6 - 40 EOSINOPHILIC DISEASES Flashcards
Eosinophil life span
**2 to 5 days **
may be increased with eosinophil survival factors for up to 14 days.
important stimulatory cytokines and growth factors for eosinophils
- interleukin (IL)-3
- granulocyte-macrophage colonystimulating factor (GM-CSF),
- IL-5
from activated T-cells
IL-3 and GMCSF, along with IL-5, promote survival, activation, and chemotaxis of eosinophils through binding to receptors that have a common β chain (CD131) with IL-5R, and unique α chains.
most selective eosinophil-active cytokine, but it is relatively late acting
IL-5
They are the most abundant granules in number in eosinophils
life span of eos in the blood
8 -18 hours
life span of eos in the tissue
2 to 5 days
This may be prolonged by cytokines that increase eosinophil survival for up to 14 days.
The recruitment of eosinophils to the gastrointestinal, thymic, uterine, and mammary tissues is under the control of this CC chemokine
CCL11
the only organ other than bone marrow in which extracellular eosinophil granule protein deposition is observed even under homeostatic conditions
gastrointestinal tract
Among eosinophil surface receptors for the Ig family members, this is the most highly expressed receptor
FcγRII (CD32)
which binds aggregated IgG, particularly of the subclasses IgG 1and IgG
most important selectin pair in eosinophil migration into tissues
P-selectin together with PSGL-1
monoclonal antibody to CD52
Alemtuzumab
used to deplete CD52+ lymphocytes in the treatment of chronic (B-cell) lymphocytic leukemia and T-cell lymphoma
Eosinophils, but not neutrophils, also express CD52, and alemtuzumab has been useful in treating patients with refractory HES, including those with abnormal T cells, 84-86 but has serious limiting side effects from cytopenias, infusion reactions and infections.
first humanized monoclonal antibody against IL-5
Mepolizumab
It has proved effective in inhibiting eosinophilia and in reducing asthma exacerbation rates
anti–IL-5 receptor α (IL-5Rα) humanized monoclonal antibody
Benralizumab
As other eosinophilopoietic factors may circumvent the requirement for IL-5 in some cases, targeting IL-5Rα is considered to be more effective in reducing eosinophils than therapies directed at IL-5 itself.
mplicated as the cause of most end-organ damage in all HES subtypes
Eosinophils
Two major HES subtypes
(1)** Lymphocytic HES **characterized by T-cell clones that produce IL-5.
- CD3– CD4+ lymphocytic HES patients exhibit a particularly high prevalence of skin manifestation, as high as 94%
- Lesions may involve the head, trunk, and extremities.
- Commonly is associated with severe pruritus, eczema, erythroderma, urticaria, and angioedema, as well as lymphadenopathy and, rarely, endomyocardial fibrosis
(2) Myeloproliferative HES associated with a deletion on chromosome 4 that produces a tyrosine kinase fusion gene Fip1-like 1/PDGFRα or other mutation associated with eosinophil clonality.
- presenting complex includes fever, weight loss, fatigue, malaise, skin lesions, and hepatosplenomegaly
- Mucosal ulcers of the oropharynx or anogenital region
- Responsive to imatinib.
- Severely debilitating mucosal ulcers portend a grim prognosis unless HES is treated.
- Overlap with mastocytosis.
- Familial HES variant, family history of documented persistent eosinophilia of unknown cause.
- Cardiac disease occurs frequently - Eosinophils adhere to endocardium and release granule proteins onto endothelial cells, thrombus formation follows, and, finally, subendocardial fibrosis with restrictive cardiomyopathy occurs
- Splinter hemorrhages and/or nail-fold infarcts may herald the onset of thromboembolic disease
frequently present with clinical features resembling those of chronic myelogenous leukemia
mutation found in myeloproliferative HES
FIP1L1-PDGFRA gene mutation
major cause of death in HES
congestive heart failure from the restrictive cardiomyopathy of eosinophilic endomyocardial disease
followed by sepsis
goal of treatment in HES
relieve symptoms and improve organ function while keeping peripheral blood eosinophils at 1000 to 2000/mm 3 and minimizing treatment side effects
target peripheral blood eosinophils during the treatment of HES
1000 to 2000/mm3
one of the most commonly used and most effective therapeutic agents in the treatment of HES
Corticosteroids
They are considered the first-line therapy in patients without the gene mutation, once Strongyloides infection has been excluded
Corticosteroids
Myeloproliferative HES is responsive to what medication?
imatinib
In patients with the mutant gene FIP1L1-PDGFRA, administration of imatinib mesylate is indicated and usually induces hematologic remission, but endomyocardial disease may worsen during the first several days of treatment.
