Erythroderma (Generalized Exfoliative Dermatitis)

Updated: Aug 12, 2019
  • Author: Sanusi H Umar, MD, FAAD; Chief Editor: Dirk M Elston, MD  more...
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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. Exfoliative dermatitis diffuse skin involvement.
Exfoliative dermatitis close-up view showing eryth Exfoliative dermatitis close-up view showing erythema and scaling.

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 often secondary to cutaneous T-cell lymphoma. Erythrodermic mycosis fungoides should be distinguished from leukemic Sézary syndrome with erythroderma. [1] 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.

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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. [2]

Chronic erythroderma in elderly men may represent a unique condition distinct from adult atopic dermatitis. [3]

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Etiology

Determining specific etiologies in exfoliative dermatitis (ED) often is not possible; however, it is necessary to attempt since etiology may impact disease course and management options. The list of conditions that can cause exfoliative dermatitis is extensive and continues to expand. Cutaneous diseases that cause exfoliative dermatitis and the systemic diseases associated with them include the following:

The most common causes of exfoliative dermatitis are best remembered by the mnemonic device ID-SCALP. The causes and their frequencies are as follows:

  • Idiopathic - 30%
  • Drug allergy - 28%
  • Seborrheic dermatitis - 2%
  • Contact dermatitis - 3%
  • Atopic dermatitis - 10%
  • Lymphoma and leukemia - 14%
  • Psoriasis - 8%

More than 135 drugs have been implicated in the causation of exfoliative dermatitis (see Table). In many cases of protracted exfoliative dermatitis classified as being of undetermined cause, careful follow-up care and reevaluation implicated atopic dermatitis in older patients, intake of drugs overlooked by the patient, and prelymphomatous eruption as causative factors. It should be noted that psoriasiform erythroderma has been induced by the tumor necrosis factor (TNF)–alpha inhibitor golimumab. [4]

Sarcoidosis-associated erythroderma may demonstrate lichenoid papules as a clue to the diagnosis. [5]

Table. Drugs Implicated in the Causation of Exfoliative Dermatitis (Open Table in a new window)

99mTC-sestamibi [6]

ACE inhibitors

Allopurinol

Aminoglutethimide

Amiodarone

Amitriptyline

Amoxicillin

Ampicillin

Angiogenetic inhibitors [7]

Arsenic

Aspirin

Atropine

Auranofin

Aurothioglucose

Barbiturates

Benactyzine

Beta-blockers

Beta carotene

Bumetanide

Bupropion

Butabarbital

Butalbital

Captopril

Carbamazepine

Carbidopa

Cephalosporins [8]

Chloroquine

Chlorpromazine

Chlorpropamide

Cimetidine

Ciprofloxacin

Cisplatin

Clofarabine [9]

Clofazimine

Clofibrate

Co-trimoxazole

Cromolyn

Cytarabine

Dapsone

Demeclocycline

Desipramine

Diazepam

Diclofenac

Diflunisal

Diltiazem

Doxorubicin

Doxycycline

Efavirenz [10]

Enalapril

Escitalopram [11]

Esomeprazole [12]

Ethambutol [13]

Etodolac

Fenofibrate [14]

Fenoprofen

Fluconazole

Fluindione [15]

Fluoxetine [16]

Fluphenazine

Flurbiprofen

Furosemide

Gemfibrozil

Gliclazide [17]

Glipizide [18]

Gold

Griseofulvin

Hydroxychloroquine

Imatinib [19, 20]

Imipramine

Indomethacin

Intravenous immunoglobulin [21]

Intravesical mitomycin C [22]

Iodixanol [23]

Isoniazid

Isosorbide

Ketoconazole

Ketoprofen

Ketorolac

Leflunomide [24]

Lithium

Meclofenamate

Mefenamic Acid

Meprobamate

Methylphenidate

Midodrine [25]

Minocycline

Morphine sulfate [26]

Nalidixic Acid

Naproxen

Nevirapine [27]

Nitrazepam [18]

Nifedipine

Nitrofurantoin

Nitroglycerin

Nizatidine

Norfloxacin

Omeprazole

Pantoprazole [28]

Penicillamine

Penicillin

Pentobarbital

Perphenazine

Phenobarbital

Phenothiazines

Phenylbutazone

Phenytoin

Piroxicam

Primidone

Prochlorperazine

Propranolol

Pyrazinamide [13]

Pyrazolones

Quinapril

Quinidine

Quinine

Retinoids

Rifampin

Sorafenib [29]

Streptomycin

Strontium ranelate [30]

Sulfadoxine

Sulfamethoxazole

Sulfasalazine

Sulfisoxazole

Sulfonamides

Sulfonylureas

Sulindac

Terbinafine [31]

Tetracycline

Tobramycin

Tocilizumab [32]

Trazodone

Trifluoperazine

Trimethoprim

Vancomycin

Verapamil

Warfarin [33]

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Epidemiology

Race

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

Sex

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

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. [34, 35]

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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 study [36] 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/μL 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, [37] 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.

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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. [38]  Excessive sweating should also be avoided.

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