Exfoliative dermatitis (erythroderma)

Erythroderma

I. What every physician needs to know.

Patients with erythroderma present with generalized erythema, involving up to 100% of the body surface area, and marked exfoliation and desquamation. Often the patient will resemble a burn victim in many ways. The skin is tender, sore or burning. The erythrodermic state predisposes the patient to significant morbidity and mortality and as such should be viewed as a medical emergency, often requiring hospitalization. Erythroderma can be categorized as acute or chronic.

Exfoliative erythroderma may be the clinical presentation of a number of cutaneous or systemic diseases. Establishing the underlying diagnosis may be very difficult initially. The etiology may vary depending on whether the erythroderma is acute or chronic. Oftentimes, drugs are implicated as the inciting agent in acute erythroderma but they can be the cause in chronic erythroderma, especially the calcium channel blockers. Fever is often an accompanying sign of erythroderma, making it difficult to differentiate it from an infection. In addition to infections and drugs, primary dermatologic diseases such as psoriasis and atopic dermatitis may be underlying causes. A careful history of pre-existing dermatologic disorders may help the clinician to establish the cause.

II. Diagnostic Confirmation: Are you sure your patient has Erythroderma?

Histology of erythroderma is not always helpful; however in approximately 40% of cases, we do see distinct histologic evidence of the primary disease process. When the histopathology is more subtle or obscured, multiple biopsies may improve the diagnosis. Specific immunophenotyping and other histologic examination may secure the diagnosis.

A. History Part I: Pattern Recognition:

Figure 1), atopic dermatitis, Cutaneous T Cell Lymphoma and Pityriasis Rubra Pilaris (PRP; See Figure 2). The general appearance of an erythrodermic patient is similar, regardless of the underlying trigger or disease process. Patients appear “red” from head to toe, with scaling or desquamating skin. When acute, the patient lay look like a toxic erythema or even like an intense sunburn.

Erythroderma secondary to Pityriasis Rubra Pialris

Keratoderma in patient with Erythroderma

When chronic, patients will have ectropion-pulling down of the eyes, with resultant exposure of the cornea resulting in red or injected conjunctiva and iritis, eclabion of the mouth, thickened keratodermic palms and soles, nail dystrophy with subungual hyperkeratosis. Regardless of acute or chronic, patients have significant dependent edema.

During skin examination, one should look for signs of pre-existing skin diseases. Additionally, many dermatologic diseases can be associated with erythroderma. These include in decreasing order of frequency, Atopic Dermatitis, Psoriasis, Pityriasis Rubra Pilaris and Cutaneous T Cell Lymphoma (CTCL), or Graft vs Host Disease (GVHD). Less commonly, autoimmune processes such as Pemphigus vulgaris or Pemphigus foliaceous or collagen vascular diseases such as systemic lupus or Dermatomyositis may present with erythroderma.

When chronic erythroderma (more than 3 months) or recurrent episodes occur, we must consider other causes as well as underlying dermatologic causes. The underlying disease processes include all the primary dermatologic disease processes listed under acute causes (Table I). When chronic, diseases such as Cutaneous T Cell Lymphoma or Pityriasis Rubra Pilaris should be considered as more likely causes. However, we must also consider drugs as a chronic cause, especially if given intermittently.

Table I.

DrugPrimary Dermatoses

Atopic Dermatitis

Psoriasis

Pityriasis Rubra Pilaris

Cutaneous T Cell Lymphoma

Blistering Diseases

Pemphigus and variants:

Bullous Pemphigoid

Acute or Chronic Contact Dermatitis

Ichthyoses

Infections

Dermatophyte

Scabies

Deep fungal Infections

HIV

Sepsis

Systemic Disease

SLE

Dermatomyositis

Acute Graft vs host Disease

Sarcoidosis

Thyrotoxicosis

Altered immunologic conditions

Immunodeficiency syndromes

Leiner’s Disease

HIV

Malignancy

Blood dyscrasias (CTCL, B cell and T cell disorders, including Lymphomas)

Internal malignancy

B. History Part 2: Prevalence:

Erythroderma is uncommon. It appears to be more common in men and more likely between 40-60 years of age.

