Transcript Case Study - NEJM - A Hard Diagnosis

A HARD DIAGNOSIS
N ENGL J MED 361;6 August 6, 2009
Florian Anzengruber
Internal Medicine B
Sheba Medical Center, Israel
Professor Schoenfeld
PATIENT
• 56 year old woman
• 4 week history of malaise
•  WBC:16,000/mm³  sulfa AB
 persistence
Symptoms
• Chest pain
• No dyspnea
• Weight loss
• Nausea
• Abd pain
• Hematuria
• Myalgias
• Arthralgias
• Urticarial rash on
her arms
(periods)
MEDICAL HISTORY
• Autoimmune thyroiditis
• Vitiligo
MEDICATIONS TAKEN
• Thyroid hormone – replacement therapy
• Recently sulfa AB
Patient denies history of…
• Alcohol abuse
• Smoking
• Illicit drugs use
• Recent travels
• Pets
PHYSICAL EXAM I
• Alert and comfortable
• 37.7°C
• 160/80 mmHg
• 93 BPM
• 100% - breathing ambient air
PHYSICAL EXAM II
• Jugular venous pressure : normal
• 2+ pitting
• Pretibial edema bilaterally
• Bilateral periorbital edema
PHYSICAL EXAM III
• Skin: diffuse patchy areas of
depigmentation on the arms, chest,
neck, face, and scalp AND vitiligo
• The rest of the physical exam including
thyroid, lungs, heart and neurological
exam was unrevealing
LABORATORY I
• WCC: 18,100/mm³
• 83% neutrophils
• Hematocrit: 28.5%
• MCV: 85µm³
• PLT: 47,000/mm³
• ESR: 99mm/hour
(4,300 - 10,800)
(45 -70)
(37- 48)
(78-102)
(150-400)
(0- (age +10/2))
LABORATORY II
SERUM LEVELS
• Creatinin: 8.9mg/dl (0.5-1.0mg/dL)
(1.0mg/dl 1 mo)
• Urea :77mg/dl
• Albumin: 2.5g/dl
(20-30 mg/dL)
(3.5-5.0 g/dl)
Urinanalysis
• Proteins: 100mg/dl
• No red or white cells or casts
• Spot urine protein to creatinine
ration: 1.6
ADDITIONAL TESTS
• Periph. blood smear: no schistocytes
• Kidney US: no obstruction
• Thyrotropin: 14.8mU/l (4 - 4,5)
• C3: 76mg/dl (71-159)
• C4: 1.9mg/dl (13-30)
In summary...
• 56 year old woman
• 4 week history of malaise
• Myalgia, arthralgia, abd. Pain, urticarial
rash
• Acute renal failure, no sign. proteinuria,
leucocytosis, anemia, thrombocytopenia,
• ESR ↑, low C4
DD
1. Autoimmune disease – possible SLE
– but C3 level would be decreased
– no microscopic hematuria (accompanies
rapidly progressive glomerulonephritis
2.Acute tubular necrosis
- no hemodynamic or toxic insult
- no muddy brown casts
3. MM
- Anemia, elevated ESR and renal insufficiency, but
no sign. proteinuria.
Hospital day 1
• Raised, erythematous, pruritic plaques
on arms and legs (as before) and uticaria
• Skin biopsy:
–Superficial perivascular and interstitial
infiltrates of lymphocytes, neutrophils,
and eosinophils
• Direct immunofluorescence:
–Neg for IgG and complement
RESULTS III
• ANA titer: > 1:640
• Negative:
– double- stranded DNA
– ribonucleoproteins (Ro and La)
– nuclear antigens (Smith and RNP)
– serine protease 3
– myeloperoxiades AB
– antistreptolysin O
RESULTS IV
•Normal:
nitrogen:
•Serum &urine
•77 99mg/dl
electrophoresis
•Creatinine level:
•Chest X-ray:
•10.7mg/dl
•Mild pulm. Edema
•Blood cultures:
•No growth
•Serum urea
WHAT TO DO
NEXT?
