Title:Erythroderma: a clinicopathological study of 47 cases from 2018-2020

Author’s name: Ozge Askin1, Rozerin Neval Altunkalem1, Tugba Kevser

Uzuncakmak1,Ferdane Şeyma Toplu2, Burhan Engin1

Affiliation
1. IstanbulUniversity-Cerrahpasa, Cerrahpaşa MedicalFaculty, Deparment of
DermatologyandVenerology, Istanbul, Turkey
2. IstanbulUniversity-Cerrahpasa, Cerrahpaşa MedicalFaculty, Deparment of
PublicHealth, Istanbul, Turkey

Corresponding author:OzgeAskin, Tel: +905303707017,

Mail: ozgee_karakus@hotmail.com
Keywords:Erythroderma, exfoliativedermatitis, diffuseerythema, scaling
Runnigtitle: Erythroderma
All authors have no conflict of interest.
OzgeAskindesignedanddirectedtheproject.
Rozerin Neval Altunkalemderivedthemodelsandanalysedthedata.
Tuğba Kevser Uzunçakmakconceived of thepresented idea.
Ferdane Şeyma Toplu performedthemeasurements.
Burhan Engin wereinvolved in planningandsupervisedthework.
Data Availability Statement : Data openly available in a public repository that issues
datasets with DOIs

This article has been accepted for publication and undergone full peer review but has not been
through the copyediting, typesetting, pagination and proofreading process which may lead to
differences between this version and the Version of Record. Please cite this article as doi:
10.1111/dth.14342

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ABSTRACT
Erythroderma, orexfoliativedermatitis, is an
inflammatorydisordercharacterizedbyerythemaandscalingaffectingmost of the skin surface.
Itmay be a result of manydifferentcausessuch as previousdermatoses (psoriasis, eczema,
atopicdermatitis, pityriasisrubrapilaris, pemphigusfoliaceous), drugreactions, malignancies
(mycosisfungoides, Sézarysyndrome, adult T-cellleukemia/lymphoma),
infectionsandidiopathicdisorders. Regardless of theetiology, theclinicalappearance of
erythroderma is similar in allpatients. Themostprominentphysicalexaminationfindings in
almostallpatientsarediffuseerythemaandscaling. In a 2 yearperiod 47
patientswhowerehospitalizedandtreated in ourdepartmentwereincluded in thestudy.
Weclassifiedpatientsinto seven subgroups: psoriasis, atopicdermatitis (AD), drug-
inducederythroderma, mycosisfungoides (MF), pityriasisrubrapilaris,
bullouspemphigoidandpolymorphouslighteruption. Allpatients had a
biopsyduringtheacutestageanddiagnoseswerehistopathologicallyconfirmed. Somepatients had
multiplebiopsiesforhistopathologicalconfirmation. Inourstudy, themajority of thepatientswere
men overtheage of 54. Themostcommonetiologicalcause of erythroderma is psoriasis.
Weaimtoanalyseclinical, laboratoryandhistopathologicalfindings of
erythrodermicinpatientsprospectively in
IstanbulUniversityCerrahpasaCerrahpasaMedicalFacultybetweenJanuary 2018 and 2020.

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INTRODUCTION
Erythroderma, or exfoliative dermatitis, is an inflammatory disorder characterized by
erythema and scaling affecting most of the skin surface.It may be a result of many different
causes such as previous dermatoses (psoriasis, eczema, atopic dermatitis, pityriasis rubra
pilaris, pemphigus foliaceous), drug reactions, malignancies (mycosis fungoides, Sézary
syndrome, adult T-cell leukemia/lymphoma), infections and idiopathic disorders. Psoriasis is
the most common underlying disorder (1-4).
Although clinical and laboratory findings help in diagnosis in some cases, it does not lead to
definitive diagnosis. Histopathology can help to identify the cause of erythroderma in up to
50% of cases (5).
Incidence was recorded as 35 per 100,000 in dermatologic outpatients in the literature(1).
We aim to analyse clinical, laboratory and histopathological findings of erythrodermic
inpatients prospectively in Istanbul University-Cerrahpasa Cerrahpasa Medical Faculty
between January 2018 and December 2020.
MATERIALS AND METHODS
47 patients who were hospitalized and treated in the Dermatology Department of Istanbul
University-Cerrahpasa Cerrahpasa Medical Faculty between 2018-2020 were included in the
study. All the patients diagnosed with erythroderma had developed erythema and scaling
affecting more than 80% of the body surface area.
The files of the patients at the time of hospitalization were examined and their age, gender,
background characteristics, physical examination, laboratory findings and treatment methods
were analysed.