C. History Part 3: Competing diagnoses that can mimic Erythroderma.

The differential diagnosis for erythroderma is limited. Staphylococcal scalded skin syndrome in children or TEN should be considered. However, most of the time the diagnosis is not in question. The crucial point is to determine the underlying cause as described in the previous section.

Exfoliative erythroderma may be the clinical presentation of a number of cutaneous or systemic diseases. The etiology may vary depending on whether the erythroderma is acute or chronic. Oftentimes, drugs are implicated as the inciting agent in acute erythroderma but they can be the cause in chronic erythroderma, especially the calcium channel blockers. Fever is often an accompanying sign of erythroderma, making it difficult to differentiate it from an infection.

In addition to infections and drugs, primary dermatologic diseases such as psoriasis and atopic dermatitis may be underlying causes. A careful history of pre-existing dermatologic disorders may help the clinician to establish the cause.

There are a number of drug reactions/syndromes that can result in erythroderma. Drug rash with eosinophilia and systemic symptoms (DRESS) as well as toxic epidermal necrolysis (TEN) can be associated with generalized erythroderma. The most common drugs implicated are the sulfa antibiotics (sulfonamides), the anticonvulsants (phenytoin, phenobarbitals, carbamazepine), allopurinol, tetracycline family, antiviral agents and terbinafine.

Typically, patients develop an eruption with 3-4 weeks of starting the medication. Diffuse exfoliation may occur. While there may be sloughing of the skin, there is no discreet bulla formation to suggest TEN and no Nikolsky sign. Mucosal involvement would support a drug-induced cause. There is usually fever, associated elevated liver enzymes, renal insufficiency, cardiac abnormalities and lymphadenopathy. Hence, the term DRESS. Thyroid abnormalities, i.e. hypothyroidism may occur months after resolution. Elimination of infectious etiologies and the temporal association of new drug ingestion, and absence of hypotension would support this etiology.

Since infections may be inciting causes, appropriate examination for Kawasaki Syndrome in children, toxin-mediated infections and toxic shock syndrome should be performed when suspected.

Once erythroderma has cleared, identification of characteristic dermatologic findings of potentially underlying causes should be identified.

D. Physical Examination Findings.

Erythroderma may occur spontaneously or develop over months. A more rapid onset would suggest drug as the cause. Clinically, one sees an acutely ill appearing individual with generalized erythema, with or without desquamation. Signs include rigors and chills due to thermoregulatory dysfunction. Frequently, there is dependent edema especially in the lower extremities. On physical exam, patients are tachycardic, possibly dysrhythmic, sometimes dyspneic and quite ill appearing.

Patients with erythroderma complain of constitutional symptoms such as fever, chills and even rigors, and pruritus. Diffuse alopecia, keratoderma, nail dystrophy and weight loss are more common in the chronic state. These patients are systemically ill and oftentimes very unstable medically. These patients are indeed a medical emergency and require hospitalization. Older patients are often hemodynamically unstable and are at risk for high output cardiac failure, adult respiratory distress syndrome, capillary leak syndrome, renal compromise and negative nitrogen balance.

E. What diagnostic tests should be performed?

Consultation with a dermatologist may provide the admitting physician with suggestions regarding biopsy and for local skin care.

1. What laboratory studies (if any) should be ordered to help establish the diagnosis? How should the results be interpreted?

Laboratory evaluation include complete blood count and differential, comprehensive metabolic panel, blood, skin and urine cultures if infection is suspected as a trigger factor. Nutritional assessment is important especially in the chronic erythrodermic, as many of the patients will have low albumin and negative nitrogen balance. Biopsy of the skin should be done if there is no history of prior dermatologic disorders. If appropriate or if suspicion of lymphoma, immunophenotyping/flow cytometry may be helpful in obtaining the diagnosis. Careful examination and identification of the triggers for erythroderma should be done to look for infection, allergy/contact hypersensitivity.

