BMC Dermatology

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Research article

Erythroderma: A clinical study of 97 cases

Maryam Akhyani*, Zahra S Ghodsi, Siavash Toosi and Hossein Dabbaghian
Address: Department of Dermatology, Tehran University of Medical Sciences, Razi Hospital, Vahdate-Eslami Sq. 11966, Tehran, Iran
Email: Maryam Akhyani* - [email protected]; Zahra S Ghodsi - [email protected]; Siavash Toosi - [email protected];
Hossein Dabbaghian - [email protected]
* Corresponding author

Published: 09 May 2005

BMC Dermatology 2005, 5:5

doi:10.1186/1471-5945-5-5

Received: 13 October 2004

Accepted: 09 May 2005

This article is available from: http://www.biomedcentral.com/1471-5945/5/5

2005 Akhyani et al; licensee BioMed Central Ltd.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0),
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract
Background: Erythroderma is a rare skin disorder that may be caused by a variety of underlying
dermatoses, infections, systemic diseases and drugs.
Methods: We reviewed the clinical, laboratory and biopsy material of 97 patients diagnosed with
erythroderma who were treated in our department over a 6-year period (1996 through 2002).
Results: The male-female ratio was 1.85:1. The mean age at diagnosis was 46.2 years. The most
common causative factors were dermatoses (59.7%), followed by drug reactions (21.6%),
malignancies (11.3%) and idiopathic causes (7.2%). Carbamazepine was the most common drug
(57.1%). The best clinicopathologic correlation was found in cutaneous T-cell lymphoma and
pityriasis rubra pilaris related erythroderma. Apart from scaling and erythema that were present in
all patients, pruritus was the most common finding (97.5%), followed by fever (33.6%),
lymphadenopathy (21.3%), edema (14.4%) and hyperkeratosis (7.2%).
Conclusion: This study outlines that underlying etiologic factors of erythroderma may show
geographic variations. Our series had a high percentage of erythroderma secondary to preexisting
dermatoses and a low percentage of idiopathic cases. There was no HIV-infected patient among
our series based on multiple serum antibody tests. The clinical features of erythroderma were
identical, irrespective of the etiology. The onset of the disease was usually insidious except in druginduced erythroderma, where it was acute. The group associated with the best prognosis was that
related to drugs.

Background
Erythroderma or exfoliative dermatitis is a rare skin disorder that may be the result of many different causes. It represents an extreme state of skin irritation involving the
whole or most of the skin surface. Because most patients
are elderly and skin involvement is widespread, the disease implies an important risk to the life of the patient [1].
Hasan and Jansen estimated the annual incidence of
erythroderma to be 1 to 2 per 100,000 patients [2].Sehgal
and Strivasta recorded the incidence of erythroderma in a

large prospective study from the Indian subcontinent as

35 per 100,000 dermatologic outpatients [3]. The causative factors can be grouped as previous dermatoses, drug
reactions, malignancies systemic diseases, infections and
idiopathic disorders. The four more common causes of
idiopathic protracted erythroderma are probably atopic
dermatitis of the elderly, intake of drugs overlooked by
the patient, pre-lymphomatous eruptions and occult
malignancies [1,4]. Histopathology can help identify the
cause of erythroderma in up to 50% of cases, particularly
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by multiple skin biopsies [5]. Many chronic dermatoses

may be histologically indistinguishable in erythrodermic
patients [6].
In Pakistan, Pal and Haroon have studied the features of
erythroderma in 90 patients and etiologically found preexisting dermatoses as the most frequent cause of erythroderma [7]. To date there are no published studies on the
frequency of underlying causes of erythroderma from
Middle East. In order to delineate the salient features of
erythroderma in our region, we have reviewed the cases of
erythroderma examined and treated in our institution
between 1996 and 2002 (six years). Finally our data are
discussed and compared with other earlier series that are
taken from Western and European populations as well as
from other Asian countries.