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We classified patients into seven subgroups: psoriasis, atopic dermatitis (AD), drug-induced
erythroderma, mycosis fungoides (MF), pityriasis rubra pilaris, bullous pemphigoid and
polymorphous light eruption.
Skin biopsy was performed all patients in the erythrodermic period and histopathological
diagnosis was confirmed.
Statistical analyses were performed using SPSS version 21 software. The compliance of the
variables to normal distribution was examined by visual (histogram and probability graphs)
and analytical methods (Kolmogorov-Smirnov / Shapiro-Wilk tests). Descriptive analyses
were given using mean and standard deviation for normally distributed variables, median and
interquartile range for non-normally distributed variables, and frequency tables for categorical
variables.
RESULTS
In a 2 year period we collected 47 cases. In our study, erythrodermic cases constituted 1% of
all patients hospitalized in our service in the same period. Of the 47 patients with
erythroderma ranging in age from 13-79 (50.7 ± 17.9), 27 were male and 20 were female.25%
of patients were under the age of 35 and 50% were over 54 years old. In the history
characteristics, 63% of the patients had at least one systemic disease. 14 patients had
hypertension, 12 patients had diabetes mellitus, 4 patients had congestive heart disease, 2
patients had urticaria and one patient had asthma.
Previous history of skin disease was observed in 30 of 47 patients (63.8%). All patients had a
biopsy during the acute stage and diagnoses were histopathologically confirmed. Some
patients had multiple biopsies for histopathological confirmation. 59.6% (28) of the patients
were diagnosed with psoriasis vulgaris. 17% (8) of the patients were diagnosed with drug
eruption, 12.8% (6) mycosis fungoides, 4.3% (2) atopic dermatitis, 2.1% (1) bullous
pemphigoid, 2.1% (1) pityriasis rubra pilaris and 2.1% (1) polymorphous light eruption.
Insert table 1 here.
Symptoms of the cases, clinical examination and laboratory findings are shown in Table 2.
While the most common symptoms observed in patients were pruritus and fever, the most
common laboratory findings were leukocytosis and an increase in C-reactive protein.
Peripheral smears of patients with leukocytosis were normal. 23% of patients had
eosinophilia. The diagnosis of the majority of patients with eosonophilia was drug eruption.
While anemia was seen in 23% of our patients, 2 of these patients were diagnosed with iron
deficiency anemia, while 3 were diagnosed with chronic disease anemia. The
histoppathological diagnosis of 5 patients with increased IgE levels were atopic dermatitis
and drug eruption. We found a high incidence of elevated ESR/CRP. This was probably
related to the inflammatory process. 10% of the patients had elevated LDH levels and all of
these patients were diagnosed with mycosis fungoides. While electrolyte imbalance is a

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common laboratory finding in erythroderma, hypopotasemia was observed in 7 of our
patients, hyponatremia in 3, and hypocalcemia in 2 of our patients.
Palmoplantarkeratoderma was observed in 16/47 (34%) patients, and it was more common in
psoriasis. Nail changes were observed in 36% of cases. Most common nail change was
subungual hyperkeratosis, pitting and shiny nails.
Insert table 2 here.
The treatment of the patients was arranged according to the etiological factors. Patients
diagnosed with psoriasis vulgaris were treated with systemic corticosteroids, systemic
acitretin, cyclosporine, methotrexate, infliximab, adalimumab or ustekinumab. Patients
diagnosed with mycosis fungoides were treated with systemic corticosteroids and systemic
acitretin. Other patients only used systemic steroids as treatment.
DISCUSSION
Erythroderma usually occurs in men over the age of 60. The reason for this could be alcohol
intake,skin structure and physiology, the effect of sex hormones and predominant outdoor
work by male patients which are known to exacerbate psoriasis and eczemas respectively
(6).In our study, the majority of the patients were men over the age of 54. The most common
etiological cause of erythroderma is psoriasis.Conditions that caused erythroderma in patients
with psoriasis include irregular use or abrupt discontinuation of drugs, stress and seasonal
changes.The most common causes after psoriasis were drug eruption and MF. In our study,
the majority of patients were diagnosed with psoriasis (6-10). Pemphigus foliaceus was not
found in our study.The relative frequency of pemphigus foliaceus has been recently evaluated
in a Tunisian retrospective study and was 6.25% (7). In the literature etiology cannot be
determined in 6.7-47% of the cases. Although there were idiopathic cases in other studies, the
histopathological diagnosis of all patients was confirmed in our study. The reason of this may
be we carried out histopathology as soon as possible and repeated in different areas and
different stages of erythroderma (10, 11). The most common drugs causing erythroderma are
anticonvulsants (especially carbamazepine), penicillin, allopurinol, trimethoprim-
sulfamethoxazole, cephalosporins, rifampicin, amoxicillin, sulfanilamide, aminopyrine,
indomethacin and albumin (12-15). Amoxicillin was the most frequent drug quoted in our
cases, with 4 of the 8 cases (50%) related to this medication.We identified the correct drug,
excluding erythroderma caused by anticonvulsants, in only 1/47 cases. This is quite a low rate
compared to other studies.
Regardless of the etiology, the clinical appearance of erythroderma is similar in all patients.
The most prominent physical examination findings in almost all patients are diffuse erythema
and scaling. Also pruritus is present in most of the patients. Other studies also report the
elevated frequency of pruritus, affecting generally more than 90% of the patients (13, 15).
While fever was as common as pruritus in our study, it was a rare finding in other studies (9).

