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An Unusual Cause Of Eosinophilia

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  • 1. An Unusual Cause Of Eosinophilia? Or much ado about nothing?
  • 2. The mysterious case of Mrs H’s Malaise………
    • 69 Year old lady presented with chest pain ? Acute coronary syndrome.
    • She had a past medical history of asthma and high cholesterol.
    • incidentally gave a 5/12 history of general malaise, “sickliness” & weight loss.
    • MI screen negative, WCC normal, eosinophils of 4.9 (32%), Na 2+ 132.
    • CXR revealed apical fibrosis ~ ? tuberculosis
    • Treated as TB with Rifinah, Ethambucol, Pyrazinamide & Isoniazid and discharged with follow up ~ awaiting AAFB results
  • 3. The Mysterious case of Mrs H’s Malaise……
    • Readmitted 8/7 later, with worsening nausea and vomiting. Thought to be dehydrated & BP low
    • Eosinophils 1.7, Na 2+ 124.
    • Given iv fluids and symptomatically improved, then Na 2+ results seen
    • Bendrofluazide stopped, fluid restricted and given antiemetics.
    • Initially pyrazinamide stopped as most likely cause of nausea & vomiting.
    • Fluid restriction stopped to allow for formal plasma/urinary osmolality & electrolytes to be sent.
  • 4. The mysterious case of Mrs H’s malaise…..
    • Plasma Osmolality 263
    • Urine Osmolality 165
    • Not SIADH ~ however Na 2+
    • continues to drop & trough’s
    • at 117.
    Mrs H was again fluid restricted despite previous results. Rpt osmolalities:Plasma 231, Urine 160, urinary Na 2+ <10. Definitely not SIADH!! No peripheral oedema Only other drugs aspirin, ramipril, atorvastatin TFTs & random cortisol normal Autoimmune screen negative AAFBs x 3 negative IgG 12.6 IgM 1.1 IgA 1.51 IgE 672
  • 5. The Mysterious Case Of Mrs H’s Malaise…..
    • On closer questioning, Mrs H believed that her non-specific symptoms could be linked to the time that her GP commenced atorvastatin.
    • All medicines were stopped except her inhalers.
    • Her symptoms then gradually improved so that she felt well enough to go home 21/7 after her re-admission.
    • On discharge Na 2+ was 133, Eosinophils 2.4.
    .
    • CXR reviewed ~ appearances significantly better so unlikely to be TB.
    • She was rehydrated and treated with antiemetics
  • 6. The Mysterious Case Of Mrs H’s Malaise……
    • We postulated that her symptoms are down to medicine SE’s ~ likely atorvastatin. Our aim was to rechallenge if her eosinophils returned to normal.
    CSM reports 1 case of pulmonary eosinophilia with atorvastatin, 1 case of peripheral eosinophilia with ramipril & 3 of hyponatraemia with ramipril.
  • 7. Pulmonary Eosinophilia
  • 8. Pulmonary Eosinophilia
    • Range from the very mild simple pulmonary eosinophilias to the often fatal polyarteritis nodosa.
  • 9. Poor/ Fair Months/years always >20% Severe Polyarteritis Nodosa Poor Months/years Always >20% Severe Hypereosinophilic syndrome Fair Years None >20% Moderate/ Severe Tropical Pulmonary Eosinophilia Fair Years None 5-20% Moderate/ Severe Asthmatic Bronchopulmonary Eosinophilia Good >1/12 None >20% Mild/ Moderate Prolonged Pulmonary Eosinophilia Good <1/12 None 10% Mild Simple Pulmonary Eosinophilia Outcome Duration Multi-system involve-ment Blood Eosino-phils% Symptoms Disease
  • 10. Simple versus Prolonged Pulmonary Eosinophilia
    • Simple Pulmonary Eosinophilia
    • Mild illness
    • Fever & cough lasting less than 2 weeks
    • Probably due to a transient allergic reaction in the alveolus
    • Self limiting
    • Prolonged Pulmonary Eosinophilia
    • Similar to simple but lasting more than a month
    • High fever
    • Peripheral eosinophilia
    • Localised or diffuse CXR opacities
    • Resolves with steroids.
  • 11. Asthmatic Bronchopulmonary Eosinophilia
      • Characterised by asthma, transient CXR shadows and blood or sputum eosinophilia.
      • Most common cause is allergy to aspergillus fumigatus.
      • Aspergillus actually grows in the wall of the bronchi and eventually produces proximal bronchiectasis.
      • Episodes of wheeze,cough,fever and malaise.
      • Association with expectoration of sputum plugs leading to clearing of CXR appearances.
      • Extremely high IgE & +ve aspergillus precipitans
      • Treatment with 30mg prednisolone ~ may need 15mg for maintenance
      • Untreated can result in progressive fibrosis that may mimic TB on CXR.
  • 12.
    • Polyarteritis Nodosa
    • Characterised by foci of necrotizing arteritis
    • Affects most organs.
    • Lung involvement unusual except in Churg-Strauss syndrome.
    • CXR may show ill-defined shadows that disappear & reappear over weeks.
    • 5 yr survival is 80% with steroid and immunosuppression
    • Churg-Strauss Syndrome .
    • Occurs in the fourth decade
    • Eosinophilic infiltration in individuals with previous history of rhinitis and asthma.
    • High eosinophils, vasculitis of small vessels and extra vascular granulomas.
    • Renal failure less likely than in PAN.
    • pANCA can be positive.
    • Responds to steroids.
  • 13. Drug induced Eosinophilia
    • Eosinophilia has been reported as a side effect of many drugs including:
    • NSAID’s
    • ACEI’s
    • Statins (peripheral)
    • Penicillins, Tetracyclines, Sulphonamides
    • Phenytoin, Carbamazepine
    • Chlorpropamide.
    • Potential drug SE’s are under reported since there is often little hard evidence
    • ? Not much known about a mechanism of eosinophilia. May precipitate a reaction in a susceptible individual.
  • 14. Conclusion….
    • Mrs H’s symptoms resolved when all meds were stopped.
    • At follow up she was well.
    • Na 2+ was 135, but eosinophils remained elevated at 3.1
    • After much excitement about possible drug causes, she was treated with steroids and made a good recovery!
    • NB: aspergillus precipitans were never measured
  • 15. Hyponatraemia & SIADH
    • ADH causes water retention
    • In hypovolaemia the action of aldosterone causes sodium retention & therefore urine Na is low
    • In SIADH only water is retained so urine Na remains inapproriately high
    • No diuretics
    • Normal adrenal & thyroid function
    • No hypotension (or low K+)
    • Low plasma osmolality with inappropriately high urine osmolality & sodium
  • 16. Hyponatraemia & SIADH
    • In this case the patient had lost salt and water in vomit and via diuretics
    • She would have tried to replace volume with water, but continued to take bendrofluazide hence ongoing salt & water loss
    • Her ACEI would interfere with the action of angiotensin 2 on the adrenals, further reducing her ability to salt conserve
    • At this sodium level treatment is simply replacing volume with saline & stopping diuretics
    • ACEI should be stopped in the short term when a patient is hypovolaemic
    • Bendrofluazide has been implicated in a few more dramatic recent cases of hyponatraemia which Dr Jones would love to tell you all about!