Troponin levels should be monitored before and during imatinib therapy
hallmark of Wells syndrome
Flame figures
characteristic for, but not diagnostic of, Wells syndrome
but, because they have been identified in biopsy specimens from other dermatoses, they are not alone sufficient for the diagnosis
Diagnostic Criteria for Hypereosinophilic Syndromes1
Hypereosinophilic syndrome (HES): classification and treatment algorithm
Identify if the following pertains to Angiolymphoid hyperplasia with eosinophilia (ALHE) or Kimura disease (KD):
occurs mainly in young adult Asian males
KD
Identify if the following pertains to Angiolymphoid hyperplasia with eosinophilia (ALHE) or Kimura disease (KD):
occurs in all races, with a female predominance
ALHE
Identify if the following pertains to Angiolymphoid hyperplasia with eosinophilia (ALHE) or Kimura disease (KD):
characterized by recurrent dermal and/or subcutaneous lesions, primarily of the head and neck area
lesions tend to be smaller, more superficial, and more numerous
ALHE
Identify if the following pertains to Angiolymphoid hyperplasia with eosinophilia (ALHE) or Kimura disease (KD):
characterized by recurrent dermal and/or subcutaneous lesions, primarily of the head and neck area; overlying skin is NORMAL
tends to involve subcutaneous tissues, regional lymph nodes, and salivary glands
KD
Identify if the following pertains to Angiolymphoid hyperplasia with eosinophilia (ALHE) or Kimura disease (KD):
may be painful, pruritic, or pulsatile
ALHE
KD is generally asymptomatic
Identify if the following pertains to Angiolymphoid hyperplasia with eosinophilia (ALHE) or Kimura disease (KD):
With peripheral blood eosinophilia
BOTH
Identify if the following pertains to Angiolymphoid hyperplasia with eosinophilia (ALHE) or Kimura disease (KD):
Dominant histopath feature is lymphoid proliferation, often with germinal centers
KD
Identify if the following pertains to Angiolymphoid hyperplasia with eosinophilia (ALHE) or Kimura disease (KD):
Increased IgE levels are found
KD
Identify if the following pertains to Angiolymphoid hyperplasia with eosinophilia (ALHE) or Kimura disease (KD):
Renal disease/ Nephropathy present in up to 20% of patients
KD
Identify if the following pertains to Angiolymphoid hyperplasia with eosinophilia (ALHE) or Kimura disease (KD):
Histopath finding characterized by vascular proliferation with numerous large epithelioid or histiocytoid endothelial cells
ALHE
Identify if the following pertains to Angiolymphoid hyperplasia with eosinophilia (ALHE) or Kimura disease (KD):
(+) Fibrosis
KD
limited or absent in ALHE
Identify if the following pertains to Angiolymphoid hyperplasia with eosinophilia (ALHE) or Kimura disease (KD):
Inconspicuous to numerous eosinophils
ALHE
Identify if the following pertains to Angiolymphoid hyperplasia with eosinophilia (ALHE) or Kimura disease (KD):
Eosinophil abscesses may occur
KD
Identify if the following pertains to Angiolymphoid hyperplasia with eosinophilia (ALHE) or Kimura disease (KD):
Small and superficial, with overlying erythema; head and neck region
ALHE
Three clinical types that are characterized by follicular papules and pustules, and may involve the head, trunk, and extremities.
EOSINOPHILIC PUSTULAR FOLLICULITIS
Typically occurs in Japanese patients, who have chronic, recurrent follicular pustules, with a tendency to form circinate plaques, in a seborrheic distribution.
Classic eosinophilic pustular folliculitis (Ofuji disease)
Most often occurs in patients with human immunodeficiency virus infection, who have severely pruritic papules of the face and upper trunk.
Eosinophilic pustular folliculitis associated with immunosuppression.
Characterized by follicular pustules of the scalp in an infant
Eosinophilic pustular folliculitis of infancy/ neonatal period.
Classic histoapth findings of eosinophilic pustular folliculitis
follicular and perifollicular eosinophil infiltration
characterized by solitary papules, plaques, or nodules. The lesions are typically asymptomatic red, brown, or violaceous plaques that are soft, smooth, and well circumscribed, often showing follicular accentuation and telangiectasia
Granuloma faciale
