Cutaneous vasculitis as a presenting feature of multiple myeloma: a report of 2 cases.

We report two male patients who presented with symmetrical, painful purpura that evolved into bullae and necrotic ulcers, predominantly on the extremities, over two months in spite of conventional therapy including oral steroids. Examination showed livedoid and purpuric patches with necrotic centers in starburst pattern over the extremities and buttocks. The first case also had similar lesions over the ears. The clinical presentation and the histopathological examination suggested a diagnosis of necrotizing leukocytoclastic vasculitis (LCV). Blood testing ruled out connective tissue disease, hepatitis B or C infection or streptococcal infection as underlying cause of vasculitis. Serum antinuclear factor, antineutrophilic cytoplasmic antibody and anticardiolipin anticoagulant were negative in both cases. Cryoglobulins were positive in case 2. An incidental finding was raised serum proteins and globulins in case 2. Further investigations revealed M band on electrophoresis and features of multiple myeloma on bone marrow biopsy in both cases. These cases emphasize the importance of simple investigations like serum proteins in the evaluation of LCV.

Activation of complement by circulating immune complexes isolated from leprosy patients.

Circulating immune complexes isolated from different types of leprosy sera as polyethylene glycol (PEG) precipitates were found to be efficient activators of the alternative pathway of complement. PEG precipitates from BL/LL leprosy patients and those with erythema nodosum leprosum were found to activate both the classical pathway and the alternative pathway of complement efficiently, while PEG precipitates from TT/BT leprosy patients and borderline tuberculoid patients in reaction were found to active the alternative pathway of complement but not the classical pathway. No significant differences were observed between the PEG precipitates from reactional and nonreactional TT/BT and BL/LL patients in their complement activating ability.

Clinical significance of changes in serum proteins, immunoglobulins, and autoantibodies in leprosy.

Changes in the level of acute phase reactants such as C-reactive protein (CRP), serum globulins, and autoantibodies have been reported previously in patients with leprosy, particularly at the lepromatous end of the spectrum. The clinical significance of these findings was investigated by comparing the same parameters of humoral immune function in populations of Australian Aboriginals with stable treated leprosy and relevant contact groups including a) noninfected European sporadic contacts and b) healthy Aboriginal relatives of patients with confirmed leprosy. Raised levels of CRP and immunoglobulins and the higher frequency of autoantibodies seen in leprosy patients compared with sporadic contacts are probably related to differences in the incidence of nonleprous infection rather than to leprosy per se. Comparable results were obtained in the leprosy patients and their family contacts. The data highlight the need to use antigen-specific assays for determining the significance of changes in acute phase reactants and for distinguishing between the primary and secondary effects of Mycobacterium leprae infection.

Studies on serum proteins in leprosy by polyacrylamide gel electrophoresis (page)--I.

Serum protein pattern was studied in the leprosy spectrum, their contacts and in normal individuals by employing polyacrylamide gel electrophoresis. Sera from 80% of untreated BL/LL, 70% of untreated TT/BT patients and 67% of contacts have shown dysproteinaemia either for 232 kD or for 175 kD or for both these proteins together. Tendency of these proteins to return to normal levels was observed after treatment. But both these proteins come back to normal levels only after subsidence of the disease.

Study of rheumatic manifestations and serologic abnormalities in patients with lepromatous leprosy.

We investigated the rheumatic and laboratory features associated with rheumatic syndromes in 32 patients with lepromatous leprosy. Twenty-seven (84%) developed a broad range of rheumatic manifestations, the most common being the presence of arthritis which was symmetric and polyarticular, resembling rheumatoid arthritis. The laboratory abnormalities included an elevated sedimentation rate in 32 cases (100%), a positive rheumatoid factor in 6 (18.7%), and antinuclear antibodies in one (3.1%). A careful history and the recognition of rheumatic manifestations will help in the identification of this type of leprosy.

Leprosy in a mangabey monkey--naturally acquired infection.

Naturally acquired leprosy was detected in an otherwise normal "sooty" mangabey monkey (Cercocebus atys). This animal was imported from West Africa in 1975 and developed clinical symptoms of leprosy in 1979. Histopathologic findings were those of subpolar-lepromatous to borderline-lepromatous leprosy in the Ridley-Jopling classification. The disease was progressive, with crippling neuropathic deformities of the hands and feet. The disease regressed under specific therapy. The etiologic agent was identified as Mycobacterium leprae by the following criteria: invasion of nerves of host, staining properties, electron microscopic findings, noncultivable on mycobacteriologic media, DOPA-oxidase positive, lepromin reactivity, infection patterns in mice and armadillos, sensitivity to sulfone, and DNA homology. We believe the animal acquired the disease from a patient with active leprosy. The mangabey monkey offers promise as a primate model for leprosy, and adds a third reported species to animals with naturally acquired leprosy.

