پاسخ:

تشخيص هاي افتراقي:

دكتر محبوبه منصوري

فوق تخصص ايمونولوژي والرژي

The Lab tests which led us to diagnosis

ž            Flowcytometry(PB):

ž            CD3=72%

ž            CD4=10%

ž            CD8=38%

ž            CD19=1.5%

ž            CD16+CD56=21%

ž            CD4/CD8=0.26

ž            IgG=0

ž            IgA=0

ž            IgM=0

ž            X-linked agammaglobulinemia (XLA) is a primary immunodeficiency caused by mutations in the gene for Bruton tyrosine kinase (BTK) that result in the deficient development of B lymphocytes

ž             Affected individuals : hypogammaglobulinemia+reduced levels of B cells

ž             an increased susceptibility to a variety of encapsulated bacteria and enteroviruses, microorganisms for which antibody plays an especially critical role in host defense

ž            both humoral and cellular immunity are important in the clearance of entroviral infection :coxsackieviruses

Diagnostic criteria for XLA

ž            1) a mutation in the BTK gene and/or defective expression of the BTK protein or

ž             2) a positive family history of a maternally related lateral male relative with XLA (for example, either a mutation of the BTK gene or defective expression of the BTK protein or markedly reduced numbers of B lymphocytes in their blood [<2%] and hypogammaglobulinemia) or

ž             3) markedly reduced numbers of B lymphocytes in their blood (<2%) and hypogammaglobulinemi

The  time of the first  infection in XLA

ž            Over half of the patients developed symptoms referable to their immunodeficiency before 1 year of age,

ž            and more than 90% by 5 years of age

ž             Fewer than 10% had symptoms in the first 3 months of life

The most common infection :

ž            otitis media( 70% )

ž             Pneumonia ( 62% )

ž             sinusitis (59%)

ž            chronic and/or recurrent diarrhea (23%)

ž             conjunctivitis (21%),

ž            infections of the skin and subcutaneous tissue(18%) 

ž            meningitis/encephalitis (11%)

ž            sepsis (10%)

ž             septic arthritis (7%)

ž            hepatitis (6%),

ž            and osteomyelitis (3%)

ž            Two patients were reported to have had vaccine-associated paralytic polio

Entroviral infection in XLA

ž            Although the majority of infections were caused by common encapsulated bacteria, there are some infections that deserve special attention

ž             Enteroviral infections, such as Coxsackievirus and ECHOvirus, Polio virus have been especially difficult infections in patients with XLA

ž             The infections are usually chronic and systemic in nature

ž             Their primary clinical manifestation is encephalitis/meningitis

ž            hepatitis, pneumonia, and dermatomyositis have also been seen

ž            Enteroviral meningoencephalitis is a life-threatening infection in  X-linked agammaglobulinemia

enteroviral infection in immunodeficiency

ž            encephalitis/meningitis,:Nuchal rigidity is present in fewer than 70 percent of patients ,Photophobia, nausea, and vomiting  and severe headache

ž            persistent daily headache, irritability, vomiting and fever for 1 month

ž            mild dementia, torticollis, bilateral optic atrophy

ž            a combination of pyramidal and extrapyramidal deficits in the limbs

ž             A cranial CT scan showed a communicating hydrocephalus with dilatation of the entire ventricular system

ž             myeloradiculitis, polyradiculitis, retinitis, or ventriculitis

ž            one case of severe rhabdomyolysis attributed to Coxsackie B in  AIDS

ž            multiple sclerosis (MS) or a MS-like condition In AIDS

CEMA

ž            More recently the complication has acquired the acronym CEMA (chronic encephalitis and meningitis with agammaglobulinaemia).

ž            Human enteroviruses can cause persistent CNS infection in B-cell-defcient patients. Despite ongoing IVIG therapy there is evidence of viral persistence as detected by PCR leading to progressive neurological deterioration in many patients

ž            For immunodeficient patients receiving immunoglobulin replacement therapy, the features of CEMA can be subtle and insidious.

