הצגת מקרה

1. הצגת מקרה מציגה ד"ר אליאס גדיר

2. תלונה עיקרית : בת שנה עם חום ממושך • מחלה נוכחית : בריאה בד"כ. שבועיים טרם קבלתה מחלת חום. אובחנה דלקת באוזניים וטופלה במוקסיפין לשבעה ימים. חום ירד. יום למחרת סיום המוקסיפין – הופיע חום שהתמשך לששה ימים ( סיבת הקבלה ). ללא שיעול הקאה או שלשול. ללא דלקת עיניים או פריחה עורית. אין חשיפה לבעלי חיים. אין טיול לאחרונה. חשיפה: מעון. התנהגות: חיונית.

3. רקע : הריון ולידה תקינים וללא גורמי סיכון לזיהום מסביב ללידה. ללא זיהומים חוזרים בעברה. מלבד דלקת אוזניים X 1. • חיסונים : כמקובל. • גדילה: נולדה משקל 4.240 ובגיל שנה משקל 8.71 ( אחוזון 23 במשקל ) . • התפתחות : תקינה לגיל • משפחה: הורים אינם קרובי משפחה . אין מחלות במשפחה. חמישה אחים בריאים .

4. בדיקה בקבלה : חום 38. דופק: 132 . לחץ דם : 108/50 בדיקה גופנית תקינה. ( ללא לימפאדינופתיה. ללא פריחה. ללא אורגנומגליה . שלד ללא רגישות ... ). • מעבדה במיון : WBC=16.4 NEUT=42% BAND=1% LYM=45% HGB=8.7 MCV= 75.4 RDW= 14.1 RETI=2% PLT=671 CRP=120.8 ESR=1 LDH=484 GOT=24 GPT=10 ALB=3.5 שאר כימיה תקינה שתן כללית מקטטר : תקין LEUC=0-1 NITRIT= NEGATIVE נלקחו תרביות דם ושתן. נלקחו סרולוגיות ל CMV I EBV .

5. רשימת בעיות : 1- חום ללא מקור ? הגדרה ..... 2- אנמיה מיקרוציטית אבחנה מבדלת ?

6. FEVER OF UNKNOWN ORIGIN Fever documented by a health care provider and for which the cause could not be identified after 3 wk of evaluation as an outpatient or after 1 wk of evaluation in hospital. 3 wk of evaluation as an outpatient 1 wk of evaluation in hospital

7. Diagnostic Considerations of Fever of Unknown Origin in Children •  Infections  Bacteria   Caused by specific organism Bartonella henselae (cat-scratch disease) BrucellosisCampylobacterFrancisella tularensis (Tularemia)Listeria monocytogenes (Listeriosis)  Meningococcemia (chronic)Mycoplasma pneumoniae  Rat-bite fever (Streptobacillus moniliformis; streptobacillary form of rat-bite fever)Salmonella  Tuberculosis  YersiniosisLocalized infections Abscesses: abdominal, brain, dental, hepatic, pelvic, perinephric, rectal, subphrenic  CholangitisInfective endocarditisMastoiditis  Osteomyelitis  Pneumonia  Pyelonephritis  Sinusitis

8.  Spirochetes •   Fungal diseases • Chlamydia • Viruses   Cytomegalovirus  Hepatitis viruses  HIV   Infectious mononucleosis (Epstein-Barr virus) • Parasitic diseases   Amebiasis   Giardiasis  Malaria  Toxoplasmosis •  Rheumatologic diseases   Behçet's disease  Juvenile dermatomyositis  Juvenile rheumatoid arthritis  Rheumatic fever  Systemic lupus erythematosus Kawasaki disease   Hypersensitivity diseases

9.  Hypersensitivity diseases Drug fever  Hypersensitivity pneumonitis  Pancreatitis  Serum sickness •   Neoplasms  Hodgkin's disease  Leukemia  Lymphoma  Neuroblastoma  Wilms' tumor •   Granulomatous diseases   Crohn's disease  Granulomatous hepatitis  Sarcoidosis •  Familial-hereditary diseases   Familial Mediterranean fever  Familial dysautonomia •  Miscellaneous   Diabetes insipidus (non-nephrogenic and nephrogenic)  Factitious fever  Hypothalamic-central fever •  Recurrent or relapsing fever