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Fever was generally more common in patients with drug reactions. This has been attributed to
drug hypersensitivity in previous studies (16). In the literature, palmoplantar keratoderma and
nail alterations are more commonly described in psoriasis. In our study palmoplantar
keratoderma and nail changes were less common than previous studies (2,9, 13, 17).
Leukocytosis and eosinophilia are common in erythrodermic patients. In our study, while
leukocyte was seen in 55% of patients, eosinophilia was seen in 23% of patients. It is similar
with previous studies (2, 12). We observed increased LDH in 10% of the patients. Elevated
LDH is a prognostic marker in cutaneous lymphomas (18). As expected all of these patients
were diagnosed with mycosis fungoides. Hypoalbuminemia is a common laboratory finding
in erythroderma patients. It may occur due to extensive protein loss by a high epidermal
turnover rate,chronic malnutrition, or dilution due to hypervolemia (4, 13).
Most of the clinical features and laboratory abnormalities are non-specific. Some findings
may help diagnose. For example; high levels of IgE are associated with atopic dermatitis and
drug reactions; palmoplantar keratoderma and nail changes are associated with psoriasis and
high levels of LDH areassociated with mycosis fungoides.
In the treatment of erythroderma, first of all, it is aimed to eliminate the triggering factor, to
protect the body hemodynamics and to prevent infections. Diagnostic treatments are added
when the patient's clinical condition stabilized (19, 20). Erythroderma is one of the
dermatological diseases that require urgent intervention. Therefore it requires rapid diagnosis
and treatment.

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TABLES
Table 1. Etiological factors in patients with erythroderma
Frequency Percent %
Psoriasis vulgaris 28 59.6
Drug eruption 8 17
Mycosis fungoides 6 12.8
Atopic dermatitis 2 4.3
Bullous pemphigoid 1 2.1
Pityriasis rubra pilaris 1 2.1
Polymorphic light eruption 1 2.1
Total 47 100

Table 2. Clinical findings and laboratory disorders in patients with erythroderma

Clinical findings and laboratory disorders Frequency
Pruritus 37
Fever 36
Nail changes 17
Palmoplantar keratoderma 16
Lymphadenopathy 12
Mucosal involvement 7
Leukocytosis (>10.000/mm3) 26
Increase in C-reactive protein (CRP) 22
Increased erythrocyte sedimentation rate (ESR) 15
High BUN, creatinine levels (> 25mg / dL,> 1.5 mg / dL) 13
Anemia (Hgb<12g/dL) 11
Eosinophilia 11
Hypoalbuminemia (<3.5 g / dL) 11
Hypoglycemia 9
High serum transaminases levels (> 40 U / L) 8
Hypopotasemia (<3.5 mmol / L) 7
High lactate dehydrogenase levels (LDH) (> 243 U / L) 5
High gamma glutamyl transferase levels (GGT) (> 50 U / L) 5
Increase in total IgE levels 5
High alkaline phosphatase levels (ALP) (> 141 U / L) 3

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Hyponatremia (<130 mmol / L) 3
Hypocalcemia (<8.2 g / dL) 2

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Accepted Article

Fo
rR
ev
iew
On
ly

Figure 1. Diffuse scaling and erythema in a patient diagnosed with psoriasis

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Accepted Article

Figure 2. Onycholysis, pitting, subungal hyperkeratosis and splinter hemorrhage of the nail in a patient
diagnosed with psoriasis

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Accepted Article

Figure 3. Subungal hyperkeratosis, oil drop, onycholysis and transverse streaking of the nail in a patient
diagnosed with psoriasis

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