8/6/2017 Erythroderma (Generalized Exfoliative Dermatitis): Background, Pathophysiology, Epidemiology

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Erythroderma (Generalized Exfoliative

Dermatitis)
Updated: Apr 14, 2017
Author: Sanusi H Umar, MD, FAAD; Chief Editor: Dirk M Elston, MD more...

OVERVIEW

Background
Exfoliative dermatitis (ED) is a definitive term that refers to a scaling erythematous dermatitis involving
90% or more of the cutaneous surface. Exfoliative dermatitis is characterized by erythema and scaling
involving the skin's surface and often obscures the primary lesions that are important clues to
understanding the evolution of the disease. Clinicians are challenged to find the cause of exfoliative
dermatitis by eliciting the history of illness prior to erythema and scaling, by probing with biopsies, and by
performing blood studies. See the images below.

Exfoliative dermatitis diffuse skin involvement.

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Exfoliative dermatitis close-up view showing erythema and scaling.

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The term red man syndrome is reserved for idiopathic exfoliative dermatitis, in which no primary cause can
be found, despite serial examinations and tests. Idiopathic exfoliative dermatitis is characterized by
marked palmoplantar keratoderma, dermatopathic lymphadenopathy, and a raised level of serum
immunoglobulin E (IgE) and is more likely to persist than other types.

The term l'homme rouge refers to exfoliative dermatitis that is secondary to cutaneous T-cell lymphoma.
The historic classification of exfoliative dermatitis into Wilson-Brocq (a chronic process associated with
exacerbation and remissions), Hebra or pityriasis rubra (relentlessly progressive disease), and Savill (self-
limiting) types lacks any clinical significance.

Pathophysiology
An increased skin blood perfusion occurs in exfoliative dermatitis (ED) that results in temperature
dysregulation (resulting in heat loss and hypothermia) and possible high-output cardiac failure. The basal
metabolic rate rises to compensate for the resultant heat loss. Fluid loss by transpiration is increased in
proportion to the basal metabolic rate. The situation is similar to that observed in patients following burns
(negative nitrogen balance characterized by edema, hypoalbuminemia, loss of muscle mass).

A marked loss of exfoliated scales occurs that may reach 20-30 g/d. This contributes to the
hypoalbuminemia commonly observed in exfoliative dermatitis. Hypoalbuminemia results, in part, from
decreased synthesis or increased metabolism of albumin. Edema is a frequent finding, probably resulting
from fluid shift into the extracellular spaces. Immune responses may be altered, as evidenced by
increased gamma-globulins, increased serum IgE in some cases, eosinophil infiltration, and CD4+ T-cell
lymphocytopenia in the absence of HIV infection. Oxidative stress is also associated with drug-induced
erythroderma. [1]

Epidemiology
Race
No racial predilection is reported for exfoliative dermatitis (ED).

Sex

Male-to-female ratio is 2-4:1.

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8/6/2017 Erythroderma (Generalized Exfoliative Dermatitis): Background, Pathophysiology, Epidemiology

Age

Exfoliative dermatitis onset usually occurs in persons older than 40 years, except when the condition
results from atopic dermatitis, seborrheic dermatitis, staphylococcal scalded skin syndrome, or a
hereditary ichthyosis. Age of onset primarily is related to etiology. [2, 3]

Prognosis
The prognosis of exfoliative dermatitis depends largely on underlying etiology.

The disease course is rapid if it results from drug allergy, lymphoma, leukemia, contact allergens, or
staphylococcal scalded skin syndrome.

A study35 of pediatric patients (aged <19 y) found that fever is a poor prognostic marker and may indicate
a susceptibility to rapid deterioration. In this group, those with the following characteristics have a higher
tendency to develop hypotension: age 3 years or younger, ill appearance, vomiting, glucose level of 110
mg/dL or less, calcium value of 8.6 mg/dL or less, platelet count of 300,000/L or less, elevated creatinine
value, polymorphonuclear leukocyte count of 80% or greater, and the presence of a focal infection. The
risk of toxic shock syndrome is increased especially in children with erythroderma and fever who have the
following additional features: age of 3 years or younger, ill appearance, elevated creatinine value, and
hypotension upon arrival.

The disease course is gradual if it results from generalized spread of a primary skin disease (eg, psoriasis,
atopic dermatitis).

The mean duration of illness typically is 5 years, with a median of 10 months.

Mortality varies according to the disease's cause. In a study of 91 of 102 patients with exfoliative dermatitis
by Sigurdsson et al, [4] a mortality rate of 43% was observed. Only 18% of the deaths were directly related
to exfoliative dermatitis. In 74% of the deaths, causes unrelated to exfoliative dermatitis were implicated.

Patient Education
Educate patients on the specifics of the underlying cause of their exfoliative dermatitis (ED) and the
importance of diligent follow-up management as indicated. Patients should be educated on the benefits of
a healthy lifestyle and to immediately treat occurrences of erythroderma to better manage their diseases in
the long term. Patients should be advised to avoid the use of and/or contact with of irritant soaps, lotions,
detergents, and chlorine, and special considerations should be made for allergies, especially for patients
with atopic dermatitis. [5] Excessive sweating should also be avoided.

Clinical Presentation

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Exfoliative dermatitis diffuse skin involvement.

Exfoliative dermatitis close-up view showing erythema and scaling.

