Exfoliative Dermatitis 

Updated: Aug 15, 2019
Author: David Vearrier, MD, MPH; Chief Editor: Barry E Brenner, MD, PhD, FACEP 

Overview

Practice Essentials

Exfoliative dermatitis is characterized by generalized erythema with scaling or desquamation affecting at least 90% of the body surface area. Systemic derangements may occur with exfoliative dermatitis, including peripheral edema, increased insensible fluid losses, disturbed thermoregulation, and high-output heart failure. See Clinical Presentation for more detail.

Etiology of exfoliative dermatitis

The underlying etiology of exfoliative dermatitis is variable; the most common causes are as follows:

  • Psoriasis
  • Drug reactions
  • Atopic dermatitis
  • Cutaneous T-cell lymphoma

Exfoliative dermatitis is frequently idiopathic in nature. See Differential Diagnosis and Workup for more detail.

Treatment of exfoliative dermatitis

Treatment in the emergency department consists of the following:

  • Fluid resuscitation to replace insensible losses

  • Correction of electrolyte and thermoregulatory disturbances if present

  • Initiation of antihistamines and corticosteroids in consultation with a dermatologist

Patients with acute or severe exfoliative dermatitis may require hospitalization to correct and manage fluid and protein losses and electrolyte disturbances. See Treatment and Medication for more detail.

Background

Exfoliative dermatitis, or erythroderma, is an erythematous, scaly dermatitis involving at least 90% of the skin surface. The diagnosis of exfoliative dermatitis is based on skin findings on physical examination and not on the underlying etiology for the dermatitis, which is variable and may be idiopathic (see Differential Diagnosis).

Exfoliative dermatitis diffuse skin involvement Exfoliative dermatitis diffuse skin involvement

The term "erythroderma" was first used by Hebra in 1868 to describe exfoliative dermatitis affecting at least 90% of the skin surface area.[1] Historically, exfoliative dermatitis was classified by its clinical course into one of three variants: Wilson-Brocq (chronic-relapsing), Hebra (chronic-persisting or progressive), and Savill (self-limited). These classifications are no longer used as clinical focus has shifted to the underlying etiology for the dermatitis.

Pathophysiology

The pathophysiologic processes resulting in exfoliative dermatitis vary with the underlying disorder responsible for the dermatitis. However, common to all conditions that cause exfoliative dermatitis is an increased rate of skin turnover. Normal epidermis has a continual turnover of epithelial cells. Cell division occurs near the basal layer. As cells move toward the periphery, they become well-keratinized. This process requires approximately 10-12 days. Cells subsequently remain in the stratum corneum for another 12-14 days prior to being sloughed.

In exfoliative dermatitis, the number of cells in the germinative layer and their mitotic rate is increased. The transit time of cells through the epidermis is shortened. As a result, the exfoliated scales are incompletely keratinized and contain material normally retained by the skin, including proteins, amino acids, and nucleic acids, which may result in a negative nitrogen balance.[2, 3] The amount of scale lost varies by underlying condition and its severity. Exfoliative dermatitis due to drug reactions, eczema, and psoriasis may result in the loss of 7.2 g, 9.6 g, and 22.6 g of scale per day, respectively (normal range, 500-1000 mg). Protein lost in that scale is 4.2 g, 5.6 g, and 12.8 g per day, respectively. The decreased transit time also results in impaired skin barrier function from incomplete keratinization, which may increase the absorption of medications administered transcutaneously through damaged skin.