Experimental murine leprosy: a biochemical study emphasizing lysosomal enzyme changes in vivo and enzyme secretion by macrophages in vitro.

This study was undertaken to identify biochemical alterations in serum, lymphoid organs, and peritoneal macrophages (PM) which reflect the histopathology of experimental Mycobacterium lepraemurium (MLM) infection in mice. A significant increase of acid phosphatase, beta-glucuronidase, N-acetyl-beta-D-glucosaminidase, and lysozyme was found in serum, spleen, and liver homogenates of mice infected intraperitoneally (ip) with MLM. PM from infected mice showed a substantially greater rate of secretion of beta-glucuronidase, N-acetyl-beta-D-glucosaminidase, and acid phosphatase than PM from normal mice. There was, however, no significant difference in the ability of PM from BALB/c and C57BL/6 mice to secrete such enzymes in vitro. There was also a significant increase in all these enzymes in PM in the early stage of infection but they dropped to values lower than normal in the advanced stage of infection despite the fact that such cells increased in size and protein content as the infection progressed. Infected mice were also found to have progressively elevated levels of serum lactic dehydrogenase, glutamic oxaloacetic, and glutamic pyruvic transaminases which indicated damages of hepatocytes and other tissues. Values of other blood components were also reported. Both BALB/c and C57BL/6 strain of mice, which are susceptible to the ip route of MLM infection, showed an indistinguishable pattern of biochemical alterations as reflected by their similar histopathological changes in various organs. BALB/c mice, which are still susceptible to subcutaneous (sc) route of infection showed similar characteristic changes in various serum components as before. In contrast, C57BL/6 mice, which are resistant to MLM infection sc, showed insignificant alterations in most of these biochemical parameters.

The effect of clofazimine on liver function tests in lepra reaction (ENL).

Twenty patients with suspected DDS resistance and repeated attacks of lepra reactions were selected for the study. Clofazimine was administered in different doses over a period of 12 months. Elevated levels of transaminases and Alkaline phosphatase prior therapy attained values to near normalcy. Progressive fall in serum Bilirubin and Proteins with normal A/G ratio at the end of therapy was also observed. Clofazimine by its anti-inflammatory and antibacterial action could inhibit the process of liver damage and happened to have minimal deleterious effect on liver by studying the liver function tests.

Identification of components of IC purified from human sera. II. Demonstration of mycobacterial antigens in immune complexes isolated from sera of lepromatous patients.

Immune complexes have been purified from sera of patients with lepromatous leprosy, using solid phase conglutinin and analysed by SDS-PAGE. Some of their components have been immunologically identified after electrophoretic blotting on nitrocellulose. First, immunoglobulins, complement components (C1q, C1s, C3) and CRP were found in IC. Secondly, one mycobacterial antigen of 67 kD was directly identified in IC while two other components (20 kD and 14.4 kD) of possible M. leprae origin were also found in IC. This study suggests that lepromatous patients develop a good antibody response against some M. leprae antigens (33 kD and 12 kD), which are rapidly eliminated from circulation, while other M. leprae antigens (e.g. 67 kD) can persist in relative antigen excess, within circulating IC.

Total and differential serum proteins and globulins in leprosy.

Total and differential serum proteins were estimated in 177 adult male patients and globulins in 135 patients. Total serum proteins were slightly lowered in BB, BL and LL patients. Total albumin was low in all types of leprosy, especially in the BL group. Alpha-1 and alpha-2 fractions were unchanged all through the leprosy spectrum. Beta globulins were significantly lowered in LL patients as compared to the controls. Gamma globulins were elevated in all types of leprosy more so in BB, BL and LL patients. Details are presented.

Electrophoretic pattern of proteins in lepromatous leprosy.

Serum total proteins and the various protein fractions were studied in fifty cases of lepromatous leprosy and in eleven cases of lepromatous leprosy with lepra reaction. The study revealed a significant increase in serum total proteins in both lepromatous leprosy and lepra reaction groups, when compared with normal healthy subjects. The percentage rise was found to be 14.5% and 22.95% for lepromatous leprosy and lepra reaction respectively. The globulin fraction showed a significant elevation, while albumin showed a decrease. Thus a reversal of A/G ratio was observed in both the disease groups. Alpha-1 and Alpha-2 globulins were found to be significantly increased in both the disease groups. Beta globulins did not reveal any significant alteration. It was interesting to note the presence of an additional globulin fraction in seventeen patients of lepromatous leprosy and two cases of lepra reaction. Gammaglobulin showed a significant rise in lepromatous leprosy (56.16%) and in lepra reaction (60.72%). The significance of the above findings are discussed in the light of available literature.