ž            This is probably due to partial neutralisation of the virus by antibodies in pooled immunoglobulin

ž             PID patients show subtle intellectual or personality changes

ž            Unlike the more dramatic and usually fatal systemic enteroviral infection that sometimes occurs in infants, CEMA often progresses slowly over many years with episodes of partial remission.

ž             Nethertheless, a recent survey shows that about half of the 72 patients described in the literature had died between 2 and 5 years after onset of symptoms

Diagnosis

ž            PCR on CSF is a sensitive and specific tool

ž             A negative PCR on CSF does not necessarily exclude the diagnosis and at least another sample of CSF should be tested if enteroviral infection is suspected.

ž            Enteroviruses have been found in the stools  and urine of some patients

ž            and occasionally have been cultured from muscle biopsies in those with myositic features.

Treatment

ž            long term  and ‘high dose ’ intravenous gamma globulin (IVIG)

ž            intraventricular gamma globulin (one patient)

ž            pleconaril (an  antiviral drug )

ž             ‘high dose’ immunoglobulin therapy for complications outside the CNS ( myocarditis, myositis)

ž            There is one report of alpha-interferon apparently curing enteroviral myocarditis in two patients following heart/lung transplantation although there is no evidence yet that alpha-interferon given systemically will inhibit viral replication in the brain

ž            echovirus 71 (in the 2001 Taiwan epidemic )is resistant to pleconaril

treatment

ž            since these RNA viruses can rapidly mutate to become resistant to drugs, combinations of drugs are likely to offer the best chance of cure and protection in the future.

ž            monoclonal antibodies to the prevalent enteroviruses in the community could be developed

ž            Following reports of paralytic poliomyelitis in PID patients after oral polio vaccination (OPV) in the 1960s (Wyatt,1973)

ž            all patients with PID were advised against having live attenuated viral vaccines

ž            In fact, only a few patients given OPV developed paralytic disease, suggesting that additional Unknown susceptibility factors had predisposed these patients to paralysis

خانم دكتر شكوفان عليزاده

رزيدنت بيمارستان مفيد

Case  presentation

•          :PI بیمار پسر 21 ماهه ای که  از 7 ماه پیش بدنبال اتیت و

   8 نوبت تزریق سفتریاکسون دچار پسرفت تکاملی وهمی پارزی سمت راست شده بطوریکه قادر به نشستن و ایستادن نبوده و دچارحرکات پرشی در سمت راست بدن میگردد که غالبا در حالت بیداری اتفاق می افتاده و درخواب وجود نداشته است . همچنین از یک ماه قبل مراجعه ،  دچار staring بوده است. در سیر بیماری دچار تب وتورم مچ پای چپ  نیز می گردد.

•           :PMHبیمار فرزند اول و حاصل زایمان سزارین از والدین منسوب (پسر عمه ،دختر دایی) بدون آسفیکسی  و ایکتر بوده است. خس خس سینه از بدو تولد داشته و تا کنون تحت درمان با    اسپری های استیروئیدی نیز بوده است.

         رشد وتکامل تا 7 ماه قبل از مراجعه کاملا نرمال بوده است.

Drug H:
phenobarbital   phenytoine
Na Valproate    Carbamazepine
Clonazepam

ceftriaxone       ceftazidime
Co-trimoxazole   Vancomycin

spray Floxitide     Ventolin
Vitamins

             P/E :

FTT / Respiratory distress / Clubbing 

RR=30   PR=130   BP=90/60  T=35.9   

 weight=7.5 kg 

 Heart sounds         NL          Abdomen     NL

 Chest         coarse rales in the base of both lungs

Neurologic findings: Hypotone /DTR++ / Downward plantar Reflex / Right Hemi paresis / Myoclonic Seizure in right upper limb more than 30 /min

