Chapter 6. Immunologic Disorders Flashcards
Darier’s sign
urticaria and erythema observed on and around a macule after stroking the lesion
diffuse cutaneous mastocytosis
- who gets it
- what is its typical course
skin variant, typical in pediatric patients (normally <3), resolves without progress to systemic mastocytosis
urticaria pigmentosa (UP)
discrete yellow-brown macular-papular or nodular plaque-like lesions with characteristic Darier’s sign
diffuse cutaneous mastocytosis (DCM)
diffuse yellow-brown thickened skin, no discrete lesion, usually occurs in patients younger than 3 years of age
mastocytoma
solitary reddish brown skin lesion that usually presents in the first 3 months of life and frequently resolves on its own
telangiectasia macularis eruptiva perstans
macular telangiectasia characterized by increased mast cells around dilated capillaries and venules. normally found in adults
review “Classification of Systemic Mastocytosis”
what is the activating mutation in systemic mastocytosis
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)
what is molecule is required for mast cell survival
stem cell factor - ligand for c-KIT
review “other symptoms of mastocytosis”
where is the most common site of mast cell infiltration and most useful biopsy site
how are mast cells identified
bone marrow
identified by immunohistochemical staining for CD117 (c-kit) and CD2 and or CD25
what are the diagnostic criteria for cutaneous mastocytosis
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
what lab should every patient with severe anaphylaxis following a hymenoptera sting get
baseline tryptase (screen for mastocytosis)
What are the major criteria for diagnosis of Systemic Mastocytosis
biopsy with multifocal, dense infiltrates of mast cells (>15 mast cells in aggregates)
What are the minor criteria for diagnosis of systemic mastocytosis
- biopsy with more than 25% of mast cells having spindle-shaped or atypical morphology
- detection of c-KIT D816V mutation in bone marrow or extracutaneous organ
- expression of CD2 and/or CD25 on CD117+ mast cells
- total serum tryptase > 20 ng/mL
what are major/minor paths to mastocytosis dx
1 major + 1 minor
–or–
3 minor
MCAS
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
what is monoclonal mast cell activation syndrome
distinguished from MCAS by the presence of the c-KIT D816V mutation, but does not meet full WHO criteria for SM
what are lifestyle treatments for MCAS/mastocytosis
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
What cytokine is required for eosinophilic infiltration of the esophagus
IL-5
What cytokine, important in EoE, is induced by IL-13
eotaxin 3
What is overexpressed in EoE biopsy tissue (besides eosinophils themselves)
TSLP
When should biopsy be done for EoE
Ideally, 8 weeks after a PPI to help exclude PPI-responsive esophageal eosinophilia
Whats the deal with skin prick testing in EoE
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
X linked SCID is associated with defects in the so-called “common gamma chain”. What ILs are affected with the common gamma chain
IL-2, IL-4, IL-7, IL-9, IL-15, IL-21
review features of VCFS/DiGeorge
what is the clinical triad and mutation in XLP (X-linked lymphoproliferative syndrome)
fatal mono, dysgammaglobulinemia, lymphoproliferative disorders
mutation in SLAM-associated protein (SAP gene)
Kabuki syndrome
mutation of KMT2D –> hypogammaglobulinemia + cleft palate, abnormal facies, developmental delay
think Kabuki theater
what is CVID + thymoma called
Good syndrome –> red cell aplasia, neutropenia, and chronic diarrhea
what flow cytometry changes are associated with hematologic autoimmune complications of CVID
low switched memory B cells
