A Case of Cryptococcal Meningitis

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A Case of Cryptococcal Meningitis

  1. 1. Dr.Jayakumar S A Prof.Dr.A.Gowrishankar unit
  2. 2.  34 year old Mrs.Hajara ,came with c/o –fever headache 2 weeks lethargy  HOPI:- Fever – intermittent ,low grade not associated with chills or rigor headache – diffuse ; - constant dull ache - progressively increasing severity
  3. 3.  h/o increasing tiredness and inability to do daily activities  h/o nausea  No h/o rash/vomiting ,loose stools  No h/o dysuria  No h/o cough with expectoration  No h/o weakness of limbs  No h/o altered sensorium  No h/o seizures  No history suggestive of jaundice  No h/o bleeding manifestations
  4. 4.  Past history:- not a known DM/HT/TB/IHD/BA/EPILEPTIC patient  Treatment history : 1 ½ months back evaluated for unexplained fever ,loss of weight and diarrhea; diagnosed HIV positive ; HAART initiated on 24.06.2010 zidovudine 300mg lamivudune 150 mg nevirapine 200 mg
  5. 5.  Personal history mixed diet RMP 3/30  Family history husband died due to HIV six yrs back two children
  6. 6.  o/e: conscious oriented febrile anemic no cyanosis/clubbing /pedal edema /icterus/ lymphadenopathy  Vitals : Pulse – 96/mt,regular ,normal volume ,felt in all peripheral pulses BP -130/80 mmhg
  7. 7.  CVS : S1, S2 heard no murmurs  RS : normal vesicular breath sounds no crepitations / wheeze  P/a : soft Bs+ no organomegaly  CNS : Higher functions normal bilateral lateral rectus weakness no weakness of limbs bilateral plantar flexor minimal neck stiffness present  Fundus : mild disc blurring seen ;
  8. 8. Impression : Retroviral disease with CNS infection cause to be evaluated
  9. 9.  CBC:- CXR –normal;  Hb -8.5 g/dl ECG –normal;  Tc -6ooo  P 55 L 42 E 3  ESR -6/15  Plt – 1.7 lac  PCV -28%  Random blood sugar – 110mg/dl  urea -18 mg/dl  creatinine – 0.8mg/dl
  10. 10.  CSF analysis : sugar – 87 mg/dl protein – 27 mg/dl cytology –acellular AFB -negative culture and sensitivity – negative cryptococcus –positive in india ink
  11. 11.  CT BRAIN : Normal ;  MRI BRAIN : 1.2 × 0.8cm T 2 hyperintensity noted in left parietal region suggestive of arachnoid cyst
  12. 12. DATE CD4 18.06.2010 – 75 cells/ųl 03.08.2010 -174 cells/ųl
  13. 13.  Neurologist opinion: headache ,fever , bilateral gaze restriction ; neckstiffness suggested : ophthalmologist opinion CT brain CSF analysis  Ophthalmologist opinion bilateral lateral rectus weakness fundus-mild blurring of disc margins
  14. 14.  Final diagnosis : RETROVIRAL DISEASE CDC STAGE C 3 WITH OPPORTUNISTIC INFECTION -CRYPTOCOCCAL MENINGITIS POSSIBLE unmasking type of cryptococcal IRIS
  15. 15.  C.neoformans , C.gattii  Encapsulated fungus ; inhalation infection immunocompromise disease
  16. 16.  Virulence factors --polysaccharide capsule --antiphagocytic ,diminish complement,enhances HIV replication --melanin --protects from antifungal agents -- ability to grow at high temperature --production of phospholipase ,urease
  17. 17. System Manifestation CNS MENINGITIS ;DEMENTIA ABSCESS ,GRANULOMA LUNG NODULES ,CAVITIES ,ARDS , PLEURAL EFFUSION PNEUMOTHORAX SKIN PAPULES ,VESICLES , PURPURA CRYPTOCOCCOMAS EYE KERATITIS ,ENDOPHTHALMITIS , OPTIC NERVE ATROPHY CVS PANCARDITIS ,MYCOTIC ANEURYSM GIT HEPATITIS ,ESOPHAGEAL NODULES OTHERS BREAST ABSCESS ,THYROIDITIS
  18. 18.  Leading infectious cause of meningitis in HIV patients -7 % HIV patients (Adam’s neurology)  Usually in CD4 < 100 cells /ųl;  Presentation : subacute course with Fever ,nausea ,vomiting ,altered mental status ,headache ,meningeal signs Cranial nerve palsies & cryptococcomas  Seizures and focal neurologic deficits is rare
  19. 19.  In HIV patients burden of yeast is higher higher antigen titres , slower CSF sterilization  Greater likelihood of second CNS event  Immune reconstitution syndrome in patients on ART
  20. 20.  CSF : Normal or modest elevations in protein  Microscopy : Indian ink stain mucicarmine stain fontana mason stain gomori methanamine silver stain  Culture : saboraud’s agar – 3 to 12 days staib’s birdseed ,dopa ,caffeic acid media  Serology: polysaccharide Ag testing in serum CSF latex agglutination test /EIA
  21. 21.  CT Brain : normal /hydrocephalus /gyral enhancement /cortical atrophy  MRI Brain : no pathognomonic feature hydrocephalus /cryptococcomas lesions may’nt decrease in size for a year despite treatment
  22. 22.  Acute phase : amphotericin B + flucytosine – 2 weeks  Consolidation phase : fluconazole -10 weeks  Maintenance fluconazole –lifelong
