Low-density lipoprotein apheresis for PLA2R-related membranous glomerulonephritis accompanied by IgG4-related tubulointerstitial nephritis.

IgG4-related disease preferentially involves the kidney by tubulointerstitial nephritis with IgG4-positive plasma cell filtration and/or membranous glomerulonephritis. We reported the case of a 68-year-old man with IgG4-related tubulointerstitial nephritis combined with antiphospholipase A2 receptor (PLA2R)-related membranous glomerulonephritis, in which distinguishing between idiopathic PLA2R-related and IgG4-related secondary membranous glomerulonephritis was difficult. We diagnosed him as having IgG4-related disease, based on a serum IgG4 level of 170 mg/dL and the presence of IgG4-related parotiditis. On renal biopsy, there was tubulointerstitial nephritis with IgG4-positive plasma cell filtration, which was compatible with IgG4-related disease and membranous glomerulonephritis, with concomitant positive staining for PLA2R on immunofluorescence microscopy. The renal function immediately recovered after steroid treatment, probably because of the improvement in the tubulointerstitial lesions, but his nephrotic syndrome was steroid-resistant. Low-density lipoprotein (LDL) apheresis therapy was effective for membranous glomerulonephritis and increased his serum albumin from 1.4 to 2.8 g/dL. Although IgG4-related kidney disease usually accompanies secondary membranous glomerulonephritis, the positive PLA2R staining suggested a concomitant primary membranous glomerulonephritis. The recent treatment strategy, including LDL apheresis, for primary and secondary membranous glomerulonephritis was discussed briefly in this report.

Facial and limb angioedema with parotitis and Kikuchi-like necrotizing lymphadenitis preceding neuropsychiatric systemic lupus erythematosus in a young African American male.

Angioedema has been observed in a few cases secondary to systemic lupus erythematosus (SLE). Herein, we report a rare case where a young healthy male initially presented with angioedema, lymphadenopathy and parotitis and later on developed neuropsychiatric manifestations at the very onset of his SLE disease. This case illustrates the importance of prompt clinical consideration of lupus with unusual and atypical preceding manifestations.

Immunoglobulin G4-related disease of the hard palate.

A 71-year-old woman presented with erythematous, nontender, bilateral hard palate nodules of 6-month duration. Biopsy showed collagenous sclerosis and a follicular lymphoplasmacytic infiltrate among the minor salivary glands. Immunoglobulin G (IgG) and IgG4 staining showed 280 IgG4(+) cells per high-power field and a ratio of IgG4(+) to IgG(+) cells of 0.8. The patient subsequently developed bilateral lacrimal gland and parotid gland enlargement associated with an increased serum IgG4 level of 3,031 mg/dL (≤ 135 mg/dL). Left lacrimal gland biopsy confirmed IgG4-related dacryoadenitis. The patient declined corticosteroid treatment for IgG4-related disease (IgG4-RD) and remained stable at 15 months after the first presentation. Spontaneous, partial resolution of the palatal lesion was observed during follow-up. IgG4-RD should be considered in the differential diagnosis of lymphoplasmacytic lesions of the hard palate.

Rare diagnosis of IgG4-related systemic disease by lip biopsy in an international Sjögren syndrome registry.

IgG4-related disease has been recently defined as a distinct clinic-pathologic entity, characterized by dense IgG-4 plasmacytic infiltration of diverse organs, fibrosis, and tumefactive lesions. Salivary and lacrimal glands are a target of this disease and, when affected, may clinically resemble Küttner tumor, Mikulicz disease, or orbital inflammatory pseudotumor. In some patients, the disease is systemic, with metachronous involvement of multiple organs, including the pancreas, aorta, kidneys, and biliary tract. We report a 66-year-old man who presented with salivary gland enlargement and severe salivary hypofunction and was diagnosed with IgG4-related disease on the basis of a labial salivary gland biopsy. Additional features of his illness included a marked peripheral eosinophilia, obstructive pulmonary disease, and lymphoplasmacytic aortitis. He was evaluated in the context of a research registry for Sjögren syndrome and was the only 1 of 2594 registrants with minor salivary gland histopathologic findings supportive of this diagnosis.

