Immunoglobulin light chain amyloidosis associated with multiple myeloma in a young patient: a case report / Amiloidosis de cadenas ligeras de asociada con mieloma múltiple en un paciente joven: reporte de un caso

The authors present an uncommon case of systemic amyloidosis associated with multiple myeloma in a 35-year old woman. Systemic amyloidosis commonly presents in association with clonal plasma cell proliferative disorders, and less frequently as secondary or of a hereditary origin. Amyloidosis is usually associated with multiple myeloma in older patients and frequently has an unfavourable prognosis.

Los autores presentan aquí un caso raro de amiloidosis sistémica asociado con mieloma múltiple en una mujer de 35 años de edad. La amiloidosis sistémica normalmente se presenta asociada con desórdenes proliferativos de las células plasmáticas clonales, y con menor frecuencia con origen secundario o hereditario. Amiloidosis se asocia normalmente con el mieloma múltiple en pacientes de mayor edad y frecuentemente tiene una prognosis desfavorable.

Immunoglobulin light chain amyloidosis associated with multiple myeloma in a young patient: a case report.

The authors present an uncommon case of systemic amyloidosis associated with multiple myeloma in a 35-year old woman. Systemic amyloidosis commonly presents in association with clonal plasma cell proliferative disorders, and less frequently as secondary or of a hereditary origin. Amyloidosis is usually associated with multiple myeloma in older patients and frequently has an unfavourable prognosis.

The role of subclass switching in the pathogenesis of endemic pemphigus foliaceus.

Endemic pemphigus foliaceus, like the sporadic form seen in the developed world, is mediated by IgG antibodies to desmoglein-1. We studied an endemic focus in Limao Verde, Brazil, where disease prevalence is 3.4%. We previously detected IgG antibodies to desmoglein-1 in 97% of patients, but also in 55% of normal subjects in the endemic focus, with progressively lower levels in normal subjects in surrounding areas. An environmental trigger is hypothesized to explain these and other findings. In this study we sought to determine if patients and enzyme-linked-immunosorbent-assay-positive normal subjects in Limao Verde differ in IgG subclass response to desmoglein-1. We developed a sensitive and specific subclass enzyme-linked immunosorbent assay using recombinant desmoglein-1 and standardized the assay to enable comparability between the four subclasses. We found that normal subjects have an IgG1 and IgG4 response, whereas patients have similar levels of IgG1 but a mean 19.3-fold higher IgG4 response. Patients in remission have a weak IgG4 response, and a 74.3-fold higher IgG4 response is associated with active disease. Finally, in five patients in whom we had blood samples from both before and after the onset of clinical disease, a mean 103.08-fold rise in IgG4 was associated with onset of clinical disease, but only a mean 3.45-fold rise in IgG1. These results suggest that the early antibody response in normal subjects living in the endemic area and in patients before the onset of clinical disease is mainly IgG1. Acquisition of an IgG4 response is a key step in the development of clinical disease.

The prevalence of antibodies against desmoglein 1 in endemic pemphigus foliaceus in Brazil. Cooperative Group on Fogo Selvagem Research.

BACKGROUND: Pemphigus foliaceus is an autoimmune skin disease mediated by autoantibodies against desmoglein 1. The endemic form is thought to have an environmental cause. The Terena reservation of Limão Verde in Mato Grosso do Sul, Brazil, is a recently identified focus of the disease, with a prevalence of 3.4 percent in the population. We tested the hypothesis that normal subjects living in an endemic area have antibodies against desmoglein 1. METHODS: We used an enzyme-linked immunosorbent assay to detect antibodies against desmoglein 1 in serum samples from 60 patients with endemic pemphigus foliaceus (fogo selvagem) who lived in Limão Verde or elsewhere in Brazil, 372 normal subjects (without pemphigus foliaceus) from Limão Verde and surrounding locations, and 126 normal subjects from the United States and Japan. RESULTS: Antibodies against desmoglein 1 were detected in 59 of the 60 patients with fogo selvagem (98 percent) but in only 3 of the 126 normal subjects from the United States and Japan (2 percent). Antibodies were also detected in 51 of the 93 normal subjects from Limão Verde (55 percent) and in 54 of the 279 normal subjects from surrounding areas (19 percent). Serum samples obtained one to four years before the onset of disease were available for five patients; all five had antibodies in the initial serum samples, and the onset of disease was associated with a marked increase in antibody values. CONCLUSIONS: The prevalence of antibodies against desmoglein 1 is high among normal subjects living in an area among where fogo selvagem is endemic, and the onset of the disease is preceded by a sustained antibody response. These findings support the concept that the production of antibodies against desmoglein 1 is initiated by exposure to an unknown environmental agent.

Desmoglein-1-specific T lymphocytes from patients with endemic pemphigus foliaceus (fogo selvagem).