Another common pathophysiologic process to all forms of exfoliative erythroderma is increased blood flow to the skin, which, in combination with impaired skin barrier function, results in increased insensible fluid loss through transpiration. Dehydration and reflex tachycardia are common. In severe cases, high-output cardiac failure may occur. Increased cutaneous blood flow also leads to increased heat loss, which may lead to a compensatory hypermetabolism and cachexia.[1]

Etiology of Exfoliative Dermatitis

Within a large series of patients with exfoliative dermatitis, the underlying etiology was preexisting dermatitis (24%), psoriasis (20%), drug eruptions (19%), and cutaneous T-cell lymphoma (8%).[1] Within the category of preexisting dermatitis, the most common causes were atopic dermatitis (9%), contact dermatitis (6%), seborrheic dermatitis (4%), and chronic actinic dermatitis (3%). Despite investigation, 25% of exfoliative dermatitis is idiopathic in nature. Less common causes include ichthyoses, bullous dermatoses, pityriasis rubra pilaris, Ofuji papuloerythroderma, hypereosinophilic syndrome,[4] systemic lupus erythematosus.

Among infants, the major causes of exfoliative dermatitis are ichthyoses, immunodeficiencies, psoriasis, and infection (eg, staphylococcal scalded skin syndrome).[1]

Common and less common causes of exfoliative dermatitis in adults and clinical clues to diagnosis are included in Table 1.[5]  

Table 1. Clinical Clues to Causes of Exfoliative Dermatitis in Adults (Open Table in a new window)

Underlying Disease History Examination

Psoriasis (common)

 

  • Medical history or family history of psoriasis
  • Withdrawal of corticosteroids, methotrexate, or cyclosporine
  • Face is spared
  • Nail pitting, translucent yellow-red nailbed discoloration, onycholysis
  • Inflammatory arthritis
Atopic dermatitis (common)
  • Past medical history or family history of atopy such as eczema, allergic rhinitis, or asthma
  • Severe pruritus
  • Cataracts
  • Flexural skin most severely affected
  • Lichenification
  • Prurigo nodularis
Drug reactions (common)
  • Recent history of morbilliform or scarlatiniform exanthem
  • No past history of skin disease
  • Medication history includes one of implicated drugs
  • Facial edema
  • Purpura in dependent areas
Idiopathic (common)
  • Elderly men
  • Severe pruritus
  • Chronic and relapsing
  • Palmoplantar keratoderma
  • Dermatopathic lymphadenopathy

Cutaneous T-cell lymphoma

(less common)

  • Intense pruritus
  • Reddish-purple hue
  • Painful, fissured keratoderma
  • Alopecia
  • Leonine facies

Pityriasis rubra pilaris 

(less common)

  • Exacerbated by sun exposure
  • Cephalocaudal progression
  • Salmon hue
  • Sharply demarcated islands of sparing ("nappes claires")
  • Waxy keratoderma
  • Perifollicular keratotic papules

Contact and stasis dermatitis with autosensitization

(less common)

  • History of localized rash
  • Distribution of initial lesions
  • Occupational exposures, hobbies
  • Oral medications (systemic contact dermatitis)

 

Paraneoplastic erythroderma 

(less common)

  • History of malignancy or lymphoproliferative disorder
  • Fine scale
  • Hyperpigmentation
  • Cachexia

Numerous drugs have been implicated in exfoliative dermatitis. Commonly and less commonly implicated medication are summarized in Table 2.[1]  

Table 2. Medications Associated With Exfoliative Dermatitis (Open Table in a new window)

Common Uncommon
  • Allopurinol
  • Beta-lactam antibiotics
  • Carbamazepine
  • Gold
  • Phenobarbital
  • Phenytoin
  • Sulfasalazine
  • Sulfonamides
  • Zalcitabine
  • ACE-inhibitors
  • Chloroquine
  • Colony-stimulating factors
  • Cytarabine
  • Dapsone
  • Diflunisal
  • Efavirenz [6]
  • Fluindione
  • Hydroxychloroquine
  • Isoniazid
  • Isotretinoin [7]
  • Lithium
  • Minocycline
  • Platinum-based antineoplastics
  • Proton-pump inhibitors
  • Ribavirin
  • Thalidomide
  • Tocilizumab [8]
  • Vancomycin (not "red man syndrome" during infusion)

Epidemiology

Frequency

The incidence and prevalence of exfoliative dermatitis have not been well-characterized.[1]  

Race

Exfoliative dermatitis occurs in all races. 

