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A case of lymphoid interstitial pneumonia in a 3-month-old boy not associated with HIV infection: immunohistochemistry of lung biopsy specimens and serum transforming growth factor-beta 1 assay.

The case of a 3-month-old boy with lymphoid interstitial pneumonia (LIP) is reported. He had cough and tachypnea, his weight gain was poor and a chest radiograph showed microgranular shadows in almost all lung areas. Histological investigations revealed severe cellular infiltration by a variety of lymphoid and plasma cells with lymphoid follicle formation in the alveolar walls and also around the bronchioles. Foamy macrophages, a few lymphocytes and exudate filled the alveolar spaces. Epithelial cells lining the air spaces expressed human leukocyte antigen (HLA)-DR. Lymphocytes and macrophages in the alveolar spaces expressed transforming growth factor (TGF)-beta strongly. Serum TGF-beta 1 concentrations were measured eight times during the course of his illness. They exceeded the upper end of the normal range in four samples and were within it in the others. These results suggested that dysfunction of the immune system, especially abnormal expression of HLA-DR in non-immune cells and exaggerated production of TGF-beta played important roles in the pathogenesis of LIP in this patient.

Antigens, CD↗

[Multicentric Castleman's disease with lymphoid interstitial pneumonia died of aggressive course with adult respiratory distress syndrome].

A 49-year-old man was admitted to our hospital with anemia and hypergammaglobulinemia. Physical examination revealed superficial lymph node swelling and no hepatosplenomegaly. Laboratory findings showed WBC 5,300/microliters with normal hemogram, microcytic and hypochromic anemia. Total protein was 11.5 g/dl and immunoglobulinemia (IgG 10,100 mg/dl, IgA 295 mg/dl, IgM 160 mg/dl) was observed without M-component in serum and urine. The CD4/CD8 ratio of lymphocyte subsets was 0.58 and the tuberuculin skin test was negative. Urinary protein was positive and renal biopsy disclosed plasma cell infiltration. Lymph node biopsy revealed multiple lymphoid follicles and infiltration of plasma cells in the interfollicular areas. A diagnosis of multicentric Castleman's disease (MCD) was made baredon clinical findings and lymph node biopsy. After therapy with plasmapheresis and the CHOP regimen, he was given etoposide. Although discharged with clinical improvement and a decrease of serum IgG, he was readmitted because of pyrexia after 4 days and died of pneumonia with adult respiratory distress syndrome. The autopsy revealed lymphoid interstitial pneumonia. It seems important to notice that some of MCD have poor prognoses because of accompanying immunodeficiency.

Castleman Disease↗

Detection of maedi-visna virus in the kidneys of naturally infected sheep.

Infections with maedi-visna virus (MVV) cause progressive inflammation in different organs, mainly the lung, mammary gland, brain and joints. The aim of the present study was to investigate whether the kidney represents a viral target in natural MVV infection. For this, kidney samples from 13 sheep naturally infected with MVV were examined by histology, polymerase chain reaction (PCR), and immunohistochemistry. The kidneys of nine animals showed membranoproliferative glomerulonephritis and interstitial nephritis. The inflammatory infiltrate consisted of lymphocytes, plasma cells and macrophages. Interestingly, lymphoid follicles resembling those known to occur in other MVV-infected tissues were observed. Lung tissue from the same animals had typical MVV lesions, such as lymphofollicular hyperplasia and interstitial pneumonia. Maedi-visna proviral DNA sequences were detected in renal and lung tissue samples from these nine sheep by PCR, and the specificity of the amplified products was further verified by DNA sequencing. Moreover, MVV-specific immunohistochemistry revealed viral antigen in affected kidneys and lungs. These results suggest that the kidney may be a common target in natural MVV infection, and raise the issue of the role of this organ in the disease.

Animals↗

Establishment of erythropoiesis following bone marrow transplantation in a patient with congenital hypoplastic anemia (Diamond-Blackfan syndrome).

