User:It's gonna be awesome/Secondary cold agglutinin syndrome

Secondary cold agglutinin syndrome (Secondary CAS, CAS) is far more uncommon than primary cold agglutinin disease (Primary CAD, CAD). Among 295 consecutive individuals with autoimmune hemolytic anemia (AIHA) described retrospectively by Dacie in a single-center series, 7 patients (2.4%) were classified as having CAS secondary to malignant disease.

Classification

 * Autoimmune hemolytic anemia.


 * Warm-antibody type
 * Primary
 * Secondary
 * Cold-antibody type
 * 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 )
 * Paroxysmal cold hemoglobinuria
 * Mixed cold- and warm-antibody type

Signs and symptoms
In occasional patients, high-titer, high-thermal amplitude productions of cold antibodies (CA) result in hemolytic anemia which is transient but can be severe.

Etiology
CAS has been described in patients diagnosed with diffuse large B-cell lymphoma, Hodgkin's lymphoma, carcinomas, sarcomas, metastatic melanoma, and chronic myeloproliferative disorders. Some of these associations have been poorly documented, and the most convincing association with malignant disease has been described with non-Hodgkin's lymphoma.

Pathophysiology
In CAS complicating aggressive lymphoma, the pathological cold sensitive antibodies are monoclonal, most often IgM, and have anti-I specificity. In contrast to pathological cold sensitive antibodies found in primary CAD, however, the Immunoglobulin light chain restriction can be λ as well as κ.

Polyclonal anti-I specific pathological cold sensitive antibodies of the IgM class are produced as part of the physiological immune response in Mycoplasma pneumoniae pneumonia. They do not usually give rise to significant hemolysis. In occasional patients, however, production of high-titer, high-thermal amplitude, pathological cold sensitive antibodies results in hemolytic anemia which is transient but can be severe.

CAS complicating mycoplasma pneumoniae infection has been reported to account for approximately 8% of AIHA. Still more uncommon but less severe, polyclonal anti-i specific CA of the IgM or IgG class can result in CAS in Epstein-Barr virus infection. Transient CAS has also been described following cytomegalovirus infection, varicella, rubella, adenovirus infection, influenza A, Legionella pneumophila pneumonia, listeriosis, and pneumonia caused by Chlamydia species.



In CAS secondary to infection or aggressive lymphoma, the Red blood cell breakdown is complement-dependent, mediated by exactly the same mechanisms as in primary cold agglutinin disease (See Figure 1).

Management
Treatment of the underlying disease, if relevant and available, is often the only possible drug therapy for the hemolytic complication. Corticosteroid therapy has been used but is not evidence-based. In severely anemic patients, blood transfusions can safely be given provided the same precautions are carefully observed as in primary cold agglutinin disease.

Epidemiology
Among 295 consecutive individuals with AIHA described retrospectively by Dacie in a single-center series, 7 patients (2.4%) were classified as having CAS secondary to malignant disease. CAS complicating mycoplasma pneumoniae infection has been reported to account for approximately 8% of AIHA.