[Amyloidosis and end-stage renal disease associated with leprosy]. / Amiloidose e insuficiência renal crônica terminal associada à hanseníase.

Renal involvement in leprosy includes glomerulonephritis, amyloidosis and tubulointerstitial nephritis. A 58-year-old man was admitted with complaints of lower limb edema and dyspnea. At admission, nitrogen retention, anemia, hyperkalemia and metabolic acidosis were observed, requiring hemodialysis. The patient had a history of lepromatous leprosy. A renal biopsy was performed that was compatible with amyloidosis. The patient had a stable outcome, but without renal function recovery and remained on regular hemodialysis. Leprosy should be investigated in every patient with renal function loss, particularly in those with cutaneous lesions or other manifestations suggestive of leprosy.

Amiloidose e insuficiência renal crônica terminal associada à hanseníase / Amyloidosis and end-stage renal disease associated with leprosy

O envolvimento renal na hanseníase é diverso, incluindo glomerulonefrites, amiloidose e nefrite túbulo-intersticial. Um homem de 58 anos foi admitido com edema de membros inferiores e dispnéia. Na admissão, havia retenção de escórias nitrogenadas, anemia, hipercalemia e acidose metabólica, com necessidade de hemodiálise. Referia história de hanseníase virchoviana. Foi realizada biopsia renal, compatível com amiloidose. O paciente evoluiu estável, sem recuperação da função renal, permanecendo em tratamento hemodialítico. A hanseníase deve ser investigada em todo paciente com perda de função renal, sobretudo naqueles que apresentam lesões cutâneas ou outras manifestações sugestivas de hanseníase.

Renal involvement in leprosy includes glomerulonephritis, amyloidosis and tubulointerstitial nephritis. A 58-year-old man was admitted with complaints of lower limb edema and dyspnea. At admission, nitrogen retention, anemia, hyperkalemia and metabolic acidosis were observed, requiring hemodialysis. The patient had a history of lepromatous leprosy. A renal biopsy was performed that was compatible with amyloidosis. The patient had a stable outcome, but without renal function recovery and remained on regular hemodialysis. Leprosy should be investigated in every patient with renal function loss, particularly in those with cutaneous lesions or other manifestations suggestive of leprosy.

La lepra y el riñon / Leprosy and the kidneys

Revisamos los efectos causados por la lepra sobre riñón, los cuales no se deben a la presencia del bacilo en los nervios o en parenquima renal, sino fenómenos secundarios, tales como formación de complejos inmunes, precipitación de proteínas resultantes de la inflamación crónica o complicaciones de la terapia antileprosa, principalmente. Se incluye: a) defectos en la concentración y acidificación de la orina, b) nefritis intersticial aguda o crónica, c) insuficiencia renal aguda, d) amiloidosis sistémica secundaria, e) glomerulonefritis. Se analizan los mecanismos por los cuales se producen estas lesiones y se describen las circunstancias documentadas sobre la lepra y transplante renal. La lepra no es una contraindicación para este transplante porque si bien se requiere de inmunosupresión, la enfermedad puede no reactivarse y si lo hace, se controla con la poliquimioterapia disponible. La lesión renal en la lepra predomina en los enfermos multibacilares y en la reacciones de tipo 2 o eritema nodoso leproso. En general es silenciosa, crónica y puede llegar a ser causa de muerte en estos enfermos. Se detecta con facilidad con el simple examen parcial de orina, que revela albuminuria, cilindruria y hematuria. Este examen debe hacerse en todo paciente con lepra y debe tener carácter obligatorio en la reacción tipo 2, en la cual, junto con los síntomas cutáneos, neuríticos y oculares, se presenta algún grado de compromiso renal, en el 100 por ciento de las reacciones. El compromiso renal que la lepra produce en los enfermos colombianos, se ha relegado a un segundo plano ante las manifestaciones dermatológicas. Se ha documentado amiloidosis secundaria sistémica y glomerulonefritis por depósito de complejos inmunes

[Inflammatory amyloidosis]. / Amylose inflammatoire.

Inflammatory amyloidosis consists of AA protein. In developed countries, its predominant causes are chronic inflammatory rheumatism (rheumatoid arthritis, chronic juvenile arthritis, spondylarthropathy, etc.). More rare are other chronic inflammatory disorders (Crohn's disease, ulcerative colitis, Whipple's disease, etc.), hemopathies and neoplasia. In developing countries, infectious causes are the most common (tuberculosis, leprosy, chronic bacterial suppuration). Other infectious diseases complicated with amyloidosis are less common (bronchial dilatation, mucoyiscidosis, heroin injection-related skin suppuration). In chronic infection, amyloidosis is observed a mean of 10 years after the beginning of the triggering disorder and is mainly localised in the kidney, the liver and the gastrointestinal tract. The course is most often slow and prolonged survival has been reported.

