Download SCHONLEIN-HENOCH PURPURA IN THE ADULT A Study of 77

461
SCHONLEIN-HENOCH PURPURA IN THE ADULT
A Study of 77 adults with Anaphylactoid or Schonlein-Henoch Purpura1
B Y J. J. CREAM,2 J. M. GUMPEL,3 AND R. D. G. PEACHEY4
(From St. Thomas' Hospital, and St. John's Hospital for Diseases
of the Skin, London)
With Plates 36 to 38
1
a
Received February 27, 1970.
Dr. J. J. Cream is now at St. John's Hospital for Diseases of the Skin, Homerton
Grove,
London.
8
Dr. J. M. Gumpel is now at the Department of Medicine, Royal Postgraduate Medical
School,
Ducane Road, London.
4
Dr. R. D. G. Peachey is now at St. John's Hospital for Diseases of the Skin, Lisle
Street, London.
Quarterly Journal of Medicine, New Series, XXXIX, No. 156, October 1970.
n
u
Downloaded from by guest on September 12, 2016
Introduction
ANAPHYiiACTOiD or Schonlein-Henoch purpura are the names generally applied
to a syndrome which may include a characteristic and usually purpuric rash,
oedema, arthritis, gastrointestinal manifestations, and nephritis. The underlying pathological process is a vasculitis affecting small vessels, which may be
mild or severe: the clinical picture depends on the site, the extent, and the
severity of the vessel involvement.
Schonlein in 1837 originally used the term 'peliosis rheumatica' for the combination of joint pains with the typical rash and noted that the internal organs,
the heart and great vessels, may also be affected. Henoch (1874) reported four
children with the rash, colic, bloody diarrhoea, and painful joints, and later
(1899) emphasized the frequent association of nephritis. Osier (1914) suggested
that anaphylactic phenomena might play a part in the aetiology of some cases
and the term 'anaphylactoid purpura' was first used by Frank (1915) and by
Glanzmann (1916). Gairdner in 1948 reviewed the clinical features of 12 patients
and noted that 10 of them as well as the majority of patients in the literature
were under 15 years of age. There have since been further descriptions of
the disease and its various features in several large series of children, with
special regard to the renal complications as these are potentially the most lifethreatening (Philpott, 1952; Oliver and Barnett, 1955; Wedgwood and Klaus,
1955; Burke, Mills, and Stickler, 1960; Sterky andThilen, 1960; Allen, Diamond,
and Howell, 1960; Roberts, Slater, and Laski, 1962).
In contrast to the extensive literature concerning paediatric cases there is
little information about adults and the classification of the disease in adults
and its terminology is very confused. Renal complications in adults are thought
462
J. J. CREAM, J. M. GUMPEL, AND R. D. G. PEACHEY
Patients and Methods
The patients who form the basis for this study were found mainly by searching
under the headings 'purpura' and 'allergic vasculitis' in the diagnostic indexes of
St. Thomas' Hospital (in-patients only) and of St. John's Hospital for Diseases
of the Skin (in and out-patients) over the period 1956 to 1968. Our criteria for
admission to the study were that patients were over 15 years old, that there
had been crops of purpura, and that the platelet count had been normal. We
Downloaded from by guest on September 12, 2016
to have a more serious prognosis, but this view is based largely on isolated
case reports.
Ruiter in a series of papers (1948, 1952, 1956, and 1964) described a group of
mainly adult patients with 'arteriolitis allergica cutis' who had intermittent
purpuric, macular, and papular rashes which persisted for variable periods of
time. In a number of cases there were joint swellings and abdominal symptoms,
and in one patient transient haematuria.
Gougerot and Blum (1950) and Gougerot and Duperrat (1954) reported a
somewhat similar group of patients under the title of 'Nodular dermal allergide'.
They described a 'trisymptome' complex with small round nodules 2 to 7 mm in
diameter, purpuric macules, and erythematopapular elements as well as 'tetrasymptome' and 'pentasymptome' complexes which had, in addition, bullae and
ulcers. The rash in these patients had a predilection for the legs and occurred in
crops lasting 15 to 60 days. Attacks in some cases recurred for many years, and
fever, arthralgia, fatigue, and headache were sometimes associated. Histological
examination showed endothelial swelling in skin capillaries and arterioles with
fibrinoid necrosis and a predominantly polymorph infiltrate. Leucocytoclasis
was often present.
In 1964 Winkelmann and Ditto reviewed the various forms of cutaneous and
systemic necrotizing vasculitis and reported 38 cases of 'allergic vasculitis'
selected because of histological evidence of leucocytoclastic angiitis. The rash
was similar to that described by Ruiter (1964) and to the description given by
Gougerot and Duperrat (1954) and in 13 per cent of cases was the sole manifestation of disease. In the others there was evidence of systemic involvement
such as joint pain, urinary abnormalities, gastrointestinal manifestations, and
occasional involvement of the lungs, heart, eyes, and nervous system. A further
group of patients selected on a similar basis was described by Wilkinson (1965),
and Ramsay and Fry (1969) reported 21 patients with a clinical diagnosis of
'allergic vasculitis'.
The common features of the various groups suggest that these are not in fact
separate disease entities but that the groupings have been arbitrarily selected
from a spectrum of disease. The histological features of the skin lesions within a
single case may vary greatly depending on the site of the biopsy and the age of
the lesion, and are not specific for any clinically definable group of patients.
In order to ascertain more clearly the clinical features and prognosis of this
condition in adults, we have studied a group of 77 adult patients with crops of
purpura and a normal platelet count.
SCHONLEIN-HENOCH PURPURA IN THE ADULT
463
excluded patients in whom the purpura appeared to be secondary to other
conditions such as malignant disease, other connective tissue disorders, venous
stasis, steroid therapy, scurvy, and capillaritis of the carbromal or Schamberg
type. Three patients were included in whom the platelet count was not recorded:
two of them had histological confirmation of vasculitis, and the third had
arthritis, gastrointestinal and renal manifestations, as well as purpura.
I
) Female
12
10
8
M
6
4
2
0
25
35
45
55
65
>65
Age in years
Fio. 1 shows the age of onset and sex ratio of 77 patients by decade.
A detailed follow-up history and examination was obtained on 34 patients,
who were either still attending the hospitals, or who had responded to a postal
request. The mean duration from onset of disease to follow-up in these 34
patients was 5-3 years. The investigations included: blood-pressure, urine
analysis, full blood count, erythrocyte sedimentation rate (Westergren), plasma
urea and creatinine clearance. Serological studies included a Rose-Waaler and
slide latex test, immunoglobulin estimations by the Mancini technique (Dr. G. L.
Scott), and immunofluorescent antinuclear antibodies (Dr. E. J. Holborow).
Follow-up information was obtained from the case notes of the remainder.
Illustrative case histories are given for seven patients in an appendix.
Results
Patients
During the 12-year period 28 patients seen at St. John's Hospital and 49 at
St. Thomas' Hospital fulfilled the criteria. The sex distribution was equal, 39
males and 38 females, both over-all and from each hospital (Fig. 1). The mean
Downloaded from by guest on September 12, 2016
"8
464
J. J. CREAM, J. M. GUMPEL, AND R. D. G. PEACHEY
age of onset for men was 43-7 years, and for women 43-3 years. There were
more men than women affected between 16 and 25 years of age, but thereafter
there was little difference in the sex distribution. Fig. 2 shows the monthly
onset of cases throughout the year.
12 -
1
•3
a
a,
2 3 4
5
6 7 8 9
10 11 12
Month
F I G . 2 shows the month of onset of Schonlein-Henoch
purpura.
Antecedent events
Possible aetiological factors were detected in 37 patients. Medications, frequently proprietary mixtures, were the commonest; 29 different preparations
had been taken by 32 patients in the three weeks before the first manifestation.
Usually, there was insufficient evidence to prove a causal relationship, but one
patient developed purpura after taking cyclopenthiazide and again six months
later after bendrofluazide. In some cases the medications may well have been
taken for prodromal symptoms.
