eMedicine Specialties > Dermatology > Papulosquamous Diseases

Erythroderma (Generalized Exfoliative Dermatitis)

Sanusi H Umar, MD, FAAD, Attending Physician, Department of Dermatology, Charles R Drew/MLK Medical Center
A Paul Kelly, MD, Chief, Clinical Professor, Department of Internal Medicine, Division of Dermatology, King/Drew Medical Center, Charles R Drew University

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.

Exfoliative dermatitis diffuse skin involvement.

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 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

• 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

Differential Diagnoses

Other Problems to Be Considered

Etiologies of exfoliative dermatitis (see Causes)

Workup

Laboratory 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 exfoliative dermatitis (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 exfoliative dermatitis 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 exfoliative dermatitis 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 exfoliative dermatitis 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 exfoliative dermatitis.
• 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 exfoliative dermatitis 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

Medical Care

Patients presenting acutely with exfoliative dermatitis (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. exfoliative dermatitis commonly resists therapy until the underlying disease is treated (eg, phototherapy, systemic medications in psoriasis). Outcome is unpredictable in idiopathic exfoliative dermatitis. 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 exfoliative dermatitis 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 exfoliative dermatitis.

Diet

Ensure adequate nutrition with emphasis on protein intake, since exfoliative dermatitis 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 exfoliative dermatitis.

Activity

As tolerated

Medication

Topical steroids are the primary category of medications used to treat exfoliative dermatitis (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 exfoliative dermatitis. Other drugs specifically indicated for management of underlying etiology of exfoliative dermatitis may be necessary.

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 exfoliative dermatitis, 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.

Triamcinolone (Aristocort)

Medium-potency topical steroid. Use creams and lotions for moist weepy lesions and with intense inflammation (eg, exfoliative dermatitis). Frequency of use in exfoliative dermatitis depends on acute nature of disease and frequency with which wet dressings are changed.

Dosing

Adult

Apply cream 0.025%, 0.1%, or 0.5% bid/qid
Apply lotion 0.025% or 0.1% bid/qid
Apply ointment 0.1% bid

Pediatric

Apply cream 0.025% qd/bid; 0.1% or 0.5% qd
Apply lotion 0.025% qd/bid; 0.1% qd
Apply ointment 0.1% qd/bid

Interactions

None reported

Contraindications

Documented hypersensitivity; infections at treatment site or pre-existing skin atrophy

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Adrenal suppression, Cushing syndrome, intracranial hypertension, and growth retardation may occur as a result of systemic absorption of topical corticosteroids; children are more susceptible

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.

Hydroxyzine (Atarax, Vistaril)

Antagonizes H1 receptors in periphery. May suppress histamine activity in subcortical region of CNS providing antipruritic effects

Dosing

Adult

25-50 mg PO q4-6h prn

Pediatric

2-3 mg/kg/d PO divided tid/qid prn for pruritus (10 mg/5 mL syr)

Interactions

May augment sedating effects of alcohol and other CNS depressants; may augment anticholinergic effects of anticholinergic drugs and drugs with anticholinergic effects

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Avoid in hepatic impairment except in exceptional conditions; ECG abnormalities may occur (eg, alteration of T waves); warn patients of expected increase in drowsiness and to avoid tasks requiring alertness or physical dexterity; may exacerbate crises in porphyric patients

Follow-up

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 exfoliative dermatitis [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 exfoliative dermatitis 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 exfoliative dermatitis (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.

Inpatient & Outpatient Medications

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

Transfer

• Transfer patients with exfoliative dermatitis to the care of a dermatologist.

Deterrence/Prevention

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

Complications

• Complications in exfoliative dermatitis 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 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 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 exfoliative dermatitis.

Patient Education

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

Miscellaneous

Medicolegal Pitfalls

• Failure to be aware of the various etiologies of exfoliative dermatitis (ED)
• Failure to elicit a thorough history to facilitate a correct diagnosis
• Failure to inform patients that etiology of exfoliative dermatitis 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 exfoliative dermatitis.

Multimedia

Media file 1: Exfoliative dermatitis diffuse skin involvement.

Media file 2: Exfoliative dermatitis close-up view showing erythema and scaling.

References

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. Bruno TF, Grewal P. Erythroderma: a dermatologic emergency. CJEM. May 2009;11(3):244-6. [Medline].

8. Burton JL, Holden WE. Lichenification and prurigo. In: Champion RH, ed. Textbook of Dermatology. 6^th ed. London, England: Blackwell Science; 1998:673-8.

9. 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.

10. 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.

11. Nakamura M, Tokura Y. Tocilizumab-induced erythroderma. Eur J Dermatol. May-Jun 2009;19(3):273-4. [Medline].

12. 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].

13. Sehgal VN, Srivastava G. Exfoliative dermatitis. A prospective study of 80 patients. Dermatologica. 1986;173(6):278-84. [Medline].

14. 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].

15. 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

Contributor Information and Disclosures

Author

Sanusi H Umar, MD, FAAD, Attending Physician, Department of Dermatology, Charles R Drew/MLK Medical Center
Sanusi H Umar, MD, FAAD is a member of the following medical societies: American Academy of Dermatology, American College of Physicians, and 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 R Drew University
A Paul Kelly, MD is a member of the following medical societies: American Academy of Dermatology, American Dermatological Association, American Medical Association, American Society for Dermatologic Surgery, National Medical Association, and Pacific Dermatologic Association
Disclosure: Nothing to disclose.

Medical Editor

James W Patterson, MD, Director of Dermatopathology, Professor of Pathology and Dermatology, Departments of Pathology and Dermatology, 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 Medical Association, American Society of Dermatopathology, Medical Society of Virginia, Royal Society of Medicine, Society for Investigative Dermatology, and United States and Canadian Academy of Pathology
Disclosure: Nothing to disclose.

Pharmacy Editor

Richard P Vinson, MD, Assistant Clinical Professor, Department of Dermatology, Texas Tech University 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, Association of Military Dermatologists, Texas Dermatological Society, and Texas Medical Association
Disclosure: Nothing to disclose.

Managing Editor

Rosalie Elenitsas, MD, Herman Beerman Associate 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 and American Society of Dermatopathology
Disclosure: Nothing to disclose.

CME Editor

Joel M Gelfand, MD, MSCE, Medical Director, Clinical Studies Unit, Assistant Professor, Department of Dermatology, Associate Scholar, Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania
Joel M Gelfand, MD, MSCE is a member of the following medical societies: Society for Investigative Dermatology
Disclosure: AMGEN Consulting fee Consulting; AMGEN Grant/research funds None; Genentech Consulting fee Consulting; Centocor Consulting fee Consulting; Centocor Grant/research funds None; Covance Consulting fee Consulting; Shire  Consulting

Chief Editor

Dirk M Elston, MD, Director, Department of Dermatology, Geisinger Medical Center
Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology
Disclosure: Nothing to disclose.

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