WHAT TO DO NEXT?
• Urticaria:
Several DD, but most causes idiopathic
• Renal failure:
1. Glomerular causes of renal failure
i.e. cryptoglobulinemia, membranoproliferative
glomerulonephritis
2. Vascular causes of renal failure
i.e. Polyarteritis nodosa
3.Coagulopathy
4.Viral disease i.e. HBV
ANA titer suggest
• SLE
• Mixed connective - tissue disease
• Sjögren‘s syndrome
• Other AD
TREATMENT
• Hypertenison  Metoprolol
100mg 2x and 10mg daily
amlodipine  sys BP 
<150mmHg
• Metaboilc acidosis & fluid
overload  hemodialysis
KIDNEY BIOPSY
• No evidence of mesangial hypercellularity
• Diffuse, mild interstitial fibrosis
• Medium-size muscular artery almost
completely occluded
• Arterial wall was preserved without
transmural inflammation /necrosis
• No glomerular or tubulointerstitial cause
Immunofluorescence microscopy:
–Negative for IgG, IgM, IgA, C1q,
fibrinogen, albumin, and light chains
–No electron- dense deposits were
seen on electron microscopy
• Heparin was initiated for the arterial
occlusion
DD: medium-size artery occlusion
• 1. APS
–pt doesnt have signs of thrombosis
anywhere else,
• 2. PAN
- No gastrointestinal or neurologic
syndromes
SLE/APS?
• Antiphospholipid - AB panel
– Dilute Russell‘s viper-venom time
– Anticardiolipin IgG and IgM AB
– Anti- Beta2-glycoprotein I AB
WERE NEGATIVE
3. COAGULOPATHIES
• Factor V Leiden, protein C, protein S
and were positive, antithrombin III
levels:
NORMAL
• Cryoglobulins:
not present
DD - Renal failure:
1. Glomerular causes of renal failure
i.e. cryptoglobulinemia,
membranoproliferative glomerulonephritis
2. Vascular causes of renal failure
i.e. Polyarteritis nodosa
3. Coagulopathy
4. Viral disease i.e. HBV
HBV & HCV
• Hepatitis B surface and core AB,
–but surface antigen and viral load
were negative
• Hep C AB
–neg
MRI & MRA of brain, chest and
abdomen:
–Large pericardial effusion and small
bilateral pleural effusions
–Cardiac function appears normal
–No evidence of vascular wall thickening,
narrowing or aneurysms  no medium
or large vessel vasculitis
Meanwhile...
• BP remained elevated despite
hemodialysis and antihypertension
medications
• Patient reported that she had
surreptitiously used 20mg of
prednisone
What is the diagnosis?
• Maybe corticosteroids...
account for leukocytosis and
concealed symptoms
• PAN?
MRI and MRA do not yield the
typical findings
SYSTEMIC SCLEROSIS? I
• Refractory hypertension despite
dialysis: progressive systemic
sclerosis  can incite
vasculopathy in the kidney
SYSTEMIC SCLEROSIS? II
• No other signs of scleroderma
– questioning for Raynaud‘s
phenomenon
–pulmonary- function tests
–high- resolution CT to look for
subclinical interstitial lung disease
TREATMENT
• ACE inhibitor
• Hemodialysis continued
• BP  130/70
• Scl-70 AB test: 6.0 ELISA U/ml
(<1.0)
DIAGNOSIS?
DIAGNOSIS!
• Systemic sclerosis sine scleroderma
• Renal crisis not accompanied by
cutaneous damage
DIAGNOSIS!
• Histopathological changes of kidney
disease due to systemic sclerosis: arcuate
and interlobular arteries
• Fibrin thrombi and areas of fibrinoid
necrosis are typically noted in the acute
stage
• The allergic rash, which was treated with
CS, was unrelated to scleroderma