Methods
We defined erythroderma as generalized erythema of the
skin (more than 90% of the body surface area) accompanied by a variable degree of scaling [4].
The population covered by our institute is difficult to
establish, because it is a tertiary reference hospital that
receives patients from distant areas. A coverage of
5,000,000 is an approximate figure. Due to the risk that
erythroderma implies for the patient's life and to study the
cause in each patient, we always treat them as inpatients.
The records of patients who were discharged with a diagnosis of erythroderma in the period from 1996 to 2002
(six years) were carefully reviewed and the following data
recorded for all the patients: personal data, history of skin
diseases, past medical history, drug history, previous episodes of erythroderma, onset of erythroderma (acute or
insidious), clinical data during the episode (scaling, pruritus, lymphadenopathy, visceral enlargement, hyperkeratosis, mucosal involvement and edema). Laboratory
investigations including complete hematological parameters, erythrocyte sedimentation rate, serum protein levels,
liver and kidney function tests, serum electrolytes, urine
microscopy, stool exam for occult blood, serum markers
for viral hepatitis B and C and HIV antibody testing,
microscopy for scabies mite and fungus, electrocardiography, and chest radiography were performed for all the
patients as a routine in the dermatology ward of our hospital. Disease-specific investigations such as skin biopsy,
lymph node biopsy, immunophenotyping, flow-cytometry, patch test and work-up for occult malignancy were
performed in special cases as indicated.

Results
In the six year study period, erythroderma was found in 97
patients. Sixty three (64.9%) patients were male and thirty
four (35.1%) were female, that means men outnumbered
women in a proportion of 1.85:1. The mean age of the

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onset of erythroderma was 46.2 20.03 (SD) years (range,

8 through 90 years). There was no significant difference in
the age of onset between male and female groups using
independent T-test. All the patients in this series were
Caucasian.
All the patients had some degree of scaling. Ninety-four
(97.5%) patients had pruritis. Thirty two (33.6 %)
patients had a fever (temperature, 38c or higher) during
the episode and lymphadenopathy was found in 20
(21.3%) patients. Visceral enlargement was found in 4
(4%) patients. Edema, hyperkeratosis and mucosal
involvement were found in 14 (14.4%), 7 (7.2%) and 1
(1%) patients respectively.
Histopathologic examination was performed in 81
(83.5%) of the 97 patients. Skin biopsy was performed in
all the cases classified as malignancy and idiopathic. A
skin biopsy was not performed in some of the cases
because the cause of erythroderma was clear from the start
(previous known dermatoses or treatment with some drug
in the days before the appearance of erythroderma).
Final diagnosis was the result of evaluation of the clinical,
biochemical and histological findings and of the evolution of erythroderma in each individual patient. The
patients were divided into four etiologic groups: (1) Previos dermatoses (58 patients, 59.8%): psoriasis, 27
(27.8%); atopic dermatitis, 13 (13.4%); pityriasis rubra
pilaris, 8 (8.2%); seborrheic dermatitis, 2 (2.1%); contact
dermatitis, 3 (3.1%); actinic reticulosis, 1 (1%); scabies,
1(1%); bullous ichthyosiformis, 1 (1%); pemphigus
foliaceus, 1 (1%) and senile xerosis, 1 (1%), (2) Malignancies (11 patients, 11.3%): Sezary syndrome, 2 (2.1%);
mycosis fungoides, 8 (8.2%); lung cancer, 1 (1%), (3)
Drug reactions (21 patients, 21.6%): carbamazepine, 12
(57.1%); phenytoin, 3 (14.3%); phenobarbital, 2 (9.5%);
lithium, 1 (4.8%); penicillin,1 (4.8%); vancomycin, 1
(4.8%) and cotrimoxazole, 1 (4.8%) and (4) Idiopathic or
undetermined: seven patients (7.2%). Relationship
between a drug and erythroderma was established from
the antecedent of intake of the incriminating drug in the
days preceding the onset of erythroderma and clearing of
the manifestations following withdrawal of the drug. Mild
anemia, increased erythrocyte sedimentation rate, leukocytosis and hypoalbuminemia were common findings but
nothing remarkable was found in the laboratory tests.
None of the patients were HIV-positive based on the multiple serum antibody tests. All the patients in the idiopathic group as well as those with seborrheic dermatitis,
actinic reticuloid and Sezary syndrome were males. All the
three patients with contact dermatitis as a cause of their
erythroderma were female. There was no statisticaly significant difference in the frequency of causes of erythroderma among men and women.