•          CBC:    WBC:4x10³/ µl

•          RBC=2.99x10-6/ µl     HGB=9g/µl   HCT=29.8 % 

•          MCV=99.7 fl   MCH=30.1 pg    MCHC= 30.2g/dl

•          Plt=379x 10³/µl   poly=34%    lym=62%  mono= 4%  

•          ESR=12  

     HIV ab=neg   

•            entrovirus RNA PCR  in CSF =neg

•          CRP=3+   then  became neg     BC= no growth

•          ABG: PH=7.39   pco2=20     HCO3=12.3

•          Bs=72   BUN=9   Cr=0.3  Na=139  k=4.7  ca=8.6  p=4.4   

•          Alk.ph=616   SGOT=17     SGPT=13   total pro=8.4   alb=4.6   

•          Bil total= 0.4   Bil direct= 0.1    wright & 2ME= neg   widal test =neg  

•           U/A= normal    stool exam =except than few yeast was normal .

•          Sweat chloride test =neg    anti TTG & anti gliadin =NL        

•          EEG = NL      Metabolic work up = Nl

•          Chest x-ray= Normal  

•          bone x-ray =bone  density  is decreased

•          Abdominal ultrasonography : normal

•          Echocardiography= normal

•          Barium swallow: regurgitation  was seen no gasteroesophagial reflux was seen.

•         Problem list :

•          Right Hemiparesis

•          Myoclonic  seizure in right upper limb 30/min

•          Regression & Hypotonicity

•          Sever FTT

•          Clubbing

•          Respiratory distress

•          Macrocytic  Anemia

•          Compensated metabolic acidosis

Missing points

•          Neurological  examination isn’t described well. Retinal examination is missing too.

•          Head circumflex  & body weight at birth?

•          Serum CL is necessary to obtain anion gap?

•          Because of the focal seizure in the patient , Brain imaging should be down at the first step.

•          Respiratory distress? CXR   NL /  RR=30? Pco2=20!

•          LP ?

•          Coagulation tests?

•          Approach to Hemiparesis

•         Vascular :

•            - CHD (VSD / AS /PFO /MS)

•          Acquired heart disease ( RF / Prosthetic Heart valve / Arrhythmia)

•          Increase or decrease clotting factors

•          Infectious Vasculitis  (meningitis: TB / VZV/HIV MYCOPLASMA/ ASPERGILOSIS)

•          Non infectious Vasculitis (PAN /Wegner/ SLE/ IBD)

•          Metabolic disorder (Homocystinuria/ MELAS )

•          Non Vascular:

•          Encephalitis

•          Brain Abscess

•          Malignancy and mass effect

•          Trauma

Congenital / acquired Heart Disease

v  In favor of :

-clubbing

-          FTT

-          Metabolic Acidosis

v  Against of :

-          NL Heart sounds

-          NL Echocardiography

-          Usually they have polycythemia

-          Cyanotic  heart disease / valvular heart disease / arrhythmia / Bacterial Endocarditis

-         Increase or decrease clotting factors

-          Against of :

-          NL  CBC

-          No hemorrhagic / clotting history (but it can’t R/O it)

-          NL    BP

-          Coagulation tests?

-         Infectious Vasculitis
(Meningitis: TB /HIV /Mycoplasma / Aspergilosis /VZV)

-          In favor of:

-          Seizure & Regression

-          Hypotonia

-          Otitis in history

-          Immunodeficiency( inhale corticosteroid spray / FTT)

-           against of :

-          HIV ab = Neg

-          NL  ESR   ( But it can ruled it out)                        

-          No Rash (against of  VZV)

-          CT ?LP?

-          PPD?

-          Gastric washing?

-         IBD & celiac

-          In Favor of:

-          FTT

-          Clubbing

-          Metabolic  Acidosis +/-

-          Macrocytic  Anemia +/-

-          Against of:

-          NL  S/E

-          Anti TTG & Anti Gliadin   NL

-          The history of Bowel  habit is missing

-         Non Vascular Reasons
* Encephalitis

-          In Favor of:

-          Regression

-          Hypotonia

-           Against of:

-          entrovirus RNA PCR  in CSF =neg

-          There isn’t Lack of consciousness

-          LP?

