the most common cause of drug-induced pemphigus, and the split is more often subcorneal (pemphigus foliaceus-like) than suprabasal (pemphigus vulgaris-like).
75- Which of the following is LEAST LIKELY to cross react with Toxicodendron plant dermatitis?
A. Japanese lacquer tree
B. Cashew nut
C. Mango rind
D. Gingko tree
E. Kiwi
►E
The Toxicodendron group of plants is the #1 cause of contact dermatitis in North America. This group of plants includes poison ivy, poison oak, and poison sumac. Because the Toxicodendron plants belong to the Anacardiaceae family, cross reactions can occur with related plants and substances such as braqzilian pepper, cashew nut, cashew oil, gingkgo tree, Indian marking nut, Japanese lacquer tree, mango, and Rengas tree. Kiwi can cross react with patients who are latexallergic.
105- What is the most common site of involvement of this autoimmune blistering disease?
A. Oral mucosa
B. Eyes
C. Skin
D. Genitalia
E. Nasopharyngeal mucosa
►A
Cicatricial pemphigoid is a heterogeneous group of diseases with characteristic involvement of the oral mucosa, eyes, skin. Rarely, it can also involve the nasopharyngeal mucosa, external genitalia, esophagus, and anus. The oral mucosa is the most common site of involvement.
166- The picture shown is considered to be diagnostic for what type of epidermolysis bullosa
A. Junctional epidermolysis bullosa- Non Herlitz type
B. Junctional epidermolysis bullosa- Herlitz type
C. Dowling-Meara form of Epidermolysis Bullous simplex
D. Dominant dystrophic epidermolysis bullosa
E. Recessive dystrophic epidermolysis bullosa
►E
The picture is shown is known as “mitten hands” and is diagnostic for recesseive type of dystrophic epidermolysis bullosa. RDEB have the Hallopeau-Siemens type, a severe life-altering bullous disease characterized by widespread dystrophic scarring and deformity and by severe involvement of mucous membranes. Much less commonly, RDEB may manifest as the non- Hallopeau-Siemens types, a mild localized form (mitis), and an inverse variant (recessive epidermolysis inversa). In the Hallopeau-Siemens form of RDEB, erosions and blisters are usually manifested at or shortly after birth. Blisters may appear to occur spontaneously, but most seem to arise at sites of pressure or trauma. Nikolsky sign is often positive. The hands and lower aspects of the legs are particularly susceptible to severe blistering and scarring. The fingers and toes may become fused, with resultant pseudosyndactyly, in which the digits become bound together by a glove-like epidermal sac, with resulting claw-like clubbing or mitten-like deformities as shown in the image.
183 - A woman in her 2nd trimester of pregnancy presents to clinic with urticarial plaques and papules around her umbilicus, chest and extremities. Tense vesicles are present within a few of the erythematous plaques. This woman”s condition is most commonly associated with:
A. Lymphoma
B. Multiparity
C. Grave”s Disease
D. Inflammatory Bowel Disease
E. Lupus
►C
Herpes gestationis (HG) typically occurs in the second or third trimester, and clinically presents as urticarial papules and plaques around the umbilicus which progress to involve the rest of the body. HG has been associated with Grave’s disease. Hormonal factors influence the disease manifestation. This condition can be seen in pregnant women, menstruating women, and women taking oral contraceptives.
184- The best substrate for pemphigus vulgaris for indirect immunofluorescent testing is:
A. Monkey esophagus
B. Rat bladder
C. Salt split skin
D. Guinea pig esophagus
E. Rat liver
►A
Pemphigus vulgaris present as flaccid bullous lesions and can affect the mucous membrane. The best substrate for pemphigus vulgaris is monkey esophagus.
189 -A 46-year-old man presents with desquamation of the bilateral hands. He reports this has been present since childhood. There are no associated systemic findings. Which enzyme is most likely implicated?
A. Tissue transglutaminase I
B. Tissue transglutaminase III
C. Tissue transglutaminase V
D. Lysyl oxidase
E. Lysyl hydroxylase
►C
Tissue transglutaminases are calcium dependent enzymes implicated in several dermatologic diseases. Transglutaminase I is faulty in lamellar icthyosis and non-bullous congenital icthyosiform erythroderma, while transglutaminase III is implicated in dermatitis herpetiformis.
Transglutaminase V mutations have been associated with keratolysis exfoliativa perstans. Lysyl oxidase and lysyl hydroxylase are implicated in Ehlers-Danlos Syndrome.
