A 76YearOld Woman With Diabetes and a Painful Foot

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A 76-Year-Old Woman With Diabetes and a Painful
Foot
Eugene G. Martin, Ph.D. Associate Professor of
Pathology Laboratory Medicine

• Based upon LABORATORY MEDICINE CASEBOOK. An
  introduction to clinical reasoning
• Jana Raskova, MD Professor of Pathology
  Laboratory MedicineStephen Shea, MD
  Professor of Pathology Laboratory
  MedicineFrederick Skvara, MD Associate
  Professor of Pathology Laboratory MedicineNagy
  Mikhail, MD Assistant Professor of Pathology
  Laboratory MedicineUMDNJ-Robert Wood Johnson
  Medical SchoolPiscataway, NJ

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Presentation

• 76 year old female brought to the ER because of
  significant pain, swelling and redness of her
  right foot.
• Two days previous patient noticed pain and
  swelling around her toes which prevented her from
  walking

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History and Findings

• History
• Long history of non-insulin dependent diabetes
  mellitus (NIDDM)
• Patient reports prescribed oral hypoglycemic
  agents and well-controlled blood glucose levels
• No other significant medical history
• Physical findings
• Alert female in no acute distress
• BP 150/90 Temp. 99 oF HR 80 bpm RR 18
  rpm
• Fungal rash present under breast and in the groin
  area
• Painful, hot, and edematous dorso-lateral aspect
  of right foot around a deep fissure between
  fourth and fifth toes.
• No peripheral adenopathy
• No splenomegaly
• Summarize Well-controlled (?)Type 2 diabetes,
  hypertension, fungal infection, possible
  bacterial super-infection, cellulitis ?

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Cellulitis

• Cellulitis most often develops on the legs but
  can be seen on the face and on any other skin on
  the body.
• It tends to affect a fairly large area of skin.
• Cellulitis is usually due to an infection of the
  skin with bacteria, but it may also be caused by
  a fungus.

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Fungal infections and Diabetes? Why?

• When the blood sugar increases, two things
  happen.
• 1. All body secretions will have an increased
  amount of glucose.
• 2. Normal defenses against intrusion by outside
  substances -- such as yeast -- will be abnormal.
  High blood sugar impairs the ability of your
  immune system to resist invading germs, such as
  fungi and bacteria.
• Common fungal infection sites include mouth,
  gums, lungs, skin, feet, bladder and genital
  area.
• High blood sugar can also damage the nerves that
  control sensation or pain that would otherwise
  alert you to a potential infection (peripheral
  neuropathy).
• Keeping blood sugar within normal or near-normal
  range greatly reduces your risk of these
  infections.

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Tinea infections

• Fungal infections are named for the part of the
  body they infect.
• Tinea corporis - skin on the body.
• Tinea pedis - foot
• Tinea unguium - toenails.
• Tinea cruris (Jock itch) - groin
• Tinea capitis ("ringworm) head
• http//www.aafp.org/afp/980700ap/noble.html

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Causative Species

• Tinea corporis (under the breast)
• Trichophyton rubrum
• M. canis
• T. tonsurans
• T. verrucosum
• Tinea cruris(groin)
• T. rubrum
• Epidermophyton floccosum

• Tinea pedis (foot)
• T. rubrum
• Trichophyton mentagrophytes var interdigitale
• E. floccosum

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Conclusion

• Possibility that a T. rubrum infection that has
  spread from groin to under her breasts to her
  feet.
• Another possibility is an infection with Candida
  Mucocutanea Chronica
• Persistent candida infection from mouth, skin and
  nails.This is not a single disease but is caused
  by a heterogenous group of disorders.
• Point Diabetic Patients in poor control often
  have problems such as these

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HEMATOLOGY
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Peripheral Blood Smear
Patient
Normal

• HEMATOLOGY SUMMARY
• Normochromic, normocytic anemia.
• Red cell population decreased in number
• Cell size and shape normal
• Platelets, neutrophils lymphocytes are
  unremarkable in appearance
• None of this information adds anything to the
  automated hematology count shown earlier
• Increased WBC, relative and absolute
  lymphocytosis, neutropenia

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When do we see absolute lymphocytosis?

• Absolute Lymphocytosis  It is seen in
• Children normally. Significance of age ranges!
• Infections
• TB, typhoid, mumps,
• Measles, cough, influenza
• Syphilis and other chronic infections.
• Infectious mononucleosis.
• Chronic lymphocytic leukemia.

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CHEMISTRY
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What is the significance of hypoalbuminemia?

