Erythroderma

A clinical and follow-up study of 102 patients, with special emphasis on

survival
Vigfts Sigurdsson, MD, a Johan Toonstra, MD, a Marianne Hezemans-Boer, MD, b and
Willem A. van Vloten, M D a Utrecht and Harderwijk, The Netherlands

Background: Erythroderma may result from different causes. There have been no publica-
tions on this subject with special emphasis on survival.
Objective: The o2trnof the study was to determine the cause of the erythroderma and the
prognosis of these patients.
Methods: Clinical and follow-up data from 102 patients with erythroderma were analyzed.
We estimated survival of patients with erythroderma, from causes other than Stzary
syndrome, mycosis fungoides, or leukemia curls. The survival was compared with that of an
age-matched control group of the general population.
Results: The main cause of erythroderma was exacerbation of a preexisting dermatosis (53 %).
Drug reactions were rarely the cause (5%). A high proportion of the patients had chronic ac-
tinic dermatitis/actinic reticuloid (12%). Survival of men with erythroderma was significantly
lower than that of the general population.
Conclusion: Men with erythroderma, from causes other than S6zary syndrome, mycosis
fungoides, or leukemia curls, have a lower survival than men in the general population.
(J Am Acad Dermatol 1996;35:53-7.)

Erythroderma (exfoliative dermatitis) is charac-
terized by generalized ornearly generalized erythema
of the skin accompanied by a variable degree of
s c a l i n g . 1,2
Reports are conflicting about the prognosis of pa-
tients with erythroderma and whether the cause of
death is related to the erythroderma. 3-s Comparison
between published series is difficult because there
are differences in the follow-up period and in causes
of the erythroderma. Furthermore, the average age of
the patients in most series is approximately 60 years,
so that a proportion of the patients may die of nat-
ural causes during the follow-up period. A compar-
ison of survival of patients with erythroderma and
survival in the general population has never been
carried out.
In this study, we collected follow-up data from
From the Departments of Dermatology, University Hospital, Utrecht,"
and St. Jansdal Hospital, Harderwijk. b
Accepted for publication Jan. 29, 1996.
Reprint requests: V. Sigurdsson, MD, Department of Dermatology,
University Hospital Utrecht, P.O. Box 85500, NL-3508 GA Utrecht,
The Netherlands.
Copyright © 1996 by the American Academy of Dermatology, Inc.
0190-9622/96 $5.00 + 0 16/1/72519
102 patients with erythroderma to estimate their
survival compared with that of an age-matched con-
trol group of the general population. Furthermore,
we analyzed various clinical data to obtain more in-
sight into the behavior of this skin disease.
PATIENTS AND METHODS
Clinical data of 102 patients with erythroderma, who
were referred between 1977 and 1994, were analyzed.
The information was collected from the patients' records
and included clinical, laboratory, and follow-up data. If
follow-up information was not available, a questionnaire
was sent to the general practitioner, the referring derma-
tologist, or both for information about the current status
of the patient.
We classified our patients into six groups depending on
the cause of the erythroderma: (1) exacerbation of a pre-
existing dermatosis, (2) drag reactions, (3) cutaneous T-
cell lymphoma, (4) paraneoplastic, (5) miscellaneous, and
(6) idiopathic. Idiopathic erythroderma was defined as
erythroderma in a patient without any history of previous
skin diseases, absence of atopic complaints, no family
history of atopic diseases, and nondiagnostic skin histo-
pathologic and immunohistochemical results. Patients
diagnosed with actinic reticuloid met the following crite-
ria: (1) either persistently infiltrated skin on light-exposed
areas or generalized erythroderma; (2) photosensitivity to
53
 Journal of the American Academy of Dermatology
54 Sigurdsson et aL July 1996

