Chapter 6. Immunologic Disorders

Question 1

Darier’s sign

Answer 1

urticaria and erythema observed on and around a macule after stroking the lesion

Question 2

diffuse cutaneous mastocytosis

• who gets it
• what is its typical course

Answer 2

skin variant, typical in pediatric patients (normally <3), resolves without progress to systemic mastocytosis

Question 3

urticaria pigmentosa (UP)

Answer 3

discrete yellow-brown macular-papular or nodular plaque-like lesions with characteristic Darier’s sign

Question 4

diffuse cutaneous mastocytosis (DCM)

Answer 4

diffuse yellow-brown thickened skin, no discrete lesion, usually occurs in patients younger than 3 years of age

Question 5

mastocytoma

Answer 5

solitary reddish brown skin lesion that usually presents in the first 3 months of life and frequently resolves on its own

Question 6

telangiectasia macularis eruptiva perstans

Answer 6

macular telangiectasia characterized by increased mast cells around dilated capillaries and venules. normally found in adults

Question 7

review “Classification of Systemic Mastocytosis”

Answer 7

Question 8

what is the activating mutation in systemic mastocytosis

Answer 8

c-kit (KIT D816V)

• increased mast cell numbers due to constitutive activation of KIT tyrosine kinase signaling and aberrant expression of antiapoptotic proteins (Bcl-1 and Bcl-2)

Question 9

what is molecule is required for mast cell survival

Answer 9

stem cell factor - ligand for c-KIT

Question 10

review “other symptoms of mastocytosis”

Answer 10

Question 11

where is the most common site of mast cell infiltration and most useful biopsy site

how are mast cells identified

Answer 11

bone marrow

identified by immunohistochemical staining for CD117 (c-kit) and CD2 and or CD25

Question 12

what are the diagnostic criteria for cutaneous mastocytosis

Answer 12

focal dense mast cell infiltrates (>15 mast cells per cluster) or diffuse mast cell infiltrates (>20 mast cells/hpf) on skin biopsy

c-KIT D816V mutation

Question 13

what lab should every patient with severe anaphylaxis following a hymenoptera sting get

Answer 13

baseline tryptase (screen for mastocytosis)

Question 14

What are the major criteria for diagnosis of Systemic Mastocytosis

Answer 14

biopsy with multifocal, dense infiltrates of mast cells (>15 mast cells in aggregates)

Question 15

What are the minor criteria for diagnosis of systemic mastocytosis

Answer 15

1. biopsy with more than 25% of mast cells having spindle-shaped or atypical morphology
2. detection of c-KIT D816V mutation in bone marrow or extracutaneous organ
3. expression of CD2 and/or CD25 on CD117+ mast cells
4. total serum tryptase > 20 ng/mL

Question 16

what are major/minor paths to mastocytosis dx

Answer 16

1 major + 1 minor

–or–

3 minor

Question 17

MCAS

Answer 17

for patients who have a variety of symptoms suggestive of mast cell activation, but who fail to meet the WHO criteria for diagnosis

tryptase = 120% of baseline + 2 with exacerbation of symptoms

so, patient with baseline tryptase of 10 –> 1.20(10)+2 = 14 would meet criteria

Question 18

what is monoclonal mast cell activation syndrome

Answer 18

distinguished from MCAS by the presence of the c-KIT D816V mutation, but does not meet full WHO criteria for SM

Question 19

what are lifestyle treatments for MCAS/mastocytosis

Answer 19

avoid triggers (alcohol, NSAIDs, narcotics, intense exercise, stinging insects)

antihistamines (first and second generation, H2 blockers)

disodium cromoglycate (gastrochrom)

epinephrine

topical steroids for UP or DCM

cytoreductive treatment –> imatinib (Gleevac) with aggressive systemic symptoms but who lack the c-KIT mutation

DEXA scanning and calcium supplementation

treat other hematologic disorders

Question 20

What cytokine is required for eosinophilic infiltration of the esophagus

Answer 20

IL-5

Question 21

What cytokine, important in EoE, is induced by IL-13

Answer 21

eotaxin 3

Question 22

What is overexpressed in EoE biopsy tissue (besides eosinophils themselves)

Answer 22

TSLP

Question 23

When should biopsy be done for EoE

Answer 23

Ideally, 8 weeks after a PPI to help exclude PPI-responsive esophageal eosinophilia

Question 24

Whats the deal with skin prick testing in EoE

Answer 24

NPV is high for less common foods (potato, chicken, peanut, beef, pork, corn)

NPV pretty good (80-90%) for egg, wheat, and soy

NPV <30% for milk

PPV is good for milk (86%) but bad for everything else

Question 25

X linked SCID is associated with defects in the so-called “common gamma chain”. What ILs are affected with the common gamma chain

Answer 25

IL-2, IL-4, IL-7, IL-9, IL-15, IL-21

Question 26

review features of VCFS/DiGeorge

Answer 26

Question 27

what is the clinical triad and mutation in XLP (X-linked lymphoproliferative syndrome)

Answer 27

fatal mono, dysgammaglobulinemia, lymphoproliferative disorders

mutation in SLAM-associated protein (SAP gene)

Question 28

Kabuki syndrome

Answer 28

mutation of KMT2D –> hypogammaglobulinemia + cleft palate, abnormal facies, developmental delay

think Kabuki theater

Question 29

what is CVID + thymoma called

Answer 29

Good syndrome –> red cell aplasia, neutropenia, and chronic diarrhea

Question 30

what flow cytometry changes are associated with hematologic autoimmune complications of CVID

Answer 30

low switched memory B cells