Evaluación inmunológica de pacientes con parotiditis recurrente / Immunological assessment of patients with recurrent parotiditis

La parotiditis recurrente se define como una inflamación parotídea, generalmente asociada a una sialectasia no obstructiva glandular. Se realizó un estudio en 74 niños menores de 15 años con diagnñstico de parotiditis recurrente en el período de 2000 a 2007. A cada paciente se le realizó interrogatorio, examen físico y estudio inmunológico mediante cuantificación de inmunoglobulinas séricas M y G, rosetas espontánea y activa e índice opsonofagocítico. La enfermedad afectó de forma similar a los 2 sexos. La edad de presentación de la primera crisis fue alrededor de los 3 años, con un promedio de 7 crisis por niño y una duración de 6 d. El 95,9 por ciento de los pacientes presentó alguna alteración de la respuesta inmune, 41,8 por ciento de células T, 12,2 por ciento de células fagocíticas, y 41,8 por ciento combinadas

Recurrent parotiditis is defined as parotic inflammation that is generally associated to non-obstructive glandular sialectasia. Seventy four children under 15 years of age, diagnosed with recurrent parotiditis from 2000 to 2007, were studied. Each patient was questioned and they also underwent physical exam and immunological study through quantification of serum M and G immunoglobulins, the spontaneous and active rosettes and the opsonocytophagic index. The disease affected males and females in a similar way. The age of onset of the first crisis was 3 years, with an average of 7 crises per child and 6 days of duration. Of these patients, 95.9 percent presented with some disorder in the immune response, that is, 41.8 percent in T-cells, 12.2 percent in phagocytic cells and 41.8 percent combined

Wegener s granulomatosis with granulomatous liver involvement.

We report on a patient with biopsy proven systemic Wegener's granulomatosis (WG) with a granulomatous necrotising manifestation of WG in the liver, lung, parotid gland and skin with subsequent death of liver failure. Liver involvement in WG is an exceedingly rare, though potentially fatal, organ manifestation of WG.

Cystic lymphoid hyperplasia of the parotid gland in HIV-positive and HIV-negative patients: quantitative immunopathology.

BACKGROUND: Benign lymphoepithelial lesions of the parotid include a spectrum of disorders ranging from lymphoepithelial sialadenitis (LESA) of Sjögren syndrome to lymphoepithelial cysts (LEC) and both human immunodeficiency virus (HIV)-related and -unrelated cystic lymphoid hyperplasia (CLH). They share a common microscopic appearance characterized by epimyoepithelial islands and/or epithelial lined cysts in a lymphoid stroma. However, they differ greatly regarding their etiology, clinical presentation, and management. OBJECTIVE: The purpose of this study was to establish specific immunophenotypic profiles for these diverse disease entities. STUDY DESIGN: Four cases of HIV+ CLH, 5 cases of HIV- CLH, 3 cases of LESA of Sjögren syndrome, and 3 cases of sporadic LEC were quantitatively analyzed for distribution of lymphoreticular cell subpopulations, using antibodies against CD20, CD45RO, CD4, CD8, CD57, and CD68. RESULTS: The cystic lesions in both the HIV+ and HIV- cases were microscopically analogous. However, a marked decrease in the interfollicular CD4:CD8 ratio was observed in all HIV+ CLH cases, which was statistically significant when compared with the HIV- cases (P = .02) and cases of LESA of Sjögren syndrome (P = .03). No significant differences regarding the distribution of CD20+ B lymphocytes in epithelial cyst lining or the interfollicular or follicular distribution of CD20+, CD45RO+, CD57+, and CD68+ cells were present among the different groups. CONCLUSION: Analysis of the interfollicular CD4:CD8 ratio may offer a simple immunophenotypic approach in the distinction of HIV+ from other lymphoepithelial lesions of the parotid gland, when HIV status is unknown and p24 immunohistochemistry is not readily available.

Cervical lymphadenitis, suppurative parotitis, thyroiditis, and infected cysts.

Neck masses are common and have a variety of infectious agents and noninfectious causes. This article reviews the more common infectious causes of neck masses-cervical lymphadenitis, suppurative parotitis, thyroiditis, and infected cysts. Important clinical pearls, diagnostic evaluation including laboratory studies, and imaging are summarized. Methods for prevention are highlighted.

