Erythroderma
Salient
features
· Erythroderma is a serious, at
times life-threatening reaction pattern of the skin characterized by a uniform
redness, infiltration, and scaling, which involves practically the entire skin.
· It is associated with
fever, malaise, shivers, and generalized lymphadenopathy.
· Two stages, acute and chronic, merge one into the other. In the acute and subacute phases, there is rapid onset of generalized vivid red erythema and fine branny scales; the patient feels hot and cold, shivers, and has a fever. In chronic erythroderma, the skin thickens, and scaling continues and becomes lamellar.
· There may be loss of
scalp and body hair, and the nails become thickened and separated from the nail
bed (onycholysis).
· There may be hyper
pigmentation or patchy loss of pigment in patients whose normal skin
pigmentation is brown or black.
· The most frequent
preexisting skin disorders are (in order of frequency) psoriasis, atopic
dermatitis, adverse cutaneous drug reaction, cutaneous T-cell lymphoma (CTCL),
allergic contact dermatitis, seborrheic dermatitis, and pityriasis rubra
pilaris.
Erythroderma is the term used to
describe intense and usually widespread reddening
of the skin due to inflammatory skin disease.
It often precedes or is associated with exfoliation,
when it may also be known as exfoliative dermatitis (ED).
Erythroderma
is the term applied to any inflammatory skin disease that affects more than 90%
of the body surface.
Introduction
Erythroderma is defined as a generalized redness and scaling
of the skin. Most commonly, erythroderma is due to generalization of
pre-existing dermatoses (such as psoriasis or atopic dermatitis), drug
reactions or cutaneous T-cell lymphoma (CTCL). Although up to 50% of the
patients have a history of more localized skin lesions prior to the onset of
the erythroderma and in approximately one-quarter of the patients, no specific
etiology is found, and these cases are called “idiopathic erythroderma”.
Attention should also be focused on the potential systemic
complications of erythroderma. Hypothermia, peripheral edema, and loss of
fluid, electrolytes and albumin with subsequent tachycardia and cardiac failure
are a serious threat to the erythrodermic patient. In addition, long-lasting
erythrodermas may be accompanied by cachexia, diffuse alopecia, palmoplantar keratoderma,
nail dystrophy and ectropion.
Epidemiology
Men are more commonly affected (male-to-female ratio is 3: 1).
An even higher ratio can be found in the subset of idiopathic erythroderma,
also referred to as “red man syndrome” (not to be confused with the cutaneous
reaction to rapid infusion of vancomycin).
Erythrodermic atopic dermatitis most
often affects children and young adults, but other forms of erythroderma are more common in middle-aged and elderly
people. The average age at onset of erythroderma is usually >5O years.
When categories within the dermatitis group were
examined, atopic dermatitis (9%) was the most common type, followed by allergic
contact dermatitis (6%), seborrheic dermatitis (4%) and chronic actinic
dermatitis (3%).
Predisposing
factors
Causes of erythroderma and relative
prevalence in adults
|
Condition
causing erythroderma |
Relative
prevalence (%) |
|
Eczema of
various subtypes |
40.0 |
|
Psoriasis |
25.0 |
|
Lymphoma and
leukaemias |
15.0 |
|
Drugs
(including phenylbutazone, phenytoin, carbamazepine, gold salts, lithium,
cimetidine) |
10.0 |
|
Unknown |
8.0 |
|
Hereditary
disorders (ichthyosiform erythroderma, pityriasis rubra pilaris) |
1.0 |
|
Pemphigus
foliaceus |
0.5 |
|
Other skin
diseases (lichen planus, dermatophytosis, crusted scabies, dermatomyositis) |
0.5 |
Pathogenesis
The number of germinative cells as well as their mitotic
rate is increased in erythrodermic skin, and the transit time of cells through
the epidermis is shortened. Consequently, scales consist of material normally
retained by the skin (nucleic acids, amino acids, soluble protein), and the
daily loss of scales increases from 500–1000 mg to 20–30 g. In acute
erythroderma, the lost material usually has marginal metabolic significance.
Pathology
Histopathology can help identify the
cause of erythroderma in up to 50% of cases, particularly if multiple skin
biopsies are examined. It depends on the type of underlying disease. In all, there
is parakeratosis, inter- and intra-cellular edema, acanthosis with elongation
of the rete ridges, exocytosis of cells, edema of the dermis, and an
inflammatory infiltrate.
Clinical
features
Erythroderma is
defined clinically as diffuse erythema and scaling of the skin
involving more than 90% of the total body skin surface area. Based upon its natural history, erythroderma
can be classified into primary or secondary types. In the primary form, the
erythema (often initially on the trunk) extends within a few days or weeks to
involve the entire skin surface, and this is followed by scaling. The secondary
form of erythroderma is defined as a generalization of a preceding localized
skin disease – for example, psoriasis or atopic dermatitis.
Presentation
With the exception of very slowly progressing secondary
erythroderma, the erythema extends rapidly, and may be universal in 12–48 h.
