rothe et al. (2005) - life-threatening erythroderma- diagnosing and treating the red man

8/10/2019 Rothe Et Al. (2005) - Life-threatening Erythroderma- Diagnosing and Treating the Red Man

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Life-threatening erythroderma: diagnosing and

treating the bred manQ

Marti Jill Rothe, MD*, Megan L. Bernstein, BS, Jane M. Grant-Kels, MD

Department of Dermatology, University of Connecticut Health Center, Farmington, CT 06030, USA

Abstract Exfoliative erythroderma, or diffuse erythema and scaling of the skin, may be the

morphologic presentation of a variety of cutaneous and systemic diseases. Establishing the diagnosis

of the underlying disease is often difficult and, not uncommonly, erythroderma is classified as

idiopathic. Several cases are presented to demonstrate the diversity of presentation of this disease.

Laboratory findings are typically unhelpful in establishing the etiology of erythroderma. Clinical data

combined with multiple skin biopsies over time are necessary. Systemic complications of erythroderma

include infection, fluid and electrolyte imbalances, thermoregulatory disturbance, high output cardiac

failure, and acute respiratory distress syndrome. The initial approach to the management of

erythroderma of any etiology includes attention to nutrition, fluid and electrolyte replacement, and

the institution of gentle local skin care measures. Oatmeal baths and wet dressings to weeping or crusted

sites should be followed by application of bland emollients and low-potency topical corticosteroids.

Systemic dermatologic therapy may be required to maintain improvement achieved with local measures

or to control erythroderma refractory to local measures. The prognosis of erythroderma is dependent onthe underlying etiology.

D 2005 Published by Elsevier Inc.

Introduction

Exfoliative erythroderma, or diffuse erythema and

scaling of the skin, may be the morphologic presentation

of a variety of cutaneous and systemic diseases (Table 1).

The dermatologist is faced with multiple challenges when

caring for the patient with exfoliative erythroderma.

Establishing the diagnosis of the underlying disease is often

difficult and, not uncommonly, erythroderma is classified as

idiopathic. Exfoliative erythroderma places the patient at

high risk for secondary infection as well as cardiovascular

and respiratory compromise. Additional risks are posed by

systemic dermatologic therapy, which is often required to

control the disease. The following case summaries highlight

these clinical challenges.

Case presentations

Case 1

In March 2000, a 55-year-old man is referred for a

second opinion to the university for a 1-year history of

abrupt-onset erythroderma refractory to cyclosporine and

acitretin. The patient complains of fissuring of the palms

and soles and of being cold and pruritic but has been able to

continue his work as a financial analyst. No new med-

ications were initiated before the onset of erythroderma, and

0738-081X/$ see front matterD 2005 Published by Elsevier Inc.

doi:10.1016/j.clindermatol.2004.06.018

* Corresponding author. Tel.: +1 860 679 4176; fax: +1 860 679 1267.

E-mail address: [email protected] (M.J. Rothe).

Clinics in Dermatology (2005) 23, 206217


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discontinuation of medications was unhelpful. The patients

past medical history is significant for hypertension and

alcoholism in recovery. Personal and family history are

negative for psoriasis and atopy. Physical examination

shows a diffuse salmon-colored erythroderma of the skin

with only rare small spared areas, keratoderma, mild

ectropion, and scattered excoriations. Multiple biopsies

show spongiotic dermatitis; one biopsy shows focalfollicular plugging and focal parakeratosis alternating with

orthokeratosis, both horizontally and vertically (Fig. 1). A

presumptive diagnosis of pityriasis rubra pilaris is made.

The patient is referred to a hepatologist for clearance to

initiate methotrexate therapy. While awaiting results of the

hepatology evaluation, the patient develops new-onset pain

in his sacroiliac joints and fingers. He is evaluated by

rheumatology and the diagnoses of psoriatic arthritis and

probable psoriatic erythroderma are made. There is a

gradual response to methotrexate 25 mg weekly with only

few small residual psoriatic plaques. The patient is

ultimately able to taper off methotrexate with remission of

his joint and skin disease.