A cold, sore throat, or 'flu-like' illness preceded the onset of the purpura in 22
patients, and at least 17 of these had taken a medication of some sort. Haemophilus parainfluenzae and pneumococcus were each cultured from the throat of
one patient, and E. coli isolated from the urine of two others.
Evidence for streptococcal infections
Evidence of streptococcal infection was shown by isolation and culture of
/3-haemolytic streptococci in three patients and by a raised anti-streptolysin
'O' (ASO) titre in a further 14. Negative throat cultures were obtained in
28 patients but are of doubtful significance, as many had received a prior course
Downloaded from by guest on September 12, 2016
1
SCHONLEIN-HENOCH PURPURA IN THE ADULT
465
of antibiotics. In 14 patients the ASO titre was normal, as it was in two of the
three patients from whom streptococci had been isolated. A comparison between
those with and without evidence of streptococcal infection showed little difference in the systems involved. The 17 patients with evidence of streptococcal
infection were on average younger, mean age 37-7 years as against 47*4 years,
but not significantly so (« = 1-65, 0-2 > P > 0-1) and 10 of them had had upper
respiratory or 'flu-like' symptoms, compared with only two of the 14 with negative ASO titres.
TABLE
Area,
Number
Lower leg
Thighs
Buttocks
Lower trunk
Upper trunk
Arms
Hands
Face
Palate
74
52
21
11
1
32
5
3
1
II. Forms of skin lesions in 77 patients
Form
Purpura
Papular lesions
Confluent areas of erythema and purpura
Confluent areas of purpura
Nodules
Blisters
Ulceration and necrosis
Livedo reticularis
Pustules
Number
involved
77
48
8
7
2
12
12
2
2
Cutaneous manifestations
All the patients had purpura, which was usually painless but there was an
occasional complaint of itching or stinging. The extent and number of the spots
varied from scanty purpura confined to the legs to a widespread and profuse
eruption over the limbs and trunk. The distribution of the rash is shown in
Table I. Purpura was commonly seen within erythematous macules or slightly
raised lesions but not infrequently appeared as the sole manifestation of the
skin involvement. In some cases a number of erythematous macules and
papules were present in which no purpura could be detected. Other forms
of the skin lesions are listed in Table II. It was common to find several
morphological forms present at the same time. Blisters, sometimes haemorrhagic, occurred in 12 patients and ulceration, which was usually painful and
followed by scarring, was noted in 12. Two patients had pustules in purpuric
patches, but no organisms were obtained on culture. Livedo reticularis was
present in two patients, one of whom had positive rheumatoid and antinuclear
factor tests (Case 68).
Downloaded from by guest on September 12, 2016
TABLE
I. Distribution of rash
466
J. J. CREAM, J. M. GUMPEL, AND R. D. G. PEACHEY
In many patients the purpura continued to appear for some time (Table III).
In 43 patients the rash had cleared completely within six weeks of the onset, but
in 20, crops of purpura appeared for over one year, and when 11 of these patients
were last seen fresh purpura was still appearing. One man had crops of purpura
over a period of 17 years coinciding with upper respiratory tract infections
(Case 72, report appended). Usually recurrences were not as severe as the
original rash and, with two exceptions, were not accompanied by arthralgia or
abdominal symptoms.
TABLE
III. Toted known duration of rash in 74 patients
Period of time over which rash recurred
Less than six weeks
Less than six months
Less than one year
Longer than one year
TABLE
No. of patients
43
9
2
20
IV. Unusual features in six patients in whom purpura recurred for over
one year
11
67
68
70
74
77
Unusual features
Raynaud's phenomenon and
hyperglobulinaemia
Widespread visceral vasculitis
Rheumatoid and antinuclear factors
present in serum
Elevated serum IgM level
Chronic hepatitis, cryoglobulinaemia
and immune complex nephritis
Late-appearing polyarthritis with
positive L.E. cell test and antinuclear factor.
Recurrences for
11 years
4
7
1
5
12
In the group of 20 patients with recurrent purpura for more than one year,
unusual features later became obvious in six (Table IV). At subsequent laparotomy one patient was found to have an extremely widespread visceral arteritis
(Case 67, report appended). Another was found 12 years later to have a positive
L.E. cell test and antinuclear antibodies, previous searches having been negative
{Case 77, report appended). Chronic hepatitis was demonstrated in one patient
who later developed renal disease {Case 74, report appended). One patient had
Raynaud's phenomenon and marked hypergammaglobulinaemia {Case 11),
while another had positive rheumatoid and immunofluorescent antinuclear
factor tests but without evidence of other disease {Case 68). One patient {Case
70) had a moderately elevated serum IgM level of 500 mg/100 ml (normal range
50-110 mg/100 ml).
Systemic involvement
Other organs, such as the gut, kidneys, joints, and lungs, were affected in
various combinations in 64 patients, and the frequency of such involvement is
Downloaded from by guest on September 12, 2016
Case no.
SCHONLEIN-HENOCH PURPURA IN THE ADULT
467
shown in Table Va. There was no correlation between the severity of the skin
lesions and the incidence or severity of systemic involvement, nor did there
appear to be a characteristic pattern in which the latter developed. The rash
came first in 36 patients, while gastrointestinal involvement was the initial
manifestation in six, and coincided with the rash in a further two. The joints
were involved initially in three, and at the same time as the skin in a further 15.
The kidneys were affected first in one patient, while in another the skin, gut,
joints, and kidneys were affected simultaneously. The clinical patterns of
systemic involvement are shown in Table V6. In all there were 15 patients who
had involvement of skin, gastrointestinal tract, joints, and kidneys, and two of
them also had pulmonary disease.
TABLE
V (O). Frequency of clinical involvement of other organs, besides the skin in
64 patients
TABLE
No. of patients
34
39
43
4
V (b). Clinical patterns of systemic involvement
Clinical patterns
No. of patients
S
13
SG
5
SR
11
SJ
11
8GB
4
SG J
8
SR J
8
SGRJ
13
SG J L
1
SGRJL
2
SGRL
1
Total 77
S = skin G = gut R = renal J = joint L = lung
Joint involvement
Arthralgia or frank arthritis was noted in 43 patients. The joints affected
(Table VI) were usually knees or ankles but other joints including those of the
hands and feet were sometimes involved. Symptoms rarely lasted for more than
a few days and signs of arthritis were transient although the arthritis, albeit
temporary, was occasionally severe.
Downloaded from by guest on September 12, 2016
Systems affected
Gastrointestinal tract
Renal tract
Joints
Lungs
468
J. J. CREAM, J. M. GUMPEL, AM) R. D. G. PEACHEY
Gastrointestinal involvement
Evidence of gastrointestinal involvement was noted in 34 patients (Table
VII). Abdominal pain, present in 26 patients, was usually colicky but occasionally severe and persistent enough to require considerable quantities of morphia
for relief. In six cases episodes of pain recurred several times during a period of
hospitalization, sometimes with intervals of several weeks between bouts.
Three patients vomited blood and nine passed blood per rectum, while in another
11 occult blood loss was detected in the faeces. Diarrhoea, nausea, and vomiting
occasionally led to gross dehydration and uraemia. One patient, with persistent
gastrointestinal irritation, remained intermittently obstructed for several weeks,
and was subjected to laparotomy on two occasions (Case 42, report appended).
Protein loss from the gut was proven, using 131Iodine polyvidone or "Chromium
chloride, in five of the seven patients in whom these investigations were performed, and probably occurred in a considerable number of the patients with
hypoalbuminaemia without significant proteinuria. Coincidental loss of protein
from the gut and kidneys in the same patient was difficult to prove unless
frequent measurements of both were performed.
