40 - Eosinophilic Diseases Flashcards
Eosinophils develop in the bone marrow from multipotential, stem cell-derived _____+ myeloid progenitor cells
CD34
Stimulatory cytokines and growth factors for eosinophils
IL-3
GM-CSF
IL-5
Most selective eosinophil-active cytokine, but is relatively late-acting
IL-5
Mature eosinophils are slight (smaller/larger) than neutrophils
Larger
Five highly basic proteins found within the eosinophil’s cystoplasmic granules
Major basic protien-1
Major basic protien-2
Eosinophil-derived neurotoxin/Ribonuclease 2
Eosinophil cationix protien/Ribonuclease 3
Eosinophil peroxidase
Other types of the eosinophil’s cystoplasmic granules
Primary granules
Small granules
Secretory vesicles
Characteristically found in asthmatic sputum and in feces from patients with helminth infections or eosinophilic gastroenteritis
Charcot-Leyden crystal protein or galectin-10
Charcot-Leyden crystal protein can also be found in
Neutrophils
Charcot-Leyden crystal protein is contained in
Primary granules
More common in immature eosinophilic promyelocyes
Primary granules
Contain acid phosphatase and arylsulfatase
Small granules
Also referred to as tubulovesicular structures or microgranules, are characterized by their small, dumbbell-shaped appearance and their albumin content
Secretory vesicles
Most abundant granules in number
Secretory vesicles
Principal stores of arachidonic acid; aso contain the enzymes cyclooxygenase, 5- and 15-lipoxygenase
Lipid bodies
Y/N: Eosinophils are present in blood permanently.
No - transiently, ranging from 8-18 hours
Eosinophils comprise _____% or less of circulating leukocytes
6
Eosinophils are primarily tissue-dwelling cells, with an average life span of
2-5 days; may reach up to 14 days
Only tissues in which eosinophils normally reside
Bone marrow Spleen Lymph node Thymus Gastrointestinal tract from the stomach to the colon, sparing the esophagus
Only organ other than the bine marrow in which extracellular eosinophil granule protein deposition is observed even under homeostatic conditions
Gastrointestinal tract
Eosinophils and their granule proteins are found in the _____ in normal gastrointestinal tract and are not found in _____
Lamina propria
Peyer patches or epithelium
The recruitment of eosinophils to the gastrointestinal, thymic, uterine, and mammary tissues is under the control of
CCL11
Eosinophils can migrate to areas of tissue injury or necrosis through the _____ released from necrotic cells
High-mobility group box-1 protein (HGMB1)
Y/N: Once eosinophils enter tissues, most do not recirculate
Yes
Among the products of eosinophils that are most damaging to the host are the
Cationic proteins (EPO, ECO, EDN, MBP-1)
All 4 of the cationic proteins (EPO, ECP, EDN, MBP-1) likely contribute to the edema observed in skin diseases because of their
Vasodilatory effect
Eosiniphil granule proteins induces direct tissue damage to
Host cellls and microbes
Comprises the crystalloid core of the specific eosinophil granule
Major basic protein
_____, but none of the other eosinophil granule proteins, stimulate histamine and LTC4 release from human basophils
MBP-1 and MBP-2
Key participant in generating reactive oxidants and free radical species in activated eosinophils
Eosinophil peroxidase
Protein that is present in the highest molar concentration in eosinophil granules
MBP
By weight, is the most abundant protein constituting approximatelt 25% of the specific eosinophil granule’s total protein mass
EPO
Play a role in viral host defense to RNA viruses
ECP and EDN
Functions as an alarmin, alerting the adaptive immune system to preferentially enhance antigen-specific Th2 responses
EDN
Y/N: No single surface protein is uniquely expressed in eosinophils
Yes
Most important selectin pair in eosinophil migration into tissues
P-selectin and PSGL-1
Among the nonselective drugs for eosinophil reduction, _____ generally are very effective
Glucocorticoids
Y/N: Glucocorticoids cause an immediate reduction in circulating eosinophils.