Antimicrobial defence mechanisms of the human parotid duct.

The parotid duct transports saliva from the gland into the oral cavity. However, its immune response properties, along with the secretion and moistening principles of the duct, have not yet been fully investigated. These properties may play an important role in protecting the parotid gland from infection and also prevent development of sialodocholithiasis, as the parotid duct -- in contrast to the submandibular salivary duct -- is often free of duct concrements. Up to now, only the parotid gland has been investigated, without regard to its duct. The present study analyses the structures of the parotid duct in their relations to antimicrobial defence mechanisms and rheological properties. Investigations were performed on 23 parotid ducts using histological, histochemical and immunohistochemical methods. Epithelial and goblet cells of the parotid duct synthesize a complex mucous layer that covers the epithelium. The viscosity is influenced by secreted mucins and TFF peptides. This layer contains carbohydrates including N-acetyl-glucosamine, N-acetyl-galactosamine, galactose, mannose, fucose and sialic acids. The lamina propria contains granulocytes, T lymphocytes and macrophages. IgA, produced by plasma cells in the subepithelial layer, is frequently integrated in the secretory product. Synthesized mucins, TFF peptides, carbohydrates and immunoglobulins form a complex layer that can be expected to prohibit infection and enables salivary flow. Our study demonstrates that the steady secretion of the parotid gland, together with the ductal cellular and biochemical immune protection system, is likely to thwart ascending infections in the parotid duct and gland.

Morphological changes of parotid glands following adjuvant arthritis and ibuprofen treatment in rats.

Drug administration and numerous systemic diseases may cause morphological changes of the parotid gland. The aim of this study was to investigate the possible relationship between experimental adjuvant arthritis following ibuprofen treatment and morphological alterations of the parotid glands in rats. Freud's adjuvant was injected intradermally into the plantar surface of the hind paw of the animals to induce experimental arthritis. Ibuprofen was administrated per os (17 mg/kg/day). Both adrenals and parotid glands were isolated and their absolute and relative weights were evaluated. A full histological examination of parotid glands took place. The diameter of the foot as well as the serum levels of rheumatoid factor was measured. In conclusion, both experimental adjuvant arthritis and ibuprofen treatment induce morphological changes of the parotid tissues, which are related to macro- and micro-structure of the gland.

[Parotid involvement in cat scratch disease: a differential diagnosis with increased significance]. / Parotisaffektionen bei Katzenkratzkrankheit: eine Differenzialdiagnose mit zunehmender Bedeutung.

BACKGROUND: Bartonella henselae is the causative agent of cat-scratch disease (CSD), an inflammatory infection of the lymph nodes. So far, only few cases of atypical manifestations in the head and neck, especially manifestations in the parotid gland have been reported. PATIENTS AND METHODS: Between January 1997 and June 1999 seven patients with manifestations of CSD in the parotid gland were observed at the ENT-department Freiburg. The positive diagnosis was confirmed serologically by an indirect immunofluorescence assay and by detection of Bartonella henselae-DNA with PCR-amplification and subsequent hybridization or sequencing. RESULTS: An intraglandular abscessed lymphadenitis was found in five patients, two of these cases were based on a Parinaud's oculoglandular syndrome. A diffuse affection of the parotid gland, initially misinterpreted as a parotid tumor, was seen in two patients. CONCLUSIONS: Antibiotic treatment is recommended in order to reduce the duration of the disease, in cases of pain and lymph node abscesses. In uncommon manifestations of CSD, the nosological assignment can be difficult on the basis of the heterogeneous symptomatic in the individual patient and the CSD diagnosis can only be confirmed by serology or PCR-based techniques. CSD should be considered in the differential diagnosis of all equivocal masses in the head and neck, even in unusual localisations like the parotid gland.