Table I. Laboratory findings in patients with Table II. Causes of erythroderma (N = 102)
erythroderma I No.of
I No. of patients patients Total
(/total) %
Preexisting dermatoses 54 (53%)
Serum IgE (kU/L) (normal value <150) Atopic dermatitis 18
150-999 18/50 36 CAD/AR 12
>1000 18/50 36 Psoriasis 9
Stzary count, lymphocytes >20% 6/52 12 Seborrheic dermatitis 7
CD4/CD8 ratio of blood lymphocytes Vesicular palmoplantar eczema 5
Normal 23/52 44 Pityriasis mbra pilaris 2
Increased 19/52 37 Contact dermatitis 1
Decreased 10/52 19 Drug reactions 5 (5%)
Immunophenotyping of skin lymphocytes Allopurinol 1
Predominance of CD8+ cells 10/53 19 Gold 1
Predominance of CD4+ cells 31/53 58 Carbamazepine 1
Lymph node biopsy Phenytoin 1
Dermatopathic changes 23/29 79 Quinidine 1
Malignant lymphoma 6/29 21 Cutaneous T-cell lymphoma 13 (13%)
Stzary syndrome 10
Mycosis fungoides 3
Paraneoplastic 2 (2%)
a wide range of wavelengths, including UVB, UVA, and Carcinoma of lung 1
part of the visible spectrum; and histologic finding of a Carcinoma of stomach 1
dermal infiltrate with atypical lymphocytes. 9Patients who Miscellaneous 1 (1%)
met the first criterion or the second (or both) were diag- Leukemia cutis/CLL 1
nosed as having chronic actinic dermatitis. Idiopathic (undetennflaed) 27 (26%)
We estimated the survival of our patients and that of an
CAD/AR, Chronic actinic dermatitis/actinic reticuloid; CLL, chronic
age-matched control group of the general population with lymphocytic leukemia.
the Kaplan-Meier method. Survival was estimated for
men and women separately and only for patients with
"benign erythroderma." We defined "benign erythro- three patients with splenomegaly, one had chronic
derma" as erythroderma from causes other than Stzary lymphatic leukemia, one had S6zary syndrome, and
syndrome, mycosis fungoides, or leukemia curls. Data for one had eczema. In the majority of patients with pit-
the estimation of survival in the general population were ting edema, it was regarded as a result of the inflam-
recruited from life-expectancy tables of the Netherlands
mation of the skin and not a sign of cardiac failure.
Central Office for StatisrlcsJ ° Confidence interval for
survival was calculated by means of log survival scale. Laboratory data

RESULTS Routine biochemical screening yielded abnormal

Clinical data
The average age of our patients was 61 - 17
(standard deviation) years (range, birth to 86 years).
Seventy-two percent of the patients were male and
28% female. The progression of the erythroderma
was variable; in 17% of the patients it happened in
weeks, in 62% in months, and in 21% in years. The
mean duration of the erythroderma before admission
was 8 months (range, up to 96 months); for male
patients, 9 months (range, up to 96 months), and for
female patients 4 months (range, up to 26 months).
Seventy-one percent of the patients had lymph-
adenopathy, 54% had pitting edema of the legs, 39%
had onychopathy, and 22% had alopecia. Only 7%
had hepatomegaly and 3% had splenomegaly. Of the
values in a minority of the patients. Eight of 13 pa-
tients with an erythrocyte sedimentation rate higher
than 30 mm/hr had idiopathic erythroderma, two had
atopic dermatitis, and one had a drug reaction. Of the
two patients with anemia, one had atopic dermatitis
and uremia and the other patient had a malignant
brain minor and drug-related erythroderma. Of the
nine patients with leukocytosis higher than 20 x 109/
L, four had Stzary syndrome, one had leukemia cu-
rls, and the others had different types of eczema.
Lymphocytosis of more than 50% was more fre-
quently seen in patients with cutaneous T-cell lym-
phoma. Eosinophilia higher than 1.0 x 109/L was
present in 20% of the patients; 10 patients had idio-
pathic erythroderma, five had atopic dermatitis, and
the rest had seborrheic dermatitis, drug reactions,
Journal of the American Academy of Demaatology
Volume 35, N u m b e r 1 Sigurdsson et aL 55

1.0 i., [ '"l

0.8

._> 0.6
"~.iL,' "'............. .,
"~.. . . . . . . . . I,, E1
0.4

general population
0.2
our group ( ::::::: 95% CI)

I I I
50 200 150 1O0
time in months
Fig. 1. Estimated survival of men (n = 63) with benign erythroderma (erythroderma from
causes other than Stzary syndrome, mycosis fungoides, or leukemia curls) compared with
that of an age-matched control group of the general population. CI, Confidence interval.