10. המשך מקרה : תרביות דם ושתן – עקרות. ש"ד : עלתה מ 1 .... 140 ( ביום שלישי למחלתה ). כבירור לאנמיה: חוסר ברזל. סרולוגיה ל CMV, EBV - שלילית. הדמייה : צילום חזה : תקין אקו : תקין

11. ביום שלישי לאשפוז ... U/S בטן : כבד וטחול תקינים. כליה שמאלית תקינה. כליה ימנית – מעט מוגדלת ללא הידרונפרוזיס . בקוטב תחתון של כליה ימנית הודגם מבנה היפואקוי בקוטר 1.7 *1.7 ס"מ עם מבנה אקוגני בתוכו ללא זרימת דם ברורה . במקום ראשון – נפרוניה עם התחלת מורסה. לא ניתן לשלול תהליך רקמתי אחר...

12. לסיכום : אבצס בכליה כמקור לחום עם שתן כללית תקין ותרבית שתן עקרה . טופלה בתזוצין ל 14 יום – לתוך הוריד. חום ירד , מדדי דלקת ירדו . הממצא הכליתי נסוג בגודל. לא נזקקה לטיפול כירורגי. הטיפול האנטביוטי הוחלף לציפרוקסים פומי לעוד שבועיים. לאחר שחרורה עברה בדיקת ציסטוגרם – שלא הדגים רפלוקס בדרכי שתן ...

13. RENAL ABSCESS TERMINOLOGY TERMINOLOGY • Acute pyelonephritis : acute bacterial infection of the kidney, without suppuration. • Intrarenal abscess: collection of purulent material within the kidney . • Perinephric (perirenal) abscess: abscess outside the kidney but within the renal (Gerota) fascia. • Renalabscess : includes both intrarenal and perinephric abscess. • Paranephric abscess: resides in the region of the kidney but, is located outside Gerota fascia. • Lobar nephronia : an acute corticomedullary phlegmon characterized by a leukocytic infiltrate with focal areas of tissue necrosis but without liquefaction, confined to a single renal lobe

15. ETIOLOGIC AGENTS ETIOLOGIC AGENTS • Before the advent of antibiotics, most abscesses in the kidney were caused byhematogenous spread (usually of Staphylococcus sp) from distant sites. Staphylococcus aureus: 80% of intrarenal and perinephric abscesses In the preantibiotic era. Continues to be an important cause during childhood • With antibiotic therapy now common, the instances of renalabscess are now primarily caused by ascending infection with enteric, aerobic, gram-negative bacilli, including Escherichia coli, Klebsiella sp, and Proteus sp Enterobacteriaceae - constitute the primary cause of renal abscess.

16. Causative Agents of RenalAbscess (1 month to 19 years of age ) : Pathogen Frequency: Staphylococcus aureus ++ Enterobacteriaceae (especially Escherichia coli and including Salmonella spp.) ++ Pseudomonas spp. + Enterococcus spp. + Coagulase-negative staphylococci + Streptococcus spp. + Actinomyces spp. + Anaerobic organisms + Fungi + Mycobacterium tuberculosis + Polymicrobial infections were described, but a single organism was recovered from most of the abscesses .

17. EPIDEMIOLOGY AND PATHOGENESIS EPIDEMIOLOGY AND PATHOGENESIS • Renalabscess is rare in children • All age groups are affected • There is no gender predominance • Occurs most often in otherwise healthy children • There are certain identifiable risk factors • Diabetes mellitus is frequently noted as a preexisting condition for renalabscess in adults, it is rarely an associated condition in children

18. RISK FACTORS FOR RENALABSCESSES RISK FACTORS FOR RENALABSCESSES • Urinary Tract Conditions   Infection   Anomalies (reflux, obstruction)    Neurogenic bladder    Urinary tract stones    Tumor    Polycystic disease   Peritoneal dialysis • Primary Infection Elsewhere With Bacteremia   Skin     Dental    Respiratory     Gastrointestinal     Abdominal    Cardiac     Genital    Intravascular catheter    Intravenous drug abuse

