White Cell Disorders Flashcards
What are the clinical features of chronic granulomatous disease and what is the enzyme defect?
Recurrent skin and lung infections. The enzyme defect is NADPH oxidase deficiency.
What is the mode of inheritance of chronic granulomatous disease?
Mostly autosomal recessive, but some can be X-linked.
How do you treat chronic granulomatous disease?
You give these patients Bactrim and Itraconazole for prophylaxis. Can consider interferon gamma, BMT, and gene therapy.
What are the clinical features of MPO deficiency?
Most patients are asymptomatic, however in those with uncontrolled diabetes the symptoms may be unmasked.
How do you make the diagnosis of MPO deficiency?
By histochemical staining for MPO
What are the clinical features of Hyper IgE syndrome?
These patients develop skin, lung, sinus infections (often yeast)
What gene is affected in Hyper IgE syndrome?
STAT3 gene.
How do you diagnose chronic granulomatous disease?
Diagnosis is with nitroblue-tetrazolium reduction (cytochrome C reduction assay)
What are the clinical features of Chediak Higashi Syndrome?
oculocutaneous albinism ,photophobia, mild neutropenia, neurologic defects (e.g. neuropathy), recurrent pyogenic infections, bleeding (dense platelet granule defect).
What is the mode of inheritance of Chediak Higahsi and what is the gene mutation?
Autosomal recessive and the gene affected is LYST gene
What is the treatment of Chediak Higahsi Syndrome?
BMT
In cyclical neutropenia what is the mode of inheritance and what gene is involved?
Autosomal dominant and it’s the ELANE gene.
What is the major complication that can occur later in life with severe congenital neutropenia? What has been associated with this?
AML. It appears the longer patients are on G-CSF the higher risk is with this occurring.
What somatic mutation occurs with G-CSF that increases the risk of AML in patients with severe congenital neutropenia?
CSF3R mutation
What is the treatment of both congenital neutropenia and cyclical neutropenia?
G-CSF
What is the treatment of congenital neutropenia refractory to treatment?
BMT
What are the clinical features of WHIM?
Warts, hypogammaglobulinemia, infections, and myelokathexis (increased marrow mature neutrophils).
What genetic mutation characterizes WHIM? What is the result of this mutation?
There is a mutation involves the CXCR4 gene. Mutations result in enhanced retention of neutrophils in the bone marrow
What is the treatment of WHIM syndrome?
IVIG, prophylactic antibiotics, and Plerixafor.
What mutation is commonly seen in Langerhans Cell Histiocytosis?
Over 70% of cases have a somatic mutation in BRAF.
What is the treatment of SS-LCH involving the bone?
Bony or soft tissue SS-LCH can be treated with surgical resection, local irradiation, or injection of steroids. NCCN lists Zoledronic Acid and Pamidronate-systemic tx for widespread disease.
What is the treatment of skin SS-LCH?
topical steroids or injection, mechlorethamine topical, or psoralen and ultraviolet A light therapy, RT low dose. NCCN-MTX, hydrea (both preferred), Lenalidomide, Thalidomide-additional, but not preferred
What is the treatment of lung SS-LCH?
Cessation of smoking, prednisone, vinblastine, and methotrexate; and immunosuppressive agents. NCCN: basically the systemic options you use for multi-system disease.
What is the tx of MS-LCH and SS-LCH with multi-focal involvement?
Preferred: Cladribine or Cytarabine. MAP kinase mutation or no actionable mutation-Cobimetinib. Vinblastine and prednisone is another option.. Those with BRAF mutation you use Vemurafenib (preferred) or Dabrafenib.
What is flow cytometry result for Erdheim Chester Disease?
Positive for CD163 and CD68, CD14, but are negative for CD1a and langerin (CD207, unlike in LCH), and only rarely positive for S100.
What is the treatment of Erdheim Chester Disease?
NCCN: Vemurafenib (preferred) or dabrafenib for BRAF mutation. MAP kinase mutation or no detectable mutation: Cobimetinib (preferred) or Trametinib. Irrespective of mutation, other recs: Cladribine, Peg Interferon alpha, Sirolimis plus prednisone, MTX, Anakinra
What is the flow phenotype of LGL?
CD3+, CD16+, CD57+, CD28-
What is the flow phenotype for LCH?
CD1a, CD207 (Langerin), S100+, Cyclin D1+
