2. INTRODUCTION
Bone marrow derived cell (CD34).
6% (400-600 per mm3).
Life span – 2- 5days (upto 14 days).
12–17 μm in diameter.
Bilobed nucleus with highly condensed peripheral
chromatin.
3.
4.
5. Lyn and Fes are other tyrosine kinases involved in the
first step; these activated by IL-3 and GM-CSF.
6.
7.
8. HYPEREOSINOPHILIC SYNDROMES
Idiopathic disease having as a common entity ,
"Hypereosinophilia", of blood and bone marrow
associated with infiltrative eosinophilia of various
organs.
Spectrum Rapidly fatal form to benign forms
90% in men .
9.
10.
11. LYMPHOCYTIC HES
Severe pruritus, eczematous , urticaria, and angioedema ,
lymphadenopathy rarely, endomyocardial fibrosis.
Abnormal T-cell clones with unusual surface phenotypes.
These T cells display activation markers, such as CD25, and secrete T
helper 2 cytokines, including high levels of interleukin 5 .
Episodic angioedema and eosinophilia (Gleich Syndrome) and
nodules, eosinophilia, rheumatism, dermatitis, and swelling (NERDS)
syndrome have developed T-cell clones.
12. MYELOPROLIFERATIVE HES.
Deletion on chromosome 4q12 that codes tyrosine kinase .
FIP1L1-PDGFRA gene mutation form a distinct subset of HES, with
cardiomyopathy and endomyocardial fibrosis, that responds to imatinib.
Elevated serum tryptase levels and atypical spindle shaped mast cells in bone
marrow. (clinical manifestations of systemic mastocytosis absent but patients
satisfy criteria for mastocytosis.)
The FIP1L1PDGFRA gene is detected
in mast cells, eosinophils,
neutrophils,
mononuclear cells
13. CLINICAL FINDINGS-
Pruritic erythematous macules, papules, plaques, wheals, or
nodules (50% of patient).
Head, trunk, and extremities.
Fever, weight loss, malaise, hepatosplenomegaly.
Mucosal ulcers (oropharynx or anogenital )an aggressive
clinical course.
Untreated-- >death is likely within 2 years of presentation .
14.
15. Cardiac manifestation--
Subendocardial fibrosis restrictive cardiomyopathy .
Tethering of chordae tendineae valvular insufficiency.
Cardiac abnormalities confined to intramural regions can
occur without peripheral blood eosinophilia.
Splinter hemorrhages , nail fold infarcts may herald the
onset of thromboembolic disease.
Nervous system, lungs, rarely, kidneys affected.
19. Imaging tests 2D Echo,CT chest, abdomen, and pelvis
GI endoscopy, Pulmonary function tests
Bone marrow aspirate with staining for tryptase
Tissue biopsy
Direct immunofluorescence
Immunostaining for eosinophil granule proteins
21. TREATMENT
Goal--- relieve symptoms & improve organ function while
keeping peripheral blood eosinophils at 1,000 to 2,000/mm3 .
Myeloproliferative HES is responsive to imatinib.
(FIP1L1-PDGFRA +/-)
Imatinib mesylate usually induces hematologic remission, but
endomyocardial disease may worsen during first several days .
Monitor Troponin levels & Glucocorticoids should be given
before and with initiation of imatinib therapy
.
22. In the absence of the gene mutation, first-line therapy
is prednisone.
Failure to glucocorticoid monotherapy have worse
prognosis .
Interferon (IFN)-α has been beneficial in both HES.
Refractory disease may respond to infliximab
(antitumor necrosis factor-α)or alemtuzumab
(antiCD52)
25. • Mostly in adult , pediatrics also.
• Preceding pain, pruritis, malaise, fever.
• Extremities.
Clinical course
Cellulitic stage localised erythema and oedema
sometimes blistering
Granulomatous stage gradual resolution from the
centre of lesions, which remains oedematous and slate
colored for several weeks.
26. Variant- plaque , annular granuloma , papulo vesicle ,
bullous , papulo nodular , fixed drug euption type
27. Histopathology
Acute stage--dermal oedema
and masses of granulocytes
mainly eosinophils.