Yes - within 3 hours
Mutation in myeloproliferative hypereosinophilic syndrome (chronic eosinophilic leukemia)
FIP1L1-PDGFRA
Approved for the treatment of chronic myelogenous leukemia and hypereosinophilic syndrome
Imatinib mesylate
Monoclonal antibody to CD52; used in the treatment of chronic (B-cell) lymphocytic leukemia and T-cell lymphoma
Alemtuzumab
Eosinophils, but not _____, also express CD52
Neutrophils
First humanized monoclonal antibody against IL-5
Mepolizumab
Anti-IL-5 receptor alpha humanized monoclonal antibody
Benralizumab
Y/N: Pathogenic influence of eosinophils may be unrelated to their numbers in tissues
Yes
Revised diagnostic criteria for hypereosinophilic syndromes: blood eosinophilia > _____ eosinophils/mm3 on at least 2 separate determinations or evidence of prominent tissue eosinophilia associated with symptoms and marked blood eosinophilia
1500
Patients with myeloproliferative hypereosinophilic syndrome frequently present with clinical features resembling those of
Chronic myelogenous leukemia
Although chromosomal abnormalities characterize this subtype of HES, the disease may evolve into definite leukemia
Myeloproliferative HES
Patients with _____ HES abnormal T-cell clones with unusual surface phenotypes
Lymphocytic
An 800-kilobase deletion on chromosome band 4q12 that codes for a tyrosine kinase has been found in _____ HES
Myeloproliferative
The FIP1L1-PDGFRA gene is detected in
Mast cells
Eosinophils
Neutrophils
Mononuclear cells
Myeloproliferative HES with documented mutations is known as
Chronic eosinophilic leukemia
Increased serum levels of IgE are often present in _____ HES
Lymphocytic
Levels of vitamin B12 and tryptase may be increased in _____ HES
Myeloproliferative
Other than in _____, vasculitis only rarely is associated with HES
Eosinophilic granulomatosis with polyangitis
Along with eosinophilia, _____ commonly are found in helminthic infections
Total serum IgE levels higher than 500 IU/mL
In patients with isolated urticarial plaques with or without angioedema, the differential diagnosis includes common and persistent urticaria, but demonstration of _____ supports HES
Multiorgan involvement
HES with episodic angioedema may resemble hereditary angioedema clinically, although patients with hereditary angioedema have a family history of the disease and rarely have the _____ that characterize HES
Markedly elevated eosinophil counts
Major cause of death in HES
Congestive heart failure from restrictive cardiomyopathy
Followed by sepsis
Corticostetoids are considered the first-line therapy in HES patients without the gene mutation, once _____ has been excluded
Strongyloides infection
Myeloproliferative HES is responsive to
Imatinib
Adverse effect of imatinib
Endomyocardial disease may worsen during the first several days of treatment
Should be monitored before and during imatinib therapy
Tropinin levels
To improve cardiac function, _____ should be given before and with initiation of imatinib therapy
Glucocorticoids
Individual lesions gradually change from bright red to brown-red and then blue-gray or greenish-gray, resembling morphea
Wells syndrome
Most frequent systemic complain in Wells syndrome
Malaise
A nonspecific hypersensitivity reaction in response to exogenous and/or endogenous stimuli is regarded as the most important pathomechanism in
Wells syndrome
Characterized by diffuse dermal infiltration with eosinophils, histiocytes, and foci of amorphous and/or granular material associated with connective tissue fibers
Wells syndrome
Y/N: Flame figured is diagnostic of Wells syndrome
No - characteristic for, but not diagnostic of
Hallmark of Wells syndrome
Flame figures
Prognosis of Wells syndrome
Resolves without scarring, usually within weeks to months, but multiple recurrences are common
Angiolymphoid hyperplasia with eosinophilia shows a predilection for the
Head and neck area, including the ears
ALHE has been reported to occur in _____, which implies thst sex hormones may be a factor in its development
Pregnancy
Also has developed in patients with T-cell clonality, which suggets that it may be an early or low-grade T-cell lymphoma
