Lupus nephritis. Part I. Histopathological classification, activity and chronicity scores.
ABSTRACT Renal biopsy has made a major contribution to the understanding and management of patients with lupus nephritis. In a 5-year retrospective study the renal morphology of 55 biopsies from 51 patients with lupus nephritis was classified according to World Health Organisation criteria. In addition, semi-quantitative activity and chronicity scores were documented. The findings were similar to series from other parts of the world. Of the biopsies reviewed, 6 were class II, 13 class III, 32 class IV and 4 class V. In situations of overlap, segmental proliferative features determined the class to which a biopsy specimen was assigned. Twenty-five of the patients, all WHO class IV, showed activity scores in the severe range. Most of the activity score features were common and easily recognised but necrotising angiitis was only seen in 1 patient. Haematoxylin bodies were difficult to document and the nature and value of the haematoxylin body is questioned.
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ABSTRACT: The clinical course of 135 patients with lupus nephritis was examined long-term as part of a prospective study. Biopsies were classified according to modified WHO criteria and showed 17 per cent of patients had mild mesangial lesions, 10 per cent focal lesions, 21 per cent mild diffuse proliferative lesions, 37 per cent severe diffuse proliferative lesions and 15 per cent membranous lesions. Overall patient survival of 83 and 65 per cent at five and 10 years respectively from onset of nephritis was similar to other recently published series. In contrast to the latter, the severe proliferative group had a significantly worse outcome than the other proliferative groups (p less than 0.01) and only patients in this group progressed to end-stage renal failure. Haematuria was more common (p less than 0.05) in the severe group and there was a striking correlation between histologic activity assessed semiquantitatively (Table 1) and urinary red cell count (p less than 0.001). There was no correlation between serum creatinine, proteinuria or chronic lesions with urinary red cell count. In contrast to a previous study there was no correlation between the presence of hyaline thrombi on initial biopsy and subsequent development of glomerular sclerosis. Although the value of renal biopsy has been questioned, we suggest that it remains a most important investigation in the management of lupus nephritis. Determination of urinary red cell count provides a most useful monitor of disease activity and response to treatment.The Quarterly journal of medicine 03/1987; 62(238):163-79.
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ABSTRACT: Systemic lupus erythematosus (SLE) was diagnosed in 31 black Zimbabweans over a six year period. Renal involvement (71%) was more common and photosensitivity (16%) and serositis (23%) less common than in the United States. Lymphopenia (48%) was the commonest haematological abnormality. Unusual complications included subarachnoid haemorrhage, cardiac rhythm disturbance, portal and superior mesenteric vein thrombosis, and a non-Hodgkin lymphoma. Tuberculosis was a common differential diagnosis that was difficult to exclude. Nine patients (29%) died within one year of diagnosis. SLE is being recognised more commonly in Zimbabwe.Annals of the Rheumatic Diseases 09/1986; 45(8):645-8. · 9.11 Impact Factor
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ABSTRACT: The 1971 preliminary criteria for the classification of systemic lupus erythematosus (SLE) were revised and updated to incorporate new immunologic knowledge and improve disease classification. The 1982 revised criteria include fluorescence antinuclear antibody and antibody to native DNA and Sm antigen. Some criteria involving the same organ systems were aggregated into single criteria. Raynaud's phenomenon and alopecia were not included in the 1982 revised criteria because of low sensitivity and specificity. The new criteria were 96% sensitive and 96% specific when tested with SLE and control patient data gathered from 18 participating clinics. When compared with the 1971 criteria, the 1982 revised criteria showed gains in sensitivity and specificity.Arthritis & Rheumatism 12/1982; 25(11):1271-7. · 7.48 Impact Factor
256SAMJVOL 792 MAR 1991
Part I. Histopathological classification, activity and c h r ~ n i c i t y scores
W. D. BATES,A.-M. HALLAND, R. D. TRIBE,D. J. ROSSOUW
Renal biopsy has made a major contribution to the under-
standing and management of patients with lupus nephritis. In
a 5-year retrospective study the renal morphology of 55
biopsies from 51 patients with lupus nephritis was classified
according to World Health Organisation criteria. In addition,
semi-quantitative activity and chronicity scores were docu-
mented. The findings were similar to series from other parts
of the world. Of the biopsies reviewed, 6 were class 11, 13
class Ill, 32 class IV and 4 class V. In situations of overlap,
segmental proliferative features determined the class to which
a biopsy specimen was assigned. Twenty-five of the patients,
all WHO class IV, showed activity scores in the severe range.
