Transcript جمال عباس عليوي 52 years old married Infertile D.O.A. 17-2

Case presentation
Dr. Sahban Almalah
Presenet by
Dr. Hasanin M.Ali
‫جمال عباس عليوي‬
52 years old
married
Infertile
D.O.A. 17-2-2011
D.O.D. 03-3-2011
• Middle age patients with 1 year history of generalized fatigability ,
progressive weight loss , poor apettite , with productive cough
yellowish to greenish sputum without hemoptysis , intermittant fever
with some time drenching sweating sp. At night.
• Last two months his condition deteriorated inform of exertional
dyspnea , orthopnea , increasing cough and fever , generalized body
swelling and decrease U.O.P.
• Nausea , vomiting with altered bowel motion.
• No joint pain or swelling, No skin manifestations
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He was admitted to Ibn Al Zuhr hospital at first of Feb.2011
Investigations at that time shows:
-B. urea
13 Mmol/L
-S. creatinin 1 mg/dl
-T. protein 48 g/L
-S. Albumin 16 g/L
-S. globulin 32 g/L
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Sputum cytology : infiltration of inflammatory cells , no malignant cells.
Sputum AFB : 3 sample negative
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CXR : ill defined consolidation seen in all zones of both sides,
blunted both costophrenic angles ( pleural effusions),
normal heart size, in conclusion highly suspecious of pulmonary. T.B.
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Abdominal U/S: normal size liver and spleen
moderate ascites and pelvic collection
Rt kidney 13.7*3 cm cortical thickness 1.7 cm
Lt kidney 12.5*5 cm cortical thickness 20 cm
•
Chest C-T scan……
Chest CT scan
 Thick regular outline cavitary lesion at apical segment of right upper
lobe measured 57*47 mm.
 Wide spread reticulonodular and fibrotic changes seen at both lung
field .
 Multiple mediastinal LAP seen at subcarainal lesion causing widening
of caraina.
 Lt side pleural effusion associated with ascites.
 The mediastinum is central.
 Normal trachea and major bronchi.
 The heart and major cardiothoracic vessels shows no abnormalities.
 The thoracic skeleton and soft tissues show no obvious
abnormalities.
 Conclusion: T.B. can not be excluded.
 So that they were started Anti T.B. medication.
• He was referred to us as there was asuspecion of renal impair.
• At admission pt. complaining from dyspnea even at rest , productive cough , low
grade fever , generalized body odema , pallor .
• Investigation at admission:
-FBS 100 g/dl
-B.urea 77 mg/dl
-S. Na 144 meq/L
-S.k 3.7 meq/L
-T.S. protein 34 g/L -S. Alb. 9 g/L
- normal LFT.
-S.creatinin 2.2 mg/dl
-S. Ca. 7 mg/dl
-S. globulin 25 g/L
- G.U.E./ turbid , Albumin +++, Rbc few , pus cell 8-10.
- Urine for protein/creatinin 5.5
- Blood film/ pcv 35%, wbc 8.500, plt 260.000 - ESR 85 mm/hr.
- normocytic normochromic with eosinophilia ( 6%).
• Kidney biopsy was done for him.
• Treatment started inform of :
-Frusemide amp. 120 mg/day.
-Spironalactone tablet 200 mg/day.
-Simvastatin tablet 20 mg/day.
-Paracetamol tablet 1500 mg/day.
-Aspirin 100mg/day.
-B6 tablet 40 mg/day.
-Anti T.B.
- Ceftriaxone vial 1g/day.
• After 3 days his dyspnea and fever subside but still there was
generalized body odema so we added:
- Albumin infusion 20% 150 cc/day .
• Serologicat test:
-ANA negative
- Anti ds DNA negative
-C3 92.7 (N 84-193)
- C4 21.9 (N 20-40).
-ANCA normal.
• S. Protein electrophoresis :
-markdly reduced albumin , reduced B and Gama globulin with increased Alpha
globulin.
• Urine for Bence Jones protein : Negative.
• At 28/2/2011 :
-B.urea 67 mg/dl
- S.Na 131 mg/dl
- S.protein 40 g/L
- S.creatinin 3 mg/dl
-S. K 2.8 meq/L
-S.Albumin 17 g/L
-G.U.E. Albumin +++ , pus cell few , Rbc few , No cast.
-WBC 12700
-PCV 32%
• At that time He was clinically better afebrile , dyspnea and odema subside.
Kidney biopsy:
Amyloidosis
• Amyloidosis is a group of diseases characterized by extracellular deposition
of beta-sheet fibrils.
• In the systemic forms, the amyloid causes progressive organ dysfunction
leading to death of the patients.
• Over 20 proteins capable of amyloid formation have been identified. They
include :
o Ig light chains (AL) in primary systemic amyloidosis,
o Ig heavy chain (AH),
o Amyloid A in secondary amyloidosis (AA),
o Beta2-microglobulin in dialysis-associated arthropathy (Ab2M),
o Amyloid beta protein (Ab) in Alzheimer disease and Down syndrome,
o Hereditary forms that include transthyretin (ATTR), apolipoprotein A-I
(AApoAI) and A-II (AApoAII), gelsolin (AGel), lysozyme (ALys), fibrinogen Aalpha chain (AFib), and others
SECONDARY (AA) AMYLOIDOSIS:
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Also called reactive amyloidosis occurs in patients with chronic inflammatory diseases.