Case 2

In November 1998, a 26-year-old woman with a 5-year

history of psoriasis vulgaris is evaluated for worsening

disease failing to clear with topical steroids. A 30-treatment

trial of broadband ultraviolet B is ineffective. Psoralen-UV-

A therapy is initiated with an initial response followed by a

flare that eventuates into erythroderma. Multiple biopsies are

obtained and only one reveals the definitive changes of

psoriasis (Figs. 2 and 3). Over the course of 5 years the

erythroderma has waxed and waned but there has been only a

partial response to topical therapy, methotrexate, and

Table 1 Differential diagnosis

Dermatoses

Psoriasis

Atopic dermatitis

CTCL

Pityriasis rubra pilaris

Superficial pemphigus

Bullous pemphigoid

Contact dermatitis

Chronic actinic dermatitis

Pseudolymphoma1

Hailey-Hailey 2

Infections

Dermatophyte3,4

Norwegian scabies

Toxoplasmosis5

Histoplasmosis6,7

Leishmaniasis8

HIV

Tuberculosis9

Systemic

Subacute cutaneous lupus10

Dermatomyositis11-14

Acute graft-vs-host disease15

Postoperative transfusion induced16

Sarcoidosis17,18

Thyrotoxicosis19

Common variable hypogammaglobulinemia20

Severe combined immune defect with Omenns syndrome21

Leiners disease

Maple syrupurine disease22

Histiocytosis23

Hypercalcitonemia24

HematologicHodgkins lymphoma3,25-27

B-cell lymphoma28

Anaplastic large cell lymphoma29

Acute myelomonocytic leukemia30

Adult T-cell leukemia31

Chronic lymphocytic leukemia25

Reticulum cellsarcoma32

Myelodysplasia33

Chronic eosinophilic leukemia34

Malignancy

Prostate3,4

Lung3,4,35

Thyroid3

Liver3,36

Breast4

Ovary4

Fallopiantube37

Rectum4

Esophagus38

Stomach35,39

Melanoma4,40

Buschke-Loewenstein tumor (a verrucous carcinoma on anogenital

mucosal surfaces)41Fig. 1 Biopsy changes consistent with pityriasis rubra pilaris

demonstrating follicular plugging and alternating orthokeratosis

and parakeratosis (hematoxylin and eosin, original magnification

20 ).

Life-threatening erythroderma: diagnosing and treating the bred manQ 207


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cyclosporine alone and in combination with mycophenolate

mofetil. The patients care is complicated by obesity,

underlying hypertension and diabetes, and noncompliance.

She is engaged to be married and interested in conceiving

within the next several years. She has required hospitaliza-

tion for secondary infection and shows partial improvement

of the erythroderma during the admission. The patients

internist has been reluctant to approve treatment with a

biologic agent because of poor control of the diabetes

secondary to noncompliance.

Case 3

A 40-year-old man reports the abrupt onset of near

erythroderma (Fig. 4) after treatment with clindamycin for a

dental abscess while on a golf trip to Florida in February

2003. There is no personal or family history of atopy or

psoriasis. Past medical history is significant for hypertension

and hyperlipidemia. There is no resolution of the eruption

upon discontinuation of his systemic medications, which are

subsequently restarted. Examination shows diffuse erythema

of the face with lichenified plaques of the forehead and

multiple excoriations of the scalp, widespread scaling and

erythema of the trunk and the extremities with some areas of

sparing, and circinate plaques with peripheral desquamation

affecting the thighs and buttocks. Biopsy reveals spongiotic

dermatitis and periodic acid-Schiff (PAS) stain is negative.

Direct immunofluorescence is negative. There is no improve-

ment with topical therapy and antihistamines, but there is

partial improvement while the patient is on a business trip to

South Carolina in the spring. The patient is reluctant to begin

empiric therapy with methotrexate and his internist believes

the patient requires ongoing treatment with atorvastatin,

which precludes concomitant treatment with cyclosporine.