-         *Brain Abscess

-          In Favor of:

-          Regression

-          Hypotonia

-          seizure

-          Fever

-          History of otitis

-          Immunodeficiency

-          Brain CT Scan?

-         Macrocytic Anemia :

-          Phenytoine

-          Co-trimaxazole

-          Vit B 12 deficiency

-          Folat deficiency

-          Clubbing:

-          Pulmonary disease(COPD / CF/ pulmonary fibrosis / lung abscess)

-          Cardiovascular( cyanotic heart disease)

-          Gastrointestinal  (cirrhosis / IBD)

-          Infectious ( Endocarditis)

-          Renal (RTA / CRF / DI)

-          Neoplastic( Hodjkin’s  Lymphoma /Graves)

-         Antibiotics esp. penicillin can  provoke seizure because of beta-lactam . cefteriaxon can cause seizure too, but it’s less than penicillin.(less than 1%) 

-        
D.Dx of Treatable disease in order to the history + P/E + para clinic findings :

-          Infectious vaculitis( Meningitis :TB / Mycoplasma /Aspergilosis)

-          Brain abscess

-          Homocystinuria

-          Coagulopathy /Hemoglobinopathy

-            evaluation :

-          Brain imaging

-          Lp

-          Coagulation tests            

اقاي دكتر منصور كمالي

رزيدنت بيمارستان امام حسين

لیست مشکلات بیمار

1- اتیت های مکرر
2-مشکلات تنفسی مزمن
3-کلابینگ
4- رال در قاعده ریه ها
5-پسرفت تکاملی
6-خیرگی
7-حرکات پرشی سمت راست بدن
8-اختلال رشد
9- کاهش تون عضلانی
10-تب و تورم مچ پای چپ ( احتمال آرتریت سپتیک)

11- کاهش تراکم استخوانی

Hb=9  

  MCV=99.7

WBC= 4000

Poly= 34

L= 62

تشخیص های افتراقی

X- linked agammaglobulinemia

:نکات مثبت

1- اتیت مدیای مکرر

2-پنومونی

3- همی پارزی

4- اختلال رشد ( کمبود هورمون رشد )

نکات منفی:

سن: معمولاً در سن 9-6 ماه ظاهر می شود

CVID

شواهد مثبت:

1-اتیت مدیای مکرر

2-پنومونی

3-همی پارزی راست

4- آنمی مگالوبلاستیک

5- نسبت فامیلی پدر و مادر

Hyper IGM 1

:شواهد مثبت

1- اتیت مدیای مکرر

2- پنومونی

3- نوتروپنی

4- سن

:شواهد منفی

همی پارزی سمت راست

  SCID

شواهد مثبت

1- اتیت مدیا

2- پنومونی

3- اختلال رشد

4- لنفوپنی

شواهد منفی

1- سن

2- اسهال از علایم شایع این بیماری است

تست های آزمایشگاهی

1- اندازه گیری ایمونوگلوبولین ها

2- فلوسیتومتری

خانم دكتر ميترا تفكري

رزيدنت بيمارستان لقمان

Problem list

q      BOY   / 21 MO / F.T.T

q      OTIT IS MEDIA that un response to usual Tx

q      FOCAL MIOCLONIC SIEZURE + HEMIPLAGIA

q      RESPIRATORY DISTREE

q      CLUBBING

q      METABULIC ASIDOSIS

q      MILD  NEUTROPENIA & LYMPHOPENIA

q      ANEMIA

CAUSES OF HEMIPLEGIA IN CHILDREN

q      CVA

q      TIA

q      MIGRAINE

q      HEAD TRAUMA

q      STURGE-WEBER SYN

q      TODD,S PARALYSIS

q      BRAIN TUMOR

q      INFECTION

q      NONKETOTIC HYPEROSMOLAR

q      VASCULITIS

q      DEMELINATING DIS.