TABLE
VI. Joints involved in 43 patients
29
26
12
10
6
2
3
ms of gastrointestinal invtilveme
Abdominal pain
Frank blood loss
Minor blood loss
Diarrhoea
Nausea with vomiting
Constipation
26
12
11
12
10
3
Oedema
Oedema was present at some time during the course of the illness in 44
patients. Most commonly it was present on the legs and ankles and coincided
in time with the development of the skin rash but was not necessarily at the
same site. In one patient swelling of the genital region occurred in association
with a profuse rash on the legs, thighs, and buttocks. In most of these patients
there were other possible causes for the swelling, such as hypoalbuminaemia,
renal disease, cardiac failure, venous thrombosis, or arthritis, but in eight the
only possible explanation for the oedema seemed to be that it was due to the
Downloaded from by guest on September 12, 2016
Knee(s)
Ankle(s)
Wrist(s)
Elbow(s)
Metacarpo-phalangeal and
interphalangeal of hands
Metatarso-phalangeal and
interphalangeal of feet
Shoulder(s)
SCHONLEIN-HENOCH PURPURA IN THE ADULT
469
cutaneous vascuhtis and, in all probability, this was responsible in many of the
others. In one patient vasculitis was found on biopsy of an oedematous, but not
purpuric, area of skin on the leg.
Renal involvement
Abnormalities in the urine were noted in 38 of the 75 patients in whom this
examination had been recorded. Renal involvement could be divided into three
main types: abnormalities of the urine only, acute nephritis, and slowly progressive renal failure without an initial acute nephritic syndrome (Table VIII).
In addition there was one patient in whom tubular dysfunction was the only
evidence of renal disease and she was found at laparotomy to have a widespread
arteritis involving muscle, liver, gall bladder, and kidney.
TABLE
VIII. Renal involvement in anaphylactoid purpura
Mean age
19
Male/
female
14-5
16
a-8
52 years
3
1-2
43 years
1
0-1
No.
47 years
Patients with abnormalities of the urine only
In 16 patients urinary abnormalities were found, without impairment of
renal function or an obvious acute nephritic episode. Microscopic haematuria
was present in all of these cases; in addition eight had albumin and eight had
casts in the urine. The abnormalities persisted for less than a month in all but
one patient, in whom they cleared after two months. Eight patients had been
seen after a period of six months or more: none had had any recurrence of
urinary abnormality and five were well at review two to six years later.
Acute nephritis
Episodes of acute nephritis with fluid retention were observed in 19 patients.
In most of these the acute nephritic episode occurred within a few days of the
onset of purpura but in eight who initially had normal urine, the renal disease
appeared much later; between three and six weeks later in five, up to three
months later in two, and five years later in one (Case 74, report appended).
Acute hypertension with left ventricular failure developed in eight of the 19
patients in this group and in three of these it followed an episode of oliguria
while the patient was in hospital. The blood-pressure returned to normal with
resolution of the nephritis in all but one patient, in whom progressive cardiac
Downloaded from by guest on September 12, 2016
Acute nephritis
Abnormalities of
urinary sediment only
Slowly progressive
renal failure
Widespread arteritis
with renal tubular
acidosis
470
J. J. CREAM, J. M. GUMPEL, AND R. D. G. PEACHEY
Progressive renal failure
Three patients, who initially had urinary abnormalities only, subsequently
developed slowly progressive renal disease. One, a boy of 17 years, passed
through a nephrotic stage into chronic renal failure and died two and a half
years later. Serial renal biopsies showed progressive focal proliferative disease.
Two women, both aged 55 years, initially had minima,! evidence of renal
disease, but within six months had shown an increasingly abnormal sediment,
Downloaded from by guest on September 12, 2016
and renal failure persisted until his death five years later {Case 37). In most
patients oliguria lasted only a few days but one patient died of anuric renal
failure 10 days after the onset of purpura despite peritoneal dialysis and massive
doses of prednisone. Almost all of the patients in this group had heavy proteinuria. Haematuria was usually microscopic but was gross in three cases and
produced 'smoky' urine in six. Casts, usually granular, were frequently seen.
Hypoproteinaemia was a marked feature in eight patients, but a number
of these also had gastrointestinal symptoms, and may have had protein-losing
enteropathy. Six patients with both gastrointestinal and renal involvement had
elevated blood-urea levels and it was difficult to be certain whether the deterioration in renal function was due solely to renal involvement, or to fluid loss from
the alimentary tract. In five patients a urinary protein loss of five or more
grammes per day was recorded as an early complication of their acute nephritis.
In four of these the blood-urea levels were raised to between 60 and 85 mg/100
ml. The nephrotic phase lasted one month in two, six weeks in two, and six
months in the fifth. This last patient received large amounts of azathioprine
and prednisone (Case 57, report appended).
The subsequent renal status of this group of patients, excluding the two
patients who died, is shown in Table IX. Within six months of the episode of
acute nephritis 13 patients (68 per cent) were normotensive, had a normal
blood-urea and had no abnormality on urine examination (Table IXa). Eight of
these patients were available for subsequent review: Two had developed
malignant hypertension, which was subsequently well controlled by hypotensive
drugs, while six were well. However, one was found to have a blood-pressure of
170/90 mmHg, and three had elevated blood-urea levels. Of the other five
patients we have little information but proteinuria had been subsequently
recorded in two.
In four patients (Table 1X6) the urinary abnormalities persisted for longer
than six months. In one who had had persistent microscopic haematuria and
proteinuria for a year, the blood urea was found to be 45 mg/100 ml, the creatinine clearance was reduced and the blood-pressure was 160/90 mmHg at review
five years later. Of the two patients with persistent urinary abnormalities for 18
months, one four years later was found to have heavy proteinuria and numerous
red cells in the urine but was otherwise well and the other, 10 years later, was
asymptomatic and had normal investigations. At the time of writing one patient
still has evidence of persistent active renal disease 18 months from the onset of
nephritis, despite treatment with both prednisone and azathioprine.
SCHONLEEN-HENOCH PURPURA IN THE ADULT
471
with casts and red cells, and in addition developed proteinuria of up to 3 g/24
hours. Renal biopsies showed nephrosclerosis in one and tubular atrophy in the
other. One year later both had reduced creatinine clearances but no other
abnormalities.
TABLE
IX. Subsequent course of 19 patients with acute nephritis
Condition at review
(a) Thirteen patients in whom the urinary abnormalities had disappeared within
six months.
Urinary
No. of
abnormal- patients
ities
lasted
Less than
6 months
Years
after
onset
B.P.
Urea
Creatinine
(mg/100 ml) clearance
(ml/min)
7
7
140/90*
140/75*
130/70
130/80
140/70
170/90
46
65
30
31
55
24
65
46
6t
5
4
l-5f
0-8
0-8
130/70
Little further information
Comment
82
Clear
Well
77
118
48
Clear
. Clear
Clear
Clear
Well
Well
..
54
Albumin
WeU
WeU
WeU
WeU
(6) Four patients in whom urinary abnormalities werestill present at six months
lyr.
l
5
160/90
45
45
Hyrs.
2
10t
4t
130/90
120/70
40
28
86
156
ljyrs.
1
Persistent activity still 1J yrs. after onset of renal disease
Clear
WeU
Clear
WeU
Protein
WeU
(2-5g/24 hrs.)
and red cells
* Treated malignant hypertension.
t Developed nephrotic syndrome during active phase.
Respiratory-tract involvement
Symptomatic evidence of respiratory disease was present in four patients.
One had persistent haemoptysis for several weeks before the onset of purpura,
but no abnormality was found on radiography or bronchoscopy. Three patients
some weeks after onset but whilst still acutely ill developed recurrent pleuritic
pain, initially unilateral but becoming bilateral, and this recurred over several
weeks. Pleural friction rubs were present, and there was clinical and radiological evidence of pleural effusion and underlying pulmonary consolidation, all
of which tended to improve and recur. The radiological sequence in Patient no.
57 is shown in Plates 36 to 38, Figs. 3 to 7. Haemoptysis occurred in two of the
three. The pulmonary lesions were extremely puzzling at the time, simulating
pneumonia or pulmonary emboli, and indeed one patient was put on anticoagulant treatment, but this resulted in an increase of haematuria. The other
Downloaded from by guest on September 12, 2016
5
Urine
472
J. J. CREAM, J. M. GUMPEL, AND R. D. G. PEACHEY
two were at the time on large doses of prednisone (40 mg/day or more). A fifth
patient, who has had recurrent crops of purpura for three years, has recently
begun to have haemoptysis coincident with attacks of purpura and on laryngoscopy was seen to have haemorrhagic lesions in the larynx.