Because of partial improvement with sun exposure, the

patient agrees to therapy with narrowband ultraviolet B in

June 2003. By October 2003, the lower extremities and

buttocks are completely clear, but there are residual small

plaques with silvery scale over the trunk and proximal

upper extremities and persistence of lichenified plaques

over the forehead. The patient declines biopsy of the residual

eruption but plans to continue phototherapy until a month-

long trip to Florida.

Case 4

A 42-year-old black woman with a history of atopic

dermatitis presented to her internist with weight loss,

fatigue, and erythroderma. Previously she had been healthy

and on no medications. Physical examination shows

erythroderma, diffuse alopecia of the scalp and loss of the

lateral eyebrows, peripheral lymphadenopathy, erosions of

the hard palate, punctate purpura affecting the pulps of

several fingers, and dilated vessels about the nail folds.

Fig. 2 Biopsy demonstrating psoriasis with epidermal hyperpla-

sia, hypogranulosis, and spongiform pustular formation (hematox-

ylin and eosin, original magnification 2.5 ).

Fig. 3 Higher magnification of spongiform pustule within the

epidermis (hematoxylin and eosin, original magnification 20 ).

Fig. 4 Patient in case 3 with widespread erythema and areas ofspared skin.

M.J. Rothe et al.208


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Laboratory examination reveals a decreased white blood cell

count and antinuclear antibody test is positive at 1:1280 rimpattern. Skin biopsy shows an interface dermatitis (vacuolar

alteration and a superficial as well as interface lymphohis-

tiocytic infiltrate) (Fig. 5). Her erythroderma clears with

oatmeal baths and mid potency topical steroids. She was

referred to rheumatology for further workup and manage-

ment of her collagen vascular disease.

Case 5

A 60-year-old man with a long history of psoriasis

vulgaris was referred to the university in November 1993

for management of a flare refractory to topical therapy and

etretinate. Physical examination shows a shivering patientwith widespread salmon-colored erythema of the face,

trunk, and extremities with some clear areas. The margins

of plaques adjacent to spared areas show collarettes (Fig. 6).

Biopsy of lesional skin shows predominantly eosinophilic

spongiosis (Fig. 7) without definitive evidence of acanthol-

ytic keratinocytes. Direct immunofluorescence of perile-

sional skin is positive for intercellular IgG particularly

prominent in the superficial portion of the epidermis.

Pemphigus foliaceus clears with pulse steroids, and meth-

otrexate provides chronic control of his psoriasis and

pemphigus for the following 10 years.

Case 6An 80-year-old woman with Alzheimers disease who

resides in a nursing home is referred to the university for

progressively worsening atopic dermatitis despite topical

and systemic steroid therapy. Physical examination reveals

widespread erythema (Fig. 8) sparing only her face and

Fig. 7 Histology demonstrated eosinophilic spongiosis (hema-

toxylin and eosin, original magnification 10 ).

Fig. 8 Elderly patient in case 6 with near erythroderma. Scabies

preparation with a burrow shows mites, eggs, and fecal material.

Fig. 5 Biopsy demonstrating an interface dermatitis (hematox-

ylin and eosin, original magnification 20 ).

Fig. 6 Clinically, collarettes are noted indicating a previously

ruptured blister.



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some areas over her chest, keratoderma, and fingernail

dystrophy. Closer examination of the primary lesions of her

chest shows coalescing burrows. Scabies preparation is

positive. The patient is successfully treated with several

courses of permethrin cream.

Epidemiologic and clinical features oferythroderma

The above cases are illustrative of the varied clinical

presentations of erythroderma. There are multiple published

epidemiologic studies of erythrodermic patients.3,4,25,26,32,35,42-48 A male predominance has been observed, with

a male-to-female ratio ranging from 2:1 to 4:1. The average

reported age of affected patients is 41 to 61 years, with most

published series excluding children. The most commonly

diagnosed etiologies are psoriasis, spongiotic dermatitis, drug

Fig. 9 Patient with erythrodermic psoriasis and classic plaques

on elbows.

