Wegener's granuloma. A series of 265 British cases seen between 1975 and 1985. A report by a sub-committee of the British Thoracic Society Research Committee.

In order to describe the British experience of Wegener's granulomatosis Hospital Activity Analysis was used to collect cases diagnosed in England, Wales and Scotland between 1975 and 1985. Where possible clinical details, histological material and chest radiographs were obtained. Two hundred and sixty five patients were considered to have Wegener's granulomatosis. In 109 a single pathologist confirmed the diagnosis by finding both granulomas and vasculitis in biopsy material. The diagnosis was made on clinical grounds or clinical grounds together with histological diagnosis in the local hospital in 156 patients. Wegener's granulomatosis was confined to the lung or upper respiratory tract in 22 per cent of patients and renal disease occurred in 58 per cent. Laboratory tests showed a pattern of mild anaemia, polymorph leucocytosis, eosinophilia and an elevated ESR and hypergammaglobulinaemia, with no specific pattern of changes. Histological confirmation was most frequently obtained by examination of nasal biopsy specimens, but multiple biopsies were often required. Renal biopsies showed focal proliferative glomerulonephritis but granulomatous glomerulonephritis was uncommon. Of available chest radiographs 61 per cent were abnormal, large opacities being most common. Small irregular opacities were found less often and other abnormalities were uncommon. Treatment varied widely and 10 per cent of patients received no drug therapy. This large series illustrates that even without specific treatment, patients with Wegener's granulomatosis can survive for several years and with modern treatment survival for more than a decade is possible. Conclusions about the effectiveness of the various therapies cannot be drawn from this retrospective study. Renal failure and disseminated vasculitis were the commonest causes of death; death was considered to result from complications of treatment with cytotoxic drugs or prednisolone in 6 per cent of patients.     

Gastrointestinal manifestations of systemic vasculitis

Systemic vasculitis is known to affect the gastrointestinal tract but the nature of the complication is poorly characterized. Out of 65 patients with systemic vasculitis, the majority of whom had renal disease, the intestine was found to be affected in 18. These comprised four of eight patients with polyarteritis nodosa, nine of seventeen with microscopic polyarteritis, four of thirty-six with Wegener's granulomatosis and one of four with Churg-Strauss syndrome. The features included abdominal pain (85 per cent), diarrhoea (50 per cent), gut haemorrhage (44 per cent) and abnormal liver function tests (50 per cent). Manifestations of gastrointestinal disease were evident at presentation in half the patients and led to a fetal outcome in five. Ileus, mucosal abnormalities, perforation and slow transit were evident radiographically, and selective visceral angiography showed aneurysms or organ infarcts in five patients. Histological assessment of gut biopsies (chiefly rectal) revealed non-specific inflammation or ulceration in nine patients and intramucosal haemorrhage in two. Focal areas of necrosis and ulceration in colonoscopic biopsies were highly suggestive of vasculitis whereas arteritis was only found in one full thickness biopsy. Hence the diagnosis of gastrointestinal complications depends largely on clinical evidence. In patients who survived, the gastrointestinal features remitted as the systemic illness improved following treatment with steroids, cyclophosphamide or plasma exchange.     

Renal disease associated with circulating antineutrophil cytoplasm activity.