The pattern of amyloidosis in Malaysia.

Congo red screening of routine biopsies at the University Hospital Kuala Lumpur revealed the following categories of amyloidosis: systemic AL (5.9%); systemic AA (3.2%); isolated atrial (14%); primary localized cutaneous (7.5%); other primary localized deposits (3.2%); localized intratumour (58%); and dystrophic (8.6%). Unlike in the West, AA amyloidosis in this population was usually secondary to leprosy or tuberculosis. Liver involvement in AL amyloidosis was shown to exhibit a sinusoidal pattern and differed from the vascular pattern of AA amyloidosis. Within the category of AA amyloidosis, there were two patterns of renal involvement--glomerular and vascular, with the glomerular pattern carrying a more ominous clinical picture. Notable among the localized amyloidoses were isolated atrial amyloidosis complicating chronic rheumatic heart disease, intratumour amyloidosis within nasopharyngeal carcinomas and dystrophic amyloidosis which occurred in fibrotic tissues.

Sarcoma de Kaposi en un paciente con lepra lepromatosa VIH negativo / Kaposi's sarcoma in a VIH negative patient with lepromatous lepra

El sarcoma de Kaposi se considera una neoplasia oportunista y ha sido descrita con frecuencia en pacientes con el síndrome de inmunodeficiencia adquirida. El propósito de la presentación de este caso es recordar que existen otros factores de inmunosupresión como la lepra y el uso crónico de corticoides que favorecen el desarrollo del sarcoma. Se presenta la evolución de un paciente masculino de 53 años de edad, con estudio negativo para la infección por VIH tipos I y II, que padecía lepra lepromatosa nodular on reacción leprosa recidivante, se automedicó por 18 meses prednisona hasta que desarrolló la neoplasia mencinada, con diseminación cutánea y visceral que se complicó con amiloidosis renal

BCC-associated amyloidosis with a peculiar pattern of deposition.

An 83-year-old Japanese woman with lepromatous leprosy had been treated in a leprosarium. More than 10 years ago, she developed a dome-like brown tumor on the dorsum of the nose which showed the histology of basal cell carcinoma. The lesion was a well bordered, rounded tumor with tumor cell nests on its periphery extending toward the center as cords of tumor nest and with amyloid depositions between the cords. The tumor nests and amyloid lessened toward the center of the tumor, being replaced by collagen fibers. Amyloidosis showing this peculiar pattern of transition was reported with a review of published cases.

Renal involvement in leprosy.

Renal involvement in Hansen's disease was evaluated in 94 Portuguese patients, average age and duration of disease of 47.6 and 6.8 years respectively. Sixty-seven were studied retrospectively and 27 prospectively; renal biopsy was obtained in 4, fat-tissue needle aspiration for amyloidosis in 20, and tubular function was tested in ten. Mild proteinuria and/or haematuria was found in 33 patients, the severity increasing during erythema nodosum leprosum reactions, but without overt nephritic or nephrotic syndrome. Two patients had renal amyloidosis on biopsy and two more were confirmed by fat biopsy, a 10.5% incidence in those studied prospectively; all but one were of the lepromatous type, with frequent bouts of erythema nodosum leprosum. The two other renal biopsies showed mesangial glomerulonephritis, and one unexplained acute tubular necrosis; none had immune deposits by immunofluorescence. Proximal acidification was always normal, distal acidification tested by bicarbonate infusion was abnormal in one of nine patients, and six of nine patients had concentration defects. Leprosy causes frequent urinary sediment changes and concentration defects, usually without clinical expression; proteinuria and/or glomerular involvement is mainly due to amyloidosis.

An immunohistochemical and morphological study of amyloidosis complicating leprosy in Malaysian patients.

Congo red screening of tissue blocks from 37 consecutive autopsies on leprosy patients revealed 7 cases of systemic amyloidosis, indicating a prevalence rate of 19%. 5 were males and 2 females. All were ethnic Chinese. Their ages ranged from 52 to 85 years with a mean of 69 years. Six had lepromatous leprosy while the remaining 1 had tuberculoid leprosy. In all 7 cases, the amyloid was AA in type, being permanganate-sensitive and immunoreactive with anti-human AA protein antiserum. Hepatic deposition was limited to blood vessels, a pattern typical of AA (secondary) amyloidosis. With regard to renal involvement, 4 showed a predominantly vascular pattern of infiltration while 3 exhibited the more ominous glomerular pattern. Three died of chronic renal failure and 2 of congestive cardiac failure attributable to renal and cardiac amyloidosis respectively. One patient succumbed to septicaemia and the remaining 1 to acute myocardial infarction. AA amyloidosis remains a serious and significant complication of leprosy among Malaysians.