Rheumatoid arthritis (adult or juvenile) currently accounts for up to 40 % of cases .
The other major conditions associated with AA amyloidosis are ankylosing spondylitis,
psoriatic arthritis.
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chronic pyogenic infections (bronchiectasis, osteomyelitis, chronic skin or decubitus ulcer
infections in intravenous drug users or paraplegics, or tuberculosis).
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Inflammatory bowel disease (primarily Crohn's disease with suppurative infections).
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Cystic fibrosis, some neoplasms (particularly renal cell carcinoma and Hodgkin lymphoma).
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A number of genetic disorders associated with chronic inflammation have also been
reported to cause AA amyloidosis. These include familial Mediterranean fever,
hyperimmunoglobulinemia D syndrome (HIDS), tumor necrosis factor receptor-associated
periodic syndrome (TRAPS), and Muckle-Wells syndrome.
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On the other hand, not all autoimmune diseases (including those associated with chronic
inflammation) lead to amyloid formation, as AA amyloidosis is rare in patients with systemic
lupus erythematosus and diabetes mellitus.
Clinical manifestations and site of deposition
• The clinical manifestations of the renal disease vary with the site of involvement:
 Glomerular deposits — common presentation.
• Nearly 75 % of patients present with proteinuria.
• The degree of proteinuria can range from mild to massive (>20 g/day).
• The urine sediment is typically benign (reflecting the lack of inflammation),
• The plasma creatinine concentration may be normal or only moderately
elevated.
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End-stage renal disease develops in approximately 20 % of those with the
nephrotic syndrome, with poor patient survival overall.
 Vascular and tubular amyloid deposits — Occasionally
the amyloid deposits are primarily limited to the vessels, leading to
narrowing of the vascular lumens.
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These patients usually present with slowly progressive chronic
kidney disease with little or no proteinuria.
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Prognosis in such patients appears to be more favorable.
• Even less common is heavy tubular deposition, potentially leading to
signs of tubular dysfunction such as type 1 (distal) renal tubular
acidosis or polyuria due to nephrogenic diabetes insipidus.
• Acquired Fanconi syndrome has been reported in rare cases
Crescentic glomerulonephritis: It is an extremely rare
complication superimposed upon renal amyloidosis.
• Almost all reported patients have had AA amyloidosis due to rheumatoid
arthritis or its variants.
• A possible mechanism is amyloid fibril-induced ruptures in the capillary
loops, leading to fibrin entry into Bowman's space.
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Another possibility is that the glomerulonephritis is related to rheumatoid
arthritis or its therapy.
• Two factors argue against this hypothesis: not all affected patients have had
rheumatoid arthritis; and crescentic glomerulonephritis is not a
characteristic feature of renal involvement in rheumatoid arthritis.
• The possible presence of crescentic glomerulonephritis should be suspected
in a patient with renal amyloidosis who develops acute renal failure in
association with an active urine sediment. Optimal therapy of this problem
is not known.
• Pathogenesis:
AA amyloidosis is associated with increased hepatocyte
production of the acute phase reactant serum amyloid A (SAA); this process may be
stimulated by the release of cytokines (perhaps interleukin-1) from activated
macrophages. Cleavage in circulating monocytes/macrophages results in the
generation of smaller fragments, called AA protein, that can then deposit in the
tissues.
• Light microscopy : Light microscopy in renal amyloidosis typically
reveals diffuse glomerular deposition of amorphous hyaline material, initially in the
mesangium and then in the capillary loops. These nodules only weakly stain with
periodic acid Schiff's (PAS) and methenamine silver stain because they are
composed mostly of amyloid fibrils and not extracellular matrix as in diabetes
mellitus.
• Scanty deposits of amyloid may go undetected by light microscopy, especially
when thin sections are used.
• . There is also a poor correlation between the extent of glomerular amyloid
deposits and the degree of proteinuria.
Immunofluorescence :
• Amyloid deposits also may be seen in the small arteries, arterioles,
and tubular basement membranes.
• Immunofluorescence microscopy is negative for immunoglobulins
and complement in AA amyloidosis but is typically positive for
lambda or kappa light chains in the AL amyloid.
• False negatives with immunofluorescence (using single commercially
prepared antisera against the kappa and lambda light chains of
immunoglobulin) can occur in 25 to 35 percent of cases. To increase
sensitivity in this setting, the antisera from multiple venders may be
used, and immunoperoxidase can also be helpful.
PROGNOSIS :
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If untreated, AA amyloidosis is a serious disease with a significant
mortality due to end-stage renal disease, infection, heart failure,
bowel perforation, or gastrointestinal bleeding .
• Patients with persistently high circulating levels of SAA are at
particular risk to develop these complications of disease.