  23. 23.  Drug Dose Side effect AMPHOTERICIN B 0.7 – 1.0 MG/KG/DAY HYPOKALEMIA HYPOTENSION ARRHYTHMIAS NAUSEA ,VOMITING RARE HEPATIC DAMAGE FLUCYTOSINE 100 MG /KG /DAY ANEMIA ,LEUKOPENIA THROMBOCYTOPENIA RENAL ,GI TOXICITY FLUCONAZOLE 400 MG /DAY – CONSOLIDATION PHASE 200 MG /DAY- MAINTENANCE REVERSIBLE HEPATOTOXICITY ALOPECIA MUSCLE WEAKNESS METALLIC TASTE
  24. 24.  High CSF pressure  Low CSF glucose  Low CSF pleocytosis ( < 2 /ųl)  CSF /serum antigen level > 1: 32  Absence of antibody to C.neoformans  Recovery of yeast cells from extraneural sites  Positive CSF assay by India ink itself is a poor prognostic factor
  25. 25. ART RAPID INCREASE IN CD 4 & DEPLETION OF VIRAL LOAD IMPROVED /EXAGGERATED IMMUNE RESPONSE
  26. 26. Is immune reconstitution always beneficial?
  27. 27.  Immune Reconstitution Paradox: inflammatory reaction to antigens that were previously not recognized by the immune system.  can sometimes lead to worsening of a current or latent opportunistic infection.  The onset of IRIS often occurs 2-8 weeks after initiation of ARV therapy but can occur earlier or later.
  28. 28.  Evidence of clinical response to ART with:  On ART  >1 log10 copies/mL decrease in HIV RNA (if available)  Infectious or Inflammatory condition within 6 months of ART initiation  Symptoms can not be explained by either:  Expected clinical course of a previously recognized and successfully treated infectious agent  Treatment failure  Side effects of ART.  Complete ART non-compliance
  29. 29. 34 “Occurrence or manifestations of new OIs within six weeks to six months after initiating ART; with increase in CD4 count” India’s National AIDS Control Organization, Antiretroviral Therapy Guidelines for HIV-infected Adults and Adolescents Including Post-exposure Prophylaxis. May 2007
  30. 30.  Paradoxical IRIS : the clinical worsening of an infection that was previously successfully treated and is caused by exaggerated activation of the immune system against persisting antigens present as dead organisms or debris following the initiation of ART.
  31. 31.  Unmasking IRIS: patients with advanced immune suppression prior to ART are unable to mount an effective immune response against the viable pathogenic organisms that are present, but improving immunity after ART allows previously unrecognized pathogens to evoke an inflammatory response (unmasking).
  32. 32.  Mycobacterium avium  Mycobacterium tuberculosis  Mycobacterium leprae  Cryptococcus neoformans  Pneumocystis jiroveci  Histoplasma capsulatum  Hepatitis B virus  Hepatitis C virus  Varicella-zoster virus  Cytomegalovirus  BK Virus  Parvovirus B19  JC virus  Papilloma virus  HHV-8 (KS)
  33. 33.  Risk factors at base line:  Lower CD4 count prior to start of ART  Higher HIV-1 RNA levels at base line  Initiating ART in close proximity to starting therapy for an OI  Response to therapy & the development of IRIS:  Rapid fall in HIV-1 RNA level during the first 3 months of therapy Source: Journal of Antimicrobial Chemotherapy (2006) 57, 167- 170;Samuel A. Shelburne, Martin Montes and Richard J.Hamill
  34. 34.  Up to 30% develop IRIS after initiation of ART  Increases in headache,  Increase intracranial pressure,  In ≈25%, serious complications like loss of vision, cranial nerve palsies, reduced cognition death.
  35. 35.  Evidence-based treatment recommendations are lacking.  Identify the inciting pathogen and treat it.  Most cases of IRIS are managed without stopping ARVs.  In severe cases, treatment options include stopping ARVs, steroids, NSAIDS, and surgical treatment (for example drainage of abscesses).
  36. 36.  Cryptococcus infection is common ; disease is rare  Entry route is nasal ;  Treatment in HIV patients is for lifelong;  Carefully watch for IRIS ;  Clinical worsening after HAART doesn’t mean failure of haart;  Don’t stop HAART for IRIS ;
  37. 37.  National Institutes of Health Clinical Center (CC) ClinicalTrials.gov Identifier: NCT00286767  JAIDS Journal of Acquired Immune Deficiency Syndromes: 15 August 2007 - Volume 45 - Issue 5 - pp 595-596 Timing of Cryptococcal Immune Reconstitution Inflammatory Syndrome After Antiretroviral Therapy in Patients With AIDS and Cryptococcal Meningitis  Journal of Immune Based Therapies and Vaccines 2005, 3:7doi:10.1186/1476-8518-3-7  HARRISON’S PRINCIPLES OF INTERNAL MEDICINE -17TH EDITION  MANSON’S TROPICAL DISEASES -22ND EDITION  MANDELL,DOUGLAS & BENNETT INFECTIOUS DISEASES -7 TH EDITION

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