AUTHOR AND EDITOR INFORMATION

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INTRODUCTION

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Background

Exfoliative dermatitis (ED) is a definitive term that refers to a scaling erythematous dermatitis involving 90% or more of the cutaneous surface. ED 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 ED 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 ED in which no primary cause can be found, despite serial examinations and tests. Idiopathic ED 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 ED that is secondary to cutaneous T-cell lymphoma. The historic classification of ED 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 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 ED. 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 ED by Sigurdsson et al,¹ a mortality rate of 43% was observed. Only 18% of the deaths were directly related to ED. In 74% of the deaths, causes unrelated to ED were implicated.

Race

No racial predilection is reported for ED.

Sex

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

Age

ED 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

Section 3 of 11  

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History

History is the most important aid in diagnosing 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 ED 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 ED 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 ED 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 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 ED is extensive and continues to expand. Cutaneous diseases that cause ED 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 ED 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 ED (see Table). In many cases of protracted ED 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.

DIFFERENTIALS

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Other Problems to be Considered

Etiologies of exfoliative dermatitis (see Causes)

WORKUP

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Lab Studies

• Increased erythrocyte sedimentation rate, anemia, hypoalbuminemia, and hyperglobulinemia are frequent findings.
• Byer and Bachur² report that the levels of glucose, calcium, and creatinine and the platelet and polymorphonuclear leukocyte counts are of prognostic significance in children who present with erythroderma and fever.
• Increased IgE may be observed in ED when caused by atopic dermatitis.
• Peripheral blood smears and bone marrow examination may be useful in a leukemia workup.
• Immunophenotyping, flow cytometry, and particularly, B- and T-cell gene rearrangement analysis may be helpful in confirming the diagnosis if lymphoma is strongly suspected.
• Skin scrapings may reveal hyphae or scabies mites.
• Cultures may show bacterial overgrowth or the herpes simplex virus.
• Perform HIV testing in the right setting; use polymerase chain reaction for viral detection, rather than enzyme-linked immunoassay, since ED has been reported to predict seroconversion in HIV infection.
• In a report by Griffiths et al,³ decreased CD4⁺ T-cell count was observed in patients with ED in the absence of HIV disease.

Imaging Studies

• Pursue further tests (eg, computed tomography scanning, magnetic resonance imaging, chest radiography, mammography) if the clinical features so indicate.

Other Tests

• If the cause of ED is in doubt, survey patients for occult tumors or cancers. Perform chest radiography and routine cancer screenings appropriate for age and sex (eg, mammogram, stool occult blood test, sigmoidoscopy, prostate examination, serum prostate specific antigen level, cervical smear).
• Patch testing can be performed to unveil contact allergens but should be performed only during periods of remission. In the patch test, include systemic drugs the patient was taking prior to the onset of ED.
• Direct immunofluorescence studies diagnosed at least 2 reported cases of pemphigoid erythroderma, according to Scrivener et al.⁴

Procedures

• Skin biopsies reveal nonspecific findings of spongiotic dermatitis; however, primary disease may be evident.

Histologic Findings

The appearance of ED usually masks the underlying disease's specific histologic features. The most common histopathologic appearance is of either subacute or chronic dermatitis; however, biopsy is indicated, since diagnostic findings are present in 40% of cases. A search for the underlying cause is necessary because of possible prognostic and therapeutic implications. Detailed histopathologic analysis with clinicopathologic correlation is mandatory in the remaining cases for which a specific cause is not apparent. Often, repeated biopsies and hematologic studies may be necessary to detect specific conditions (eg, cutaneous T-cell lymphoma). Repeated biopsies have been reported to result in a diagnosis in 50% of cases that do not reveal specific findings initially.

TREATMENT

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Medical Care

Patients presenting acutely with ED often require admission for inpatient management because their total body functions (including intake and output) can require monitoring. Hospital admission should be seriously considered in pediatric patients who present with erythroderma and fever because this presentation is a predictor of hypotension and even toxic shock syndrome. The principle of management is to maintain skin moisture, avoid scratching, avoid precipitating factors, apply topical steroids, and treat the underlying cause and complications. ED commonly resists therapy until the underlying disease is treated (eg, phototherapy, systemic medications in psoriasis). Outcome is unpredictable in idiopathic ED. The course is marked by multiple exacerbations, and prolonged glucocorticoid therapy often is needed.

• Discontinue all unnecessary medications. Carefully monitor and control fluid intake, since patients can dehydrate or go into cardiac failure; monitor body temperature, since patients may become hypothermic.
• Apply tap water–wet dressings (made from heavy mesh gauze); change every 2-3 hours. Apply intermediate-strength topical steroids (eg, triamcinolone cream 0.025-0.5%) beneath wet dressings. Suggest a tepid bath (may be comforting) once or more daily between dressing changes. Reduce frequency of dressings and gradually introduce emollients between dressing applications as ED improves.
• Institute systemic antibiotics if signs of secondary infection are observed. Antihistamines help reduce pruritus and provide needed sedation.
• Systemic steroids may be helpful in some cases but should be avoided in suspected cases of psoriasis and staphylococcal scalded skin syndrome.
• Increased capillary permeability occasionally is severe enough to justify plasma infusion.
• Preexisting malnutrition may become more marked and require nutritional intervention in older patients.

Consultations

Consult a dermatologist for all cases of ED.

Diet

Ensure adequate nutrition with emphasis on protein intake, since ED patients lose a lot of protein through excessive desquamation and show a tendency toward hypoalbuminemia. Alter diet as necessary if ingestion of a certain food group is suspected as the etiology of ED.

