Infectious diseases clinical cases by kse10139

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									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 39.5°c
  –   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 40°c
   –   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 37°c
• 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 – sarcoidosis-
•   Vasculitis
•   Behçet 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:
   Adalinumab is stopped 
   prednisone 20mg/d
   Isoniazid
   Rifampin
   Ethambutol
   pyrazinamide

Excellent immediate outcome:
   Disparition of fever and 
   hepatalgia
   CPR normal
                 One month later
Fever, polyarthralgia 
CRP 90
Liver cytolysis
No infection found
No MT found
MT was sensible to treatment
Compliance to treatment was 
excellent
Presence of a necrotic 
pulmonary node



                 What is your diagnosis?
  Immune Restoration
Inflammatory Syndrome
                     TB‐IRIS: acute restoration of  a Th1 anti‐
                              mycobacterial response
                                                              P = 0,005
              4000
                        PPD                                           4000
                        CMV


              3000                                                    3000
SFC/10 PBMC




              2000                                                    2000
                                                          p = 0.005
6




              1000                                                    1000



                 0                                                        0
                      T BK   M0   T IRS   M3   M6   M12                       T BK   M0    M1   M3    M6   M12



                                    IRIS +                                                 IRIS -
                                     n=11                                                  n=13



                                                                                     Bourgarit et al, AIDS 2006
                                        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
     doctor…any 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              8



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

								
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