Sections

Erythroderma (Generalized Exfoliative Dermatitis)

Sections Erythroderma (Generalized Exfoliative Dermatitis)
Overview
Presentation
DDx
Workup
Treatment
Medication
Questions & Answers
Media Gallery
Tables
References

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 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.

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]

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^{[4, 5, 6, 7]}:

Atopic dermatitis - Acute and chronic leukemia
Contact dermatitis - Reticulum cell sarcoma
Dermatophytosis - Carcinoma of rectum
Hailey-Hailey disease - Carcinoma of fallopian tubes
Leiner disease - Graft versus host disease
Lichen planus - HIV infection
Lupus erythematosus - Lymphoma (including Hodgkin disease)
Mycosis fungoides - Multiple myeloma
Pemphigoid - Carcinoma of lung
Pemphigus foliaceus - Mycosis fungoides
Pityriasis rubra pilaris - Reactive arthritis
Psoriasis
Sarcoid
Seborrheic dermatitis
Stasis dermatitis

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.^[8]

Sarcoidosis-associated erythroderma may demonstrate lichenoid papules as a clue to the diagnosis.^[9]

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

99mTC-sestamibi^[10]	ACE inhibitors	Allopurinol	Aminoglutethimide	Amiodarone
Amitriptyline	Amoxicillin	Ampicillin	Angiogenetic inhibitors^[11]	Arsenic
Aspirin	Atropine	Auranofin	Aurothioglucose	Barbiturates
Benactyzine	Beta-blockers	Beta carotene	Bumetanide	Bupropion
Butabarbital	Butalbital	Captopril	Carbamazepine	Carbidopa
Cephalosporins^[12]	Chloroquine	Chlorpromazine	Chlorpropamide	Cimetidine
Ciprofloxacin	Cisplatin	Clofarabine^[13]	Clofazimine	Clofibrate
Co-trimoxazole	Cromolyn	Cytarabine	Dapsone	Demeclocycline
Desipramine	Diazepam	Diclofenac	Diflunisal	Diltiazem
Doxorubicin	Doxycycline	Efavirenz^[14]	Enalapril	Escitalopram^[15]
Esomeprazole^[16]	Ethambutol^[17]	Etodolac	Fenofibrate^[18]	Fenoprofen
Fluconazole	Fluindione^[19]	Fluoxetine^[20]	Fluphenazine	Flurbiprofen
Furosemide	Gemfibrozil	Gliclazide^[21]	Glipizide^[22]	Gold
Griseofulvin	Hydroxychloroquine	Imatinib^{[23, 24]}	Imipramine	Indomethacin
Intravenous immunoglobulin^[25]	Intravesical mitomycin C^[26]	Iodixanol^[27]	Isoniazid	Isosorbide
Ketoconazole	Ketoprofen	Ketorolac	Leflunomide^[28]	Lithium
Meclofenamate	Mefenamic Acid	Meprobamate	Methylphenidate
Midodrine^[29]	Minocycline	Morphine sulfate^[30]	Nalidixic Acid	Naproxen
Nevirapine^[31]	Nitrazepam^[22]	Nifedipine	Nitrofurantoin	Nitroglycerin
Nizatidine	Norfloxacin	Omeprazole	Pantoprazole^[32]	Penicillamine
Penicillin	Pentobarbital	Perphenazine	Phenobarbital	Phenothiazines
Phenylbutazone	Phenytoin	Piroxicam	Primidone	Prochlorperazine
Propranolol	Pyrazinamide^[17]	Pyrazolones	Quinapril	Quinidine
Quinine	Retinoids	Rifampin	Sorafenib^[33]	Streptomycin
Strontium ranelate^[34]	Sulfadoxine	Sulfamethoxazole	Sulfasalazine	Sulfisoxazole
Sulfonamides	Sulfonylureas	Sulindac	Terbinafine^[35]	Tetracycline
Tobramycin	Tocilizumab^[36]	Trazodone	Trifluoperazine	Trimethoprim
Vancomycin	Verapamil	Warfarin^[37]

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.^{[38, 39]}

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^[40]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,^[41]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.^[42]Excessive sweating should also be avoided.

Clinical Presentation

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Media Gallery

Exfoliative dermatitis diffuse skin involvement.
Exfoliative dermatitis close-up view showing erythema and scaling.

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Table. Drugs Implicated in the Causation of Exfoliative Dermatitis

Table. Drugs Implicated in the Causation of Exfoliative Dermatitis

99mTC-sestamibi^[10]	ACE inhibitors	Allopurinol	Aminoglutethimide	Amiodarone
Amitriptyline	Amoxicillin	Ampicillin	Angiogenetic inhibitors^[11]	Arsenic
Aspirin	Atropine	Auranofin	Aurothioglucose	Barbiturates
Benactyzine	Beta-blockers	Beta carotene	Bumetanide	Bupropion
Butabarbital	Butalbital	Captopril	Carbamazepine	Carbidopa
Cephalosporins^[12]	Chloroquine	Chlorpromazine	Chlorpropamide	Cimetidine
Ciprofloxacin	Cisplatin	Clofarabine^[13]	Clofazimine	Clofibrate
Co-trimoxazole	Cromolyn	Cytarabine	Dapsone	Demeclocycline
Desipramine	Diazepam	Diclofenac	Diflunisal	Diltiazem
Doxorubicin	Doxycycline	Efavirenz^[14]	Enalapril	Escitalopram^[15]
Esomeprazole^[16]	Ethambutol^[17]	Etodolac	Fenofibrate^[18]	Fenoprofen
Fluconazole	Fluindione^[19]	Fluoxetine^[20]	Fluphenazine	Flurbiprofen
Furosemide	Gemfibrozil	Gliclazide^[21]	Glipizide^[22]	Gold
Griseofulvin	Hydroxychloroquine	Imatinib^{[23, 24]}	Imipramine	Indomethacin
Intravenous immunoglobulin^[25]	Intravesical mitomycin C^[26]	Iodixanol^[27]	Isoniazid	Isosorbide
Ketoconazole	Ketoprofen	Ketorolac	Leflunomide^[28]	Lithium
Meclofenamate	Mefenamic Acid	Meprobamate	Methylphenidate
Midodrine^[29]	Minocycline	Morphine sulfate^[30]	Nalidixic Acid	Naproxen
Nevirapine^[31]	Nitrazepam^[22]	Nifedipine	Nitrofurantoin	Nitroglycerin
Nizatidine	Norfloxacin	Omeprazole	Pantoprazole^[32]	Penicillamine
Penicillin	Pentobarbital	Perphenazine	Phenobarbital	Phenothiazines
Phenylbutazone	Phenytoin	Piroxicam	Primidone	Prochlorperazine
Propranolol	Pyrazinamide^[17]	Pyrazolones	Quinapril	Quinidine
Quinine	Retinoids	Rifampin	Sorafenib^[33]	Streptomycin
Strontium ranelate^[34]	Sulfadoxine	Sulfamethoxazole	Sulfasalazine	Sulfisoxazole
Sulfonamides	Sulfonylureas	Sulindac	Terbinafine^[35]	Tetracycline
Tobramycin	Tocilizumab^[36]	Trazodone	Trifluoperazine	Trimethoprim
Vancomycin	Verapamil	Warfarin^[37]

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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, 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.