Other investigations
During the acute stage the erythrocyte sedimentation rate (ESR Westergren)
was 20 mm/hr or less in 32 patients, elevated above 20 mm/hr in 35 patients, and
above 100 mm/hr in four patients. Two of the four patients with grossly elevated sedimentation rates are described in attached case reports (Cases 42 and 67),
a third was still having recurrent purpura two years later, while the fourth was
well with a normal ESR seven years later.
Serum protein abnormalities, other than hypoalbuminaemia, were found in 16
out of 45 patients: increased alpha2 globulins were found in eight, and increased
gamma globulins in nine.
TABLE
X. Details of positive Rose-Waaler and latex slide tests in seven patients
Interval of test from onset of purpura
11
68
72
74
69
70
63
6 yrs. 512,1
H yrs. 4
13 yrs. 64
4 yrs. 512
6 yrs. 64
1 yr. < 4
iyr-
<4
++
—
++
+
++
+
7 yrs. 1024+ +
H yrs. 206 + +
14 yrs. 16 —
9 yrs. 64 2 yrs. 64 -
10 yrs. <4
ih y^. <4 + +
1
Result of Rose-Waaler test, expressed as titre.
* Result of Latex slide test, expressed + + , + , or —.
L.E. cell preparations were performed in 27 patients whilst in a phase of
active disease, and were negative in all: L.E. cells were subsequently found in
one patient 12 years later (Case no. 77). Rheumatoid factor tests were positive
in seven patients but without clinical or radiological evidence of rheumatoid
arthritis, and are shown with subsequent tests in Table X. Two patients early
in the course of the disease were noted to have antinuclear antibodies (Cases 68
and 74). Serum immunoglobulin levels were measured in eight patients with
active disease and were normal in seven whilst one had an IgM level of 500 mg/
100 ml. Seventeen patients who were seen at follow-up and whose disease was
no longer active had normal immunoglobulin levels. Antinuclear factors were
not found in 25 patients.
Skin biopsies
The skin biopsies of 25 patients were reviewed by Dr. G. C. Wells, without any
clinical information. All but six of these patients had shown evidence of systemic involvement. Evidence of vasculitis was present in 19, and non-specific
inflammatory changes in six. In 16 the vasculitis was confined to a particular
Downloaded from by guest on September 12, 2016
Patient no.
SCHONLEIN-HENOCH PURPURA IN THE ADULT
473
level in the dermis, while in the others it affected vessels throughout the dermis.
Leucocytoclasis was seen in 18, and fibrinoid necrosis in 13 of these. Both were
present in the nine patients with changes throughout the dermis but there was
no correlation between the depth or extent of vessel involvement, the presence
of fibrinoid necrosis or leucocytoclasis, and the clinical pattern, duration of
disease, or unusual clinical features. One patient had biopsies from three different sites on the same occasion, two of which showed vasculitis at all levels in the
dermis, whilst in the third the vasculitis was confined to the sub-papillary and
mid dermal zones.
Downloaded from by guest on September 12, 2016
Discussion
Although it was expected that the patients referred to St. John's Hospital for
Diseases of the Skin might have had less systemic involvement than those
referred to St. Thomas' Hospital, in fact there was little difference between the
two groups with regard to the frequency of joint, gut, and renal involvement.
The degree of involvement of these was greater in the St. Thomas' patients, and
severe renal involvement was considerably more common at St. Thomas'. The
over-all sex incidence was identical, but in the age groups 16 to 25 years, males
predominated, and this would fit with the male predominance noted in several
large paediatric series (Gairdner, 1948; Philpott, 1952; Wedgwood and Klaus,
1955; Panos, 1957).
Anaphylactoid purpura is rarely attributable to any definite cause. On rare
occasions food allergy has been reported as a precipitant, and the evidence
for this was reviewed by Ackroyd (1953). Drugs such as tetracycline (Calnan
and Lister, 1950), diphenhydramine (Benadryl), and the weed killer 2,4-D
(Winkelmann, 1958) have been considered causative in individual cases, and
Winkelmann and Ditto (1964) commented that in 20 out of 36 cases of allergic
angiitis drugs or chemicals such as aspirin, phenacetin, phenothiazines, penicillin,
sulphonamides, griseofulvin, tetracycline, erythromycin, quinidine, and iodides
were considered as possible aetiological agents. There are, however, very few
reports in which there is unquestionable evidence of an association between
drug and rash, such as recurrence of the rash following re-exposure to the agent.
Evidence which is satisfactory is produced by BjQmberg and Gisslen (1965) for
thiazides, Symmers (1958) for aspirin, and by Oreger and Houseworth (1954) for
quinine. One patient of ours (Case 60) provides further confirmation that thiazides may induce vasculitis. Insect bites and stings have also been reported as
possible aetiological agents (Burke and Jellinek, 1954; Sharan, Anand, and
Sinha, 1966) as have immunizations and vaccinations (De Angelis, 1960; Giordano and Cordone, 1965).
SchSnlein (1837) and Glanzmann (1916, 1920) stressed that an infection often
precedes the disease, and Gairdner (1948) reported the isolation of streptococci
from 11 out of 18 patients. He suggested that infections, particularly streptococcal infections of the respiratory tract, played a dominant aetiological role in
many patients. In a first attack precipitated by a sore throat, he noted that the
time interval between infection and the onset of the rash was from 10 days to
474
J. J. CREAM, J. M. GUMPEL, AND R. D. G. PEACHEY
Downloaded from by guest on September 12, 2016
four weeks, and that in subsequent attacks precipitated by a sore throat, this
interval was often considerably reduced. Lewis (1955) found that the proportion
of patients from whom haemolytic streptococci was isolated was approximately
the same in anaphylactoid purpura (24-3 per cent), acute nephritis (22-1 per
cent), and acute rheumatism (19-3 per cent), whereas in control patients a much
lower rate of isolation (7-3 per cent) was obtained. Bywaters, Isdale, and Kempton (1957) who investigated 64 cases of Sch5nlein-Henoch purpura, mainly
in children, found that the ASO titres were raised in a third, but this was
similar to the prevalence in a control group of children with non-rheumatic
disorders, and half that found in children with rheumatic fever. Group A /?haemolytic streptococci were found in a quarter of patients with anaphylactoid
purpura, and this rate of isolation was intermediate between the rheumatic and
non-rheumatic groups. Vernier, Worthen, Peterson, Colle, and Good (1961)
found a similar prevalence of raised ASO titres in 45 children, and isolated /?haemolytic streptococci in only seven. In the present series the ASO titre was
elevated in half of those in whom the test was performed and /J-haemolytic
streptococci were isolated in only a small number, but many of our patients,
like those of Vernier, Worthen, Peterson, Colle, and Good (1961) had received
prior antibiotic therapy. Streptococcal antigen has been demonstrated in the
glomeruli in post-streptococcal nephritis (Andres, Accinni, Hsu, Zabriskie, and
Seegal, 1966) and in the skin vessels in nodular vasculitis (Parish and Rhodes,
1967), but until streptococcal antigen has been identified in the lesions in
SchOnlein-Henoch syndrome, the role of the streptococcus must remain in doubt.
In the present series of adults the morphology and distribution of the rash
closely resembles that described by Winkelmann and Ditto (1964) and by
Wilkinson (1965) in patients with leucocytoclastic angiitis and by Ramsay and
Fry (1969) in patients with allergic vasculitis. Although the distribution of the
rash in adults is similar to that seen in paediatric cases certain differences are
apparent when the adults in this series are compared with the children described
by Gairdner (1948), Bywaters, Isdale, and Kempton (1957) and Allen, Diamond,
and Howell (1960). In the adults it was common for the purpura to appear
without any preceding lesion or in erythematous macules which were never
raised, whereas in children the lesions usually progressed slowly from pink
maculopapules or urticaria to flat purpuric spots. Blistered, necrotic, or ulcerated lesions, which were present in 16 per cent of the adults, were uncommon in
children and are mentioned as an occasional feature only (Bywaters, Isdale, and
Kempton, 1957; Derham and Rogerson, 1956; Bilaloglu, 1963).
