Opportunistic Infections Diagnosis & Management...

KLINIK UND POLIKLINIK FÜR INNERE MEDIZIN I

Fakultät für Medizin

Opportunistic Infections Diagnosis & ManagementCasesCases

B. Salzberger

UKR MEDIZIN I UNIVERSITÄT REGENSBURG

OIs in HIV-Infection

• Ois are still frequent – even in the developped world

• In Europe, about 50% of HIV-infected patients present late (<350 CD4 at first visit) or very late present late (<350 CD4 at first visit) or very late (<200 CD4 at first visit)

• Ois first presentation or complication of ART initiation (IRIS)

• Relatively strict correlation between CD4-cells and OIs –except for Tb


CD4 cell count and OIs

Years


OIs by organ system

• Pulmonary– Pneumocystis pneumonia; recurrent pneumococcal

pneumonia, tb, fungal infections (rare in Europe)

• GI• GI

• CNS– Cryptococcosis, Toxoplasmosis, Cysticercosis, PML,

CMV retinitis and encephalitis

• Disseminated– Salmonella sepsis, atypical mycobacteriosis

Research Centre for Health Economics and Evaluation (ReCHEE)


One View Quiz

• Minor manifestations – not to be missed

• Opportunity for diagnosis of HIV..


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UKR MEDIZIN I UNIVERSITÄT REGENSBURG UKR MEDIZIN I UNIVERSITÄT REGENSBURG



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Case I

• 35yo male, weight loss of 2kgs over 4 weeks, dry cough for three weeks, increasing in frequency and severity. Shortness of breath with exercise, not able to workexercise, not able to work

• Physical exam: – Underweight male (BMI 18), oral thrush, no skin rash,

no rales, no abnormal pulmonary sounds

– Neck supple, no path findings in abdomen exam

– HR 100, Respiratory rate 30, fever of 39 C

• Workup??


Case I Workup

• Workup of pulmonary symptoms?– chest x-ray?

– pulmonary function testing?

– Invasive testing (bronchoscopy– Invasive testing (bronchoscopy

• HIV-testing?

• Other lab exams?


Most frequent pulmonary manifestation in HIV-infection?

• Pulmonary Histoplasmosis

• Pulmonary TB

• Pneumocystis jirovecii Pneumonia

• Pneumoccal pneumonia

• CMV-pneumonia


Most frequent pulmonary manifestation in HIV-infection?

• Pulmonary Histoplasmosis (rare)

• Pulmonary TB (1,2)*

• Pneumocystis jirovecii Pneumonia (1,2)*

• Pneumoccal pneumonia (3)

• CMV-pneumonia (very rare)

• *depends on geographic location



Chest X-Ray

Arterial blood gas

paO2 = 62mmHgpaO2 = 62mmHgpaCO2 = 32mmHg


Lab-Exams

• HIV-rapid test: positive

• Hemoglobin 10.5g/dl, leukocytes 4/nl, differential 88% neutrophils, 8% lymphocytesdifferential 88% neutrophils, 8% lymphocytes

• Others: LDH 320U/l, other liver function tests normal, renal function normal


Your diagnosis?

• miliary tuberculosis

• viral pneumonia

• legionellosis

• pneumocystis jirovecii • pneumocystis jirovecii pneumonia


Further workup

• What can you do to ascertain your clinical diagnosis?– Testing before treatment?

• Empirical therapy?• Empirical therapy?



Diagnostic workup

• Bronchoscopy with cytology– Giemsa stain

– Immunofluorescence

– PCR– PCR

• Throat gargle– PCR

• PCR very sensitive! Caution in cases without clear clinical findings


What happened to our patient?

• Empirical treatment started with Cotrimoxazole and steroids

• PcP diagnosed with bronchoscopy


Further clinical course

• Lab exam: CD4 cell count 110 (6%)

• Respiratory failure, intubation for 6d

• Rapid recovery, started on tenofovir, emtricitabin, efavirenz day 14emtricitabin, efavirenz day 14

• Discharged day 28 on ART and PcP-prophylaxis


PjP Grocott Stain



Case II

• 26yo female

• HIV-infection diagnosed in pregnancy two years earlier, premature delivery at week 18, no clinical follow upclinical follow up

• Severe headache for 2 weeks, blurred vision in last two days, fever and weight loss


Case II: Clinical presentation

• Acutely ill, lethargic, BMI 16, HR 72, respir. Rate 22, Temp. 38.5 C. No shortness of breath, cardiac and pulmonary exam without findings, multiple cervical, axillary and inguinal multiple cervical, axillary and inguinal lymphnodes up to 1,5 cm, spleen palpable, slightly enlarged

• Neurologic exam: neck supple, no meningeal signs, no focal neurologic deficits

• Workup?


