Alexis Harris

Amyloid myopathy : Characteristic features of a still underdiagnosed disease

A 62‐year‐old man with progressive proximal weakness underwent extensive evaluation including muscle biopsy without a clear diagnosis being established. A repeat muscle biopsy including Congo red–stained sections revealed infiltration of blood‐vessel walls and endomysium with amyloid protein, as well as an unusual pattern of pathologic changes to muscle fibers. From a review of 79 cases of amyloid myopathy reported in the English‐language literature, the characteristic features of this disorder are described. Congo red–stained sections of muscle biopsy viewed under fluorescent or polarized optics, and serum or urine protein immunoelectrophoresis, play an important role in the evaluation of myopathy. Amyloid myopathy should be a consideration in adults with progressive neuromuscular weakness of uncertain cause. Muscle Nerve, 2004

Epidemic of Diabetic and Nondiabetic Renal Disease among the Zuni Indians: The Zuni Kidney Project

There is an epidemic of renal disease among the Zuni Indians. The prevalence of end-stage renal disease among the Zuni Indians is 18.4-fold and 7.4-fold higher than among European Americans and American Indians/Alaskan Natives, respectively. In contrast to other American Indian tribes, nondiabetic renal disease accounts for a significant percent of the renal disease burden among the Zuni Indians. To explore this hypothesis, a community epidemiologic study of the Zuni Pueblo was conducted. A questionnaire was administered, blood and urine samples were collected, and BP, height, and weight were measured. Neighborhood household clusters were used as the sampling frame to maximize ascertainment and minimize bias. Age and gender distributions in the sample (n = 1483) were similar to those of the eligible Zuni population (n = 9228). The prevalence, age-adjusted and gender-adjusted to the Zuni population, of incipient (0.03 < or = UACR < 0.3) albuminuria (IA) (15.0% [95% confidence interval, 13.1 to 16.9%]), and overt (UACR > or = 0.3) albuminuria (OA) (4.7% [3.6 to 5.8%]) was high. The prevalence estimates for IA and OA were higher among diabetic participants (IA: 33.6% [27.6 to 39.7%]; OA: 18.7% [13.7 to 23.7%]) than nondiabetic participants (IA: 10.8% [9.0 to 12.6%]; OA: 1.8% [1.0 to 2.5%]). However, there were more nondiabetic participants; therefore, they comprised 58.0% [51.4 to 64.6%] and 30.9% [20.0 to 41.7%] of participants with IA and OA, respectively. In contrast to most other American Indian tribes, nondiabetic renal disease contributes significantly to the overall burden of renal disease among the Zuni Indians.

Relaxin Improves Renal Function and Histology in Aging Munich Wistar Rats

Administration of recombinant human relaxin (rhRLX) to conscious, chronically instrumented rats increases GFR and effective renal plasma flow (ERPF) and decreases effective renal vascular resistance (ERVR) with no significant change in mean arterial pressure. The Munich Wistar albino rat shows progressive chronic nephrosis with age and therefore was used to determine the functional and histologic consequences of rhRLX on matrix remodeling in the kidney of older rats. RLX-infused rats showed increased GFR and ERPF with decreased ERVR. Furthermore, in a double-blinded examination, the renal histology showed a significant decrease in glomerular and tubular collagen deposition in the rhRLX-infused aged rats. During short-term rhRLX administration (24 h), gelatinase activity was found to be essential for renal vasodilation and hyperfiltration. Surprisingly, after 20 d, improved renal function was insensitive to the inhibition of gelatinase activity, suggesting that collagen degradation in these rats had permanently altered the matrix of the renal vasculature. In conclusion, long-term administration of rhRLX improves renal function and ameliorates renal pathology in an aging rat model. The biphasic action of rhRLX on the kidney indicates that, acutely, the vessels dilate, causing increased filtration and renal blood flow with decreased vascular resistance as a result of upregulation of gelatinase activity. Subsequently, the renal vessels undergo alteration in supporting matrix, showing increased blood supply even in the face of acute matrix metalloproteinase inhibition, most likely as a result of the inhibitory properties of RLX on collagen production or increased collagen breakdown.

Symptomatic anti-neutrophil cytoplasmic antibody-positive disease complicating subacute bacterial endocarditis: to treat or not to treat?