Allen, Diamond, and Howell (1960) noted that symptoms persisted for longer
than a month in only one-third of their children with Schonlein-Henoch purpura.
About 40 per cent of their cases had one or more recurrences—usually of the
rash and of gastrointestinal symptoms. In some cases symptoms may persist
longer and Burke, Mills, and Stickler (1960), reviewing 88 cases of SchonleinHenoch purpura in children followed up by questionnaire, stated that purpura
continued in cases with nephritis on average for 6-8 months and in those without
nephritis for 4-6 months. In the present series of adults the rash had cleared
SCHONLEIN-HENOCH PURPURA IN THE ADULT
475
Downloaded from by guest on September 12, 2016
completely within six weeks in the majority of cases, and we could find no correlation between either the severity, the duration, or the extent of the skin
involvement and the prevalence or severity of systemic involvement. A few
patients in this series had cutaneous disease only, but the skin lesions were in
no way distinguishable clinically or histologically from those in patients with
systemic disease, and systemic features later appeared in several patients whose
disease had been confined for several years to the skin. In 20 patients, crops of
rash continued to appear for a year or more. Recurrence of the rash over long
periods was noted in a few cases by Winkelmann and Ditto (1964) and by
Ramsay and Fry (1969) and seems, therefore, to be a feature of some adult cases.
I t was amongst the 20 cases with chronic recurrent skin disease that we found
six with manifestations that are unusual in Schonlein-Henoch purpura and more
suggestive of other disease, but in only one was a definitive diagnosis made of
systemic lupus erythematosus. Besides these six, there were several in this
group who were thought because of their recurrent purpura to have, for instance,
WaldenstrDm's macroglobulinaemia or systemic lupus erythematosus and received treatment for them before these diagnoses were discarded. We feel,
however, that all 77 patients were fairly diagnosed as having had the clinical
syndrome of Schonlein-Henoch purpura. Winkelmann and Ditto (1964) had also
noted unusual features in some of their patients with allergic vasculitis, such as
mononeuritis multiplex, peripheral neuropathy, and segmental myelitis. It is
clear that in adults the spectrum of disease is wider than in children.
Localized oedema, especially of the hands, feet, face, and scalp, is well recognized as a feature of Schonlein-Henoch purpura in children, and was present in
two-thirds of the 131 patients reported by Allen, Diamond, and Howell (1960).
Bywaters, Isdale, and Kempton (1957) sampled the oedema fluid in one of their
patients and found a high protein content (5-6 g per 100 ml) suggestive of an
inflammatory origin. Winkelmann and Ditto (1964) noted dependent oedema,
which was sometimes painful, at the onset, or during exacerbation of the disease,
in 18 of their 38 adults. In the present series localized oedema, usually of the
dependent parts, was a feature in 44 patients and it seems probable that this
was either wholly or in part due to the cutaneous vasculitis.
Over 80 per cent of our patients developed systemic involvement and in most
of them the skin was apparently the first organ affected, although symptoms
and signs of internal involvement could precede the rash by as long as 28 days.
Similar observations were reported in children by Allen, Diamond, and Howell
(1960) and in adults by Winkelmann and Ditto (1964).
Joint involvement in the adult is similar to that seen in childhood. Symptoms
were often relatively mild and transient but could on occasions be disabling.
Joint involvement occurred in about 60 per cent of the paediatric cases and in
55 per cent of the present group of adults.
The frequency of gastrointestinal involvement in the paediatric series of
Schonlein-Henoch purpura varies from 29 per cent (Sterky and Thilen, 1960) to
69 per cent (Allen, Diamond, and Howell, 1960) and was 44 per cent in the
present series of adult cases. In children with gastrointestinal symptoms,
476
J. J. CREAM, J. M. GUMPEL, AND R. D. G. PEACHEY
Downloaded from by guest on September 12, 2016
abdominal pain was the most frequent manifestation in over 80 per cent, gross
melaena occurred in over 50 per cent, minor blood loss in another 27 per cent,
while vomiting was common and haematemesis occurred in about 10 per cent
(Allen, Diamond, and Howell, 1960). Our adults were very similar. In children
surgery has occasionally been undertaken before the diagnosis has become apparent as gastrointestinal symptoms may precede the rash (Feldt and Stickler,
1962). This is a hazard to which adults may also be exposed and indeed in
this series six patients presented with gastrointestinal manifestations. Intussusception is a well recognized complication of SchOnlein-Henoch purpura in
children (Wolfsohn, 1947) and may also occur rarely in adults (Emanuel, Lieberman, and Rosen, 1962) but did not occur in any of our patients. In cases
submitted to laparotomy, localized areas of oedema and haemorrhage involving
the bowel wall have been found and in rare instances perforation has been
reported (Lindenauer and Tank, 1966). Objective evidence of protein-losing
enteropathy was presented by Jones, Creamer, and Gimlette (1966) in five
patients who are also included in this study, and is certainly more common than
is immediately obvious.
Pulmonary manifestations have usually only been noted at post-mortem,
when peri-arteriolar infiltrates andfibrinoidnecrosis have been found (Lecutier,
1952; Norkin and Wiener, 1960). Jacome (1967) described a patient who had
haemoptysis, moderate dyspnoea, and multiple areas of consolidation, but without evidence of cardiac failure. At post-mortem very extensive intra-alveolar
haemorrhage was found, with widespread arteriolitis elsewhere. The transient
nature of the infiltrates in our patients would fit in well with intra-pulmonary
haemorrhage, and it is quite probable that these four patients had pulmonary
vasculitis.
Neurological involvement has been described although much of this, transient
hemiplegia (Osier, 1914), convulsions (Lewis and Philpott, 1956), and subarachnoid haemorrhage (Green, 1946) may have been related to hypertensive phenomena.
The main forms of renal disease: abnormalities of the urinary sediment, acute
nephritis, and slowly progressive renal damage, are well known to occur in
children with Schonlein-Henoch purpura. It has long been felt that renal
disease in children is more common in older than in younger children (Burke,
Mills, and Stickler, 1960; Allen, Diamond, and Howell, 1960) and that the
renal disease in adults is more serious and of worse prognosis than in children
(Berlyne, 1967), but the evidence for this is scanty (Levitt and Burbank, 1953;
McCombs, 1965). In the series of Allen, Diamond, and Howell (1960), there
were two deaths (1*5 per cent) from renal disease, 10 and 11 months after onset,
while in the series of Burke, Mills, and Stickler (1960) two deaths occurred
between one and five years after onset and two more after five years (4-5 per
cent). One child (2 per cent) died within a week of onset in the 46 children
reported by Bywaters, Isdale, and Kempton (1957). The prevalence (49 per
cent) and the mortality (4 per cent) of renal disease in our cases was thus comparable to that found in several paediatric series.
SCHONLEEST-HENOCH PURPURA IN THE ADULT
477
ii
Downloaded from by guest on September 12, 2016
The patterns of renal disease in our group were very similar to those in children, well described by Heptinstall (1966). We were impressed by the way in
which renal disease could occur suddenly late in the course of an acute attack or
could be insidious with a slow progressive deterioration of renal function. As
has been the experience of others, renal function could be surprisingly little
impaired in patients after long periods of persistently active and serious renal
disease. The histological features have recently been reviewed by Heptinstall
(1966) and by Berlyne (1967). The early and milder forms are characterized by
a focal glomerulonephritis while in the florid and progressive forms glomeruli
are uniformly involved with crescent formation and there is a necrotizing angiitis
of the interlobular arteries and afferent arterioles. In chronic disease with
uraemia hyalinization of glomeruli occurs.