ALHE
Well-defined area in the dermis and/or subcutis of prominent vascular proliferation with large epithelioid or histiocytoid endothelial cells that contain abundant eosinophilic cytoplasm, often with cytoplasmic vacuoles
ALHE
The stroma of ALHE is typically
Myxoid
KD vs ALHE: lesions
ALHE - smaller, more superficial, more numerous, often asymptomatic
Peripheral blood eosinophilia and increase IgE levels in (KD/ALHE)
KD
Dominant histologic feature is lymphoid proliferation, often with germinal centers with prominent infiltration of eosinophils. Fibrosis is characteristic, and eosinophil abscesses may occur
KD
Represent the dominant characteristic of KD
Lymphoid follicles
KD vs ALHE: nephropathy
KD - present in up to 20% of patients
ALHE course
Chronic and nonremitting
KD treatment of choice
Surgical excision
Variants of eosinophilic pustular folliculitis
- Classical EPF
- Immunosuppresion-associated EPF
- Infantile EPF
Immunosuppression EPF may be subdivided into
- HIV-associated type
2. Malignancy-associated type
Presents as recurrent crops or clusters of follicular papules and pustules, which form an annular pattern and usually resolve in 7-10 days; predominantly on the face and trunk
Classical EPF
Infantile type of EPF typically are located on the
Scalp
Extremely pruritic discrete follicular papules, typically involving thr head and neck and often the proximal extremities
HIV-associated EPF
Although patients with classical EPF usually have eosinophilia with leukocytosis, HIV-positive patients often exhibit
Eosinophilia with lymphopenia
Elevated serum IgE is uncommon in _____ EPF
Infantile
Infiltration of eosinophils into hair follicles and perifollicular areas, sometimes with follicular damage
EPF
EPF prognosis based on type
Infantile - good
Classical and HIV-associated - recurrences
First approach to the treatment of all types of EPF
Topical glucocorticoids
Topical calcineurin inhibitors
Also NSAIDs, particularly indomethacin
Papuloerythroderma of Ofuji frequently occur in
Elderly males, especially in the eighth or ninth decade
Itchy erythroderma-like eruptions formed by the coalescence of flat-topped, red-to-brown papules with a cobblestone appearance
Papuloerythroderma of Ofuji
Papuloerythroderma of Ofuji affects the
Limbs and trunk
Sparing of the abdominal skin folds
Deck-chair sign
Y/N: Papuloerythroderma of Ofuji affects the mucous membranes, hair, and nails
No - Mucous membranes, hair, and nails are always spared
Approximately 20% of cases of papuloerythroderma of Ofuji are associated with
Hematologic neoplasms or
Visceral malignancies
Deck-chair sign is observed in
Papuloerythroderma of Ofuji
Other erythrodermas, such as psoriasis and atopic dermatitis
Histopathology of papuloerythroderma of Ofuji
Nonspecific spongiotic dermatitis-like patterns
Papuloerythroderma of Ofuji course
Chronic and non-self-limiting
Y/N: Papuloerythroderma of Ofuji is frequently refractory to treatment
Yes
Asymptomatic red, brown, or violaceous plaques that are soft, smooth, and well circumscribed, often showing follicular s accentuation and telangiectasia
Granuloma faciale
Can be considered a localized chronic fibrosing vasculitis
Granuloma faciale
Normal-appearing epidermis, narrow grenz zone, dense and diffuse infiltrate of lymphocytes, plasma cells, eosinophils, and neutrophils with evidence of leukocytoclasis
Granuloma faciale
Primary histologic differential diagnosis of granuloma faciale
Erythema elevatum diutinum
Granuloma faciale vs EED: histology
Grenz zone is not typical of EED
Eosinophils and plasma cells are more prominent in granuloma faciale
Neutrophils are more frequently found in EED
Granuloma faciale course
Chronic and rarely resolves spontaneously
Depression along the course of the superficial vein that is more marked upon the elevation of the affected limb
Groove sign
Groove sign is a characteristic finding of
Eosinophilic fasciitis
Historically related to ingestion of certain lots of L-tryptophan
Eosinophilia-myalgia syndrome
Dermoscopic finding of ALHE
Polymorphous vascular pattern
