Printed Case 1

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Printed Case 1

• Altered Mental Status in a Middle Aged Male
• Helpful slides
• Eugene Martin, Ph.D.

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Patient Presentation - 1

• As you read the patient presentation you might
  ask the following questions
• What is the significance of the ? jugular venous
  pressure? What might it represent?
• What is the significance of the patients mental
  status? What might it represent? Is it related to
  possible systemic disease? How might it relate?
  How would you rule it in or out?

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Significance of the Increased Jugular Venous
Pressure.

• JVP can be elevated in
• heart failure
• reduced right ventricular compliance (eg. RVH)
• pericardial effusion, tamponade, constriction
  (Kussmaul's sign- JVP rises paradoxically in
  constrictive pericarditis (or sometimes in severe
  right- sided heart failure or tricuspid
  stenosis))
• http//www.eboncall.org/CATs/2035.htm
• Pericardial and pleural effusions sometimes
  represent manifestations of SLE

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Patient Presentation - 2

• Patient presents with slight dull heart and lung
  sounds and sharp chest pains. What do those
  symptoms suggest?

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Pleural Effusion

• 1 million pleural effusions in the United
  States each year.
• Importance Incidental manifestations of
  cardiopulmonary diseases or symptomatic of
  inflammatory or malignant diseases
• Most common symptom Dyspnea
• Caused by distortion of the diaphragm and chest
  wall during respiration
• Less common symptoms - mild, nonproductive cough
  or chest pain
• Other symptoms suggest etiology
• More severe cough or production of purulent or
  bloody sputum suggests an underlying pneumonia or
  endobronchial lesion.
• Constant chest wall pain may reflect chest wall
  invasion by bronchogenic carcinoma or malignant
  mesothelioma.
• Pleuritic chest pain suggests either pulmonary
  embolism or an inflammatory pleural process.
• Systemic toxicity evidenced by fever, weight
  loss, and inanition suggests empyema

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Pleural Effusion Cytospin

• A Wright's stained cytospin preparation
• What are the arrows pointing to?
• Phagocytosed nuclear components of other cells in
  an antibody (ANA)-mediated process.

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Our Patients Striking Lab Values

• Pleural effusion, positive for LE cells
• Urine, increased random and 24-hour protein
  concentration, the presence of blood, and a
  positive screen for cocaine metabolite
  (benzoylecgonine)
• Whole blood, normocytic-normochromic anemia
• Serum
• ?? LD
• ? BUN, creatinine, and AST levels,
• ? ANA with diffusely staining pattern by IFA
• ? dsDNA and Smith antibody tilers
• ? decreased C3 and C4 levels
• CSF, markedly increased total protein
  concentration.

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Antinuclar antibodies

• Staining Patterns originally thought to be
  indicative of specific disease
• Homogenous
• Nucleolar
• Speckled
• Centromere
• Less important today because sensitivity and
  specificity than autoantibody testing
• Lack of specifity Conditions associated w\
  positive ANA infections, pulm. Disease, liver
  disease, DM, MS, age, silicone gel implants,
  thyroid disease, medications
• Significance of ANA in an asymptomatic
  individual?

• Associated Conditions
• SLE - gt99 ANA
• Drug-induced lupus
• Discoid lupus
• Rheumatoid arthritis
• Scleroderma 68 ANA
• Mixed connect. Tiss. Dis
• Sjögrens Syndrome
• Polymyositis/dermatomyositis

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ANA Profile

• Abs to double-stranded DNA
• Highly specific for SLE
• 40-60 prevalence
• Titers fluctuate w\ disease
• Correlation w\ renal disease
• Ab to Smith Ag
• Highly specific, but in only 25 of SLE
• Abs to histones
• 70 of SLE patients
• in drug-induced lupus as well as other
  connective tissue diseases
• Abs to Ro (SSA)
• Associated with Sjogrens syndrome, subacute
  cutaneous lupus, neonatal lupus, photosensitivity
  complement deficiency
• Abs to LA (SSB)
• Associated with Sjogrens syndrome, subacute
  cutaneous lupus neonatal lupus
• Abs to single-stranded DNA
• Freq. found in SLE BUT NOT SPECIFIC for SLE.
• Found in other connect. Tissue diseases

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Renal Status

• Patient Urine, increased random and 24-hour
  protein concentration, the presence of blood, and
  a positive screen for cocaine metabolite