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The onset of erythroderma was generalized in 23 (23.7%)

patients. In others the initial site of involvement of erythroderma was head and neck in 20 (20.6%), upper or
lower limbs in 18 (18.5%), trunk in 11 (11.3%), genitalia
in one (1%), flexural regions in five (5.2%) and extensor
areas in 19 (19.6%) patients. On follow-up, only one
patient with lung cancer died due to erythroderma or its
underlying causes. None of the patients with drug reactions and pityriasis rubra pilaris relapsed. With therapy,
erythroderma improved in all the patients with mycosis
fungoides and Sezary syndrome but relapse occured in all
of them at least once again. All the patients with psoriasis
was hospitalized for the second time during the study
period.

Discussion
The approach to patients with erythroderma depends on
their previous dermatologic history. Patients with dermatologic disorders recalcitrant to therapy may develop
erythroderma during a flare up. In such cases, the etiologic
diagnosis is easy to establish, otherwise, erythroderma
remains a diagnostic challenge. The clinical features of
erythroderma are non-specific and certain clues such as
scaling or pruritis could not be related to any specific
cause. Erythroderma of long duration may cause hair loss
or nail dystrophy regardless of its origin, so these changes
are also non-specific. In erythrodermic patients clinicopathologic correlation is usually poor, because the specific
cutaneous changes of dermatoses or drug reacions are
obscured by the non-specific changes induced by the
inflammatory process of erythroderma [1]. In a patient
without history of dermatologic diseases and who denies
having recently taken any medication, the diagnosis is
more difficult and it is of great importance to perform skin
biopsies in such cases although the histologic picture
shows either a subacute or chronic dermatitis and psoriasiform reaction. Thus each case of undetermined origin
requires thorough histologic examination through multiple skin biopsies and a lymph node biopsy to rule out
lymphoma. A drawback in our study was that it was a retrospective survey and, therefore, we were not able to verify
the diagnosis ourselves. In spite of these drawbacks we
believe that our data on causes of erythroderma would
add to the already existing literature on erythroderma.

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lower percentage of lymphadenopathy, visceral enlargement, edema and mucosal involvement in comparison
with Pal and Haroon's series [7]. Many drugs can cause
erythroderma. Among the more commonly implicated
are pyrazalone derivatives, carbamazepine, hydantoin
derivatives, cimetidine, lithium salts and gold salts [9,11].
According to our findings, the agents of greatest erythroderma-inducing potential are carbamazepine, phenytoin
and phenobarbital. The drugs responsible for erythroderma in our series have been previously incriminated as
a cause of this disorder in literature [9]. Carbamazepine
was the drug most frequently quoted in our cases, with 12
of the 21 cases (57.1%) related to this medication. This
drug has been mentioned as a less frequent cause of erythroderma in other series [1,2,12,13]. Thus carbamazepine
as a frequent cause of erythroderma in the present population warrants particular attention and may be due to a
genetic sensitivity to this drug or a high rate of its
prescription.
Surprisingly, in spite of the fact that, allupurinol is prescribed frequently in this country we observed no erythroderma related to this drug. Allopurinol has been
mentioned as one of the most common causes of drugs
inducing erythroderma in some other recent series
[1,2,12,13].
Comparison of the etiologic groups among the recent previous series and our own is given in table 1. Our series has
a high percentage of erythroderma secondary to preexisting dermatoses that are mentioned as the most common
cause of adult erythroderma in the majority of studies [14,9,13,14]. Drug reactions were the most common cause
of erythroderma in the HIV-positive patietns in one report
[8]. The percentage of cases in which no underlying disease is demonstrable diminishes with the thoroughness of
investigation and the duration of observation, but in any
series of cases it is rarely below 10% [1,2,4,12-15]. In our
cases we found a particularly low percentage of idiopathic
cases.

