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Exfoliative Dermatitis

Editor: Leela Athalye Updated: 5/1/2023 6:00:22 PM


Von Hebra first described erythroderma (exfoliative dermatitis) in 1868. It characteristically demonstrates diffuse erythema and scaling of greater than 90% of the body surface area. It is a reaction pattern and cutaneous manifestation of a myriad of underlying ailments, including psoriasis and eczema, or a reaction to the consumption of certain drugs. Though some experts believe it does not pose a significant risk of death, erythroderma is a potentially life-threatening condition that requires proper diagnosis, identification of underlying etiology, and management.[1][2]


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Several factors have been implicated as triggers for erythroderma and can be grouped into several general categories, including preexisting dermatoses, drugs, and malignancies, while some cases of erythroderma are idiopathic.[3] Bullous congenital ichthyosiform erythroderma, more commonly referred to as epidermolytic hyperkeratosis, is a rare congenital cause of erythroderma.[4]

The most common cause of erythroderma is preexisting cutaneous conditions, and multiple analyses implicate psoriasis as the most common causal dermatosis accounting for roughly half of erythroderma cases in certain analyses.[1][3][5][6] Eczematous dermatoses are also a well-established cause [1][3][2] and have also been implicated as the predominant cause of erythroderma in at least one analysis.[5] Other less common dermatoses leading to an erythroderma reaction include pityriasis rubra pilaris, acquired ichthyosis, cutaneous lupus, scabies, bullous pemphigoid, pemphigus foliaceus, actinic dermatoses, and actinic keratosis, among others.[3][5]

Exfoliative dermatitis may also be elicited by certain drugs and heralded by a more typical morbilliform, lichenoid, or urticarial eruption.[1] These drugs include antiepileptics (phenytoin, carbamazepine, and phenobarbital), antibiotics (sulfonamides, penicillins, and vancomycin), lithium, and allopurinol, among others.[1][3][5][2]

1% of patients with erythroderma have an underlying malignancy.[1] Certain malignancies also have a strong association with erythroderma, including but not limited to CTCL (cutaneous T-cell lymphoma) such as mycosis fungoides and Sezary syndrome, B-cell chronic lymphocytic leukemia, and solid organ malignancies such as gastric, esophageal, colon, liver, prostate, and lung cancer, among others.[1][3][5]


The actual incidence of exfoliative dermatitis in the U.S. and worldwide is unknown.[1] Several studies have recorded the incidence of erythroderma in varying clinical settings. In one study from India, for example, the incidence of erythroderma in outpatient dermatology offices was 35 per 100000 patients (0.035%), while another study in Portugal showed the incidence of erythroderma in hospitalized patients to be 11.9%.[7][3] Yet another study suggested a general incidence of 1 to 2 patients per 100000.[8] 

Generally speaking, erythroderma has a predilection of males to females varying between 2 and 4 to 1 and a mean age of onset between 40 and 60.[9] 


The exact pathogenesis of erythroderma is unknown. Some have postulated that increased expression of adhesion molecules in epithelial cells ultimately increases dermal inflammation and epidermal proliferation.[1] An increase in mitosis causes an increased number of overall epidermal cells, increased cell turnover, and a decrease in transit time through the epidermis. This condition manifests itself as the characteristic dramatic exfoliation seen in erythrodermic patients.[6]


Though biopsies are routinely used in conjunction with clinical findings to establish the underlying cause of erythroderma, nonspecific histopathologic findings are commonly present.[6] They include perivascular dermal infiltrate with or without eosinophils, acanthosis, hyperkeratosis, and parakeratosis. Additionally, the typical histopathologic presentation of underlying and causal dermatoses may not be evident due to confounding histology in patients with erythroderma, although this occurs in less than half of cases.[10][6]

History and Physical

The classical physical finding of erythroderma is bright red patches that coalesce to cover almost the entire skin surface, followed by the appearance of a white or yellow scale. The skin may appear glossy and thin, and the patient may complain of tight skin due to progressive lichenification and edema.[1] Pruritis occurs in nearly all patients, and fever may be present in more than half.[3] Lymphadenopathy, splenomegaly, and hepatomegaly may be present in almost half of patients and may suggest a drug hypersensitivity or malignancy.[3][1]

Some patients may also present with hair loss and nail findings, including subungual hyperkeratosis, onycholysis, ridging, dry or brittle nails, or nail shedding. Additionally, patients may have evidence of the underlying causal dermatoses, such as psoriasiform plaques in psoriasis or palmoplantar keratoderma in patients with pityriasis rubra pilaris.[1]


Erythroderma is a clinical finding, but correlation with laboratory studies and histopathology is common practice to corroborate clinical suspicion and identify an underlying cause.[6] Direct immunofluorescence may be useful to identify underlying bullous or connective tissue disease.[1] Laboratory abnormalities are nonspecific, though ESR and CRP are elevated in a vast majority of cases.[3] Anemia, leukocytosis, eosinophilia, and abnormal serum protein levels may also be present in some patients.[1]