Marrow transplantation was attempted in a 13-yr-old boy with congenital hypoplastic anemia who had never responded to corticosteroid therapy. Prior to the transplant, he had received 238 transfusions, at least 12 of which were from his father. He was prepared for grafting with antilymphocyte globulin, procarbazine, and total body irradiation (1000 rads). The patient, whose red cells were Group B, then received marrow cells from his Group O, histocompatible, sister. Thereafter, reticulocytes, Group O erythrocytes, and female leukocytes appeared in the peripheral blood. Erythroid precursors were seen in the patient's marrow for the first time in his life, and all lacked fluorescent Y chromosomes. Dividing cells were all female. After initially progressing well, the patient developed interstitial pneumonia and died 55 days after the transplant. The successful erythroid graft suggested that this patient's failure to produce red blood cells was due to a defective stem cell rather than to a humoral defect, plasma inhibitor, or abnormal marrow microenvironment. It suggested further that sibling marrow may be engrafted in patients who have received multiple transfusions, even from a parent.

Adolescent↗

Effects of inducible nitric oxide synthase and xanthine oxidase inhibitors on SEB-induced interstitial pneumonia in mice.

The authors have previously reported that intratracheal instillation of staphylococcal enterotoxin-B (SEB) induced interstitial pneumonia (IP) in autoimmune-prone mice. SEB-reactive T-cells were critically involved in the development of IP in this model. Concern has arisen about the hazards of reactive oxygen species (ROS) and reactive nitrogen species (RNS) in the process of lung injury and fibrosis. Therefore, the involvement of nitric oxide (NO) and superoxide anion (O2-) in the pathogenesis of IP in this autoimmune-prone model has been investigated. Nitrite/nitrate levels were increased in bronchoalveolar lavage (BAL) fluid and serum from SEB-injected mice. The signal of the NO-(N-(dithiocarboxy) sarcosine)2-Fe2+ complex was detected in the SEB-injected lung and whole blood by electron paramagnetic resonance (EPR) spectroscopy. NO production was significantly decreased by aminoguanidine (AG) treatment. Xanthine oxidase (XO) activity in the lung, BAL fluid, and plasma was increased with instillation of SEB, and 4-amino-6-hydroxypyrazolo(3,4-d)-pyrimidine (AHPP) significantly inhibited XO activity. Moreover, both AG and AHPP significantly decreased production of pro-inflammatory cytokines, numbers of infiltrated cells in BAL fluid, and the area of thickened alveolar septa in the SEB-injected lung. In conclusion, the overproduction of nitric oxide and super oxide anion were implicated in the pathogenesis of interstitial pneumonia, and inducible nitric oxide synthase and xanthine oxidase inhibitors had protective effects against interstitial pneumonia in this model.

Animals↗

Low-grade B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) of thymus.

This report describes a low-grade B-cell lymphoma of mucosa associated lymphoid tissue (MALT) involving the thymus of a 63-year-old woman with features suggestive of a connective tissue disease. Sections of the thymic lesion and of a lung biopsy performed at the same operation were examined histologically and by immunohistochemistry using the monoclonal antibodies CD45, CD20, CD79a, CD3, CD45RO, and AE1/AE3. Polymerase chain reaction (PCR) for immunoglobulin heavy chain gene rearrangement was also performed. The dense infiltrate of small lymphoid cells intimately admixed with ramifying epithelial elements, some of which had undergone cystic change, closely resembled a thymoma. The lymphoid infiltrate comprised centrocyte-like cells, small lymphocytes, plasma cells, and blasts. Most of the lymphoid cells were immunoreactive with the B-cell markers CD20 and CD79a, and PCR showed clonal immunoglobulin heavy chain gene rearrangement. The lung biopsy showed dense infiltration by small lymphoid cells, morphologically suggestive of lymphoid interstitial pneumonia. However, PCR showed a weak band in the amplification for immunoglobulin heavy chain gene rearrangement, identical to that within the thymus and suggesting either recirculation of cells to accumulated MALT or subhistological lymphoma. MALT lymphoma may rarely involve the thymus, and pathologists should be aware of this to avoid misdiagnosis as a thymoma. Immunohistochemical and/or molecular studies are of value in this regard. MALT lymphomas of the thymus, common with those arising in other organs, may develop in the setting of a connective tissue disease.