Table 2 Drugs implicated in erythroderma

Allopurinol25,44,47,53

Amiodarone54

Antimalarials3,25,32,50,55

Arsenicals54

Aspirin54

Aztreonam54

Barbiturates55

Bromodeoxyuridine56

Bupropion57

Captopril58

Carbamazepine47,53,59

Carboplatin60

Cefoxitin61,62

Chlorpromazine44

Chlorpropamide54

Cimetidine63

Cisplatin64

Clodronate65

Clofazimine66

Codeine3

Dapsone67,68

Dideoxyinosine69

Diltiazem70

Doxycycline71

Ephedrine72

Epoprostenol73

Etumine47

Erythropoietin74

Ethylenediamine75

Fluindione76

Fluorouracil54

Gentamicin77

Gold3,32,44,53

Hypericum (St. Johns wort)78

Indinavir79

Interleukin-280

Iodine3

Isoniazid25,26,46

Isosorbide dinitrate25

Lamotrigine81

Lithium82

Mercurials3,26

Mexiletine54

Minocycline54

Neomycin54

Nifedipine83

Omeprazole84

Penicillin3,25,26,32

Phenobarbital85

Phenolphthalein3

Phenothiazines54

Phenylbutazone46

Phenytoin25,35,51,86,87

Practolol44

Propolis88

Pseudoephedrine89

Quinidine32,53

Ranitidine54

Retinoids90

Rhus (lacquer)91

Ribostamycin92

Streptomycin3,46

Sulfasalazine52

Sulfonamide antibiotics3,25

Sulfonylureas54

Terbinafine93

Terbutaline25

Tetrachloroethylene3

Thalidomide94,95

Thiacetazone46

Thiazide25

Timolol eyedrops96

Trimethoprim44

Tumor necrosis factor-a80

Vancomycin97

Zidovudine98

Table 2 (continued)



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reactions, and cutaneous T-cell lymphoma (CTCL). Eryth-

roderma is classified as idiopathic in 9% to 47% of cases.

Erythroderma may be attributable to an exacerbationof a

preexisting dermatosis in more than half of patients.49

Usually, patients with erythroderma secondary to psoriasis

or spongiotic dermatitis have a history of more localized

disease before the onset of erythroderma.43 In a review of50

patients with psoriatic erythroderma, Boyd and Menter

50

observed an average age of onset of 48 years, a male-to-

female ratio of 2:1, and an average of 14 years between the

onset of psoriasis and the development of erythroderma.

Triggers of psoriatic erythroderma include withdrawal of

topical or systemic corticosteroids; abrupt discontinuation of

methotrexate; topical irritants such as tars; systemic

medications such as antimalarials, lithium, and terbinafine;

phototherapy burns; infection, including HIV; pregnancy;

emotional stress; and systemic illness. Classic plaques of

psoriasis vulgaris may be evident in early and remitting

stages of erythroderma (Fig. 9). Psoriatic arthritis and

psoriatic nail changes may be present in some cases.

It is important to consider other possible etiologies even

in patients who may have a clear history of psoriasis or

atopic dermatitis or who may have features of psoriasis

vulgaris on examination. Eugster et al49 describe 7 patients

with malignancy-related erythroderma, 5 of whom had a

history of preexisting dermatosis.

Onset of erythroderma due to drug reactions is typically

sudden and rapid and its resolution is typically faster than

cases of erythroderma due to other causes. A notable

exception occurs when erythroderma accompanies systemic

drug hypersensitivity reactions due to antibiotics, anticon-

vulsants, and allopurinol. Hypersensitivity develops within

2 to 5 weeks after the medication is started and may persistfor weeks despite discontinuation of the medication. Fever,

leukocytosis with eosinophilia, edema, lymphadenopathy,

organomegaly, and liver and renal dysfunction are charac-

teristic.51,52 Table 2provides a comprehensive list of drugs

implicated in drug-induced erythroderma.