We report our detailed observations on a group of 30 consecutive patients with renal disease, histologically demonstrated glomerulitis or necrotizing vasculitis, and circulating antineutrophil cytoplasm activity (ANCA). The annual incidence of ANCA-related renal disease was seven cases per million population. The sensitivity of serum ANCA for histologically proved glomerular vasculitis was 79 per cent, with a specificity of 87 per cent. Most patients responded to treatment with cyclophosphamide and steroids but complications of therapy occurred in just over half the patients and were serious in 20 per cent. Actuarial survival at 1 year was 60 per cent. Age and dialysis requirement did not influence outcome and the only identified adverse prognostic factor was hypoxic lung disease. We conclude that the association of ANCA with renal disease is not rare and that positive serology accurately identifies a homogeneous group of patients with similar clinical, histological, and prognostic features. Separation of these patients into those with the disease entities of Wegener's granulomatosis and microscopic polyarteritis is not straightforward on clinical and histological criteria, and such a distinction does not yield useful therapeutic or prognostic information. Simple urinalysis should always be carried out in patients with undiagnosed systemic illness in order to identify renal disease. ANCA-related renal disease can be treated successfully with cyclophosphamide and steroids and elderly patients should not be excluded from treatment, including dialysis if necessary. The ANCA test is simple and quick to perform and, in the appropriate clinical setting, accurately identifies patients who may benefit from immunosuppressive treatment before a histological diagnosis can be established.     

Comparison of flexible fiberoptic bronchoscopy and scalene lymph node biopsy in the diagnosis of sarcoidosis

The diagnostic accuracy achieved by taking bronchial mucosal and lung biopsies through flexible fiberoptic bronchoscopes was compared with scalene lymph node biopsy in 55 patients with sarcoidosis. The diagnostic yield with flexible fiberoptic bronchoscopy was 62 per cent in the whole material and increased to 76 per cent in patients with stage II sarcoidosis. Scalene lymph node biopsy was positive in 80 per cent. Flexible fiberoptic bronchoscopy is a useful method for obtaining biopsy material in sarcoidosis, especially in stage II sarcoidosis. We consider flexible fiberoptic bronchoscopy and scalene lymph node biopsy the methods of choice in the diagnosis of sarcoidosis.     

Systemic Lupus with Nephritis: A Long-Term Study

Seventy-one patients with systemic lupus erythematosus and clinicalevidence of nephritis were seen during a 15-year period, andfollowed for a mean of seven years. Survival was calculatedto be 76 per cent at five years and 57 per cent at ten yearsfrom onset of clinical nephritis; and 80, 65, 55 and 55 percent five, ten, fifteen and twenty years from onset of clinicallupus. Renal biopsies showed mild or focal lesions in 30 percent of patients, membranous lesions in 14 per cent and diffuseproliferative lesions in 55 per cent. However, there was nodifference in the long-term outcome of the different histologicalgroups. Nineteen patients (27 per cent) died during follow up,eleven from renal failure, six from sepsis and two from cerebrallupus. Death in renal failure is now usually a late event inlupus even in patients with clinical evidence of severe nephritis. The prognosis of even severe lupus nephritis is now better thanformerly reported. Reducing the dose of corticosteroid drugs,by the use of cytotoxic drugs such as azathio prine may havediminished the mortality from cardiovascular complications.Side effects of treatment, however, remain an important causeof death and morbidity.     

Primary nephrotic syndrome in Qatar (Arabian Gulf)

Sixty-two children with primary nephrotic syndrome were studied. The mean age at diagnosis was 5.5 years (range 1.5-11 years). Fifty-five were initially steroid sensitive (88.7 per cent) and seven (11.2 per cent) were steroid resistant. Renal biopsies performed on six of the steroid-resistant cases showed focal glomerulosclerosis in three, minimal change disease in two and membranoproliferative glomerulonephritis in one. Of the 55 children who were initially steroid responsive, 12 (21.8 per cent) had a frequently relapsing course, while three (5.5 per cent) became steroid resistant. Two out of the 12 who had frequent relapses became steroid resistant and one became steroid dependent. Renal biopsies performed on six of these patients showed minimal change disease in five and segmental glomerulosclerosis in one. Renal biopsies of two out of three patients who were initially steroid responsive but who later became resistant showed minimal change disease in one and segmental sclerosis in one.     