19. Surgery Urinary tract, including transplantation    Abdominal • Immunodeficiency States • Trauma to Area of Kidney • Diabetes Mellitus

20. Intrarenal abscess - can result from hematogenous spread or as a complication of ascending infection from the lower urinary tract. • The affected kidney can be previously normal or abnormal (e.g., dysplastic or hydronephrotic). • Hematogenous infection - usually is caused by invasion of the blood stream by S. aureus from the skin, another site of infection, or as a spontaneous infection. • Intrarenal abscess that follows urinary tract infection is usually caused by a gram-negative bacillus. • Vesicoureteral reflux is the most frequently associated urinary tract abnormality. • Intrarenal abscess can remain confined to the renal parenchyma, or can extend into the perinephric space or the renal pelvis.

21. Most perinephric abscesses are caused by gram-negative bacilli. • Direct extension from an intrarenal abscess, or infection occurs in association with vesicoureteral reflux or urinary tract obstruction following urinary tract or abdominal surgery. • Perinephric abscesses also can result from hematogenous seeding by S. aureus from a distant primary site.

22. CLINICAL MANIFESTATIONS AND DIFFERENTIAL DIAGNOSIS CLINICAL MANIFESTATIONS AND DIFFERENTIAL DIAGNOSIS • The average duration of symptoms before diagnosis- less than 1 week to approximately 3 weeks • Nonspecific symptoms: malaise, lethargy, decreased appetite, weight loss, nausea, and vomiting • Fever : occurred in 89% ( patients 1 month to 18 months of age ) • Pain : in the flank or abdomen or tenderness in the costovertebral angle - in 85%. most abscesses are unilateral, pain or tenderness is usually unilateral. pain can be referred to the back, periumbilical area, or hip. • Dysuria or frequency - When a renalabscess is preceded by a urinary tract infection • A palpable mass - occurs in about 5% of cases . More likely in infant. • Other findings are (1) scoliosis with splinting of the affected side, (2) pain on bending to the contralateral side, and (3) chest abnormalities, such as decreased respiratory excursion, tenderness over the lower ribs, and pulmonary dullness, decreased breath sounds, and rales on the affected side.

23. Differential diagnosis…. • Acute pyelonephritis : the most likely diagnosis in a febrile patient with symptoms or signs referable to the urinary tract is. • Unilateral renal mass in a neonate : hydronephrosis, multicystic dysplastic kidney, mesoblastic nephroma, and renal vein thrombosis. In an older child, Wilms tumor, other tumors, hematoma, and hydronephrosis are considered.

24. The diagnosis of renal abscess should be considered in : • Failure of response of presumed pyelonephritis to therapy • Fever without an identifiable source after urinary tract or abdominal surgery or dialysis • Fever and urinary tract obstruction • Fever after trauma to the area of the kidney • Fever and pain in the flank or abdomen, or tenderness at the costovertebral angle • Unilateral renal mass • Fever of undetermined origin.

25. LABORATORY LABORATORY • WBC • ESR • Urinalysis • Culture of urine and blood (multiple specimens) . • Cultures of skin lesions, wounds, respiratory tract, and other sites can be useful in selected patients. • An abscess specimen - by aspiration or at the time of surgery for Gram stain and culture.

