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Background: Episodic angioedema with eosinophilia is a new syndrome associating hypereosinophilia, episodic angioedema and elevation of immunoglobulin M. This syndrome, first described by Gerald Gleich, has a good prognosis and no organ involvement., Case Report: A 39-year old woman developed for 10 years, recurrent episodes of swelling, weight gain of 4 to 6 kg, hypereosinophilia and hyperimmunoglobulinemia M and G. All symptoms disappeared spontaneously within a few days. Numerous investigations (cutaneous, cardiac, pulmonary, immunologic, parasitologic) were negative. The patient was recently hospitalized because of increased recurrence of episodes and major discomfort. We noted hypereosinophilia up to 30. 731 eosinophils/mm(3), elevated lactate dehydrogenase to 902 U/l (N: 204-412), elevated eosinophile cationic protein to 371 microg/l (N<12) and elevated immunoglobulin E to 140 U/l (N<100). Renal, pulmonary and cardiac functions were normal. Bone marrow biopsy showed no abnormality., Discussion: Gleich's syndrome is a benign but often incapacitating disease of unknown etiology. Systemic glucocorticoids may control flare-ups.

A 75 year old woman died of predominantly motor peripheral neuropathy with amyotrophy and fasciculations progressing to tetraplegia and death within 19 months. There was a mild distal sensory loss. At electrophysiology, the pattern was initially demyelinating and later became axonal. Nerve biopsy disclosed severe myelinated and unmyelinated fiber loss with wallerian degeneration. The remaining fibers had demyelination widening of the external myelin lamellae and intense hypermyelination. Serum contained an anti-MAG monoclonal IgM reacting with SGPG. Two siblings without monoclonal gammopathy had died of definite amyotrophic lateral sclerosis. This family association is discussed.

An 8-year old girl suffering from chronic relapsing staphylococcal skin infection since the first days of life was found to have extremely high (up to 26,500 units/ml) serum IgE levels and impaired polymorphonuclear chemotaxis. The other immunological tests appeared to be normal. There seemed to be a correlation between impaired chemotaxis and rise in IgE, the latter perhaps being related to a deficiency in some thymus-dependent lymphocyte functions.

12 cases of polyneuropathy with IgM monoclonal gammapathy are reported. An analysis of the clinical, electrophysiological, histological and immunological features of these cases and of those reported in the literature allows to distinguish 2 groups. In the first group (8./12 cases), the neuropathy showed clinical and electrophysiological features of a mainly demyelinating mechanism involving large fibers. Electromicroscopy disclosed a widening of the spaces between the lamellae of the myelin in half of these cases. A monoclonal deposit of IgM was demonstrated by direct immunofluorescence, on the remaining myelinated fibers in most cases. In this first group, the M-component always reacted with the myelin sheaths of a monkey's peripheral nerve. The results of indirect immunofluorescence were closely correlated with those of immunoblotting, which revealed an anti-M.A.G. (Myelin Associated Glycoprotein) activity. The second group is more heterogeneous: there was an predominantly motor neuropathy (1 case), an asymmetrical and painful neuropathy with an endoneural deposit of IgM (1 case). In 2 other cases which in no other ways differed from those of the first group, the M-component seemed devoid of antimyelinic activity. Nevertheless, the presence of IgM on the myelin sheaths of these 2 cases suggested a relationship between the neuropathy and the gammapathy. In both groups, results from the association of apheresis and chlorambucil were difficult to assess and vary greatly. Therapy appeared beneficent in half of the cases, but only one patient was markedly improved.

Angio-lymphoblastic lymphadenopathies are a newly described haematological entity, though not rare, characterised by a histological triad (vascular neogenesis, highly polymorphic or predominantly immunoblastic cellular proliferation and the presence of acidophilic protein deposits), a clinical syndrome consisting essentially of voluminous disseminated lymphadenopathy and hepatosplenomegaly and abnormal laboratory findings dominated by a polyclonal dysproteinaemia. This disorder, the first four French cases of which are described here, does not appear to be malignant in its early stages and is sensitive to corticosteroid therapy at that time. Secondary sarcomatous transformation is possible.