Sex

The male-to-female ratio is approximately 2:1 to 4:1.

Age

The average age at onset is 52 years.[1] When children are excluded, the average age of onset in adults is 60 years. 

Prognosis

Prognosis depends on the underlying etiology causing the exfoliative dermatitis.

In general, long-term prognosis is good for patients with drug-induced disease after the offending agent is withdrawn and proper supportive measures are undertaken. Typically, symptoms resolve within 2-6 weeks after cessation of the offending agent.

For patients with idiopathic exfoliative dermatitis, the prognosis is poor. Frequent recurrences or chronic symptoms require long-term steroid therapy and its attendant sequelae.

For patients with underlying disease or malignancy, prognosis rests on the outcome and course of the disease process.

Patient Education

Patients should be educated on the risks of secondary bacterial infections (eg, skin and soft tissue infections), fluid loss and dehydration, and hyperthermia/hypothermia. Patients should be advised to avoid known or suspected etiologic agents (eg, medications, allergens). Educate patients with underlying disease about symptomatic treatment and advise that many cases spontaneously remit. Advise patients to drink plenty of fluids and follow a high-protein diet to counteract increased fluid and protein losses.

 

Presentation

History

A thorough history may elucidate the underlying etiology for the exfoliative dermatitis. The most common cause of exfoliative dermatitis is generalization of a preexisting dermatitis. Therefore, patients should be queried about a history of psoriasis or atopic, contact, seborrheic, or chronic actinic dermatitis. Drug eruption is a common cause of exfoliative dermatitis, so a thorough medication history is essential. Drug-induced exfoliative dermatitis may occur with oral or topical medications. A history of a localized exanthem followed by generalization is more common with topical medications, while a history of a morbilliform or scarlatiniform eruption is common with oral medications.

The most common complaint in patients with exfoliative dermatitis aside from rash is pruritus, which occurs in approximately 90% of patients.[1] The severity of the pruritus varies by underlying condition, being most severe in atopic dermatitis and cutaneous T-cell lymphoma. Complaints of hair loss and nail changes are common. Sun exposure may worsen the rash, particularly in pityriasis rubra pilaris.

 

Physical Examination

Vital sign derangements include tachycardia, hyperthermia, and hypothermia. Tachycardia is reflexive in nature, occurring from increased insensible fluid losses and third spacing of fluid.[1] Hyperthermia occurs in 37% of patients and may be due to a hypermetabolic state, while hypothermia occurs in 4% of patients and may be due to excessive heat loss from increased cutaneous blood flow.

Abdominal examination may reveal hepatomegaly (20%), which is most common in drug-induced exfoliative dermatitis.[1] Splenomegaly is uncommon and suggestive of lymphoma.

By virtue of the definition of exfoliative dermatitis, skin examination is significant for erythema and scaling of at least 90% of the skin area. In acute exfoliative dermatitis, erythema may precede exfoliation by 2-6 days and so may not be present when a patient first seeks medical attention.[1] The character of the scale may provide clues to the underlying etiology: fine in atopic dermatitis and dermatophytosis, greasy in seborrheic dermatitis, large exfoliative scale in drug eruptions, and crusted in pemphigus foliaceus.

In chronic exfoliative dermatitis, hyperpigmentation (45%), hypopigmentation or depigmentation (20%), palmoplantar keratoderma (30%), lichenification (one third), nonscarring alopecia (20%), and multiple seborrheic keratoses may be seen.[1] Nail changes may be present in 40% of patients and may include shininess, brittleness, dullness, discoloration, subungual hyperkeratosis, Beau lines, paronychia, splinter hemorrhages, and nail loss. 