Hepatocellular Carcinoma and the Hepatitis B Virus: A Study of British Patients

We have examined the relationship between hepatitls B virusinfection and hepatocellular carcinoma in a series of 50 Britishpatients with histologically-proven hepatocellular carcinoma.Serum HBsAg was detected in 10 patients (20 per cent), and ofthe remainder, 21 per cent of those tested had serological evidenceof past hepatitis B virus exposure. None of nine tumour specimensfrom serum HBsAg negative patients had detectable HBV-DNA integrationinto the tumour cell genome. The presence or absence of serumHBsAg was of no prognostic significance in British patientswith hepatocellular carcinoma. Liver cell dysplasia, a possiblepre-malignant lesion, was noted in 53 per cent of patients whohad had liver biopsies before the diagnosis of hepatocellularcarcinoma, and in 79 per cent of biopsies taken at the timeof diagnosis of hepatocellular carcinoma. The presence of livercell dysplasia was not more common in serum HBsAg positive patients.     

Polyarteritis and the kidney

We report data on 43 patients with polyarteritis affecting the kidneys. The majority (41 patients) had renal histological evidence of microscopic polyarteritis. Although most patients (30 of 43) had significant renal impairment at the time of diagnosis (serum creatinine greater than 250 mumol/l) only five had a symptom, macroscopic haematuria, that directed attention to the kidneys. In the majority of patients in whom data was available there was rapid deterioration in renal function between presentation and diagnosis. Renal function at diagnosis was worse in patients aged over 50 of whom 20 out of 29 had a serum creatinine greater than 500 mumol/l compared with only four of 14 patients aged less than 50. The prognosis was worse in patients over 50 (41 per cent died), in patients with a serum creatinine higher than 500 mumol/l (54 per cent died) and in patients treated with intravenous methylprednisolone, (four also had intravenous cyclophosphamide) (38 per cent died). The major cause of death was sepsis and the actuarial one-year survival was 62 per cent. These results suggest that our approach to treatment should be modified towards lessening immunosuppression in older patients and in patients with renal failure at diagnosis.     

The nature of mycosis fungoides

Thirty-four patients with a clinical diagnosis of plaque stage mycosis fungoides, poikiloderma atrophicans vasculare (poikiloderma) and parapsoriasis en plaques (parapsoriasis) were investigated for evidence of extracutaneous disease using a biochemical screen, blood films, bone marrow examination, chest radiograph, abdominal ultrasound, isotope liver scan, liver biopsy and lymphangiography. Skin biopsies were also taken from these patients and, in order to rule out non-specific histological change, from 29 controls with inflammatory skin disease; the slides were examined blind by two independent observers for evidence of mycosis fungoides or poikiloderma and graded accordingly. Both observers were able to differentiate significantly histological grades of mycosis fungoides corresponding to the clinical diagnosis although exact histological grades only corresponded on 35 per cent of slides. Features graded as classical or probable mycosis fungoides were found in between 22 and 67 per cent of patients with parapsoriasis and between 67 and 100 per cent of those with poikiloderma. We found no evidence of extracutaneous disease in any of our patients. Lymphangiograms were abnormal in 30 of 31 examinations but the changes were non-specific and did not correspond to disease type, duration or extent. Four patients had apparently unrelated co-existing disease including chronic lymphatic leukaemia in two, a monoclonal gammopathy and autoimmune haemolytic anaemia. This study shows that in its early stages mycosis fungoides is predominantly if not primarily a cutaneous disease. The findings also suggest that parapsoriasis and poikiloderma are part of the same disorder as mycosis fungoides or evolve into it. Aggressive treatment to prevent progression to mycosis fungoides plaque and tumour stage should therefore be tried. The findings support the idea that mycosis fungoides is a reactive rather than a neoplastic disorder.     