Do we need a CT-scan?


Do we need a CT-scan?

I agree, but why?



Differential diagnosis

• Toxoplasmic encephalitis

• Cryptococcal meningitis

• Cerebral Cysticercosis

• CMV encephalitis

• Progressive multifocal leukencephalopathy (PML)


Differential diagnosis

• Toxoplasmic encephalitis (1,2)*

• Cryptococcal meningitis (2,1)*

• Cerebral Cysticercosis (rare)

• CMV encephalitis (rare, very late)

• Progressive multifocal leukencephalopathy (PML) (rare)


Case II: Lab results

• Hemoglobin 8.5 g/dl, leukocytes 2.5/nl, thrombocytes 125/nl

• Differential: 6% lymphocytes

• CSF results: 20 cells, mononuclear, glucose 40mg/ml, protein 85 mg/dl, obviously high pressure

• Differential?



Case II: Lab results

• Hemoglobin 8.5 g/dl, leukocytes 2.5/nl, thrombocytes 125/nl

• Differential: 6% lymphocytes

• CSF results: 20 cells, mononuclear, glucose 40mg/ml, protein 85 mg/dl, obviously high pressure

• Differential?– Anything special for the CSF exam?


Cryptococcus neoformansPapanicolaou stain


Case II: Therapy

• Fluconazole?

• Itraconazole?

• Amphotericin B?

• Amphotericin B + 5-FC?

• Amphotericin B + fluconazole?

• What else? Steroids e.g.?


Case II: Therapy

• First choice: Amphotericin B 0.7mg/kg + Flucytosine 100mg/kg/d

• Frequent spinal taps, monitoring of lumbar • Frequent spinal taps, monitoring of lumbar pressure

• What are the most frequent toxicities?

• Can we prevent those?



Case II: ICP

• Elevated intracranial pressure (ICP) associated with cerebral edema, clinical deterioration, and higher risk of death

• Opening pressure should always be measured when • Opening pressure should always be measured when lumbar puncture (LP) is performed

• Management of elevated ICP: – Lower pressure if signs of elevated pressure or pressure high

(>25cm)

– Daily LP with removal of CSF, or CSF shunting if LP is not effective or not tolerated


Toxicity Amphotericin B/5-FC

• Amphotericin B– Nephrotoxicity – preinfusion 500ml saline, decrease

dose of 5-FC with

– Chills – acetaminophenone, diphenhydramine, rarely – Chills – acetaminophenone, diphenhydramine, rarely steroids

– Liposomal Ampho B less toxic, as effective, more expensive

• 5-FC– leukopenia


Case II: Further course

• Tolerated two weeks of Ampho B/5-FC well

• Sterilization of CSF at day 10

• Switched to Fluconazol 400mg/d at day 15 for further 6 weeksfurther 6 weeks

• Switched to Fluconazole maintenance 200mg/d week 8

• ART? Any special recommendations? When should we start? How long should we give fluconazole?




PML – another point for early treatment

• Encephalitis due to JC-virus (DNA-virus, polyoma virus, infects > 90% of population)

• Classic form and inflammatory form• Classic form and inflammatory form– Both with probably lifelong neurologic deficits, most

prominently neurocognitive

• No specific therapy– Cidofovir in vitro, no consistent clinical data


Case III

• 35 yo male

• Complains of diminished vision

• Has lost 15kgs over the last two years

• Has had two episodes of Herpes zoster, one (C4/C5) in the last year

• HIV testing has not been done

• What kind of illness do you suspect?


Case III

• Clinical exam: unremarkable except for– severe seborrhoic dermatitis and

– Malnutrition

– No clinical abnormalities externally in both eyes– No clinical abnormalities externally in both eyes

– But vision is clearly dramatically diminished in the right eye

• Lab results– HIV-rapid test positive

– TPHA negative

– Hemoglobin 8g/dl, leukocytes 1,5/nl, 10% lymphocytes


Case III : retinal exam



Differential diagnosis?