In our series the mean age of onset was in fifth decade and
men outnumbered wemon. Such findings are in accordance with many other studies [1,7-10]. The best clinicopathologic correlation was found in mycosis fungoides
and pityriasis rubra pilaris. Previously, Botella-Estrada et
al have also reported similar findings [1].

Eight (8.2%) of our patients were diagnosed as pityriasis

rubra pilaris which is uncommonly reported as a cause of
erythroderma in other studies [1,2,12,13]. Pal and
Haroon reported pityriasis rubra pilaris as a causative factor of erythroderma in 2.2% of their patients [7]. As a
result, we concluded that there might be a higher frequency of pityriasis rubra pilaris or a greater tendency to
its generalization in our environment. Psoriasis was the
most common underlying cause, which is in accordance
with Pakistanian and Indian series [7,3].

Like many other series [2,3,9], diffuse scaling and pruritus

was found in almost all of our patients. Although we
examined each patient in several occasions, we found a

The onset of erythroderma was usually insidious except in

drug-induced cases, where it was abrupt and florid. This is
in accordance with three other studies [1-3], which

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Table 1: classification of patients with erythroderma by cause in some previous publications and in the present series.

Relative incidence,(%)
Causes

Sigurdsson et
al14, 1996

Pal and
Haroon7,1998

Nicolis and
Helwig15, 1973

Hasan and
jansan2, 1983

Botellaestrad
a et al1, 1994

Sehgal and
strivastava12,1986

King et al13,
1986

The present
series 2004

Preexisting
dermatoses
Drug reacions
malignancies
Idiopathic

53

74.4

25

42

62.5

52.5

30

57.9

5
13
26

5.5
5.5
14.6

42
21
12

22
4
32

16
12.5
9

24.7
0
22.5

34
20
16

21.6
11.3
7.2

reported gradual onset in most cases. In Pal and Haroon's

series, erythroderma started with an acute onset in more
than two-thirds of the patients which is assumed to be
related to the injudicious use of medication [7]. In our
patients, the group associated with the best prognosis was
that related to drugs such findings have been observed in
literature [9].

opathic cases. The clinical features of erythroderma were

identical, irrespective of the etiology. The onset of the disease was usually insidious except in drug-induced erythroderma, where it was acute. This study outlines that
underlying etiologic factors of erythroderma may show
geographic variations.

Abbreviations
Because erythroderma is occasionally associated with
internal malignancies, even patients with previous history
of known dermatoses whose clinicopathologic features
are inconclusive, should be investigated carefully to rule
out malignant neoplastic causes.

HIV: Human Immunodeficiency virus

We observed no remarkable laboratory results in our

patients. this finding was similarly reported by Haroon
and Pal [7]. There was no HIV-infected patient in the
present series. Erythroerma is reported frequently due to
different dermatoses or drug reactions in HIV-positive
patients. In one series reported by Morar et al, a large proportion of erythrodermic patients were HIV-positive but
they did not have a significant increase in he number of
episodes of erythroderma. It is concluded that in the
young black patients erythroderma may be a marker for
HIV infection [8]. In harmony with its low frequency, HIV
seems to be a lesser threat in our community.

Authors' contributions

In initial documented studies, the recorded death rate due

to erythroderma varied from 18 to 64% [9]. On followup, we found only one death related to erythroderma or
its underlying causes, which was the patient with lung
cancer. Our findings support Hassan and Jansen's view [2]
that erythroderma does not pose a significant risk to the
patient's life.
This study outlines that some important features of erythroderma may show geographic variations.

Conclusion
Our series had a high percentage of erythroderma secondary to preexisting dermatoses and a low percentage of idi-

Competing interests
The author(s) declare that they have no competing
interests.

All authors contributed equally in the study design, literature search, data analysis and manuscript preparation. All
authors read and approved the final manuscript.

References
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