Maria Regina V. Pelobello, M.D.September 3, 2009

To present a case of an unusual infection in a a 26-year-old male

To discuss the disease course, management and prognosis

R.P., 26M Single call center agent residing in Makati 

headache

3 ½ weeks PTA HeadacheGr 1-2/10 10/10, generalized, throbbingParacetamolOut-px consult: given pain

medications

2 ½ wks PTA Dizziness, vomiting Headache MMC: admitted for 4 days

EEG : abnormal MRI / MRA of the brain and

intracranial vessels : normal Imp: Mixed Type Headache

(Migraine with Tension Headache)

etoricoxib, betahistine, flunarizine, eperisone, diazepam

6 days PTA Headache bitemporal, frontal throbbing Gr 5/10 10/10 30 minutes to an hour Occasionally awakened from

sleep Associated with vomiting

Drowsiness Dizziness, rotatory

2 days PTA

Day of adm

Undocumented fever

blurring of vision increased drowsiness several episodes of

disorientation No loss of consciousness,

tremors, tonic-clonic movements, slurring of speech

No weight loss, anorexia, weakness No skin rashes No tinnitus No gum bleeding No cough, colds No dysuria No diarrhea

No hypertension, diabetes or asthma No history of treatment for PTB No seizure disorder s/p knee surgery No previous blood transfusion No previous steroid therapy No known allergies

(-) Hypertension

(+) Diabetes Mellitus (-) Bronchial Asthma (-) Pulmonary Tuberculosis (-) Seizure disorder

Functions independently 10 sticks per day for the past 3 years occasional alcoholic beverage drinker denies use of illicit drugs No history of recent travel Multiple sexual partners, same gender

preference

lethargic, not in cardio-respiratory distress BP 110/80, HR 82, regular, RR 20, T 36 C Height 61cm, weight 59 kg Warm moist skin, no active dermatoses Pink palpebral conjunctivae, anicteric sclerae Moist buccal mucosa, no oral thrush Initially with supple neck, no palpable cervical

lymphadenopathies

Symmetrical chest expansion, no retractions, clear breath sounds

Adynamic precordium, AB 5th LICS, MCL , (-) murmurs

Flabby Abdomen, normoactive bowel sounds, soft, non-tender, no hepatosplenomegaly

Extremities no edema, no cyanosis, pulses full and equal

drowsy, oriented 3 spheres, follows commands, no right-left confusion, no finger agnosia, no

apraxiaCranial nerves intact

Pupils 3mm ERTL, full EOMs, no nystagmusV1 – V3 intactNo facial asymmetry, tongue and uvula midline

No sensory deficitsMMT 5/5 on all extremitiesNo dysmetria, dysdiadokinesia. Steady gait.

Nuchal rigidity, (+) brudzinskiunsteady gait (falls to either side)

26M CC: headache Vomiting Dizziness blurring of vision Undocumented fever Nuchal rigidity

Increased intracranial pressure Consider Meningitis

Bacterial vs Viral vs Fungal

Assessment consider increased intracranial pressure consider meningitis

Diagnostics CBC, stat 5, urinalysis CT scan (plain and contrast): normal Lumbar puncture

Therapeutics Mannitol 20 % 100ml q4hrs Dexamethasone 5mg IV q8hrs Citicoline 1g IV q8hrs Ceftriaxone 2g IV q12hrs

Na 134 K 3.0 RBS 182 Hgb 11.2 Hct 33

Urinalysis: +2 blood, 1/1/1/23

11stst HD HD

Opening Pressure 290290

Closing Pressure 210210

Cell countDifferential count

1.5 ml non xanthochromic1.5 ml non xanthochromic2 RBC / mcL, 7 WBC/mcL2 RBC / mcL, 7 WBC/mcL

4 seg seen, 3 lym seen4 seg seen, 3 lym seen

Protein 76.876.8

Glucose 4444

normal patient bacterial fungal ViralOP 50 – 200 290 high

PMN 0PMN 0lym < 5lym < 5

7 WBC7 WBC4 seg4 seg3 lym 3 lym

High WBC

Low wbc No WBCDifferential Protein

15 – 45 15 – 45 76.876.8 High High or normal

Low

Glucose40 – 7540 – 75 4444 Low Low or

normalHigh

Infectious disease referral Continue ceftriaxone 2g IV q12hrs

11stst HD HD

Gram YeastYeastKOH ++AFB --

India Ink ++Cryptococcal Antigen Latex

Agglutination Study ++

• Ceftriaxone was discontinued • Fluconazole 400 IV q24hrs

amphotericin B 50mg q24hrs (0.85 mg/kg/day)

Culture light growth of Cryptococus spp

TB culture no growth after 6 weeks incubation

Assessment Rule out HIV

Diagnostics CD 4 = 28 per microliter

Therapeutics (5th HD) cotrimoxazole 800/160 mg/tab OD azithromycin 500mg/tab, 2 tabs once a

week 

6th Hospital Day Amphotericin B discontinued Fluconazole 400mg IV every 24hours cotrimoxazole 800/160 mg/tab 3x a week continue antifungal treatment for 2 weeks

before starting anti-retroviral therapy 20th Hospital Day 

lamivudine + zidovudine 1 tab 2x a day efavirenz 600mg daily

paradoxical worsening of preexisting, untreated, or partially treated opportunistic infections after initiation of ARV

CD4+ T cell counts <50 cells/L who have a precipitous drop in HIV RNA levels following the initiation of HAART

localized lymphadenitis, prolonged fever, pulmonary infiltrates, increased intracranial pressure, uveitis

reflects the immediate improvements in immune function

7th HD Upward rolling of eyeballs, fully awake Impression: increased intracranial pressure Diagnostics