A monoclonal gammopathy (M.G.) is usually associated with multiple myeloma or macroglobulinemia. Cases whose follow up have not demonstrated myeloma or lymphoma for several years are called "benign monoclonal gammopathies" (B.M.G.). Numerous criteria were suggested to distinguish multiple myeloma from B.M.G., chiefly an abnormal medullary plasmacytosis. But frequently it is only beyond 15 to 20 % that this plasmacytosis is considered as significative. Some authors have reported the peculiarities of these plasma cells immune labelling with rather conflicting results. We reviewed semi-thin sections of bone marrow biopsies with a low grade plasmacytosis (less than or equal to 10 %) by histological cytological and immunological methods in a group of 39 patients with a M.G. A diagnosis of multiple myeloma or of B.M.G. was made on the initial examination of these biopsies. The 24 cases of multiple myeloma were diagnosed using : --topographical criteria : inhomogenous sharing, nests of plasmocytes exclusively away from the periphery of vessels, --cytological criteria such as frequent cellular immaturity, nuclear immaturity in binucleated cells, bizarre shaped nuclei . . . --immunological criteria obtained by immunofluorescence method : strictly monoclonal labelling of plasma cells or "limit"-monoclonal labelling in 50 % of cases. The latter is less characteristic because of its presence in 25 % of B.M.G. In this prospective study, the initial diagnosis was maintained in 37 out of the 39 cases according to clinical and laboratory data. These results seem to demonstrate the practical value of the proposed criteria.

Two cases of polyneuropathy with IgM gammopathy are reported. Myelin associated glycoprotein is the antigen for the monoclonal antibody in both of these patients. The same antigenic specificity has now been identified in other patients having a paraproteinemia with a polyneuropathy. These findings suggest the existence of a new syndrome characterized by: a) a primary demyelinating neuropathy; b) a monoclonal IgM antibody to a specific glycoprotein component of myelin, referred to as myelin associated glycoprotein (MAG). As in other humorally mediated autoimmune diseases, it is suggested that demyelination is caused by circulating anti-MAG antibodies. The role of immunosuppressive drugs and plasmapheresis is discussed.

Pyoderma gangrenosum (PG) is a rare condition remarkable for its association with particular diseases, notably haemopathies and gastrointestinal diseases. As regards haemopathies, the associations most frequently encountered are with myeloid malignancies and monoclonal dysglobulinaemia. The association of PG with mainly inflammatory digestive tract diseases is also classical. The lack of publications concerning gastric atrophy and the dual haematological and gastric pathology which characterizes our case have prompted us to report it. A 60-year-old woman without significant history was admitted for PG on both knees, following vesiculo-bullous lesions. Laboratory examinations detected a normochromic anaemia tending to be macrocytic, a marked inflammatory syndrome and a monoclonal lambda light chain IgA peak at protein immunoelectrophoresis. Bone marrow biopsy, skeletal radiography and a search for Bence-Jones proteinuria were normal or negative. Colonoscopy showed no abnormality, but fibroscopy of the upper digestive tract revealed a severe gastric atrophy en plaques. Serum vitamin B12 level was moderately low, but there was no other sign of pernicious anaemia. After one month treatment with systemic corticosteroids, healing was obtained under replacement vitamin therapy. PG recurred a few months later; serum vitamin B12 level was normal, and the lesions healed after systemic corticosteroid treatment. In non-myelomatous dysglobulinaemia IgA is frequently found and there is no light chain predominance. PG often precedes dysglobulinaemia. Evolution towards a true myeloma seems to be exceptional. In a recent publication, 17 cases of association between PG and myeloma were mentioned, the IgA type being most common. Protein electrophoresis is indispensable in patients with PG. Five cases of congenital hypogammaglobulinaemia have been recorded, including three with IgA deficiency.(ABSTRACT TRUNCATED AT 250 WORDS)

The study concerned 13 cases of angio-immunoblastic lymphadenopathy. This systemic lymphoid disorder has been identified only recently and is surely more common than has been thought. It is characterised by specific changes in the lymph nodes, which are infiltrated by plasmocytic and immunoblastic cells, associated with a marked degree of vascular neogenesis. This anatomical involvement is accompanied by numerous immunological manifestations, the most important of which are a positive Coombs test and a polyclonal hyperimmunoglobulinaemia. Despite the severe course of the disorder, its benign or malignant nature is uncertain and the therapeutic approach remains a subject of discussion.