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Renal Disease in SLE

• Renal disease in SLE common (40)
• At the time of SLE diagnosis 50 of patients have
  urinalysis abnormalities (proteinuria, hematuria,
  or pyuria)
• Types of lupus nephritis
• Mesangial
• (10-20 of lupus nephritis)
• Hematuria /or proteinuria mild
• Hypertension uncommon
• Renal function normal
• Nephrotic syndrome unusual
• Focal Proliferative
• (10-20 of lupus nephritis)
• Hematuria /or proteinuria in almost all patients
• Some nephrotic syndrome present
• Hypertension not uncommon
• Elevated serum creatinine

• Types of lupus nephritis (cont)
• Diffuse Proliferative
• Most common type of lupus neprhitis
• Most severe
• Hematuria /or proteinuria - all patients
• Nephrotic syndrome common
• Hypertension common
• Renal insufficiency common
• Hypocomplementemia usually present
• Anti-ds-DNA abs usually present
• Membranous
• (10-20 of lupus nephritis)
• Proteinuria all patients
• Nephrotic syndrome common
• Micro. Hematuria may be present
• Hypertension may be present
• Serum creatinine USUALLY normal, but may be
  mildly elevated.

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Urine Protein Electropheresis

• Electrophoretic pattern demonstrates
• Non-selective proteinuria
• Pattern is consistent with
• Nephrotic Syndrome www.emedicine.com/ped/topic1564
  .htm
• Nephrotic Syndrome is characterized by a urine
  protein concentration gt3.5 g/24 hr.
• 50 of patients with SLE have nephritis
  characterized by functional abnormalities of the
  kidneys

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Fluorescent Probe (400x)

• Demonstration of patients antibody to mitotic
  figures
• Patient's serum added to HEp-2 human epithelioid
  cells with mitotic figures Immunoconcepts, M)
  followed by the addition of a second antibody
  goat anti-human IgG (heavy and light chains)
  labeled with a fluorescent probe (FITC)

What are these?
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Significance of Red Cell Casts

• The presence of red cell casts is generally a
  clear indication of glomerular injury, or
  hemorrhage within the kidney.

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Questions from the Hematology Lab Results

• Patient demonstrates
• 3.44 x 10-6 cells/ml normal 4.3-6.2 x 10-6
• MCV 85.9 normal 82-105 fL
• MCH 29.5 normal 28-34 pg
• MCHC 34.3 normal 31-35 g/dL
• Does this patient have anemia? If so, what kind?
  What is the significance of these values?

• Normochromic, normocytic anemia
• IF
• Reticulocyte ?
• Hemolytic disease
• Acute blood loss
• Reticulocyte normal
• Malignancy
• Myeloma
• Chronic Disease
• If this patient had a chronic blood loss for more
  than 6 months you would expect a hypochromic,
  microcytic anemia
• The cases failed to tell you anything about the
  presence of reticulocytes, but SLE commonly
  presents with an Anemia of Chronic DIsease

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Question from the Hematology Lab Data

• Does this patient have anemia? If so, what kind?

• Normochromic, normocytic anemia
• Reticulocyte ?
• Hemolytic disease
• Acute blood loss
• Reticulocyte normal
• Malignancy
• Myeloma
• Chronic Disease
• If this patient had a chronic blood loss for more
  than 6 months you would expect a hypochromic,
  microcytic anemia

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Autopsy Finding

• What happened?
• A subdural hemorrhage
• Darkened purplish area on the left side of the
  dura represents extravascular blood below the
  dura (dark arrows)
• What might cause this?
• Anti-phospholipid antibodies common in SLE ?
  prolonged PTT ? Bleeding disorders

• Whats this?

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SLE

• Epidemiology
• Prevalence of SLE worldwide is 4-250 per 100,000.
  