• As an example, in a Japanese study of 42 patients with AA
amyloidosis associated with rheumatoid arthritis the ten-year survival
was 19 % ; survival was adversely impacted by the presence of
azotemia and/or cardiac involvement at the time of diagnosis
Treatment:
• Importance of control of the underlying disease — Successful
treatment of the underlying inflammatory process (as with
cytotoxic agents in rheumatoid arthritis or antibiotics with
chronic infection) can lead to stabilization of or improvement in
renal function, reduction in protein excretion, and partial
resolution of amyloid deposits.
• Serial serum amyloid P component (SAP) scintigraphy was
carried out in 221 patients, with evidence of regression from
baseline in 87 (39 %). SAA levels in those regressing were
significantly lower than those in whom the amyloid was
unchanged (48 %) or increased (12 %).
Colchicine:
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IT has become accepted therapy for secondary amyloidosis.
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In familial Mediterranean fever (FMF), for example, colchicine (in a dose of 1 to 1.2 mg/day)
markedly reduces the frequency of attacks of abdominal pain, diminishes the incidence of
clinical renal disease (including prevention of recurrence in the renal transplant), and can
stabilize the glomerular filtration rate in patients with mild proteinuria.
IT is not likely to be effective in FMF patients who already have chronic renal failure, since
irreversible glomerular injury is probably present.
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Anecdotal successes with chronic colchicine therapy (0.6 mg BID) have also been reported in
patients with AA amyloid due to inflammatory bowel disease, Behcet's disease, and in
intravenous drug users with suppurative skin lesions; proteinuria due to renal amyloidosis
may be markedly reduced and renal function may remain stable over long periods of time.
However, repeat renal biopsy in one such patient did not demonstrate a reduction in total
amyloid deposition despite almost complete resolution of proteinuria.
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It is not clear whether the efficacy of colchicine in some of these settings is related to a
direct reduction in amyloid fibril production or to decreased activity of the primary disease
(as may be the case in FMF, in which attacks may be associated with massive neutrophilic
infiltration into affected tissues).
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Regardless of the mechanism, colchicine must be continued indefinitely unless the
underlying inflammatory disease can be corrected.
Anti-cytokine therapy (under investigation):
• Increasing use of biologics with activities against proinflammatory
cytokines (tumour necrosis factor alpha and Interleukin-1) for
diseases such as RA and AS may impact risk factors for the
development of AA amyloid, and also be associated with reversal of
established disease .
• Tumor necrosis factor receptor-associated periodic syndrome
(TRAPS), which is responsive to etanercept or infliximab , or MuckleWells disease/familial cold autoinflammatory disease, which appears
to be responsive to interleukin-1 receptor antagonism, is under
investigation .
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An anti-interleukin-6 receptor antibody has been shown to attenuate
experimental AA amyloid, and to reverse AA amyloidosis complicating
juvenile idiopathic arthritis
Cyclophosphamide:
• A small retrospective study reported that cyclophosphamide may provide a
significant survival benefit in French patients with rheumatoid arthritis and
renal AA amyloid
• In this study of 15 such patients, of whom six received monthly
cyclophosphamide following confirmation of renal involvement, the survival
of patients treated with pulse cyclophosphamide was longer than that of
those administered non-alkylating drug regimens (mean survival of 165 and
46 months, respectively).
• Trends toward decreased proteinuria and maintenance of renal function
were also noted with cyclophosphamide.
• Similar results were confirmed in cohort study reported from Japan.
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Prospective studies are required to properly assess the role and toxicity of
this agent in this setting.
Eprodisate:
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IT is the first of the low molecular weight anionic sulfonates whose efficacy in slowing renal
disease progression in patients with AA amyloidosis has been reported.
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A two-year double-blind multicenter international study randomly assigned 183 patients
with AA amyloidosis with renal involvement to receive oral eprodisate (800 mg to 2400
mg/day in divided doses depending upon renal function) or placebo.
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Significantly more patients on active treatment had renal function that remained stable or
improved compared to those receiving placebo (40 versus 27 percent, respectively).
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There was no significant difference in mortality, proteinuria, or the tissue content of AA
amyloid.
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The drug was well-tolerated. A nonsignificant trend toward a higher proportion of patients
with chronic diarrhea was noted (four percent versus one percent for eprodisate and
placebo, respectively).
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Further studies of this novel approach to treatment of amyloidosis are anticipated.
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At present, eprodisate is not available for clinical use.
DIALYSIS AND RENAL TRANSPLANTATION:
• Patients with renal amyloidosis who progress to end-stage renal
disease can be treated with either dialysis or renal transplantation.
• Hemodialysis and continuous ambulatory peritoneal dialysis (CAPD)
appear to be equally effective, with the limiting factors being the
degree of extrarenal amyloid deposition, hypotension with
hemodialysis, and peritonitis with CAPD.
• The experience with renal transplantation in renal amyloidosis is
mostly limited to AA amyloidosis, since patient survival is often
relatively short in AL amyloidosis. However, increased survival and
renal transplantation in AL amyloidosis has been reported.
• Recurrent amyloid deposition in the transplant occurs in 20 to 33 %
of cases due to continued activity of the underlying disease.
However, graft loss due to recurrence is uncommon.
Thank you