Advised repeat CT scan and LP Therapeutics

Valproic acid 250mg TIDMannitol

11th HD Recurrent seizure episodes Patient appears very drowsy and confused Impression

Increased intracranial pressure Diagnostic and Therapeutic

Stat Lumbar tap

13th HD Recurrence of

seizures India ink still

positive Amphotericin

resumed

1st HD 11th HD

OP 290 380

CP 210 180

CHON 76.8 31.3

Glu 44 43

India + +

CALAS + +

VDRL -

1 11 16 17 18 20Opening

Pressure 290 380 400 550 550 390

Closing Pressure 210 180 420 460 350

Protein 76.8 31.3 36.7Glucose 44 43 52

Gram-Stain YeastKOH +AFB -

India Ink + + + +CALAS + + + +VDRL -

21 23 25 27 28 31Opening

Pressure 380 340 280 550 520

Closing Pressure 320 310 240 110 80

India +CALAS + +

Quanti 1:32 1:1024 1:1024

16th HD Serum creatinine (1.6)

amphotericin B was discontinued  fluconazole 200mg IV every 24 hours

26th HD Referral to Nephrology for fluid and

electrolyte management

1 2 4 7 10 13

Na 131 133

K 2.9 4.7 4.0 4.1 3.1 2.9

BUN 19.9

Crea 1.2 1.0 0.9 0.9 0.8 1.0

Mg

CO2

16 18 21 26 28 29 31 32 33

Na 136 139 142 144 142

K 3.6 2.8 2.6 2.8 3.4 3.9 7.0

BUN 7.99

Crea 1.6 1.4 0.9 0.8 0.6 0.7 0.6 0.6 2.1

Mg 2.3 1.5 1.6 1.8 1.9

CO2 20

32rd HD Patient went into CP arrest, but was revived

33rd HD Patient expired

1st HD 21st HD 28th HD

Hgb 12.8 10.8 11.1

Hct 36.9 33.4 33.3

WBC 5.96 2.7 7.33

Seg 82 61 84

Lym 10 21 8

Plt 120 150 330

family of Retroviridae subfamily lentiviridae

four recognized human retroviruses human T lymphotropic

viruses (HTLV)-I and HTLV-II human immunodeficiency

viruses, HIV-1 and HIV-2 most common cause of

HIV disease throughout the world: HIV-1

Phil J Microbiol Infect Dis. 2003; 32(1): 11-21.

enters directly into the bloodstream via infected blood or blood products transfusions use of contaminated needles sharp-object injuries maternal-to-fetal

transmission sexual intercourse

CD4 count generally accepted as the best indicator of

the immediate state of immunologic competence of the patient with HIV infection

correlates very well with the level of immunologic competence

Measurements should be performed at the time of diagnosis and every 3–6 months thereafter

<350/L : consider initiating ARV therapy >25% decline : consider change in therapy <200/L : P. jiroveci prophylaxis <50/L : prophylaxis for MAC infection

Cryptococcus neoformans Etiologic agent Yeast-like fungus

rare in the absence of impaired immunity Individuals at high risk for cryptococcosis

hematologic malignancies recipients of solid organ transplants who require

ongoing immunosuppressive therapy medical conditions necessitate glucocorticoid

therapy advanced HIV infection and CD4+ T lymphocyte

counts of <200/L

leading infectious cause of meningitis in patients with AIDS

initial AIDS-defining illness in ~2% of patients CD4+ T cell counts <100/L subacute meningoencephalitis: fever, nausea,

vomiting, altered mental status, headache, and meningeal signs

acquired by inhalation of aerosolized infectious particles

May be acquired in childhood, but it is not known whether the initial infection is symptomatic

state of latency in which viable organisms are harbored for prolonged periods, possibly in granulomas

Thus the inhalation of C. neoformans can be followed by clearance of the organism or establishment of the latent state

chronic meningitis (headache, fever, lethargy, sensorium deficits, memory deficits, cranial nerve paresis, vision deficits, and meningismus)

classic characteristics of meningeal irritation may be absent in cryptococcal meningitis

subacute dementia sudden catastrophic vision loss

demonstration of C. neoformans in normally sterile tissues

India ink - distinctive appearance because their capsules exclude ink particles

Cultures of CSF and blood that are positive for C. neoformans are diagnostic for cryptococcosis

In cryptococcal meningitis, CSF examination usually reveals evidence of chronic meningitis with mononuclear cell pleocytosis and increased protein levels

Cryptococcosis in patients with HIV infection always requires aggressive therapy and is considered incurable unless immune function improves.

Two phases of therapy for cryptococcosis in the setting of AIDS: induction therapy

intended to reduce the fungal burden and alleviate symptoms

lifelong maintenance therapy to prevent a symptomatic clinical relapse

Cryptococcal meningoencephalitis is often associated with increased intracranial pressure

management of intracranial pressure reduction of pressure by repeated

therapeutic lumbar puncture placement of shunts.

Even with antifungal therapy, cryptococcosis is associated with high rates of morbidity and death

most important prognostic factor : extent and the duration of the underlying immunologic deficits

poor prognostic markers positive CSF assay for yeast cells by initial India ink

examination (evidence of a heavy fungal burden) high CSF pressure low CSF glucose levels low CSF pleocytosis (<2/L) recovery of yeast cells from extraneural sites the absence of antibody to C. neoformans a CSF or serum cryptococcal antigen level of 1:32 concomitant glucocorticoid therapy or hematologic malignancy

Opening pressure 50–200 mm H2O CSF

Color Colorless

Turbidity Crystal clear

Mononuclear cells <5 per mm3

PMNs 0

Total protein 22–38 mg/dl

 Range 9–58 mg/dl (mean ± 2.0 SD)

Glucose 60–80% of blood glucose

   Normal Values for Adults (Lumbar CSF)