The widespread multifocal vasculitis found in Schonlein-Henoch purpura
resembles an animal model of vasculitis, that of experimental serum sickness—
a circulating immune complex disease. In this model antigen, antibody, and
complement can be detected, by immunofluorescent techniques, in the affected
vessels (Dixon, Vazquez, Weigle, and Cochrane, 1958), and in the glomeruli
where there is a characteristic appearance—discrete, irregular lumpy deposits
along the outer aspect of the basement membrane beneath the epithelial cells
(Andres, Seegal, Hsu, Rothenberg, and Chapeau, 1963). In addition the serum
complement level is low. These histological and serum complement changes
have been observed in man in systemic lupus erythematosus (Koffler, Schur,
and Kunkel, 1967), and in acute post-streptococcal nephritis (Andres, Accinni,
Hsu, Zabriskie, and Seegal, 1966). It has been suggested that Schonlein-Henoch
purpura may be another example of a circulating immune complex disease and
confirmatory evidence has been provided by Stringa, Bianchi, Casala, and
Bianchi (1967) who demonstrated gammaglobulin and complement in skin
vessels in allergic vasculitis, although Miescher, Paronetto, and Koffler (1965)
failed to find such deposits and the serum complement levels in anaphylactoid
purpura are normal (Ayoub and Hoyer, 1969). The renal histopathology in
anaphylactoid purpura may be indistinguishable from that in systemic lupus
erythematosus (Heptinstall, 1966) but using immunofluorescence and electron
microscopy, Urizar, Michael, Sisson, and Vernier (1968) found granular deposits
of gammaglobulin and complement predominantly in the glomerular mesangium
in anaphylactoid purpura. These appearances were quite different from those in
systemic lupus erythematosus, post-streptococcal nephritis, or experimental
serum sickness and also did not resemble the appearances in Goodpasture's
syndrome (Duncan, Drummond, Michael, and Vernier, 1965). However, Feizi
and Gitlin (1969) demonstrated the constituents of a circulating cryoglobulin,
IgM and IgG, and complement deposited in the renal glomeruli in one patient
included in this series.
Both the clinical and also the histological classification of these patients
presents a problem. The clinical picture depends on the extent and site of the
small-vessel involvement and the histological appearances may depend on such
variables as the age of the lesion and the cut of the section. It is also apparent
478
J. J. CREAM, J. M. GUMPEL, AND R. D. G. PEACHEY
that thefindingsin a given patient may vary from site to site if multiple simultaneous biopsies are obtained. In our patients, no particular form of rash could
be picked out as being especially prone to occur without systemic involvement
and we feel there is little to be gained at present by attempting to subdivide and
classify what is probably a spectrum of disease on the basis of minor clinical
and histological appearances. Any rational classification of this group of patients
must await a clear understanding of the aetiology andpathogenesisof vasculitis.
We are indebted to Dr. H. J. Wallace and Dr. N. F. Jones for stimulating our
interest in different aspects of this study and for their continued interest and
advice, and to Dr. G. C. Wells and Dr. I. W. Whimster for helpful criticism.
Our thanks are also due to the Physicians of St. Thomas' Hospital and
St. John's Hospital for Diseases of the Skin who have allowed us to include
their patients, and to those in other hospitals who have supplied further
details of these patients. We thank Mrs. Jean Garnet for her help with the
manuscript.
Downloaded from by guest on September 12, 2016
Summary
The case histories of 77 adult patients with crops of purpura of SchOnleinHenoch type were reviewed. Thirty-four of these patients were seen and examined by us at varying intervals after the onset of disease.
In the majority of cases the aetiology of the condition was uncertain. Thirtytwo patients had taken medicinal preparations in the three weeks prior to the
first manifestation, but in only one patient was there good evidence of a causal
relationship—with a thiazide diuretic. Evidence of streptococcal infection was
found in 17 patients, and the significance of this finding is discussed.
Although cases with the typical cutaneous manifestations of childhood
Schonlein-Henoch purpura were seen, it was more common for the purpura to
appear in erythematous macules, which were never raised, or without any
preceding skin lesion. Skin necrosis was more frequently seen than in childhood.
Localized oedema, especially of the lower legs, was common and probably
attributable to the vasculitis in many cases. The rash in adults, as in children,
affected predominantly the lower extremities, and tended to occur in shortlived crops, which ceased completely in a few weeks in most patients. In a group
of 20 adults however, crops of purpura continued to appear for a year or more,
and subsequently six were found at follow-up to have developed unusual features, or evidence of other disease. Systemic involvement occurred in over 80
per cent of patients, and was similar in general to that seen in children. Joint
symptoms were usually short lived, and occurred in 55 per cent of patients.
Gastro-intestinal involvement occurred in 44 per cent with abdominal pain and
overt or occult blood loss as the most frequent manifestation. Haemoptysis or
pulmonary lesions occurred in 6-5 per cent. Renal disease was present in 49 per
cent, and presented as an acute nephritic syndrome in 19 patients, as slowly
progressive renal disease in three patients, and as a urinary abnormality by
itself with no impairment of renal function or evidence of acute nephritis in 16
patients.
SCHONLEIN-HENOCH PURPURA IN THE ADULT
479
The confusion of terminology and classification in the literature concerning
this group of patients is discussed. It is our opinion that there is little to be
gained by attempting to subdivide what is probably a spectrum of disease on
the basis of arbitrary minor clinical and histological criteria, and we believe any
further classification should await a clearer understanding of aetiology and
pathogenesis.
APPENDIX
Downloaded from by guest on September 12, 2016
Illustrative Case Histories
Case No. 42. Schonlein-Henoch purpura with severe gastrointestinal disease and
nephritis
At age 33, in 1951, this young woman developed ankylosing spondylitis and
was treated with codeine compound, aspirin and phenylbutazone, but the latter
drug was stopped after six weeks because of buccal ulceration. She had been
treated since childhood with phenobarbitone for petit mal.
In 1956 she began to have attacks of abdominal colic which lasted for a few
hours on each occasion and occurred every few weeks. There was no vomiting or
diarrhoea.
In 1961 she developed a purpuric rash on her legs, together with severe colicky
abdominal pain, vomiting, and constipation. She was admitted to a hospital
where her abdomen was noted to be distended and tender in the right iliac fossa.
At laparotomy some free fluid was present in the abdominal cavity but no other
abnormality was noted and the appendix, which was normal, was removed.
Four days later she was again vomiting, her abdomen was distended, and bowel
sounds were absent. A diagnosis of small-bowel obstruction was made and a
second laparotomy was performed. On this occasion several areas of the lower
ileum were found to be hyperaemic with a red and oedematous wall and thickening of the adjacent mesentery. This was thought at the time to be Crohn's
disease but the terminal ileum was spared and this diagnosis did not fit with the
purpuric rash. Following the second operation the patient developed gross
oedema and at this time albumin, red cells, and casts were noted in her urine.
She was transferred to St. Thomas' Hospital where she was found to be extremely oedematous with fading purpura on her legs, and to have tenderness
and guarding all over her abdomen. Over the course of the next two months
attacks of colicky abdominal pain recurred with abdominal distension, absent
bowel sounds, and occasional diarrhoea, and fresh crops of purpura appeared on
her legs. The proteinuria increased up to 20 g a day and a clinical diagnosis of
SchOnlein-Henoch purpura was made. Occult loss of blood was frequently
found in the stools. The plasma albumin level fell to 20 g/100 ml. In view of
the severe illness and the renal involvement she was started on prednisone 60 mg
daily, with a marked improvement in the haematuria, proteinuria, and purpura.
She continued, however, to have attacks of abdominal colic and two months
after admission developed severe right-sided abdominal pain with pain in the
right shoulder. At this stage she also developed attacks of intense pleuritic
pain, involving one or both sides of the chest, with areas of patchy consolidation
shown on X-ray. There was a marked positive release sign in the right hypochondrium and a third laparotomy was performed. A stricture of the small
bowel with numerous surrounding fibrinous adhesions was found and excised.
Examination of the excised specimen showed mucosal ulceration with fibrosis
beneath the ulcer. The mucous membrane adjacent to the ulcer showed chronic
480
J. J. CREAM, J. M. GUMPEL, AND R. D. G. PEACHEY
inflammatory cell infiltration. The patient made an uneventful post-operative
recovery with no further abdominal symptoms. The dose of prednisone was
gradually tailed off and the plasma proteins returned to normal. No certain
cause for the small-bowel ulcer was established and in particular the patient had
not received slow-release potassium preparations such as have been known to
produce small-bowel ulceration.