Subacute stage--dermal
eosinophils and histiocytes
around angular, focal, fibrinoid
masses. The "flame figures" were
composed of granules,
eosinophilic material adherent
to collagen and surrounded by
granulomatous inflammation.
Late stage -- resolution
characerised by histiocytic
necrobiosis and persistence of
"flame figures".
30. TREATMENT
Systemic corticosteroids (most effective ) 20~30 mg/day .
Recurrent low-dose (5 mg) A/D prednisone .
Alternative Dapsone , tacrolimus, cyclosporine
Adalimumab (TNF)-α inhibitor.
(triggered by TNF-α inhibitor, adalimumab and
etanercept .)
Treating underlying condition /triggering factor.
Antihistamine.
Antibiotics hold no effect .
31. Granuloma Faciale
Unknown etiology.
Localized chronic fibrosing vasculitis
Extrafacial lesions isolated/ in conjunction with facial
lesions.
Photoexacerbation of lesions.
Immunoglobulins, fibrin and complement deposited
along dermal–epidermal junction in a granular pattern
and around blood vessels by direct immunofluorescence
32. The lesions are typically
asymptomatic red,
brown, or violaceous
plaques that are soft
smooth , and well
circumscribed, often
showing follicular
accentuation and
telangiectasia
33. Mixed infiltrate of
lymphocytes, histiocytes,
neutrophils, plasma cells,
and eosinophils. There is
sparing of a narrow grenz
zone between the
inflammatory
infiltrate and the overlying
epidermis.
34. Angiocentric eosinophil fibrosis
It may accompany granuloma faciale in rare cases.
Rare , bening , fibrosing condition.
Involve sinonasal tract and upper respiratory tract.
Variant of mucosal counterpart of GA.
36. Erythema Elevatum Diutinum
Multiple ,symmetrical,
primarily on extensor
,acrally distributed.
Trunk and face are spared.
Grenz zone absent.
Neutrophils more frequently
than eosinophils and plasma
cells .
Associated with systemic
conditions, primarily
monoclonal gammopathies,
Excellent response to
dapsone.
39. Associated with human immunodeficiency virus
(HIV) infection, malignancy.
May occur as a consequence of immune
reconstruction syndrome ( IRIS ) rather than
immunodeficiency in HAART-treated cases / after
a bone marrow or stem cell transplantation
40. Pathogenesis expression of limited to follicular
epithelium.
intercellular adhesion molecule 1 (ICAM-1) ,
vascular cell adhesion molecule 1 (VCAM-1),
lymphocyte function-associated antigen 1 (LFA-1)
Role of prostaglandin D2( good therapeutic
response to indomethacin )
42. Classic type / Ofuji disease
Japanese population
Adult(35–40 years)
Recurrent.
Typically last more than 1–2 weeks, involute and relapse
in average interval of every 3–4 weeks
Initially on face, may also affect trunk, extremities, scalp,
palms or soles, where follicles are absent
43. Recurrent clusters of
pruritic, sterile follicular
papules and pustules
arranged in arcuate
plaques with central
clearing and centrifugal
extension.
44. Prominent eosinophilic
infiltration with spongiosis
that mainly involves the
infundibular region of hair
follicles.
Dermis perifollicular and
perivascular infiltration of
eosinophils and lymphocytes
are common.
Perifollicular eosinophilic
congregation and formation
of eosinophilic microabscess
in the follicular infundibula
are hallmark findings .
45. Infantile
Rare variant.
Predisposition with ethnicity ,
atopy
Males .
70 % affected within 6 months
resolves spontaneously by 3 years
of age (80 % ).
Recurrent, isolated, or grouped,
crusted papulo-pustules,severely
pruriginous .
Scalp, palms & soles .
Topical corticosteroid.
46. Histology-
Eosinophilic inflammatory infiltration is always present
but true follicular involvement is observed only in 62 %
of cases.
