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Erythroderma (Generalized Exfoliative Dermatitis)
Updated: Aug 24, 2009
Introduction
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.
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 (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 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, and CD4+ T-cell lymphocytopenia in the absence of HIV infection.
Mortality/Morbidity
Mortality varies according to the disease's cause. In a study of 91 of 102 patients with exfoliative dermatitis by Sigurdsson et al,1 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.
Race
No racial predilection is reported for exfoliative dermatitis.
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.
Clinical
History
History is the most important aid in diagnosing exfoliative dermatitis (ED).
- Patients may have a history of the primary disease (eg, psoriasis, atopic dermatitis).
- Elicit a comprehensive drug history, including over-the-counter drugs.
- Disease usually evolves rapidly when it results from drug allergens, lymphoma, leukemia, or staphylococcal scalded skin syndrome.
- Disease evolution is more gradual when it results from psoriasis, atopic dermatitis, or the spread of primary disease.
- Pruritus is a prominent and frequent symptom.
- Malaise, fever, and chills may occur.
Physical
- Patients often present with generalized erythema.
- Scaling appears 2-6 days after the onset of erythema, usually starting from flexural areas.
- Pruritus commonly results in excoriations.
- When exfoliative dermatitis persists for weeks, hair may shed; nails may become ridged and thickened and also may shed.
- Periorbital skin may be inflamed and edematous, resulting in ectropion (with consequent epiphora).
- In chronic cases, pigmentary disturbances can occur (especially in darker-skinned races); patchy or widespread loss of pigment (resembling vitiligo) has been reported.
- Diligent search for residual signs of underlying disease occasionally yields dividends. Residual signs may include the following:
- Islands of sparing in pityriasis rubra pilaris
- Few typical psoriatic plaques in psoriasis
- Papules or oral lesions of lichen planus
- Superficial blisters of pemphigus foliaceus
- Erythematous papular lesions of an early drug eruption
- Dermatopathic lymphadenopathy can occur in exfoliative dermatitis not caused by lymphoma or leukemia. A lymph node biopsy is advised when lymph nodes exhibit lymphomatous characteristics (eg, large size, rubbery consistency) and the cause of exfoliative dermatitis is undetermined.
- The general picture is modified according to the nature of the underlying disease and the patient's general physical condition.
Causes
Determining specific etiologies in exfoliative dermatitis 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:- 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 - Reiter syndrome
- 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 60 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.
Drugs Implicated in the Causation of Exfoliative Dermatitis
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Table
| ACE inhibitors | Allopurinol | Aminoglutethimide | Amiodarone | Amitriptyline |
| Amoxicillin | Ampicillin | Arsenic | Aspirin | Atropine |
| Auranofin | Aurothioglucose | Barbiturates | Benactyzine | Beta-blockers |
| Beta carotene | Bumetanide | Bupropion | Butabarbital | Butalbital |
| Captopril | Carbamazepine | Carbidopa | Chloroquine | Chlorpromazine |
| Chlorpropamide | Cimetidine | Ciprofloxacin | Clofazimine | Clofibrate |
| Co-trimoxazole | Cromolyn | Cytarabine | Dapsone | Demeclocycline |
| Desipramine | Diazepam | Diclofenac | Diflunisal | Diltiazem |
Doxorubicin | Doxycycline | Enalapril | Etodolac | Fenoprofen |
Fluconazole | Fluphenazine | Flurbiprofen | Furosemide | Gemfibrozil |
Gold | Griseofulvin | Hydroxychloroquine | Imipramine | Indomethacin |
Isoniazid | Isosorbide | Ketoconazole | Ketoprofen | Ketorolac |
Lithium | Meclofenamate | Mefenamic Acid | Meprobamate | Methylphenidate |
Minocycline | Nalidixic Acid | Naproxen | Nifedipine | Nitrofurantoin |
