Benign monoclonal gammapathy.

The natural history of benign monoclonal gammapathy (BMG) has been followed by repeated studies of patients with M components through periods up to two decades. The disappearance of an M component is quite exceptional--in this material only once. Populations with increase in IgG, IgA and IgM have been studied separately. Slow, but steady, increase through many years may be found without development of myeloma (MM). Rapid transition from a steady state of the M component to progression is rare and usually, but not always, indicates the development of clearcut myeloma. Intermediate patterns are not uncommon and make it very difficult in rare individual cases to draw a sharp line between myeloma that should be treated and the benign state that should only be observed. The cause of pain may be difficult to judge. Osteolytic foci in the skull are usually diagnostic for MM, but vertebral fracture may also occur in osteopenia. It is evident that a period of at least three years of close observation without treatment should be the routine. "Prophylactic" treatment of BMG with cytostatic drugs should never be attempted.

Genes and geography.

The author discusses a number of genetically determined diseases, such as hemoglobinopathies, acute intermittent porphyria, familial Mediterranean fever and so-called acquired hypogammaglobulinemia from the geographical point of view. Possible factors explaining localized increases in incidence are discussed. The importance of isolates for the development of such foci is stressed.

Plasmapheresis and cold sensitivity of immunoglobulin molecules. II. A study of macroglobulinemia polyclonalis spuria and immune complex disease.

The indications for plasmapheresis in the different hyperviscosity syndromes are discussed on the basis of data on relative serum viscosity at 13 and 37 degrees C. Beside monoclonal macroglobulinemia there are conditions with a high content of polyclonal IgM and also of IgG and IgA where hyperviscosity is a dominant symptom. The importance of what may be called macroglobulinemia polyclonalis spuria is stated and a number of patients belonging to this type are discussed. Polyclonal increase in IgG, even at high levels, usually does not cause severe hyperviscosity. Case histories of patients with rheumatoid disease and marked hyperviscosity constitute one group. Another is formed by diseases leading to the development of immune complexes. Such complexes are usually caused by binding of polyclonal IgG to monoclonal IgM, but other combinations are also known. A number of clinical examples of these different disease conditions, some probably indicating intense plasmapheresis, are analyzed. The limited value of plasmapheresis alone without cytostatic treatment is stressed as regards hyperviscosity. Another indication is removal of noxious protein components.

Plasmapheresis and cold sensitivity of immunoglobulin molecules. I. A study of hyperviscosity, cryoglobulinemia, euglobulinemia and macroglobulinemia vera.

There is a close connection between molecular changes of the Ig molecule with sinking temperature and the syndrome of hyperviscosity. The cryoglobulins are usually macroglobulins or complexes between IgM and other immunoglobulin classes. Many of these molecules can also be characterized as euglobulins. The connection between precipitation in the cold and in solutions with low electrolyte content is studied. Data on these connections are presented. The dependence of relative viscosity on the temperature has been investigated in a large number of sera from patients with different diseases. It is clear that most of these cold-sensitive globulins are macroglobulins (IgM). A number of viscosity curves at different temperatures in such sera are given. Also a few sera from patients with IgG myeloma have similar curves. The change in viscosity with lower temperatures implies that relative viscosity has to be determined at 37 degrees C in order to correspond to the condition in the living body. In practice, however, it is usually correct to state that IgM levels above 40 g/l are an indication that plasmapheresis should be considered. The best clinical sign is obtained by ophthalmoscopy. Difficulties with the counting of leukocytes and platelets in electronic counters may be caused by the presence of macroglobulins, usually but not always, cryoglobulins.

Relapsing annular erythema and myeloma successfully treated with cyclophosphamide.

We report the history of a patient, who had recurrent patches of erythema on the trunk and extremities for some years. The diagnosis of erythema elevatum diutinum or annulare centrifugum was discussed. The patient developed a monoclonal IgA lambda fraction and clinical signs of myeloma. Treatment with cyclophosphamide stopped the development of erythema and also caused the M-component to disappear. This improvement has persisted even without cytostatic treatment. Another patient with prostatic carcinoma and relapsing annular erythema was cured of his skin lesions, when his carcinoma was treated with estrogens. The literature is reviewed.

A new improved clinical staging system for multiple myeloma based on analysis of 123 treated patients.

