Infectious diseases clinical cases

Daniel Sereni ESIM, London 2009

This is an infectious disease What is its name ? What is the causal agent?

 HHV-8 Endemic Kaposi sarcoma More frequent in Africa and in the mediteranen region Immunocompetent Treatment
Local:cryotherapy radiation, local chemotherapy Systemic chemotherapy: bleomycin, vinblastin,

Fever 15 days after delivery

Fever 15 days after delivery

Female 29 Congenital ventricular septal defect
well tolerated

No other medical history No pets, No recent travel No contact with any one with an infection Newborn in perfect health First pregnancy 15 days after delivery Fever 38-39 c presumed to be due to a painful tooth The tooth has been extracted Amixicillin 2 g + clavulanic acid for 4 days

 uncomplicated delivery Patient received amoxicillin +gentamycin as prophylaxis Fever continues 38 39 c for ten days Clinical examination : normal -except heart murmur Chest X ray normal Usual biology normal

Your first line hypotheses ?

first line hypotheses Infection linked to recent delivery frequent peri partum problems:
urinary infection deep venous thrombosis

endocarditis

First step mandatory procedures ?

First step mandatory procedures

Refer the patient to the obstretrician Blood cells count D-dimers PCR, fibrin Blood cultures Urin test for infection Repeat usual biology Ultrasounds legs and pelvis

Gynecologic infection ruled out by specialist examination and echography

Endocarditis negative blood cultures TT and TO echocardiographies :normal Venous thrombosis or pulmonary Emboli: D-dimers: normal Echography of the pelvis: normal sinuses CT scan :normal thorax-pelvis-abdomen CT scan : normal ASAT x 3N , ALAT x 2.5N

The patient has now been febrile for 20 days She feels tired but has no specific symptom Clinical examination non contributive Hematocrit 30% Haemoglobin 10.3 g/dl 8000 leukocytes
Neutophils 17% Lymphocytes 72% Monocytes 8% Eosiniphils 2% Basophils 1%

New abdominal echography shows discret liver and splenic homogeneous enlargement ASAT x 2N ALATx 1.5N Alkalin phosphatasis, bilirubin: NL

What are the main causes of cytolytic hepatitis in this context ?

causes of cytolytic hepatitis in post delivery context

HELLP syndrome and pre-eclampsia Acute liver steatosis during pregnancy Heart failure autoimmune diseases
Auto-immune hepatitis Primary biliary cirrhosis

Toxic infections

Non bacterial liver infections

Mycobacterias viruses Fungi Parasites

What would you look for first ?

 Viruses
HIV negative

HBV : vaccinated HCV negative

other viruses?

coexistence of liver cytolysis and blood lymphocytosis

EBV presence of IGg antibodies CMV: positive plasma PCR IgG negative IgM positive CMV primary infection

Brutal onset of fever and painful swelling of the hand

In the emergency room

Brutal onset of fever and painful swelling of the hand

82 years old lady No relevant medical history Fever 40.5 Intense pain 14 200 leukocytes , 82% neutrophils CPR 154mg/l When asked,she says that she may have knocked her hand in her kitchen two days before.

What is your next step?

Insert a needle into the wrist for synovial aspiration and culture Obtain an echography Obtain an CT scan Obtain an MRI Obtain an Xray Refer the patient without any delay to the surgeon

 pseudogout attack
Acute arthritis due to calcium pyrophosphate crystals deposition Chondrocalcinosis >30% after 80 Attacks may be precipitated by trauma, acute disease ,surgery, diuretics,.. Intense inflammatory synovial fluid
20 000 to 100 000 cells (~80% neutrophils ) Presence of CPP crystals

Treatment:
colchicine (start with 2 to 3 mg/d) NSAIDs Intra articular corticosteroids

What treatment would you prescribe to this immunocompromised man with a painful eruption?

Herpes zoster (shingles)

in HIV infected persons CD4< 200 and severe cases
acyclovir IV 30 to 45 mg/day For a minimum of 10 days

CD4 >200 and non extensive cutaneous lesion

valacyclovir orally 3 g /day For 10 days

Fever in a frequent traveller

Fever in a frequent traveller

Female 64, journalist and writer travels several times per year in Asia and Africa No relevant medical history Temperature 38.5 to 39.5 one month after her last trip India Started insidiously Becoming progressively more severe with shivers No associated symptom diarrhea or other..

Clinical examination by her family doctor normal Examined by an otorhinolaryngologist: nothing abnormal

What would you prescribe?

Blood cells count

Normal No hypereosinophilia

CPR 88 mg/ l Blood culture negative No plasmodium on blood smears No bacteriuria No parasit in faeces Chest X ray normal HIV,HCV,HBV negative IgG HVA antibodies Usual biochemistry normal TSH normal And

 Legs ultrasound normal Liver tests

ASAT 1.5 x N ALAT 2 x N Gamma GT 3 x N Alkaline phospahatase 3.5 x N

Tenderness in the liver region, no hepatomegaly What do you need now?