Sezary syndrome is by definition manifested as eryth-

roderma, lymphadenopathy, hepatosplenomegaly, and cir-

culating Sezary cells. Pruritus is typically severe. Long-

standing disease is characterized by painful fissured

keratoderma (Fig. 10) and leonine facies secondary to

lymphomatous infiltration of the skin (Fig. 11).99

Pityriasis rubra pilaris often begins as a seborrheicdermatitis-like eruption of the scalp that quickly evolves,

especially after intense sun exposure, into a generalized

salmon-colored erythema with islands of sparing. Kerato-

derma is a prominent and early feature. Follicular pink

papules affecting the dorsal fingers, wrists, and elbows may

be present.

The diagnosis of erythroderma secondary to immuno-

bullous disease is most readily made when blisters and

erosions are present. Superficial pemphigus may show

impetigo-like erosions or collarettes indicative of a ruptured

blister. Tense blisters are usually, but not always, a feature of

erythrodermic bullous pemphigoid.100

Pathognomonic features may facilitate the diagnosis of

erythrodermic dermatomyositis (eg, Gottrons papules,

heliotrope,poikiloderma, periungual telangiectasis, muscle

weakness),12,13 chronic actinic dermatitis (eg, photoaccen-

tuation), erythrodermic sarcoidosis (eg, apple jelly

lesions),17 and Norwegian scabies (eg, burrows).

Symptoms common to erythroderma of any etiology are

thermoregulatory disturbance, malaise, fatigue, and pruritus.

Lichenification, diffuse alopecia, dermatopathic lymphade-

nopathy, keratoderma, nail dystrophy, and ectropion are

signs common to long-standing erythrodermas of anyFig. 10 Patient with fissuring of Sezary.

Fig. 11 Histology demonstrating epidermotropism of enlarged

mononuclear cells with minimal spongiosis consistent with CTCL

(hematoxylin and eosin, original magnification 25 ).



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etiology47 (Fig. 12). Pitting pretibial and pedal edema is

observed in 50% of erythrodermic patients.73,94

Laboratory investigations

Laboratory findings are most often not diagnostic for

etiology of erythroderma. Common abnormalities found in

erythrodermic patients include leukocytosis, anemia, elevat-

ed erythrocyte sedimentation rate, lymphocytosis, eosino-

philia, and increased serum IgE.3,25,32,43,44,46,47,53,101 In a

clinical study by Sigurdsson et al,53 13 of 102 patients had

an erythrocyte sedimentation rate higher than 30 mm/h, 8 of

whom had idiopathic erythroderma. Other findings include

elevated creatinine level, elevated uric acid level, and

lowered serum protein levels.26,47 Eosinophilia is not

diagnostic for etiology. Eosinophil count greater than1.0

109/L, however, was found in 20% of patients.53 The

negative nitrogen balance found in chronic erythroderma

can lead to findings of hypoalbuminemia.

32

Sezary cell count analysis can be used for diagnosis of

Sezary syndrome. More than 20% circulating Sezary cells is

diagnostic for Sezary syndrome, whereas less than 10% is

nonspecific.45,53 Sezary cells are found in these lower

numbers in many benign dermatoses, including atopic

dermatitis, psoriasis, lichen planus, discoid lupus, and

parapsoriasis.102

Immunophenotyping of skin lymphocytes can be used to

differentiate Sezary syndrome from actinic reticuloid.

Sigurdsson et al53 found predominance of CD8+ lympho-

cytes in 7 of 12 patients with actinic reticuloid. Differen-

tiation between Sezary syndrome and actinic reticuloid can

also be accomplished via nuclear contour index of

peripheral blood lymphocytes.103

Clinical data combined with multiple skin biopsies over

time are necessary. T-cell receptorb gene rearrangement on

peripheral blood smears is used for sensitive and specific

differentiation ofSezary syndrome from other benign forms

of erythroderma.104 This technique has been applied to skin

biopsies as well; in recent studies, specificity has been 100%

Fig. 12 Diffuse alopecia in patient with chronic idiopathic

erythroderma.