• Incidence is most frequent in women age 15-25
  years.
• 9x as many females as males
• Blacks and Asians are affected more often than
  other races
• Broad age category between 10 ?50
• Course of disease ranges from mild ? severe/fatal
• lt50 have lupus nephritis
• 25 have neurologic symptoms

• Clinical Presentation
• Varies between different patients and within a
  patient Constitutional symptoms (fatigue and
  fever) are common.
• Vast majority have arthralgia, mostly of the
  hands.
• one-half of the patients have cutaneous
  features, such as malar rash and discoid lupus as
  well as photosensitivity.
• 30 have oral ulcerations.
• 50 have nephropathy from mild proteinuria and
  microscopical hematuria to end-stage renal
  failure.
• 20-40 of the patients have pleurisy.
• Pericarditis is somewhat more uncommon than
  pleuritis. T-wave changes in the
  electrocardiogram (ECG) are usual.
• Depression and headache are the most common of
  the neuropsychiatric symptoms. Grand-mal seizures
  and organic psychoses are rare. A peripheral
  neuropathy is observed in about 10 of the
  patients
• 10 get a thromboembolic or hemorrhagic
  complication of the brain.
• The lymph nodes may enlarge especially in active
  disease.

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SLE COMMON SYMPTOMS

• fever
• fatigue
• general discomfort, uneasiness or ill feeling
  (malaise)
• weight loss
• v skin rash
• v "butterfly" rash
• v sunlight aggravates skin rash
• v sensitivity to sunlight
• v joint pain and swelling virtually all

• arthritis
• swollen glands
• muscle aches
• nausea and vomiting
• v pleuritic chest pain
• v seizures
• ? psychosis
• v - Our patient exhibited

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Laboratory Correlations

• ANA antibodies
• 97 of patients with SLE,
• 30 to 40 of patients with RA,
• 70 of patients with scleroderma.
• dsDNA antibodies
• 70 to 80 of patients with SLE
• 15 of patients with RA
• 30 of patients with scleroderma.
• Anti-Sm antibodies
• High specificity, low sensitivity for SLE

• Immunfluorescent Patterns
• Rim, diffuse, and speckled patterns - SLE
• nucleolar scleroderma
• centromere - CREST (Calcinosis cutis-Raynaud's
  phenomenon-Esophogeal dysfunction-Sclerodactyly-Te
  langiectasia) syndrome

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Less Common Symptoms

• Blood in the urine
• Coughing up blood
• Nosebleed - symptom
• Swallowing difficulty
• Skin color is patchy
• Red spots on skin
• Abdominal pain
• Visual disturbance

• Fingers that change color upon pressure or in the
  cold (Raynaud's phenomenon), numbness and
  tingling
• Mouth sores
• Hair loss

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Blood disorders effect up to 85 of those with SLE

• Venous or arterial blood clots can form and are
  associated with strokes and pulmonary embolism,
  or pregnancy loss.
• Predisposition to blood clots, or less commonly
  bleeding, occurs due to antibodies against lipids
  involved in blood clotting and is referred to as
  anti-phospholipid antibody syndrome (APS). (See
  Lupus anticoagulant.)
• Often platelets are decreased which may cause
  bleeding or clotting problems.
• Anemia of chronic disease often develops at some
  point in the course SLE.

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Diagnosis of SLE

• v antinuclear antibody (ANA) panel including
  anti-DNA and anti-Smith antibodies, with the
  latter two tests generally positive in lupus
  alone
• v characteristic skin rash or lesions
• v chest X-ray showing pleuritis or pericarditis
• v Hematologic abnormalities hemolytic anemia. 2
  or more instances of lymphopenia. Anemia of
  chronic disease.
• listening to the chest with a stethoscope to
  reveal heart friction rub or pleural friction rub
  
• v urinalysis to show blood, casts, or protein in
  the urine
• v CBC showing a decrease in some cell types
• v kidney biopsy demonstrates glomerulonephritis
• v neurological examination demonstrates seizure
  activity or psychosis
• v Our patient demostrates.

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Lab Values Frequently Affected in SLE

• WBC count
• Serum globulin electrophoresis
• Rheumatoid factor
• Protein, urine
• Protein electrophoresis - serum
• Mononucleosis spot test
• ESR
• cryoglobulins

• Coombs' test, direct
• complement component 3 (C3)
• complement
• Anti-thyroid microsomal antibody
• Anti-thyroglobulin antibody
• Anti-mitochondrial antibody
• Anti-smooth muscle antibody

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Complications of SLE

• Infection
• Renal failure
• Thrombocytopenia
• Hemolytic anemia
• Myocarditis
• Seizures

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Treatment

• Multiple manifestations with variable severity,
  determine individual treatment
• Mild disease (rash, headaches, fever, arthritis,
  pleurisy, pericarditis) requires little therapy.
• Nonsteroidal anti-inflammatory medications
  (NSAIDS) - arthritis and pleurisy.
• Corticosteroid creams are used to treat skin
  rashes.
• Antimalarial drugs (hydroxychloroquine) and low
  dose corticosteroids are sometimes used for skin
  and arthritis symptoms.
• Severe disease (hemolytic anemia, extensive
  heart or lung involvement, kidney disease,
  central nervous system involvement)
• Corticosteroid therapy or medications to suppress
  the immune system
• Cytotoxic drugs for patients people who do not
  have a good response to corticosteroids or who
  are dependent on high doses of corticosteroids.