Biopsy↗

Pathogenesis of visna. IV. Spinal fluid studies.

Visna is a persistent retrovirus infection of sheep which produces a chronic progressive paralytic disease after an incubation period lasting from months to years. The cerebrospinal fluid (CSF) was repeatedly sampled in a group of Icelandic sheep which were infected intracerebrally and followed up to 42 months. Minimal levels of infectious virus were isolated from the cerebrospinal fluid (CSF) up to 4 months after infection after which CSF neutralizing antibodies appeared in many sheep. These antibodies varied in titer and in some animals exceeded serum antibody levels which were moderate to high. CSF antibody is apparently produced within the CNS by local proliferation of B cell clones, and is accompanied by the appearance of considerable numbers of plasma cells in the neural parenchyma. Some sheep raised serum antibody to a second serotype of visna virus and in a number of these animals heterotypic antibody was also found in the CSF. An increase in CSF leukocytes often occurs within 1 to 3 months following infection and may then persist or wane. A persistent high level of CSF cells is an indicator of progressive CNS disease and such animals are more likely to yield virus, have higher CSF antibody levels, more severe CNS lesions, and an enhanced risk of clinical illness (progressive paralysis). CSF cells are predominantly macrophages and lymphocytes, with a consistent minority of plasma cells.

Animals↗

[High-resolution x-ray computed tomography in lymphoid interstitial pneumonia].

Three patients with lymphoid interstitial pneumonia (two HIV 1+ patients with chronic lymphadenopathic syndromes and one with a not-characterized autoimmune disease) have been studied with high-resolution computed tomography (HR-CT). This technique reveals septal lines, small reticulonodular opacities, polyhedral micronodular opacities, "ground-glass" opacities and a dense, subpleural, curved broken line in one patient. The lesions dominate in the bases of the lungs. They are not characteristic for lymphoid interstitial pneumonia. If a patient present with a chronic lymphadenopathic syndrome, the diagnosis of an opportunistic infection should not be automatically made, since the syndrome can be caused by lymphoid interstitial pneumonia.

Adult↗

Chronic eosinophilic pneumonia associated with Schizophyllum commune.

We describe the first known Japanese patient with chronic eosinophilic pneumonia caused by Schizophyllum commune. The patient presented to Social Insurance Tagawa Hospital, Fukuoka, Japan with cough, wheezing, dyspnoea, and fever. Computed tomograms of the chest showed bilateral areas of consolidation with air bronchograms as well as interstitial infiltrates in the upper lobe, without ectasia of proximal bronchi. Fibreoptic bronchoscopy revealed no impacted mucus in the bronchi. BAL fluid from the right upper lobe yielded an increased total cell count with a high percentage of eosinophils. A transbronchial lung biopsy specimen showed a bronchoalveolar chronic inflammatory infiltrate composed of eosinophils, lymphocytes and plasma cells, associated with fibrosis of the alveolar walls. S. commune was identified in lavage fluid. Antibodies to this organism were present in the serum, confirming that S. commune was the cause of chronic eosinophilic pneumonia. Inhaled corticosteroids without accompanying oral corticosteroids or antifungal agents decreased the respiratory symptoms, and the infiltrates disappeared from the chest radiograph within a few days

Aged↗

[The pathology and pathogenesis of experimental Mycoplasma hyorhinis infection of piglets with and without thermomotor stress. 2. Electron microscopic study results].