What is your diagnosis?

What procedure do you prescribe?

Amebiasis serology

Amebic liver abcess Diagnostic issues

Fever may be isolated in 15 to 20% of cases The absence of dysenteria or diarrhea at onset is frequent Faeces examination may be negative Serology ELISA- is highly sensitive and specific aspiration of the abcess is possible but may be at risk is not usually done may be usefull when diagnosis is uncertain

 Treatment
metronidazole 500mg x 5 x 1month Followed by a luminal anti amebic agent tiliquinol- x 10 d

Aspiration is not necessary in most cases Surgery only in case of rupture

Acute fever in a patient with SLE

acute fever in a patient with SLE

Female 33 y History of systemic Lupus
onset in 2001 cutaneous rash pericarditis + polyarthritis prednisone for one year Hydroxychloroquine sulfate since 2002 No SLE relapse

Office work Married, one child

 Her sister has been diagnosed with pulmonary TB Her family doctor found no evidence of active tuberculosis in our patient:
Clinically asymptomatic Normal chest Xray 20mm positive ppd skin test

however, he prescribed :
Rifampin 600mg /d Isonazid 300mg/d.

 Ten days later she presents an acute illness:

Fever 39.5c Cephalalgia nausea Lumbar pain

A treatment by amoxicilline ( 2g/d) is prescribed, but her condition worsens and she is refered to the ER of Saint-Louis hospital in Paris

 At entry
Temperature 40c Headache Arterial BP 80/60mm Hg Nausea Low back pain with unilateral sciatalgia Normal consciousness No stifness of the neck No Brudzinski or Kernig signs Skin, joints, mouth, ears : normal Pulmonary, cardiac examinations : normal No hepatomegaly or splenomegaly or anormal lymph nodes

questions
What are your first conclusions? What do you need?
Imaging? Biology ?

 Main hypothesis at this stage

Tuberculosis Any other infection Lupus relapse

Infections: more specifically, because of low back pain and radiculagia

Spondilitis Meningitis with radiculitis Renal/urinary infection

 Major biology findings at admission:

Hematocrit 33% Leukocytes 10 700 / microl 100 200 platelets CPR 66 mg/l ASAT 218 u ( N< 31) ALAT 156 u ( N < 31) No bacteriuria, leukocyturia, hematuria No proteinuria Blood cultures negative

 Chest X ray: normal Lombar spine Xray: normal What would you prescribe now?

 brain MRI Spine MRI Renal echography Renal CT scan Lumbar puncture

 Brain MRI: normal Dorsal and lombar spine MRI : normal Lumbar puncture
158 cells
62 % neutrophils 34% lymphocytes

Proteins 0.84 g/l Glucose ~ 50 % glycemia No microorganism at examination

 What is your diagnosis? Do you start a treatment?

Possible bacterial meningitis

Patient transfered to intensive care unit IV Treatment by
Cefotaxime Amoxicillin Vancomycin Dexamethason

Other medications are interrupted

Two days later..

Strictly asymptomatic, temperature 37c Leukocytes, platelets, CPR, ASAT, ALAT normalised Lumbar puncture:
CSF strictly normal < 5 cells

CSF and blood cultures are negative Antibiotics and dexamethasone are interrupted after 6 days of treatment The patient is discharged and treatment by hydroxychloroquine sulfate, isoniazid and rifampin is reintroduced

One hour after intake of the tablets

Temperature 40 c, shivers, intense cutaneous rash with oedema, pruritis Diffuse arthralgias, headache ,lumbar pain, abdomibnal pain, diarrhea, vomiting At examination: neck stifness, rash and oedema of face Biology:
20 300 leukocytes, 19 900 neutrophils 410 eosinophils PCR 114 mg/l

One more lumbar puncture

175 cells ( 99% neutrophils) Proteins 0.6g/l Glucose ~ 50% glycemia No microorganism

Two days later

All treatment have been stopped

Patient feels perfect, totally asymptomatic All biologic tests are now normal, including another ( and last..) lumbar puncture.

What is your diagnosis?

Non infectious meningitis

Lymphoma Carcinoma Granulomatosis sarcoidosisVasculitis Behet disease recurrent inflammatory meningitis Allergic or hypersensibility

Final diagnosis
Drug Induced Aseptic Meningitis DIAM-due to Rifampin
Typical clinical features reintroduction ( unplanned) Confirmed by skin test

Drug Induced Aseptic Meningitis

NSAIDs Antibiotics IV Immuno- globulins vaccines biotherapies

More frequent in patients with connective tissue disease, like Lupus, Sharp , Sjogren,..
One recommanded paper
Moris G, Garcia-Monco JC.The Challenge of drug induced aseptic meningitis . Arch. Intern. Med. 1999, 1185- 1194.