Most of the activity score features were common and easily
recognised but necrotising angiitis was only seen in 1 patient.
Haematoxylin bodies were difficult to document and the
nature and value of the haematoxylin body is questioned.
S Air Med J 1991; 79: 256-259.
A recent large Australian series! on lupus nephritis emphasises
the value ofrenal biopsy together with urinalysis as an accurate
guide to activity and progression of disease and as the major·
guide to treatment. In view of this and as there has been little
detailed_ documentation of lupus nephritis in southern
Africa,2-' a retrospective study of lupus nephritis at Tygerberg
Hospital was undertaken using recent developments in the
histological classification as well as the quantification ofactivity
and chronicity indices. The aim was to determine whether the
histological features of lupus nephritis in our centre were
comparable to other studies, to provide an accepted basis for
clinicopathological correlation and comparison, and to add our
experience of lupus nephritis to the growing number of pub-
lications on this important disease in southern Africa.
Patients and methods
The morphological material from 51 patients who underwent
renal biopsies for clinically significant lupus nephritis from
1983 to 1987 was reviewed. All biopsies were assigned to
World Health Organisation classes, and activity and chronicity
scores were determined. In 1 patient only, autopsy tissue was
examined, since fulminant disease precluded a biopsy during
life. Four patients underwent two biopsies each,. providing a
total of 55 specimens. Patients were classified according to
their latest biopsy. All patients fulfilled the 1982 American
Departments ofAnatomical Pathology and Internal Medi-
cine, University of Stellenbosch and Tygerberg Hospital,
W. D. BATES, M.MED.(A."IAT.PATH.)
A.-M. HALLAND, M. MED. (INT.), F.C.P. (S.A.)
R. D. TRIBE, F.c.P.(S.A.)
D. J. ROSSQUW, M. MED. (ANAT. PATH.), PH.D.
Accepted 17 July 1990.
Rheumatism Association (ARA) criteria for systemic lupus
erythematosus (SLE/ -47 were women (39 coloured,S
white, 3 black) and 4 were men (2 coloured, 2 white).
Renal biopsy material for light and electron microscopy was
initially fIxed in 2,5% glutaraldehyde in O,IM phosphate buffer
and then halved under a dissecting microscope. Serial 2-3 }.Lm
sections were stained with haematoxylin and eosin, Alciari
blue, periodic acid-Schiff, periodic acid-methenamine silver,
Masson trichrome and Verhoeff-Van Gieson stains. Electron
microscopy (EM) specimens were post-fIxed in osmium
tetroxide embedded in Spurr's resin. Sections were stained
with uranyl acetate and lead nitrate. Material for immuno-
fluorescence was received on saline and then frozen. Cryostat
sections were cut and labelled for IgA, IgG, IgM, C3 and
The WHO classification7was used: class I -
light microscopic level; class II -
proliferative; class IV - diffuse proliferative; and class V -
membranous glomerulonephritis. All segmental lesions were
classified as focal or diffuse proliferative. Some ofthese classes
are illustrated in Fig. 1. Severity of disease does not correlate
entirely with increasing class, since I, II and V are the milder
forms of disease. Classes III and IV are the more severe forms
with at least segmental proliferation in less than or more than
80% of glomeruli, respectively. Biopsies were then scored
semi-quantitatively using a table as proposed by Morel-
Maroger et al. 8 and modified by Leaker et al.! Ten morpho-
logical changes constitute the activity score: endocapillary
proliferation; nuclear debris; wire loops; hyaline thrombi; inter-
stitial inflammation; tubular epithelial lesions; fIbrinoid
necrosis; epithelial crescents; haematoxylin (haematoxyphil)
bodies; and necrotising angiitis. Several of these features are
illustrated in Fig. 2. The histological features were scored on a
scale of 0 - 3 denoting the absence or mild, moderate or
prominent presence, respectively, of the particular feature.
The scores of the last four features on the activity index are
doubled to weight them as they are believed to be more
significant markers of activity.8The maximum total score is
42. Class IV lesions were then divided into class IV(a), where
the activity score was 8 or less, while scores of 9 or more were
placed in class IV(b).!