Pretibial or pedal edema may be seen in 50% of patients with exfoliative dermatitis.[1] Facial edema may occur with drug-induced exfoliative dermatitis. Diffuse lymphadenopathy is common, seen in approximately 50% of patients, and may be reactive in nature (ie, reactive dermatopathic lymphadenopathy) or may be due to lymphoma.

Complications

The most common complications of exfoliative dermatitis include dehydration, disturbed thermoregulation, poor nutritional status, and secondary bacterial infections (eg, skin and soft tissue infections). Secondary cutaneous infections may occur in patients with exfoliative dermatitis due to colonization of the skin with S aureus and impaired skin barrier function.

Use of corticosteroids or immunomodulators and impaired skin barrier function may result in opportunistic infections, including fungal infections.

 

DDx

 

Workup

Approach Considerations

The primary emergency department role in the workup of exfoliative dermatitis is evaluation for systemic derangements as a result of increased insensible fluid loses, changes in fluid distribution, and disturbed thermoregulation. While the underlying cause of some cases of exfoliative dermatitis (eg, drug-induced or generalization of a preexisting dermatitis) may be presumptively identified in the emergency department, identification and/or confirmation of the underlying condition is typically beyond the scope of emergency department care. Therefore, appropriate follow up with a dermatologist for further testing such as skin biopsy and/or lymph node biopsy is critical.

Laboratory Studies

Laboratory studies that may be performed from the emergency department include the following:

  • Complete blood count: May demonstrate iron-deficiency anemia or anemia of chronic disease; eosinophilia may be present in cases due to generalization of atopic dermatitis; eosinophilia should also prompt consideration of DRESS (drug rash with eosinophilia and systemic symptoms)/DIHS (drug-induced hypersensitivity) in the differential diagnosis

  • Chemistry panel: May demonstrate hypernatremia, prerenal azotemia, or acute renal failure due to insensible fluid losses

  • Serum albumin and prealbumin: May be decreased owing to poor nutritional status from protein loss through exfoliation

  • Erythrocyte sedimentation rate and serum quantitative C-reactive protein: May demonstrate systemic inflammatory state

  • Urinalysis, blood cultures: May be obtained if there is suspicion of infection as a cause of exacerbation of preexisting skin disease (eg, generalization of psoriasis)

  • Nasal swab for methicillin-resistant Staphylococcus aureus (MRSA)

 

Imaging Studies

In most cases, imaging is not necessary. Chest radiograph and other imaging may obtained if there is suspicion of infection as a cause of exacerbation of preexisting skin disease (eg, generalization of psoriasis) or if high-output cardiac failure is suspected.

Procedures

No procedures are typically necessary in the emergency department evaluation of exfoliative dermatitis. Peripheral intravenous access by nursing may be difficult to obtain because of overlying skin changes, and ultrasound-guided venous access may be necessary. Inpatient or outpatient follow-up procedures include skin biopsy, which may give histologic clues to the underlying disease. In patients with diffuse lymphadenopathy, follow up includes lymph node biopsy with flow cytometry.

 

Treatment

Medical Care

Many patients with acute exfoliative dermatitis require hospitalization for correction of fluid losses and disturbed thermoregulation.[9] Interventions include the following:

  • Discontinue any medications suspected as cause of drug-induced exfoliative dermatitis

  • Application of bland emollients (eg, petrolatum) to reduce insensible fluid losses and enhance skin barrier function

  • Weeping or crusted sites may be covered with nonadherent dressings and petrolatum to reduce damage to newly formed adjacent skin

  • Correction of hyperthermia or hypothermia

  • Antibiotic administration when underlying infection is suspected or identified as cause of exfoliative dermatitis or when a secondary skin and soft tissue infection is present

  • Intravenous fluids to correct dehydration

  • Sedating antihistamines for pruritus

  • Systemic or topical corticosteroid therapy or immunosuppressants should be guided by a dermatologist as it may worsen some forms of exfoliative dermatitis; of note, increased absorption of topical medications when applied to damaged skin should be anticipated.