26. Laboratory Findings Associated with Renal Abscess in 91 Patients 1 Month to 19 Years of Age

27. 1: Pediatr Nephrol. 2007 Nov;22(11):1897-901. Epub 2007 Sep 14. Links Acute focal bacterial nephritis in 25 children. Acute focal bacterial nephritis (AFBN), formerly known as lobar nephronia, is a rare form of interstitial bacterial nephritis…….. From 1984 to 2005, AFBN was diagnosed in 30 children at the University Hospital Münster and the General Hospital Celle, Germany. Data of 25 cases (14 girls, 11 boys) were available for retrospective evaluation. Twenty-five children with AFBN, mean age 4.5 years (range: 0.25-17.5 years), were followed up on average 4.2 years (range: 0.5-11 years). All children were admitted to hospital due to fever and rapid deterioration of clinical condition, initially suspected of having meningitis (four patients), urinary tract infections (five patients), renal tumor (three patients), pneumonia (two patients), appendicitis (one patient), or with only unspecific symptoms (ten patients). AFBN was diagnosed by ultrasound on average 3 days (range: 1-10 days) after onset of symptoms. Pyuria was found in 18/25 children, bacteriuria in 20/25 children, and hematuria in one patient. Blood cultures were negative in all but one patient. Urinary tract abnormalities were found in 12 children, including vesicoureteral reflux (8), megaureter (1), urethral valves (1), unilateral renal hypoplasia (1), and one patient with megacystis, megaureter, caudal dystopic left kidney combined with hypoplasia and dysplasia of the right kidney. High-resolution ultrasound showed AFBN lesions to have resolved completely within 12 weeks after onset of intravenous antibiotic therapy in 20/25 children. Renal parenchymal cysts remained in three cases and focal scarring in two. Blood pressure and renal function was normal in 24/25 cases. AFBN should be suspected in children with fever and rapid deterioration of clinical condition. Residual lesions such as cysts or scarring of renal parenchyma could remain. • AFBN should be suspected in children with fever and rapid deterioration of clinical condition • Residual lesions such as cysts or scarring of renal parenchyma could remain.

28. IMAGING STUDIES Detection, localization, characterization, and guidance in aspiration and for follow-up. • Ultrasonography: Quickest and least expensive The usual initial examination Should be performed in individuals presumed to have acute pyelonephritis that gives rise to atypical findings or is unresponsive to antibiotic treatment May not permit distinction between abscess, phlegmon (nephronia), and uncomplicated pyelonephritis. • Doppler ultrasonography: absence of blood flow in a liquefied abscess • Contrast-enhanced (MRI) and (CT): devascularized nonexcreting areas replacing normal renal parenchyma CT appears to be the diagnostic procedure of choice for renal abscesses • Renal cortical scintigraphy, gallium-67 citrate scanning, and technetium 99—labeled leukocyte scanning : reveal focal masses in the kidney,

31. Patients recovering from a renalabscess should undergo serial sessions of renal ultrasonography to document progress. • Resolution of the ultrasonographic abnormality lags behind clinical and laboratory signs of improvement. • Renal “masses” often take months to resolve. • In many instances, it will be difficult to definitively distinguish a renalabscess from a renal tumor. …..radiologic-guided drainage with analysis of fluid can be helpful in establishing the diagnosis.

32. 1: Pediatr Infect Dis J. 2004 Jan;23(1):11-4. Links Effective ultrasonographic predictor for the diagnosis of acute lobar nephronia. BACKGROUND: Correct identification of acute lobar nephronia (ALN) is necessary to prevent progression to renal abscess. The goal of this retrospective study was to determine whether the sonographic finding of severe nephromegaly (i.e. renal length greater than mean + 3 sd) is a preselection criterion for computed tomographic (CT) scanning in diagnosing pediatric ALN among children with an acute upper urinary tract infection. DESIGN/METHODS: ……All patients with urinary tract infection were evaluated with ultrasonography. If a markedly enlarged kidney or focal mass was present sonographically, CT scanning was done immediately. CT scanning was also performed when the patient had borderline nephromegaly and remained febrile for 72 h after start of antibiotic treatment. ALN diagnosis was made on the basis of positive CT findings. RESULTS: Thirty patients with ALN (13 left, 7 right, 10 bilateral) and one with acute pyelonephritis were identified. …..Thirty-nine of the 62 kidneys evaluated showed severe nephromegaly, and 10 had focal renal masses. With CT diagnosis of ALN as the reference standard, the sensitivity of severe nephromegaly was 90.0% and the specificity was 86.4%. When the focal renal mass was added as a combining predictor, the sensitivity further increased to 95%. CONCLUSIONS: Pediatric ALN was effectively predicted using sonographic findings of severe nephromegaly and/or focal mass before CT scanning. • CONCLUSIONS: Pediatric ALN was effectively predicted using sonographic findings of • severe nephromegaly and/or focal mass before CT scanning.