Scaling begins
2-6 days after the onset of erythema, often first in the flexures. The associated scaling varies extensively in
size and color depending upon the stage of the erythroderma and nature of the
underlying disease. In more acute phases, scales are usually large and crusted,
whereas in chronic states they tend to be smaller and drier. Occasionally, the
cause of the erythroderma is suggested by the character of the scale – for example,
fine in atopic dermatitis or dermatophytosis, bran-like in seborrheic
dermatitis, crusted in pemphigus foliaceus, and exfoliative in drug reactions. Dermatitis is uniform involving the entire
body surface, except for pityriasis rubra pilaris, where ED spares sharply
defined areas of normal skin
Despite the varied causes,
erythrodermas have several common clinical features. Pruritus, the most
frequent complaint, is observed in up to 90% of patients. This symptom varies
according to the underlying cause, and it is most severe in patients with
dermatitis or Sézary syndrome. Given the itch–scratch cycle, the skin may
become lichenified. At this stage the
skin is bright red, hot and dry, and palpably thickened. The intensity of the
erythema may fluctuate over periods of a few days or even a few hours.
Irritation is sometimes severe, but a sensation of tightness is more
characteristic. Many patients complain of feeling cold, especially when the
erythema is increasing.
When the erythroderma has been
present for some weeks, the scalp and body hair may be shed and the nails
become ridged and thickened and they may also be shed. The periorbital skin is
inflamed and edematous, resulting in ectropion, with consequent epiphora. In
very chronic cases there may be pigmentary disturbances, with hyper
pigmentation observed more frequently, but hypo- or depigmentation especially
seen in dark skin people. Palmoplantar keratoderma appears in approximately 30%
of erythrodermic patients, and it is often an early sign in pityriasis rubra pilaris.
The most common extracutaneous
manifestation of erythroderma is generalized peripheral lymphadenopathy, which
is found in approximately half of the patients. It is important that this
dermatopathic lymphadenopathy is not mistaken for lymphoma. In difficult cases,
lymph node biopsy may be advisable, but the pathologist must be told that the
patient is erythrodermic for a reliable histological interpretation to be made.
Clinical variants
Clinical variants are considered in
terms of the underlying cause of the erythroderma:
Eczematous
dermatoses
Generalization
of eczema occurs most frequently in the sixth and seventh decades when venous
eczema is a common precedent. However, atopic erythroderma may occur at any
age. Exacerbation of existing lesions usually precedes the generalization,
which follows the usual pattern. Pruritus is often intense. Some elderly
patients have increased serum IgE and lactic dehydrogenase levels, with
eosinophilia.
Psoriasis
Psoriasis is the most common
underlying disorder in adults. As a rule, psoriatic erythroderma is preceded by
typical psoriatic plaques. In erythrodermic psoriasis the clinical picture may
be highly desquamative, but when the erythroderma is fully developed the
typical features of psoriatic plaques are lost. In some cases, crops of miliary
sterile subcorneal pustules may develop at intervals, and transition to
generalized pustular psoriasis may occur, especially in cases treated with
potent topical corticosteroids or systemic steroids. Emotional stress,
intercurrent illness and phototherapy over dosage may also precipitate
erythroderma. Due to a slower turnover rate, nail changes, such as oil-drop
changes, onycholysis or nail pits, may still be visible and provide valuable
clues to the diagnosis of psoriatic erythroderma. Treatment of the erythroderma
may result in the reappearance of more characteristic plaques of psoriasis.
Lymphoma, leukemia and other
malignancy
Cutaneous T‐cell lymphoma is the commonest malignancy
to cause erythroderma, followed by Hodgkin disease. Non‐Hodgkin lymphoma, leukemias and
myelodysplasia have also been reported as causes.
Erythroderma due to CTCL is subdivided into Sézary syndrome
and erythrodermic mycosis fungoides. Sézary syndrome is defined by the triad of
erythroderma, circulating malignant T lymphocytes, and generalized
lymphadenopathy. Additional clinical features include a painful and fissured
keratoderma, diffuse alopecia, and leonine facies. The skin may be quite
infiltrated or hyper pigmented (melano erythroderma), and severe pruritus is
common. To aid in distinguishing between Sézary syndrome and erythrodermic
mycosis fungoides, revised criteria were recently proposed by the International
Society of Cutaneous Lymphomas and the Cutaneous Lymphoma Task Force of the
EORTC for the diagnosis of Sézary syndrome – erythroderma and evidence of a
T-cell clone in the blood plus one of the following: (1) ≥1000 Sézary cells/mm3;
(2) a CD4 : CD8 ratio of ≥10 : 1; or (3) an increased percentage of CD4+
cells with an abnormal phenotype (≥40% CD4+/CD7− or ≥30%
CD4+/CD26−).
Drugs
A wide range of drugs can cause erythroderma. Among the more
commonly implicated are phenytoin, phenobarbitol, carbamazepine, beta lactam
antibiotics, allopurinol, sulphonamides and lithium. Whereas erythroderma
resulting from topical medications usually begins as eczema which then become
generalized, eruptions due to systemic drugs begin as a morbilliform or
scarlatiniform exanthem, often accompanied by some irritation, which increases
steadily in severity. In areas of
greatest hydrostatic pressure (ankles and feet), the lesions may become
secondarily purpuric. This group has the
best prognosis of all the causes of erythroderma, often resolving in 2–6 weeks after withdrawal of
responsible drug; possible exception is DIHS/DRESS which may be accompanied by the involvement of other organs,
for example hematological abnormalities, hepatitis, nephritis or pneumonitis.