Nitroglycerin | Nizatidine | Norfloxacin | Omeprazole | Penicillamine |
Penicillin | Pentobarbital | Perphenazine | Phenobarbital | Phenothiazines |
Phenylbutazone | Phenytoin | Piroxicam | Primidone | Prochlorperazine |
Propranolol | Pyrazolones | Quinapril | Quinidine | Quinine |
Retinoids | Rifampin | Streptomycin | Sulfadoxine | Sulfamethoxazole |
Sulfasalazine | Sulfisoxazole | Sulfonamides | Sulfonylureas | Sulindac |
Tetracycline | Tobramycin | Trazodone | Trifluoperazine | Trimethoprim |
| Vancomycin | Verapamil | |||
| ACE inhibitors | Allopurinol | Aminoglutethimide | Amiodarone | Amitriptyline |
| Amoxicillin | Ampicillin | Arsenic | Aspirin | Atropine |
| Auranofin | Aurothioglucose | Barbiturates | Benactyzine | Beta-blockers |
| Beta carotene | Bumetanide | Bupropion | Butabarbital | Butalbital |
| Captopril | Carbamazepine | Carbidopa | Chloroquine | Chlorpromazine |
| Chlorpropamide | Cimetidine | Ciprofloxacin | Clofazimine | Clofibrate |
| Co-trimoxazole | Cromolyn | Cytarabine | Dapsone | Demeclocycline |
| Desipramine | Diazepam | Diclofenac | Diflunisal | Diltiazem |
Doxorubicin | Doxycycline | Enalapril | Etodolac | Fenoprofen |
Fluconazole | Fluphenazine | Flurbiprofen | Furosemide | Gemfibrozil |
Gold | Griseofulvin | Hydroxychloroquine | Imipramine | Indomethacin |
Isoniazid | Isosorbide | Ketoconazole | Ketoprofen | Ketorolac |
Lithium | Meclofenamate | Mefenamic Acid | Meprobamate | Methylphenidate |
Minocycline | Nalidixic Acid | Naproxen | Nifedipine | Nitrofurantoin |
Nitroglycerin | Nizatidine | Norfloxacin | Omeprazole | Penicillamine |
Penicillin | Pentobarbital | Perphenazine | Phenobarbital | Phenothiazines |
Phenylbutazone | Phenytoin | Piroxicam | Primidone | Prochlorperazine |
Propranolol | Pyrazolones | Quinapril | Quinidine | Quinine |
Retinoids | Rifampin | Streptomycin | Sulfadoxine | Sulfamethoxazole |
Sulfasalazine | Sulfisoxazole | Sulfonamides | Sulfonylureas | Sulindac |
Tetracycline | Tobramycin | Trazodone | Trifluoperazine | Trimethoprim |
| Vancomycin | Verapamil | |||
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References
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Byer RL, Bachur RG. Clinical deterioration among patients with fever and erythroderma. Pediatrics. Dec 2006;118(6):2450-60. [Medline].
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Zackheim HS, Kashani-Sabet M, Hwang ST. Low-dose methotrexate to treat erythrodermic cutaneous T-cell lymphoma: results in twenty-nine patients. J Am Acad Dermatol. Apr 1996;34(4):626-31. [Medline].
Sigurdsson V, Toonstra J, van Vloten WA. Idiopathic erythroderma: a follow-up study of 28 patients. Dermatology. 1997;194(2):98-101. [Medline].
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Cohen LM, Skopicki DK, Harrist TJ. Non-infectious vesiculobullous and vesiculopostular diseases. In: Elenitsas R, ed. Lever's Histopathology of Skin. 8th ed. Philadelphia, Pa: Lippincott Williams & Wilkins; 1997:216.
Freedberg IM. Exfoliative dermatitis. In: Freedburg IM, Fitzpatrick TB, Goldsmith LA, et al, eds. Fitzpatrick's Dermatology in General Medicine. 5th ed. New York, NY: McGraw-Hill; 1999:534-7.
Nakamura M, Tokura Y. Tocilizumab-induced erythroderma. Eur J Dermatol. May-Jun 2009;19(3):273-4. [Medline].
Prakash BV, Sirisha NL, Satyanarayana VV, Sridevi L, Ramachandra BV. Aetiopathological and clinical study of erythroderma. J Indian Med Assoc. Feb 2009;107(2):100, 102-3. [Medline].
Sehgal VN, Srivastava G. Exfoliative dermatitis. A prospective study of 80 patients. Dermatologica. 1986;173(6):278-84. [Medline].
Torres-Camacho P, Tirado-Sánchez A, Ponce-Olivera RM. A study of erythroderma: clues from eosinophilia and elevated lactate dehydrogenase levels. Indian J Dermatol Venereol Leprol. Sep-Oct 2008;74(5):499-500. [Medline].
Wong KS, Wong SN, Tham SN, Giam YC. Generalised exfoliative dermatitis--a clinical study of 108 patients. Ann Acad Med Singapore. Oct 1988;17(4):520-3. [Medline].
Keywords
exfoliative erythroderma, ED, erythematous dermatitis, generalized exfoliative dermatitis, red man syndrome, idiopathic ED, idiopathic exfoliative dermatitis, erythrodermatitis




Overview: Erythroderma (Generalized Exfoliative Dermatitis)