Exfoliative Dermatitis

Etiology

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]

Epidemiology

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] 

Pathophysiology

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]

Histopathology

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]

Evaluation

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

Prognosis

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] 

Complications

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]