Complications Toxicity Case 7: Mitchell

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Complications ToxicityCase 7 Mitchell

• Sanjay Bhagani

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Complications ToxicityCase 7 Mitchell

• 38 year old fashion designer
• First diagnosed positive 1990
• CD4 count 380
• HBcAb positive, sAg negative

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Complications ToxicityCase 7 Mitchell
Antiviral History

• 1996 - 1997
• AZT/3TC/SAQ
• 1998
• D4T/DDI/Efavirenz
• 1998
• DDI/HU/RIT/IND

• CD4 292
• CD4 242
• VL 220000
• Peripheral neuropathy/CNS toxicity
• CD4 298
• VL lt400

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Complications ToxicityCase 7 Mitchell

• Lost to follow-up Australia
• No HAART since 1998
• Jan 2002 acute hepatitis, fevers and night
  sweats
• CD4 2
• VL 450000
• Acute CMV hepatitis and MAI infection
• Rx iv Gancyclovir, Azithromycin, Ofloxacin and
  Ethambutol

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Complications ToxicityCase 7 Mitchell
Back to the hospital June 2002

• On DDI (400mg)/Tenofovir/Abacavir
• i.v. Gancyclovir 5mg/kg/day
• Azithromycin, Ofloxacin, Ethambutol
• CD4 2
• VL lt400
• Started on Cotrimoxazole 960mg/day
• Gancyclovir stopped (CMV-PCR ve, No
  retinitis or retinal scars)

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Complications ToxicityCase 7 Mitchell

• July 2002
• Intractable Oesophageal candidiasis
• No response to Itraconazole, fluconazole
• Admitted to the ward for i.v Amphotericin B
• Reduced CrCl within 48hours 58 l/min
• Switched to liposomal amphotericin
• 2 days later abdominal pain, nausea and
  vomiting, increasing shortness of breath

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Complications ToxicityCase 7 Mitchell
Blood

• HB 13.3
• Plats 138
• WCC 12.3 (n11.1)
• Clotting (N)
• Blood cultures nil
• Mid stream urine (MSU) - nil

• Na 136
• K 3.1
• Urea 9.8
• Creatinine 110
• Amylase 983
• Bicarbonate 14
• Lactate 2.6
• Chloride 113
• Liver enzymes (N)
• CRP 110

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Complications ToxicityCase 7 Mitchell

• Chest X-Ray
• No abnormalities detected

• ABGs
• pH 7.18
• pO2 11.4
• pCO2 2.8
• Bicarb 12

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Complications ToxicityCase 7 Mitchell

• TWO Diagnoses

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Complications ToxicityCase 7 Mitchell

• Acute Pancreatitis
• DDI/Tenofovir ?role of renal impairment
• Metabolic acidosis
• Anion gap (Na K) (HCO3 Cl)
• 10 (NR 10-20)
• Hyperchloraemic metabolic acidosis

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Complications ToxicityCase 7 Mitchell

• Causes of normal anion gap acidosis
• Gastrointestinal HCO3 loss
• pancreatic fistula ?
• Renal Tubular Acidosis (RTA)
• drug-induced ?
• Ingestion/Infusion Ammonium chloride/cationic
  amino acids
• Dilutional acidosis

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Complications ToxicityCase 7 Mitchell

• Type 1 RTA
• Low urine pH/low K
• Type 2 RTA
• Low/High urine pH/low K
• Type 3 RTA
• Low urine pH/High K

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Complications ToxicityCase 7 Mitchell

• Management
• ALL drugs except septrin stopped
• Supportive and fluids
• Bicarbonate supplements
• Over the next two weeks
• Amylase returned to normal
• RTA resolved bicarbonate eventually withdrawn

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Complications ToxicityCase 7 Mitchell

• BUT
• Progressive increase in ALT/AST/ALP
• Acute cholestatic hepatitis

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Complications ToxicityCase 7 Mitchell
Investigations

• U/S scan NAD
• ERCP normal intrahepatic ducts and CBD and
  pancreatic ducts. Samples taken

• HBV DNA ve
• HDV IgM ve
• HAV total Ab ve
• HVC-RNA ve
• Blood CMV-PCR ve
• Blood Toxo-PCR ve
• MAI cultures taken
• Bile microscopy -ve

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Complications - Mr MM 38 years

• Liver biopsy moderate periportal and hepatic
  inflammation with a predominant eosinophilic
  infiltrate. No AAFBs or other organisms
• Diagnosis Drug-induced hepatitis
• SEPTRIN INDUCED!

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Summary Complications - Mr MM 38 years

• DDI/Tenofovir pancreatitis
• Drug-induced Type 1 RTA - ?Amphotericin/TFV
• Septrin related hepatitis
• Rx for oesophageal candidiasis
• Anti-retroviral therapy