Erythroderma
of unknown origin
In approximately one-third of
erythrodermic patients, no underlying disease is detectable. This group
consists primarily of elderly men, in whom the condition runs a very long
course with partial remissions and relapse, sometimes known as the ‘red man
syndrome’. It is characterized by marked palmoplantar keratoderma,
dermatopathic lymphadenopathy and a raised serum IgE. When this group was compared
with the entire group of erythrodermic patients, lymphadenopathy (68% vs 44%)
and peripheral edema (54% vs 40%) were found to be more common than in other
types of erythroderma, and hypothermia exceeded hyperthermia. The three
commonest causes of idiopathic protracted erythroderma are probably atopic
eczema of the elderly, intake of drugs overlooked by the patient and pre lymphomatous
eruptions.
Complications
and co‐morbidities
The main complications of
erythroderma are hemodynamic and metabolic disturbances. The patient is unwell
with fever, temperature dysregulation and losing a great deal of fluid by
transpiration through the skin.
· Because of the markedly increased blood flow through the
skin, there is a risk of high-output cardiac failure, particularly in elderly
persons.
· Heat loss leads to hypothermia, most patients describe
chilly sensations.
· Fluid loss leads to electrolyte abnormalities and
dehydration.
· Hypo albuminemia is due to increased protein loss from
exfoliated scale, which may reach >9 g/m2 of body surface each
day and due
to increased metabolic rate. Leg edema may
be due to inflamed skin, high output cardiac failure and/or hypo albuminemia.
· The chronic and excessive loss of heat leads to a
compensatory hyper metabolism with subsequent development of cachexia.
· Anemia, characterized by features of both iron deficiency
and anemia of chronic disease, is also observed in patients with chronic erythroderma.
Disease
course and prognosis
Erythroderma is a potentially fatal
condition as erythroderma remains particularly dangerous in elderly people. Secondary skin infection and
respiratory infections are common and pneumonia remains the commonest cause of
death. Complications resulting from systemic treatment of the erythroderma also
contribute to mortality rates.
The
more frequent forms of erythroderma, including eczematous, psoriatic or of
unknown origin, may continue for months or years and often follow a relapsing‐remitting course.
Management
Erythroderma can represent a serious
medical threat to the patient, therefore hospitalization may be required.
Regardless of the underlying disease, the initial management consists of
nutritional assessment, correction of fluid and electrolyte imbalances,
prevention of hypothermia, and treatment of secondary infections. All non‐essential drugs should be withdrawn
if they might be responsible for the erythroderma.
The cutaneous inflammation should be
treated in the first instance with greasy emollients in order to restore skin
barrier function. Other topical
treatments should be used with caution because systemic absorption is greatly
increased. The majority of patients will improve over a week or two with this
regimen, during which time the diagnosis of the underlying condition will
probably be established.
Sedating oral antihistamines may ease the often severe
pruritus. Systemic corticosteroids may be necessary in idiopathic erythroderma
and drug reactions. With an initial dose of 1–2 mg/kg/day of prednisone,
and a maintenance dose of 0.5 mg/kg/day or less, rapid and often continued
clearing of the erythroderma can be achieved. Caution must be exercised upon
tapering, as rebound may occur. Topical therapy includes open wet dressings and
bland emollients or low-potency corticosteroid ointments. High-potency topical
corticosteroids should be reserved for lichenified areas, and chronic,
extensive application should be avoided. Coal tar ointments may aggravate the
condition.
Treatment of specific underlying
diseases
In the case of psoriatic erythroderma, administration of
methotrexate, acitretin, cyclosporine or targeted immunomodulators (biologic
agents) is preferred over systemic corticosteroids, given the risk of a
pustular flare when corticosteroids are tapered. For drug reactions, following
the discontinuation of all non-essential drugs and all suspected drugs,
erythroderma usually improves within 2–6 weeks (with the exception of some
patients with DRESS/DIHS). After careful exclusion of any underlying cause,
idiopathic erythroderma may be treated with low-potency topical corticosteroids
and oral antihistamines. In refractory cases, cyclosporine has been used
successfully, with an initial dosage of 5 mg/kg/day, and subsequent
reduction to 1–3 mg/kg/day. Additional steroid-sparing agents include methotrexate,
azathioprine and mycophenolate mofetil, all of which have been used
anecdotally, with dosages similar to those for recalcitrant atopic dermatitis.
Therapeutic ladder
First line
·
Consider hospital admission
·
Withdraw or switch medications that
may be implicated as a cause
·
Monitor and correct loss of
homeostasis including temperature and fluid balance
·
Treat any secondary infection
·
Frequent application of greasy
emollients
Second line
·
Systemic therapy dependent on
underlying cause