Fogo selvagem (FS), the endemic form of pemphigus foliaceus, is a cutaneous autoimmune disease characterized by subcorneal blistering of the epidermis and the production of autoantibodies against the desmosomal antigen desmoglein-1 (Dsg1). Previously, we showed that mice injected with autoantibodies from FS patients develop a skin disease that reproduces the clinical, histological, and immunological features of FS, indicating that autoantibodies play an essential role in the development of this disease. The purpose of this study was to characterize the autoimmune T-cell response associated with FS. We provide here the first evidence, to our knowledge, that the great majority of FS patients have circulating T lymphocytes that specifically proliferate in response to the extracellular domain of Dsg1. Long-term T cells developed from these patients also responded to Dsg1, and this antigen-specific response was shown to be restricted to HLA-DR molecules. These Dsg1-reactive FS T cells exhibited a CD4-positive memory T-cell phenotype and produced a T helper 2-like cytokine profile. These findings represent the initial steps in defining the role of T cells in FS autoimmunity.

Comparison of black fly species (Diptera: Simuliidae) on an Amerindian reservation with a high prevalence of fogo selvagem to neighboring disease-free sites in the State of Mato Grosso do Sul, Brazil. The Cooperative Group on Fogo Selvagem Research.

Fogo selvagem is an autoimmune blistering skin disease that principally occurs among rural Brazilians living in geographically clumped disease foci. Exposure to hematophagous black flies possibly is related to the cause of the disease. We compared the occurrence, proportions, and richness of simuliid species immatures and the biting activity of adult females within a recently discovered, high prevalence focus of fogo selvagem, the Limão Verde Terena Reservation, to that of neighboring regions with no reported cases of fogo selvagem. Nine black fly species were collected from 12 stream sites during 5 trips to the fogo selvagem focus. The species showed longitudinal (upstream-downstream) trends in occurrence, proportions, and richness, and the abundance of simuliid immatures was greater at downstream sites. The most prevalent species at the focus, Simulium nigrimanum (Macquart), dominated the stream sites with highly abundant simuliid assemblages, and was the most common black fly in human bait collections. This species was absent or in very low numbers in neighboring valleys and villages that did not have cases of fogo selvagem.

An active focus of high prevalence of fogo selvagem on an Amerindian reservation in Brazil. Cooperative Group on Fogo Selvagem Research.

Fogo Selvagem (FS) is an autoimmune disease characterized by subcorneal vesicles and antidesmoglein-1 autoantibodies. Previous epidemiologic data have linked the onset of FS to exposure to an environmental antigen(s). This investigation describes a unique human settlement with an extraordinarily high prevalence of FS. This community is made up of Amerindians belonging to the Terena tribe, which has settled on the Limao Verde reservation in the state of Mato Grosso do Sul in Brazil. Twenty-six well-characterized FS cases have been identified within a total population of 998, yielding a prevalence of 2.6%. Seventeen of the patients (65 %) were males, and over 50% were older than 30 y of age. The incidence of the disease shows temporal periodicity, i.e., years with several cases of FS alternating with years with no cases. Over one-half of the cases occurred in genetically related family members. Another Terena reservation, the Ipegue/Taunay, located 90 km west of the Limao Verde reservation, was also evaluated as a control group. This reservation, with a population of 2203, had no recorded cases of FS. Thus, the Limao Verde reservation represents a new focus of FS in which the disease exhibits temporal, geographic, and familial clustering. These results suggest that the environmental antigen or antigens precipitating FS are endemic to the Limao Verde reservation. This reservation appears to be an ideal population for carrying out sero-epidemiologic, genetic, and environmental studies aimed at disclosing the etiology of FS.

[Epidemiologic study on tegumentary leishmaniasis in the municipality of Corguinho, Mato Grosso do Sul -- Studies in the human population]. / Estudo epidemiológico sobre leishmaniose tegumentar (LT) no município de Corguinho, Mato Grosso do Sul-Estudos na população humana.

A study on the resident population of 150 inhabitants of Boa Sorte in the Municipality of Corguinho, Mato Grosso do Sul State, Brazil was made, from March 1991 to March 1994, to establish the prevalence of South American Cutaneous Leishmaniasis (SACL), and to characterize the affected population, in an area of recent transmission. Twelve of the inhabitants showed lesions suspected to be SACL, and in 8 cases it was possible to confirm this by biopsy and parasitology. The mucosal form was found in one patient only, the rest showed the following cutaneous forms: ulcerated (3), ulcero-verrucose (1), hyperkeratotic ulcer (1), infiltrated maccule (1), nodule with florid regional adenopathy (1). All patients reacted favorably to treatment with glucantime, with lesion scarring. Side-effects were rare. The parasite isolated from all patients was identified as Leishmania (Viannia) braziliensis. The Montenegro skin test, applied to the 150 inhabitants, showed 32 reactive ones. Of these, six were carriers of the disease, 21 showed sequelae suggestive of the disease and five showed no signs of infection. The age grouping of the cohort ranged from 22 to 78 years, 75% being male. To date, transmission is suspected to be in the peridomicile.