HYPEREOSINOPHILIC SYNDROME

      Differential History ,Diagnosis ,Pathophysiology ,Treatment Of HYPEREOSINOPHILIC SYNDROME

• A persistently elevated eosinophil count >1,500 cells/µL for at least 6 months
• Eosinophil-induced end-organ damage
• Exclusion of other causes (e.g., parasitic infection, allergy, malignancy, collagen-vascular disease)
• Almost any organ can be affected, but most patients have bone marrow, cardiac, and central nervous system involvement.
• It is characterized by more than 1500 eosino­phils/l-JI of peripheral-blood for 6 months or longer.
• It may also follow lung and bone marrow trans­plantation.
• Lungs, liver, spleen, skin, nervous system may be affected.
• Multisystem injury and organ damage caused by excessive numbers of eosinophils in the body.
• The disease is one of the myelodysplastic disorders.
• There is dyspnoea, cough, crepts in lungs, of unknown cause.
• There may be tricuspid valve abnormalities, endomyocardial fibrosis, restrictive cardiomyopa­thy with tissue infiltration by eosinophils.

Pathophysiology HYPEREOSINOPHILIC SYNDROME

• Organ damage is similar among HES subsets and results from high eosinophil levels.
• Cytokines IL-3, IL-5, and GM-CSF stimulate bone marrow eosinophil production; IL-5 is most specific.
• Blood levels, organ migration regulated by chemokines, especially IL-5 and eotaxins
• HES: Eosinophils infiltrate organs and release toxic granules containing major basic protein, eosinophil peroxidase, eosinophil cationic protein (ECP), eosinophil-derived neurotoxin (EDN), Charcot Leyden crystal, VIP, and substance P. Neurotoxic, cytotoxic, and prothrombotic; creates oxidative burst, reactive oxygen species
• Cytokine release (IL-1, IL-3, IL-5, TNF-) incites damage and activates inflammatory pathways.
• EDN and ECP activate fibroblasts: Fibrosis and organ dysfunction

History —

• Cardiac manifestations (50–60%) may cause heart failure symptoms and chest pain.
• Cutaneous manifestations (50%) may cause pruritus.
• Fatigue, anemia
• GI manifestations (20–30%):
  • Gastritis/enteritis: Diarrhea, vomiting, abdominal pain (embolic bowel infarction)
  • Hepatic manifestations of hepatitis, Budd-Chiari syndrome
• Left upper quadrant pain (from splenomegaly)
• Neurologic manifestations (50%) may result from thromboembolic disease: Behavioral changes, memory loss, confusion.
• Ocular manifestations (20%): Blurry vision/blindness from microemboli
• Other: Myalgias, arthralgias
• Pulmonary manifestations (40%) may cause nonproductive cough.

Differential Diagnosis HYPEREOSINOPHILIC SYNDROME

• Extensive; first rule out secondary causes of eosinophilia: Parasitic infection, allergy, malignancy, drug hypersensitivity, connective-tissue disorders
  • Chronic eosinophilic leukemia: Clonality like F/P+ HES but differs by having 2–20% blasts peripherally or 5–20% blasts in the marrow
  • Acute eosinophilic leukemia: A form of AML with 50–80% eosinophils; may cause bronchospasm, heart failure
• Other conditions with high eosinophil levels: Hodgkin lymphoma, mastocytosis, chronic myelomonocytic leukemia (eosinophil variant), cutaneous T-cell lymphoma, Churg-Strauss syndrome/other vasculitides, toxicity (the eosinophilia–myalgia syndrome), HIV, HTLV, bronchopulmonary aspergillosis

Treatment Of HYPEREOSINOPHILIC SYNDROME

First Line

• Treatment with corticosteroids orally or IV
• Dosage and duration are dependent on the patient’s condition.
• Treatment for 2–4 weeks beyond clinical improvement has been suggested.
• Discontinuing offending drug.
• Treatment of underlying parasite infestation

Second Line

• Some patients may require oxygen therapy.

• Glucocorticoids Hydroxyurea
• Anticoagulants for patients with thromboembolic complication; corticosteroids.
• Patients unresponsive to corticosteroids have shown marked improvement when given cytotoxic agents such as hydroxyurea
• Treatment of associated conditions.