Summary
Immunoproliferative small intestinal disease (IPSID) is a malabsorption disease classified as a subtype of mucosa-associated lymphoid tissue (MALT) lymphoma and is now the term used to include Mediterranean lymphoma and alpha chain disease (alpha-CD). Prevalence is unknown but the incidence of IPSID is decreasing, probably as a result of improving socioeconomic status and sanitary conditions in developing countries. The majority of IPSID cases were reported from Israel, Northern Africa, and other Middle Eastern and Mediterranean countries but cases have also been described from the Indian subcontinent, the Far East, Central and Subsaharian Africa, and Central and South America. IPSID mainly affects adults. It is clinically characterised by severe diarrhoea, weight loss, abdominal pain and other malabsorption manifestations. Three characteristic pathological stages have been defined: A) diffuse, dense, and apparently benign lymphoproliferative mucosal infiltration, classed as purely plasmacytic or mixed lymphoplasmacytic; B) mucosal infiltration with a circumscribed immunoblastic lymphoma in the intestine and/or mesenteric lymph nodes and C) a diffuse immunoblastic lymphoma with or without apparently benign lymphoplasmacytic infiltration. IPSID can be further divided into three subgroups, depending on the type of immunoglobulin (Ig) synthesised by the proliferative cells: 1) alpha-CD: the most common form of IPSID with synthesis and secretion of alpha-heavy chains,.2) nonsecretory alpha-CD: IPSID with synthesis but without secretion of alpha-heavy chains, and 3) non-alpha-CD: IPSID with synthesis and/or secretion of other monoclonal Igs, free light chains or polyclonal IgA. IPSID, like gastric MALT lymphoma, appears to have an infectious aetiology and the clonal cell expansion results from chronic antigenic stimulation. The oncogene translocations detected in alpha-CD patients may result from DNA deletions and duplications occurring during somatic hypermutation. Although the putative infectious agents are generally unknown, recent studies have identified an association between IPSID and Helicobacter pylori or Campylobacter jejuni infection. Diagnosis is confirmed by serum immunoelectrophoresis for free alpha-chains, small bowel histology, and exploratory laparotomy. Differential diagnosis should include malabsorption syndromes, inflammatory bowel disease and other forms lymphoma. The following treatment scheme has been proposed for IPSID: first-line treatment with tetracycline and metronidazole for patients with early-stage disease followed by chemotherapy with CHOP (cyclophosphamide, doxorubicin, vincristine, prednisolone) if there is no marked improvement after a six month course of antibiotics or complete remission within 12 months. Chemotherapy with antibiotics as a first-line treatment is recommended for patients with advanced disease at presentation. More recently, combination chemotherapies including COP (cyclophosphamide, vincristine, prednisolone), MOPP (nitrogen mustard, vincristine, prednisolone, procarbazine), and BACOP (bleomycin, doxorubicin, cyclophosphamide, vincristine, prednisolone), as well as abdominal irradiation, have been used mainly for stage B and C disease. Supportive therapies, such as intravenous infusion of minerals and albumin, or even total parenteral nutrition, are also beneficial. Prolonged conservative treatment with tetracycline is advised to avoid recurrences. In general, the prognosis of IPSID is poor and the morbidity is high. The overall 5-year survival rate is 67%. There is no long-term follow up of surviving patients but few cases have long-term survival and can be considered as cured. *Author: Prof. J.K. Triantafillidis (June 2008)*.