Treatment / Management

Erythroderma can be severe and life-threatening and may require admission to the hospital.[11] Management of erythroderma predominantly involves monitoring and ensuring metabolic and hemodynamic stability.[1] Additionally, emphasis should focus on symptom management with bed rest and proper wound care, including lukewarm baths, wet dressings, mild topical corticosteroids, and bland emollients.[1][10] Oral antihistamines may also be helpful.[10] Findings suggestive of secondary infection warrant antibiotic therapy.[1] Once identified, the underlying disease process requires attention and appropriate treatment.[1](B3)

Management of idiopathic cases may include emollients, oral or topical steroids, methotrexate, azathioprine, PUVA, or other modalities depending on patient response.[10]

Differential Diagnosis

Erythroderma is a clinical finding overlying one of a myriad of potential triggers, including dermatoses, drugs, malignancies, and idiopathic causes.[1] Identifying a cause requires correlation between patient history, clinical presentation, biopsy and direct immune fluorescent test findings, and laboratory studies. Other differentials include:

  • Acanthosis nigricans
  • Acute complications of sarcoidosis
  • Cutaneous T-cell lymphoma
  • Dermatologic manifestations of graft versus host disease
  • Allergic contact dermatitis
  • Bullous pemphigoid
  • Familial benign pemphigus (Hailey-Hailey disease)
  • Irritant contact dermatitis
  • Lichen planus
  • Pityriasis rubra pilaris
  • Plaque psoriasis
  • Reactive arthritis
  • Pediatric atopic dermatitis
  • Pemphigus foliaceus
  • Seborrheic dermatitis
  • Stasis dermatitis


Response to therapy varies by the underlying causal disease or agent. Drug-associated erythroderma tends to resolve quickly with discontinuation of the offending agent and prompt treatment. Erythroderma associated with primary skin disease tends to have a slower course and may also resolve more slowly. Malignancy-associated erythroderma may be more progressive and its course dictated by the prognosis of the underlying malignancy and response to therapy, while idiopathic erythrodermic cases may be unpredictable with periods of relapse and remission.[1][10] 


Exfoliative dermatitis had previously reported mortality ranging from 4% to 64%, though these numbers are outdated with improved quality of care and management.[1][2] Several case studies have calculated much smaller mortality numbers ranging from 0 to 6% and postulated that erythroderma does not pose a significant risk of death.[2][6] Another case suggested that the risk of death for non-malignant cases of erythroderma is small.[3] 

Elderly patients that develop complications such as infection, fluid or electrolyte balance, or heart failure are at most risk for mortality. Heart failure, septicemia, and pneumonia are the most common cause of death in patients with erythroderma.[1][10]

Deterrence and Patient Education

In the case of drug-induced erythroderma, patients need counsel on avoidance of the specific trigger drug. For patients with underlying dermatoses, emphasis should be on ensuring proper management and follow-up for their underlying condition to decrease the risk of relapse. Those with psoriatic arthritis, atopic dermatitis, or other steroid-responsive dermatoses should understand that abrupt withdrawal of oral steroids may trigger an erythrodermic reaction.[1] Additionally, patients with an underlying malignancy should receive proper attention and follow-up with appropriate hematology/oncology professionals.

Lastly, reasonable expectations are necessary with regard to the clearance of their clinical findings, which varies from case to case. Patients should also be made aware of possible long-term sequelae, though rare, including postinflammatory hyperpigmentation or hypopigmentation in darker skin types, permanent nail changes, and keloid formation, among others.[10]

Enhancing Healthcare Team Outcomes

The process of delivering quality, patient-centered care to an erythrodermic patient presenting to a clinic or emergency department is a multi-step process requiring the coordination and communication of a multitude of healthcare providers from different backgrounds. It requires proper training for healthcare staff, including triage nurses, and excellent clinical acumen from physicians and other medical providers in inpatient and outpatient settings for appropriate diagnosis and management of erythroderma cases. The dermatology department should be consulted if not already involved in the patient's care. Additionally, infectious disease, cardiology, and pulmonology specialists should be consulted and engaged if severe erythroderma complications arise. Hematology/oncology should be included in the interprofessional team if an underlying malignancy is suspected or confirmed.

A thorough history and physical is necessary, and appropriate pharmacy staff should be included in the discussion if drugs are suspected culprits. Clear communication and collaboration with the laboratory staff and pathologist should be a priority to help establish the underlying cause. The pharmacy team also has an essential role in helping develop a treatment regimen in conjunction with the managing provider to ensure optimal management. Finally, appropriate follow-up with the next echelon of care must take place before discharge from an inpatient setting. The patient's primary care manager should be informed, and the patient should have follow-up care established with a dermatologist if they don't already. In the case of underlying malignancy, proper continuity with hematology/oncology should also be arranged to ensure appropriate monitoring and treatment.

Nursing and pharmacy will also contribute to the interprofessional team management of the condition. Nursing can counsel, verify treatment progress and patient compliance, and answer patient questions. Pharmacists will verify all dosing on drug therapy, counsel patients on administration and adverse effects, and contact the provider if any interactions present secondary to the therapy regimen. These interprofessional strategies will optimize outcomes for patients. [Level 5]



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