Amyloid goiter--a case report.

A rare case of Amyloid Goiter in association with leprosy is reported.

DMSO and colchicine therapy in amyloid disease.

There is no specific therapy for primary amyloidosis, and acquired generalised amyloidosis can be treated only if the underlying disease is eliminated. In this study we have investigated the role of colchicine therapy in primary amyloidosis, and dimethylsulphoxide (DMSO) in leprosy associated secondary amyloidosis. No effect on creatinine clearance or 24 h proteinuria could be observed in the patients with primary amyloidosis. In the DMSO group renal function was considerably improved in 3 patients with moderate renal failure but not in those with severe renal impairment (creatinine clearance less than 10 ml/min). Serum SAA determinations were not particularly informative. These findings point to a beneficial effect of DMSO in human secondary amyloidosis when given at an early stage of renal involvement.

Renal lesions in leprosy amongst north Indian patients.

Sixty consecutive patients with leprosy were investigated for renal involvement. Clinically overt renal disease was present in 4 patients; 3 presented with a nephrotic state and one patient with progressive renal failure. Urinalysis showed daily protein loss ranging from 0.4 to 8.9 g in 8 patients and microscopic haematuria in 4 cases. Elevated levels of blood urea and creatinine were seen only in one patient with diffuse proliferative glomerulonephritis. Of the 36 patients in whom distal tubular functions were evaluated, concentration and/or acidification defects were detected in 9 patients (25%). Renal histology revealed no abnormality in any of these patients. Serum C3 levels were decreased in 5 patients with lepromatous leprosy and 3 patients with borderline leprosy. Histological evidence of renal involvement was detected in 9 patients (15%). Amyloid deposits were seen in 3 (5%) patients of whom 2 had lepromatous leprosy and one had tuberculoid leprosy with chronic trophic ulcers. Mesangial proliferative lesions were seen in 5 (8.3%) and diffuse proliferative lesions (with crescents in more than 70% of glomeruli) in one patient. All of them had lepromatous leprosy. Three of the 5 patients with mesangial proliferative glomerulonephritis had erythema nodosum leprosum at the time of biopsy. Immunofluorescence studies revealed granular deposits of IgA, IgM and C3 in one patient with mesangial proliferation and IgA/IgM with or without C3 in 3 more patients in whom renal histology was normal. Glomerulonephritis associated with leprosy appears to be immune mediated but confirmation requires identification of lepra antigen in the glomerular immune complex deposits.

Amyloidosis and the serum amyloid A protein response to muramyl dipeptide analogs and different mycobacterial species.

Serum amyloid A protein (SAA) elevation accompanies induction of secondary amyloidosis in mice given Mycobacterium butyricum in Freund adjuvant. The synthesis of SAA by cultured hepatocytes is induced by a macrophage-derived mediator, which has been identified as interleukin 1. In these studies, SAA synthesis has been used as an index of macrophage activation to examine the in vivo response of mice to challenge with seven different mycobacteria and with synthetic analogs of the immunoadjuvant N-acetylmuramyl-L-alanyl-D-isoglutamine [MDP(L-D)]. SAA synthesis was stimulated by administration (by the intraperitoneal route) of the mycobacteria dissolved in saline, with Mycobacterium vaccae being the most active and Mycobacterium leprae being the least stimulatory. MDP(L-D), which is the minimal structure (molecular weight, 492) able to substitute for mycobacteria in Freund adjuvant, stimulated SAA synthesis, whereas the MDP(D-D) isomer was inactive. The butyl ester of MDP, which induces no detectable pyrogenicity but retains adjuvanticity, required a 100-fold greater dosage than MDP(L-D) in stimulating SAA synthesis. Amyloidosis was detected histologically only when active SAA inducers MDP(L-D), M. vaccae, and M. butyricum, were administered in incomplete Freund adjuvant, with amyloid-enhancing factor. These studies demonstrated that SAA elevation was a sensitive in vivo marker of the capacity of antigens to stimulate macrophages to produce interleukin 1. A point of considerable relevance to the human use of MDP was the observation that repeated injections of the adjuvant MDP in saline did not induce secondary amyloidosis.

Amyloïdose associée à un myélome à IGD (lambda), chez un hansénien / Amyloidosis associated with IGD (lambda) myeloma in a Hansen's disease patient

M. F.., 56 nos, portugais présentant comme antécédent une lèpre lépromateuse traitée par les sulfones de 1948 à 1958 nus est adressé pour le bilan d'une amyloidose généralisée.