Case No. 57. Acute nephritis with a nephrotic phase; active disease for over six
months; recurrent pulmonary infiltrate with pleurisy
Case No. 72. Recurrent attacks of Schonlein-Henoch purpura over 17 years
Since the age of 17 this 34-year-old man has had recurrent attacks of purpura
on the buttocks and lower limbs, associated with pain and swelling in his joints.
In addition, at least twice a year after sore throats and colds, he has had more
severe episodes, with confluent purpuric lesions up to six inches across on the
buttocks and legs and occasionally on the trunk, arms, and face. With these
Downloaded from by guest on September 12, 2016
Ten weeks after a sore throat treated with tetracycline, this 22-year-old man
developed a purpuric rash on the hands, buttocks, legs, and feet, and noted
arthralgia of the ankles, knees, and elbows. He had abdominal cramps and
nausea, and dark urine. On admission to St. John's Hospital the urine was
'smoky', with heavy proteinuria and granular casts were seen Over the next
days the urine output dropped to 400 ml/24 hours, and the blood-urea level rose
from 28 mg/100 ml to 52 mg/100 ml. Because of his renal disease, he was transferred to another hospital.
During the two months of his admission heavy proteinuria persisted with
recurrent haematuria and cylindriuria as well as fresh crops of purpura associated with episodes of joint and abdominal pains and gastrointestinal bleeding.
He was therefore treated with prednisone, but because of an increase in the
blood-pressure this was stopped. Despite a low-protein diet, the blood-urea
remained slightly raised. Just before discharge from hospital he was re-started
on prednisone 15 mg daily to prevent a relapse of his renal disease.
Two weeks after discharge he had a further relapse and was admitted to
another hospital. At this time the blood-pressure ranged from 160/120 to 140/
100 mmHg, red cells and casts were regularly found in his urine, the blood-urea
level varied from 40 to 70 mg/100 ml, the serum albumen was maintained at
3-4 g/100 ml, and the urinary protein loss was 12 g/24 hours. Rheumatoid
factor tests and an immuno-fluorescent A.N.F. test were negative. His prednisone dose was increased to 60 mg/day for six weeks, and over this time proteinuria varied from 5 to 12 g/24 hours and the blood-urea from 40 to 65 mg/100 ml.
The prednisone was not immediately effective and was reduced to 15 mg/day
and azathioprine 100 mg daily started. At this stage the blood-urea and proteinuria gradually diminished. The creatinine clearance had always remained at
normal levels. Some five months after onset he developed severe recurrent
bilateral pleural pain with bilateral friction rubs and pulmonary opacities were
noted on the radiographs (see Plates, 36 to 38, Figs. 3 to 7). These cleared and
recurred over several weeks. No bacterial or embolic cause was shown.
One year after stopping treatment, 20 months after onset, he was well with a
normal blood-pressure, a blood-urea level of 28 mg/100 ml, and a 24-hour protein loss of only 180 mg. When seen four years after onset he was well and had
had no recurrence, and no abnormality was found on examination. The bloodurea and creatinine clearance were normal, but numerous red cells and casts
were present in the urine, which contained 2-5 g protein in a 24-hour collection.
SCHONLEIN-HENOCH PURPURA IN THE ADULT
481
severe attacks he has had episodes of abdominal pain, melaena, and a severe
arthritis affecting the metacarpo-phalangeal joints, wrists, elbows, knees, and
metatarso-phalangeal joints.
In the past these attacks had been variously diagnosed as rheumatic fever and
gout. They have continued unchanged for 17 years and a skin biopsy in 1968
showed a typical vasculitis. In one such attack Haemophilia influenzae was
cultured from the throat, and the ASO titre was normal. On two occasions, the
Rose-Waaler test was positive to a titre of 1/64.
Case No. 56. Slowly progressive renal failure, without an initial nephritic episode
A 17-year-old Anglo-Indian boy was seen with purpura and raised urticarial
lesions. At that time he had moderate proteinuria and red cells in the urine.
The blood-urea and plasma protein levels were normal. The proteinuria increased with persistent red cells and casts, and within six months the blood-urea
was up to 87 mg/100 ml and the serum albumen reduced at 2-3 g/100 ml. A
renal biopsy showed focal proliferative changes. Despite the use of steroids, the
renal disease continued unchecked. Within 30 months of onset he died of renal
failure. At autopsy most of the renal glomeruli appeared destroyed, with endothelial proliferation, crescent formation, and hyahnization of the remainder.
Case No. 74. Schonlein-Henoch purpura, chronic hepatitis, and cryoglobulinaemia complicated by the late development of immune-complex nephritis
This case has been reported in detail by Peizi and Gitlin (1969), and is therefore only described briefly here. When first seen in 1967 this 22-year-old man
Downloaded from by guest on September 12, 2016
Case No. 67. Renal tubular acidosis, juxta-glomerular apparatus hyperplasia,
interstitial nephritis, and renal wastage of potassium in a patient with recurrent
purpura, arthritis, gastrointestinal disease, and a widespread arteritis
This 40-year-old woman was referred to St. Thomas' Hospital with a threeyear history of intermittent purpura, arthritis, and two episodes of gastrointestinal bleeding which had required transfusion. She had a persistent low
grade fever and neutropenia, an E.S.B. of 100 mm/hr, and hypergammaglobulinaemia.
A plasma potassium of 2-0 mEq/1 led to the diagnosis of renal tubular acidosis
and renal potassium wastage. There was, however, no proteinuria or haematuria
and L.E. cells, antinuclear factor, and rheumatoid factor were not found. Skin
biopsy showed a severe vasculitis, and a percutaneous renal biopsy showed an
interstitial nephritis with prominent juxta-glomerular apparatus. The juxtaglomerular cells contained many granules and there was also tubular atrophy.
An exploratory laparotomy showed no obvious abnormality apart from
cholelithiasis but histological examination of biopsy material showed widespread
arteritis with a fibrinoid necrosis in the gall bladder, liver, and kidney. She has
since remained well on small doses of prednisone, now discontinued, and potassium supplements.
A possible disease mechanism in this patient is of renal tubular acidosis
supervening on long-standing hyperglobulinaemia and vasculitis (Jones,
Barraclough, and Prunty, 1969). Such widespread vasculitis is uncommon in
Schonlein-Henoch purpura, but of the other possibilities the persistently negative anti-nuclear factor makes systemic lupus erythematosus unlikely, and the
clinical features and long subsequent course would be most unusual for such
widespread vasculitis occuring in polyarteritis nodosa.
482
J. J. CREAM, J. M. GUMPEL, AND R. D. G. PEACHEY
gave a four-year history of recurrent purpura, principally on the legs. A skin
biopsy showed intense haemorrhagic vasculitis. At that time he was found to
have an enlarged liver and abnormal liver function tests, a liver biopsy
showed chronic hepatitis not typical of active chronic hepatitis, and he was
referred to Professor S. Sherlock. Repeated L.E. cell tests were negative, but
antinuclear antibodies were found in a titre of 1:10, and rheumatoid factor was
also present. A cryoglobulin was found in the serum. Urinalysis and renal
function were repeatedly normal.
Five years after the onset of his disease the patient was readmitted to the
Royal Free Hospital with left ventricular failure, hypertension, and oliguric
renal failure occurring after he had slept out in the open in extremely cold
weather. A renal biopsy showed hypercellular glomeruli and variable thickening
of the basement membrane. Both IgG and IgM, reflecting the composition of
the cryoprecipitate, were found in quantity in the renal glomeruli.
Subsequent to the renal disease, he has had persistent and heavy proteinuria
up to 2-6 g per day, haematuria, persistent hypertension requiring hypotensive
treatment, and a blood-urea reducing from 180 mg/100 ml to 45 mg/100 ml.
After an initial satisfactory response to prednisone 60 mg per day, his condition
worsened, but the introduction of azathioprine enabled the prednisone to be cut
to 10 mg per day. He has, however, continued to have recurrent attacks of
purpura on the legs, and the renal lesion is still active over 18 months later.
At the age of 30 this woman in 1956 started to have attacks of purpura on the
legs. She was admitted to St. Thomas' Hospital in 1962 and was noted to have
an E.S.R. of 42 mm in the first hour and hypergammaglobulinaemia. L.E. cells
were not found. No definite diagnosis was made despite repeated investigation
and she continued to have recurrent purpura. In 1968, she developed a symmetrical polyarthritis. Numerous L.E. cells were found and a diagnosis of
systemic lupus erythematosus was made.