q      LEACODYSTROPHIES

q      METABULIC

Epilepsy Difficult to Control DDX

q      AVM

q      SUBDURAL.H

q      NON COMPLIANCE.Tx

q      FOCAL.CNS.DIS

q      INFECTION:

BRAIN ABSCESS          

q      POST TRAUMATIC

q      DRUG

Diseases associated with bilateral clubbing

q      Neoplastic

q      Pulmonary

CF /ASBESTOSIS/  
H.P/IPF/AVM

q      Cardiac:CHD

q      G.I :

•          IBD /Liver disease Celiac sprue/ Juvenile

•          polyposis coli

q      Infectious

•          endocarditis

•          TB

•          Parasite Inf. Chronic

•          HIV

q      Vascular

q      Endocrine

CHILD WITH AN IMMUNDEFICIENCY

q      Family history of immunodeficiency

or unexplained early death

q      failure to thrive

q      Six or more new infections within 12 months

q      Two or more serious sinus infections or pneumonias within one year

q      Need for intravenous antibiotics and/or hospitalization to clear infections

CHILD WITH AN IMMUNDEFICIENCY

q      Recurrent tissue or organ abscesses

q      Infection with an opportunistic organism

q      Complications from a live vaccine

q      Chronic diarrhea

q      Nonhealing wounds

q      Persistent lymphopenia

q      Unexplained autoimmunity

IMMUNODEFFICIENCY

T CELL DEFFICIENCY

BCELL  DEFFICIENCY

COMPLEMENT DEFFICIENCY

PHAGOCYTIC DEFFICIENCY

DEFFICIENCY      ANTIBODY

q      XL AGAMMAGLOBULINEMIA

q      AR AGGAMMAGLOBULINEMIA

q      HYPER IgM SYNDROM  

q      SELECTIVE IgA DEFFICIENCY

q      CVID

OTHER IMMUNE DEFFICIENCY

q      ATAXI TELANGIECTASIA

q      DIGEORGE ANOMALY

q      HYPER IgE SYNDROME 

q      CID

q      JOb syn

q      TORCH

q      SCID

q      CGD

q      COMPLEMENT  DEFFICIENCY

q      METHYL MALONIC ACIDEMIA

q      G.S.D TYPE 1

q      WISKOTT-ALDRICH  SYN

SPECIAL PHYSICAL FEATURES ASSOCIETED WITH
IMMUNODEFICIENCY

q      RECURRENT ABSCESS : CGD  / HYPER IgE 

q      CLUBBING  :

DEFFICIENCY Ab CHRONIC LUNG DIS. DUE TO  

q      ARTHRITIS:

Ab DEFFICIENCY / HYPER IgM /

q      NEUTROPENIA :

HYPER IgM / WISKOTT ALDERICH

LABORATORY TEST IN
IMMUNE DEFFICIENCY

q      B CELL DEFFICIENCY

IgG  /  IgM / IgA / IgE  LEVEL  

Ab RESPONSE TO VACCINE

q      T CELL DEFFICIENCY  

LYMPH . COUNT / CHEST X RAY / DELAY SKIN T

q      PHAGOCYTE DEFICIENCY

WBC COUNT / RESPIRATORY BRUST ASSAY

q      COMPLIMENT DEFFICIENCY

CH50 /C3 LEVEL / C4 LEVEL

SUMMERY

•          BOY + FTT +CLUBBING +NEUTROPENIA

•          CHRONIC CNS  DISORDER  

•          R/O SOLID .T & ABSCESS

•          OTITIS MEDIA : MASTOIDITIS :  PARA MENANGEAL FOCI  :    ABSCESS    

•          IMMUNE DEFFICIENCY₊ BOY

ONE TEST

CHECK OF Ig

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