• Is this patient malnourished or losing albumin?
• Diabetes r/o nephropathy.
• Type 1 Diabetes Hypertension and fluid retention
  are secondary to glomerular and tubular damage,
  thus they become manifest with increasing
  albuminuria.
• Type 2 Diabetes Hypertension is present in
  gt25 of patients at diagnosis and is a part of
  the metabolic syndrome of insulin resistance. The
  resulting hyperinsulinemia has secondary effects
  on the renal tubule, leading to salt and water
  retention and sympathetic nervous system
  activation.
• When persistent proteinuria developed after the
  diagnosis of non-insulin-dependent diabetes
  mellitus, the cumulative risk for chronic renal
  failure 10 years after the diagnosis of
  persistent proteinuria was 11.

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Urinalysis
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Hemoglobin A1c

• Glycosylated hemoglobin measure of glucose
  control over the last 2-3 months.
• Glucose in blood binds irreversibly to hemoglobin
  to form a stable glycated hemoglobin complex
• Life span RBCs 90-120 days
• A1C will only be eliminated when the red cells
  are replaced
• The A1C value is an index of mean blood glucose
  over the past 2-3 months

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Additional Studies
Electrolytes
Glycosylated Hemoglobin
Diabetics good control lt9.0 mg/dL
- fair control 9-12 -
poor control gt12
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Microbiology

• Blood cultures pending
• Wound culture (fissure of foot) Staphylococcus
  aureus
• WBC is only modestly elevated. Is it related to
  her Staphyloccus aureus infection? Will treatment
  with IV antibiotics normalize it? Why? Why not?
• What happens next?
• Repeat the CBC?

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HEMATOLOGY
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Follow-up

• Absolute lymphocytosis
• Suspicion builds that this is a hematologic
  malignancy
• Physician orders
• Bone marrow biopsy
• Flow cytometry of peripheral blood/bone marrow

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Flow Cytometry

• Most patients suspected of leukemia are assessed
  by flow cytometry. One plot
• Cell size (Y axis
• Cytochemical reaction for peroxidase (X axis).
• A second plot defines cells on the basis of size
  and lobularity of the nucleus.
• Well-recognized patterns
• http//www.meds.com/leukemia/flow/flow0.html

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Flow Cytometric Analysis
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Chronic Lymphocytic Leukemia

• Why isnt this an infectious process?
• Proportion of lambda light chains a process of
  restricted B cell clonality would not occur in an
  infection
• Early stage of CLL? Yes
• Hgb and platelets are almost normal
• Lymphocytosis is mild (lt 15K)
• No splenomegaly or lymphadenopathy
• Treatment with alkylating agents has risks and
  progression is usually slow ordinarily delay
  treatment

• Normal peripheral blood 80 of all lymphocytes
  are T lymphocytes NOT in CLL
• Majority of cells - B-cell phenotype (CD19)
  88.4
• Restricted clonality
• Lambda light chain 84.8
• Normal kappa/lambda ratio - 21
• Co-expression of CD5 (T cell) antigen on leukemic
  CD19 cells
• T lymphocyte subsets ? show a CD4/CD8 ratio
  (11) (normal 2-31)

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Histologic patterns of Chronic Lymphocytic
Leukemia

• ? Lymphocytes in bone marrow
• Occasional normoblasts and cells of the myeloid
  series are present
• Low power micrograph
• Several nodules of lymphocytes are present with
  normal intervening marrow
• This is the nodular pattern in CLL

PATIENT Wright/Giemsax197
PATIENTHEx31
Nodules
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Histologic patterns of Chronic Lymphocytic
Leukemia

• Low power micrograph
• Several nodules of lymphocytes are present with
  normal intervening marrow
• This is the nodular pattern in CLL
• Low power micrograph
• Normocellular
• Shows heterocellular hematopoietic cells

PATIENT HEx31
Nodules
NormalHEx31
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Prognosis Chronic Lymphocytic Leukemia

• Major prognostic indicator for survival is the
  pattern of infiltration of the bone marrow
• Proportion of lymphocytes in the bone marrow
  ranges from 30-100
• Four patterns ranging from a bone marrow
  architecture which is largely preserved and is
  prognostically favorable to a pattern of marked
  hypercellularity with replacement of normal
  hematopoetic elements which has a poor prognosis

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CLL Patterns of infiltration
MixedPattern
Normal
InterstitialPattern
DiffusePattern
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Case Summary

• Poorly controlled NIDDM
• Cellulitis
• Candidiasis
• Chronic Lymphocytic Leukemia