Flashcards in Chapter 26 - Eosinophilic Dermatoses Deck (49):
Is the histologic dye eosin basic or acidic?
*Eosinophils were named this way because eosin binds to them. This is because eosinophils contain basic intracellular granules.
What molecule is constitutively expressed by eosinophils that binds to vascular cell adhesion molecule 1 (VCAM-1) on endothelial cells?
Very late antigen 4 (VLA-4)
What is the name of the protein that comprises the main constituent of eosinophilic granules?
Major basic protein 1 (MBP1)
True or false: major basic protein 1 (MBP1) released from eosinophil granules stimulates the release of histamine from basophils.
True or false: granuloma faciale can occur on non-facial skin.
True; although when this occurs, there is usually also involvement of the face
List the systemic diseases associated with granuloma faciale.
There are none
True or false: a Grenz zone is typically seen in biopsies of granuloma faciale.
What condition is at the top of the clinical (and histological!) differential diagnosis for extra-facial granuloma faciale?
Erythema elevatum diutinum (EED)
*EED has a predilection for skin overlying joints
**EED typically lacks a Grenz zone
What is first-line therapy for granuloma faciale?
*Granuloma faciale is often very treatment resistant
**Oral dapsone or clofazimine can be tried
What population is most commonly affected by granuloma faciale?
White middle-aged men
What is the most common systemic complaint in patients with Well's syndrome?
Malaise, but fever can also occur (in less than 25% of cases)
True or false: in patients with Well's syndrome (eosinophilic cellulitis), eosinophils are present both peripherally and in the biopsy tissue.
True or false: flame figures are specific to Well's syndrome (eosinophilic cellulitis).
False; they can also be seen in arthropod bites and stings, mastocytomas, scabies, prurigo nodularis, and eczema
What are the two most common clinical mimics of Well's syndrome?
Bacterial cellulitis and erysipelas
What is first-line therapy for Well's syndrome?
Oral steroids; there's usually a dramatic improvement in a few days
*Tapering of the steroid over one month is usually well tolerated
True or false: the FIP1L1-PDGFRA fusion gene responsible for hypereosinophilic syndrome is over 100 times more sensitive to imatinib than the BCR-ABL kinase fusion gene responsible for some cases of CML.
True or false: patients with the FIP1L1-PDGFRA positive hypereosinophilia syndrome are almost always female.
False; they're almost always male (with a few female case reports)
What is the major cause of death in patients with hypereosinophilic syndrome?
True or false: all cases of hypereosinophilic syndrome are related to FIP1L1-PDFRA fusion genes, and will thus be sensitive to imatinib.
False; only some cases are due to this fusion gene, and thus, not all patients will be appropriate candidates for imatinib
What are some of the products of eosinophil during inflammation?
Reactive oxygen intermediates, enzymes, garnule-derived proteins, lipid mediators, cytokines, chemokines
What are 2 members of the C-C chemokine gene superfamily that act as chemoattractants for eosinophils?
1. Eotaxin family; 2. regulated on activation normal T cell expressed and secreted (RANTES) family
Are eotaxins 1-3 chemotactic for eosinophils only?
Are RANTES chemotactic for eosinophils only?
No. They are also chemotactic for monocytes, T lymphocytes, NK cells, basophils, NOT neutrophils
Which of the chemoattractants are stronger at inducing eosinophil function? Eotaxin 1, 2, 3 or RANTES?
Eotaxins 1 and 2 > 3 > RANTES
Which epidermal and dermal cells produce which chemoattractants?
Dermal fibroblasts produce Eoataxin 1-3, RANTES; keratinocytes produce RANTES
Give one example of an integrin that helps eosinophils transmigrate across blood vessels.
Very late antigen 4 (VLA-4); its corresponding ligand is vascular cell adhesion molecule 1 (VCAM-1)
Which integrin expression is critical for eosinophil effector function, eg. degranulation?
In addition to T cells, what other cells also produce cytokines that contribute to eosinophil activation?
Mast cells, NK cells, eosinophils, all via cytokines
How are eosinophil granules released?
Cytolytic degranulation, piece-meal degranulation, regulated secretion
What are the components of eosinophil granules?
1) Major basic protein 1 (MBP1), direct damage of helminths, mammalian cells and tissues; also stimulate histamine release from basophils; induce neutrophil release of superoxide and lysozyme. 2) Eosinophil cationic protein (ECP/RNase3), potent toxin for parasites. 3) Eosinophil derived neurotoxin (EDN/RNase2), neurotoxin, antiviral activity against RNA viruses.
In addition to MBP1, ECP, EDN, what are other products of eosinophil that help in the anti-microbial/iflammatory response?
Eosinophil peroxidase (EPO) = hydrogen peroxide kills microorganisms; also a platelet agonist causing serotonin release and increase clotting
What is the nasal mucosal variant of granuloma faciale?
Eosinophilic angiocentric fibrosis
What might you see on histology for granuloma faciale?
Dermal infiltrate made up of eosinophil and other lymphocytes, neutrophils, plasma cells; Grenz zone; normal epidermis
What are flame figures?
Hallmark, but not specific for Well's syndrome. On histology, eosinophilic staining figures consisting of non-necrobiotic collagen fibers coated with eosinophil granules
What is the diagnostic criteria for hypereosinophilic syndrome (HES)?
1. Peripheral blood eosinophilia (ie. >1500 eosinophils/uL) x 6mths -or- <6mths + organ damage; 2. no other cause of eosinophilia; 3. organ involvement
What are some of the subtypes of HES?
Myeloproliferative type (FIP1L1-PDGFRA fusion gene mutation), lymphoproliferative type, eosinophilic vasculitis, episodic angioedema with eosinophilia (EAE), NERDS syndrome (nodules, eosinophilia, rheumatism, dermatitis, swelling)
What are possible complications of HES according to their subtypes?
Generally speaking, all HES subtypes can cause eosinophilic endomyocardial disease from prolonged eosinophilia, and embolic events. The leading cause of death is CHF, followed by sepsis. For the myeloproliferative type - leukemia; for the lymphoproliferative type - lymphoma.
What is the 1st line treatment for those with FIP1L1-PDGFRA fusion gene mutation vs those without this mutation?
Imatinib mesylate (Gleevec) vs prednisone
True or false: granuloma faciale has been associated with systemic disease
True or false : granz zone a leukocytoclastic vasculitis are present in granuloma faciale
What is the first line of treatment for granuloma faciale
Intralesional triamcinolone 2.5-5 mg/ml
What is characteristic about well's syndrome pathology?
* not specific
What are the possible triggers for well's syndrome?
What are the most common mimics of well's syndrome!
What is the first line of treatment for well's syndrome?
Prednisone 10-80 mg daily.
Tapered over 1 month
What cytokine is mainly produced in lymphocytic form of HES?
What is NERDS syndrome
What is the major cause of death in HES?
CHF from restrictive cardiomyopathy