Table 3 Histologic differential diagnosis of the erythrodermic patient

Disease Diagnostic histological clue

Actinic reticuloid Atypical mononuclear cells admixed in a superficial, lichenoid, and deep dermal infiltrate;overlying lichen simplex chronicus with or without spongiosis

Atopic dermatitis Superficial perivascular dermal infiltrate containing eosinophils with overlying spongiosis;

can be seen with eosinophilic spongiosis; with or without lichen simplex chronicus

Contact dermatitis Same as atopic dermatitis

CTCL/Sezary Mononuclear cells within the epidermis (exocytosis) unassociated with significant spongiosis (Fig. 7)

Dermatomyositis/Subacute

cutaneous lupus erythematosus

Interface dermatitis with vacuolar alteration, often thickening of the basement membrane,

colloid bodies, increased dermal mucin

Dermatophytosis Hyphae within stratum corneum, mounds of parakeratosis

Drug eruption Interface dermatitis with necrotic keratinocytes

Acute graft-vs-host disease Vacuolar alteration often with bsatellite cell necrosisQof keratinocytes (Fig. 8)

Ichthyoses Changes of the specific type of inherited ichthyosis (epidermolytic hyperkeratosis) or nondiagnostic changes

Idiopathic Nonspecific changes (usually subacute or chronic spongiotic dermatitis-like changes)

Lymphoproliferative diseases Superficial, deep, and interstitial dermal infiltrate of atypical mononuclear cells

Paraneoplastic Nonspecific changesPemphigoid Subepidermal bulla with dermal eosinophils and/or eosinophilic spongiosis (Fig. 9)

Pemphigus Intraepidermal bulla with acantholysis and/or eosinophilic or neutrophilic spongiosis

Paraneoplastic pemphigus Suprabasal acantholysis, dyskeratotic keratinocytes, vacuolar alteration with lichenoid inflammation

Pityriasis rubra pilaris Epidermal hyperplasia with horizontal and vertical alternating orthokeratosis

and parakeratosis; dilated plugged follicular infundibulum

Psoriasis Psoriasiform epidermal hyperplasia with mounds or confluent parakeratosis layered

with neutrophils, hypogranulosis, and dilated tortuous papillary blood vessels (Fig. 10)

Sarcoidosis Epithelioid dermal granulomas with little or no mantle of surrounding lymphocytes

Scabies Superficial and deep perivascular and interstitial inflammation with many eosinophils;

frequent spongiosis; stratum corneum with mite, excreta, crusting possible

Seborrheic dermatitis Spongiotic psoriasiform dermatitis with parakeratosis often with neutrophils at the lips of the follicular ostia

Stasis with autoeczematization Spongiotic dermatitis often with some eosinophils



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when used in conjunction with clinical and histological

features.105,106

Histopathology

The histopathology of erythroderma varies depending on

the underlying etiology (Table 3). Therefore, careful

examination of the epidermis and dermis from a punch

biopsy is recommended. In approximately one third of

erythrodermic patients, however, the biopsies fail to reveal

the diagnostic features of any specific disease. In addition,

only 50% of any specific biopsy submittedon these patients

are likely to reveal the underlying cause.107,108 This is in

part because the specific features of the disease can be

masked by nonspecific features associated with the eryth-

roderma. Therefore, multiple simultaneous punch skin

biopsies are recommended to enhance the possibility that

one might show the distinctive changes of the underlying

disease process that has resulted in the patients erythro-

derma. In addition to routine histology, special stains,immunoperoxidase studies, gene rearrangement studies, and

direct immunofluorescence have proven to be very helpful.