The two features in the chronicity score are glomerular
sclerosis and interstitial sclerosis. The demarcation lines
between mild, moderate and severe glomerular sclerosis are
30% and 80% involvement. The chronicity score is therefore
out of a maximum of6.
mesangial; class III -focal
Fig. 3 shows the age, race and sex of the patients. The well-
documented dominance offemale patients below the age of40
years is seen, as well as the prominence of coloured patients in
all decades. The rate of biopsied lupus nephritis per 1000
patients admitted to the medical wards during the study
period was calculated for males and females of each racial
group. The rates for the females were as follows: coloured 1,4;
black 0,85; white 0,33. The WHO classes ofthe latest biopsies
in each ofthe 51 patients were as follows: class I - 0; class II
SAMJ VOL 792 MAR 1991
Fig. 1. WHO classification of lupus nephritis -
mesangial; whole glomerulus (above) shows enlarged mesangial areas with normal peripheral capillary lumina. Ultrastructure
(below) shows Bowman's capsule (top left) with peripheral capillaries (below). The mesangium is prominent with increased
cellularity. Deposits present in the mesangium are not easily seen. Centre: class IV -
(above) appears irregular with thick wire-loop-type capillary wall lesions especially in lower left- quadrant Capillary lumina
show narrowing and obliteration. Ultrastructure (below) shows large deposits especially subendothelially but also mesangial,
subepithelial and in capillary lumina. Right: class V -membranous; the glomerulus (above) is relatively symmetrical with
patent capillary lumina and thickened capillary walls. Ultrastructure (below) shows the dark subepithelial deposits alternating
with lighter basement membrane-like material ('spikes'), which in places incorporates the deposits.
light and electron microscopic features of some of the classes. Left: class 11 -
diffuse proliferative; the glomerulus
class V -
the disease (class IV) and within that class most showed high
activity scores> 8 (class IV(b)). Table I compares the relative
frequency of WHO classes from series from all five continents
over a 20-year period. The incidence of class IV is remarkably
constant, being also the commonest class in all 5 series.
Activity and chronicity scores in the various WHO "classes are
shown in Fig. 4. Classes 11 and V tended to show low activity
scores with class III a linle higher. Class IV was characterised
by prominent activity scores with the majority being above 8,
making class IV(b) the largest single group. The pattern of
chronicity scores was less clear, with classes Ill, IV(a) and
IV(b) tending to show similar ranges of figures. Immuno-
fluorescence positivity in glomeruli was as follows: IgA -
24/40 (60%); IgG -33/40 (82,5%); IgM -
-28/39 (72%); and fibrinogen -
Four patients underwent second renal biopsies. The histo-
logical pattern had changed from class V to class IV(b) in 2
and from III to IV(a) in 1. The fourth patient changed from
class Il to class Ill. Activity and chronicity scores increased
markedly in all 4 patients.
5; class III - 12; class IV(a) -
2. The majority of patients had the severest form of
7; class IV(b) -25; and
22/36 (61%); C3
The WHO classification scheme for lupus nephritis' is at
present accepted world-wide and provides a standard that
enables comparison to be made between clinical studies. Since
1973 at least four series of southern African patients with SLE
TABLE I. RELATIVE FREQUENCIES OF WHO CLASSES IN
WHO classes (%)
Baldwin et al.9(1970)
Sinniah and Feng10(1976)
Cameran et al.11(1979)
Leaker et al.1(1987)
This study (RSA)
have been documented.2-5 All included patients with lupus
nephritis, but while the series from Natal' gave a detailed list
of renal histological changes in its patients, the others gave
little renal morphological data. Moreover, none of these studies
has provided a detailed correlation of both clinical and histo-
logical manifestations using the WHO classification. The rela-
tive frequencies of the different histological classes demon-
strated in our studr. is comparable with that from other
continents (Table I), ,9-11 with 50-60% of biopsies demonstra-
ting class IV disease on histologiCal examination. The variations
may be due in part to varied biopsy criteria, since some groups
SAMJVOL 792 MAR 1991
Fig. 2. Composite microphotograph to illustrate some morphological features used in the activity score. Top left: cellular
proliferation in the glomerulus surrounded by a cellular crescent. Bottom left: a silver stain outlines a disrupted Bowman's
capsule and the glomerular tuft with a crescent between them. Prominent interstitial inflammatory infiltrate is present in the left
upper area. Top right: hyaline thrombi in capillary lumina and thickened capillary walls are prominent in this proliferative
glomerulus. Bottom right: necrotising angiitis with fibrinoid necrosis in a vessel in the renal interstitium.