Paradoxical outcome in an immuno-compromised patient

 Female 69 1999 treated by azathioprin for Crohn disease 2005 diagnosed with gigantocellular temporal arteritis
corticosteroids cannot be lowered below 40mg/d

January 2007: initiation of treatment by Humira adalinumab- 40mg / 2weeks

What do you think of this decision?

March 2007 persistant fever

PPD skin test negative Multiple nodes in liver and spleen Liver biopsy: epitheliod granuloma non necrotic thorax CT scan normal Presence of M Tuberculosis at direct examination of sputum

Treatment: Adalinumabisstopped prednisone20mg/d Isoniazid Rifampin Ethambutol pyrazinamide Excellentimmediateoutcome: Disparitionoffeverand hepatalgia CPR normal

One month later

Fever,polyarthralgia CRP90 Livercytolysis Noinfectionfound NoMTfound MTwassensibletotreatment Compliancetotreatmentwas excellent Presenceofanecrotic pulmonarynode

What is your diagnosis?

Immune Restoration Inflammatory Syndrome

TBIRIS:acuterestoration ofaTh1anti mycobacterial response

P=0,005
4000

PPD CMV

4000

3000

3000

SFC/10 PBMC

2000

p = 0.005

2000

1000

1000

T BK

M0

T IRS

M3

M6

M12

T BK

M0

M1

M3

M6

M12

IRIS +
n=11

IRIS n=13

Bourgarit etal,AIDS2006

intense Th1 anti-mycobacteria response

ELISpot IFN-gamma
3500

3000

2500 SFC/106 PBMC

2000

1500

1000

500

0 PPD ESAT 6 CFP10

favorable outcome without any change in her treatment

The immune inflammatory reconstitution syndrome in a patient infected with HIV-1 who had central nervous system toxoplasmosis

Tremont-Lukats, I. W. et. al. Ann Intern Med 2009;150:656-657

A case of recurrent bronchiolitis

31 y old male From Mali In France since 2004 Medical history

Typhoid fever malaria

 Refered to our clinic for fever and cough after two episodes of bronchitis in the last three months
Fever 38 38. 9 c Cough Purulent sputum

both treated by antibiotics

A Macrolid Amoxicillin 6 g/d

Main symptoms and lab results

Temperature 39. Polypnea 25/mn , PaO2 66 mm Hg Purulent sputum Crackles and ronchi at auscultation ppd skin test negative Leukocytes 12.000 78 neutrophils 0% eosinophils HIV negative ASAT 2.5xN, ALAT 1.5xN Alkaline Phosphatasis 3xN

3 Sputum smears negative for bacterias and Mycobacterias

What are your hypotheses?

The next morning the patient brings the diagnosis to the doctorany idea?

Ascaris lumbricoides
Endemic worldwide Up to 40 cms long After Oral ingestion develops the intestine, migrates to rthe lungs,and return to the intestine Complications:
Respiratory: cough, interstitial bronchiloitis, Loeffler syndrome, Digestive: intestinal or biliary obstruction

Diagnosis and treatment

Diagnosis
Hypereosinophilia Eggs in faeces

Treatment
Mebendazole Albendazole Pyrantel pamoate (combantrin)

A patient with fever, peripheral oedema and a swelling of the calf

A patient with fever, peripheral oedema and a swelling of the calf

Male patient 59 Asian origin Truck driver No alcohol, non smoker Medical history: -peptic duodenal ulcer operated 25 years earlier -prostatic benign hypertrophy treated by tamsulosine ( alpha blocker)

Admitted for
fever 39 - 40 c shivers synovitis of left ankle peripheral oedema painful inflammatory mass of the left calf

58 kg/ 168 cm BP 132/ 75 mg hg, HR 92/ mn No other abnormal clinical finding

Your hypotheses ?

 Septicaemia Inflammatory disease The leg mass could be

Abscess Haematoma Phlebitis tumour

What about the bilateral oedema?

Heart failure Nephropathy Others?

biology
Leukocytes 9600 / 78%neutrophils Hematocrit 32 % Haemoglobin 8.7 g/ dl CPR 251 mg/l Fibrinogen 6.70 g/l Creatinin clearance 30 ml/mn Albumin 30 g/l Gamma G 3.9g/l Proteinuria 3,8 g / 24h Calcemia 2.34 mmol /l ASAT x 3N, ALAT x 3N

diagnoses septicaemia S. aureus beta-lactam sensitive

Abcess left calf due to SA Context of hypogamma globulinemia Nephrotic syndrome Monoclonal gammapathy with lambda light chains in urin Bone marrow plasmocytosis 8 % heart, kidneys, liver hypertrophy

Staphyloccocus aureus septicemia

Treatment
Piperacilline / tazobactam IV fluids and electrolytes Oxycodone ( oral morphin analog) heparin calcium 5000 UI sub-cutaneaous, bid.

Amyloidosis AL
after successful treatment of the SA infection chemotherapy prednisone bortezomib (velcade) / melphalan