Clinical and morphological aspects of the management of crescentic anti-glomerular basement membrane antibody (anti-GBM) nephritis/Goodpasture's syndrome

Twenty-two patients with crescentic anti-GBM nephritis or Goodpasture's syndrome with renal impairment were reviewed. All patients were treated with a combination of plasma exchange and immunosuppression. Sixteen patients (73 per cent) showed improvement in renal function (greater than 30 per cent reduction in serum creatinine level) apparently in response to treatment, and nine patients (41 per cent) made long-term recoveries in renal function. The most important features carrying a bad prognosis were total anuria, and/or a very high percentage of glomeruli showing crescents (greater than 85 per cent) in the initial renal biopsy. Some patients with other so-called 'bad' prognostic features, including severely impaired renal function at presentation, oliguria and the need to institute dialysis had unexpected marked improvement in renal function and/or recovered renal function in the long term provided treatment with plasma exchange was begun promptly and maintained for a sufficient period to allow resolution of the disease process. Renal biopsies at the beginning and later proved to be an extremely valuable guide for the progress and outcome of the disease.     

The clinical course of mesangial IgA associated nephropathy in adults

Clinical data in 244 patients with IgA nephropathy and biopsy findings in 519 biopsies (107 patients had at least two biopsies) were analysed. Males predominated (73 per cent) and had more severe disease and a worse prognosis than females. The most frequent symptom was macroscopic haematuria, often with associated loin pain; however, this was typical only in young males. Hypertension was the major presenting feature in 23 per cent of patients. Urinary erythrocyte counts correlated with the presence of crescents on biopsy (p less than 0.0001). Serum IgA levels wer elevated in only 21 per cent, while IgM levels were raised in 43 per cent of patients. Two hundred and seventeen patients were followed for at least one year (mean 59.7 months, range 12-255 months). In 82 patients five-year follow-up and in 33 patients ten-year follow-up data were available. Five- and 10-year survival figures were 91.5 and 87.5 per cent respectively. Clinical resolution occurred in only 6 per cent of patients but in those who had biopsies following clinical resolution, diffuse mesangial cell proliferation and IgA deposits persisted in all. The rate of clinical deterioration correlated with proteinuria, hypertension, impaired renal function, crescents and sclerosed glomeruli on biopsy. Continuing high urinary erythrocyte counts were the strongest predictor of a progressive course.     

A prospective study of hepatic tuberculosis in 41 black patients

Forty-one black patients aged 21 to 75 years with hepatic tuberculosis diagnosed at liver biopsy were studied prospectively. The liver varied in size and consistency and was tender in 44 per cent of patients. Abdominal symptoms, weight loss, pyrexia, hepatomegaly, splenomegaly and anaemia were absent in 54, 39, 37, 5, 68 and 27 per cent of patients respectively. Twenty-two per cent of chest radiographs were normal. Liver function tests were of little diagnostic value and hepatic imaging techniques often gave normal results. Acid-fast bacilli, caseation and coexistent liver disease were detected in 59, 51 and 37 per cent of patients respectively. Since there was no consistent clinical pattern a high index of suspicion is necessary if this disease is to be detected in communities in which tuberculosis is endemic. In patients with unexplained hepatomegaly or hepatosplenomegaly or pyrexia of unknown origin liver biopsy provides the only means of making this diagnosis.     

An Assessment of Laparotomy in the Management of Patients with Hodgkin's Disease

Planned laparotomy and splenectomy has been a safe investigationfor sixty patients with clinical Stage I, II or III Hodgkin'sdisease. Twenty-four of the 60 patients (40 per cent) changedstage and 18 patients had their treatment altered as a consequenceof the procedure. Forty-three per cent of patients without apalpably enlarged spleen had unsuspected disease when the organwas examined pathologically, although a false positive spleenwas uncommon. Eight of 55 patients (14·5 per cent) hadintra-abdominal disease which was not detected by lymphangiography.Intra-abdominal disease occurred with all histological sub-typesand was found in two patients who had clinical Stage I diseaseand lymphocyte predominance in their node histology. Sarcoid-like granulomata were found in ten patients, seven inthe spleen, one in the liver and spleen, one in the skin andone in the original node biopsy. In the majority of patients,granulomata were associated with nodular sclerosing or mixedcellular histology. In all ten patients the Hodgkin's diseasewas suppressed by appropriate chemotherapy and disease has notrecurred. No patient has shown any clinical evidence of sarcoidosisand the Kveim test done in three patients was negative. Our experience encourages us to recommend staging laparotomyfor all adult patients with Hodgkin's disease which does notshow obvious generalized spread beyond lymph nodes.     

