User:It's gonna be awesome/Primary chronic cold agglutinin disease

Source: Wikipedia, the free encyclopedia.

Primary chronic cold agglutinin or Chronic cold agglutinin disease (CAD) and Primary cold agglutinin disease is a subgroup of

pentameric IgM. It has been known for decades that, in patients with CAD, IgM-antibodies with CA-activity are monoclonal and, in more than 90% of the patients, show κ light chain restriction.[2]
.

Classification

Autoimmune hemolytic anemia.
  • Warm-antibody type
     
  • Primary  
  • Secondary  
  • Primary chronic cold agglutinin disease
  • Secondary cold agglutinin syndrome  
  • Associated with malignant disease  
  • Acute, infection-associated (acute cold antibody mediated AIHA complicating Mycoplasma pneumoniae or viral infections [3])

[2]

Signs and symptoms

Pathophysiology

CAD patients must have a clonal

lymphoplasmacytic lymphoma (LPL) was the most frequent finding, while marginal zone lymphoma (MZL), unclassified clonal lymphoproliferation, and reactive lymphocytosis were also frequently reported. [4] The explanation for this perceived heterogeneity was probably revealed by a recent study in which bone marrow biopsy samples and aspirates from 54 patients with CAD were systematically reexamined by a group of lymphoma pathologists, using a standardized panel of morphological, immunohistochemical, flow cytometric, and molecular methods. [6]. The bone marrow findings in these patients were consistent with a surprisingly homogeneous disorder termed “primary CA-associated lymphoproliferative disease” by the authors and distinct from LPL, MZL, and other previously recognized lymphoma entities. The MYD88 L265P somatic mutation, typical for LPL, could not be detected in the samples from patients with CAD[6][7]
.

Mechanisms of Erythrocyte Destruction

Figure 3

CA are usually directed against the

IgG.[4][2]

Complement activation may proceed beyond the C3b formation step, resulting in C5 activation, formation of the

Febrile infections, major trauma, or major surgery can result in acute exacerbation of hemolytic anemia in at least two-thirds of patients with CAD. [4][16][2] The explanation for this paradoxical exacerbation is that, during steady-state chronic disease, most patients are complement-depleted with low levels of C3 and often undetectable levels of C4. During acute phase reactions, C3 and C4 are repleted and exacerbation of complement-induced hemolysis ensues.[9][2]

Management

In textbooks and review articles, it is often postulated that typical patients with CAD are just slightly anemic and do not need pharmacological therapy. This holds true for a minority only; the

W-AIHA, corticosteroids and other unspecific immunosuppressive drugs are of little or no value in CAD. [14][17]

The relative success in therapy for CAD during the last 10–12 years has been achieved by targeting the pathogenic

lymphopenia and hypogammaglobulinemia[19][20][4] Data from rituximab maintenance in follicular lymphoma indicate that, in adults, even prolonged or repeated administration is safe with regard to infections [21]. Very rare cases of progressive multi-focal leukoencephalopathy and hepatitis B reactivation have been reported, however, in patients receiving rituximab for polyclonal autoimmune disorders. Any causal associations are uncertain because of concomitant immunosuppressive therapies and immune dysregulation as part of the autoimmune disease itself. [22]

Prognosis

In a more recent prospective trial, combined therapy with rituximab and fludarabine produced very high response rates (remission in 75% of the patients, including 20% complete remissions) and the median response duration was more than 66 months. [23] This regimen was, however, found to be significantly more toxic than rituximab monotherapy. No other immunochemotherapy regimens have been studied in published clinical trials. According to single case reports, favorable outcome has been observed following bortezomib-based regimens [24] and rituximab-bendamustine combination therapy. [25]

Transfusion can safely be given in CAD provided specific precautions are undertaken, although these precautions are entirely different from those required in W-AIHA. Such requirements have been extensively described elsewhere[26][27].

Free PMC articles (For self-reminding)

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2409172/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4326213/

https://www.ncbi.nlm.nih.gov/pmc/?term=primary+cold+agglutinin+disease

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4396542/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6129358/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3096571/

External links (Self-reminding only)

Basic overview:

Reference

  1. ^
    PMID 17891600. {{cite journal}}: External link in |type= (help
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  2. ^
    PMID 25705656. {{cite journal}}: External link in |type= (help
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  3. PMID 17891600. {{cite journal}}: External link in |type= (help
    )
  4. ^
    PMID 13292836. {{cite journal}}: |first2= missing |last2= (help); |first3= missing |last3= (help); |first4= missing |last4= (help); |first= missing |last= (help
    )
  5. ^
    PMID 23757733
    .
  6. ^
    PMID 24143001. {{cite journal}}: Check date values in: |year= / |date= mismatch (help
    )
  7. PMID 22931316
    .
  8. PMID 13292836. {{cite journal}}: |first2= missing |last2= (help); |first3= missing |last3= (help); |first4= missing |last4= (help); |first= missing |last= (help
    )
  9. ^
    S2CID 34579070
  10. PMID 14452388. {{cite journal}}: |first2= missing |last2= (help); |first3= missing |last3= (help); |first= missing |last= (help
    )
  11. ^
    PMID 965497. Cite error: The named reference "57 Jaffe Atkinson Frank 1976 pp. 942–949" was defined multiple times with different content (see the help page
    ).
  12. PMID 24695853
    .
  13. PMID 96137
    .
  14. ^
    PMID 16585012
    .
  15. S2CID 11609721
    .
  16. S2CID 1520868
    .
  17. ^ Dacie J. Auto-immune haemolytic anaemia (AIHA): treatment. In: Dacie J., editor. The Haemolytic Anaemias. Vol. 3. London, UK: Churchill Livingstone; 1992. pp. 452–520.
  18. PMID 17896962
    .
  19. ^
    S2CID 14448112
    .
  20. ^
    S2CID 44472438
    .
  21. S2CID 20068244
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  22. S2CID 32033126
    .
  23. S2CID 206892631
    .
  24. PMID 20110437
  25. PMID 23399352
    .
  26. PMID 22330255
    .
  27. S2CID 6159402
    .

Category:Cold autoimmune hemolytic anemia

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