Activity

As tolerated

MEDICATION

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Topical steroids are the primary category of medications used to treat ED. A sedative antihistamine may be a useful adjunct for pruritic patients, since it helps patients to sleep at night, thus limiting nocturnal scratching and excoriations. Antimicrobial agents often are used if an infection is suspected to be precipitating or complicating ED. Other drugs specifically indicated for management of underlying etiology of ED may be necessary.

Drug Category: Topical steroids

Exert anti-inflammatory effects by inhibiting early processes (eg, edema, fibrin deposition, capillary dilatation, movement of phagocytes into the area, phagocytic activities). In ED, they may inhibit the increased epidermal cell turnover that occurs. Indications include symptomatic relief of inflammation and/or pruritus associated with acute and chronic corticosteroid-responsive disorders.

Drug Category: Antihistamines

Exert both antipruritic and sedating effects. Used in treating histamine-mediated allergic reactions by competitively inhibiting H1 receptors on effector cells. To varying degrees, they exert sedative effects by crossing the blood-brain barrier and blocking central histaminogenic receptors.

FOLLOW-UP

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Further Outpatient Care

• Follow patients discharged from the hospital on an outpatient basis for continued management of underlying disease.
• Closely follow patients with no discernible underlying disease (idiopathic ED) using multiple serial biopsies to exclude cutaneous T-cell lymphoma. Since low-dose methotrexate has been shown to be efficacious in the management of erythrodermic cutaneous T-cell lymphoma (as reported by Zackheim et al⁵), some have advocated the use of methotrexate between rebiopsy periods in patients with idiopathic ED that is unremitting despite the use of topical steroids. However, this novel approach should be taken with the understanding that cutaneous T-cell lymphoma develops only in a minority of patients with idiopathic ED (7%), especially in the subgroup with persistent chronic disease on long-term follow-up care (as reported by Sigurdsson et al⁶), and that methotrexate is associated with many adverse effects, including toxicities of the liver, lungs, and bone marrow.

In/Out Patient Meds

• Appropriate in/outpatient medications are influenced by the underlying etiology of ED. For example, prednisone may be contraindicated in ED secondary to psoriasis, while retinoids are an excellent choice for this disease.

Transfer

• Transfer patients with ED to the care of a dermatologist.

Deterrence/Prevention

• Prevention of ED depends on adequate control of underlying etiology. For example, gentle skin care is key to preventing ED flare-ups in atopic dermatitis, while specific treatments for psoriasis should be adhered to when it is the underlying cause.

Complications

• Complications in ED depend on underlying disease. Secondary infection, dehydration, electrolyte imbalance, temperature dysregulation, and high-output cardiac failure are potential complications in all cases.

Prognosis

• The prognosis of ED 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 study² of pediatric patients (age <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.
• The overall mortality is in the range of 20-40%; in 20% of fatalities, the cause of death is from factors unrelated to ED.

Patient Education

• Educate patients on the specifics of the underlying cause of their ED and the importance of diligent follow-up management as indicated.

MISCELLANEOUS

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Medical/Legal Pitfalls

• Failure to be aware of the various etiologies of ED
• Failure to elicit a thorough history to facilitate a correct diagnosis
• Failure to inform patients that etiology of ED is not found 30-40% of cases (see Causes for a list of possible etiologies)

Special Concerns

• Special concerns differ according to the underlying etiology of ED.

MULTIMEDIA

Section 10 of 11  

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Media file 1:  Exfoliative dermatitis diffuse skin involvement.
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Media file 2:  Exfoliative dermatitis close-up view showing erythema and scaling.
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REFERENCES

Section 11 of 11

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1. Sigurdsson V, Toonstra J, Hezemans-Boer M, van Vloten WA. Erythroderma. A clinical and follow-up study of 102 patients, with special emphasis on survival. J Am Acad Dermatol. Jul 1996;35(1):53-7. [Medline].
2. Byer RL, Bachur RG. Clinical deterioration among patients with fever and erythroderma. Pediatrics. Dec 2006;118(6):2450-60. [Medline].
3. Griffiths TW, Stevens SR, Cooper KD. Acute erythroderma as an exclusion criterion for idiopathic CD4+ T lymphocytopenia. Arch Dermatol. Dec 1994;130(12):1530-3. [Medline].
4. Scrivener Y, Cribier B, Le Coz C, Boehm N, Jelen G, Heid E, et al. [Erythroderma with immunoglobulin deposits along the basal membrane. Pemphigoid erythroderma?]. Ann Dermatol Venereol. Jan 1998;125(1):13-7. [Medline].
5. 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].
6. Sigurdsson V, Toonstra J, van Vloten WA. Idiopathic erythroderma: a follow-up study of 28 patients. Dermatology. 1997;194(2):98-101. [Medline].
7. Burton JL, Holden WE. Lichenification and prurigo. In: Champion RH, ed. Textbook of Dermatology. 6^th ed. London, England: Blackwell Science; 1998:673-8.
8. Cohen LM, Skopicki DK, Harrist TJ. Non-infectious vesiculobullous and vesiculopostular diseases. In: Elenitsas R, ed. Lever's Histopathology of Skin. 8^th ed. Philadelphia, Pa: Lippincott Williams & Wilkins; 1997:216.
9. Freedberg IM. Exfoliative dermatitis. In: Freedburg IM, Fitzpatrick TB, Goldsmith LA, et al, eds. Fitzpatrick's Dermatology in General Medicine. 5^th ed. New York, NY: McGraw-Hill; 1999:534-7.
10. Sehgal VN, Srivastava G. Exfoliative dermatitis. A prospective study of 80 patients. Dermatologica. 1986;173(6):278-84. [Medline].
11. 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].

Article Last Updated: Jul 24, 2007