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Tables

Table. Drugs Implicated in the Causation of Exfoliative Dermatitis

Table. Drugs Implicated in the Causation of Exfoliative Dermatitis

99mTC-
ACE inhibitors Allopurinol Aminoglutethimide Amiodarone
sestamibi [9]

Angiogenetic
Amitriptyline Amoxicillin Ampicillin Arsenic
inhibitors [10]

Aspirin Atropine Auranofin Aurothioglucose Barbiturates

Benactyzine Beta-blockers Beta carotene Bumetanide Bupropion

Butabarbital Butalbital Captopril Carbamazepine Carbidopa

Cephalosporins
[11]
Chloroquine Chlorpromazine Chlorpropamide Cimetidine

Ciprofloxacin Cisplatin Clofarabine [12] Clofazimine Clofibrate

Co-trimoxazole Cromolyn Cytarabine Dapsone Demeclocycline

Desipramine Diazepam Diclofenac Diflunisal Diltiazem

Doxorubicin Doxycycline Efavirenz [13] Enalapril Escitalopram [14]

Esomeprazole
[15] Ethambutol [16] Etodolac Fenofibrate [17] Fenoprofen

Fluconazole Fluindione [18] Fluoxetine [19] Fluphenazine Flurbiprofen

Furosemide Gemfibrozil Gliclazide [20] Glipizide [21] Gold

Griseofulvin Hydroxychloroquine Imatinib [22] Imipramine Indomethacin

Intravenous Intravesical
immunoglobulin Iodixanol [25] Isoniazid Isosorbide
[23] mitomycin C [24]

Ketoconazole Ketoprofen Ketorolac Leflunomide [26] Lithium

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Meclofenamate Mefenamic Acid Meprobamate Methylphenidate

Morphine sulfate
Midodrine [27] Minocycline [28]
Nalidixic Acid Naproxen

Nevirapine [29] Nitrazepam [21] Nifedipine Nitrofurantoin Nitroglycerin

Nizatidine Norfloxacin Omeprazole Pantoprazole [30] Penicillamine

Penicillin Pentobarbital Perphenazine Phenobarbital Phenothiazines

Phenylbutazone Phenytoin Piroxicam Primidone Prochlorperazine

Propranolol Pyrazinamide [16] Pyrazolones Quinapril Quinidine

Quinine Retinoids Rifampin Sorafenib [31] Streptomycin

Strontium
Sulfadoxine Sulfamethoxazole Sulfasalazine Sulfisoxazole
ranelate [32]

Sulfonamides Sulfonylureas Sulindac Terbinafine [33] Tetracycline

Tobramycin Tocilizumab [34] Trazodone Trifluoperazine Trimethoprim

Vancomycin Verapamil Warfarin [35]

Back to List

Contributor Information and Disclosures

Author

Sanusi H Umar, MD, FAAD Clinical Instructor of Medicine, Department of Medicine, Division of
Dermatology, University of California, Los Angeles, David Geffen School of Medicine

Sanusi H Umar, MD, FAAD is a member of the following medical societies: American Academy of
Dermatology, American College of Physicians, American Medical Association

Disclosure: Nothing to disclose.

Coauthor(s)

A Paul Kelly, MD Chief, Clinical Professor, Department of Internal Medicine, Division of Dermatology,
King/Drew Medical Center, Charles Drew University of Medicine and Science

A Paul Kelly, MD is a member of the following medical societies: American Academy of Dermatology,

http://emedicine.medscape.com/article/1106906-overview 9/10
8/6/2017 Erythroderma (Generalized Exfoliative Dermatitis): Background, Pathophysiology, Epidemiology

American Medical Association, American Society for Dermatologic Surgery, National Medical Association,
Pacific Dermatologic Association

Disclosure: Nothing to disclose.

Specialty Editor Board

Richard P Vinson, MD Assistant Clinical Professor, Department of Dermatology, Texas Tech University
Health Sciences Center, Paul L Foster School of Medicine; Consulting Staff, Mountain View Dermatology,
PA

Richard P Vinson, MD is a member of the following medical societies: American Academy of Dermatology,
Texas Medical Association, Association of Military Dermatologists, Texas Dermatological Society

Disclosure: Nothing to disclose.

Rosalie Elenitsas, MD Herman Beerman Professor of Dermatology, University of Pennsylvania School of

Medicine; Director, Penn Cutaneous Pathology Services, Department of Dermatology, University of
Pennsylvania Health System

Rosalie Elenitsas, MD is a member of the following medical societies: American Academy of Dermatology,
American Medical Association, American Society of Dermatopathology, Pennsylvania Academy of
Dermatology

Disclosure: Received royalty from Lippincott Williams Wilkins for textbook editor.

Chief Editor

Dirk M Elston, MD Professor and Chairman, Department of Dermatology and Dermatologic Surgery,
Medical University of South Carolina College of Medicine

Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

Additional Contributors

James W Patterson, MD Professor of Pathology and Dermatology, Director of Dermatopathology,

University of Virginia Medical Center

James W Patterson, MD is a member of the following medical societies: American Academy of

Dermatology, American College of Physicians, American Society of Dermatopathology, Royal Society of
Medicine, Society for Investigative Dermatology, United States and Canadian Academy of Pathology

Disclosure: Nothing to disclose.

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