Algorithm of approach to the erythrodermicpatient

Erythrodermic patient presents to your office.

q

Obtain history of possible precipitating causes and

pertinent past medical history and family history. Check

medication history.q

Full skin examination of patient for any telltale sign of

underlying skin diseases. Check nails and mucosa. Check

lymph nodes and rule out organomegaly. Take vital signs to

establish patient stability.

q

Perform multiple skin biopsies for routine histology.

Simultaneously initiate cool down topical therapies and

supportive care immediately.

q

If appropriate, biopsy enlarged lymph nodes.

If appropriate, evaluate complete blood cell count,

CD4:CD8 ratio, and antinuclear antibodies.

If appropriate order chest x-ray.

Consider patch testing if appropriate.

If appropriate, rebiospy for direct immunofluoresence to

rule out immunobullous disease and/or rebiopsy for gene

rearrangement studies to rule out lymphoproliferative

disease.

If no underlying etiology identified, refer to primary care

physician to rule out underlying systemic disease.

q

Onceunderlyingetiologyis established, treatappropriately.

Systemic complications

Systemic complications of erythroderma include infec-

tion, fluid and electrolyte imbalances, thermoregulatory

disturbance, high output cardiac failure,109 acute respiratory

distress syndrome,110 and gynecomastia. The inflamed,

fissured, and excoriated skin is susceptible to bacterial

colonization, and sepsis occurs occasionally. Staphylococcal

sepsis is especially a risk forpatients with CTCL and HIV-

positive erythroderma.110-112 Fluid and electrolyte imbal-

ances occur from loss of fluid, electrolytes, and protein from

leaky capillaries.

Increased perfusion of the skin is associated with high

output cardiac failure and temperature dysregulation. High

output cardiac failure is associated with the shunting of

blood through the inflamed skin, and is of particular concern

in elderly patients or patients with preexisting cardiac

conditions.109 These leaky dilated capillaries also allow

evaporation of heat, which contributes to thermoregulatory

disturbance, in addition to inability to respond to changes in

temperature via vasoconstriction and vasodilation.113 Thereis also an increase in the basal metabolic rate, which

elevates the skin temperature.50

Erythroderma increases protein loss by 25% to 30% in

psoriatic erythroderma, and 10% to 15% from nonpsoriatic

erythroderma.114 This protein loss causes a negative

nitrogen balance that can be manifest by edema, muscle

wasting, and hypoalbuminemia.

Increased circulating levels of adhesion molecules

intercellular adhesion molecule-1, vascular cell adhesion

molecule-1, and E-selectin have been found in patients with

erythroderma secondary to psoriasis, eczema, and patients

with CTCL. The adhesion molecule expression on endo-thelial cells was examined in patients with erythroderma,

and there were no differences found in adhesion molecule,

vascular cell adhesion molecule-1, intercellular adhesion

molecule-1, P-selectin, and E-selectin expression in differ-

ent types of erythroderma. Sezary syndrome was found to

have higher mean expression of all adhesion molecules than

patients with other forms of CTCL, but it was not

statistically significant. Sigurdsson et al115 suggest that the

similarities in adhesion molecule expression in various types

of erythroderma may correlate with the similarities in the

clinical examination of patients with erythroderma of

diverse etiologies. Cytokine profiles in dermal infiltrates

show differences between types of erythroderma, with

benign erythroderma showing a T-helper 1 cytokine profile,

whereas Sezary syndrome shows a T-helper 2 cytokine

profile. This may indicate that there are different pathophy-

siogical mechanisms for development of erythroderma.116

Treatment

The initial approach to the management of erythroderma

of any etiology includes attention to nutrition and fluid and



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electrolyte replacement and the institution of gentle local

skin care measures. Oatmeal baths and wet dressings to

weeping or crusted sites should be followed by application

of bland emollients and low-potency topical corticosteroids.

Higher potency topical corticosteroids are not recommended

because of risk for systemic absorption secondary to the

extensive body surface area and the enhanced cutaneous

permeability.