A Prospective Study of Hepatic Tuberculosis in 41 Black Patients

Forty-one black patients aged 21 to 75 years with hepatic tuberculosisdiagnosed at liver biopsy were studied prospectively. The livervaried in size and consistency and was tender in 44 per centof patients. Abdominal symploms, weight loss, pyrexia, hepatomegaly,splenomegaly and anaemia were absent in 54, 39, 37, 5, 68 and27 per cent of patients respectively. Twenty-two per cent ofchest radiographs were normal. Liver function tests were oflittle diagnostic value and hepatic imaging techniques oftengave normal results. Acid-fast bacilli, caseation and coexistentliver disease were detected in 59, 51 and 37 per cent of patientsrespectively. Since there was no consistent clinical pattern a high indexof suspicion is necessary if this disease is to be detectedin communities in which tuberculosis is endemic. In patientswith unexplained hepatomegaly or hepatosplenomegaly or pyrexiaof unknown origin liver biopsy provides the only means of makingthis diagnosis.     

Clinicopathological Features of Childhood Nephrotic Syndrome in Northern Nigeria

The clinicopathological features of childhood nephrotic syndromein northern Nigeria were studied in 100 consecutive patients.The patients presented with gross anasarca and very low serumalbumin, which was <15 g/1 in 30 patients. The three mostfrequent histological diagnoses in 98 renal biopsies were membranoproliferativeglomerulonephritis (25), quartan malarial nephropathy (20),and proliferative glomerulonephritis (19): together they accountedfor 65 per cent of all biopsies. Only nine patients had minimalchange nephropathy. Antigens were detected by immunofluorescencein the glomeruli of 70 of 76 biopsies (92 per cent): Plasmodiummalariae was detected in 25 per cent and hepatitis B surfaceantigen in 24 per cent. The disease was characterized by progressivedeterioration in renal function and a high mortality rate of13 per cent. Nine of the 13 deaths occurred within one yearof diagnosis.     

Non-cirrhotic Intrahepatic Portal Hypertension: A Long Term Follow-up Study

The clinico-pathological features and prognosis of 59 casesof non-cirrhotic portal hypertension seen at one hospital overa 30-year period are described. Diagnosis was made on operativewedge liver biopsy in most cases. All but two had clinical featuresof portal hypertension and 47 had bled from oesophageal varices.In 53, portal decompression was performed without operativedeath or variceal rebleeding. Subsequent liver histology in16 cases up to 18 years after diagnosis showed no change inthe majority. The relatively static morphology was reflectedin the clinical course. Twenty-two patients have died but only11 as a result of liver disease or its treatment Actuarial analysisshows the five year survival to be 90 per cent and the 30-yearsurvival 55 per cent in strong contrast to the grim prognosisfor cirrhosis. The infrequency of operative liver biopsies andunfamiliarity with the disease lead to underdiagnosis.     

Hepatocellular carcinoma and the hepatitis B virus: a study of British patients

We have examined the relationship between hepatitis B virus infection and hepatocellular carcinoma in a series of 50 British patients with histologically-proven hepatocellular carcinoma. Serum HBsAg was detected in 10 patients (20 per cent), and of the remainder, 21 per cent of those tested had serological evidence of past hepatitis B virus exposure. None of nine tumour specimens from serum HBsAg negative patients had detectable HBV-DNA integration into the tumour cell genome. The presence or absence of serum HBsAg was of no prognostic significance in British patients with hepatocellular carcinoma. Liver cell dysplasia, a possible pre-malignant lesion, was noted in 53 per cent of patients who had had liver biopsies before the diagnosis of hepatocellular carcinoma, and in 79 per cent of biopsies taken at the time of diagnosis of hepatocellular carcinoma. The presence of liver cell dysplasia was not more common in serum HBsAg positive patients.     