• CMV retinitis– Cotton wool spots, bleeding, necrosis

• Acute retinal necrosis (herpes zoster virus)– Outer retinal necrosis, occluding vasculitis– Outer retinal necrosis, occluding vasculitis

– Rapid progression

• Ocular toxoplasmosis– Pale rounded lesions

• Ocular syphilis – Uveitis, retrobulbar neuritis


Spectrum of CMV-Disease

• CMV-Syndrome

• Interstitial Pneumonia

• Gastrointestinal ulcerative disease

• Retinitis

• Hepatitis

• Encephalitis

• Polyneuritis


CMV-GI-Disease

• Ulcerative, necrotizing inflammations of large bowel, gastro-esophageal region, stomach, small bowel, e.g. causing bloody diarrhea or dysphagia

• 2nd most common manifestation in SC-/BM-transplant • 2nd most common manifestation in SC-/BM-transplant patients, in HIV-infected patients and in solid organ transplant patients


CMV-Retinitis

• Most common manifestation in HIV-infected patients, rare in SC-/BM- and solid organ transplant patients

• diffuse necrosis and bleeding, causing rapid loss of vision

• treated with iv GCV, oral VCV or topic GCV• treated with iv GCV, oral VCV or topic GCV



Diagnosis of pathogen?

• Serology not helpful – IgM might be present with reactivation, correlation is quite bac

• systemic replication present in 50% of patients early in the diseaseearly in the disease– pp65-Antigen can be demonstrated on leukocytes

– DNA-PCR has same sensitivity and specifity, easier in large volumes


Case III: pp65 Antigen


CMV viremia as a prognostic marker

Durier , CID 2013


Case III: therapy

• Ganciclovir iv 2x5mg/kg/d or Valganciclovir 900mg/d po for 3 weeks

• Continue maintenance with half dose until CD4> 100 with ART100 with ART

• Alternatives (acute therapy): – foscarnet 2x90mg/kg/d,

– cidofovir 300mg/ weekly iv



Further clinical course

• Lab exam: CD4 cell count 110 (6%)

• Respiratory failure, intubation for 6d

• Rapid recovery, started on tenofovir, emtricitabin, efavirenz day 14emtricitabin, efavirenz day 14

• Discharged day 28 on ART and PcP-prophylaxis


ART works evidently...

• Clinic visits monthly

• On month 2 : CD4 220/mcl, viral load negative –PcP-prophylaxis discontinued

• Month 3: telephone call, patient cannot come in due to severe norovirus diarrhoea, reports dysesthesia in right arm

• Presents two days later with paresis in right arm


What to do with a cerebral mass lesion in HIV?

• Treat empirically for toxo and/or cysticercosis (dependant on your geographic location

• Watch carefully

• If no clinical recovery, think of lymphoma• If no clinical recovery, think of lymphoma– Primary brain lymphoma

– Cerebral manifestation of diss. Lymphoma

• Biopsy of extracerebral manifestation or stereotactic biopsy



Cerebral toxoplasmosis

• Risk factor: previous toxo infection, advanced HIV-infection with CD4 < 150/mcl

• Presents as slowly progressive or rapid focal neurological signsneurological signs

• No specific diagnostic test

• Treatment for 6 weeks– First Choice: Pyrimethamin 150/75mg + Sulfadiazin

8g

– Alternative: Pyrimethamine + Clindamycin


Where did we fail?

• Cotrimoxazole gives some degree of protection against toxoplasmic enzephalitis

• Discontinued rapidly with CD4 cell increase– 3 months further recommended– 3 months further recommended

• Toxoplasmic encephalitis as IRIS?


Simple cases? A word of caution..

• Especially in severely ill patients multiple Ois can be present concomitantly

• Constant clinical vigilance is essential !!


Starting ART on OI-therapy

• Pro:– More rapid recovery of immune system

– Better long term outcome

• Con:– Risk of

additional toxicity, difficult to ascertain to specific drug (eg hematology)

Interactions with OI treatment

– Risk of IRIS


Opportunistic Infections Diagnosis & Management...

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