Stzary syndrome, mycosis fungoides, or actinic
reticuloid.
More specific laboratory findings are shown in
Table I. Eighteen patients had a high level of serum
lgE (>1000 kU/L), of which eight had atopic
dermatitis, five, idiopathic erythroderma; two, S6zary
syndrome; two, actinic reticuloid; and one, drug re-
action. All six patients with more than 20% circulat-
ing Stzary cells had Stzary syndrome but less than
10% was not specific for any diagnosis in our series.
A normal or increased CD4/CD8 ratio of peripheral
blood lymphocytes was not a specific finding in our
series but a reversed ratio was found in five of the
patients with actinic reticuloid. Predominance of
CD8 + lymphocytes in the skin was found in seven
patients with actinic reticuloid.
Cause of erythroderma
As shown in Table II, the most frequent cause of
the erythroderma was an exacerbation of a preexist-
ing dermatosis. Only five patients had drug-related
erythroderma. Of patients with chronic actinic der-
matitis/actinic reticuloid, 10 had actinic reticuloid.
Follow-up
We were able to collect data from 91 patients
(89%). These findings are summarized in Table HI.
The mean follow-up time was 51 + 43 months
(range, 1 to 177 months). Fifty-two patients (57%)
were alive, and 39 (43%) had died. In seven of the
Table III. Follow-up data of patients with
erythroderma (n = 91)
Alive (n = 52) Dead (n = 39)
Without skin disease 8 (15%) 11 (28%)
With limited disease 39 (75%) 12 (44%)
With erythroderma 5 (10%) 11 (28%)
patients who died, the immediate cause of death was
directly related to the erythroderma, in three it was
undetermined, and in 29, it was unrelated. All
patients whose death was related to the eryt_hroderma
had malignancy; six had Sdzary syndrome and one
had leukemia cutis. Of the patients whose death was
not related to the erythroderma, 12 died of cardio-
vascular diseases, nine of various nonhematologic
malignancies, four of lung diseases, and the rest of
sepsis, trauma, kidney failure, or leukemia.
Survival
Figs. 1 and 2 show the survival in our group of
patients with "benign erythroderma" and that of an
age-matched control group of the general popula-
tion. The survival of men was significantly lower
than that of the general population. In women it was
also lower but not significantly.
DISCUSSION
As in other series, we found erythroderma almost
exclusively in adults; the mean age at onset was
 Journal of the American Academy of Dermatology
56 Sigurdsson et al. July 1996

._> 0.6- : ........................... .... I--L--

]
tO

0.4-
9
general population
0.2-
our group ( ::::::: 95% CI)

I I I I
50 200 150 1O0
time in months

Fig. 2. Estimated survival of women (n = 25) with benign erythroderma (erythroderma

from causes other than S6zary syndrome, mycosis fungoides, or leukemia cuds) compared
with that of an age-matched control group of the general population.

T a b l e IV. Causes of erythroderma in previous publications compared with the present series
Preexisting Drug
No. of dermatoses reactions CTCL Paraneoplastic Miscellaneous Idiopathic
Author(s) (year) patients (%)* (%) (%) (%) (%) (%)

Wilson4 (1954) 50 46 8 4 0 4 38
Gentele, Lodin, Skog11 (1958) 135 45 8 11 0 4 32
Abrahams, McCarthy, Sanders5 (1963) 101 35 11 2 0 6 46
Nicolis and Helwig6 (1973) 135 27 40 8 3 10 12
Ndiaya et al.12 (1979) 77 51 14 4 0 0 31
Hasan and Jans6n13 (1983) 50 54 10 4 0 0 32
King et al.7 (1986) 82 31 34 18 0 1 16
Sehgal and Srivastava14 (1986) 80 58 20 0 0 0 22
BoteUa-Estrada et al.8 (1994) 56 66 12.5 12.5 0 0 9
Present series 102 53 5 13 2 1 26
CTCL, Cutaneous T-cell lymphoma.
*Percentages represent relative frequency.

slightly higher than in most other series. 1, 3-s, 11-14
The mean duration of the erythroderma before
admission was much longer in men than in women.
We have no explanation for this. In other series this
has not been investigated.
As shown in Tables II and IV, the main cause of
the erythroderma in our series was exacerbation of
a preexisting dermatosis, as has also been described
by others. 4-8,11-14 Drag reactions were rarely the
cause. A high proportion of the patients had chronic
actinic dermatitis/actinic reticuloid. This is much
higher than in other series, in which 10 of 766 pa-
tients had erythroderma secondary to photoderma-
toses.4-s, a1-14 Only one of these patients had actinic
reticuloid] The high prevalence of photodermatoses
in our series is most likely because our department
is a referral center for photodermatoses.
The mortality rate in the whole group of patients
was 43%, which is high in comparison to other
studies in which it has been between 11% and
64%.4-a This high mortality rate is partly explained
by the long follow-up period and by the relatively
high prevalence of lymphoma in the group.
In our series the estimated survival of men with
"benign erythroderma" was significantly lower
than in an age-matched control group of the general
population. This has never been studied before so it
is not possible to compare this with other studies. The
Journal of the American Academy of Dermatology
Volume 35, Number 1
difference in survival between the men in our group
and in the general population is difficult to explain.
One possibility is that because of the erythroderma,
in some patients high-output cardiac failure devel-
oped from shunting of large amounts of blood
through inflamed skin. This might lead to increased
mortality from cardiovascular diseases. However,
most patients died with fimited or no skin disease and
had no signs of high-output cardiac failure. Another
possible explanation is that most patients were
treated with topical corticosteroids and sometimes
systemic prednisone. It is known that corticosteroids
can induce atherosclerosis and, as a consequence, an
increase in cardiovascular deaths. 15
Estimated survival of women with "benign eryth-
roderma" was lower than the estimated survival in
the general population, but was statistically not sig-
nificant. Perhaps the group was too small, but it is
also possible that women with erythroderma have a
better prognosis than men.
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