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Printed Case 2

• 38 year old white man seen by his family
  physician two months ago for a chief complaint of
  fever, fatigue, malaise, and pain localized over
  his nose and maxillary sinuses

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Chest X-ray

• What do you see?
• Right mid-lung field lesion (about 4cm in
  diameter) - Tomogram Lobulated Central Cavity
  (Below)
• Left mid-lung field lesion (about 1.5cm in
  diameter),
• Ill-defined area of increased left-based
  density.

What do you see?
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Paranasal sinus x-rays

• What do you see?
• Mucosal thickening left antrum
• Mass - upper portion nose, without bone
  destruction.

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Ulcer adjacent to the middle turbinate

• Giant cells
• Necrotizing vasculitis

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Differential Dx. Hemoptysis

• Intrinsic benign and malignant tumors of the
  larynx, pharynx, trachea, bronchi, and lungs
• Granulomatous disease (i.e. Tb. fungal,
  parasitic, Wegener's)
• Bronchogenic cyst
• Broncholithiasis
• Bronchiectesis
• Erosion of trachea or bronchi by extrinsic tumor
• Acute chronic bronchitis

• Pulmonary abscess pneumonia
• Hemosiderosis
• Goodpasture's syndrome trauma
• Left ventricular failure pulmonary
  embolism/infarction
• Pulmonary arteriovenous fistula
• Primary pulmonary hypertension Thrombocytopenia
• DIC
• Anticoagulant therapy, etc.

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Wegeners Granulomatosis

• Wegeners Triad
• Acute necrotizing granulomas of upper/lower
  respiratory tract.
• Focal necrotizing or granulomatous vasculitis of
  small to medium-sized vessels, most prominent in
  lungs and upper airways.
• Focal or necrotizing (often crescentic)
  glomerulitis.
• Necrosis may cavitate-diff dx includes TB,
  fungus.
• Common normochromic, normocytic anemia and
  hypergammaglobulinemia
• c-ANCA in 90 patients with active generalized
  disease.
• Peak incidence is in the 30-40s (Malefemale
  32).
• gt 50 ocular inflammation
• -Persistent pneumonitis with bilateral
  nodular/cavitary infiltrates (95)
• -Chronic sinusitis (90)
• -Nasopharyngeal ulcerations (75)
• -Renal disease (80) http//www.emedicine.com/emer
  g/topic219.htm
• -Also, rash, myalgias, arthralgias, neuritis,
  fever.

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• http//www.emedicine.com/emerg/topic219.htm

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Characterize the slides

• Necrotizing Vasculitis
• Giant Cells
• Top HE 40X
• Bottom HE 80X

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ANCA
p-ANCA is perinuclear against MPO.
C-ANCA shows cytoplasmic localization

• ANCA - heterogenous autoantibodies against
  enzymes in primary granules of neutrophils though
  also found in lysosomes of monocytes and
  endothelial cells
• C-ANCA Most common against serine protease in
  neutrophils (proteinase 3)
• p-ANCA is perinuclear against MPO.

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C-ANCA

• Very sensitive for diagnosis of Wegeners
  granulomatosis
• Sensitivity/Specificity
• Active disease sensitivity gt 90
• Organ limited disease sensitivity 60
• Remission sensitivity 40
• Specificity 90
• A positive c-anca in a patient who exhibits class
  SS of Wegeners may obviate biopsy

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P-ANCA

• Present 70 of Churg-Strauss syndrome and
  microscopic polyangitis patients however test is
  neither sensitive or specific enough to establish
  a dx. (biopsy recommended)
• Maybe in
• Wegeners
• RA
• SLE
• Goodpastures syndrome
• Ulcerative colitis
• Autoimmune hepatitis
• Etc.
• Titer association w\ disease state not tight ?
  ? patient monitoring