Electron microscopic investigations on the respiratory tract of piglets with and without Mycoplasma hyorhinis infection (10th day of life) partly combined with swim stress (15 degrees C water temperature) (n = 20/20) yielded the following results: colonization of Mycoplasma hyorhinis in the ciliary zone of trachea and bronchi in 15 out of 40 piglets (37.5%); the evidence rate of Mycoplasma hyorhinis in pneumonic lungs (8 out of 12 = 66.7%) was significantly higher than in nonpneumonic lungs (7 out of 28 = 25.0%) and highest in experimentally infected piglets with swim stress (9 out of 16 = 56.2%). Ultrastructural lesions: loss of cilia; bleb-formation; hydropic degeneration and desquamation of ciliary cells; the occurrence of cilia-free and immature epithelial cells; alveolar collapse; microatelectasis; oedematous swelling of pneumocyte I; accumulation of surfactant in the alveoli; hyperplasia of pneumocyte II; exudation of mononuclear macrophages and neutrophils with numerous digestion vacuoles; several lymphocytes and plasma cells, only a little lymphohistiocytic interstitial and peribronchial infiltration. Phagocytized mycoplasmas were found within the resorption vacuoles of neutrophils in the tracheobronchial area, for this once in alveoli, not (more) against in alveolar macrophages. The results were discussed with regard to etiology and pathogenicity of enzootic pneumonia in pigs.

Animals↗

[Specific anti-cytomegalovirus immunoglobulins in the prevention of cytomegalovirus infections in bone marrow allografts].

In order to assess the role of specific anti-CMV immunoglobulins in the prevention of severe cytomegalovirus infection in bone marrow transplant recipients, 46 consecutive patients were treated from day 1 to day 90 with injection of hyperimmune immunoglobulin with titres greater than 10,000 (ELISA) prepared from plasma selected for its high antibody titre (greater than 1,250). None of the patients developed CMV interstitial pneumonia; 5 patients developed diffuse pneumonitis, 2 of the aspergillus type and 3 apparently idiopathic, which progressed to fibrosis. There were no deaths directly attributable to CMV infection. This study confirms the efficacy of high dose immunoglobulin therapy in the high risk period for the prevention of sever CMV infection. In the absence of effective antiviral therapy, it is important to use all measures of prevention in patients with bone marrow transplants. The double identification of seronegative and hyperimmune blood donors allows preparation of uncontaminated cell fractions (with respect to CMV) and the selection of hyperimmune plasmas for the preparation of specific immunoglobulins.

Adolescent↗

Acute interstitial pneumonia in mink kits inoculated with defined isolates of Aleutian mink disease parvovirus.

The present study addressed the causal role of Aleutian mink disease parvovirus (ADV) in acute interstitial pneumonia in mink kits. All the examined isolates of ADV caused interstitial pneumonia in newborn kits, although the severity of disease and the mortality varied. These findings indicate that ADV is the direct causal agent of this disease in mink kits and that cofactors, which could have been present in the original ADV-K isolate, do not play a role. Acute interstitial pneumonia characterized by hypertrophy and hyperplasia of alveolar type II cells, intranuclear viral inclusions, interstitial edema, and hyaline membrane formation was experimentally reproduced in mink kits infected as newborns with five different isolates of ADV. Four hundred forty-nine newborn mink kits were included in the study, of which 247 were necropsied. The lesions caused by the different isolates were indistinguishable by histopathologic examination, but the incidence (50-100%) and severity (mortality of 30-100%, n = 218) of disease among the mink kits varied. Also, the content of ADV antigens in the lungs of infected kits varied among the groups. According to these features, the examined isolates could be placed in groups of high and low virulence. ADV-K, ADV-Utah I, and ADV-DK were in a highly virulent group producing a mortality of 90-100% (n = 110) in mink inoculated as newborns. ADV-GL and ADV-Pullman belonged to a group of low virulence, with an incidence of clinical disease of 50-70% and a mortality of approximately 30-50% (n = 118) in kits inoculated as newborns. The mortality in the control group receiving a mock inoculum was around 12% (n = 34). The period from infection to development of fatal disease varied from approximately 12 days for the highly virulent isolates up to around 20 days for the isolates of low virulence. The 107 mink kits that survived inoculation with ADV as newborns developed lesions typical of classical Aleutian disease irrespective of the ADV isolate used. The lesions consisted of chronic immune complex-mediated glomerulonephritis and infiltrations with mononuclear cells, including plasma cells in lung, liver, spleen, kidney, mesenteric lymph node, and intestine. Surviving kits also had hypertrophy of the bronchus-associated lymphoid tissue and focal subpleural, intraalveolar accumulations of large cells with foamy cytoplasm, so-called lipid pneumonia.