Consultations

Urgent consultation with a dermatologist is recommended.

Long-Term Monitoring

For patients who do not require hospitalization, outpatient follow up with a dermatologist should be arranged to avoid delays in care and further diagnostic testing.

 

Medication

Medication Summary

Treatment of the underlying illness is key since exfoliative dermatitis resists treatment until the basic disease is treated. Cyclosporine has been reported to be effective,[10]  as has etanercept.[11]

Corticosteroids

Class Summary

These agents have anti-inflammatory properties and cause profound and varied metabolic effects. They modify the body's immune response to diverse stimuli. They also are used to treat idiopathic and acquired autoimmune disorders.

Prednisone (Deltasone, Orasone, Meticorten)

Prednisone is a glucocorticoid that readily is absorbed from the GI tract. It is used primarily for anti-inflammatory effects in disorders of many organ systems.

Antihistamines

Class Summary

These agents are used to treat minor allergic reactions and anaphylaxis. They are used for relief of pruritus.

Diphenhydramine (Benadryl, Benylin)

Diphenhydramine is for symptomatic relief of symptoms caused by the release of histamine in allergic reactions. It may control itching by blocking the effects of endogenously released histamine.

Immunosuppressives

Class Summary

These agents interfere in the immune processes that promote inflammation. They are used to relieve chronic severe dermatitis.

Cyclosporine (Neoral, Sandimmune, Gengraf)

Cyclosporine has been demonstrated to cause remission in some patients. It has improved the overall prognosis of exfoliative dermatitis.

Antirheumatic, Disease Modifying

Class Summary

These agents modulate inflammatory and immune responses.

Etanercept (Enbrel)

Etanercept is a soluble p75 TNF receptor fusion protein (sTNFR-Ig). It inhibits TNF binding to cell surface receptors, which, in turn, decreases inflammatory and immune responses. It has been reported to be effective. There is no current FDA approval/indication for the use of this drug with exfoliative dermatitis.

 

Questions & Answers

Overview

What are the signs and symptoms of exfoliative dermatitis?

How is exfoliative dermatitis treated in the emergency department (ED)?

What are the most common causes of exfoliative dermatitis?

What is exfoliative dermatitis?

What is the pathophysiology of exfoliative dermatitis?

What causes exfoliative dermatitis?

Which medications may cause exfoliative dermatitis?

What is the prevalence of exfoliative dermatitis?

What are the racial predilections of exfoliative dermatitis?

What are the sexual predilections of exfoliative dermatitis?

Which age groups have the highest prevalence of exfoliative dermatitis?

What is the prognosis of exfoliative dermatitis?

What is included in patient education about exfoliative dermatitis?

Presentation

Which clinical history findings are characteristic of exfoliative dermatitis?

Which physical findings are characteristic of exfoliative dermatitis?

What are the possible complications of exfoliative dermatitis?

DDX

What are the differential diagnoses for Exfoliative Dermatitis?

Workup

What is included in the emergency department (ED) workup of exfoliative dermatitis?

Which lab tests are performed in the workup of exfoliative dermatitis?

What is the role of imaging studies in the workup of exfoliative dermatitis?

Which clinical procedures are performed in the workup of exfoliative dermatitis?

Treatment

How is exfoliative dermatitis treated?

Which specialist consultations are beneficial to patients with exfoliative dermatitis?

What is included in the long-term monitoring of exfoliative dermatitis?

Medications

Which medications are used in the treatment of exfoliative dermatitis?

Which medications in the drug class Antirheumatic, Disease Modifying are used in the treatment of Exfoliative Dermatitis?

Which medications in the drug class Immunosuppressives are used in the treatment of Exfoliative Dermatitis?

Which medications in the drug class Antihistamines are used in the treatment of Exfoliative Dermatitis?

Which medications in the drug class Corticosteroids are used in the treatment of Exfoliative Dermatitis?