A 54-year-old man was diagnosed with Streptococcus mutans endocarditis of the mitral valve. Serological tests disclosed the presence of multiple autoantibodies including c-ANCA, anti-PR3 and anti-MPO. While the fever subsided with antibiotics, mental status and renal function deteriorated rapidly. Kidney biopsy revealed pauci-immune glomerulonephritis and acute eosinophilic interstitial nephritis. The abnormal clinical features improved rapidly after addition of corticosteroids and cyclophosphamide to the antibiotics. Immunosuppressive agents may be required in a fraction of the patients with infective endocarditis who develop ANCA and ANCA-mediated renal disease. Histological identification of the type of renal disease is imperative for the choice of the treatment.

Cutaneous extrarenal rhabdoid tumor with myogenic differentiation.

Background:  The rhabdoid phenotype is characterized by large epithelioid cells with abundant eosinophilic cytoplasm and paranuclear inclusions of intermediate filaments. Although originally described in tumors from pediatric kidneys, the rhabdoid phenotype has since been described in a variety of patient ages and extrarenal sites. Extraordinarily, the rhabdoid phenotype has emerged in cutaneous neoplasms, either as a pure extrarenal rhabdoid tumor or a composite phenotype coupled with another malignancy. Regardless of the clinical setting, the rhabdoid phenotype is uniformly associated with aggressive biological behavior. We report the findings from a rare and very aggressive primary extrarenal rhabdoid tumor of the skin with myogenic differentiation.

Tubulointerstitial Nephritis and Uveitis Syndrome: Use of Gallium Scintigraphy in its Diagnosis and Treatment

Prompt diagnosis and treatment with corticosteroids of the tubulointerstitial nephritis with uveitis (TINU) syndrome may assist in the preservation of renal function. We present a case illustrating the characteristic clinical features of this syndrome. Gallium scintigraphy assisted in the diagnosis and management of this case, which was complicated by relapsing pyelonephritis.

Mucous membrane pemphigoid with fatal bronchial involvement in a seventeen-year-old girl

Purpose: This study was designed to report a case of biopsy-proven mucous membrane pemphigoid with severe bronchial involvement in a young woman. Methods: Case report of a 17-year-old girl who presented with worsening dyspnea, skin rash, and bilateral ocular injection, symblepharon, and fornix foreshortening. Conjunctival, skin, and bronchial biopsies were performed along with imaging and serological tests in an effort to establish a diagnosis for this unusual constellation of findings. The surprising occurrence of a cerebrovascular accident during her hospitalization also prompted a search for a concurrent coagulation disorder. Results: Immunofluorescence studies of conjunctival, skin, and bronchial tissue specimens revealed deposition of multiple antibody classes at the basement membrane zone. The patient also possessed circulating basement membrane zone antibodies in her serum and a significant titer of antiphospholipid antibodies. She underwent dilation and stent placement for subglottic tracheal and left bronchial stenosis and was treated with immunosuppressive agents. After a favorable initial response, the patient experienced progressive bronchial stenosis and respiratory compromise, culminating in her death from bronchospasm and cardiopulmonary arrest. Conclusion: To our knowledge, this is the first report of mucous membrane pemphigoid involving the lower airways that was confirmed by immunofluorescence analysis. It highlights the potentially lethal, systemic nature of mucous membrane pemphigoid and underscores the need to question patients about symptoms of respiratory dysfunction.

Sustained Remission of Antineutrophil Cytoplasmic Antibody-Mediated Glomerulonephritis and Nephrotic Syndrome in Mixed Connective Tissue Disease

A woman diagnosed with mixed connective tissue disease (MCTD) developed an anti-myeloperoxidase (MPO) antineutrophil cytoplasmic antibody (ANCA) and nephrotic syndrome with normal serum creatinine. Percutaneous kidney biopsy showed pauci-immune glomerulonephritis with superimposed immune complex deposition. After treatment with cyclophophamide and prednisone, proteinuria decreased progressively to a level of 0.4 g/g creatinine, ANCA became undetectable, while serum creatinine remained normal seven years after the beginning of treatment. Sustained remission of nephrotic proteinuria with preserved renal function may follow treatment of ANCA-mediated disease developing in patients with MCTD.

C1q nephropathy in a child presenting with recurrent gross hematuria

C1q nephropathy is a rare glomerular disease characterized by mesangial immune deposits with dominant or codominant staining for C1q. The exact pathogenesis leading to the mesangial immune deposits of C1q remains unknown. C1q nephropathy often presents with proteinuria in the nephrotic range, with an unpredictable or poor response to corticosteroid therapy. It is seen more commonly in older children and young adults and is more common in African Americans compared with Caucasians. We present a 4-year-old African American girl who presented with recurrent gross hematuria in the absence of proteinuria or hypertension and whose renal biopsy demonstrated dominant mesangial deposits of C1q. We conclude that C1q nephropathy should be considered in patients who present with recurrent gross hematuria.