Fig. 3. Histogram to illustrate the spectrum of age, race and sex
in the patient population,
AGE BY DECADE
biopsy only patients with clinical evidence of renal disease and
others all patients with SLE. The greater range in the mem-
branous pattern (class V) may reflect different approaches to
mixed and pure forms ofdisease.
SLE, and more specifically lupus nephritis, have been found
to be more common in France, the UK and the USA in
Fig. 4. Distribution of activity and chronicity scores in histological
patients other than whites,II-13 but the situation in South
Africa is still not clear. Our study supports the previolls
fmdings from this region2that the disease is disproportionately
common in the coloured hospital patient.
As pointed out by many authors,14 the morphological classifi-
cation is arbitrary and overlapping forms are seen. The WHO
classification presents various options for dealing with cases
showing features of two categories (combinations of prolifera-
tive and membranous lesions being the most common overlap
siruation).ls Banfi er aI.IScreated class VI in which to place
combinations of class V and class III or IV. In our study we
followed an option used by, among others, Leaker er ai.I In
this approach all biopsies containing segmental lesions are
classified in either the focal or diffuse proliferative group. The
small number of class V biopsies in our study may be partly
explained by this approach. Furthermore, 2 patients with class
V disease at the outset transformed to class IV at re-biopsy
and are classified under the latter class.
oThe semi-quantitative scoring system is a helpful adjunct to
the WHO classification and is relatively reliable and repro-
ducible. This type ofsystem was originally described by Pirani
er al. 16 but the system used in this study was according to the
method of Morel-Maroger er ai.8as used by Leaker er al.l
These methods have shown a poor prognosis f o r o ~ a t i e n t s with
high activity scores or advanced chronic disease. I, It has been
shown that active treatment brings about rapid resolution of
active lesions but that chronic lesions progress despite
therapy.I,8 Patients with inactive or chronic lesions may thus
be spared unnecessary immunosuppressive treatment -
important consideration, since sepsis remains a major cause of
As McCluskeyl4 notes, the list ofglomerular changes seen in
lupus nephritis is virtually a catalogue of glomerular abnor-
malities. The activity score includes features noted to be
indicative of active glomerular damage, and some of these
factors are probably interrelated.17
The haematoxylin body was the only activity score feature
that provided major difficulties, since we could not confirm its
presence or absence with any confidence. The major review of
lupus nephritis morphology by McCluskeyl4 in 1970 indicated
that these bodies were so uncommon, at least in a form suffi-
ciently recognisable even to seasoned observers, as to be of
little value. Our experience concurs with this assessment. It
appears unlikely that a morphological feature can survive and
remain useful u n I e s ~ it is easily recognised on routine stains or
has distinctive histochemical, immunological or ultrastructural
features, none of which is shown by the haematoxylin body.
The widely used scoring system of the National Institutes of
Health, Bethesda, Maryland USA,18 does not have a category
for haematoxylin bodies and thereby avoids these uncertainties.
ecrotising angiitis is rare in our experience (only shown in
the autopsy case), and difficulties with haematoxylin bodies
have already been discussed. The remaining 8 features in the
activity table were relatively common, especially in class IV.
It is not easy to compare activity and chronicity scores
between series, since slightly different systems have been used,
SAMJVOL 792 MAR 1991
but comparing with Banfi er ai.,IS the extent of activity and
chronicity changes in our patients appears similar. For example,
our worst group on histological examination did not show
more advanced features than their series. Our immunofluo-
r e s c e ~ figures are similar to other serieslo-I2,IS and confirm the
frequent presence ofespecially IgG and C3 in the deposits.
Since this study was undertaken, re-biopsy is being more
frequently employed in our institution and it seems likely that
the documented incidence of transformations will increase.
Transformations were noted in the re-biopsies of4 patients.
We thank the medical illustration unit ofthe Bureau for Medical
and Dental Education of the University of Stellenbosch and
Tygerberg Hospital for help with figures and the Diagnostic
Electron Microscopy Laboratory for assistance with photographs.
We also thank Mrs L. L. Eygelaar for typing the manuscript:
W.D.B. is in receipt of a short-term South African Medical
Research Council grant.
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