REFERENCES
Ackroyd, J. F. (1953) Amer. J. Med. 14, 605.
Allen, D. M., Diamond, L. K., and Howell, D. A. (1960) Amer. J. Dis. Child. 99, 833.
Andres, G. A., Acoinni, L., Hsu, K. C, Zabriskie, J. B., and Seegal, B. C. (1966) J. exp.
Med. 123, 399.
Seegal, B. C, Hsu, K. C, Rothenberg, K. C, and Chapeau, M. D. (1963) Ibid. 117,
691.
Ayoub, E. M., and Hoyer, J. (1969) J. Pediat. 75, 193.
Berlyne, G. M. (1967) Renal Disease, ed. D. A. K. Black, 2nd edn., p. 507, Oxford and
Edinburgh.
Bilaloglu, N. (1963) Clin. Pediat. (Phila), 2, 541.
Bjornberg, A., and Gisslen, H. (1965) Lancet, 2, 982.
Burke, D. M., and Jellinek, H. L. (1954) Amer. J. Die. Child. 88, 772.
Burke, E. C , Mills, S. D., and Stickler, G. B. (1960) Proc. Mayo Clin. 35, 641.
Bywaters, E. G. L., Isdale, I., and Kempton, J. J. (1957) Quart. J. Med. N.S. 26, 161.
Calnan, C. D., and Lister, D. J. M. (1950) Trans. St. John's Hosp. derm. Soc. (Lond.), 44,
69.
Creger, W. P., and Houseworth, J. H. (1954) Amer. J. Med. 17, 423.
De Angelis, P. (1960) Pediatria (Napoli), 68, 308.
Downloaded from by guest on September 12, 2016
Case No. 77. Schdrdein-Henoch purpura for 12 years developing systemic lupus
eryihemabosus
SCHONLEIN-HENOCH PURPURA IN THE ADULT
483
Downloaded from by guest on September 12, 2016
Derham, R. J., and Rogerson, M. M. (1956) Arch. Dis. ChUdh. 3 1 , 364.
Dixon, F. J., Vazquez, J. J., Weigle, W. 0., and Cochrane, C. G. (1958) Arch. Pathol. 65,
18.
Duncan, D. A., Drummond, K. N., Michael, A. F., and Vernier, R. L. (1965) Ann. intern.
Med. 62, 920.
Emanuel, B., Lieberman, A. D., and Rosen, S. (1962) Illinois med. J. 122, 162.
Feizi, T., and Gitlin, N. (1969) Lancet, 2, 873.
Feldt, R. H., and Stickler, G. B. (1962) Proe. Mayo Clin. 37, 465.
Frank, E. (1915) Berl. klin Wschr. 52, 454.
Gairdner, D. (1948) Quart. J. Med. N.S. 17, 95.
Giordano, S., and Cordone, G. (1965) Minerva pediat. 17, 59.
Glanzmann, E. (1916) Jb. Kinderheilk. 83, 271.
(1920) Ibid. 91, 391.
Gougerot, H., and Blum, P. (1950) Buli. Soc. franc. Derm. Syph. 57, 336.
and Duperrat, B. (1954) Brit. J. Derm. 66, 283.
Green, B. (1946) Brit. med. J. 1, 836.
Henoch, E. (1874) Berl. klin. Wschr. 11, 641.
(1899) Vorlesungen uber Kinderkrankheiten, Berl. 10 Aufl. 839.
Heptinstall, R. H. (1966) Pathology of the Kidney, p. 335, London.
Jacome, A. F. (1967) Sth. med. J (Bgham., Ala.), 60, 1003.
Jones, N. F., Creamer, B., and Gimlette, T. M. D. (1966) Brit. med. J. 2, 1166.
Barraclough, M. A., and Prunty, F. T. G. (1969) Quart. J. Med. N.S. 38, 524.
Koffler, D., Schur, P. H., and Kunkel, H. G. (1967) J. exp. Med. 126, 607.
Lecutier, M. A. (1952) J. din. Path. 5, 336.
Levitt, L. M., and Burbank, B. (1953) New Engl. J. Med. 248, 530.
Lewis, I. C. (1955) Arch. Die. ChUdh. 30, 212.
and Philpott, M. G. (1956) Ibid. 31, 369.
Lindenauer, S. M., and Tank, E. S. (1966) Surgery, 59, 982.
McCombs, R. P. (1965) J. Amer. med.'Ass. 194, 1059.
Miescher, P. A., Paronetto, F., and Koffler, D. (1965) IVth International Symposium on
Immunopathology, ed. P. Graber and P. A. Miescher.
Norkin, S., and Wiener, J. (1960) Amer. J. clin. Path. 33, 55.
Oliver, T. K. Jnr., and Barnett, H. L. (1955) Amer. J. Dis. Child. 90, 544.
Osier, W. (1914) Brit. med. J. I, 517.
Panos, T. C. (1957) Report of the 22nd Ross. Paediatric Research Conference, Columbus, Ohio,
88.
Parish, W. E., and Rhodes, E. L. (1967) Brit. J. Derm. 79, 131.
Philpott, M. G. (1952) Arch. Dis. ChUdh. 27, 480.
Ramsay, C, and Fry, L. (1969) Brit. J. Derm. 81, 96.
Roberts, F. B., Slater, R. J., and Laski, B. (1962) Canad. med. Ass. J. 87, 49.
Ruiter, M., and Brandsma, C. H. (1948) Dermatologica (Basel), 97, 265.
(1952) Ada derm, venereol. (Stockh), 32, 274.
(1956) Brit. J. Derm. 68, 16.
(1964) Dermatologica (Basel), 129, 217.
Sohonlein, J. L. (1837) Allgemeine u. specielle Pathologie u. Therapie, Freyburg, 2, 48.
Sharan, G., Anand, R. K., and Sinha, K. P. (1966) Brit. med. J. 1, 656.
Sterky, G., and Thilen, A. (1960) Acta paediat. (Uppsala), 49, 217.
Stringa, S. G., Bianchi, C, Casala, A. M., and Bianchi, O. (1967) Arch. ital. Derm.
95, 23.
Symmer8, W. St. C. (1958). A symposium organized by the Council for International
Organisations of Medical Sciences, ed. M. L. Rosenheim and R. Moulton. Oxford and
Edinburgh.
Urizar, R. E., Michael, A., Sisson, S., and Vernier, R. L. (1968) Lab. Invest. 19, 437.
Vernier, R. L., Worthen, H. G., Peterson, R. D., Colle, E., and Good, R. A. (1961) Pediatrics, 27, 181.
484
J. J. CREAM, J. M. GUMPEL, AND R. D. G. PEACHEY
Wedgwood, R. J. P., and Klaus, M. H. (1955) Pediatrics, 16, 196.
Wilkinson, D. S. (1965) Brit. J. Derm. 77, 186.
Winkelmann, R. K. (1958) Proc. Mayo Clin. 33, 277.
and Ditto, W. B. (1964) Medicine (Baltimore), 43, 59.
Wolfsohn, H. (1947) Arch. Dis. Childh. 22, 242.
Downloaded from by guest on September 12, 2016
New Series, Vol. XXXIX, PI. 36
FIG. 4. Radiograph on July 4, 1966.
3-7. A series of chest radiographs taken at two-week intervals to show
the rapidly changing sequence of pulmonary and pleural changes (Case no. 57).
FIGS.
Downloaded from by guest on September 12, 2016
FIG. 3. Radiograph on June 20, 1966.
Quarterly Journal of Medicine
New Series, Vol. XXXIX,
FIG. 6. Radiograph on July 25, 1966.
Downloaded from by guest on September 12, 2016
~Eia. 5. Radiograph on July 18, 1966.
PL 37
New Series, Vol. XXXIX, PI. 38
Downloaded from by guest on September 12, 2016
FIG. 7. Radiograph on August 9, 1966.
Downloaded from by guest on September 12, 2016