Clinical and Morphological Aspects of the Managment of Crescentic Anti-glomerular Basement Membrane Antibody (Anti-GBM) Nephritis/Goodpasture's Syndrome

Twenty-two patients with crescentic anti-GBM nephritis or Goodpasture'ssyndrome with renal impairment were reviewed. All patients weretreated with a combination of plasma exchange and immunosuppression. Sixteen patients (73 per cent) showed improvement in renal function(> 30 per cent reduction in serum creatinine level) apparentlyin response to treatment, and nine patients (41 per cent) madelong-term recoveries in renal function. The most important features carrying a bad prognosis were totalanuria, and/or a very high percentage of glomeruli showing crescents(> 85 per cent) in the initial renal biopsy. Some patientswith other so-called ‘bad’ prognostic features,including severely impaired renal function at presentation,oliguria and the need to institute dialysis had unexpected markedimprovement in renal function and/or recovered renal functionin the long term provided treatment with plasma exchange wasbegun promptly and maintained for a sufficient period to allowresolution of the disease process. Renal biopsies at the beginning and later proved to be an extremelyvaluable guide to the progress and outcome of the disease.     

Clinicopathological features of childhood nephrotic syndrome in northern Nigeria

The clinicopathological features of childhood nephrotic syndrome in northern Nigeria were studied in 100 consecutive patients. The patients presented with gross anasarca and very low serum albumin, which was less than 15 g/l in 30 patients. The three most frequent histological diagnoses in 98 renal biopsies were membranoproliferative glomerulonephritis (25), quartan malarial nephropathy (20), and proliferative glomerulonephritis (19): together they accounted for 65 per cent of all biopsies. Only nine patients had minimal change nephropathy. Antigens were detected by immunofluorescence in the glomeruli of 70 of 76 biopsies (92 per cent): Plasmodium malariae was detected in 25 per cent and hepatitis B surface antigen in 24 per cent. The disease was characterized by progressive deterioration in renal function and a high mortality rate of 13 per cent. Nine of the 13 deaths occurred within one year of diagnosis.     

The Nephrotic Syndrome in Adults with 'Minimal Change' Glomerular Lesions

We describe 49 patients who developed a nephrotic syndrome afterthe age of 15 years, and who showed a ‘minimal change’pattern in their renal biopsies. Patients with sclerosing lesionsaffecting only part of the glomerulus were excluded, but 39biopsies showed some minor changes. Glomerulosclerosis affectingwhole glomeruli was present in 21 biopsies, and related stronglyto increasing age. Focal tubular atrophy and vascular changeswere also common but less related to age. Mesangial matrix increasewas not age-related, and presumably is a component of the glomerulardisease. At onset, these patients showed features differing from thosefound in nephrotic children with similar histology: the sexincidence of the adults was equal, non-selective differentialprotein clearances (51 per cent) hypertension (31 per cent)and diminished renal function (70 per cent) were all more common.No clinical tests distinguished these patients clearly fromother adult nephrotics, and renal biopsy remains essential intheir management. The subsequent behaviour of the adult patientshowever, resembled that of the childhood group very closely.Forty four patients were treated with prednisolone for at leasteight weeks, and 82 per cent responded with early loss of proteinuria.Of the 36 responding patients, 70 per cent later relapsed, 63per cent repeatedly. Five corticosteroid-resistant, and 12 corticosteroidintolerantpatients were treated with cyclophosphamide: one died aftera pulmonary embolus, but 14 lost their proteinuria and 11 remainin remission. Follow-up data were available for all 49 patients for up to19 years (mean 4.1 years). Nine patients were dead, only onein uraemia but three from probable complications of treatment.Ten still relapse and require corticosteroid treatment, butonly one now has persistent symptomless proteinuria. Twenty-nineare well, off all treatment.