Respuesta inmune humoral de glándulas salivales menores en pacientes con parotiditis crónica recurrente / Humoral immunity response of minor salival glands in patients with chronic recurrent parotiditis

La parotiditis crónica recurrente inespecífica, es una enfermedad que afecta las glándulas parótidas de niños prepúberes, siendo de carácter inflamatorio. A pesar de ser la segunda enfermedad parotídea de mayor prevalencia en niños, no se sabe con certeza su etiología, y su tratamiento sigue siendo sólo paliativo. Dentro de las posibles etilogías que se proponen se encuentran algunas enfermedades de carácter inmune, es por esto que se investigó, si existían variaciones en la cantidad de inmunoglobulina G y M presente en las glándulas de estos niños. Para esto se tomó biopsias de glándulas salivales de labio inferior de niños enfermos y se sometieron a tinción inmunohistoquímica policlonal para IgG e IgM. Se realizó el conteo de los plasmocitos que presentaban IgG y M, comparándose con glándulas salivales menores sanas, sometidas a la misma tinción. Los resultados obtenidos permiten descartar, como causante de la enfermedad, respuestas anormales del sistema humoral, ya que la presencia de IgM e IgG no presentó diferencias significativas entre glándulas de pacientes enfermos y sanos

Vacuna contra la parotiditis / Vaccine against mumps

La parotiditis es una enfermedad infecciosa aguda causada por un virus que por lo general afecta a las glándulas parótidas y ocasionalmente a otros órganos y sistemas; clínicamente se le reconoce como una inflamación de las glándulas salivales. Es un padecimiento autolimitado y casi siempre de curso benigno que afecta primordialmente a los niños y adultos jóvenes. La primera vacuna antiparotiditis que se aplicó en humanos fue en 1950, con una preparación de virus inactivado con formol. Los primeros estudios con esa vacuna demostraron que tenía una tasa de protección del 80 por ciento, que se mantenía por tiempo corto y por lo tanto se requería de revacunaciones cada año, por lo que no se logró su aceptación. En 1967 se aceptó una nueva vacuna atenuada, producida a partir de un virus aislado de una paciente, que se atenuó a través de 27 pasos en embriones de pollo. Esta vacuna induce anticuerpos neutralizantes protectores en el 93 y 97 por ciento de adultos y niños vacunados, respectivamente. La persistencia de anticuerpos es de unos 20 años cuando se aplica sola, ya que también se produce combinada con las vacunas de sarampión y de la rubéola en cuyo caso los anticuerpos se producen en menor cuantía y con duración de 9.5 años

Parotiditis crónica recurrente infantil: alternativa de tratamiento / Recurrent chronic parotiditis in childhood: alternative of treatment

El presente reporte es un estudio clínico microbiológico radiográfico, histológico inmunológico y de tratamiento en 20 pacientes con parotiditis crónica recurrente infantil. El rango de edad de los pacientes es entre 1 y 10 años. Los microorganismos aislados de saliva parotídea fueron: S. pneumoniae (7), H. influenzae (3), S. viridans (5), y H. influenzae más S. viridans (3). Las técnicas radiográficas realizadas mediante sialografía demuestran que el 100 por ciento tenía sialectasia, ya sea unilateral o bilateral. En biopsia de glándulas salivales de labio se observó sialectasia en el 60 por ciento de los pacientes. Como resultados del tratamiento se encontró recuperación de la glándula en el 80 por ciento de los casos comprobada por sialografía

Recurrent parotitis and sialectasis in childhood. Clinical, radiologic, immunologic, bacteriologic, and histologic study.

Twenty children with juvenile recurrent parotitis, between 3 months and 16 years of age at onset, were followed up over a period of 7 to 22 years. Radiologic, histopathologic, cytologic, immunologic, and bacteriologic studies were performed to investigate the cause of sialectasis, commonly found in juvenile recurrent parotitis, and the pathogenesis of the disease. It was considered that a combination of a congenital malformation of portions of the salivary ducts and infections ascending from the mouth following dehydration of the children are contributory to the pathogenesis of the disease. The results of the investigations into the cause of the disease appear to exclude an auto-immunologic response or an allergic condition, an immature immune response, mumps, a sensitivity to upper respiratory tract infection, and familial factors.