Lepra: algunos aspectos inmunologicos / Leprae: some immunological aspects

Se estudiaron 252 pacientes con Lepra:156 hombres y 96 mujeres. 108 hombres y 48 mujeres con Lepra Lepromatosa; 48 hombres y 52 mujeres con Lepra Tuberculoide. En esta muestra se estudiaron su patron electroforetico, la concentracion de C3 y los niveles circulantes de IgG, IgA e IgM. Se encontro que no existe un patron definido electroforetico que pueda asociarse con la Lepra, solo la fraccion gamma muestra niveles altos en Lepra Lepromatosa y esta alteracion comparada con la poblacion general tiene significancia estadistica. Unicamente la IgG e IgM muestran aumentos considerables con significacion estadistica para Lepra Lepromatosa. IgA se encuentra aumentada en los dos tipos de Lepra. No se encontro ninguna alteracion en los niveles circulantes de C3

[Hepatic function in the clinical spectrum of Hansen's disease]. / La función hepática a través del espectro clínico de la hanseniasis.

The liver function was studied in 100 hanseniasis patients. They were classified in the following 10 groups: quiescent LL (20 patients), quiescent BL (13 patients), quiescent BB (7 patients), quiescent BT (9 patients), quiescent TT (12 patients), reactional LL (12 patients), reactional BL (10 patients), reactional BB (7 patients), reactional BT (5 patients), reactional TT (5 patients); a comparison was made with a control group (10 healthy individuals). It was found a hyperproteinemia with high levels of globulin and normal levels of albumin in the serum of all clinical forms, and a typical pattern of "light damage hepatic cells" with raised in the enzymatic activity of GOT, GPT and alkaline phosphatase with no changes in turbidity tests and bilirrubinemia, in all reactional patients. The physiopathology of this problem and the types III and IV hypersensitivity phenomena are discussed.

A study of serum protein in leprosy.

Total serum protein albumin, globulin and A/6 ratio were determined in 50 patients of different types of Leprosy and 15 healthy controls. A significant elevation of total serum proteins (P < 0.001) was observed in 25 patients of Lepromatous leprosy and 10 patients of lepra reaction. No statistically significant alteration in total serum protein (P < 0.05) was observed in 15 patients of non-lepromatous leprosy. A significant fall in serum albumin with concomitant rise in serum globulin level (P < 0.001) was observed in non-lepromatous leprosy, lepromatous and patients having lepra-reaction.

Liver in leprosy--I. Functional changes.

Liver function tests were carried out in 79 leprosy patients, out of which 28 patients were being treated and 42 patients were not receiving any treatment. The rest 9 patients were clinically quiescent. In the untreated group there were 28 tuberculoid and 14 lepromatus cases. The 28 patients receiving treatment were composed of equal number of lepromatus and tuberculoid groups. The liver function tests of 10 of the untreated tuberculoid patients were repeated after six months of specific therapy with D.D.S. The values of liver function tests of these patients were compared with that of 20 normal adults. The most important abnormality observed in the patients were a reversal of albumin/globulins ratio which was more common in the lepromatus group than in the tuberculoid group. Treatment with D.D.S. has resulted in the reduction of the serum globulin. There were no changes in transaminases and alkaline phosphatase activities in the untreated patients. But however a rise in the above enzymes were observed in patients on treatment. The mean serum cholesterol values of the patients were lower than that of the controls.

Immunoglobulins in leprosy.

Serum immunoglobulins IgG, IgA and IgM were estimated in 22 lepromatous (LL) patients, 28 tuberculoid (TT), 9 borderline tuberculoid (BT), and 8 borderline lepromatous (BL), and compared with 50 normal healthy adult males belonging to a low socio-economic class. Immunoglobulin IgM was invariably significantly raised in TT, BT and LL subgroups of leprosy patients compared to the control but variation among different subgroups was statistically insignificant. Mean serum IgA levels were also raised in TT, BL and LL subgroups but statistically the rise was not significant. In the BT subgroup, significantly low IgA levels were observed both compared to the control and the other leprosy subgroups. Immunoglobulin G levels were significantly raised only in the LL subgroups compared to the control and the other subgroups of leprosy patients. It is proposed that persistently raised gamma globulins and immunoglobulin G, A and M levels observed in lepromatous leprosy patients could be caused by macrophage blockade hindering the suppressor T-cell mediated homeostatic control for immunoglobulins.