117

Similarly, increased absorption of topicaltacrolimus has been observed in a patient with leukemic

erythroderma, posing the risk for nephrotoxicity and

warranting monitoring of tacrolimus blood levels.118

Topical immunomodulators may also be irritating and

poorly tolerated by the erythrodermic patient. Other skin

irritants such as tars and hydroxy acid moisturizers are also

avoided. A warm and humidified environment will increase

patient comfort, prevent hypothermia, and improve mois-

turizing of the skin. Sedating oral antihistamines are

prescribed to relieve pruritus and anxiety. Systemic

antibiotics are required for patients with secondary infec-

tion. In cases in which a drug-induced erythroderma has not

been excluded, consideration should be given to discontin-

uation of all nonessential medications. Diuretics may be

necessary when peripheral edema fails to respond to leg

elevation and local skin care. Patients with evidence of

cardiovascular or respiratory failure require hospitalization

for urgent care.

Systemic dermatologic therapy may be required to

maintain improvement achieved with local measures or to

control erythroderma refractory to local measures. Systemic

corticosteroids are recommended for patients with systemic

drug hypersensitivity reactions and should obviously be

avoided in patients with possible underlying psoriasis. Bio-

logics are an important therapeutic advance in the treatment oflabile psoriasis; published reports describe rapid and dramatic

control of erythrodermic and generalized pustular psoriasis

with infliximab. Infusions of 5 to 10 mg/kg infliximab have

been found to substantially completely clear erythrodermic

psoriasis in 3 to 4 weeks and may be an effective alternative to

conventional treatments for acutely ill patients.119,120

When the specific cause of erythroderma remains

undiagnosed, empiric therapy can be considered with agents

such as systemic corticosteroids, methotrexate, cyclosporine,

mycophenolate mofetil, and acitretin. A strong but not

confirmed suspicion for the diagnosis of psoriasis should

preclude the use of systemic corticosteroids. Similarly,

immunosuppressive agents such as cyclosporine should be

avoidedunless a diagnosis of CTCL has been excluded by the

most sophisticated and up-to-date laboratory testing

available.

Natural course of disease

The prognosis of erythroderma is dependent on the

underlying etiology. With the exception of severe systemic

hypersensitivity reactions, drug-induced erythroderma

clears r eadily with discontinuation of the causative

drug.44,121 Erythroderma secondary to psoriasis and spongi-

otic dermatitis usually improves within several weeks to

several months, although cases of chronic psoriatic atopic

erythroderma are not uncommon. Erythrodermic psoriasis

may recur in 15% of patients after initial clearing.50

Erythroderma secondary to CTCL or other malignancy is

often persistent and refractory. One third of patients withidiopathic erythroderma have been observed to show

complete remission,4,45 whereas 50% of patients demon-

strate partial remission.45 Those with chronic idiopathic

erythroderma are at high risk to evolve to CTCL.25,45,47

Early published series of erythroderma reported a

significant mortality rate from complications including

pneumonia, cardiac failure, and sepsis.3,32,42 Deaths were

most common in patients with pemphigus foliaceus,

lymphoproliferative malignancy, severe drug reactions,

and idiopathic erythroderma.32 More recent series have

found a decreased mortality rate with most deathsoccurring

in patients with malignancy-related erythroderma.25,44,53

Deaths have alsobeen reported in patients with high output

cardiac failure.47

Conclusions

The erythrodermic patient requires immediate attention.

Unfortunately, physical examination, routine laboratory

findings, and even initial biopsies may be nondiagnostic,

often making these patients challenging to diagnose and

treat. Multiple biopsies and, often, repeat biopsies may be

necessary to make a definitive diagnosis. Although death

from cardiac failure, sepsis, capillary leakage syndrome, andeven respiratory distress syndrome have been reported, early

medical intervention and newer dermatologic therapies have

improved the prognosis of this devastating dermatologic

condition.

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