Estudio inmunológico en niños con riesgo de padecer de diabetes tipo I como secuela de infección por virus de la parotiditis / Immunologic study in children with risk of suffering type I diabetes as sequela of infection by parotiditis virus

Se estudiaron 68 niños con el diagnóstico de parotiditis o con antecedentes de la misma, se encontró que el 34,37% presentaba anticuepos contra las células insulares pancreáticas (ICA) en la fase aguda de la infección, así como otras alteraciones de la inmunidad celular. La frecuencia de estas alteraciones disminuyó según el tiempo transcurrido después de la infección. A dos niños sin ICA en el diagnóstico, se les detectaron estos anticuerpos al mes después de la infección. No encontramos manifestaciones de autoinmunidad tiroideespecífica en estos pacientes. Los resultados obtenidos evidencian un daño pancreático transitorio en parte de los niños estudiados y deben alertarnos sobre el posible peligro que pudiera representar la infección por virus de la parotiditis en pacientes con alto riesgo genético de diabetes tipo I

Natural history of patients with recurrent parotitis and punctate sialectasis.

The clinical features of 68 patients (26 children and 42 adults) who suffered recurrent attacks of parotitis and in whom sialography had revealed punctate sialectasis of the affected gland is described. The sex incidence was equal in those patients in whom symptoms commenced during childhood (younger than 15). When symptoms commenced later in life, however, there was a marked preponderance of females (female:male = 7.5:1). Bilateral sialography in 16 patients with unilateral symptoms revealed punctate sialectasis in the asymptomatic gland in 11 (69 per cent) of patients. Neither the presence of the sicca syndrome nor auto-antibodies had a significant predictive value as to the outcome of the disease. Five-year follow-up of 52 patients revealed that 56 per cent of adults and 64 per cent of children had shown spontaneous improvement of symptoms with symptomatic treatment alone. In 40 per cent of adults and 4 per cent of children, however, the persistence or worsening of symptoms necessitated parotidectomy. We believe that these results of conservative management indicate that, at least in the first instance and particularly in children, conservative management is justified and that the use of radiotherapy or steroids (with their attendant morbidity) is unnecessary.

ABO (H) cell surface antigens in benign and malignant parotid neoplasms.

Twenty-two inflammatory, benign, or malignant parotid lesions were studied by means of the specific red cell adherence test (SRCA), a modification of the Coombs' mixed cell agglutination reaction. In 22 normal parotid tissues the acinar structures were devoid of red cell agglutination, but it was present in ductal epithelium. Findings were similar in 2 cases of parotitis, 11 benign mixed tumors, and 1 malignant mixed tumor. All lacked red cell agglutination in areas of neoplastic change. Benign Warthin's tumors (4 cases) demonstrated antigenicity in the columnar epithelial component of the tumor, but lacked red cell agglutination in areas of the lymphoid component. One malignant Warthin's tumor showed agglutination in areas of normal columnar epithelium but not in areas of malignant dedifferentiation. Undifferentiated carcinoma (1 case) and adenoid cystic carcinoma (2 cases) did not possess detectable ABO (H) antigens in neoplastic areas of the gland. The absence of ABO antigens in normal acinar glands supports their suggested myoepithelial or mesenchymal derivation, as the absence of antigen in benign and malignant mixed tumors supports their proposed mesenchymal derivation. Ductular epithelium and the epithelial components of benign Warthin's tumors have ABO (H) antigens, while the loss of antigen in the epithelial portion of the malignant Warthin's tumor is characteristic of epithelial neoplastic dedifferentiation. Loss of antigen in adenoid cystic and undifferentiated carcinomas of the parotid supports the concept that antigen is absent in epithelially derived malignant neoplasms.

Unique pattern of Epstein-Barr virus specific antibodies in recurrent parotitis.

Sera from 34 children with recurrent parotitis were measured by indirect immunofluorescence technique for antibody levels to several Epstein-Barr virus (EBV) antigens. IgG antibodies to EBV-capsid antigen (VCA) and EBV-associated nuclear antigen, often at high titres, were found in 29 of these patients, of whom 20 also had IgA antibody to VCA. Antibody level to early antigen complex (R and D) rose in 19 patients, of whom 18 had antibody to the R component alone. The abnormal patterns of EBV antibodies persisted for 3-14 months during and after the illness in 8 patients. These observations suggest that EBV infection may be important in the pathogenesis of recurrent parotitis.