In 1000 patients with monoclonal gammapathies, heavy and light chains typing of the monoclonal Ig was performed. Class distribution of the heavy chains showed the following percentages : IgG = 56.60%; IgA = 17.0%; IgM = 14.5%; IgD = 0.3%; Light chain gammapathies (including Bence-Jones proteinuria without serum M-component) = 11.6%. The chi/lambda ratio was 663/337. Such results agree with figures from most statistical studies. Beside the well-known linkage between IgM and chi types in pathological macroglobulinemia, the quite high incidence of lambda chain type of light chain components is to be noticed. The frequency of gamma G type of M-component is significantly higher in patients demonstrating no symptoms of myeloma or lymphoma. chi/lambda ratio seems to be slightly affected by aetiological features.

The purpose of this work was to evaluate the genetic propensity importance in the monoclonal gammapathies occurrence. Systematic serum-electrophoreses were performed on 172 relatives of 37 reported patients and on 10,784 controls over 30. The 4 families including one or more "paraproteinemia" other than the proband's were investigated. Experimental, epidemiologic, immunologic and genetic arguments are discussed.

Four hundred C.S.F. electrophoreses were carried out in black West Africans (Ivory Coast) suffering from inflammatory disorders of the nervous system. In the normal state, the C.S.F. of the black African contains more gamma globulins than that of the white (15.8% as opposed to 10%). The study provides indirect evidence of the classical notion of the extreme rarity of DS (Disseminated sclerosis) in the tropics. Hypergammaglobulinorachia was demonstrated in 22% of cases, the two principal disorders responsible being trypanosomiasis (57.3%) and sub-acute sclerosing panencephalitis (16.8%). The oligoclonal distribution described in trypanosomiasis was not found. On the contrary, a homogeneous appearance of the gamma zone was constantly demonstrated (49/50). It is possible that these differences are related to the various phases in the course of the disease, and that oligoclonal disturbation is a marker of the auto-immune phase.

We have studied seven human monoclonal gammopathies using anti-idiotypic sera. In benign and malignant gammopathies, we have observed a similar number of B lymphocytes bearing idiotypic specificities also found on the monoclonal protein. These observations suggest that the plasma cell population is only a phenotypic expression of a tumoral event occurring in a B lymphocytes precursor which can still completely differentiate. In four myeloma patients and one benign monoclonal gammopathy, we also observed T lymphocytes bearing receptors idiotypically cross-reactive with the monoclonal protein. The values ranged from 1.8 to 8.0% within the purified T-cell population. In a first hypothesis, these T lymphocytes can belong to the tumoral clone itself. The tumoral event must occur at the level of a common precursor not yet determined to B or T pathway of differentiation. In a second hypothesis, these T lymphocytes are not cancerous but are induced by a strong perturbation of the idiotypic network, due to the enormous amount of the idiotypic B-cell tumoral subset.

Eleven cases of monoclonal gammopathy associated with chronic hepato-biliary diseases are reported. The gammopathy was benign and the majority of hepato-biliary diseases consisted of cirrhosis complicated or not by hepatocellular carcinoma. The small number of cases reported and the absence of distinctive clinical, biochemical and evolutive features of the gammopathy and hepato-biliary disease suggest that the association was fortuitous.

A case of benign monoclonal gammapathy associated with an auto-immune hyperlipidaemia and a chronic glomerulopathy is reported. Extraction of the monoclonal immunoglobulin made it possible to demonstrate its anti-lipoprotein antibody activity. Parallel changes in serum lipid levels and monoclonal immunoglobulin levels under the influence of melphalan confirmed the direction relationship between the lipid and protein disorders. The pathogenesis of the glomerulopathy and of the massive and prolonged activation of the classical complement pathway is more difficult to affirm. It is nevertheless possible that the renal involvement is due to an auto-immune complex disease.