Heavy chain disease
The four heavy chain diseases are exceedingly rare conditions associated with the production, circulation in blood, and often presence in urine of  a free clonal heavy chain with no detected clonal light chains. The heavy chain is non-functional and altered by having deletions, insertions, and point mutations due to somatic mutations in their respective coding genes. Beyond this commonality, however, these diseases have very different clinical differences. Furthermore, each of the heavy chain diseases appears to be due to rare variants of lymphoma and therefore is sometimes regarded as a B cell dyscrasia However, heavy chain diseases are still often classified with plasma cell dyscrasias. The heavy chain diseases are classified as α, γ, and μ heavy chain diseases and are based respectively on >400, 130, and 30-40 case reports as reviewed in a 2014 publication. α Heavy chain disease
α Heavy chain disease (also termed immunoproliferative small intestinal disease or IPSID, Mediterranean lymphoma, and Seligmann disease) afflicts primarily individuals of  Mediterranean, North African, and Middle Eastern descent of lower economic status. Many cases are centered in the Middle East and associated with relatively unsanitary living conditions. The disease usually appears between the ages 10 and 30 and in some cases may be an aberrant immune response to a parasite or other microorganism. The disease commonly effects the gastrointestinal tract leading to signs and symptoms of a malabsorption syndrome or, far less commonly, the respiratory tract with signs and symptoms of respiratory dysfunction.
Type III cryoglobulinemia (15-30% of cases) involves circulating polyclonal IgM protein with rheumatoid factor activity bound to polyclonal IgG and blood complement components; autoimmune diseases and, less commonly, hepatitis virus C infection or lymphoproliferative disorders are the cause of this type of croglobulinemia. Only types I and II are defined as plasma cell dyscrasias.Patients suffering type 1 cryoglobulinemia present with symptoms due to cold temperature-induce blood hyperviscosity and consequential interruptions of blood flow, e.g. skin lesions (lower extremity purpuric spots and papules, acrocyanosis, necrosis skin ulcers, livedo reticularis urticaria), peripheral neuropathy, blurred vision, loss of vision, hearing loss, headaches, confusion, transient ischemic attacks, chest pain, heart failure, glomerulonephritis, kidney failure, oral bleeding, and nasal bleeding. Rarely, patients may present with catastrophic decreases in blood flow to vital tissues and require emergency treatment. Symptomatic patients typically exhibit levels of a myeloma protein >5 gram/liter and can be diagnosed by simple observing the temperature-induced, reversible induction of serum precipitate formation. Patients, particularly those with catastrophic presentations, are treated with plasma exchange and/or plasmapharesis to reduce the load of circulating myeloma proteins and relieve acute symptoms. Patients with an overt malignancy are treated with the chemotherapy regimens used for Waldenstroms macroglobulinemia or multiply myeloma; patients with MGUS precursors to these diseases appear less responsive to these chemotherapeutic regimens.