Heavy chain disease with kapppa light chains in urine-
Correct Answer: Mu chain disease
Description: Ans. is 'a' i.e., Mu chain disease o The heavy chain diseases are rare B cell proliferative disorders characterized by the production of a monoclonal (M) protein consisting of a portion of the immunoglobulin heavy chain without a bound light chain. The heavy chain in heavy chain disease is often incomplete or truncated and a sharp, localized peak may not be seen on the electrophoretic tracing of serum or urine.o Three types of heavy chain disease (HCD) are recognized, based upon the class of immunoglobulin heavy chain produced (eg, alpha, gamma, mu) by the malignant cell.o Alpha HCD is:# A form of mucosa associated lymphoid tissue (MALT) lymphoma that is also called immunoproliferative small intestinal disease (IPSID)# Mediterranean lymphoma or# Seligmann diseaseo Gamma HCD (Franklin's disease) is:# Typically associated with the presence of a systemic lymphoma# Often of mixed lymphoid-plasmacytic character.o Mu HCD has:# Clinical features resembling small lymphocytic lymphoma/chronic lymphocytic leukemia, often with distinctive vacuolated lymphocytes/plasma cells in the bone marrow.Pathophysiologyo The normal immunoglobulin molecule:# The immunoglobulin molecule is composed of two heavy and two light chains Joined by disulfide bonds. The normal heavy chain constant region (CH region) has a number of domains, of which CH1 is responsible for light chain binding. In the absence of an associated light chain, the CHI domain binds to heat shock protein 78 (heavy chain binding protein, BiP), and the heavy chain undergoes proteasomal degradation rather than secretion. As a result, normal heavy chains without light chains are not detected in the serum.o The abnormal heavy chain in HCD:# In the heavy chain diseases, noncontiguous deletions in the switch-CHl region prevent binding of the abnormal heavy chain to light chains as well as to heat shock protein 78, thereby avoiding proteasomal degradation. The heavy chains are then secreted into the plasma (or jejunal fluid in the case of alpha HCD) and, if small enough, may appear in the urine.Alpha HCDo Alpha HCD (also called immunoproliferative small intestinal disease (IPSID), Mediterranean lymphoma, Seligmann disease) is a form of MALT lymphoma, with the same histologic features of MALT type gastrointestinal lymphomas with marked plasma cell differentiation.o It is the most common form of HCD and occurs in patients from the Mediterranean region or Middle East, usually young males, and is often associated with relatively poor sanitation.o The gastrointestinal tract is involved in alpha HCD, resulting in abdominal pain, severe malabsorption with chronic diarrhea, steatorrhea, and loss of weight.o Growth retardation (in children), digital clubbing, and mesenteric lymphadenopathy may also be present.o Infiltration of the jejunal mucosa with plasmacytoid cells is the most frequent pathologic feature. The duodenum and ileum are less often affected.o The diagnosis depends upon the recognition of a monoclonal alpha heavy chain without an associated light chain in the serum, urine, intestinal secretions, or cells infiltrating the intestinal mucosa.o The serum protein electrophoretic pattern is normal in one-half of cases, and in the remainder an unimpressive broad band may appear in the alpha-2 or beta mobility regions.o The amount of alpha heavy chain in the urine is small.o In the absence of therapy, alpha HCD typically is progressive and fatal.o The usual treatment is with antibiotics such as tetracyclines and eradication of any concurrent infection (eg, parasites, viruses, Helicobacter pylori, Campylobacter jejuni).Gamma HCDo Typically present with systemic symptoms, lymphadenopathy, splenomegaly, and/or anemia, and occasionally with palatal and uvular swelling.o Median age of patients with gamma HCD is 60 to 70 years.o The clinical findings ranged from an asymptomatic state (eg, monoclonal gammopathy of undetermined significance, MGUS) to an aggressive lymphoproliferative process.o Autoimmune manifestations are seen in about one-third of patients (eg, idiopathic thrombocytopenia purpura, hemolytic anemia, vasculitis, systemic lupus erythematosus, rheumatoid arthritis).o Typically associated with a polymorphous infiltrate, including admixtures of lymphocytes, plasmacytoid lymphocytes, plasma cells, immunoblasts, and eosinophils.o Electrophoretic pattern often shows a broad-based band more suggestive of a polyclonal increase but the gamma chains are monoclonal.o Diagnosis is established by immunofixation, which shows that the abnormal protein consists only of gamma heavy chains without associated light chains.o The monoclonal gamma chains have significant deletions of amino acids, including the CH 1 domain of the constant region.o Treatment is indicated only for symptomatic patients.# Therapy has consisted of chemotherapy with varying combinations such as cyclophosphamide, vincristine, and prednisone (CVP), or cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP regimen) or, if the abnormal cells express CD20, the anti-CD20 antibody rituximab plus CHOP (R-CHOP).MuHCDo Mu HCD is the least common of the HCDs and is characterized by a monoclonal mu chain fragment in the serum. It has features resembling chronic lymphocyticleukemia/small lymphocytic lymphoma (eg, anemia, hepatosplenomegaly), although peripheral adenopathy is less common than in CLL. Osteolytic lesions or pathologic fractures have been reported in occasional patients.o Unlike alpha and gamma HCD, some patients with mu HCD have increased free light chain secretion (Bence Jones proteinuria), and may develop cast nephropathy or amyloidosis,o Common features include characteristic vacuolated plasma cells or lymphoid cells in the bone marrow and panhypogammaglobulinemia.o The serum protein electrophoretic pattern is usually normal except for hypogammaglobulinemia.o The course of mu HCD is variable, and survival ranges from a few months to many years.o Asymptomatic patients are observed without therapyo Symptomatic patients are treated similar to patients with chronic lymphocytic leukemia or non-Hodgkin lymphoma.
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