33. MANAGEMENT • Medical management : intravenous antibiotic • Surgical : ( If it is not successful) percutaneous drainage open surgical drainage nephrectomy • Initial antibiotic- agents active against Enterobacteriaceae and S. aureus. • Nafcillin plus an aminoglycoside - is a suitable combination • Aminoglycoside, or a fluoroquinolone • Addition or substitution of an antibiotic with anaerobic activity, such as metronidazole, clindamycin, or ticarcillin—clavulanic acid, should be considered • Piperacillin and tazobactam sodium Adjustment of therapy - based on the results of culture of an abscess specimen. Therapy for the spectrum of potential pathogens should not be narrowed on the basis of blood or urine culture results alone, because they do not always correlate with isolates from abscess specimens. A clinical response should be expected in 48 to 72 hours. Ten to 14 days of parenteral therapy followed by 2 to 4 weeks of oral therapy is usually sufficient.

34. 1: Pediatrics. 2006 Jan;117(1):e84-9. Epub 2005 Dec 1. Links Effective duration of antimicrobial therapy for the treatment of acute lobar nephronia. OBJECTIVE: Effective treatment of acute lobar nephronia (ALN) can prevent its progression to renal abscess. The goal of this prospective study was to compare the treatment efficacy for pediatric patients who had ALN with a 3- vs 2-week intravenous plus oral antimicrobial-therapy regimen. METHODS: Patients who were suspected of having an upper urinary tract infection underwent a systematic scheme of ultrasonographic and computed tomographic (CT) evaluation for ALN diagnosis. Patients with positive CT findings were enrolled and randomly allocated with serial entry for either a total 2-week or a 3-week antibiotic treatment regimen. Antibiotics were changed from an intravenous form to an oral form 2 to 3 days after defervescence of fever. Follow-up clinical evaluations and urine-culture analyses were performed 3 to 7 days after cessation of antibiotic treatment. Patients with persistent infection or relapse were considered as treatment failures. RESULTS: A total of 80 patients with ALN were enrolled. Forty-one patients were treated with a 2-week antimicrobial protocol, and the other 39 patients were treated with a 3-week course. Seven treatment failures, 1 persistent infection, and 6 infection relapses were identified, all of which were in the 2-week treatment group. Prolonged fever before admission and positive Escherichia coli growth (>10(5) colony-forming units per mL) in urine culture were noted as risk factors for treatment failure…. CONCLUSION: A total of 3 weeks of intravenous and oral antibiotic therapy tailored to the pathogen noted in cultures should be the treatment of choice for pediatric patients with ALN. • CONCLUSION: A total of 3 weeks of intravenous and oral antibiotic therapy tailored to the • pathogen noted in cultures should be the treatment of choice for pediatric patients with ALN.

35. Percutaneous aspiration for diagnosis, culture, and cytologic studies is usually performed with ultrasonographic guidance. • Therapeutic drainage - indicated with perinephric abscess or when obstruction or severe reflux exists • Early aggressive drainage is recommended in immunocompromised patients. • Open surgical drainage- when antibiotic therapy and percutaneous drainage do not result in a favorable clinical response. OR when an abscess ruptured into an adjacent space • Nephrectomy - reserved for the patient with massive abscess in whom function of the involved kidney is unlikely to be preserved.

36. (Urology….) • Abscesses 3 to 5 cm in diameter and smaller abscesses in immunocompromised hosts or those that do not respond to antimicrobial therapy should be drained percutaneously . • Surgical drainage - the procedure of choice for most renalabscesses greater than 5 cm in diameter.

37. COMPLICATIONS • loss of renal function • An abscess can extend within the kidney or perinephric space, causing additional tissue destruction and organ dysfunction. • Can rupture into an adjacent space (abdominal, pulmonary). • Bacteremia from abscess leakage- can result in hematogenous spread of infection to other organs.

38. PROGNOSIS Depends on the presence of : • Underlying conditions • The timeliness of diagnosis • The appropriateness of treatment • Sequelae : is directly related to the loss of renal function and to dysfunction of other organs .

39. PREVENTION • Effective prevention of renalabscesses depends on the appropriate management of the conditions (skin, dental, respiratory, cardiac, abdominal, and other infections, vesicoureteral reflux, urinary tract obstruction, and others) that predispose to their development .

40. תודה להקשבה ........