Acute Disease↗

Lymphoid interstitial pneumonia as a pulmonary lesion of idiopathic plasmacytic lymphadenopathy with hyperimmunoglobulinemia.

A case of idiopathic plasmacytic lymphadenopathy with hyperimmunoglobulinemia is reported. A 71-year-old man was admitted to the hospital because of the abnormal shadow on chest roentgenogram. Chest X-ray taken on admission showed remarkable diffuse infiltration and pleural thickening. Laboratory examinations revealed an elevated total protein level of 10.1 g/dl, and a gammaglobulin level of 7.0 g/dl including 6,790 mg/dl IgG. Mediastinal lymphadenopathy was observed on a chest CT. The patient underwent open lung biopsy. Heavy infiltration of lymphocytes and plasma cells were seen in the moderately fibrotic pulmonary interstitium. LIP was diagnosed. Lymph node biopsy was also performed. Follicular hyperplasia with prominent germinal centers and plasma cell proliferation in the interfollicular area were seen. Treatment with prednisolone resulted in an improvement in the chest X-ray findings, as well as a diminished polyclonal hypergammaglobulin level.

Aged↗

HIV-associated lymphocytic interstitial pneumonia: radiologic manifestations and pathologic correlation.

The authors reviewed chest radiographs of 16 patients with biopsy-proved lymphocytic interstitial pneumonia (LIP) who also had acquired immunodeficiency syndrome (AIDS) or AIDS-related complex (ARC). Radiographs revealed fine reticular or reticulonodular infiltrates in the pulmonary interstitium in five patients, coarse reticulonodular infiltrates in two, and reticular or reticulonodular opacities with superimposed patchy alveolar infiltrates in nine. Pathologic examination of biopsy specimens revealed lymphocytes, plasma cells, and reticulum cells aggregated about the small arteries and compressing the distal airways. Throughout the course of AIDS or ARC, the radiographic findings of LIP remained stable in 12 of 16 patients. AIDS/ARC-related LIP appears to be a benign reaction of bronchial-associated lymphatic tissue to the human immunodeficiency virus (HIV). However, this indolent process cannot be correctly diagnosed based on radiographic findings alone; the use of lung biopsy is required to differentiate LIP from other infections. The authors suggest that patients with these radiographic findings, HIV seropositivity, but no other signs of opportunistic infection or neoplasia should be classified as having AIDS.

AIDS-Related Complex↗

Expression of the thioredoxin system in interstitial lung disease.

The thioredoxin system containing thioredoxin (Trx) and thioredoxin reductase (TrxR) has profound effects on cell proliferation and protection against exogenous oxidants. The significance of the Trx system in human lung and lung diseases is, however, largely unresolved. Altogether, 66 specimens of human lung were investigated by immunohistochemistry for their expression of Trx and TrxR. The diseases included interstitial pneumonias such as usual interstitial pneumonia (UIP), desquamative interstitial pneumonia (DIP), and UIP associated with collagen vascular diseases (CVD-ILD), and granulomatous diseases such as sarcoidosis and allergic alveolitis. The ultrastructural localization of Trx and TrxR was analysed by immunoelectron microscopy. In healthy lung, Trx and TrxR were expressed in bronchial epithelium and alveolar macrophages. Trx and TrxR were highly concentrated in areas of metaplastic epithelium in UIP and in alveolar macrophages in DIP, though fibrotic areas in UIP were mainly negative. The expression of both enzymes was clearly weaker in CVD-ILD than in UIP. Granulomas of sarcoidosis showed moderate to intense Trx immunoreactivity. Ultrastructurally, Trx and TrxR were expressed diffusely in the cytosolic compartment and plasma membrane of metaplastic type II pneumocytes, macrophages, and bronchial epithelial cells. This study highlights the importance of Trx and TrxR in primary defence in bronchial epithelium, alveolar epithelium, and macrophages in human lung, but also indicates that elevated expression of these proteins may serve as markers of ongoing cell regeneration and inflammation.

Alveolitis, Extrinsic Allergic↗