Other cases present with perifollicular, interfollicular,
and/or periadnexal infiltrates instead
NEONATAL EOSINOPHILIC PUSTULOSIS
Occasionally Flame figures can be observed.
47. Immunosuppression-Associated
HIV infection, hematological or other malignancies.
A male predominance.
Papular lesions are less likely to coalesce into plaques or be
arranged in an annular configuration (LIKE IN CLASSIC )
Hematologic malignancy associated EPF shows relatively
better response.
48. intensely itchy ,perifollicular
erythematous papules and
pustules.
upper trunk, upper limbs,
head, and neck.
In female patients
,predominantly affects face
and mimics acne excoriée .
predominance of CD8+
lymphocytes in the lesional
infiltration
52. Recurrent Cutaneous Eosinophilic
Vasculitis
Cutaneous necrotizing predominantly eosinophilic
vasculitis.
Idiopathic ,may be a part of systemic disease CTD
Recurrent, pruritic ,erythematous or purpuric papules
with peripheral blood eosinophilia and hypo
complementemia , generally responsive to
corticosteroids .
53. Necrotizing vasculitis of small vessels in the dermis, with
exclusively eosinophilic infiltration.
The small-vessel necrotizing vasculitis and fibrinoid
degeneration on small-vessel walls are featured for RCEV,
distinct from that of other eosinophilic cutaneous
disorders such as episodic angioedema with eosinophilia,
WS, and hypereosinophilic syndrome.
55. Eosinophilic fasciitis/SHULMAN
SYNDROME
Uncommon connective tissue disease characterized by
symmetrical painful swelling with a progressive
induration and thickening of the skin and soft tissues
of the distal extremities, with uncertain etiology.
57. No age and sex predilection.
Groove sign (depression appearance along the
course of a vein or between muscle groups).
Peau d’orange sign with hyperpigmentation.
Prayer sign( the inability to close a fist or restricted
joint movement)
Morphea-like lesions are considered risk factor for
residual fibrosis
Hide bound chest progressive respiratory
limitation due to the restriction of chest movement
and reduced expansibility of chest wall
58.
59. Spontaneous or provoked myalgia, weight loss, and
asthenia, are common
Inflammatory polyarthritis causing arthralgia and
morning stiffness, carpal tunnel syndrome
Visceral involvement is absent with very few exceptions
Laboratory and Imaging Findings
Peperipheral eosinophilia, elevated serum levels of CRP
and ESR, hypergammaglobulinemia.
Low titers of antinuclear antibodies (ANA) without
detectable anti-extractable nuclear antibody.
60. MRI findings shows abnormal fascial signal intensity
and enhancement, both of which are directly
proportional to disease activity .
Deposition of IgG and C3 in affected fascia, and
hypergammaglobulinemia
Elevated serum levels of soluble CD40 ligand (sCD40L
(disease activity)
Decreased Matrix metalloproteinase-13 (MMP-13)
Predominancy of macrophages and CD8+ T lymphocytes
61. Histopathology
Requires a full thickness, or skin-to-muscle, wedge biopsy.
Epidermis, dermis are usually unaltered or mildly affected
Inflammatory and fibrous thickening of fascia, usually 2 to
15 times thicker than normal, with inflammatory infiltrates
mainly composed of lymphocytes and/or eosinophils .
62. Differential Diagnosis
Systemic sclerosis
Eosinophilia-myalgia syndrome (EMS) after l-tryptophan ingestion
Churg–strauss syndrome
Hypereosinophilic syndrome
Silica exposure
Cutaneous metastatic malignancy, should also be ruled out
65. ANGIOLYMPHOID HYPERPLASIA WITH
EOSINOPHILIA (EPITHELIOID HEMANGIOMA)
Vasoproliferative, idiopathic condition.
Manifests in adults ( female).
Isolated or grouped papules, plaques,
or nodules in the skin of the head
and neck
66. KIMURA DISEASE
Chronic inflammatory disorder.
Unknown etiology.
Painless lymphadenopathy or subcutaneous masses in
the head and neck region.
Unusual granulation combined
with hyperplastic changes in lymphoid
tissue.