2. What imaging studies (if any) should be ordered to help establish the diagnosis? How should the results be interpreted?

Imaging studies are not usually done unless patient has specific co-morbidities such cardiac or renal disease.

Histology of erythroderma is not always helpful but in approximately 40% of cases, we see distinct histologic evidence of the primary disease process. Multiple biopsies may improve the diagnosis. Specific immunophenotyping and other histologic examination may secure the diagnosis.

F. Over-utilized or “wasted” diagnostic tests associated with this diagnosis.

III. Default Management.

When the diagnosis is apparent, therapy and management can be directed to the erythroderma and the underlying primary disease process. Regardless of the cause or trigger, management is directed towards fluid and electroyte management, nutrition, restoring the normal skin barrier and to correction of the cardiac and nutritional aspects.

Patients presenting with erythroderma should be viewed as a medical emergency. They should be admitted to the hospital. Once admitted, a complete history and physical may help with the diagnosis – pay attention to the patient’s drug history and their past dermatologic history. Questions to ask include: recent drug history; past history of skin disorders; recent history of oral or injectable corticosteroids in the past month?

Since patients are at risk for high output failure, erythrodermic patients require strict fluid management, electrolyte management and evaluation and treatment of underlying cardiac issues as well as nutritional assessment.

Consultation with a dermatologist may provide the admitting physician with suggestions regarding biopsy and for local skin care.

A. Immediate management.

Management during hospitalization involves re-establishing the normal skin barrier and correction of transepidermal water loss. This can be accomplished quickly by application of mid-potency topical corticosteroids and occlusion (with disposable occlusive “jump suits”) or cotton pajama suits (long sleeve and long pants). If unavailable, one can use plastic wrap to occlude. Whirlpool therapy may be beneficial if available. If scalp is crusting, keratolytic agents such as salicylic acid shampoos or urea based shampoos can be used. If drug allergy is suspected, withdrawal of the offending agent is paramount. As there is extensive transepidermal water loss, careful management of fluids is important. Restriction of fluid intake may be required.

Evaluation and treatment of the co-morbidities such as cardiac and renal function are also important. Some of these co-morbidities may be improved with management and improvement in skin barrier function. Once the patient is stabilized and the etiology of the erythroderma is apparent, appropriate therapy for the underlying disease should be initiated. If the biopsy demonstrates a drug eruption, withdrawal of the drug will often result in rapid clearing. However, in the case of some drug eruptions, especially in the elderly, the eruption may continue for months after discontinuation of the drug.

If the underlying pathogenesis is psoriasis, therapy with oral retinoids, cyclosporine A or an anti-TNF agent may be initiated depending on the patient’s co-morbidities. When Atopic Dermatitis is the basis of the erythroderma, treatment with topical steroids may be sufficient. If not, systemic steroid sparing agents may be recommended.

B. Physical Examination Tips to Guide Management.

Management of fluids and nutrition is important. Prompt recognition and management of co-morbidities will significantly shorten the hospital stay. If cardiac complications are present those should be dealt with accordingly. Prompt management of the skin will often correct the co-morbidities which develop as a consequence of the erythroderma, i.e. edema, water loss fluid and electrolyte imbalance. Consultation with the dermatologist can provide skin care regimens.

C. Laboratory Tests to Monitor Response To, and Adjustments in, Management.

Fluid and electroyte balance should be monitored closely. One should start to address any nutritional deficits but this can be managed as an outpatient.

D. Long-term management.

Good nutrition, with attention to replacement of protein should be addressed. Treatment of the underlying disease process decreases the episodes of erythroderma and may correct the nutritional and fluid imbalances. Treatment of underlying dermatologic processes is complex and is best done by the dermatologist.

E. Common Pitfalls and Side-Effects of Management.

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