The effect of the presenting clinical features on survival time was evaluated in 173 patients of a population of 201 individuals with multiple myeloma observed at Malmö General Hospital during the 11-yr period 1960 to January 1, 1971. Complete follow-up was continued until December 1978. One-hundred and five of the patients came from the city of Malmö and constitute a complete nonselected myeloma population. Bivariate correlation and multivariate regression analyses showed that the survival (i.e., the prognosis) could be accurately predicted in IgG and pure Bence Jones myeloma patients from (A) serum creatinine level, (B) serum calcium level, and (C) bone marrow plasma cell percentage; and in IgA myeloma patients from (A) hemoglobin level, (B) serum calcium level, and (C) serum M-component level. The results were synthesized to produce a simple and reliable clinical staging system with three stages (i.e., risks of death). To facilitate the clinical application, multivariate regression equations were developed to optimally predict the prognosis, and graphs were constructed in order to make the staging of the myeloma patients easier and quicker. The comparison of the duration of survival between the three groups of staged patients confirmed the high reliability of the present staging system.

Complete reversibility of paraneoplastic acanthosis nigricans after operation.

A patient with widespread acanthosis nigricans is described. No abdominal tumour was found. Explorative thoracotomy disclosed numerous enlarged lymph glands containing squamous cell carcinoma. The left lung was removed but meticulous search did not disclose any tumour. The glands were removed as radically as possible. After the operation the skin improved and the lesions have disappeared completely. The observation time is over three years.

Surgical treatment of myelomatosis--a review of 18 cases.

The authors review 18 patients with multiple myeloma who had bone destruction of a kind that indicated surgical therapy. Eight patients had paralegic myelopathy and one had compression of the cauda equina. Four of them displayed partial to complete regression. One patient lived for 77 months after the operation, most of the time in excellent condition. The operative technique is discussed, with laminectomy, exeresis, filling of bone with cement and, in some instances, mechanical support from metal plates. Early diagnosis and operation is imperative, postoperative irradiation obligatory in severe cases. Radiation alone may be the method of choice in early stages. The other 9 patients were operated upon for bone destruction in the limbs. A Moore operation on the destroyed hip was performed in one patient, who lived in excellent condition for about four years. Active surgical therapy combined with radiation and cytostatics seems to be of value in many patients with multiple myeloma.

Pyoderma gangraenosum (dermatitis ulcerosa) and monoclonal (IgA) globulin healed after melphalan treatment. Case report and review of the literature.

Since 1968 we have been treating a patient, who has had a combination of pyoderma gangraenosum (dermatitis ulcerosa) and signs that may indicate early multiple myeloma. She also had carcinoma of the colon, which was successfully operated. The pyoderma healed later after intensive and successful cytostatic treatment of the "myeloma". The ulcers remain practically healed and the protein pattern is normal in May 1977. Such cases are rare and a search in the literature has not been very rewarding. In our own series of more than 200 cases with myeloma this combination is unique. The lieterature is discussed in detail with data on the follow-up on some of the patients.

Osteosclerotic "plasmocytoma" with polyneuropathy, hypertrichosis and diabetes.

The combination of osteosclerosis, polyneuropathy, monoclonal immunoglobulin, hypertrichosis, serositis and a number of other symptoms is described. It seems probable that this is a special type of myeloma. Similar cases have been described in Japan and out findings are compared with the Japanese picture. The age of the patients is unusually low. The M-component in the plasma is small. There is very little Bence Jones protein in the urine and osteolytic lesions in the skull do not seem to have occurred. The polyneuropathy may improve during treatment with cytostatic drugs.

Comparison of trends in the incidence of multiple myeloma in Malmö, Sweden, and other countries, 1950-1979.

Dramatic increases in mortality from multiple myeloma have been reported in the United States and the United Kingdom over the past three decades. To assess what fraction of this increase, if any, might be attributable to a change in the incidence of this disease, we examined the incidence of multiple myeloma during 1950 to 1979 in Malmö, Sweden, a city chosen because of its medical community's longstanding interest in this disease. The average annual incidence rates per 100,000 population were 4.9 for males and 3.7 for females (adjusted to the European age-standardized population). These rates are among the highest in the world. Unlike secular trends for myeloma in the United States and the United Kingdom, where large increases in mortality rates have been reported, the rates in Malmö have increased only slightly, and the increase was restricted to males, suggesting the possibility of environmental causes. We suggest that the rates in Malmö may represent the asymptote of myeloma's incidence that will be approached in other white populations as case ascertainment among them becomes complete.